bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated NMR and MS analysis of plasma metabolome reveals major changes in inflammatory markers, one-carbon, lipid, and amino acid metabolism in severe and fatal COVID-19 subjects
Authors: Gama-Almeida Marcos C. , Teixeira Lívia , Hottz Eugenio D. , Ivens Paula , Ribeiro Hygor , Pinto Gabriela D. A. , Garrett Rafael , Torres Alexandre G. , Carneiro Talita I. A. , Barbalho Bianca de O , Ludwig Christian , Struchiner Claudio J. , Assunção-Miranda Iranaia , Valente Ana Paula C. , Bozza Fernando A. , Bozza Patrícia T. , dos Santos Gilson C. , El-Bacha Tatiana 
Published: May 2023

AbstractBrazil has the second highest COVID-19 death rate while Rio de Janeiro is among the states with the highest rate in the country. Although effective vaccines have been developed, it is anticipated that the ongoing COVID-19 pandemic will transition into an endemic state. Under this scenario, it is worrisome that the underlying molecular mechanisms associated with the disease clinical evolution from mild to severe, as well as the mechanisms leading to long COVID are not yet fully understood. In this study,1H Nuclear Magnetic Resonance spectroscopy and Liquid Chromatography-Mass spectrometry-based metabolomics were used to identify potential pathways and metabolites involved in COVID-19 pathophysiology and disease outcome. We prospectively enrolled 35 severe RT-PCR confirmed COVID-19 cases within 72 hours from intensive care unit admission, between April and July 2020 from two reference centers in Rio de Janeiro, and 12 samples from non-infected control subjects. Of the 35 samples from COVID-19 patients, 18 were from survivors and 17 from non-survivors. We observed that patients with severe COVID-19 had their plasma metabolome significantly changed if compared to control subjects. We observed lower levels of glycerophosphocholine and other choline-related metabolites, serine, glycine, and betaine, indicating a dysregulation in methyl donors and one-carbon metabolism. Importantly, non-survivors had higher levels of creatine/creatinine, 4-hydroxyproline, gluconic acid andN-acetylserine compared to survivors and controls, reflecting uncontrolled inflammation, liver and kidney dysfunction, and insulin resistance in these patients. Lipoprotein dynamics and amino acid metabolism were also altered in severe COVID-19 subjects. Several changes were greater in women, thus patient’s sex should be considered in pandemic surveillance to achieve better disease stratification and improve outcomes. The incidence of severe outcome after hospital discharge is very high in Brazil, thus these metabolic alterations may be used to monitor patients’ organs and tissues and to understand the pathophysiology of long-post COVID-19.
Prognostic value of flow-mediated dilation and computed tomography angiography findings for determining cardiovascular risk in patients with subclinical atherosclerosis
Authors: Kawai Hideki , Sarai Masayoshi , Sugimoto Kunihiko , Motoyama Sadako , Sato Yoshihiro , Nagahara Yasuomi , Miyajima Keiichi , Matsuyama Takahiro , Takahashi Hiroshi , Yamada Akira , Naruse Hiroyuki , Toyama Hiroshi , Ozaki Yukio , Izawa Hideo 
Published: May 2023

AbstractBackgroundFlow-mediated dilation (FMD) tests endothelial function, and computed tomography angiography (CTA) estimates the extent of coronary atherosclerosis and plaque vulnerability. This study aimed to examine the prognostic value of combining FMD and CTA in patients with no history of atherosclerotic disease.MethodsThe study retrospectively examined patients who underwent CTA and FMD within 3 months between 2012 and 2020. Patients with a history of cardio-cerebrovascular disease or significant stenoses on CTA were excluded. The study endpoint was defined as major cardiac and cerebrovascular events (MACCE): a composite of cardio-cerebrovascular death, acute coronary syndrome, fatal arrhythmia, ischaemic and haemorrhagic stroke, and late revascularisation of the coronary or carotid arteries 6 months after CTA. Finally, the patients were stratified into four groups based on the following factors: FMD <6.0%, per cent atheroma volume (PAV) ≥21.0%, and the presence of high-risk plaques (HRPs).ResultsDuring a mean follow-up of 4.7 years, MACCE occurred in 19 of 154 patients (mean age: 61.0±12.9 years, 89 males). FMD, PAV, and HRPs were independent predictors of MACCE after adjusting for age, sex, and hypertension. Compared with the patients with 0 points, hazard ratios of those with 1, 2, and 3 points were 2.76 (P=0.322), 9.89 (P=0.004), and 28.43 (P<0.001), respectively. Adding FMD, PAV, and HRPs to the baseline model, including age, sex, and hypertension, improved the C-index (0.712–0.831, P=0.023).ConclusionsAlthough FMD and CTA findings are useful for predicting cardiovascular events, their combination synergises their prognostic abilities.
Associations between rheumatoid arthritis clinical factors with synovial cell types and states
Authors: Weisenfeld Dana , Zhang Fan , Donlin Laura , Jonsson Anna Helena , Apruzzese William , Campbell Debbie ,   Accelerating Medicines Partnership Program: Rheumatoid Arthritis Network, Holers V. Michael , Gravallese Ellen , Moreland Larry , Goodman Susan , Brenner Michael , Raychaudhuri Soumya , Filer Andrew , Anolik Jennifer , Bykerk Vivian , Liao Katherine P. 
Published: May 2023

ABSTRACTObjectiveRecent studies have uncovered diverse cell types/states in the RA synovium; however limited data exist correlating these findings with patient-level clinical information. Using the largest cohort to date with clinical and multi-cell data, we determined associations between RA clinical factors with cell types/states in the RA synovium.MethodsThe Accelerated Medicines Partnership Rheumatoid Arthritis study recruited subjects with active RA on no DMARDs or inadequate response to methotrexate (MTX) or tumor necrosis factor inhibitors. RA clinical factors were systematically collected. Biopsies were performed on an inflamed joint and tissue disaggregated and processed with a CITE-seq pipeline from which cell type percentages and cell type abundance phenotypes (CTAP) were derived: endothelial/fibroblast/myeloid (EFM), fibroblasts (F), myeloid (M), T/B cells (TB), T cells/fibroblasts (TF), T/myeloid cells (TM). Correlations were measured between RA clinical factors, % cell type, and CTAPs.ResultsWe studied 72 subjects, mean age 57 years, 75% female, 83% seropositive, mean RA duration 6.6 years, mean DAS28-CRP3 4.8. Higher DAS28-CRP3 correlated with higher % T cells (p<0.01). Subjects on MTX not on bDMARD had higher %B cells vs no DMARDs (p<0.01). The majority of subjects on bDMARDs were categorized as EFM (57%), while none were TF. No significant difference was observed across CTAPs for age, sex, RA disease duration, DAS28-CRP3.ConclusionIn this comprehensive screen of clinical factors, we observed differential associations between DMARDs and cell phenotypes, suggesting that RA therapies, more than other clinical factors may impact cell type/state in the synovium and ultimately response to subsequent therapies.
Researching COVID to enhance recovery (RECOVER) autopsy tissue pathology study protocol: Rationale, objectives, and design
Authors: Troxel Andrea B. , Bind Marie-Abele C. , Flotte Thomas J. , Cordon-Cardo Carlos , Decker Lauren A. , Finn Aloke V. , Padera Robert F. , Reichard R. Ross , Stone James R. , Adolphi Natalie L. , Casimero Faye Victoria C. , Crary John F. , Elifritz Jamie , Faustin Arline , Ghosh Saikat Kumar B. , Krausert Amanda , Martinez-Lage Maria , Melamed Jonathan , Mitchell Roger A. , Sampson Barbara A. , Seifert Alan C. , Simsir Aylin , Adams Cheryle , Haasnoot Stephanie , Hafner Stephanie , Siciliano Michelle A. , Vallejos Brittany B. , Boccio Phoebe Del , Lamendola-Essel Michelle F. , Young Chloe E. , Kewlani Deepshikha , Akinbo Precious A. , Parent Brendan , Chung Alicia , Cato Teresa C. , Mudumbi Praveen C. , Esquenazi-Karonika Shari , Wood Marion J. , Chan James , Monteiro Jonathan , Shinnick Daniel J. , Thaweethai Tanayott , Nguyen Amber N. , Fitzgerald Megan L. , Perlowski Alice A. , Stiles Lauren E. , Paskett Moira L. , Katz Stuart D. , Foulkes Andrea S. 
Published: May 2023

AbstractImportanceSARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or organ dysfunction after the acute phase of infection, termed Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are poorly understood. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Tissue Pathology Study (RECOVER-Pathology) are to: (1) characterize prevalence and types of organ injury/disease and pathology occurring with PASC; (2) characterize the association of pathologic findings with clinical and other characteristics; (3) define the pathophysiology and mechanisms of PASC, and possible mediation via viral persistence; and (4) establish a post-mortem tissue biobank and post-mortem brain imaging biorepository.MethodsRECOVER-Pathology is a cross-sectional study of decedents dying at least 15 days following initial SARS-CoV-2 infection. Eligible decedents must meet WHO criteria for suspected, probable, or confirmed infection and must be aged 18 years or more at the time of death. Enrollment occurs at 7 sites in four U.S. states and Washington, DC. Comprehensive autopsies are conducted according to a standardized protocol within 24 hours of death; tissue samples are sent to the PASC Biorepository for later analyses. Data on clinical history are collected from the medical records and/or next of kin. The primary study outcomes include an array of pathologic features organized by organ system. Casual inference methods will be employed to investigate associations between risk factors and pathologic outcomes.DiscussionRECOVER-Pathology is the largest autopsy study addressing PASC among US adults. Results of this study are intended to elucidate mechanisms of organ injury and disease and enhance our understanding of the pathophysiology of PASC.Clinicaltrials.govnumber:NCT05292274
Classifying Glaucoma Using Machine Learning Techniques
Authors: Santos Dheiver Francisco 
Published: May 2023

ABSTRACTGlaucoma is a common eye disease that can lead to blindness if not detected and treated early. In this paper, we present a machine learning-based approach for classifying glaucoma. We use a publicly available dataset of retinal images and extract features using convolutional neural networks. We compare the performance of different classifiers, including random forest, support vector machine, and XGBoost, and evaluate their accuracy, precision, recall, and F1 score. Our results show that the XGBoost classifier achieves the highest accuracy and F1 score, indicating its potential for diagnosing glaucoma in clinical practice.
Improving patient flow through hospitals with machine learning based discharge prediction
Authors: Wei Jia , Zhou Jiandong , Zhang Zizheng , Yuan Kevin , Gu Qingze , Luk Augustine , Brent Andrew J , Clifton David A. , Walker A. Sarah , Eyre David W. 
Published: May 2023

AbstractAccurate predictions of hospital discharge events could help improve patient flow through hospitals and the efficiency of care delivery. However, the potential of integrating machine learning with diverse electronic health records (EHR) data for this task has not been fully explored. We used EHR data from 01 February 2017 to 31 January 2020 in Oxfordshire, UK to predict hospital discharges in the next 24 hours. We fitted separate extreme gradient boosting models for elective and emergency admissions, trained using the first two years of data and tested using the final year of data. We examined individual-level and hospital-level model performance and evaluated the impact of training data size and recency, prediction time of day, and performance in different subgroups. Our individual patient level models for elective and emergency admissions achieved AUCs of 0.87 and 0.86, AUPRCs of 0.66 and 0.64 and F1 scores of 0.61 and 0.59, respectively, substantially better than a baseline logistic regression model. Aggregating individual probabilities, the total daily number of hospital discharges could also be accurately estimated, with mean absolute errors of 8.9% (elective admissions) and 4.9% (emergency admissions). The most informative predictors included antibiotic prescriptions, other medications, and hospital capacity factors. Performance was generally robust across patient subgroups and different training strategies, but lower in patients with longer lengths of stay and those who eventually died in hospital. Our findings highlight the potential of machine learning in optimising hospital patient flow and facilitating patient care and recovery.
Quantile regressions as a tool to evaluate how an exposure shifts and reshapes the outcome distribution: A primer for epidemiologists
Authors: Khadka Aayush , Hebert Jillian , Maria Glymour M. , Jiang Fei , Irish Amanda , Duchowny Kate , Vable Anusha M. 
Published: May 2023

AbstractMost regression models estimate an exposure’s association with the mean value of the outcome, but quantifying how an exposure affects the entire outcome distribution is often important (e.g., when the outcome has non-linear relationships with risk of other adverse outcomes). Quantile regressions offer a powerful way of estimating an exposure’s relationship with the outcome distribution but remain underused in epidemiology. We introduce quantile regressions and then present an empirical example in which we fit mean and quantile regressions to investigate the association of educational attainment with later-life systolic blood pressure (SBP). We use data on 8,875 US-born respondents aged 50+ years from the Health and Retirement Study. More education was negatively associated with mean SBP. Conditional and unconditional quantile regressions both suggested a negative association between education and SBP at all levels of SBP, but the absolute magnitudes of these associations were higher at higher SBP quantiles relative to lower quantiles. While all estimators showed more education was associated with a leftward shift of the SBP distribution, quantile regression results additionally revealed that education may have reshaped the SBP distribution through larger protective associations in the right tail, thus benefiting those at highest risk of cardiovascular diseases.
Oral anticoagulation in heart failure complicated by atrial fibrillation: Outcomes in routine data
Authors: Möckel Martin , Pudasaini Samipa , Baberg Henning Thomas , Levenson Benny , Malzahn Jürgen , Mansky Thomas , Michels Guido , Günster Christian , Jeschke Elke 
Published: May 2023

AbstractBackgroundAim of this study was to test if oral anticoagulant (OAC) use in patients with heart failure (HF), accompanied by atrial fibrillation (AF), leads to a favorable outcome. Further, the specific impact of non-vitamin K oral anticoagulants (NOACs) is analyzed.MethodsAnonymous data from all patients with a health insurance at the largest entity which covers approximately 30% of the German population. Patients with a claims record for hospitalization with the main diagnosis of HF and AF from the years 2017 to 2019 were included. A hospital stay in the previous year was an exclusion criterion. Mortality and readmission for all-cause and stroke/intracranial bleeding (ICB) were analyzed 91-365 days after the index hospitalization. Kaplan-Meier survival curves and multivariable Cox regression models were used to evaluate the impact of medication on outcome.Results180,316 cases were included [81 years (IQR 76 to 86), 55.6% female, CHA2DS2-VASc score ≥ 2 (96.81%)]. In 80.6%, OACs were prescribed (vitamin K antagonists (VKA): 21.7%; direct factor Xa inhibitors (FXaI): 60.0%; direct thrombin inhibitors (DTI): 3.4%; with multiple prescriptions per patient included). The mortality rate was 19.1%, readmission rate was 29.9% and stroke/ICB occurred in 1.9%. Risk of death was lower with the any OAC (HR 0.77, 95% CI 0.75 to 0.79) but without significant differences in OAC type (VKA: HR 0.73, 95% CI 0.71 to 0.76; FXaI: HR 0.77, 95% CI 0.75 to 0.78; DTI: HR 0.71, 95% CI 0.66 to 0.77). The total readmission rate (HR 0.97, 95% CI 0.94 to 0.99) and readmission for stroke/ICB (HR 0.71, 95% CI 0.65 to 0.77) was lower with OAC.ConclusionsRoutine data confirm the positive effect of OACs in HF-AF. There are no additional benefits regarding mortality with the use of NOACs.Clinical PerspectiveWhat is new?This routine data analysis on a study population of 180,316 indicates a decreasing mortality rate, 91 to 365 days after index hospital stay, in patients with HF complicated by AF in case oral anticoagulants (OACs) were prescribed.Secondly, the findings imply no additional benefits of new OACs (NOACs) compared to vitamin K antagonists.What are the clinical implications?Our study highlights the benefits of a permanent oral anticoagulation therapy in patients with heart failure (HF) complicated by atrial fibrillation (AF).For patients with HF and AF, the results indicate room for personalizationin choosing the specific OAC type for anticoagulation as NOACs show no survival benefit over vitamin K antagonists.
Population-based surveillance of drug-resistant tuberculosis in Southern Mozambique based on whole genome sequencing
Authors: Mariner-Llicer Carla , Cervera Belén Saavedra , Mambuque Edson , Munguambe Shilzia , Gomes Neide , Villamayor Luis , Cancino-Muñoz Irving , Torres-Puente Manuela , Nguenha Dinis , Respeito Durval , Tembe Gustavo , López Mariana G. , Comas Iñaki , García-Basteiro Alberto L. 
Published: May 2023

ABSTRACTMozambique is considered a high multidrug-resistant (MDR-TB) country by the World Health Organization (WHO) (3.7% new MDR-TB cases). The last national WHO survey was performed in 2008. Nowadays, South Africa and Eswatini are reporting an increase in MDR-TB cases heightened, in Eswatini, by the spread of a MDR-TB strain harbouring therpoB_I491F mutation not detected by XpertUltra/RIF. Due to the concerning MDR-TB situation in its neighbouring countries, it is crucial to review the current resistance status in Mozambique. Our aim is to depict the current prevalence of drug-resistance to first and second-line drugs and track its trends since 2008. We analysed 312Mycobacterium tuberculosisgenomes from a population-based survey conducted in Manhiça in 2018 and looked for drug-resistance mutations included in the recently published WHO catalogue and compared with the prevalences reported in 2014 and 2008. We found that the overall resistance increased in 2014 (15.9%) and 2018 (14.4%) was slightly higher than the one reported in 2008. Although, new multidrug/rifampicin resistance cases remained consistent with the 2008 prevalence study (3.5%) indicating that MDR-TB is not spreading as rapidly as in neighbouring countries. Importantly, we detected a high isoniazid (INH) prevalence not associated with MDR-TB (4.2%, 5.5% and 7.6% in 2008, 2014 and 2018, p-value=0.03) suggesting that a sizeable number of cases are INH-resistant before starting treatment and not detected by XpertUltra/RIF. Fortunately, no mutations associated with second-line drug-resistance were found in the dataset. Our results show a stable drug-resistance situation in Manhiça with the need to monitor isoniazid resistance, and highlight the potential of WGS to be used in national surveys to expand our knowledge of drug-resistance prevalence throughout all Mozambican provinces.
Profiling small RNAs in CRC screening samples such as the widely used fecal immunochemical test, is it possible?
Authors: Birkeland Einar , Ferrero Giulio , Pardini Barbara , Umu Sinan U. , Tarallo Sonia , Bulfamante Sara , Hoff Geir , Senore Carlo , Rounge Trine B , Naccarati Alessio 
Published: May 2023

AbstractFaecal microRNAs represent promising molecules with potential clinical interest as non-invasive diagnostic and prognostic biomarkers for their stability and detectability. Colorectal cancer (CRC) screening based on the fecal immunochemical test (FIT) is an effective tool for prevention of cancer development. However, due to the poor sensitivity of FIT for premalignant lesions, there is a need for implementation of complementary tests. Improving the identification of individuals who would benefit from further investigation with colonoscopy using molecular analysis, such as miRNA profiling of the FIT leftover buffer, would be ideal due to its widespread use.In the present study, we applied small RNA sequencing to FIT leftover samples collected from two European screening populations. We showed robust detection of miRNA and microbial profiles, which were similar to those obtained from specimens sampled using RNA stabilising buffers and archived fecal samples. Detected miRNAs exhibited differential abundance between CRC and control samples that was consistent between sampling methods, suggesting a promising potential to identify small RNA CRC biomarkers using FIT leftovers. We demonstrated that it is possible to analyse gut miRNAs in FIT leftover samples and envision that these potential biomarkers can complement the FIT in large scale screening settings.
Duration and Frequency Mismatch Negativity in Schizophrenia, unaffected first-degree relatives, and healthy controls
Authors: Bose Anushree , Agarwal Sri Mahavir , Nawani Hema , Shivakumar Venkataram , Sreeraj Vanteemar S. , Narayanaswamy Janardhanan C. , Kumar Devvarta , Venkatasubramanian Ganesan 
Published: May 2023

ABSTRACTBackgroundMismatch negativity (MMN) is elicited upon detecting background irregularities in the sensory environment and subsequent updating of the sensory context. Auditory MMN amplitude is reliably attenuated in schizophrenia patients. However, due to diversity in MMN deviant types (duration, frequency, intensity, gap, etc.), considerable variability exists in MMN findings reported from the early course and chronic samples. MMN is sometimes reported to be impaired or associated with schizotypy, but MMN and schizotypy are yet to be well examined in unaffected first-degree relatives of schizophrenia patients.MethodsFifty-two schizophrenia patients (SZ) were compared with thirty-six unaffected first-degree relatives (FDR) of schizophrenia patients and thirty-two age and sex-matched healthy controls (HC) on MMN indices using a two-tone passive auditory oddball paradigm with two conditions – duration deviant (MMNd) and frequency deviant (MMNf) event-related potential experiment. SZ sample was further split into two sub-groups 1) early-course/drug-naïve or drug-free (dSZ), and 2) chronic/medicated (cSZ) to examine the effect of illness chronicity and medication on MMN indices. We also checked whether schizotypy scores associated with MMNd and MMNf amplitudes in the FDR group.ResultsAt baseline, SZ group had significantly diminished MMNd amplitude compared to both HC and FDR groups (p<0.001). The SZ group also had significantly lower MMNd latency than the FDR group (p<0.014). The cSZ and dSZ groups did not differ from each other on MMN amplitude or latency, though cSZ group had lower MMN amplitude. Only cSZ patients showed negative correlation of MMNd amplitude with hallucinations scores and total duration of illness. In FDRs, MMNd and MMNf amplitudes showed negative correlation with the cognitive-perceptual factor of schizotypy.DiscussionDeficient MMNd in SZ patients adds further support to the prediction error estimation abnormalities in schizophrenia. MMNd is a more robust measure than MMNf in differentiating SZ from FDR and HC. MMNd amplitude could be more impaired in hallucinating SZ patients and associate with illness chronicity. Though unaffected FDRs have MMN comparable to healthy controls, higher schizotypy in FDR is associated with lower MMN amplitude. MMN and schizotypy are potentially linked and deserve a nuanced examination.