Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Mitochondria-targeted oligomeric α-synuclein induces TOM40 degradation and mitochondrial dysfunction in Parkinson's disease and parkinsonism-dementia of Guam.

Mitochondrial dysfunction is a central aspect of Parkinson's disease (PD) pathology, yet the underlying mechanisms are not fully understood. This study investigates the link between α-Synuclein (α-Syn) pathology and the loss of translocase of the outer mitochondrial membrane 40 (TOM40), unraveling its implications for mitochondrial dysfunctions in neurons. We discovered that TOM40 protein depletion occurs in the brains of patients with Guam Parkinsonism-Dementia (Guam PD) and cultured neurons expressing α-Syn proteinopathy, notably, without corresponding changes in TOM40 mRNA levels.

High prevalence of hepatitis C virus infection among adolescents and young adults attending HIV and sexual health clinics.

Background: The prevalence of hepatitis C virus (HCV) infection among Thai adults is 0.5%-1.0%.

Carbapenem-resistant Enterobacterales in solid organ transplant recipients.

Carbapenem-resistant Enterobacterales (CRE) are an important threat to the health of solid organ transplant recipients (SOTr); data comparing outcomes of SOTr with CRE to non-SOTr with CRE are lacking. A matched cohort study was performed within 2 prospective, multicenter, cohort studies (Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacterales and Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacterales 2). The epidemiology, desirability of outcome rankings outcomes, and mortality of SOTr and non-SOTr hospitalized in the United States (December 2011-August 2017) with clinical isolates with Centers for Disease Control and Prevention-defined CRE were compared.

Increased brain iron deposition in the basial ganglia is associated with cognitive and motor dysfunction in type 2 diabetes mellitus.

Objective: Compared with those in type 2 diabetes mellitus (T2DM) patients without diabetic peripheral neuropathy (DPN), alterations in brain iron levels in the basal ganglia (an iron-rich region) and motor and cognitive dysfunction in T2DM patients with DPN have not been fully elucidated. We aimed to explore changes in brain iron levels in the basal ganglia in T2DM patients with DPN using quantitative susceptibility mapping (QSM).

Methods: Thirty-four patients with DPN, fifty-five patients with diabetes without DPN (non-DPN, NDPN), and fifty-one healthy controls (HCs) were recruited and underwent cognitive and motor assessments, blood biochemical tests, and brain QSM imaging.

The association of type and number of high-risk criteria with cancer-specific mortality in prostate cancer patients treated with radical prostatectomy.

Objectives: This study aimed to test the association between of type and number of D'Amico high-risk criteria (DHRCs) with cancer-specific mortality (CSM) in high-risk prostate cancer patients treated with radical prostatectomy.

Materials And Methods: In the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 31,281 radical prostatectomy patients with at least 1 DHRC, namely, prostate-specific antigen (PSA) >20 ng/mL (hrPSA), biopsy Gleason Grade Group (hrGGG) score of 4 and 5, or clinical tumor stage ≥T3 (hrcT). Multivariable Cox regression models and competing risks regression models (adjusting for other cause mortality) tested the association between DHRCs and 5-year CSM.

CHRONOS-4: phase 3 study of copanlisib plus rituximab-based immunochemotherapy in relapsed indolent B-cell lymphoma.

Copanlisib, a pan-class I phosphatidylinositol 3-kinase inhibitor with predominant activity against the α and δ isoforms, previously demonstrated durable responses as monotherapy and improved progression-free survival (PFS) in combination with rituximab in patients with relapsed indolent non-Hodgkin lymphoma (iNHL). CHRONOS-4 was a phase 3, randomized, double-blind, placebo-controlled study to investigate the efficacy and safety of copanlisib in combination with standard immunochemotherapy in patients with relapsed iNHL. Patients (n = 524) were randomized (1:1) to copanlisib (60 mg IV) plus immunochemotherapy (rituximab and bendamustine [R-B] or placebo plus R-B).

Factors influencing research productivity among Syrian medical professionals amidst conflict: a case-control study.

Background: Medical research productivity is globally increasing, with a lagging progress in third-world countries due to significant challenges, including inadequate training and brain drain. Syria had been showing a slow upward trend until the war broke out and severely hindered academic growth and productivity. A deeper understanding of the factors influencing research productivity in this context are fundamental to guide educational policies and resource allocation.

Evaluating the robustness of an AI pathfinder application on eligibility criteria in multiple myeloma trials using real-world data and historical trials.

Eligibility criteria are pivotal in achieving clinical trial success, enabling targeted patient enrollment while ensuring the trial safety. However, overly restrictive criteria hinder enrollment and study result generalizability. Broadening eligibility criteria enhances the trial inclusivity, diversity and enrollment pace.

Zolbetuximab plus chemotherapy for locally advanced unresectable or metastatic stomach or gastroesophageal junction cancers: a plain language summary.

What Is This Summary About?: This is a summary of two articles. The first article is about a clinical trial called SPOTLIGHT and it was published in the medical journal in in April of 2023. The second article is about a clinical trial called GLOW and it was published in the medical journal in July of 2023.

Trends in hospital price transparency after implementation of the CMS Final Rule.

Objective: To assess trends in hospital price disclosures after the Centers for Medicare & Medicaid Services (CMS) Final Rule went into effect.

Data Sources And Study Setting: The Turquoise Health Price Transparency Dataset was used to identify all US hospitals that publicly displayed pricing from 2021 to 2023.

Study Design: Price-disclosing versus nondisclosing hospitals were compared using Pearson's Chi-squared and Wilcoxon rank sum tests.

Somatic mutations in FAS pathway increase hemophagocytic lymphohistiocytosis risk in patients with T- and/or NK-cell lymphoma.

Although significant progress has been made in understanding the genetic basis of primary hemophagocytic lymphohistiocytosis (HLH), the pathogenesis of secondary HLH, the more prevalent form, remains unclear. Among the various conditions giving rise to secondary HLH, HLH in patients with lymphoma (HLH-L) accounts for a substantial proportion. In this study, we investigated the role of somatic mutations in the pathogenesis of HLH-L in a cohort of patients with T- and/or natural killer-cell lymphoma.

Efficacy and safety of tepotinib in Asian patients with advanced NSCLC with MET exon 14 skipping enrolled in VISION.

Background: Tepotinib, a MET inhibitor approved for the treatment of MET exon 14 (METex14) skipping NSCLC, demonstrated durable clinical activity in VISION (Cohort A + C; N = 313): objective response rate (ORR) 51.4% (95% CI: 45.8, 57.

Integrating Genome Sequencing and Untargeted Metabolomics in Monozygotic Twins with a Rare Complex Neurological Disorder.

Multi-omics approaches, which integrate genomics, transcriptomics, proteomics, and metabolomics, have emerged as powerful tools in the diagnosis of rare diseases. We used untargeted metabolomics and whole-genome sequencing (WGS) to gain a more comprehensive understanding of a rare disease with a complex presentation affecting female twins from a consanguineous family. The sisters presented with polymicrogyria, a Dandy-Walker malformation, respiratory distress, and multiorgan dysfunctions.

FUS unveiled in mitochondrial DNA repair and targeted ligase-1 expression rescues repair-defects in FUS-linked motor neuron disease.

This study establishes the physiological role of Fused in Sarcoma (FUS) in mitochondrial DNA (mtDNA) repair and highlights its implications to the pathogenesis of FUS-associated neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Endogenous FUS interacts with and recruits mtDNA Ligase IIIα (mtLig3) to DNA damage sites within mitochondria, a relationship essential for maintaining mtDNA repair and integrity in healthy cells. Using ALS patient-derived FUS mutant cell lines, a transgenic mouse model, and human autopsy samples, we discovered that compromised FUS functionality hinders mtLig3's repair role, resulting in increased mtDNA damage and mutations.

Omission and Commission in Morally Injurious Experiences Among COVID-19 Health Care Professionals.

To produce a qualitative description of the impact of moral injury on medical providers during the COVID-19 pandemic. A convergent mixed-methods study design was used to explore experiences of health care workers during the first 12 months of the COVID-19 pandemic. Participants completed the Moral Injury Symptom Scale-HP (MISS-HP) and a 60-minute interview, in which they described their work experiences from March 2020 through January 2021.

A guideline on the molecular ecosystem regulating ferroptosis.

Ferroptosis, an intricately regulated form of cell death characterized by uncontrolled lipid peroxidation, has garnered substantial interest since this term was first coined in 2012. Recent years have witnessed remarkable progress in elucidating the detailed molecular mechanisms that govern ferroptosis induction and defence, with particular emphasis on the roles of heterogeneity and plasticity. In this Review, we discuss the molecular ecosystem of ferroptosis, with implications that may inform and enable safe and effective therapeutic strategies across a broad spectrum of diseases.