bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mining drug-target interactions from biomedical literature using chemical and gene descriptions-based ensemble transformer model
Authors: Aldahdooh Jehad , Tanoli Ziaurrehman , Tang Jing 
Published: July 2023

AbstractDrug-target interactions (DTIs) play a pivotal role in drug discovery, as it aims to identify potential drug targets and elucidate their mechanism of action. In recent years, the application of natural language processing (NLP), particularly when combined with pre-trained language models, has gained considerable momentum in the biomedical domain, with the potential to mine vast amounts of texts to facilitate the efficient extraction of DTIs from the literature. In this article, we approach the task of DTIs as an entity-relationship extraction problem, utilizing different pretrained transformer language models, such as BERT, to extract DTIs. Our results indicate that an ensemble approach, by combining gene descriptions from the Entrez Gene database with chemical descriptions from the Comparative Toxicogenomics Database (CTD), is critical for achieving optimal performance. The proposed model achieves an F1 score of80.6on the hidden DrugProt test set, which is the top-ranked performance among all the submitted models in the official evaluation. Furthermore, we conduct a comparative analysis to evaluate the effectiveness of various gene textual descriptions sourced from Entrez Gene and UniProt databases to gain insights into their impact on the performance. Our findings highlight the potential of NLP-based text mining using gene and chemical descriptions to improve drug-target extraction tasks. Datasets utilized in this study are accessible athttps://dtis.drugtargetcommons.org/.
Data-driven probabilistic definition of the low energy conformational states of protein residues
Authors: Gavalda-Garcia Jose , Bickel David , Roca-Martinez Joel , Raimondi Daniele , Orlando Gabriele , Vranken Wim 
Published: July 2023

AbstractProtein dynamics and related conformational changes are essential for their function but difficult to characterise and interpret. Amino acids in a protein behave according to their local energy landscape, which is determined by their local structural context and environmental conditions. The lowest energy state for a given residue can correspond to sharply defined conformations,e.g., in a stable helix, or can cover a wide range of conformations,e.g., in intrinsically disordered regions. A good definition of such low energy states is therefore important to describe the behavior of a residue and how it changes with its environment. We propose a data-driven probabilistic definition of six low energy conformational states typically accessible for amino acid residues in proteins. This definition is based on solution NMR information of 1,322 proteins through a combined analysis of structure ensembles with interpreted chemical shifts. We further introduce a conformational state variability parameter that captures, based on an ensemble of protein structures from molecular dynamics or other methods, how often a residue moves between these conformational states. The approach enables a different perspective on the local conformational behavior of proteins that is complementary to their static interpretation from single structure models.
Immune Profiling among Colorectal Cancer Subtypes using Dependent Mixture Models
Authors: Duan Yunshan , Guo Shuai , Wang Wenyi , Mueller Peter 
Published: July 2023

AbstractComparison of transcriptomic data across different conditions is of interest in many biomedical studies. In this paper, we consider comparative immune cell profiling for early-onset (EO) versus late-onset (LO) colorectal cancer (CRC). EOCRC, diagnosed between ages 18-45, is a rising public health concern that needs to be urgently addressed. However, its etiology remains to be poorly understood. We work towards filling this gap by identifying homogeneous T cell subpopulations that show significantly distinct characteristics across the two tumor types, and to identify others that are shared between EOCRC and LOCRC. Such inference may reveal underlying determinants of clinically observed differences in the two disease subpopulations. We develop dependent finite mixture models where immune subtypes enriched under a specific condition are characterized by terms in the mixture model with common atoms but distinct weights across conditions, whereas common subtypes are characterized by sharing both atoms and relative weights. The proposed model defines a variation of mixtures of finite mixture models, facilitating the desired comparison by introducing highly structured multi-layer Dirichlet priors. The model allows us to explicitly compare features across conditions. We illustrate inference with simulation studies and data examples. Results identify EO-enriched and LO-enriched T cells subtypes whose biomarkers are found to be linked to mechanisms of tumor progression. The findings reveal distinct characteristics of the immune profiles in EOCRC and LOCRC, and potentially motivate insights into treatment and management of CRC.
Identification of novel pathogenic genes of childhood epileptic encephalopathies
Authors: Shi Yi-Wu , Zhang Jian-Guo , He Na , Ye Zi-Long , Li Wen-Bin , Liu Han-Kui , Liu Zhi-Gang , Shen Nan-Xiang , Qu Xiao-Chong , Fan Cui-Xia , Wang Jie , Luo Sheng , Lv Yu-Dan , Gao Li , Chen Jing , Huang Shao-Ping , Lu Xin-Guo , Yu Jing , Zhang Jie , Wang Xiu-Xia , Gao Qu-Wen , Jiang Li , Chen Yan-Hui , Qi Hui , Qiao Jing-Da , Chen Li-Zhi , Zeng Yuan-Jin , Yang Xiao-Xue , Yan Hong-Jun , Li Cheng-Yan , Zeng Tao , Min Fu-Li , Qin Bing , Xu Hai-Qing , Xu Lin , Li Bing-Mei , Yi Yong-Hong , Zhuo Zhi-Hong , Guo Qing-Hui , He Su-Li , Zhang Hong-Wei , Guan Li-Ping , Deng Wei-Yi , Ren Xiao-Fan , Zou Dong-Fang , Gu Wei-Yue , Su Tao , Liu Xiao-Rong , Qu Yi-Bo , Yang Xin-Ping , Liao Wei-Ping 
Published: July 2023

AbstractBackgroundEpileptic encephalopathy is a devastating epilepsy with etiologies largely elusive, despite whole-gene/exon sequencing of large cohorts. This study targeted the genetic causes of childhood epileptic encephalopathy, typically Lennox-Gastaut syndrome (LGS) featured by age-dependent onset and characteristic clinical manifestations.MethodsTrio-based whole-exome sequencing was performed in 235 LGS cases with individualized analyses on each trio by explainable inheritance origin with stratified frequency filtration and on each gene in four aspects, and specified statistical analyses including that on compound heterozygous variants with controls of 1942 asymptomatic parents. Animal models were used to validate the roles of novel candidate genes.ResultsWe identified three novel causative genes, includingSBF1withde novo,CELSR2with recessive, andTENM1with X-linked recessive variants. Significantly higher excesses ofde novo SBF1variants and biallelicCELSR2variants, aggregated variant frequencies ofSBF1,CELSR2, andTENM1, and frequency of compound heterozygousCELSR2variants in the cases were detected. Phenotype severity/outcome was correlated with the genotype of the variants in these genes. InDrosophila, knockdown of these genes showed increased seizure-like behavior and increased firing of excitatory neurons.Sbf1knockout zebrafish showed seizure-like behavior, premature death, and increased firing of neurons.Celsr2knockout mice showed spontaneous seizures with epileptiform discharges. Additional 42 genes were identified as novel candidate pathogenic genes with evidence of the four genetic aspects/statistics.ConclusionsThis study suggestsSBF1,CELSR2, andTENM1are pathogenic genes of LGS and highlights the implications of phenotype subclassification and individualized analyses protocol in identifying genetic causes of human diseases.
Flexibility of brain dynamics is increased and predicts clinical impairment in Relapsing-Remitting but not in Secondary Progressive Multiple Sclerosis
Authors: Cipriano Lorenzo , Minino Roberta , Liparoti Marianna , Polverino Arianna , Romano Antonella , Bonavita Simona , Jirsa Viktor , Sorrentino Giuseppe , Sorrentino Pierpaolo , Lopez Emahnuel Troisi 
Published: July 2023

ABSTRACTBackgroundLarge-scale brain activity has long been investigated under the erroneous assumption of stationarity. Nowadays, we know that resting state functional connectivity is characterised by aperiodic, scale-free bursts of activity (i.e. neuronal avalanches) that intermittently recruit different brain regions. These different patterns of activity represent a measure of brain flexibility, whose reduction has been found to predict clinical impairment in multiple neurodegenerative diseases such as Parkinson’s disease, Amyotrophic Lateral Sclerosis, and Alzheimer’s disease. Brain flexibility has been recently found increased in Multiple Sclerosis (MS) but its relationship with clinical disability remains elusive. Also, potential differences in brain dynamics according to the MS clinical phenotypes remain unexplored so far.MethodsWe studied brain flexibility through source-reconstruction of magnetoencephalography (MEG) signals in a cohort of 25 MS patients (10 RRMS and 15 SPMS) and 25 healthy controls (HC).ResultsRRMS patients showed greater brain flexibility than HC. On the contrary, no differences in brain dynamics were found in SPMS patients as compared to HC. Finally, brain dynamics showed a different predictive power on clinical disability according to the MS type.ConclusionFor the first time, we investigated brain dynamics in MS patients through high temporal resolution techniques, unveiling differences in brain flexibility according to the MS phenotype and its relationship with clinical disability.
Modelling seasonality of Lassa fever in Nigeria
Authors: McKendrick James , Tennant Warren , Tildesley Michael J. 
Published: July 2023

AbstractLassa fever (Lf) is a viral haemorrhagic disease endemic to West Africa and is caused by theLassa mammarenavirus. The rodentMastomys natalensisserves as the primary reservoir and its ecology and behaviour have been linked to the distinct spatial and temporal patterns in the incidence of Lf. Nigeria has experienced an unprecedented epidemic that lasted from January until April of 2018, which has been followed by subsequent epidemics of Lf in the same period every year since. While previous research has modelled the case seasonality within Nigeria, this did not capture the seasonal variation in the reproduction of the zoonotic reservoir and its effect on case numbers. To this end, we introduce an approximate Bayesian computation scheme to fit our model to the case data from 2018–2020 supplied by the NCDC. In this study we used a periodically forced seasonal nonautonomous system of ordinary differential equations as a vector model to demonstrate that the population dynamics of the rodent reservoir may be responsible for the spikes in the number of observed cases in humans. The results show that in December through to March, spillover from the zoonotic reservoir drastically increases and spreads the virus to the people of Nigeria. Therefore to effectively combat Lf, attention and efforts should be concentrated during this period.Author summaryLassa fever is a viral disease prevalent in West Africa, withMastomys natalensisserving as the primary reservoir. In Nigeria, annual outbreaks occur from December to March. Using a novel model and data from 2018-2020, we demonstrate that the population dynamics of the reservoir contribute to spikes in human cases. Specifically, spillover transmission increases drastically during this period, highlighting the need for concentrated efforts and interventions. Understanding the seasonal dynamics of the reservoir is crucial for effective Lassa fever control and prevention strategies in Nigeria.
Plasma proteomic profiles of UK Biobank participants with Multiple Sclerosis
Authors: Jacobs Benjamin M , Vickaryous Nicola , Giovannoni Gavin , Proitsi Petroula , Waters Sheena , Dobson Ruth 
Published: July 2023

AbstractObjectiveWe aimed to describe plasma protein biomarkers of Multiple Sclerosis risk and to explore protein biomarkers of disease severity using radiological outcome measures.MethodsMultiple Sclerosis cases and controls were identified in UK Biobank, a longitudinal cohort study of ∼500,000 British adults. Plasma proteins were assayed in ∼50,000 UK Biobank participants using the Olink proximity extension assay. We performed case-control association testing to examine the association between 2911 proteins and Multiple Sclerosis, using linear models adjusted for confounding covariates. Associations with radiological lesion burden and brain volume were determined in a subset of the cohort with available magnetic resonance imaging, using normalised T2-hyperintensity volume or whole brain volume as the outcome measure.Results407 prevalent Multiple Sclerosis cases and 39,979 healthy controls were included. We discovered 72 proteins associated with Multiple Sclerosis at a Bonferroni-adjusted p-value of 0.05, including established markers such as Neurofilament Light Chain and Glial Fibrillary Acidic Protein. We observed a decrease in plasma Granzyme A, a marker of T cell and NK cell degranulation, which was specific to Multiple Sclerosis. Higher levels of plasma proteins involved in coagulation were associated with lower T2 lesion burden and preserved brain volume.InterpretationWe report the largest plasma proteomic screen of Multiple Sclerosis, replicating important known associations and suggesting novel markers, such as the reduction in granzyme A. While these findings require external validation, they demonstrate the power of biobank-scale datasets for discovering new biomarkers for Multiple Sclerosis.
Oral health vulnerability and its associated risk factors among tribal elderly people in Bangladesh: a pilot study
Authors: Barua Shomrita , Bosu Sunanda , Haque Mohammad Farhadul , Bosak Liza , Rashid Md Rezowan , Zaman Shaikh Riaduz , Rahman Md. Foyzur , Rahman Mohammad Meshbahur 
Published: July 2023

AbstractBackgroundTribal elderly is a vulnerable population due to their geographic location and lack of access to healthcare services. This study aims to assess the oral health status of tribal elderly in Bangladesh and identify any associated risk factors.MethodsThis cross-sectional pilot survey was conducted among 280 tribal elderlies aged 60 years and above residing in the main tribal residing region in Bangladesh. The data was collected through cluster sampling methods using a semi-structured questionnaire and oral examination. Different statistical tools including frequency distribution, Chi-square association test and multivariable logistic regression model were performed in data analysis.ResultsThe results showed that 25.35% of the tribal elderly had high DMFT score, indicating poor oral health. Respondents’ age, sex, marital status, occupational status, sweet eater, tobacco, and alcohol consumption were significantly associated with oral health. The major oral clinical sign and symptoms were dental carries, teeth sensitivity, loose teeth, broken teeth, calculus and staining in teeth, tongue pain and bad breath. The logistic regression analysis suggested that elderly aged 80 and above had 3.33 times more, males were 4.6 time less, tobacco user (smoked/smokeless) were 2.03 times more and alcohol consumers were 6.83 times more likely to experienced poor oral health condition than their counterparts.ConclusionsElderly individuals were found to be more likely to suffer from poor oral health condition than younger individuals, and certain lifestyle factors such as tobacco and alcohol consumption, meal frequency, and sweet consumption can further increase the risk of poor oral health condition.
Patterns of social-affective responses to trauma exposure and their relation to psychopathology
Authors: Thomas Sarah , Schäfer Judith , Kanske Philipp , Trautmann Sebastian 
Published: July 2023

IntroductionTraumatic event exposure is an important risk factor for the development and maintenance of psychopathology. Social-affective responses to trauma exposure (e.g. shame, guilt, revenge, social alienation) could moderate this relationship, but little is known about their relevance for different types of psychopathology. Moreover, the interplay of different social-affective responses in predicting psychopathology is poorly understood.MethodsIn a sample ofN=1321 trauma-exposed German soldiers, we examined cross-sectional associations of trauma-related social alienation, revenge, guilt and shame with both categorical (depressive disorder, alcohol use disorder, posttraumatic stress disorder) and dimensional (depression, anxiety) measures of psychopathology. Latent class analysis was conducted to identify possible patterns of trauma-related social-affective responses, and their relation to psychopathology.ResultsAll trauma-related social-affective responses predicted the presence of posttraumatic stress disorder, depressive disorder, alcohol use disorder and higher depressive and anxiety symptoms. Three latent classes were identified that fitted the data best, reflecting groups with (1) low, (2) moderate and (3) high risk for social-affective responses. The low-risk group demonstrated the lowest expressions on all psychopathology measures. Compared to the moderate-risk group, the high-risk group demonstrated no increased psychopathology.ConclusionsTrauma-related social alienation, shame, guilt, and revenge are characteristic of individuals with posttraumatic stress disorder, depressive disorder, alcohol use disorder, as well as with higher anxiety and depressive symptoms. There was little evidence for distinctive patterns of social-affective responses despite variation in the overall proneness to show trauma-related social-affective responses. Trauma-related social-affective responses could represent promising treatment targets which might be included in both cognitive and emotion-focused interventions.
Treatment of Acute Myocardial Infarction and Cardiogenic Shock: Outcomes of the RECOVER III Post-Approval Study by SCAI Shock Stage
Authors: Hanson Ivan , Rusia Akash , Palomo Andres , Tawney Adam , Pow Timothy , Dixon Simon R. , Meraj Perwaiz , Sievers Eric , Johnson Michael , Wohns David , Ali Omar , Kapur Navin , Grines Cindy , Burkhoff Daniel , Anderson Mark , Lansky Alexandra , Naidu Srihari S. , Basir Mir B , O’Neill William 
Published: July 2023

AbstractBackgroundThe Society for Cardiovascular Angiography and Interventions (SCAI) proposed a staging system (A-E) to predict prognosis in cardiogenic shock. Herein, we report clinical outcomes of the RECOVER III study for the first time, according to SCAI shock classification.MethodsRECOVER III is an observational, prospective, multicenter, single-arm, post-approval study of patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) undergoing percutaneous coronary intervention (PCI) with Impella support. Patients enrolled in RECOVER III were assigned a baseline SCAI shock stage. Staging was then repeated within 24 hours after initiation of Impella. Kaplan-Meier survival curve analyses were conducted to assess survival across SCAI shock stages at both timepoints.ResultsAt baseline assessment, 16.5%, 11.4%, and 72.2% were classified as Stage C, D, and E, respectively. At ≤24 hour assessment, 26.4%, 33.2%, and 40.0% were Stage C, D, and E respectively. Thirty-day survival amongst patients with Stage C, D and E shock at baseline was 59.7%, 56.5% and 42.9%, respectively (p=0.003). Survival amongst patients with Stage C, D and E shock at ≤24 hours was 65.7%, 52.1% and 29.5%, respectively (p<0.001). After multivariate analysis of impact of shock stage classifications at baseline and ≤ 24 hours, only Stage E classification at ≤24 hours was a significant predictor of mortality (OR 4.8, p<0.001).ConclusionsIn a real-world cohort of patients with AMICS undergoing PCI with Impella support, only Stage E classification at ≤ 24 hours was significantly predictive of mortality, suggesting that response to therapy may be more important than clinical severity of shock at presentation.Clinical PerspectiveMany patients with AMICS treated with Impella present in SCAI Stage E shock, but may improve to a more favorable shock stage within 24 hours of their presentation.In-hospital and 30-day outcomes correlate with SCAI shock stage at presentation, but the correlation is more robust upon repeat assessment within 24 hours after Impella initiation.The SCAI shock staging system may be a useful clinical tool to guide in-hospital management of patients with AMICS, especially within the first 24 hours, and to provide prognostic information to patients and/or their families.
Reversion of the inflammatory markers in patients with chronic limb threatening ischaemia
Authors: Ferreira Joana , Roque Susana , Carneiro Alexandre Lima , Longatto-Filho Adhemar , Vila Isabel , Cunha Cristina , Silva Cristina , Mesquita Amílcar , Cotter Jorge , Correia-Neves Margarida , Mansilha Armando , Cunha Pedro 
Published: July 2023

ABSTRACTIntroductionPeripheral arterial disease (PAD) affects over 202 million individuals worldwide, with 1.3% suffering from chronic limb-threatening ischaemia (CLTI). Atherosclerosis, characterized by intense inflammation, is the primary cause of PAD. Inflammation is linked to higher mortality rates, especially in CLTI patients. This study aims to compare the evolution of inflammatory markers between claudication and CLTI patients over three, six, and twelve months.MethodsA prospective, single-center observational study was conducted from January 2018 to July 2022. A PAD cohort was observed at admission and at three, six, and twelve months, with data on clinical, analytical, and inflammatory markers collected. The analyzed markers included positive acute phase proteins (C-reactive protein - CRP and fibrinogen) and negative acute phase proteins (albumin, total cholesterol, and high-density lipoprotein - HDL).ResultsThe study involved 119 subjects (mean age: 67.58 ± 9.60 years; 79.80% males), with 65 patients having claudication and 54 with CLTI. At admission, CLTI patients exhibited significantly higher serum levels of CRP and fibrinogen (positive acute phase proteins) and lower levels of albumin, total cholesterol, and HDL (negative acute phase proteins) compared to claudication patients. Three months after CLTI resolution, negative acute phase proteins increased, and positive acute phase proteins decreased. However, no significant changes in inflammatory proteins were observed in patients with claudication over time.ConclusionCLTI patients demonstrate an inflammatory state, which may have deleterious consequences and be partially reversible after the resolution of the ischemic process. Recognizing the potential for reversibility through revascularization/amputation underscores the significance of timely intervention.