bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shape-changing electrode array for minimally invasive large-scale intracranial brain activity mapping
Authors: Wei Shiyuan , Jiang Anqi , Sun Hongji , Zhu Jingjun , Liu Xiaojun , Xu Zheng , Zhang Jing , Jia Shengyi , Shang Yuanyuan , Fu Xuefeng , Li Gen , Wang Puxin , Xia Zhiyuan , Jiang Tianzi , Cao Anyuan , Duan Xiaojie 
Published: July 2023

AbstractLarge-scale brain activity mapping is important for understanding the neural basis of behaviour. Electrocorticograms (ECoGs) have high spatiotemporal resolution, bandwidth, and signal quality. However, the invasiveness and surgical risks of electrode array implantation limit its application scope. We developed an ultrathin, flexible shape-changing electrode array (SCEA) for large-scale ECoG mapping with minimal invasiveness. SCEAs were inserted into cortical surfaces in compressed states through small openings in the skull or dura and fully expanded to cover large cortical areas. MRI and histological studies on rats proved the minimal invasiveness of the implantation process and the high chronic biocompatibility of the SCEAs. High-quality micro-ECoG activities mapped with SCEAs from rodent brains during seizures and canine brains during the emergence period revealed the spatiotemporal organization of different brain states with resolution and bandwidth that cannot be achieved using existing noninvasive techniques. The biocompatibility and ability to map large-scale physiological and pathological cortical activities with high spatiotemporal resolution, bandwidth, and signal quality in a minimally invasive manner offer SCEAs as a superior tool for applications ranging from fundamental brain research to brain-machine interfaces.
Applying Artificial Intelligence to Identify Common Targets for Treatment of Asthma, Eczema, and Food Allergy
Authors: Man Liu Bonnie Hei , Rayner Andre , Mendelsohn Andrew R. , Shneyderman Anastasia , Chen Michelle , Pun Frank W. 
Published: July 2023

AbstractAllergic disorders are common diseases marked by the abnormal immune response towards foreign antigens that are not pathogens. Often patients with food allergy also suffer from asthma and eczema. Given the similarities of these diseases and a shortage of effective treatments, developing novel therapeutics against common targets of multiple allergies would offer an efficient and cost-effective treatment for patients. Herein, we employed the artificial intelligence-driven target discovery platform, PandaOmics, to identify common targets for treating asthma, eczema, and food allergy. Thirty-two case-control comparisons were generated from 15, 11, and 6 transcriptomics datasets related to asthma (558 cases, 315 controls), eczema (441 cases, 371 controls), and food allergy (208 cases, 106 controls) respectively, and allocated into three meta-analyses for target identification. Top-100 high-confidence targets and Top-100 novel targets were prioritized by PandaOmics for each allergic disease. Six common high-confidence targets (i.e.,IL4R,IL5,JAK1,JAK2,JAK3, andNR3C1) across all three allergic diseases have approved drugs for treating asthma and eczema. Based on the targets’ dysregulated expression profiles and their mechanism of action in allergic diseases, three potential therapeutic targets were proposed.IL5was selected as a high-confidence target due to its strong involvement in allergies.PTAFRwas identified for drug repurposing, whileRNF19Bwas selected as a novel target for therapeutic innovation. Analysis of the dysregulated pathways commonly identified across asthma, eczema, and food allergy revealed the well-characterized disease signature and novel biological processes that may underlie the pathophysiology of allergies. Altogether, our study dissects the shared pathophysiology of allergic disorders and reveals the power of artificial intelligence in the exploration of novel therapeutic targets.
Exploiting the therapeutic vulnerability of IDH-mutant gliomas with zotiraciclib
Authors: Pang Ying , Li Qi , Sergi Zach , Yu Guangyang , Sang Xueyu , Kim Olga , Wang Herui , Ranjan Alice , Merchant Mythili , Oudit Belene , Robey Robert W. , Soheilian Ferri , Tran Bao , Núñez Felipe J. , Zhang Meili , Song Hua , Zhang Wei , Davis Dionne , Gilbert Mark R. , Gottesman Michael M. , Liu Zhenggang , Khan Javed , Thomas Craig J. , Castro Maria G. , Gujral Taranjit S. , Wu Jing 
Published: July 2023

SummaryIsocitrate dehydrogenase (IDH)-mutant gliomas have distinctive metabolic and biological traits that may render them susceptible to targeted treatments. Here, by conducting a high-throughput drug screen, we pinpointed a specific susceptibility of IDH-mutant gliomas to zotiraciclib (ZTR). ZTR exhibited selective growth inhibition across multiple IDH-mutant gliomain vitroandin vivomodels. Mechanistically, ZTR at low doses suppressed CDK9 and RNA Pol II phosphorylation in IDH-mutant cells, disrupting mitochondrial function and NAD+ production, causing oxidative stress. Integrated biochemical profiling of ZTR kinase targets and transcriptomics unveiled that ZTR-induced bioenergetic failure was linked to the suppression of PIM kinase activity. We posit that the combination of mitochondrial dysfunction and an inability to adapt to oxidative stress resulted in significant cell death upon ZTR treatment, ultimately increasing the therapeutic vulnerability of IDH-mutant gliomas. These findings prompted a clinical trial evaluating ZTR in IDH-mutant gliomas towards precision medicine (NCT05588141).HighlightsZotiraciclib (ZTR), a CDK9 inhibitor, hinders IDH-mutant glioma growthin vitroandin vivo.ZTR halts cell cycle, disrupts respiration, and induces oxidative stress in IDH-mutant cells.ZTR unexpectedly inhibits PIM kinases, impacting mitochondria and causing bioenergetic failure.These findings led to the clinical trial NCT 05588141, evaluating ZTR for IDH-mutant gliomas.
Proteomic associations with forced expiratory volume – a Mendelian randomisation study
Authors: Axelsson GT , Jonmundsson T , Woo YJ , Frick EA , Aspelund T , Loureiro JJ , Orth AP , Jennings LL , Gudmundsson G , Emilsson V , Gudmundsdottir V , Gudnason V 
Published: July 2023

AbstractA decline in forced expiratory volume (FEV1) is a hallmark of obstructive respiratory diseases, an important cause of morbidity among the elderly. While some data exist on biomarkers that are related to FEV1, we sought to do a systematic analysis of causal relations of biomarkers with FEV1.Data from the general population-based AGES-Reykjavik study were used. Proteomic measurements were done using 4,782 DNA aptamers (SOMAmers). Data from 1,648 participants with spirometric data were used to assess the association of SOMAmer measurements with FEV1 using linear regression. Bi-directional Mendelian randomisation (MR) analyses were done to assess causal relations of observationally associated SOMAmers with FEV1, using genotype and SOMAmer data from 5,368 AGES-Reykjavik participants and genetic associations with FEV1 from a publicly available GWAS (n = 400,102).In observational analyses, 473 SOMAmers were associated with FEV1 after multiple testing adjustment. The most significant were R-Spondin 4, Alkaline Phosphatase, Placental Like 2 and Retinoic Acid Receptor Responder 2. Of the 235 SOMAmers with genetic data, eight were associated with FEV1 in MR analyses. Three were directionally consistent with the observational estimate, Thrombospondin 2 (THBS2), Endoplasmic Reticulum Oxidoreductase 1 Beta and Apolipoprotein M. THBS2 was further supported by a colocalization analysis. Analyses in the reverse direction, testing whether changes in SOMAmer levels were caused by changes in FEV1, were performed but no significant associations were found after multiple testing adjustments.In summary, this large scale proteogenomic analyses of FEV1 reveals protein markers of FEV1, as well as several proteins with potential causality to lung function.
S4D-ECG: A shallow state-of-the-art model for cardiac abnormality classification
Authors: Huang Zhaojing , Contrera Luis Fernando Herbozo , Yu Leping , Truong Nhan Duy , Nikpour Armin , Kavehei Omid 
Published: July 2023

AbstractAn algorithm for processing raw 12-lead ECG data has been developed and validated in this study that is based on the S4D model. Among the notable features of this algorithm is its strong resilience to noise, enabling the algorithm to achieve an average F1-score of 81.2% and an AUROC of 95.5%. It is characterized by the elimination of pre-processing features as well as the availability of a low-complexity architecture that makes it suitable for implementation on numerous computing devices because it is easily implementable. Consequently, this algorithm exhibits considerable potential for practical applications in analyzing real-world ECG data.
Pre-pandemic activity on a myalgic encephalomyelitis/chronic fatigue syndrome support forum is highly associated with later activity on a long COVID support forum for a variety of reasons: a mixed methods study
Authors: Meyerson William U , Hoyle Rick H 
Published: July 2023

AbstractEncephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID share some clinical and social characteristics. We predicted that this would lead to an increased interaction between pre-pandemic members of an ME/CFS online support community and a long COVID community. We performed a mixed-methods retrospective observational study of the Reddit activity of 7,544 users active on Reddit’s long COVID forum. From among 1600 forums, pre-pandemic activity specifically on a ME/CFS forum is the top predictor of later participation on the long COVID forum versus an acute COVID support forum. In the qualitative portion, motives for this co-participation included seeking mutual support and dual identification with both conditions. Some of this effect may be explained by pre-existing ME/CFS possibly being a risk factor for long COVID and/or SARS-CoV-2 infection being a cause of ME/CFS relapse. The high rate of ME/CFS patients seeking mutual support on a long COVID forum speaks to the longsuffering experience of these patients not feeling heard or respected, and the hope of some ME/CFS patients to gain legitimacy through the public’s growing recognition of long COVID.
A Mendelian randomization study with clinical follow-up links metabolites to risk and severity of pulmonary arterial hypertension
Authors: Alhathli Elham , Julian Thomas , Girach Zain Ul Abideen , Thompson A A Roger , Rhodes Christopher , Gräf Stefan , Errington Niamh , Wilkins Martin R , Lawrie Allan , Wang Dennis , Cooper-Knock Johnathan 
Published: July 2023

AbstractPulmonary arterial hypertension (PAH) exhibits phenotypic heterogeneity and variable response to therapy. The metabolome has been implicated in the pathogenesis of PAH, but previous works have lacked power to implicate specific metabolites. Mendelian randomisation (MR) is a method for causal inference between exposures and outcomes. Using GWAS summary statistics, we implemented hypothesis-free MR methodology to test for causal relationships between serum concentration of 575 metabolites and PAH. Unbiased MR causally associated five metabolites with risk of PAH after stringent multiple testing correction; of the five candidates, serine and homostachydrine were validated in a different larger PAH GWAS, and associated with clinical severity of PAH via direct measurement in an independent clinical cohort of 449 PAH patients. We used conditional and orthogonal approaches to explore the biology underlying our lead metabolites. A rare variant analysis demonstrated that loss of function (LOF) mutations within ATF4, a transcription factor responsible for upregulation of serine synthesis under conditions of serine starvation, are associated with higher risk for PAH. Homostachydrine is a xenobiotic metabolite that is structurally related to L-proline betaine, which has been previously linked to modulation of inflammation and tissue remodelling in PAH. Our MVMR analysis suggests that the effect of L-proline betaine is actually mediated indirectly via homostachydrine. Our data presents a new method for study of the metabolome in the context of PAH, and suggests several candidates for further evaluation and translational research.
Modified Rankin Scale Disability Status at Day 4 Poststroke is an Informative Predictor of Long-Term Day 90 Outcome
Authors: Taleb Shayandokht , Lee Jenny Ji-hyun , Asanad Samuel , Starkman Sidney , Hamilton Scott , Conwit Robin A. , Sanossian Nerses , Saver Jeffrey L 
Published: July 2023

AbstractBackgroundLong-term disability after stroke is standardly assessed 3 months post-onset, using the modified Rankin Scale (mRS). The value of an early, day 4 mRS assessment for projecting the 3-month disability outcome has not been formally investigated.MethodsIn this cohort of patients with acute cerebral ischemia and intracranial hemorrhage, we analyzed day 4 and day 90 mRS assessments in the NIH Field Administration of Stroke Therapy– Magnesium (FAST-MAG) Phase 3 trial. The performance of day 4 mRS, alone and as part of multivariate models, in predicting day 90 mRS was assessed using correlation coefficients, percent agreement, and the kappa statistics.ResultsAmong the 1573 acute cerebrovascular disease (ACVD) patients, 1206 (76.7%) had acute cerebral ischemia (ACI), while 367 (23.3%) had intracranial hemorrhage. Among all 1573 ACVD patients, day 4 mRS and day 90 mRS correlated strongly, Spearman’s rho=0.79, in unadjusted analysis with weighted kappa of 0.59. For dichotomized outcomes, simple carry-forward of the day 4 mRS performed fairly well in agreeing with day 90 mRS: mRS 0-1 (k=0.67), 85.4%; mRS 0-2 (k=0.59), 79.5%; fatal outcome, 88.3% (k=0.33). Correlations of 4d and 90d mRS were stronger for ACI than ICH patients, 0.76 vs 0.71.ConclusionsIn this acute cerebrovascular disease patient cohort, assessment of global disability performed on day 4 is highly informative regarding long-term, 3-month mRS disability outcome, alone, and even more strongly in combination with baseline prognostic variables. The day 4 mRS is a useful measure for imputing the final patient disability outcome in clinical trials and quality improvement programs.
Specific gut pathobionts escape antibody coating and are enriched during flares in patients with severe Crohn’s disease
Authors: Eriksen Carsten , Danneskiold-Samsøe Niels B. , Moll Janne M. , Myers Pernille N. , Bondegaard Pi W. , Vejrum Simone , Hansen Tine B. , Rosholm Lisbeth B. , Rausch Philipp , Allin Kristine H. , Jess Tine , Kristiansen Karsten , Penders John , Jonkers Daisy MAE. , Brix Susanne 
Published: July 2023

AbstractPatients with Crohn’s disease (CD) exhibit great heterogeneity in disease presentation and treatment responses, where distinct gut microbiota-host interplays may play part in the yet unresolved disease etiology. We here characterized absolute and relative single and multi-coating of gut bacteria with immunoglobulin (Ig)A, IgG1, IgG2, IgG3 and IgG4 in CD patients and healthy controls. Patients with severe disease exhibited distinctly higher gut bacterial IgG2-coating. IgG2-coated bacteria included both known pathogenic and non-pathogenic bacteria that co-existed in communities with two non-coated gut pathobiontsCampylobacterandMannheimia. These latter two exhibited low prevalence, rarely coincided, and were strongly enriched during disease flares in CD patients across independent and geographically distant cohorts. Since antibody-coating of gut pathobionts diminishes epithelial invasion and inflammatory processes, escape from coating by specific gut pathobionts may be a mechanism related to disease flares in the subgroup of CD patients with severe disease.
Restriction of the growth and biofilm formation ofESKAPEpathogens by caprine gut-derived probiotic bacteria
Authors: Saini Prerna , Ayyanna Repally , Kumar Rishi , Bhowmick Sayan Kumar , Dey Bappaditya 
Published: July 2023

AbstractThe accelerated rise of antimicrobial resistance (AMR) poses a significant global health risk, necessitating the exploration of alternative strategies for combating pathogenic infections. Biofilm-related infections, which are unresponsive to standard antibiotics, often require the use of higher-order antimicrobials with toxic side effects and a potential for disrupting the microbiome. Probiotic therapy, with its diverse benefits and inherent safety, is emerging as a promising approach for preventing and treating various infections and as an alternative to antibiotic therapy. In this study, we isolated novel probiotic bacteria from the gut of domestic goats (Capra hircus) and evaluated their antimicrobial and antibiofilm activities against the ‘ESKAPE’ group of pathogens. We performed comprehensive microbiological, biochemical, and molecular characterizations, including analysis of the 16S-rRNA gene V1-V3 region and the 16S-23S ISR region, on 20 caprine gut-derived lactic acid bacteria (LAB). Among these, six selected LABs demonstrated substantial biofilm formation in anaerobic conditions, and exhibited robust cell surface hydrophobicity and autoaggregation properties highlighting their superior enteric colonization capability. Notably, these LAB isolates exhibited broad-spectrum growth inhibitory and anti-biofilm properties against ‘ESKAPE’ pathogens. Additionally, the LAB isolates were susceptible to antibiotics listed by the European Food Safety Authority (EFSA), within the prescribed Minimum Inhibitory Concentration limits, suggesting their safety as feed additives. The remarkable probiotic characteristics exhibited by the caprine gut-derived LAB isolates in this study strongly endorse their potential as compelling alternatives to antibiotics and as direct-fed microbial (DFM) feed supplements in the livestock industry, addressing the escalating need for antibiotic-free animal products.
Objective QC for diffusion MRI data: artefact detection using normative modelling
Authors: Cirstian Ramona , Forde Natalie J. , Andersson Jesper L.R. , Sotiropoulos Stamatios N. , Beckmann Christian F. , Marquand Andre F. 
Published: July 2023

AbstractDiffusion MRI is a neuroimaging modality used to evaluate brain structure at a microscopic level and can be exploited to map white matter fibre bundles and microstructure in the brain. One common issue is the presence of artefacts, such as acquisition artefacts, physiological artefacts, distortions or image processing-related artefacts. These may lead to problems with other downstream processes and can bias subsequent analyses. In this work we use normative modelling to create a semi-automated pipeline for detecting diffusion imaging artefacts and errors by modelling 24 white matter imaging derived phenotypes from the UK Biobank dataset. The considered features comprised 4 microstructural features (from models with different complexity such as fractional anisotropy and mean diffusivity from a diffusion tensor model and parameters from neurite orientation, dispersion and density models), each within six pre-selected white matter tracts of various sizes and geometrical complexity (corpus callosum, bilateral corticospinal tract and uncinate fasciculus and fornix). Our method was compared to two traditional quality control approaches: a visual quality control protocol performed on 500 subjects and quantitative quality control using metrics derived from image pre-processing. The normative modelling framework proves to be comprehensive and efficient in detecting diffusion imaging artefacts arising from various sources (such as susceptibility induced distortions or motion), as well as outliers resulting from inaccurate processing (such as erroneous spatial registrations). This is an important contribution by virtue of this methods’ ability to identify the two problem sources (i) image artefacts and (ii) processing errors, which subsequently allows for a better understanding of our data and informs on inclusion/exclusion criteria of participants.
Effects of blood meal source and seasonality on reproductive traits ofCulex quinquefasciatus(Diptera: Culicidae)
Authors: Rucci Kevin Alen , Barco Gabriel , Onorato Andrea , Beranek Mauricio , Pueta Mariana , Díaz Adrián 
Published: July 2023

AbstractHost selection by mosquitoes is a keystone to understanding viral circulation and predicting future infection outbreaks.Culexmosquitoes frequently feed on birds during spring and early summer, shifting into mammals towards late summer and autumn. This host switch may be due to changes in mosquito fitness. The aim of this study was to assess if the interaction effect of blood meal source and seasonality may influence reproductive traits ofCulex quinquefasciatusmosquitoes. For this purpose,Cx. quinquefasciatusmosquitoes were reared in simulated summer and autumn conditions and fed on two different hosts, chickens and mice, in a factorial design. Fecundity, fertility, and hatchability during two consecutive gonotrophic cycles were estimated. We found greater fecundity and fertility for mosquitoes fed upon birds than mammals. Fecundity and fertility did not vary between seasons for chicken-fed mosquitoes, whereas in autumn they decreased for mouse-fed mosquitoes. These traits decreased in the second gonotrophic cycle for mouse-fed mosquitoes, whereas they did not vary between cycles for chicken-fed mosquitoes. There was no statistically significant variation of hatchability among treatments. These results indicate a statistically significant interaction effect of blood meal source and seasonality on fecundity and fertility. However, the pattern was opposite in relation to our hypothesis, suggesting that further studies are needed to confirm and expand our knowledge about mosquito biology and its relationship with seasonal host use shifting.
Independent component analysis reveals the transcriptional regulatory modules inBradyrhizobium diazoefficiensUSDA110
Authors: Gao Zhi-Peng , Gu Wei-Cheng , Li Jie , Qiu Qin-Tian , Ma Bin-Guang 
Published: July 2023

AbstractThe dynamic adaptation of bacteria to environmental changes is achieved through the coordinated expression of many genes, which constitutes a transcriptional regulatory network (TRN).Bradyrhizobium diazoefficiensUSDA110 is an important model strain for the study of symbiotic nitrogen fixation (SNF), and its SNF ability largely depends on the TRN. In this study, independent component analysis was applied to 226 high-quality gene expression profiles ofB. diazoefficiensUSDA110 microarray datasets, from which 64 iModulons were identified. Using these iModulons and their condition-specific activity levels, we (1) provided new insights into the connection between the FixLJ-FixK2-FixK1regulatory cascade and quorum sensing, (2) discovered the independence of the FixLJ-FixK2-FixK1and NifA/RpoN regulatory cascades in response to oxygen, (3) identified the FixLJ-FixK2cascade as a mediator connecting the FixK2-2 iModulon and the Phenylalanine iModulon, (4) described the differential activation of iModulons inB. diazoefficiensUSDA110 under different environmental conditions, and (5) proposed a notion of active-TRN based on the changes in iModulon activity to better illustrate the relationship between gene regulation and environmental condition. In sum, this research offered an iModulon-based TRN forB. diazoefficiensUSDA110, which formed a foundation for comprehensively understanding the intricate transcriptional regulation during SNF.