bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of Medroxyprogesterone Acetate and Risk of Meningiomas: A Comparative Safety Study
Authors: Frey Connor , Sodhi Mohit , Fatehi Mostafa , Kezouh Abbas , Etminan Mahyar 
Published: February 2025

AbstractMedroxyprogesterone acetate (MPA), a popular contraceptive agent has recently been associated with meningiomas. However, this risk compared to other available contraceptive agents has not been elucidated.We sought to quantify the risk of meningiomas in women on MPA compared to those using oral contraceptives containing ethinylestradiol-levonorgestrel (EE-LNG) by undertaking a nested case-controls study using the PharMetrics Plus database (IQVIA, USA). After creating a cohort of new users of MPA and EE-LNG from 2006 to 2020 new cases of meningioma were identified. Cases were and matched to controls by age and calendar time. Conditional logistic regression was used to adjust for previous exposure to radiotherapy, previous use of hormonal contraceptives, and obesity The adjusted incident rate ratio (IRR) for meningioma for greater than one year of use was 3.55 (95%ICI: 1.85-6.55). Women using MPA have an increased risk of developing meningioma compared to users of EE-LNG.
Cutaneous leishmaniasis in Casablanca-Settat region (Morocco): spatio-temporal analysis of disease dynamic and machine learning based case prediction
Authors: El Idrissi Saik Imane , Talimi Hasnaa , Badri Bouchaib , Bouhout Souad , Fissoune Rachida , Riyad Myriam , Lemrani Meryem 
Published: February 2025

AbstractCutaneous leishmaniasis (CL) caused byLeishmaniaprotozoa and transmitted through infected sandfly bites, poses a significant public health burden in Morocco. Our research aims to retrospectively assess spatio-temporal patterns of CL in the most densely populated region of the country, Casablanca-Settat, during a period of 14 years (2009–2022). We investigate epidemiological trends, seasonal fluctuations and climatic factors influence on CL prevalence and predict cases in the region’s most important CL focus. Using Geographic Information Systems (GIS) and statistical methods, we analyzed CL data obtained from the Moroccan Ministry of Health and Social Protection with demographic information and climate-related parameters. Four machine learning prediction models for CL cases in the El Brouj focus were compared and their performance was evaluated. Our results revealed a steady increase in CL cases until 2019, followed by a significant surge, withLeishmania tropicaidentified as the causative agent for all documented cases. The incidence rates varied among demographic groups, with higher rates observed in females and children aged 5-14. Seasonal analysis indicated a notable increase in cases during spring. Spatial distribution analysis identified El Brouj as the sole endemic CL focus_and the highest hotspot in the area, underscoring the necessity of targeted interventions in this location. Furthermore, Spearman correlation analysis revealed a significant association between CL cases and low temperature and precipitation, emphasizing climate variables role in disease incidence. Prediction modeling for future CL cases in El Brouj focus was assessed with six different models and Linear Regression was the most suitable. This retrospective study provides crucial insights into CL epidemiology in the Casablanca-Settat region, highlighting the need for implementing a coordinated approach tailored to the region that could help curb the spread of CL in Settat province, given the predictive model’s outlook on future CL trends in this area.
Improving Efficiency in the Inpatient Echocardiography Laboratory: A Quality Improvement Project
Authors: Samples Stefani , Roytman Zhanna , McCaw Carrie , Jone Pei-Ni 
Published: February 2025

AbstractBackgroundPediatric echocardiograms are performed daily on inpatient hospital units, predominantly in the Cardiac Intensive Care Unit. Understanding the precise study indication from the ordering providers is critical for completing imaging. Given the volume of echocardiograms ordered daily and staffing shortages, timely completion of echocardiograms is important for maintaining efficiency and productivity. The aim of this study was to identify areas to improve efficiency using quality improvement methodologies.MethodsThe SMART aim was to decrease the total echo completion time by 10% within 6 months. Using a fishbone diagram, limitations in the ordering system and inadequate ordering provider knowledge were identified as areas for improvement. Primary process and outcome metrics included total echo completion time, pre-echocardiogram buffer time, and order documentation of pertinent clinical history. PDSA 1 implemented order updates to provide increased specificity in orders with a picklist of common reasons for inpatient echocardiograms. PDSA 2 implemented a physician alert for STAT studies to reduce the number of inappropriate orders. PDSA 3 implemented additional order updates and staff education.ResultsTotal echo completion time decreased with each cycle for total 25% reduction. This correlated with a decrease in the pre-echocardiogram buffer time of 56% without any significant changes in the number of images obtained per study or the daily inpatient volume. The documentation of pertinent clinical history increased by 18% and maintained at 99% appropriate documentation for the final two PDSA cycles. Pre and post intervention surveys indicated an overall improvement in the ordering process for both the inpatient ordering providers and echocardiography laboratory staff.ConclusionsEchocardiography laboratory efficiency significantly improved throughout the course of this project without negative effects on the ordering providers or echocardiography laboratory staff. Our project demonstrates the ability to affect clinically relevant improvements utilizing simple workflow process changes in the pediatric echocardiography laboratory.
sciLaMA: A Single-Cell Representation Learning Framework to Leverage Prior Knowledge from Large Language Models
Authors: Hu Hongru , Zhang Shuwen , Choi Yongin , Malladi Venkat S. , Quon Gerald 
Published: February 2025

AbstractSingle-cell RNA sequencing (scRNA-seq) enables high-resolution exploration of cellular diversity and gene regulation, yet analyzing such data remains challenging due to technical and methodological limitations. Existing task-specific deep generative models like Variational Auto-Encoder (VAE) and its variants struggle to incorporate external biological knowledge, while transformer-based foundational large Language Models (LLMs or large LaMs) face limitations in computational cost and applicability to tabular gene expression data. Here, we introduce sciLaMA (single-cell interpretable Language Model Adapter), a novel representation learning framework that bridges these gaps by integrating static gene embeddings from multimodal LaMs with scRNA-seq tabular data through a paired-VAE architecture. Our approach generates context-aware representations for both cells and genes and outperforms state-of-the-art methods in key single-cell downstream tasks, including batch effect correction, cell clustering, and cell-state-specific gene marker and module identification, while maintaining computational efficiency. sciLaMA offers a computationally efficient, unified framework for comprehensive single-cell data analysis and biologically interpretable gene module discovery.
Association of human gut microbiota with Alzheimer’s disease pathogenesis: An exploratory clinical study
Authors: Ohara Tadashi , Taki Yasuyuki , Yamamoto Shinya 
Published: February 2025

AbstractThe relationship between Alzheimer’s disease (AD) onset and the brain–gut axis has garnered increasing attention. This study aimed to investigate the potential role of the brain–gut axis in AD pathogenesis, with a specific focus on microbiota composition. This exploratory study enrolled 10 patients with AD and 13 healthy adults, grouped by age (≤30 years, 31–40 years, and ≥41 years). Fecal samples were collected, and 16S rRNA gene sequencing was employed to analyze differences in fecal microbiota composition at the bacterial species level. Certain bacterial species appeared more abundant in the AD group (e.g.,Ruminococcus inulinivoransandRuminococcus torques), while others were relatively more abundant in healthy adults (e.g.,Prevotella vulgatus 1,Bacteroides wexlerae,Clostridium butyricum, andAlistipes rectalis). However, these differences were not statistically significant, likely because of the limited sample size. These findings suggest that fecal microbiota composition may differ between patients with AD and healthy individuals, with a potential intermediate group at risk of AD development. Larger-scale clinical studies are necessary to further elucidate the bacterial species associated with AD pathogenesis, potentially enabling the use of microbiota composition as a screening tool to distinguish between healthy individuals, patients with AD, and those with preclinical AD.
Targeting Mycobacterial Transpeptidases: Evaluating the Roles of Ldt and PBP Inhibition in SuppressingMycobacterium smegmatis
Authors: de Munnik Mariska , Calvopiña Karina , Rabe Patrick , Schofield Christopher J. 
Published: February 2025

Abstractβ-Lactams demonstrate promising in vitro activity againstMycobacteriumspecies and are being explored for tuberculosis treatment; however, evidence of their in vivo efficacy versusMycobacterium tuberculosisremains limited. To achieve broad clinically relevant potency, optimisation of the classical β-lactam scaffolds or development of new or non-β-lactam inhibitors for mycobacterial transpeptidases is likely required. In mycobacteria, potential targets of β-lactams include L,D-transpeptidases (Ldts) and penicillin-binding proteins (PBPs). Reports suggest that dual inhibition of Ldts and PBPs may be necessary to achieve effective anti-mycobacterial activity, yet the specific contributions of Ldt and PBP inhibition to the β-lactam antibacterial mechanisms are not understood. We used fluorogenic substrate mimics to investigate the effects of β-lactams and reported LdtMt2inhibitors onMycobacterium smegmatis(Msm), assessing their impacts on the transpeptidase activities of Ldts and PBPs in living cells. The results reveal a statistically significant correlation between both Ldt and PBP inhibition andMsmgrowth suppression; though under the tested conditions a stronger correlation between Ldt inhibition andMsmgrowth suppression was observed. Notably, inhibition of both PBPs and Ldts was observed in all active inhibitors, though β-lactams manifest increased potency of PBP inhibition. The combination of the β-lactams meropenem and faropenem with selected LdtMt2inhibitors manifested an additive inhibitory effect againstMsm. Our results highlight the importance of further optimising PBPs and Ldt transpeptidase inhibition, particularly of Ldts, to improve β-lactam efficacy versus mycobacteria.
Outcomes of low-risk non-gynecological abdominal surgery in pregnant and nonpregnant women: a comparative study
Authors: Alotaibi Abdulrahman Muaod 
Published: February 2025

AbstractWomen typically undergo an appendectomy and cholecystectomy, which are the most commonly performed non-gynecological abdominal surgeries. Despite advancements, research on the safety and efficacy of laparoscopic surgery for low-risk, non-gynecological abdominal conditions in later-stage pregnant women remains limited. This study aimed to assess the efficacy and postoperative outcomes of low-risk non-gynecological abdominal surgery in female patients, including pregnant women. Female patients diagnosed with appendicitis and biliary disease were included. Based on the pregnancy status, the participants were divided into pregnant and nonpregnant groups. The study identified 11 (1%) cases of pregnancy among the 1029 female patients enrolled. Patients in the pregnant group were younger (30 ± 4.7 years vs. 39 ± 13.5 years, p = 0.002), more likely to undergo emergency surgery (90 vs. 21%, p = 0.001), had a higher rate of undergoing the open-entry approach (18.2 vs. 2.1%, p = 0.002), and more frequently required a postoperative drain (36.4 vs. 10.4%, p = 0.023) than did those in the nonpregnant group. The comorbidities, American Society of Anesthesiologists score, length of hospital stay, operative time, blood loss, postoperative complications, 30-day readmission rate, and mortality rate remained statistically consistent across both groups. Surgery was performed primarily for acute appendicitis in 72% of pregnant women and for biliary disease in 83% of nonpregnant women. None of the pregnant patients experienced preterm labor or fetal mortality after surgery. One patient had an abortion 8 weeks after laparoscopic appendectomy. In conclusion, the overall complication rate of non-gynecological abdominal surgery for appendicitis and biliary disease is 2%. Biliary disease is the most common indication of non-gynecological abdominal surgery among nonpregnant women, whereas appendicitis is the most common indication among pregnant women. Emergency surgery is a significant predictor of complications in pregnant women.
The Influence of NIHSS and Onset-to-Angiography Time on Neurological Outcomes Among Patients with Acute Ischemic Stroke Receiving Endovascular Thrombectomy-A Retrospective Observation Study
Authors: Lin Kuei-Ming , Lu Shuang-Yu , Shih Hong-Mo , Hsu Tai-Yi , Huang Fen-Wei , Wu Shih-Hao , Tsai Sheng-Ta , Liu Chien-Yu , Lin Chin-Han 
Published: February 2025

AbstractBackgroundAcute ischemic stroke is a life-threatening condition requiring urgent intervention. For patients with large vessel occlusion (LVO), timely endovascular thrombectomy (EVT) is critical. This retrospective observational study investigates the impact of the National Institute of Health Stroke Scale (NIHSS) and onset-to-angiography time (OAT) on one-month neurological outcomes in acute ischemic stroke patients.MethodsA total of 300 acute ischemic stroke patients with LVO who underwent EVT at a tertiary medical center in Taiwan from Jan. 2015 to Dec. 2018 were included. The NIHSS-time score was calculated by multiplying the pre-EVT NIHSS score by OAT. Favorable outcomes were defined as a modified Rankin Scale (mRS) ≤ 2 at one month. Multivariate logistic regression was used to identify the association between NIHSS-time scores and outcomes, adjusting for confounders.ResultsPatients with a NIHSS-time score < 4093 had significantly higher odds of achieving favorable outcomes (adjusted OR = 2.94, 95% CI = 1.56–5.56, p < 0.001). This highlights the importance of early EVT and initial stroke severity assessment in predicting recovery.ConclusionThis study demonstrates that lower NIHSS-time scores are strongly associated with favorable neurological outcomes. Patients with a NIHSS-time score less than 4093 had a significantly higher ratio of favorable neurological function after one month. The NIHSS-time score offers a practical tool for prognostic evaluation, emphasizing the urgency of EVT in acute ischemic stroke patients. However, further studies are needed to validate these findings and explore their generalizability.
Neoadjuvant anti-4-1BB confers protection against spontaneous metastasis through low-affinity intratumor CD8+T cells in triple-negative breast cancer
Authors: Lim Bryan Jian Wei , Liu Mingyong , Wang Liuyang , Kong Sharleen Li Ying , Yin Tao , Yan Chengsong , Xiang Kun , Cao Chengjie , Wu Haiyang , Mihai Ariana , Tay Felicia Pei-Ling , Wang Ergang , Jiang Qizhou , Ma Zhehao , Tan Lianmei , Chia Rui Ning , Qin Diyuan , Pan Christopher C. , Wang Xiao-Fan , Li Qi-Jing 
Published: February 2025

ABSTRACTNeoadjuvant immunotherapy seeks to harness the primary tumor as a source of relevant tumor antigens to enhance systemic anti-tumor immunity through improved immunological surveillance. Despite having revolutionized the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC), a significant portion of patients remain unresponsive and succumb to metastatic recurrence post-treatment. Here, we found that optimally scheduled neoadjuvant administration of anti-4-1BB monotherapy was able to counteract metastases and prolong survival following surgical resection. Phenotypic and transcriptional profiling revealed enhanced 4-1BB expression on tumor-infiltrating intermediate (Tint), relative to progenitor (Tprog) and terminally exhausted (Tterm) T cells. Furthermore, Tintwas enriched in low-affinity T cells. Treatment with anti-4-1BB drove clonal expansion of Tint, with reduced expression of tissue-retention marker CD103 in Tprog. This was accompanied by increased TCR clonotype sharing between paired tumors and pre-metastatic lungs. Further interrogation of sorted intratumor T cells confirmed enhanced T cell egress into circulation following anti-4-1BB treatment. In addition, gene signature extracted from anti-4-1BB treated Tintwas consistently associated with improved clinical outcomes in BRCA patients. Combinatorial neoadjuvant anti-4-1BB and ablation of tumor-derived CXCL16 resulted in enhanced therapeutic effect. These findings illustrate the intratumor changes underpinning the efficacy of neoadjuvant anti-4-1BB, highlighting the reciprocity between local tissue-retention and distant immunologic fortification, suggesting treatment can reverse the siphoning of intratumor T cells to primary tumor, enabling redistribution to distant tissues and subsequent protection against metastases.
Dude, Everyone Wants Pattern Analysis Tools (DEWPAT): Tools for measuring visual pattern diversity from digital images
Authors: Sanderson Jillian A , Aumentado-Armstrong Tristan , Dufresne-Camaro Charles-Olivier , Mahler D Luke 
Published: February 2025

AbstractExploring the diversity and function of complex colour patterns is a fundamental interest in ecology and evolutionary biology, but progress on many questions is limited by our ability to quantify diverse visual patterns. We address this problem by introducing Dude, Everyone Wants Colour Pattern Analysis Tools (DEWPAT), a Python package for characterizing multidimensional pattern complexity.DEWPATis a flexible framework designed to extract a diversity of components of visual pattern complexity from standard RGB and multispectral images, including entropy (information content), average gradient magnitude (edge content), high frequency content (detail granularity), generalized variance (heterogeneity), and patch dissimilarity.DEWPAToffers optional image transformation functionality, including blurring to model receiver acuity and segmentation to reduce noise.Functions in this package return both quantitative measurements and graphical representations of color and pattern diversity. We demonstrateDEWPAT’s key functions and applications with three empirical examples (longhorn beetles, anole lizards, and flowers).DEWPAThas the potential to quantitatively characterize previously intractable pattern phenotypes in ways that make their features available for biological analysis.
On CA1 ripple oscillations: reevaluating asynchronicity evidence
Authors: Scheffer-Teixeira Robson , Tort Adriano 
Published: February 2025

AbstractSharp-wave ripples (SWRs) are hippocampal network oscillations associated with memory consolidation. They are characterized by the co-occurrence of fast and slow field potentials across CA1 layers: the fast-frequency oscillations, known as ripples, are prominent in the pyramidal cell layer, where they coincide with increased neuronal spiking, while slower negative transients, referred to as sharp waves, occur simultaneously in thestratum radiatum. SWRs have traditionally been considered globally synchronous across the hippocampus; however, recent evidence suggests that ripples may be less synchronous than previously thought, particularly between the two hemispheres (Villalobos et al., 2017). In this study, we revisited this question using a unique dataset from probes spanning the septo-temporal axis of CA1. Our results demonstrate that ripples are phase-locked within but not between hemispheres, although their occurrence remains time-locked across both the septo-temporal axis and hemispheres. We also observed a similar synchronicity pattern for spiking activity: neurons are locally phase-coupled and globally time-coupled to ripple events. Interneurons exhibit a much stronger phase coupling to both ipsilateral and contralateral ripples than pyramidal neurons. These findings suggest that ripples are locally phase-coupled through pyramidal-interneuron interactions, with global time-locking likely driven by a common bilateral CA3 input and potentially modulated by interneuron circuits.
Decoding bacterial methylomes in four public health-relevant microbial species: Nanopore sequencing enables reproducible analysis of DNA modifications
Authors: Galeone Valentina , Dabernig-Heinz Johanna , Lohde Mara , Brandt Christian , Kohler Christian , Wagner Gabriel E. , Hölzer Martin 
Published: February 2025

AbstractInvestigating bacterial methylation profiles provides essential complementary information to the native DNA sequence, significantly extending our understanding of how DNA modifications influence virulence, antibiotic resistance, and the ability of bacteria to evade the immune system. Recent advancements in real-time Nanopore sequencing and basecalling algorithms have enabled the direct detection of modified bases from raw signal data, eliminating the need for bisulfite treatment of DNA. However, decoding methylation signals remains challenging due to rapid technological and methodological progress.In this study, we focus on public health-relevant bacterial strains to analyze their methylation profiles and identify methylation motifs. Our dataset includes samples fromStaphylococcus aureus,Listeria monocytogenes,Enterococcus faecium, andKlebsiella pneumoniae, sequenced on the Nanopore GridION platform using the latest flow cell chemistry (R10.4.1) and modification basecalling models (Dorado basecalling SUP model v5).We investigated distinct methylation patterns within and between species, focusing on heavily modified genes or genomic regions. Our results reveal distinct species-specific methylation profiles, with each strain exhibiting unique modification patterns. We developed a modular pipeline using Nextflow and the Nanopore Modkit tool to streamline the detection of methylated motifs. We compared the results with outputs from MicrobeMod, a recent toolkit for exploring prokaryotic methylation and base modifications in nanopore sequencing. Our pipeline is publicly available for further use (github.com/rki-mf1/ont-methylation).We identified known methylation motifs already described in the literature and novelde novomotifs, providing deeper insights into the diversity of bacterial DNA modifications. Furthermore, we identified genomic regions that are extensively methylated, which could have implications for bacterial behavior and pathogenicity. We also assess improvements in basecalling accuracy, specifically how methylated bases can influence neighboring basecalls. Recent advances in basecalling models, particularly v5 models as part of Dorado, have reduced these issues, improving the reliability of methylation detection in bacterial genomes.In conclusion, our study highlights the potential of current nanopore sequencing tools for detecting DNA modifications in prokaryotes. By making our pipeline and results publicly available, we facilitate further research into bacterial DNA modifications and their role in microbial pathogenesis.