bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative observational evidence of indirect herd benefits from COVID-19 vaccination or prior infection on SARS-CoV-2 infections and COVID-19 deaths: a population-based retrospective cohort study in Ontario, Canada
Authors: Wang Linwei , Swayze Sarah , Siddiqi Arjumand , Baral Stefan D. , Sander Beate , Sbihi Hind , Kwong Jeffrey C. , Mishra Sharmistha 
Published: February 2025

AbstractBackgroundEmpirical evidence on the indirect herd benefits of COVID-19 vaccination and/or prior infection is limited. We aimed to examine how area-level immunity interacts with individual-level immunity to affect COVID-19 diagnoses and deaths.MethodsOntario residents aged ≥18 years were followed from August-01-2021 to January-30-2022. Individual-level immunity was defined as received a primary series of COVID-19 vaccines or a positive SARS-CoV-2 test in the past 165 days. Area-level immunity was determined based on the proportion of immune individuals in an individual’s residing area. We used logistic regression and cause-specific hazard models to examine the relationship between immunity and COVID-19 diagnosis, and between immunity and COVID-19 death, respectively. We included an interaction term between individual-level and area-level immunity in each model.ResultsOf 11,122,816 adults, 7,518,015 (67.6%) were immune at baseline. After accounting for individual-level demographics, baseline health, and area-level social determinants of health, area-level immunity (highest vs. lowest quintiles) was associated with lower odds of COVID-19 diagnosis; the association was larger among non-immune (odds ratios [95% confidence interval]: 0.72 [0.70, 0.75]) than immune individuals (0.93 [0.90, 0.96]). Higher area-level immunity (highest vs. lowest quintiles) was also associated with lower hazard of COVID-19 death among non-immune individuals (hazard ratio: 0.77 [0.60, 1.00]).ConclusionsOur study provides observational evidence supporting the herd benefits of vaccination or prior infection on SARS-CoV-2 infections and COVID-19 deaths. Findings reinforce the need for high vaccination coverage to protect vaccinated and unvaccinated populations, while providing insights for interpreting vaccine effectiveness estimates in the context of herd immunity.Main pointsUsing area-level immunity coverage as a proxy for herd immunity, our study demonstrates observational evidence of indirect herd benefits from vaccination and/or prior infection on SARS-CoV-2 infections and COVID-19 deaths. Moreover, herd benefits are greater among non-immune individuals.
Prevalence and correlates of contraceptive use among parenting adolescents: results from a cross-sectional survey in Ouagadougou, Burkina Faso, and Blantyre, Malawi
Authors: Otukpa Emmanuel Oloche , Munthali Alister , Sawadogo Nathalie , Ushie Boniface Ayanbekongshie , Ajayi Anthony Idowu 
Published: February 2025

AbstractBackgroundContraceptive use among sexually active adolescent mothers can prevent repeat pregnancy with positive implications for their health, education, and economic prospects. Few studies have examined the prevalence and correlates of contraceptive uptake among adolescent mothers in sub-Saharan Africa. Our study examines contraceptive use, its correlates, and reasons for non-use of contraception among adolescent mothers (aged 12-19) in Ouagadougou, Burkina Faso and Blantyre, Malawi.MethodologyThe data analyzed for this study were part of a larger cross-sectional survey on the lived experiences of pregnant and parenting girls. For this study, we limited our analysis to 628 (Ouagadougou) and 500 (Blantyre) adolescent mothers who were neither pregnant nor trying to get pregnant. We randomly selected urban and rural enumeration areas (EAs) in the study settings, conducted household listing, and identified eligible participants whom we interviewed. We used interviewer-administered questionnaires to obtain information on contraceptive awareness, use, and reason for non-use and analyzed the data using descriptive and inferential statistics.ResultsKnowledge of contraceptive methods is nearly universal among parenting girls, and the contraceptive prevalence was higher than the national average in both study settings. Single adolescent mothers were significantly less likely to be currently using any contraceptive methods (AOR: 0.75; 95% CI: 0.61-0.93 in Burkina Faso vs. AOR: 0.60; 95% CI: 0.50-0.71 in Malawi) or any modern methods (AOR: 0.66; 95% CI: 0.49-0.90 in Burkina Faso vs. AOR: 0.55; 95% CI: 0.46-0.66 in Malawi) compared to their married counterparts in both countries. Adolescent mothers aged 19 were more likely to be current users of any contraceptives compared to those aged 16 or younger in Burkina Faso (AOR: 1.55; 95% CI: 1.07-2.26) and were also more likely to have ever used any methods in Malawi (AOR: 1.28; 95% CI: 1.07-1.53). Infrequent sex (Malawi, 64.9%; Burkina |Faso, 36.6%) was the main reason for contraceptive non-use though fear of side-effects (17.7%) and religious prohibition (16.6%) also stood out.ConclusionA substantial proportion of adolescent mothers, especially single and younger adolescents, are not using any contraceptive methods or relying on less effective methods. These results underscore the need for more interventions targeting adolescent mothers with accurate information on contraceptive methods. These interventions should address the religious objection to contraceptives in Burkina Faso and infrequent sex in Malawi.
Modelling exposure to aerosols from showers: implications for microbial risk assessment
Authors: Tang Lizhan , Eichelberg Antonia , Böni Franziska , Hamilton Kerry A. , Sylvestre Émile , Hammes Frederik , Julian Timothy R 
Published: February 2025

AbstractInhalation of aerosols produced during showering exposes people to chemical and microbial contaminants present in the water. To improve quantitative estimates of exposure and to inform the efficacy of potential interventions to reduce exposures, we conducted empirical measurements of aerosol concentration and size distribution during showering events. We measured aerosol count concentrations and size distributions with an aerodynamic particle sizer over the duration of mock showering events under various conditions, including different water temperatures and different showerhead types (conventional and rain showers). The empirical data were then used to fit a mass balance model to obtain aerosol generation rates and decay rates for each aerosol size class through least square fitting. We observed an initial high peak concentration of aerosols under hot water conditions relative to cold water conditions which resulted in a rapid increase in aerosol exposure during the first 1-2 minutes of showering. This suggests that people showering in hot water conditions will have a potentially increased exposure during the first 1-2 minutes. The model-fitted values suggest large inter-experiment variation in estimated aerosol generation and decay rates, even among triplicates of the same showering conditions. Current exposure assessment approaches assume constant aerosol concentrations during showers which might lead to miscalculated cumulative risk. Thus, considering aerosol dynamics is beneficial during shower exposure assessments to inform risk management interventions. The data set and associated modeling results provided can support this, as they can be readily integrated into microbial risk assessment for waterborne pathogens such asLegionellaspp., nontuberculousMycobacteria(NTM) andPseudomonas aeruginosa.
Sub-national estimation of surveillance sensitivity to inform declaration of disease elimination: A retrospective validation against the elimination of wild poliovirus in Nigeria
Authors: Nightingale Emily S , Pham-Minh Ly , Bello Isah Mohammed , Okrior Samuel , Erbeto Tesfaye Bedada , Baba Marycelin , Adeneji Adekunle , Auzenbergs Megan , Edmunds W John , O’Reilly Kathleen M 
Published: February 2025

AbstractA fundamental question in the global commitment to polio eradication is how long a period of absence would be consistent with regional elimination, and the safe withdrawal of the oral polio vaccine is contingent on the answer. We present a statistical framework to estimate time-varying sensitivity of two key components of polio surveillance - environmental sampling and clinical cases of acute flaccid paralysis - for detecting infection at the local government authority level. We estimate the probability of freedom from infection (FFI) at a critical prevalence level that is consistent with interruption of transmission, given the absence of virus in collected samples. We validated this framework against two periods of poliovirus absence in Nigeria (2014-2016 and 2016-2020).We observed substantial heterogeneity in surveillance sensitivity over time and space and, given this, concluded an 85% probability (95% uncertainty interval: 77.1-90.2%) of the country being free from WPV1 infection after 23 months without detection from July 2014. Detection of WPV1 in July 2016 demonstrated that circulation had indeed persisted during this time. In contrast, we conclude a probability of 98% (97.9-98.7%) by the time elimination of the serotype was officially declared in 2020.The inferred probability of FFI during both time periods was found to be consistent with the retrospectively known status of regional elimination. This supports the validity of applying this framework prospectively to inform the certification of wild poliovirus elimination from remaining endemic regions, and to determine the resolution of cVDPV2 outbreaks.
Designing AI-powered healthcare assistants to effectively reach vulnerable populations with health care services: A discrete choice experiment among South African university students
Authors: Zheng A , Long L , Govathson C , Chetty-Makkan C , Morris S , Rech D , Fox MP , Pascoe S 
Published: February 2025

ABSTRACTIntroductionSouth African young adults are at increased risk for HIV acquisition and other non-communicable diseases and face significant barriers to accessing healthcare services. The rapid development of artificial intelligence (AI), in particular AI-powered healthcare assistants (AIPHA), presents a unique opportunity to increase access to health information and linkage to healthcare services and providers. While successful implementation and uptake of such tools require understanding user preferences, limited understanding of these preferences exist. We sought to understand what preferences are important to university students in South Africa when engaging with a hypothetical AIPHA to access health information using a discrete choice experiment.MethodsWe conducted an unlabeled, forced choice discrete choice experiment among adult South African university students through Prolific Academic, an online research platform, in 2024. Each choice option described a hypothetical AIPHA using eight attribute characteristics (cost, confidentiality, security, healthcare topics, language, persona, access, services). Participants were presented with ten choice sets each comprised of two choice options and asked to choose between the two. A conditional logit model was used to evaluate preferences.Results300 participants were recruited and enrolled. Most participants were Black, born in South Africa, heterosexual, working for a wage, and a mean age of 26.5 years (SD: 6.0). Results from the discrete choice experiment identified that language, security, and receiving personally tailored advice were the most important attributes for AIPHA. Participants strongly preferred the ability to communicate with the AIPHA in any South African language of their choosing instead of only English and to receive information about health topics specific to their context including information on clinics geographically near them. Results were consistent when stratified by sex and socioeconomic status.ConclusionsParticipants had strong preferences for security and language which is in line with previous studies where successful uptake and implementation of such health interventions clearly addressed these concerns. These results build the evidence base for how we might engage young adults in healthcare through technology effectively.
The Association of the Microbiome with Melanoma Tumor Response to Immune Checkpoint Inhibitor Treatment and Immune-Related Adverse Events (NCT05102773)
Authors: Dravillas Caroline , Williams Nyelia , Husain Marium , Hoyd Rebecca , Hussein Ahmed , Meara Alexa , Lynn Mari , Bibi Amna , Conrad Bailey , Lepola Noah , Gray Shannon , Bodnar Michael , Arya Namrata , Roberts Scott , Hoang Phuong , Apparicio Jessica , Merrill Deanna , Wu Richard , Verschraegen Claire , Burd Christin E. , Kendra Kari , Spakowicz Dan 
Published: February 2025

AbstractImproved understanding of the factors that underlie immune checkpoint inhibitor (ICI) response and toxicity are needed as only half of patients with metastatic melanoma respond, and 10-40% experience immune-related adverse events (irAEs). Modifying the gut microbiome could positively affect response to ICIs and reduce toxicities. Here, we sought to determine if the pre-treatment gut microbiome predicts ICI response or toxicity in the setting of metastatic melanoma. Melanoma patients (n=88) over 18 years of age, planning to receive ICI therapy enrolled in a prospective observational cohort study at The Ohio State University Comprehensive Cancer Center Skin Cancer Clinic. Patients taking corticosteroids for indications other than adrenal physiologic replacement were excluded. Stools were collected at baseline, within 10 days of an irAE as determined by CTCAE v 5.0 criteria, and at 12 weeks. ICI response and progression-free survival (PFS) were evaluated q12 weeks using Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Metagenomic whole-genome shotgun sequencing of the microbiome was classified using MetaPhlAn4/HUMAnN3 and differential abundance analyzed with ANCOM-BC2. Of the 88 patients enrolled, 41 had metastatic disease and complete data. There were 25 participants classified as responders, defined as having complete response or partial response according to RECIST criteria, or stable disease with 6-month PFS. Grade ≥ 1 irAEs were observed in 15/41 participants. The abundance ofIntestinimonas butyriciproducens(q-value = 0.002) andLongicatena caecimuris(q-value = 0.003) were enriched in responders,Tenericutes(q-value= 0.001) andLachnospira sp. NSJ 43(q-value =0.002) in non-responders.Blautia luti, as well as several otherLachnospiraceae, were associated with response and no irAE (response q-value = 0.02, no irAE q-value = 0.02). The association of response to ICIs with several taxa in the familyLachnospiraceae, a prevalent microbial family in the gut, is consistent with prior research, which has found that this family may influence treatment outcomes through various mechanisms, such as immune regulation, metabolism, and pathogen exclusion. While no statistical relationship was observed between response and irAEs in this cohort, the microbes associated with both could serve as biomarkers. Future studies to assign causal roles for (specific microbes) in response and toxicity could identify mechanisms to improve patient outcomes.
Measuring weak effects in high dimensional mediation analysis
Authors: Li Chunlin , Chen Li , Pankow James S. , Yang Tianzhong 
Published: February 2025

AbstractExisting mediation analysis methods have often fallen short in accurately quantifying the contribution of omics mediators, particularly those with weak effects. To address this issue, we propose two new variance-based causal measures for the global mediation effect. Then, we develop a flexible and computationally efficient estimation procedure based on a mixed-effects working model. Through this approach, we are able to accurately quantify the total mediation effect and discover the weak effects that are largely mis-estimated by existing methods. The proposed approach is general and complements the existing mediation analysis methodologies by offering new perspectives on the global and weak effects.
Interpretable Kolmogorov-Arnold Networks for Enzyme Commission Number Prediction
Authors: Dumontet Louis , Han So-Ra , Prouvost Axel , Lee Jun Hyuck , Oh Tae-Jin , Kang Mingon 
Published: February 2025

AbstractAccurate prediction of enzyme commission (EC) numbers remains a significant challenge in bioinformatics, limiting our ability to fully understand enzyme functions and their roles in biological processes. This paper presents the integration and evaluation of the next paradigm of deep learning architecture, named Kolmogorov-Arnold network (KAN), in state-of-the-art models for predicting EC numbers. KAN modules are incorporated into current state-of-the-art models to assess their impact on predictive performance. Additionally, we introduce a novel interpretation method, specifically designed for KANs, to identify relevant input features for a given prediction, addressing a current limitation in KANs. Our evaluation demonstrates that the integration of KANs significantly enhances predictive performance compared to the state-of-the-art deep learning models, with up to a 4.35% increase in micro-averagedF1score and a 4.1% increase in macro-averagedF1score. Moreover, our novel interpretation method not only enhances the predictions’ trustworthiness but also facilitates the discovery of motif sites within enzyme sequences. This innovative approach provides deeper insights into enzyme functionality and highlights potential new targets for research. The results underscore KANs’ effectiveness in improving enzymatic classification and advancing our understanding of enzyme structures and functions. The open-source code is publicly available at:https://github.com/datax-lab/kan_ecnumber.
Comparative genomics of sex determination related genes reveals shared evolutionary patterns between bivalves and mammals, but notDrosophila
Authors: Nicolini Filippo , Nuzhdin Sergey , Ghiselli Fabrizio , Luchetti Andrea , Milani Liliana 
Published: February 2025

AbstractThe molecular basis of sex determination (SD), while being extensively studied in model organisms, remains poorly understood in many animal groups. Bivalves, a diverse class of molluscs with a variety of reproductive modes, represent an ideal yet challenging clade for investigating SD and the evolution of sexual systems. However, the absence of a comprehensive framework has limited progress in this field, particularly regarding the study of sex-determination related genes (SRGs). In this study, we performed a genome-wide sequence evolutionary analysis of the Dmrt, Sox, and Fox gene families in more than 40 bivalve species. For the first time, we provide an extensive and phylogenetic-aware dataset of these SRGs, and we find support to the hypothesis thatDmrt-1LandSox-Hmay act as primary sex-determining genes, by showing their high levels of sequence diversity within the bivalve genomic context. To validate our findings, we studied the same gene families in two well-characterized systems, mammals andDrosophila. In the former, we found that the male sex-determining geneSryexhibits a pattern of amino acid sequence diversity similar to that ofDmrt-1LandSox-Hin bivalves, consistent with its role of master SD regulator. In contrast, no such pattern was observed among genes of the fruit fly SD cascade, which is controlled by a chromosomic mechanism. Overall, our findings highlight similarities in the sequence evolution of some mammal and bivalve SRGs, possibly driven by a comparable architecture of SD cascades. This work underscores once again the importance of employing a comparative approach when investigating understudied and non-model systems.
Exploring the Role of PEDOT Electrodes in Electrostimulation of Vascular Endothelial Cells
Authors: Víteček Jan , Kratochvíl Matouš , Weiter Martin 
Published: February 2025

AbstractThe potential of electrical stimulation for cell control in tissue engineering remains largely underestimated, as does the use of organic semiconductors. The tunable physico-chemical properties of organic semiconductors offer advantages over commonly used inert metals.This study investigates the effects of pulsed electrostimulation and electrode materials, gold and poly(3,4-ethylenedioxythiophene) (PEDOT), on the physiological functionality of human vascular endothelial cells. A novel electrostimulation platform incorporating gold or PEDOT electrodes was developed and characterized for electrical performance. Human umbilical vein endothelial cells were cultured on this platform, and the effects of electrostimulation and electrode material were assessed through morphological analysis, nitric oxide (NO) production, and expression of key endothelial marker genes.PEDOT electrodes produced higher electrical current during electrostimulation. Interestingly, cell morphology, including elongation and alignment, showed minimal changes under electrostimulation. NO production, a key marker of vascular health, was enhanced by electrostimulation, with PEDOT electrodes showing a trend toward greater NO accumulation than gold. Gene expression analysis revealed material- and stimulation-specific trends: electrostimulation generally upregulated KLF2, KLF4, and CYP1B1 on PEDOT electrodes but suppressed their expression on gold electrodes.These findings suggest that PEDOT electrodes, with their enhanced electrochemical properties and ability to support endothelial functionality, provide a safe and efficient platform for endothelial cell electrostimulation. This study advances understanding of the interplay between material properties and electrostimulation and highlights PEDOT as a promising candidate for vascular tissue engineering and regenerative medicine.
Illuminating oncogenic KRAS signaling by multi-dimensional chemical proteomics
Authors: Kabella Nicole , Bayer Florian P. , Stamatiou Konstantinos , Abele Miriam , Sakhteman Amirhossein , Chang Yun-Chien , Wagner Vinona , Gabriel Antje , Krumm Johannes , Reinecke Maria , Holzner Melanie , Aigner Michael , The Matthew , Hahne Hannes , Bassermann Florian , Ludwig Christina , Vagnarelli Paola , Kuster Bernhard 
Published: February 2025

AbstractMutated KRAS is among the most frequent activating genetic alterations in cancer and drug discovery efforts have led to inhibitors that block its activity. To better understand oncogenic KRAS signaling and the cytostatic effects of drugs, we performed comprehensive dose-dependent proteome-wide target deconvolution, pathway engagement and protein expression characterization of KRAS, MEK, ERK, SHP2 and SOS1 inhibitors in pancreatic (KRAS G12C, G12D) and lung cancer (KRAS G12C) cells. Analysis of the resulting 687,954 dose-response curves available online revealed both common and cell line-specific signaling networks dominated by oncogenic KRAS activity. Time-dose experiments separated early KRAS-MEK-ERK from CDK-mediated signaling that cause cells to exit from the cell cycle. This transition to a quiescent state occurred without substantial proteome re-modelling but extensive changes of protein phosphorylation and ubiquitylation. The collective data highlights the complexity of KRAS signaling in cancer and places a large number of new proteins into this functional context.