bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lemur: A Single-Cell Foundation Model with Fine-Tuning-Free Hierarchical Cell-Type Generation forDrosophila melanogaster
Authors: Botas Jorge , Jia Johnathan , Pasupuleti Sasidhar , Chen Hu , Hu Xia , Xu Zhaozhuo , Liu Zhandong 
Published: February 2025

AbstractSingle-cell genomics has revolutionized our understanding of cellular heterogeneity, but automating its analysis remains an open challenge. Cell-type annotation represents a critical bottleneck, particularly as datasets grow in size and complexity. While foundation models have shown promise in addressing this challenge, existing approaches require extensive fine-tuning for effective cell-type annotation. Here, we present Lemur (LargeExpressionModel forUnderstanding scRNA-seq), a single-cell foundation model specifically designed forDrosophila melanogaster. Lemur achieves fine-tuning-free cell-type annotation through comprehensive pre-training on an integrated whole-organism atlas with a unified cell-type annotation schema. To leverage this unified schema, we developed a dedicated hierarchical cell-type decoder architecture. This approach enables Lemur to generate consistent cell-type predictions across multiple levels of granularity without requiring additional training on new datasets. The model demonstrates strong performance across diverse tissue types, experimental conditions, and sequencing technologies. It also achieves batch-effect correction without explicitly training for this task. This automated analysis capability positions Lemur as an effective tool for the fly research community. Beyond its immediate applications, Lemur establishes a framework for accelerating biological discovery. It enables rapid iteration between computational predictions and experimental validation in the highly controlledDrosophila melanogastersystem, with potential implications for translational research in human biology, particularly in aging and neurodegenerative disease studies.
Monitoring Whole-Body Inflammation with Gallium-68 Labeled Polydopamine Iron Oxide Particles via Hybrid Immuno-PET-MRI
Authors: Pedron Swannie , Guillou Amaury , Fillesoye Fabien , Jacqmarcq Charlène , Perrio Cécile , Caruso Frank , Li Shiyao , Ju Yi , Vivien Denis , Gauberti Maxime , Vigne Jonathan , Bonnard Thomas 
Published: February 2025

AbstractMonitoring immune reactions via inflammation imaging provides valuable disease prognosis but remains limited by currently available probes and imaging capabilities. In this study, a bimodal imaging probe was developed from microsized polydopamine matrix-based magnetic particles (M3P) functionalized with antibodies that target vascular cell adhesion molecule-1 (VCAM-1) and that are radiolabeled with the radioisotope Gallium-68. This probe combines sensitive inflammation detection via Positron Emission Tomography (immuno-PET) and high-resolution mapping via Magnetic Resonance Imaging (immuno-MRI). The probe represents a powerful disease diagnosis tool to assess the status of systemic inflammation in sepsis as whole-body immuno-PET enables rapid evaluation of the situation, and immuno-MRI provides a more detailed characterization of the identified affected tissues. The elimination profile of the M3P probe is restricted to the mononuclear phagocyte system and does not undergo renal clearance, which is suitable for application in kidney disorders. The efficacy of the hybrid immuno-PET-MRI diagnosis protocol was tested in a murine model of rhabdomyolysis. Kidney inflammation was detected by whole-body immuno-PET, and vascular inflammation patterns could be revealed by high-resolution immuno-MRI. This bimodal PET-MRI probe could significantly improve inflammation monitoring in pathologies characterized by systemic inflammation or lung and kidney dysfunction.
Noncoding and Coding Mechanisms of Aging Heart Failure with Preserved Ejection Fraction with Thyroid Dysfunction
Authors: Chakraborty Sankalpa , Dickerson Bryce , Bounds Curren , Lemus Sophia , Hickman Caleb , Rajagopalan Viswanathan 
Published: February 2025

AbstractHeart Failure with preserved Ejection Fraction (HFpEF) is a heterogeneous geriatric syndrome with complex pathophysiology and comorbidities. Long noncoding RNAs (lncRNAs) account for a large majority of the functional mammalian transcriptome and act as key regulators in complex physiological and pathological processes. However, the role of lncRNAs and the development of thyroid dysfunction in aging HFpEF is not clear. We investigated the ZSF1 model in both early and more severe stages of HFpEF (5-, 13- and 20-months old [mo]). We assessed molecular, biochemical, and pathophysiological roles involving lncRNAs, mRNAs, and inflammatory markers. Thyroid hormone (TH) immuno-sorbent assays showed significant decreases in serum T3 levels in 5-mo and serum T4 levels in 5-mo and 13-mo obese HFpEF groups compared to lean controls. Morphometric analyses showed significant increases in heart and LV weights in obese HFpEF rats indicating cardiac hypertrophy. LncRNA microarray and RT-qPCR revealed that three key lncRNAs were significantly increased in 13-mo obese HFpEF but not in 5-mo obese HFpEF left ventricles compared to the ZSF1 lean controls. Microarray analyses showed thatSik1mRNA was significantly upregulated andAnxa13 was downregulated in early obese HFpEF hearts compared to the lean controls. Additionally, we also uncovered previously unreported tissue and serum inflammatory cytokine profiles in early and late HFpEF. This study has identified key novel lncRNA and inflammatory markers in early and late hypothyroid HFpEF. Further studies may help in better understanding and development of diagnostic and therapeutic targets for HFpEF that presents with severe morbidity and mortality.
Towards a comprehensive view of the pocketome universe – biological implications and algorithmic challenges
Authors: Zillmer Hanne , Walther Dirk 
Published: February 2025

AbstractWith the availability of reliably predicted 3D-structures for essentially all known proteins, characterizing the entirety of protein - small-molecule interaction sites (binding pockets) has become a possibility. The aim of this study was to identify and analyze all compound-binding sites, i.e. the pocketomes, of eleven different species’ from different kingdoms of life to discern evolutionary trends as well as to arrive at a global cross-species view of the pocketome universe. All protein structures available in the AlphaFold database for each species were subjected to computational binding site predictions. The resulting set of potential binding sites was inspected for overlaps with known pockets and annotated with regard to the protein domains in which the pockets are located. 2D-projections of all pockets embedded in a 128-dimensional feature space and characterizing them with regard to selected physicochemical properties, provide informative, global pocketome maps that reveal differentiating features between pockets. Our study revealed a sub-linear scaling law of the number of unique binding sites relative to the number of unique protein structures per species. Thus, larger proteomes harbor less than proportionally more different binding sites than species with smaller proteomes. However, this relationship is mainly driven by large numbers of singletons, i.e. binding sites that are not similar to any other binding site in the same species. We discuss the significance of this finding as well as identify critical and unmet algorithmic challenges.
Consumer resilience suppresses the recovery of overgrazed ecosystems
Authors: Spindel Nathan B. , Galloway Aaron W. E. , Schram Julie B. , Mcneill Gwiisihlgaa Daniel , Vanessa Bellis Sg̱iids Ḵung , Guujaaw Niisii , Yakgujanaas Jaasaljuus , Pontier Ondine , Thompson Markus , Lee Lynn C. , Okamoto Daniel K. 
Published: February 2025

AbstractFood availability is among the strongest determinants of fitness. For many systems, ecosystemwide collapse in food availability can result from overgrazing with cascading ecological impacts. Yet, the mechanisms through which the responsible consumers persist in food-poor environments and their role in suppressing productivity recovery remain uncertain. This study examines how food abundance, quality, deprivation, and reintroduction shape plastic energetic traits and nutritional assimilation in an invertebrate herbivore. To evaluate how food composition and quantity affect energetic performance and biomarker composition in herbivore tissues, we analyzed fatty acids in producer and consumer tissues bothin situand in laboratory feeding trials. Sea urchins have a history of periodic overgrazing of kelp forests, followed by their extraordinary long-term persistence in the resulting barrens. Despite a two-fold difference in baseline metabolic rates (RMR) between kelp forest and barrens urchins, both consumed algae at equivalent rates in the laboratory. Starvation and feeding of urchins from kelp forests and barrens, respectively, induced reciprocal shifts in RMR and energy reserves over one month. Urchins fed lower-quality diets consumed more calories with lower efficiency in converting food to gonadal tissue. This metabolic resilience could hinder the recovery of kelp, a foundation species critical to nearshore ecosystems.
Local Topological Structures and Global Connectivity Patterns in aTrachelospermum jasminoides: a Pilot Study
Authors: Tozzi Arturo 
Published: February 2025

ABSTRACTTopological approaches to biological systems provide insights into their growth patterns, network connectivity and spatial organization. This perspective explores how biological structures self-organize, maintain stability and adapt to environmental constraints, revealing fundamental principles of efficiency, robustness, resilience and functional optimization. In this pilot study, we analysed the local and global topological properties of aTrachelospermum jasminoidesbush (commonly known as star jasmine) using persistent homology, graph theory, spectral analysis and percolation theory. The spatial positions of individual flowers were extracted from an image of the bush and represented as a point cloud to capture their structural distribution and spatial relationships. Using Delaunay triangulation, a connectivity graph revealed a dominant connected component with minimal isolated structures. DBSCAN analysis identified a large number of small, localized clusters, reflecting biological and environmental influences. Most flowers connected to five to six neighbours, forming a uniform network with high clustering. Shortest path analysis showed efficient long-range connectivity, with paths avoiding sparse regions. Spectral analysis indicated smooth percolation without bottlenecks, while percolation analysis simulations revealed resilience up to 18% flower removal, after which connectivity broke down. In sum, we showed that the star jasmine bush topology balances local structural constraints with global connectivity, ensuring efficient resource distribution and structural integrity. By integrating topological data analysis with ecological modeling, we suggested a methodological approach to understanding natural growth networks. These insights can inform broader studies on biological pattern formation, network resilience and plant architecture modeling in ecology, agricultural sciences and biomimetic design.
Overexpression of GITRL by B cell IgD low (BDL) B cells is a therapeutic strategy to increase endogenous CD4+Foxp3+T regulatory cells for the treatment of autoimmunity
Authors: Khalil Mohamed I. , Gurski Cody J. , Burns Robert , Zander Ryan , Sommers Kelli C. , Beltrame Angela K. , Dittel Bonnie N. 
Published: February 2025

AbstractAutoimmune diseases, such as multiple sclerosis (MS), are often chronic with no cures. An underlying commonality of autoimmune diseases is immune-mediated inflammation. Control of inflammation is achieved by steroids and disease-modifying therapies, which can result in severe side-effects. CD4+Foxp3+T regulatory cells (Treg), are essential to controlling autoimmune responses and are considered a strong therapeutic target with minimal side effects. To that end, we leveraged our identification of B cell IgD low (BDL) B cells that control Treg homeostatic levels in the mouse spleen in a GITRL-dependent manner to demonstrate that overexpression of GITRL by BDLusing a B cell-specific GITRL transgene (tg) was sufficient to increase endogenous Treg numbers and attenuate the disease severity of experimental autoimmune encephalomyelitis (EAE), the mouse model of MS. To determine whether increased GITRL expression by BDLcould be a therapeutic strategy, WT mice were transplanted with bone marrow from GITRLtg mice. After reconstitution, GITRL expression was increased on BDL, Treg numbers were significantly elevated, and EAE was dramatically attenuated. These cumulative data further demonstrate that GITRL is a functional receptor on BDLand its overexpression in B cells is a therapeutic strategy to increase endogenous Treg numbers for treating autoimmunity.
Gene regulatory logic of the interferon-β enhancer contains multiple selectively deployed modes of transcription factor synergy
Authors: Schiffman Allison , Cheng Zhang , Ourthiague Diana , Hoffmann Alexander 
Published: February 2025

ABSTRACTType I interferon IFNβ is a key regulator of the immune response, and its dysregulated expression causes disease. The regulation of IFNβ promoter activity has been a touchpoint of mammalian gene control research since the discovery of functional synergy between two stimulus-responsive transcription factors (TFs) nuclear factor kappa B (NFκB) and interferon regulatory factors (IRF). However, subsequent gene knockout studies revealed that this synergy is condition-dependent such that either NFκB or IRF activation can be dispensable, leaving the precise regulatory logic of IFNβ transcription an open question. Here, we developed a series of quantitative enhancer states models of IFNβ expression control and evaluated them with stimulus-response data from TF knockouts. Our analysis confirmed that TF synergy is a hallmark of the regulatory logic but that it need not involve NFκB, as synergy between two adjacent IRF dimers is sufficient. We found that a sigmoidal binding curve at the distal site renders the dual IRF synergy mode ultrasensitive, allowing it only in conditions of high IRF activity upon viral infection. In contrast, the proximal site has high affinity and enables expression in response to bacterial exposure through synergy with NFκB. However, its accessibility is controlled by the competitive repressor p50:p50, which prevents basal IRF levels from synergizing with NFκB, such that NFκB-only stimuli do not activate IFNβ expression. The enhancer states model identifies multiple synergy modes that are accessed differentially in response to different immune threats, enabling a highly stimulus-specific but also versatile regulatory logic for stimulus-specific IFNβ expression.SIGNIFICANCEPrecise regulation of the immune cytokine IFNβ is essential for human health. Classic studies established that the transcription factors NFκB and IRF function synergistically in activating IFNβ expression. However, more recent data revealed that either factor may be dispensable in certain conditions, leaving the regulatory logic of IFNβ transcription an open question. In this study, we evaluated several quantitative models to determine what regulatory logic can account for the available data. We found that the enhancer exhibits multiple synergy modes with specific transcription capabilities that are deployed in a condition-dependent manner. The resulting IFNβ regulatory logic model reveals how stimulus-specificity is achieved, and may be tuned, thereby overcoming a bottleneck in predictive modeling the control of innate immune responses.
Real-world experience with switching from originator to biosimilar natalizumab
Authors: Høgestøl Einar August , Brustad Åge Winje , Celius Elisabeth Gulowsen , Meling Martine , Berg-Hansen Pål , Kro Grete Birkeland , König Marton , Warren David J. , Gehin Johanna E. , Bolstad Nils , Nygaard Gro Owren 
Published: February 2025

AbstractIn January 2024, all persons with multiple sclerosis (pwMS) treated with natalizumab (NTZ) at Oslo University Hospital switched from originator to biosimilar NTZ. We prospectively monitored 39 pwMS during the first year of treatment with biosimilar NTZ and evaluated change in disease activity, side effects, serum NTZ levels, anti-drug antibodies (ADAb), and anti-John Cunningham virus (JCV) antibody levels. Serum NTZ levels and ADAb were measured using in-house assays, while JCV antibody levels were evaluated using Stratify (Biogen) and Immunowell (Sandoz) platforms. One new relapse occurred during the first year and 11 pwMS (28%) reported new side effects after switching to the biosimilar; whereof fatigue, headache, and muscle pain were most frequent. Serum NTZ levels were similar between pwMS on originator (15.1 mg/L, SD 8.9) and biosimilar NTZ (14.9 mg/L, SD 9.0; p = 0.63). We identified ADAb in one pwMS, present both before and after switching. The proportion of pwMS with positive JCV antibody levels increased from 13% in 2023 (Stratify) to 52% in 2024 (Immunowell). Four pwMS discontinued NTZ due to high anti-JCV antibody levels (in the Immunowell assay) in the first 10 months.
Thalamic connectivity-based Biomarkers for Neuromodulation in Patients with Refractory Epilepsies
Authors: Aiello Giovanna , Soper Daniel J. , Hadar Peter N. , Paulk Angelique C. , Cash Sydney S. , Polania Rafael , Imbach Lukas , Salami Pariya 
Published: February 2025

AbstractThalamic electrical stimulation is being used as a treatment for drug-resistant epilepsy, yet current strategies benefit only about half the patients. Advancing patient outcomes necessitates tailored target selection for stimulation including the development of biomarkers for successful treatment. Here, we analyzed intracranial recordings of the most discussed thalamic nuclei for neuromodulation in epilepsy: anterior nucleus (ANT), centromedian nucleus (CM), pulvinar (PLV), and mediodorsal nucleus (MD) in 38 patients, to evaluate how their functional connectivity to epileptogenic areas may differ from that of non-epileptogenic areas in both sleep and wake states. We found that the thalamocortical connectivity to seizure onset areas is region and frequency-dependent. Additionally, we showed that thalamic connectivity is modulated in high versus low seizure risk conditions, further emphasizing its role in ictogenesis. Most importantly, we used the connectivity signature to predict the outcomes in patients receiving RNS within CM or PLV for neuromodulatory treatment and showed that these connectivity measures could serve as biomarkers of responsiveness to the treatment. These findings suggest that interictal connectivity data can inform patient-specific neuromodulation targeting, providing insights into the neurostimulation efficacy for specific epilepsy phenotypes.
Calibrated Functional Data Decreases Clinical Uncertainty for Tier 1 Monogenic Disease: Application to Long QT Syndrome
Authors: Ng Chai-Ann , O’Neill Matthew J. , Padigepati Samskruthi R. , Ting Yi-Lee , Facio Flavia M. , Vatta Matteo , Poll Sarah R. , Reuter Jason , Vandenberg Jamie I. , Kroncke Brett M. 
Published: February 2025

AbstractRare missense variants are often classified as variants of uncertain significance (VUS) due to insufficient evidence for classification. These ambiguous findings create anxiety and frequently lead to inappropriate workup, colloquially referred to as the ‘diagnostic odyssey’. Well-validated high-throughput experimental data have the potential to significantly reduce the number of VUS identified by clinical genetic testing, though the extent of this reduction and the optimal strategies to achieve it remain unclear.1
Prevalence of HIV history and associated factors in people affected by mpox in Colombia, 2022
Authors: Muñoz Lozada Claudia Marcela , Madero Reales Javier Alberto , Chaparro Narvaez Pablo Enrique , Prieto Alvarado Franklyn Edwin 
Published: February 2025

AbstractThe 2022 mpox outbreak disproportionately affected men who have sex with men (MSM) and individuals with history of HIV. This study investigated the prevalence of HIV infection and associated factors among mpox cases in Colombia. A cross-sectional analysis of 4,046 confirmed mpox cases reported to the Public Health Surveillance System between June 25 and December 31, 2022, was conducted. The prevalence of a history of HIV infection in mpox cases was determined, and associated factors were assessed using bivariate and multivariate logistic regression. Most mpox patients were male (97%), with a median age of 31 years (IQR = 27, 37). The most affected age group was 25 to 34 years (52%), and 83.7% were MSM. The prevalence of HIV history was 60%, with the highest rates in Manizales, Medellín, and Itagüí. Common symptoms included genital lesions (59.6%) and fever (67.6%). Factors associated with HIV history in mpox patients were male sex [OR = 9.6, 95% CI = 4.35, 21.31], having sexually transmitted infections: hepatitis B [OR = 2.9, 95% CI = 1.91, 4.40], hepatitis C [OR = 7.0, 95% CI = 3.50, 13.97], syphilis [OR = 2.1, 95% CI = 1.46-3.12], hospitalization [OR = 2.2, 95% CI = 1.65, 2.93], Colombian nationality [OR = 2.5, 95% CI = 1.86, 3.48] and being homosexual [OR = 2.5, 95% CI = 2.09, 3.06]. A high prevalence of HIV infection (60%) was found among mpox patients in Colombia, predominantly among MSM. This highlights the need for targeted interventions, such as priority care for people with HIV, active surveillance, and education for timely diagnosis and prevention of complications.