Immune Checkpoint Inhibitors +/- Chemotherapy for Patients With NSCLC and Brain Metastases: A Systematic Review and Network Meta-Analysis.

Background: Multiple studies have demonstrated the intracranial efficacy of immune checkpoint inhibitors (ICI) +/- chemotherapy. The efficacy of chemoimmunotherapy compared to ICI alone in patients with metastatic NSCLC and brain metastases (BM) remains unknown.

Methods: A systematic review and network meta-analysis were performed to evaluate ICI efficacy and the influence of additional chemotherapy on survival outcomes in treatment-naïve metastatic NSCLC with BM.

Noncanonical role of Golgi-associated macrophage TAZ in chronic inflammation and tumorigenesis.

Until now, Hippo pathway-mediated nucleocytoplasmic translocation has been considered the primary mechanism by which yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) transcriptional coactivators regulate cell proliferation and differentiation via transcriptional enhanced associate domain (TEAD)-mediated target gene expression. In this study, however, we found that TAZ, but not YAP, is associated with the Golgi apparatus in macrophages activated via Toll-like receptor ligands during the resolution phase of inflammation. Golgi-associated TAZ enhanced vesicle trafficking and secretion of proinflammatory cytokines in M1 macrophage independent of the Hippo pathway.

Exosome-based targeted delivery of NF-κB ameliorates age-related neuroinflammation in the aged mouse brain.

Neuroinflammation, a significant contributor to various neurodegenerative diseases, is strongly associated with the aging process; however, to date, no efficacious treatments for neuroinflammation have been developed. In aged mouse brains, the number of infiltrating immune cells increases, and the key transcription factor associated with increased chemokine levels is nuclear factor kappa B (NF-κB). Exosomes are potent therapeutics or drug delivery vehicles for various materials, including proteins and regulatory genes, to target cells.

Homologous recombination promotes non-immunogenic mitotic cell death upon DNA damage.

Double-strand breaks (DSBs) can initiate mitotic catastrophe, a complex oncosuppressive phenomenon characterized by cell death during or after cell division. Here we unveil how cell cycle-regulated DSB repair guides disparate cell death outcomes through single-cell analysis of extended live imaging. Following DSB induction in S or G2, passage of unresolved homologous recombination intermediates into mitosis promotes non-immunogenic intrinsic apoptosis in the immediate attempt at cell division.

Genome-Wide Association Study to Identify Genetic Factors Linked to HBV Reactivation Following Liver Transplantation in HBV-Infected Patients.

This study utilized a genome-wide association study (GWAS) to investigate the genetic variations linked to the risk of hepatitis B virus (HBV) reactivation in patients who have undergone liver transplantation (LT), aiming to enhance understanding and improve clinical outcomes. Genotyping performed on a selected patients from the Korean Organ Transplantation Registry (KOTRY) data using high-throughput platforms with the Axiom Korea Biobank array 1.1.

Guidelines for plasma membrane protein detection by surface biotinylation.

Plasma membrane proteins are crucial for signal transduction, trafficking, and cell-cell interactions, all of which are vital for cell survival. These proteins, including G-protein coupled receptors, ion channels, transporters, and receptors, are key drug targets due to their central role in receiving and amplifying cellular signals. However, the isolation and purification of plasma membrane proteins pose significant challenges because of their integration with phospholipid bilayers and the small fraction of these proteins present in the plasma membrane.

Common genetic etiologies of sensorineural hearing loss in Koreans.

Hearing loss is the most common sensory disorder. Genetic factors contribute substantially to this condition, although allelic heterogeneity and variable expressivity make a definite molecular diagnosis challenging. To provide a brief overview of the genomic landscape of sensorineural hearing loss in Koreans, this article reviews the genetic etiologies of nonsyndromic hearing loss in Koreans as well as the clinical characteristics, genotype-phenotype correlations, and pathogenesis of hearing loss arising from common variants observed in this population.

Inhibition of Mitochondrial Bioenergetics and Hypoxia to Radiosensitize Diffuse Intrinsic Pontine Glioma.

Background: Diffuse Intrinsic Pontine Gliomas (DIPG) and other H3K27M-mutated diffuse midline gliomas (DMGs) are brain tumors that primarily affect children. Radiotherapy is the standard of care but only provides temporary symptomatic relief due to radioresistance. While hypoxia is a major driver of radioresistance in other tumors, there is no definitive evidence that DIPGs are hypoxic.

Predictive Value of the nProfiler 1 Assay for the Efficacy of Adjuvant S-1-Based Doublet Chemotherapy in Stage III Gastric Cancer: A Post-Hoc Analysis of a Randomized Phase III Trial.

Purpose: The nProfiler 1 Stomach Cancer Assay (nProfiler1), designed to predict responses to fluorouracil-based adjuvant chemotherapy, measures the expression of four gastric cancer target genes (GZMB, WARS, SFRP4, and CDX1). The randomized phase III POST trial aimed to compare the efficacies of two adjuvant S-1-based doublet chemotherapies: S-1 plus cisplatin (SP) and S-1 plus docetaxel (DS). This study aimed to validate the nProfiler1 assay using a distinct cohort from the POST trial.

Radiotherapy Improves Survival in NSCLC After Oligoprogression on Immunotherapy: A Cohort Study.

Introduction: The patterns of oligoprogression after first-line immune checkpoint inhibitors (ICIs) for metastatic NSCLC are yet to be well established. An increasing volume of data suggests that directed radiotherapy improves survival outcomes in patients with progression after ICIs.

Methods: A retrospective cohort study was performed on patients with metastatic NSCLC who had completed first-line programmed death-(ligand) 1 inhibitor therapy with or without chemotherapy at two high-volume cancer centers.

Genotype-Phenotype Correlations in 83 Korean X-linked Retinoschisis Patients: Impact of Retinoschisin 1 Secretion Profiles on Clinical Phenotypes.

Purpose: To assess the correlation between genotype and phenotype severity in X-linked juvenile retinoschisis (XLRS) by examining clinical and genetic features of a cohort of Korean XLRS patients.

Design: Retrospective, observational study.

Participants: Data from 83 consecutive male patients with molecularly confirmed XLRS were collected retrospectively.

Clinical Characteristics and Audiological Profiles of Patients with Pathogenic Variants of .

Mutations in Wolfram syndrome 1 () cause Wolfram syndrome and autosomal dominant non-syndromic hearing loss DFNA6/14/38. To date, more than 300 pathogenic variants of have been identified. Generally, the audiological phenotype of Wolfram syndrome or DFNA6/14/38 is characterized by low-frequency hearing loss; however, this phenotype is largely variable.

PARK2 as a susceptibility factor for nontuberculous mycobacterial pulmonary disease.

Background: The genetic signatures associated with the susceptibility to nontuberculous mycobacterial pulmonary disease (NTM-PD) are still unknown. In this study, we performed RNA sequencing to explore gene expression profiles and represent characteristic factor in NTM-PD.

Methods: Peripheral blood samples were collected from patients with NTM-PD and healthy individuals (controls).

Regenerative Role of Lrig1+ Cells in Kidney Repair.

Key Points: cells exist long term during kidney homeostasis and become activated upon injury, contributing to regeneration. cells and their progeny emerge during tubulogenesis and contribute to proximal tubule and inner medullary collecting duct development. cells expand and differentiate into a mature nephron lineage in response to AKI to repair the proximal tubule.

Vestibular hair cells are more prone to damage by excessive acceleration insult in the mouse with KCNQ4 dysfunction.

KCNQ4 is a voltage-gated K channel was reported to distribute over the basolateral surface of type 1 vestibular hair cell and/or inner surface of calyx and heminode of the vestibular nerve connected to the type 1 vestibular hair cells of the inner ear. However, the precise localization of KCNQ4 is still controversial and little is known about the vestibular phenotypes caused by KCNQ4 dysfunction or the specific role of KCNQ4 in the vestibular organs. To investigate the role of KCNQ4 in the vestibular organ, 6-g hypergravity stimulation for 24 h, which represents excessive mechanical stimulation of the sensory epithelium, was applied to p.

Site-Specific Response and Resistance Patterns in Patients with Advanced Non-Small-Cell Lung Cancer Treated with First-Line Systemic Therapy.

Patients with advanced NSCLC have heterogenous responses to immune checkpoint inhibitors (ICIs) with or without chemotherapy. In NSCLC, the impact of the distribution of metastatic sites and the response to systemic therapy combinations remain poorly understood. In a retrospective cohort study of patients with unresectable stage III/IV NSCLC who received first-line systemic therapy, we sought to assess the association between the site of metastases with patterns of response and progression.

Exploring the clinical transition of engineered exosomes designed for intracellular delivery of therapeutic proteins.

Extracellular vesicles, particularly exosomes, have emerged as promising drug delivery systems owing to their unique advantages, such as biocompatibility, immune tolerability, and target specificity. Various engineering strategies have been implemented to harness these innate qualities, with a focus on enhancing the pharmacokinetic and pharmacodynamic properties of exosomes via payload loading and surface engineering for active targeting. This concise review outlines the challenges in the development of exosomes as drug carriers and offers insights into strategies for their effective clinical translation.

Anchorage Dependence and Cancer Metastasis.

The process of cancer metastasis is dependent on the cancer cells' capacity to detach from the primary tumor, endure in a suspended state, and establish colonies in other locations. Anchorage dependence, which refers to the cells' reliance on attachment to the extracellular matrix (ECM), is a critical determinant of cellular shape, dynamics, behavior, and, ultimately, cell fate in nonmalignant and cancer cells. Anchorage-independent growth is a characteristic feature of cells resistant to anoikis, a programmed cell death process triggered by detachment from the ECM.

Immune Cells Are Differentially Affected by SARS-CoV-2 Viral Loads in K18-hACE2 Mice.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×10 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×10 PFU.

Reprogramming anchorage dependency to develop cell lines for recombinant protein expression.

As the biopharmaceutical industry continues to mature in its cost-effectiveness and productivity, many companies have begun employing larger-scale biomanufacturing and bioprocessing protocols. While many of these protocols require cells with anchorage-independent growth, it remains challenging to induce the necessary suspension adaptations in many different cell types. In addition, although transfection efficiency is an important consideration for all cells, especially for therapeutic protein production, cells in suspension are generally more difficult to transfect than adherent cells.

Radiation therapy for ventricular arrhythmias.

Ventricular arrhythmias (VA) can be life-threatening arrhythmias that result in significant morbidity and mortality. Catheter ablation (CA) is an invasive treatment modality that can be effective in the treatment of VA where medications fail. Recurrence occurs commonly following CA due to an inability to deliver lesions of adequate depth to cauterise the electrical circuits that drive VA or reach areas of scar responsible for VA.