bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sialidases derived from Gardnerella vaginalis remodel the sperm glycocalyx and impair sperm function
Authors: Dohadwala Sarah , Shah Purna , Farrell Maura , Politch Joseph , Marathe Jai , Costello Catherine E , Anderson Deborah J 
Published: February 2025

AbstractBacterial vaginosis (BV), a dysbiosis of the vaginal microbiome, affects approximately 29 percent of women worldwide (up to 50% in some regions) and is associated with several adverse health outcomes including preterm birth and increased incidence of sexually transmitted infection (STI). BV-associated bacteria, such asGardnerella vaginalisandPrevotella timonensis,damage the vaginal mucosa through the activity of sialidase enzymes that remodel the epithelial glycocalyx and degrade mucin glycoproteins. This damage creates an inflammatory environment which likely contributes to adverse health outcomes. However, whether BV-associated glycolytic enzymes also damage sperm during their transit through the reproductive tract has not yet been determined. Here, we show that sialidase-mediated glycocalyx remodeling of human sperm increases sperm susceptibility to damage within the female reproductive tract. In particular, we report that desialylated human sperm demonstrate increased susceptibility to complement lysis and agglutination, as well as decreased sperm transit through cervical mucus. Our results demonstrate a mechanism by which BV-associated sialidases may affect sperm survival and function and potentially contribute to adverse reproductive outcomes such as preterm birth and infertility.Significance statementSperm surface glycans are crucial for reproductive and immune processes in the female reproductive tract. We found that sialidases derived from BV-associated bacteria remodel the sperm glycocalyx resulting in aberrant agglutination, mucus trapping, and complement-mediated cytolysis of sperm. These results implicate glycolytic damage to sperm as a potential mechanism for BV-associated adverse reproductive outcomes.Classification:Biological Sciences, Immunology and Inflammation,
Loss of a major venom toxin gene in a Western Diamondback rattlesnake population
Authors: Dowell Noah L. , Cahill Elizabeth , Carroll Sean B. 
Published: February 2025

AbstractThe biochemical complexity and evolutionary diversity of snake venom composition reflects adaptation to the diversity of prey in their diets. However, the genetic mechanisms underlying the evolutionary diversity of venoms are not well understood. Here, we explored the potential extent of and genetic basis for venom protein variation in the widely-distributed Western Diamondback rattlesnake (Crotalus atrox). As in many rattlesnake venoms, metalloproteinases (SVMPs) are the major component ofC. atroxvenom, with three proteins belonging to three distinct major structural SVMP classes, MDC4, MAD3a, and MPO1, constituting the most abundant SVMPs. We found that while most venom proteins, including MDC4 and MAD3a, vary little among individuals, the MPO1 protein is completely absent from some animals, most commonly those from the western part of the species’ geographic range. This distribution correlates with the previous finding of two distinct lineages withinC. atroxand indicates that different ecological factors have shaped venom composition across the species’ range. We further show that the loss of MPO1 expression is not due to transcriptional down-regulation, but to several independent inactivating mutations at the locus, including whole gene deletion. The recurrent inactivation of a major toxin gene within aC. atroxpopulation may reflect relaxed selection on the maintenance ofMPO1function, but we also raise the possibility that the loss of venom components may be favored if there is a cost to producing a less effective toxin in protein-rich venoms.
Impact of intestinal parasitic infections on gut epithelial barrier and inflammation among foreign-born persons living with HIV
Authors: Reimer-McAtee Melissa , Serpa Jose , McAtee Casey , Ortega Emma , Somasunderam Anoma , Arduino Roberto , Mejia Rojelio , Utay Netanya S. 
Published: February 2025

AbstractSystemic inflammation is a major driver of comorbidities in people with HIV (PWH). Increased levels of biomarkers of enterocyte turnover, microbial translocation, and systemic inflammation have been shown to predict morbidity and mortality in PWH on antiretroviral therapy (ART). We conducted a prospective cohort study of foreign-born PWH with undetectable HIV RNA (<20 copies/mL) with and without intestinal parasitic coinfection. Biomarkers of enterocyte turnover (intestinal fatty acid binding protein [I-FABP]), microbial translocation (soluble CD14), and systemic inflammation (soluble CD163) were measured. Stool parasite quantitative PCR (qPCR) testing andStrongyloides stercoralisrecombinant IgG ELISA (StrongyIgG) were utilized to diagnose parasitic infection. Of the 52 participants, 14 (27%) tested positive for infection withStrongyloides stercoralisbyStrongyIgG, and 7 (16%) of the 45 participants who provided stool samples tested positive for a parasitic infection (not includingBlastocystis) by stool qPCR. The median sCD14 level in PWH with (+)StrongyIgG was significantly higher than PWH with (-)StrongyIgG (1.69 ug/ml versus 1.48 ug/ml, p=0.03). The median sCD163 in PWH with parasitic infections by qPCR was not significantly different from sCD163 in PWH negative for parasitic infections. I-FABP levels did not differ significantly between groups. Participants with both HIV and intestinal parasite infections had increased levels of sCD14, a marker of microbial translocation that is an independent predictor of mortality in PWH, compared to PWH without parasitic infections. These findings raise concern about the long-term sequelae of intestinal parasitic infections in PWH.
Abnormal Blood Pressure Dipping Pattern in Smokers
Authors: Arslan Muhammed Ömer , Acar Tijen , Doğan Yunus , Koç Şahbender , Güneş İbrahim Sefa 
Published: February 2025

AbstractAimHypertension with non-dipper or reverse dipper patterns has worse outcomes. Smokers have some risk factors for abnormal dipping. There are conflicting results about the association between smoking and blood pressure (BP) dipping patterns, thus we aimed to examine it in essential hypertension.Methods178 essential hypertension patients (ages 30-83) completed Fagerström Nicotine Dependence Test (FNDT) and our custom Patient Data Collection Test (PDCT). We analyzed these data with the ambulatory BP measurements (ABPM) and performed logistic regression analysis.ResultsAbnormal dipping patterns were significantly more frequent among patients with a history of smoking (75,0%) than those without history of smoking (47,4%), (p<0,001). Among smokers, abnormal dipping patients had significantly higher FNDT Scores (5 (0-10) versus 2 (0-9), p=0,046), longer smoking years (25 (6-50) versus 20 (5-50), p=0,017), and more smoking exposure in terms of pack.years (25 (3-135) versus 15 (1-75), p=0,023). Patients with history of smoking had significantly higher nocturnal systolic (128,10±15,54 versus 120,56±12,84 mmHg, p=0,001), nocturnal diastolic (80,82±12,60 versus 76,44±10,89 mmHg, p=0,016), and 24-hour mean systolic (133,15±13,52 versus 127,90±12,03 mmHg, p=0,008) BP values; and more blunted systolic and diastolic dipping ratios than non-smokers. Patients with a history of smoking were 3,484 (1,693-7,171 CI:0,95 p=0,001) times more likely to have abnormal dipping. Smoking was also associated with diabetes mellitus, dyslipidemia, and metabolic syndrome.ConclusionSmoking was associated with abnormal dipping patterns; higher nocturnal systolic, diastolic, and 24-hour systolic BP values; and lower systolic and diastolic dipping rates. FNDT score and smoking exposure parameters were significantly higher in abnormal dipping.
Developing a Data Note reporting guideline for qualitative health and social care research datasets (the DeNOTE study): A study protocol
Authors: Long Hannah A. , Toomey Elaine , Stevenson Fiona , Brooks Joanna M. , Stewart Andrew J. , French David P. 
Published: February 2025

ABSTRACTBackgroundData Note articles provide concise descriptions of research datasets, detailing how and why the data were created and facilitating reuse of the data. Additionally, Data Notes are typically believed to have the added value of increasing research transparency and making the data comply with the FAIR principles (i.e., Findable, Accessible, Interoperable, and Reusable). However, existing guidelines and templates for Data Note articles are designed for quantitative research datasets and there are no equivalents for qualitative research datasets.AimTo develop a novel reporting guideline for Data Note articles describing qualitative health and social care datasets (i.e., the DeNOTE reporting guideline).MethodsOur plans to develop the DeNOTE reporting guideline have been registered on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network. In summary, the DeNOTE study consists of (a) a rapid scoping exercise of existing literature, resources, and expert knowledge to identify and synthesise ‘items’ or ‘statements’ of a reporting guideline that are relevant to a Data Note article describing qualitative health and social care data, (b) an online questionnaire with expert participants to rate their agreement with items identified in (a) and to propose new or amended items, (c) an online workshop with participants to further co-develop the reporting items, with the aim to reach consensus on the items, (d) eliciting feedback from participants on the draft reporting guideline, and (e) finalising the DeNOTE reporting guideline.ConclusionOur goal is to produce a novel reporting guideline to support researchers when producing a Data Note article describing qualitative health and social care research data. In the process, we will produce tailored open research infrastructure to better support qualitative researchers engaging in open research practices.
Epigenome-wide association study of cerebrospinal fluid-based biomarkers of Alzheimer’s disease in cognitively normal individuals
Authors: Hüls Anke , Liu Jiaqi , Konwar Chaini , Conneely Karen N. , Levey Allan I. , Lah James J. , Wingo Aliza P. , Wingo Thomas S. 
Published: February 2025

AbstractINTRODUCTIONCerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) are reliable predictors of future AD risk. We investigated whether pre-clinical changes in AD CSF biomarkers are reflected in blood DNA methylation (DNAm) levels in cognitively normal participants.METHODSWe profiled blood-based DNAm with the EPIC array in participants without a diagnosis of cognitive impairment in the Emory Healthy Brain Study (EHBS; N=495) and ADNI (N=122). Their CSF Aβ42, tTau, and pTau levels were quantified using Elecsys immunoassays. We conducted epigenome-wide association studies to assess associations between DNAm and CSF biomarkers of AD.RESULTSIn EHBS, no loci were Bonferroni-significant after adjusting for confounding factors. In ADNI, two loci were significant, but they were not replicated in EHBS. There was little agreement between the top loci from EHBS and ADNI.DISCUSSIONOur study showed little evidence of an association between differential blood-based DNAm and pre-clinical AD CSF biomarkers.
Effectiveness of Social Networks in Enhancing the Uptake of Artemisinin-based Combination Therapy (ACT) in Malaria-Prone Zones of Kenya
Authors: Nyongesa Florence Nelima , Gathiaka John Kamau , Mwabu Germano 
Published: February 2025

AbstractIntroductionMalaria remains a critical health challenge in Kenya, particularly among children under five years who are highly vulnerable to its complications. Artemisinin-based combination therapies (ACTs) are the recommended first-line treatment for uncomplicated malaria. However, their uptake varies due to socio-economic inequalities, geographic disparities, and the influence of social networks. Understanding how social interactions, particularly those mediated by religious affiliations, impact ACT uptake can inform strategies to improve malaria treatment outcomes in malaria-prone regions.MethodsThis study utilized data from the Kenya Malaria Indicator Survey (KMIS) 2020, employing a cross-sectional design and stratified two-stage cluster sampling. Data on malaria prevalence, treatment-seeking behavior, and ACT usage were analyzed using descriptive statistics and logistic regression. The analysis focused on socio-demographic factors, geographic differences, and the role of social networks mediated through religious affiliations.ResultsACT uptake among children under five was 52%. Male children were less likely to receive ACTs, with probabilities 6.3% lower in rural areas and 3.1% lower in urban areas. Younger children in rural areas, particularly those aged one, had a 5.7% higher likelihood of ACT usage, while uptake declined with age. Caregivers’ education significantly enhanced ACT uptake in rural areas, increasing the likelihood by 25%. Rural Muslim households were 17.2% more likely to use ACTs, while urban Christian households showed modest improvements. Wealth disparities also affected uptake, with wealthier urban households less likely to use ACTs.ConclusionThe study highlights the critical role of social networks, particularly religious affiliations, in shaping ACT uptake in malaria-prone zones of Kenya. Addressing barriers to access through these networks offers a promising avenue for increasing ACT utilization and improving health outcomes. Leveraging community-driven approaches and religious institutions could enhance equitable malaria treatment coverage across vulnerable populations.
The burden of rheumatic heart disease and issues affecting the provision of care in Malawi: A scoping review
Authors: Blennerhassett E , Brady Bates O , O’Connor M , Gondwe H , Msimuko L , Ledwidge M , Mbakaya B , Gallagher J 
Published: February 2025

AbstractBackgroundRheumatic heart disease (RHD) is an autoimmune sequela of group A streptococcal (GAS) pharyngitis. Single or recurrent episodes of acute rheumatic fever (ARF), a complication arising 2-3 weeks after GAS infection, can cause damage to the valves of the heart and RHD. This trajectory towards severe disease is now rare in high-income countries. The appropriate use of antibiotics has contributed to this decline in RHD prevalence, but socio-economic factors have also had a profound impact. In Malawi, as in many low-income countries, RHD continues to pose a significant challenge. Limited access to healthcare and poor education likely contribute to the disease burden, and actionable solutions are needed to eradicate RHD in these communities.AimTo determine the present burden of GAS, ARF and RHD in Malawi, the issues affecting the provision of care and the solutions that have been proposed.Design and settingA scoping review encompassing four electronic databases from which relevant articles were drawn.MethodA systematic search of ‘PubMed’, ‘EMBASE’, ‘Cochrane Library’ and ‘Clinicaltrials.gov’ was conducted to identify research related to the study objectives. Supplemental grey literature and internet searches were carried out and collaboration with experts in the field ensured a comprehensive review of the available data. The selected articles spanned from 2008 to October 2024 and addressed one or more of the diseases of interest. A scoping review was carried out according to the Arksey and O’Malley procedure.ResultsThis scoping review includes thirty papers, which focus primarily on RHD burden, screening, treatment, and barriers to care in Malawi. There was significantly less research on ARF and GAS infections. A wide variety of study designs were employed (mostly descriptive, cross-sectional and retrospective studies) and the number of participants varied significantly across the different studies. Two government reports were also included. The primary findings included a shift in the focus of research towards solutions to the high burden of RHD in Malawi.ConclusionThe significant morbidity and mortality associated with RHD are a major concern in the communities and healthcare systems of Malawi. As in many low-income countries, resource mobilisation and improved education are areas requiring attention. To address the high burden of disease in the country, ongoing research is largely focused on establishing a sufficiently large and appropriately trained workforce to diagnose and monitor RHD using the resources available within the constraints of the country’s socioeconomic context.
Dysregulated Immune Proteins in Plasma in the UK Biobank Predict Multiple Myeloma 12 years Before Clinical Diagnosis
Authors: Fieggen Josh , Thakur Anshul , Butler Christopher C , Ramasamy Karthik , Thakurta Anjan , Clifton David A. , Clifton Lei 
Published: February 2025

AbstractHigh-throughput proteomics has emerged as a potentially rich data source to improve capacity to forecast disease. This study explores the utility of plasma proteomics for identifying novel predictors of Multiple myeloma (MM), combining machine learning with statistical approaches. Utilising data from the UK Biobank, including proteomic profiles of over 50k participants, we applied an “extreme gradient boosting” (XGBoost) algorithm with SHapley Additive exPlanation (SHAP) feature-importance measures to identify key proteomic biomarkers to predict onset of MM. At least seven of the top 10 identified proteins are related to immune function and activation of lymphoid cells; two are validated MM targets with approved therapies. The top 10 proteins along with key clinical predictors were further analysed using Cox proportional hazards models to assess their contribution to incident MM risk. 10 proteomic biomarkers ranked by SHAP value substantially outperformed traditional clinical predictors. This superior performance was maintained over the 12-year follow-up period, demonstrating the predictive ability of these proteomic biomarkers for early detection of MM. The demonstration of the dysregulated expression of proteins in serum from healthy individuals, if confirmed in prospective cohorts and independent datasets, could lead to novel approaches to screening for MM and precursor conditions.
Brain size dependent speciation and extinction rates in birds and the cognitive buffer hypothesis
Authors: Oyston Jack W. , May Michael R. , Felice Ryan N 
Published: February 2025

AbstractBoth brain and body size vary greatly across birds, with both traits hypothesized to play a key role in diversification patterns across the group. Larger brains facilitate the evolution of greater behavioural plasticity, which could facilitate diversification in two ways, either by driving increased speciation (behavioural drive) or by making lineages more resilient to extinction (cognitive buffer). Here, we model brain size dependent diversification dynamics from published endocranial volume data for a sample of 2291 extant and fossil bird taxa, jointly modelling speciation rate, extinction rate and fossilisation rate separately for perching birds and other groups. We find that increasing relative brain size primarily increases diversification rate through decreasing extinction rate, supporting the cognitive buffer hypothesis and suggesting that larger brains in birds promote diversification by making species more resilient to extinction. Although speciation and extinction are dependent on relative brain size in both perching birds and other groups, this dependence is non-linear. In perching birds, the highest diversification rates are found over a narrow range of relative brain sizes, in contrast to other bird groups which show lower diversification rates over a broader range of relative brain sizes.SignificanceThe potential for speciation and extinction are thought to be shaped by key phenotypic traits. In birds, brain size is one important trait hypothesized to have an impact on diversification. Testing this hypothesis requires the evolution of brain size, speciation rate, and extinction rate to be jointly modelled across the bird phylogeny. The inclusion of information on past diversity has been shown to be important in inferring diversification patterns, and so we include not only data from a broad sample of living birds but also information from the fossil record. Our study reveals patterns of brain size dependent diversification in birds which are consistent with the cognitive buffer hypothesis, with higher relative brain sizes being associated with lower extinction rates.
Effectivein vivoRNA base editingviaengineered cytidine deaminase APOBECs fused with PUF proteins
Authors: Han Wenjian , Yuan Bo , Fan Xiaojuan , Li Weike , Yuan Yiting , Zhang Yuefang , Wang Shu , Shan Shifang , Hafner Markus , Wang Zefeng , Qiu Zilong 
Published: February 2025

SummaryBase editing stands at the forefront of genetic engineering, heralding precise genetic modifications with broad implications. While CRISPR-based DNA and RNA base editing systems capitalize on sgRNA-guided specificity and diverse deaminase functionalities, the pursuit of efficient C-to-U RNA editing has been hampered by the inherent constraints of cytidine deaminases. Here, we report an RNA base editing platform by refining cytidine deaminases, termed professional APOBECs (ProAPOBECs), through systematic enhancements and AI-driven protein engineering. ProAPOBECs demonstrate unprecedented catalytic versatility, particularly fused with RNA-recognizing Pumilio and FBF (PUF) proteins. We present the first effective use of RNA base editing in the brain with ProAPOBECs in Mef2c mutant mice, a model for autism. The AAV-mediated RNA base editing via ProAPOBEC not only corrects genetic mutation in mRNAs but significantly alleviates autistic-like behaviors in the mice. This work introduces a pioneering collection of RNA base editing instruments, emphasizing their therapeutic potential in combatting genetic disorders.
Chimeric Antigen Receptors Discriminate Between Tau and Distinct Amyloid-Beta Species
Authors: Siebrand Cynthia J. , Bergo Nicholas J. , Lee Suckwon , Andersen Julie K. , Walton Chaska C. 
Published: February 2025

Abstract/SummaryThe lack of a definitive cure for Alzheimer’s disease (AD) is fueling the search for innovative therapeutic strategies. Having revolutionized cancer immunotherapy, immune cell engineering with chimeric antigen receptors (CAR) is being explored to target AD. Whether CARs can recognize distinct amyloid-β (Aβ) species and tau neurofibrillary tangles (NFTs)—hallmark pathologies of AD—remains unclear. To investigate this, we engineered CARs based on AD antibodies targeting tau (E2814), Aβ (Lecanemab and Aducanumab), and truncated pyroglutamate form of Aβ (Aβp3-42; Donanemab and Remternetug). To evaluate CAR function, we established the murine DO11.10 hybridoma T-cell line as a practical and scalable testing platform. Our findings demonstrate that CARs can detect and discriminate between tau preformed fibrils (PFFs), Aβ1-42, and Aβp3-42 aggregates. This highlights the potential of repurposing AD antibodies for CAR-based therapies to selectively target tau NFTs and distinct forms of Aβ senile plaques.