IL-4-mediated Pro-Regenerative Cellular Reprogramming in 3D Liver Culture.

Background & Aims: Interleukin-4 (IL-4) is a key contributor to liver regeneration but its effects remain poorly understood due to a lack of models that preserve the complex cellular interactions of the liver. Here, we use murine precision-cut liver slices (PCLS), a 3D tissue culture system that maintains both parenchymal and non-parenchymal cells, to investigate the role of IL-4 in hepatic cell reprogramming. Through longitudinal single-cell transcriptomics and protein-level validation, we demonstrate the pro-regenerative potential of IL-4.

Differential effects of sport type on brain versus orthopedic injury and sports benefits in the adolescent brain cognitive development study.

Background: Sports participation benefits children but increases the risk of mild traumatic brain injury (mTBI) and orthopedic injury (OI). This study examines risks of mTBI vs. OI associated with specific sports and benefits of sports participation.

Emulating Six Cardiovascular Outcome Trials of Antidiabetic Drugs in Individuals with Type 2 Diabetes: Analyses Based on Real-World Databases from Korea and Taiwan.

With the increasing volume of clinical evidence derived from large-scale Asian real-world data (RWD) and the growing interest in its use in regulatory decision-making, it is important to conduct benchmarking exercises that evaluate whether studies using Asian RWD can generate similar conclusions as randomized controlled trials (RCTs). We aimed to assess whether observational studies based on Korea and Taiwan RWD can yield comparable results with trials by emulating six cardiovascular outcome trials (CVOTs) of antidiabetic drugs in individuals with type 2 diabetes (T2D). We emulated six CVOTs using nationwide claims of Korea and Taiwan.

Trimethylamine--Oxide Affects Cell Type-Specific Pathways and Networks in Mouse Aorta to Promote Atherosclerotic Plaque Vulnerability.

Background: Trimethylamine--oxide (TMAO) has been significantly linked to atherosclerosis via several mechanisms, but its direct effect on the atherosclerosis-prone vasculature remains unclear. The objective of this study was to characterize the cell type-dependent and independent effects of TMAO on key vascular cell types involved in atherosclerosis progression in vivo.

Methods: We performed single-cell RNA-sequencing on aortic athero-prone regions of female mice fed normal laboratory, high-cholesterol, or high-cholesterol+TMAO diets for 3 months to identify which aortic cell types, differentially expressed genes, and biological pathways are affected by TMAO.

Predicting Infection Risk in Rheumatoid Arthritis Patients Treated with Biological and Targeted Synthetic Disease-Modifying Anti-Rheumatic Drugs: An Application of Machine Learning.

Patients with rheumatoid arthritis (RA) on biologic or targeted synthetic DMARDs (b/ts DMARDs) face increased serious infection risk. This study developed and validated a machine learning model to predict one-year risk using data from Hong Kong's CDARS and the U.S.

A qualitative study of a new metric for estimating early-onset colorectal cancer risk in male veterans: "Colon Age".

Background: In several Western nations, cancers of the colon and rectum have been steadily increasing in persons younger than age 50. Although the age at which to begin colorectal cancer (CRC) screening in the U.S.

Multi-selective RAS(ON) Inhibition Targets Oncogenic RAS Mutations and Overcomes RAS/MAPK-Mediated Resistance to FLT3 and BCL2 Inhibitors in Acute Myeloid Leukemia.

Aberrant activation of the RAS/MAPK signaling limits the clinical efficacy of several targeted therapies in acute myeloid leukemia (AML). In -mutant AML, the selection of clones harboring heterogeneous RAS mutations drives resistance to FLT3 inhibitors (FLT3i). RAS activation is also associated with resistance to other AML targeted therapies, including the BCL2 inhibitor venetoclax.

Safety of combination therapy of azilsartan medoxomil and amlodipine: a population-based cohort study.

Objectives: This study investigated the safety of azilsartan and amlodipine combination therapy versus other angiotensin receptor blockers (ARBs) and amlodipine in patients with hypertension.

Methods: We conducted a cohort study utilizing healthcare databases from Korea and Taiwan. Patients aged between 18 years and 75 years who were newly prescribed both an ARB and amlodipine within 6 months of hypertension diagnosis were included.

Key Connectomes and Synaptic-Compartment-Specific Risk Genes Drive Pathological α-Synuclein Spreading.

Previous studies have suggested that pathological α-synuclein (α-Syn) mainly transmits along the neuronal network, but several key questions remain unanswered: 1) How many and which connections in the connectome are necessary for predicting the progression of pathological α-Syn? 2) How to identify risk genes that affect pathology spreading functioning at presynaptic or postsynaptic regions, and are these genes enriched in different cell types? Here, these questions are addressed with novel mathematical models. Strikingly, the spreading of pathological α-Syn is predominantly determined by the key subnetworks composed of only 2% of the strongest connections in the connectome. Genes associated with the selective vulnerability of brain regions to pathological α-Syn transmission are further analyzed to distinguish those functioning at presynaptic versus postsynaptic regions.

Boys Versus Girls Youth Sports Participation Risk for Mild Traumatic Brain Injury and Behavioral, Physical Health, and Neurocognitive Outcomes.

Objective: Investigate sex-related differences in mild traumatic brain injury (mTBI) risks due to sports among children aged 9 to 10 years and examine whether the benefits of sports participation, specifically in behavioral, neurocognitive, and psychiatric health, differ between boys and girls.

Setting: The Adolescent Brain Cognitive Development study involves 21 sites across the United States. The data were collected through comprehensive evaluations including neuroimaging, cognitive tests, mental health evaluations, family and environmental factors, and genetic data.

Distinguish risk genes functioning at presynaptic or postsynaptic regions and key connectomes associated with pathological α-synuclein spreading.

Previous studies have suggested that pathological α-synuclein (α-Syn) mainly transmits along the neuronal network, but several key questions remain unanswered: (1) How many and which connections in the connectome are necessary for predicting the progression of pathological α-Syn? (2) How to identify risk gene that affects pathology spreading functioning at presynaptic or postsynaptic regions, and are these genes enriched in different cell types? Here, we addressed these key questions with novel mathematical models. Strikingly, the spreading of pathological α-Syn is predominantly determined by the key subnetworks composed of only 2% of the strongest connections in the connectome. We further explored the genes that are responsible for the selective vulnerability of different brain regions to transmission to distinguish the genes that play roles in presynaptic from those in postsynaptic regions.

Novel Computational Pipeline Enables Reliable Diagnosis of Inverted Urothelial Papilloma and Distinguishes It From Urothelial Carcinoma.

Purpose: With the aid of ever-increasing computing resources, many deep learning algorithms have been proposed to aid in diagnostic workup for clinicians. However, existing studies usually selected informative patches from whole-slide images for the training of the deep learning model, requiring labor-intensive labeling efforts. This work aimed to improve diagnostic accuracy through the statistic features extracted from hematoxylin and eosin-stained slides.

Trimethylamine-N-oxide affects cell type-specific pathways and networks in mouse aorta to promote atherosclerotic plaque vulnerability.

Background: Trimethylamine-N-oxide (TMAO) has been significantly linked to atherosclerosis via several mechanisms, but its direct effect on the atherosclerosis-prone vasculature remains unclear. The objective of this study was to characterize the cell type-dependent and independent effects of TMAO on key vascular cell types involved in atherosclerosis progression .

Methods: We performed single cell RNA-sequencing (scRNAseq) on aortic athero-prone regions of female mice fed control Chow, high-cholesterol (HC), or HC+TMAO diets for three months to identify which aortic cell types, differentially expressed genes, and biological pathways are affected by TMAO.

Global Trends in Analgesic Opioid Use in Pregnancy: A Retrospective Cohort Study.

Background: Pain is common during pregnancy, yet there are few contemporary studies of opioid use in pregnancy. This study aimed to describe prescription analgesic opioid use during pregnancy across four regions: Oceania (New South Wales, Australia, and New Zealand), North America (Ontario, Canada, and United States), Northern Europe (Denmark, Finland, Iceland, Norway, Sweden, and United Kingdom), and East Asia (Hong Kong, South Korea, and Taiwan).

Methods: A common protocol was applied to population-based data to measure analgesic opioid dispensing or prescriptions during pregnancy before birth in 2000 to 2020.

Glucagon-Like Peptide 1 Receptor Agonists and Risk of Thyroid Cancer: An International Multisite Cohort Study.

Concerns have been raised that glucagon-like peptide 1 receptor agonists (GLP1-RAs) may increase the risk of thyroid cancer, but evidence remains conflicting. We therefore investigated if GLP1-RA use, compared with use of dipeptidyl peptidase-4 inhibitors (DPP-4is), was associated with thyroid cancer risk in patients with type 2 diabetes. This multisite cohort study with subsequent meta-analysis included six population-based databases from Canada (Ontario), Denmark, Norway, South Korea, Sweden, and Taiwan.

Associations of frailty with survival, hospitalization, functional decline, and toxicity among older adults with advanced non-small cell lung cancer.

Introduction: Among older adults with cancer receiving chemotherapy, frailty indices predict OS and toxicity. Given the increased use of immunotherapy and targeted therapy for advanced non-small cell lung cancer (aNSCLC), we evaluated frailty and Karnofsky Performance Status (KPS) among older adults with aNSCLC receiving chemotherapy, immunotherapy, and/or targeted therapy.

Methods: Patients aged ≥ 65 with aNSCLC starting systemic therapy with non-curative intent underwent geriatric assessments over 6 months.

Key Regulatory Elements of the TGFβ-LRRC15 Axis Predict Disease Progression and Immunotherapy Resistance Across Cancer Types.

Transforming growth factor-beta (TGFβ) has dual roles in cancer, initially suppressing tumors but later promoting metastasis and immune evasion. Efforts to inhibit TGFβ have been largely unsuccessful due to significant toxicity and indiscriminate immunosuppression. Leucine-rich repeat-containing protein 15 (LRRC15) is a TGFβ-regulated antigen expressed by mesenchymal-derived cancer cells and cancer-associated fibroblasts (CAFs).

A Translational Study of the ATR Inhibitor Berzosertib as Monotherapy in Four Molecularly Defined Cohorts of Advanced Solid Tumors.

Purpose: Preclinical studies have identified molecular correlates of sensitivity to ATR inhibition. This translational study was designed to test the ATR inhibitor berzosertib in patients with advanced solid tumors carrying alterations in ATRX, ataxia-telangiectasia-mutated (ATM), genes conferring replication stress (RS), or SDH.

Patients And Methods: Patients were recruited to four cohorts: T1: ATRX-mutant leiomyosarcoma; T2: ATM-mutant solid tumors; T3: solid tumors with mutations in RS-associated genes; and T4: SDH-deficient gastrointestinal stromal tumors (GIST).

Nature and impact of symptoms at time of initial presentation for patients with glioblastoma.

Introduction: In patients diagnosed with glioblastoma (GBM), minimal data exist on the pathway to presentation and the impact of symptoms on survival outcomes. This study aims to detail the symptoms that occur at time of initial presentation, the response to subsequent intervention, and the factors that predict survival in patients managed for GBM.

Methods: A retrospective audit was performed from established prospective databases in patients managed consecutively with radiation therapy (RT) for GBM between 2016 and 2019.

Telementoring to Strengthen Child and Youth Mental Health Care Capacity in Primary Care Providers: Session Duration and Learning Outcomes.

Primary care providers (PCPs) report insufficient capacity for child and youth mental health care (CYMH). The telementoring program Project ECHO (Extension for Community Healthcare Outcomes) can build capacity, but 75- to 120-minute sessions are a participation barrier. Using a Lean health care paradigm, we designed a 60-minute session, and compared self-reported CYMH capacity strengthening (10 constructs) and satisfaction between 60- and 90-minute sessions.

Thyroid hormone T4 mitigates traumatic brain injury in mice by dynamically remodeling cell type specific genes, pathways, and networks in hippocampus and frontal cortex.

The complex pathology of mild traumatic brain injury (mTBI) is a main contributor to the difficulties in achieving a successful therapeutic regimen. Thyroxine (T4) administration has been shown to prevent the cognitive impairments induced by mTBI in mice but the mechanism is poorly understood. To understand the underlying mechanism, we carried out a single cell transcriptomic study to investigate the spatiotemporal effects of T4 on individual cell types in the hippocampus and frontal cortex at three post-injury stages in a mouse model of mTBI.