bluuebunny/crossref_metadata_2025_split huggingface dataset:
Body Mass Index, Waist Circumference, and Cognitive Decline Among Chinese Older Adults: A Nationwide Retrospective Cohort Study
Authors: Liang Fang , Fu Jialin , Moore Justin B. , Zhang Xinge , Xu Yijia , Qiu Nan , Wang Yechuang , Li Rui 
Published: March 2022

BackgroundThe reported associations between body mass index (BMI), waist circumference (WC), and cognitive decline are not consistent, especially in older adults.ObjectiveThis study aims to investigate the longitudinal associations of BMI, WC, and their change values with cognitive decline among Chinese adults aged 60 years and older and to examine the potential moderating effect of sex on these relationships.MethodsThe participants in this study were from waves one to four (2011–2018) of the China Health and Retirement Longitudinal Study (CHARLS). Cognition function, BMI, and WC were measured at four examinations over 7 years. The interview-based cognitive assessments of memory, orientation and attention, and visuospatial ability were recorded. Standardized global cognitive scores were generated. BMI and WC were objectively measured. Mixed-effects models were performed to evaluate the associations.ResultsA final sample of 3,035 Chinese older adults [mean (SD) age, 66.94 (5.43) years; 40.16% (n = 1,219) women] were included. Higher BMI (estimate = 0.0107; SE = 0.0024; p &lt; 0.0001) and WC (estimate = 0.0019; SE = 0.0006; p = 0.0037) were associated with slower cognition score decline over a 7-year follow-up, while greater BMI variability (estimate = −0.0365; SE = 0.0116; p = 0.0017) was related to faster cognition score decline. The results were not modified by sex. BMI-defined overweight (estimate = 0.0094; SE = 0.0043; p = 0.0298) was associated with a slower cognition score decline, and both large weight gain (estimate = −0.0266; SE = 0.0074; p = 0.0003) and large WC loss (estimate = −0.0668; SE = 0.0329; p = 0.0426) were associated with faster cognition score decline.ConclusionAmong Chinese older adults, higher BMI, higher WC, and overweight are related to slower cognitive decline, while greater BMI variability, large weight gain, and large WC loss are associated with faster cognitive decline.
Comparative Effectiveness of Abiraterone and Enzalutamide in Patients With Metastatic Castration-Resistant Prostate Cancer in Taiwan
Authors: Li Pei-Yu , Lu Ying-Hao , Chen Chung-Yu 
Published: March 2022

BackgroundAbiraterone and enzalutamide are widely used as first-line treatment for metastatic castration-resistant prostate cancer (mCRPC); however, their efficacy in mCRPC has been inconsistently demonstrated in other outcome studies from real-world databases. The aim of our study was to assess the comparative effectiveness of abiraterone and enzalutamide in patients with mCRPC using real-world data from Taiwan.MethodsThis retrospective cohort population-based study included patients identified in the Taiwan National Health Insurance Research Database who had been diagnosed with mCRPC and who had taken abiraterone or enzalutamide between December 2014 and August 2017. The study’s outcome evaluated the differences in overall survival (OS) and time to treatment failure (TTF) between abiraterone and enzalutamide over a 15-month follow-up period. The patients were followed from the index date to when the outcome occurred, to December 31, 2018, or to the patients’ withdrawal from the National Health Insurance program. The estimated relative treatment effects of abiraterone and enzalutamide on OS and TTF were adjusted by the inverse probability of treatment weighting (IPTW) using the Kaplan–Meier method and a Cox proportional hazards model.ResultsThe abiraterone and enzalutamide groups consisted of 1,046 and 118 patients, respectively. After IPTW adjustment, 1,164 patients in the abiraterone group and 1,158 in the enzalutamide group underwent an outcome evaluation. Enzalutamide showed a similar OS rate to that of abiraterone (57.58% vs. 49.51%, p = 0.095 by log-rank test). Enzalutamide significantly reduced the risk of death for mCRPC when compared with abiraterone [adjusted hazard ratio (aHR), 0.828; 95% CI 0.731–0.938]. However, similar results were not observed in the TTF outcomes (63.84% vs. 67.79%, p = 0.2651 by log-rank test; aHR, 0.902; 95% CI 0.812–1.002).ConclusionIn conclusion, enzalutamide was associated with better OS for mCRPC than abiraterone in the Taiwan population. Our study showed that there was no statistically significant difference in TTF between enzalutamide and abiraterone. Studies with longer surveillance of enzalutamide and abiraterone using real-world databases are needed.
Etiologic Classification of 541 Infantile Spasms Cases: A Cohort Study
Authors: Peng Pan , Kessi Miriam , Mao Leilei , He Fang , Zhang Ciliu , Chen Chen , Pang Nan , Yin Fei , Pan Zou , Peng Jing 
Published: March 2022

ObjectiveTo explore the etiology of infantile spasms (IS) in a large Chinese cohort based on the United States National Infantile Spasms Consortium (NISC) classification.MethodsIn the present study, we recruited IS patients diagnosed at a single center (Xiangya Hospital, Central South University) between Jan 2010 and Aug 2019. Thereafter, we collected their clinical and genetic information retrospectively. Their underlying etiologies were classified according to the NISC classification and then compared in different scenarios to understand their distribution.ResultsA total of 541 patients with IS from 18 provinces were included in this study. The underlying etiology was identified in 53.2% of the cases: structural-acquired, 25.3%; genetic, 12.9%; genetic-structural, 7.2%; structural-congenital, 5.0%; metabolic, 2.4%; infections, 0.4% and immune, 0%. Whole-exome sequencing (WES) provided the highest diagnostic yield (26.9%). In structural-acquired IS, the proportion of hypoglycemic brain injuries was significant, second only to hypoxic-ischemic encephalopathy. There was no patient discovered to have Down syndrome. STXBP1, CDKL5, TSC2, KCNQ2, IRF2BPL, and TSC1 were the most frequently implicated genes. Genetic causes were found to be the most common cause of IS in the early onset group, while structural-acquired etiologies were common in males and preterm babies. Patients with pre-spasm seizures were associated with a higher proportion of identified causes than those without. Non-acquired structural etiologies were more common in patients without hypsarrhythmia than in those with hypsarrhythmia.SignificanceThe most prevalent cause of IS was structural acquired followed by genetic causes. When brain MRI fails to detect the etiology, we propose WES as the next step. Structural-acquired IS and cases with genetic disorders are characteristic of the Chinese cohort, however, the etiology differs with the patient's age of onset, gestation age at birth, sex, and the presence/absence of both pre-spasm seizures, and hypsarrhythmia.
Specific HER2 Exon 20 Gly776 Deletion-Insertions in Non-Small Cell Lung Cancer: Structural Analysis and Sensitivity to HER2-Targeted Tyrosine Kinase Inhibitors
Authors: Yang Guangjian , Xu Haiyan , Hu Jiaqi , Liu Runze , Hu Peizeng , Yang Yaning , Li Weihua , Hao Xuezhi , Zhang Shuyang , Xu Fei , Ai Xin , Li Junling , Wang Yan 
Published: March 2022

Background:HER2 exon 20 insertions remain a subset heterogeneous alterations in lung cancer, with currently unmet need for precision targeted therapy. G776delinsVC, a typical HER2 exon 20 deletion-insertion at codon Gly776, was reported to respond discrepantly to afatinib compared with the predominant insertion A775_G776insYVMA (YVMA). However, it lacks structural evidence to illustrate the possible mechanism and predict the binding activities of its similar variants over YVMA insertion to HER2-targered tyrosine kinase inhibitors (TKIs).Methods: Real-world cohort study was performed to investigate clinical outcomes with HER2-targeted TKI afatinib and pyrotinib, and structural analysis for exon 20 Gly776 deletion-insertions G776delinsVC, G776delinsLC and G776delinsVV, and YVMA by molecular dynamics simulation and cellular kinase inhibition assay were provided for full exploration.Results: Afatinib revealed low objective response rate (ORR) of 0–9.5% and short median progression-free survival (mPFS) of 2.8–3.2 months for YVMA, but with higher ORR of 20–28.6% and longer mPFS of 4.3–7.1 months for G776delinsVC. Pyrotinib presented significantly improved PFS benefit than afatinib for G776delinsVC and YVMA as first-line (median, 6.8 vs. 3.4 months, p = 0.010) or second-line therapy (median, 5.8 vs. 2.8 months, p &lt; 0.001). No significant difference was observed on drug binding pocket and TKI binding activity between G776delinsVC, G776delinsLC and G776delinsVV, and both afatinib and pyrotinib showed favorable binding activity. YVMA insertion significantly affected the loop region with altering HER2 protein secondary structure and forming steric hindrance to binding of afatinib. Pyrotinib showed the best selectivity to HER2, with more favorable activity to YVMA than afatinib indicated by cellular inhibition assay.Conclusion: Both afatinib and pyrotinib showed favorable activity for NSCLC patients with HER2 exon 20 Gly776 deletion-insertions. Pyrotinib revealed more potent activity to A775_G776insYVMA insertion than afatinib due to the steric binding hindrance induced by YVMA.
Effectiveness and Economic Evaluation of Polyene Phosphatidyl Choline in Patients With Liver Diseases Based on Real-World Research
Authors: Fan Jian-Gao , Li Ying , Yu Ze , Luo Xing-Xian , Zheng Ping , Hao Xin , Wang Ze-Yuan , Gao Fei , Zhang Guo-Qing , Feng Wan-Yu 
Published: March 2022

Aims: Liver disease has high prevalence, number, and disease burden in China, and polyene phosphatidyl choline (PPC) is a widely used liver protective drug. We aim to explore the effectiveness and economy of PPC in patients with liver diseases based on real-world research and compare with other hepatoprotective drugs.Methods: This is a “three-phase” study from three medical centers, including descriptive study of patients using PPC injection, self-control case study of patients using PPC injection, and specific-disease cohort study of patients using PPC injection or control drugs. The major measurements of liver function for effectiveness analysis were the alanine transaminase (ALT) level changes and recovery rate. The main statistical methods were Wilcoxon signed rank test, χ2 test, and Mann–Whitney U test. Propensity score matching was applied to reduce bias. Cost-effectiveness analysis, cost minimization analysis, and sensitivity analysis were used for economic evaluation.Results: PPC alone or in combination with glutathione and magnesium isoglycyrrhizinate shows less total hospitalization cost (p &lt; 0.05) and smaller cost-effectiveness ratio and was effective in protecting liver function, especially in patients with liver transplantation or postoperation of nontumor liver disease (ALT decreased significantly after PPC treatment; p &lt; 0.05). Glutathione and magnesium isoglycyrrhizinate combined with PPC could enhance the protective function of liver.Conclusion: PPC was an effective and economic liver protective drug in patients with specific liver diseases, and PPC could enhance the liver protective function of glutathione and magnesium isoglycyrrhizinate.
Dehydrocostus Lactone Suppresses Dextran Sulfate Sodium-Induced Colitis by Targeting the IKKα/β-NF-κB and Keap1-Nrf2 Signalling Pathways
Authors: Yuan Yun , Hu Qiongying , Liu Lu , Xie Fan , Yang Luyao , Li Yuchen , Zhang Chuantao , Chen Hongqing , Tang Jianyuan , Shen Xiaofei 
Published: March 2022

Dehydrocostus lactone (DCL) is a major sesquiterpene lactone isolated from Aucklandia lappa Decne, a traditional Chinese herbal medicine that used to treat gastrointestinal diseases. This study aimed to examine the therapeutic effects of DCL on dextran sulfate sodium (DSS)-induced colitis with a focus on identifying the molecular mechanisms involved in DCL-mediated anti-inflammatory activity in macrophages. First, oral administration of DCL (5–15 mg/kg) not only ameliorated symptoms of colitis and colonic barrier injury, but also inhibited the expression of proinflammatory cytokines and myeloperoxidase in colon tissues in DSS-challenged mice. Furthermore, DCL also exhibited significant anti-inflammatory activity in LPS/IFNγ-stimulated RAW264.7 macrophages. Importantly, DCL significantly suppressed the phosphorylation and degradation of IκBα and subsequent NF-κB nuclear translocation, and enhanced the nuclear accumulation of Nrf2 in LPS/IFNγ-treated RAW264.7 cells. Mechanistically, DCL could directly interact with IKKα/β and Keap1, thereby leading to the inhibition of NF-κB signalling and the activation of Nrf2 pathway. Furthermore, DCL-mediated actions were abolished by dithiothreitol, suggesting a thiol-mediated covalent linkage between DCL and IKKα/β or Keap1. These findings demonstrated that DCL ameliorates colitis by targeting NF-κB and Nrf2 signalling, suggesting that DCL may be a promising candidate in the clinical treatment of colitis.
Intravitreal Administration of rhNGF Enhances Regenerative Processes in a Zebrafish Model of Retinal Degeneration
Authors: Cocchiaro Pasquale , Di Donato Vincenzo , Rubbini Davide , Mastropasqua Rodolfo , Allegretti Marcello , Mantelli Flavio , Aramini Andrea , Brandolini Laura 
Published: March 2022

Nerve growth factor (NGF) is the best characterized neurotrophin, and it is known to play an important role in ocular homeostasis. Here, we demonstrated the expression of NGF receptors in adult zebrafish retina and optimized a light-induced retina degeneration (LID) zebrafish model that mimics human cone-rod disorders, demonstrating that intravitreal (IV) administration of rhNGF can boost zebrafish retinal regeneration in this model. Adult zebrafish retinae exposed to 60 h of light irradiation (60 h LID) displayed evident reduction of outer nuclear layer (ONL) thickness and cell number with presence of apoptotic cells. Retinal histologic evaluation at different time points showed that IV therapeutic injection of rhNGF resulted in an increase of ONL thickness and cell number at late time points after damage (14 and 21 days post injury), ultimately accelerating retinal tissue recovery by driving retinal cell proliferation. At a molecular level, rhNGF activated the ERK1/2 pathway and enhanced the regenerative potential of Müller glia gfap- and vim-expressing cells by stimulating at early time points the expression of the photoreceptor regeneration factor Drgal1-L2. Our results demonstrate the highly conserved nature of NGF canonical pathway in zebrafish and thus support the use of zebrafish models for testing new compounds with potential retinal regenerative properties. Moreover, the pro-regenerative effects of IV-injected NGF that we observed pave the way to further studies aimed at evaluating its effects also in mammals, in order to expedite the development of novel rhNGF-based therapeutic approaches for ophthalmological disorders.
Efficacy and Safety of Neostigmine Adjunctive Therapy in Patients With Sepsis or Septic Shock: A Randomized Controlled Trial
Authors: El-Tamalawy Mona M. , Soliman Moetaza M. , Omara Amany F. , Rashad Amal , Ibrahim Osama M. , El-Shishtawy Mamdouh M. 
Published: March 2022

Background: Neostigmine has been found to improve survival in animal models of sepsis. However, its feasibility, efficacy, and safety in patients with sepsis or septic shock have not been investigated.Aim: This parallel randomized controlled double-blinded design aimed to investigate the efficacy and safety of neostigmine as an adjunctive therapy in patients with sepsis or septic shock.Patients and Methods: A total of 167 adult patients with sepsis or septic shock were assessed for eligibility; 50 patients were randomized to receive a continuous infusion of neostigmine (0.2 mg/h for 120 h; neostigmine arm) or 0.9% saline (control arm) in addition to standard therapy. The primary outcome was the change in Sequential Organ Failure Assessment (SOFA) scores 120 h after therapy initiation. Secondary outcomes included mortality rates and changes in procalcitonin level.Results: The median (interquartile range) change in SOFA scores improved significantly in the neostigmine arm [−2 (−5, 1)] as compared with the control arm [1.5 (0, 2.8); p = 0.007]. Progression from sepsis to septic shock was more frequent in the control arm (p = 0.01). The incidence of shock reversal in patients with septic shock was significantly lower in the control arm than in the neostigmine arm (p = 0.04). Differences in 28-days mortality rates did not reach statistical significance between the control and neostigmine arms (p = 0.36). Percentage change in procalcitonin levels was similar in both arms (p = 0.74).Conclusion: Neostigmine adjunctive therapy may be safe and effective when administered in patients with sepsis or septic shock.Clinical Trial Registration: NCT04130230.
Promising Antioxidative Effect of Berberine in Cardiovascular Diseases
Authors: An Na , Zhang Guoxia , Li Yingjian , Yuan Chao , Yang Fan , Zhang Lijing , Gao Yonghong , Xing Yanwei 
Published: March 2022

Berberine (BBR), an important quaternary benzylisoquinoline alkaloid, has been used in Chinese traditional medicine for over 3,000 years. BBR has been shown in both traditional and modern medicine to have a wide range of pharmacological actions, including hypoglycemic, hypolipidemic, anti-obesity, hepatoprotective, anti-inflammatory, and antioxidant activities. The unregulated reaction chain induced by oxidative stress as a crucial mechanism result in myocardial damage, which is involved in the pathogenesis and progression of many cardiovascular diseases (CVDs). Numerous researches have established that BBR protects myocardium and may be beneficial in the treatment of CVDs. Given that the pivotal role of oxidative stress in CVDs, the pharmacological effects of BBR in the treatment and/or management of CVDs have strongly attracted the attention of scholars. Therefore, this review sums up the prevention and treatment mechanisms of BBR in CVDs from in vitro, in vivo, and finally to the clinical field trials timely. We summarized the antioxidant stress of BBR in the management of coronary atherosclerosis and myocardial ischemia/reperfusion; it also analyzes the pathogenesis of oxidative stress in arrhythmia and heart failure and the therapeutic effects of BBR. In short, BBR is a hopeful drug candidate for the treatment of CVDs, which can intervene in the process of CVDs from multiple angles and different aspects. Therefore, if we want to apply it to the clinic on a large scale, more comprehensive, intensive, and detailed researches are needed to be carried out to clarify the molecular mechanism and targets of BBR.
Pathways of Parental Education on Children's and Adolescent's Body Mass Index: The Mediating Roles of Behavioral and Psychological Factors
Authors: Seum Teresa , Meyrose Ann-Katrin , Rabel Matthias , Schienkiewitz Anja , Ravens-Sieberer Ulrike 
Published: March 2022

AimThe increasing body mass index (BMI) often followed by overweight and obesity is a global health problem of the 21st century. Children and adolescents with lower socioeconomic status are more affected than their counterparts. The mechanisms behind these differences must be well understood to develop effective prevention strategies. This analysis aims at examining the association of parental education as an indicator of the socioeconomic status on children's and adolescent's body mass index and the role of behavioral and psychological risk factors for a higher BMI longitudinally.MethodsThe analysis was based on a nationwide sample of N = 460 children and adolescents, aged 11 to 17 at baseline (2009–2012), who took part in the representative BELLA study, the mental health module of the German National Health Interview and Examination Survey among Children and Adolescents (KiGGS). A follow-up was conducted 5 years later. Using mediation analyses, the mediating effects of breakfast consumption, consumption of sugar-sweetened beverages, screen time, physical activity, mental health problems (Strengths and Difficulties Questionnaire), and health-related quality of life (KIDSCREEN-10) on the association of parent's years of education on their children's BMI were investigated.ResultsA lower level of parental education was significantly associated with a higher BMI in children and adolescents 5 years later. The association was partially mediated by breakfast consumption and total screen time, with breakfast consumption mediating 16.7% and total screen time 27.8% of the association. After controlling for age, gender, and migration status, only breakfast consumption remained a partial mediator (8.5%). Other included variables had no mediating effects.ConclusionsPreventive measures should be mainly targeted at children and adolescents of parents with lower educational levels. Tailored strategies to prevent the development of overweight and obesity in this population among children and adolescents should promote daily breakfast consumption at home and reducing screen time.
Sexually Transmitted Infections and Associated Risk Factors Among Male Clients of Sex Workers: A Cross-Sectional Pilot Project in Antwerp, Belgium
Authors: Platteau Tom , De Baetselier Irith , Van Mieghem Heleen , Tsoumanis Achilleas , Keersmaekers Kris , Ooms Lieselot , Cuylaerts Vicky , Florence Eric 
Published: March 2022

IntroductionPrevalence of sexually transmitted infections (STIs) is increasing in Belgium in recent years. Clients of sex workers form a key population for acquisition of STIs, due to their sexual relations, with or without a condom, with sex workers. STI testing uptake is low among clients of sex workers, and prevalence of STIs remains to be investigated in Belgium. Therefore, we offered STI-testing to clients of sex workers during outreach sessions in Antwerp.MethodsTime location sampling (TLS) was used to improve representativeness of the sample during ten test sessions in the red light district, Antwerp in May and September 2019 by using a passive approach. Individuals that were interested to get tested for STIs could enter the study. Participants completed an online survey and samples for STI testing were collected. Testing included HIV, syphilis, Chlamydia trachomatis (Ct) and Neisseria gonorrhoeae (Ng). Test results were communicated via a cell phone message (for negative test results) or by phone (for positive test results).ResultsIn total, 154 male clients of sex workers with a median age of 38 participated. A total of eight Ct and one Ng infections were detected. TLS analysis revealed a Ct/Ng prevalence of 8.2%. No new HIV nor syphilis infections were detected. Using univariate analysis, testing positive for STI was associated with younger age and anorectal sex with a sex worker. Using multivariate analysis, an STI-positive test result was associated with being younger, having non-Belgian nationality, and being in a relationship.ConclusionOur study found a substantial prevalence of Ct/Ng which highlights the need for sensitization and facilitation of STI testing among clients of sex workers. It is difficult to compare results due to the lack of reference material. Moreover, our relatively small convenience sample limits generalizability of results. However, phone counseling (for positive test results) was accepted, linkage to care was provided, and partner notification was facilitated.