bluuebunny/crossref_metadata_2025_split huggingface dataset:
Susceptibility of bacterial species commonly found in abdominal abscesses to low-dose photodynamic therapy: Effects of methylene blue concentration, fluence rate, and fluence
Authors: Hawryluk Darrian S. , Pavelka Martin S. , Baran Timothy M. 
Published: January 2025

AbstractObjectivesThe objective of this study was to determine the effects of methylene blue (MB) concentration, laser fluence rate, and laser fluence on efficacy ofin vitrophotodynamic therapy (PDT) for four bacteria commonly found in human abscesses.Materials and MethodsPDT experiments were performed with four of the most common bacteria found in abdominal abscesses:Escherichia coli(E. coli),Enterococcus faecalis(E. faecalis),Staphylococcus aureus(S. aureus), andPseudomonas aeruginosa(P. aeruginosa). MB concentration was varied from 50-300 µg/mL, and laser fluence rate was varied from 1-4 mW/cm2at a fluence of 7.2 J/cm2. Higher fluence rates and fluences were explored forP. aeruginosa. Primary outcomes were reduction in colony forming units (CFU) following PDT, and measured MB uptake following drug incubation.ResultsGram-positive bacteria (E. faecalisandS. aureus) were eradicated at all MB concentrations and laser fluence rates tested. Efficacy was reduced forE. coli, but still resulted in >6 log10reduction in CFU when MB concentration was at least 100 µg/mL.P. aeruginosarequired higher fluence (28.8 J/cm2) to achieve comparable efficacy, while increasing fluence rate did not have a significant effect on PDT efficacy. MB uptake was reduced in Gram-negative species compared to Gram-positive, particularlyP. aeruginosa, although uptake was not significantly correlated with CFU reduction.ConclusionsGram-positive bacteria can be eradicatedin vitrowith low levels of MB (50 µg/mL), laser fluence (7.2 J/cm2), and laser fluence rate (1 mW/cm2).E. colishowed substantial cell killing (>6 log10CFU reduction) with these same parameters. Low MB uptake and PDT efficacy inP. aeruginosacould be overcome by increasing the laser fluence, while increasing fluence rate did not have an effect.
Equity-Enhanced Glaucoma Progression Prediction from OCT with Knowledge Distillation
Authors: Afolabi Sulaiman O. , Gheisi Leila , Shan Jing , Shen Lucy Q. , Wang Mengyu , Shi Min 
Published: January 2025

AbstractPurposeTo develop an equitable deep learning model with knowledge distillation to enhance the demographic equity in glaucoma progression prediction.MethodsWe developed a novel deep learning model called FairDist which used baseline optical coherency tomography (OCT) scans to predict glaucoma progression. First, an equity-aware EfficientNet termed EqEffNet was trained for glaucoma detection. Next, the pretrained detection model was adapted for progression prediction using knowledge distillation which minimizes image and identity feature differences between the detection and progression models. Progression was defined based on longitudinal visual field maps from at least five visits up to six years. Model performance was measured by the area under the receiver operating characteristic curve (AUC), Sensitivity, Specificity, and equity was assessed using equity-scaled AUC (ES-AUC), which adjusts AUC by accounting for subgroup disparities, focusing on gender and racial groups.ResultsTwo types of glaucoma progression including mean deviation (MD) Fast progression and Total Deviation (TD) Pointwise progression were explored. For MD Fast Progression, FairDist achieved the highest AUC and ES-AUC for gender (AUC: 0.738, ES-AUC: 0.693) and race (AUC: 0.778, ES-AUC: 0.677) compared with methods with and without integrating inequity mitigation strategies. For TD Pointwise progression, FairDist achieved the best AUC and ES-AUC for gender (AUC: 0.743, ES-AUC: 0.719) and race (AUC: 0.746, ES-AUC: 0.645) among all methods.ConclusionsFairDist enhances both model performance and equity in glaucoma progression prediction after integrating the equity-aware learning and knowledge distillation components. The proposed deep learning model shows promise in improving glaucoma diagnosis while reducing disparities across demographic groups.
AncestryHub: A web server for local ancestry analysis
Authors: Jiang Sukun , Deng Yangyang , Li Shuxin , Liu Changsheng Jonathan , Luo Jianjun , Zhu Xiaojun , Song George D. , Zhang Kui , Song Qing , Ma Li 
Published: January 2025

AbstractSummaryAncestryHub is a web version of local ancestry analysis software. It contains four built-in software and a set of built-in population reference panels. AncestryHub will significantly reduce the efforts and requirements for the users on their personal computational skills and computational hardware environment for ancestry analysis.Availabilityhttps://www.ancestryhub.4dgenome.comContact:lima@4dgenome.com
The Drosophila EGF domain protein Uninflatable sets the switch between wrapping glia growth and axon wrapping instructed by Notch
Authors: Baldenius Marie , Kautzmann Steffen , Kottmeier Rita , Klämbt Christian 
Published: January 2025

AbstractIn the peripheral nervous system, sensory and motor axons are generally covered by wrapping glial cell processes. This neuron-glia interaction requires an intricate coordination of glial growth and differentiation. How this is controlled molecularly is largely unknown. At the example of Drosophila larval nerves, we show that glial growth is initially triggered by the FGF-receptor tyrosine kinase Heartless (Htl). In a screen for genes acting downstream of activated FGF-receptor, we identified the large membrane protein Uninflatable (Uif), which supports the formation of plasma membrane domains but not axon wrapping. Uif is also known to inhibit Notch. Surprisingly, we find that Notch signaling is required in postmitotic wrapping glia. While compromisedNotchsignaling results in a reduced wrapping efficiency, gain ofNotchactivity in wrapping glial cells leads to a hyperwrapping phenotype. Thus, Notch signaling is both necessary and sufficient for glial wrapping in Drosophila larvae. In addition,Notchsuppresses bothuifandhtlfunction and thus stabilizes the switch between growth and differentiation. Given the general conservation of signaling mechanisms controlling glia development in mice and flies, similar mechanisms may act in the mammalian nervous system to control final glial differentiation.
Revisiting Tumor Mutational Burden Cutoff: Multi-Study Replicability in Immunotherapy
Authors: Jaljuli Iman , Whiting Karissa , Rosenbaum Evan , Qin Li-Xuan 
Published: January 2025

AbstractPURPOSETumor Mutational Burden (TMB) is a crucial biomarker for predicting the effectiveness of cancer immunotherapy. However, ongoing debates about the optimal cutoff significantly impact the clinical application of immunotherapy. The purpose of our study is to comprehensively evaluate TMB cutoffs for predicting immunotherapy outcomes across multiple studies, considering both cancer type and outcome endpoint, using statistically principled approaches.METHODSWe analyzed data from PredictIO, curated through a PubMed search for studies involving immune checkpoint blockade treatment in the adjuvant setting, excluding those involving combinations with chemotherapy, targeted treatment, or radiation. The included studies, published between January 2015 and June 2022, required tumor sequencing data from whole exomes or targeted gene panels for TMB assessment. Outcome endpoints included clinical benefit rate (CBR), progression-free survival (PFS), and overall survival (OS). CBR was defined as the rate of complete response, partial response, or stable disease lasting at least six months, according to RECIST 1.1 criteria. OS and PFS were defined as the interval from treatment initiation to death and disease progression, respectively. TMB was uniformly derived from tumor sequencing data, representing the count of nonsynonymous mutations relative to the target sequencing size. TMB cutoffs were evaluated for outcome associations using study replicability analysis, alongside individual-study analysis and random-effects meta-analysis for comparison.RESULTSThe data provided sufficient evidence of replicable outcome associations for specific TMB cutoffs in melanoma, lung cancer, and bladder cancer. The FDA-recommended cutoff of 10 mutations per megabase showed replicable associations in melanoma for OS (p-value < 0.01) and CBR (p-value < 0.01), though more replicable cutoffs were identified for the latter. Lower cutoffs of 4 and 2 were found to be replicable in lung cancer for CBR (p-value = 0.04) and in bladder cancer for OS (p-value < 0.01), respectively. No cutoff was deemed replicable for the other cancer type and outcome combinations, due to no association, inadequate power, or insufficient data.CONCLUSIONA pan-cancer cutoff of 10 mutations per megabase may not be optimal for predicting immunotherapy outcomes. Further studies are needed to determine appropriate cutoffs specific to cancer types and outcomes through statistically principled replicability analyses.
Food pairing independently associated with cardiometabolic traits beyond dietary patterns across western and eastern populations
Authors: Deng Qiufeng , Sun Yuhao , Gu Mingxia , Fu Jingxiang , Xu Fengzhe , Jiao Yuwen , Zhou Yan , Ma Beining , Liu Lu , Wang Xiuchao , Dong Quanbin , Wu Tingting , Zou Huayiyang , Shi Jing , Wang Yifeng , Sheng Yanhui , Tang Liming , Sun Wei , Li An , Hu Shixian , Zheng Jusheng , He Yan , Zhou Hongwei , Wu Wei , Kong Xiangqing , Chen Lianmin 
Published: January 2025

AbstractCardiometabolic health is closely linked to diet. Both specific food choices and dietary indices are commonly used to guide cardiometabolic protection strategies. However, the balance between foods may also significantly impact cardiometabolic health.Here, we explore the balance and imbalance in long-term dietary food intake to quantify food pairing patterns (FPs), providing insights beyond conventional dietary indices and single-food intake frequencies. Using data from our GGMP (n = 6,994) and the NHANES (n = 7,350) cohorts, we observed that long-term food pairing patterns are independent of single food intake frequency and dietary indices. We identified 1,759 and 306 cardiometabolic-related long-term food pairing patterns from two cohorts (FDR < 0.05), respectively. Notably, around 80% of these pairing foods not individually associated with cardiometabolic traits, and food pairing pattern associations with cardiometabolic traits at hyper food group level were consistent across Eastern and Western populations. Besides, mediation analysis revealed that 72.7% of long-term food pairing patterns affected cardiometabolic traits through 31 microbial genera, withClostridiumsensustricto1playing a predominant role. Moreover, multi-step mediation analysis found that microbes mediated the impact of long-term food pairing patterns on cardiometabolic traits primarily through their metabolic pathways, such as pyruvate fermentation to propanoate and ergothioneine biosynthesis pathways.Our data suggest that balance between dietary foods is broadly associated with cardiometabolic traits by modulating gut microbial functionalities, in contrast to the lower occurrence when considering individual foods in isolation. These results offer a novel perspective for designing personalized dietary strategies beyond present dietary indices to enhance cardiometabolic health.
ABA-induced MYB transcriptional module regulates the differentiation trajectory of chickpea exodermis
Authors: Jo Leonardo , Kluck Rianne , Buti Sara , Holbein Julia , Chhillar Himanshu , Ding Pingtao , Franke Rochus Benni , Kajala Kaisa 
Published: January 2025

AbstractAbscisic acid (ABA) regulates plant responses to stress and influences the differentiation of root barrier cell types, such as the endodermis and exodermis. Despite the importance of the exodermis in limiting water and solute fluxes, its regulation remains poorly understood in legumes. Here, we characterize the ABA-induced suberization and lignification of root tissues across eight galegoid legumes. Chickpea exhibited suberin deposition specifically in the outermost cortex, forming a functional apoplastic barrier. Transcriptomics of chickpea roots revealed ABA-induced programs that were temporally separated, specifically, a rapid program with the general ABA response, and a delayed program of suberin biosynthesis. We identified putative MYB transcription factors that link the ABA response to the suberin biosynthesis in chickpea. Single-cell RNA-seq of chickpea roots uncovered putative cell-type-specific regulatory networks, suggesting that ABA-induced suberization in the exodermis is mediated by the canonical ABA signaling inducing the expression of suberin-regulating MYBs.
Semaphorin7A and PD-L1 cooperatively drive immunosuppression during mammary involution and breast cancer
Authors: Elder Alan M , Fairchild Heather R , Kines Kelsey T , Cozzens Lauren M , Becks Alexandria R , Lyons Traci R 
Published: January 2025

SummaryPostpartum mammary gland remodeling after a pregnancy/lactation cycle is characterized by mechanisms of immunosuppression. Here we show that SEMA7A promotes PD-L1 expression in immune cells of the mammary tissue during involution. These same phenotypes are mimicked in the microenvironment of SEMA7A-expressing tumors, which partially respond to αPD-1/αPD-L1 treatments in vivo. However, cells that remain after treatment are enriched for SEMA7A expression. Therefore, we tested a novel monoclonal antibody that directly targets SEMA7A-expressing tumors, in part, by reducing SEMA7A-mediated upregulation of PD-L1. In vivo, the SEMA7A monoclonal antibody also reduces tumor growth or promotes complete regression of mouse mammary tumors, reduces the immunosuppressive phenotypes in the tumor microenvironment and restores cytotoxic T cells suggesting that SEMA7A may be a candidate for a novel immune-based therapy for breast cancer patients.
Early Noise Exposure and Changes in Medial Olivocochlear Strength Alters Auditory Pathway Development
Authors: Castagna Valeria C. , Boero Luis E. , Di Guilmi Mariano N. , Fuchs Paul A. , Lauer Amanda M. , Elgoyhen Ana Belén , Gomez-Casati Maria Eugenia 
Published: January 2025

ABSTRACTPeriodic spontaneous activity is a key feature of developing sensory systems, essential for the formation and refinement of neural circuits. Before the onset of hearing in altricial mammals, cochlear inner hair cells exhibit spontaneous electrical activity that activates primary afferents to propagate into the central nervous system. This activity, modulated by the medial olivocochlear efferent feedback via α9α10 nicotinic cholinergic receptors present in inner hair cells, is crucial for auditory system maturation. In this study, we examined the impact of sound exposure at levels below those causing hair cell damage during the critical developmental period by using genetically modified mice - α9 knockout and α9 knock-in models - with either absent or enhanced cholinergic activity. We further assessed how varying levels of medial olivocochlear feedback interact with early-age noise exposure to affect auditory development. Our findings reveal that both increased and absent olivocochlear activity result in altered auditory sensitivity at the onset of hearing and affect ribbon synapse number and morphology. Additionally, early exposure to loud noise caused long lasting changes in the inner ear of wild-type and α9 knockout mice, underscoring the heightened vulnerability during early development. In contrast, mice with enhanced cholinergic activity were protected from these changes. Overall, this work highlights the critical role of medial olivocochlear modulation in proper auditory system development and indicates that early noise exposure can interfere with normal cochlear maturation, resulting in pronounced long-term effects.
The Association between Proteomic Aging Clocks and the Risk of Cancer in Midlife Individuals
Authors: Wang Shuo , Rao Zexi , Li Aixin , Blaes Anne H. , Blaha Michael J. , Coresh Josef , Dubin Ruth , Deo Rajat , Joshu Corinne E. , Marshall Catherine Handy , Pankow James S. , Rotter Jerome I. , Thyagarajan Bharat , Whelton Seamus P. , Ganz Peter , Guan Weihua , Platz Elizabeth A. , Prizment Anna 
Published: January 2025

AbstractBackgroundTo measure the aging process before a cancer diagnosis, we developed the first cancer-specific proteomic aging clock (CaPAC) and examined its association with cancer risk in the Atherosclerosis Risk in Communities (ARIC) and Multi-Ethnic Study of Atherosclerosis (MESA) studies.MethodsUsing the SomaScan assay, ARIC measured 4,712 proteins in plasma samples collected in 1990-92 from 3,347 participants who developed cancer over follow-up until 2015 and 7,487 who remained cancer-free, all aged 46-70. We constructed CaPAC0 using elastic net regression among two-thirds randomly selected cancer-free participants (N=4,991, training set) and calculated age acceleration for CaPAC0 (CaPAA0) as residuals of CaPAC0 on chronological age in all remaining ARIC participants. We used multivariable-adjusted Cox proportional hazards regression to calculate hazard ratios (HRs) for the risk of overall, obesity-related, smoking-related, and the most common cancers (prostate, lung, breast, colorectal) with CaPAA0 using a case-cohort design. We replicated the analysis in 3,893 MESA participants aged 46-70 at Exam 1 (456 incident cancer).ResultsCaPAC0 was correlated with chronological age in ARIC and MESA (r=0.82 and 0.86, respectively). In both ARIC and MESA, CaPAA0 was significantly (p<0.05) associated with the risk of overall [HRs per 5-years=1.08 and 1.23, respectively], smoking-related [HRs=1.30 and 1.54, respectively], and lung cancers [HRs=1.54 and 1.94, respectively]. CaPAA0 was also significantly associated with colorectal cancer risk in ARIC [HR=1.31], but not in MESA. CaPAA0 was not associated with obesity-related, breast, or prostate cancers.ConclusionCaPAA0 was associated with several types of cancer with the strongest association observed for lung cancer risk.
Psychological distress and compliance with sanitary measures during the Covid-19 pandemic: effect modification by participant gender and socioeconomic characteristics, an IPD meta-analysis.
Authors: Hecker Irwin , Wallez Solene , Scarlett Honor , Ayuso-Mateos Jose Luis , Bryant Richard , Caggiu Giulia , Conflitti Claudia , Gemes Katalin , Haro Josep Maria , Lorant Vincent , Mediavilla Roberto , Mittendorffer-Rutz Ellenor , Monistrol-Mula Anna , Monzio-Compagnoni Matteo , Petri-Romao Papoula , Pinucci Irene , Sijbrandij Marit , Stoffers-Winterling Jutta , Walter Henrik , Mary-Krause Murielle , Melchior Maria 
Published: January 2025

Background: This study aims to understand how individuals’ psychological distress is related to compliance with COVID-19 sanitary measures. In addition, we explored whether gender and socioeconomic status (i.e educational level and employment status) modify the relationship between psychological distress and compliance with COVID-19 sanitary measures. Methods: Data from four European cohort studies (n=13,635), were analysed using an Individual Participant Data (IPD) meta-analytic approach. Mixed effect models were employed to examine associations between mental health difficulties and compliance with sanitary measures as well as the interaction with socioeconomic status. Models were additionally stratified by gender to capture gender-specific patterns. Results: We found a significant positive association between mental health difficulties and compliance with sanitary measures in women, while amongst men the association was also significant but negative. Moreover, there was a statistically significant interaction between participants’ educational level and mental health difficulties amongst men only, indicating even lower compliance levels amongst those with only primary schooling. Conclusion: The association between psychological distress and compliance with sanitary measures is unclear - positive for women, negative for male. Men experiencing mental health difficulties, especially those with lower educational attainment, exhibited lower compliance with sanitary measures.
Unsupervised Ensemble Learning for Efficient Integration of Pre-trained Polygenic Risk Scores
Authors: Gao Chenyin , Tubbs Justin D. , Han Yi , Guo Min , Li Sijia , Ma Erica , Luo Dailin , Smoller Jordan W. , Lee Phil H. , Duan Rui 
Published: January 2025

AbstractThe growing availability of pre-trained polygenic risk score (PRS) models has enabled their integration into real-world applications, reducing the need for extensive data labeling, training, and calibration. However, selecting the most suitable PRS model for a specific target population remains challenging, due to issues such as limited transferability, data het-erogeneity, and the scarcity of observed phenotype in real-world settings. Ensemble learning offers a promising avenue to enhance the predictive accuracy of genetic risk assessments, but most existing methods often rely on observed phenotype data or additional genome-wide association studies (GWAS) from the target population to optimize ensemble weights, limiting their utility in real-time implementation. Here, we present theUNsupervised enSemble PRS(UNSemblePRS), an unsupervised ensemble learning framework, that combines pre-trained PRS models without requiring phenotype data or summaries from the target population. Unlike traditional supervised approaches, UNSemblePRS aggregates models based on prediction concordance across a curated subset of candidate PRS models. We evaluated UNSemblePRS using both continuous and binary traits in the All of Us database, demonstrating its scalability and robust performance across diverse populations. These results underscore UNSemblePRS as an accessible tool for integrating PRS models into real-world contexts, offering broad applicability as the availability of PRS models continues to expand.
CHOPOFF: symbolic alignments enable fast and sensitive CRISPR off-target detection
Authors: Labun Kornel , Rio Oline , Tjeldnes Håkon , Swirski Michał , Komisarczuk Anna Zofia , Haapaniemi Emma , Valen Eivind 
Published: January 2025

ABSTRACTCRISPR/Cas is a revolutionary technology for genome editing. Although hailed as a potential cure for a wide range of genetic disorders, CRISPR/Cas translation faces severe challenges due to unintended off-target editing. Predicting these off-targets are difficult and necessitates trade-offs between speed and sensitivity, and we show that some tools fail to recover even those they claim to be able to find Here, we develop the original concept of symbolic alignments to efficiently identify off-targets without sacrificing sensitivity. We also introduce data structures that allow near-instant alignment-free probabilistic ranking of guides based on their off-target counts. Implemented in the tool CHOPOFF, these innovations support mismatches, bulges and genomic sequence variation for personalized genomes while outperforming state-of-the-art methods in both speed and accuracy.AvailabilityThe CHOPOFF is available at https://github.com/JokingHero/CHOPOFF.jl
H→Zγ
decay and
CP
violation
Authors: Hernández-Juárez A. I. , Gaitán R. , Martinez R. 
Published: January 2025

This study examines the impact of CP-violation on the signal strength μZγ, which was reported as 2.2±0.7 by the LHC. We obtain constraints on the real and absorptive parts of the CP-violating form factor h3Zγ and find that they are less than 1.15 GeV. Additionally, we revisit the leading order Standard Model (SM) contributions to the H→Zγ decay and calculate contributions to h3Zγ from flavor-changing neutral current (FCNC) complex couplings mediated by the Z and H bosons. By using the current bounds on such couplings, we find that the FCNC contribution to h3Zγ with top and charm quarks in the loop is of order 10−5  GeV. While in a model with new quarks that preserves the SM predictions on Higgs decays, the CP-violating form factor h3Zγ can be of order 10−1  GeV and could explain the excess on the signal strength μZγ.

Published by the American Physical Society
2025