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Background Low protein intake (LPI) has been suggested as a treatment for chronic kidney disease (CKD). However, protein intake is essential for bone health.Methods We studied the database of the National Health and Nutrition Examination Survey, 2005–2010. Basic variables, metabolic diseases, and bone density of different femoral areas were stratified into four subgroups according to different protein intake (DPI) (that is, 1.2 g/kg/day).Results Significant differences were found among all lumbar area bone mineral density (BMD) and T-scores (p 1.2 g/day/kg over L2 (relative risk (RR)=1.326, 95% confidence interval (CI)=1.062–1.656), subgroup >1.2 g/day/kg over L3 (RR = 1.31, 95%CI = 1.057–1.622), subgroup 1.2 g/day/kg over all L spines (RR = 0.333, 95%CI = 1.098–1.618). However, a higher risk of osteoporosis was observed only in the non-CKD group. There was an apparent trend of higher DPI coexisting with lower BMD and T scores in patients with CKD. For osteoporosis (reference:0.8–1.0 g/day/kg), lower (1.2 g/day/kg) was associated with higher risks in the non-CKD group, but not in the CKD group.Conclusions In the CKD group, LPI for renal protection was safe without threatening L spine bone density and without causing a higher risk of osteoporosis.

Background: Prior to 2022, Taiwan had effectively contained the domestic COVID-19 epidemic. However, during 2022, the country encountered multiple large outbreaks of COVID-19, with patients experiencing their first or second infection (reinfection) were both predominantly caused by the Omicron variant. Data are lacking on the risk factors and mortality of COVID-19 reinfection in Omicron era. Methods: In this retrospective population-based cohort study, we recruited COVID-19 patients with their first episode confirmed between April 1, 2022 and June 11, 2022. A reinfection patient was defined as an individual who infected again by SARS-CoV-2 with an interval of more than 90 days. Demographic characteristics, severity of underlying diseases, and vaccination status were adjusted to identify risk factors for reinfection and to further evaluate the hazard of all-cause mortality within 30 days between reinfection and non-reinfection patients. Results: There were 28,588 reinfection patients matched with 142,940 non-reinfection patients included in this study. We found that being female, younger in age, having more severe underlying diseases, and not being fully vaccinated against COVID-19 were risk factors for reinfection. After adjusting for confounding factors, reinfection patients were at a significantly higher risk of all-cause mortality within 30 days (aHR = 4.29, 95% CI: 3.00–6.12, p

Abstract Chronic kidney disease (CKD) imposes a substantial burden, and patient prognosis remains grim. The impact of AST-120 (AST-120) on the survival of CKD patients lacks a consensus. This study aims to investigate the effects of AST-120 usage on the survival of CKD patients and explore the utility of artificial intelligence models for decision-making. We conducted a retrospective analysis of CKD patients receiving care in the pre-end-stage renal disease (ESRD) program at Taichung Veterans General Hospital from 2000 to 2019. We employed Cox regression models to evaluate the relationship between AST-120 use and patient survival, both before and after propensity score matching. Subsequently, we employed Deep Neural Network (DNN) and Extreme Gradient Boosting (XGBoost) models to assess their performance in predicting AST-120's impact on patient survival. Among the 2584 patients in our cohort, 2199 did not use AST-120, while 385 patients received AST-120. AST-120 users exhibited significantly lower mortality rates compared to non-AST-120 users (13.51% vs. 37.88%, p

The present study investigated the potential anti-obesity properties of Citrus depressa Hayata (CDH) juice in HBV transgenic mice, as well as the impact of fermentation on the effectiveness of the juice. The results revealed that fermentation increased the levels of polyphenols and hesperidin in CDH juice. The animal study demonstrated that both juices were effective in mitigating the weight gain induced by a high-fat diet by correcting metabolic parameter imbalances, reducing hepatic lipid accumulation, and reversing hepatic immune suppression. Furthermore, fermented juice exhibited superior efficacy in managing body weight and inhibiting the expansion of white adipose tissue (WAT). Fermented juice significantly enhanced adiponectin production and PPARγ expression in WAT, while also reducing hypertrophy. This study offers valuable insights into the potential role of CDH juices in combating obesity associated with high fat consumption and underscores the promise of CDH juice as a functional beverage.

Abstract Introduction Hyperuricemia and diabetes mellitus (DM) are associated with increased mortality risk in patients with chronic kidney disease (CKD). Here we aimed to evaluate the independent and joint risks of these two conditions on mortality and end stage kidney disease (ESKD) in CKD-patients. Methods This retrospective cohort study enrolled 4380 outpatients (with CKD stage 3–5) with mortality and ESKD linkage during a 7-year period (from 2007 to 2013). All-causes mortality and ESKD risks were analyzed by multivariable-adjusted Cox proportional hazards models (adjusted for age, sex, smoke, previous coronary arterial disease, blood pressure, and medications for hyperlipidemia, hyperuricemia and renin–angiotensin system inhibitors). Results Overall, 40.5% of participants had DM and 66.4% had hyperuricemia. In total, 356 deaths and 932 ESKD events occurred during the 7 years follow-up. With the multivariate analysis, increased risks for all-cause mortality were: hyperuricemia alone, HR = 1.48 (1–2.19); DM alone, and HR = 1.52 (1.02–2.46); DM and hyperuricemia together, HR = 2.12 (1.41–3.19). Similar risks for ESKD were: hyperuricemia alone, HR = 1.34 (1.03–1.73); DM alone, HR = 1.59 (1.15–2.2); DM and hyperuricemia together, HR = 2.46 (1.87–3.22). Conclusions DM and hyperuricemia are strongly associated with higher all-cause mortality and ESKD risk in patients with CKD stage 3–5. Hyperuricemia is similar to DM in terms of risk for all-cause mortality and ESKD. DM and hyperuricemia when occurred together further increase both risks of all-cause mortality and ESKD.

Summary: Background: Insulin resistance (IR) is associated with diabetes mellitus, cardiovascular disease (CV), and mortality. Few studies have used machine learning to predict IR in the non-diabetic population. Methods: In this prospective cohort study, we trained a predictive model for IR in the non-diabetic populations using the US National Health and Nutrition Examination Survey (NHANES, from JAN 01, 1999 to DEC 31, 2012) database and the Taiwan MAJOR (from JAN 01, 2008 to DEC 31, 2017) database. We analysed participants in the NHANES and MAJOR and participants were excluded if they were aged 0.8 (highest being XGboost, 0.87). In the test group, all AUC were also >0.80 (highest being XGboost, 0.88). Among all 9 features (age, gender, race, body mass index, fasting plasma glucose (FPG), glycohemoglobin, triglyceride, total cholesterol and high-density cholesterol), BMI had the highest value of feature importance on IR (0.43 for XGboost and 0.47 for RF algorithms). All participants from the TWB database were separated into the IR group and the non-IR group according to the XGboost algorithm. The Kaplan–Meier survival curve showed a significant difference between the IR and non-IR groups (p

Objectives: We investigated the associations of mean levels of leisure-time physical activity (LTPA) and latent LTPA trajectories with all-cause mortality risk.Methods: Trajectories of LTPA were established using group-based trajectory analysis with a latent class growth model in a population-based cohort between 1996 and 2014. A Cox-proportional hazard model was conducted to examine the associations of LTPA quintiles and LTPA trajectories with all-cause mortality.Results: A total of 21,211 participants (age 18–90 years) were analyzed (median follow-up 16.8 years). The study participants were divided into five groups according to percentiles of LTPA (

Background: Coronavirus disease 2019 (COVID-19) manifests symptoms as common etiologies of respiratory tract infections (RTIs). During the pandemic of COVID-19, identifying the etiologies correctly from patients with RTI symptoms was crucial in not only disease control but preventing healthcare system from collapsing. By applying sensitive PCR-based molecular assays, we detected the etiologic agents and delineated the epidemiologic picture of RTIs in the early phase of COVID-19 pandemic. Methods: From December 2019 to February 2020, we screened patients presented with RTIs using multiplex PCR-based diagnostic assays. Data from pediatric and adult patients were compared with different months and units in the hospital. Results: Of all 1631 patients including 1445 adult and 186 pediatric patients screened, 8 viruses and 4 bacteria were identified. Positive rates were 25% in December, 37% in January, and 20% in February, with pediatric patients having higher positive rates than adults (Ps

Background: Respiratory viruses (RVs) are among the most common pathogens for both upper and lower respiratory tract infections (RTIs). However, the viral epidemiology of RV-associated RTIs in adults has long been under-recognized. Through a sensitive molecular assay, it would be possible to have a better understanding of the epidemiology of RV-associated RTIs. Material and methods: Respiratory tract (RT) specimens from adults hospitalized due to RTIs were tested for RVs, using the multiplex PCR-based Luminex xTAG® Respiratory Viral Panel assay. A total of nineteen RVs, including influenza viruses and non-influenza respiratory viruses (NIRVs) were detected. Positive rates were compared using a chi-square test. Results: A total of 2292 samples from adult patients hospitalized with RTIs were screened for RVs. The overall positive rate was 22%, with 17.8% samples positive for at least one NIRV. NIRVs had a higher positive rate in non-winter seasons. As many as 12.7% (46/363) of the samples collected through broncho-alveolar lavage and 20.5% (176/859) of the samples collected in ICUs were positive for RVs. Distribution of corona virus (CoV), human metapneumovirus (hMPV) and parainfluenza virus (PIV) demonstrated seasonal variation. Also, temperature was associated with the positive rates of specific viruses, including CoV, respiratory syncytial virus (RSV), hMPV and PIV. Conclusion: Respiratory viruses, notably NIRVs, were frequently detected in adults hospitalized with RTIs. Several RVs were detected with distinctive seasonal variations. A substantial number of RVs were identified in lower RT specimens or from patients admitted to ICU, highlighting their important role in causing severe respiratory infection.

Abstract Aims/Introduction The convergence of tuberculosis (TB) and diabetes mellitus (DM) is a new challenge in Asia as a result of the rising prevalence of diabetes mellitus with higher TB infection rates, and also because diabetes mellitus itself enhances TB disease activity and consequently the spread of TB. We aimed to address the risk presented by diabetes mellitus for TB infection. Materials and Methods Patients with diabetes mellitus were retrospectively recruited. The baseline assessments included age, sex, body mass index, fasting blood glucose, glycated hemoglobin, urine albumin‐to‐creatinine ratio and estimated glomerular filtration rate. TB was determined by meeting the international classification of disease, for TB diagnosis and receiving anti‐TB treatment for at least 2 months. Results In total, 9,750 individuals with diabetes mellitus were recruited. The event rate of TB was 47 (0.48%). Younger age, lower proportion of men, higher fasting blood glucose and glycated hemoglobin values, and better renal function (estimated glomerular filtration rate and urine albumin‐to‐creatinine ratio) were observed in the metformin‐exposed groups. Old age and male sex were associated with higher TB infection risk on multivariate analysis. Metformin users had a significantly lower risk for TB infection, whereas insulin users had a higher risk for TB infection. However, glycemic status had no effect on TB infection risk. Conclusions This study provides clinical evidence from a survey of TB in individuals with diabetes mellitus. Old age, male sex and insulin use were risk factors for TB infection. Metformin remains the first choice of treatment for diabetes mellitus and has a potential protective effect against TB infection.

We investigated the associations of insulin resistance and β-cell secretion with bone mineral density (BMD) and osteoporosis using data from the National Health and Nutrition Examination Survey. Data on BMD assessed using dual-energy x-ray absorptiometry from 5292 participants were analyzed. Insulin resistance and β-cell secretion were assessed using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and β-cell function (HOMA-β), respectively. We divided the study population into four groups according to HOMA-IR (

Background and aimsWe investigated the association of adherence to the Dietary Approaches to Stop Hypertension (DASH) diet with all-cause mortality in patients with a history of heart failure.MethodsWe analyzed data from the National Health and Nutrition Examination Survey (NHANES). Dietary information was obtained from a 24-h dietary recall interview. Adherence to the DASH diet was assessed using the DASH score. The primary outcome was all-cause mortality which was confirmed by the end of 2011. Weighted Cox proportional hazards regression models were used to determine the hazard ratios and 95% CI for the association of the DASH score and all-cause mortality with multivariate adjustment.ResultsThe median DASH score was 2 among the 832 study participants. There were 319 participants who died after a median follow-up duration of 4.7 years. A higher DASH score (>2 vs. ≤ 2) was not associated with a decrease in the risk of all-cause mortality (adjusted HR 1.003, 95% CI 0.760–1.323, p = 0.983). With respect to the components of the DASH score, a lower sodium intake was not associated with a decreased risk of mortality (adjusted HR 1.045, 95% CI 0.738–1.478, p = 0.803).ConclusionA higher DASH score (>2 vs. ≤ 2) was not associated with all-cause mortality in patients with heart failure.

Abstract Controversy remains regarding the relationship between bone health and sleep. In the literature, the effect of sleep on bone density in the clinical setting varies depending on the definition of normal sleep duration, sleep quality, selected population, and diagnostic tools for bone density. The aim of this study was to examine the association between bone mineral density (BMD)assessed by dual-energy X-ray absorptiometry and sleep duration/quality in the defined adult population from the National Health and Nutrition Examination Survey (NHANES) (a national household survey) within a 6-year period (2005–2010) and explore age differences. The basic variables, metabolic diseases, and bone density in the femoral neck as determined through dual-energy X-ray absorptiometry, were segregated, and analyzed according to different sleep durations (1–4, 5–6,7–8, and > 9 h/day) and sleep quality using multinomial regression models. A total of 12,793 subjects were analyzed. Our results reveal that women aged > 50 years with sleep duration

Integrating education practices and measurements of brain activity has the potential to make learning more engaging and productive. Direct recordings of electrical activity in the brain provide important information about the complex dynamics of the cognitive processes and mental states that occur during learning, which can ultimately empower learners. In this article, electroencephalographic (EEG) methodologies, including the time-frequency and event-related potential techniques, are introduced, and the application of these techniques to studies of digital learning studies is discussed. Considerations of how to collect high quality data in both laboratory and real world settings are also presented, along with potential research directions. Finally, a general guideline for publishing results is offered. These issues are critical for producing useful applications of EEG studies to the digital learning research community.

ABSTRACT BACKGROUND: Findings regarding the effects of hyperuricemia on renal function and mortality have been inconsistent. OBJECTIVES: To investigate the effects of hyperuricemia on incident renal replacement therapy and all-cause mortality among patients with chronic kidney disease (CKD). DESIGN AND SETTING: Retrospective cohort study conducted in a medical center in Taiwan. METHODS: Patients with CKD in stages 3-5, without histories of renal replacement therapy, were consecutively recruited from 2007 to 2013. Their medical history, laboratory and medication data were collected from hospital records. The mean uric acid level in the first year of follow-up was used for analyses. Hyperuricemia was defined as mean uric acid level ≥ 7.0 mg/dl in men or ≥ 6.0 mg/dl in women. The primary outcomes were incident renal replacement therapy and all-cause mortality, and these data were retrospectively collected from hospital records until the end of 2015. RESULTS: A total of 4,381 patients were analyzed (mean age 71.0 ± 14.8 years; males 62.7%), and the median follow-up period was 2.5 years. Patients with hyperuricemia were at increased risk of incident renal replacement therapy and all-cause mortality, especially those with CKD in stages 4 or 5. Compared with patients with CKD in stage 3 and normouricemia, patients with CKD in stages 4 or 5 presented significantly higher risk of all-cause mortality only if they had hyperuricemia. CONCLUSIONS: In patients with CKD in stages 3-5, hyperuricemia was associated with higher risk of incident renal replacement therapy and all-cause mortality. Whether treatment with uric acid-lowering drugs in these patients would improve their outcomes merits further investigation.

Background and AimsA dietary pattern concordant with either the Dietary Approaches to Stop Hypertension (DASH) diet or the Mediterranean diet has been associated with a lower risk of all-cause mortality in general population. We investigated the associations of adherence to the DASH diet and the Mediterranean diet with all-cause mortality across three glucose regulation states (normal glucose tolerance, prediabetes, and diabetes) using data from the National Health and Nutrition Examination Survey (NHANES).MethodsData from the NHANES participants from 1999 to 2010, including their vital status linked to the National Death Index through the end of 2011, were analyzed. Adherence to the DASH diet and the Mediterranean diet was assessed using the DASH score and the alternative Mediterranean Diet Index (aMED), respectively. Weighted Cox proportional hazards regression models were used to compare the hazard ratios for the associations of adherence (diet score >median vs. ≤ median) to the DASH diet and the Mediterranean diet with all-cause mortality.ResultsA total of 28,905 participants were analyzed, and 2,598 of them had died after a median follow-up of 6.3 years. The median DASH score and aMED were 2 and 3, respectively. Adherence to the Mediterranean diet (aMED >3 vs. ≤ 3), but not the DASH diet, was associated with a lower risk of all-cause mortality (adjusted HR 0.74, 95% CI 0.66–0.83, p < 0.001) in the overall population. The findings were consistent across the three glucose regulation states. A joint effect of aMED >3 and DASH score >2 (adjusted HR 0.71, 95% CI 0.52–0.99, p = 0.042) was noted in participants with diabetes.ConclusionsAdherence to the Mediterranean diet (aMED >median) was associated with reduced all-cause mortality in a general population. For people with diabetes, a dietary pattern concordant with both the DASH diet and the Mediterranean diet (DASH score >median and aMED >median) was associated with a lower risk of mortality.

The present study aimed to investigate the neural mechanism underlying semantic processing in Mandarin Chinese adult learners, focusing on the learners who were Indo-European language speakers with advanced levels of proficiency in Mandarin Chinese. We used functional magnetic resonance imaging technique and a semantic judgment task to test 24 Mandarin Chinese adult learners (L2 group) and 26 Mandarin Chinese adult native speakers (L1 group) as a control group. In the task, participants were asked to indicate whether two-character pairs were related in meaning. Compared to the L1 group, the L2 group had greater activation in the bilateral occipital regions, including the fusiform gyrus and middle occipital gyrus, as well as the right superior parietal lobule. On the other hand, less activation in the bilateral temporal regions was found in the L2 group relative to the L1 group. Correlation analysis further revealed that, within the L2 group, increased activation in the left middle temporal gyrus/superior temporal gyrus (M/STG, BA 21) was correlated with higher accuracy in the semantic judgment task as well as better scores in the two vocabulary tests, the Assessment of Chinese character list for grade 3 to grade 9 (A39) and the Peabody Picture Vocabulary Test-Revised. In addition, functional connectivity analysis showed that connectivity strength between the left fusiform gyrus and left ventral inferior frontal gyrus (IFG, BA 47) was modulated by the accuracy in the semantic judgment task in the L1 group. By contrast, this modulation effect was weaker in the L2 group. Taken together, our study suggests that Mandarin Chinese adult learners rely on greater recruitment of the bilateral occipital regions to process orthographic information to access the meaning of Chinese characters. Also, our correlation results provide convergent evidence that the left M/STG (BA 21) plays a crucial role in the storage of semantic knowledge for readers to access to conceptual information. Moreover, the connectivity results indicate that the left ventral pathway (left fusiform gyrus-left ventral IFG) is associated with orthographic-semantic processing in Mandarin Chinese. However, this semantic-related ventral pathway might require more time and language experience to be developed, especially for the late adult learners of Mandarin Chinese.

Abstract Background Circulating tumor cells (CTCs) are associated with breast cancer prognosis. Research is limited regarding the role of circulating cancer stem-like cells (cCSCs) considering the treatment response and survival among patients with metastatic breast cancer. Accordingly, we performed this prospective study to clarify the prognostic significance of baseline cCSCs for metastatic breast cancer in terms of first-line chemotherapy. Methods Between April 2014 and January 2016, we prospectively enrolled 48 patients with stage IV breast invasive ductal carcinoma who underwent first-line chemotherapy. We identified and analyzed CTCs and cCSCs by using a protocol based on negative selection and flow cytometry before chemotherapy. CTCs were identified as EpCAM+Hoechst+CD45– cells and cCSCs as CD133+EpCAM+Hoechst+CD45– cells. cCSCs were expressed as a percentage of CTCs. The associations between CTCs, cCSCs, and the clinicopathological variables that were predictive of the treatment response and survival outcome were analyzed using univariate and multivariate analyses. Results We identified CTCs in all the enrolled patients, with a median number of 33.9/mL CTCs. CSCs were isolated in 97.9% of the patients; the median percentage of cCSCs was 14.7%. A high baseline level of cCSCs was correlated with an inferior tumor response rate (54.2% vs. 95.8%, p

Background: We investigated the associations between glycated hemoglobin (HbA1c) trajectories and cardiovascular outcomes using data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. Methods: We used HbA1c values within the first 2 years of treatment for modeling with a latent class growth model. Groups of HbA1c trajectories were modeled separately in the standard (group 1–group 4) and intensive (group 5–group 8) treatment arms. The primary outcome in the ACCORD study was a composite of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes. Effects of HbA1c trajectories on cardiovascular outcomes were analyzed using a Cox-proportional hazard model. Results: Baseline HbA1c levels for the eight trajectories (group 1–group 8) were 7.8 ± 0.8, 8.2 ± 0.9, 9.3 ± 1.1, 9.6 ± 1.2, 7.8 ± 0.7, 10.1 ± 0.8, 8.3 ± 0.7, and 9.5 ± 1.1%, respectively. The respective values after 2 years of treatment were 7.0 ± 0.6, 7.7 ± 0.7, 8.5 ± 0.9, 10.3 ± 1.3, 6.2 ± 0.4, 6.5 ± 0.6, 7.2 ± 0.6, and 8.5 ± 1.1%. After a median follow-up of 4.8 years, group 5 and group 6 had similar outcomes compared with group 1 (reference group). In contrast, group 3, group 4, and group 8 had higher risks of the primary composite outcome compared with group 1. Conclusion: HbA1c trajectory was associated with cardiovascular outcomes in type 2 diabetes patients with high cardiovascular risk.

Background: Acute lung injury (ALI) is a severe life-threatening inflammatory disease. Neutrophil activation is a major pathogenic factor in ALI. Protein kinase B (PKB)/AKT regulates diverse cellular responses, but the significance in neutrophilic inflammation and ALI remains unknown. Methods: Human neutrophils and neutrophil-like differentiated HL-60 (dHL-60) cells were used to examine the anti-inflammatory effects of 5,7-dimethoxy-1,4-phenanthrenequinone (CLLV-1). The therapeutic potential of CLLV-1 was determined in a mouse model of lipopolysaccharide (LPS)-induced ALI. Findings: CLLV-1 inhibited respiratory burst, degranulation, adhesion, and chemotaxis in human neutrophils and dHL-60 cells. CLLV-1 inhibited the phosphorylation of AKT (Thr308 and Ser473), but not of ERK, JNK, or p38. Furthermore, CLLV-1 blocked AKT activity and covalently reacted with AKT Cys310 in vitro. The AKT309–313 peptide-CLLV-1 adducts were determined by NMR or mass spectrometry assay. The alkylation agent-conjugated AKT (reduced form) level was also inhibited by CLLV-1. Significantly, CLLV-1 ameliorated LPS-induced ALI, neutrophil infiltration, and AKT activation in mice. Interpretation: Our results identify CLLV-1 as a covalent allosteric AKT inhibitor by targeting AKT Cys310. CLLV-1 shows potent anti-inflammatory activity in human neutrophils and LPS-induced mouse ALI. Our findings provide a mechanistic framework for redox modification of AKT that may serve as a novel pharmacological target to alleviate neutrophilic inflammation. Keywords: Acute lung injury, AKT, 5,7-dimethoxy-1,4-phenanthrenequinone, Inflammation, Neutrophil

Background: Studies have suggested that intravenous patient-controlled analgesia (IV-PCA) can be used safely for the treatment of background pain in burn patients. However, no comprehensive protocols have been published. How patient or surgical factors correlate with the amount of opioid consumption remains unclear. The aim of this study is to provide an IV-PCA protocol for alleviating pain for burn injuries, and to assess factors correlated with opioid consumption. Methods: At the Mackay Memorial Hospital, a retrospective analysis from June 27th to October 31st of 2015 was carried out to investigate the use of IV-PCA in relation to the demographic and clinical data of patients who suffered from burn injuries due to a massive explosion of flammable powder. A standardized morphine IV-PCA protocol with rapid escalation was implemented. Variables assessed included age, weight, gender, days of usage, total surface area burned (TBSAB) and operations. Results: Among the 23 patients who received IV-PCA for burn pain control, it was noted that the larger the TBSAB and the higher the visual analogue scale (VAS), the more amount of morphine was consumed. Correlations between morphine consumption positively with weight (P

Background: The effect of glucose control, especially variability of glycated hemoglobin (HbA1c), on estimated glomerular filtration rate (eGFR) decline in type 2 diabetes is still debatable. Methods: We used tertiles of coefficient of variation (CV) to determine the variability of HbA1c (HbA1c_CV). Mixed model repeated measures (MMRM) were used to evaluate the annual eGFR decline rate. Results: In 1383 type 2 diabetic patients, we found the greater the HbA1c_CV, the greater the eGFR decline ( p = 0.01, −0.99 in low, −1.73 in mid, and −2.53 ml/min/1.73 m 2 /year in high HbA1c_CV). Regardless of eGFR (⩾60 or

Sarcopenia is a wild chronic disease among elderly people. Although it does not entail a life-threatening risk, it will increase the adverse risk due to the associated unsteady gait, fall, fractures, and functional disability. The import factors in diagnosing sarcopenia are muscle mass and strength. The examination of muscle mass must be carried in the clinic. However, the loss of muscle mass can be improved by rehabilitation that can be performed in non-medical environments. Electronic impedance myography (EIM) can measure some parameters of muscles that have the correlations with muscle mass and strength. The goal of this study is to use machine learning algorithms to estimate the total mass of thigh muscles (MoTM) with the parameters of EIM and body information. We explored the seven major muscles of lower limbs. The feature selection methods, including recursive feature elimination (RFE) and feature combination, were used to select the optimal features based on the ridge regression (RR) and support vector regression (SVR) models. The optimal features were the resistance of rectus femoris normalized by the thigh circumference, phase of tibialis anterior combined with the gender, and body information, height, and weight. There were 96 subjects involved in this study. The performances of estimating the MoTM used the regression coefficient (r2) and root-mean-square error (RMSE), which were 0.800 and 0.929, and 1.432 kg and 0.980 kg for RR and SVR models, respectively. Thus, the proposed method could have the potential to support people examining their muscle mass in non-medical environments.

Oxaliplatin-based chemotherapy is an alternative systemic treatment for patients with metastatic hepatocellular carcinoma (HCC) who were refractory or intolerant to sorafenib. To date, there have been no biomarkers reported to monitor the therapeutic efficacy and to predict the outcomes of HCC patients receiving oxaliplatin-based chemotherapy. Methods: Eighty-one HCC patients with elevated baseline α-fetoprotein (AFP) levels and extrahepatic spreading who received oxaliplatin-based chemotherapy between 2012 and 2014 were retrospectively enrolled in this study. Two AFP tests were performed, at baseline and 2–4 weeks after the initiation of chemotherapy. The change in AFP levels was calculated for survival analysis. Results: In the AFP decline group (decreased compared to baseline), the median progression-free survival (PFS) and overall survival (OS) were 7.0 months and 12.3 months, respectively. In the AFP nondecline group, the median PFS and OS were 2.3 months and 3.0 months, respectively. The difference in OS between the two groups was significant (p

Three new tuliposides H–J (1–3) and 11 known compounds were obtained from the methanolic extracts of the bulbs of Amana edulis for the first time. Their structures were elucidated by NMR, MS, and IR spectroscopic data, optical rotation, and Mosher’s method. The melanogenesis properties of all the isolates were evaluated in B16 melanoma cells. Consequently, tributyl citrate (9) had anti-melanogenesis activity but was cytotoxic toward B16. (+)-Pyroglutamic acid (4), (+)-butyl 5-oxopyrrolidine-2-carboxylate (6), (–)-3-hydroxy-2-methylbutyrolactone (10), and 5-(hydroxymethyl)furfural (12) had increased melanin productions and tyrosinase activities. Those active components could be further studied as the candidates against melanoma and vitiligo for skin diseases or whitening/hypopigmentation for hair.

Researchers do not fully understand consumers’ responses to negative co-branding events; thus, they report inconsistent evidence regarding the negative impact on the partnering brands. Our research bridges a gap in this research stream, and answers an important question: When a service failure occurs, could the two different models of consumers’ brand schema change affect their negative perception of each brand partner? By using a theoretical and mathematical modeling approach, we offer two propositions. The first proposition shows that, under consumers’ book-keeping cognitive process, the negative spillover effect occurs for both brands. The second proposition argues that, when the sub-typing model is assumed, it is possible that one brand suffers while the other escapes the blame for the failure. To our knowledge, this is one of the first few studies to identify circumstances in which a negative spillover effect may or may not occur to brand partners in co-branding service failures.

Cause-related Marketing (CrM) has become an increasingly popular marketing approach over the past two decades. However, neither researchers nor organizations fully understand the determinants of a successful CrM partnership. This research fills this gap. Specifically, we employ the schema theory to explore circumstances in which the CrM alliance cannot achieve a success. We use a theoretical modeling approach to report that, when consumers’ typicality-based cognitive process is assumed, the CrM activity with the partners’ more-discrepant attribute profile cannot be evaluated favorably, but the attribute-level uncertainty about the CrM alliance is less likely to feedback to the two partners. Furthermore, we argue that, under the schema-plus-tag model, consumers may not like the CrM program with a similar attribute profile. Therefore, this CrM approach may fail. To our knowledge, we are the first to apply the schema theory to explain how a CrM alliance can achieve a success.

Target of rapamycin complex 1 (TORC1) and AMP-activated protein kinase (AMPK) antagonistically modulate metabolism and aging. However, how they coordinate to determine longevity and if they act via separable mechanisms is unclear. Here, we show that neuronal AMPK is essential for lifespan extension from TORC1 inhibition, and that TORC1 suppression increases lifespan cell non autonomously via distinct mechanisms from global AMPK activation. Lifespan extension by null mutations in genes encoding raga-1 (RagA) or rsks-1 (S6K) is fully suppressed by neuronal-specific rescues. Loss of RAGA-1 increases lifespan via maintaining mitochondrial fusion. Neuronal RAGA-1 abrogation of raga-1 mutant longevity requires UNC-64/syntaxin, and promotes mitochondrial fission cell nonautonomously. Finally, deleting the mitochondrial fission factor DRP-1 renders the animal refractory to the pro-aging effects of neuronal RAGA-1. Our results highlight a new role for neuronal TORC1 in cell nonautonomous regulation of longevity, and suggest TORC1 in the central nervous system might be targeted to promote healthy aging.

A reliable temporary bonding scheme with both inorganic amorphous silicon release layer and HD-3007 polyimide based on high 355-nm-wavelength laser absorption coefficient in release layer is proposed and investigated. Effects of laser absorption coefficient and laser ablation path are also studied to develop a high throughput laser ablation process. The bonding scheme can be achieved within the optimized temperature of 210 °C under 1 MPa bonding force. In addition, chemical resistance, mechanical strength with reliability assessment, and thermal stability test for bonded structure are inspected. There is no obvious degradation in electrical characterization after laser ablation, indicating that the temporary bonding scheme has high potential to be used for 3-D integration applications.

Product involvement is an important factor in consumer evaluation of co-branding. However, academic discussions over this factor have largely been neglected. This paper bridges this gap and investigates how product involvement moderates the strength of the reciprocal effect on each brand partner. We validate two theory-driven propositions by using a theoretical modeling approach. Proposition 1 explains that the negative reciprocal effect on partnering brands is stronger in the scenario of higher-involved categories than in lower-involved categories. Proposition 2 argues that the positive reciprocal effect on partnering brands can be more significant in the case of lower-involved categories than in higher-involved categories. To the best of our knowledge, we are the first to explore the influence of product involvement on reciprocal effects in the scenario of a moderately-incongruent co-branding alliance.

Background: The role of circulating tumor cells (CTCs) for predicting the recurrence of cancer in lung cancer patients after surgery remains unclear. Methods: A negatively selected protocol of CTC identification was applied. For all the enrolled patients, CTC testing was performed before and after surgery on the operation day (day 0), postoperative day 1, and day 3. The daily decline and trend of CTCs were analyzed to correlate with cancer relapse. The mixed model repeated measures (MMRM) adjusted by cancer characteristics was applied for statistical significance. Results: Fifty patients with lung mass undergoing surgery were enrolled. Among 41 primary lung cancers, 26 (63.4%) were pathological stage Tis and I. A total of 200 CTC tests were performed. MMRM analysis indicated that surgery could contribute to a CTC decline after surgery in all patients with statistical significance (p = 0.0005). The daily decrease of CTCs was statistically different between patients with and without recurrence (p = 0.0068). An early rebound of CTC counts on postoperative days 1 and 3 was associated with recurrence months later. Conclusion: CTC testing can potentially serve as a tool for minimal residual disease detection in early-staged lung cancer after curative surgery.

Strobilanthes cusia (Nees) Kuntze is a Chinese herbal medicine used in the treatment of respiratory virus infections. The methanol extract of S. cusia leaf contains chemical components such as β-sitosterol, indirubin, tryptanthrin, betulin, indigodole A, and indigodole B that have diverse biological activities. However, the antiviral action of S. cusia leaf and its components against human coronavirus remains to be elucidated. Human coronavirus NL63 infection is frequent among immunocompromised individuals, young children, and in the elderly. This study investigated the anti-Human coronavirus NL63 (HCoV-NL63) activity of the methanol extract of S. cusia leaf and its major components. The methanol extract of S. cusia leaf effectively inhibited the cytopathic effect (CPE) and virus yield (IC50 = 0.64 μg/mL) in HCoV-NL63-infected cells. Moreover, this extract potently inhibited the HCoV-NL63 infection in a concentration-dependent manner. Among the six components identified in the methanol extract of S. cusia leaf, tryptanthrin and indigodole B (5aR-ethyltryptanthrin) exhibited potent antiviral activity in reducing the CPE and progeny virus production. The IC50 values against virus yield were 1.52 μM and 2.60 μM for tryptanthrin and indigodole B, respectively. Different modes of time-of-addition/removal assay indicated that tryptanthrin prevented the early and late stages of HCoV-NL63 replication, particularly by blocking viral RNA genome synthesis and papain-like protease 2 activity. Notably, tryptanthrin (IC50 = 0.06 μM) and indigodole B (IC50 = 2.09 μM) exhibited strong virucidal activity as well. This study identified tryptanthrin as the key active component of S. cusia leaf methanol extract that acted against HCoV-NL63 in a cell-type independent manner. The results specify that tryptanthrin possesses antiviral potential against HCoV-NL63 infection.

INTRODUCTION:A high hemoglobin glycation index (HGI) and glycated hemoglobin (HbA1c) level are associated with greater inflammatory status, and dipeptidyl peptidase-4 (DPP-4) inhibitors can suppress inflammation. We aimed to evaluate the relationship between HGI and the therapeutic effect of DPP-4 inhibitors. METHODS:This retrospective cohort study followed 468 patients with type 2 diabetes receiving DPP-4 inhibitor treatment for 1 year. Estimated HbA1c was calculated using a linear regression equation derived from another 2969 randomly extracted patients with type 2 diabetes based on fasting plasma glucose (FPG) level. The subjects were divided into two groups based on HGI (HGI = observed HbA1c - estimated HbA1c). Mixed model repeated measures were used to compare the treatment efficacy after 1 year in patients with a low (HGI

This paper applies the stereotype change theory to help bridge a major literature gap on co-branding partner selection: why both identical and highly different brand pairs often fail. We argue that, given that a primary goal of establishing a co-branding alliance is to positively revise consumers’ beliefs about important attributes of the allying brands, the case of no belief-revision can lead to a failure of the alliance. We show that both an identical and a highly incongruent partnership in terms of attribute-level difference can fail due to the lack of belief-revision. We report that a moderately incongruent brand pair is a promising decision on co-branding partner selection. In doing so, our research contributes to the explanation of why the two “extreme” types of co-branding alliances may fail from the perspective of consumer evaluation. For brand managers, we offer a normative guideline for co-branding partner selection.

Two new alkaloids, 9-methoxy-18,19-dehydrocamptothecin (1) and 5- hydroxymappicine-20-O-β-glucopyranoside (2a/2b as a racemic mixture), together with nine known compounds: camptothecin (3), 9-methoxy-camptothecin (4), 5-hydroxycamptothecin (5a/5b racemic mixture), 5-hydroxy-9-methoxycamptothecin (6a/6b racemic mixture), diosmetin (7), apigenin (8), apigenin-7-O-glucopyranoside (9), rosin (cinnamyl- O-β-D-glucopyranoside) (10) and amarantholidoside IV (11) were isolated from the immature seeds of Nothapodytes foetida (Wight) Sleumer. The structures were elucidated by spectroscopic analyses. In the present research, compounds 1, 3, 4, 5a/5b and 6a/6b, also showed in vitro cytotoxicity against six cancer cell lines (HepG2, Hep3B, MDA-MB- 231, MCF-7, A549, and Ca9-22). Among them, compound 1 exhibited significant cytotoxicity against these cancer cell lines, with IC50 of 0.24-6.57 μM. Furthermore, HPLC profiles were developed for qualitative and quantitative analysis of these active constituents in different parts of this plant, including mature and immature seeds, leaves, stems and roots. The results revealed that compounds 3 and 4 have the highest concentrations, which are found in the roots part of the plant.

Visual crowding-the inability to see an object when it is surrounded by flankers in the periphery-does not block semantic activation: unrecognizable words due to visual crowding still generated robust semantic priming in subsequent lexical decision tasks. Based on the previous finding, the current study further explored whether unrecognizable crowded words can be temporally integrated into a phrase. By showing one word at a time, we presented Chinese four-word idioms with either a congruent or incongruent ending word in order to examine whether the three preceding crowded words can be temporally integrated to form a semantic context so as to affect the processing of the ending word. Results from both behavioral (Experiment 1) and Event-Related Potential (Experiment 2 and 3) measures showed congruency effect in only the non-crowded condition, which does not support the existence of unconscious multi-word integration. Aside from four-word idioms, we also found that two-word (modifier + adjective combination) integration-the simplest kind of temporal semantic integration-did not occur in visual crowding (Experiment 4). Our findings suggest that integration of temporally separated words might require conscious awareness, at least under the timing conditions tested in the current study.

Ipomoea batatas has long been used in folk medicine for the treatment of hyperglycemia or as a food additive for the prevention of type 2 diabetes. However, neither the plant extract nor its active components have been evaluated systematically. In this work four crude extracts, including n-hexane- (IBH), 95% MeOH- (IBM), n-BuOH- (IBB), and H2O-soluble (IBW) fractions, were prepared by fractionation of a methanolic extract of purple I. batatas leaves. Twenty-four pure compounds 1–24 were then isolated by various chromatographic techniques and their structures identified from NMR and MS data. Glucose uptake assays in differentiated 3T3-L1 adipocytes and rat primary hepatocytes, as well as western blot analysis, were carried out to evaluate the antidiabetic activity of this species. The IBH crude fraction, with methyl decanoate (22) as a major and active compound, showed the greatest effect on glucose uptake, most likely via activation of Glut4 and regulation of the PI3K/AKT pathway. Quercetin 3-O-β-d-sophoroside (1), quercetin (3), benzyl β-d-glucoside (10), 4-hydroxy-3-methoxybenzaldehyde (12), and methyl decanoate (22) could be important components contributing to the antidiabetic effects. We conclude that purple I. batatas leaves have potential as an antidiabetic plant source and the active constituents 1, 3, 10, 12, and 22 are promising lead candidates for future investigation.

In a structure-activity relationship (SAR) study, 3-methoxy-1,4-phenanthrenequinones, calanquinone A (6a), denbinobin (6b), 5-OAc-calanquinone A (7a) and 5-OAc-denbinobin (7b), have significantly promising cytotoxicity against various human cancer cell lines (IC(50) 0.08-1.66 µg/mL). Moreover, we also established a superior pharmacophore model for cytotoxicity (r = 0.931) containing three hydrogen bond acceptors (HBA1, HBA2 and HBA3) and one hydrophobic feature (HYD) against MCF-7 breast cancer cell line. The pharmacophore model indicates that HBA3 is an essential feature for the oxygen atom of 5-OH in 6a-b and for the carbonyl group of 5-OCOCH(3) in 7a-b, important for their cytotoxic properties. The SAR for moderately active 5a-b (5-OCH(3)), and highly active 6a-b and 7a-b, are also elaborated in a spatial aspect model. Further rational design and synthesis of new cytotoxic phenanthrene analogs can be implemented via this model. Additionally, employing a ChemGPS-NP based model for cytotoxicity mode of action (MOA) provides support for a preliminary classification of compounds 6a-b as topoisomerase II inhibitors.

Protoapigenone, a natural flavonoid possessing an unusual p-quinol moiety on its B-ring, is a novel prospective anticancer agent with low toxicity that is currently in development. The first economical, one-step synthesis of protoapigenone from apigenin is described on up to gram scale. 13 new 1'-O-alkylflavone analogs were also synthesized, either from apigenin or β-naphthoflavone. The in vitro cytotoxic activity of each compound was tested on six human cancer cell lines (HepG2, Hep3B, Ca9-22, A549, MCF-7 and MDA-MB-231). In the case of 1'-O-alkyl-protoapigenone derivatives, structure-activity relationships were found depending on the side-chain, and protoapigenone 1'-O-butyl ether was found to exert significantly stronger activity against three of the cell lines (Hep3B, MCF-7 and MDA-MB-231) than its non-substituted analog, protoapigenone itself. In contrast to this, all β-naphthoflavone derivatives bearing the same pharmacophore on their B-ring showed decreased cytotoxic activities when substituted with an O-alkyl side-chain at position 1', comparing to that of the non-substituted compound.