bluuebunny/crossref_metadata_2025_split huggingface dataset:
Momentary Brain Imaging Assessment of Neuroplasticity in Psychiatric Illness: Protocol for Systematic Review
Authors: Brown A. , Upadhyay S. , Lloyd E. C. 
Published: February 2025

AbstractBackgroundNeuroplasticity describes the brain’s ability to adapt in response to alterations in the environment, and is fundamental to learning. Reduced neuroplasticity has been proposed to underlie several psychiatric symptoms and disorders. Advances in neuroimaging have provided new methods for examining or indexing the potential for neuroplastic changes in-vivo. The proposed systematic review and meta-analysis will synthesize research utilizing neuroimaging assessments to compare the potential for rapid brain changes between individuals with commonly-studied psychiatric disorders relative to healthy control peers (HC).MethodsThis systematic review will include studies comparing the potential for neuroplastic changes between individuals with commonly-studied psychiatric disorders (mood, anxiety, compulsive, trauma-related, eating, and schizophrenia and other psychotic disorders). Included studies will assess neuroplasticity using established or putative neuroimaging biomarkers. Longitudinal studies, studies using non-neuroimaging methods to assess neuroplastic potential, and animal studies will be excluded. PubMed, Web of Science, Embase, and PsycINFO will be searched using predefined terms. Two independent reviewers will screen titles, abstracts, and full texts using Rayyan, with conflicts resolved by a third reviewer. Data including study and participant characteristics will be extracted. Summary statistics will be combined and analyzed using random-effects meta-analyses to estimate the average difference in neuroplasticity between groups. In the event of heterogeneity, subgroup analyses and meta-regression will explore potential moderators of the between-group difference. The extent to which publication bias is likely to impact the findings of the review will be assessed using Egger’s test.DiscussionThis review will summarize alterations in neuroplasticity, as indicated by momentary neuroimaging assessments, among individuals with major psychiatric disorders. As research increasingly links psychiatric conditions to neuroplasticity, this review will offer a valuable resource for understanding how neuroplasticity can be measured in-vivo to examine mechanisms of psychiatric illness.Systematic review registrationThis review is registered in PROSPERO (registration number: CRD42025630626)
Detecting Monogenic Obesity: A Systematic Exome-Wide Workup of Over 500 Individuals
Authors: Künzel Robert , Faust Helene , Bundalian Linnaeus , Blüher Matthias , Jasaszwili Mariami , Kirstein Anna , Kobelt Albrecht , Körner Antje , Popp Denny , Wenzel Eric , Abou Jamra Rami , Lemke Johannes R. , Schöneberg Torsten , Stein Robert , Garten Antje , Le Duc Diana 
Published: February 2025

ABSTRACTBackground/ObjectivesObesity poses a major public health concern. Although BMI heritability is estimated at 40–80%, genetic diagnostics remain challenging. This study aims to (i) assess the diagnostic yield of monogenic obesity in a large patient sample using exome-wide data, (ii) identify predictors to improve genetic testing criteria, and (iii) evaluate whether the identified genes are included in public obesity gene panels.Subjects/MethodsWe reviewed the genetic test results of 521 patients with obesity. 84.7% underwent whole-exome analysis, 15.3% were analyzed using a multi-thousand gene panel.ResultsMonogenic obesity was diagnosed in 5.8% of patients, while 7.1% carried a potentially obesogenic variant. Diagnostic yield was higher in children (6.3%) and patients with syndromic obesity (7.0%). Surprisingly, diagnostic yield was lower in severe obesity cases. 40% of patients with monogenic obesity carried variants in genes not included in current obesity panels.ConclusionOverall, 12.9% of patients had monogenic obesity or a potentially obesogenic variant. These findings suggest that genetic testing should not be limited to patients with extreme obesity. Current obesity panels miss crucial syndromic genes, demonstrating a need for more comprehensive panels and the superiority of whole exome sequencing in obesity.
A Streamlined Point-of-Care CRISPR Test for Tuberculosis Detection Directly from Sputum
Authors: Dunkley Owen R. S. , Bell Alexandra G. , Modi Nisha H. , Huang Yujia , Tseng Soleil , Reiss Robert , Daivaa Naranjargal , Davis J. Lucian , Vargas Deninson Alejandro , Banada Padmapriya , Xie Yingda L. , Myhrvold Cameron 
Published: February 2025

AbstractMycobacterium tuberculosis(Mtb) is a major threat to global health and is responsible for over one million deaths each year. To stem the tide of cases and maximize opportunities for early interventions, there is an urgent need for affordable and simple means of tuberculosis diagnosis in under-resourced areas. We sought to develop a CRISPR-based isothermal assay coupled with a compatible, straightforward sample processing technique for point-of-care use. Here, we combine Recombinase Polymerase Amplification (RPA) with Cas13a and Cas12a, to create two parallelised one-pot assays that detect two conserved elements ofMtb(IS6110andIS1081) and an internal control targeting human DNA. These assays were shown to be compatible with lateral flow and can be readily lyophilized. Our finalized assay exhibited sensitivity over a wide range of bacterial loads (105to 102CFU/mL) in sputum. The limit of detection (LoD) of the assay was determined to be 69.0 (51.0 – 86.9) CFU/mL forMtbstrain H37Rv spiked in sputum and 80.5 (59.4 – 101.6) CFU/mL forM. bovisBCG. Our assay showed no cross reactivity against a wide range of bacterial/fungal isolates. Clinical tests on 13 blinded sputum samples revealed 100% (6/6) sensitivity and 100% (7/7) specificity compared to culture. Our assay exhibited comparable sensitivity in clinical samples to the microbiological gold standard, TB culture, and to the nucleic acid state-of-the-art, GeneXpert MTB/RIF Ultra. This technology streamlines TB diagnosis from sample extraction to assay readout in a rapid and robust format, making it the first test to combine amplification and detection while being compatible with both lateral flow and lyophilization.
Correlation between the NRS-2002 score and PD-1/CTLA-4 levels in patients with CAP
Authors: Zhang Chenguang , Zhang Mingqiang , Wu Sheng , Mu Xiangdong 
Published: February 2025

AbstractObjectiveTo investigated the relationship between nutritional status and PD-1/CTLA-4 in CAP patients to determine whether the nutritional status is associated with the immunosuppression generated by T cells.MethodsAccording the enrollment strategy, we enrolled 60 patients and collected their medical records.Take their blood samples and analyzed the distribution of PD-1 and CTLA-4 in different T cell subgroups.ResultsThe level of PD-1 and CTLA-4 in the CD4+, CD8+and Tregs were inclusive with the SCAP occurrence, mortality and PSI score.The malnutrition risk group suffered higher percentage of SAP, longer hospital-stay days and higher mortality when compared with the no-risk group.The higher the PD-1/CTLA-4 levels were, the higher the NRS-2002 score was.ConclusionA high NRS-2002 score may increase the length of hospital stay and the occurrence of SCAP. Higher PD-1 and CTLA-4 levels were associated with a higher PSI grade. Nutritional status influenced the occurrence of immunosuppression. Malnutrition status may increase the risk of immunosuppression, which is regulated by PD-1 and CTLA-4.
A Climate-Driven Mechanistic Transmission Model to Characterize Dengue Epidemiology in Dhaka, Bangladesh
Authors: Paul Kishor K , Regan David G , Green Donna , Macadam Ian , Gray Richard T 
Published: February 2025

AbstractDengue is a major public health concern in tropical and sub-tropical areas of the world. Dengue virus is transmitted to humans primarily by femaleAedes aegyptimosquitoes and its epidemiology is heavily influenced by the climate. We developed a mechanistic compartmental model to characterize how climate and the evolution of population-level immunity influence changes in the epidemiology of dengue. The model explicitly incorporates aquatic and adult stages of the mosquito vector and cross-immunity (to another serotype) to better represent the transmission of dengue compared to previous models. It incorporates parameters related to mosquito development, behaviour, and mortality that are dependent on temperature, rainfall, and humidity. We calibrated the model to available dengue seroprevalence estimates for Dhaka, Bangladesh as it is a well-observed densely populated endemic area for dengue and will be strongly impacted by climate change. We then simulated dengue epidemiology for the period of 1995-2014 and compared the simulation output with available epidemiologic data. The model produced repeating annual outbreaks of dengue with strong seasonality, as observed in the dengue case reports for Dhaka. The median number of annual dengue infections produced by the model was 1.6 million cases (IQR: 0.6-2.3 million) and the median of the annual daily peak size of dengue infections was 24,121 (IQR: 7,807-39,308) across the simulations. These figures while exceeding reported cases in Dhaka, which do not include asymptomatic infections or cases not seeking healthcare, align with previous estimates. The modelled seroprevalence of 62% (IQR: 58– 75%) aligned with survey results from Dhaka. In most model simulations, dengue infections occurred during August to December with the median peak occurring in October. The model outputs demonstrated a high degree of conformity to the reported data in terms of seasonality, and seroprevalence, indicating that the model provides a good representation of overall dengue epidemiology in Dhaka. By accounting for climate variables, host immunity, and their interplay, our model is well-suited for evaluating the long-term impact of climate change on dengue transmission in Dhaka and other settings where climate and epidemiological data are available.
A multistage, multitask transformer-based framework for multi-disease diagnosis and prediction using personal proteomes
Authors: Li Han , Li Yongkang , Liu Yukuan , Cooper-Knock Johnathan , Gao Peng , Shen Xiaotao , Chen Shengquan , Xing Xudong , Zhang Sai 
Published: February 2025

AbstractRecent advances in cohort-level proteomic profiling have offered unprecedented opportunities for discovering novel biomarkers and developing diagnostic and predictive tools for complex human diseases. However, the inherent complexity of proteomics data and the scarcity of phenotypic labels, particularly for rare diseases, pose significant challenges in modeling proteome-phenome relationships. Utilizing proteomics data from 2,924 plasma proteins measured in 53,014 UK Biobank participants, we introduce Prophet, an interpretable deep learning framework that combines transformer architecture with a multistage, multitask training strategy to improve disease prediction and biological discovery from personal proteomic profiles. Prophet begins with self-supervised pretraining to model protein interactions, followed by prompt-based fine-tuning for disease diagnosis, and concludes with continuous fine-tuning for disease prediction. Extensive benchmarking across more than 100 diseases demonstrates Prophet’s superior performance over multiple baseline methods, achieving the highest increase in the area under the precision-recall curve (AUPRC) by 132.71% for disease diagnosis and 60.29% for disease prediction. Specifically, Prophet enhances diagnostic accuracy for 95.83% of diseases and boosts predictive accuracy for 94.02% of diseases. Through model interpretation, Prophet identifies 21,549 and 25,915 protein-disease associations for prevalent and incident diseases, respectively, and uncovers prevailing proteomics-based similarities among diseases. Our work provides a powerful framework for proteomics-based disease diagnosis, prediction, and biomarker discovery.
Co-production of informal settlement health: A community based participatory research program for building healthy communities in urban informal settlements of Salvador, Brazil
Authors: Mogaji Hammed , Yeimi Alexandra Alzate Lopez , Almeida Figuerêdo Lívia , Araujo Virgens João Henrique , Aliaga Marie Agnes , Argibay Hernan D , Salles Inajara , Pereira Moreira Andreane , Lima e Silva Terezinha de Jesus , Cristina dos Santos Suzana , Batista Rita , Cardoso Elizete , Cardoso Neves Santos Elenilda , Leal dos Santos Edlane , Rodrigues dos Santos Edlana , Barreto Thiago da Mata , Auxiliadora dos Santos Mattos Thais , Nery Júnior Nivison , Cruz Jaqueline , Carneiro Ianei , Lustosa Ricardo , Dedavid Ferreira Victoria C. , Reis Mitermayer , Ko Albert I , Costa Federico , Begon Mike , Khalil Hussein 
Published: February 2025

AbstractMore than 15% of Brazil’s urban population lives in slums characterized by limited access to essential urban services, heightened vulnerability to infectious pathogens and environmental hazards, and deprivation of citizenship rights. These conditions exacerbate social inequality, perpetuate cycles of poverty, and fuel violence, underscoring the urgent need for sustainable interventions. Following a social justice framework, we developed a community development program rooted in participatory research methods and popular health education to foster collaboration between university researchers and communities. The aim was to identify priorities and co-create locally driven, cost-effective, and sustainable solutions. This article describes our ongoing project in three prominent urban slums of Salvador, Brazil (Alto do Cabrito, Pau da Lima and Marechal Rondon), detailing the methodologies employed, activities initiated, and interventions developed. We conducted ethnographic, eco-epidemiological, and collaborative mapping surveys to contextualize diverse health and well-being challenges. Furthermore, we organized consultative and socialization events with dynamic community groups identified local priorities, leading to the design of 13 interventions targeting citizenship rights, social cohesion, environmental restoration, waste management, and unemployment. Here, we described how our interdisciplinary approach leveraged social capital and fostered inter-sectoral partnerships to empower marginalized urban communities towards addressing their health and environmental challenges through sustainable, locally tailored solutions. While the program has strengthened community trust, facilitated partnerships, and achieved notable environmental improvements, further evaluation is needed to assess the long-term impacts of these interventions on broader social health determinants.
Genetics of cardiovascular outcomes in individuals with chronic kidney disease: the Chronic Renal Insufficiency Cohort (CRIC) study
Authors: Wen Jia , Lin Bridget M , Sun Quan , Jiang Min-Zhi , Linchangco Greg , Li Gang , Chen Ruochen , Go Alan S. , Miller-Fleming Tyne W. , Shuey Megan M. , Cohen Debbie L. , Rao Panduranga S. , Rahman Mahboob , Cox Nancy J. , Lash James P. , Guan Wyliena , Posner Daniel C. , Hui Qin , Houghton Serena C. , Hung Adriana M. , Cho Kelly , Wilson Peter W.F. , Zhou Haibo , Sun Yan V. , Li Yun , Franceschini Nora ,   Million Veteran Program and the CRIC Study Investigators
Published: February 2025

AbstractGenome-wide association studies (GWAS) identified multiple loci for cardiovascular disease, but their relevance to individuals with chronic kidney disease (CKD), who are at higher risk of cardiovascular disease, is unknown. In this study, we performed GWAS analyses of coronary heart disease (CHD) or all-cause stroke in African (AFR) and European (EUR) American participants with CKD of the Chronic Renal Insufficiency Cohort (CRIC). Mixed- effect logistic regression models were race-stratified and adjusted for age, sex, site of recruitment, estimated glomerular filtration rate (eGFR), and principal components, followed by meta-analysis. We attempted replication in participants from two biobanks with biomarker or ICD-10 (International Classification of Diseases, 10th Revision) diagnostic codes for CKD. We assessed the association of single nucleotide variants (SNVs) at known CHD and stroke loci in CRIC and tested the genetic correlation among CRIC, a biobank-based cohort and published GWAS of cardiovascular disease. Among 3,588 CRIC participants, 1,203 had CHD and 535 had all-cause stroke. We identified six SNVs across three loci (LINC02744,AZIN1- AS1, andATP6V0A4) associated with all-cause stroke, and two intronic SNVs at thePPARGlocus associated with CHD. However, SNV associations were not significant in replication studies. Published SNVs for CHD or stroke were not associated with cardiovascular outcomes in CRIC. When testing the genetic correlations between published GWAS and CRIC GWAS, they were significant for CHD (genetic correlations (rg) range of 0.39 to 0.51,p-value<0.007). These findings suggest some differences in the genetic architecture of CHD and stroke among individuals with CKD compared to those from the general population, although large numbers of CKD participants are needed to assess if findings are related to participant selection and CKD severity, or non-traditional risk factors in people with CKD.
Identifying the genetic constraint characteristics and biological correlates of sudden unexplained death susceptibility genes
Authors: Lin Junyi , Xu Chenyang , Shen Qi , Tao Ruiyang , Wang Shouyu 
Published: February 2025

AbstractSudden unexplained death (SUD) refers to sudden death in which the cause of death could not be established after a comprehensive medico-legal investigation, including pathological/toxicological assessment and forensic investigation of the circumstances of death. In the past decade, molecular autopsy has proved to be an efficient diagnostic tool in the multidisciplinary management of SUD. Though numerous pathogenic/likely pathogenic (P/LP) variants have been identified, there is still a large proportion of SUD cases without clear molecular autopsy findings, suggesting that the genetic predisposition contributing to SUD might be more complicated than expected. In this study, we analyzed published datasets to characterize the distribution pattern of rare P/LP variants. Enrichment analyses were subsequently conducted to identify the most affected canonical pathways/biological processes and phenotypes/cell types with strongest correlation to SUD. In addition, the constraint metrics of genes harboring P/LP variants were also assessed to investigate the role of selective pressure in shaping the genetic features of SUD.
Impact of multiple phosphorylations on the tau-R2/tubulin interface
Authors: Marien Jules , Prévost Chantal , Sacquin-Mora Sophie 
Published: February 2025

AbstractThe phosphorylation of the microtubule-associated tau protein plays a key role in the regulation of its physiological function. In particular, tau hyperphosphorylation affects its binding on the tubulin surface, destabilizing the tau-microtubule interface and leading to the accumulation of fibrillar aggregates in the brain. In this work, we performed classical Molecular Dynamics simulations for the tau-R2/tubulin assembly with various phosphorylations states of serines 285, 289 and 293. We analyze the resulting trajectories to obtain a detailed view of the protein interface in the complex, and the impact of tau phosphorylations on the stability of this assembly, and on the tubulin disordered C-Terminal tails (CTTs) mobility. We show how the tubulin CTTs help maintaining the tau-R2 fragment on the tubulin surface despite the destabilizing effect induced by phosphorylations. Conversely, tau phosphorylation affects the CTTs flexibility and their potential activity as MAP recruiting hooks. Furthermore, counterion mediated bridges between the phosphate groups and tubulin glutamates also contribute to the binding of tau-R2 on the MT.
Comparative analysis of novelPseudobdellovibrionaceaegenera and species yields insights into the genomics and evolution of bacterial predation mode
Authors: Maher Rebecca L. , Wülbern Janna , Zimmermann Johannes , Yeh Emily , Benda Liesl , Repnik Urska , Fuß Janina , Künzel Sven , Schulenburg Hinrich , Bohannan Brendan J.M. , Adair Karen L. , Johnke Julia 
Published: February 2025

AbstractBacteria of the familyPseudobdellovibrionaceaebelong to a group of bacteria that kill and feed on other bacteria. The diversity of predation strategies, habitats, and genome characteristics of these bacteria are largely unexplored, despite their ecological and evolutionary importance in microbial communities. Therefore, we characterized newPseudobdellovibrionaceaestrains isolated from the direct environments of three animal hosts: the zebrafish (Danio rerio), the threespine stickleback fish (Gasterosteus aculeatus), and the nematodeCaenorhabditis elegans. We used transmission electron microscopy (TEM) and genomic analyses to characterize the morphology and predation modes of our isolates. While most of our isolates exhibited periplasmic (i.e. endoparasitic) predation, one isolate clearly exhibited epibiotic (i.e. exoparasitic) predation and represents only the third confirmed epibiotic strain within its clade. Of our isolates, six are members of five new species in the genusBdellovibrioand two strains likely represent new genera within the familyPseudobdellovibrionaceae. From metabarcoding data, we found indications thatPseudobdellovibrionaceaeare widespread among our three animal hosts. Genomic analyses showed that epibiotic predators lack genes involved in host independence (i.e. prey-independent feeding) and peptidoglycan modification. However, genes unique to epibiotic predators may underlie this predation mode, particularly those involved in cell wall remodeling and recycling. With robust phylogenomic analyses, we show that our novel isolates cluster with previously describedPseudobdellovibrionaceaeisolates according to predation mode. Further, by placingPseudobdellovibrionaceaepredators within a wider evolutionary history including other predatory and non-predatory bacteria, we postulate periplasmic predation as the ancestral mode, with more derived epibiotic predators exhibiting genome streamlining.