Immune cell-enriched single-cell RNA sequencing unveils the interplay between infiltrated CD8 T resident memory cells and choroid plexus epithelial cells in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurological disorder and the leading cause of dementia. Despite significant efforts, treatment strategies targeting amyloid-β have been less successful than anticipated. Recently, the role of neuroinflammation and adaptive immune response in AD pathogenesis has gained attention.

Antibiotic Exposure and Risk of Parkinson Disease in South Korea: A Nationally Representative Retrospective Cohort Study.

Background And Objectives: Recent studies have suggested that antibiotics could be a contributing factor to Parkinson disease (PD), but validation in other population cohorts, such as Asians, is needed. This study examined the association between exposure to antibiotics and PD risk in the Korean population.

Methods: Using the National Health Insurance Service (NHIS) database, this population-level cohort research study from Korea included 298,379 people aged 40 years and older who underwent a national health examination in 2004-2005.

Metagenomic Analysis Identifies Sex-Related Gut Microbial Functions and Bacterial Taxa Associated With Skeletal Muscle Mass.

Background: This study aimed to explore the association between gut microbiota functional profiles and skeletal muscle mass, focusing on sex-specific differences in a population under 65 years of age.

Methods: Stool samples from participants were analysed using metagenomic shotgun sequencing. Skeletal muscle mass and skeletal muscle mass index (SMI) were quantified (SMI [%] = total appendage muscle mass [kg]/body weight [kg] × 100) using bioelectrical impedance analysis.

Breast tumor microbiome regulates anti-tumor immunity and T cell-associated metabolites.

Background: Breast cancer, the most common cancer type among women, was recently found to contain a specific tumor microbiome, but its impact on host biology remains unclear. CD8 tumor-infiltrating lymphocytes (TILs) are pivotal effectors of anti-tumor immunity that influence cancer prognosis and response to therapy. This study aims to elucidate interactions between CD8 TILs and the breast tumor microbiome and metabolites, as well as how the breast tumor microbiome may affect the tumor metabolome.

Critical evaluation of the current landscape of pharmacogenomics in Parkinson's disease - What is missing? A systematic review.

Introduction: The first-line treatment for Parkinson's disease (PD) involves dopamine-replacement therapies; however, significant variability exists in patient responses. Pharmacogenomics has been explored as a potential approach to understanding and predicting treatment outcomes. This review aims to evaluate the current state of knowledge regarding the role of pharmacogenomics in PD, focusing on identifying challenges and proposing future directions.

Germline Genetic Susceptibility Testing Among Emirati Nationals at Risk for Hereditary Breast and Ovarian Cancer Syndrome.

Purpose: Breast cancer among Emirati patients is characterized by early-onset disease and later stages at presentation. Little is known about the germline genetic variants that may contribute to these observations. The goal of this study is to characterize the rate and implications of germline genetic variants among a cohort of Emirati patients at risk for hereditary breast and ovarian cancer syndrome.

Update on Pediatric Surveillance Recommendations for PTEN Hamartoma Tumor Syndrome, DICER1-Related Tumor Predisposition, and Tuberous Sclerosis Complex.

Phosphate and tensin homolog hamartoma tumor syndrome, DICER1-related tumor predisposition, and tuberous sclerosis complex are rare conditions, which each increases risk for distinct spectra of benign and malignant neoplasms throughout childhood and adulthood. Surveillance considerations for each of these conditions focus on patient and family education, early detection, and multidisciplinary care. In this article, we present updated surveillance recommendations and considerations for children and adolescents with phosphate and tensin homolog hamartoma tumor syndrome, DICER1-related tumor predisposition, and tuberous sclerosis complex and provide suggestions for further research in each of these conditions.

Quantifying neurobehavioral profiles across neurodevelopmental genetic syndromes and idiopathic neurodevelopmental disorders.

Aim: To examine neurobehavioral findings in three genetic syndromes (PTEN hamartoma tumor syndrome, Malan syndrome [mutations in the NFIX gene], and SYNGAP1-related disorder), a mixed group of other neurodevelopmental genetic syndromes (NDGS), idiopathic neurodevelopmental disorder, and neurotypical control participants.

Method: Using a longitudinal case-control design, caregivers reported neurobehavioral information for 498 participants (PTEN hamartoma tumor syndrome n = 112, Malan syndrome n = 24, SYNGAP1-related disorder n = 47, other NDGS n = 72, idiopathic neurodevelopmental disorder n = 54, neurotypical siblings n = 74, and unrelated neurotypical control participants n = 115) at three timepoints (baseline, and 1-month and 4-month follow-ups) using the online-administered Neurobehavioral Evaluation Tool (NET).

Results: NET scales had good scale and test-retest reliability.

NSDHL contributes to breast cancer stem-like cell maintenance and tumor-initiating capacity through TGF-β/Smad signaling pathway in MCF-7 tumor spheroid.

Background: NAD(P)-dependent steroid dehydrogenase-like protein (NSDHL), which is involved in breast tumor growth and metastasis, has been implicated in the maintenance of cancer stem cells. However, its role in regulating breast cancer stem-like cells (BCSCs) remains unclear. We have previously reported the clinical significance of NSDHL in patients with estrogen receptor-positive (ER +) breast cancer.

A molecular video-derived foundation model for scientific drug discovery.

Accurate molecular representation of compounds is a fundamental challenge for prediction of drug targets and molecular properties. In this study, we present a molecular video-based foundation model, named VideoMol, pretrained on 120 million frames of 2 million unlabeled drug-like and bioactive molecules. VideoMol renders each molecule as a video with 60-frame and designs three self-supervised learning strategies on molecular videos to capture molecular representation.

Artificial intelligence machine learning based evaluation of elevated left ventricular end-diastolic pressure: a Cleveland Clinic cohort study.

Background: Left ventricular end-diastolic pressure (LVEDP) is a key indicator of cardiac health. The gold-standard method of measuring LVEDP is invasive intra-cardiac catheterization. Echocardiography is used for non-invasive estimation of left ventricular (LV) filling pressures; however, correlation with invasive LVEDP is variable.

Network medicine informed multiomics integration identifies drug targets and repurposable medicines for Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a devastating, immensely complex neurodegenerative disease by lack of effective treatments. We developed a network medicine methodology via integrating human brain multi-omics data to prioritize drug targets and repurposable treatments for ALS. We leveraged non-coding ALS loci effects from genome-wide associated studies (GWAS) on human brain expression quantitative trait loci (QTL) (eQTL), protein QTL (pQTL), splicing QTL (sQTL), methylation QTL (meQTL), and histone acetylation QTL (haQTL).

Application of computational algorithms for single-cell RNA-seq and ATAC-seq in neurodegenerative diseases.

Recent advancements in single-cell technologies, including single-cell RNA sequencing (scRNA-seq) and Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq), have greatly improved our insight into the epigenomic landscapes across various biological contexts and diseases. This paper reviews key computational tools and machine learning approaches that integrate scRNA-seq and scATAC-seq data to facilitate the alignment of transcriptomic data with chromatin accessibility profiles. Applying these integrated single-cell technologies in neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, reveals how changes in chromatin accessibility and gene expression can illuminate pathogenic mechanisms and identify potential therapeutic targets.

Distinct Impacts of Clinicopathological and Mutational Profiles on Long-Term Survival and Recurrence in Medullary Thyroid Carcinoma.

Backgruound: Medullary thyroid carcinoma (MTC) has a poorer prognosis than differentiated thyroid cancers; however, comprehensive data on the long-term outcomes of MTC remain scarce. This study investigated the extended clinical outcomes of MTC and aimed to identify prognostic factors.

Methods: Patients diagnosed with MTC between 1980 and 2020 were retrospectively reviewed.

Large DNA deletions occur during DNA repair at 20-fold lower frequency for base editors and prime editors than for Cas9 nucleases.

When used to edit genomes, Cas9 nucleases produce targeted double-strand breaks in DNA. Subsequent DNA-repair pathways can induce large genomic deletions (larger than 100 bp), which constrains the applicability of genome editing. Here we show that Cas9-mediated double-strand breaks induce large deletions at varying frequencies in cancer cell lines, human embryonic stem cells and human primary T cells, and that most deletions are produced by two repair pathways: end resection and DNA-polymerase theta-mediated end joining.

A network-based systems genetics framework identifies pathobiology and drug repurposing in Parkinson's disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. However, current treatments are directed at symptoms and lack ability to slow or prevent disease progression. Large-scale genome-wide association studies (GWAS) have identified numerous genomic loci associated with PD, which may guide the development of disease-modifying treatments.

Diet Changes and Colorectal Cancer Risk in the UK Biobank.

Background: Modifying dietary behaviors into healthier habits may attenuate the risk of colorectal cancer. This study aimed to investigate the association between dietary changes and the risk of colorectal cancer.

Methods: Following dietary recommendations for red and processed meat, fruit and vegetables, and alcohol consumption, we classified 50,640 participants into poor and good adherence groups in the UK Biobank.

Assembly of glioblastoma tumoroids and cerebral organoids: a 3D in vitro model for tumor cell invasion.

Glioblastoma (GBM) has a fatal prognosis because of its aggressive and invasive characteristics. Understanding the mechanism of invasion necessitates an elucidation of the relationship between tumor cells and the tumor microenvironment. However, there has been a scarcity of suitable models to investigate this.

A structurally informed human protein-protein interactome reveals proteome-wide perturbations caused by disease mutations.

To assist the translation of genetic findings to disease pathobiology and therapeutics discovery, we present an ensemble deep learning framework, termed PIONEER (Protein-protein InteractiOn iNtErfacE pRediction), that predicts protein-binding partner-specific interfaces for all known protein interactions in humans and seven other common model organisms to generate comprehensive structurally informed protein interactomes. We demonstrate that PIONEER outperforms existing state-of-the-art methods and experimentally validate its predictions. We show that disease-associated mutations are enriched in PIONEER-predicted protein-protein interfaces and explore their impact on disease prognosis and drug responses.

In Vivo Differentiation of Endogenous Bone Marrow-Derived Cells into Insulin-Producing Cells Using Four Soluble Factors.

Four soluble factors-putrescine, glucosamine, nicotinamide, and signal transducer and activator of transcription 3 (STAT3) inhibitor BP-1-102-were shown to differentiate bone marrow mononucleated cells (BMNCs) into functional insulin-producing cells (IPCs) in vitro. Transplantation of these IPCs improved hyperglycemia in diabetic mice. However, the role of endogenous BMNC regeneration in this effect was unclear.