bluuebunny/crossref_metadata_2025_split huggingface dataset:
GPS-Health: A Novel Analytic Infrastructure for Capturing, Visualizing, and Analyzing Multi-Level, Multi-Domain Geographically Distributed Social Determinants of Health
Authors: Huang Shuo Jim , Davis Esa M. , Nguyen Thu T. , Brooks Justin R. , Abaku Olohitare , Chun Se Woon , Akintoye Oluwadamilola , Aktay Sinan , Chin Matthew , Bandos Matthew , Pateel Sunil , Gohimukkula Vineeth , Felix Victor , Mahurkar Anup A. , McCoy Rozalina G. 
Published: January 2025

AbstractBackgroundHealth disparities across a range of conditions and outcomes exist across the life course and are driven by the uneven geographic distribution of multidimensional social determinants of health (SDOH). Previous multidimensional measures of SDOH (e.g. Area Deprivation Index, Social Vulnerability Index, Social Deprivation Index) collapse multiple measures into a single summary value applied to everyone living within a predefined map unit, engendering construct and internal validity issues.MethodsWe present a new SDOH data approach: the Geographic Patterns of Social Determinants of Health (GPS-Health). We use a theoretical framework weaving together kyriarchy, intersectionality, and structural violence to select SDOH domains that can elucidate how individuals experience multidimensional spatial distributions of SDOH. We apply the approach to Maryland.ResultsOur dataset includes 2,369,365 property parcels, from which we calculate distances to 8 types of SDOH exact locations.DiscussionGPS-Health will aid in the understanding of how the SDOH influence individual health outcomes.
Safety Monitoring of Multiple Health Outcomes Following 2023–2024 COVID-19 Vaccination among Medicare Beneficiaries Aged 65 Years and Older in the United States
Authors: Gruber Joann F. , Ondari Michelle , Zelaya Carla E. , Xia Chunyi , Zhang Fengdi , Hervol Jessica R. , Ye Jin , Chen Meng , Qin Yutong , Hu Mao , Chillarige Yoganand , Forshee Richard A. , Anderson Steven A. 
Published: January 2025

AbstractBackgroundCOVID-19 vaccines are well-established as safe. However, continued surveillance of COVID-19 vaccines is important to ensure the safety of newly formulated vaccines. This study evaluated the association between vaccination with 2023-2024 formula COVID-19 vaccines and multiple health outcomes among Medicare beneficiaries aged 65 years and older in the United States.MethodsThe study used health plan data from the Medicare Fee-for-Service (FFS) claims database and extended from September 2023 to April 2024. We monitored the uptake of 2023–2024 COVID-19 vaccines (Pfizer-BioNTech, Moderna, Novavax), and where case counts were available, we used a self-controlled case series design to assess the association between vaccination and prespecified health outcomes. We used conditional Poisson regression to estimate incidence rate ratios (IRRs), attributable risks (ARs) and corresponding 99% confidence intervals (CIs). Analyses were adjusted for outcome seasonality, event-dependent observation time for outcomes with high case fatality rates, and outcome misclassification where feasible.ResultsApproximately 7.6 million Medicare FFS beneficiaries received a 2023–2024 COVID-19 vaccination. There was an even distribution of people who received Pfizer-BioNTech (3,689,356; 48.80%) or Moderna (3,841,245; 50.80%) vaccinations and very few who received Novavax (30,171; 0.40%). There was a statistically significant elevation in anaphylaxis risk associated with 2023–2024 Pfizer-BioNTech vaccines in the seasonality-adjusted analysis (IRR: [99% CI: 1.07, 15.30]) that was no longer statistically significant after accounting for potential outcome misclassification (IRR: 3.90 [99% CI: 0.49, 30.90]). Anaphylaxis cases attributable to 2023–2024 Pfizer-BioNTech vaccination were rare (AR per 100,000 doses: 0.09 [99% CI: −0.08, 0.25]). No other statistically significant elevations in risk were observed.ConclusionThere were no new safety signals identified following 2023–2024 COVID-19 vaccinations among U.S. Medicare beneficiaries aged 65 years and older. A potential, but rare, elevation in anaphylaxis incidence rates following 2023–2024 Pfizer-BioNTech COVID-19 vaccination was observed.HIGHLIGHTSWe studied 7,560,772 Medicare enrollees ≥65 years old who received 2023–2024 COVID-19 vaccinesNo new safety signals were identified in the Medicare population ≥65 years oldA potential–but rare–elevation in anaphylaxis risk was associated with vaccinationNo increased risk of any other prespecified health outcomes was found
Lateralized Circuitry for Verbal Fluency Changes After Subthalamic Nucleus Deep Brain Stimulation
Authors: Kim Min Jae , Zuccaroli Isabella , Del Bene Victor A. , Brinkerhoff Sarah A. , Martin Roy C. , Olson Joseph W. , Nelson Matthew J. , Gonzalez Christopher L. , Kamath Vidyulata , Bentley J. Nicole , Knight Robert T. , Walker Harrison C. , Mills Kelly A. 
Published: January 2025

ABSTRACTBackgroundSubthalamic nucleus deep brain stimulation (STN-DBS) improves motor symptoms but can be associated with subtle cognitive changes, including declines in verbal fluency (VF). Network-based mechanisms underlying stimulation-induced fluency declines are not fully understood.ObjectiveThis study investigates how STN-DBS stimulation locations interact with brain connectivity patterns, and whether this differentially drives VF changes.Methods20 patients with Parkinson’s disease and unilateral STN-DBS were analyzed. Electrodes were localized with estimates for volume of tissue activation (VTA). VTAs were seeded in normative functional and structural connectomes to identify connectivity profiles correlating with VF changes (R-maps). Additionally, amongst the fibers passing through VTAs, a two-samplet-test assigned fibers associated with VF improvement or decline.ResultsVF declines occurred following unilateral left but not right STN-DBS. R-maps revealed that improvements correlated with greater connectivity to prefrontal structures in right hemisphere such as inferior and superior frontal gyrus, whereas declines localized to structures on the left. Fibers filtered from right VTAs were associated with VF improvements. Fibers from left VTAs were associated with declines, but the gradient of fiber t-scores were distributed across an anterior-posterior axis ranging from supplementary motor area to paracentral lobule.ConclusionUnilateral STN-DBS interacts with distributed cognitive networks that display strong hemispheric lateralization. Beyond the effects of implant hemisphere, our findings suggest that connectivity between local STN subregions to larger whole-brain networks impact VF performance, in a manner that could yield more tailored approaches to electrode targeting and clinical programming.
Brain-heart-eye axis revealed by multi-organ imaging genetics and proteomics
Authors: Boquet-Pujadas Aleix , Anagnostakis Filippos , Duggan Michael R. , Joynes Cassandra M. , Toga Arthur W. , Yang Zhijian , Walker Keenan A. ,   the MULTI consortium, Davatzikos Christos , Wen Junhao 
Published: January 2025

AbstractMulti-organ research investigates interconnections among multiple human organ systems, enhancing our understanding of human aging and disease mechanisms. Here, we used multi- organ imaging (N=105,433), individual- and summary-level genetics, and proteomics (N=53,940) from the UK Biobank, Baltimore Longitudinal Study of Aging, FinnGen, and Psychiatric Genomics Consortium to delineate a brain-heart-eye axis via 2003 brain patterns of structural covariance1(PSC), 82 heart imaging-derived phenotypes2(IDP) and 84 eye IDPs3–5. Cross-organ phenotypic associations highlight the central autonomic network between the brain and heart and the central visual pathway between the brain and eye. Proteome-wide associations of the PSCs and IDPs show both within-organ specificity and cross-organ interconnections, verified by the RNA and protein expression profiles of the 2923 plasma proteins. Pleiotropic effects of common genetic variants are observed across multiple organs, and key genetic parameters, such as SNP-based heritability, polygenicity, and selection signatures, are comparatively evaluated among the three organs. A gene-drug-disease network shows the potential of drug repurposing for cross-organ diseases. Colocalization and causal analyses reveal cross-organ causal relationships between PSC/IDP and chronic diseases, such as Alzheimer’s disease, heart failure, and glaucoma. Finally, integrating multi-organ/omics features improves prediction for systemic disease categories and cognition compared to single-organ/omics features. This study depicts a detailed brain-heart-eye axis and highlights future avenues for modeling human aging and disease across multiple scales. All results are publicly available athttps://labs-laboratory.com/medicine/.
From dimer to tetramer: the evolutionary trajectory of C4 photosynthetic-NADP-ME oligomeric state in Poaceae
Authors: Böhm Jonas M. , Willms Simone , Ferrao Oja , Buitrago-Arango Martin , Hüdig Meike , Poschmann Gereon , Fazelnia Nazanin , Nagel-Steger Luitgard , Klinke Sebastián , Drakonaki Athina , Gatsogiannis Christos , Tronconi Marcos A. , Alvarez Clarisa E. , Maurino Veronica G. 
Published: January 2025

AbstractThe C4 carbon concentrating mechanism relies on specialized enzymes that have evolved unique expression patterns and biochemical properties distinct to their ancestral housekeeping forms. In maize and sorghum, the evolution of C4-NADP-malic enzyme (C4-NADP-ME) involved gene duplication and neofunctionalization, leading to the emergence of two plastidic isoforms: C4-NADP-ME and nonC4-NADP-ME, each with distinct kinetic and structural features. While C4-NADP-ME functions primarily as a tetramer, nonC4-NADP-ME exists in an equilibrium between dimeric and tetrameric forms, favoring the dimer in solution. This study shows which evolutionary changes in amino acid sequences influence the structure and function of these isoforms. By integrating X-ray crystallography, cryo-electron microscopy, computational molecular modeling and targeted biochemical analysis of mutant and truncated protein variants, we identify crucial roles for the N- and C-terminal regions and specific amino acid residues in governing isoform oligomerization. Our results reveal that the N-terminal region is essential for stabilizing the dimeric form of nonC4-NADP-ME, whereas specific adaptive substitutions and interactions with the C-terminal region enhance the stability of the tetrameric state characteristic of the C4-adapted isoform. We propose that differences in the N-terminal domain between the C4 and nonC4 isoforms reflect distinct selective pressures, which have driven their evolutionary divergence to fulfill specialized cellular functions.
The single amino acid change of R516K enables efficient generation of vesicular stomatitis virus-based Crimean-Congo hemorrhagic fever reporter virus
Authors: Ma Xue , Ma Yanlong , Wang Ziqiao , Feng Fei , Han Yutong , Sun Xinran , Li Liushuai , Gao Zhichao , Wang Manli , Zhang Rong 
Published: January 2025

AbstractCrimean-Congo hemorrhagic fever virus (CCHFV) is a medically important tick-borne virus, causing severe hemorrhagic diseases in humans. There is no approved vaccines and therapeutics for CCHFV infection. The study of CCHFV authentic virus requires biosafety level 3 facilities, hindering the research and development of antivirals. Here we report the generation of a recombinant vesicular stomatitis virus (VSV) bearing both CCHFV glycoprotein precursor (GPC) and EGFP reporter (rVSV-CCHFV-GFP). We also find that the acquisition of an unexpected single R516K mutation in the GPC protein enables the packaging of high-titer pseudotyped particles. The replication-competent rVSV-CCHFV-GFP reporter virus resembles the entry properties of authentic virus and allows for rapid assessment of susceptible cell lines, neutralizing antibodies, and host entry factors such as heparan sulfate in fluorescence-based assays. This study provides valuable strategy for packaging of high-titer CCHFV pseudovirus, and the tool generated here can be served for the identification and evaluation of countermeasures against the cell entry of CCHFV.
TERT prevents obesity-induced metabolic disorders by promoting adipose stem cell expansion and differentiation
Authors: Braud Laura , Bernabe Manuel , Vernerey Julien , Miranda Antonio M.A. , Dominguez Andrea , Churikov Dmitri , Richaud Manon , Mc Allan Liam , Lachaud Christophe , Gil Jesus , Scott Will , Géli Vincent 
Published: January 2025

AbstractObesity is linked to limited adipose tissue (AT) remodeling capacity, leading to hypertrophic adipocytes, senescence, and inflammation. We used a mouse model expressingmTert(p21+/Tert) from the Cdkn1a locus to investigate the role of mTERT in obesity-induced metabolic disorders. Conditional expression of mTERT reduces metabolic disorders associated with obesity. In AT, this is accompanied by a decrease in the number of senescent p21-positive cells, very short telomeres, and oxidative DNA damage. Single nucleus RNA-seq data reveal TERT expression attenuates senescence induced by HFD in particular in adipose stem and progenitor cells (ASPC). We show that ASPC expansion and differentiation are promoted in p21+/Tertobese mice, thereby reducing metabolic disorders. We further report that mTERT remodels the landscape of macrophages in AT of obese mice. Strikingly, inactivation of mTERT catalytic activity in p21+/Tert(p21+/TertCi) mice suppresses the promotion of adipocyte formation, but neither affects attenuation of senescence nor macrophage remodeling. These results highlight mTERT’s canonical and non-canonical functions in reducing obesity-associated metabolic disorders. Conditional expression of TERT thus appears as a potential therapeutic option for obesity.
Tastes and retronasal odours evoke a shared flavour-specific neural code in the human insula
Authors: Khorisantono Putu Agus , Veldhuizen Maria G. , Seubert Janina 
Published: January 2025

ABSTRACTDuring food consumption, tastes combine with retronasal odours to form flavour, which leads to a link so robust that retronasal odours can elicit taste sensations without concurrent taste stimulation. However, the cortical integration of these parallel sensory signals remains unclear. Here, we combine a flavour-binding paradigm and functional neuroimaging to test whether retronasal odorants evoke encoding patterns in the insula similar to those of their paired tastants. Healthy participants attended a familiarisation session with congruent sweet and savoury flavours followed by two fMRI sessions where they separately received the constituent tastants and odorants. Multivariate pattern analysis revealed classification of retronasal odours within the insula, exhibiting overlapping representations with their associated tastes, particularly in the ventral anterior insula. Additionally, we observed temporal instability in insular taste representations, paralleling findings in rodent gustatory cortex. These findings underscore the robust integration of gustatory and retronasal olfactory processing that underpin the flavour percept.
Optimising CAR-T cell sensitivity by engineering matched extracellular sizes between CAR/antigen and CD2/CD58 adhesion complexes
Authors: Burton Jake , Siller-Farfán Jesús A. , Andre Violaine , Jenkins Edward , Barton Michael I. , Bustamante Eguiguren Sofia , Cabezas Caballero Jose , Davis Simon J. , Weikl Thomas R , van der Merwe P. Anton , Dushek Omer 
Published: January 2025

AbstractChimeric antigen receptor (CAR)-T cells exhibit low antigen sensitivity, which restricts their therapeutic efficacy and leads to patient relapses when cancer cells downregulate antigen expression. Despite the pressing need to overcome this limitation, the underlying mechanisms remain poorly understood. Here, we demonstrate that enhancing CAR sensitivity to match the sensitivity of the T-cell receptor (TCR) can be achieved by engineering matched extracellular sizes of CAR/antigen and CD2/CD58 complexes. We find that different CAR/antigen sizes, which are generated by different CAR architectures and different target antigens, require a different CD2/CD58 size to optimise sensitivity. This extracellular size-matching improves antigen engagement and co-localisation of CAR/antigen and CD2/CD58 complexes. We also find that size-matching controls co-inhibition of CARs by PD-1/PD-L1. These findngs highlight the importance of size-matching for signal integration by surface receptors and offers a new approach to tune CAR-T cell sensitivity by matching or mismatching extracellular sizes.One sentence summaryThe antigen sensitivity of CAR-T cells can be tuned to match the sensitivity of TCR-T cells by varying the relative extracellular size of CAR/antigen and CD2/CD58 complexes.Graphical abstract
Corticotropin-releasing hormone in melanoma and non-melanoma skin cancer
Authors: Mueller Marcel , Melchers Susanne , Mueller Iris , Utikal Jochen , Krug Julia , Schmieder Astrid 
Published: January 2025

AbstractBackgroundCorticotropin-releasing hormone (CRH) is involved in the regulation of immunological and cellular processes. Recently, CRH has been found to be expressed in skin cancers, where its expression appears to correlate with the degree of malignancy.ObjectiveThis study correlates CRH expression in melanoma metastases with patient survival and compares the intensity of CRH expression in melanoma to that in less aggressive skin cancer entities.MethodsTissue microarrays with cores from 94 melanomas and 40 melanocytic nevi and 51 slides from 41 basal cell carcinomas (BCC) and 10 squamous cell carcinomas (SCC) were immunohistochemically stained for CRH. The intensity of CRH expression in melanoma metastases was stratified by sex and correlated with patient survival. Furthermore, proliferation and apoptosis were assessed in CRH-stimulated A431 cells using enzyme-linked immunosorbent assays and an apoptosis detection kit.ResultsThe intensity of CRH expression was higher in primary melanomas than in melanocytic nevi. Higher CRH expression was also found in melanoma metastases from women compared to men. However, higher CRH expression was correlated with reduced overall survival only in men. Compared to melanoma, BCCs and SCCs showed weaker CRH expression, which was in line with the finding that in vitro, CRH stimulation of the A431 cells reduced their proliferative activity.ConclusionCRH does not necessarily correlate with the degree of malignancy, as semi-malignant cancers such as BCC show higher levels of CRH expression than SCCs. In melanoma, CRH expression in metastases may be an important prognostic factor for overall survival in men, which needs further evaluation.Statement of contributionMarcel Mueller and Susanne Melchers performed all experiments and wrote the first draft of the manuscript. Iris Mueller helped with the experiments and reviewed the manuscript, Jochen Utikal assembled the tissue microarrays and reviewed the manuscript, Julia Krug helped with the figures and reviewed the manuscript, and Astrid Schmieder designed and supervised the project and corrected the manuscript.
NNMT promotes tubular senescence and fibrosis in chronic kidney disease
Authors: Chanvillard Lucie , Lantermans Hildo , Wall Christopher , Thevenet Jonathan , Butter Loes , Tauzin Loic , Claessen Nike , Christen Stefan , Karaz Sonia , Lassueur Steve , Lizzo Giulia , Sanchez-Garcia José Luis , Métairon Sylviane , Holzwarth James A. , Ferro Valentina , Moco Sofia , van Bommel Erik J.M. , van Baar Michael J.B. , Hesp Anne C. , van Raalte Daniel H. , Roelofs Joris J.T.H. , Sanders Matthew J. , Feige Jerome N. , Sorrentino Vincenzo , Tammaro Alessandra 
Published: January 2025

ABSTRACTChronic kidney disease (CKD) is a major global health issue, projected to become the fifth leading cause of mortality by 2040. Renal tubular cell senescence is a key driver of kidney fibrosis, the final manifestation of CKD. However, current treatment strategies, do not target senescent cells, as the underlying mechanisms driving this dysfunctional phenotype remain poorly described. Here, we identify nicotinamide-N-methyltransferase (NNMT), as a critical mediator of tubular senescence and fibrosis in CKD. Using human RNAseq profiles of CKD, we show that NNMT expression in the renal tubulointerstitium is strongly associated with CKD pathology and transcriptional signatures of cellular senescence. In human diabetic kidney disease biopsies, NNMT levels correlate with the senescence marker p21, kidney function decline, and fibrosis. Spatial transcriptomics further highlights that NNMT-positive tubules are senescent, fibrotic, and surrounded by a pro-inflammatory microenvironment. Preclinical models of early-stage CKD, show upregulation of NNMT and association with senescence. Overexpression of NNMT in TGF-β-stimulated tubular epithelial cells promotes senescence and partial epithelial-to-mesenchymal transition (EMT), while inhibition of NNMT in kidney cells and organoids is protective. Altogether, we identify NNMT as a novel therapeutic target in the early stages of CKD with the potential to reduce tubular senescence, fibrosis and significantly slow disease progression.
Understanding the biochemical significance of the mitochondrial pyruvate carrier in the rodent malarial parasite,Plasmodium berghei
Authors: Pandey Nivedita , Sen Roy Chitralekha , Bellur Asutosh , Balaram Hemalatha 
Published: January 2025

AbstractMitochondrial pyruvate carrier (MPC) protein has been established as the key pyruvate transporter across the inner mitochondrial membrane. InPlasmodium, flux through the tricarboxylic acid (TCA) cycle is low in the asexual stages that is upregulated in the gametocytes with greater utilization of glutamine than glucose to drive the cycle. Acetyl-CoA in the mitochondrion has been established to be essential for the parasite. In this context, we established the biochemical function ofP. bergheiMPC as a pyruvate transporter through functional complementation in yeast. InP. berghei, both subunits, MPC1 and MPC2 were found to localize to the mitochondrion and surprisingly, were found to be non-essential for the blood stages and for ookinete formation. Through metabolite tracing studies using13C6-glucose and13C515N2L-glutamine, we have derived the biochemical basis for this observed phenotype of Δmpc1Δmpc2parasites. Our studies suggest the presence of an aminotransferase localized to the mitochondrion that converts alanine to pyruvate, leading to the continued production of acetyl-CoA in the organelle even in the absence of MPC. This highlights the existence of metabolic plasticity, a survival strategy, that enables the utilization of different metabolic precursors for the generation of acetyl-CoA in the mitochondrion.