bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diet-induced obesity mediated through Estrogen-Related Receptor α is independent of intestinal function
Authors: Vemuri Kiranmayi , Iqbal Jahangir , Kumar Sneha , Logerfo Alexandra , Verzi Michael P. 
Published: July 2024

SummaryObesity has become an epidemic, prompting advances in therapies targeting this condition. Estrogen-related receptor α (ESRRA), a transcription factor, plays pivotal roles in energy metabolism across diverse tissues. Studies have demonstrated that loss ofEsrraleads to fat malabsorption and resistance to diet-induced obesity. However, the reliance of these studies on germlineEsrramutants overlooks the tissue-specific implications of ESRRA in diet-induced obesity. Notably,Esrraexhibits high expression in the gastrointestinal (GI) tract relative to other tissues. Given the critical role of the GI tract in dietary lipid metabolism, this study employs mouse genetics and genomics approaches to dissect the specific impact of intestinal ESRRA along with investigating its role in diet-induced obesity.Data TransparencyChIP-seq and RNA-seq data from this publication have been deposited to GEO accession numbers GSE269824 and GSE269825, respectively. Any additional information required to reanalyze the data reported in this paper is available from the corresponding author upon request.Grant SupportThis research was funded by grants from the National Institutes of Health (NIH) to M.P.V. (R01DK121915 and R01DK126446). K.V. was supported by an American Heart Association pre-doctoral fellowship (906006). S.K. was supported by a Rutgers DLS Summer Undergraduate Research Fellowship. A.L. was supported by grants from the NIH grant F31DK137596 and the NIH T32 Biotechnology Training Program (GM135141). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.DisclosuresThe authors declare no competing interests.
MAGE-A4-Responsive Plasma Cells Promote Non-Small Cell Lung Cancer
Authors: Armstrong Dominique , Chang Cheng-Yen , Hong Monica J. , Green Linda , Hudson William , Shen Yichao , Song Li-Zhen , Jammi Sheetal , Casal Benjamin , Creighton Chad J. , Carisey Alexandre , Zhang Xiang H.-F. , McKenna Neil J. , Kang Sung Wook , Lee Hyun-Sung , Corry David B. , Kheradmand Farrah 
Published: July 2024

AbstractAdaptive immunity is critical to eliminate malignant cells, while multiple tumor-intrinsic factors can alter this protective function. Melanoma antigen-A4 (MAGE-A4), a cancer-testis antigen, is expressed in several solid tumors and correlates with poor survival in non-small cell lung cancer (NSCLC), but its role in altering antitumor immunity remains unclear. We found that expression of MAGE-A4 was highly associated with the loss ofPTEN, a tumor suppressor, in human NSCLC. Here we show that constitutive expression of humanMAGE-A4combined with the loss ofPtenin mouse airway epithelial cells results in metastatic adenocarcinoma enriched in CD138+CXCR4+plasma cells, predominantly expressing IgA. Consistently, human NSCLC expressing MAGE-A4 showed increased CD138+IgA+plasma cell density surrounding tumors. The abrogation of MAGE-A4-responsive plasma cells (MARPs) decreased tumor burden, increased T cell infiltration and activation, and reduced CD163+CD206+macrophages in mouse lungs. These findings suggest MAGE-A4 promotes NSCLC tumorigenesis, in part, through the recruitment and retention of IgA+MARPs in the lungs.
Use of Nicotine Products, Prescription Drug Products, and Other Methods to Stop Smoking by US Adults in the 2022 National Health Interview Survey
Authors: Foxon Floe , Niaura Raymond 
Published: July 2024

AbstractRecent data on methods used by adults to stop smoking can inform tobacco control policies. Nationally representative Centers for Disease Control and Prevention survey data from the 2022 National Health Interview Survey (N=27,651) were used to analyze populations of US adults who self-reported having stopped smoking cigarettes for 6 months or longer in the last year and the methods they used, or who did not stop smoking but tried in the last year (n=1,735). In 2022, an estimated 2.9 million [95% CI:2.5 million–3.2 million] US adults had stopped smoking in the past year. Most were male, non-Hispanic White, aged <55 years, college-educated, identified as straight, were not depressed, and currently drank alcohol. The most popular methods used to stop smoking were nicotine products (53.9% [47.4%–60.3%]; 1.5 [1.3– 1.8] million adults), especially e-cigarettes in combination with other methods (40.8% [34.4%– 47.5%]; 1.2 [0.9–1.4] million) and e-cigarettes alone (26.0% [20.4%–32.3%]; 0.7 [0.6–0.9] million). Prescription drug products (8.1% [5.3%–11.8%]; 0.2 [0.1–0.3] million) and non-nicotine, non-prescription drug methods (6.3% (3.9%–9.7%); 0.2 [0.1–0.3] million) were less popular. A further 13.1 [12.2–14.0] million tried but did not stop smoking. Compared to those who tried but didn’t stop smoking, those who successfully stopped were more likely to be younger, degree-educated, and to use e-cigarettes to stop smoking. Many adults still attempt to stop smoking unaided. Interventions to reduce smoking could focus on populations that stopped smoking the least and encourage use of evidence-based methods.
Left atrial wall shear stress distribution correlates with atrial endocardial electrogram voltage and fibrosis in patients with atrial fibrillation
Authors: Adamopoulos Dionysios , Rovas Georgios , Johner Nicolas , Müller Hajo , Deux Jean-François , Crowe Lindsey A. , Vallée Jean-Paul , Mach François , Stergiopulos Nikolaos , Shah Dipen 
Published: July 2024

AbstractLeft atrial (LA) wall fibrosis plays an important role in the perpetuation of atrial fibrillation (AF) since the abnormal electrophysiological properties of the fibrotic areas sustains the arrhythmia by favoring both re-entry circuits as well as abnormal impulse generation. Despite its crucial contribution, the mechanisms by which LA fibrosis develops are not well understood.The LA wall is constantly exposed to the hydraulic forces exerted by the blood flow arriving from the pulmonary veins. The purpose of the present study was to examine the association between regional wall shear stress and areas with fibrosis in the LA of patients with AF.15 patients (13 males, mean age 61±11 years) with AF, no significant mitral regurgitation and clinical indication for a primary catheter ablation were prospectively recruited for the study. All participants underwent a baseline three-dimensional electro-anatomical mapping of the LA during the ablation procedure and a pre-interventional cardiovascular magnetic resonance (CMR) imaging with phase contrast for mitral flow estimation and Gadolinium injection for LA fibrosis detection. Fibrotic areas were detected either by low bipolar voltage (BV≤0.5mV) and/or by areas with enhanced late Gadolinium uptake as assessed by the image intensity ratio (IIR≥1.2). For all subjects, a detailed 3D anatomical model of the LA was extracted from the invasive electro-anatomical maps and was used to calculate regional time-averaged wall shear stress (TAWSS) and blood age (BA), an index of blood stagnation, by performing patient-specific computational fluid dynamic simulations.Globally, areas around the pulmonary veins and the LA roof exhibited the highest values of TAWSS. In all cases, high TAWSS was strongly correlated with low voltage (n=15, r from -0.002 to -0.449, p<0.01) and enhanced late Gadolinium uptake (n=12, r from 0.071 to 0.475, p<0.001). Fibrotic areas as detected by both low BV and high IIR were more prevalent in areas exposed to high TAWSS (21.6% vs 8.1% and 26.2% vs 13.2% respectively, p<0.001). Inversely, in all but one case, areas with low TAWSS presented more intense blood stagnation as assessed by the highest BA (r from -0.268 to - 0.688, p<0.001).In patients with AF, regional high TAWSS is associated with corresponding CMR biomarkers of left atrial wall fibrosis and electrical scaring. Inversely, areas with low TAWSS are associated with blood stagnation and could favor thrombus formation. This may provide insights of a novel pathophysiological mechanism explaining the characteristic atrial electrical remodeling and thrombus formation seen in patients with AF.
Deficiencies in accessibility to point-of-care (POC) diagnostics in PMTCT services in rural primary health care clinics in Zambia: Implementation Science perspective
Authors: Katoba J 
Published: July 2024

IntroductionPoint-of-care (POC) innovations are healthcare interventions that have great potential to improve diagnostic capacities of healthcare systems in low- and middle-income countries (LMICs). From the implementation science perspective, this study explores perceptions of key stakeholders on deficiencies in accessibility of POC diagnostics in the context of prevention of mother-to-child transmission (PMTCT) services in Zambia.MethodsA retrospective qualitative evaluation was conducted to understand factors that influence POC diagnostic implementation in rural primary healthcare (PHC) settings. The study was conducted among key implementing stakeholders in Zambia. In-depth interviews were held with 11 purposefully selected key informants, including clinical officers, midwives, nurses, environmental health technicians (EHTs), government and private health officials. The interviews were audio-recorded and transcribed verbatim. Following coding, thematic content analysis was applied and the main emerging themes were analysed through the lens of the Consolidated Framework for Implementation Research (CFIR). The CFIR was identified as the most appropriate model to interpret our findings.ResultsFactors influencing implementation were represented in all five domains. Major constructs as facilitators were the relative advantage of the intervention, external partnership, education and training, knowledge and belief, self-efficacy, and engagement of champions. Barriers were mainly found in the outer and inner settings, including constraints in financial resources, supply chain challenges resulting in stock-outs, insufficient human resources leading to increased workload, and other infrastructural issues like space limitations and lack of electricity in most rural primary healthcare settings.ConclusionsThe study identified key determinants that supported or hindered the implementation of POC diagnostics in the rural PHCs. Greater efforts are needed to overcome barriers at multi-sectoral level for effective implementation while leveraging on facilitators through a health system strengthening approach. These findings are key to informing future implementations, sustainability and scale-up of POC diagnostics interventions.
Changing feeding levels reveal plasticity in elasmobranch life history strategies
Authors: Lucas Sol , Berggren Per , Barrowclift Ellen , Smallegange Isabel M. 
Published: July 2024

AbstractLife history strategies are shaped by phylogeny, environmental conditions and individual energy budgets, and have implications for population performance. Here, we used an approach that merges demography with energy budget theory to structure life history traits of 151 elasmobranch species into life history strategies for two contrasting feeding levels. We assessed how phylogeny and habitat impacted life history strategies, and tested if these strategies predict population performance and conservation status. Elasmobranch life history strategies are structured along the fast-slow continuum and reproductive strategy axes. However, species’ positions in this life history space were not fixed, but instead moved in an anticlockwise ‘whirlpool’ manner along the two axes in response to an increase in feeding level. We also found that population growth rate does not necessarily inform on a species demographic resilience. Finally, only at the higher feeding level does the fast-slow continuum predict IUCN conservation status, with the slowest species at the highest risk of extinction. Our analyses reveal plasticity in species life history strategies, and warn against extrapolating the fast-slow continuum and reproductive strategy framework from one environment to another when predicting a species’ response to (climate) change, perturbations, and, particularly in case of elasmobranchs, (over)exploitation.
Comparative evaluation of four exome enrichment solutions in 2024: Agilent, Roche, Vazyme and Nanodigmbio
Authors: Belova Vera , Vasiliadis Iuliia , Repinskaia Zhanna , Samitova Alina , Shmitko Anna , Ponikarovskaya Natalya , Suchalko Oleg , Cheranev Valery , Peter Shatalov , Peter Shegai , Andrey Kaprin , Rebrikov Denis , Korostin Dmitriy 
Published: July 2024

AbstractWhole exome sequencing (WES) is essential for identifying genetic variants linked to diseases. This study compares available to date four exome enrichment kits: Agilent SureSelect Human All Exon v8, Roche KAPA HyperExome Probes, Vazyme VAHTS Target Capture Core Exome Panel, and Nanodigmbio NEXome Plus Panel v1. We evaluated target design, coverage statistics, and variant calling accuracy across these four different exome capture products. All kits showed high coverage completeness, with mean x10 coverage exceeding 97.5% and x20 coverage above 95%. Roche exhibited the most uniform coverage, indicated by the lowest fold-80 scores, while Nanodigmbio had more on-target reads due to fewer off-target reads. Variant calling performance, evaluated using in-lab standard E701 DNA sample, showed high recall rates for all kits, especially Agilent v8. All kits achieved an F-measure above 95.87%. Nanodigmbio had the highest precision with the fewest false positives but a slightly lower F-measure than other kits. This study also highlights the performance of new Chinese solutions from Vazyme and Nanodigmbio, which were comparable to Agilent v8 and Roche KAPA kits. These findings assist researchers and clinicians in selecting appropriate exome capture solutions.
Gut-specific H3R signaling orchestrates microglia-dependent resolution of peripheral inflammation
Authors: Dürholz Kerstin , Linnerbauer Mathias , Schmid Eva , Danzer Heike , Lößlein Lena , Amend Lena , Ehnes Leona , Frech Michael , Azizov Vugar , Schälter Fabian , Gessner Arne , Lucas Sébastien , Lesker Till-Robin , Taudte R. Verena , Hofmann Jörg , Beyer Felix , Bootz-Maoz Hadar , Reich Yasmin , Romano Hadar , Mauro Daniele , Beckervordersandforth Ruth , Xiang Wei , Haghikia Aiden , Akdis Cezmi A. , Ciccia Francesco , Bäuerle Tobias , Sarter Kerstin , Strowig Till , Yissachar Nissan , Schett Georg , Rothhammer Veit , Zaiss Mario M. 
Published: July 2024

AbstractChronic inflammatory diseases, like rheumatoid arthritis (RA) have been described to cause central nervous system (CNS) activation. Less is known about environmental factors that enable the CNS to suppress peripheral inflammation in RA. Here, we identified gut microbiota-derived histamine as such factor. We show that low levels of histamine activate the enteric nervous system, increase inhibitory neurotransmitter concentrations in the spinal cord and restore homeostatic microglia, thereby reducing inflammation in the joints. Selective histamine 3 receptor (H3R) signaling in the intestine is critical for this effect, as systemic and intrathecal application did not show effects. Microglia depletion or pharmacological silencing of local nerve fibers impaired oral H3R agonist-induced pro-resolving effects on arthritis. Moreover, therapeutic supplementation of the SCFA propionate identified one way to expand local intestinal histamine concentrations in mice and humans. Thus, we define a gut-CNS-joint axis pathway where microbiota-derived histamine initiates the resolution of arthritis via the CNS.Graphical AbstractGut microbiota-derived histamine activates enteric neurons via H3RLocal intestinal H3R activation induces shift to homeostatic microglia in the spinal cordCNS controlled decrease in endothelial leakiness resolves synovial inflammation
Prophage-DB: A comprehensive database to explore diversity, distribution, and ecology of prophages
Authors: Dieppa-Colón Etan , Martin Cody , Anantharaman Karthik 
Published: July 2024

AbstractBackgroundViruses that infect prokaryotes (phages) constitute the most abundant group of biological agents, playing pivotal roles in microbial systems. They are known to impact microbial community dynamics, microbial ecology, and evolution. Efforts to document the diversity, host range, infection dynamics, and effects of bacteriophage infection on host cell metabolism are extremely underexplored. Phages are classified as virulent or temperate based on their life cycles. Temperate phages adopt the lysogenic mode of infection, where the genome integrates into the host cell genome forming a prophage. Prophages enable viral genome replication without host cell lysis, and often contribute novel and beneficial traits to the host genome. Current phage research predominantly focuses on lytic phages, leaving a significant gap in knowledge regarding prophages, including their biology, diversity, and ecological roles.ResultsHere we develop and describe Prophage-DB, a database of prophages, their proteins, and associated metadata that will serve as a resource for viral genomics and microbial ecology. To create the database, we identified and characterized prophages from genomes in three of the largest publicly available databases. We applied several state-of-the-art tools in our pipeline to annotate these viruses, cluster and taxonomically classify them, and detect their respective auxiliary metabolic genes. In total, we identify and characterize over 350,000 prophages and 35,000 auxiliary metabolic genes. Our prophage database is highly representative based on statistical results and contains prophages from a diverse set of archaeal and bacterial hosts which show a wide environmental distribution.ConclusionProphages are particularly overlooked in viral ecology and merit increased attention due to their vital implications for microbiomes and their hosts. Here, we created Prophage-DB to advance our comprehension of prophages in microbiomes through a comprehensive characterization of prophages in publicly available genomes. We propose that Prophage-DB will serve as a valuable resource for advancing phage research, offering insights into viral taxonomy, host relationships, auxiliary metabolic genes, and environmental distribution.
Hemogenic endothelium of the vitelline and umbilical arteries is the major contributor to mouse fetal lympho-myelopoiesis
Authors: Barone Cristiana , Quattrini Giulia , Orsenigo Roberto , Timóteo-Ferreira Filipa , Muratore Alessandro , Cazzola Anna , Patelli Arianna , Soares-da-Silva Francisca , Nicholls Matthew , Mauri Mario , Bombelli Silvia , De Marco Sofia , D’Aliberti Deborah , Spinelli Silvia , Bonalume Veronica , Domingues Alison , Sala Gianluca , Colonna Arianna , D’Errico Elisabetta , D’Orlando Cristina , Bianchi Cristina , Perego Roberto A. , Meneveri Raffaella , De Bruijn Marella F.T.R. , Cumano Ana , Fantin Alessandro , Brunelli Silvia , Piazza Rocco , Azzoni Emanuele 
Published: July 2024

SummaryEmbryonic hematopoiesis consists of distinct waves originating in rapid succession from different anatomical locations. Hematopoietic progenitors appearing earlier than definitive hematopoietic stem cells (HSCs) play key roles in fetal and postnatal life. However, their precise origin, identity and the extent of their contribution need further clarification. To this aim, we took advantage of a genetic fate-mapping strategy in mice that allows labeling and tracking of distinct subsets of hemogenic endothelium (HE). Time-course labeling of hematopoietic progenitors emerging from HE between E8.5 and E9.5, before intra-embryonic definitive HSC generation, revealed a major fetal lympho-myeloid contribution which declined in the adult. Lineage tracing coupled with whole-mount imaging and single-cell RNA sequencing located its source within hematopoietic clusters of vitelline and umbilical arteries. Functional assays confirmed the transient nature of these progenitors. We therefore unveiled a hitherto unidentified early wave of fetal-restricted hematopoietic stem/progenitor cells poised for differentiation that provide a major contribution to pre-natal hematopoiesis.
Coordinated network of T cells and antigen presenting cells regulate tolerance to food
Authors: Rudnitsky Anna , Oh Hanna , Talmor Joanathan , Kedmi Ranit 
Published: July 2024

AbstractTo efficiently absorb nutrients and facilitate microbial commensalism, the host establishes tolerogenic immune programs against dietary and commensal antigens, promoted by peripheral regulatory T cells (pTregs)1,2. Previous research into which antigen-presenting cells (APCs) initiate dietary pTreg responses focused on type 1 DCs (cDC1)3. However, we now report that food-specific pTreg cells are exclusively induced by the recently identified RORγt+ APCs4–8, and not by cDC1. Instead, pTregs interact with cDC1 to regulate the response of food-specific CD8αβ T cells that accumulate in the lamina propria (LP) and epithelial layer of the small intestine (SI) and express memory markers. Upon infection with pathogens that mimic dietary antigens, food-specific CD8αβ cells activate an effector program to potentially guard against ‘Trojan horse’ attacks. Uniquely, after the infection resolves, these cells do not respond to their corresponding dietary antigens, allowing for safe food consumption. Based on our findings, we propose that in response to dietary antigens, dedicated antigen-presenting cells direct a unique CD8αβ response that is coupled to the pTreg program to facilitate protective acute effector responses within the overall strategy of tolerance.
How do brain regions specialised for concrete and abstract concepts align with functional brain networks? A neuroimaging meta-analysis
Authors: Hoffman Paul , Bair Matthew 
Published: July 2024

AbstractIdentifying the brain regions that process concrete and abstract concepts is key to understanding the neural architecture of thought, memory and language. We review current theories of concreteness effects and test their neural predictions in a meta-analysis of 72 neuroimaging studies (1400 participants). Our analysis includes more than twice as many studies as previous meta-analyses, allowing for a more sensitive mapping of these effects across the brain. We also conducted a quantitative assessment of the degree to which concreteness effects aligned with a range of large-scale functional brain networks. Our results suggest that concrete and abstract concepts vary both in the information-processing modalities they engage and in the demands they place on cognitive control processes. Abstract concepts preferentially activated networks for social cognition (particularly for sentences), language and semantic control (particularly when presented as single words). Concrete concepts preferentially activated action processing regions when presented in sentences, though we found no evidence that they activated visual networks. Specialisation for both concept types was present in different parts of the default mode network (DMN), with effects dissociating along a social-spatial axis. Concrete concepts generated greater activation in a medial temporal DMN component, implicated in constructing mental models of spatial contexts and scenes. In contrast, abstract concepts showed greater activation in frontotemporal DMN regions involved in social and language processing. These results align with prior claims that generating models of situations and events is a core DMN function and indicate specialisation within DMN for different aspects of these models.