bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling inflammation-induced peripheral sensitization in a dish—more complex than expected?
Authors: Li Yuening , Lock Amy , Fedele Laura , Zebochin Irene , Sabate Alba , Siddle Matthew , Cainarca Silvia , Röderer Pascal , Montag Katharina , Tarroni Paola , Brüstle Oliver , Shaw Tanya , Taams Leonie , Denk Franziska 
Published: February 2025

Abstract
Peripheral sensitization of nociceptors is believed to be a key driver of chronic pain states. Here, we sought to study the effects of a modified version of inflammatory soup on the excitability of human stem cell–derived sensory neurons. For this, we used a preexisting and a novel stem cell line, modified to stably express the calcium sensor GCamP6f. Upon treatment with inflammatory soup, we observed no changes in neuronal transcription or functional responses upon calcium imaging and only a very minor increase in resting membrane potential (RMP) via whole cell patch clamping: control RMP (−71.31 ± 1.1 mV) vs inflammatory soup RMP (−67.74 ± 1.29 mV), uncorrected 2-tailed independent samples t test, P = 0.0383. Similarly, small changes were observed when treating mouse primary sensory neurons with inflammatory soup. A semi-systematic reexamination of past literature further indicated that observed effects of inflammatory mediators on dissociated sensory neuron cultures are generally small. We conclude that modelling inflammation-induced peripheral sensitization in vitro is nontrivial and will require careful selection of mediators and/or more complex, longitudinal multicellular setups. Especially in the latter, our novel GCamP6f-induced pluripotent stem cell line may be of value.
Content Analysis of Social Determinants of Health Accelerator Plans Using Artificial Intelligence: A Use Case for Public Health Practitioners
Authors: DePriest Kelli , Feher John , Gore Kailen , Glasgow LaShawn , Grant Clint , Holtgrave Peter , Hacker Karen , Chew Robert 
Published: February 2025

Context:
Public health practice involves the development of reports and plans, including funding progress reports, strategic plans, and community needs assessments. These documents are valuable data sources for program monitoring and evaluation. However, practitioners rarely have the bandwidth to thoroughly and rapidly review large amounts of primarily qualitative data to support real-time and continuous program improvement. Systematically examining and categorizing qualitative data through content analysis is labor-intensive. Large language models (LLMs), a type of generative artificial intelligence (AI) focused on language-based tasks, hold promise for expediting content analysis of public health documents, which, in turn, could facilitate continuous program improvement.

Objectives:
To explore the feasibility and potential of using LLMs to expedite content analysis of real-world public health documents. The focus was on comparing semiautomated outputs from GPT-4o with human outputs for abstracting and synthesizing information from health improvement plans.

Design:
Our study team conducted a content analysis of 4 publicly available community health improvement plans and compared the results with GPT-4o’s performance on 20 data elements. We also assessed the resources required for both methods, including time spent on prompt engineering and error correction.

Main outcome measure(s):
Accuracy of data abstraction and time required.

Results:
GPT-4o demonstrated abstraction accuracy of 79% (n = 17 errors) compared to 94% accuracy by the study team for individual plans, with 8 instances of falsified data. Out of the 18 synthesis data elements, GPT-4o made 9 errors, demonstrating an accuracy of 50%. On average, GPT-4o abstraction required fewer hours than study team abstraction, but resource savings diminished when accounting for time for developing prompts and identifying/correcting errors.

Conclusions:
Public health professionals who explore the use of generative AI tools should approach the method with cautious curiosity and consider the potential tradeoffs between resource savings and data accuracy.
Multi-view gene panel characterization for spatially resolved omics
Authors: Kim Daniel , Ding Wenze , Shaw Akira Nguyen , Torkel Marni , Turtle Cameron J , Yang Pengyi , Yang Jean 
Published: February 2025

AbstractSpatially resolved transcriptomics has transformed our ability to study complex tissues at the cellular and subcellular resolution. However, targeted spatial technologies require pre-selected gene panels, which are typically curated based on existing biological knowledge and prior research hypotheses. While current methods often prioritize capturing cell type information, we argue that an effective gene panel should also capture cell type diversity, cell states, pathway-level information, and minimize redundancy. To address these broader requirements, we developed a gene panel characterization platform that characterizes panels across multiple perspectives, thus allowing us to compare panels comprehensively. Notably, computationally constructed gene panels performed competitively in capturing major cell types when compared to our in-house manually curated panel. However, refined manual curation offered distinct advantages, particularly in capturing minor and rare cell types and exhibited lower information redundancy comparatively. Building on this framework, we integrated these metrics into a deep learning platform, panelScope, leveraging them as a loss function to design holistic gene panels. Using an acute myeloid leukemia (AML) dataset with 42 well-defined cell types and the 5K Xenium panel from 10X Genomics, we demonstrate the utility of our framework in comprehensively characterizing gene panels, enabling the design of tailored panels that address diverse research needs.
Integration of CA attention and KAN algorithm to predict EGFR mutation status in lung cancer
Authors: Jia Nan , Xing Junfeng , Tang Siyuan , Liu Liang , Guo Jingxia , Wu Yan , Bai Jiniu , Li Yan 
Published: February 2025

AbstractEpidermal Growth Factor Receptor (EGFR) mutations are critical biomarkers for targeted therapies in non-small cell lung cancer (NSCLC). However, conventional diagnostic methods rely on invasive tissue biopsies, which are costly, time-consuming, and pose significant limitations. As an alternative, non-invasive approaches using lung CT imaging to predict EGFR mutation status have gained attention for their rapid and user-friendly nature. This study explores EGFR mutation prediction by analyzing seven distinct 2D regions of interest (ROI): the nodule itself, 2-pixel, 4-pixel, and 6-pixel extensions around the nodule, CT slices containing the nodule, single-lung segmented images with the nodule, and bilateral lung segmented images with the nodule. We developed a deep learning model combining EfficientNet-B0 with a Coordinate Attention (CA) mechanism, replacing the traditional MLP classifier with a KAN classifier. Results show that analyzing single-lung images containing the nodule captures additional relevant information, achieving the highest predictive performance. This suggests that regions surrounding the nodule contain valuable discriminatory biomarkers. The model achieved 92.73% accuracy on the single-lung test set with only 6.82M parameters, demonstrating its potential as a clinical tool to optimize targeted treatment decision-making.
The vaginal microbiota composition influences cervicovaginal and systemic inflammation induced byChlamydia trachomatisinfection
Authors: Adapen Cindy , Réot Louis , Nunez Natalia , Cannou Claude , Marlin Romain , Lemaitre Julien , Lakoum Sabrine , Diry Ségolène , d’Agata Léo , Gros Wesley , Gallouët Anne-Sophie , Leonec Marco , Bossevot Laetitia , Dereuddre-Bosquet Nathalie , Le Grand Roger , Nugeyre Marie-Thérèse , Menu Elisabeth 
Published: February 2025

ABSTRACTBackgroundChlamydiosis, a sexually transmitted infection (STI) induced byChlamydia trachomatis(CT), increases local inflammation (cytokine production, recruitment of immune cells such as neutrophils). Few is known on the impact of CT infection on the phenotype of cervicovaginal neutrophils. Vaginal microbiota (VM) is a key factor in the regulation of local immune responses and STI acquisition whereLactobacillus sppare associated with protection. In this study, the VM of cynomolgus macaques was enriched withLactobacillus crispatusafter local metronidazole treatment followed by repeated intravaginal inoculations of CT. VM composition, CT infection and local and systemic inflammation were monitored.ResultsFirst, we observed that metronidazole treatment induced drastic modifications of the VM by reducing the abundance of several anaerobes and increasing the number of naturalLactobacillus spp(Lactobacillus johnsoniiand its prophage mainly) as well as opportunistic bacteria (Streptococcus sppandStaphylococcus spp). After CT exposure ofL. crispatustreated or not animals, a non-persisting CT infection and no association betweenL. crispatusenrichment and a lower susceptibility to CT infection were detected. However, the production of serum specific anti-CT IgG was higher inL. crispatustreated animals. Moreover, the production of anti-CT IgG was associated with various bacterial species. An increased production of peripheral blood cytokines after CT infection was observed in untreated animals, whereasL. crispatustreated animals exhibited an increased production of cervicovaginal cytokines. Peripheral blood neutrophils were more mature and activated after CT infection/inoculation in both groups. Very few alterations of the cervicovaginal neutrophil phenotype were noticed after CT infection. Markers expressed on neutrophils were associated with bacterial species and differences were detected according to groups.ConclusionThese results suggest a better local immune response as well as a better control on systemic inflammation upon CT infection inL. crispatustreated animals compared to untreated animals. Indeed, it highlight an impact of VM composition on the local and systemic immune responses induced by CT infection. This study confirmed that VM composition can be a powerful tool to modulate local inflammation and STI susceptibility.
Calcium starvation leads to strain-specific gene regulation of lipid and carotenoid production inMucor Circinelloides
Authors: Baalsrud HT , Byrtusova D , To TH , Larsen IE , Bøe VA , Grønvold L , Fu J , Árnyasi M , Shapaval V , Sandve SR 
Published: February 2025

AbstractFungi are pivotal in transitioning to a bio-based, circular economy due to their ability to transform organic material into valuable products such as organic acids, enzymes, and drugs.Mucor circinelloidesis a model organism for studying lipogenesis and it particularly promising for its metabolic capabilities in producing oils like TAGs and carotenoids, influenced by environmental factors such as nutrient availability. Notably, strains VI04473 and FRR5020 have been identified for their potential in producing single-cell oils and carotenoids, respectively. Calcium starvation have previously been shown to have strain-specific effects, with VI04473 accumulating more lipids and FRR5020 producing more carotenoids. Here we used genome sequencing, comparative genomics, transcriptomics, and metabolite phenotyping to explore the genetic basis of lipid and carotenoid production under calcium starvation in these strains. We found extensive genomic rearrangements between these strains, as well as low conservation of gene regulatory responses to calcium depletion. This lack of conservation also applies to genes involved in lipid and carotenoid production, i.e. the lipidome. Several pathways show divergent regulation between strains, which explains the phenotypic divergence between VI04473 and FRR5020. The complex gene family evolution of several lipidome genes probably also affected specialization of these strains to calcium stress. Our study sheds light on the complexity of the evolution of metabolic networks inM. circinelloides. Understanding these genetic underpinnings can optimize the industrial use ofM. circinelloides, enhancing lipid productivity and stress tolerance, and tailoring metabolic profiles for specific applications. This research advances our knowledge on complexity of fungal lipid metabolism and the role of calcium in regulating metabolic pathways.
PEAKQC: Periodicity Evaluation in scATAC-seq data for quality assessment
Authors: Detleffsen Jan , Kuenne Carsten , Bentsen Mette , Looso Mario 
Published: February 2025

AbstractATAC-seq is a common protocol to identify regulatory regions in the genome. While quality control (QC) standards are well-established for bulk ATAC-seq, application to single-cell ATAC-seq remains challenging due to data sparsity, noise, and a lack of consensus on effective QC metrics and thresholds. Existing methods, such as fragment length ratio offer limited resolution and fail to fully utilize fragment length distribution (FLD) patterns. We present PEAKQC, a Python-based tool designed to assess single-cell ATAC-seq data quality using a wavelet-based convolution of FLD patterns. Benchmarking PEAKQC against established QC metrics demonstrates an overall more consistent, linear quality assessment of ATAC data. PEAKQC improves downstream analyses by effectively filtering low-quality cells while preserving biologically meaningful data. When combined with other metrics, such as the ratio of fragments in peaks and total counts, PEAKQC enhances clustering accuracy and cell-type identification. The tool is modular, easily installable via Python Package Index, and integrates seamlessly into Python-based single-cell analysis frameworks. PEAKQC provides a robust and scalable solution for single-cell ATAC-seq QC, addressing current gaps in the field and suggesting FLD patterns as a new standard for data quality assessment.
Multi-omic subtypes of Alzheimer’s dementia are differentially associated with psychological traits
Authors: Zammit Andrea R. , Yu Lei , Poole Victoria N. , Arfanakis Konstantinos , Schneider Julie A. , Petyuk Vladislav A. , De Jager Philip L. , Kaddurah-Daouk Rima , Iturria-Medina Yasser , Bennett David A. 
Published: February 2025

AbstractImportancePsychological traits reflecting neuroticism, depressive symptoms, loneliness, and purpose in life are risk factors of AD dementia; however, the underlying biologic mechanisms of these associations remain largely unknown.ObjectiveTo examine whether one or more multi-omic brain molecular subtypes of AD is associated with neuroticism, depressive symptoms, loneliness, and/or purpose in life.DesignTwo cohort-based studies; Religious Orders Study (ROS) and Rush Memory and Aging Project (MAP), both ongoing longitudinal clinical pathological studies that began enrollment in 1994 and 1997.SettingOlder priests, nuns, and brothers from across the U.S. (ROS) and older adults from across the greater Chicago metropolitan area (MAP).Participants822 decedents with multi-omic data from the dorsolateral prefrontal cortex.Exposure(s)Pseudotime, representing molecular distance from no cognitive impairment (NCI) to AD dementia, and three multi-omic brain molecular subtypes of AD dementia representing 3 omic pathways from no cognitive impairment (NCI) to AD dementia that differ by their omic constituents.Main outcome(s) and measure(s)We first ran four separate linear regressions with neuroticism, depressive symptoms, loneliness, purpose in life as the outcomes, and pseudotime as the predictor, adjusting for age, sex and education. We then ran four separate analyses of covariance (ANCOVAs) with Bonferroni-corrected post-hoc tests to test whether the three multi-omic AD subtypes are differentially associated with the four traits, adjusting for the same covariates.ResultPseudotime was positively associated (p<0.05) with neuroticism and loneliness. AD subtypes were differentially associated with the traits: AD subtypes 1 and 3 were associated with neuroticism; AD subtype 2 with depressive symptoms; AD subtype 3 with loneliness, and AD subtype 2 with purpose in life.Conclusions and RelevanceThree multi-omic brain molecular subtypes of AD dementia differentially share omic features with four psychological risk factors of AD dementia. Our data provide novel insights into the biology underlying well-established associations between psychological traits and AD dementia.Key pointsQuestionAre three distinct multi-omic brain molecular subtypes of Alzheimer’s disease (AD) dementia associated with four well-established psychological AD risk factors (neuroticism, depressive symptoms, loneliness and purpose in life)?FindingsWe found differential associations: AD subtypes 1 and 3 were associated with neuroticism, AD subtype 2 was associated with depressive symptoms, AD subtype 3 was associated with loneliness; and AD subtype 2 was associated with purpose in life.MeaningPsychological risk factors might be associated with AD dementia via shared multi-omic molecular pathways.
Penetration of Inner Scleral Fibers into Peripapillary Sclera Revealed by Polarization-Sensitive OCT
Authors: Xiong Jianping , Lu Hongshuang , Zhou Nan , Wu Yijin , Yamanari Masahiro , Takahashi Hiroyuki , Okamoto Michiaki , Sugisawa Keigo , Yoshida Takeshi , Chen Changyu , Wang Yining , Wang Ziye , Ohno-Matsui Kyoko 
Published: February 2025

AbstractPurposeTo determine the structural characteristics of the peripapillary sclera in myopic eyes using polarization-sensitive optical coherence tomography (PS-OCT).MethodsPatients with myopia who underwent PS-OCT imaging between April and June 2023 were studied. The intensity, optic axis, and birefringence of PS-OCT images were analyzed to determine the surface of the lamina cribrosa (LC). The direction and arrangement of the scleral collagen fibers in the peripapillary region and scleral ridge were determined.ResultsOne hundred and ten eyes of 59 patients with myopia (mean axial length, 30.00 ± 1.98 mm) were studied. The scleral fibers around the optic nerve were arranged circularly in all eyes regardless of the presence or size of the peripapillary atrophy. Inner scleral fibers that penetrated beneath this circular arrangement were detected in 98 eyes (89.1%). There was a Y-shaped split at the point of penetration in 77 eyes (70.0%). The integrity of the circular arrangement and penetrating scleral fiber complexes remained intact even in cases of severe peripapillary scleral deformation. A scleral ridge was identified in 27 eyes (24.5%), and it appeared as a full-thickness protrusion composed primarily of outer scleral fibers. The ridge was consistently located outside the circular arrangement.ConclusionsThe penetration of the radial inner scleral fibers into the circular arrangement and extension to the LC suggest that they act as stabilizing anchors for the circular structure. The differences of the scleral ridges from those in eyes with dome-shaped macula suggest that unique mechanisms cause the scleral differences.
Estimating Direct and Spillover Vaccine Effectiveness with Partial Interference under Test-Negative Design Sampling
Authors: Jiang Cong , Fang Fei , Talbot Denis , Schnitzer Mireille E 
Published: February 2025

AbstractThe Test-Negative Design (TND), which involves recruiting care-seeking individuals who meet predefined clinical case criteria, offers valid statistical inference for Vaccine Effectiveness (VE) using data collected through passive surveillance, making it cost-efficient and timely. Infectious disease epidemiology often involves interference, where the treatment and/or outcome of one individual can affect the outcomes of others, rendering standard causal estimands ill-defined; ignoring such interference can bias VE evaluation and lead to ineffective vaccination policies. This article addresses the estimation of causal estimands for VE in the presence of partial interference using TND samples. Partial interference means that the vaccination of units within the same group/cluster may influence the outcomes of other members of the cluster. We define the population direct, spillover, total, and overall effects using the geometric risk ratio, which are identifiable under TND sampling. We investigate various stochastic policies for vaccine allocation in a counterfactual scenario, and identify policy-relevant VE causal estimands. We propose inverse-probability weighted (IPW) estimators for estimating the policy-relevant VE causal estimands with partial interference under the TND, and explore the statistical properties of these estimators.
Corrections in single cell migration path in vivo are controlled by pulses in polar Rac1 activation
Authors: Hoffmann Dennis , Agranov Tal , Kühl Lucas , Simons Benjamin D. , Gov Nir , Raz Erez 
Published: February 2025

SummaryDirected migration of single cells is central to a large number of processes in development and adult life. Corrections to the migration path of cells are often characterized by periodic loss of polarity that is followed by the generation of a new leading edge in response to guidance cues, a behavior termed ‘run and tumble’. While this phenomenon is essential for accurate arrival at migration targets, the precise molecular mechanisms responsible for the periodic changes in cell polarity are unknown. To investigate this issue, we employ germ cells in live zebrafish embryos as anin vivomodel and show that a tunable molecular network controls periodic pulsations of Rac1 activity and actin polymerization. This process, which we term ‘polar pulsations’, is responsible for the transitions between the run and tumble phases. In addition, we provide evidence for the role of apolar blebbing activity during tumble phases in erasing the memory of the previous front-back polarity of the migrating cell. To understand how the molecular components give rise to this distinct behavior, we develop a minimal mathematical model of the biochemical network that accounts for the observed cell behavior. Together, ourin vivofindings and the mathematical model suggest that a pulsatory signaling network regulates the accuracy of individual cell migration.
Maternal Transfer of Vaccine-Induced Anti-OspA Antibodies in Peromyscus spp Protects Pups from Tick-TransmittedBorrelia burgdorferi
Authors: Azevedo Jose F. , Joyner Greg , Kundu Suman , Samanta Kamalika , Gomes-Solecki Maria 
Published: February 2025

AbstractMaternal antibody transfer provides passive immunity to offspring; however, the efficacy and duration of this protection depends on maternal antibody levels and transfer efficiency. We investigated whether oral vaccination ofPeromyscus leucopusdams with recombinant OspA-expressingE. colicould induce maternal transfer of anti-OspA antibodies and protect pups fromBorrelia burgdorferichallenge. Dams were vaccinated for different durations: (i) until breeding, (ii) until birth of pups, or (iii) until pups were 2 weeks old. Pups were challenged withIxodes scapularisnymph-transmittedB. burgdorferiat ∼ 4 weeks of age. Anti-OspA IgG were quantified in dams and pups, andB. burgdorferianti-PepVF IgG were quantified in pups. Furthermore,B. burgdorferiburden was assessed by qPCR targeting theflaBgene in pups’ heart and bladder tissues > 4 weeks after tick challenge.P. leucopuspups born to dams vaccinated until breeding, exhibited low anti-OspA antibody and were not protected from tick transmittedB. burgdorferiinfection. However, when maternal vaccination extended until pups were born and until pups were two weeks old, significant anti-OspA antibody transfer and protection occurred. This was evidenced by absence of antibody toB. burgdorferiPepVF, absence ofB. burgdorferi flaBDNA in heart and bladder tissues, and absence offlaBin culture from heart tissues from pups euthanized >9 weeks after birth. We show that transfer of anti-OspA antibodies fromP. leucopusdams to offspring prevents tick transmission ofB. burgdorferiin the major reservoir host of this spirochete in the United States.ImportanceThis study contributes to our understanding of how reservoir targeted vaccines designed to block transmission ofB. burgdorferifrom infectedIxodes scapularisticks may disrupt the enzootic cycle of this spirochete and reduce incidence of Lyme disease.