bluuebunny/crossref_metadata_2025_split huggingface dataset:
From genome to phenome via the proteome: broad capture, antibody-based proteomics to explore disease mechanisms
Authors: Koprulu Mine , Carrasco-Zanini Julia , Wheeler Eleanor , Lockhart Sam , Kerrison Nicola D. , Wareham Nicholas J. , Pietzner Maik , Langenberg Claudia 
Published: August 2022

AbstractStudying the plasma proteome as the intermediate layer between the genome and the phenome has the potential to identify disease causing genes and proteins and to improve our understanding of the underlying mechanisms. Here, we conducted acis-focused proteogenomic analysis of 2,923 plasma proteins measured in 1,180 individuals using novel antibody-based assays (Olink® Explore 1536 and Explore Expansion) to identify disease causing genes and proteins across the human phenome. We describe 1,553 distinct credible sets of protein quantitative trait loci (pQTL), of which 256 contained cis-pQTLs not previously reported. We identify 224 cis-pQTLs shared with 578 unique health outcomes using statistical colocalization, including, gastrin releasing peptide (GRP) as a potential therapeutic target for type 2 diabetes. We observed convergence of phenotypic consequences of cis-pQTLs and rare loss-of-function gene burden for twelve protein coding genes (e.g.,TIMD4and low-density lipoprotein metabolism), highlighting the complementary nature of both approaches for drug target prioritization. Proteogenomic evidence also improved causal gene assignment at 40% (n=192) of overlapping GWAS loci, includingDKKL1as the candidate causal gene for multiple sclerosis.Our findings demonstrate the ability of broad capture, high-throughput proteomic technologies to robustly identify new gene-protein-disease links, provide mechanistic insight, and add value to existing GWASs by enabling and refining causal gene assignment.
Prevalence, Pattern and Risk Factors for Work-Related Musculoskeletal Disorders among Nigerian Plumbers
Authors: Mbada Chidozie E. , Abegunrin Aanuoluwa Feyisike , Egwu Michael Ogbonnia , Fatoye Clara Toyin , Moda Haruna , Falade Olatomiwa , Fatoye Francis 
Published: August 2022

AbstractPlumbing work is more manually driven in low-and-middle income countries (LMICs), and the prevalence of work-related musculoskeletal disorders (WMSDs) among workers who engage in plumbing in LMICs may be worse than earlier reports from developed countries. This study aimed to assess the prevalence, pattern and risk factors for work-related musculoskeletal disorders (WMSDs) among Nigerian plumbers.A total of 130 consenting plumber participated in this cross-sectional study. The Nordic Musculoskeletal questionnaire and the Job Factor Questionnaire were used to assess information on prevalence and pattern of WMSDs; and perceptions regarding work-related risks factors for WMSDs. Descriptive (mean, frequency, range, percentage and standard deviation) and inferential (Chi-square) statistics were used to analyze data. Alpha level was set at p<0.05.The mean age of the respondents is 36.56 + 10.418 years. The mean years of experience and working hours per day are 14.15 + 9.161 years and 8.28 + 2.512 hours. Job characteristics were mostly installation of pipes and fixtures (99.2%), equipment and fixtures prior to installation (96.9%), and testing of plumbing system for leaks (88.5%). 12-month and 7-day prevalence of WMSDS were 84.6% and 50.8%. Low-back (63.8%), neck (55.4%) and knee (50%) were the most affected body sites. Having WMSDs limits normal activities involving the low-back (32.3%), knee (25.4%) and neck (23.8%). There was significant association between 12-month prevalence of WMSDs and use of saws and pipe cutters (χ2 = 4.483; p = 0.034), while sites of affectation had significant association with 12-month and 7-day prevalence of WMSDs (p<0.05) respectively.Nigerian plumbers have a high prevalence of WMSDs affecting most commonly the low back, neck and knee. Plumbing job factors pose mild to moderate risk to developing WMSDs, and use of saws and pipe cutters significantly influence WMSDs.
Improving visual attention following right hemisphere stroke: A preliminary study
Authors: Edwards Grace , Buxbaum Laurel J. , Chen Gang , Edwards Dylan , Battelli Lorella 
Published: August 2022

AbstractLeft inattention is common in individuals following right cerebrovascular accident (RCVA). In neurotypical adults, we have previously found prolonged rightward visual attention resulted in a subsequent increase in leftward attention. Here we applied the same method in neurological patients with RCVA and found improved post-intervention attention both to the left and right of visual fixation in participants with mild to no leftward inattention in comparison to a control. No such benefit was detected in participants with more pronounced leftward inattention. Given the feasibility of the intervention which leverages performance in the right unaffected visual space, future studies should examine the longevity and generalizability of such an intervention to other attention demanding tasks.
Thermotaxis in an apolar, non-neuronal animal
Authors: Zhong Grace , Kroo Laurel , Prakash Manu 
Published: August 2022

AbstractNeuronal circuits are hallmarks of complex decision making processes in the animal world. How animals without neurons process information and respond to environmental cues promises a new window into studying precursors of neuronal control and origin of the nervous system as we know it today. Robust decision making in animals, such as in chemotaxis or thermotaxis, often requires internal symmetry breaking (such as A-P axis) provided naturally by a given body plan of an animal. Here we report the discovery of robust thermotaxis behavior in Trichoplax adhaerens, an early-divergent, enigmatic animal with no anterior-posterior symmetry breaking (apolar), and no known neurons or muscles. We present the first quantitative and robust behavioral response assay in placozoan, which present an apolar flat geometry. By exposing T. adhaerens to a thermal gradient under a long-term imaging setup, we observe robust thermotaxis that occurs over timescale of hours, independent of any circadian rhythms. We quantify that T. adhaerens can detect thermal gradients of at least 0.1 °C/cm. Positive thermotaxis is observed for a range of baseline temperatures from 17-22.5 °C with motility trajectories to be well-described by a Lévy distribution. Interestingly, the organism does not maintain a fixed orientation while performing thermotaxis. Utilizing natural diversity in size of adult organisms (100um to a few mm), we also demonstrate a critical animal size above which thermotaxis behavior is hindered. Several TRP family homologs have been previously reported to be conserved in metazoans, including in T. adhaerens. We discover naringenin, a known TRPM3 antagonist, inhibits thermotaxis in T. adhaerens. The discovery of robust thermotaxis in T. adhaerens provides a tractable handle to interrogate information processing in a brainless animal. Understanding how divergent marine animals process thermal cues is also critical due to rapid temperature rise in our oceans.
Texture coding in higher order somatosensory cortices of primates
Authors: Long Katie H. , Greenspon Charles M. , van Driesche Ashley , Lieber Justin D. , Bensmaia Sliman J. 
Published: August 2022

AbstractOur sense of touch confers to us the ability to perceive textural features over a broad range of spatial scales and material properties, giving rise to a complex sensory experience. To understand the neural basis of texture perception requires that the responses of somatosensory neurons be probed with stimuli that tile the space of spatial scales and material properties experienced during everyday interactions with objects. We have previously shown that neurons in early stages of somatosensory processing – the nerves and somatosensory cortex (S1) – are highly sensitive to texture and carry a representation of texture that is highly informative about the surface but also predicts the evoked sensory experience. In contrast, the texture signals in higher order areas – secondary somatosensory cortex (S2) and the parietal ventral area (PV) – have never been investigated with a rich and naturalistic textural set. To fill this gap, we recorded single-unit activity in S2/PV of macaques while they performed a texture discrimination task. We then characterized the neural responses to texture and compared these to their counterparts in somatosensory cortex (S1). We found that the representation of texture in S2/PV differs markedly from its counterpart in S1. In particular, S2/PV neurons carry a much sparser representation of texture identity and also information about task variables, including the animal’s eventual perceptual decision. S2/PV thus seems to carry a labile representation of texture that reflects task demands rather than faithfully encoding the stimulus.
Annotation of biologically relevant ligands in UniProtKB using ChEBI
Authors: Coudert Elisabeth , Gehant Sebastien , de Castro Edouard , Pozzato Monica , Baratin Delphine , Neto Teresa Batista , Sigrist Christian J.A. , Redaschi Nicole , Bridge Alan ,   The UniProt Consortium
Published: August 2022

AbstractMotivationTo provide high quality, computationally tractable annotation of binding sites for biologically relevant (cognate) ligands in UniProtKB using the chemical ontology ChEBI (Chemical Entities of Biological Interest), to better support efforts to study and predict functionally relevant interactions between proteins and small molecule ligands.ResultsWe structured the data model for cognate ligand binding site annotations in UniProtKB and performed a complete reannotation of all cognate ligand binding sites using stable unique identifiers from ChEBI, which we now use as the reference vocabulary for all such annotations. We developed improved search and query facilities for cognate ligands in the UniProt website, REST API and SPARQL endpoint that leverage the chemical structure data, nomenclature, and classification that ChEBI provides.AvailabilityBinding site annotations for cognate ligands described using ChEBI are available for UniProtKB protein sequence records in several formats (text, XML, and RDF), and are freely available to query and download through the UniProt website (www.uniprot.org), REST API (www.uniprot.org/help/api), SPARQL endpoint (sparql.uniprot.org/), and FTP site (https://ftp.uniprot.org/pub/databases/uniprot/).Contactalan.bridge@sib.swissSupplementary informationSupplementary Table 1.
3-D structure based prediction of SUMOylation sites
Authors: Ramtirtha Yogendra , Madhusudhan M. S. 
Published: August 2022

ABSTRACTSUMOylation is a posttranslational modification that involves lysine residues from eukaryotic proteins. Misregulation of the modification has been linked to neuro-degenrative diseases and cancer. All the presently available tools to predict SUMOylation sites are sequence based. Here, we propose a novel structure based prediction tool to discriminate between SUMOylated and non-SUMOylated lysines. We demonstrate the method by carrying out a proof-of-concept study. The method achieved an accuracy of 81% and a Matthews’ Correlation Coefficient of 0.4.
Mechanical and Heat Hyperalgesia upon Withdrawal from Chronic Intermittent Ethanol Vapor depends on Sex, Exposure Duration and Blood Alcohol Concentration in Mice
Authors: Brandner AJ , Baratta AM , Rathod RS , Ferguson C , Taylor BK , Farris SP 
Published: August 2022

AbstractApproximately half of patients with alcohol use disorder (AUD) report pain and this can be severe during withdrawal. However, many questions remain regarding the importance of sex, blood alcohol concentration (BAC), time course, and pain modality. To examine the impact of sex and BAC on the time course of the development of mechanical and heat hyperalgesia, we characterized a mouse model of Chronic Alcohol Withdrawal Induced Pain (CAWIP) in the presence or absence the alcohol dehydrogenase inhibitor, pyrazole. Male and female C57BL/6J mice underwent chronic intermittent ethanol vapor (CIEV) ± pyrazole exposure for 4 weeks, 4 days/week to induce ethanol dependence. Hind paw sensitivity to the plantar application of mechanical (von Frey filaments) and radiant heat stimuli were measured during weekly observations at 1, 3, 5, 7, 24, and 48 hr after cessation of ethanol exposure. In the presence of pyrazole, males developed mechanical hyperalgesia after the first week of CIEV exposure, peaking at 48 hours after cessation of ethanol. By contrast, females did not develop mechanical hyperalgesia until the fourth week; this also required pyrazole and did not peak until 48 hours. Heat hyperalgesia was consistently observed only in females exposed to ethanol and pyrazole; this developed after the first weekly session and peaked at 1 hour. We conclude that CAWIP develops in a sex –, time –, and BAC – dependent manner in C57BL/6J mice.
Exposure to a hypercaloric diet produces long lasting changes in motivation1
Authors: Zepeda-Ruiz Wendy Andrea , Abonza Paez Héctor Alan , Cerbon Marco , Velazquez Martinez David N. 
Published: August 2022

AbstractChanges in motivation have been observed following induction of diet-induced obesity. However, to date, results have been contradictory, some authors reporting an increase in motivation to obtain palatable food, but others observing a decrease. Observed differences might be associated with the length of both the evaluation period and exposure to the diet. Therefore, the aim of this study was to evaluate changes in motivation during 20 weeks of exposure to a hypercaloric diet. Performance of the subjects in a progressive ratio schedule was evaluated before and during the exposure to a high-fat, high-sugar choice diet (HFHSc). A decrease in motivation was observed after 2 weeks of diet exposure, low levels of motivation remained throughout 20 weeks. A comparable decrease in motivation took longer (3 weeks) to develop using chow diet in the control group. Overall, our results suggest that, when changes in motivation are being evaluated, long periods of diet exposure made no further contribution, once motivation decreased, it remained low up to 18 weeks. Exposure to a HFHSc diet is a useful animal model of obesity, since it replicates some pathophysiological and psychological features of human obesity such as an increase in fasting glucose levels, body weight and the weight of adipose tissue.
Uncovering personalised glucose responses and circadian rhythms from multiple wearable biosensors with Bayesian dynamical modelling
Authors: Phillips Nicholas E. , Collet Tinh-Hai , Naef Felix 
Published: August 2022

MotivationWearable biosensors measure physiological variables with high temporal resolution over multiple days and are increasingly employed in clinical settings, such as continuous glucose monitoring in diabetes care. Such datasets bring new opportunities and challenges, and patients, clinicians and researchers are today faced with a common challenge: how to best capture and summarise relevant information from multimodal wearable time series? Here, we aim to provide insights into individual blood glucose dynamics and their relationships with food and drink ingestion, time of day, and coupling with other physiological states such as physical and heart activity. To this end, we generate and analyse multiple wearable device data through the lens of a parsimonious mathematical model with interpretable components and parameters. A key innovation of our method is that the models are learnt on a personalised level for each participant within a Bayesian framework, which enables the characterisation of inter-individual heterogeneity in features such as the glucose response time following meals or underlying circadian rhythms. This framework may prove useful in other populations at risk of cardiometabolic diseases.SummaryWearable biosensors and smartphone applications can measure physiological variables over multiple days in free-living conditions. We measure food and drink ingestion, glucose dynamics, physical activity, heart rate (HR) and heart rate variability (HRV) in 25 healthy participants over 14 days. We develop a Bayesian framework to learn personal parameters that quantify circadian rhythms and physiological responses to external stressors. Modelling the effects of ingestion events on glucose levels reveals that slower glucose decay kinetics elicit larger postprandial glucose spikes, and we uncover a circadian baseline rhythm of glucose with high amplitudes in some individuals. Physical activity and circadian rhythms explain as much as 40-65% of the HR variance, whereas the variance explained for HRV is more heterogeneous across individuals (20-80%). A more complex model incorporating activity, HR and HRV explains up to 15% additional glucose variability, highlighting the relevance of integrating multiple biosensors to better predict glucose dynamics.
Transdiagnostic Clinical Features Delineate Trajectories of Serious Mental Illness
Authors: De la Hoz Juan F. , Arias Alejandro , Service Susan K. , Castaño Mauricio , Diaz-Zuluaga Ana M. , Song Janet , Gallego Cristian , Ruiz-Sánchez Sergio , Escobar Javier I , Bui Alex A. T. , Bearden Carrie E. , Reus Victor , Lopez-Jaramillo Carlos , Freimer Nelson B. , Olde Loohuis Loes M. 
Published: August 2022

AbstractBackgroundElectronic health record (EHR) databases, increasingly available in low- and middle-income countries (LMIC), provide an opportunity to study transdiagnostic features of serious mental illness (SMI) and delineate illness trajectories using clinical data.AimsCharacterize transdiagnostic features and diagnostic trajectories of SMI using structured and unstructured data from an EHR database in an LMIC institution.MethodsWe conducted a retrospective cohort study using EHR data from 2005-2022 at Clínica San Juan de Dios Manizales, a specialized mental health facility in Caldas, Colombia. We included 22,447 patients treated for schizophrenia (SCZ), bipolar disorder (BD), severe or recurrent major depressive disorder (MDD). We extracted diagnostic codes, clinical notes, and healthcare use data from the EHR database. Using natural language processing, we analyzed the frequency of suicidality and psychosis across SMI diagnoses. Using the diagnostic trajectories, we studied patterns of diagnostic switching and accumulation of comorbidities. Mixed-effect logistic regression was used to assess factors influencing diagnostic stability.ResultsHigh frequencies of suicidality and psychosis were observed across diagnoses of SCZ, BD, and MDD. Most SMI patients (64%) received multiple diagnoses over time, including switches between primary SMI diagnoses (19%), diagnostic comorbidities (30%), or both (15%). Predictors of diagnostic switching included mentions of delusions in clinical notes (OR=1.50, p=2e-18), prior diagnostic switching (OR=4.02, p=3e-250), and time in treatment, independent of age (log of visit number; OR=0.56, p=5e-66). Over 80% of patients reached diagnostic stability within six years of their first record.ConclusionsThis study demonstrates that integrating structured and unstructured EHR data can reveal clinically relevant, transdiagnostic patterns in SMI, including early predictors of disease trajectories. Our findings underscore the potential of EHR-based tools to aid etiological research and the development of personalized treatment strategies, particularly in LMIC.
Clinical profile of scrub typhus patients during COVID pandemic: A sub-Himalayan single center experience
Authors: Singh Moirangthem Bikram , Bahurupi Yogesh A. , Panda Prasan Kumar , Kalita Deepjyoti 
Published: August 2022

AbstractIntroductionScrub typhus is tropical zoonotic disease, commonly presented with multi organ dysfunction and high mortality rate in untreated patients. This study was done to identify clinical features commonly associated with scrub typhus during COVID pandemics, parameters associated with severe scrub typhus and mortality.MethodsThis retrospective study was done in a tertiary care hospital with a total of 52 admitted scrub typhus positive patients in October 2020 to February 2022. Diagnosis was established by scrub IgM ELISA or Rapid antigen test. The clinical and laboratory data, duration of hospital stay and outcomes were collected. Common clinical and laboratory findings were of descriptive analysis. Factors associated with mortality were analysed using Chi-square test.ResultsFever was the most common presenting symptoms on admission (94.2%) followed by respiratory abnormalities (38.46%). Acute kidney injury was the most common organ failure on admission (67.3%), followed by acute liver injury (46.2%) and thrombocytopenia (32.7%). MODS was seen in 46.15%. Of the total, 30.8% were admitted in ICU. Mortality was seen in 7.7% of all patients. On Chi-square analysis, altered mental status and coagulopathy were associated with significant mortality with p value <0.05.ConclusionScrub typhus can manifest with potentially life-threatening complications such as acute kidney injury, acute liver injury, thrombocytopenia and MODS. The overall case-fatality rate was 7.7%, and presence of altered mental status and coagulopathy were associated with higher mortality. As per literature, COVID has changed few clinical profiles of scrub typhus compared to same center experience before.
Somatic mosaic chromosomal alterations and death of cardiovascular disease causes among cancer survivors: an analysis of the UK Biobank
Authors: Sun Maxine , Cyr Marie-Christyne , Sandoval Johanna , Perreault Louis-Philippe Lemieux , Busque Lambert , Tardif Jean-Claude , Dubé Marie-Pierre 
Published: August 2022

ABSTRACTCancer survivors are at an increased risk of cardiovascular disease (CVD) compared to the general population. Here, we evaluated the impact of somatic mosaic chromosomal alterations (mCAs) on death of CVD causes, coronary artery disease (CAD) causes, from cancer, and of any cause in patients with a cancer diagnosis within the UK Biobank (n=48 919). mCAs were derived from DNA genotyping array intensity data and long-range chromosomal phase inference from participants. Overall, 10 070 individuals (20.6%) carried ≥1 mCA clone. In adjusted analyses, mCA was associated with an increased risk of death of CAD causes (hazard ratio [HR]: 1.37, 95% confidence interval [CI]: 1.09-1.71, P=0.006), from cancer (HR: 1.06, 95% CI: 1.00-1.11, P=0.041), and death of any cause (HR: 1.07, 95% CI: 1.02-1.12, P=0.005). Among cancer survivors, carriers of any mCA are at an increased risk of death of CAD causes and of any cause as compared to non-carriers.