bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Comparison of Cilostazol versus Clopidogrel in Secondary Prevention of Noncardioembolic Ischemic Stroke
Authors: Lee Yu Jeong , Je Nam Kyung 
Published: February 2023

AbstractBackgroundCilostazol is a widely used antiplatelet drug for secondary stroke prevention in Asia, but its comparison with clopidogrel, another commonly used antiplatelet drug, is not well understood. This study aims to investigate the effectiveness and safety of cilostazol compared to clopidogrel for the secondary prevention of noncardioembolic ischemic stroke.MethodsA retrospective comparative effectiveness research analysis was conducted using 1:1 propensity-matched data from insured individuals between Jan 1, 2012, and Dec 31, 2019. The study used administrative claims data in Health Insurance and Review Assessment in Korea. Patients with diagnosis codes for ischemic stroke without atrial fibrillation, heart failure, valvular diseases, and myocardial infarction were included and divided into two groups, those receiving cilostazol and those receiving clopidogrel. The primary outcome was a recurrent ischemic stroke. Secondary outcomes included all-cause death, myocardial infarction, hemorrhagic stroke, and a composite of these outcomes. The safety outcome was major gastrointestinal bleeding.ResultsA total of 4754 patients were included in the propensity-matched population, with a median age of 67 years, 3080 (40.7%) were male, and 4480 (59.3%) were female. The study found no statistically significant difference in recurrent ischemic stroke (cilostazol group vs clopidogrel group, 2.7% vs 3.2%; 95% CI, 0.62-1.21), the composite outcome of recurrent ischemic stroke, all-cause death, myocardial infarction, and hemorrhagic stroke (5.1% vs 5.5%; 95% CI 0.75-1.22), and major gastrointestinal bleeding (1.3% vs 1.5%; 95% CI 0.57-1.47) between cilostazol and clopidogrel use patients. In subgroup analysis, cilostazol was associated with a lower incidence of recurrent ischemic stroke compared to clopidogrel in hypertensive patients (2.5% vs 3.9%; interaction P = 0.41).ConclusionsThis real-world, comparative effectiveness research study suggests that cilostazol is effective and safe for noncardioembolic ischemic stroke and may be associated with better effectiveness in hypertensive patients compared to clopidogrel over an 8-year period.
The Alfin-like transcription factor GmAlfin09 regulates endoplasmic reticulum stress in soybean via a peroxidase GmPRDX6
Authors: Chen Kai , Guo Dongdong , Yan Jiji , Zhang Huijuan , He Zhang , Wang Chunxiao , Tang Wensi , Zhou Yongbin , Chen Jun , Xu Zhaoshi , Ma Youzhi , Chen Ming 
Published: February 2023

ABSTRACTSoybean is a valuable oil crop cultivated throughout the world, but also highly susceptible to environmental stressors. The development of approaches to enhancing soybean stress resistance is thus vital to improving yields. In prior studies, Alfin has been shown to serve as an epigenetic regulator of plant growth and development. No studies of Alfin have yet been reported in soybean, however. In this study, the endoplasmic reticulum (ER) stress- and reactive oxygen species (ROS)-related transcription factor GmAlfin09 was identified. Screening of genes co-expressed withGmAlfin09unexpectedly led to the identification of the peroxidase GmPRDX6. Further analyses revealed that bothGmAlfin09andGmPRDX6were responsive to ER stress, with GmPRDX6 localizing to the ER under stress. Promoter binding experiments confirmed the ability of GmAlfin09 to directly bind theGmPRDX6promoter. WhenGmAlfin09andGmPRDX6were overexpressed in soybean, enhanced ER stress resistance and decreased ROS levels were observed. Together, these findings suggest that GmAlfin09 can promote the upregulation ofGmPRDX6, which subsequently localizes to the ER, reduced ROS levels, promotes ER homeostasis, and helps ensure the normal growth of soybean even under ER stress. This study highlights a novel genetic target for the future molecular breeding of stress-resistant soybean cultivars.HIGHLIGHTGmAlfin09 can increase the expression ofGmPRDX6to reduce ROS level under ER stress.
Parental body mass index and offspring childhood body size and eating behaviour: causal inference via parental comparisons and extended children of twins structural equation modelling
Authors: Bond Tom A , McAdams Tom A , Warrington Nicole M , Hannigan Laurie J , Eilertsen Espen Moen , Ayorech Ziada , Torvik Fartein A , Smith George Davey , Lawlor Deborah A , Ystrøm Eivind , Havdahl Alexandra , Evans David M 
Published: February 2023

AbstractBackgroundThe intergenerational transmission of obesity-related traits could propagate an accelerating cycle of obesity, if parental adiposity causally influences offspring adiposity via intrauterine or periconceptional mechanisms. We aimed to establish whether associations between parental peri-pregnancy body mass index (BMI) and offspring birth weight (BW), BMI until 8 years and 8-year eating behaviour are due to genetic confounding.MethodsWe used data from the Norwegian Mother, Father and Child Cohort Study and the Medical Birth Registry of Norway. We compared the strength of the associations of maternal versus paternal BMI with offspring outcomes, and used an extended children of twins structural equation model (SEM) to quantify the extent to which associations were due to genetic confounding (n = 17001 to 85866 children).FindingsMaternal BMI was more strongly associated than paternal BMI with offspring BW, but the maternal-paternal difference decreased for offspring BMI after birth. Greater parental BMI was associated with obesity-related offspring eating behaviours. SEM results indicated that genetic confounding did not explain the association between parental BMI and offspring BW, but explained the majority of the association with offspring BMI from 6 months onwards. For 8-year BMI, genetic confounding explained 79% (95% CI: 62%, 95%) of the covariance with maternal BMI and 94% (95% CI: 72%, 113%) of the covariance with paternal BMI.InterpretationWe found strong evidence that parent-child BMI associations are primarily due to genetic confounding, arguing against a strong causal effect of maternal or paternal adiposity on childhood adiposity via intrauterine or periconceptional mechanisms.
Acquisition and Clearance Dynamics ofCampylobacterin Children in Low- and Middle-Income Countries
Authors: Chen Dehao , Havelaar Arie H. , Platts-Mills James A. , Yang Yang 
Published: February 2023

SummaryBackgroundThe burden ofCampylobacterinfection is high in children under five years of age in low- and middle-income countries (LMIC), but its acquisition and clearance process is understudied due to scarcity of longitudinal data. We aim to quantify this process using a statistical modeling approach, leveraging data from a multi-nation study.MethodsMotivated by the MAL-ED study in which children from eight low- and middle- income countries were followed up for enteric infections during their first two years of life, we developed a two-stage Markov model to compare the dynamics of acquisition and clearance ofCampylobacterin children across countries and to explore antibiotic effectiveness onCampylobacterclearance. This model was validated using simulations and applied to the longitudinal data from MAL-ED.FindingsThe clearance rate was higher than the acquisition rate at most sites and times, but the temporal trend of these rates varied across countries. ForCampylobacter jejuni/coli, clearance was faster than acquisition under two years of age at all sites. ForCampylobacterspp., the acquisition rate surpassed the clearance rate in the second half of the first year in Bangladesh, Pakistan and Tanzania, leading to high prevalence in these countries. Bangladesh had the shortest (28 and 57 days) while Brazil had the longest (328 and 306 days) mean times to acquisition forCampylobacterspp. andC. jejuni/coli, respectively. South Africa had the shortest (10 and 8 days) while Tanzania had the longest (53 and 41 days) mean times to clearance forCampylobacterspp. andC. jejuni/colrespectively. The use of macrolides was associated with accelerated clearance ofC. jejuni/coliin Bangladesh and Peru and ofCampylobacterspp. in Bangladesh and Pakistan. The use of fluoroquinolones showed statistically meaningful effectiveness only in Bangladesh but for bothC. jejuni/coliandCampylobacterspp.InterpretationHigher burden ofCampylobacterinfection was mainly driven by high acquisition rate that was close to or surpassing the clearance rate. Acquisition usually peaked in 11-17 months in the LMIC setting, indicating the importance of targeting the first year of life for effective intervention.FundingBill & Melinda Gates Foundation.
Diabetes-related Distress and the Association to Hypertension and Cardiovascular Disease Among Individuals Living with Type 2 Diabetes in Rural areas in Vietnam
Authors: Sahl Amalie Sophie , Khong Thi Diep , Nguen Duc Thanh , Huyen Dieu , Søndergaard Jens , Nielsen Janni , Bygbjerg Ib Christian , Gammeltoft Tine , Meyrowitsch Dan W. 
Published: February 2023

ABSTRACTObjectiveThe prevalence of diabetes has been rising in rural areas of Vietnam over the last years to the extend where it has become a public health burden. Individuals with diabetes-related distress (DRD) is in greater risk of adverse health outcomes e.g. lower blood sugar control and polypharmacy. The objective of this study is to assess the association between hypertension and cardiovascular disease (CVD) and the occurrence of DRD among individuals with type 2 diabetes (T2D) in rural areas of Vietnam.MethodThis is a cross-sectional study of 806 individuals who had been receiving treatment for T2D at a district hospital in the northern Vietnamese province Thai Binh. Based on self-reported data DRD was assessed through Problem Areas in Diabetes scale 5 (PAID5) and defined as a score of 8 or above. The occurrence of the comorbid conditions hypertension and CVD were self-reported.ResultsAmong 806 individuals with T2D 37.7% of the men and 62.3% of the women presented with DRD. Out of the total group 35.6% reported hypertension, 7.3% reported CVD and 21.2% reported a combination of hypertension and CVD. The results of the multivariate analyses showed that the odds ratio of DRD was significantly higher (OR=1.67, CI95: 1.11-2.52) in the group who reported a combination of hypertension and CVD.ConclusionAmong individuals with T2D in rural areas of Vietnam there is an increased risk of DRD if a combination of hypertension and cardiovascular disease is also present. Hence, considering diabetes-related comorbidities can be useful in order to successfully identify individuals in risk of DRD.
Optimising the construction of outcome measures for impact evaluations of intimate partner violence (IPV) prevention interventions
Authors: Chatterji Sangeeta , Boyer Christopher , Sharma Vandana , Abramsky Tanya , Levtov Ruti , Doyle Kate , Harvey Sheila , Heise Lori 
Published: February 2023

AbstractMost impact evaluations of IPV prevention interventions use binary measures of “any” versus “no” physical and/or sexual IPV as their primary outcome measure, missing opportunities to capture nuance. In this study, we reanalysed secondary data from six randomised controlled trials conducted in low and middle-income countries- Bandebereho (Rwanda), Becoming One (Uganda), Indashyikirwa (Rwanda), MAISHA CRT01, MAISHA CRT02 (Tanzania), Stepping Stones Creating Futures (South Africa), and Unite for a Better Life (Ethiopia), to assess how different conceptualisations and coding of IPV variables can influence interpretations of the impact of an intervention. We compared standard outcome measures to new measures that reflect the severity and intensity of violence and whether interventions prevent new cases of IPV or reduce or stop ongoing violence. Results indicate that traditional binary indicators masked some of the more subtle intervention effects, and the use of the new indicators allowed for a better understanding of the impacts of the interventions. Conclusions on whether a program is perceived “to work” are highly influenced by the IPV outcomes investigators choose to report and how they are measured and coded. Lack of attention to outcome choice and measurement could lead to prematurely abandoning strategies useful for violence reduction or missing essential insights into how programs may or may not affect IPV. While these results must be interpreted cautiously, given differences in intervention types, the underlying prevalence of violence, sociodemographic factors, sample sizes and other contextual differences across the trial sites, they can help us move toward a new approach to reporting multiple outcomes that allow us to unpack the ‘impact’ of an intervention by assessing intervention effect by the severity of violence and type of prevention, whether primary and secondary.
Quantification of impact of COVID-19 pandemic on cancer screening programmes -a case study from Argentina, Bangladesh, Colombia, Morocco, Sri Lanka and Thailand
Authors: Lucas Eric , Murillo Raul , Arrossi Silvina , Bárcena Martin , Chami Youssef , Nessa Ashrafun , Perera Suraj , Silva J Padmaka , Sangrajrang Suleeporn , Muwonge Richard , Basu Partha 
Published: February 2023

AbstractIt is quite well-documented that the COVID-19 pandemic disrupted cancer screening services in all countries, irrespective of their resources and healthcare settings. While quantitative estimates on reduction in volume of screening tests or diagnostic evaluation are readily available from the high-income countries, very little data is available from the low- and middle-income countries (LMICs). From the CanScreen5 global cancer screening data repository we identified six LMICs through purposive sampling based on the availability of cancer screening data at least for the years 2019 and 2020. These countries represented different human development index (HDI) categories and were from Asia (Bangladesh and Thailand), Africa (Morocco) and Latin America (Argentina and Colombia). The reduction in the volume of tests in 2020 compared to the previous years ranged from 14.1% in Bangladesh to 72.9% in Argentina (regional programme) for cervical screening, from 14.1% in Bangladesh to 52.2% in Morocco for breast cancer screening and 30.7% in Thailand for colorectal cancer screening. Number of colposcopies was reduced in 2020 compared to previous year by 88.9% in Argentina, 38.2% in Colombia, 27.4% in Bangladesh and 52.3% in Morocco. The reduction in detection rates of CIN 2 or worse lesions ranged from 20.7% in Morocco to 45.4% in Argentina. Reduction of breast cancer detection by 19.2% was reported from Morocco. No association of the impact of pandemic could be seen with HDI categories. Quantifying the impact of service disruptions in screening and diagnostic tests will allow the programmes to strategize how to ramp up services to clear the backlogs in screening and more crucially in further evaluation of screen-positives. The data can be used to estimate the impact on stage distribution and avoidable mortality from these common cancers.
Emergence and suppressive function of Tr1 cells in glomerulonephritis
Authors: Soukou-Wargalla Shiwa , Kilian Christoph , Velasquez Lis , Machicote Andres , Bertram Franziska , Stumme Friederike , Bedke Tanja , Giannou Anastasios , Kempski Jan , Sabihi Morsal , Song Ning , Paust Hans-Joachim , Borchers Alina , Perez Laura Garcia , Pelczar Penelope , Liu Beibei , Ergen Can , Steglich Babett , Muscate Franziska , Huber Tobias B. , Panzer Ulf , Gagliani Nicola , Krebs Christian F. , Huber Samuel 
Published: February 2023

SummaryT regulatory type 1 (Tr1) cells, which are defined by their regulatory function, lack of Foxp3, high expression of IL-10, CD49b, and LAG3, are known to be able to suppress Th1 and Th17 in the intestine. Th1 and Th17 cells are also the main drivers of crescentic glomerulonephritis, the most severe form of renal autoimmune disease. However, whether Tr1 cells emerge in renal inflammation and moreover, whether they exhibit regulatory function during glomerulonephritis has not been thoroughly investigated yet. To address these questions, we used a mouse model of experimental crescentic glomerulonephritis and double Foxp3mRFPIL-10eGFPreporter mice. We found that Foxp3negIL-10-producing CD4+T cells infiltrate the kidneys during glomerulonephritis progression. Using single-cell RNA- sequencing, we could show that these cells express the core transcriptional factors characteristic of Tr1 cells. In line with this, Tr1 cells showed a strong suppressive activityex vivoand were protective in experimental crescentic glomerulonephritisin vivo. Finally, we could also identify Tr1 cells in the kidneys of patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis and define their transcriptional profile. Tr1 cells are currently used in several immune-mediated inflammatory diseases, e.g. as T- cell therapy. Thus, our study provides proof of concept for Tr1 cell-based therapies in experimental glomerulonephritis.
Disentangling the neurobiological bases of temporal impulsivity in Huntington’s disease
Authors: Pardina-Torner Helena , De Paepe Audrey E. , Garcia-Gorro Clara , Rodriguez-Dechicha Nadia , Calopa Matilde , Ruiz-Idiago Jesus , Mareca Celia , de Diego-Balaguer Ruth , Camara Estela 
Published: February 2023

AbstractBackgroundDespite its impact on daily life, impulsivity in Huntington’s disease (HD) is understudied as a neuropsychiatric symptom. Our aim is to characterize temporal impulsivity in HD, evaluated through a Delay Discounting (DD) task, and to disentangle the underlying white matter correlates in HD.MethodsForty-seven HD individuals and thirty-six healthy controls conducted a DD task and complementary Sensitivity to Punishment and Sensitivity to Reward (SR) Questionnaire. Diffusion-tensor imaging was employed to characterize the structural connectivity of two limbic tracts: the uncinate fasciculus (UF) and the accumbofrontal tract (NAcc-OFC). Multiple linear regression analyses were applied to analyze the relationship between impulsive behavior and white-matter microstructural integrity.ResultsAltered structural connectivity in both the NAcc-OFC and UF in HD individuals was observed. Moreover, the variability in structural connectivity of these tracts was associated with the individual differences in temporal impulsivity. Specifically, increased structural connectivity in the right NAcc-OFC predicted increased temporal impulsivity, while reduced connectivity in the left UF was associated with higher temporal impulsivity scores.LimitationsOther cognitive mechanisms and white matter tracts may play a role in temporal impulsivity.ConclusionsThis study provides evidence that individual differences observed in impulsivity may be explained by variability in limbic fronto-striatal tracts. We emphasize the importance of investigating the spectrum of impulsivity in HD, less prevalent than other psychiatric features, but impacting the quality of life of patients and their caregivers.
Pgc-1α is an exercise-responsive regulator of myosteatosis in older individuals
Authors: Iijima Hirotaka , Ambrosio Fabrisia , Matsui Yusuke 
Published: February 2023

SUMMARYAccumulated fat in skeletal muscle, common in sedentary older individuals, compromises skeletal muscle health and function. Mechanistic understanding ofhowphysical activity levels dictate fat accumulation represents a critical step towards establishment of therapies that promote healthy aging. Using a network paradigm that characterized the transcriptomic response of aged muscle to exercise versus immobilization protocols, this study uncovered a novel molecular cascade that regulates the fate of fibro-adipogenic progenitors (FAPs), the cell population primarily responsible for the fat accumulation. Specifically, gene set enrichment analyses (GSEA) with network propagation revealedPgc1α as a functional hub of a large gene regulatory network underlying the regulation of FAPs by physical activity. Integratedin silicoandin situapproaches to inducePgc-1α overexpression promoted mitochondrial fatty acid oxidation and inhibited FAPs adipogenesis. These findings suggest thatPgc1α is a master regulator by which physical activity regulates fat accumulation in aged skeletal muscle.GRAPHICAL ABSTRUCT
Mechanisms of spinophilin-dependent pancreas dysregulation underlying diabesity
Authors: Stickel Kaitlyn C. , Mosley Amber L. , Doud Emma H. , Belecky-Adams Teri L. , Baucum Anthony J. 
Published: February 2023

ABSTRACTObjectiveSpinophilin is an F-actin binding and protein phosphatase 1 (PP1) targeting protein that acts as a scaffold of PP1 to its substrates. Spinophilin knockout (Spino-/-) mice have decreased fat mass, increased lean mass, and improved glucose tolerance, with no difference in feeding behaviors. While spinophilin is enriched in neurons, its roles in non-neuronal tissues, such as beta cells of the pancreatic islets, are unclear.Methods & ResultsWe have corroborated and expanded upon previous studies to determine that Spino-/-mice have decreased weight gain and improved glucose tolerance in two different models of obesity. Using proteomics and immunoblotting-based approaches we identified multiple putative spinophilin interacting proteins isolated from intact pancreas and observed increased interactions of spinophilin with exocrine, ribosomal, and cytoskeletal protein classes that mediate peptide hormone production, processing, and/or release in Leprdb/dband/or high fat-fed (HFF) models of obesity. Moreover, loss of spinophilin specifically in pancreatic beta cells improved glucose tolerance without impacting body weight.ConclusionOur data further support a role for spinophilin in mediating pathophysiological changes in body weight and whole-body metabolism associated with obesity and provide the first evidence that spinophilin mediates obesity-dependent pancreatic dysfunction that leads to deficits in glucose homeostasis or diabesity.
Insights into substrate coordination and glycosyl transfer of poplar cellulose synthase-8
Authors: Verma Preeti , Kwansa Albert L. , Ho Ruoya , Yingling Yaroslava G. , Zimmer Jochen 
Published: February 2023

SummaryCellulose is an abundant cell wall component of land plants. It is synthesized from UDP-activated glucose molecules by cellulose synthase, a membrane-integrated processive glycosyltransferase. Cellulose synthase couples the elongation of the cellulose polymer with its translocation across the plasma membrane. Here, we present substrate and product-bound cryogenic electron microscopy structures of the homotrimeric cellulose synthase isoform-8 (CesA8) from hybrid aspen (poplar). UDP-glucose binds to a conserved catalytic pocket adjacent to the entrance to a transmembrane channel. The substrate’s glucosyl unit is coordinated by conserved residues of the glycosyltransferase domain and amphipathic interface helices. Site-directed mutagenesis of a conserved gating loop capping the active site reveals its critical function for catalytic activity. Molecular dynamics simulations reveal prolonged interactions of the gating loop with the substrate molecule, particularly across its central conserved region. These transient interactions likely facilitate the proper positioning of the substrate molecule for glycosyl transfer and cellulose translocation.HighlightsCryo-EM structures of substrate and product bound poplar cellulose synthase provide insights into substrate selectivitySite directed mutagenesis signifies a critical function of the gating loop for catalysisMolecular dynamics simulations support persistent gating loop – substrate interactionsGating loop helps in positioning the substrate molecule to facilitate cellulose elongationConserved cellulose synthesis substrate binding mechanism across the kingdoms