Identification of Novel Genetic Risk Variants Associated with Hidradenitis Suppurativa in an Exome Sequencing Cohort of 92,455 Individuals.

Introduction: Hidradenitis suppurativa (HS) is a prevalent and persistent inflammatory skin disorder, lacking a known cure or effective biomarkers for early diagnosis at present. The genetic determinants of HS have not been fully documented, but it is believed to result from a combination of genetic and environmental factors.

Methods: To identify relevant HS gene variants in sporadic HS patients, this study utilized longitudinal electronic health records (EHRs) and whole-exome sequencing.

Mechanisms of Chemical Atrial Defibrillation by Flecainide and Ibutilide.

Background: Effective and safe pharmacological approaches for atrial defibrillation offer several potential advantages over techniques like ablation. Pharmacological therapy is noninvasive, involving no risk associated with the procedure or resulting complications. Moreover, acute drug intervention with existing drugs is likely to be low cost and broadly accessible, thereby addressing a central tenet of health equity.

Loss of PI5P4Kα Slows the Progression of a Pten Mutant Basal Cell Model of Prostate Cancer.

Although early prostate cancer depends on the androgen receptor signaling pathway, which is predominant in luminal cells, there is much to be understood about the contribution of epithelial basal cells in cancer progression. Herein, we observe cell type-specific differences in the importance of the metabolic enzyme phosphatidylinositol 5-phosphate 4-kinase alpha (PI5P4Kα; gene name PIP4K2A) in the prostate epithelium. We report the development of a basal cell-specific genetically engineered mouse model targeting Pip4k2a alone or in combination with the tumor suppressor phosphatase and tensin homolog (Pten).

Negative results from DNA-based population screening for adult-onset diseases: the recipients' experience.

DNA-based population screening for adult-onset diseases holds promise for advancing personalized medicine and improving public health. Yet as most individuals pursuing such screening receive negative results, the return of results process must ensure that negative results and their implications are clearly understood. We explored the experiences of adults who received negative results from such screening as part of the Electronic Medical Records and Genomics consortium Phase 3 project (eMERGE-3) at Columbia University.

Prediction of testicular histology in azoospermia patients through deep learning-enabled two-dimensional grayscale ultrasound.

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model.

Serum cytokines and inflammatory proteins in individuals with heroin use disorder: potential mechanistically based biomarkers for diagnosis.

Opioid use disorders cause major morbidity and mortality, and there is a pressing need for novel mechanistic targets and biomarkers for diagnosis and prognosis. Exposure to mu-opioid receptor (MOR) agonists causes changes in cytokine and inflammatory protein networks in peripheral blood, and also in brain glia and neurons. Individuals with heroin use disorder (iHUD) show dysregulated levels of several cytokines in the blood.

Facilitating integrative and personalized oncology omics analysis with UCSCXenaShiny.

The continuous generation of multi-omics and phenotype data is propelling advancements in precision oncology. UCSCXenaShiny was developed as an interactive tool for exploring thousands of cancer datasets available on UCSC Xena. However, its capacity for comprehensive and personalized pan-cancer data analysis is being challenged by the growing demands.

Ataluren-mediated nonsense variant readthrough in D-bifunctional protein deficiency: A case report.

D-bifunctional protein (DBP) deficiency, a fatal peroxisomal enzyme disorder, typically manifests with life-threatening symptoms in the first two years of childhood. We present the case of an infant with elevated lysophosphatidylcholine C26:0 (C26:0-LPC) levels identified during X-linked adrenoleukodystrophy (ALD) screening, leading to a diagnosis of DBP deficiency due to a homozygous c.1041T>A, p.

VSIG4 induces the immunosuppressive microenvironment by promoting the infiltration of M2 macrophage and Tregs in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma and has a poor prognosis. Despite the impressive advancements in treating ccRCC using immune checkpoint (IC) blockade, such as PD-1/PD-L1 inhibitors, a considerable number of ccRCC patients experience adaptive resistance. Therefore, exploring new targetable ICs will provide additional treatment options for ccRCC patients.

Predictive etiological classification of acute ischemic stroke through interpretable machine learning algorithms: a multicenter, prospective cohort study.

Background: The prognosis, recurrence rates, and secondary prevention strategies varied significantly among different subtypes of acute ischemic stroke (AIS). Machine learning (ML) techniques can uncover intricate, non-linear relationships within medical data, enabling the identification of factors associated with etiological classification. However, there is currently a lack of research utilizing ML algorithms for predicting AIS etiology.

Biological Insights from Schizophrenia-associated Loci in Ancestral Populations.

Large-scale genome-wide association studies of schizophrenia have uncovered hundreds of associated loci but with extremely limited representation of African diaspora populations. We surveyed electronic health records of 200,000 individuals of African ancestry in the Million Veteran and All of Us Research Programs, and, coupled with genotype-level data from four case-control studies, realized a combined sample size of 13,012 affected and 54,266 unaffected persons. Three genome-wide significant signals - near , , and - are the first to be independently identified in populations of predominantly African ancestry.

Insights into oral lentinan immunomodulation: Dectin-1-mediated lymphatic transport from Peyer's patch M cells to mononuclear phagocytes.

Lentinan (LNT), a natural polysaccharide, has been reported to exhibit immunomodulatory effects in the intestine after oral administration. Herein, we aimed to investigate the lymphatic transport of LNT in Peyer's patches (PPs) by traceable fluorescent labeling and to explore whether/how LNT contacts related immune cells. Near-infrared imaging confirmed the absorption of LNT in the small intestinal segment and its accumulation within PPs after oral administration.

Imatinib adherence prediction using machine learning approach in patients with gastrointestinal stromal tumor.

Background: Nonadherence to imatinib is common in patients with gastrointestinal stromal tumor (GIST), which is associated with poor prognosis and financial burden. The primary aim of this study was to investigate the adherence rate in patients with GIST and subsequently develop a model based on machine learning (ML) and deep learning (DL) techniques to identify the associated factors and predict the risk of imatinib nonadherence.

Methods: All eligible patients completed four sections of questionnaires.