Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis.

Background: For decades, poor treatment options and low-quality evidence plagued care for patients with rifampin-resistant tuberculosis. The advent of new drugs to treat tuberculosis and enhanced funding now permit randomized, controlled trials of shortened-duration, all-oral treatments for rifampin-resistant tuberculosis.

Methods: We conducted a phase 3, multinational, open-label, randomized, controlled noninferiority trial to compare standard therapy for treatment of fluoroquinolone-susceptible, rifampin-resistant tuberculosis with five 9-month oral regimens that included various combinations of bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx) or moxifloxacin (M), clofazimine (C), and pyrazinamide (Z).

Harnessing Human-Centered Design for Evidence-Based Psychosocial Interventions and Implementation Strategies in Community Settings: Protocol for Redesign to Improve Usability, Engagement, and Appropriateness.

Background: Although substantial progress has been made in establishing evidence-based psychosocial clinical interventions and implementation strategies for mental health, translating research into practice-particularly in more accessible, community settings-has been slow.

Objective: This protocol outlines the renewal of the National Institute of Mental Health-funded University of Washington Advanced Laboratories for Accelerating the Reach and Impact of Treatments for Youth and Adults with Mental Illness Center, which draws from human-centered design (HCD) and implementation science to improve clinical interventions and implementation strategies. The Center's second round of funding (2023-2028) focuses on using the Discover, Design and Build, and Test (DDBT) framework to address 3 priority clinical intervention and implementation strategy mechanisms (ie, usability, engagement, and appropriateness), which we identified as challenges to implementation and scalability during the first iteration of the center.

Prevalence and predictors of cirrhosis and portal hypertension in the united states.

Background And Aim: There is paucity of data about the prevalence of cirrhosis and portal hypertension in the US general population.

Methods: We used National Health and Nutrition Examination Surveys (NHANES 2017-2020) to estimate the prevalence of cirrhosis and clinically significant (CS)-portal hypertension in alcoholic liver disease (ALD), MetALD, viral hepatitis (VH) to include chronic hepatitis B (CHB) and chronic hepatitis C (CHC), and metabolic dysfunction-associated steatotic liver disease (MASLD). Cirrhosis was evaluated using liver stiffness measurement (LSM) by transient elastography or FIB-4 score; CS-portal hypertension was defined via LSM and platelet count or the use of non-selective beta-blockers in the presence of cirrhosis.

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.

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.

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.

Early-life Exposure to Tobacco Smoke and the Risk of Idiopathic Pulmonary Fibrosis: A Population-based Cohort Study.

Rationale: Tobacco smoking is a well-established risk factor for idiopathic pulmonary fibrosis (IPF), yet the influence of early-life tobacco exposure on future IPF risk remains poorly understood.

Objectives: To test the hypothesis that early-life tobacco exposure may elevate the risk of developing IPF, with this effect potentially modified by genetic susceptibility to IPF and mediated through accelerated biological aging.

Methods: Using data from over 430,000 participants in the UK Biobank, we performed a prospective cohort study to examine the associations of maternal smoking around birth and age of smoking initiation with IPF risk.

Fatuamide A, a Hybrid PKS/NRPS Metallophore from a sp. Marine Cyanobacterium Collected in American Samoa.

A structurally novel metabolite, fatuamide A (), was discovered from a laboratory cultured strain of the marine cyanobacterium sp., collected from Faga'itua Bay, American Samoa. A bioassay-guided approach using NCI-H460 human lung cancer cells directed the isolation of fatuamide A, which was obtained from the most cytotoxic fraction.

Cutting-edge: bionanomaterial solutions in the battle against Severe Acute Respiratory Syndrome Coronavirus 2.

Amidst the ongoing COVID-19 pandemic, the imperative of our time resides in crafting stratagems of utmost precision to confront the relentless SARS-CoV-2 and quell its inexorable proliferation. A paradigm-shifting weapon in this battle lies in the realm of nanoparticles, where the amalgamation of cutting-edge nanochemistry begets a cornucopia of inventive techniques and methodologies designed to thwart the advances of this pernicious pathogen. Nanochemistry, an artful fusion of chemistry and nanoscience, provides a fertile landscape for researchers to craft innovative shields against infection.

Patient-derived Organoids and Xenografts Uncover Therapeutic Vulnerabilities in Colorectal Signet Ring Cell Carcinomas.

Purpose: Identifying therapeutic targets for Signet Ring Cell Carcinoma (SRCC) of the colon and rectum is a clinical challenge due to the lack of Patient-Derived Organoids (PDO) or Xenografts (PDX). We present a robust method to establish PDO and PDX models to answer address this unmet need. We demonstrate that these models identify novel therapeutic strategies targeting therapy resistance and peritoneal metastasis.

Economic impact of initial glaucoma treatment with selective laser trabeculoplasty on the Brazilian Public Health System.

Purpose: To evaluate the economic impact of the following initial treatment scenarios for glaucoma on the Brazilian Public Health System (SUS): (1) traditional continuous instillation of hypotensive eye drops and (2) single session of selective laser trabeculoplasty.

Methods: Economic impact was analyzed in three scenarios, from the least to the most conservative, for a hypothetical cohort of 5,000 individuals with open-angle glaucoma. Thereafter, projections were made on the basis of a glaucoma prevalence of 3% in the 2021 Brazilian population size.

Assessment of the content and quality of YouTube videos on retinopathy of prematurity: a cross-sectional study.

Purpose: This study aimed to evaluate the quality and reliability of YouTube videos as an educational resource about retinopathy of prematurity.

Methods: Videos were sourced from YouTube using the search terms "retinopathy of prematurity" and "premature retinopathy" with the default settings. Each video was assessed on the following metrics: views, likes, dislikes, comments, upload source, country of origin, view ratio, like ratio, and video power index.

Dispersal of Sensu Lato Conidia from Infected Citrus and Strawberry Under Simulated Rainfall and Different Laminar and Turbulent Wind Speeds.

Species of the complex cause postbloom fruit drop of citrus and anthracnose fruit rot of strawberries. produces acervuli in diseased citrus flowers and strawberry fruit, surviving asymptomatically on vegetative tissues. Previous studies have suggested that dispersal mechanisms other than windblown rain may be involved in dispersal of conidia of sensu lato.

Classification-based pathway analysis using GPNet with novel P-value computation.

Pathway analysis plays a critical role in bioinformatics, enabling researchers to identify biological pathways associated with various conditions by analyzing gene expression data. However, the rise of large, multi-center datasets has highlighted limitations in traditional methods like Over-Representation Analysis (ORA) and Functional Class Scoring (FCS), which struggle with low signal-to-noise ratios (SNR) and large sample sizes. To tackle these challenges, we use a deep learning-based classification method, Gene PointNet, and a novel $P$-value computation approach leveraging the confusion matrix to address pathway analysis tasks.

Targeting AXL inhibits the growth and metastasis of prostate cancer in bone.

Purpose: After failing primary and secondary hormonal therapy, castration-resistant and neuroendocrine prostate cancer metastatic to the bone is invariably lethal, although treatment with docetaxel and carboplatin can modestly improve survival. Therefore, agents targeting biologically relevant pathways in PCa and potentially synergizing with docetaxel and carboplatin in inhibiting bone metastasis growth are urgently needed.

Experimental Design: Phosphorylated (activated) AXL expression in human prostate cancer bone metastases was assessed by immunohistochemical staining.

Phase I Clinical Trial of High Doses of Seleno-L-methionine in Combination with Axitinib in Patients with Previously Treated Metastatic Clear Cell Renal Cell Carcinoma.

Background: Data in clear cell renal cell carcinoma (ccRCC) xenografts defined the seleno-L-methionine (SLM) dose and the plasma selenium concentrations associated with the enhancement of HIF1α/2α degradation, stabilization of tumor vasculature, enhanced drug delivery, and efficacy of axitinib. The data provided the rationale for the development of this phase I clinical trial of SLM and axitinib in advanced or metastatic relapsed ccRCC.

Patients And Methods: Patients were ≥18 years with histologically and radiologically confirmed advanced or metastatic ccRCC who had received at least one prior systemic therapy, which could include axitinib (last dose ≥6 months prior to enrollment).

New PPARα Agonist A190-Loaded Microemulsion for Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect of anticancer agents with limited effective preventive or therapeutic interventions. Although fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, has demonstrated neuroprotective and analgesic properties, its clinical utility is hindered by low receptor affinity, poor subtype selectivity, and suboptimal bioavailability. A190, a highly selective and potent nonfibrate PPARα agonist, offers a promising alternative but is limited by poor aqueous solubility, resulting in reduced oral bioavailability and therapeutic efficacy.

Program Director Perspectives on DEI Initiatives in the Dermatology Residency Selection Process.

The American Academy of Dermatology (AAD) has maintained a commitment to diversity, equity, and inclusion (DEI) initiatives; however, a recent strike down of affirmative action by the US Supreme Court has caused similar efforts to be called into question. This prompted our investigation into dermatology program director (PD) perceptions of DEI programming and its integration into resident selection. A cross-sectional survey of PDs at US dermatology residency programs was conducted from April 2024 to July 2024 (N=30).

Iron Deficiency and All-Cause Hospitalization Risk in a Clinical Cohort of COPD.

Background: The impact of iron deficiency on COPD morbidity independent of anemia status is unknown. Understanding the association between iron deficiency, anemia status, and risk of hospitalization in COPD may inform an approach to these comorbidities.

Study Design And Methods: Adults ≥40 years from the Johns Hopkins COPD Precision Medicine Center of Excellence data repository with an outpatient iron profile and 1 year of subsequent follow-up time were included in the study.