A Novel Point-of-Care Prediction Model for Steatotic Liver Disease: Expected Role of Mass Screening in the Global Obesity Crisis.

Background/aims: The incidence of steatotic liver disease (SLD) is increasing across all age groups as the incidence of obesity increases worldwide. The existing noninvasive prediction models for SLD require laboratory tests or imaging and perform poorly in the early diagnosis of infrequently screened populations such as young adults and individuals with healthcare disparities. We developed a machine learning-based point-of-care prediction model for SLD that is readily available to the broader population with the aim of facilitating early detection and timely intervention and ultimately reducing the burden of SLD.

Heat-Killed subsp. 557 Extracts Protect Chondrocytes from Osteoarthritis Damage by Reducing Inflammation: An In Vitro Study.

Background: Osteoarthritis (OA) is a chronic condition characterized by joint pain and disability, driven by excessive oxidative stress and inflammatory cytokine production in chondrocytes, resulting in cell death and cartilage matrix breakdown. Our previous study showed that in monosodium iodoacetate (MIA)-induced OA rats, oral administration of heat-killed subsp. 557 (LDL557) could significantly decrease OA progression.

Medium-Sized Rotator Cuff Tears Repaired With Transosseous-Equivalent Technique Plus Bone Marrow Stimulation Yielded Similar Short-Term Outcomes Regardless of Whether Complete or Incomplete Footprint Coverage Was Achieved.

Purpose: To compare clinical outcomes and retear rates of medium-sized rotator cuff tears repaired with incomplete footprint coverage using the transosseous-equivalent technique versus those with complete footprint coverage plus bone marrow stimulation.

Methods: The retrospective study, conducted from March 2019 to December 2021, included consecutive patients with medium-sized (1-3 cm) posterosuperior rotator cuff tears repaired using the transosseous-equivalent technique and bone marrow stimulation, with a minimum follow-up of 2 years. Patients were divided into 2 groups based on the degree of footprint coverage achieved: group C (complete coverage) and group I (incomplete coverage).

Engineered extrachromosomal oncogene amplifications promote tumorigenesis.

Focal gene amplifications are among the most common cancer-associated mutations but have proven challenging to engineer in primary cells and model organisms. Here we describe a general strategy to engineer large (more than 1 Mbp) focal amplifications mediated by extrachromosomal DNAs (ecDNAs) in a spatiotemporally controlled manner in cells and in mice. By coupling ecDNA formation with expression of selectable markers, we track the dynamics of ecDNA-containing cells under physiological conditions and in the presence of specific selective pressures.

A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis.

The cohesin complex is a critical regulator of gene expression. STAG2 is the most frequently mutated cohesin subunit across several cancer types and is a key tumor suppressor in lung cancer. Here, we coupled somatic CRISPR-Cas9 genome editing and tumor barcoding with an autochthonous oncogenic KRAS-driven lung cancer model and showed that STAG2 is uniquely tumor-suppressive among all core and auxiliary cohesin components.

Enhancing transcription-replication conflict targets ecDNA-positive cancers.

Extrachromosomal DNA (ecDNA) presents a major challenge for cancer patients. ecDNA renders tumours treatment resistant by facilitating massive oncogene transcription and rapid genome evolution, contributing to poor patient survival. At present, there are no ecDNA-specific treatments.

Coordinated inheritance of extrachromosomal DNAs in cancer cells.

The chromosomal theory of inheritance dictates that genes on the same chromosome segregate together while genes on different chromosomes assort independently. Extrachromosomal DNAs (ecDNAs) are common in cancer and drive oncogene amplification, dysregulated gene expression and intratumoural heterogeneity through random segregation during cell division. Distinct ecDNA sequences, termed ecDNA species, can co-exist to facilitate intermolecular cooperation in cancer cells.

Origins and impact of extrachromosomal DNA.

Extrachromosomal DNA (ecDNA) is a major contributor to treatment resistance and poor outcome for patients with cancer. Here we examine the diversity of ecDNA elements across cancer, revealing the associated tissue, genetic and mutational contexts. By analysing data from 14,778 patients with 39 tumour types from the 100,000 Genomes Project, we demonstrate that 17.

Deciphering regulation of FOXP3 expression in human conventional T cells.

FOXP3 is a lineage-defining transcription factor that controls differentiation and maintenance of suppressive function of regulatory T cells (Tregs). Foxp3 is exclusively expressed in Tregs in mice. However, in humans, FOXP3 is not only constitutively expressed in Tregs; it is also transiently expressed in stimulated CD4+CD25- conventional T cells (Tconvs).

The Oral Administration of subsp. 557 (LDL557) Ameliorates the Progression of Monosodium Iodoacetate-Induced Osteoarthritis.

Low-grade body inflammation is a major cause of osteoarthritis (OA), a common joint disease. Gut dysbiosis may lead to systemic inflammation which can be prevented by probiotic administration. The subsp.

Disparate Pathways for Extrachromosomal DNA Biogenesis and Genomic DNA Repair.

Our study harnesses a CRISPR-based method to examine ecDNA biogenesis, uncovering efficient circularization between double-strand breaks. ecDNAs and their corresponding chromosomal scars can form via nonhomologous end joining or microhomology-mediated end joining, but the ecDNA and scar formation processes are distinct. Based on our findings, we establish a mechanistic model of excisional ecDNA formation.

Automated Comprehensive CT Assessment of the Risk of Diabetes and Associated Cardiometabolic Conditions.

Background CT performed for various clinical indications has the potential to predict cardiometabolic diseases. However, the predictive ability of individual CT parameters remains underexplored. Purpose To evaluate the ability of automated CT-derived markers to predict diabetes and associated cardiometabolic comorbidities.

Incidence and Outcomes of Cardiocerebral Infarction: A Cohort Study of 2 National Population-Based Registries.

Background: Cardiocerebral infarction (CCI), which is concomitant with acute myocardial infarction (AMI) and acute ischemic stroke (AIS), is a rare but severe presentation. However, there are few data on CCI, and the treatment options are uncertain. We investigated the characteristics and outcomes of CCI compared with AMI or AIS alone.

Effects of Shoulder Corrective Training Program on Pitching Loads and Sonographic Morphology in Elbow Joint in Youth Baseball Players.

Chen, P-T, Lin, Y-C, Chang, H-Y, Chiu, C-H, Chen, C-Y, Chen, P, and Lin, Y-H. Effects of shoulder corrective training program on pitching loads and sonographic morphology in elbow joint in youth baseball players. J Strength Cond Res 38(8): e440-e447, 2024-We assessed the effects of a 12-week shoulder corrective training program for shoulder flexibility and strengthening on pitching loads and sonographic morphology of the elbow joints in youth baseball players.

Cohesin prevents cross-domain gene coactivation.

The contrast between the disruption of genome topology after cohesin loss and the lack of downstream gene expression changes instigates intense debates regarding the structure-function relationship between genome and gene regulation. Here, by analyzing transcriptome and chromatin accessibility at the single-cell level, we discover that, instead of dictating population-wide gene expression levels, cohesin supplies a general function to neutralize stochastic coexpression tendencies of cis-linked genes in single cells. Notably, cohesin loss induces widespread gene coactivation and chromatin co-opening tens of million bases apart in cis.

Screening Outcomes of Mammography with AI in Dense Breasts: A Comparative Study with Supplemental Screening US.

Background Comparative performance between artificial intelligence (AI) and breast US for women with dense breasts undergoing screening mammography remains unclear. Purpose To compare the performance of mammography alone, mammography with AI, and mammography plus supplemental US for screening women with dense breasts, and to investigate the characteristics of the detected cancers. Materials and Methods A retrospective database search identified consecutive asymptomatic women (≥40 years of age) with dense breasts who underwent mammography plus supplemental whole-breast handheld US from January 2017 to December 2018 at a primary health care center.

Discovery of a mu-opioid receptor modulator that in combination with morphinan antagonists induces analgesia.

Morphinan antagonists, which block opioid effects at mu-opioid receptors, have been studied for their analgesic potential. Previous studies have suggested that these antagonists elicit analgesia with fewer adverse effects in the presence of the mutant mu-opioid receptor (MOR; S196A). However, introducing a mutant receptor for medical applications represents significant challenges.

Clonal inactivation of TERT impairs stem cell competition.

Telomerase is intimately associated with stem cells and cancer, because it catalytically elongates telomeres-nucleoprotein caps that protect chromosome ends. Overexpression of telomerase reverse transcriptase (TERT) enhances the proliferation of cells in a telomere-independent manner, but so far, loss-of-function studies have provided no evidence that TERT has a direct role in stem cell function. In many tissues, homeostasis is shaped by stem cell competition, a process in which stem cells compete on the basis of inherent fitness.

Optimizing immunofluorescence with high-dynamic-range imaging to enhance PD-L1 expression evaluation for 3D pathology assessment from NSCLC tumor tissue.

Assessing programmed death ligand 1 (PD-L1) expression through immunohistochemistry (IHC) is the golden standard in predicting immunotherapy response of non-small cell lung cancer (NSCLC). However, observation of heterogeneous PD-L1 distribution in tumor space is a challenge using IHC only. Meanwhile, immunofluorescence (IF) could support both planar and three-dimensional (3D) histological analyses by combining tissue optical clearing with confocal microscopy.

Implementation of First-Trimester Screening and Prevention of Preeclampsia: A Stepped Wedge Cluster-Randomized Trial in Asia.

Background: This trial aimed to assess the efficacy, acceptability, and safety of a first-trimester screen-and-prevent strategy for preterm preeclampsia in Asia.

Methods: Between August 1, 2019, and February 28, 2022, this multicenter stepped wedge cluster randomized trial included maternity/diagnostic units from 10 regions in Asia. The trial started with a period where all recruiting centers provided routine antenatal care without study-related intervention.

hnRNPM protects against the dsRNA-mediated interferon response by repressing LINE-associated cryptic splicing.

RNA splicing is pivotal in post-transcriptional gene regulation, yet the exponential expansion of intron length in humans poses a challenge for accurate splicing. Here, we identify hnRNPM as an essential RNA-binding protein that suppresses cryptic splicing through binding to deep introns, maintaining human transcriptome integrity. Long interspersed nuclear elements (LINEs) in introns harbor numerous pseudo splice sites.

The CD8 T cell tolerance checkpoint triggers a distinct differentiation state defined by protein translation defects.

Peripheral CD8 T cell tolerance is a checkpoint in both autoimmune disease and anti-cancer immunity. Despite its importance, the relationship between tolerance-induced states and other CD8 T cell differentiation states remains unclear. Using flow cytometric phenotyping, single-cell RNA sequencing (scRNA-seq), and chromatin accessibility profiling, we demonstrated that in vivo peripheral tolerance to a self-antigen triggered a fundamentally distinct differentiation state separate from exhaustion, memory, and functional effector cells but analogous to cells defectively primed against tumors.