bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular benefits of statin plus ezetimibe combination therapy versus statin monotherapy in acute coronary syndrome: a meta-analysis of randomized controlled trials
Authors: de Oliveira Almeida Gustavo , Balieiro Caroline , Bertoli Edmundo Damiani , Moreira Maria Eduarda Liporaci , Silva Ana Laura Soares , Minucci Bárbara Silvestre , Zapparoli Isabella , Maluf Marcela Silva , Carvalho Henrique Champs Porfírio , dos Santos Borges Rafael , Pasqualotto Eric , Nienkötter Thiago , Alves Vinícius , Guida Camila Mota 
Published: September 2024

Background
The efficacy of adding ezetimibe to statin therapy for event reduction in patients with acute coronary syndromes (ACS) remains a topic of ongoing debate.

Methods
We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing ezetimibe plus statin versus statin monotherapy in patients with ACS. We searched PubMed, Embase, and Cochrane for eligible trials. The random-effects model was used to calculate the risk ratios with 95% confidence intervals (CIs). Statistical analyses were performed using RStudio version 4.2.3 (RStudio, PBC).

Results
Six RCTs comprising 20 574 patients with ACS were included, of whom 10 259 (49.9%) were prescribed ezetimibe plus statin. The patient population had an average age of 63.8 years, and 75.1% were male. Compared with statin monotherapy, ezetimibe plus statin significantly reduced major adverse cardiovascular events (MACE) (risk ratio 0.93; 95% CI 0.90–0.97; P < 0.01) and nonfatal myocardial infarction (risk ratio 0.88; 95% CI 0.81–0.95; P < 0.01). There was no significant difference between groups for revascularization (risk ratio 0.94; 95% CI 0.90–1.00; P = 0.03), all-cause mortality (risk ratio 0.87; 95% CI 0.63–1.21; P = 0.42), or unstable angina (risk ratio 1.05; 95% CI 0.86–1.27; P = 0.64).

Conclusion
In this meta-analysis of patients with ACS, the combination of ezetimibe plus statin was associated with a reduction in MACE and nonfatal myocardial infarction, compared with statin monotherapy.
Current opinion in refractory and/or unexplained chronic cough
Authors: Misono Stephanie , Novaleski Carolyn K. 
Published: September 2024

Purpose of review
Otolaryngologists are vital to successfully managing chronic cough in adults. This review presents updates regarding rapidly evolving concepts in chronic cough.

Recent findings
Significant growth is occurring in chronic cough research, strengthening the evidence of its major psychosocial impacts. Elucidation of the neural underpinnings of normal and abnormal cough within both the peripheral and central nervous systems highlight the previously underappreciated complexity of cough. Recent clinical practice recommendations emphasize personalized treatment approaches through addressing treatable traits of chronic cough. Investigations are ongoing to better distinguish chronic cough subgroups, and multiple types of important clinical outcome measures are being characterized. Newer research about chronic cough treatment encompasses pharmacologic and nonpharmacologic interventions, including oral and inhaled medications, superior laryngeal nerve blocks, and behavioral therapy.

Summary
As knowledge about chronic cough in adults continues to expand in both research and clinical practice, otolaryngologists can continue to raise awareness of the role of the larynx in cough and promote ongoing multidisciplinary collaborations. In the coming years, more pharmacologic options and personalized treatment approaches will likely emerge for chronic cough.
Non-invasive central nervous system stimulation to improve bladder and pelvic floor function in the aging population
Authors: Chen Annie , Hwang Kuemin , Khavari Rose 
Published: September 2024

Purpose of review
The literature was reviewed for all noninvasive central nervous system (CNS) stimulation techniques, which includes transcranial brain or trans-spinal stimulation, in the aging population. Given the rising ubiquity of this technology, noninvasive nature, and low side-effect profile reported, this technology can have a big impact on the aging population. As patients afflicted with neurogenic disorders are living longer lives, a special emphasis is placed on the aging neurogenic population.

Recent findings
Noninvasive CNS stimulation techniques have been applied to major bladder and pelvic floor disorders such as voiding dysfunction, chronic pelvic pain, urgency and urge incontinence, lower urinary tract dysfunction, and situational urge incontinence in both the idiopathic and neurogenic populations. Overall, these noninvasive technologies demonstrate effectiveness for the treatment of these conditions with some studies showing effectiveness with longer-term follow-up suggesting lasting CNS remodeling.

Summary
Most manuscripts had a generally small number of patients and an even smaller number of geriatric patients represented. No studies were specifically designed to investigate geriatric outcomes. It is the hope of this systematic review to help model future studies according to existing literature, but with a focus on the geriatric population as they stand to gain the most from noninvasive technologies with limited adverse events.
Optimisation of a multiplexed, high throughput assay to measure neutralising antibodies against SARS-CoV-2 variants
Authors: Ashley Caroline L. , Bloul Malik , Alca Sibel , Smith Lachlan , Jin Wang , Khoury David , Counoupas Claudio , Davenport Miles , Triccas James A. , Steain Megan 
Published: September 2024

AbstractA multiplexed, lentivirus-based pseudovirus neutralisation assay (pVNT) was developed for high-throughput measurement of neutralising antibodies (nAbs) against three distinct SARS-CoV-2 spike variants. Intra-assay variability was minimised by optimising the plate layout and determining an optimal percentage transduction for the pseudovirus inoculum. Comparison of monoclonal antibody EC50titres between single and multiplexed pVNT assays showed no significant differences, indicating reliability of the multiplexed assay. Evaluation of convalescent human sera confirmed assay validity, with consistent fold drops in EC50for variant pseudoviruses relative to the ancestral strain observed across single and multiplexed assays. This multiplexed pVNT provides a reliable tool for assessing nAb responses against SARS-CoV-2 variants and could be used to accelerate preclinical vaccine assessment in preparation for the next coronavirus pandemic.
Protective Effects of Psychiatric Medications against COVID-19 Mortality Before Vaccines
Authors: Machado-Vieira Rodrigo , Krause Trudy M. , Jones Gregory , Teixeira Antonio L. , Shahani Lokesh R. , Lane Scott D. , Soares Jair C. , Truong Chau 
Published: September 2024

Objectives: To investigate the relationship between neuropsychiatric medication usage and COVID-19 outcomes before COVID-19 usage. Methods: This cross-sectional study used Optum’s de-identified Clinformatics® Data Mart Database to identify patients diagnosed with COVID-19 in 2020 and their psychiatric medication prescriptions in the United States. Ordered logistic regression was used to predict the likelihood of a higher COVID-19 severity level for long-term and new users. Results were adjusted for demographic characteristics and medical and psychiatric comorbidities. Results: Individuals taking all psychiatric medications were less likely to have a high severity score. Overall, users of psychiatric medications were less likely to have a higher severity score than those not taking any medications. Within individual classes, the results varied across long-term and short-term users. Conclusions: Results of the current study suggest that psychopharmacological agents are associated with reduced COVID-19 severity levels. Specifically, our results show that antidepressant medications may be associated with a protective role against COVID-19. Considering the heightened risk of severe COVID-19 outcomes associated with depression and psychoses, early treatment with antidepressants and benzodiazepines could potentially lower the incidence of severe cases and mortality rates.
Prevalence, awareness and factors associated with hypertension among adults in rural south-western Uganda: a cross-sectional study
Authors: Kansiime Grace , Nuwagira Edwin , Obwoya Paul Stephen , Baluku Joseph Baruch , Kanyesigye Michael , Twesiime Christine , Ssebutinde Peter , Muhindo Rose , Muyingo Anthony , Kananura Keneth , Tusingwire Pliers Denis , Atukunda Esther C. , Kalyesubula Robert , Bajunirwe Francis , Muiru Anthony 
Published: September 2024

AbstractBackgroundHypertension is the leading cause of preventable deaths globally, yet there have been inconsistent reports on its burden and risk factors in rural Sub-Saharan Africa. This study aimed to assess the prevalence, awareness, and risk factors associated with hypertension among adults in a rural community in southwestern Uganda.MethodsA baseline survey was conducted as part of an ongoing implementation science cohort study in Ngango, a rural parish in the Mbarara district of southwestern Uganda. The study included adults aged 18-79 years from eleven villages. Research assistants and community health workers visited homes to enroll consenting adults. Data collection involved administering the WHO STEPS questionnaire, which gathered demographic information, behavioral characteristics, and lifestyle data, including tobacco and alcohol use, salt intake, fruit and vegetable consumption, and physical activity. Participants were also asked about prior blood pressure (BP) measurements. BP readings were taken three times, two minutes apart, along with anthropometric measurements. Hypertension was defined as BP ≥140/90 mmHg, based on the average of the last two readings, or self-reported use of antihypertensive medication. The primary outcome was the prevalence and factors associated with hypertension, assessed using logistic regression. Secondary outcomes included hypertension awareness and the proportion of participants with controlled hypertension.ResultsA total of 953 adults were enrolled. The median age was 43 years, with most participants being female (61.5%). Hypertension prevalence was 27.3% (260/953). Among those with hypertension, 61.5% were unaware, 27.7% were on treatment, and 65.3% had controlled BP. Despite 66.8% of participants reporting physical activity, 63.7% were overweight. Factors associated with hypertension were age > 40 years (OR 2.26, 95% CI 1.53-3.33; p <0.001), consuming <3 servings of fruit or vegetables per week (OR 1.62, 95% CI 1.11-2.35, p = 0.012), overweight (OR 1.57, 95% CI 1.05-2.34, p = 0.028), and obesity (OR 2.73, 95% CI 1.80-4.15, p <0.001).ConclusionThe prevalence of hypertension in rural southwestern Uganda is high, despite a relatively young and physically active population, indicating the need for targeted interventions.Key PointsMore than 1 in 4 adults in rural Uganda have hypertension, despite high levels of physical activity (67%)Hypertension awareness and control rates remain below the global targetsOur data shows that interventions targeting modifiable risk factors are urgently needed to reduce rural hypertension burden.
USP37 prevents premature disassembly of stressed replisomes by TRAIP
Authors: Kochenova Olga V. , D’Alessandro Giuseppina , Pilger Domenic , Schmid Ernst , Richards Sean L. , Garcia Marcos Rios , Jhujh Satpal S. , Voigt Andrea , Gupta Vipul , Carnie Christopher J. , Wu R. Alex , Gueorguieva Nadia , Stewart Grant S. , Walter Johannes C. , Jackson Stephen P. 
Published: September 2024

AbstractThe E3 ubiquitin ligase TRAIP associates with the replisome and helps this molecular machine deal with replication stress. Thus, TRAIP promotes DNA inter-strand crosslink repair by triggering the disassembly of CDC45-MCM2-7-GINS (CMG) helicases that have converged on these lesions. However, disassembly of single CMGs that have stalled temporarily would be deleterious, suggesting that TRAIP must be carefully regulated. Here, we demonstrate that human cells lacking the de-ubiquitylating enzyme USP37 are hypersensitive to topoisomerase poisons and other replication stress-inducing agents. We further show that TRAIP loss rescues the hypersensitivity ofUSP37knockout cells to topoisomerase inhibitors. InXenopusegg extracts depleted of USP37, TRAIP promotes premature CMG ubiquitylation and disassembly when converging replisomes stall. Finally, guided by AlphaFold-Multimer, we discovered that binding to CDC45 mediates USP37’s response to topological stress. In conclusion, we propose that USP37 protects genome stability by preventing TRAIP-dependent CMG unloading when replication stress impedes timely termination.
Decoupling Coldness and Softness in Tactile Wetness Perception Using Tunable Hydrogels
Authors: Becerra Laura L. , Root Nicholas , Clark Ainsley , Rafeedi Tarek , Brown William , Chen Alexander X. , Qie Yi , Blau Rachel , Miller Juliana , Kapadia Kabir , Ng Tse Nga , Rouw Romke , Lipomi Darren J. 
Published: September 2024

AbstractThis study investigates the perception of tactile wetness, a complex sensation experienced by humans. Previous research has primarily focused on either thermal or mechanical cues separately, or has used textiles as stimuli whose parameters are difficult to control. Here, we employed polyacrylamide hydrogels with varying stiffness levels soaked in liquids of distinct thermal conductivities. By psychophysically evaluating participants’ perception of wetness, we showed that the wetness judgments for the samples exhibit a transitive relationship based on the mechanical and thermal cues from an intrinsically tunable organic material. We developed a prediction model of human wetness judgment with an accuracy of 90% and found that the best metrics for the most accurate model were those that were the most human-adjacent: change in temperature at the skin-sample interface (thermal) and compressive force from 2 mm indentation of the sample (mechanical). Given these parameters, we developed a perceptual space capable of recreating 7 distinct levels of wetness perception with the physical parameters used in this study. The results provide insights into the relative contributions of mechanical and thermal stimulus properties in wetness perception. Most notably, this work highlights that the physical characteristics of the skin-stimulus interface can provide ample information for creating a wetness perceptual space, as opposed to the chemical composition of the hydrogels.
Co-circulation of two lineages of Oropouche virus in the Amazon basin, Colombia, 2024
Authors: Usuga Jaime , Limonta Daniel , Perez-Restrepo Laura S. , Ciuoderis Karl A. , Moreno Isabel , Arevalo Angela , Vargas Vanessa , Berg Michael G. , Cloherty Gavin A. , Hernandez-Ortiz Juan P. , Osorio Jorge E. 
Published: September 2024

AbstractIn early 2024, explosive outbreaks of Oropouche virus (OROV) linked to a novel viral lineage were documented in the Brazilian Amazon. Here, we report the introduction of this emerging orthobunyavirus into Colombia and its co-circulation with another OROV lineage. This investigation highlights the complex arbovirus dynamics in South America.
Pharmacogenetic Study of Antipsychotic-Induced Lipid and BMI Changes in Chinese Schizophrenia Patients: A Genome-Wide Association Study
Authors: Wong Kenneth Chi-Yin , Leung Perry Bok-Man , Lee Benedict Ka-Wa , Zheng Zoe Zi-Yu , Tsang Emily Man-Wah , Liu Meng-Hui , Lee Kelly Wing-Kwan , Rao Shi-Tao , Sham Pak-Chung , Lui Simon Sai-Yu , So Hon-Cheong 
Published: September 2024

AbstractSecond-generation antipsychotics (SGAs) are widely used to treat schizophrenia (SCZ), but they often induce metabolic side effects, including dyslipidemia and obesity, posing significant clinical challenges. While genetic factors are believed to contribute to the variability of these side effects, pharmacogenetic studies remain limited. This study aimed to identify genetic variants associated with SGA-induced lipid and BMI changes in a Chinese SCZ cohort using genome-wide association studies (GWASs). A naturalistic longitudinal cohort of Chinese SCZ patients receiving SGAs was followed for up to 18.7 years. We analyzed the patients’ genotypes (N=669), lipid profiles and BMI, utilizing 19 316 prescription records and 3 917 to 7 596 metabolic measurements per outcome. Linear mixed models were used to estimate the random effects of SGAs on lipid profiles and BMI changes for each patient. GWAS and gene set analyses were conducted with false discovery rate (FDR) correction. Two genome-wide significant SNPs were identified under an additive genetic model: rs6532055 inABCG2(olanzapine-induced LDL changes) and rs2644520 nearSORCS1(aripiprazole-induced triglyceride changes). Three additional SNPs achieved genome-wide significance under non-additive models: rs115843863 nearUPP2(clozapine-induced HDL changes), rs2514895 nearKIRREL3(paliperidone-induced LDL changes), and rs188405603 inSLC2A9(quetiapine-induced triglyceride changes). Gene-based analysis revealed six genome-wide significant (p<2.73e-06, Bonferroni correction) genes:ABCG2,APOA5,ZPR1,GCNT4,MAST2, andCRTAC1. Four gene sets were significantly associated with SGA-induced metabolic side effects. This pharmacogenetic GWAS identified several genetic variants associated with metabolic side effects of seven SGAs, potentially informing personalized treatment strategies to minimize metabolic risk in SCZ patients.
Short-term and Long-Term Healthcare Costs Attributable to diagnosed COVID-19 in Ontario; Canada: A Population-Based Matched Cohort Study
Authors: Sander Beate , Mishra Sharmistha , Swayze Sarah , Sahakyan Yeva , Duchen Raquel , Quinn Kieran , Janjua Naveed , Sbihi Hind , Kwong Jeffrey 
Published: September 2024

AbstractObjectivesEstimates of health system costs due to COVID-19, especially for long-term disability (post COVID-19 condition [PCC]) are key to health system planning, but attributable cost data remain scarce. We characterized COVID-19-attributable costs from the health system perspective.MethodsPopulation-based matched cohort study in Ontario, Canada, using health administrative data. To assign attribution to COVID-19, individuals, defined as exposed (positive SARS-CoV-2 PCR test, 01/2020-12/2020) were matched 1:1 to an unexposed individuals (01/2016-12/2018). Historical matching was used to reduce biases due to overall reductions in healthcare during the pandemic and contamination bias. The index date was defined as the first occurrence of positive SARS-CoV-2 PCR test. We used phase-of-care costing to calculate mean attributable per-person costs (2023 CAD), standardized to 10 days, during four phases of illness: pre-index date, acute care, post-acute care (suggestive of PCC), and terminal phase (stratified by early and late deaths). Finally, we estimated total costs at 360 days by combining costs with survival estimates.ResultsOf 165,838 exposed individuals, 159,817 were matched (mean age 40±20 years, 51% female). Mean (95%CI) attributable 10-day costs per person were $1 ($-4, $6) pre-index, $240 ($231, $249) during acute care, and $18 ($14, $21) during post-acute phases. During the terminal phase, mean attributable costs were $3,928 ($3,471, $4,384) for early deaths and $1,781 ($1,182, $2,380) for late deaths. Hospitalizations accounted for 42% to 100% of total costs. Compared to males, costs among females were lower during the acute care phase, but higher during the post-acute care phase. Mean cumulative per-person cost at 360 days was $2,553 ($2,348, $2,756); females had lower costs ($2,194 [$1,945, $2,446]) than males ($2,921 [$2,602, $3,241]).ConclusionsSARS-CoV-2 infection is associated with substantial long-term healthcare costs, consistent with our understanding of the PCC. Understanding phase-specific costs can inform health sector budget planning, future economic evaluations, and pandemic planning.
Bacterial metabolic remodelling by convergent evolution in response to host niche-dependent nutrient availability
Authors: Pickering Amy C. , Gorzynski Jamie , Taylor-Joyce Grace , Fox Willow , Melo Pedro , Alves Joana , Schlauch Hannah , Sargison Fiona , Yebra Gonzalo , Fitzgerald J. Ross 
Published: September 2024

AbstractNew pathogens often arise after host jump events between species. However, our understanding of how bacterial pathogens pivot to distinct nutrient availabilities in a new host niche is limited.Staphylococcus aureusis a multi-host pathogen responsible for a global burden of disease in humans and farmed animals. Multiple human-to-bovine host switching events led to the emergence ofS. aureusas a leading cause of intramammary infection in dairy cattle. Here, we employedex vivomilk infections to investigate how bovineS. aureushas adapted to the dairy niche revealing metabolic remodelling including upregulation of genes for lactose utilisation and branched-chain amino acid biosynthesis in response to nutrient availability. Notably, infection of milk by bovineS. aureusresults in a milk clotting phenotype associated with enhanced bacterial growth that is dependent on the protease aureolysin. The same adaptive phenotype has evolved convergently in different bovineS. aureuslineages via mutations in distinct regulatory gene loci that promote enhanced aureolysin expression. Taken together, we have dissected a key adaptive trait for a bacterial pathogen after a host-switch event, involving metabolic remodelling in response to the availability of nutrients. These findings highlight the remarkable evolutionary plasticity ofS. aureusunderpinning its multi-host species tropism.
LevSeq: Rapid Generation of Sequence-Function Data for Directed Evolution and Machine Learning
Authors: Long Yueming , Mora Ariane , Gürsoy Emre , Johnston Kadina E. , Zhoufan-Li Francesca , Arnold Frances H. 
Published: September 2024

AbstractSequence-function data provides valuable information about the protein functional landscape, but is rarely obtained during directed evolution campaigns. Here, we present Long-read every variant Sequencing (LevSeq), a pipeline that combines a dual barcoding strategy with nanopore sequencing to rapidly generate sequence-function data for entire protein-coding genes. LevSeq integrates into existing protein engineering workflows and comes with open-source software for data analysis and visualization. The pipeline facilitates data-driven protein engineering by consolidating sequence-function data to inform directed evolution and provide the requisite data for machine learning-guided protein engineering (MLPE). LevSeq enables quality control of mutagenesis libraries prior to screening, which reduces time and resource costs. Simulation studies demonstrate LevSeq’s ability to accurately detect variants under various experimental conditions. Finally, we show LevSeq’s utility in engineering protoglobins for new-to-nature chemistry. Widespread adoption of LevSeq and sharing of the data will enhance our understanding of protein sequence-function landscapes and empower data-driven directed evolution.