bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topic modelling with ICD10-informed priors identifies novel genetic loci associated with multimorbidities in UK Biobank
Authors: Zhang Yidong , Jiang Xilin , Mentzer Alexander J , McVean Gil , Lunter Gerton 
Published: October 2022

SummaryStudies of disease incidence have identified thousands of genetic loci associated with complex traits. However, many diseases occur in combinations that can point to systemic dysregulation of underlying processes that affect multiple traits. We have developed a data-driven method for identifying such multimorbidities from routine healthcare data that combines topic modelling through Bayesian binary non-negative matrix factorization with an informative prior derived from the hierarchical ICD10 coding system. Through simulation we show that the method, treeLFA, typically outperforms both Latent Dirichlet Allocation (LDA) and topic modelling with uninformative priors in terms of inference accuracy and generalisation to test data, and is robust to moderate deviation between the prior and reality. By applying treeLFA to data from UK Biobank we identify a range of multimorbidity clusters in the form of disease topics ranging from well-established combinations relating to metabolic syndrome, arthropathies and cancers, to other less well-known ones, and a disease-free topic. Through genetic association analysis of inferred topic weights (topic-GWAS) and single diseases we find that topic-GWAS typically finds a much smaller, but only partially-overlapping, set of variants compared to GWAS of constituent disease codes. We validate the genetic loci (only) associated with topics through a range of approaches. Particularly, with the construction of PRS for topics, we find that compared to LDA, treeLFA achieves better prediction performance on independent test data. Overall, our findings indicate that topic models are well suited to characterising multimorbidity patterns, and different topic models have their own unique strengths. Moreover, genetic analysis of multimorbidity patterns can provide insight into the aetiology of complex traits that cannot be determined from the analysis of constituent traits alone.
PREVALENCE AND FACTORS ASSOCIATED WITH ASYMPTOMATIC HYPOGLYCEMIA AMONG PRETERM NEWBORNS IN DAR ES SALAAM REGIONAL REFERRAL HOSPITALS, TANZANIA: A CROSS SECTIONAL ANALYTICAL STUDY PROTOCOL
Authors: Salum Shani Shamsi , Kalabamu Florence Salvatory , Fataki Maulidi Rashid , Omary Salha Ally , Mohamed Ummulkheir Hamid , Kizwi Hillary Abdillah , Leshabari Kelvin Melkizedeck 
Published: October 2022

AbstractBackgroundHypoglycemia is the most common metabolic abnormality in newborns. It is still unclear whether the condition is truly pathological, especially if it occurs transiently during the 1st 24 hours of birth in an asymptomatic phase. Besides, there is hardly any data on the burden of asymptomatic neonatal hypoglycemia and its associated factors among preterm newborns in Africa.AimTo assess the prevalence and associated factors of asymptomatic neonatal hypoglycemia among preterm newborns in a typical African settings.Design and MethodsWe plan to conduct a quick, cross-sectional analytical hospital-based survey at all public regional referral hospitals in Dar es Salaam, Tanzania. We will consider all preterm newborns delivered in the specified settings between June 2022 and December 2022. Our study population will be all preterm newborns delivered at Dar es Salaam public regional referral hospitals. Our target population will be all preterm newborns with asymptomatic hypoglycemia. All newborns with clinically detected congenital anomalies and those who will be delivered at home but brought to the facilities for care will thus be excluded from the study. Our primary outcome measure will be neonatal RBG < 2.6 mmol/L without any symptoms associated with hypoglycemia. Maternal, fetal and early neonatal (> 6 hours but within 24 hours post-delivery) factors will be logistically regressed against the outcome variable after appropriate model validation. Unless otherwise stated, an α-level of 5% will be used as a limit of type I error in findings. Written informed consent will be obtained from mothers of each newborn prior to inclusion into the study.Main Outcome measurePrevalence of asymptomatic hypoglycemia among preterm newborns in Dar es Salaam hospitals.Relevance of the findings to science, policy & practiceCurrent clinical practice does not provide evidence for routine glycaemic screening among preterm newborns asymptomatic for hypoglycemia. The study will have a potential to assess stata of preterm newborn with asymptomatic hypoglycemia
Potential risk polarization for acute myocardial infarction during the COVID-19 pandemic: Single-center experiences in Osaka, Japan
Authors: Furui Masato , Kawajiri Kenji , Yoshida Takeshi , Kakii Bunpachi , Oshiro Norikazu , Asanuma Mai , Nishioka Hiroaki , Wada Hideichi 
Published: October 2022

AbstractThis study compared the time course and outcomes of acute myocardial infarction, including mechanical complications and hospital mortality, before and after the coronavirus disease 2019 (COVID-19) pandemic at a regional core hospital in South Osaka, Japan. Moreover, it identified predictors for hospital mortality and mechanical complications. In total, 503 patients who underwent emergency percutaneous coronary intervention between January 2011 and December 2021 at our institution were examined retrospectively. The time course of acute myocardial infarction, mechanical complications, and mortality rate before and after the COVID-19 emergency declaration were compared. Overall, 426 patients with ST-segment elevation myocardial infarction and 77 patients with non-ST-segment elevation myocardial infarction were identified. For patients with ST-segment elevation myocardial infarction, the onset-to-door time was longer (181 vs. 156 min, P = 0.001) and mechanical complications were worse (7.8% vs. 2.6%, P = 0.025) after the emergency declaration of COVID-19 than before the pandemic. Age, low ejection fraction, out-of-hospital cardiac arrest, and mechanical complications were identified as independent risk factors for hospital mortality among patients with ST-segment elevation myocardial infarction, using multivariable analysis. Post-declaration, age, walk-ins, referrals, and intra-aortic balloon pump use were independent predictors of mechanical complications among patients with ST-segment elevation myocardial infarction. Onset-to-door time and mechanical complication rate increased after the COVID-19 declaration among patients with ST-segment elevation myocardial infarction. Arrival by walk-in and a referral that caused treatment delay were identified as independent risk factors for mechanical complication, in addition to age, use of intra-aortic balloon pump, and post-declaration of COVID-19. Therefore, the risks posed by the COVID-19 pandemic might have a polarization tendency resulting from the relief or worsening of cardiac symptoms.
Association of gamma-glutamyl transferase variability with risk of osteoporotic fractures: A nationwide cohort study
Authors: Kim Dongyeop , Kim Jee Hyun , Lee Heajung , Hong Iksun , Chang Yoonkyung , Song Tae-Jin 
Published: October 2022

AbstractObjectivesGamma-glutamyl transferase (GGT) is related to inflammation, osteoporosis, and vascular diseases. Recently, changes in metabolic parameters have been proposed as disease biomarkers. We aimed to assess longitudinally the association of GGT variability with osteoporotic fractures.MethodsFrom the National Health Insurance Service-Health Screening Cohort database, participants who underwent three or more health examinations between 2003 and 2008 were included (n=1,072,432). Variability indexes were as follows: (1) coefficient of variation (CV), (2) standard deviation (SD), and (3) variability independent of the mean (VIM). The primary outcome was occurrence of osteoporotic fracture, defined as identification of one of the following international classification of diseases-10 codes: vertebral fracture (S22.0, S22.1, S32.0, S32.7, T08, M48.4, M48.5, M49.5), hip fracture (S72.0, S72.1), distal radius fracture (S52.5, S52.6), or humerus fracture (S42.2, S42.3).ResultsDuring a median of 12.3 years (interquartile range 12.1 – 12.6), osteoporotic fractures occurred in 49,677 (4.6%) participants. In multivariable analysis, GGT variability based on CV positively correlated with the occurrence of osteoporotic fracture (adjusted hazard ratio [HR] of the highest quartile compared with the lowest quartile 1.15, 95% confidence interval [CI] 1.12-1.18,P< 0.001). These results were consistent even when GGT variability was defined by SD (adjusted HR 1.22, 95% CI 1.19-1.25,P< 0.001) and VIM (adjusted HR 1.12, 95% CI 1.09-1.15,P< 0.001).ConclusionsIncreased GGT variability is associated with an increased risk of osteoporotic fractures in the Korean population. Maintaining constant and stable GGT level may help reduce the risk of osteoporotic fractures.
Diencephalic or hippocampal amnesia – different etiologies, common mechanisms
Authors: Segobin Shailendra , Ambler Melanie , Laniepce Alice , Platel Hervé , Chételat Gael , Groussard Mathilde , Pitel Anne-Lise 
Published: October 2022

ABSTRACTObjectivesTo compare regional volume deficits within the Papez circuit in Alzheimer’s disease (AD) and Korsakoff’s syndrome (KS), taking into account the neurodegenerative nature of AD.Methods18 KS patients, 40 AD patients (20 with Moderate AD (MAD) matched on cognitive deterioration with KS patients and 20 with Severe AD (SAD)), and 70 healthy controls underwent structural MRI examination. Volumes of the hippocampi, thalami, cingulate gyri, mammillary bodies (MB) and mammillothalamic tracts (MTT) were extracted.ResultsFor the anterior and posterior cingulate gyri, and anterior thalamic nuclei, all patient groups were significantly affected compared to controls but did not differ between each other. Lower volumes were observed in all patient groups compared to controls in the entire thalamus, mediodorsal thalamic nuclei and MB, but these regions were more severely damaged in KS compared to AD. MTT volumes were significantly damaged in KS only. Hippocampi were affected in all patient groups but more severely in the SAD than in the KS and MAD.InterpretationThe specificity of KS compared to AD relies on the severity of the MB and mediodorsal nuclei shrinkage, as well as the atrophy of the MTT. Several nodes of the Papez circuit were damaged to the same extent in AD and KS: the anterior thalamic nuclei, the cingulate cortex and the hippocampus (in MAD only). Our results encourage considering common mechanisms in the pathophysiology of amnesia regardless of etiology and question the relevance of the classical distinction between hippocampal and diencephalic amnesia.
Low back pain service utilization and costs: association with number of visits of chiropractic manipulation, active care, manual therapy or acupuncture. A retrospective cohort study
Authors: Elton David , Zhang Meng 
Published: October 2022

AbstractBackgroundFor individuals with low back pain (LBP), in the absence of serious pathology clinical practice guidelines (CPG) recommend a stepped approach to management with first-line emphasis on natural history, self-care, and non-pharmaceutical therapies. For individuals with non-surgical LBP initially contacting a chiropractor (DC), physical therapist (PT), or licensed acupuncturist (LAc), the purpose of this retrospective cohort study was to examine the dose response association between the number of visits of chiropractic manipulative therapy (CMT), active care (AC), manual therapy (MT), or acupuncture, exposure to second- and third-line services, and total episode cost.MethodsA national sample of individuals with a single episode of non-surgical LBP occurring in 2017-2019 was analyzed using episode of care as the unit of analysis. The primary independent variables were initial contact with either a DC, PT, or LAc, and the number of visits of CMT, AC, MT, or acupuncture. Dependent measures included rate and timing of use of 13 types of health care services and total episode cost.Results132,199 continuously insured individuals aged 18 years and older initially contacted 21,336 different DCs, 2,734 PTs and 1,339 LAcs for a single episode of non-surgical LBP. These individuals were associated with $62,185,930 in expenditures. The most common number of visits was 1 to 3 - CMT (48.2% of episodes), AC (29.7%), MT (32.1%), and acupuncture (27.0%). For each service, 1 to 3 visits was associated with the lowest rate of exposure to second- and third-line services although rate differences between visit dose categories were generally not significant or clinically. Episode total cost and duration increased significantly with increasing number of visits. CMT was associated with lowest median total episode cost at each level of visit utilization.ConclusionsFor non-surgical LBP episodes initially contacting a DC, PT or LAc, 1 to 3 visits of CMT, AC, MT, or acupuncture was the most common level of utilization, associated with the lowest exposure to second- and third-line services and lowest total episode cost. Among, CMT, AC, MT, and acupuncture, CMT was associated with the lowest total episode cost at each level of utilization. A higher number of visits of CMT, AC, MT or acupuncture was associated with significantly higher total cost, without meaningful impact on exposure to second- or third-line services. Unmeasured clinical benefits may be associated with higher visit counts and warrants further study.
Prediction of atrial fibrillation and stroke using machine learning models in UK Biobank
Authors: Papadopoulou A. , Harding D. , Slabaugh G. , Marouli E. , Deloukas P. 
Published: October 2022

AbstractWe employed machine learning (ML) approaches to evaluate 2,199 clinical features and disease phenotypes available in the UK Biobank as predictors for Atrial Fibrillation (AF) risk. After quality control, 99 features were selected for analysis in 21,279 prospective AF cases and equal number of controls. Different ML methods were employed, including LightGBM, XGBoost, Random Forest (RF), Deep Neural Network (DNN),) and Logistic Regression with L1 penalty (LR). In order to eliminate the black box character of the tree-based ML models, we employed Shapley-values (SHAP), which are used to estimate the contribution of each feature to AF prediction. The area-under-the-roc-curve (AUROC) values and the 95% confidence intervals (CI) per model were: 0.729 (0.719, 0.738) for LightGBM, 0.728 (0.718, 0.737) for XGBoost, 0.716 (0.706,0.725) for DNN, 0.715 (0.706, 0.725) for RF and 0.622 (0.612, 0.633) for LR. Considering the running time, memory and stability of each algorithm, LightGBM was the best performing among those examined. DeLongs test showed that there is statistically significant difference in the AUROCs between penalised LR and the other ML models. Among the top important features identified for LightGBM, using SHAP analysis, are the genetic risk score (GRS) of AF and age at recruitment. As expected, the AF GRS had a positive impact on the model output, i.e. a higher AF GRS increased AF risk. Similarly, age at recruitment also had a positive impact increasing AF risk. Secondary analysis was performed for the individuals who developed ischemic stroke after AF diagnosis, employing 129 features in 3,150 prospective cases of people who developed ischemic stroke after AF, and equal number of controls in UK Biobank. The AUC values and the 95% CI per model were: 0.631 (0.604, 0.657) for XGBoost, 0.620 (0.593, 0.647) for LightGBM, 0.599 (0.573, 0.625) for RF, 0.599 (0.572, 0.624) for SVM, 0.589 (0.562, 0.615) for DNN and 0.563 (0.536, 0.591) for penalised LR. DeLongs test showed that there is no evidence for significant difference in the AUROCs between XGBoost and all other examined ML models but the penalised LR model (pvalue=2.00 E-02). Using SHAP analysis for XGBoost, among the top important features are age at recruitment and glycated haemoglobin. DeLongs test showed that there is evidence for statistically significant difference between XGBoost and the current clinical tool for ischemic stroke prediction in AF patients, CHA2DS2-VASc (pvalue=2.20E-06), which has AUROC and 95% CI of 0.611 (0.585, 0.638).
Engineered vasculature induces functional maturation of pluripotent stem cell-derived islet organoids
Authors: Nguyen-Ngoc Kim-Vy , Jun Yesl , Sai Somesh , Bender R. Hugh F. , Kravets Vira , Zhu Han , Hatch Christopher J. , Schlichting Michael , Gaetani Roberto , Mallick Medhavi , Hachey Stephanie J. , Christman Karen L. , George Steven C. , Hughes Christopher C.W. , Sander Maike 
Published: October 2022

AbstractBlood vessels play a critical role in pancreatic islet health and function, yet current culture methods to generate islet organoids from human pluripotent stem cells (SC-islets) lack a vascular component. Here, we engineered 3D vascularized SC-islet organoids by assembling SC-islet cells, human primary endothelial cells (ECs) and fibroblasts both in a non-perfused model and a microfluidic device with perfused vessels. Vasculature improved stimulus-dependent Ca2+influx into SC-β-cells, a hallmark of β-cell function that is blunted in non-vascularized SC-islets. We show that an islet-like basement membrane is formed by vasculature and contributes to the functional improvement of SC-β-cells. Furthermore, cell-cell communication networks based on scRNA-seq data predicted BMP2/4-BMPR2 signaling from ECs to SC-β-cells. Correspondingly, BMP4 augmented the SC-β-cell Ca2+response and insulin secretion. These vascularized SC-islet models will enable further studies of crosstalk between β-cells and ECs and can serve asin vivo-mimicking platforms for disease modeling and therapeutic testing.
Versatile methanotrophs form an active methane biofilter in the oxycline of a seasonally stratified coastal basin
Authors: Venetz Jessica , Żygadłowska Olga M. , Lenstra Wytze K. , van Helmond Niels A.G.M. , Nuijten Guylaine H.L. , Wallenius Anna J. , Martins Paula Dalcin , Slomp Caroline P. , Jetten Mike S.M. , Veraart Annelies J. 
Published: October 2022

AbstractThe potential and drivers of microbial methane removal in the water column of seasonally stratified coastal ecosystems and the importance of the methanotrophic community composition for ecosystem functioning are not well explored. Here, we combined depth profiles of oxygen and methane with 16S rRNA gene amplicon sequencing, metagenomics, and methane oxidation rates at discrete depths in a stratified coastal marine system (Lake Grevelingen, The Netherlands). Three amplicon sequence variants (ASVs) belonging to different genera of aerobicMethylomonadaceaeand the corresponding three methanotrophic metagenome-assembled genomes (MOB-MAGs) were retrieved by 16S rRNA sequencing and metagenomic analysis respectively. The abundances of the different methanotrophic ASVs and MOB-MAGs peaked at different depths along the methane oxygen counter-gradient and the MOB-MAGs show a quite diverse genomic potential regarding oxygen metabolism, partial denitrification, and sulfur metabolism. Moreover, potential aerobic methane oxidation rates indicated high methanotrophic activity throughout the methane oxygen counter-gradient, even at depths with lowin situmethane or oxygen concentration. This suggests that niche-partitioning with high genomic versatility of the presentMethylomonadaceaemight contribute to the functional resilience of the methanotrophic community and ultimately the efficiency of methane removal in the stratified water column of marine Lake Grevelingen.
Visual Occlusions Result in Phase Synchrony Within Multiple Brain Regions Involved in Sensory Processing and Balance Control
Authors: Symeonidou Evangelia-Regkina , Ferris Daniel P. 
Published: October 2022

AbstractThere is a need to develop appropriate balance training interventions to minimize the risk of falls. Recently, we found that intermittent visual occlusions can substantially improve the effectiveness and retention of balance beam walking practice (Symeonidou and Ferris 2022). We sought to determine how the intermittent visual occlusions affect electrocortical activity during beam walking. We hypothesized that areas involved in sensorimotor processing and balance control would demonstrate spectral power changes and inter-trial coherence modulations after loss and restoration of vision. Ten healthy young adults practiced walking on a treadmill-mounted balance beam while wearing high-density EEG and experiencing reoccurring visual occlusions. Results revealed spectral power fluctuations and inter-trial coherence changes in the visual, occipital, temporal, and sensorimotor cortex as well as the posterior parietal cortex and the anterior cingulate. We observed a prolonged alpha increase in the occipital, temporal, sensorimotor, and posterior parietal cortex after the occlusion onset. In contrast, the anterior cingulate showed a strong alpha and theta increase after the occlusion offset. We observed transient phase synchrony in the alpha, theta, and beta bands within the sensory, posterior parietal, and anterior cingulate cortices immediately after occlusion onset and offset. Our results provide support for cross-modal phase resetting and enhanced processing in areas involved in sensory processing and balance control as an explanation for increased long-term balance improvement when training with intermittent visual occlusions. Our training intervention could be implemented in senior and rehabilitation centers, improving the quality of life of elderly and neurologically impaired individuals.
Comparative analysis of primary auditory cortical responses in bats and mice to repetitive stimuli trains
Authors: Deane Katrina E. , García-Rosales Francisco , Klymentiev Ruslan , Hechavarria Julio C. , Happel Max F. K. 
Published: October 2022

AbstractThe brains of black 6 mice (Mus musculus) and Seba’s short-tailed bats (Carollia perspicillata) weigh roughly the same and share mammalian neocortical laminar architecture. Bats have highly developed sonar calls and social communication and are an excellent neuroethological animal model for auditory research. Mice are olfactory and somatosensory specialists, used frequently in auditory neuroscience for their advantage of standardization and wide genetic toolkit. This study presents an analytical approach to overcome the challenge of inter-species comparison with existing data. In both data sets, we recorded with linear multichannel electrodes down the depth of the primary auditory cortex (A1) while presenting repetitive stimuli trains at ~5 and ~40 Hz to awake bats and mice. We found that while there are similarities between cortical response profiles in both, there was a better signal to noise ratio in bats under these conditions, which allowed for a clearer following response to stimuli trains. Model fit analysis supported this, illustrating that bats had stronger response amplitude suppression to consecutive stimuli. Additionally, continuous wavelet transform revealed that bats had significantly stronger power and phase coherence during stimulus response and mice had stronger power in the background. Better signal to noise ratio and lower intertrial phase variability in bats could represent specialization for faster and more accurate temporal processing at lower metabolic costs. Our findings demonstrate a potentially different general auditory processing principle; investigating such differences may increase our understanding of how the ecological need of a species shapes the development and function of its nervous system.