bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of undiagnosed hypertension and prehypertension among bankers of Bangladesh: a cross-sectional study
Authors: Munira Sira Jam , Hasan Mohammad Jahid , Rafi Md Abdur , Shaheen Shafia , Kabir Md. Iqbal 
Published: January 2023

ABSTRACTObjectiveBankers lead a sedentary and highly stressful life that often leads to developing noncommunicable diseases (NCDs) such as hypertension, diabetes, mental disorders, etc. The study aims to assess the prevalence of undiagnosed hypertension and prehypertension among bankers in Bangladesh.MethodsData from 365 bankers from five public and private banks in Bangladesh were collected using a pretested semistructured questionnaire. Prehypertension was defined as having systolic blood pressure of 120-139 mmHg and diastolic blood pressure of 80-89 mmHg. Multivariate logistic regression models were created to investigate the factors associated with them.ResultsThe prevalence of undiagnosed hypertension and prehypertension were 22.5% and 55.3%, respectively. Most of the bankers were males and 35-44 years of age. The risk of hypertension and prehypertension was significantly higher among males (OR, 16.59; OR, 6.42), longer duration of services (F, 3.56), prolonged working hours (OR, 3.8; OR, 3.09), smoking (OR, 6.18; OR, 3.43), overweight (OR, 6.81; OR, 2.41) and obese (OR, 8.94; OR, 3.36) bankers, respectively. After controlling for all confounders, the predictors of hypertension were males (aOR, 12.8; CI, 2.73-60.02), current smokers (aOR,2.87; CI, 1.03-8), overweight (aOR,5.11; CI, 1.46-17.93), and obesity (aOR, 9.59; CI, 2.41-38.22). For prehypertension, males (aOR, 9.72; CI, 3.06-30.87) and obesity (aOR, 3.95; CI, 1.52-10.25) were found as predictors.ConclusionMore than three fourth of bankers in Bangladesh have either undiagnosed hypertension or prehypertension associated with several contributing factors to occur. A large-scale study is recommended to understand the clear picture of the overall NCD risk factors burden among bankers in Bangladesh.WHAT IS ALREADY KNOWN ON THIS TOPICThe prevalence of hypertension and prehypertension are already higher in Bangladesh. Sedentary lifestyles and work stress make bankers a vulnerable community to developing these NCD risk factors.WHAT THIS STUDY ADDSBankers have a higher prevalence of undiagnosed hypertension and prehypertension in Bangladesh.Several factors gender, long duration of service, prolonged working hours, and physical inactivity leading to overweight or obesity were found to be significant predictors of developing them.HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICYThis research suggests that it is now a national demand to conduct large scale surveys to assess the NCD risk factors burden among high risk occupational groups like bankers.
SARS-CoV-2 molecular testing and whole genome sequencing following RNA recovery from used BinaxNOW COVID-19 Antigen Self Tests
Authors: Nguyen Phuong-Vi , Carmola Ludy Registre , Wang Ethan , Bassit Leda , Rao Anuradha , Greenleaf Morgan , Sullivan Julie A. , Martin Greg S. , Lam Wilbur A. , Waggoner Jesse J. , Piantadosi Anne 
Published: January 2023

AbstractWidespread use of over-the-counter rapid diagnostic tests for SARS-CoV-2 has led to a decrease in availability of clinical samples for viral genomic surveillance. As an alternative sample source, we evaluated RNA isolated from BinaxNOW swabs stored at ambient temperature for SARS-CoV-2 rRT-PCR and full viral genome sequencing. 81 of 103 samples (78.6%) yielded detectable RNA, and 46 of 57 samples (80.7 %) yielded complete genome sequences. Our results illustrate that SARS-CoV-2 RNA extracted from used Binax test swabs provides an important opportunity for improving SARS-CoV-2 genomic surveillance, evaluating transmission clusters, and monitoring within-patient evolution.
Sex differences in the associations between risk for late-life AD, protective lifestyle factors and cognition in mid-life
Authors: Qi Qing , Deng Feng , Ritchie Karen , Muniz-Terrera Graciela , Koychev Ivan , Malhotra Paresh , O’Brien John T. , Ritchie Craig W. , Lawlor Brian , Naci Lorina 
Published: January 2023

AbstractIt is now acknowledged that Alzheimer’s Disease (AD) processes are present decades before the onset of clinical symptoms, but whether lifestyle activities can protect against these early AD processes in mid-life remains poorly understood. Furthermore, the impact of sex as a biological variable on associations between dementia risk, protective lifestyle activities and cognition is unknown. In this study, we aimed to replicate findings from our two recent studies [Deng et al. (2022) and Heneghan et al. (2022)] on the contribution of mid-life modifiable activities to cognition in individuals with dementia risk, in a larger independent cohort of the PREVENT–Dementia research program (N = 461 vs N = 208 used previously). Second, we investigated associations between biological sex, dementia risk, protective lifestyle activities and cognitive performance. Participants (40–59 years; N = 461) completed cognitive and clinical assessments cross-sectionally. Mid-life activities were measured with the Lifetime of Experiences Questionnaire. Known risk factors for sporadic late-onset AD (Apolipoprotein EƐ4 allele status, family history of dementia, and the Cardiovascular Risk Factors Aging and Dementia score [CAIDE]) were investigated. Replicating our key previous findings (Deng et al., 2022 and Heneghan et al., 2022), we found that episodic and relational memory was (a) significantly negatively associated with the CAIDE risk score, (b) positively associated with stimulating lifestyle activities, and (c) that females performed significantly better than males in episodic and relational memory. The key novel finding of this study was that inherited dementia risk (i.e., APOEƐ4 genotype) modulated the association between sex, lifestyle and cognition. Only for APOEƐ4+ females, not APOEƐ4-, higher occupational attainment was associated with better episodic and relational memory. Conversely, only for APOEƐ4+ males, not APOEƐ4-, higher occupational attainment was associated with worse episodic and relational memory. These findings suggest that modifiable lifestyle activities offset cognitive decrements due to inherited AD risk in mid-life and support the targeting of modifiable lifestyle activities for the prevention of Alzheimer’s disease. Furthermore, these findings suggest an urgent need for targeted research on female-specific risk factors, to inform personalised strategies for AD prevention and the promotion of female brain health.
Pericoronary adipose tissue radiomics from coronary CT angiography identifies vulnerable plaques characteristics in intravascular OCT
Authors: Kim Justin N. , Gomez-Perez Lia , Zimin Vladislav N. , Makhlouf Mohamed H. E. , Al-Kindi Sadeer , Wilson David L. , Lee Juhwan 
Published: January 2023

AbstractPericoronary adipose tissue (PCAT) features on CT have been shown to reflect local inflammation, and signals increased cardiovascular risk. Our goal was to determine if PCAT radiomics extracted from coronary CT angiography (CCTA) images are associated with intravascular optical coherence tomography (IVOCT)-identified vulnerable plaque characteristics (e.g., microchannels [MC] and thin-cap fibroatheroma [TCFA]). CCTA and IVOCT images of 30 lesions from 25 patients were registered. Vessels with vulnerable plaques were identified from the registered IVOCT images. PCAT radiomics features were extracted from CCTA images for the lesion region of interest (PCAT-LOI) and the entire vessel (PCAT-Vessel). We extracted 1356 radiomics features, including intensity (first-order), shape, and texture features. Features were reduced using standard approaches (e.g., high feature correlation). Using stratified three-fold cross-validation with 1000 repeats, we determined the ability of PCAT radiomics features from CCTA to predict IVOCT vulnerable plaque characteristics. In identification of TCFA lesions, PCAT-LOI and PCAT-Vessel radiomics models performed comparably (AUC±standard deviation 0.78±0.13, 0.77±0.14). For identification of MC lesions, PCAT-Vessel radiomics model (0.89±0.09) was moderately better associated than that of PCAT-LOI model (0.83±0.12). Both PCAT-LOI and PCAT-Vessel radiomics models also similarly identified coronary vessels thought to be highly vulnerable (i.e., both TCFA and MC) (0.88±0.10, 0.91±0.09). Favorable radiomics features tended to be those describing texture and size of PCAT. PCAT radiomics can identify coronary vessels with TCFA or MC, consistent with IVOCT. CCTA radiomics may improve risk stratification by noninvasively detecting vulnerable plaque characteristics that are only visible with IVOCT.
Differential COVID-19 mortality in the United States: Patterns, causes and policy implications
Authors: Stoto Michael A. , Schlageter Samantha , degl’Innocenti Duccio Gamannossi , Zollo Fabiana , Kraemer John D. 
Published: January 2023

AbstractA “two Americas” narrative emerged in the summer of 2021: one with high demand for COVID-19 vaccines, and a second with widespread vaccine hesitancy and opposition to mask mandates. But our analysis of excess mortality shows that the U.S. has been a divided nation at least since the start of the pandemic. Through April, 2022, there were 1,335,292 excess deaths associated with COVID-19, 37% more than reported as such. After the first wave, death rates in the South were more than double those in the Northeast; 45% of deaths were in the South, with 38% of the population.While some regard vaccination and other measures as matters of personal choice, the population impact is striking. If every region had the same mortality rate as the lowest regional rate in each period, more than 418,763 COVID-19 deaths were “avoidable,” more than half (58%) in the South and almost half before vaccines were available. These results show that population-based COVID-19 policies can still play an important role in protecting those most vulnerable to severe disease and death and reducing the spread of the virus.This example illustrates the importance of excess mortality measures as part of a comprehensive surveillance system. Official mortality counts rely on complete recording of COVID-19 as a cause of death, but COVID-19 deaths are under reported for many reasons. Indeed, the proportion of COVID-19 deaths reported as such varied markedly over time, and from 67% in the West to 87% the Northeast. In 2022, some regions cut back on testing making it harder to see a re-emergence of COVID-19 in those places. More extensive surveillance based on wastewater testing and other means that do not depend on testing are needed to get a more accurate picture. Excess mortality estimates are more tenuous years beyond the pre-pandemic period.
Systematic elucidation of genetic mechanisms underlying cholesterol uptake
Authors: Hamilton Marisa C. , Fife James D. , Akinci Ersin , Yu Tian , Khowpinitchai Benyapa , Cha Minsun , Barkal Sammy , Thi Thi Tun , Yeo Grace H.T. , Barroso Juan Pablo Ramos , Francoeur Matthew Jake , Velimirovic Minja , Gifford David K. , Lettre Guillaume , Yu Haojie , Cassa Christopher A. , Sherwood Richard I. 
Published: January 2023

SummaryGenetic variation contributes greatly to LDL cholesterol (LDL-C) levels and coronary artery disease risk. By combining analysis of rare coding variants from the UK Biobank and genome-scale CRISPR-Cas9 knockout and activation screening, we have substantially improved the identification of genes whose disruption alters serum LDL-C levels. We identify 21 genes in which rare coding variants significantly alter LDL-C levels at least partially through altered LDL-C uptake. We use co-essentiality-based gene module analysis to show that dysfunction of the RAB10 vesicle transport pathway leads to hypercholesterolemia in humans and mice by impairing surface LDL receptor levels. Further, we demonstrate that loss of function ofOTX2leads to robust reduction in serum LDL-C levels in mice and humans by increasing cellular LDL-C uptake. Altogether, we present an integrated approach that improves our understanding of genetic regulators of LDL-C levels and provides a roadmap for further efforts to dissect complex human disease genetics.
CeLab, a Microfluidic Platform for the Study of Life History Traits, reveals Metformin and SGK-1 regulation of Longevity and Reproductive Span
Authors: Sohrabi Salman , Cota Vanessa , Murphy Coleen T. 
Published: January 2023

AbstractThe potential to carry out high-throughput assays in a whole organism in a small space is one of the benefits ofC. elegans, but worm assays often require a large sample size with frequent physical manipulations, rendering them highly labor-intensive. Microfluidic assays have been designed with specific questions in mind, such as analysis of behavior, embryonic development, lifespan, and motility. While these devices have many advantages, current technologies to automate worm experiments have several limitations that prevent widespread adoption, and most do not allow analyses of reproduction-linked traits. We developed a miniatureC. eleganslab-on-a-chip device,CeLab, a reusable, multi-layer device with 200 separate incubation arenas that allows progeny removal, to automate a variety of worm assays on both individual and population levels.CeLab enables high-throughput simultaneous analysis of lifespan, reproductive span, and progeny production, refuting assumptions about the Disposable Soma hypothesis. BecauseCeLab chambers require small volumes, the chip is ideal for drug screens; we found that drugs previously shown to increase lifespan also increase reproductive span, and we discovered that low-dose metformin increases both.CeLab reduces the limitations of escaping and matricide that typically limit plate assays, revealing that feeding with heat-killed bacteria greatly extends lifespan and reproductive span of mated animals.CeLab allows tracking of life history traits of individuals, which revealed that the nutrient-sensing mTOR pathway mutant,sgk-1, reproduces nearly until its death. These findings would not have been possible to make in standard plate assays, in low-throughput assays, or in normal population assays.
The splicing isoform Foxp3Δ2 releases the autoinhibitory conformation and differentially regulates tTregs and pTregs homeostasis
Authors: Gu Qianchong , Zhao Xiufeng , Guo Jie , Xu Wei , Zhang Jianhua , Zhang Wei , Zhang Fuping , Hou Baidong , Zhou Xuyu 
Published: January 2023

SummaryFoxp3 is the master transcription factor for the development and function of regulatory T cells (Tregs). So far, little is known about whether the conformation change in Foxp3 could impact the Tregs biology. Alternative splicing of human Foxp3 results in the expression of two major isoforms: the full-length protein or an exon 2-deleted protein (Foxp3Δ2). Here, AlphaFold2 structure predictions andin vitroexperiments demonstrated that the N-terminal domain of Foxp3 inhibits DNA binding by moving toward the C-terminus and that this movement is mediated by exon 2. Consequently, we generated exon 2 deficient mice and found Foxp3Δ2-bearing Tregs in the peripheral lymphoid organ were less sensitive to TCR due to the enhanced binding of Foxp3Δ2 to theBatfpromoter and were unsusceptible to IL-2. In contrast, among RORγt+Tregs in the large intestine, Foxp3Δ2 Tregs expressed much more RORγt-related genes, and more strikingly, the deletion of exon 2 of Foxp3 conferred a competitive advantage over WT RORγt+Tregs. Together, our results reveal that alternative splicing of exon 2 generates a constitutively active form of Foxp3, which plays a differential role in regulating tTregs and pTregs homeostasis.HighlightsFoxp3Δ2 broke the inhibitory loop and generated constitutive DNA-binding activity.Foxp3 isoforms differentially regulate tTregs and pTregs homeostasisFoxp3Δ2-bearing Tregs in the peripheral lymphoid organ were less sensitive to TCR and were unsusceptible to IL-2Foxp3Δ2 RORγt+pTregs benefited them for better adapting to the gut environmental conditions
A cinnamyl alcohol dehydrogenase (CAD) like enzyme leads to a branch in the shikonin biosynthetic pathway inArnebia euchroma
Authors: Wang Ruishan , Liu Changzheng , Wang Sheng , Sun Jiahui , Guo Juan , Lyu Chaogeng , Kang Chuanzhi , Wan Xiufu , Shi Linyuan , Wang Jinye , Huang Luqi , Guo Lanping 
Published: January 2023

SummaryShikonin derivatives are natural naphthoquinone compounds and the main bioactive components produced by several boraginaceous plants, such asLithospermum erythrorhizonandArnebia euchroma. Phytochemical researches utilizingL. erythrorhizonandA. euchromacultured cells both indicate the existence of a competing route branching out from the shikonin biosynthetic pathway toward benzo/hydroquinones. A previous study has shown that the branch point is a putative alcohol dehydrogenase converting (Z)-3’’-hydroxygeranylhydroquinone [(Z)-3’’-OH-GHQ] to an aldehyde intermediate (E)-3’’-oxo-GHQ. However, the enzyme involved in the branch reaction is not characterized at the molecular level yet. In this study, we clone a candidate gene belonging to the cinnamyl alcohol dehydrogenase (CAD) family,AeHGO, through coexpression analysis of transcriptome data sets of shikonin-proficient and shikonin-deficient cell lines ofA. euchroma. In biochemical assays, purified AeHGO protein reversibly oxidizes (Z)-3’’-OH-GHQ to produce (E)-3’’-oxo-GHQ followed by reversibly reducing (E)-3’’-oxo-GHQ to (E)-3’’-OH-GHQ, resulting in an equilibrium mixture of the three compounds. Time course analysis and kinetic parameters show that the reaction with (Z)-3’’-OH-GHQ is about twice as efficient as with (E)-3’’-OH-GHQ, which leads to the predominance of (E)-3’’-OH-GHQ and (E)-3’’-oxo-GHQ in the equilibrium mixture. According to a previous report, (E)-3’’-oxo-GHQ can be converted to deoxyshikonofuran, a hydroquinone metabolite produced by boraginaceous plants. Considering there is a competition for accumulation between shikonin derivatives and benzo/hydroquinones in bothL. erythrorhizonandA. euchromacultured cells, AeHGO is supposed to play an important role in the metabolic regulation of shikonin biosynthetic pathway.
General solution to inflated type I and II errors in multi-subject single-cell differential gene expression analysis
Authors: Lee Hanbin , Han Buhm 
Published: January 2023

AbstractLarge-scale multi-subject single-cell data have become very common. For differential gene expression (DGE) analysis of these datasets, a common practice is to choose any of the two: pseudobulk methods or cell-wise methods. However, multi-subject single-cell studies have highly heterogeneous study designs. Some studies have case/control samples to be compared and tested, and some make within-sample perturbations. In this work, we report that to prevent severely inflated errors, we must treat the two categories of study designs differently in the DGE analysis. In studies with case/control labels, pseudobulk methods work the best, and cell-wise methods produce severe inflation of type II errors. Cell-wise methods work best in studies with within-sample perturbations, and pseudobulk methods produce severe inflation of type I errors. We provide mathematical proofs to support this argument. Surprisingly, many existing studies, even published ones, often choose an inappropriate DGE method. The most common temptation is to use cell-wise methods for case/control studies, which will only make p-values falsely look significant. Our analyses and proofs warn that choosing an appropriate DGE method is not an option but a requirement.
Modular transcriptional responses to environmental changes
Authors: Beringer Marc , Mattam Bella , Choudhury Rimjhim Roy , Parisod Christian 
Published: January 2023

SummaryKnowledge about the molecular underpinnings of phenotypic plasticity is still scarce and quantifying gene expression in response to abiotic and biotic factors enables to investigate transcriptional plasticity. RNAseq data on clones of the alpine plantBiscutella laevigata(Brassicaceae) subjected to control, cold, heat, drought and herbivory treatments assessed differentially expressed genes (DEGs) and transposable elements (DE-TEs) in comparison to similar experiments inArabidopsis thaliana. Synergistic and trade-off DEGs presenting parallel and antagonistic regulation among treatments were further identified and used with networks of co-expressed DEGs to characterize transcriptional plasticity in response to environmental changes. Compared toA. thaliana,B. laevigatapresented fewer DEGs that were mostly up-regulated by stronger expression shifts in response to environmental treatments.Biscutella laevigatashowed constitutive expression of half of theA. thalianaDEGs. It further presented a higher proportion of synergistic DEGs, a lower number of trade-off DEGs and a transcriptome organized in environment-specific subnetworks. Several DE-TEs were identified as activated by heat and herbivory. The stress-tolerant perennialB. laevigatapresents a highly modular transcriptional plasticity in response to environmental changes, contrasting with the more integrated transcriptome ofA. thaliana.Significance statementLittle is known about the molecular underpinnings of phenotypic plasticity. Here, focusing on expression shifts during changes in abiotic and biotic conditions, we highlight environment-responsive genes acting synergistically or antagonistically among treatments and underlying modular transcriptional plasticity in two Brassicacea species.
T-cell derived extracellular vesicles prime macrophages for improved STING based cancer immunotherapy
Authors: Hansen Aida S. , Jensen Lea S. , Ryttersgaard Kristoffer G. , Krapp Christian , Just Jesper , Gammelgaard Kristine R. , Jønsson Kasper L. , Johansen Mogens , Etzerodt Anders , Deleuran Bent W. , Jakobsen Martin R. 
Published: January 2023

SummaryA key phenomenon in cancer is the establishment of a highly immunosuppressive tumor microenvironment (TME). Despite advances in immunotherapy, where the purpose is to induce tumor recognition and hence hereof tumor eradication, the majority of patients applicable for such treatment still fail to respond. It has been suggested that high immunological activity in the tumor is essential for achieving effective response to immunotherapy, which therefore have led to exploration of strategies that triggers inflammatory pathways. Here activation of the stimulator of interferon genes (STING) signaling pathway has been considered an attractive target, as it is a potent trigger of pro-inflammatory cytokines and type I and III interferons. However, immunotherapy combined with targeted STING agonists has not yielded sustained clinical remission in humans. This suggest a need for exploring novel adjuvants to improve the innate immunological efficacy. Here, we demonstrate that extracellular vesicles (EVs), derived from activated CD4+T cells (T-EVs), sensitizes macrophages to elevate STING activation, mediated by IFNγ carried on the T-EVs. Our work support that T-EVs can disrupt the immune suppressive environment in the tumor by reprogramming macrophages to a pro-inflammatory phenotype, and priming them for a robust immune response towards STING activation.