First-Line Mobocertinib Versus Platinum-Based Chemotherapy in Patients With Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer in the Phase III EXCLAIM-2 Trial.

Purpose: Mobocertinib is an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that targets exon 20 insertion (ex20ins) mutations in non-small cell lung cancer (NSCLC). This open-label, phase III trial (EXCLAIM-2: ClinicalTrials.gov identifier: NCT04129502) compared mobocertinib versus platinum-based chemotherapy as first-line treatment of ex20ins+ advanced/metastatic NSCLC.

Inherent CeO Pore Structure Confined Pd for the Catalytic Performance Regulation.

In this study, we synthesized CeO possessing an open pore structure and verified its structural differences compared to CeO lacking such an open pore structure. Using these two CeO samples as catalyst supports and loading them with Pd metals, a series of characterizations were carried out on the resultant catalysts to analyze their structures and properties meticulously. We have elucidated the influence of the open pore structure on the loading position of Pd.

Impact of the Adverse Social Exposome on Survival in Individuals With Amyotrophic Lateral Sclerosis.

Background And Objectives: An adverse social exposome negatively affects many diseases, but its association with amyotrophic lateral sclerosis (ALS) survival is unknown. This study examined the association between the social exposome measure Area Deprivation Index (ADI) and ALS survival.

Methods: This is a retrospective analysis of patients with ALS at the University of Michigan Pranger ALS Clinic diagnosed after January 1, 2012.

Association of Year-to-Year Lipid Variability With Risk of Cognitive Decline and Dementia in Community-Dwelling Older Adults.

Background And Objectives: Lipid metabolism in older adults is affected by various factors including biological aging, functional decline, reduced physiologic reserve, and nutrient intake. The dysregulation of lipid metabolism could adversely affect brain health. This study investigated the association between year-to-year intraindividual lipid variability and subsequent risk of cognitive decline and dementia in community-dwelling older adults.

Key Strategies to Promote Professional Wellness and Reduce Burnout in Oncology Clinicians.

Burnout in oncologists has been increasing, especially after the COVID-19 pandemic. This is concerning because burnout can have both personal and professional repercussions, as well as a negative impact on patients and organizational financial health. Drawing on information and ideas discussed at an ASCO Town Hall session at the 2023 Annual Meeting developed by the State of Cancer Care in America Editorial Board, this study reviews key organizational strategies for improving professional well-being and argues for the importance of measuring and researching the well-being of the oncology workforce to ensure healthy work environments.

Ten-Year Trends in Clinician Well-Being and Burnout Among Oncology Fellows in Training: An ASCO State of Cancer Care in America Study.

Purpose: To better understand burnout in oncology and clinician well-being along the career continuum starting with training, we sought to characterize the professional well-being of physicians training in medical oncology in 2023 and to identify trends over time comparing to fellows from a decade prior.

Methods: All US medical oncology fellows taking the 2023 ASCO Medical Oncology In-Training Exam (ITE) were invited to complete an optional post-exam survey evaluating fatigue, satisfaction with work-life integration (WLI), emotional exhaustion and depersonalization. 2023 ITE survey responses were compared to the 2013 ASCO post-ITE survey (n=1345).

Evaluation of the Recent Dynamics for Funding Medicinal Chemistry Projects in Academia. Results of a Survey Conducted by IUPAC Division VII (Chemistry and Human Health).

Data collected from scholars across twenty-three countries over the past decade (2010-2019) reveals a 40% decrease in financial support for medicinal chemistry projects. The decline is especially notable among projects focused on small organic molecules. This drop in grants indicates a troubling trend that could jeopardize future drug development by undermining research in this crucial field.

Cognitive Deficits in Anti-LGI1 Encephalitis Are Linked to Immunotherapy-Resistant White Matter Network Changes.

Background And Objectives: Cognitive deficits represent a major long-term complication of anti-leucine-rich, glioma-inactivated 1 encephalitis (LGI1-E). Although severely affecting patient outcomes, the structural brain changes underlying these deficits remain poorly understood. In this study, we hypothesized a link between white matter (WM) networks and cognitive outcomes in LGI1-E.

Helping authors produce FAIR taxonomic data: evaluation of an author-driven phenotype data production prototype.

It is well-known that the use of vocabulary in phenotype treatments is often inconsistent. An earlier survey of biologists who create or use phenotypic characters revealed that this lack of standardization leads to ambiguities, frustrating both the consumers and producers of phenotypic data. Such ambiguities are challenging for biologists, and more so for Artificial Intelligence, to resolve.

The TOXIN knowledge graph: supporting animal-free risk assessment of cosmetics.

The European Union's ban on animal testing for cosmetic products and their ingredients, combined with the lack of validated animal-free methods, poses challenges in evaluating their potential repeated-dose organ toxicity. To address this, innovative strategies like Next-Generation Risk Assessment (NGRA) are being explored, integrating historical animal data with new mechanistic insights from non-animal New Approach Methodologies (NAMs). This paper introduces the TOXIN knowledge graph (TOXIN KG), a tool designed to retrieve toxicological information on cosmetic ingredients, with a focus on liver-related data.

How a Medical Student Found Himself in a Human Genome Free for All.

In this short memoir, I recount the series of improbable interactions and events that led me from medical school to a leadership role in the Human Genome Project.

Treating Opioid Use Disorder and Opioid Withdrawal in the Context of Fentanyl.

The opioid crisis, driven by illicitly manufactured fentanyl, presents significant challenges in treating opioid use disorder (OUD) and opioid withdrawal syndrome. Fentanyl is uniquely lethal due to its rapid onset and respiratory depressant effects, driving the surge in overdose deaths. This review examines the limitations of traditional diagnostic criteria like those of the , Fifth Edition, Text Revision (DSM-5-TR) and explores the potential of dimensional models such as the Hierarchical Taxonomy of Psychopathology (HiTOP) for a more nuanced understanding of OUD.

Organic Mixed Conductors for Neural Biomimicry and Biointerfacing.

Organic mixed ionic-electronic conductors (OMIECs) could revolutionize bioelectronics by enabling seamless integration with biological systems. This review explores their role in neural biomimicry and biointerfacing, with a focus on how backbone design, sidechain optimization, and antiambipolarity impact performance. Recent advances highlight OMIECs' biocompatibility and mechanical compliance, making them ideal for bioelectronic applications.

Development and Functions of MAIT Cells.

Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved T cells that recognize microbial metabolites. They are abundant in humans and conserved during mammalian evolution, which suggests that they have important nonredundant functions. In this article, we discuss the evolutionary conservation of MAIT cells and describe their original developmental process.

Chromosome length genome assembly of the stone marten (Martes foina, Mustelidae): a new view on one of the cornerstones in carnivore cytogenetics.

The stone marten (Martes foina) is an important species for cytogenetic studies in the order Carnivora. ZooFISH probes created from its chromosomes provided a strong and clean signal in chromosome painting experiments and were valuable for studying the evolution of carnivoran genome architecture. The research revealed that the stone marten chromosome set is similar to the presumed ancestral karyotype of the Carnivora, which added an additional value for the species.

Mechanisms for DNA Interplay in Eukaryotic Transcription Factors.

Like their prokaryotic counterparts, eukaryotic transcription factors must recognize specific DNA sites, search for them efficiently, and bind to them to help recruit or block the transcription machinery. For eukaryotic factors, however, the genetic signals are extremely complex and scattered over vast, multichromosome genomes, while the DNA interplay occurs in a varying landscape defined by chromatin remodeling events and epigenetic modifications. Eukaryotic factors are rich in intrinsically disordered regions and are also distinct in their recognition of short DNA motifs and utilization of open DNA interaction interfaces as ways to gain access to DNA on nucleosomes.

Moral Injury: An Overview of Conceptual, Definitional, Assessment, and Treatment Issues.

Moral injury (MI) is a potential clinical problem characterized by functionally impairing moral emotions, beliefs, and behaviors as well as adverse beliefs about personal or collective humanity and life's meaning and purpose. MI can arise from personal transgressive acts or from being a victim of or bearing witness to others' inhumanity. Despite widespread interest in MI, until recently, there was no reliable measure of MI as an outcome, and prior research has revealed little about its causes, consequences, and intervention approaches.

Type I Interferon Targets Alveolar Macrophages to Promote Bacterial Pneumonia after Viral Infection.

Exposure to influenza A virus (IAV), respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) is well-known to increase the risk of pneumonia in humans. Type I interferon (IFN-I) is a hallmark response to acute viral infections, and alveolar macrophages (AMs) constitute the first line of airway defense against opportunistic bacteria. Our study reveals that virus-induced IFN-I receptor (IFNAR1) signaling directly impairs AM-dependent antibacterial protection.

US Medical Schools' 2024 Commencements and Antisemitism: Addressing Unprofessional Behavior.

Introduction: Antisemitism and antisemitic incidents have been increasing in United States medical institutions since the Hamas attack of October 7, 2023. Such incidents include anecdotal reports of antisemitic displays at medical school commencements. This study examined unprofessional behavior observed at the commencement ceremonies of the 25 US medical schools top-ranked for research excellence.