bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosomal microRNA following severe trauma: Role in bone marrow dysfunction
Authors: Munley Jennifer A. , Willis Micah L. , Gillies Gwendolyn S. , Kannan Kolenkode B. , Polcz Valerie E. , Balch Jeremy A. , Barrios Evan L. , Wallet Shannon M. , Bible Letitia E. , Efron Philip A. , Maile Robert , Mohr Alicia M. 
Published: December 2023

INTRODUCTION
Severe trauma disrupts bone marrow function and is associated with persistent anemia and altered hematopoiesis. Previously, plasma-derived exosomes isolated after trauma have been shown to suppress in vitro bone marrow function. However, the cargo contained in these vesicles has not been examined. We hypothesized that trauma plasma–derived exosomes exhibit microRNA (miRNA) changes that impact bone marrow function after severe injury.

METHODS
Plasma was collected from a prospective cohort study of trauma patients (n = 15; 7 males, 8 females) with hip and/or femur fractures and an Injury Severity Score of ≥15; elective total hip arthroplasty (THA) patients (n = 8; 4 males, 4 females) served as operative controls. Exosomes were isolated from plasma with the Invitrogen Total Exosome Isolation Kit (Thermo Fisher Scientific, Waltham, MA), and RNA was isolated using a miRNeasy Mini Kit (Qiagen, Hilden, Germany). Direct quantification of miRNA was performed by NanoString Technologies on a human miRNA gene panel and analyzed with nSolver with significance defined as p < 0.05.

RESULTS
There were no differences in age or sex distribution between trauma and THA groups; the average Injury Severity Score was 23. Trauma plasma–derived exosomes had 60 miRNA identities that were significantly downregulated and 3 miRNAs that were upregulated when compared with THA (p < 0.05). Twelve of the downregulated miRNAs have a direct role in hematopoiesis regulation. Furthermore, male trauma plasma–derived exosomes demonstrated downregulation of 150 miRNAs compared with male THA (p < 0.05). Female trauma plasma–derived exosomes demonstrated downregulation of only four miRNAs and upregulation of two miRNAs compared with female THA (p < 0.05).

CONCLUSION
We observed downregulation of 12 miRNAs linked to hematopoiesis along with sexual dimorphism in miRNA expression from plasma-derived exosomes following severe trauma. Understanding sexually dimorphic miRNA expression provides new insight into sex-based changes in postinjury systemic inflammation, immune system dysregulation, and bone marrow dysfunction and will aid us in more precise future potential therapeutic strategies.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level III.
Comparison of Lasmiditan 200 mg Versus 100 mg for Migraine Patients: A Meta-analysis of Randomized Controlled Studies
Authors: Zhong Chuan , Zhang Xuanqin , Qin Guoyong , Wu Jixiang , Tian Yongpan 
Published: December 2023

Introduction
The ideal dose of lasmiditan for migraine is not clear. This meta-analysis aims to compare the efficacy of lasmiditan 200 mg versus 100 mg for migraine patients.

Methods
We have searched several databases including PubMed, Embase, Web of Science, EBSCO, and Cochrane Library Databases and selected the randomized controlled trials comparing the efficacy of lasmiditan 200 mg versus 100 mg for migraine patients. This meta-analysis was conducted using the random-effect model.

Results
Five randomized controlled trials were included in this meta-analysis. Compared with lasmiditan 100-mg group in migraine patients, lasmiditan 200-mg group was associated with substantially increased pain free at 2 hours (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.12–1.44; P = 0.0002) and pain free at 24 hours (OR, 1.31; 95% CI, 1.08–1.60; P = 0.007) but demonstrated no obvious impact on pain relief at 2 hours (OR, 1.02; 95% CI, 0.91–1.16; P = 0.72) or MBS free at 2 hours (OR, 0.94; 95% CI, 0.77–1.14; P = 0.52). In addition, the incidence of adverse events was higher in lasmiditan 200-mg group than that in lasmiditan 100-mg group (OR, 1.29; 95% CI, 1.15–1.45; P < 0.0001).

Conclusions
Lasmiditan 200 mg is better for the treatment of migraine patients than lasmiditan 100 mg.
Identification of Hypertrophic Cardiomyopathy on Electrocardiographic Images with Deep Learning
Authors: Sangha Veer , Dhingra Lovedeep Singh , Oikonomou Evangelos , Aminorroaya Arya , Sikand Nikhil V , Sen Sounok , Krumholz Harlan M , Khera Rohan 
Published: December 2023

ABSTRACTBackgroundHypertrophic cardiomyopathy (HCM) affects 1 in every 200 individuals and is the leading cause of sudden cardiac death in young adults. HCM can be identified using an electrocardiogram (ECG) raw voltage data and deep learning approaches, but their point-of-care application is limited by the inaccessibility of these signal data. We developed a deep learning-based approach that overcomes this limitation and detects HCM from images of 12-lead ECGs across layouts.MethodsWe identified ECGs from patients with HCM features present on cardiac magnetic resonance imaging (CMR) or those within 30 days of an echocardiogram documenting thickened interventricular septum (end-diastolic interventricular septum thickness > 15mm). Patients with CMR-confirmed HCM were considered as cases during the final model evaluation. The model was validated within clinical settings at YNHH and externally on ECG images from the prospective, population-based UK Biobank cohort. We localized class-discriminating signals in ECG images using gradient-weighted class activation mapping.ResultsOverall, 124,553 ECGs from 66,987 individuals (HCM cases and controls) were used for model development. The model demonstrated high discrimination for HCM across various ECG image formats and calibrations in internal validation (area under receiving operation characteristics [AUROC] 0.96) and external sets of ECG images from UK Biobank (AUROC 0.94). A positive screen for HCM was associated with a 100-fold higher odds of CMR-confirmed HCM (OR 102.4, 95% Confidence Interval, 57.4 – 182.6) in the held-out set. Class-discriminative patterns localized to the anterior and lateral leads (V4-V5).ConclusionsWe developed and externally validated a deep learning model that identifies HCM from ECG images with excellent discrimination. This approach represents an automated, efficient, and accessible screening strategy for HCM.
Mapping inherited genetic variation with opposite effects on autoimmune disease and cancer identifies candidate drug targets associated with the anti-tumor immune response
Authors: Chen Junyu , Epstein Michael P. , Schildkraut Joellen M. , Kar Siddhartha P. 
Published: December 2023

AbstractBackgroundGermline alleles near genes that encode certain immune checkpoints (CTLA4,CD200) are associated with autoimmune/autoinflammatory disease and cancer but in opposite directions. This motivates a systematic search for additional germline alleles which demonstrate this pattern with the aim of identifying potential cancer immunotherapeutic targets using human genetic evidence.MethodsPairwise fixed effect cross-disorder meta-analyses combining genome-wide association studies (GWAS) for breast, prostate, ovarian and endometrial cancers (240,540 cases/317,000 controls) and seven autoimmune/autoinflammatory diseases (112,631 cases/895,386 controls) coupled within silicofollow-up. To ensure detection of alleles with opposite effects on cancer and autoimmune/autoinflammatory disease, the signs on the beta coefficients in the autoimmune/autoinflammatory GWAS were reversed prior to meta-analyses.ResultsMeta-analyses followed by linkage disequilibrium clumping identified 312 unique, independent lead variants with Pmeta<5×10-8associated with at least one of the cancer types at Pcancer<10-3and one of the autoimmune/autoinflammatory diseases at Pauto<10-3. At each lead variant, the allele that conferred autoimmune/autoinflammatory disease risk was protective for cancer. Mapping each lead variant to its nearest gene as its putative functional target and focusing on genes with established immunological effects implicated 32 of the nearest genes. Tumor bulk RNA-Seq data highlighted that the tumor expression of 5/32 genes (IRF1,IKZF1,SPI1,SH2B3,LAT) were each strongly correlated (Spearman’s ρ>0.5) with at least one intra-tumor T/myeloid cell infiltration marker (CD4,CD8A,CD11B,CD45) in every one of the cancer types. Tumor single-cell RNA-Seq data from all cancer types showed that the five genes were more likely to be expressed in intra-tumor immune versus malignant cells. The five lead SNPs corresponding to these genes were linked to them via expression quantitative trait locus mechanisms and at least one additional line of functional evidence. Proteins encoded by the genes were predicted to be druggable.ConclusionWe provide population-scale germline genetic and functional genomic evidence to support further evaluation of the proteins encoded byIRF1,IKZF1,SPI1,SH2B3, andLATas possible targets for cancer immunotherapy.
The Pattern of rpoB gene mutation ofMycobacterium tuberculosisand predictors of rifampicin resistance detected by gene Xpert MTB/Rif in Tanzania
Authors: Torokaa Peter Richard , Kileo Heledy , Urio Loveness , Mbwana Mariam R. , Monah Mariam C. , Ntibabara Sephord Saul , Kimambo Jasper , Seleman Paschal , Franklin Collins , Balama Robert , Kisonga Riziki M. , Majigo Mtebe V. , Joachim Agricola 
Published: December 2023

ABSTRACTIntroductionAntimicrobial resistance associated withMycobacterium tuberculosis (MTB)is the challenge facing Tuberculosis (TB) management worldwide. Rifampicin resistance (RR) has been associated with the rpoB gene mutation. No study was conducted in Tanzania to determine the commonest mutation. The inconsistent findings from various studies support the need to determine whether reported mutation patterns are applicable in our setting. We determined the frequency of rpoB gene mutation and factors associated with RR detected using GeneXpert MTB/Rif.MethodsWe conducted a retrospective cross-sectional study involving data from the National Tuberculosis and Leprosy Program database from 2020 to 2022 for cases investigated using GeneXpert. Descriptive analysis was performed as the frequency for categorical variables. The chi-square test and regression analysis assessed the relationship between the independent variables and outcome. The 95% confidence interval and a significance level of p<0.05 were used to assess the association strength.ResultsA total of 56,004 participants had status of MTB and RR. Most, 38,705/56,004 (69.11%) were male. Probe E, 89/219 (40.64%) was the predominant. Human immunodeficiency virus (HIV)-positive patients had a higher gene mutation, 134/10601 (1.26%) than HIV-negative, 306/45016 (0.68%) (p<0.001). Patients with both pulmonary and extra-pulmonary TB had about four times greater odds of developing rifampicin resistance (AOR 3.88, 95%CI: 1.80 – 8.32). RR was nearly nine times higher in previously treated patients than new patients (AOR 8.66, 95%CI: 6.97–10.76). HIV-positive individuals had nearly twice the odds of developing RR than HIV-negative individuals (AOR 1.91, 95%CI: 1.51 – 2.42).ConclusionThe rate of RR was low compared to other studies in Tanzania, with probe E mutations the most prevalent. Patients with disseminated TB, HIV co-infection and those with prior exposure to anti-TB had more risk of RR. The findings highlight the need to strengthen surveillance of multidrug-resistant-TB among patients with a higher risk of RR.
Polygenic prediction of major depressive disorder and related traits in African ancestries UK Biobank participants
Authors: Kanjira SC , Adams MJ , Jiang Yunxuan , Tian Chao ,   23andMe Research Team, Lewis CM , Kuchenbaecker K , McIntosh AM 
Published: December 2023

AbstractIntroductionGenome-Wide Association Studies (GWAS) over-represent European ancestries compared to the global population, neglecting all other ancestry groups and low-income nations. Consequently, polygenic risk scores (PRS) more accurately predict complex traits in Europeans than African Ancestries groups. Very few studies have looked at the transferability of European-derived PRS for behavioural and mental health phenotypes to non-Europeans. We assessed the comparative accuracy of PRS for Major Depressive Disorder (MDD) trained on European and African Ancestries GWAS studies to predict MDD and related traits in African Ancestries participants from the UK Biobank.MethodsUK Biobank participants were selected based on Principal component analysis (PCA) clustering with an African genetic similarity reference population and MDD was assessed with the Composite International Diagnostic Interview (CIDI). Polygenic Risk Scores (PRS) were computed using PRSice2 using either European or African Ancestries GWAS summary statistics.ResultsPRS trained on European ancestry samples (246,363 cases) predicted case control status in Africans of the UK Biobank with similar accuracies (190 cases, R2=2%) to PRS trained on far much smaller samples of African Ancestries participants from 23andMe, Inc. (5045 cases, R2=1.8%). This suggests that prediction of MDD status from Africans to Africans had greater efficiency per unit increase in the discovery sample size than prediction of MDD from Europeans to Africans. Prediction of MDD status in African UK Biobank participants using GWAS findings of causal risk factors from European ancestries was non-significant.ConclusionGWAS studies of MDD in European ancestries are an inefficient means of improving polygenic prediction accuracy in African samples.
Multimodal Diverse Granularity Fusion Network based on US and CT Images for Lymph Node Metastasis Prediction of Thyroid Carcinoma
Authors: Li Guojun , Yao Jincao , Peng Chanjuan , Hu Yinjie , Zhao Shanshan , Feng Xuhan , Yang Jianfeng , Xu Dong , Li Xiaolin , Sha Chulin , He Min 
Published: December 2023

AbstractAccurately predicting the risk of cervical lymph node metastasis (LNM) is crucial for surgical decision-making in thyroid cancer patients, and the difficulty in it often leads to over-treatment. Ultrasound (US) and computed tomography (CT) are two primary non-invasive methods applied in clinical practice, but both contain limitations and provide unsatisfactory results. To address this, we developed a robust and explainable multimodal deep-learning model by integrating the above two examinations. Using 3522 US and 7649 CT images from 1138 patients with biopsy-confirmed LNM status, we showed that multimodal methods outperformed unimodal counterparts at both central and lateral cervical sites. By incorporating a diverse granularity fusion module, we further enhanced the area under the curve (AUC) to 0.875 and 0.859 at central and lateral cervical sites respectively. This performance was also validated in an external cohort. Additionally, we quantified the modality-specific contributions for each nodule and systematically evaluated the applicability across various clinical characteristics, aiding in identifying individuals who can benefit most from the multimodal method.
Empowering Transformers for Evidence-Based Medicine
Authors: Mohammed Sabah , Fiaidhi Jinan , Shaik Hashmath 
Published: December 2023

AbstractBreaking the barrier for practicing evidence-based medicine rely on effective methods for rapidly identifying relevant evidences from the body of biomedical literature. An important challenge confronted by the medical practitioners is the long time needed to browse, filter, summarize and compile information from different medical resources. Deep learning can help in solving this based on the automatic question answering (Q&A) and transformers. However, Q&A and transformers technologies are not trained to answer clinical queries that can be used for evidence-based practice nor it can respond to structured clinical questioning protocol like PICO (Patient/Problem, Intervention, Comparison and Outcome). This article describes the use of deep learning techniques for Q&A that is based on transformer models like BERT and GPT to answer PICO clinical questions that can be used for evidence-based practice extracted from sound medical research resources like PubMed. We are reporting acceptable clinical answers that are supported by findings from PubMed. Our transformer methods are reaching an acceptable state of the art performance based on two staged bootstrapping process involving filtering relevant articles followed by identifying articles that support the requested outcome expressed by the PICO question. Moreover, we are also reporting experimentations to empower our bootstrapping techniques with patch attentions to the most important keywords in the clinical case and the PICO questions. Our bootstrapped patched with attention is showing relevancy of the evidences collected based on an entropy metrics.
Integrated Systems Analysis Deciphers Transcriptome and Glycoproteome Links in Alzheimer’s Disease
Authors: Matsui Yusuke , Togayachi Akira , Sakamoto Kazuma , Angata Kiyohiko , Kadomatsu Kenji , Nishihara Shoko 
Published: December 2023

AbstractGlycosylation is increasingly recognized as a potential therapeutic target in Alzheimer’s disease. In recent years, evidence of Alzheimer’s disease-specific glycoproteins has been established. However, the mechanisms underlying their dysregulation, including tissue- and cell-type specificity, are not fully understood. We aimed to explore the upstream regulators of aberrant glycosylation by integrating multiple data sources using a glycogenomics approach. We identified dysregulation of the glycosyltransferase PLOD3 in oligodendrocytes as an upstream regulator of cerebral vessels and found that it is involved in COL4A5 synthesis, which is strongly correlated with amyloid fiber formation. Furthermore, COL4A5 has been suggested to interact with astrocytes via extracellular matrix receptors as a ligand. This study suggests directions for new therapeutic strategies for Alzheimer’s disease targeting glycosyltransferases.Graphical Abstract
The long-term effect of bariatric/metabolic surgery versus pharmacologic therapy in type 2 diabetes mellitus patients: A systematic review and meta-analysis
Authors: Yang Yumeng , Miao Chuhan , Wang Yingli , He Jianxun , Bo Yan 
Published: December 2023

AbstractBackgroundMetabolic/bariatric surgery as a treatment for obesity and related diseases, such as type 2 diabetes mellitus (T2DM), has been increasingly recognized. However, the long-term effect (≥ five years) of metabolic surgery in T2D patients is still unclear compared with conventional pharmacologic therapy. This study aims to evaluate the diabetes remission rate, diabetic microvascular complications incidence, macrovascular complications incidence, and mortality in T2D patients who received metabolic surgery versus pharmacologic therapy more than five years after the surgery.MethodsSearching the database, including PubMed, Embase, Web of Science, and Cochrane Library from the inception to recent (2022), for randomized clinical trials (RCTs) or cohort studies comparing T2D patients treated with metabolic surgery versus pharmacologic therapy reporting on the outcomes of the diabetes remission rate, diabetic microvascular complications, macrovascular complications, or mortality over five years or more.ResultsA total of 13 articles with a total of 68,280 patients with T2D were eligible for review and meta-analysis in this study. There is a significant long-term increase in diabetes remission for metabolic surgery compared with conventional medical therapy in the overall pooled estimation and RCT studies or cohort studies separately (overall: OR = 8.39, 95%CI: 3.58-19.67, P<0.001). Significant long-term decreases showed in the pooled results of microvascular complications incidence (HR = 0.43, 95%CI: 0.37-0.49, P<0.001), macrovascular complications incidence (HR = 0.60, 95%CI: 0.48-0.75, P<0.001) and mortality (HR = 0.44, 95%CI: 0.37-0.49, P<0.001).ConclusionMetabolic surgery showed more significant long-term effects than pharmacologic therapy on diabetes remission, macrovascular complications, microvascular complications incidence, and all-cause mortality in patients with T2D using currently available evidence. More high-quality evidence is needed to validate the long-term effects of metabolic surgery versus conventional treatment in the management of diabetes.
PNLDC1 catalysis and postnatal germline function are required for piRNA trimming, LINE1 silencing, and spermatogenesis in mice
Authors: Wei Chao , Yan Xiaoyuan , Mann Jeffrey M. , Geng Ruirong , Xie Huirong , Demireva Elena Y. , Sun Liangliang , Ding Deqiang , Chen Chen 
Published: December 2023

ABSTRACTPIWI-interacting RNAs (piRNAs) play critical and conserved roles in transposon silencing and gene regulation in the animal germline. Two distinct piRNA populations are present during mouse spermatogenesis: pre-pachytene piRNAs in fetal/neonatal testes and pachytene piRNAs in adult testes. PNLDC1 is required for both pre-pachytene piRNA and pachytene piRNA 3’ end maturation in multiple species. However, whether PNLDC1 is the bona fide piRNA trimmer and the physiological role of 3’ trimming of two distinct piRNA populations in spermatogenesis remain unclear. Here, by inactivatingPnldc1exonuclease activity in vitro and in mice, we reveal that PNLDC1 trimmer activity is required for both pre-pachytene piRNA and pachytene piRNA 3’ end trimming and male fertility. Furthermore, conditional inactivation ofPnldc1in postnatal germ cells causes LINE1 transposon de-repression and spermatogenic arrest in mice. This indicates that pachytene piRNA trimming, but not pre-pachytene piRNA trimming, is essential for mouse germ cell development and transposon silencing. Our findings highlight the potential of inhibiting germline piRNA trimmer activity as a potential means for male contraception.
Revealing the spatial characteristics of rice heat exposure in Japan through panicle temperature analysis
Authors: Toda Yusuke , Ishigooka Yasushi , Yoshimoto Mayumi , Takimoto Takahiro , Kuwagata Tsuneo , Makowski David , Hasegawa Toshihiro 
Published: December 2023

AbstractElevated temperatures during the flowing stage contribute to heat-induced spikelet sterility in rice, posing a major threat to production considering climate change projections. Developing effective strategies for stable rice production through breeding and crop management is critical; however, our understanding of regional, seasonal, and long-term trends in rice heat exposure remains limited. Previous studies on spikelet sterility revealed that panicle temperature, estimated using a micrometeorological model and common meteorological factors, serves as a reliable indicator of rice heat exposure. In this study, we employed this model to identify the differences between panicle and air temperatures (DPAT) and their causes over the past 45 years in Japan. A gridded daily meteorological dataset covering Japan was interpolated at an hourly time step and used as input data of the micrometeorology model for estimating panicle temperatures during flowering. Statistical analysis of the resulting data revealed an increasing trend in the frequency of rice panicle heat exposure over time across many locations in Japan. During heat-receptive periods, panicle temperature generally exceeded air temperature, indicating the inadequacy of relying solely on air temperature to gauge rice heat stress. DPAT values showed substantial inter-regional variations in both mean values (from −0.5℃ to 3.0℃) and seasonality. Through machine learning and statistical methods, the relationship between DPAT and meteorological factors was characterized, delineating the effects of the meteorological factors on regional and seasonal DPAT variations. Focusing on major high-risk regions, we show that mitigation strategies should be adapted to consider regional characteristics and avoid high DPAT conditions during rice heading periods.