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1. Raw Garlic Consumption and Risk of Liver Cancer: A Population-Based Case-Control Study in Eastern China.

Author: Liu, Xing, Baecker, Aileen, Wu, Ming, Zhou, Jin-Yi, Yang, Jie, Han, Ren-Qiang, Wang, Pei-Hua, Liu, Ai-Min, Gu, Xiaoping, Zhang, Xiao-Feng, Wang, Xu-Shan, Su, Ming, Hu, Xu, Sun, Zheng, Li, Gang, Jin, Zi-Yi, Jung, Su Yon, Mu, Lina, He, Na, Lu, Qing-Yi, Li, Liming, Zhao, Jin-Kou, and Zhang, Zuo-Feng
Subjects: Humans, Garlic, Liver Neoplasms, Diet, Odds Ratio, Risk Factors, Case-Control Studies, Adult, Aged, Middle Aged, China, Female, Male, Raw Foods, Chinese population, garlic, hepatitis B virus, interaction, liver cancer, Chronic Liver Disease and Cirrhosis, Alcoholism, Alcohol Use and Health, Digestive Diseases, Substance Abuse, Liver Disease, Emerging Infectious Diseases, Nutrition, Infectious Diseases, Cancer, Clinical Research, Hepatitis, Oral and gastrointestinal, Food Sciences, Nutrition and Dietetics
Abstract: Although the major risk factors for liver cancer have been established, preventive factors for liver cancer have not been fully explored. We evaluated the association between raw garlic consumption and liver cancer in a large population-based case-control study in Eastern China. The study was conducted in Jiangsu, China, from 2003 to 2010. A total of 2011 incident liver cancer cases and 7933 randomly selected population-controls were interviewed. Epidemiological data including raw garlic intake and other exposures were collected, and serum markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were assayed. Overall, eating raw garlic twice or more per week was inversely associated with liver cancer, with an adjusted odds ratio (aOR) of 0.77 (95% confidence interval (CI): 0.62-0.96) compared to those ingesting no raw garlic or less than twice per week. In stratified analyses, high intake of raw garlic was inversely associated with liver cancer among Hepatitis B surface antigen (HBsAg) negative individuals, frequent alcohol drinkers, those having history of eating mold-contaminated food or drinking raw water, and those without family history of liver cancer. Marginal interactions on an additive scale were observed between low raw garlic intake and HBsAg positivity (attributable proportion due to interaction (AP) = 0.31, 95% CI: -0.01-0.62) and heavy alcohol drinking (AP = 0.28, 95% CI: 0.00-0.57). Raw garlic consumption is inversely associated with liver cancer. Such an association shed some light on the potential etiologic role of garlic intake on liver cancer, which in turn might provide a possible dietary intervention to reduce liver cancer in Chinese population.
Published: 2019

2. Family history of liver cancer may modify the association between HBV infection and liver cancer in a Chinese population

Author: Liu, Xing, Baecker, Aileen, Wu, Ming, Zhou, Jin‐Yi, Yang, Jie, Han, Ren‐Qiang, Wang, Pei‐Hua, Jin, Zi‐Yi, Liu, Ai‐Min, Gu, Xiaoping, Zhang, Xiao‐Feng, Wang, Xu‐Shan, Su, Ming, Hu, Xu, Sun, Zheng, Li, Gang, Fu, Alan, Jung, Su Yon, Mu, Lina, He, Na, Li, Liming, Zhao, Jin‐Kou, and Zhang, Zuo‐Feng
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Hepatitis, Cancer, HIV/AIDS, Hepatitis - B, Liver Disease, Chronic Liver Disease and Cirrhosis, Infectious Diseases, Digestive Diseases, Clinical Research, Good Health and Well Being, Aged, Aged, 80 and over, Case-Control Studies, China, Female, Hepatitis B, Humans, Liver Neoplasms, Male, Middle Aged, family history, hepatitis B Virus, hepatocellular carcinoma, interaction, serological marker, Gastroenterology & Hepatology, Clinical sciences
Abstract: Background & aimsThe potential interaction between family history of liver cancer and HBV infection on liver cancer has not been fully examined.MethodsWe conducted a population-based case-control study composed of 2011 liver cancer cases and 7933 controls in Jiangsu province, China from 2003 to 2010. Data on major risk or protective factors were collected and HBV/HCV sero-markers were assayed using blood samples. Semi-Bayes (SB) adjustments were applied to provide posterior estimates.ResultsBoth family history of liver cancer (adjusted odds ratios [OR]: 4.32, 95% confidence intervals [CI]: 3.25-5.73) and hepatitis B surface antigen (HBsAg) positivity (adjusted OR: 9.94, 95% CI: 8.33-11.87) were strongly associated with liver cancer development. For individuals with different combinations of serological markers, the adjusted ORs were 8.45 (95% CI: 5.16-13.82) for HBsAg- and HBcAb-positive; 7.57 (95% CI: 4.87-11.77) for HBsAg-, HBeAg- and HBcAb-positive; and 3.62 (95% CI: 2.47-5.31) for HBsAg-, HBeAb- and HBcAb-positive, compared to all negatives in HBV serological markers. One log increase in HBV DNA level was associated with 17% increased risk (adjusted OR: 1.17, 95% CI: 1.03-1.32). The SB-adjusted OR of HBV-positive individuals with family history of liver cancer was 41.34 (95% posterior interval [PI]: 23.69-72.12) compared with those HBV-negative without family history. Relative excess risk due to additive interaction, the attributable proportion and synergy index were 73.13, 0.87 and 8.04 respectively. Adjusted ratio of OR for multiplicative interaction was 2.84 (95% CI: 1.41-5.75).ConclusionsSuper-additive and super-multiplicative interactions may exist between family history of liver cancer and HBV infection on the development of liver cancer.
Published: 2019

3. Consumption of garlic and its interactions with tobacco smoking and alcohol drinking on esophageal cancer in a Chinese population

Author: Jin, Zi-Yi, Wallar, Gina, Zhou, Jin-Yi, Yang, Jie, Han, Ren-Qiang, Wang, Pei-Hua, Liu, Ai-Min, Gu, Xiao-Ping, Zhang, Xiao-Feng, Wang, Xu-Shan, Su, Ming, Hu, Xu, Sun, Zheng, Li, Gang, Mu, Li-Na, Lu, Qing-Yi, Liu, Xing, Li, Li-Ming, He, Na, Wu, Ming, Zhao, Jin-Kou, and Zhang, Zuo-Feng
Subjects: Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Public Health, Health Sciences, Nutrition, Cancer, Tobacco Smoke and Health, Substance Misuse, Prevention, Clinical Research, Alcoholism, Alcohol Use and Health, Tobacco, 3.1 Primary prevention interventions to modify behaviours or promote wellbeing, Prevention of disease and conditions, and promotion of well-being, Stroke, Oral and gastrointestinal, Cardiovascular, Good Health and Well Being, Aged, Alcohol Drinking, Case-Control Studies, China, Diet Surveys, Esophageal Neoplasms, Feeding Behavior, Female, Garlic, Humans, Male, Middle Aged, Risk Factors, Tobacco Smoking, alcohol drinking, esophageal cancer, garlic, interaction, smoking, Oncology and Carcinogenesis, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis, Public health
Abstract: Garlic consumption has been associated inversely with esophageal cancer (EC); however, its interactions with tobacco smoking and alcohol consumption have never been evaluated in an epidemiological study. We evaluated the potential interactions between garlic intake and tobacco smoking as well as alcohol consumption in a population-based case-control study with 2969 incident EC cases and 8019 healthy controls. Epidemiologic data were collected by face-to-face interviews using a questionnaire. The adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated and additive and multiplicative interactions were evaluated using unconditional logistic regression models, adjusting for potential confounding factors. Semi-Bayes (SB) adjustments were used to reduce potential false-positive findings. EC was associated inversely with raw garlic intake [SB-adjusted OR for more than once a week=0.68, 95% CI: 0.57-0.80], with a strong dose-response pattern in the overall analysis and in the stratified analyses by smoking and drinking. EC was associated positively with smoking and alcohol drinking, with SB-adjusted OR of 1.73 (95% CI: 1.62-1.85) and 1.37 (95% CI: 1.28-1.46) in dose-response effects of increased intensity and longer duration of smoking/drinking. Moreover, garlic intake interacts with smoking [synergy index (S)=0.83, 95% CI: 0.67-1.02; ratio of OR=0.88, 95% CI: 0.80-0.98] and alcohol drinking (S=0.73, 95% CI: 0.57-0.93; ratio of OR=0.86, 95% CI: 0.77-0.95) both multiplicatively and additively. Our findings suggested that high intake of raw garlic may reduce EC risk and may interact with tobacco smoking and alcohol consumption, which might shed a light on the development of EC as well as a potential dietary intervention among high-risk smokers and drinkers for EC prevention in the Chinese population.
Published: 2019

4. Interaction between tobacco smoking and hepatitis B virus infection on the risk of liver cancer in a Chinese population

Author: Liu, Xing, Baecker, Aileen, Wu, Ming, Zhou, Jin‐Yi, Yang, Jie, Han, Ren‐Qiang, Wang, Pei‐Hua, Jin, Zi‐Yi, Liu, Ai‐Min, Gu, Xiaoping, Zhang, Xiao‐Feng, Wang, Xu‐Shan, Su, Ming, Hu, Xu, Sun, Zheng, Li, Gang, Mu, Lina, He, Na, Li, Liming, Zhao, Jin‐Kou, and Zhang, Zuo‐Feng
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Chronic Liver Disease and Cirrhosis, Hepatitis, Hepatitis - B, Digestive Diseases, Tobacco Smoke and Health, Infectious Diseases, Clinical Research, HIV/AIDS, Cancer, Emerging Infectious Diseases, Tobacco, Liver Disease, Infection, Good Health and Well Being, Asian People, Bayes Theorem, Case-Control Studies, Female, Hepatitis B, Hepatitis B Surface Antigens, Hepatitis B virus, Humans, Liver Neoplasms, Male, Middle Aged, Odds Ratio, Risk Factors, Smoking, Tobacco Smoking, liver cancer, tobacco smoking, population attributable risk, interaction, Chinese population, Oncology and Carcinogenesis, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract: Although tobacco smoking has been reported as a risk factor for liver cancer, few studies have specifically explored the association among Chinese females and the potential interaction between smoking and other risk factors. A population-based case-control study was conducted and 2,011 liver cancer cases and 7,933 healthy controls were enrolled in Jiangsu, China from 2003 to 2010. Epidemiological data were collected, and serum hepatitis B surface antigen (HBsAg) and anti-HCV antibody were measured. Unconditional logistic regression was used to examine association and potential interaction, while semi-Bayes (SB) method was employed to make estimates more conservative. The prevalence of serum HBsAg positivity was 43.2% among cases and 6.5% among controls. The adjusted odds ratios (OR) for ever smoking were 1.62 (95% confidence interval [CI]: 1.33-1.96) among male and 0.82 (95% CI: 0.53-1.26) among female. Age at first cigarette, duration of smoking and pack-years of smoking were all significantly associated with liver cancer among men. Compared to HBsAg-negative never smokers, the adjusted ORs were 1.25 (95% CI: 1.03-1.52) for HBsAg-negative ever smokers, 7.66 (95% CI: 6.05-9.71) for HBsAg-positive never smokers, and 15.68 (95% CI: 12.06-20.39) for HBsAg-positive ever smokers. These different odds ratios indicated super-additive (RERI: 7.77, 95% CI: 3.81-11.73) and super-multiplicative interactions (ROR: 1.64, 95% CI: 1.17-2.30) between hepatitis B virus (HBV) infection and tobacco smoking. Most associations and interactions detected remained statistically significant after SB adjustments. Tobacco smoking and HBV infection positively interact in the development of liver cancer.
Published: 2018

5. A pharmacokinetics and safety phase 1/1b study of oral ixazomib in patients with multiple myeloma and severe renal impairment or end-stage renal disease requiring haemodialysis.

Author: Gupta, Neeraj, Hanley, Michael, Harvey, R, Badros, Ashraf, Lipe, Brea, Kukreti, Vishal, Berdeja, Jesus, Yang, Huyuan, Hui, Ai-Min, Qian, Mark, Zhang, Xiaoquan, Venkatakrishnan, Karthik, and Chari, Ajai
Subjects: dialysis, ixazomib, multiple myeloma, pharmacokinetics, renal impairment, Administration, Oral, Adult, Aged, Aged, 80 and over, Anemia, Blood Proteins, Boron Compounds, Drug Dosage Calculations, Female, Glycine, Humans, Kidney Failure, Chronic, Male, Middle Aged, Multiple Myeloma, Protease Inhibitors, Renal Dialysis, Renal Insufficiency
Abstract: Renal impairment (RI) is a major complication of multiple myeloma (MM). This study aimed to characterize the single-dose pharmacokinetics (PK) of the oral proteasome inhibitor, ixazomib, in cancer patients with normal renal function [creatinine clearance (CrCl) ≥90 ml/min; n = 20), severe RI (CrCl
Published: 2016

6. Right and left ventricular function and flow quantification in pediatric patients with repaired tetralogy of Fallot using four-dimensional flow magnetic resonance imaging

Author: Yao Xiaofen, Yumin Zhong, Rongzhen Ouyang, Ai-Min Sun, Yafeng Peng, Wei-Hui Xie, Liwei Hu, Qian Wang, and Fei Feng
Subjects: Male, Cardiac magnetic resonance, Intraclass correlation, Heart Ventricles, Cardiac-Gated Imaging Techniques, 4D flow, Magnetic Resonance Imaging, Cine, Ventricular Function, Left, medicine.artery, Ascending aorta, Image Interpretation, Computer-Assisted, Repaired tetralogy of Fallot, medicine, Medical technology, Humans, Radiology, Nuclear Medicine and imaging, R855-855.5, Child, Tetralogy of Fallot, Retrospective Studies, Reproducibility, medicine.diagnostic_test, Ventricular function, business.industry, Research, Reproducibility of Results, Magnetic resonance imaging, medicine.disease, Flow (mathematics), Flow quantification, Ventricular Function, Right, cardiovascular system, Female, Nuclear medicine, business, Blood Flow Velocity
Abstract: Background To assess the accuracy and reproducibility of right ventricular (RV) and left ventricular (LV) function and flow measurements in children with repaired tetralogy of Fallot (rTOF) using four-dimensional (4D) flow, compared with conventional two-dimensional (2D) magnetic resonance imaging (MRI) sequences. Methods Thirty pediatric patients with rTOF were retrospectively enrolled to undergo 2D balanced steady-state free precession cine (2D b-SSFP cine), 2D phase contrast (PC), and 4D flow cardiac MRI. LV and RV volumes and flow in the ascending aorta (AAO) and main pulmonary artery (MPA) were quantified. Pearson’s or Spearman’s correlation tests, paired t-tests, the Wilcoxon signed-rank test, Bland–Altman analysis, and intraclass correlation coefficients (ICC) were performed. Results The 4D flow scan time was shorter compared with 2D sequences (P 0.05), and showed strong correlations (r > 0.90, P 0.60, P 0.85). Conclusions RV and LV function and flow quantification in pediatric patients with rTOF using 4D flow MRI can be measured accurately and reproducibly compared to those with conventional 2D sequences.
Published: 2021

7. Different oxytocin and corticotropin-releasing hormone system changes in bipolar disorder and major depressive disorder patients

Author: Lei Guo, Yang-Jian Qi, Hong Tan, Dan Dai, Rawien Balesar, Arja Sluiter, Joop van Heerikhuize, Shao-Hua Hu, Dick F. Swaab, Ai-Min Bao, and Netherlands Institute for Neuroscience (NIN)
Subjects: Male, Depressive Disorder, Major, Mice, Bipolar Disorder, Corticotropin-Releasing Hormone, Animals, Female, General Medicine, RNA, Messenger, Oxytocin, General Biochemistry, Genetics and Molecular Biology
Abstract: BACKGROUND: Oxytocin (OXT) and corticotropin-releasing hormone (CRH) are both produced in hypothalamic paraventricular nucleus (PVN). Central CRH may cause depression-like symptoms, while peripheral higher OXT plasma levels were proposed to be a trait marker for bipolar disorder (BD). We aimed to investigate differential OXT and CRH expression in the PVN and their receptors in prefrontal cortex of major depressive disorder (MDD) and BD patients. In addition, we investigated mood-related changes by stimulating PVN-OXT in mice. METHODS: Quantitative immunocytochemistry and in situ hybridization were performed in the PVN for OXT and CRH on 6 BD and 6 BD-controls, 9 MDD and 9 MDD-controls. mRNA expressions of their receptors (OXTR, CRHR1 and CRHR2) were determined in anterior cingulate cortex and dorsolateral prefrontal cortex (DLPFC) of 30 BD and 34 BD-controls, and 24 MDD and 12 MDD-controls. PVN of 41 OXT-cre mice was short- or long-term activated by chemogenetics, and mood-related behavior was compared with 26 controls. FINDINGS: Significantly increased OXT-immunoreactivity (ir), OXT-mRNA in PVN and increased OXTR-mRNA in DLPFC, together with increased ratios of OXT-ir/CRH-ir and OXTR-mRNA/CRHR-mRNA were observed in BD, at least in male BD patients, but not in MDD patients. PVN-OXT stimulation induced depression-like behaviors in male mice, and mixed depression/mania-like behaviors in female mice in a time-dependent way. INTERPRETATION: Increased PVN-OXT and DLPFC-OXTR expression are characteristic for BD, at least for male BD patients. Stimulation of PVN-OXT neurons induced mood changes in mice, in a pattern different from BD. FUNDING: National Natural Science Foundation of China (81971268, 82101592).
Published: 2022

8. Sex differences in the neuropathological hallmarks of Alzheimer’s disease: focus on cognitively intact elderly individuals

Author: Hugo McGurran, Jackson Boonstra, Ai-Min Bao, Dick F. Swaab, Rawien Balesar, Arja A. Sluiter, Jochem Stormmesand, Yu-Ting Hu, Ronald W.H. Verwer, and Netherlands Institute for Neuroscience (NIN)
Subjects: Male, 0301 basic medicine, Aging, Histology, Amyloid, Physiology, tau Proteins, Disease, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, β amyloid, Physiology (medical), mental disorders, Entorhinal Cortex, Humans, Medicine, Aged, Aged, 80 and over, Sex Characteristics, Amyloid beta-Peptides, business.industry, Brain, Neurofibrillary Tangles, Entorhinal cortex, 030104 developmental biology, Neurology, Female, Brain bank, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: AIMS Women are more vulnerable to Alzheimer's disease (AD) than men. We investigated (i) whether and at what age the AD hallmarks, that is, β-amyloid (Aβ) and hyperphosphorylated Tau (p-Tau) show sex differences; and (ii) whether such sex differences may occur in cognitively intact elderly individuals. METHODS We first analysed the entire post-mortem brain collection of all non-demented 'controls' and AD donors from our Brain Bank (245 men and 403 women), for the presence of sex differences in AD hallmarks. Second, we quantitatively studied possible sex differences in Aβ, Aβ42 and p-Tau in the entorhinal cortex of well-matched female (n = 31) and male (n = 21) clinically cognitively intact elderly individuals. RESULTS Women had significantly higher Braak stages for tangles and amyloid scores than men, after 80 years. In the cognitively intact elderly, women showed higher levels of p-Tau, but not Aβ or Aβ42, in the entorhinal cortex than men, and a significant interaction of sex with age was found only for p-Tau but not Aβ or Aβ42. CONCLUSIONS Enhanced p-Tau in the entorhinal cortex may play a major role in the vulnerability to AD in women.
Published: 2021

9. Hydrogen sulfide protects against IL‐1β‐induced inflammation and mitochondrial dysfunction‐related apoptosis in chondrocytes and ameliorates osteoarthritis

Author: Daoliang Xu, Ben Wang, Jiaoxiang Chen, Xiaoyun Pan, Mingbao Gu, Libin Ni, Yingzhao Yan, Zhenxuan Shao, Haiming Jin, Yifeng Shi, and Ai-Min Wu
Subjects: Male, 0301 basic medicine, MAPK/ERK pathway, Physiology, Interleukin-1beta, Clinical Biochemistry, Apoptosis, Inflammation, Sodium hydrosulfide, Sulfides, Chondrocyte, Proinflammatory cytokine, 03 medical and health sciences, chemistry.chemical_compound, Chondrocytes, 0302 clinical medicine, Osteoarthritis, medicine, Animals, Humans, Hydrogen Sulfide, Phosphorylation, Protein kinase B, Cells, Cultured, PI3K/AKT/mTOR pathway, Aged, NF-kappa B, Cell Biology, Middle Aged, Mitochondria, Cell biology, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, chemistry, Antirheumatic Agents, Case-Control Studies, 030220 oncology & carcinogenesis, Female, Joints, Inflammation Mediators, Mitogen-Activated Protein Kinases, Phosphatidylinositol 3-Kinase, medicine.symptom, Proto-Oncogene Proteins c-akt, Signal Transduction
Abstract: The inflammatory environment and excessive chondrocyte apoptosis have been demonstrated to play crucial roles in the onset of osteoarthritis (OA). Hydrogen sulfide (H2 S), a gaseous signalling molecule, exerts an inhibitory effect on inflammation and apoptosis in several degenerative diseases. However, the protective effect of H2 S against OA has not been fully clarified, and its underlying mechanism should be examined further. In the current study, the role of endogenous H2 S in the pathogenesis of OA and its protective effects on interleukin (IL)-1β-induced chondrocytes were identified. Our data revealed decreased H2 S expression in both human degenerative OA cartilage tissue and IL-1β-induced chondrocytes. Pretreatment with the H2 S donor sodium hydrosulfide (NaHS) dramatically attenuated IL-1β-induced overproduction of inflammatory cytokines and improved the balance between anabolic and catabolic chondrocyte capacities, and these effects were dependent on PI3K/AKT pathway-mediated inhibition of nuclear factor kappa B (NF-κB). Moreover, mitochondrial dysfunction-related apoptosis was significantly reversed by NaHS in IL-1β-stimulated chondrocytes. Mechanistically, NaHS partially suppressed IL-1β-induced phosphorylation of the mitogen-activated protein kinase (MAPK) cascades. Furthermore, in the destabilization of the medial meniscus mouse model, OA progression was ameliorated by NaHS administration. Taken together, these results suggest that H2 S may antagonize IL-1β-induced inflammation and mitochondrial dysfunction-related apoptosis via selective suppression of the PI3K/Akt/NF-κB and MAPK signalling pathways, respectively, in chondrocytes and may be a potential therapeutic agent for the treatment of OA.
Published: 2020

10. Deletion of P110δ promotes the development of myocarditis in ApoE-deficient mice by increasing mononuclear cell peritoneal infiltration

Author: Wei Wei, Ai‑Min Pang, Ai‑Ying Xue, Fang Liu, Qi‑Zhi Zhang, and Li‑Na Cao
Subjects: Apolipoprotein E, Male, Cancer Research, medicine.medical_specialty, Class I Phosphatidylinositol 3-Kinases, Mice, Knockout, ApoE, Biochemistry, Peripheral blood mononuclear cell, Monocytes, Flow cytometry, Gene Knockout Techniques, Mice, Apolipoproteins E, Internal medicine, Genetics, medicine, Animals, Molecular Biology, Peritoneal Cavity, medicine.diagnostic_test, Chemistry, Monocyte, P110δ, apoptosis, Stroke Volume, Articles, Myocardial Contraction, Disease Models, Animal, Myocarditis, Endocrinology, medicine.anatomical_structure, Oncology, Apoptosis, Molecular Medicine, Female, Gene Deletion, Lipoprotein, Chylomicron, ApoE
Abstract: Phosphoinositide 3-kinase catalytic subunit δ isoform (P110δ) is mainly expressed in white blood cells. It is involved in T and B lymphocyte differentiation, maturation and the neutrophil chemotaxis process. Apolipoprotein E (ApoE) is an arginine-rich alkaline protein, which is present in plasma chylomicron, low-density lipoprotein and very low-density lipoprotein. The present study aimed to determine the effects of P110δ deletion on myocarditis in ApoE−/− mice. A mouse model of ApoE and P110δ double deletion was initially constructed; hematoxylin and eosin (H&E) staining was performed to detect the histological alterations in the mouse myocardium. Systolic and diastolic alterations, and alterations in the left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) were examined by electrocardiogram. Blood cell of ApoE and P110δ double mice was used to detect changes in white blood cells and monocytes. Western blotting was used to detect the expression levels of apoptosis-associated proteins, whereas flow cytometry was used to detect the percentage of apoptosis. Morphological alterations in myocardial cells were observed under a microscope. The results of polymerase chain reaction demonstrated that double deletion mice were successfully constructed. H&E staining revealed that cells in the ApoE−/− mice were spindle-shaped; however, the nuclei were smaller in the double deletion mice. There was no change in cardiac contraction in normal mice; however, in double deletion mice, the systolic and diastolic contractions were markedly reduced. LVFS and LVEF were decreased compared with in the control group. Blood cell analysis indicated that the content of white blood cells and monocytes in the experimental group was significantly higher than that in the control group. Western blotting demonstrated that the expression levels of apoptotic proteins in double deletion mice were significantly higher compared with in the control group. Flow cytometry revealed that the apoptotic ratio was increased in double deletion mice compared with in the control group (42 vs. 21%). These findings suggested that deletion of P110δ may induce monocyte peritoneal infiltration and increase apoptosis, thus promoting the development of myocarditis.
Published: 2020

11. Clinical impact of cardiovascular disease on patients with bronchiectasis

Author: Zhang Tao, Shanshan Chen, Hai-Lin Zhang, and Ai-Min Qiu
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, China, Microbiological culture, Exacerbation, Disease, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Medicine, Humans, Pseudomonas Infections, 030212 general & internal medicine, Lung, Aged, Retrospective Studies, Clinical impact, lcsh:RC705-779, Bronchiectasis, business.industry, Sputum, Odds ratio, lcsh:Diseases of the respiratory system, Middle Aged, Brain natriuretic peptide, medicine.disease, Cardiovascular disease, Confidence interval, Logistic Models, 030228 respiratory system, Cardiovascular Diseases, Cohort, Pseudomonas aeruginosa, Disease Progression, Female, business, Research Article
Abstract: Background Patients with bronchiectasis have a higher cardiovascular risk than their matched controls. However, the effect of cardiovascular (CV) disease on bronchiectasis remains unclear. Thus, we aimed to investigate the clinical impacts of cardiovascular disease on adult patients with bronchiectasis. Methods The study cohort comprised 603 consecutive inpatients diagnosed with bronchiectasis in the Affiliated Yancheng Hospital of Southeast University Medical College (Jiangsu, China) from January 2014 to December 2017. Symptoms, bacterial cultures, blood biochemical indicator levels, and chest high-resolution computed tomography scans were assessed during their initial hospitalization for bronchiectasis. Three hundred and thirty five subjects finished 1 year follow-up after their hospital discharge. Results Three hundred thirty five patients had at least one bronchiectasis exacerbation during the 1-year follow-up period. Patients with CV comorbidities were more likely to present with symptoms of wheezing (65.3%) and had a higher levels of brain natriuretic peptide (P P = 0.006), the isolation of Pseudomonas aeruginosa (OR 2.076, 95% CI 1.100–3.919; P = 0.024), and extension to more than two lobes (OR 2.485, 95% CI 1.195–5.168; P = 0.015). Conclusion The existence of cardiovascular disease was independently associated with increased bronchiectasis exacerbation.
Published: 2020

12. Estimating global injuries morbidity and mortality

Author: Zohreh Arefi, Rasmus Havmoeller, Pietro Ferrara, Vijay Kumar Chattu, Payman Salamati, Agegnehu Bante Getenet, Seyedeh Zahra Masoumi, Alexander C. Tsai, Andrew T Olagunju, Carl Abelardo T. Antonio, Morteza Abdullatif Khafaie, Tim Driscoll, Reza Rawassizadeh, Vishnu Renjith, Taras Kavetskyy, Ejaz Ahmad Khan, Gebreamlak Gebremedhn Gebremeskel, Richard C. Franklin, Naznin Hossain, Bhaskaran Unnikrishnan, Fariborz Mansour-Ghanaei, Arash Tehrani-Banihashemi, Morteza Naserbakht, Sangram Kishor Patel, Vera Marisa Costa, Suzanne Polinder, Ziad El-Khatib, Ashish Pathak, Mika Shigematsu, Bryan L. Sykes, David M. Pigott, Zeleke Aschalew Melketsedik, Hadi Hassankhani, Nuworza Kugbey, Lal B. Rawal, Masoud Foroutan, Dejana Braithwaite, Muluken Bekele Sorrie, Grant M. A. Wyper, Joht Singh Chandan, Akbar Barzegar, Hamid Safarpour, Kate E. LeGrand, Giulio Castelpietra, Dina Nur Anggraini Ningrum, Seth Christopher Yaw Appiah, Amin Soheili, Azeem Majeed, Akshaya Srikanth Bhagavathula, Nikolay Ivanovich Briko, Vahid Yazdi-Feyzabadi, Walter Mendoza, Ghulam Mustafa, Cuong Tat Nguyen, Pengpeng Ye, Mahesh P A, Carlos Miguel Rios González, Ahmad Daryani, Ibrahim Abdollahpour, Masoud Moradi, Haileab Fekadu Wolde, Mohammad Rabiee, Jaya Prasad Tripathy, Jack T Fox, Diep Ngoc Nguyen, Pallab K. Maulik, Ai-Min Wu, Félix Carvalho, Yun Jin Kim, Fatemeh Rajati, Nathaniel J Henry, David C. Schwebel, Ali H. Mokdad, Akine Eshete Abosetugn, Leonardo Roever, Ketema Bizuwork Gebremedhin, Khalid A Altirkawi, Hayimro Edemealem Merie, Farhad Ghamari, Ramesh Holla, Arash Sarveazad, Devasahayam J. Christopher, Kedir Hussein Abegaz, Suresh Jungari, Rohan Borschmann, Irfan Ullah, Nitin Joseph, Catalina Liliana Andrei, Abdallah M. Samy, Roman Topor-Madry, Michal Grivna, Ivo Rakovac, Mohammad Zamani, Antonio Maria Borzì, Atif Amin Baig, Mohsen Bayati, Mohammad Ali Mansournia, Fatemeh Heydarpour, Juanita A. Haagsma, Segun Emmanuel Ibitoye, Mehdi Sayyah, Teshome Abegaz Kamil, Fakher Rahim, Dillon O Sylte, Feng Sha, Palash Chandra Banik, Mohan Bairwa, Mariya Vladimirovna Titova, Yong Yu, Delia Hendrie, Spencer L. James, Anusha Ganapati Bhat, Seok Jun Yoon, Siavash Rahimi, Jost B. Jonas, Michael R. Phillips, Diana Silva, Amir Hossein Goudarzian, Samath D Dharmaratne, Roba Khundkar, Jemal Abdu Mohammed, Joemer C. Maravilla, Eleonora Dubljanin, Arun Balachandran, Arman Latifi, Randah R. Hamadeh, G. K. Mini, Alessandra C. Goulart, Andreea Mirica, Fatemeh Zarei, Habte Belete, Telma Zahirian Moghadam, Maseer Khan, Morenike Oluwatoyin Folayan, Atte Meretoja, Jasvinder A. Singh, Guilherme Borges, Yasir Waheed, Fahad Alanezi, Masoud Moghadaszadeh, Guoqing Hu, Archith Boloor, Luca Ronfani, Olayinka Stephen Ilesanmi, Vahid Rashedi, Mehran Shams-Beyranvand, Trang Huyen Nguyen, Yonatal Mesfin Tefera, Yousef Khader, Adnan Kisa, Simon I. Hay, Takeshi Fukumoto, Shahrzad Bazargan-Hejazi, Yuichiro Yano, Carlos A Castañeda-Orjuela, Suzanne Barker-Collo, Ghasem Azarian, Sezer Kisa, Basema Saddik, Leake Gebremeskel, Yetunde O. John-Akinola, Jennifer Rickard, Ilais Moreno Velásquez, Priya Rathi, Ali Bijani, Smita Pakhale, Francesco Saverio Violante, Neeraj Bedi, Efat Mohamadi, Deborah Carvalho Malta, Marek Majdan, Feleke Mekonnen Demeke, Chukwudi A Nnaji, Richard Ofori-Asenso, Prateek Rastogi, Xuefeng Liu, Monika Sawhney, Ayman Grada, Prasanna Mithra, Shanshan Li, Masood Ali Shaikh, Erin B Hamilton, Hung Chak Ho, Zichen Liu, Irini Chatziralli, Paulo A. Lotufo, Yuming Guo, Daniel N. 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Z.A., Memiah, P.T.N., Mendoza, W., Menezes, R.G., Mengesha, M.M., Meretoja, T.J., Meretoja, A., Merie, H.E., Mestrovic, T., Miazgowski, B., Miazgowski, T., Miller, T.R., Mini, G.K., Mirica, A., Mirrakhimov, E.M., Mirzaei-Alavijeh, M., Mithra, P., Moazen, B., Moghadaszadeh, M., Mohamadi, E., Mohammad, Y., Darwesh, A.M., Mohammadian-Hafshejani, A., Mohammadpourhodki, R., Mohammed, S., Mohammed, J.A., Mohebi, F., Bandpei, M.A.M., Molokhia, M., Monasta, L., Moodley, Y., Moradi, M., Moradi, G., Moradi-Lakeh, M., Moradzadeh, R., Morawska, L., Velásquez, I.M., Morrison, S.D., Mossie, T.B., Muluneh, A.G., Musa, K.I., Mustafa, G., Naderi, M., Nagarajan, A.J., Naik, G., Naimzada, M.D., Najaf, F., Nangia, V., Nascimento, B.R., Naserbakht, M., Nayak, V., Nazari, J., Ndwandwe, D.E., Negoi, I., Ngunjiri, J.W., Nguyen, T.H., Nguyen, C.T., Nguyen, D.N., Nguyen, H.L.T., Nikbakhsh, R., Ningrum, D.N.A., Nnaji, C.A., Ofori-Asenso, R., Ogbo, F.A., Oghenetega, O.B., Oh, I.-H., Olagunju, A.T., Olagunju, 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Yazdi-Feyzabadi, V., Ye, P., Yip, P., Yisma, E., Yonemoto, N., Yoon, S.-J., Youm, Y., Younis, M.Z., Yousef, Z., Yu, C., Yu, Y., Moghadam, T.Z., Zaidi, Z., Zaman, S.B., Zamani, M., Zandian, H., Zarei, F., Zhang, Z.-J., Zhang, Y., Ziapour, A., Zodpey, S., Dandona, R., Dharmaratne, S.D., Hay, S.I., Mokdad, A.H., Pigott, D.M., Reiner, R.C., Vos, T., Instituto de Saúde Pública da Universidade do Porto, James, Spencer L, Castle, Chris D, Dingels, Zachary V, Fox, Jack T, Adema, Bereket Duko, Yisma, Engida, Vos, Theo, and Public Health
Subjects: Male, Populations/contexts, 1106 Human Movement and Sports Sciences, Global injuries, population, 030204 cardiovascular system & hematology, Global Health, contexts, context, Global Burden of Disease, 0302 clinical medicine, Quality-Adjusted Life Year, Global health, 030212 general & internal medicine, Original Research, Data, populations/contexts, Incidence (epidemiology), Incidence, methodology, 3142 Public health care science, environmental and occupational health, Female, Public Health, TERRITORIES, Quality-Adjusted Life Years, descriptive epidemiology, Human, Disabilities, 195 COUNTRIES, statistical issue, 1117 Public Health and Health Services, 03 medical and health sciences, AGE, Life Expectancy, Environmental health, Injury prevention, SYSTEMATIC ANALYSIS, statistical issues, Humans, Mortality, Estimation, SEX-SPECIFIC MORTALITY, DISABILITY, Public Health, Environmental and Occupational Health, populations, Morbidity, Wounds and Injuries, 1106 Human Movement and Sports Sciences, 1117 Public Health and Health Services, 1701 Psychology, Quality-adjusted life year, Years of potential life lost, 1701 Psychology, Life expectancy, Estimates, Human medicine, populations/context
Abstract: Background. While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. Methods. In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. Results. GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. Conclusions. GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future. Seyed Aljunid acknowledges the Department of Health Policy and Management, Faculty of Public Health, Kuwait University and International Centre for Casemix and Clinical Coding, Faculty of Medicine, National University of Malaysia for the approval and support to participate in this research project. Alaa Badawi acknowledges support by the Public Health Agency of Canada. Till Bärnighausen acknowledges support by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research. Traolach Brugha received support from NatCen Social Research (http://natcen.ac.uk/) via NHS Digital and Department of Health and Social Care London, for the Adult Psychiatric Morbidity Survey (APMS) programme. Felix Carvalho received support from UID/MULTI/04378/2019 with funding from FCT/MCTES through national funds. Vera M Costa acknowledges support from grant (SFRH/BHD/110001/2015), received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006. Kebede Deribe is supported by a grant from the Wellcome Trust [grant number 201900] as part of his International Intermediate Fellowship. Tim Driscoll acknowledges that work on occupational risk factors was partially supported by funds from the World Health Organization. Eduarda Fernandes acknowledges support from UID/QUI/50006/2019 with funding from FCT/MCTES through national funds. Yuming Guo acknowledges support from Career Development Fellowships of the Australian National Health and Medical Research Council (numbers APP1107107 and APP1163693). Sheikh Mohammed Shariful Islam is funded by a Fellowship from National Heart Foundation of Australia and Institute for Physical Activity and Nutrition, Deakin University. Mihajlo Jakovljevic acknowledges support by the Ministry of Education Science and Technological Development of the Republic of Serbia through the Grant number OI175014; publication of results was not contingent upon Ministry's censorship or approval. Sudha Jayaraman acknowledges support from: NIH R21: 1R21TW010439-01A1 (PI); Rotary Foundation Global Grant #GG1749568 (PI); NIH P20: 1P20CA210284-01A1 (Co-PI) and DOD grant W81XWH-16-2-0040 (Co-I), during the period of this study. Yun Jin Kim acknowledges support from a grant from the Research Management Centre, Xiamen University Malaysia [grant number: XMUMRF/2018-C2/ITCM/0001]. Kewal Krishan is supported by UGC Centre of Advanced Study (CAS II) awarded to the Department of Anthropology, Panjab University, Chandigarh, India. Mansai Kumar acknowledges support from FIC/ NIH K43 1K43MH114320-01. Amanda Mason-Jones acknowledges support by the University of York. Mariam Molokhia is supported by the National Institute for Health Research Biomedical Research Center at Guy’s and St Thomas’s National Health Service Foundation Trust and King’s College London. Ilais Moreno Velasquez is supported by the Sistema Nacional de Investigación (SNI, Senacyt, Panama). Mukhammad David Naimzada acknowledges support from Government of the Russian Federation (Agreement No – 075-02-2019-967). Duduzile Ndwandwe acknowledges support from Cochrane South Africa, South African Medical Research Council. Stanislav S. Otstavnov acknowledges the support from the Government of the Russian Federation (Agreement No – 075-02-2019-967). Ashish Pathak acknowledges support from Indian Council of Medical Research (ICMR), New Delhi, India (Grant number 2013-1253). Michael R Phillips acknowledges support in part by a grant from the National Natural Science Foundation of China (No.81761128031). Abdallah M. Samy received a fellowship from the Egyptian Fulbright Mission Program. Milena Santric Milicevic acknowledges the support from the Ministry of Education, Science and Technological Development, Republic of Serbia (Contract No. 175087). Seyedmojtaba Seyedmousavi was supported by the Intramural Research Program of the National Institutes of Health, Clinical Center, Department of Laboratory Medicine, Bethesda, MD, USA. Rafael Tabarés-Seisdedos was supported in part by the national grant PI17/00719 from ISCIII-FEDER. Sojib Bin Zaman acknowledges support from an "Australian Government Research Training Program (RTP) Scholarship.
Published: 2020

13. Stachydrine ameliorates the progression of intervertebral disc degeneration via the PI3K/Akt/NF-κB signaling pathway: in vitro and in vivo studies

Author: Jiajie Lu, Zhenxuan Shao, Xiaolei Zhang, Xiang-Yang Wang, Boda Chen, Guoling Zeng, Ai-Min Wu, Haibo Liang, and Chen-Xi Zhang
Subjects: Male, Proline, Interleukin-1beta, Intervertebral Disc Degeneration, digestive system, Rats, Sprague-Dawley, Extracellular matrix, Phosphatidylinositol 3-Kinases, 03 medical and health sciences, 0302 clinical medicine, In vivo, medicine, Animals, Protein kinase B, PI3K/AKT/mTOR pathway, Inflammation, Chemistry, Catabolism, NF-kappa B, General Medicine, In vitro, Hedgehog signaling pathway, Extracellular Matrix, Rats, Cell biology, Molecular Docking Simulation, Mechanism of action, 030220 oncology & carcinogenesis, Disease Progression, medicine.symptom, Proto-Oncogene Proteins c-akt, 030217 neurology & neurosurgery, Signal Transduction, Food Science
Abstract: Intervertebral disc degeneration (IDD) has been reported to be a major cause of low back pain. Stachydrine (STA) is present in the fruit juice of the Citrus genus and Leonurus heterophyllus, in non-negligible concentrations. In our study, we examined the protective effects of STA against IDD development as well as its underlying mechanism of action using both in vitro and in vivo experiments. STA exerted protective effects on the anabolism and catabolism of the extracellular matrix (ECM) in IL-1β-treated NPCs and inhibited the expression of pro-inflammatory factors in vitro. Mechanistically, STA suppressed the IL-1β-induced activation of PI3K/Akt/NF-κB signalling pathway cascades. Moreover, it was also demonstrated in molecular docking studies that STA has strong binding abilities to PI3K. Furthermore, STA ameliorated the progression of the IDD process in vivo in the puncture-induced rat model. In summary, our findings demonstrated that STA ameliorates the progression of IDD via the PI3K/Akt/NF-κB signalling pathway, which makes STA a promising therapeutic agent for the treatment of IDD.
Published: 2020

14. Examining how our brain determines gender identity

Author: Ai-Min, Bao
Subjects: Male, Brain, Gender Identity, Humans, Female
Published: 2022

15. Limonin Inhibits IL-1β-Induced Inflammation and Catabolism in Chondrocytes and Ameliorates Osteoarthritis by Activating Nrf2

Author: Jingtao Jiang, Naifeng Tian, Chenghao Ren, Jie Jin, Ximiao Chen, Xinhuang Lv, Xiang-Yang Wang, Zongyou Pan, Liaojun Sun, Ben Wang, Hongyu Chen, Yaosen Wu, Mingbao Gu, Ai-Min Wu, Weiyang Gao, Yifei Zhou, and Xiaolei Zhang
Subjects: Limonins, Male, Aging, Article Subject, Limonin, NF-E2-Related Factor 2, Interleukin-1beta, Arthritis, Inflammation, Pharmacology, Biochemistry, Menisci, Tibial, Proinflammatory cytokine, chemistry.chemical_compound, Mice, Chondrocytes, In vivo, Osteoarthritis, medicine, Animals, QH573-671, Chemistry, Catabolism, NF-kappa B, Cell Biology, General Medicine, medicine.disease, Chondrogenesis, Arthritis, Experimental, Mice, Inbred C57BL, Gene Expression Regulation, Heme Oxygenase (Decyclizing), Signal transduction, medicine.symptom, Cytology, Research Article
Abstract: Osteoarthritis (OA), a degenerative disorder, is considered to be one of the most common forms of arthritis. Limonin (Lim) is extracted from lemons and other citrus fruits. Limonin has been reported to have anti-inflammatory effects, while inflammation is a major cause of OA; thus, we propose that limonin may have a therapeutic effect on OA. In this study, the therapeutic effect of limonin on OA was assessed in chondrocytes in vitro in IL-1β induced OA and in the destabilization of the medial meniscus (DMM) mice in vivo. The Nrf2/HO-1/NF-κB signaling pathway was evaluated to illustrate the working mechanism of limonin on OA in chondrocytes. In this study, it was found that limonin can reduce the level of IL-1β induced proinflammatory cytokines such as INOS, COX-2, PGE2, NO, TNF-α, and IL-6. Limonin can also diminish the biosynthesis of IL-1β-stimulated chondrogenic catabolic enzymes such as MMP13 and ADAMTS5 in chondrocytes. The research on the mechanism study demonstrated that limonin exerts its protective effect on OA through the Nrf2/HO-1/NF-κB signaling pathway. Taken together, the present study shows that limonin may activate the Nrf2/HO-1/NF-κB pathway to alleviate OA, making it a candidate therapeutic agent for OA.
Published: 2021

16. Changes of hypocretin (orexin) system in schizophrenia

Author: Tingting Mou, Rolf Fronczek, Dick F. Swaab, Kangyu Jin, Jinfeng Duan, Haimei Li, Weijuan Xu, Ai-Min Bao, Jing Lu, Jin-Hui Li, Manli Huang, and Netherlands Institute for Neuroscience (NIN)
Subjects: Adult, Male, medicine.medical_specialty, Prefrontal Cortex, superior frontal gyrus, Neurotransmission, cerebrospinal fluid, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Sex Factors, Orexin Receptors, Internal medicine, mental disorders, medicine, Humans, hypothalamus, Receptor, orexin, hypocretin receptor, plasma, Orexins, hypocretin receptor, business.industry, Middle Aged, medicine.disease, 030227 psychiatry, Orexin, schizophrenia, Psychiatry and Mental health, Endocrinology, Superior frontal gyrus, orexin, nervous system, Schizophrenia, Hypothalamus, Female, Autopsy, hypocretin, business, 030217 neurology & neurosurgery, psychological phenomena and processes, Hypocretin orexin, Regular Articles
Abstract: Hypocretin (also called orexin) regulates various functions, such as sleep-wake rhythms, attention, cognition, and energy balance, which show significant changes in schizophrenia (SCZ). We aimed to identify alterations in the hypocretin system in SCZ patients. We measured plasma hypocretin-1 levels in SCZ patients and healthy controls and found significantly decreased plasma hypocretin-1 levels in SCZ patients, which was mainly due to a significant decrease in female SCZ patients compared with female controls. In addition, we measured postmortem hypothalamic hypocretin-1-immunoreactivity (ir), ventricular cerebrospinal fluid (CSF) hypocretin-1 levels, and hypocretin receptor (Hcrt-R) mRNA expression in the superior frontal gyrus (SFG) in SCZ patients and controls We observed a significant decrease in the amount of hypothalamic hypocretin-1 ir in SCZ patients, which was due to decreased amounts in female but not male patients. Moreover, Hcrt-R2 mRNA in the SFG was decreased in female SCZ patients compared with female controls, while male SCZ patients showed a trend of increased Hcrt-R1 mRNA and Hcrt-R2 mRNA expression compared with male controls. We conclude that central hypocretin neurotransmission is decreased in SCZ patients, especially female patients, and this is reflected in the plasma.
Published: 2021

17. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Author: Sorin Hostiuc, Shaun Wen Huey Lee, Jorge R. Ledesma, Carsten Flohr, Masoumeh Sadeghi, João Mauricio Castaldelli-Maia, Behzad Karami Matin, Cyrus Alinia, Mehdi Bohluli, Félix Carvalho, Yun Jin Kim, Catalina Liliana Andrei, Seyyed Meysam Mousavi, Bernhard T. Baune, Ehsan Ahmadpour, Dinh-Toi Chu, Beatrix Haddock, Gianfranco Alicandro, Vasily Vlassov, Mohammad Taghi Khodayari, Gianna Gayle Herrera Amul, Arash Tehrani-Banihashemi, Govinda Prasad Dhungana, Fereshteh Ansari, Michael K. Hole, Azeem Majeed, Iman Halvaei, Saqib Ali, Arianna Maever L. Amit, Tomas Y. Yeheyis, John S. Ji, Martin McKee, Jamileh Shadid, Leonardo Roever, Peng Jia, Ettore Beghi, Pablo M. Lavados, Young Eun Kim, Vahid Alipour, Sowmya J. Rao, Ahmad Daryani, Cathleen Keller, Ibrahim Abdollahpour, Nicole K. DeCleene, Ebrahim Babaee, Saman Esmaeilnejad, Boris Bikbov, William M. Gardner, Lydia M. Haile, Luca Ronfani, Azalea M. Thomson, Irena Ilic, Ruth W. Kimokoti, Yingxi Zhao, Guoqing Hu, Mehran Shams-Beyranvand, Ilais Moreno Velásquez, Nathaniel J. Henry, Brijesh Sathian, Daniel Kim, Peter Memiah, Mohammad Hadi Abbasi, Andrea Farioli, Zahra Kamiab, Bolajoko O. Olusanya, Matthew C. Doxey, Tommi Vasankari, Hamideh Salimzadeh, Luisa Sorio Flor, Priya Rathi, Shanshan Li, Tanvir M. Huda, Dillon O Sylte, Rosario Cárdenas, Agegnehu Bante, Helen Ippolito, Alyssa Acebedo, Jeffrey D. Stanaway, Anwar Faraj, João Pedro Silva, Amin Mousavi Khaneghah, Pushpendra Kumar, Sangram Kishor Patel, Josephine W. Ngunjiri, Holly E. Erskine, Eugene Sobngwi, Filippo Ariani, Shane D. Morrison, Mohammad Aghaali, Meghan D. Mooney, Vera Marisa Costa, Palash Chandra Banik, Rupak Desai, Ken Takahashi, Maigeng Zhou, Morteza Oladnabi, Bogdan Oancea, Daniela Ribeiro, Mohammad Farahmand, Irmina Maria Michalek, Yetunde O. John-Akinola, Khem Narayan Pokhrel, Emilie R Maddison, Syed Mohamed Aljunid, Damian G. Hoy, Hosni Salem, V. Prakash, Shuhei Nomura, Inga Dora Sigfusdottir, Anders Larsson, Sharareh Eskandarieh, Abdollah Mohammadian-Hafshejani, Somayeh Bohlouli, Joana Morgado-da-Costa, Siamak Sabour, Theo Vos, Han Yong Wunrow, Khaled Khatab, Alireza Zangeneh, Ann Kristin Knudsen, Marissa B Reitsma, Hannah J. Henrikson, Randah R. Hamadeh, Tuomo J. Meretoja, Ireneous N. Soyiri, Giuseppe Grosso, Ziyad Al-Aly, Taraneh Yousefinezhadi, Joseph L Ward, Roba Khundkar, Ricardo Santiago Gomez, Reza Malekzadeh, John J. McGrath, Sandra B. Munro, Shahin Soltani, Amy E. Peden, Rufus Akinyemi, Marcel Ausloos, Naohiro Yonemoto, Bogdan Wojtyniak, Ahmad Ghashghaee, Guilherme Borges, Sadia Bibi, Farhad Islami, Hamed Mirzaei, Mohammad Ali Sahraian, M. Ashworth Dirac, Hosna Janjani, Kairat Davletov, Hermann Brenner, Yuichiro Yano, Elissa M. 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Bennitt, Maciej Banach, Antonio Biondi, Donal Bisanzio, Josip Car, Ronny Westerman, Shafiu Mohammed, Biniyam Sahiledengle Geberemariyam, Kenji Shibuya, Meghdad Pirsaheb, Milena Santric-Milicevic, Karen M. Tabb, Paula Moraga, Soheil Hassanipour, Hasan Yusefzadeh, Avina Vongpradith, Dara K. Mohammad, Ralph Maddison, Babak Moazen, Getachew Mullu Kassa, Rahman Shiri, Fernando Neves Hugo, Hmwe H Kyu, Zachary V Dingels, Florian Fischer, Valentin Yurievich Skryabin, Rafael Tabarés-Seisdedos, Massimo Cirillo, Nikita Otstavnov, Robert C. Reiner, Van C. Lansingh, Rodrigo Sarmiento-Suarez, Ashkan Afshin, Benjamin A Stark, Mohsen Abbasi-Kangevari, Natalie C. Galles, Behnam Heidari, Eun-Kee Park, Mohammad Ali Jahani, Suzanne Polinder, Mahalaqua Nazli Khatib, Farhad Jadidi-Niaragh, Amir Radfar, Mowafa Househ, Derrick A Bennett, Gaorui Guo, Hesam Ghiasvand, Taweewat Wiangkham, Tamás Joó, Cristiana Abbafati, Kathryn Mei Ming Lau, Anita K. Nandi, Miklós Szócska, Manasi Kumar, Eduardo A. 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L., Department of Public Health, Clinicum, Department of Neurosciences, HUS Comprehensive Cancer Center, Environmental Sciences, Public Health, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Value, Affordability and Sustainability (VALUE), Microbes in Health and Disease (MHD), Sálfræðideild (HR), Department of Psychology (RU), Samfélagssvið (HR), School of Social Sciences (RU), Háskólinn í Reykjavík, Reykjavik University, GBD 2019 Diseases and Injuries Collaborator, Violante FS, Department of Earth Observation Science, Faculty of Geo-Information Science and Earth Observation, and UT-I-ITC-ACQUAL
Subjects: Male, Life expectancy, Disability-Adjusted Life Year, Diseases, Disease, communicable disease, systematic analysis, Global Burden of Disease, 0302 clinical medicine, 80 and over, Medicine, 10. No inequality, Child, 11 Medical and Health Sciences, injuries, Aged, 80 and over, education.field_of_study, Sjúkdómar, DEMENTIA, FALLS, General Medicine, Forvarnir, 3. Good health, Child, Preschool, Human, GBD, Population health, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Humans, Global Burden of Disease Study, education, Aged, Spatial Analysis, Global burden, Disability, Prevention, DISABILITY, Infant, Spatial Analysi, Mortality rate, Global Burden of Disease, Diseases, Injuries, Systematic analysis, PREVENTION, Years of potential life lost, Risk factors, Disease study, ITC-ISI-JOURNAL-ARTICLE, RISK-FACTORS, Clinical Medicine, RA, Demography, Fötlun, Dánartíðni, Áhættuþættir, 030204 cardiovascular system & hematology, Risk Factors, Cause of Death, Global health, 030212 general & internal medicine, 1. No poverty, Disability-Adjusted Life Years, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, 3142 Public health care science, environmental and occupational health, Adolescent, Adult, Age Distribution, Female, Infant, Newborn, Young Adult, Lýðheilsa, CLINICAL-TRIALS, Population, Settore MED/01 - Statistica Medica, diseases, ITC-HYBRID, Heilbrigðisvísindi, General & Internal Medicine, Mortality, Preschool, Disease burden, business.industry, Risk Factor, Klinisk medicin, Newborn, purl.org/pe-repo/ocde/ford#3.02.00 [https], Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Áverkar, Systematic analysis, NA, business
Abstract: Publisher's version (útgefin grein), Background In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990-2010 time period, with the greatest annualised rate of decline occurring in the 0-9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10-24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10-24 years were also in the top ten in the 25-49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50-74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and development investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd., Research reported in this publication was supported by the Bill & Melinda Gates Foundation; the University of Melbourne; Queensland Department of Health, Australia; the National Health and Medical Research Council, Australia; Public Health England; the Norwegian Institute of Public Health; St Jude Children's Research Hospital; the Cardiovascular Medical Research and Education Fund; the National Institute on Ageing of the National Institutes of Health (award P30AG047845); and the National Institute of Mental Health of the National Institutes of Health (award R01MH110163). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders. The authors alone are responsible for the views expressed in this Article and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated, the National Health Service (NHS), the National Institute for Health Research (NIHR), the UK Department of Health and Social Care, or Public Health England; the United States Agency for International Development (USAID), the US Government, or MEASURE Evaluation; or the European Centre for Disease Prevention and Control (ECDC). This research used data from the Chile National Health Survey 2003, 2009-10, and 2016-17. The authors are grateful to the Ministry of Health, the survey copyright owner, for allowing them to have the database. All results of the study are those of the authors and in no way committed to the Ministry. The Costa Rican Longevity and Healthy Aging Study project is a longitudinal study by the University of Costa Rica's Centro Centroamericano de Poblacion and Instituto de Investigaciones en Salud, in collaboration with the University of California at Berkeley. The original pre-1945 cohort was funded by the Wellcome Trust (grant 072406), and the 1945-55 Retirement Cohort was funded by the US National Institute on Aging (grant R01AG031716). The principal investigators are Luis Rosero-Bixby and William H Dow and co-principal investigators are Xinia Fernandez and Gilbert Brenes. The accuracy of the authors' statistical analysis and the findings they report are not the responsibility of ECDC. ECDC is not responsible for conclusions or opinions drawn from the data provided. ECDC is not responsible for the correctness of the data and for data management, data merging and data collation after provision of the data. ECDC shall not be held liable for improper or incorrect use of the data. The Health Behaviour in School-Aged Children (HBSC) study is an international study carried out in collaboration with WHO/EURO. The international coordinator of the 1997-98, 2001-02, 2005-06, and 2009-10 surveys was Candace Currie and the databank manager for the 1997-98 survey was Bente Wold, whereas for the following surveys Oddrun Samdal was the databank manager. A list of principal investigators in each country can be found on the HBSC website. Data used in this paper come from the 2009-10 Ghana Socioeconomic Panel Study Survey, which is a nationally representative survey of more than 5000 households in Ghana. The survey is a joint effort undertaken by the Institute of Statistical, Social and Economic Research (ISSER) at the University of Ghana and the Economic Growth Centre (EGC) at Yale University. It was funded by EGC. ISSER and the EGC are not responsible for the estimations reported by the analysts. The Palestinian Central Bureau of Statistics granted the researchers access to relevant data in accordance with license number SLN2014-3-170, after subjecting data to processing aiming to preserve the confidentiality of individual data in accordance with the General Statistics Law, 2000. The researchers are solely responsible for the conclusions and inferences drawn upon available data. Data for this research was provided by MEASURE Evaluation, funded by USAID. The authors thank the Russia Longitudinal Monitoring Survey, conducted by the National Research University Higher School of Economics and ZAO Demoscope together with Carolina Population Center, University of North Carolina at Chapel Hill and the Institute of Sociology, Russia Academy of Sciences for making data available. This paper uses data from the Bhutan 2014 STEPS survey, implemented by the Ministry of Health with the support of WHO; the Kuwait 2006 and 2014 STEPS surveys, implemented by the Ministry of Health with the support of WHO; the Libya 2009 STEPS survey, implemented by the Secretariat of Health and Environment with the support of WHO; the Malawi 2009 STEPS survey, implemented by Ministry of Health with the support of WHO; and the Moldova 2013 STEPS survey, implemented by the Ministry of Health, the National Bureau of Statistics, and the National Center of Public Health with the support of WHO. This paper uses data from Survey of Health, Ageing and Retirement in Europe (SHARE) Waves 1 (DOI:10.6103/SHARE. w1.700), 2 (10.6103/SHARE.w2.700), 3 (10.6103/SHARE.w3.700), 4 (10.6103/SHARE.w4.700), 5 (10.6103/SHARE.w5.700), 6 (10.6103/SHARE.w6.700), and 7 (10.6103/SHARE.w7.700); see Borsch-Supan and colleagues (2013) for methodological details. The SHARE data collection has been funded by the European Commission through FP5 (QLK6-CT-2001-00360), FP6 (SHARE-I3: RII-CT-2006-062193, COMPARE: CIT5-CT-2005-028857, SHARELIFE: CIT4-CT-2006-028812), FP7 (SHARE-PREP: GA N degrees 211909, SHARE-LEAP: GA N degrees 227822, SHARE M4: GA N degrees 261982) and Horizon 2020 (SHARE-DEV3: GA N degrees 676536, SERISS: GA N degrees 654221) and by DG Employment, Social Affairs & Inclusion. Additional funding from the German Ministry of Education and Research, the Max Planck Society for the Advancement of Science, the US National Institute on Aging (U01_AG09740-13S2, P01_AG005842, P01_AG08291, P30_AG12815, R21_AG025169, Y1-AG-4553-01, IAG_BSR06-11, OGHA_04-064, HHSN271201300071C), and from various national funding sources is gratefully acknowledged. This study has been realised using the data collected by the Swiss Household Panel, which is based at the Swiss Centre of Expertise in the Social Sciences. The project is financed by the Swiss National Science Foundation. The United States Aging, Demographics, and Memory Study is a supplement to the Health and Retirement Study (HRS), which is sponsored by the National Institute of Aging (grant number NIA U01AG009740). It was conducted jointly by Duke University and the University of Michigan. The HRS is sponsored by the National Institute on Aging (grant number NIA U01AG009740) and is conducted by the University of Michigan. This paper uses data from Add Health, a program project designed by J Richard Udry, Peter S Bearman, and Kathleen Mullan Harris, and funded by a grant P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 17 other agencies. Special acknowledgment is due to Ronald R Rindfuss and Barbara Entwisle for assistance in the original design. Information on how to obtain the Add Health data files is available on the Add Health website. No direct support was received from grant P01-HD31921 for this analysis. The data reported here have been supplied by the United States Renal Data System. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US Government. Collection of data for the Mozambique National Survey on the Causes of Death 2007-08 was made possible by USAID under the terms of cooperative agreement GPO-A-00-08-000_D3-00. This manuscript is based on data collected and shared by the International Vaccine Institute (IVI) from an original study IVI conducted. L G Abreu acknowledges support from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (Brazil; finance code 001) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, a Brazilian funding agency). I N Ackerman was supported by a Victorian Health and Medical Research Fellowship awarded by the Victorian Government. O O Adetokunboh acknowledges the South African Department of Science and Innovation and the National Research Foundation. A Agrawal acknowledges the Wellcome Trust DBT India Alliance Senior Fellowship. S M Aljunid acknowledges the Department of Health Policy and Management, Faculty of Public Health, Kuwait University and International Centre for Casemix and Clinical Coding, Faculty of Medicine, National University of Malaysia for the approval and support to participate in this research project. M Ausloos, C Herteliu, and A Pana acknowledge partial support by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. A Badawi is supported by the Public Health Agency of Canada. D A Bennett was supported by the NIHR Oxford Biomedical Research Centre. R Bourne acknowledges the Brien Holden Vision Institute, University of Heidelberg, Sightsavers, Fred Hollows Foundation, and Thea Foundation. G B Britton and I Moreno Velasquez were supported by the Sistema Nacional de Investigacion, SNI-SENACYT, Panama. R Buchbinder was supported by an Australian National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship. J J Carrero was supported by the Swedish Research Council (2019-01059). F Carvalho acknowledges UID/MULTI/04378/2019 and UID/QUI/50006/2019 support with funding from FCT/MCTES through national funds. A R Chang was supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases grant K23 DK106515. V M Costa acknowledges the grant SFRH/BHD/110001/2015, received by Portuguese national funds through Fundacao para a Ciencia e Tecnologia, IP, under the Norma Transitaria DL57/2016/CP1334/CT0006. A Douiri acknowledges support and funding from the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care South London at King's College Hospital NHS Foundation Trust and the Royal College of Physicians, and support from the NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. B B Duncan acknowledges grants from the Foundation for the Support of Research of the State of Rio Grande do Sul (IATS and PrInt) and the Brazilian Ministry of Health. H E Erskine is the recipient of an Australian NHMRC Early Career Fellowship grant (APP1137969). A J Ferrari was supported by a NHMRC Early Career Fellowship grant (APP1121516). H E Erskine and A J Ferrari are employed by and A M Mantilla-Herrera and D F Santomauro affiliated with the Queensland Centre for Mental Health Research, which receives core funding from the Queensland Department of Health. M L Ferreira holds an NHMRC Research Fellowship. C Flohr was supported by the NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust. M Freitas acknowledges financial support from the EU (European Regional Development Fund [FEDER] funds through COMPETE POCI-01-0145-FEDER-029248) and National Funds (Fundacao para a Ciencia e Tecnologia) through project PTDC/NAN-MAT/29248/2017. A L S Guimaraes acknowledges support from CNPq. C Herteliu was partially supported by a grant co-funded by FEDER through Operational Competitiveness Program (project ID P_40_382). P Hoogar acknowledges Centre for Bio Cultural Studies, Directorate of Research, Manipal Academy of Higher Education and Centre for Holistic Development and Research, Kalaghatagi. F N Hugo acknowledges the Visiting Professorship, PRINT Program, CAPES Foundation, Brazil. B-F Hwang was supported by China Medical University (CMU107-Z-04), Taichung, Taiwan. S M S Islam was funded by a National Heart Foundation Senior Research Fellowship and supported by Deakin University. R Q Ivers was supported by a research fellowship from the National Health and Medical Research Council of Australia. M Jakovljevic acknowledges the Serbian part of this GBD-related contribution was co-funded through Grant OI175014 of the Ministry of Education Science and Technological Development of the Republic of Serbia. P Jeemon was supported by a Clinical and Public Health intermediate fellowship (grant number IA/CPHI/14/1/501497) from the Wellcome Trust-Department of Biotechnology, India Alliance (2015-20). O John is a recipient of UIPA scholarship from University of New South Wales, Sydney. S V Katikireddi acknowledges funding from a NRS Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_12017/13, MC_UU_12017/15), and the Scottish Government Chief Scientist Office (SPHSU13, SPHSU15). C Kieling is a CNPq researcher and a UK Academy of Medical Sciences Newton Advanced Fellow. Y J Kim was supported by Research Management Office, Xiamen University Malaysia (XMUMRF/2018-C2/ITCM/00010). K Krishan is supported by UGC Centre of Advanced Study awarded to the Department of Anthropology, Panjab University, Chandigarh, India. M Kumar was supported by K43 TW 010716 FIC/NIMH. B Lacey acknowledges support from the NIHR Oxford Biomedical Research Centre and the BHF Centre of Research Excellence, Oxford. J V Lazarus was supported by a Spanish Ministry of Science, Innovation and Universities Miguel Servet grant (Instituto de Salud Carlos III [ISCIII]/ESF, the EU [CP18/00074]). K J Looker thanks the NIHR Health Protection Research Unit in Evaluation of Interventions at the University of Bristol, in partnership with Public Health England, for research support. S Lorkowski was funded by the German Federal Ministry of Education and Research (nutriCARD, grant agreement number 01EA1808A). R A Lyons is supported by Health Data Research UK (HDR-9006), which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, NIHR (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation, and Wellcome Trust. J J McGrath is supported by the Danish National Research Foundation (Niels Bohr Professorship), and the Queensland Health Department (via West Moreton HHS). P T N Memiah acknowledges support from CODESRIA. U O Mueller gratefully acknowledges funding by the German National Cohort Study BMBF grant number 01ER1801D. S Nomura acknowledges the Ministry of Education, Culture, Sports, Science, and Technology of Japan (18K10082). A Ortiz was supported by ISCIII PI19/00815, DTS18/00032, ISCIII-RETIC REDinREN RD016/0009 Fondos FEDER, FRIAT, Comunidad de Madrid B2017/BMD-3686 CIFRA2-CM. These funding sources had no role in the writing of the manuscript or the decision to submit it for publication. S B Patten was supported by the Cuthbertson & Fischer Chair in Pediatric Mental Health at the University of Calgary. G C Patton was supported by an aNHMRC Senior Principal Research Fellowship. M R Phillips was supported in part by the National Natural Science Foundation of China (NSFC, number 81371502 and 81761128031). A Raggi, D Sattin, and S Schiavolin were supported by grants from the Italian Ministry of Health (Ricerca Corrente, Fondazione Istituto Neurologico C Besta, Linea 4-Outcome Research: dagli Indicatori alle Raccomandazioni Cliniche). P Rathi and B Unnikrishnan acknowledge Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal. A L P Ribeiro was supported by Brazilian National Research Council, CNPq, and the Minas Gerais State Research Agency, FAPEMIG. D C Ribeiro was supported by The Sir Charles Hercus Health Research Fellowship (#18/111) Health Research Council of New Zealand. D Ribeiro acknowledges financial support from the EU (FEDER funds through the Operational Competitiveness Program; POCI-01-0145-FEDER-029253). P S Sachdev acknowledges funding from the NHMRC of Australia Program Grant. A M Samy was supported by a fellowship from the Egyptian Fulbright Mission Program. M M Santric-Milicevic acknowledges the Ministry of Education, Science and Technological Development of the Republic of Serbia (contract number 175087). R Sarmiento-Suarez received institutional support from Applied and Environmental Sciences University (Bogota, Colombia) and ISCIII (Madrid, Spain). A E Schutte received support from the South African National Research Foundation SARChI Initiative (GUN 86895) and Medical Research Council. S T S Skou is currently funded by a grant from Region Zealand (Exercise First) and a grant from the European Research Council under the EU's Horizon 2020 research and innovation program (grant agreement number 801790). J B Soriano is funded by Centro de Investigacion en Red de Enfermedades Respiratorias, ISCIII. R Tabares-Seisdedos was supported in part by the national grant PI17/00719 from ISCIII-FEDER. N Taveira was partially supported by the European & Developing Countries Clinical Trials Partnership, the EU (LIFE project, reference RIA2016MC-1615). S Tyrovolas was supported by the Foundation for Education and European Culture, the Sara Borrell postdoctoral programme (reference number CD15/00019 from ISCIII-FEDER). S B Zaman received a scholarship from the Australian Government research training programme in support of his academic career., "Peer Reviewed"
Published: 2020

18. [Clinical and prognostic features of the patients with esophageal squamous cell carcinomas as a first primary malignancy]

Author: Zhen, Wen, Yan Qiu, Zhang, Rong, Wu, Xue Mei, Peng, Bin, Chen, and Ai Min, Leng
Subjects: Aged, 80 and over, Male, Esophageal Neoplasms, Carcinoma, Squamous Cell, Humans, Esophageal Squamous Cell Carcinoma, Kaplan-Meier Estimate, Middle Aged, Prognosis, Aged, Neoplasm Staging, Retrospective Studies
Published: 2021

19. Sexual differentiation of the human hypothalamus: Relationship to gender identity and sexual orientation

Author: Dick F, Swaab, Samantha E C, Wolff, and Ai-Min, Bao
Subjects: Male, Sex Differentiation, Pregnancy, Sexual Behavior, Hypothalamus, Gender Identity, Humans, Female, Transsexualism
Abstract: Gender identity (an individual's perception of being male or female) and sexual orientation (heterosexuality, homosexuality, or bisexuality) are programmed into our brain during early development. During the intrauterine period in the second half of pregnancy, a testosterone surge masculinizes the fetal male brain. If such a testosterone surge does not occur, this will result in a feminine brain. As sexual differentiation of the brain takes place at a much later stage in development than sexual differentiation of the genitals, these two processes can be influenced independently of each other and can result in gender dysphoria. Nature produces a great variability for all aspects of sexual differentiation of the brain. Mechanisms involved in sexual differentiation of the brain include hormones, genetics, epigenetics, endocrine disruptors, immune response, and self-organization. Furthermore, structural and functional differences in the hypothalamus relating to gender dysphoria and sexual orientation are described in this review. All the genetic, postmortem, and in vivo scanning observations support the neurobiological theory about the origin of gender dysphoria, i.e., it is the sizes of brain structures, the neuron numbers, the molecular composition, functions, and connectivity of brain structures that determine our gender identity or sexual orientation. There is no evidence that one's postnatal social environment plays a crucial role in the development of gender identity or sexual orientation.
Published: 2021

20. Matching of the postmortem hypothalamus from patients and controls

Author: Dick F, Swaab and Ai-Min, Bao
Subjects: Male, Postmortem Changes, Hypothalamus, Brain, Gender Identity, Humans, Female, Neuropathology, Aged, Netherlands
Abstract: The quality of postmortem hypothalamus research depends strongly on a thorough clinical investigation and documentation of the patient's disorder and therapies. In addition, a systematic and professional neuropathological investigation of the entire brain of both the cases and the controls is absolutely crucial. In the experience of the Netherlands Brain Bank (NBB), about 20% of the clinical neurological diagnoses, despite being made in first rate clinics, have to be revised or require extra diagnoses after a complete and thorough neuropathologic review by the NBB. The neuropathology examination may reveal for instance that the elderly "controls" already have preclinical neurodegenerative alterations. In postmortem studies, the patient and control groups must be matched for as many as possible of the known confounding factors. This is necessary to make the groups as similar as possible, except for the topic being investigated. Confounding factors are present (i) before, (ii) during, and (iii) after death. They are, respectively: (i) genetic background, systemic diseases, duration and gravity of illness, medicines and addictive compounds used, age, sex, gender identity, sexual orientation, clock- and seasonal time of death, and lateralization; (ii) agonal state, stress of dying; and (iii) postmortem delay, freezing procedures, fixation, and storage time. Agonal state is generally estimated by measuring the pH of the brain. However, there are disorders in which pH is lower as a part of the disease process. Because of the large number of potentially confounding factors that differ according to, for instance, brain area and disease, a brain bank should have a large number of controls at its disposal for appropriate matching. If matching fails for some confounders, the influence of the confounders may be determined by statistical methods, such as analysis of variance or the regression models.
Published: 2021

21. Tumor-infiltrating CD8+ T cells combined with tumor-associated CD68+ macrophages predict postoperative prognosis and adjuvant chemotherapy benefit in resected gastric cancer

Author: Chao-Hui Zheng, Yuan Wu, Jia-Bin Wang, Yu Xu, Ping Li, Chang-Ming Huang, Jun Lu, Jian-Wei Xie, Xiao-yan Huang, Ai-Min Huang, and Jian-Xian Lin
Subjects: Oncology, Male, Cancer Research, medicine.medical_specialty, Kaplan-Meier Estimate, TNM staging system, CD8-Positive T-Lymphocytes, lcsh:RC254-282, Tumor-infiltrating neutrophils, Lymphocytes, Tumor-Infiltrating, Surgical oncology, Stomach Neoplasms, Internal medicine, Genetics, medicine, Humans, Clinical significance, Neoplasm Metastasis, skin and connective tissue diseases, Aged, Neoplasm Staging, Aged, 80 and over, Cluster of differentiation, CD68, business.industry, Macrophages, Tumor-associated macrophages, Cancer, Adjuvant chemotherapy benefit, Middle Aged, medicine.disease, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Immunohistochemistry, Female, B7-2 Antigen, business, Gastric cancer, CD8, Biomarkers, Research Article
Abstract: Background Tumor-infiltrating immune cells are present in various malignant tumors, but their clinical significance in gastric cancer (GC) remains unclear. This study aimed to investigate the prognostic significance of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs). Methods Using a prospective database containing 401 cases of GC, we evaluated TIL (cluster of differentiation 8 (CD8) expression) and TAM (cluster of differentiation 68 (CD68) expression) statuses via immunohistochemical staining. Results Compared with CD8+ TIL-negative cases (n = 196, 48.6%), CD8+ TIL-positive cases (n = 205, 51.1%) showed significantly better recurrence-free survival (RFS) [log-rank ppn = 217, 54.1%), CD68+ TAM-positive cases (n = 184, 45.9%) had significantly poor RFS [log-rank pp Conclusions CD8+ TIL and CD68+ TAM statuses were identified as independent prognostic factors that may be integrated into the current TNM staging system to refine risk stratification and to better predict the survival benefit from PAC in patients with GC. Trial registration The current controlled trial was registered at ClinicalTrials.gov (ID: NCT02327481) on December 30, 2014.
Published: 2019

22. Design and Application of Individualized, 3-Dimensional-Printed Navigation Template for Placing Cortical Bone Trajectory Screws in Middle-Upper Thoracic Spine: Cadaver Research Study

Author: Jiaoxiang Chen, Xiang-Yang Wang, Ai-Min Wu, Ke Wang, Sunren Sheng, and Zengjie Zhang
Subjects: Adult, Male, musculoskeletal diseases, Adolescent, Thoracic spine, Radiography, Computed tomography, Prosthesis Design, Thoracic Vertebrae, Upper thoracic spine, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pedicle Screws, Cadaver, Cortical Bone, medicine, Humans, Aged, Orthodontics, Human cadaver, medicine.diagnostic_test, business.industry, Middle Aged, equipment and supplies, musculoskeletal system, Inferior pedicle, surgical procedures, operative, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Printing, Three-Dimensional, Female, Surgery, Cortical bone, Neurology (clinical), Tomography, X-Ray Computed, business, 030217 neurology & neurosurgery
Abstract: Objective To evaluate the safety and accuracy of use of a 3-dimensional printed navigation template in the placement of a cortical bone trajectory (CBT) screw in the middle-upper thoracic spine. Methods Ten human cadavers were included in the study. Sixty CBT screws were placed on 1 side, using the free-hand technique, and 60 CBT screws were placed on the other side, using the navigation template that was designed and printed using data from 10 cadavers. The safety and accuracy of use of the CBT screws were directly evaluated by radiography and computed tomography. Results Computed tomography revealed that 2 and 3 of 60 screws, placed using the navigation template, were broken in the medial or lateral areas and in the superior or inferior pedicle wall, respectively. Furthermore, 8 screws were broken in the medial or lateral areas and 11 screws were broken in the superior or inferior pedicle wall when the free-hand technique was used. Radiography revealed that 3 screws in zone I, 55 screws in zone II, and 2 screws in zone III were placed using the navigation template. Furthermore, 7 screws in zone I, 45 screws in zone II, and 8 screws in zone III were placed using the free-hand technique. Conclusions In this cadaver study, insertion of the CBT screws in the middle-upper thoracic spine with the assistance of the navigation template was safe and convenient.
Published: 2019

23. The protective effect of sinapic acid in osteoarthritis: In vitro and in vivo studies

Author: Zhi-Chao Hu, Xingyu Zhu, Xiaobin Li, Jiang-Wei Xuan, Xiaoxia Ding, Dengying Wu, Wen-Fei Ni, Zhenhua Feng, Jian Lin, and Ai-Min Wu
Subjects: 0301 basic medicine, Male, Coumaric Acids, Interleukin-1beta, chondrocytes, IL‐1β, Nitric Oxide Synthase Type II, Pharmacology, Nitric Oxide, Protective Agents, Nrf2, Dinoprostone, Nitric oxide, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, In vivo, Matrix Metalloproteinase 13, Osteoarthritis, Animals, Humans, sinapic acid, Cells, Cultured, Thrombospondin, biology, Chemistry, Interleukin-6, Tumor Necrosis Factor-alpha, ADAMTS, NF‐κB, NF-kappa B, Cell Biology, Original Articles, Middle Aged, In vitro, Heme oxygenase, Nitric oxide synthase, Mice, Inbred C57BL, 030104 developmental biology, inflammation, Cyclooxygenase 2, 030220 oncology & carcinogenesis, biology.protein, Molecular Medicine, Original Article, Female, Cyclooxygenase, Heme Oxygenase-1
Abstract: The anti‐inflammatory effect of sinapic acid (SA) has been reported in several studies. However, whether SA has the same effect on osteoarthritis (OA) has yet to be clearly elucidated. We designed a series of in vitro and in vivo procedures to verify the above conjecture. Compared with controls, SA‐pretreated human chondrocytes showed lower levels of interleukin (IL)‐1β‐induced IL‐6, prostaglandin E2 (PGE2), nitric oxide (NO) and tumour necrosis factor‐α (TNF‐α) in vitro. Meanwhile, SA could also reverse the degradation of type II collage and aggrecan, as well as the overproduction of matrix metalloproteinase‐9 (MMP‐9) and matrix metalloproteinase‐13 (MMP‐13), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)‐2 and a disintegrin and metalloproteinase thrombospondin motifs (ADAMTS)‐5. Furthermore, activation of nuclear factor κB (NF‐κB), which was induced by IL‐1β, was also inhibited by SA through the pathway of nuclear factor‐erythroid 2‐related factor‐2 (Nrf2)/heme oxygenase 1. In vivo, SA could delay the progress of mice OA models. We propose that SA may be applied as a potential therapeutic drug in OA treatment.
Published: 2019

24. Effects of n-3 fatty acid supplements on cardiometabolic profiles in hypertensive patients with abdominal obesity in Inner Mongolia: a randomized controlled trial

Author: Ai-min Wang, Bo Yang, Duo Li, Xiao-juan Guo, Lin Shi, Zi-hao Li, and Mei-qi Shi
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Population, Blood lipids, 03 medical and health sciences, chemistry.chemical_compound, Internal medicine, Fatty Acids, Omega-3, medicine, Humans, education, Abdominal obesity, Aged, education.field_of_study, 030109 nutrition & dietetics, Triglyceride, business.industry, General Medicine, Middle Aged, Fish oil, Eicosapentaenoic acid, 030104 developmental biology, Endocrinology, chemistry, Docosahexaenoic acid, Obesity, Abdominal, Hypertension, Female, medicine.symptom, business, Corn oil, Food Science
Abstract: Daily supplementation with n-3 fatty acid (FA) has been believed to be an adjunct or alternative to drug treatments to reduce blood pressure (BP) and triglyceride (TG) levels in western patients with high risk of cardiovascular disease. The BP-lowering effect of n-3 FA supplements among Chinese hypertensive patients has been reported in our previous 12-week, double-blind, randomized controlled trial (RCT), but the benefits on cardiometabolic profiles among obese Chinese populations are not well known. We therefore used the data from the previous RCT to investigate the effects of marine- and plant-derived n-3 FA supplements on cardiometabolic profiles in middle-aged and elderly Chinese hypertensive patients with abdominal obesity. In total, 108 eligible volunteers from Inner Mongolia, China were randomly assigned to three treatments for 12 weeks: fish oil (FO, n = 35, 2 g day-1 eicosapentaenoic acid + docosahexaenoic acid), flaxseed oil (FLO, n = 39, 2.5 g day-1 α-linolenic acid), and corn oil served as a control (CO, n = 34). BP, blood lipids, waist circumference (WC) and fasting glucose-insulin were measured at baseline and after 12-week intervention by using standard methods. Clustered cardiometabolic risk was expressed as a continuously distributed z-score calculated by standardizing and then summing WC, insulin, glucose, TG, HDL-cholesterol and BP values. The cardiometabolic risk scores were significantly lower in the FO group than in the CO group after the 12-week intervention (-0.41 ± 0.92 vs. 0.02 ± 0.95, p = 0.016), but not in the FLO group (-0.23 ± 1.02 vs. 0.02 ± 0.95, p = 0.109). For individual risk factors, compared with CO, FO significantly decreased LDL-cholesterol (-0.25 ± 0.78 mmol L-1vs. -0.05 ± 0.65 mmol L-1, p = 0.010), ApoB (-012 ± 0.28 mmol L-1vs. -0.03 ± 0.23 mmol L-1, p = 0.036), and WC (-1.58 ± 3.67 cm vs. -0.52 ± 3.27 cm, p = 0.031), whereas no significant difference was found between FLO and CO groups in LDL-cholesterol (p = 0.081), ApoB (p = 0.102) and WC (p = 0.093). The present findings suggest that marine n-3 FA intervention may improve the cardiometabolic traits in this Chinese hypertensive population comorbid with abdominal obesity.
Published: 2019

25. Safety and pharmacokinetic profile of pretomanid in healthy Chinese adults: Results of a phase I single dose escalation study

Author: Yue, Liu, Yan, Tan, Gang, Wei, Zhifei, Lu, Yazhou, Liu, Bo, Yang, Ai-Min, Hui, and Kexin, Li
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, China, Dose-Response Relationship, Drug, Biochemistry (medical), Healthy Volunteers, Young Adult, Asian People, Double-Blind Method, Nitroimidazoles, Area Under Curve, Humans, Female, Pharmacology (medical), Hyperbilirubinemia
Abstract: We investigated the safety, tolerability and pharmacokinetic (PK) profile of pretomanid (formerly PA-824) in healthy Chinese volunteers. This was a single-center, double-blind, placebo-controlled, phase I dose escalation study, in which healthy volunteers were consecutively allocated to increasing pretomanid dose groups (50, 100, 200, 400, 600, 800, or 1000 mg) and randomized to receive pretomanid or matching placebo. The primary objective was to evaluate the safety, tolerability and PK profile of pretomanid. In total, 306 volunteers were screened, and 60 were assigned to treatment (pretomanid: n = 46, placebo: n = 14) of whom 83.3% were male, age ranged from 19 to 39 years and BMI ranged from 19.2 to 25.9 kg/m
Published: 2022

26. Acceptable Chin–Brow Vertical Angle for Neutral Position Radiography: Preliminary Analyses Based on Parameters of the Whole Sagittal Spine of an Asymptomatic Chinese Population

Author: Xiangxiang Pan, Ying-Zhao Yan, Xiang-Yang Wang, Naifeng Tian, Zhenxuan Shao, Ai-Min Wu, Yaosen Wu, and Shao-qing Chen
Subjects: Adult, Male, Chin, Percentile, Radiography, Asymptomatic, Patient Positioning, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Asian People, medicine, Humans, Kyphosis, Aged, Retrospective Studies, Orthodontics, 030222 orthopedics, Cobb angle, business.industry, Middle Aged, Healthy Volunteers, Spine, Sagittal plane, Neutral position, Cross-Sectional Studies, Tilt (optics), medicine.anatomical_structure, Cervical Vertebrae, Female, Surgery, Neurology (clinical), Eyebrows, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: We sought to acquire the whole sagittal spine parameters and investigated the acceptable chin-brow vertical angle (CBVA) for neutral position radiography in an asymptomatic Chinese population.The parameters measured in 257 asymptomatic volunteers included CBVA, occipital slope, orbital tilt, occipital incidence, C0-C2 Cobb angle, C2-C7 Cobb angle, C1-C7 Cobb angle, C2-C7 sagittal vertical axis and absolute rotation angle, cervical tilt, cranial tilt, T1 slope, and thoracic kyphosis, and others. We used Pearson correlation analyses to find relationships between CBVA and other variables. The subjects were divided into 5 groups according to the CBVA percentile: group A, 0%-20% CBVA; group B, 20%-40% CBVA; group C, 40%-60% CBVA; group D, 60%-80% CBVA; and group E, 80%-100% CBVA. We used analysis of variance to analyze differences among the 5 groups.Orbital tilt, Occipital incidence, C1-C7 Cobb angle, C2-C7 sagittal vertical axis, and cranial tilt all increased with increasing CBVA (P0.001). The occipital slope, C2-C7 Cobb angle, C2-C7 absolute rotation angle, cervical tilt, T1 slope, and thoracic kyphosis decreased with decreasing CBVA (P0.05). No correlations between other sagittal parameters and the CBVA were found. A slight deviation was found in groups B-D, with a greater deviation in groups A, C, and E.An acceptable range of -1.5° to 5.8° is recommended for the CBVA for cervical radiography in the neutral position. When spinal surgeons evaluate the cervical plane, the effects of the CBVA deviation on cervical curvature must be considered.
Published: 2018

27. Genomic profiling of a patient with quadruple synchronous colorectal cancer: a case report

Author: Junjie Sun, Hengxue Lin, Tianliang Bai, Xiongjie Jia, Ai-Min Zhang, Tao Zhang, and Xinyu Peng
Subjects: Male, Pathology, medicine.medical_specialty, Colorectal cancer, Rectum, Case Report, RC799-869, Adenocarcinoma, Neoplasms, Multiple Primary, Synchronous colorectal cancer, Carcinoma, Medicine, Ascending colon, Humans, Retrospective Studies, Intraepithelial neoplasia, business.industry, Gastroenterology, Sigmoid colon, General Medicine, Genomics, Diseases of the digestive system. Gastroenterology, Middle Aged, medicine.disease, Primary tumor, digestive system diseases, Oxaliplatin, medicine.anatomical_structure, Quadruple, Next-generation sequencing, Heterogeneity, business, Colorectal Neoplasms, medicine.drug
Abstract: Background Synchronous colorectal cancer (SCRC) is featured by the presence of multiple primary tumor lesions in a single patient at initial diagnosis. It is less common with the prevalence of approximately 3.5% among colorectal cancer (CRC). Some studies of SCRC have been performed in patients with two tumor lesions. However, SCRC cases with three or more tumor lesions were rare and remained to be investigated. Case presentation In this case report, we presented a 56-year-old male SCRC case with quadruple tumor lesions which is rarely seen in clinical practice. After laparoscopic radical resection of sigmoid carcinoma and partial rectum resection, the four tumor samples were subjected to pathological evaluation and next-generation sequencing (NGS) based genetic profiling. The four tumor lesions included two adenocarcinomas with moderate differentiation at sigmoid colon and rectum respectively, a grade 1 neuroendocrine tumor (NET) at rectum and a high-grade intraepithelial neoplasia at ascending colon. Each tumor exhibited distinct histology types and mutation profiles. After surgical resection, the patient remained disease-free after four cycles of chemotherapy with oxaliplatin and capecitabine (XELOX). Conclusions The tumor lesions in this case showed different pathological and genetic features which indicats the heterogeneity of SCRC. The genomic profilling might provide novel insights to understand SCRC at molecular level.
Published: 2021

28. Clinical Features of Aortic Dissection in the Emergency Department: A Single-center Experience from South China

Author: Xiang-Min Li, Guo-Qing Huang, Ai-min Wang, Li-Ping Zhou, Xiao-Ye Mo, and Fang-Jie Zhang
Subjects: Adult, Male, General Medicine, Middle Aged, Aortic Dissection, Logistic Models, Risk Factors, Hypertension, Emergency Medicine, Humans, Female, Emergency Service, Hospital, Aged, Retrospective Studies
Abstract: Objectives: Our goal in this study was to determine 1) whether there are any differences in clinical characteristics between Chinese and Western patients with aortic dissection (AD), and 2) the mortality rate of AD patients in the emergency department (ED) and identify the risk predictors for death. Methods: We retrospectively analyzed patients who were diagnosed with AD and admitted to our ED between September 1, 2017–August 31, 2020. Data on age, gender, clinical manifestation, medical history, routine blood tests, liver and kidney function, coagulation, myocardial enzymology, and mortality were collected. Results: We enrolled 535 AD patients (422 men and 113 women) with a mean age of 54.7±14.1 years. Type A AD constituted 40% of the total number of AD cases, while type B AD constituted 60%. The proportion of those who were females, 10-92 years, with type A AD, and hypertension in the Chinese population was lower than that in the Western population (P
Published: 2021

29. Cardamonin protects nucleus pulposus cells against IL-1β-induced inflammation and catabolism via Nrf2/NF-κB axis

Author: Ben Wang, Chenglong Xie, Yifei Zhou, Xiang-Yang Wang, Yifeng Shi, Chongan Huang, Yaosen Wu, Haiwei Ma, Ai-Min Wu, Naifeng Tian, Weiyang Gao, Xiaolei Zhang, Hongqiang Wu, Jiaoxiang Chen, Jun-Li Li, Liaojun Sun, and Zhenxuan Shao
Subjects: 0301 basic medicine, Male, Nucleus Pulposus, Cell Survival, NF-E2-Related Factor 2, Interleukin-1beta, Inflammation, Pharmacology, Nitric oxide, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Chalcones, In vivo, medicine, Animals, Prostaglandin E2, Cells, Cultured, Thrombospondin, biology, NF-kappa B, NF-κB, General Medicine, Rats, Nitric oxide synthase, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, biology.protein, Tumor necrosis factor alpha, medicine.symptom, Food Science, medicine.drug, Signal Transduction
Abstract: Intervertebral disc degeneration (IVDD) is one of the major causes of low back pain, but effective therapies are still lacking because of its complicated pathology. It has been demonstrated that increased levels of interleukin-1β (IL-1β) may promote the development of IVDD. Cardamonin (CAR) is a chalcone extracted from Alpinia katsumadai and other plants. It exhibits an anti-inflammatory effect in multiple diseases. In the present study, we investigated the protective effects of CAR on rat nucleus pulposus (NP) cells under IL-1β stimulation in vitro and in a puncture-induced rat IVDD model in vivo. We explored the CAR treatment's inhibition of the expression of inflammatory factors such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2), nitric oxide (NO), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in rat NP cells. Moreover, the up-regulation of matrix metalloproteinase-13 (MMP-13) and thrombospondin motifs 5 (ADAMTS-5) and the degradation of aggrecan and collagen II induced by IL-1β were reversed by CAR. Mechanistically, we demonstrated that CAR inhibited nuclear factor kappa B (NF-κB) signaling by activating the nuclear factor erythroid-derived 2-like 2 (Nrf2) in IL-1β-induced rat NP cells. Furthermore, the protective effect of CAR was shown in the IVDD model through persistent intragastric administration. Taken together, our results revealed that CAR could activate the Nrf2/HO-1 signaling axis and be a novel agent for IVDD therapy.
Published: 2021

30. Elevated Serum Small Dense Low-Density Lipoprotein Cholesterol May Increase the Risk and Severity of Coronary Heart Disease and Predict Cardiovascular Events in Patients with Type 2 Diabetes Mellitus

Author: Junxu Gu, Shanshan Li, Yang Li, Yue Yin, Huizhang Bao, Mei Jia, Na Zhang, Ai-Min Zhang, Ming Yang, Juan Huang, Xiao-Qin Yao, and Ming Su
Subjects: Adult, Male, Medicine (General), medicine.medical_specialty, Article Subject, Clinical Biochemistry, Subgroup analysis, Disease, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Logistic regression, 03 medical and health sciences, R5-920, 0302 clinical medicine, Risk Factors, Internal medicine, Genetics, medicine, Humans, 030212 general & internal medicine, cardiovascular diseases, Molecular Biology, Aged, business.industry, Incidence (epidemiology), Biochemistry (medical), Confounding, Patient Acuity, Type 2 Diabetes Mellitus, General Medicine, Cholesterol, LDL, Middle Aged, medicine.disease, Logistic Models, Quartile, Diabetes Mellitus, Type 2, Case-Control Studies, Cardiology, Female, business, Dyslipidemia, Biomarkers, Follow-Up Studies, Research Article
Abstract: Background. Coronary heart disease (CHD) is a common and severe complication in type 2 diabetes mellitus (T2DM) patients. Increased amount of circulatory small dense low-density lipoprotein cholesterol (sdLDL-C) particles is known to be a sign of dyslipidemia and can result in atherosclerosis. However, the association between serum sdLDL-C levels and CHD in T2DM patients remains unclear. Methods. A total of 3684 T2DM patients who received selective coronary angiography (CAG) were selected. For analyzing the association between sdLDL-C and CHD severity in T2DM, the patients with CHD were further divided into four subgroups according to the quartiles of sdLDL-C. A multivariate logistic regression was used for analyzing the risks and severity of CHD. A total of 3427 patients with continuous stable CHD were recruited and followed up for 5 years. Results. Serum sdLDL-C levels in the CHD group were significantly increased compared with those in the non-CHD group [0.80 (0.49) mmol/L vs. 0.70 (0.30) mmol/L, p < 0.001 ]. The results from CHD subgroup analysis indicated that the sdLDL-C levels in patients with multiple-vessel disease and high Gensini score (GS) were significantly increased. By adjusting the confounding factors and analyzing with multiple logistic regression, we found that sdLDL-C independently correlated with the presence and severity of CHD (CHD: OR = 2.257 ; multiple-vessel disease: OR = 3.288 ; high GS: OR = 2.554 ). A total of 484 major cardiovascular events (MACEs) were documented. After Kaplan-Meier analysis and chi-squared analysis, the incidence of MACEs in the high sdLDL-C group was higher than that in the low sdLDL-C group (16.04% vs. 12.25%, p = 0.002 ). Conclusion. In T2DM patients, elevated serum sdLDL-C may increase the severity of CHD and predict cardiovascular events in the future. Therefore, serum sdLDL-C may be a potential biomarker for the surveillance of CHD in T2DM patients.
Published: 2021
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31. RNA‐binding protein HuR suppresses senescence through Atg7 mediated autophagy activation in diabetic intervertebral disc degeneration

Author: Weiyang Gao, Xiang-Yang Wang, Linwei Chen, Yifei Zhou, Sunli Hu, Zongyou Pan, Libin Ni, Xiaolei Zhang, Zaher Meftah, Ai-Min Wu, Zupo Yu, Tianzhen Xu, Naifeng Tian, Liaojun Sun, Yaosen Wu, and Zhenxuan Shao
Subjects: Male, 0301 basic medicine, Senescence, autophagy, senescence, Nucleus Pulposus, Immunoprecipitation, RNA-binding protein, Intervertebral Disc Degeneration, Autophagy-Related Protein 7, Diabetes Mellitus, Experimental, ELAV-Like Protein 1, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, In vivo, Sequestosome-1 Protein, Transcriptional regulation, Animals, Humans, RNA, Messenger, RNA, Small Interfering, 3' Untranslated Regions, Cells, Cultured, Cellular Senescence, Messenger RNA, diabetes, Chemistry, Autophagy, Original Articles, Cell Biology, General Medicine, Rats, Cell biology, Glucose, 030104 developmental biology, 030220 oncology & carcinogenesis, HuR, Original Article, RNA Interference, Atg7, Microtubule-Associated Proteins
Abstract: Objectives Diabetes is a risk factor for intervertebral disc degeneration (IVDD). Studies have demonstrated that diabetes may affect IVDD through transcriptional regulation; however, whether post‐transcriptional regulation is involved in diabetic IVDD (DB‐IVDD) is still unknown. This study was performed to illustrate the role of HuR, an RNA‐binding protein, in DB‐IVDD development and its mechanism. Materials and Methods The expression of HuR was evaluated in nucleus pulposus (NP) tissues from diabetic IVDD patients and in high glucose‐treated NP cells. Senescence and autophagy were assessed in HuR over‐expressing and downregulation NP cells. The mRNAs that were regulated by HuR were screened, and immunoprecipitation was applied to confirm the regulation of HuR on targeted mRNAs. Results The results showed that the expression of HuR was decreased in diabetic NP tissues and high glucose‐treated NP cells. Downregulation of HuR may lead to increased senescence in high glucose‐treated NP cells, while autophagy activation attenuates senescence in HuR deficient NP cells. Mechanistic study showed that HuR prompted Atg7 mRNA stability via binding to the AU‐rich elements. Furthermore, overexpression of Atg7, but not HuR, may ameliorate DB‐IVDD in rats in vivo. Conclusions In conclusion, HuR may suppress senescence through autophagy activation via stabilizing Atg7 in diabetic NP cells; while Atg7, but not HuR, may serve as a potential therapeutic target for DB‐IVDD., With high‐glucose treatment, the expression of HuR is decreased, which induces autophagy inactivation and increased senescence. Mechanistic study reveals that HuR regulates Atg7 expression through binding to Atg7 AU‐rich element and adjusting its mRNA stability
Published: 2020

32. Akebia Saponin D suppresses inflammation in chondrocytes via the NRF2/HO-1/NF-κB axis and ameliorates osteoarthritis in mice

Author: Naifeng Tian, Weiyang Gao, Ai-Min Wu, Jie Jin, Xiaolei Zhang, Yifei Zhou, Yaosen Wu, Xiang-Yang Wang, Chenghao Ren, Ximiao Chen, Zongyou Pan, and Mingbao Gu
Subjects: 0301 basic medicine, Male, NF-E2-Related Factor 2, Interleukin-1beta, Anti-Inflammatory Agents, Nitric Oxide Synthase Type II, Inflammation, Osteoarthritis, Pharmacology, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Chondrocytes, In vivo, Matrix Metalloproteinase 13, medicine, Animals, Aggrecan, business.industry, Therapeutic effect, NF-kappa B, Akebia saponin D, NF-κB, General Medicine, Saponins, medicine.disease, In vitro, Mice, Inbred C57BL, 030104 developmental biology, chemistry, Cyclooxygenase 2, 030220 oncology & carcinogenesis, Heme Oxygenase (Decyclizing), Female, medicine.symptom, Inflammation Mediators, business, Food Science
Abstract: As an ordinary joint vestigial disease, osteoarthritis (OA) contributes to a considerable proportion of disability cases worldwide. Inflammation, as the main pathological factor, mediates the occurrence and development of OA. Akebia Saponin D (ASD), also known as Asperosaponin VI, is one of the active components extracted from Dipsaci Radix and is rich in Dipsacus loose tea. It has shown sound therapeutic effects on various diseases; nevertheless, its role in OA therapy is not completely understood. This study demonstrated the anti-inflammatory activity of ASD in OA through a series of in vivo and in vitro experiments. In vitro experiments revealed that ASD might prohibit the production of inflammatory mediators in IL-1β treated chondrocytes such as COX-2, iNOS, NO, PGE2, IL-6, and TNF-α. Meanwhile, it may also inhibit the production of ADAMTS-5 and MMP13 and promote the production of Aggrecan and Collagen II. The mechanism study demonstrated that ASD exerted an anti-inflammatory effect by activating the NRF2 target, upregulating the expression of HO-1, and preventing P65 from binding to DNA. In vivo experiments demonstrated that ASD might improve the progression of OA in a DMM mouse model. These research results provide evidence for the potential application of ASD in OA therapy.
Published: 2020

33. Postoperative evaluation of left ventricular global strain using cardiac computed tomography in pediatric patients with congenital heart disease: A comparison with echocardiography

Author: Yu-Qi Zhang, Yumin Zhong, Chen Guo, Qin Yan, Wei-Hui Xie, Hai-Sheng Qiu, Ai-Min Sun, Li-Jun Chen, Qian Wang, Rongzhen Ouyang, and Liwei Hu
Subjects: Heart Defects, Congenital, Male, medicine.medical_specialty, genetic structures, Heart disease, Cardiac computed tomography, Correlation coefficient, Ventricular Function, Left, Ventricular Dysfunction, Left, Internal medicine, Circumferential strain, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Child, Tomography, Retrospective Studies, Reproducibility, business.industry, Reproducibility of Results, General Medicine, medicine.disease, Global strain, Echocardiography, Cardiology, Female, sense organs, Cardiac magnetic resonance, business, Radial stress
Abstract: We explored the feasibility and reproducibility of cardiac computed tomography (CCT)-derived left ventricular (LV) global strain in postoperative children with congenital heart disease (CHD) and compared its correlation and agreement with transthoracic echocardiography (TTE).Fifty-one patients (28 males, 23 females) were included who underwent clinically indicated retrospective electrocardiography-triggered CCT. and all patients underwent additional TTE on the same day. LV global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were measured. Correlations of global strains between CCT and TTE were assessed using Pearson's correlation coefficient. Intra-class correlation coefficients (ICC) were used to assess CCT intra-observer and inter-observer reproducibility.GLS and GCS were not significantly different between CCT and TTE (GLS: -23.54 ± 3.24 vs. -23.85 ± 3.72, respectively, p = 0.415; GCS: -28.21 ± 3.55 vs. -28.79 ± 3.69, respectively, p = 0.155). GRS was significantly different between CCT and TTE (60.79 ± 15.11 vs. 41.73 ± 4.27, respectively, p 0.001). There was good correlation between CCT- and TTE-derived GLS (r = 0.70, p 0.001) and GCS (r = 0.68, p 0.001), but GRS showed no correlation between CCT and TTE (r = 0.09, p = 0.54). CCT-derived global strain showed good intra- and inter-observer reproducibility (ICC = 0.86-0.92), except the inter-observer reproducibility for GRS (ICC = 0.77).CCT was feasible for postoperative evaluation of LV global strain in pediatric patients with CHD with sufficient reproducibility. CCT-derived global strain can provide additional information in selected CHD patients with poor acoustic windows and who are intolerant to or have contraindications for cardiac magnetic resonance.
Published: 2020

34. Clinical outcomes and prognostic factors in bloodstream infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae among patients with malignancy: a meta-analysis

Author: Tao Tian, Chao-Xin Fan, Yu Yao, Na Liu, Rui Zhao, Xiaoqiang Zheng, Xiao Fu, Hao-Ran Zheng, Ai-Min Jiang, Rui Zhang, and Xue Chen
Subjects: Microbiology (medical), Male, medicine.medical_specialty, ESBL-PE, Drug resistance, Cochrane Library, Bloodstream infection, Malignancy, beta-Lactamases, 03 medical and health sciences, 0302 clinical medicine, Medical microbiology, Extended-spectrum β-lactamase, Bacterial Proteins, Enterobacteriaceae, Internal medicine, Neoplasms, Sepsis, medicine, Humans, 030212 general & internal medicine, Mortality, Aged, Aged, 80 and over, 0303 health sciences, biology, 030306 microbiology, business.industry, Septic shock, Research, Enterobacteriaceae Infections, General Medicine, Middle Aged, medicine.disease, biology.organism_classification, Prognosis, Anti-Bacterial Agents, Pneumonia, Meta-analysis, Infectious Diseases, Female, business
Abstract: Background The colonization of Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) in bloodstream infections (BSIs) has been increased dramatically worldwide, and it was associated with worse clinical outcomes in patients with malignancy. We performed the meta-analysis to investigate the prognosis and risk factors in BSIs caused by ESBL-PE in oncological patients. Methods PubMed, EMBASE, and Cochrane Library were searched for related studies. All-cause mortality was considered as the primary outcome. Subgroup analyses, meta-regression analyses, and sensitivity analysis were used to investigate heterogeneity and reliability in results. Results 6,729 patients from 25 studies were eligible. Six studies enrolled oncological patients with BSIs caused by ESBL-PE only, while 19 studies both enrolled ESBL-PE and non-ESBL-PE infections. The results showed that BSIs caused by ESBL-PE in patients with malignancy was associated with higher mortality than non-ESBL-PE infections (RR = 2.21, 95% CI: 1.60–3.06, P I2 =78.3%, P P P Conclusions Our study identified that BSIs caused by ESBL-PE in patients with malignancy were associated with worse clinical outcomes compared with non-ESBL-PE infections. Furthermore, children and hematological malignancy were associated with higher mortality. Severe sepsis/ septic shock, pneumonia, and ICU admission were the most common predictors of mortality.
Published: 2020

35. CCDC65 as a new potential tumor suppressor induced by metformin inhibits activation of AKT1 via ubiquitination of ENO1 in gastric cancer

Author: Jiahao Liu, Huiling Yang, Zhe Hu, Rentao Hou, Xiaojie Deng, Zibo Tang, Peng Shen, Zhen Liu, Ziyan Zhang, Xuemei Peng, Tongyuan Deng, Ai-Min Li, and Weiyi Fang
Subjects: Male, ENO1, Medicine (miscellaneous), Gene Expression, medicine.disease_cause, Metastasis, Mice, Cell Movement, Genes, Tumor Suppressor, CCDC65, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Mice, Inbred BALB C, biology, Chemistry, Prognosis, Metformin, Ubiquitin ligase, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Female, medicine.drug, Signal Transduction, Research Paper, China, Ubiquitin-Protein Ligases, Mice, Nude, In vivo, Stomach Neoplasms, Cell Line, Tumor, medicine, Biomarkers, Tumor, Animals, Humans, Cell Proliferation, Glycoproteins, AKT1, Cell growth, Tumor Suppressor Proteins, Ubiquitination, Cancer, Oncogenes, medicine.disease, Phosphopyruvate Hydratase, Cancer cell, biology.protein, Cancer research, Carcinogenesis, Gastric cancer, Proto-Oncogene Proteins c-akt
Abstract: The coiled-coil domain containing protein members have been well documented for their roles in many diseases including cancers. However, the function of the coiled-coil domain containing 65 (CCDC65) remains unknown in tumorigenesis including gastric cancer. Methods: CCDC65 expression and its correlation with clinical features and prognosis of gastric cancer were analyzed in tissue. The biological role and molecular basis of CCDC65 were performed via in vitro and in vivo assays and a various of experimental methods including co-immunoprecipitation (Co-IP), GST-pull down and ubiquitination analysis et al. Finally, whether metformin affects the pathogenesis of gastric cancer by regulating CCDC65 and its-mediated signaling was investigated. Results: Here, we found that downregulated CCDC65 level was showed as an unfavourable factor in gastric cancer patients. Subsequently, CCDC65 or its domain (a.a. 130-484) was identified as a significant suppressor in GC growth and metastasis in vitro and in vivo. Molecular basis showed that CCDC65 bound to ENO1, an oncogenic factor has been widely reported to promote the tumor pathogenesis, by its domain (a.a. 130-484) and further promoted ubiquitylation and degradation of ENO1 by recruiting E3 ubiquitin ligase FBXW7. The downregulated ENO1 decreased the binding with AKT1 and further inactivated AKT1, which led to the loss of cell proliferation and EMT signal. Finally, we observed that metformin, a new anti-cancer drug, can significantly induce CCDC65 to suppress ENO1-AKT1 complex-mediated cell proliferation and EMT signals and finally suppresses the malignant phenotypes of gastric cancer cells. Conclusion: These results firstly highlight a critical role of CCDC65 in suppressing ENO1-AKT1 pathway to reduce the progression of gastric cancer and reveals a new molecular mechanism for metformin in suppressing gastric cancer. Our present study provides a new insight into the mechanism and therapy for gastric cancer.
Published: 2020

36. Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Author: Soufiane Boufous, Yousef Veisani, Mehran Asadi-Aliabadi, Sharath Burugina Nagaraja, Maziar Moradi-Lakeh, Getachew Mullu Kassa, Edward J Mills, Dimas Ria Angga Pribadi, William James Dangel, Mohamad-Hani Temsah, Catherine O. Johnson, Gregory A. Roth, Giuseppe Gorini, Fariborz Mansour-Ghanaei, Alberto Ortiz, Samad Azari, Assefa Ayalew Ayalew Ayalew Gebreslassie, Salime Goharinezhad, Stephanie R. M. Zimsen, Peng Zheng, Michael Assmus, Elisabetta Pupillo, Bach Xuan Tran, Lal B. Rawal, Narayanaswamy Venketasubramanian, Noushin Mohammadifard, Stephen S Lim, Ata Rafiee, Maria Inês Schmidt, Vincent C. Iannucci, Suzanne Lyn Barker-Collo, Leah E. Cahill, Tauseef Ahmad, Platon D. Lopukhov, Kazumasa Yamagishi, Abdullah Al Mamun, Iqbal R. F. Elyazar, Giovanni Damiani, Mohammad Hossein Bakhshaei, Mehdi Fazlzadeh, Virginia Núñez-Samudio, Alyssa Pennini, Dietrich Plass, Atkilt Esaiyas Etisso, Gebre Teklemariam Demoz, Alexandrea Watson, Arvin Haj-Mirzaian, Paul S Briant, Frank B. Osei, Blair R. Bumgarner, Maciej Banach, Ravensara S. Travillian, Kai-Lan Chang, Shirin Djalalinia, Hasan Yusefzadeh, Silvano Gallus, Seyyed Meysam Mousavi, Bernhard T. Baune, Aaron van Donkelaar, Azeem Majeed, Hans Kromhout, Robert Ancuceanu, Blessing J. Akombi, Pushpendra Singh, Nayu Ikeda, William M. Gardner, Zahid A Butt, Mohammad Abdollahi, Temesgen Yihunie Akalu, Rahman Shiri, Benn Sartorius, Ai-Min Wu, Bing Fang Hwang, Flavia M. Cicuttini, Hiroyasu Iso, Luis Camera, Amin Soheili, Félix Carvalho, Yun Jin Kim, Caleb Mackay Salpeter Irvine, Mehdi Mirzaei-Alavijeh, Iman Halvaei, Saqib Ali, Giulio Castelpietra, Catalina Liliana Andrei, Ali Kazemi Karyani, Parkes J Kendrick, Hamidreza Haririan, Lucas Guimarães Abreu, Mukhammad David Naimzada, Jeff T. Zhao, Samiah Alam, Sorin Hostiuc, Shaun Wen Huey Lee, João Mauricio Castaldelli-Maia, Behzad Karami Matin, Cyrus Alinia, Takahiro Tabuchi, Manu Raj Mathur, Søren Thorgaard Skou, Thomas Khaled Dwayne Classen, Reza Heidari-Soureshjani, Massimo Cirillo, Nikita Otstavnov, Mehdi Bohluli, Ruth W. Kimokoti, Animut Tagele Tamiru, Masoumeh Sadeghi, Mohammad Ali Jahani, Itamar S. Santos, Mekdes Tigistu Yilma, Lars Johansson, Arielle Wilder Eagan, Nevine El Nahas, Silvia Schiavolin, Kevin D. Shield, Dinh-Toi Chu, Shiva Borzouei, Paul S. F. Yip, Beatrix Haddock, Gianfranco Alicandro, Vasily Vlassov, Deanna Anderlini, Giuseppe Remuzzi, Khalid A Altirkawi, Farahnaz Joukar, Aso Mohammad Darwesh, Ratilal Lalloo, Panniyammakal Jeemon, Rohollah Kalhor, Daniel Youngwhan Cho, Weijia Fu, João Pedro Silva, Rodrigo Sarmiento-Suarez, Seth Christopher Yaw Appiah, Mehdi Ahmadi, Jacob Olusegun Olusanya, José Neves, Gaorui Guo, Tomas Y. Yeheyis, John S. Ji, Charles D. H. Parry, Maryam Ghadimi, Seyed-Mohammad Fereshtehnejad, Serge Resnikoff, Anna E. Torre, Vinod C Nayak, Jamileh Shadid, Susanne Breitner, Mohammad Khammarnia, Mathilde Touvier, Ensiyeh Jenabi, Hosna Janjani, Floriane Ausloos, Irmina Maria Michalek, Alexandra S. Boon-Dooley, Jessica A. Cruz, Syed Mohamed Aljunid, Abiodun M. Adeoye, André Faro, Bartosz Miazgowski, Jobert Richie Nansseu, Erin C Mullany, Giannina Ferrara, Martin McKee, Emmanuel Peprah, Oommen John, Reza Saeedi, Yasser Vasseghian, Dragos Virgil Davitoiu, Sarah Wulf Hanson, Yingxi Zhao, Omid Shafaat, Ali Rajabpour-Sanati, Farid Najafi, Ana Maria Mantilla Herrera, Fatemeh Rajati, Tarun Gupta, Łukasz Szumowski, Mohammed Ibrahim Mohialdeen Gubari, Peter Njenga Keiyoro, Dharmesh Kumar Lal, Zhi Jiang Zhang, Osayomwanbo Osarenotor, Tanvir M. Huda, Perminder S. Sachdev, Farhad Ghamari, Era Upadhyay, Vivek Kumar, Guoqing Hu, Vinay Nangia, Vladimir Andreevich Korshunov, Saeed Shahabi, Golnaz Heidari, Ashraf Nabhan, Robert C. Reiner, Aziz Rezapour, Justin J. Lang, Rakhi Dandona, Josephine W. Ngunjiri, Anna-Karin Danielsson, André Karch, Filippo Ariani, Ahmed Abdelalim, Masih Tajdini, Stefanos Tyrovolas, Mohamed Hsairi, Jae Il Shin, Jasvinder A. Singh, Meghan D. Mooney, Fiona B. Bennitt, Hesam Alizade, Segun Emmanuel Ibitoye, Pradhum Ram, Soraya Siabani, Evanson Z. Sambala, Reza Malekzadeh, Falk Schwendicke, Lalit Dandona, Masoud Moradi, Molly R Nixon, Roya Mirzaei, Rachel Feldman, Hosni Salem, Alberto L. García-Basteiro, Lorainne Tudor Car, Sharareh Eskandarieh, Ramesh Holla, Ritesh G. Menezes, Taraneh Yousefinezhadi, Hai Quang Pham, Hamideh Salimzadeh, Luisa Sorio Flor, Priya Rathi, Ali Bijani, Harvey Whiteford, Shanshan Li, Aleksandr Y. Aravkin, Joshua A. Salomon, Franz Castro, Lisa M. Force, Abdilahi Yousuf Yousuf, Mina Anjomshoa, Ken Takahashi, Maigeng Zhou, Telma Zahirian Moghadam, Maseer Khan, Irina Filip, Santi Martini, Randah R. Hamadeh, Somayeh Bohlouli, Joana Morgado-da-Costa, Tim Driscoll, Jingkai Wei, Hermann Brenner, Reza Rawassizadeh, Radoslaw Sierpinski, Saman Esmaeilnejad, Emmanuel Wandera Okunga, Marisa Freitas, Srikanta Banerjee, Feleke Mekonnen Demeke, Shahin Soltani, Naser Mohammad Gholi Mezerji, Reed J D Sorensen, Elena V. Gnedovskaya, Johan Ärnlöv, Ivo Rakovac, Reza Mohammadpourhodki, Hussain Jafari, Atte Meretoja, Yasir Waheed, Fahad Alanezi, Arya Haj-Mirzaian, Sezer Kisa, Jaifred Christian F. Lopez, Khalid F. Alhabib, Basema Saddik, Michael R. Phillips, Vishnu Renjith, Yafeng Wang, Kevan R. Polkinghorne, Liliana G Ciobanu, Jacek Jerzy Jozwiak, Gelin Xu, Richard C. Franklin, Junjie Wu, Thomas R. Hird, Mohammad Zamani, Diana Silva, Fotis Topouzis, Irena Ilic, Jeffrey D. Stanaway, Hadi Pourjafar, Huong Lan Thi Nguyen, Khaled Khatab, Ammas Siraj Mohammed, Ziyad Al-Aly, A. A. Fomenkov, Charlie Ashbaugh, Mowafa Househ, Paul I. Dargan, Endalkachew Worku Mengesha, Shaimaa I. El-Jaafary, Ernoiz Antriyandarti, Iffat Elbarazi, Dara K. Mohammad, Naznin Hossain, Reza Shirkoohi, João M. Furtado, Arash Ziapour, Morteza Jafarinia, M. Mofizul Islam, Anamika Pandey, Ahmed I. Hasaballah, Tanuj Kanchan, Lee Ling Lim, Muktar Omer Omer, Charles D.A. Wolfe, Ulrich O Mueller, Helen Bitew, V. Prakash, Fereshteh Mehri, Randall V. Martin, Claudiu Herteliu, Constance D. Pond, Min Jeong Shin, Morteza Oladnabi, Antonio Maria Borzì, Yousef Mohammad, Yuichiro Yano, Luke D. Knibbs, Kevin S Ikuta, Maryam Mirzaei, Andreea Mirica, Sofia Boston Redford, Siamak Sabour, Mariya Vladimirovna Titova, Davood Anvari, Ghobad Moradi, Jordi Alonso, Shiwei Liu, Theo Vos, Tuomo J. Meretoja, Ireneous N. Soyiri, Owen R. Cooper, Seyed Sina Naghibi Irvani, Kejia Hu, Hannah J. Henrikson, Sanni Yaya, Robert P. Dellavalle, Chidozie Declan Iwu, Sergey Soshnikov, Jee-Young Jasmine Choi, Satinath Mukhopadhyay, Zabihollah Yousefi, Iman El Sayed, Biresaw Wassihun Alemu, Neeti Kapoor, Ahmad Daryani, Cathleen Keller, Ibrahim Abdollahpour, Nuno Taveira, Masoud Foroutan, Fatemeh Amiri, Mariam Molokhia, Songhomitra Panda-Jonas, Amy E. Peden, Rufus Akinyemi, Ejaz Ahmad Khan, Mostafa Amini-Rarani, J. Becker, Hamidreza Pazoki Toroudi, Ben Lacey, Kidanemaryam Berhe, Simon Yadgir, Spencer L. James, Cory N. Spencer, Aletta E. Schutte, Mu'awiyyah Babale Sufiyan, Arash Tehrani-Banihashemi, Govinda Prasad Dhungana, Fereshteh Ansari, Rixing Xu, Jonathan F. Mosser, Josep Maria Haro, Enrico Rubagotti, Anurag Agrawal, Zahiruddin Quazi Syed, Hoa Thi Do, Ettore Beghi, Seyed Mohammad Kazem Aghamir, Abraham Geremew, Alireza Esteghamati, Paramjit Gill, Farzad Jalilian, J. Jason West, Mikhail Sergeevich Zastrozhin, Albertino Damasceno, Bruce Bartholow Duncan, Nazir Fattahi, Daniel Cury Ribeiro, Michael Brauer, Mark A. Stokes, Veincent Christian Filipino Pepito, Lidia Morawska, Fiona J Charlson, Babak Moazen, Dejana Braithwaite, Jonathan M. Kocarnik, Sergio I. Prada, Andrea Farioli, Zahra Atafar, Heather Orpana, Daniela Balzi, Marco Vacante, Rahmatollah Moradzadeh, Jacek A. Kopec, Iván Landires, Robert G. Weintraub, Leonardo Roever, Yannick Béjot, Markus P. Schlaich, Hamed Zandian, Subramanian Senthilkumaran, Klara Dokova, Vahid Alipour, Sowmya J. Rao, Rakesh Ghosh, Omar Mukhtar Salman, Faris Lami, Marcos Roberto Tovani-Palone, Hamid Reza Tohidinik, Seyed Mohammad Riahi, Adnan Kisa, Ghasem Azarian, Caroline Stein, Zulfiqar A. Bhutta, Sinead Langan, Kunihiro Matsushita, Lauren E. Schaeffer, Kathryn H. Jacobsen, Mehdi Naderi, Mehdi Hosseinzadeh, Nizal Sarrafzadegan, Bahram Armoon, Dan J. Stein, Jessica Fanzo, Morenike Oluwatoyin Folayan, Luca Ronfani, Phetole Walter Mahasha, Nicholas J K Breitborde, Adrian Oţoiu, Arash Sarveazad, Marc L. Serre, Mostafa Hosseini, Nicolas Cherbuin, George D. Thurston, Jalal Arabloo, Mokhtar Mahdavi, Andre Rodrigues Duraes, Ana Laura Manda, Ahmed Abualhasan, Nima Rezaei, Yuan-Pang Wang, Theodore Patrick Younker, Alireza Ansari-Moghaddam, Borhan Mansouri, Adam E. Berman, Khezar Hayat, Rosario Cárdenas, Bolajoko O. Olusanya, Tommi Vasankari, Simon I. Hay, Fatemeh Ghaffarifar, Leo Stockfelt, Ai Koyanagi, Giorgia Giussani, Yuming Guo, Sonia Saxena, Deborah Carvalho Malta, Mehedi Hasan, Negar Rezaei, Maja Pasovic, Jukka Takala, Bogdan Oancea, Sare Safi, A. Werdecker, Florian Fischer, Beatriz Paulina Ayala Quintanilla, Muhammad Shahdaat Bin Sayeed, Takeshi Fukumoto, Maha Atout, Brijesh Sathian, Cristina Bosetti, Mitchell T. Wallin, Agegnehu Bante, Helen Ippolito, Anthony Masaka, Chantal Huynh, Justin Lo, Jordan Weiss, Joemer C. Maravilla, Alberto Raggi, Peter W. Gething, Cristiana Abbafati, Daniela Ribeiro, Mohammad Farahmand, Yetunde O. John-Akinola, Isabela M. Benseñor, Emilie R Maddison, John J. McGrath, Salman Khazaei, Scott B. Patten, Jean Jacques Noubiap, Emmanuela Gakidou, Celine M. Barthelemy, Ashish Badiye, George C. Patton, Obinna Onwujekwe, Peter Allebeck, Victor Aboyans, Olayinka Stephen Ilesanmi, Mousa Yaminfirooz, Neeraj Bedi, Nicholas L S Roberts, Joht Singh Chandan, Hans W. Hoek, Usman Iqbal, Nima Hafezi-Nejad, Haley Lescinsky, Naohiro Yonemoto, Ahmad Ghashghaee, Anders Larsson, David C. Schwebel, Milena Ilic, Richard T. Burnett, Yang Liu, Carlo La Vecchia, Felix Akpojene Ogbo, Morteza Naserbakht, Sangram Kishor Patel, Melanie S. Hammer, Prasanna Mithra, Mohammad Amin Bahrami, Kanyin L. Ong, Mona Pathak, Afshin Maleki, Saeid Safiri, Masood Ali Shaikh, Kate Causey, Michael R.M. Abrigo, Jost B. Jonas, Dian Kusuma, Jagadish Rao Padubidri, Mihajlo Jakovljevic, Ali S. Shalash, Abdiwahab Hashi, Ionut Negoi, Nataliya A. Foigt, Andrey Nikolaevich Briko, François Alla, Giuseppe Grosso, Houman Goudarzi, Di H. Cross, Vera Marisa Costa, Eduarda Fernandes, Chandrashekhar T Sreeramareddy, Odgerel Chimed-Ochir, Sonia Rodríguez-Ramírez, Bo Norrving, Kerem Shuval, Jacob L. Stubbs, Muhammad Ali, Shuhei Nomura, Man Mohan Mehndiratta, Chisom Joyqueenet Akunna, Abdollah Mohammadian-Hafshejani, Navid Rabiee, Dana Bryazka, Hussen Mohammed, Asadollah Gholamian, Ashley Marks, Rizwan Kalani, Molly E. Herbert, Islam Y. Elgendy, Moritz U. G. Kraemer, Chuanhua Yu, Suzanne Polinder, Pascual R. Valdez, Jennifer Rickard, Kylie Ball, Turki Alanzi, Mohsen Bayati, Hamed Mirzaei, Christopher M Odell, Amira Shaheen, Ziad A. Memish, Thirunavukkarasu Sathish, Michael A. Piradov, Hamed Kalani, Lorenzo Monasta, Christopher S Yilgwan, Desalegn Getnet Demsie, Riaz Uddin, Rizwan Suliankatchi Abdulkader, Vinay Srinivasan, Hamid Ahmadieh, Claudio Alberto Dávila-Cervantes, Raffaele Palladino, Chukwudi A Nnaji, Mika Shigematsu, Stein Emil Vollset, Abbas Sheikhtaheri, Paulo A. Lotufo, Nasir Salam, Binyam Minuye Birihane, Mohammad Ali Mansournia, Tomislav Mestrovic, Samer Hamidi, Rajesh Sagar, Mayowa O. Owolabi, Kara Estep, Ester Cerin, Michael T. Chung, Simon Øverland, Amir Taherkhani, Sheng Chia Chung, Martin Amogre Ayanore, Nikolaos Dervenis, Joan B. Soriano, Tahereh Javaheri, Victor Adekanmbi, Seid Tiku Mereta, Gbenga A. Kayode, Christopher R. Cederroth, Razique Anwer, Rajan Nikbakhsh, Kaja Abbas, Fatemeh Heydarpour, Louisa Degenhardt, Tahiya Alam, Mohammad Miri, Alibek Mereke, David Laith Rawaf, Ippazio Cosimo Antonazzo, Erkin M. Mirrakhimov, Seyed Hossein Yahyazadeh Jabbari, Desta Debalkie Atnafu, Davide Sattin, Moslem Soofi, Edris Hasanpoor, Krittika Bhattacharyya, Mika Kivimäki, Nikolay Ivanovich Briko, Joanna L Whisnant, Christopher J L Murray, Simin Mouodi, Alize J. Ferrari, Damian Santomauro, Katrin Burkart, Tudorel Andrei, Alberto Baldasseroni, Hafiz Ansar Rasul Suleria, Valery L. Feigin, Nauman Khalid, Ewerton Cousin, S. Mohammad Sajadi, Francisco Rogerlândio Martins-Melo, Shankar M Bakkannavar, Themba G.G. Ginindza, Sadaf G. Sepanlou, Sheikh Mohammed Shariful Islam, Sanjay Basu, Getinet Ayano, Paula Moraga, Soheil Hassanipour, Jason A. Anderson, Catherine Bisignano, Iyad Sultan, Deepak Kumar Pasupula, Keivan Ahmadi, Fariba Dorostkar, Rajeev Gupta, David M. Pereira, Mustafa Z. Younis, Adel Spotin, Rasmus Havmoeller, Yeshambel T. Nigatu, Barthelemy Kuate Defo, Mithila Faruque, Alan D. Lopez, Shailesh Advani, Behshad Naghshtabrizi, Shane D. Morrison, Inga Dora Sigfusdottir, Konrad Pesudovs, Anna Gershberg Hayoon, Raaj Kishore Biswas, Reshmi Bhageerathy, H. Dean Hosgood, Giulia Carreras, Sarika Chaturvedi, James L. Fisher, In-Hwan Oh, G Anil Kumar, Christoph Nowak, Vijay Kumar Chattu, Puja C Rao, Marcel Ausloos, Ali Kabir, Rannveig Sigurvinsdottir, Leeberk Raja Inbaraj, Edgar Denova-Gutiérrez, Rafael Tabarés-Seisdedos, Minh Nguyen, Ashkan Afshin, Payman Salamati, Colin Angus, Mona M. Khater, Ehsan Sadeghi, Mahalaqua Nazli Khatib, Antonio Biondi, Valentin Yurievich Skryabin, Mohsen Abbasi-Kangevari, Andrew T Olagunju, Amir Radfar, Laith J. Abu-Raddad, Marcello Tonelli, Hesam Ghiasvand, Hanne Christensen, Juan Jesus Carrero, Maryam Adabi, Saravanan Muthupandian, Kurt Straif, Hossein Samadi Kafil, Lope H Barrero, Harish Chander Gugnani, Mohammad Fareed, Morteza Shamsizadeh, Jemal Abdu Mohammed, Juan A Rivera, Shai Linn, Saad M.A. Dahlawi, Janni Leung, Shokofeh Maleki, Mohd Anisul Karim, Kamarul Imran Musa, Farshad Pourmalek, Dietrich Rothenbacher, Kiomars Sharafi, Alessandra C. Goulart, Leila Doshmangir, Gabriele Nagel, Helena Manguerra, Olatunji O. Adetokunboh, Srinivasa Vittal Katikireddi, Nermin Ghith, Maha El Tantawi, Awoke Misganaw, Yunquan Zhang, Carl Abelardo T. Antonio, Vahid Rashedi, Mehran Shams-Beyranvand, Bhaskaran Unnikrishnan, Holly E. Erskine, Ann Kristin Knudsen, Marissa B Reitsma, Getayeneh Antehunegn Tesema, Javad Javidnia, Ismael R. Campos-Nonato, Biniyam Sahiledengle Geberemariyam, Godfrey Mutashambara Rwegerera, Alaa Badawi, James Leigh, Morteza Arab-Zozani, Kyle E. Simpson, Muluken Bekele Sorrie, Roghiyeh Faridnia, Vivekanand Jha, Tomasz Miazgowski, Aaron J Cohen, Chukwuma David Umeokonkwo, Alessandra Lugo, Adhanom Gebreegziabher Baraki, Akshaya Srikanth Bhagavathula, Caitlyn Steiner, Gholamreza Roshandel, Cuong Tat Nguyen, Tania G Sánchez-Pimienta, Ahamarshan Jayaraman Nagarajan, Laura Kemmer, Ihoghosa Osamuyi Iyamu, Seyedeh Zahra Masoumi, Vivian Chia-Rong Hsieh, Kris J. Krohn, Phoebe Anne Rhinehart, Sarah Wozniak, Sahar Saeedi Moghaddam, Kate E. LeGrand, Christian Kieling, Vahid Yazdi-Feyzabadi, Robin Room, Zelalem Nigussie Azene, Kelly Cercy, Paul H. Lee, Stanislav S. Otstavnov, Dinesh Bhandari, Rafael Alves Guimarães, Zemenu Tadesse Tessema, Aziz Sheikh, Michellr L. Bell, Marwa Rashad Salem, Kirsten E. Wiens, Emma U.R. Smith, Hassan Abolhassani, Cristiano Piccinelli, Kedir Hussein Abegaz, G.K. Mini, Christian Razo, Manuela L. Ferreira, Diego De Leo, Francesco Saverio Violante, Aristidis Tsatsakis, Zahra Sadat Dibaji Forooshani, Tea Lallukka, Dickson A. Amugsi, Anna Poznańska, Graeme J. Hankey, Kewal Krishan, Maryam Zamanian, Eirini Skiadaresi, Jai K Das, Felix Greaves, Tessa M. Pilz, Sameer Vali Gopalani, Mansour Ghafourifard, M. DeLang, Morteza Mahmoudi, Alton Lu, Brian J. Hall, Ravi Prakash Jha, David Edvardsson, Xiu Ju George Zhao, Farshad Farzadfar, Hadi Hassankhani, Samuel M. Ostroff, Gerhard Sulo, Keyghobad Ghadiri, Neeraj Bhala, Stefan Lorkowski, Mohammad Rabiee, Sivan Yegnanarayana Iyer Saraswathy, Amirhossein Sahebkar, Rashid Abdi Guled, Abdallah M. Samy, Roman Topor-Madry, Michal Grivna, Afsaneh Arzani, Ayesha Humayun, Simin Liu, Maryam Khayamzadeh, Davoud Adham, Ahad Bakhtiari, Shafiu Mohammed, Paolo Lauriola, Abbas Mosapour, Sophia Emmons-Bell, Khurshid Alam, Rajat Das Gupta, Matilde Leonardi, Muktar Beshir Ahmed, Jeffrey V. Lazarus, Mohamed M. Gad, Kelly Compton, Leila R Kalankesh, Abdelrahman Ibrahim Abushouk, Mikk Jürisson, Catherine M. Antony, Ali A. Asadi-Pooya, Daniel Diaz, Salman Rawaf, Gina Agarwal, Ted R. Miller, Rebecca Ivers, João Vasco Santos, Savita Lasrado, Abdul Moiz Hafiz, Amir Almasi-Hashiani, Praveen Hoogar, Fares Alahdab, Om P Kurmi, Anbissa Muleta Senbeta, Tomi Akinyemiju, Boris Bikbov, Muhammad Aziz Rahman, Amin Mousavi Khaneghah, Yahya Safari, Guilherme Borges, Carlos A Castañeda-Orjuela, Kenji Shibuya, Bahman Yousefi, Berrin Serdar, Karen M. Tabb, Sonali Kochhar, Till Bärnighausen, Kala M. Mehta, Mostafa Dianatinasab, Arash Etemadi, Melissa Y. Wei, Kiana Ramezanzadeh, Lingkan Barua, Zubair Kabir, Rade Vukovic, Hesham M. Al-Mekhlafi, Shoshana H. Ballew, Miriam Levi, Zainab Samad, Florentino Luciano Caetano dos Santos, Juan Sanabria, Ramu Rawat, Chinwe Juliana Iwu, Gabrielle B. Britton, Colm McAlinden, Mohsen Naghavi, Maarten J. Postma, Chhabi Lal Ranabhat, Jalil Jaafari, Walter Mendoza, Mahesh P A, Pallab K. Maulik, Ali H. Mokdad, Andre M. N. Renzaho, Milena Santric-Milicevic, Parvaiz A Koul, Foad Abd-Allah, Mihaela Hostiuc, Richard G. Cowden, Ronny Westerman, Meghdad Pirsaheb, Department of Earth Observation Science, UT-I-ITC-ACQUAL, Faculty of Geo-Information Science and Earth Observation, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Value, Affordability and Sustainability (VALUE), Microbes in Health and Disease (MHD), Tampere University, Tays Research Services, Health Sciences, Murray, C. J. L., Aravkin, A. Y., Zheng, P., Abbafati, C., Abbas, K. M., Abbasi-Kangevari, M., Abd-Allah, F., Abdelalim, A., Abdollahi, M., Abdollahpour, I., Abegaz, K. H., Abolhassani, H., Aboyans, V., Abreu, L. G., Abrigo, M. R. M., Abualhasan, A., Abu-Raddad, L. J., Abushouk, A. I., Adabi, M., Adekanmbi, V., Adeoye, A. M., Adetokunboh, O. O., Adham, D., Advani, S. 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W., Ausloos, F., Ausloos, M., Ayala Quintanilla, B. P., Ayano, G., Ayanore, M. A., Azari, S., Azarian, G., Azene, Z. N., Badawi, A., Badiye, A. D., Bahrami, M. A., Bakhshaei, M. H., Bakhtiari, A., Bakkannavar, S. M., Baldasseroni, A., Ball, K., Ballew, S. H., Balzi, D., Banach, M., Banerjee, S. K., Bante, A. B., Baraki, A. G., Barker-Collo, S. L., Barnighausen, T. W., Barrero, L. H., Barthelemy, C. M., Barua, L., Basu, S., Baune, B. T., Bayati, M., Becker, J. S., Bedi, N., Beghi, E., Bejot, Y., Bell, M. L., Bennitt, F. B., Bensenor, I. M., Berhe, K., Berman, A. E., Bhagavathula, A. S., Bhageerathy, R., Bhala, N., Bhandari, D., Bhattacharyya, K., Bhutta, Z. A., Bijani, A., Bikbov, B., Bin Sayeed, M. S., Biondi, A., Birihane, B. M., Bisignano, C., Biswas, R. K., Bitew, H., Bohlouli, S., Bohluli, M., Boon-Dooley, A. S., Borges, G., Borzi, A. M., Borzouei, S., Bosetti, C., Boufous, S., Braithwaite, D., Breitborde, N. J. K., Breitner, S., Brenner, H., Briant, P. S., Briko, A. N., Briko, N. I., Britton, G. B., Bryazka, D., Bumgarner, B. R., Burkart, K., Burnett, R. T., Burugina Nagaraja, S., Butt, Z. A., Caetano dos Santos, F. L., Cahill, L. E., Camera, L. L. A., Campos-Nonato, I. R., Cardenas, R., Carreras, G., Carrero, J. J., Carvalho, F., Castaldelli-Maia, J. M., Castaneda-Orjuela, C. A., Castelpietra, G., Castro, F., Causey, K., Cederroth, C. R., Cercy, K. M., Cerin, E., Chandan, J. S., Chang, K. -L., Charlson, F. J., Chattu, V. K., Chaturvedi, S., Cherbuin, N., Chimed-Ochir, O., Cho, D. Y., Choi, J. -Y. J., Christensen, H., Chu, D. -T., Chung, M. T., Chung, S. -C., Cicuttini, F. M., Ciobanu, L. G., Cirillo, M., Classen, T. K. D., Cohen, A. J., Compton, K., Cooper, O. R., Costa, V. M., Cousin, E., Cowden, R. G., Cross, D. H., Cruz, J. A., Dahlawi, S. M. A., Damasceno, A. A. M., Damiani, G., Dandona, L., Dandona, R., Dangel, W. J., Danielsson, A. -K., Dargan, P. I., Darwesh, A. M., Daryani, A., Das, J. K., Das Gupta, R., das Neves, J., Davila-Cervantes, C. 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A., Rajabpour-Sanati, A., Rajati, F., Rakovac, I., Ram, P., Ramezanzadeh, K., Ranabhat, C. L., Rao, P. C., Rao, S. J., Rashedi, V., Rathi, P., Rawaf, D. L., Rawaf, S., Rawal, L., Rawassizadeh, R., Rawat, R., Razo, C., Redford, S. B., Reiner, R. C., Reitsma, M. B., Remuzzi, G., Renjith, V., Renzaho, A. M. N., Resnikoff, S., Rezaei, N., Rezapour, A., Rhinehart, P. -A., Riahi, S. M., Ribeiro, D. C., Ribeiro, D., Rickard, J., Rivera, J. A., Roberts, N. L. S., Rodriguez-Ramirez, S., Roever, L., Ronfani, L., Room, R., Roshandel, G., Roth, G. A., Rothenbacher, D., Rubagotti, E., Rwegerera, G. M., Sabour, S., Sachdev, P. S., Saddik, B., Sadeghi, E., Sadeghi, M., Saeedi, R., Saeedi Moghaddam, S., Safari, Y., Safi, S., Safiri, S., Sagar, R., Sahebkar, A., Sajadi, S. M., Salam, N., Salamati, P., Salem, H., Salem, M. R. R., Salimzadeh, H., Salman, O. M., Salomon, J. A., Samad, Z., Samadi Kafil, H., Sambala, E. Z., Samy, A. M., Sanabria, J., Sanchez-Pimienta, T. G., Santomauro, D. F., Santos, I. 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Leonardi, M, Lescinsky, H, Leung, J, Levi, M, Li, S, Lim, L, Linn, S, Liu, S, Liu, Y, Lo, J, Lopez, A, Lopez, J, Lopukhov, P, Lorkowski, S, Lotufo, P, Lu, A, Lugo, A, Maddison, E, Mahasha, P, Mahdavi, M, Mahmoudi, M, Majeed, A, Maleki, A, Maleki, S, Malekzadeh, R, Malta, D, Mamun, A, Manda, A, Manguerra, H, Mansour-Ghanaei, F, Mansouri, B, Mansournia, M, Mantilla Herrera, A, Maravilla, J, Marks, A, Martin, R, Martini, S, Martins-Melo, F, Masaka, A, Masoumi, S, Mathur, M, Matsushita, K, Maulik, P, Mcalinden, C, Mcgrath, J, Mckee, M, Mehndiratta, M, Mehri, F, Mehta, K, Memish, Z, Mendoza, W, Menezes, R, Mengesha, E, Mereke, A, Mereta, S, Meretoja, A, Meretoja, T, Mestrovic, T, Miazgowski, B, Miazgowski, T, Michalek, I, Miller, T, Mills, E, Mini, G, Miri, M, Mirica, A, Mirrakhimov, E, Mirzaei, H, Mirzaei, M, Mirzaei, R, Mirzaei-Alavijeh, M, Misganaw, A, Mithra, P, Moazen, B, Mohammad, D, Mohammad, Y, Mohammad Gholi Mezerji, N, Mohammadian-Hafshejani, A, Mohammadifard, N, 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Pasovic, M, Pasupula, D, Patel, S, Pathak, M, Patten, S, Patton, G, Toroudi, H, Peden, A, Pennini, A, Pepito, V, Peprah, E, Pereira, D, Pesudovs, K, Pham, H, Phillips, M, Piccinelli, C, Pilz, T, Piradov, M, Pirsaheb, M, Plass, D, Polinder, S, Polkinghorne, K, Pond, C, Postma, M, Pourjafar, H, Pourmalek, F, Poznanska, A, Prada, S, Prakash, V, Pribadi, D, Pupillo, E, Syed, Z, Rabiee, M, Rabiee, N, Radfar, A, Rafiee, A, Raggi, A, Rahman, M, Rajabpour-Sanati, A, Rajati, F, Rakovac, I, Ram, P, Ramezanzadeh, K, Ranabhat, C, Rao, P, Rao, S, Rashedi, V, Rathi, P, Rawaf, D, Rawaf, S, Rawal, L, Rawassizadeh, R, Rawat, R, Razo, C, Redford, S, Reiner, R, Reitsma, M, Remuzzi, G, Renjith, V, Renzaho, A, Resnikoff, S, Rezaei, N, Rezapour, A, Rhinehart, P, Riahi, S, Ribeiro, D, Rickard, J, Rivera, J, Roberts, N, Rodriguez-Ramirez, S, Roever, L, Ronfani, L, Room, R, Roshandel, G, Roth, G, Rothenbacher, D, Rubagotti, E, Rwegerera, G, Sabour, S, Sachdev, P, Saddik, B, Sadeghi, E, Sadeghi, M, Saeedi, R, Saeedi Moghaddam, S, Safari, Y, Safi, S, Safiri, S, Sagar, R, Sahebkar, A, Sajadi, S, Salam, N, Salamati, P, Salem, H, Salem, M, Salimzadeh, H, Salman, O, Salomon, J, Samad, Z, Samadi Kafil, H, Sambala, E, Samy, A, Sanabria, J, Sanchez-Pimienta, T, Santomauro, D, Santos, I, Santos, J, Santric-Milicevic, M, Saraswathy, S, Sarmiento-Suarez, R, Sarrafzadegan, N, Sarveazad, A, Sathian, B, Sathish, T, Sattin, D, Saxena, S, Schaeffer, L, Schiavolin, S, Schlaich, M, Schmidt, M, Schutte, A, Schwebel, D, Schwendicke, F, Senbeta, A, Senthilkumaran, S, Sepanlou, S, Serdar, B, Serre, M, Shadid, J, Shafaat, O, Shahabi, S, Shaheen, A, Shaikh, M, Shalash, A, Shams-Beyranvand, M, Shamsizadeh, M, Sharafi, K, Sheikh, A, Sheikhtaheri, A, Shibuya, K, Shield, K, Shigematsu, M, Shin, J, Shin, M, Shiri, R, Shirkoohi, R, Shuval, K, Siabani, S, Sierpinski, R, Sigfusdottir, I, Sigurvinsdottir, R, Silva, J, Simpson, K, Singh, J, Singh, P, Skiadaresi, E, Skou, S, Skryabin, V, Smith, E, Soheili, A, Soltani, S, 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Whiteford, H, Wiens, K, Wolfe, C, Wozniak, S, Wu, A, Wu, J, Wulf Hanson, S, Xu, G, Xu, R, Yadgir, S, Yahyazadeh Jabbari, S, Yamagishi, K, Yaminfirooz, M, Yano, Y, Yaya, S, Yazdi-Feyzabadi, V, Yeheyis, T, Yilgwan, C, Yilma, M, Yip, P, Yonemoto, N, Younis, M, Younker, T, Yousefi, B, Yousefi, Z, Yousefinezhadi, T, Yousuf, A, Yu, C, Yusefzadeh, H, Moghadam, T, Zamani, M, Zamanian, M, Zandian, H, Zastrozhin, M, Zhang, Y, Zhang, Z, Zhao, J, Zhao, X, Zhao, Y, Zheng, P, Zhou, M, Ziapour, A, Zimsen, S, Lim, S, Murray, C, GBD 2019 Risk Factors Collaborator, Violante FS, Biosciences, Department of Public Health, Clinicum, Department of Neurosciences, HUS Comprehensive Cancer Center, Environmental Sciences, Sub Foundations&PhilosophyofNaturSc begr, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Public Health, Bin Sayeed, M. S. B., Caetano Dos Santos, F. L., Camera, L. A., Elyazar, I. R. F., Ayalew Gebreslassie, A. A. A., Ginindza, T. G., Matin, B. K., Morgado-Da-Costa, J., Khaneghah, A. M., Mahesh, P. A., Toroudi, H. P., Syed, Z. Q., Salem, M. R., Skou, S. T., Tovani-Palone, M. R., Tudor Car, L. T., and Moghadam, T. Z.
Subjects: Male, Nutritional Sciences, Specific risk, Contaminación del Aire Interior, 030204 cardiovascular system & hematology, Socioeconomic Factor, systematic analysis, Global Health, Body Mass Index, Global Burden of Disease, Health Risk Behavior, Health Risk Behaviors, Disease studies, 0302 clinical medicine, Risk Factors, METABOLIC RISKS, 030212 general & internal medicine, 11 Medical and Health Sciences, Factores de Riesgo, 2. Zero hunger, education.field_of_study, Public health, Injuries, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, GBD, risck factors, attributable burden of disease, 3142 Public health care science, environmental and occupational health, 3. Good health, Relative risk, Environmental health, Health, Hypertension, Global Burden of Diseases, Injuries, Risk Factors, A990 Medicine and Dentistry not elsewhere classified, Female, Leading risk factors, Global Health Metrics, Cohort study, Human, medicine.medical_specialty, Substance-Related Disorders, Population, UNITED-STATES, Risk Assessment, DIET, ITC-HYBRID, 03 medical and health sciences, Life Expectancy, MORTALITY, DISABILITY, POLLUTION, CLUSTERS, SDG 3 - Good Health and Well-being, General & Internal Medicine, medicine, Humans, Global Burden of Disease Study, Risk factor, education, Global burden, business.industry, Risk Factor, Malnutrition, Klinisk medicin, Global Burden of Diseases, Environmental Exposure, medicine.disease, Enfermedades, purl.org/pe-repo/ocde/ford#3.02.00 [https], Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Years of potential life lost, Socioeconomic Factors, Risk factors, Disease study, Hyperglycemia, ITC-ISI-JOURNAL-ARTICLE, NA, Clinical Medicine, business, RA
Abstract: Background Rigorous analysis of levels and trends in exposure to leading risk factors and quantification of their effect on human health are important to identify where public health is making progress and in which cases current efforts are inadequate. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a standardised and comprehensive assessment of the magnitude of risk factor exposure, relative risk, and attributable burden of disease. Methods GBD 2019 estimated attributable mortality, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 87 risk factors and combinations of risk factors, at the global level, regionally, and for 204 countries and territories. GBD uses a hierarchical list of risk factors so that specific risk factors (eg, sodium intake), and related aggregates (eg, diet quality), are both evaluated. This method has six analytical steps. (1) We included 560 risk-outcome pairs that met criteria for convincing or probable evidence on the basis of research studies. 12 risk-outcome pairs included in GBD 2017 no longer met inclusion criteria and 47 risk-outcome pairs for risks already included in GBD 2017 were added based on new evidence. (2) Relative risks were estimated as a function of exposure based on published systematic reviews, 81 systematic reviews done for GBD 2019, and meta-regression. (3) Levels of exposure in each age-sex-location-year included in the study were estimated based on all available data sources using spatiotemporal Gaussian process regression, DisMod-MR 2.1, a Bayesian meta-regression method, or alternative methods. (4) We determined, from published trials or cohort studies, the level of exposure associated with minimum risk, called the theoretical minimum risk exposure level. (5) Attributable deaths, YLLs, YLDs, and DALYs were computed by multiplying population attributable fractions (PAFs) by the relevant outcome quantity for each age-sex-location-year. (6) PAFs and attributable burden for combinations of risk factors were estimated taking into account mediation of different risk factors through other risk factors. Across all six analytical steps, 30 652 distinct data sources were used in the analysis. Uncertainty in each step of the analysis was propagated into the final estimates of attributable burden. Exposure levels for dichotomous, polytomous, and continuous risk factors were summarised with use of the summary exposure value to facilitate comparisons over time, across location, and across risks. Because the entire time series from 1990 to 2019 has been re-estimated with use of consistent data and methods, these results supersede previously published GBD estimates of attributable burden. Findings The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure. Global declines also occurred for tobacco smoking and lead exposure. The largest increases in risk exposure were for ambient particulate matter pollution, drug use, high fasting plasma glucose, and high body-mass index. In 2019, the leading Level 2 risk factor globally for attributable deaths was high systolic blood pressure, which accounted for 10.8 million (95% uncertainty interval [UI] 9.51-12.1) deaths (19.2% [16.9-21.3] of all deaths in 2019), followed by tobacco (smoked, second-hand, and chewing), which accounted for 8.71 million (8.12-9.31) deaths (15.4% [14.6-16.2] of all deaths in 2019). The leading Level 2 risk factor for attributable DALYs globally in 2019 was child and maternal malnutrition, which largely affects health in the youngest age groups and accounted for 295 million (253-350) DALYs (11.6% [10.3-13.1] of all global DALYs that year). The risk factor burden varied considerably in 2019 between age groups and locations. Among children aged 0-9 years, the three leading detailed risk factors for attributable DALYs were all related to malnutrition. Iron deficiency was the leading risk factor for those aged 10-24 years, alcohol use for those aged 25-49 years, and high systolic blood pressure for those aged 50-74 years and 75 years and older. Interpretation Overall, the record for reducing exposure to harmful risks over the past three decades is poor. Success with reducing smoking and lead exposure through regulatory policy might point the way for a stronger role for public policy on other risks in addition to continued efforts to provide information on risk factor harm to the general public. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.
Published: 2020

37. Sex differences in stress-related disorders: Major depressive disorder, bipolar disorder, and posttraumatic stress disorder

Author: Dick F, Swaab and Ai-Min, Bao
Subjects: Adult, Male, Stress Disorders, Post-Traumatic, Depressive Disorder, Major, Sex Characteristics, Bipolar Disorder, Humans, Pituitary-Adrenal System, Female
Abstract: Stress-related disorders, such as mood disorders and posttraumatic stress disorder (PTSD), are more common in women than in men. This sex difference is at least partly due to the organizing effect of sex steroids during intrauterine development, while activating or inhibiting effects of circulating sex hormones in the postnatal period and adulthood also play a role. Such effects result in structural and functional changes in neuronal networks, neurotransmitters, and neuropeptides, which make the arousal- and stress-related brain systems more vulnerable to environmental stressful events in women. Certain brainstem nuclei, the amygdala, habenula, prefrontal cortex, and hypothalamus are important hubs in the stress-related neuronal network. Various hypothalamic nuclei play a central role in this sexually dimorphic network. This concerns not only the hypothalamus-pituitary-adrenal axis (HPA-axis), which integrates the neuro-endocrine-immune responses to stress, but also other hypothalamic nuclei and systems that play a key role in the symptoms of mood disorders, such as disordered day-night rhythm, lack of reward feelings, disturbed eating and sex, and disturbed cognitive functions. The present chapter focuses on the structural and functional sex differences that are present in the stress-related brain systems in mood disorders and PTSD, placing the HPA-axis in the center. The individual differences in the vulnerability of the discussed systems, caused by genetic and epigenetic developmental factors warrant further research to develop tailor-made therapeutic strategies.
Published: 2020

38. 20-Deoxyingenol alleviates osteoarthritis by activating TFEB in chondrocytes

Author: Yifei Zhou, Mingbao Gu, Ximiao Chen, Weiyang Gao, Zhongke Lin, Naifeng Tian, Liaojun Sun, Chenghao Ren, Jie Jin, Yaosen Wu, Ai-Min Wu, Xiaolei Zhang, and Zongyou Pan
Subjects: 0301 basic medicine, Senescence, Male, Aging, Fluorescent Antibody Technique, Apoptosis, medicine.disease_cause, 03 medical and health sciences, Mice, 0302 clinical medicine, Chondrocytes, In vivo, Osteoarthritis, medicine, Autophagy, Animals, Transcription factor, Cells, Cultured, Pharmacology, business.industry, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, humanities, Cell biology, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, 030220 oncology & carcinogenesis, TFEB, Diterpenes, business, Nuclear localization sequence, Oxidative stress
Abstract: Osteoarthritis (OA) is an age-related degenerative disease and currently cannot be cured. Transcription factor EB (TFEB) is one of the major transcriptional factors that regulates autophagy and lysosomal biogenesis. TFEB has been shown to be an effective therapeutic target for many diseases including OA. The current study explores the therapeutic effects of 20-Deoxyingenol (20-DOI) on OA as well as its working mechanism on TFEB regulation. The in vitro study showed that 20-DOI may suppress apoptosis and senescence induced by oxidative stress in chondrocytes; it may also promote the nuclear localization of TFEB in chondrocytes. Knock-down of TFEB compromised the effects of 20-DOI on apoptosis and senescence. The in vivo study demonstrated that 20-DOI may postpone the progression of OA in mouse destabilization of the medial meniscus (DMM) model; it may also suppress apoptosis and senescence and promote the nuclear localization of TFEB in chondrocytes in vivo. This work suggests that 20-Deoxyingenol may alleviate osteoarthritis by activating TFEB in chondrocytes, while 20-DOI may become a potential drug for OA therapy.
Published: 2020

39. Nosocomial infections due to multidrug-resistant bacteria in cancer patients: a six-year retrospective study of an oncology Center in Western China

Author: Xin Shi, Xiao Fu, Xuan Liang, Tao Tian, Xiaoqiang Zheng, Na Liu, Ai-Min Jiang, Meng-Di Ren, Yu Yao, Zhiping Ruan, and Huan Gao
Subjects: Male, 0301 basic medicine, China, Imipenem, medicine.medical_specialty, Multidrug-resistant bacteria, 030106 microbiology, Meropenem, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Medical microbiology, Antibiotic resistance, Enterobacteriaceae, Drug Resistance, Multiple, Bacterial, Neoplasms, Internal medicine, Nosocomial infections, Prevalence, medicine, Humans, lcsh:RC109-216, Hospital Mortality, Aged, Retrospective Studies, Cross Infection, biology, business.industry, Enterobacteriaceae Infections, Cancer patients, Middle Aged, Prognosis, biology.organism_classification, Anti-Bacterial Agents, Acinetobacter baumannii, Stenotrophomonas maltophilia, 030104 developmental biology, Infectious Diseases, Risk factors, Amikacin, Urinary Tract Infections, Population study, Female, business, Research Article, medicine.drug
Abstract: Background Bacterial infections are the most frequent complications in patients with malignancy, and the epidemiology of nosocomial infections among cancer patients has changed over time. This study aimed to evaluate the characteristics, antibiotic resistance patterns, and prognosis of nosocomial infections due to multidrug-resistant (MDR) bacteria in cancer patients. Methods This retrospective observational study analyzed cancer patients with nosocomial infections caused by MDR from August 2013 to May 2019. The extracted clinical data were recorded in a standardized form and compared based on the survival status of the patients after infection and during hospitalization. The data were analyzed using independent samples t-test, Chi-square test, and binary logistic regression. P-values Results One thousand eight patients developed nosocomial infections during hospitalization, with MDR strains detected in 257 patients. Urinary tract infection (38.1%), respiratory tract infection (26.8%), and bloodstream infection (BSI) (12.5%) were the most common infection types. Extended-spectrum β-lactamase producing Enterobacteriaceae (ESBL-PE) (72.8%) members were the most frequently isolated MDR strains, followed by Acinetobacter baumannii (11.7%), and Stenotrophomonas maltophilia (6.2%). The results of multivariate regression analysis revealed that smoking history, intrapleural/abdominal infusion history within 30 days, the presence of an indwelling urinary catheter, length of hospitalization, and hemoglobin were independent factors for in-hospital mortality in the study population. The isolated MDR bacteria exhibited high rates of sensitivity to amikacin, meropenem, and imipenem. Conclusions The burden of nosocomial infections due to MDR bacteria is considerably high in oncological patients, with ESBL-PE being the most predominant causative pathogen. Our findings suggest that amikacin and carbapenems actively against more than 89.7% of MDR isolates. The precise management of MDR bacterial infections in cancer patients may improve the prognosis of these individuals.
Published: 2020

40. Stereotactic body radiotherapy versus hepatic resection for hepatocellular carcinoma (≤ 5 cm): a propensity score analysis

Author: Wei-Ping He, Yu-Ze Fan, Li Zheng, Quan Wang, Jing Sun, Wengang Li, Zhi-Xian Hong, Ai-Min Zhang, Ying-Zhe Sun, Tao Zhang, and Xuezhang Duan
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, China, Cirrhosis, Carcinoma, Hepatocellular, Hepatitis, Viral, Human, medicine.disease_cause, Radiosurgery, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Cyberknife, Internal medicine, medicine, Hepatectomy, Humans, Propensity Score, Neoplasm Staging, Hepatitis, Hepatitis B virus, Hepatology, business.industry, Liver Neoplasms, Retrospective cohort study, Hepatitis B, Middle Aged, medicine.disease, Prognosis, Tumor Burden, Survival Rate, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Female, business, Follow-Up Studies
Abstract: CyberKnife stereotactic body radiation therapy (CK-SBRT) has been applied to hepatocellular carcinoma (HCC) patients for several years. The study aim was to compare the efficacy of hepatic resection (HR) and CK-SBRT in naive small hepatocellular carcinoma (sHCC) patients with hepatitis virus-related cirrhosis using a 5-year follow-up study. This retrospective cohort study included 317 naive sHCC patients (246 men and 71 women) with hepatitis B or C virus cirrhosis who were treated with HR (n = 195) or CK-SBRT (n = 122) from November 2011 to December 2015. Cumulative overall survival (OS) rates and progression-free survival (PFS) rates were calculated using Kaplan–Meier method. After the propensity score-matched analysis, 104 patients were selected from each group for further analysis. The 1-, 2-, 3-, and 5-year OS rates were 96.2%, 89.4%, 85.5% and 70.7% in the HR group and 93.3%, 89.4%, 83.7% and 71.0% in the CK-SBRT group, respectively. The 1-, 2-, 3-, and 5-year PFS rates were 78.8%, 64.3%, 56.4% and 47.3% in the HR group and 84.5%, 67.8%, 58.9% and 49.0% in the CK-SBRT group, respectively. No significant difference was found between the two groups in the OS and PFS rates (OS, p = 0.673; PFS, p = 0.350). No death occurred due to the toxicity or complications of HR or CK-SBRT. CK-SBRT could be an effective alternative to HR for sHCC naive patients with hepatitis-related cirrhosis, especially if patients have higher CP scores and lower PLT counts. PLT counts should be factored into survival evaluation of HCC treatment.
Published: 2020

41. Dysregulation of bile acids increases the risk for preterm birth in pregnant women

Author: Ai-Min Cui, Christina Nadolny, Yuan Chen, Qiwen Chen, Ruitang Deng, Sangmin You, Winifer Ali, Syed F. Hashmi, Zachary Hurd, Xin Bush, Gang Qin, and Xinmu Zhang
Subjects: 0301 basic medicine, Male, Reproductive disorders, General Physics and Astronomy, Physiology, environment and public health, Mice, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Pregnancy, Medicine, Prospective Studies, lcsh:Science, Carbon Tetrachloride, Multidisciplinary, Bile acid, integumentary system, Perinatal mortality, Pregnancy Outcome, Treatment options, Middle Aged, Hospitals, Premature Birth, 030211 gastroenterology & hepatology, Female, Cohort study, Signal Transduction, Adult, Adolescent, medicine.drug_class, Science, macromolecular substances, Cholic Acid, General Biochemistry, Genetics and Molecular Biology, Article, Bile Acids and Salts, 03 medical and health sciences, Young Adult, Animals, Humans, Liver diseases, business.industry, Extramural, Infant, Newborn, General Chemistry, Disease Models, Animal, 030104 developmental biology, Etiology, Pregnancy, Animal, Farnesoid X receptor, lcsh:Q, business, Homeostasis
Abstract: Preterm birth (PTB) is the leading cause of perinatal mortality and newborn complications. Bile acids are recognized as signaling molecules regulating a myriad of cellular and metabolic activities but have not been etiologically linked to PTB. In this study, a hospital-based cohort study with 36,755 pregnant women is conducted. We find that serum total bile acid levels directly correlate with the PTB rates regardless of the characteristics of the subjects and etiologies of liver disorders. Consistent with the findings from pregnant women, PTB is successfully reproduced in mice with liver injuries and dysregulated bile acids. More importantly, bile acids dose-dependently induce PTB with minimal hepatotoxicity. Furthermore, restoring bile acid homeostasis by farnesoid X receptor activation markedly reduces PTB and dramatically improves newborn survival rates. The findings thus establish an etiologic link between bile acids and PTB, and open an avenue for developing etiology-based therapies to prevent or delay PTB., Preterm birth (PTB) is the leading cause of perinatal mortality and newborn complications with limited treatment options. Here the authors show that dysregulation of bile acids increases risk for PTB in pregnant women while restoring bile acid homeostasis delays or prevents PTB in the mouse models.
Published: 2020

42. Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

Author: Kinyoki, Damaris K., Ross, Jennifer M., Lazzar-Atwood, Alice, Munro, Sandra B., Schaeffer, Lauren E., Abbasalizad-Farhangi, Mahdieh, Abbasi, Masoumeh, Abbastabar, Hedayat, Abdelalim, Ahmed, Abdoli, Amir, Abdollahi, Mohammad, Abdollahpour, Ibrahim, Abdulkader, Rizwan Suliankatchi, Abebe, Nebiyu Dereje, Abebo, Teshome Abuka, Abegaz, Kedir Hussein, Abolhassani, Hassan, Abreu, Lucas Guimarães, Abrigo, Michael R. M., Abushouk, Abdelrahman I., Accrombessi, Manfred Mario Kokou, Acharya, Dilaram, Adabi, Maryam, Adebiyi, Akindele Olupelumi, Adedeji, Isaac Akinkunmi, Adekanmbi, Victor, Adeoye, Abiodun Moshood, Adetokunboh, Olatunji O., Adham, Davoud, Aduroja, Posi Emmanuel, Advani, Shailesh M., Afarideh, Mohsen, Aghaali, Mohammad, Agrawal, Anurag, Ahmad, Tauseef, Ahmadi, Keivan, Ahmadi, Sepideh, Ahmed, Muktar Beshir, Ahmed, Rushdia, Ajumobi, Olufemi, Akal, Chalachew Genet, Akalu, Temesgen Yihunie, Akinyemiju, Tomi, Akombi, Blessing, Al-Aly, Ziyad, Alam, Samiah, Alamene, Genet Melak, Alanzi, Turki M., Rabanal, Jacqueline Elizabeth Alcalde, Alema, Niguse Meles, Ali, Beriwan Abdulqadir, Ali, Muhammad, Alijanzadeh, Mehran, Alinia, Cyrus, Alipour, Vahid, Alizade, Hesam, Aljunid, Syed Mohamed, Almasi, Afshin, Almasi-Hashiani, Amir, Al-Mekhlafi, Hesham M., Al-Raddadi, Rajaa M., Altirkawi, Khalid, Alvis-Guzman, Nelson, Alvis-Zakzuk, Nelson J., Amare, Azmeraw T., Amegah, Adeladza Kofi, Amini, Saeed, Rarani, Mostafa Amini, Amiri, Fatemeh, Amit, Arianna Maever Loreche, Anber, Nahla Hamed, Andrei, Catalina Liliana, Ansari, Fereshteh, Ansari-Moghaddam, Alireza, Anteneh, Zelalem Alamrew, Antonio, Carl Abelardo T., Antriyandarti, Ernoiz, Anvari, Davood, Anwer, Razique, Appiah, Seth Christopher Yaw, Arabloo, Jalal, Arab-Zozani, Morteza, Araya, Ephrem Mebrahtu, Arefi, Zohreh, Aremu, Olatunde, Ärnlöv, Johan, Arzani, Afsaneh, Asadi-Aliabadi, Mehran, Asadi-Pooya, Ali A., Asgari, Samaneh, Asghari, Babak, Ashagre, Alebachew Fasil, Asrat, Anemaw A., Ataeinia, Bahar, Atalay, Hagos Tasew, Atnafu, Desta Debalkie, Atout, Maha Moh’d Wahbi, Ausloos, Marcel, Avokpaho, Euripide F. G. A., Awasthi, Ashish, Quintanilla, Beatriz Paulina Ayala, Ayanore, Martin Amogre, Aynalem, Yared A. Asmare, Azadmehr, Abbas, Azari, Samad, Azarian, Ghasem, Azene, Zelalem Nigussie, Babaee, Ebrahim, Badawi, Alaa, Badiye, Ashish D., Bahrami, Mohamad Amin, Baig, Atif Amin A., Bakhtiari, Ahad, Bakkannavar, Shankar M., Balakrishnan, Senthilkumar, Bali, Ayele Geleto, Banach, Maciej, Banik, Palash Chandra, Baradaran-Seyed, Zahra, Baraki, Adhanom Gebreegziabher, Barboza, Miguel A., Bärnighausen, Till Winfried, Barua, Lingkan, Basaleem, Huda, Basu, Sanjay, Bayati, Mohsen, Bayih, Mulat Tirfie, Baynes, Habtamu Wondifraw, Bedi, Neeraj, Behzadifar, Masoud, Behzadifar, Meysam, Bekele, Yibeltal Alemu, Bennett, Derrick A., Berbada, Dessalegn Ajema, Berhe, Kidanemaryam, Berhe, Abadi Kidanemariam, Berman, Adam E., Bernstein, Robert S., Bhageerathy, Reshmi, Bhandari, Dinesh, Bharadwaj, Pankaj, Bhattacharjee, Natalia V., Bhattacharyya, Krittika, Bijani, Ali, Bikbov, Boris, Bilano, Ver, Bililign, Nigus, Sayeed, Muhammad Shahdaat Bin, Birara, Setognal, Birhane, Minuye Biniam Biniam, Birhanu, Minyichil, Biswas, Raaj Kishore, Bitew, Zebenay Workneh, Bogale, Kassawmar Angaw, Bohlouli, Somayeh, Bolla, Srinivasa Rao, Boloor, Archith, Borzì, Antonio M., Borzouei, Shiva, Brady, Oliver J., Bragazzi, Nicola Luigi, Braithwaite, Dejana, Briko, Nikolay Ivanovich, Britton, Gabrielle, Budhathoki, Shyam S., Nagaraja, Sharath Burugina, Busse, Reinhard, Butt, Zahid A., Cahuana-Hurtado, Lucero, Cámera, Luis Alberto, Campos-Nonato, Ismael R., Cano, Jorge, Car, Josip, Cárdenas, Rosario, Carrero, Juan J., Carvalho, Félix, Castaldelli-Maia, João Mauricio, Castañeda-Orjuela, Carlos A., Castro, Franz, Cerin, Ester, Chansa, Collins, Charan, Jaykaran, Chatterjee, Pranab, Chattu, Vijay Kumar, Chauhan, Bal Govind, Chavshin, Ali Reza, Chehrazi, Mohammad, Chichiabellu, Tesfaye Yitna, Chin, Ken Lee, Christopher, Devasahayam J., Chu, Dinh-Toi, Cicuttini, Flavia M., Collison, Michael L., Cork, Michael A., Cormier, Natalie, Cortesi, Paolo Angelo, Costa, Vera M., Dadi, Abel Fekadu Fekadu, Dagnew, Baye, Dahlawi, Saad M. A., Damiani, Giovanni, Darwish, Amira Hamed, Daryani, Ahmad, Das, Jai K., Gupta, Rajat Das, Dávila-Cervantes, Claudio, Davis Weaver, Nicole, Leo, Diego De, Neve, Jan-Walter De, Demeke, Feleke Mekonnen, Demis, Asmamaw Bizuneh, Demissie, Dereje Bayissa, Demoz, Gebre Teklemariam, Denova-Gutiérrez, Edgar, Deribe, Kebede, Desai, Rupak, Desalegn, Beruk Berhanu, Desalew, Assefa, Deshpande, Aniruddha, Dey, Sagnik, Dharmaratne, Samath Dhamminda, Dhillon, Preeti, Dhimal, Meghnath, Dhungana, Govinda Prasad, Nasab, Mostafa Dianati, Diaz, Daniel, Forooshani, Zahra Sadat Dibaji, Dinsa, Girmaye Deye, Dipeolu, Isaac Oluwafemi, Djalalinia, Shirin, Do, Hoa Thi, Do, Huyen Phuc, Doku, Paul Narh, Dorostkar, Fariba, Doshmangir, Leila, Dubey, Manisha, Adema, Bereket Duko, Dunachie, Susanna J., Duncan, Bruce B., Cousin, Ewerton, Durães, Andre R., Earl, Lucas, Leylabadlo, Hamed Ebrahimzadeh, Eftekhari, Aziz, El Sayed, Iman, El Sayed Zaki, Maysaa, El Tantawi, Maha, Elbarazi, Iffat, Elemineh, Demelash Abewa, El-Jaafary, Shaimaa I., El-Khatib, Ziad, Elsharkawy, Aisha, El-Sherbiny, Yasser Mohamed, Elyazar, Iqbal R. F., Emamian, Mohammad Hassan, Enany, Shymaa, Endalew, Daniel Adane, Endalifer, Melese Linger, Eskandari, Khalil, Eskandarieh, Sharareh, Esmaeilnejad, Saman, Esteghamati, Alireza, Etemadi, Arash, Etisso, Atkilt Esaiyas, Fanzo, Jessica, Farahmand, Mohammad, Faraj, Anwar, Farashi, Sajjad, Fareed, Mohammad, Farioli, Andrea, Faro, Andre, Farzadfar, Farshad, Farzam, Hossein, Fatima, Syeda Sadia, Fattahi, Nazir, Fauk, Nelsensius Klau, Fazaeli, Ali Akbar, Fentahun, Netsanet, Ferede, Tomas Y., Fereshtehnejad, Seyed-Mohammad, Fernandes, Eduarda, Fernandes, João C., Feyissa, Garumma Tolu, Filip, Irina, Fischer, Florian, Flohr, Carsten, Foigt, Nataliya A., Folayan, Morenike Oluwatoyin, Fomenkov, Artem Alekseevich, Foroutan, Masoud, Förster, Jana, Francis, Joel Msafiri, Fukumoto, Takeshi, Gayesa, Reta Tsegaye, Geberemariyam, Biniyam Sahiledengle, Gebrehiwot, Tsegaye Tewelde, Gebremariam, Hadush, Gebremariam, Kidane Tadesse, Gebremedhin, Ketema Bizuwork Bizuwork, Gebremeskel, Gebreamlak Gebremedhn, Gebreslassie, Assefa Ayalew Ayalew, Gebretsadik, Gebretsadkan G. G., Gedefaw, Getnet Azeze, Geramo, Yilma Chisha Dea, Gesesew, Hailay Abrha, Geta, Birhanu, Getenet, Agegnehu Bante, Gezae, Kebede Embaye, Ghaffarifar, Fatemeh, Ghafourifard, Mansour, Ghajar, Alireza, Ghajarzadeh, Mahsa, Ghashghaee, Ahmad, Ghiasvand, Hesam, Gholamian, Asadollah, Gilani, Syed Amir, Gill, Tiffany K., Ginawi, Ibrahim Abdelmageed, Goli, Srinivas, Gomes, Nelson G. M., Gopalani, Sameer Vali, Goudarzi, Houman, Goulart, Alessandra C., Govindakarnavar, Arunkumar, Grada, Ayman, Grivna, Michal, Guimarães, Rafael Alves, Guled, Rashid Abdi, Guo, Yuming, Gupta, Rahul, Gupta, Rajeev, Hafezi-Nejad, Nima, Haile, Michael Tamene, Haj-Mirzaian, Arvin, Haj-Mirzaian, Arya, Hall, Brian J., Halvaei, Iman, Hamadeh, Randah R., Hamidi, Yadollah, Handiso, Demelash Woldeyohannes, Hankey, Graeme J., Haririan, Hamidreza, Hariyani, Ninuk, Hasaballah, Ahmed I., Hasan, Md. Mehedi, Hasankhani, Milad, Hasanpoor, Edris, Hasanzadeh, Amir, Hashemian, Maryam, Hassanipour, Soheil, Hassen, Hamid Yimam, Havmoeller, Rasmus, Hawkes, Corinna, Hayat, Khezar, Hayelom, Desta Haftu, Heidari, Behnam, Heidari-Soureshjani, Reza, Hendrie, Delia, Henok, Andualem, Henry, Nathaniel J., Herrero, Mario, Herteliu, Claudiu, Heydarpour, Fatemeh, de Hidru, Hagos D., Hoang, Chi Linh, Hoek, Hans W., Hole, Michael K., Holla, Ramesh, Hollerich, Gillian, Rad, Enayatollah Homaie, Hong, Sung Hwi, Hoogar, Praveen, Horino, Masako, Hossain, Naznin, Hosseini, Mostafa, Hosseinzadeh, Mehdi, Hostiuc, Mihaela, Hostiuc, Sorin, Househ, Mowafa, Hsairi, Mohamed, Hu, Guoqing, Huda, Tanvir M., Humayun, Ayesha, Hwang, Bing-Fang, Ibitoye, Segun Emmanuel, Ilesanmi, Olayinka Stephen, Ilic, Milena D., Imani-Nasab, Mohammad Hasan, Inbaraj, Leeberk Raja, Iqbal, Usman, Irvani, Seyed Sina Naghibi, Islam, Sheikh Mohammed Shariful, Iwu, Chidozie C. D., Iwu, Chinwe Juliana, Izadi, Neda, Jaafari, Jalil, Jaca, Anelisa, Jadidi-Niaragh, Farhad, Balalami, Nader Jafari, Jafarinia, Morteza, Jahani, Mohammad Ali, Jakovljevic, Mihajlo, Jalali, Amir, Jalilian, Farzad, Jayatilleke, Achala Upendra, Jeemon, Panniyammakal, Jehan, Fyezah, Jenabi, Ensiyeh, Jha, Ravi Prakash, Jha, Vivekanand, Ji, John S., Jia, Peng, John, Oommen, John-Akinola, Yetunde O., Johnson, Kimberly B., Jonas, Jost B., Joseph, Nitin, Joukar, Farahnaz, Jozwiak, Jacek Jerzy, Jungari, Suresh Banayya, Jürisson, Mikk, Kabir, Ali, Kabir, Zubair, Kahsay, Amaha, Kahssay, Molla, Kalani, Hamed, Kalankesh, Leila L., Kalhor, Rohollah, Kamiab, Zahra, Kanchan, Tanuj, Kapil, Umesh, Kapoor, Neeti, Karami, Manoochehr, Matin, Behzad Karami, Karch, André, Karim, Mohd A., Karki, Surendra, Kasaeian, Amir, Kasahun, Gebremicheal Gebreslassie, Kasaye, Habtamu Kebebe, Kassa, Tesfaye Dessale, Kassaye, Hagazi Gebremedhin, Kassebaum, Nicholas J., Karyani, Ali Kazemi, Kengne, Andre Pascal, Ketema, Daniel Bekele, Khader, Yousef Saleh, Khafaie, Morteza Abdullatif, Khaksarian, Mojtaba, Khalid, Nauman, Khalil, Ibrahim A., Khalilov, Rovshan, Khan, Asad, Khan, Ejaz Ahmad, Khan, Md Nuruzzaman, Khan, Mohammad Saud, Khan, Muhammad Shahzeb, Khatab, Khaled, Khater, Amir, Khater, Mona M., Khatib, Mahalqua Nazli, Khayamzadeh, Maryam, Khazaei-Pool, Maryam, Khazaei, Mohammad, Khazaei, Salman, Khodayari, Mohammad Taghi, Khosravi, Mohammad Hossein, Khundkar, Roba, Kiadaliri, Ali, Kianipour, Neda, Kiirithio, Daniel N., Kim, Yun Jin, Kimokoti, Ruth W., Kisa, Adnan, Kisa, Sezer, Kolola, Tufa, Komaki, Hamidreza, Kondlahalli, Shivakumar K. M., Koolivand, Ali, Koul, Parvaiz A., Koyanagi, Ai, Kraemer, Moritz U. G., Krishan, Kewal, Krohn, Kris J., Kugbey, Nuworza, Kumar, Manasi, Kumar, Pushpendra, Kumar, Vivek, Kurmi, Om P., Kuti, Oluwatosin, Vecchia, Carlo La, Lacey, Ben, Lad, Deepesh P., Lal, Aparna, Lal, Dharmesh Kumar, Lami, Faris Hasan, Lamichhane, Prabhat, Lang, Justin J., Lansingh, Van C., Lasrado, Savita, Lebedev, Georgy, Lee, Paul H., Lee, Shaun Wen Huey, Leili, Mostafa, Letourneau, Ian D., Lewycka, Sonia, Li, Shanshan, Lim, Lee-Ling, Linn, Shai, Liu, Shiwei, Liu, Simin, Lodha, Rakesh, Longbottom, Joshua, Lopez, Jaifred Christian F., Lorkowski, Stefan, Macarayan, Erlyn Rachelle King, Madadin, Mohammed, El Razek, Hassan Magdy Abd, El Razek, Muhammed Magdy Abd, Maghavani, Dhaval P., Mahasha, Phetole Walter, Mahotra, Narayan Bahadur, Maled, Venkatesh, Maleki, Afshin, Maleki, Shokofeh, Malta, Deborah Carvalho, Manafi, Ali, Manafi, Farzad, Manafi, Navid, Manohar, Narendar Dawanu, Mansour-Ghanaei, Fariborz, Mansouri, Borhan, Mansournia, Mohammad Ali, Mapoma, Chabila Christopher, Marami, Dadi, Marczak, Laurie B., Arnedo, Carlos Alberto Marrugo, Martins-Melo, Francisco Rogerlândio, Masaka, Anthony, Massenburg, Benjamin Ballard, Maulik, Pallab K., Mayala, Benjamin K., Mazidi, Mohsen, Mehndiratta, Man Mohan, Mehri, Freshteh, Mehta, Kala M., Meitei, Wahengbam Bigyananda, Mekonnen, Fantahun Ayenew, Mekonnen, Teferi, Meles, Gebrekiros Gebremichael, Meles, Hagazi Gebre, Melese, Addisu, Mendoza, Walter, Menezes, Ritesh G., Mengesha, Meresa Berwo, Mensah, George A., Meretoja, Tuomo J., Miazgowski, Tomasz, Kostova, Neda Milevska, Miller, Ted R., Mills, Edward J., Mini, G. K., Mir, Seyed Mostafa, Miri, Mohammad, Mirjalali, Hamed, Mirrakhimov, Erkin M., Mirzaei, Hamed, Mirzaei, Maryam, Mirzaei, Roya, Mirzaei-Alavijeh, Mehdi, Mithra, Prasanna, Moazen, Babak, Mohamadi, Efat, Mohamadi-Bolbanabad, Amjad, Mohammad, Karzan Abdulmuhsin, Mohammad, Yousef, Mohammad, Dara K., Darwesh, Aso Mohammad, Mezerji, Naser Mohammad Gholi, Mohammadian-Hafshejani, Abdollah, Mohammadnia-Afrouzi, Mousa, Mohammadoo-Khorasani, Milad, Mohammadpourhodki, Reza, Mohammed, Salahuddin, Mohammed, Shafiu, Mohammed, Jemal Abdu, Mohammed, Ammas Siraj, Mohebi, Farnam, Mokari, Amin, Mokdad, Ali H., Montañez, Julio Cesar, Montero-Zamora, Pablo A., Moodley, Yoshan, Moossavi, Maryam, Moradi, Ghobad, Moradi, Masoud, Moradi, Yousef, Moradi-Joo, Mohammad, Moradi-Lakeh, Maziar, Moradpour, Farhad, Moradzadeh, Rahmatollah, Moraga, Paula, Morrison, Shane Douglas, Mosapour, Abbas, Mosser, Jonathan F., Mouodi, Simin, Khaneghah, Amin Mousavi, Mozaffarian, Dariush, Mueller, Ulrich Otto, Murray, Christopher J. L., Murthy, G. V. S., Musa, Kamarul Imran, Mustafa, Ghulam, Muthupandian, Saravanan, Nabavizadeh, Behnam, Naderi, Mehdi, Nadkarni, Girish N., Nagarajan, Ahamarshan Jayaraman, Naghavi, Mohsen, Naheed, Aliya, Naik, Gurudatta, Najafi, Farid, Nansseu, Jobert Richie, Narayan, K. M. Venkat, Nascimento, Bruno Ramos, Nayak, Vinod, Nazari, Javad, Ndwandwe, Duduzile Edith, Negoi, Ionut, Negoi, Ruxandra Irina, Ngunjiri, Josephine W., Nguyen, Cuong Tat, Nguyen, Huong Lan Thi, Nigatu, Dabere, Nigatu, Yeshambel T., Nikbakhsh, Rajan, Ningrum, Dina Nur Anggraini, Nnaji, Chukwudi A., Nong, Vuong Minh, Noubiap, Jean Jacques, Nowak, Christoph, Oancea, Bogdan, Ofori-Asenso, Richard, Oghenetega, Onome Bright, Oh, In-Hwan, Oladimeji, Olanrewaju, Oladnabi, Morteza, Olagunju, Andrew T., Olagunju, Tinuke O., Olusanya, Bolajoko Olubukunola, Olusanya, Jacob Olusegun, Oluwasanu, Mojisola Morenike, Omer, Muktar Omer, Onwujekwe, Obinna E., Asante, Kwaku Oppong, Oren, Eyal, Orisakwe, Orish Ebere, Ortiz, Alberto, Osarenotor, Osayomwanbo, Osgood-Zimmerman, Aaron E., Owolabi, Mayowa Ojo, P. A., Mahesh, Padubidri, Jagadish Rao, Pakshir, Keyvan, Pana, Adrian, Panda-Jonas, Songhomitra, Parsian, Hadi, Pashaei, Tahereh, Pasupula, Deepak Kumar, Patel, Sangram Kishor, Pathak, Ashish, Pathak, Mona, Pati, Sanghamitra, Patle, Ajay, Patton, George C., Paulos, Kebreab, Toroudi, Hamidreza Pazoki, Pepito, Veincent Christian Filipino, Perico, Norberto, Petri, William A., Pickering, Brandon V., Pigott, David M., Pirestani, Majid, Piroozi, Bakhtiar, Pirsaheb, Meghdad, Pokhrel, Khem Narayan, Postma, Maarten J., Pourjafar, Hadi, Pourmalek, Farshad, Kalhori, Reza Pourmirza, Pourshams, Akram, Poustchi, Hossein, Prada, Sergio I., Preotescu, Liliana, Pribadi, Dimas Ria Angga, Syed, Zahiruddin Quazi, Rabiee, Mohammad, Rabiee, Navid, Radfar, Amir, Rafiei, Alireza, Rahim, Fakher, Rahimi-Movaghar, Vafa, Rahman, Muhammad Aziz, Rahman, Sajjad ur, Rai, Rajesh Kumar, Rajabpour-Sanati, Ali, Rajati, Fatemeh, Ramezanzadeh, Kiana, Rana, Saleem Muhammad, Ranabhat, Chhabi Lal, Rao, Sowmya J., Rasella, Davide, Rashedi, Vahid, Rastogi, Prateek, Rathi, Priya, Rawaf, Salman, Rawaf, David Laith, Rawal, Lal, Ray, Sarah E., Remuzzi, Giuseppe, Renjith, Vishnu, Renzaho, Andre M. N., Resnikoff, Serge, Rezaei, Nima, Rezaeian, Shahab, Rezai, Mohammad Sadegh, Rezapour, Aziz, Riahi, Seyed Mohammad, Ribeiro, Ana Isabel, Rickard, Jennifer, Rodriguez, Alina, Roever, Leonardo, Roro, Elias Merdassa, Roshandel, Gholamreza, Rostami, Ali, Rubagotti, Enrico, Saad, Anas M., Saadatagah, Seyedmohammad, Sabde, Yogesh Damodar, Sabour, Siamak, Sadeghi, Ehsan, Sadeghi, Masoumeh, Safari, Saeed, Safari, Yahya, Safarpour, Hamid, Sagar, Rajesh, Sahebkar, Amirhossein, Sahraian, Mohammad Ali, Sajadi, S. Mohammad, Salahshoor, Mohammad Reza, Salam, Nasir, Salehi, Farkhonde, Zahabi, Saleh Salehi, Salem, Hosni, Salem, Marwa R. 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Departamento de Medicina, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-IP), Veritati - Repositório Institucional da Universidade Católica Portuguesa, Biosciences, University of Helsinki, Clinicum, HUS Comprehensive Cancer Center, Institute for Molecular Medicine Finland, Department of Earth Observation Science, UT-I-ITC-ACQUAL, Faculty of Geo-Information Science and Earth Observation, Sálfræðideild (HR), Department of Psychology (RU), Samfélagssvið (HR), School of Social Sciences (RU), Háskólinn í Reykjavík, Reykjavik University, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (ISS-FJD), Kinyoki, D, Ross, J, Lazzar-Atwood, A, Munro, S, Schaeffer, L, Abbasalizad-Farhangi, M, Abbasi, M, Abbastabar, H, Abdelalim, A, Abdoli, A, Abdollahi, M, Abdollahpour, I, Abdulkader, R, Abebe, N, Abebo, T, Abegaz, K, Abolhassani, H, Abreu, L, Abrigo, M, Abushouk, A, Accrombessi, M, 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Fareed, M, Farioli, A, Faro, A, Farzadfar, F, Farzam, H, Fatima, S, Fattahi, N, Fauk, N, Fazaeli, A, Fentahun, N, Ferede, T, Fereshtehnejad, S, Fernandes, E, Fernandes, J, Feyissa, G, Filip, I, Fischer, F, Flohr, C, Foigt, N, Folayan, M, Fomenkov, A, Foroutan, M, Forster, J, Francis, J, Fukumoto, T, Gayesa, R, Geberemariyam, B, Gebrehiwot, T, Gebremariam, H, Gebremariam, K, Gebremedhin, K, Gebremeskel, G, Gebreslassie, A, Gebretsadik, G, Gedefaw, G, Geramo, Y, Gesesew, H, Geta, B, Getenet, A, Gezae, K, Ghaffarifar, F, Ghafourifard, M, Ghajar, A, Ghajarzadeh, M, Ghashghaee, A, Ghiasvand, H, Gholamian, A, Gilani, S, Gill, T, Ginawi, I, Goli, S, Gomes, N, Gopalani, S, Goudarzi, H, Goulart, A, Govindakarnavar, A, Grada, A, Grivna, M, Guimaraes, R, Guled, R, Guo, Y, Hafezi-Nejad, N, Haile, M, Haj-Mirzaian, A, Hall, B, Halvaei, I, Hamadeh, R, Hamidi, Y, Handiso, D, Hankey, G, Haririan, H, Hariyani, N, Hasaballah, A, Hasan, M, Hasankhani, M, Hasanpoor, E, Hasanzadeh, A, Hashemian, M, Hassanipour, S, Hassen, H, Havmoeller, R, Hawkes, C, Hayat, K, Hayelom, D, Heidari, B, Heidari-Soureshjani, R, Hendrie, D, Henok, A, Henry, N, Herrero, M, Herteliu, C, Heydarpour, F, de Hidru, H, Hoang, C, Hoek, H, Hole, M, Holla, R, Hollerich, G, Rad, E, Hong, S, Hoogar, P, Horino, M, Hossain, N, Hosseini, M, Hosseinzadeh, M, Hostiuc, M, Hostiuc, S, Housseh, M, Hsairi, M, Hu, G, Huda, T, Humayun, A, Hwang, B, Ibitoye, S, Ilesanmi, O, Ilic, M, Imani-Nasab, M, Inbaraj, L, Iqbal, U, Irvani, S, Islam, S, Iwu, C, Izadi, N, Jaafari, J, Jaca, A, Jadidi-Niaragh, F, Balalami, N, Jafarinia, M, Jahani, M, Jakovljevic, M, Jalali, A, Jalilian, F, Jayatilleke, A, Jeemon, P, Jehan, F, Jenabi, E, Jha, R, Jha, V, Ji, J, Jia, P, John, O, John-Akinola, Y, Johnson, K, Jonas, J, Joseph, N, Joukar, F, Jozwiak, J, Jungari, S, Jurisson, M, Kabir, A, Kabir, Z, Kahsay, A, Kahssay, M, Kalani, H, Kalankesh, L, Kalhor, R, Kamiab, Z, Kanchan, T, Kapil, U, Kapoor, N, Karami, M, Matin, B, Karch, A, Karim, M, Karki, S, Kasaeian, A, Kasahun, G, Kasaye, H, Kassa, T, Kassaye, H, Kassebaum, N, Karyani, A, Kengne, A, Ketema, D, Khader, Y, Khafaie, M, Khaksarian, M, Khalid, N, Khalil, I, Khalilov, R, Khan, A, Khan, E, Khan, M, Khatab, K, Khater, A, Khater, M, Khatib, M, Khayamzadeh, M, Khazaei-Pool, M, Khazaei, M, Khazaei, S, Khodayari, M, Khosravi, M, Khundkar, R, Kiadaliri, A, Kianipour, N, Kiirithio, D, Kim, Y, Kimokoti, R, Kisa, A, Kisa, S, Kolola, T, Komaki, H, Kondlahalli, S, Koolivand, A, Koul, P, Koyanagi, A, Kraemer, M, Krishan, K, Krohn, K, Kugbey, N, Kumar, M, Kumar, P, Kumar, V, Kurmi, O, Kuti, O, Vecchia, C, Lacey, B, Lad, D, Lal, A, Lal, D, Lami, F, Lamichhane, P, Lang, J, Lansingh, V, Lasrado, S, Lebedev, G, Lee, P, Lee, S, Leili, M, Letourneau, I, Lewycka, S, Li, S, Lim, L, Linn, S, Liu, S, Lodha, R, Longbottom, J, Lopez, J, Lorkowski, S, Macarayan, E, Madadin, M, El Razek, H, El Razek, M, Maghavani, D, Mahasha, P, Mahotra, N, Maled, V, Maleki, A, Maleki, S, Malta, D, Manafi, A, Manafi, F, Manafi, N, Manohar, N, Mansour-Ghanaei, F, Mansouri, B, Mansournia, M, Mapoma, C, Marami, D, Marczak, L, Arnedo, C, Martins-Melo, F, Masaka, A, Massenburg, B, Maulik, P, Mayala, B, Mazidi, M, Mehndiratta, M, Mehri, F, Mehta, K, Meitei, W, Mekonnen, F, Mekonnen, T, Meles, G, Meles, H, Melese, A, Mendoza, W, Menezes, R, Mengesha, M, Mensah, G, Meretoja, T, Miazgowski, T, Kostova, N, Miller, T, Mills, E, Mini, G, Mir, S, Miri, M, Mirjalali, H, Mirrakhimov, E, Mirzaei, H, Mirzaei, M, Mirzaei, R, Mirzaei-Alavijeh, M, Mithra, P, Moazen, B, Mohamadi, E, Mohamadi-Bolbanabad, A, Mohammad, K, Mohammad, Y, Mohammad, D, Darwesh, A, Mezerji, N, Mohammadian-Hafshejani, A, Mohammadnia-Afrouzi, M, Mohammadoo-Khorasani, M, Mohammadpourhodki, R, Mohammed, S, Mohammed, J, Mohammed, A, Mohebi, F, Mokari, A, Mokdad, A, Montanez, J, Montero-Zamora, P, Moodley, Y, Moossavi, M, Moradi, G, Moradi, M, Moradi, Y, Moradi-Joo, M, Moradi-Lakeh, M, Moradpour, F, Moradzadeh, R, Moraga, P, Morrison, S, Mosapour, A, Mosser, J, Mouodi, S, Khaneghah, A, Mozaffarian, D, Mueller, U, Murray, C, Murthy, G, Musa, K, Mustafa, G, Muthupandian, S, Nabavizadeh, B, Naderi, M, Nadkarni, G, Nagarajan, A, Naghavi, M, Naheed, A, Naik, G, Najafi, F, Nansseu, J, Narayan, K, Nascimento, B, Nayak, V, Nazari, J, Ndwandwe, D, Negoi, I, Negoi, R, Ngunjiri, J, Nguyen, C, Nguyen, H, Nigatu, D, Nigatu, Y, Nikbakhsh, R, Ningrum, D, Nnaji, C, Nong, V, Noubiap, J, Nowak, C, Oancea, B, Ofori-Asenso, R, Oghenetega, O, Oh, I, Oladimeji, O, Oladnabi, M, Olagunju, A, Olagunju, T, Olusanya, B, Olusanya, J, Oluwasanu, M, Omer, M, Onwujekwe, O, Asante, K, Oren, E, Orisakwe, O, Ortiz, A, Osarenotor, O, Osgood-Zimmerman, A, Owolabi, M, P. A, M, Padubidri, J, Pakshir, K, Pana, A, Panda-Jonas, S, Parsian, H, Pashaei, T, Pasupula, D, Patel, S, Pathak, A, Pathak, M, Pati, S, Patle, A, Patton, G, Paulos, K, Toroudi, H, Pepito, V, Perico, N, Petri, W, Pickering, B, Pigott, D, Pirestani, M, Piroozi, B, Pirsaheb, M, Pokhrel, K, Postma, M, Pourjafar, H, Pourmalek, F, Kalhori, R, Pourshams, A, Poustchi, H, Prada, S, Preotescu, L, Pribadi, D, Syed, Z, Rabiee, M, Rabiee, N, Radfar, A, Rafiei, A, Rahim, F, Rahimi-Movaghar, V, Rahman, M, Rahman, S, Rai, R, Rajabpour-Sanati, A, Rajati, F, Ramezanzadeh, K, Rana, S, Ranabhat, C, Rao, S, Rasella, D, Rashedi, V, Rastogi, P, Rathi, P, Rawaf, S, Rawaf, D, Rawal, L, Ray, S, Remuzzi, G, Renjith, V, Renzaho, A, Resnikoff, S, Rezaei, N, Rezaeian, S, Rezai, M, Rezapour, A, Riahi, S, Ribeiro, A, Rickard, J, Rodriguez, A, Roever, L, Roro, E, Roshandel, G, Rostami, A, Rubagotti, E, Saad, A, Saadatagah, S, Sabde, Y, Sabour, S, Sadeghi, E, Sadeghi, M, Safari, S, Safari, Y, Safarpour, H, Sagar, R, Sahebkar, A, Sahraian, M, Sajadi, S, Salahshoor, M, Salam, N, Salehi, F, Zahabi, S, Salem, H, Salem, M, Salimi, Y, Salimzadeh, H, Kafil, H, Sambala, E, Samy, A, Santos, I, Jose, B, Saraswathy, S, Sarker, A, Sartorius, B, Sarveazad, A, Sathian, B, Satpathy, M, Saxena, S, Sayyah, M, Sbarra, A, Schipp, M, Schmidt, M, Schutte, A, Schwebel, D, Senbeta, A, Senthilkumaran, S, Seyedmousavi, S, Shaahmadi, F, Shafaat, O, Shahabi, S, Shaikh, M, Shalash, A, Shams-Beyranvand, M, Shamshirian, A, Shamsizadeh, M, Shannawaz, M, Sharafi, K, Sharif, M, Sharma, R, Shehata, H, Sheikhtaheri, A, Shibuya, K, Shiferaw, W, Shigematsu, M, Shin, J, Shiri, R, Shirkoohi, R, Shiue, I, Shuval, K, Siabani, S, Siddiqi, T, Sigfusdottir, I, Silva, D, Simonetti, B, Singh, A, Singh, P, Singh, V, Singh, J, Sinha, D, Sintayehu, Y, Sisay, M, Soheili, A, Soleymani, B, Soltani, F, Soltani, S, Soriano, J, Sorrie, M, Soshnikov, S, Soyiri, I, Spotin, A, Sreeramareddy, C, Srivastava, R, Starodubova, A, Sudaryanto, A, Sufiyan, M, Suleria, H, Sulo, G, Sunguya, B, Sykes, B, Tabares-Seisdedos, R, Tabuchi, T, Tadesse, B, Taherkhani, A, Tamirat, K, Tassew, S, Taveira, N, Teklehaimanot, B, Tekulu, G, Temsah, M, Terkawi, A, Tessema, Z, Thomas, N, Titova, M, Tlaye, K, Tohidinik, H, Tonelli, M, Tovani-Palone, M, Traini, E, Tran, K, Tripathi, M, Uddin, R, Ullah, I, Unnikrishnan, B, Upadhyay, E, Useh, U, Usman, M, Uthman, O, Vacante, M, Vaezghasemi, M, Valdez, P, Vanderheide, J, Varavikova, E, Varughese, S, Vasankari, T, Vasseghian, Y, Veisani, Y, Venkatesh, S, Venketasubramanian, N, Verma, M, Vidale, S, Violante, F, Vlassov, V, Vollmer, S, Vukovic, R, Waheed, Y, Wang, H, Wang, Y, Weldesamuel, G, Werdecker, A, Wiangkham, T, Wiens, K, Wijeratne, T, Wolde, H, Wondafrash, D, Wonde, T, Wondmieneh, A, Wu, A, Xu, G, Yadegar, A, Yadollahpour, A, Jabbari, S, Yamada, T, Yano, Y, Yaya, S, Yazdi-Feyzabadi, V, Yeshaneh, A, Yeshaw, Y, Yeshitila, Y, Yilma, M, Yip, P, Yonemoto, N, Yoon, S, Youm, Y, Younis, M, Yousefi, Z, Yousof, H, Yu, C, Yusefzadeh, H, Moghadam, T, Zaki, L, Zaman, S, Zamani, M, Zamanian, M, Zandian, H, Zarafshan, H, Zepro, N, Zerfu, T, Zewale, T, Zhang, Y, Zhang, Z, Zhao, X, Zodpey, S, Zomorodian, K, Zotor, F, Afshin, A, Hay, S, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Value, Affordability and Sustainability (VALUE), and Microbes in Health and Disease (MHD)
Subjects: Male, Local patterns, Double burden, Börn, Research & Experimental Medicine, Sjúkdómseinkenni, DOUBLE BURDEN, Childhood overweight, Lífefnafræði, Læknisfræði, 0302 clinical medicine, Syndemic, Child, 11 Medical and Health Sciences, under 5 years of age, General Medicine, 3. Good health, Geography, Medicine, Research & Experimental, Child, Preschool, Income, GROWTH, AFRICA, medicine.medical_specialty, Biochemistry & Molecular Biology, RJ, Medicina, Immunology, education, MODELS, wa_395, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Humans, Author Correction, Developing Countries, Poverty, Biology, LBD Double Burden of Malnutrition Collaborators, Demography, Science & Technology, Wasting Syndrome, Public health, MORTALITY, Infant, Næringarskortur, medicine.disease, Obesity, TRENDS, signs and symptoms, Social Class, Risk factors, Sameindalíffræði, ITC-ISI-JOURNAL-ARTICLE, UNDERNUTRITION, Human medicine, Clinical Medicine, 030217 neurology & neurosurgery, Pediatric Obesity, obesity, Offita, Áhættuþættir, Geographic Mapping, Overweight, RA0421, Global health, risk factors, 030212 general & internal medicine, Signs and symptoms, Wasting, Malnutrition, Global Burden of Diseases, Global Nutrition, low- and middle-income countries, 2. Zero hunger, 1. No poverty, Public Health, Global Health, Social Medicine and Epidemiology, A900 Others in Medicine and Dentistry, Childhood wasting, PREVALENCE, Chemistry, Mapping, Female, Lýðheilsa, medicine.symptom, Life Sciences & Biomedicine, GROWTH FAILURE, Nutritional Status, malnutrition, ITC-HYBRID, ws_115, children, Environmental health, medicine, Erfðafræði, wd_200, Malnutrition, Infant, Newborn, Klinisk medicin, Cell Biology, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, 3121 General medicine, internal medicine and other clinical medicine, NA
Abstract: Artículo con numerosos autores, sólo se mencionan el primero, los de la UAM y grupo colectivo, A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of, This work was primarily supported by grant OPP1132415 from the Bill & Melinda Gates Foundation awarded to S.I.H.
Published: 2020

43. Epidemiological characteristics of pulmonary tuberculosis in Anhui Province, Eastern China from 2013 to 2018

Author: Xun-Di Bao, Fang-Jin Bao, Ze-Kun Zhang, Qing-Qing Zhu, Jun-Wei Yan, Song Yao, Xue-Hui Fang, Ling Li, Rong Wang, Ai-Min Wang, Qian Wu, Yong-Zhong Zhang, Hai-Feng Pan, and Jie Liu
Subjects: Male, Bacterial Diseases, 0301 basic medicine, Epidemiology, Social Sciences, Geographical Locations, Medical Conditions, 0302 clinical medicine, Medicine and Health Sciences, Medicine, 030212 general & internal medicine, Young adult, Child, Multidisciplinary, Geography, Incidence, Incidence (epidemiology), Respiratory disease, Age Factors, Middle Aged, Actinobacteria, Infectious Diseases, Research Design, Child, Preschool, Female, Research Article, Adult, China, medicine.medical_specialty, Asia, Tuberculosis, Adolescent, Science, 030106 microbiology, Human Geography, Research and Analysis Methods, Infectious Disease Epidemiology, Urban Geography, Young Adult, 03 medical and health sciences, Sex Factors, Pulmonary tuberculosis, Humans, Cities, Tuberculosis, Pulmonary, Aged, Retrospective Studies, Bacteria, business.industry, Organisms, Infant, Biology and Life Sciences, Retrospective cohort study, Tropical Diseases, medicine.disease, People and Places, Earth Sciences, business, Mycobacterium Tuberculosis, Demography
Abstract: ObjectivePulmonary tuberculosis (TB) is a severe infectious respiratory disease, the burden of which remains high in China. To provide scientific evidence for developing more targeted prevention and control strategies, this study aimed to determine the incidence trends and explore the epidemiological characteristics of pulmonary TB in Anhui Province, Eastern China between 2013 and 2018.MethodsThe retrospective study analyzed information regarding pulmonary TB cases reported by the National Infectious Disease Reporting System and census data collected from the Anhui Provincial Bureau of Statistics.ResultsOverall, 211,892 cases of TB patients were reported in Anhui Province, China between 2013 and 2018, with an average annual reported incidence rate of 57.7 per 100,000 persons. A significant decrease in the incidence rate of pulmonary TB (p < 0.001) was observed during the study period. Men had a higher incidence rate of pulmonary TB than women (p < 0.001). The highest annual average reported incidence rate was 204.2 per 100,000 persons in those aged 70-74 years. The number of farmers with pulmonary TB, i.e., 155,415, accounted for 73.4% of all cases. Moreover, the peak period of reported cases was from January to March. Four cities along the Yangtze River-Anqing, Tongling, Chizhou, and Wuhu-reported significantly higher incidence rates of pulmonary TB than other cities (p < 0.001).ConclusionsFrom 2013 to 2018, there was a significant decline in the incidence rate of pulmonary TB in Anhui Province, with peaks occurring from January to March. Prevention and control strategies targeting men, people aged 70-74 years, farmers, and the four cities along the Yangtze River should be strengthened.
Published: 2020

44. Minimally invasive surgery for degenerative spondylolisthesis: transforaminal or oblique lumbar interbody fusion

Author: Ai-Min Wu, Wen-Fei Ni, Sunren Sheng, Xiang-Yang Wang, Yi-Bo Geng, and Kailiang Zhou
Subjects: Male, medicine.medical_specialty, endocrine system diseases, Radiography, Less invasive, 03 medical and health sciences, 0302 clinical medicine, Patient satisfaction, Blood loss, Lumbar interbody fusion, otorhinolaryngologic diseases, Medicine, Humans, Minimally Invasive Surgical Procedures, Aged, Retrospective Studies, 030222 orthopedics, Lumbar Vertebrae, business.industry, Health Policy, Length of Stay, Middle Aged, Degenerative spondylolisthesis, Surgery, Clinical trial, Spinal Fusion, Treatment Outcome, Patient Satisfaction, Invasive surgery, Female, Spondylolisthesis, business, Spinal Canal, 030217 neurology & neurosurgery
Abstract: Aim: To compare the outcomes of minimally invasive surgery (MIS) for degenerative spondylolisthesis transforaminal lumbar interbody fusion (TLIF) and oblique lumbar interbody fusion (OLIF). Materials & methods: The clinical and surgical characteristics and outcomes of 38 patients with MIS–OLIF and 55 with MIS–TLIF were retrospectively evaluated. Results: Procedures and hospital stay were shorter and blood loss was less, with MIS–OLIF than with MIS–OLIF. The clinical and radiographic outcomes were similar. Postoperative changes in disk height and foraminal dimension were greater and patient satisfaction was better with MIS–OLIF than with MIS–TLIF. Conclusion: The clinical findings associated with the two procedures were similar; but patients preferred MIS–OLIF, which is less invasive, to MIS–TLIF. Clinical trial registration number: ChiCTR1800019443.
Published: 2019

45. High Oleic Acid Peanut Oil and Extra Virgin Olive Oil Supplementation Attenuate Metabolic Syndrome in Rats by Modulating the Gut Microbiota

Author: Jin-Rong Zhou, Zhi-hao Zhao, Qiang Wang, and Ai-min Shi
Subjects: 0301 basic medicine, high-fructose-high-fat diet, Male, food.ingredient, 030209 endocrinology & metabolism, Gut flora, Diet, High-Fat, digestive system, Article, extra virgin olive oil, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, Random Allocation, 0302 clinical medicine, food, medicine, Animals, Food science, Olive Oil, Metabolic Syndrome, Nutrition and Dietetics, biology, Triglyceride, gut microbiota, Cholesterol, Lachnospiraceae, Fructose, high oleic acid peanut oil, medicine.disease, biology.organism_classification, Gastrointestinal Microbiome, Rats, Oleic acid, Disease Models, Animal, 030104 developmental biology, chemistry, Dietary Supplements, Peanut oil, Metabolic syndrome, Peanut Oil, Food Science, Oleic Acid
Abstract: Unhealthy dietary patterns are important risk factors for metabolic syndrome (MS), which is associated with gut microbiota disorder. High oleic acid peanut oil (HOPO) and extra virgin olive oil (EVOO), considered as healthy dietary oil, are rich in oleic acid and bioactive phytochemicals, yet efficacy of MS prevention and mechanisms linking to gut microbiota remain obscure. Herein, we investigated HOPO and EVOO supplementation in attenuating diet-induced MS, and the potential mechanisms focusing on modulation of gut microbiota. Physiological, histological and biochemical parameters and gut microbiota profiles were compared among four groups fed respectively with the following diets for 12 weeks: normal chow diet with ordinary drinking water, high-fat diet with fructose drinking water, HOPO diet with fructose drinking water, and EVOO diet with fructose drinking water. HOPO or EVOO supplementation exhibit significant lower body weight gain, homeostasis model assessment-insulin resistance (HOMA-IR), and reduced liver steatosis. HOPO significantly reduced cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) level, while EVOO reduced these levels without significant difference. HOPO and EVOO prevented gut disorder and significantly increased &beta, diversity and abundance of Bifidobacterium. Moreover, HOPO significantly decreased abundance of Lachnospiraceae and Blautia. These findings suggest that both HOPO and EVOO can attenuate diet-induced MS, associated with modulating gut microbiota.
Published: 2019

46. The Protective Effect of Ligustilide in Osteoarthritis: An in Vitro and in Vivo Study

Author: Jiang-Wei Xuan, Ai-Min Wu, Xiaoxia Ding, Wen-Fei Ni, Zhenhua Feng, Xiaobin Li, Zhi-Chao Hu, Gang Zheng, and Dengying Wu
Subjects: Male, 0301 basic medicine, Cell Survival, Physiology, Interleukin-1beta, Nitric Oxide Synthase Type II, Osteoarthritis, Pharmacology, Chondrocyte, lcsh:Physiology, Extracellular matrix, PIK3/NF-κB, lcsh:Biochemistry, Mice, 03 medical and health sciences, 0302 clinical medicine, Chondrocytes, 4-Butyrolactone, NF-KappaB Inhibitor alpha, In vivo, Ligustilide, medicine, Animals, Humans, lcsh:QD415-436, Protein kinase B, Cells, Cultured, PI3K/AKT/mTOR pathway, Aggrecan, Aged, Inflammation, lcsh:QP1-981, Chemistry, Middle Aged, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, IκBα, 030104 developmental biology, medicine.anatomical_structure, Cyclooxygenase 2, IL-1β, 030220 oncology & carcinogenesis, Cytokines, Matrix Metalloproteinase 3, ADAMTS5 Protein
Abstract: Background/Aims: Osteoarthritis is a degenerative joint disease characterized by cartilage degeneration and a chondrocyte inflammatory response that induces an inflammatory environment closely linked to extracellular matrix (ECM) degradation. Ligustilide (LIG) is a major component of the herb Radix Angelicae Sinensis, with demonstrated anti-inflammatory effects. To confirm whether LIG has an equally inhibitory effect on inflammation in human osteoarthritis chondrocytes, we performed in vivo and in vitro experiments to validate the above conjectures and determine the relevant mechanisms. Methods: Quantitative realtime PCR and western blotting were performed to evaluate the expression of MMP-3, MMP-13, ADAMTS-5, iNOS, and COX-2 at both gene and protein levels. An enzyme-linked immunosorbent assay was used to evaluate the levels of other inflammatory factors (PGE2, TNF-α, and IL-6). The PI3K/AKT and nuclear factor kappa B (NF-κB) signaling pathways were also analyzed by western blotting, whereas immunofluorescence was used to assess the expression of collagen II and aggrecan. The in vitro effect of LIG was evaluated by intraperitoneal injection into a mouse osteoarthritis model induced by destabilization of the medial meniscus. Results: LIG lowered the phosphorylation levels of p65, IκBα, and IKKα/β and suppressed the IL-1β-induced expression of MMP-3, ADAMTS-5, iNOS, and COX-2 and the inflammatory factors PGE2, TNF-α, and IL-6. LIG markedly decreased IL-1β-induced degradation of collagen II and aggrecan. In vivo results showed that LIG-treated mouse cartilage showed less damage than the control group; the Osteoarthritis Research Society International (OARSI) score was also lower. LIG further reduced the thickness of the subchondral bone plate and alleviated the synovitis. Conclusion: LIG may act as a promising therapeutic agent for osteoarthritis by attenuating IL-1β-induced inflammation in chondrocytes and ECM degradation via suppression of NF-κB activation by the PI3K/AKT pathway.
Published: 2018

47. Isatuximab plus pomalidomide/dexamethasone versus pomalidomide/dexamethasone in relapsed/refractory multiple myeloma: ICARIA Phase III study design

Author: Michel Attal, Paul G. Richardson, Kathryn P. Corzo, Kenneth C. Anderson, Ai-Min Hui, Frank Campana, Solenn Le-Guennec, and Marie-Laure Risse
Subjects: Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Combination therapy, Antibodies, Monoclonal, Humanized, Dexamethasone, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Clinical endpoint, Humans, Progression-free survival, Multiple myeloma, Aged, Isatuximab, business.industry, Antibodies, Monoclonal, General Medicine, Middle Aged, medicine.disease, Pomalidomide, Thalidomide, 030104 developmental biology, Tolerability, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Female, Neoplasm Recurrence, Local, Multiple Myeloma, business, medicine.drug
Abstract: Treatment for relapsed/refractory multiple myeloma (RRMM) remains an unmet need. Isatuximab, an anti-CD38 monoclonal antibody has shown efficacy and tolerability as a monotherapy and combination therapy in Phase I/II studies in RRMM. Here, we describe the design of the Phase III ICARIA-MM study (NCT02990338) which will evaluate isatuximab in combination with pomalidomide (Pom) and low-dose dexamethasone (dex) (Pom/dex) versus Pom/dex alone in RRMM. Patients will be randomized in a 1:1 ratio. The primary endpoint is progression-free survival. Response will be determined by an independent response review committee using IMWG criteria (2016) and safety will be assessed throughout. Approximately 300 patients (150 in each arm) are expected to enroll. The first patient was recruited in January 2017 and accrual is ongoing.
Published: 2018

48. Biomechanical Role of the Thoracolumbar Ligaments of the Posterior Ligamentous Complex: A Finite Element Study

Author: Ai-Min Wu, Haiming Jin, Ying-Zhao Yan, Ke Wang, Zengjie Zhang, Xiang-Yang Wang, Cong-Cong Wu, Jian Chen, and Jianle Wang
Subjects: Adult, Male, musculoskeletal diseases, Interspinous ligament, Facet (geometry), Finite Element Analysis, Bending, Thoracic Vertebrae, Finite element study, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Range of Motion, Articular, Lumbar Vertebrae, Articular capsule of the knee joint, business.industry, Thoracolumbar spine, Anatomy, musculoskeletal system, Biomechanical Phenomena, body regions, medicine.anatomical_structure, Ligaments, Articular, Ligament, Surgery, Neurology (clinical), Range of motion, business, 030217 neurology & neurosurgery
Abstract: Objectives To investigate the effect of sequential ligament failure on the range of motion (ROM) and location of the instantaneous axes of rotation (IAR) of the thoracolumbar spine (T12–L1) finite element (FE) model, and to verify the role of the supraspinous ligament (SSL) in maintaining the stability of the injured thoracolumbar spine. Methods An FE model of the fractured thoracolumbar spine was developed and validated against published data. The posterior ligamentous complex (PLC) in the fractured T12–L1 segment was then reduced in a sequential manner from the facet capsular ligament (FCL), part of the interspinous ligament (ISL), SSL, and entire ISL, to the ligamentum flavum (LF). The ROM and IAR of the T12–L1 segment were measured at the fracture and at each reduced ligament step under 4 directions of flexion, extension, lateral bending, and rotation, and 4 bending motions of 1.5, 3.0, 4.5, 6.0 Nm. Results The FE model showed a consistent increase in the ROM and location of the IAR as the ligaments were removed sequentially. Furthermore, failure of the SSL had the most significant influence on the change in the ROM and IAR in flexion. In extension, removal of the FCL caused the largest shift. Conclusions The SSL is a significant ligament that allows the PLC to maintain the stability of the thoracolumbar spine during injury.
Published: 2018

49. A Novel Technique for Cervical Facet Joint Hyperplasia-Spondylotic Radiculopathy by Laminar and Lateral Mass Screw Cofixations

Author: Sun-Ren Sheng, Ke Wang, Majid Nisar, Xiang-Yang Wang, Ai-Min Wu, and Jiaoxiang Chen
Subjects: Male, musculoskeletal diseases, medicine.medical_specialty, Visual analogue scale, Decompression, Bone Screws, Zygapophyseal Joint, Facet joint, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Minimally Invasive Surgical Procedures, 030212 general & internal medicine, Radiculopathy, Aged, Retrospective Studies, Pain, Postoperative, Neck pain, Hyperplasia, Neck Pain, medicine.diagnostic_test, business.industry, Retrospective cohort study, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Surgery, Treatment Outcome, medicine.anatomical_structure, Radicular pain, Cervical Vertebrae, Female, Spondylosis, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: We sought to describe the novel technique and report the outcomes of cervical spondylotic radiculopathy caused by facet joint hyperplasia treated with minimally invasive surgery by laminar and lateral mass screw cofixations.In this retrospective study, patients with spondylotic radiculopathy caused by facet joint hyperplasia underwent this technique in our unit between January 2010 and June 2015. Hospital charts, magnetic resonance imaging studies, and follow-up records for all the patients were reviewed. Outcomes were assessed on the basis of neurologic status, magnetic resonance imaging, and visual analog scale for neck and radicular pain and by the short form-36 health survey questionnaire.Thirteen men and 5 women, aged 47-73 years (mean, 61.8 years), were included in this study. The follow-up time ranged from 19-50 months (mean, 32.4 months). The mean visual analog scale scores for radicular pain and neck pain, as well as the scores for all 8 domains of the short form-36 health survey questionnaire, showed significant improvements (P0.05). Cervical lordosis showed bending, whereas the height of the targeted disk segment showed no change (P0.05). Complications included 2 cases of neck pain that lasted for 3 months.Minimally invasive surgery by lamina and lateral mass screw cofixation is safe and effective for the treatment of cervical spondylotic radiculopathy caused by facet joint hyperplasia. In addition to sufficient decompression, this technique provides relative stability to the cervical spine.
Published: 2018

50. Percutaneous anterior C1/2 transarticular screw fixation: salvage of failed percutaneous odontoid screw fixation for odontoid fracture

Author: Ai-Min Wu, Haiming Jin, Xiang-Yang Wang, Yong-Long Chi, and Lin Zhongke
Subjects: Male, Percutaneous, lcsh:Diseases of the musculoskeletal system, Radiography, Bone Screws, Fracture Fixation, Internal, 0302 clinical medicine, lcsh:Orthopedic surgery, Technical Note, Orthopedics and Sports Medicine, Spinal cord injury, Odontoid fracture, Pain Measurement, Transarticular screw, 030222 orthopedics, Neck pain, Articular facet, Neck Pain, Middle Aged, musculoskeletal system, Treatment Outcome, Cervical Vertebrae, Spinal Fractures, Female, medicine.symptom, Adult, musculoskeletal diseases, Atlantoaxial, medicine.medical_specialty, Screw fixation, 03 medical and health sciences, Odontoid Process, medicine, Humans, Minimally Invasive Surgical Procedures, Minimally invasive, Aged, Salvage Therapy, business.industry, medicine.disease, equipment and supplies, Surgery, lcsh:RD701-811, Orthopedic surgery, lcsh:RC925-935, business, Tomography, X-Ray Computed, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Background The objective of this study is to investigate the outcomes and safety of using percutaneous anterior C1/2 transarticular screw fixation as a salvage technique for odontoid fracture if percutaneous odontoid screw fixation fails. Methods Fifteen in 108 odontoid fracture patients (planned to be treated by percutaneous anterior odontoid screw fixation) were failed to introduce satisfactory odontoid screw trajectory. To salvage this problem, we chose the percutaneous anterior C1/2 transarticular screw fixation technique in treatment of these patients. The visual analogue score (VAS) of neck pain and Neck Disability Index (NDI) of all patients were scored at pre-operation, 3 months after operation, and final follow-up. Additional, technique-related complications were recorded and collected. Results Percutaneous C1/2 transarticular screw fixation was performed successfully in all 15 patients whose odontoid screw fixation failed. No technique-related complications (such as nerve injury, spinal cord injury, and esophageal injury) occurred. The VAS of neck pain and NDI score improved significantly (P = 0.000) after operation, and no significant differences were found when compared to 93 non-salvage patients who successfully performed the percutaneous anterior odontoid screw fixation. No screw loose or breakage occurred, all of the odontoid fractures achieve radiographic fusion, bony fusion bridge could be observed at the C1/2 lateral articular facet on 9/15 patients. Conclusions We suggest that percutaneous anterior C1/2 transarticular screw fixation is a good alternative salvage technique if percutaneous odontoid screw fixation failed, and it is a minimally invasive, feasible, and safe technique.
Published: 2017

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