bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conformational plasticity of human acid-sensing ion channel 1a
Authors: Cahill James , Hartfield Kimberly A. , Heusser Stephanie Andrea , Poulsen Mette Homann , Yoshioka Craig , Pless Stephan Alexander , Baconguis Isabelle 
Published: December 2024

SummaryAcid-sensing ion channels (ASICs) are typically activated by acidic environments and contribute to nociception and synaptic plasticity. ASIC1a is the most abundant subunit in the central nervous system and forms homomeric channels permeable to Na+and Ca2+, making it a compelling therapeutic target for acidotic pathologies including stroke and traumatic brain injury. However, a complete conformational library of human ASIC1a in its various functional states has yet to be described. Using cryo-EM, we obtained hASIC1a structures across a pH range between 8.5 and 5.7, as well as in the presence of a toxin agonist and a gating-modulating mutation. We identify six major conformations that establish linear transmembrane helices to be associated with an open state, delineate mechanistic differences between proton and toxin activation, and demonstrate that desensitization leads to unexpected conformational diversity in the transmembrane domain. Together, they provide a three-dimensional rationalization of decades of structure-function studies on ASIC.
MetaBiome: A Multiscale Model Integrating Agent-Based Modeling and Metabolic Networks Reveals Spatial Regulation in Mucosal Microbial Communities
Authors: Aminian-Dehkordi Javad , Dickson Andrew , Valiei Amin , Mofrad Mohammad R.K. 
Published: December 2024

AbstractMucosal microbial communities (MMCs) are complex ecosystems near the mucosal layers of the gut, essential for maintaining health and modulating disease states. Despite advances in high-throughput omics technologies, current methodologies struggle to capture the dynamic metabolic interactions and spatiotemporal variations within MMCs. In this work, we presentMetaBiome, a multiscale model integrating agent-based modeling (ABM), finite volume methods, and constraint-based models to explore the metabolic interactions within these communities. Integrating ABM allows for the detailed representation of individual microbial agents, each governed by rules that dictate cell growth, division, and interactions with their surroundings. Through a layered approach—encompassing environmental conditions, agent information, and metabolic pathways—we simulated different communities to showcase the potential of the model. Using ourin-silicoplatform, we explored the dynamics and spatiotemporal patterns of MMCs in the proximal small intestine and the cecum, simulating the physiological conditions of the two gut regions. Our findings revealed how specific microbes adapt their metabolic processes based on substrate availability and local environmental conditions, shedding light on spatial metabolite regulation and informing targeted therapies for localized gut diseases.MetaBiome provides a detailed representation of microbial agents and their interactions, surpassing the limitations of traditional grid-based systems. This work marks a significant advancement in microbial ecology as it offers new insights into predicting and analyzing microbial communities.ImportanceOur study presents a novel multiscale model that combines agent-based modeling, finite volume methods, and genome-scale metabolic models to simulate the complex dynamics of mucosal microbial communities in the gut. This integrated approach allows us to capture spatial and temporal variations in microbial interactions and metabolism that are difficult to study experimentally.Key findings from our model include:Prediction of metabolic cross-feeding and spatial organization in multi-species communitiesInsights into how oxygen gradients and nutrient availability shape community composition in different gut regionsIdentification of spatially-regulated metabolic pathways and enzymes in E. coliWe believe this work represents a significant advance in computational modeling of microbial communities and provides new insights into the spatial regulation of gut microbiome metabolism. The multiscale modeling approach we have developed could be broadly applicable for studying other complex microbial ecosystems.
Host-microbiome determinants of ready-to-use supplemental food efficacy in acute childhood malnutrition
Authors: Jamil Zehra , Hanson Gabriel F. , Iqbal Junaid , Moreau G. Brett , Iqbal Najeeha Talat , Ahmed Sheraz , Hotwani Aneeta , Kabir Furqan , Umrani Fayaz , Sadiq Kamran , Ahmed Kumail , Mallawaarachchi Indika , Ma Jennie Z. , Aziz Fatima , Ali S Asad , Moore Sean 
Published: December 2024

AbstractReady-to-use supplemental foods (RUSF) are energy-dense meals formulated to prevent and treat moderate and severe childhood acute malnutrition (MAM and SAM) in high-risk settings. Although lifesaving, the degree and durability of weight recovery with RUSF is unpredictable. We examined whether environmental enteric dysfunction (EED) and gut microbiota perturbations are risk factors for RUSF failure in a birth cohort of 416 rural Pakistani children followed for growth, common childhood illnesses, and biomarkers from blood, urine, and stool. Infants who developed wasting (weight-for-length Z score <-2, n=187, 45%) during surveillance received Acha Mum (a chickpea-based RUSF) daily for eight weeks. Machine learning identified seven biomarkers that predicted RUSF response (n=75) vs. non-response (n=112) with 73% accuracy. Remarkably, gut microbiome composition predicted RUSF response with 93% (pre-supplementation) and 98% (post-supplementation) accuracy. Seven outliers whose microbiome falsely predicted positive response experienced extraordinary burdens of inflammation and illness during supplementation. These findings identify gut microbial signatures and biomarkers of gut and systemic inflammation as robust predictors of RUSF response in infants free from intercurrent illness during recovery, setting the stage for predictive models to guide precision use of RUSF and adjunct therapies in undernourished children.
Assessment of Awareness and Willingness to Use Pre-Exposure Prophylaxis for HIV Prevention among Female Sex Workers in Rwanda
Authors: Nzungize Albert , Munyaneza Athanase 
Published: December 2024

AbstractBackgroundFemale sex workers (FSWs) in sub Saharan Africa bear a disproportionate burden of HIV infection. While pre exposure prophylaxis (PrEP) is increasingly accessible in the region, limited data exist on FSWs awareness of and willingness to use PrEP. This study aimed to assess PrEP awareness and willingness to use it, along with associated factors, among FSWs in Kigali, Rwanda.MethodsThis cross sectional study, conducted from April to September 2024, evaluated PrEP awareness and willingness to use it among 333 FSWs recruited through community based FSW associations. Data were analyzed using SPSS, with logistic regression employed to explore associations between participant characteristics and PrEP awareness and willingness. Ethical approval was obtained from the Rwanda National Ethics Committee.ResultsThe mean age of participants was 30 years (SD: 7.26), with 47% aged between 25 and 34. Most were single (67%) and unemployed (66%), with nearly half (49.5%) reporting only primary education. A significant proportion (81%) had undergone HIV testing in the past six months, and 50% had been involved in sex work for 2 to 5 years. The median number of sexual partners in the past week was 7.Awareness of PrEP was high (81%), however, consistent condom users were less likely to be aware of PrEP (adjusted odds ratio (aOR): 0.40, 95% confidence interval (CI): 0.19, 0.83), as were those not screened for sexually transmitted infections (STIs) compared to those who were screened (aOR: 0.43, 95% CI: 0.22, 0.85). Willingness to use PrEP was reported by 80% of participants. Those with a primary education were more willing to use PrEP compared to those with no formal education (aOR: 4.09, 95% CI: 1.62, 10.33). Conversely, participants screened for STIs were less likely to report willingness compared to those not screened (aOR: 0.28, 95% CI: 0.12, 0.62).ConclusionThis study demonstrates high awareness and willingness to use PrEP among FSWs in Kigali. However, consistent condom users and those unscreened for STIs were less aware of PrEP, and willingness to use it varied based on education and STI screening status. These findings underscore the need for targeted health education and STI screening initiatives to enhance PrEP uptake and strengthen HIV prevention efforts in this vulnerable population.
Quantification of Brain Functional Connectivity Deviations in Individuals: A Scoping Review of Functional MRI Studies
Authors: Toloknieiev Artur , Voitsekhivskyi Dmytro , Kholodkov Hlib , Lvovich Roman , Matiushko Petro , Rekretiuk Daria , Dikhtiar Andrii , Viter Antonii , Pokras Volodymyr , Wunderlich Stephan , Stoecklein Sophia 
Published: December 2024

AbstractFunctional connectivity magnetic resonance imaging (fcMRI) is a well-established technique for studying brain networks in both healthy and diseased individuals. However, no fcMRI-based biomarker has yet achieved clinical relevance. To establish better understanding of the state of the art in quantifying abnormal connectivity in comparison to a reference distribution, for potential use in individual patients, we have conducted a scoping review over 5672 entries from the last 10 years. We have located five publications proposing methods of abnormal connectivity quantification, reported these methods and formalized them. We also illustrated the emerging trends and technical innovations in fcMRI research that may facilitate development of individualized fcMRI-based abnormal connectivity metrics.
Long-term Effects of Text Messages with Financial Incentives for Men with Obesity: Two-year Follow-up of the Game of Stones trial
Authors: Dombrowski Stephan U , Hoddinott Pat , Swingler James , Macaulay Lisa , O’Dolan Catriona , Cotton Seonaidh , Avenell Alison , Getaneh Abraham M , Gray Cindy M , Hunt Kate , Kee Frank , MacLean Alice , McKinley Michelle C , Torrens Claire , Turner Katrina , van der Pol Marjon , MacLennan Graeme 
Published: December 2024

AbstractObjectivesTo compare the difference in percentage weight change at 24 months following a 12-month text messaging with financial incentive intervention compared to a waiting list control group, and to compare the text messaging alone group to the control group.DesignAssessor-blinded three-arm randomised clinical trial.SettingThree disadvantaged communities from the UK.Participants585 men with body mass index (BMI) of ≥30kg/m2enrolled between July 2021 and May 2022, of which 377 participants (64%) completed 24 months’ follow-up.Interventions12 months of daily behavioural text messages combined with financial incentives; 12 months of the same text messages alone; or waiting for 12 months followed by receipt of the first 3 months (months 12-15) of text messages (control).Main outcome measuresWithin-participant change from baseline weight.ResultsAt 24 months, the mean percent weight change (standard deviation) was −3.9% (6.9%) for the text messaging with financial incentives group, −2.6% (6.8%) for the text messaging alone group, and −2.2% (6.8%) for the control group. Compared with the control group, the mean percent weight change was not significantly greater in the text messaging with financial incentives group (mean difference, −1.0%; 97.5% CI, −2.6 to 0.6; P = .22) or the text messaging alone group (mean difference, −0.0%; 97.5% CI, −1.6 to 1.5; P = .95). At least 5% weight loss at 24 months was achieved by 52 (40%) participants in the text messaging with financial incentives group; 32 (28%) in the text messaging alone group and 43 (32%) in the control group.ConclusionsA scalable, low-cost text message with financial incentives intervention supported clinically relevant maintenance of weight loss 12 months after the intervention ceased, including those from disadvantaged backgrounds.What is already known on this topicMen, particularly those in lower socio-economic groups, engage less frequently in existing weight loss interventions and services, and might benefit from gender-sensitized interventions.The Game of Stones trial showed that a 12-month intervention consisting of text messaging with endowment financial incentives resulted in statistically significant weight loss in men with obesity compared with control.What this study addsAt 24 months, participants receiving 12 months of behavioural text messages with financial incentives displayed continued weight loss which is likely to be clinically important for some men.This digital, scalable, low risk text messaging with financial incentives intervention, with low participant and staff burden, shows promise for longer-term weight maintenance in men, including those living in the most deprived areas.
Quantitative bias analysis for mismeasured variables in health research: a review of software tools
Authors: Wood Codie J.C. , Tilling Kate M. , Bartlett Jonathan W. , Hughes Rachael A. 
Published: December 2024

AbstractBackgroundMismeasurement (measurement error or misclassification) can cause bias or loss of power. However, sensitivity analyses (e.g. using quantitative bias analysis, QBA) are rarely used.MethodsWe reviewed software tools for QBA for mismeasurement in health research identified by searching Web of Science, the CRAN archive, and the IDEAS/RePEc software components database. Tools were included if they were purpose-built, had documentation and were applicable to epidemiological research.Results16 freely available software tools for QBA were identified, accessible via R and online web tools. The tools handle various types of mismeasurement, including classical measurement error and binary misclassification. Only one software tool handles misclassification of categorical variables, and few tackle non-classical measurement error.ConclusionsEfforts should be made to create tools that can assess multiple mismeasurement scenarios simultaneously, to increase the clarity of documentation for existing tools, and provide tutorials for their usage.
UVESCREEN1: A randomised feasibility study of imaging-based uveitis screening for children with juvenile idiopathic arthritis- Study Protocol
Authors: Dave Sonali , Rahi Jugnoo , Petrushkin Harry , Testi Ilaria , Patel Dipesh E , Solebo Ameenat Lola 
Published: December 2024

AbstractChildren with Juvenile Idiopathic Arthritis (JIA) are at a currently unpredictable risk of a blinding, often asymptomatic, co-existent eye disorder, anterior uveitis which requires prompt treatment. The unpredictability of this insidious disorder commits children with JIA to three-monthly expert clinical examination in specialist eye centres often located far from their homes. Optical coherence tomography of the ocular anterior segment (AS-OCT) has been shown to be an acceptable, repeatable and sensitive modality for uveitis detection, but is not standard care. This feasibility randomised controlled trial (RCT) aims to inform a future full-scale RCT comparing current routine practice (expert slit lamp examination, SLE) to AS-OCT for the surveillance of uveitis in children at risk.Eighty children aged between 2 and 12 years old and diagnosed with JIA within the preceding year will be included. Participants with an existing diagnosis of uveitis, other ocular co-morbidities or those unable to complete examinations or provide informed assent will be excluded. Participants will be randomised to SLE (control) or AS-OCT (intervention) examination at a frequency consistent with the current national programme for childhood uveitis surveillance. Children in the intervention arm will also have standard examination at 6 and 12 months after study entrance. Outcomes of interest will be feasibility (recruitment and attrition rates), clinical metrics (proportion diagnosed with uveitis or other ocular disorders at 12 months after study entrance), quality of life outcomes (PedsQL), and resource use. Additionally, comparative analysis of AS-OCT versus SLE (‘gold standard’ reference testing) findings at 6 and 12 months for those in the intervention arm will provide the proof-of-concept data necessary to develop and undertake a larger scale trial.Trial registration: This trial has been registered withclinicaltrails.gov(NCT05984758).SummaryAnterior uveitis is a rare form of eye disease that is commonly associated with Juvenile Idiopathic Arthritis (JIA). Childhood uveitis is potentially blinding, so children with JIA must travel to a specialist centre every two to three months for an eye examination to pick up signs of uveitis. This feasibility study will compare routine Slit Lamp Examination (SLE) with imaging-based surveillance using Optical Coherence Tomography of the Anterior Segment (AS-OCT) to support the design of a future study. Eighty children between the ages of two and twelve years old who have been diagnosed with JIA in the past year will be invited to take part. Children will be randomised into one of two arms (SLE or AS-OCT) and will have their routine uveitis screening appointments over one year using either of the screening modalities. This study will provide the proof-of-concept data necessary to develop and undertake a larger scale trial.
Sex-specific Risk Factors for Survival in B-cell Non-Hodgkin Lymphoma Patients after Anti-CD19 CAR T-Cell Therapy
Authors: Patel Manishkumar S. , Mian Agrima , Jalota Akansha , Bazeley Peter , Patil Sujata , Hill Brian T. , Gupta Neetu 
Published: December 2024

AbstractSex bias is well documented in autoimmune diseases, cancer and immune responses to infectious agents. Here, we investigated if pre-treatment risk factors that influence the survival of B-cell non-Hodgkin lymphoma (NHL) patients after anti-CD19 CAR T-cell therapy are sexually dimorphic. We measured pre-leukapheresis tumor burden (lactate dehydrogenase levels), C-reactive protein (CRP) and serum cytokine and chemokine concentration in 67 B-cell NHL patients treated with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel). Association of relative abundance of each factor with progression-free survival (PFS) and overall survival (OS) was analyzed in male and female patients together, or only within the male cohort or only within the female cohort. No differences in PFS or OS or in pre-treatment tumor burden, CRP and cytokine/chemokine levels were observed between male and female patients undergoing axi-cel or tisa-cel therapy. However, within the male group, patients with higher pre-treatment tumor burden and greater relative abundance of CRP and pro-inflammatory cytokines and chemokines conferred greater risk of poor progression-free survival (PFS) and/or overall survival (OS). In contrast, within the female group, patient survival was largely agnostic to variations in tumor burden, CRP and cytokine/chemokine abundance. Specifically, higher relative abundance of IL-6, IL-8, IL-27, TNF-α, Eotaxin-1, MIP-1β and MCP-1 was associated with poor PFS and/or OS after CAR T-cell therapy within the male group, whereas higher IL-27 and IFNα2 abundance was associated with better PFS and poorer OS, respectively, within the female group. Our data suggest that biological sex may modulate the impact of baseline risk factors on survival outcomes of CAR T-cell therapy in B-cell NHL.
PNEUMOCOCCAL SEROTYPE DISTRIBUTION AND COVERAGE OF EXISTING AND PIPELINE PNEUMOCOCCAL VACCINES
Authors: King Laura M , Andrejko Kristin L , Kobayashi Miwako , Xing Wei , Cohen Adam L , Self Wesley H , Resser J Jackson , Whitney Cynthia G , Baughman Adrienne , Kio Mai , Grijalva Carlos G , Traenkner Jessica , Rouphael Nadine , Lewnard Joseph A 
Published: December 2024

ABSTRACTBackgroundStreptococcus pneumoniae(pneumococcus) causes invasive pneumococcal disease (IPD) and non-invasive acute respiratory infections (ARIs). Three pneumococcal conjugate vaccines (PCVs) are recommended in the United States with additional products in clinical trials. We aimed to estimate 1) proportions of IPD cases and pneumococcal ARIs caused by serotypes targeted by existing and pipeline PCVs and 2) annual U.S. pneumococcal burdens potentially preventable by PCVs.MethodsWe estimated serotype distribution and proportions of non-invasive pneumococcal ARIs (AOM [children only], sinusitis, non-bacteremic pneumonia) and IPD attributable to serotypes targeted by each PCV using Markov chain Monte Carlo approaches incorporating data from studies of serotype distribution in ARIs and Active Bacterial Core Surveillance (ABCs) data. We then estimated annual numbers of outpatient-managed pneumococcal ARIs, non-bacteremic pneumococcal pneumonia hospitalizations, and IPD cases potentially preventable by PCVs in the United States by multiplying pneumococcal disease incidence rates by PCV-targeted proportions of disease and vaccine effectiveness estimates.ResultsIn children, PCV15, PCV20, PCV24, PCV25, and PCV31 serotypes account for 16% (95% confidence interval: 15–17%), 31% (30–32%), 34% (32–35%), 43% (42–44%), and 68% (67–69%) of pneumococcal acute otitis media cases, respectively. In adults, PCV15, PCV20, PCV21, PCV24, PCV25, and PCV31 serotypes account for 43% (38–47%), 52% (47–57%), 69% (64–73%), 65% (61–70%), 62% (57–67%), and 87% (83–90%) of pneumococcal non-bacteremic pneumonia cases. For IPD, 42–85% of pediatric and 42–94% of adult cases were due to PCV-targeted serotypes. PCV-preventable burdens encompassed 270 thousand–3.3 million outpatient-managed ARIs, 2–17 thousand non-bacteremic pneumonia hospitalizations, and 3–14 thousand IPD cases in the United States annually.ConclusionsAcross pneumococcal conditions, coverage and preventable burdens were lowest for PCV15 and highest for PCV31, with PCV21 also targeting sizeable burdens of adult disease. Serotype distribution across syndromes may inform vaccine formulations and policy.
HIV Risk and Intention to use PrEP among Sexually Active Female University Students in Zambia: A Cross-Sectional Survey to Understand Influential Factors
Authors: Hampanda K , Bolt M , Nayame L , Hamoonga T , Sehrt M , Thorne J , Harrison M , Pintye J , Amstutz A , Abuogi L , Mweemba O 
Published: December 2024

ABSTRACTBackgroundLimited research exists on pre-exposure prophylaxis (PrEP) interest or use among female university students in high HIV-prevalence African settings. This study sought to establish the relationship between epidemiologic and perceived HIV risk and PrEP intention among Zambian female university students.MethodsWe recruited female students at an urban university to complete a survey on intention to use PrEP in the next year (primary outcome); other PrEP knowledge, attitudes, and behaviors; demographics; epidemiologic HIV risk and risk perception. Descriptive statistics, regression and mediation analyses were used.ResultsOf the 454 sexually active participants, 118 (26%) reported PrEP intention. Actual PrEP use was rare (< 5%). The odds of PrEP intention increased for those with perceived high HIV risk (aOR 3.08; 95% CI 1.71-5.55) and with each year at university (aOR 1.47; 95% CI 1.21-1.80) but decreased with higher PrEP stigma (aOR 0.91; 95% CI 0.86-0.96) and more negative PrEP perceptions (aOR 0.91; 95% CI 0.85-0.97). More epidemiologic risk factors were originally associated with PrEP intention (OR 1.24; 95% CI 1.01-1.53 for each risk factor), though this relationship weakened after adjustment for perceived HIV risk, which mediated 69% of the relationship between epidemiologic HIV risk and PrEP intention. Only 29% of high-risk participants recognized their high epidemiological HIV risk (3+ risk factors).ConclusionsAlong with PrEP education and stigma reduction, there is a need for approaches that help female university students in Zambia accurately identify their HIV risk to make informed PrEP decisions.