bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide study of half a million individuals with major depression identifies 697 independent associations, infers causal neuronal subtypes and biological targets for novel pharmacotherapies
Authors: McIntosh Andrew M , Lewis Cathryn M ,   Mark J Adams for the Psychiatric Genomics Consortium Major Depressive Disorder Working Group
Published: May 2024

AbstractIn a genome-wide association study (GWAS) of 685,808 individuals with major depression (MD) and 4,364,225 controls from 29 countries and across diverse and admixed ancestries, we identify 697 independent associations at 636 genetic loci, 293 of which are novel. Using fine-mapping and functional genomic datasets, we find 308 high-confidence gene associations and enrichment of postsynaptic density and receptor clustering. Leveraging new single-cell gene expression data, we conducted a causal neural cell type enrichment analysis that implicated excitatory and inhibitory midbrain and forebrain neurons, peptidergic neurons, and medium spiny neurons in MD. Critically, our findings are enriched for the targets of antidepressants and provide potential antidepressant repurposing opportunities (e.g., pregabalin and modafinil). Polygenic scores (PGS) from European ancestries explained up to 5.7% of the variance in liability to MD in European samples and PGS trained using either European or multi-ancestry data significantly predicted case control status across all four diverse ancestries. These findings represent a major advance in our understanding of MD across global populations. We provide evidence that MD GWAS reveals known and novel biological targets that may be used to target and develop pharmacotherapies addressing the considerable unmet need for effective treatment.
A microbiota-directed complementary food intervention in 12-18-month-old Bangladeshi children improves linear growth
Authors: Mostafa Ishita , Hibberd Matthew C. , Hartman Steven J. , Rahman Md Hasan Hafizur , Mahfuz Mustafa , Hasan S. M. Tafsir , Ashorn Per , Barratt Michael J. , Ahmed Tahmeed , Gordon Jeffrey I. 
Published: May 2024

SUMMARYBackgroundGlobally, stunting affects ∼150 million children under five, while wasting affects nearly 50 million. Current interventions have had limited effectiveness in ameliorating long-term sequelae of undernutrition including stunting, cognitive deficits and immune dysfunction. Disrupted development of the gut microbiota has been linked to the pathogenesis of undernutrition, providing potentially new treatment approaches.Methods124 Bangladeshi children with moderate acute malnutrition (MAM) enrolled (at 12-18 months) in a previously reported 3-month RCT of a microbiota-directed complementary food (MDCF-2) were followed for two years. Weight and length were monitored by anthropometry, the abundances of bacterial strains were assessed by quantifying metagenome-assembled genomes (MAGs) in serially collected fecal samples and levels of growth-associated proteins were measured in plasma.FindingsChildren who had received MDCF-2 were significantly less stunted during follow-up than those who received a standard ready-to-use supplementary food (RUSF) [linear mixed-effects model, βtreatmentgroupxstudyweek(95% CI) = 0.002 (0.001, 0.003);P=0.004]. They also had elevated fecal abundances ofAgathobacter faecis,Blautia massiliensis,LachnospiraandDialister, plus increased levels of a group of 37 plasma proteins (linear model; FDR-adjustedP<0.1), including IGF-1, neurotrophin receptor NTRK2 and multiple proteins linked to musculoskeletal and CNS development, that persisted for 6-months post-intervention.InterpretationMDCF-2 treatment of Bangladeshi children with MAM, which produced significant improvements in wasting during intervention, also reduced stunting during follow-up. These results suggest that the effectiveness of supplementary foods for undernutrition may be improved by including ingredients that sponsor healthy microbiota-host co-development.FundingThis work was supported by the BMGF (Grants OPP1134649/INV-000247).ClinicalTrials.govidentifier:NCT04015999
Protocol on an Integrative review on nomenclature and outcomes in children with complex critical illness in Paediatric Intensive Care - The basis for consensus definition
Authors: Cuevas-Asturias Sofia , Tremlett Will , Mitchell Hannah K , Rafferty Claire , Ramnarayan Padmanabhan , Pattison Natalie 
Published: May 2024

AbstractPaediatric Critical Care (PCC) supports the recovery of children with severe illness. Nationally, there are 30 PCC units with a total of approximately four hundred beds. There is constant demand for these beds with a mean five-day length of stay and admissions increasing at a greater rate than age-specific population growth [1, 2]. Prolonged stay patients account for approximately half of all PCC patient bed days [3].Children with complex critical illness (CCI) need input from multiple different teams alongside support for their family [4, 5]. CCI often become prolonged PCC-stay patients too [6]. Internationally, there is variation in the definition of CCI [4, 8], this creates service variation and tensions around what resources can be provided including discharge planning, provision, and support.ObjectiveThe face of Paediatric Critical Care, in the UK and internationally has changed over the course of the last ten years with a growing cohort of complex critically ill patients. This integrative review aims to look at current nomenclature, definitions, and outcome measures of priority in this undefined patient population.Inclusion criteriaAll types of studies looking at children with complex critical illness (age <18 years) admitted to any paediatric intensive care unit (PICU).MethodsThe review is registered on Prospero. Medline, Embase, Maternity and Infant care, The Cochrane library, the Cumulative Index to Nursing and Allied Health literature (CINAHL) and Trip database will be searched from 2014 to May 2024.Search limits will include all languages, exclude the setting of neonatal intensive care and age>18 years old. Four independent reviewers will screen citations for eligible studies and perform data extraction. The final search strategy will be developed in Medline and peer-reviewed by a health research librarian not involved in the study. This will be translated to other databases as appropriate.Author approvalAll authors have seen and approved the manuscript.
Exercise Training Improves Cognitive Function and Neurovascular Control in Patients With Heart Failure and Atrial Fibrillation: A Randomized Clinical Trial
Authors: Guimarães Guilherme Veiga , Chizzola Paulo Roberto , D’Avila Veridiana Moraes , Santo-Silva Paulo Roberto , Grohes Miranda Raphaela Villar , Alves Leandro Silva , Bocchi Edimar Alcides 
Published: May 2024

AbstractBackgroundAtrial fibrillation (AF) may be linked to cognitive impairment in heart failure (HF) patients. Regular exercise training has numerous benefits, including improving adults’ overall health and cognitive function. However, the effects of exercise training on cognitive function in heart failure patients with reduced ejection fraction and permanent atrial fibrillation (HFAF) are not well understood.ObjectiveTo test the hypothesis that exercise training improves cognitive function and neurovascular control in patients with HFAF.MethodsThis randomized clinical trial included patients with HFAF, LVEF ≤40%, and resting HR ≤80 bpm. Montreal Cognitive Assessment score (MoCA), muscle sympathetic nerve activity (MSNA), and forearm blood flow (FBF) assessment were performed before and after the 12-week protocol period.ResultsTwenty-six patients were randomized to exercise training (HFAF-trained, n=13) or no training (HFAF-untrained, n=13). At baseline, no differences between groups were found. Exercise significantly improved the MoCA score from 14.85 to 22.62 (P<0.0001), as well as those measuring processing visuospatial, memory, and attention function from 2.23 to 3.31 (P=0.02); from 1.92 to 2.69 (P=0.01); and from 2.62 to 3.85 (P=0.002), respectively. HFAF-training significantly decreased MSNA from 49.6±9.5 to 32.0±7.2 burst/min (P<0.0001) and forearm vascular resistance from 48.8±13.1 to 28.1±7 units (P<0.0001). Concomitantly, FBF increased from 1.9±0.5 to 3.0±0.7 mL/min/100mL (P<0.0001). The untrained group increased MSNA from 50.9±10.6 to 57.6±9.2 burst/min (P=0.004). No significant changes were found in the other variables in untrained patients.ConclusionExercise training improves cognitive function and neurovascular control in patients with heart failure with reduced ejection fraction and permanent atrial fibrillation.
Intensity of habitual physical activity and maintenance of normal blood pressure – findings from the SUN longitudinal cohort study
Authors: Gribble Anne Katherine , Hershey Maria S. , López-Gil José Francisco , Lan Fan-Yun , Kales Stefanos N. , Martínez-González Miguel Ángel , Bes-Rastrollo Maira , Fernandez-Montero Alejandro 
Published: May 2024

(2)ABSTRACTBackgroundPhysical activity (PA) is a modifiable protective factor against hypertension, but the optimum intensity of PA for prevention of hypertension remains unknown. It has been suggested that total energy expenditure is the crucial factor while intensity is non-differential provided it is moderate or above. Yet it is possible that higher intensity PA may produce a distinct effect.MethodsWe used data from theSeguimiento Universidad de Navarra(SUN) cohort – a large prospective longitudinal cohort study in Spain - to investigate how intensity of habitual PA may affect hypertension incidence. Average intensity of PA was calculated incorporating incidental walking and stairclimbing in addition to leisure-time PA (LTPA). Hazard ratios (HRs) for incident hypertension and their 95% confidence intervals (CI) were estimated using Cox regression analyses, and modelling adjusted for EE and body mass index (BMI) as well as other important covariables. Comparative models investigated how time spent in PA and EE in PA relate to hypertension incidence.Results17,146 normotensive participants (63.6% female, mean age 36.7 years, mean BMI 23.2kg/m2) were followed for 204,677 person-years. 2,495 cases of incident hypertension emerged. After adjustment for covariables, including EE, intensity of PA was monotonically associated with decreased risk for incident hypertension (aHR for Q5 vs Q1: 0.81, 95% CI 0.71-0.93). In comparison, increasing time in PA was associated with increasing risk for incident hypertension following adjustment for EE (aHR for Q5 vs Q1: 1.60, 95% CI 1.10- 2.32).ConclusionIntensity of habitual PA is independently and inversely associated with incidence of hypertension.
Influenza vaccine effectiveness against hospital-attended influenza infection in 2023/24 season in Hangzhou, China
Authors: Lei Hao , Niu Beidi , Sun Zhou , Wang Yaojing , Che Xinren , Du Shengqiang , Liu Yan , Zhang Ke , Zhao Shi , Yang Shigui , Wang Zhe , Zhao Gang 
Published: May 2024

AbstractBackgroundFrom 2020, influenza activities were largely affected by the coronavirus disease (COVID-19) pandemic at the global scale. The B/Yamagata lineage has become extinct since 2020, raising concerns regarding the quadrivalent influenza vaccine. Evaluating vaccine effectiveness (VE) against influenza infections is important to guide future influenza vaccine programs.MethodsA test-negative case-control study was conducted in five tertiary hospitals in Hangzhou, the capital city of Zhejiang province, China. Hospital-attended patients aged >6 months who presented with influenza-like illness (ILI) from October 1, 2023 to March 31, 2024 were enrolled in this study. The VE was estimated using multivariate logistic regression models, adjusted by sex, age, influenza detection methods and influenza testing timing.ResultsIn total, 157291 hospital-attended ILI participants were enrolled. 56704 (36%) were tested positive for influenza virus. The adjusted estimates of overall VE against any hospital-attended influenza infection was 48% (95% Confidence interval [CI]: 46%-51%). The overall VE of trivalent inactivated influenza vaccine (IIV3) was 59% (95% CI: 50%-66%), followed by trivalent live attenuated vaccine (LAIV3) (VE=53%, 95% CI: 42%-62%) and quadrivalent inactivated influenza vaccine (IIV4) (VE=47%, 95% CI: 45%-50%). IIV3 provided even much better protection against hospital-attended influenza B infection than IIV4 (VE=87% (95% CI: 81%-92%) for IIV3 versus VE=53%, 95% CI: 50%-57% for IIV4).ConclusionsThe influenza vaccine provided moderate protection against influenza infection in the 2023/24 season in Hangzhou, China, during a massive epidemic. The results supported the World Health Organization recommendation regarding the exclusion of B/Yamagata lineage antigen in quadrivalent influenza vaccines in 2023.
Identification and validation of drugs for repurposing in Glioblastoma: a computational and experimental workflow
Authors: Gonzalez Nazareno , Pérez Küper Melanie , Garcia Fallit Matías , Peña Agudelo Jorge A. , Nicola Candia Alejandro J. , Suarez Velandia Maicol , Videla-Richardson Guillermo A. , Candolfi Marianela 
Published: May 2024

ABSTRACTPurposeGlioblastoma (GBM) remains a formidable challenge in oncology due to its invasiveness and resistance to treatment, i.e. surgery, radiotherapy, and chemotherapy with temozolomide. This study aimed to develop and validate an integrated model to predict the sensitivity of GBM to alternative chemotherapeutics and to identify novel candidate drugs and combinations for the treatment of GBM.Patients and MethodsWe utilized the drug sensitivity response data of 272 compounds from CancerRxTissue, a validated predictive model, to identify drugs with therapeutic potential for GBM. Using the IC50, we selected ’potentially effective’ drugs among those predicted to be blood-brain barrier permeable viain silicoalgorithms. We ultimately selected drugs with targets overexpressed and associated with worse prognosis in GBM for experimentalin vitrovalidation.ResultsThe workflow proposed predicted that GBM is more sensitive to Etoposide and Cisplatin, in comparison with Temozolomide, effects that were validatedin vitroin a set of GBM cellular models. Using this workflow, we identified a set of 5 novel drugs to which GBM would exhibit high sensitivity and selected Daporinad, a blood-brain barrier permeant NAMPT inhibitor, for further preclinicalin vitroevaluation, which aligned with thein silicoprediction.ConclusionOur results suggest that this workflow could be useful to select potentially effective drugs and combinations for GBM, according to the molecular characteristics of the tumor. This comprehensive workflow, which integrates computational prowess with experimental validation, could constitute a simple tool for identifying and validating compounds with potential for drug reporpusing in GBM and other tumors.
The effect of head orientation on vestibular signal-based modulation of paraspinal muscle activity during walking
Authors: Li Yiyuan C. , Lemaire Koen K. , Bruijn Sjoerd M. , Brumagne Simon , van Dieën Jaap H. 
Published: May 2024

AbstractVestibulospinal reflexes play a role in maintaining the upright posture of the trunk. Head orientation has been shown to modify the vestibulospinal reflexes during standing. This study investigated how vestibular signals affect paraspinal muscle activity during walking, and whether head orientation changes these effects. Sixteen participants were instructed to walk on a treadmill for 8 min at 78 steps/min and 2.8 km/h in four conditions defined by the presence of electrical vestibular stimulation (EVS) and by head orientation (facing forward and facing leftward), while bipolar electromyography (EMG) was recorded bilaterally from the paraspinal muscles from cervical to lumbar levels. In both head orientations, significant phasic EVS-EMG coherence (p< 0.01) in the paraspinal muscles was observed at ipsilateral and/or contralateral heel strikes. Compared to walking with the head forward, a significant decrease (p< 0.05) was found in EVS evoked responses (i.e., EVS-EMG coherence and gain) when participants walked with the leftward head orientation, with which EVS induced disturbance in the sagittal plane. This overall decrease may be explained by less need of feedback control for walking stabilization in the sagittal plane compared to in the frontal plane. The decrease in coherence was only significant at the left lower vertebral levels and at the right upper vertebral levels around left heel strikes (p< 0.05). Together, these findings confirm the contribution of the vestibular afferent signals to the control of paraspinal muscle activity during walking and indicate that this control is changed in response to different head orientations.Key Point SummaryVestibulospinal reflexes simultaneously contribute to stabilizing the centre of mass trajectory and to maintaining an upright posture of the trunk.Head orientation, which challenges stability via altered visual, vestibular and proprioceptive signals, modifies vestibulospinal reflexes during standing.To explore the impact of head orientation during walking, we recorded bilateral surface EMG of cervical to lumbar paraspinal muscles, and characterized coherence, gain and delay between EMG and electrical vestibular stimulation, during walking with head facing forward and leftward.When walking with head facing leftward, vestibular stimulation caused disturbance in sagittal plane. Phasic response in paraspinal muscles with a significant smaller magnitude was found compared to facing forward.Our results agree with the idea that less feedback control is required for walking stabilization in the sagittal plane and confirm that vestibular afference modulates paraspinal muscle activity for trunk control during walking, and this modulation is changed in response to head orientation.
Histological and gene-expression analyses of pyloric sphincter formation during stomach metamorphosis inXenopus laevis
Authors: Nagura Kei , Ikeda Takafumi , Hasebe Takashi , Satou-Kobayashi Yumeko , Udagawa Sumio , Shigenobu Shuji , Ishizuya-Oka Atsuko , Taira Masanori 
Published: May 2024

AbstractDuring anuran metamorphosis from herbivorous tadpoles to carnivorous frogs, the gastrointestinal (GI) tract undergoes drastic remodeling, such as the formation of the stomach-intestine boundary and the development of the pyloric sphincter at the posterior end of the stomach. However, the morphogenetic process and molecular mechanisms of how the pyloric sphincter is formed during metamorphosis, instead of during embryogenesis as in amniotes, are largely uninvestigated. Using the African clawed frogXenopus laevis, we histologically examined the development of the pylorus region from embryonic to froglet stages and performed spatiotemporal gene expression analyses. We found that the pyloric sphincter is formed at a flexure within the pyloric region during metamorphic climax, and that the pyloric and duodenal epithelia, which are morphologically indistinguishable before sphincter formation, become clearly demarcated by the sphincter at the end of metamorphosis. Consistent with these morphological changes, expression domains of a stomach markerbarx1and an intestine markercdx2overlapped until late metamorphic climax, but became separated after metamorphosis. Despite the absence of the sphincter before metamorphosis, various genes crucial for sphincter formation in amniotes were already expressed in the pylorus region ofXenopusembryos. RNA-sequencing analysis at pre-metamorphic and metamorphic-climax stages suggest unappreciated roles of genes, such as those for retinoic acid signaling and various transcription factors, in suppressing or promoting sphincter formation. These data provide histological and molecular insights into the heterochrony of the pyloric sphincter formation in amniotes and anurans.
Exploring Neuroscience Researchers’ Trust in Preprints through Citation Analysis
Authors: Rasuli Behrooz , Seyfzadehdarabad Fatemeh , Cardone Paolo , Thibaut Aurore , Gosseries Olivia 
Published: May 2024

AbstractPreprints have emerged as efficient tools for fast and free dissemination of scientific findings. The present study explores the evolving landscape of preprints among the field of neuroscience and examines patterns and evolution of citations to preprints over time in this field. Leveraging bibliometric methods, we identified over 33,000 citations (1993-2022) to preprints within neuroscience publications indexed in Scopus. The findings elucidate a significant temporal increase in the number of documents citing preprints, reaching a peak of around 60 per 1,000 Scopus documents in 2021. Diverse document types, particularly reviews, exhibit a growing reliance on preprints as references. The most frequently cited preprint servers include bioRxiv, ArXiv, medRxiv, and PsyArXiv. Leading journals such as eLife and PLOS Computational Biology have cited preprints more than others. The United States takes the lead in citing preprints, followed by the United Kingdom and Germany. Using Scite.ai, motivations underlying preprint citations and the context in which they were cited were explored and the results are indicative of the “mentioning” nature of 93% of citations to preprints. Furthermore, the introduction and discussion sections have shown to include the highest number of citations to preprints. The findings highlight the dynamic transformation of preprints in neuroscience field.
Time-restricted feeding prevents memory impairments induced by obesogenic diet consumption in mice, in part through hippocampal thyroid hormone signaling
Authors: Helbling Jean-Christophe , Ginieis Rachel , Mortessagne Pierre , Ruiz-Gayo Mariano , Ducourneau Eva Gunnel , Ciocca Dominique , Boulete Illona-Marie , Favereaux Alexandre , Ces Aurélia , Montalban Enrica , Capuron Lucile , Jeanneteau Freddy , Ferreira Guillaume , Challet Etienne , Moisan Marie-Pierre 
Published: May 2024

AbstractThe consumption of calorie-rich diet has adverse effects on short and long-term memory, especially when introduced early in life when the brain is still maturing. Time-restricted feeding (TRF) without calorie restriction has proven to be an efficient strategy to reduce the deleterious effects of diet-induced obesity on metabolism. TRF was also shown to be beneficial to restore long-term memory in Alzheimer rodent models. Here, we provide evidence that four weeks of TRF restore the rhythmicity of some metabolic parameters together with short and long-term memory in mice fed a high fat-high sucrose (HFS) diet since weaning. Hippocampal translatome analyses indicated that impaired memory of mice underad libitumHFS diet is accompanied by changes in genes associated with thyroid hormone signaling and astrocytic genes involved in the regulation of glutamate neurotransmission. TRF restored the diurnal expression variation of part of these genes and intra-hippocampal infusion of T3, the active form of thyroid hormone, rescued the memory performances ofad libitumHFS diet-fed mice. Thus, TRF demonstrates positive effects on both metabolism and memory in mice fed an obesogenic diet, highlighting this nutritional approach as a powerful tool in addressing obesity and its related comorbidities in mice. The analogous time-restricted eating in humans is an easy to implement lifestyle intervention that should now be tested in obese adolescents with memory alterations.