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Background: Sleep disorders are common in Parkinson's disease (PD). However, the longitudinal relationship between sleep quality and the other non-motor symptoms of PD has not been well characterized, especially in early PD., Objective: To explore the value of baseline sleep quality in predicting the progression of other non-motor symptoms in early PD., Methods: 109 early PD patients were recruited to the study. Patients were stratified into good and poor sleepers using the Pittsburgh Sleep Quality Index (PSQI). Assessments performed at baseline and 1 year follow-up included the Epworth Sleepiness Scale, Fatigue Severity Scale, Non-Motor Symptom Scale, Geriatric Depression Scale, Hospital Anxiety and Depression Scale, Apathy Scale, Montreal Cognitive Assessment and detailed neuropsychological assessments. Multivariable linear regression was performed at baseline to investigate differences in clinical scores between poor and good sleepers, while multivariable regression models were used to investigate associations between sleep quality and progression of test scores at 1 year follow-up., Results: 59 poor sleepers and 50 good sleepers were identified. At baseline, poor sleepers had greater HADS anxiety scores ( p = 0.013) [2.99 (95% CI 2.26, 3.73)] than good sleepers [1.59 (95% CI 0.75, 2.42)]. After 1 year, poor sleepers had greater fatigue (FSS scores +3.60 as compared to -2.93 in good sleepers, p = 0.007) and depression (GDS scores +0.42 as compared to -0.70, p = 0.006)., Conclusion: This study shows a longitudinal association between sleep quality, fatigue, and depression in early PD patients, independent of medication effect and disease severity, this may support the hypothesis that a common serotonergic pathway is implicated in these non-motor symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Koh, Chua, Ng, Chia, Saffari, Chen, Choi, Heng, Neo, Tay, Au, Tan, Tan and Xu.)

Background: Phase 1 immuno-oncology (IO) trials frequently involve pharmacodynamic (PD) biomarker assessments involving tumour biopsies and/or blood collection, with increasing use of molecular imaging. PD biomarkers are set to play a fundamental role in early drug development of immuno-oncology (IO) agents. In the IO era, the impact of PD biomarkers for confirmation of biologic activity and their role in subsequent drug development have not been investigated., Methods: Phase 1 studies published between January 2014 and December 2020 were reviewed. Studies that reported on-treatment PD biomarkers [tissue-derived (tissue-PD), blood-based (blood-PD) and imaging-based (imaging-PD)] were analysed. PD biomarker results and their correlation with clinical activity endpoints were evaluated. Authors' statements on the influence of PD biomarkers on further drug development decisions, and subsequent citations of PD biomarker study results were recorded., Results: Among 386 trials, the most frequent IO agent classes evaluated were vaccines (32%) and PD-(L)1 inhibitors (25%). No PD biomarker assessments were reported in 100 trials (26%). Of the remaining 286, blood-PD, tissue-PD, and imaging-PD data were reported in 270 (94%), 94 (33%), and 12 (4%) trials, respectively. Assessments of more than one PD biomarker type were reported in 82 studies (29%). Similar proportions of blood-PD (9%), tissue-PD (7%), and imaging-PD studies (8%) had positive results that correlated with clinical activity. Results of 22 PD biomarker studies (8%) were referenced in subsequent clinical trials., Conclusions: Most phase 1 IO studies performed PD biomarker assessments. Overall, positive PD biomarker results were infrequently correlated with clinical activity or cited in subsequent trials, suggesting a limited impact on subsequent drug development. With emerging health regulatory emphasis on optimal dose selection based on PD activity, more informative and integrative multiplexed assays that capture the complexity of tumour-host immunity interactions are warranted to improve phase 1 IO trial methodology., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A. Hernando Calvo: Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merk Serono; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Kyowa Kirin Internati-onal. D.V. Araujo: Financial Interests, Personal, Other, honoraria: MSD; Financial Interests, Personal, Other, honoraria: Pfizer; Financial Interests, Institutional, Educational Grant: Astellas; Financial Interests, Institutional, Non-financial support: Novartis. M. Oliva: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel/Accommodation expenses: MSD Oncology; Merck. Financial Interests, Personal and Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: Merck; Personal and Institutional, Research Grant: Roche. L.L. Siu: Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: MedImmune; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Astellas Pharma; Financial Interests, Institutional, Research Grant: Shattuck Labs; Financial Interests, Institutional, Research Grant: Symphogen; Financial Interests, Institutional, Research Grant: AVID Radiopharmaceuticals; Financial Interests, Institutional, Research Grant: Mirati Therapeutics; Financial Interests, Institutional, Research Grant: Intensity Therapeutics; Financial Interests, Institutional, Research Grant: Karyopharm Therapeutics; Financial Interests, Personal, Stocks/Shares, An Immediate Family Member: Agios; Financial Interests, Personal, Leadership Role, An Immediate Family Member: Treadwell Therapeutics; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: AstraZeneca/MedImmune; Financial Interests, Personal, Advisory Role: MorphoSys; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Loxo; Financial Interests, Personal, Advisory Role: Voronoi; Financial Interests, Personal, Advisory Role: Oncorus; Financial Interests, Personal, Advisory Role: Symphogen; Financial Interests, Personal, Advisory Role: Mirati Therapeutics; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Treadwell Therapeutics; Financial Interests, Personal, Advisory Role: Arvinas; Financial Interests, Personal, Advisory Role: Navire; Financial Interests, Personal, Advisory Role: Janpix; Financial Interests, Personal, Advisory Role: Relay Therapeutics; Financial Interests, Personal, Advisory Role: Daiichi Sankyo/UCB Japan; Financial Interests, Personal, Advisory Role: Marengo Therapeutics; Financial Interests, Personal, Advisory Role: LTZ Therapeutics. All other authors have declared no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the risk factors of infectious diseases in adult kidney transplantation recipients and to establish a simple and novel nomogram to guide the prophylactic antimicrobial therapy., Methods: Patients who received kidney transplantation between January 2018 and October 2021 were included in the study and were divided into a training and a testing set at a 1:1 ratio. Risk factors correlated to infectious diseases were selected using a Least Absolute Shrinkage and Selection Operator (LASSO) regression model. The prediction model was built by incorporating the variables selected by the LASSO model into a logistic regression equation. Calibration curves and receiver operating characteristic (ROC) curves were also applied to assess the model calibration and discrimination. A nomogram consisting of the selected factors was established to provide individualized risks of developing infections. Decision curve analysis (DCA) was adopted to estimate the net benefit and reduction in interventions for a range of clinically reasonable risk thresholds., Results: In all, 863 adult kidney recipients were included in the study, and 407 (47.16%) of them developed infectious diseases during the 3-year follow-up period. A total of 8 variables were selected using LASSO regression and were retained for subsequent model construction and infection prediction. The area under the curve (AUC) was 0.83 and 0.81 in the training and testing sets, with high F scores of 0.76 and 0.77, sensitivity of 0.76 and 0.81, and specificity of 0.88 and 0.74, respectively. A novel nomogram was developed based on 8 selected predictors (requirement for albumin infusion, requirement for red blood cell infusion, triglyceride, uric acid, creatinine, globulin, neutrophil percentage, and white blood cells). The net benefit indicated that the nomogram would reduce unnecessary interventions at a wide range of threshold probabilities in both sets., Conclusions: Adult kidney transplantation recipients are high-risk hosts for infectious diseases. The novel nomogram consisting of 8 factors reveals good predictive performance and may promote the reasonable antimicrobial prescription. More external validations are required to confirm its effectiveness for further clinical application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Zhang, Zhuang, Li, Zhang, Zhu, Yu and Yuan.)

Objective: Much of our knowledge of patient autonomy of DNR (do-not-resuscitate) is derived from the cross-sectional questionnaire surveys. Using signatures on statutory documents and medical records, we analyzed longitudinal data to understand the fact of terminal cancer patients' autonomous DNR decision-making in Taiwan., Methods: Using the medical information system database of one public medical center in Taiwan, we identified hospitalized cancer patients who died between Jan. 2017 and Dec. 2018, collected their demographic and clinical course data and records of their statutory DNR document types, letter of intent (DNR-LOI) signed by the patient personally and the consent form signed by their close relatives., Results: We identified 1,338 signed DNR documents, 754 (56.35%) being DNR-LOI. Many patients had the first DNR order within their last week of life (40.81%). Signing the DNR-LOI was positively associated with being under the care of a family medicine physician prior to death at last hospitalization and having hospice palliative care and negatively associated with patient age ≥ 65 years, no formal education, having ≥ 3 children, having the first DNR order to death ≤ 29 days, and the last admission in an intensive care unit., Conclusions: A substantial proportion of terminal cancer patients did not sign DNR documents by themselves. It indicates they may not know their actual terminal conditions and lose the last chance to grasp time to express their life values and wishes. Medical staff involving cancer patient care may need further education on the legal and ethical issues revolving around patient autonomy and training on communicating end-of-life options with the patients. We suggest proactively discussing DNR decision issues with terminal cancer patients no later than when their estimated survival is close to 1 month., (© 2022. The Author(s).)

The article "The carcinogenic complex lncRNA FOXP4-AS1/EZH2/LSD1 accelerates proliferation, migration and invasion of gastric cancer, by R.-Y. Chen, Q. Ju, L.-M. Feng, Q. Yuan, L. Zhang, published in Eur Rev Med Pharmacol Sci 2019; 23 (19): 8371-8376-DOI: 10.26355/eurrev_201910_19148-PMID: 31646567" has been retracted by the authors. After publication, the authors raised concerns about the reliability of the data used to conduct the study by stating that some data cannot be repeated by further research. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19148.

Background: Postoperative delirium is common in patients who undergo neurosurgery for craniocerebral injury. However, there is no specific medical test to predict postoperative delirium to date., Aim: To explore risk factors for postoperative delirium in patients with craniocerebral injury in the neurosurgery intensive care unit (ICU)., Methods: A retrospective analysis was performed in 120 patients with craniocerebral injury admitted to Hainan People's Hospital/Hainan Hospital Affiliated to Hainan Medical University, The First Affiliated Hospital of Hainan Medical University, and The Second Affiliated Hospital of Hainan Medical University between January 2018 and January 2020. The patients were categorized into groups based on whether delirium occurred. Of them, 25 patients with delirium were included in the delirium group, and 95 patients without delirium were included in the observation group. Logistic regression analysis was used to explore the association between sex, age, educational level, Glasgow coma scale (GCS), complications (with or without concussion, cerebral contusion, hypoxemia and ventricular compression) and site of injury and delirium., Results: The GCS score above 8 and concomitant disease of cerebral concussion, cerebral contusion, hypoxemia and ventricular compression, and damage to the frontal lobe were associated with delirium in patients admitted to neurosurgical intensive care unit (ICU) (all P < 0.05). However, age, sex, administration more than three medicines, and educational level were not significantly associated with the onset of delirium in patients with craniocerebral injury in the neurosurgical ICU ( P < 0.05). Multivariate logistic regression analysis showed that GCS score above 8, cerebral concussion, cerebral contusion, hypoxemia, ventricle compression, and frontal lobe disorders were independent risk factors for delirium in patients with craniocerebral injury in the neurosurgical ICU ( P < 0.05)., Conclusion: GCS score, concussive concussion, cerebral contusion, hypoxemia, ventricle compression, and damage to frontal lobe are risk factors of postoperative delirium., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Collective migration is important to embryonic development and cancer metastasis, but migratory and nonmigratory cell fate discrimination by differential activity of signal pathways remains elusive. In Drosophila oogenesis, Jak/Stat signaling patterns the epithelial cell fates in early egg chambers but later renders motility to clustered border cells. How Jak/Stat signal spatiotemporally switches static epithelia to motile cells is largely unknown. We report that a nuclear protein, Dysfusion, resides on the inner nuclear membrane and interacts with importin α/β and Nup153 to modulate Jak/Stat signal by attenuating Stat nuclear import. Dysfusion is ubiquitously expressed in oogenesis but specifically down-regulated in border cells when migrating. Increase of nuclear Stat by Dysfusion down-regulation triggers invasive cell behavior and maintains persistent motility. Mammalian homolog of Dysfusion (NPAS4) also negatively regulates the nuclear accumulation of STAT3 and cancer cell migration. Thus, our finding demonstrates that Dysfusion-dependent gating mechanism is conserved and may serve as a therapeutic target for Stat-mediated cancer metastasis.

Objective: Patients with breast cancer who have indeterminate extra-mammary lesions, for example in lung, liver or bone, without other metastatic lesions pose a clinical dilemma regarding subsequent management. This study aimed to investigate the prevalence, characteristics and outcomes of such lesions detected on initial staging imaging, and address the clinical significance of these incidental findings., Materials and Methods: Medical records of patients with newly diagnosed breast cancer who underwent computed tomography scans and bone scintigraphy between January 1, 2015 and June 30, 2021 were reviewed. Patients with indeterminate extra-mammary lesions on imaging were included. Patients with obvious metastatic disease were excluded. Lesion characteristics, breast cancer staging, duration of follow-up and natural history of disease progression were analysed., Results: The study included 52 patients with indeterminate lesions on pre-operative imaging. The median follow-up duration was 14 (range: 6-41) months. The most common site of occurrence of indeterminate lesions was the lung (60.9%) followed by the liver (26.1%). Forty-six had lesions that remained stable (88.5%), while six (11.5%) had progression to metastatic disease. Out of these six, only two (3.8%) developed metastasis in the same site as the original indeterminate lesion, whereas the remaining four developed metastases in other sites., Conclusion: Patients with breast malignancy found to have indeterminate extra-mammary lesions without obvious distant metastasis on initial staging scans are associated with a small risk of subsequently developing metastatic disease. Although most of these lesions remain quiescent, surveillance imaging is recommended because a small but significant proportion of patients with such lesions eventually harbour actual metastatic disease., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2022 by the the Turkish Federation of Breast Diseases Societies / European Journal of Breast Health published by Galenos Publishing House.)

The quality markers(Q-markers) of Shujin Huoxue Capsules were comprehensively discriminated based on the five principles of transfer and traceability, specificity, compatibility, effectiveness and measurability. The compounds that could be transferred from the original medicinal materials to the preparation were selected with the principle of transfer and traceability. The specific components in the prescription were screened by reviewing literature with the principle of specificity. According to the principle of compatibility, the attributes of compounds were evaluated by the sovereign, minister, assistant and guide combination rules of the original medicinal materials in the prescription. According to the principle of measurability, the measurable components were summarized by reference to the pharmacopoeia and literature combined with the content. The mechanism of Shujin Huoxue Capsules in the treatment of osteoporosis was studied through network pharmacology based on the principle of effectiveness, which was the evaluation index of effectiveness. The chemical components screened out above were regarded as candidate Q-markers, and the cobweb model was plotted to obtain the comprehensive score of Q-markers. Hydroxysafflor yellow A, trachelosid, eleutheroside B, α-cyperone, protocatechuic acid, protocatechualdehyde and 4-methoxy salicylaldehyde were discriminated as the Q-markers of Shujin Huoxue Capsules based on the five principles combined with cobweb model.

Two new sesquiterpene dimers, lappadimers A and B, were isolated from the roots of Saussurea lappa (Yunmuxiang). Their structures were established on the basis of spectroscopic methods. They were found to have potential anti-inflammatory activity at 10  µ M and could reduce LPS-induced NO levels in murine macrophage, with inhibitory rates of 67% and 47%, respectively.

Background: Breast cancer mainly occurs in young and premenopausal women; its incidence is increasing annually. Patients with triple-negative breast cancer (TNBC) have relatively high recurrence and transfer rates during the operation and 3 years after postoperative adjuvant chemotherapy. Currently, the treatment for patients with TNBC is mainly based on a comprehensive combination of surgery and chemotherapy. Therefore, identifying additional effective treatments to improve patient prognosis is important., Aim: To explore and discuss the effects and prognostic factors of neoadjuvant chemotherapy in TNBC., Methods: In total, 118 patients diagnosed with TNBC from January 2016 to January 2020 in our hospital were selected and divided into the observation ( n = 60) and control ( n = 58) groups according to therapeutic regimen. The control group received routine chemotherapy, and the observation group received neoadjuvant chemotherapy. The therapeutic effects of the two groups were observed, and the survival of patients was followed up., Results: The karyopherin A2 (KPNA2)-positive and SRY-related HMG box-2 (SOX2)-positive expression rates of patients with TNBC with intravascular tumor thrombus and tumor-node-metastasis (TNM) stage IV were 92.00% and 91.67% and 96.00% and 95.83%, respectively, which were significantly higher than those of patients with no intravascular tumor thrombus and TNM stage III ( P < 0.05). KPNA2 was positively associated with SOX2 expression ( r s = 0.514, P < 0.50). The short-term curative effect of the observation group was better than that of the control group ( P < 0.05), and the total effective rate was 58.33%. After treatment, carcinoembryonic antigen, cancer antigen (CA) 19-9, and CA125 Levels in the observation group were 11.40 ± 2.32 mg/L, 19.92 ± 3.42 kU/L, and 54.30 ± 12.28 kU/L, respectively, which were significantly lower than those in the control group ( P < 0.05). The median survival time of the observation group was 33 mo (95%CI: 31.21-34.79), which was significantly longer than that of the control group ( P < 0.05). TNM stage, degree of differentiation, lymph node metastasis, KPNA2 and SOX2 expressions, and treatment plan were prognostic factors of TNBC (relative risk = 1.575, 1.380, 1.366, 1.433, 1.411, and 0.581, respectively, P < 0.05)., Conclusion: Neoadjuvant chemotherapy for TNBC treatment can achieve good curative effects. TNM stage, differentiation degree, lymph node metastasis, KPNA2 and SOX2 expressions, and treatment plan are prognostic factors of TNBC., Competing Interests: Conflict-of-interest statement: No conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To investigate the utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in assessing disease activity in Takayasu arteritis (TA)., Methods: Ninety-one patients with TA were recruited from a Chinese cohort. Clinical data, acute-phase reactants and 18F-FDG-PET/CT findings were simultaneously recorded. The value of using 18F-FDG-PET/CT to identify active disease was evaluated, using ESR as a reference. Disease activity assessment models were constructed and concordance index (C-index), net reclassification index (NRI), and integrated discrimination index (IDI) were evaluated to compare the benefits of the new modes with ESR and the Kerr score., Results: In total, 64 (70.3%) cases showed active disease. Higher levels of ESR and CRP, and lower IL-2 receptor (IL-2R) levels were observed in active cases. 18F-FDG-PET/CT parameters measured by determining the standard uptake value (SUV), including SUVmean, SUVratio1, SUVratio2, sum of SUVmean and sum of SUVmax, were significantly higher in active disease groups. The C-index threshold of ESR to indicate active disease was 0.78 (95% CI: 0.69, 0.88). The new activity assessment model combining ESR, sum of SUVmean and IL-2R showed significant improvement in C-index over the ESR method (0.96 vs 0.78, P < 0.01; NRI 1.63, P < 0.01; and IDI 0.48, P < 0.01). The new model also demonstrated modest superiority to the Kerr score assessment (0.96 vs 0.87, P = 0.03; NRI 1.19, P < 0.01; and IDI 0.33, P < 0.01)., Conclusions: A novel 18F-FDG-PET/CT-based method that involves combining the sum of SUVmean with ESR score and IL-2R levels demonstrated superiority in identifying active TA compared with conventional methods., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: A large number of residents in US advanced specialty education programmes are foreign-trained dentists. When faced with the career dilemma of applying for US residency training, foreign-trained dentists may wonder whether it is worth proceeding along that path. In addiditon, studies capturing benefits from receiving US residency training are rare. Therefore, this study compared the life satisfaction amongst 3 dentist groups in Taiwan (ie, US-trained specialists, Taiwan-trained specialists, and general dentists)., Methods: Cross-sectional surveys were distributed to dentists currently residing in Taiwan. Participants were surveyed about demographic information, career-related information, and life satisfaction. Life satisfaction was measured with a structured Satisfaction With Life Scale (SWLS). Nonparametric bivariate analyses and multivariable adjusted generalised linear model (GLM) were used to examine the differences between mean SWLS scores and examined variables. We included 134 US-trained specialists, 134 Taiwan-trained specialists, and 134 general dentists matched for age, sex, and marital status., Results: With the mean age of 51.4 ± 10.8 years old, specialists had significantly higher mean life satisfaction scores than general dentists. US-trained specialists had significantly higher mean life satisfaction scores than Taiwan-trained specialists when health and family relationships were not considered. Career-rated factors (eg, spending more clinical hours with patients, having more expenses related to continuing education, publishing more peer-reviewed articles, and being a frequent speaker) were not associated with better life satisfaction., Conclusions: US-trained specialists were more likely to be satisfied with their lives than Taiwan-trained specialists and general dentists. However, health and social relationships contribute more to dentists' life satisfaction than do career-rated factors., Competing Interests: Conflict of interest None disclosed., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: The aim of this study was to develop and validate a new diabetes distress scale suitable for Chinese and Taiwanese culture., Methods: This study collected the current diabetes distress measurement tools, re-organized current definitions about the domains of diabetes distress, and then developed a new tool. Three hundred and ninety-five participants from four hospitals in northern Taiwan were recruited by cluster randomized sampling for validity test., Results: We found the new diabetes distress scale had appropriate reliability and validity, including an acceptable model fit for the 12-item scale., Conclusions: This new diabetes distress scale might be more directly related to emotional distress issues blood glucose control, improve the clinical conspicuity of diabetes distress, and even benefit the overall care of diabetic patients in Taiwan. Further studies about the validity and reliability of this new tool in a nationwide setting are needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Chang, Liu, Huang, Tsao, Chen and Chen.)

Randomly arranged irregular inclined conical structure-covered dragonfly wings, distinguished from periodic conical structure-covered cicada wings, are with high optical transparency for wide viewing angles. Bioinspired by the antireflective structures, we develop a colloidal lithography approach for engineering randomly arranged irregular conical structures with shape memory polymer-based tips. The structures establish a gradual refractive index transition to suppresses optical reflection in the visible spectrum. By manipulating the configuration of structure tips through applying common solvent stimulations or contact pressures under ambient conditions, the resulting unidirectional antireflection and omnidirectional antireflection performances are able to be instantaneously and reversibly switched. The dependences of structure shape, structure inclination, structure arrangement, and structure composition on the switchable antireflection capability are also systematically investigated in this study., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Echinococcosis is a neglected zoonotic disease and a worldwide public health problem caused by infection with the larval stages of taeniid cestodes of the genus Echinococcus . In vitro studies have demonstrated a protoscolecidal effect of eosinophilic cationic protein (ECP), a granule protein of eosinophilic granulocytes, against E. granulosus . Therefore, the main objective of this study was to evaluate ECP as a biomarker in the treatment of alveolar echinococcosis (AE) and cystic echinococcosis (CE). Data were collected retrospectively from the Vienna Echinococcosis Cohort over 7 years until December 2020. Altogether, 32 patients (16 AE and 16 CE) were included. In the selected patients, serum ECP values were compared before and after the beginning of an operative and/or benzimidazole (BMZ) therapy. Mean ECP serum levels before intervention were significantly ( p < 0.05) elevated at 34.0 ± 22.9 μg/L in AE patients and at 38.6 ± 19.9 μg/L in CE patients compared to the control group. After the intervention, mean ECP levels decreased significantly ( p < 0.05) to 20.4 ± 14.6 μg/L in AE patients and to 22.4 ± 8.3 μg/L in CE patients. Furthermore, ECP showed a significant ( p < 0.05) correlation of k = 0.56 with PET-CTI. Based on the significant decrease after operative and/or BMZ treatment and the correlation with clinical markers such as PET-CTI, it is recommended to investigate ECP more intensively as a marker of AE and CE in prospective studies with larger cohorts.

Background: Despite the lack of official COVID-19 statistics, various workplaces and occupations have been at the center of COVID-19 outbreaks. We aimed to compare legal measures and governance established for managing COVID-19 infection risks at workplaces in nine Asia and Pacific countries and to recommend key administrative measures., Methods: We collected information on legal measures and governance from both general citizens and workers regarding infection risks such as COVID-19 from industrial hygiene professionals in nine countries (Indonesia, India, Japan, Malaysia, New Zealand, Republic of the Philippines, Republic of Korea, Taiwan, and Thailand) using a structured questionnaire., Results: A governmental body overseeing public health and welfare was in charge of containing the spread and occurrence of infectious diseases under an infectious disease control and prevention act or another special act, although the name of the pertinent organizations and legislation vary among countries. Unlike in the case of other traditional hazards, there have been no specific articles or clauses describing the means of mitigating virus risk in the workplace that are legally required of employers, making it difficult to define the responsibilities of the employer. Each country maintains own legal systems regarding access to the duration, administration, and financing of paid sick leave. Many workers may not have access to paid sick leave even if it is legally guaranteed., Conclusion: Specific legal measures to manage infectious disease risks, such as providing proper personal protective equipment, education, engineering control measures, and paid sick leave are recommended to be stipulated in Industrial safety and health-related acts., Competing Interests: All authors have no conflicts of interest to declare., (© 2021 The Authors.)

Introduction: The aim of this study was to explore associations of workplace health culture and workplace health promotion (WHP) performance with employees' healthy lifestyles and health statuses. Methods: In total, 27 enterprises and 1,732 participants were recruited for a cross-sectional designed survey. At the group level, Workplace Health Scorecard was used to measure WHP performance, and it was filled out by the WHP representative at each workplace. At the personal level, a personal questionnaire was used to measure workplace health culture, healthy lifestyles, and health statuses. A hierarchical linear model analysis was used to assess correlations between these variables. Results: Workplace health culture was significantly related to WHP performance, healthy lifestyles, and health statuses. In particular, the peer support domain was greatly related to healthy behaviors like physical activity ( β = 0.596, p < 0.001), vegetable consumption ( β = 0.291, p < 0.001) and fruit consumption ( β = 0.285, p < 0.05), and it may illustrate the importance of establishing peer support to promote healthy behaviors. Conclusions: WHP performance was significantly related to workplace health culture especially health policies, health climate, and peer and supervisor support. Hence, building a good workplace health culture should be taken seriously, and more studies exploring associations of health culture and WHP performance with employees' health are needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chang, Tsai, Yeh and Chen.)

Extracellular traps (ETs) released from vertebrate and invertebrate immune cells consist of chromatin and toxic granule contents that are capable of immobilizing and killing microbes. This recently described innate immune response is not well documented in insects. The present study found that ETs were released by hemocytes of Galleria mellonella (Linnaeus) (Lepidoptera: Pyralidae) in vivo and ex vivo after bacterial stimulation. ET release (ETosis), hemolymph coagulation, and melanization likely contributed to the immobilization and killing of the bacteria. The injection of G. mellonella hemocyte deoxyribonucleic acid (DNA) in the presence of bacteria increased bacterial clearance rate and prolonged insect survival. Taken together, these results indicate the presence of insect hemocyte extracellular traps (IHETs) that protect the insect against microbial infection in the hemocoel and represent the first documentation of ETs in insects in vivo., (© The Author(s) 2021. Published by Oxford University Press on behalf of Entomological Society of America.)

Background: The study aimed to look into the effectiveness of a 6-month health coaching intervention for HbA1c and healthy diet in the treatment of patients with type 2 diabetes., Methods: The study was carried out via a two-armed, randomized controlled trial that included 114 diabetic patients at a medical center in Taiwan. During the 6-month period, the intervention group had health coaching and usual care for 6 months, and the control group had usual care only. The outcome variables were HbA1c level and healthy diet for follow-up measurement in the third and sixth month., Results: The study discovered a significant decrease in HbA1c and health diet improvement after the 6-month health coaching. Patients in the intervention group decreased their daily intake of whole grains, fruits, meats and protein, and fats and oils while increasing their vegetables intake., Conclusions: Health coaching may be conducive to the blood sugar control and healthy diet of patients with type 2 diabetes. Further study on health coaching with higher-quality evidence is needed.

Introduction: Cerebral palsy (CP) is the leading cause of childhood-onset physical disability. Children with CP often have impaired upper limb (UL) function. Constraint-induced therapy (CIT) is one of the most effective UL interventions for children with unilateral CP. However, concerns about CIT for children have been repeatedly raised due to frustration caused by restraint of the child's less-affected UL and lack of motivation for the intensive protocol. Virtual reality (VR), which can mitigate the disadvantages of CIT, potentially can be used as an alternative mediator for implementing CIT. Therefore, we developed a VR-based CIT program for children with CP using the Kinect system. Aims: The feasibility of the Kinect-based CIT program was evaluated for children with unilateral CP using a two-phase study design. Materials and Methods: In phase 1, ten children with unilateral CP were recruited. To confirm the achievement of the motor training goals, maximal UL joint angles were evaluated during gameplay. To evaluate children's perceptions of the game, a questionnaire was used. In phase 2, eight children with unilateral CP were recruited and received an 8 weeks Kinect-based CIT intervention. Performance scores of the game and outcomes of the box and block test (BBT) were recorded weekly. Results: In phase 1, results supported that the design of the program was CIT-specific and was motivational for children with unilateral CP. In phase 2, game performance and the BBT scores began showing stable improvements in the fifth week of intervention. Conclusion: It suggested the Kinect-based CIT program was beneficial to the motor function of the affected UL for children with unilateral CP. According to the results of this feasibility study, larger and controlled effectiveness studies of the Kinect-based CIT program can be conducted to further improve its clinical utility. Clinical Trial Registration: ClinicalTrials.gov, NCT02808195; Comparative effectiveness of a Kinect-based unilateral arm training system vs. CIT for children with CP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Lin, Yeh, Chen, Tang, Ruan and Wang.)

Chronic and persistent inflammation is a well-known carcinogenesis promoter. Hepatocellular carcinoma (HCC) is one of the most common inflammation-associated cancers; most HCCs arise in the setting of chronic inflammation and hepatic injury. Both NF-κB and STAT3 are important regulators of inflammation. Centrosomal P4.1-associated protein (CPAP), a centrosomal protein that participates primarily in centrosome functions, is overexpressed in HCC and can increase TNF-α-mediated NF-κB activation and IL-6-induced STAT3 activation. A transgenic (Tg) mouse model with hepatocyte-specific CPAP expression was established to investigate the physiological role of CPAP in hepatocarcinogenesis. Obvious inflammatory cell accumulation and fatty change were observed in the livers of CPAP Tg mice. The alanine aminotransferase (ALT) level and the expression levels of inflammatory genes, such as IL-6, IL-1β and TNF-α, were higher in CPAP Tg mice than in wild type (WT) mice. High-dose/short-term treatment with diethylnitrosamine (DEN) increased the ALT level, proinflammatory gene expression levels, and STAT3 and NF-κB activation in CPAP Tg mice; low-dose/long-term DEN treatment induced more severe liver tumor formation in CPAP Tg mice than in WT mice. CPAP can increase the expression of chemokine (C-C motif) ligand 16 (CCL-16), an important chemotactic cytokine, in human hepatocytes. CCL-16 expression is positively correlated with CPAP and TNF-α mRNA expression in the peritumoral part of HCC. In summary, these results suggest that CPAP may promote hepatocarcinogenesis through enhancing the inflammation pathway via increasing the expression of CCL-16., (© 2021. The Author(s).)

Introduction: As patients with recurrent inguinal hernia (RIH) are at a higher risk of perioperative complications, international guidelines have been developed to mitigate these risks by recommending the reverse approach for repair. We aim to study the characteristics of RIH, compliance to guidelines-based repair (GR) and determine factors influencing compliance to guidelines., Methods: A retrospective study of patients with RIH was carried out at two tertiary institutions in Singapore, over 10 years from January 2010 to 2020., Results: There were 16 patients with bilateral recurrences and 214 patients with unilateral recurrences. The characteristics of patients with non-guidelines-based repair (NGR) versus GR were similar, p > 0.05. GR was performed for 128 (52.1%) hernias as compared to NGR for 118 (47.9%) hernias. The open approach was more common in NGR than GR, 115/118 (89.8%) versus 58/128 (45.3%), p < 0.001. Forty (n = 40, 16.3%) RIH presented emergently, of which 37 underwent NGR while 3 underwent GR, p < 0.0001. More consultants were present during GR 103/128 (80.5%) as compared to NGR 78/118 (66.1%), p = 0.018. Emergency presentation of hernia recurrence, OR 7.74 (CI 6.11-9.20), p = 0.005, and open repair during the index repair were significantly associated with NGR, OR 6.63 (CI 4.42-8.84), p = 0.01. Median length of stay was shorter in the GR 1 day (IQR 1-2 days) versus 2 days (IQR 2-5 days) in the NGR group, p = 0.02., Conclusion: The compliance rate of GR for RIH is 52%. NGR for RIH had acceptable short-term outcomes. For elective presentation of RIH, GR should be encouraged given a shorter length of hospital stay., (© 2020. Springer-Verlag France SAS, part of Springer Nature.)

Background: Direct bronchial spread of tuberculosis was extensively described in pre-antibiotic human pathology literature but this description has been overlooked in the post-antibiotic era, in which most pathology data come from animal models that emphasise the granuloma. Modern techniques, such as [ 18 F]2-fluoro-2-deoxy-D-glucose (FDG) PET-CT scans, might provide further insight. Our aim was to understand normal early tuberculosis resolution patterns on pulmonary PET-CT scans in treated patients with tuberculosis who were subsequently cured., Methods: In this observational analysis, we analysed data from PredictTB, an ongoing, prospective, randomised clinical trial that examined sequential baseline and week 4 FDG-PET-CT scans from participants successfully treated (sputum culture negative 18 months after enrolment) for drug-susceptible pulmonary tuberculosis in South Africa and China. Participants who were aged 18-75 years, GeneXpert MTB/RIF positive for tuberculosis and negative for rifampicin resistance, had not yet started tuberculosis treatment, had not been treated for active tuberculosis within the previous 3 years, and met basic safety laboratory criteria were included and participants with diabetes, HIV infection, or with extrapulmonary tuberculosis including pleural tuberculosis were excluded. Scans were assessed by two readers for the location of tuberculosis lesions (eg, cavities and consolidations), bronchial thickening patterns, and changes from baseline to week 4 of treatment., Findings: Among the first 124 participants (enrolled from June 22, 2017, to Sept 27, 2018) who were successfully treated, 161 primarily apical cavitary lesions were identified at baseline. Bronchial thickening and inflammation linking non-cavitary consolidative lesions to cavities were observed in 121 (98%) of 124 participants' baseline PET-CT scans. After 4 weeks of treatment, 21 (17%) of 124 participants had new or expanding lesions linked to cavities via bronchial inflammation that were not present at baseline, particularly participants with two or more cavities at baseline and participants from South Africa., Interpretation: In participants with pulmonary tuberculosis who were subsequently cured, the location of cavitary and non-cavitary lesions at baseline and new lesions at week 4 of treatment suggest a cavitary origin of disease and bronchial spread through the lungs. Bronchial spread from cavities might play a larger role in the spread of pulmonary tuberculosis than has been appreciated. Elucidating cavity lesion dynamics and Mycobacterium tuberculosis viability within cavities might better explain treatment outcomes and why some patients are cured and others relapse., Funding: Bill & Melinda Gates Foundation, European and Developing Countries Clinical Trials Partnership, China Ministry of Science and Technology, National Natural Science Foundation of China, and National Institutes of Health., Translations: For the Chinese, Afrikaans and Xhosa translations of the abstract see Supplementary Materials section., Competing Interests: RJW is supported by Francis Crick Institute, which receives funding from UK Research and Innovation (FC0010218), Wellcome (FC0010218), and Cancer Research UK (FC0010218). RJW also receives support from Wellcome (104803, 203135), the European and Developing Countries Clinical Trials Partnership (EDCTP; SRIA2015-1065), and US National Institutes of Health (NIH; AI115940). GW receives funding from the South African Research Chair Initiative from the National Research Foundation (86535). STM receives grants from the South African Medical Research Council (grant number CDF1576). KA is employed by the Bill & Melinda Gates Medical Research Institute which is a grantee of the Bill & Melinda Gates Foundation but a separate legal entity. All other authors declare no competing interests., (© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)

Periodontitis is a highly prevalent chronic inflammatory disease leading to periodontal tissue breakdown and subsequent tooth loss, in which excessive host immune response accounts for most of the tissue damage and disease progression. Despite of the imperative need to develop host modulation therapy, the inflammatory responses and cell population dynamics which are finely tuned by the pathological microenvironment in periodontitis remained unclear. To investigate the local microenvironment of the inflammatory response in periodontitis, 10 periodontitis patients and 10 healthy volunteers were involved in this study. Single-cell transcriptomic profilings of gingival tissues from two patients and two healthy donors were performed. Histology, immunohistochemistry, and flow cytometry analysis were performed to further validate the identified cell subtypes and their involvement in periodontitis. Based on our single-cell resolution analysis, we identified HLA-DR-expressing endothelial cells and CXCL13 + fibroblasts which are highly associated with immune regulation. We also revealed the involvement of the proinflammatory NLRP3 + macrophages in periodontitis. We further showed the increased cell-cell communication between macrophage and T/B cells in the inflammatory periodontal tissues. Our data generated an intriguing catalog of cell types and interaction networks in the human gingiva and identified new inflammation-promoting cell subtypes involved in chronic periodontitis, which will be helpful in advancing host modulation therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qian, Huang, Chen, Mo, Zhou, Zhao, Li and Lai.)

Background: To investigate the value of D-dimer combined with red blood cell distribution width (RDW) in evaluating the disease activity of systemic lupus erythematosus (SLE)., Methods: A total of 105 SLE patients confirmed in our hospital from July 2018 to September 2020 were collected as the SLE group, and 60 healthy persons matched in age and gender during the same period were collected as the control group. According to the SLEDAI score, SLE patients were divided into SLE active group and SLE inactive group, and RDW and D-Dimer levels were detected., Results: The level of RDW in the SLE active group [14.8 (13.4, 16.8)] was significantly higher than that in the SLE inactive group [13.4 (12.6, 14.37)] and control group [12.3 (12, 12.7)], with statistically significant differences (p < 0.05). The D-dimer level in the SLE active group was 1.36 (0.9, 2.25) mg/L, which was significantly higher than that in SLE inactive group [0.34 (0.22, 0.52)] mg/L and control group [0.15 (0.08, 0.19)] mg/L, with statistically significant differences (p < 0.05). Both RDW and D-dimer were positively correlated with the SLEDAI score (r = 0.393, p = 0.000), (r = 0.483, p = 0.000). The results of receiver operating characteristic curve showed that the area under the curve of RDW and D-Dimer alone was 0.875 and 0.954, respectively, while the area under the curve of RDW combined with D-Dimer was the largest, 0.984., Conclusions: The levels of RDW and D-dimer are closely related to the disease activity of SLE patients, and RDW combined with D-dimer is more valuable in assessing the disease activity of SLE patients.

NK-lysins (NKLs) are a family of multifunctional antimicrobial peptides that have activity against various microorganisms. However, the immunomodulatory activity of NKL in fish remains unclear. In this study, the cDNA sequence of barbel steed (Hemibarbus labeo) NKL gene was cloned. Barbel steed NKL amino acid sequence comprised a signal peptide and a mature peptide. The saposin B domain in the mature peptide has six conserved cysteines that form three disulfide bonds. Phylogenetic analysis showed that the barbel steed NKL was most closely related to that of the common carp (Cyprinus carpio) NKL. Differential expression analysis showed that the barbel steed NKL gene was expressed in all tested tissues, with the highest expression in the spleen. In response to Aeromonas hydrophila infection, NKL was significantly upregulated in the liver, spleen, head kidney, and gill. The barbel steed NKL showed strong antibacterial activity against Vibrio parahaemolyticus, V. alginolyticus, V. vulnificus, and Listeria monocytogenes. However, NKL had no antibacterial activity against the pathogenic bacteria A. hydrophila. Lactate dehydrogenase release assays showed that NKL damaged the V. parahaemolyticus cell membrane. NKL significantly increased barbel steed survival rate after A. hydrophila infection and upregulated IL-1β and TNF-α expression in the spleen and head kidney. NKL induced monocyte/macrophage chemotaxis and enhanced the respiratory burst and proinflammatory cytokine expression. Our study shows that fish NKL exhibits immunomodulatory effects and protects the host from pathogenic infections independent of direct bacterial clearance., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To understand the status of tobacco use and related influencing factors in population in Shandong province. Methods: Stratified multi-stage cluster sampling was used to select respondents from 216 villages (communities) of 36 districts (counties) in Shandong province. Influencing factors on smoking were analyzed by logistic regression model. Results: The adequate sample size was 6 271 participants. After complex weighted, the current smoking prevalence was 23.93%,45.58% in males and 1.18% in females. The Public's smoking rates varied widely among different groups in the population. 45-64 age group had the highest smoking rate (25.07%). Smoking rates were substantially different in education levels, with the highest in junior high school (28.94%). The rate was higher in the rural area (24.98%) than that in the urban areas (23.08%). The average daily smoking rate was 20.23%. The average age of initiating smoking was 21.21 years. The average daily cigarette intake was 16.31 cigarettes. Among all the former and current smokers, the quitting rate was 20.79%. Multiple logistic regression model analysis showed that gender, age, occupation, region, and health knowledge score were correlated with smoking behavior. The current smoking rate of men was much higher than that of women ( OR =49.625, 95% CI : 37.832-65.093). The current smoking rate in 45-64 age group was higher than that in the 15-24 age group ( OR =1.830, 95% CI : 1.048-3.194). The current smoking rate of medical ( OR =0.403, 95% CI : 0.187-0.866) and retired personnel ( OR =0.648, 95% CI : 0.481-0.873) were lower than those engaging in agriculture, forestry, animal husbandry and the fishery ,respectively. The prevalence of residents living in the central part showed lower rate on current smoking than that in the eastern region ( OR =0.724, 95% CI : 0.606-0.865). The current smoking prevalence of smoke hazard in 1-3 score group was higher than that in the group with 4-6 score ( OR =1.432, 95% CI : 1.240-1.654). Conclusions: Smoking rate in adults in Shandong remained stable and at a high level. Comprehensive intervention measures such as tobacco control and health education should be carried out to reduce the smoking rate.

The use of Galleria mellonella (Linnaeus) (Lepidoptera: Pyralidae), an economical insect model, for the study of enteropathogenic Escherichia coli (Migula) (EPEC), a diarrheagenic human pathogen, has been demonstrated previously but remains poorly understood. The present study characterizes the Galleria-EPEC system extensively for future studies using this system. We found that EPEC causes disease in G. mellonella larvae when injected intrahemocoelically but not orally. Disease manifests as increased mortality, decreased survival time, delayed pupation, decreased pupal mass, increased pupal duration, and hemocytopenia. Disease symptoms are dose-dependent and can be used as metrics for measuring EPEC virulence in future studies. The type III secretion system was only partially responsible for EPEC virulence in G. mellonella while the majority of the virulence remains unknown in origin. EPEC elicits insect anti-bacterial immune responses including melanization, hemolymph coagulation, nodulation, and phagocytosis. The immune responses were unable to control EPEC replication in the early stage of infection (≤3 h post-injection). EPEC clearance from the hemocoel does not guarantee insect survival. Overall, this study provided insights into EPEC virulence and pathogenesis in G. mellonella and identified areas of future research using this system., (© The Author(s) 2021. Published by Oxford University Press on behalf of Entomological Society of America.)

Changing food preferences brought about by westernization that have deleterious health effects 1,2 -combined with myriad forces that are contributing to increased food insecurity-are catalysing efforts to identify more nutritious and affordable foods 3 . Consumption of dietary fibre can help to prevent cardiovascular disease, type 2 diabetes and obesity 4-6 . A substantial number of reports have explored the effects of dietary fibre on the gut microbial community 7-9 . However, the microbiome is complex, dynamic and exhibits considerable intra- and interpersonal variation in its composition and functions. The large number of potential interactions between the components of the microbiome makes it challenging to define the mechanisms by which food ingredients affect community properties. Here we address the question of how foods containing different fibre preparations can be designed to alter functions associated with specific components of the microbiome. Because a marked increase in snack consumption is associated with westernization, we formulated snack prototypes using plant fibres from different sustainable sources that targeted distinct features of the gut microbiomes of individuals with obesity when transplanted into gnotobiotic mice. We used these snacks to supplement controlled diets that were consumed by adult individuals with obesity or who were overweight. Fibre-specific changes in their microbiomes were linked to changes in their plasma proteomes indicative of an altered physiological state.

Background: Studies on the health impacts of being locked in a job are primarily conducted in Western countries, with the theory based on the value of individualism. But the socially-oriented concerns should be considered in workers' locked-in status in Chinese society. So the current study aims at evaluating socially-oriented concerns on workers' locked-in status in Taiwan., Methods: Anonymous surveys were conducted with 1102 workers at high-tech companies in Taiwan from October 2015 to January 2016 to assess their "face" needs-- a sociological concept linked to the dignity, prestige, and reputation that a person has in terms of their social relationships, locked-in status of the job, and burnout. In addition to being separated into three groups by lock-in score, participants were categorized by the conflict of preference of the job between themselves and their family. Chi-square, ANOVA, Pearson correlation, and regression tests were conducted., Results: Among the 1102 participants, 18% had jobs that they did not prefer but their family preferred. Participants with higher face needs and higher locked-in status had a significantly higher risk of developing personal and work-related burnout. However, the analysis using "locked-in job conflict of preference between themselves and their family" showed a more coherent result. Participants with a job which "self does not prefer but family do" had twice the risk of having personal and work-related burnout (OR = 2.03 and 2.34, respectively). Participants with a job which neither themselves nor their family prefer had four times the risk of having personal and work-related burnout (OR = 4.10 and 4.17, respectively)., Conclusions: The current study suggests an importance in considering a socially-oriented job preference in locked-in status evaluations within the Chinese culture. Workers' whose locked-in status preference conflicted with their family's preference showed a significantly negative impact on their health.

Background: Medical staff may have difficulties in using conventional medicine to manage symptoms among terminally ill patients, including adverse effects of the treatment. Traditional Chinese medicine (TCM) is regarded as a complementary or alternative medicine, and has been increasingly used in the field of palliative medicine in recent years. This study aimed to investigate the experiences of and attitudes toward using TCM among palliative care professionals, and to provide preliminary information about its use in palliative care., Methods: This was a cross-sectional survey study conducted in eight inpatient hospice wards in Taiwan between December 2014 and February 2016. The questionnaire was self-administered, and was analyzed with descriptive statistics including Pearson's Chi-square test and Fisher's exact test., Results: A total of 251 palliative care professionals responded to the questionnaire, of whom 89.7% and 88.9% believed that the use of TCM could improve the physical symptoms and quality of life in terminally ill patients, respectively. Overall, 59.8%, of respondents suggested that TCM had rare side effects, and 58.2% were worried that TCM could affect the liver and kidney function of patients. In total, 89.7% and 88.0% of professionals agreed there were no suitable clinical practice guidelines and educational programs, respectively, for TCM use in palliative care., Conclusions: Most of the respondents agreed there was insufficient knowledge, skills-training, and continuing education on the use of TCM in terminally ill patients in Taiwan. These results show that to address patient safety considerations, guidelines about use of TCM in palliative care should be established., (© 2020 Korea Institute of Oriental Medicine. Publishing services by Elsevier B.V.)

The objective of this study was to determine how coronary computed tomography angiography (CCTA) can be employed to detect coronary artery disease in hospital employees, enabling early treatment and minimizing damage. All employees of our hospital were assessed using the Framingham Risk Score. Those with a 10-year risk of myocardial infarction or death of >10% were offered CCTA; the Coronary Artery Disease Reporting and Data System (CAD-RADS) score was the outcome. A total of 3923 hospital employees were included, and the number who had received CCTA was 309. Among these 309, 31 (10.0%) had a CAD-RADS score of 3-5, with 10 of the 31 (32.3%) requiring further cardiac catheterization; 161 (52.1%) had a score of 1-2; and 117 (37.9%) had a score of 0. In the multivariate logistic regression, only age of ≥ 55 years ( p < 0.05), hypertension ( p < 0.05), and hyperlipidemia ( p < 0.05) were discovered to be significant risk factors for a CAD-RADS score of 3-5. Thus, regular and adequate control of chronic diseases is critical for patients, and more studies are required to be confirmed if there are more significant risk factors.

The early characterization of ligands at the dopamine and serotonin transporters, DAT and SERT, respectively, is important for drug discovery, forensic sciences, and drug abuse research. 4-Methyl amphetamine (4-MA) is a good example of an abused drug whose overdose can be fatal. It is a potent substrate at DAT and SERT where its simplest secondary amine (N-methyl 4-MA) retains substrate activity at them. In contrast, N-n-butyl 4-MA is very weak, therefore it was categorized as inactive at these transporters. Here, N-octyl 4-MA and other related compounds were synthesized, and their activities were evaluated at DAT and SERT. To expedite this endeavor, cells expressing DAT or SERT were co-transfected with a voltage-gated Ca 2+ channel and, the genetically-encoded Ca 2+ sensor, GCaMP6s. Control compounds and the newly synthesized molecules were tested on these cells using an automated multi-well fluorescence plate reader; substrates and inhibitors were identified successfully at DAT and SERT. N-Octyl 4-MA and three bivalent compounds were inhibitors at these transporters. These findings were validated by measuring Ca 2+ -mobilization using quantitative fluorescence microscopy. The bivalent molecules were the most potent of the series and were further characterized in an uptake-inhibition assay. Compared to cocaine, they showed comparable potency inhibiting uptake at DAT and higher potency at SERT. These observations support a previous hypothesis that amphetamine-related (and, here, N-extended alkyl and) bivalent arylalkylamine molecules are active at monoamine transporters, showing potent activity as reuptake inhibitors, and implicate the involvement of a distant auxiliary binding feature to account for their actions at DAT and SERT., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: The aim of this study was to explore the impact of diabetes self-management and HbA1c affected by the COVID-19 pandemic and the epidemic prevention work. Methods: This quasi-experimental study collected a pooled data from a randomized-control study between February and May 2020 in which 114 participants who presented type 2 diabetes were recruited. The intervention group had health coaching and usual care, whereas the control had usual care only. The main outcome variables of this observation study were the change of HbA1c, physical activity, and eating out behavior within this time interval. Results: We found that the eating out behavior of both groups had decreased, and if a health coach helped the patients set physical activity goals in the two groups, the physical activity behavior will not be impacted due to the pandemic. Conclusions: While every country is focusing on COVID-19 pandemic prevention, especially when strict home quarantine measures and social distancing are adopted, reminding and assisting chronic patients to maintain good self-management behavior may lessen the social and medical system burdens caused by the deterioration of chronic conditions due to the excessive risk prevention behavior and the epidemic prevention work. Trial Registration: www.isrctn.com, identifier number: ISRCTN14167790, date: 12 July, 2019., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lin, Huang, Chang, Chen and Yang.)

Objectives: This study investigated the synergistic in vitro and in vivo activity of cefazolin plus fosfomycin against methicillin-susceptible and methicillin-resistant S. aureus (MSSA and MRSA) to provide the basis for a potential treatment alternative. Methods: Antimicrobial susceptibility and in vitro synergy tests were performed with five MSSA and five MRSA isolates using the broth microdilution and chequerboard assays, respectively. The in vivo efficacy of cefazolin plus fosfomycin for the treatment of MRSA infections was assessed using the Galleria mellonella survival assay. Results: Using fractional inhibitory concentration index (FICI), the evaluated combination of cefazolin plus fosfomycin showed synergistic in vitro activity against all MSSA and MRSA isolates tested. In addition, cefazolin susceptibility was recovered in all MRSA isolates except one fosfomycin-resistant strain when combined with fosfomycin at readily achievable concentrations. The G. mellonella survival assay demonstrated highly synergistic in vivo activity of cefazolin plus fosfomycin, resulting in a 44-52% reduction in mortality when compared to cefazolin-alone and fosfomycin-alone, respectively. Conclusion: If susceptibility to fosfomycin is either confirmed or can be assumed based on local resistance patterns, combination therapy with cefazolin plus fosfomycin could be a valuable treatment option for empirical as well as targeted therapy of S. aureus and MRSA infections. Future studies proving the clinical significance of this combination therapy are therefore warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kussmann, Obermueller, Karer, Kriz, Chen, Hohl, Schneider, Burgmann, Traby and Vossen.)

Objectives: To investigate age-related changes on passive muscle stiffness in healthy individuals and measure the shear modulus in different age groups., Methods: Shear wave elastography (SWE) movies of gastrocnemius medialis (GM) were collected during passive stretching induced by ankle rotation from plantarflexion (PF) to dorsiflexion (DF). A series of SWE images at ankle angles of PF 40°, PF 30°, PF 20°, PF 10°, 0°, DF 10°, DF 20°, and DF 30° were collected and shear moduli measured accordingly for analyses., Results: Eighty-six healthy volunteers (27 children, 31 middle-aged adults, and 28 older people) were recruited. No significant difference was observed in the shear modulus between the three groups at ankle angles of PF 40°, PF 30°, PF 20°, PF 10°, and 0° (p > 0.05). The difference in the shear modulus among the three groups became significant as DF increased. At ankle angles of DF 10°, DF 20°, and DF 30°, the shear modulus was the greatest in the older group, followed by the middle-aged group and then the children group (p = 0.007, 0.000, and 0.000, respectively)., Conclusions: Passive muscle stiffness increases with age, and the difference between age groups was pronounced only after reaching a certain degree of stretching., Key Points: • The influence of age on passive muscle stiffness becomes pronounced only after reaching a certain degree of stretching. • Age should be considered when evaluating passive muscle stiffness in muscular disorders.

Background: Virtual reality (VR) training are regarded as promising new tools for rehabilitation, but the effect on patients' daily participation is controversial. This study aimed to evaluate the effect of virtual reality (VR) training on different types of patients' daily participation through a meta-analysis., Methods: The PubMed, Cochrane central register of controlled trials, Embase, and web science databases were searched for studies published through September 2020. Thirty-five randomized controlled trials of virtual reality (VR) training compared with conventional treatment, Other electronic rehabilitation systems, usual care for various types of patients were included. All of the studies were available in English. Standardized mean differences (SMD), 95 % confidence intervals (CI), publication bias, and heterogeneity were calculated., Results: The Virtual reality (VR) training group is better than the control group in daily participation improvement on all types of patients. There was a small, significant effect(p＜0.001; SMD = 0.25[95 %CI,0.14 to 0.36], I 2 = 0.00 %). Observing only the type of Stroke, the VR training group is still better than the control group in improving patients' daily participation (p＜0.001, SMD = 0.24[95 %CI, 0.11 to 0.37], I2 = 0.00 %). Using the cumulative Meta-analysis method to observe the included literature according to the timeline, Using the cumulative Meta-analysis method to observe the included literature according to the timeline, and it has only achieved positive results since 2015 (Nam-YoNg Lee 2015, p = 0.048, SMD = 0.22[95 %CI,0.00 to 0.44]). The heterogeneity of the studies was not detected, but there is obvious publication bias., Conclusions: Because of controversy over obvious publication bias, we need to be cautious about the conclusion that VR is better than the control group in promoting the patient's daily participation., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: More than 30 million children worldwide have moderate acute malnutrition. Current treatments have limited effectiveness, and much remains unknown about the pathogenesis of this condition. Children with moderate acute malnutrition have perturbed development of their gut microbiota., Methods: In this study, we provided a microbiota-directed complementary food prototype (MDCF-2) or a ready-to-use supplementary food (RUSF) to 123 slum-dwelling Bangladeshi children with moderate acute malnutrition between the ages of 12 months and 18 months. The supplementation was given twice daily for 3 months, followed by 1 month of monitoring. We obtained weight-for-length, weight-for-age, and length-for-age z scores and mid-upper-arm circumference values at baseline and every 2 weeks during the intervention period and at 4 months. We compared the rate of change of these related phenotypes between baseline and 3 months and between baseline and 4 months. We also measured levels of 4977 proteins in plasma and 209 bacterial taxa in fecal samples., Results: A total of 118 children (59 in each study group) completed the intervention. The rates of change in the weight-for-length and weight-for-age z scores are consistent with a benefit of MDCF-2 on growth over the course of the study, including the 1-month follow-up. Receipt of MDCF-2 was linked to the magnitude of change in levels of 70 plasma proteins and of 21 associated bacterial taxa that were positively correlated with the weight-for-length z score (P<0.001 for comparisons of both protein and bacterial taxa). These proteins included mediators of bone growth and neurodevelopment., Conclusions: These findings provide support for MDCF-2 as a dietary supplement for young children with moderate acute malnutrition and provide insight into mechanisms by which this targeted manipulation of microbiota components may be linked to growth. (Supported by the Bill and Melinda Gates Foundation and the National Institutes of Health; ClinicalTrials.gov number, NCT04015999.)., (Copyright © 2021 Massachusetts Medical Society.)

Hodgkin lymphoma (HL) is composed of neoplastic Hodgkin and Reed-Sternberg cells in an inflammatory background. The neoplastic cells are derived from germinal center B cells that, in most cases, are infected by Epstein-Barr virus (EBV), which may play a role in tumorigenesis. Given that EBV-latent membrane protein 1 (LMP1) regulates autophagy in B cells, we explored the role of autophagy mediated by EBV or LMP1 in HL. We found that EBV-LMP1 transfection in HL cells induced a modest increase in autophagy signals, attenuated starvation-induced autophagic stress, and alleviated autophagy inhibition- or doxorubicin-induced cell death. LMP1 knockdown leads to decreased autophagy LC3 signals. A xenograft mouse model further showed that EBV infection significantly increased expression of the autophagy marker LC3 in HL cells. Clinically, LC3 was expressed in 15% (19/127) of HL samples, but was absent in all cases of nodular lymphocyte-predominant and lymphocyte-rich classic HL cases. Although expression of LC3 was not correlated with EBV status or clinical outcome, autophagic blockade effectively eradicated LMP1-positive HL xenografts with better efficacy than LMP1-negative HL xenografts. Collectively, these results suggest that EBV-LMP1 enhances autophagy and promotes the viability of HL cells. Autophagic inhibition may be a potential therapeutic strategy for treating patients with HL, especially EBV-positive cases., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objectives: To identify valuable ultrasonography findings combined with clinical markers for predicting carotid progression of Takayasu's arteritis (TAK) on imaging during a 1-year follow-up period., Methods: From May 2016 to June 2019, 77 Chinese TAK patients with carotid artery involvement were enrolled in the present study. The patients' clinical characteristics and serological test and carotid ultrasonography results were recorded at baseline and each visit. Carotid progression was evaluated by ultrasonography every 3 months during the 1-year follow-up. Baseline clinical characteristics and ultrasonography results for predicting progression on imaging were identified., Results: Sixteen (20.8%) patients presented with carotid progression on imaging during the 1-year follow-up period. The patients in the progressive group were younger (23.4±3.7 vs. 32.3±9.8 years, p<0.01) than those in the non-progressive group. At baseline, the vessel wall was thicker in the progressive group than in the non-progressive group (2.4±0.8 vs. 1.9±0.5 mm, p=0.041). Furthermore, the proportion of patients with refractory disease (87.5% vs. 16.4%, p<0.01) was higher in the progressive group than in the non-progressive group. Patients with a thickened carotid wall (≥1.9 mm), refractory disease, and younger age (≤30 years) might be at a high risk of carotid progression on imaging (75%, AUC: 0.93, sensitivity: 75%, specificity: 93.4%)., Conclusions: Younger patients with early vascular structural changes at baseline as well as refractory disease seemed more likely to show carotid progression on imaging.

Early bactericidal activity studies monitor daily sputum bacterial counts in individuals with tuberculosis (TB) for 14 days during experimental drug treatment. The rate of change in sputum bacterial load over time provides an informative, but imperfect, estimate of drug activity and is considered a critical step in development of new TB drugs. In this clinical study, 160 participants with TB received isoniazid, pyrazinamide, or rifampicin, components of first-line chemotherapy, and moxifloxacin individually and in combination. In addition to standard bacterial enumeration in sputum, participants underwent 2-deoxy-2-[ 18 F]fluoro-d-glucose positron emission tomography and computerized tomography ([ 18 F]FDG-PET/CT) at the beginning and end of the 14-day drug treatment. Quantitating radiological responses to drug treatment provided comparative single and combination drug activity measures across lung lesion types that correlated more closely with established clinical outcomes when combined with sputum enumeration compared to sputum enumeration alone. Rifampicin and rifampicin-containing drug combinations were most effective in reducing both lung lesion volume measured by CT imaging and lesion-associated inflammation measured by PET imaging. Moxifloxacin was not superior to rifampicin in any measure by PET/CT imaging, consistent with its performance in recent phase 3 clinical trials. PET/CT imaging revealed synergy between isoniazid and pyrazinamide and demonstrated that the activity of pyrazinamide was limited to lung lesion, showing the highest FDG uptake during the first 2 weeks of drug treatment. [ 18 F]FDG-PET/CT imaging may be useful for measuring the activity of single drugs and drug combinations during evaluation of potential new TB drug regimens before phase 3 trials., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

To determine whether curcumin (Cur) can treat mice with experimentally-induced colitis by regulating follicular helper T cells (Tfh) and follicular regulatory T cells (Tfr) by inhibiting interleukin (IL)-21. In this study, 40 male C57BL/6 mice were randomly grouped into four groups, i.e., normal, trinitrobenzene sulfonic acid (TNBS), TNBS + curcumin, and TNBS + anti-IL-21. Mice with experimental colitis were induced by 100 mg/kg TNBS. The mice in the TNBS + Cur group were treated with 100 mg/kg curcumin for seven days, and mice in the TNBS + anti-IL-21 group were treated with anti-IL-21 (150 μg/mouse) once per week, intraperitoneally, starting on the second day after establishing the experimental colitis model. On day eight, the therapeutic effect of curcumin was evaluated by colon mucosa damage index (CMDI), histological examination, and disease activity index (DAI). Furthermore, the number of CD4 + CXCR5 + PD-1 + Tfh and CD4 + CXCR5 + FoxP3 + Tfr cells were measured by flow cytometry. The mRNA and protein expression of IL-21, Bcl-6, FOXP3, ICOS, and PD-1 in colonic mucosa was detected by reverse transcription polymerase chain reaction and the Western blot technique. Compared with the TNBS group, the DAI, CMDI, histological score, the number of CD4 + CXCR5 + PD-1 + Tfh cells, the expression of IL-21, Bcl-6, ICOS, and PD-1 were significantly decreased in the TNBS + curcumin group and TNBS + anti-IL-21 group; body weight, number of CD4 + CXCR5 + FoxP3 + Tfr cells, and the expression of FoxP3 were observably elevated in the TNBS + curcumin group (all P < 0.05). Curcumin may have a potential therapeutic effect on mice with colitis treated experimentally through regulation of the balance of Tfh and Tfr cells via inhibiting the synthesis of IL-21.

Chitosan and its derivative, chitosan oligosaccharide (CO), possess hypolipidemic and anti-obesity effects. However, it is still unclear if the mechanisms are different or similar between chitosan and CO. This study was designed to investigate and compare the effects of CO and high-molecular-weight chitosan (HC) on liver lipogenesis and lipid peroxidation, adipose lipolysis, and intestinal lipid absorption in high-fat (HF) diet-fed rats for 12 weeks. Rats were divided into four groups: normal control diet (NC), HF diet, HF diet+5% HC, and HF diet+5% CO. Both HC and CO supplementation could reduce liver lipid biosynthesis, but HC had a better effect than CO on improving liver lipid accumulation in HF diet-fed rats. The increased levels of triglyceride decreased lipolysis rate, and increased lipoprotein lipase activity in the perirenal adipose tissue of HF diet-fed rats could be significantly reversed by both HC and CO supplementation. HC, but not CO, supplementation promoted liver antioxidant enzymes glutathione peroxidase and superoxide dismutase activities and reduced liver lipid peroxidation. In the intestines, CO, but not HC, supplementation reduced lipid absorption by reducing the expression of fabp2 and fatp4 mRNA. These results suggest that HC and CO have different mechanisms for improving lipid metabolism in HF diet-fed rats.