A Phase 1 Study of FHD-609, a Heterobifunctional Degrader of Bromodomain-Containing Protein 9, in Patients With Advanced Synovial Sarcoma or SMARCB1-Deficient Tumors.

Purpose: FHD-609, a potent, selective, heterobifunctional degrader of bromodomain-containing protein 9 (BRD9), was evaluated for treatment of patients with advanced synovial sarcoma (SS) or SMARCB1-deficient tumors.

Patients And Methods: In this multinational, open-label, phase 1 study (NCT04965753), patients received FHD609 intravenously at escalating doses either twice weekly (BIW) (5 to 80 mg; n=40) or once weekly (QW) (40 to 120 mg; n=15).

Results: Fifty-five patients received FHD-609 for a median of 43 days.

The 2021 US Preventive Services Task Force lung cancer screening eligibility criteria disproportionately exclude younger Black patients with lung cancer.

Background: The 2021 US Preventive Services Task Force (USPSTF) lung cancer screening guideline may continue to exclude many younger Black individuals who have not yet accumulated enough smoking pack-years to be eligible for screening. The objective of this study was to evaluate the proportions of Black and White patients with lung cancer, stratified by age at diagnosis, who would have been eligible for lung cancer screening.

Methods: Incident lung cancer cases among Black and White individuals aged 50-80 years with a smoking history in the Southern Community Cohort Study (SCCS) were identified for analysis.

Genomic tumor evolution dictates human medulloblastoma progression.

Background: Medulloblastoma (MB) is the most common high-grade pediatric brain tumor, comprised of 4 main molecular subgroups-sonic-hedgehog (SHH), Wnt, Group 3, and Group 4. Group 3 and Group 4 tumors are the least characterized MB subgroups, despite Group 3 having the worst prognosis (~50% survival rate), and Group 4 being the most prevalent. Such poor characterization can be attributed to high levels of inter- and intratumoral heterogeneity, making it difficult to identify common therapeutic targets.

Enhancing clinical decision-making: An externally validated machine learning model for predicting isocitrate dehydrogenase mutation in gliomas using radiomics from presurgical magnetic resonance imaging.

Background: Glioma, the most prevalent primary brain tumor, poses challenges in prognosis, particularly in the high-grade subclass, despite advanced treatments. The recent shift in tumor classification underscores the crucial role of isocitrate dehydrogenase (IDH) mutation status in the clinical care of glioma patients. However, conventional methods for determining IDH status, including biopsy, have limitations.

A unified framework for diagnostic test development and evaluation during outbreaks of emerging infections.

Evaluating diagnostic test accuracy during epidemics is difficult due to an urgent need for test availability, changing disease prevalence and pathogen characteristics, and constantly evolving testing aims and applications. Based on lessons learned during the SARS-CoV-2 pandemic, we introduce a framework for rapid diagnostic test development, evaluation, and validation during outbreaks of emerging infections. The framework is based on the feedback loop between test accuracy evaluation, modelling studies for public health decision-making, and impact of public health interventions.

Integration of lipidomics with targeted, single cell, and spatial transcriptomics defines an unresolved pro-inflammatory state in colon cancer.

Background: Over a century ago, Virchow proposed that cancer represents a chronically inflamed, poorly healing wound. Normal wound healing is represented by a transitory phase of inflammation, followed by a pro-resolution phase, with prostaglandin (PGE2/PGD2)-induced 'lipid class switching' producing inflammation-quenching lipoxins (LXA4, LXB4).

Objective: We explored if lipid dysregulation in colorectal cancers (CRCs) is driven by a failure to resolve inflammation.

Classification and functional characterization of regulators of intracellular STING trafficking identified by genome-wide optical pooled screening.

Stimulator of interferon genes (STING) traffics across intracellular compartments to trigger innate responses. Mutations in factors regulating this process lead to inflammatory disorders. To systematically identify factors involved in STING trafficking, we performed a genome-wide optical pooled screen (OPS).

Ongoing evolution of SARS-CoV-2 drives escape from mRNA vaccine-induced humoral immunity.

With the onset of the COVID-19 pandemic 4 years ago, viral sequencing continues to document numerous individual mutations in the viral spike protein across many variants. To determine the ability of vaccine-mediated humoral immunity to combat continued SARS-CoV-2 evolution, we construct a comprehensive panel of pseudoviruses harboring each individual mutation spanning 4 years of the pandemic to understand the fitness cost and resistance benefits of each. These efforts identify numerous mutations that escape from vaccine-induced humoral immunity.

Practical and statistical aspects of subgroup analyses in surgical neuro-oncology: A comprehensive review from the PIONEER Consortium.

Subgroup analyses are essential to generate new hypotheses or to estimate treatment effects in clinically meaningful subgroups of patients. They play an important role in taking the next step towards personalized surgical treatment for brain tumor patients. However, subgroup analyses must be used with consideration and care because they have significant potential risks.

Investigation of hydrogen peroxide yields and oxygen consumption in high dose rate irradiation: a TOPAS-nBio Monte Carlo study.

TOPAS-nBio enables users to simulate dose rate-dependent radiation chemical yields in water radiolysis accounting for inter-track and long-term chemistry for pulsed irradiation. This study aims to extend the TOPAS-nBio chemistry for the special case of continuous high-dose rate scenario, where both intertrack and longer time reactions need to be considered, and to quantitatively validate the extended framework by comparing the results with experimental data.The inter-track chemistry and escape-values were first evaluated by the independent reaction time method.

The QIBA Profile for Dynamic Susceptibility Contrast MRI Quantitative Imaging Biomarkers for Assessing Gliomas.

The dynamic susceptibility contrast (DSC) MRI measures of relative cerebral blood volume (rCBV) play a central role in monitoring therapeutic response and disease progression in patients with gliomas. Previous investigations have demonstrated promise of using rCBV in classifying tumor grade, elucidating tumor viability after therapy, and differentiating pseudoprogression and pseudoresponse. However, the quantification and reproducibility of rCBV measurements across patients, devices, and software remain a critical barrier to routine or clinical trial use of longitudinal DSC MRI in patients with gliomas.

Leptomeningeal metastatic disease: new frontiers and future directions.

Leptomeningeal metastatic disease (LMD), encompassing entities of 'meningeal carcinomatosis', neoplastic meningitis' and 'leukaemic/lymphomatous meningitis', arises secondary to the metastatic dissemination of cancer cells from extracranial and certain intracranial malignancies into the leptomeninges and cerebrospinal fluid. The clinical burden of LMD has been increasing secondary to more sensitive diagnostics, aggressive local therapies for discrete brain metastases, and improved management of extracranial disease with targeted and immunotherapeutic agents, resulting in improved survival. However, owing to drug delivery challenges and the unique microenvironment of LMD, novel therapies against systemic disease have not yet translated into improved outcomes for these patients.

Current State of Community-Driven Radiological AI Deployment in Medical Imaging.

Artificial intelligence (AI) has become commonplace in solving routine everyday tasks. Because of the exponential growth in medical imaging data volume and complexity, the workload on radiologists is steadily increasing. AI has been shown to improve efficiency in medical image generation, processing, and interpretation, and various such AI models have been developed across research laboratories worldwide.

Serum levels of total bile acids are associated with an increased risk of HCC in patients with cirrhosis.

Background: Previous studies have reported higher circulating bile acid levels in patients with HCC compared to healthy controls. However, the association between prediagnostic bile acid levels and HCC risk among patients with cirrhosis is unclear.

Methods: We measured total BA (TBA) concentration in serum samples collected from a prospective cohort of patients with cirrhosis who were followed until the development of HCC, death, or last study date.

Adolescents' Self-Reported Exposure to Advertisements for Flavored Tobacco Products After Implementation of a Statewide Ban on Flavored Tobacco Product Sales and Advertising in Massachusetts.

Objectives: Massachusetts signed into law An Act Modernizing Tobacco Control (hereinafter, the Act) in 2019, which restricted retail sales of flavored tobacco products, including menthol cigarettes. This study assessed differences in advertising exposure to flavored tobacco products among adolescents in Massachusetts compared with adolescents in 4 neighboring states after passage of the Act.

Methods: We collected monthly cross-sectional survey data from April 2021 through August 2022 among a convenience sample of adolescents (aged 13-17 y) in Massachusetts and 4 control states: Connecticut, New Hampshire, Rhode Island, and Vermont.

Liver-related mortality in homeless-experienced adults over a 16-year period.

Homeless-experienced adults have higher liver-related mortality than the general population. The objective of our study was to examine temporal liver-related mortality trends and assess cause-specific liver-related mortality disparities in a large cohort of homeless-experienced adults. We linked a cohort of 60,092 adults who received care at Boston Health Care for the Homeless Program (BHCHP) from 2003-2017 to Massachusetts death occurrence files spanning 2003-2018.

Treatment sequence with tebentafusp and immune checkpoint inhibitors in patients with metastatic uveal melanoma and metastatic GNA11/GNAQ mutant melanocytic tumors.

Background: Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study.

The burden of diseases, injuries, and risk factors by state in the USA, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021.

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides a comprehensive assessment of health and risk factor trends at global, regional, national, and subnational levels. This study aims to examine the burden of diseases, injuries, and risk factors in the USA and highlight the disparities in health outcomes across different states.

Methods: GBD 2021 analysed trends in mortality, morbidity, and disability for 371 diseases and injuries and 88 risk factors in the USA between 1990 and 2021.

Novel loci and biomedical consequences of iron homoeostasis variation.

Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported.