Latrunculin U: a potent actin-disrupter from the Red Sea marine sponge .

During our efforts to identify biologically active compounds from Red Sea marine invertebrates, a new compound, latrunculin U (), was identified from the Red Sea sponge along with latrunculins A (), B (), and 16--latrunculin B (). The structures of the latrunculins were elucidated based on a combination of comprehensive 1D and 2D NMR analyses and high-resolution mass spectral determinations. The antiproliferative potency of each compound in HeLa cells was evaluated, and they had IC values ranging from 0.

Early achievement of hemostasis defined by transfusion velocity: A possible mechanism for whole blood survival benefit.

Introduction: Whole blood resuscitation is associated with survival benefits in observational cohort studies. The mechanisms responsible for outcome benefits have not been adequately determined. We sought to characterize the achievement of hemostasis across patients receiving early whole blood versus component resuscitation.

Abuse potential and analgesic efficacy of intravenous hydromorphone bolus administration among hospitalized patients with cancer pain: A double-blind, double dummy, randomized crossover trial.

Background: There is much concern that opioids administered as intravenous (iv) bolus for pain relief may inadvertently increase their risk for abuse. However, there is insufficient data to support this. The authors compared the abuse liability potential, analgesic efficacy, and adverse effect profile of fast (iv push) versus slow (iv piggyback) administration of iv hydromorphone among hospitalized patients requiring iv opioids for pain.

Cryo-EM SPR structures of Salmonella typhimurium ArnC; the key enzyme in lipid-A modification conferring polymyxin resistance.

Polymyxins are last-resort antimicrobial peptides administered clinically against multi-drug resistant bacteria, specifically in the case of Gram-negative species. However, an increasing number of these pathogens employ a defense strategy that involves a relay of enzymes encoded by the pmrE (ugd) loci and the arnBCDTEF operon. The pathway modifies the lipid-A component of the outer membrane (OM) lipopolysaccharide (LPS) by adding a 4-amino-4-deoxy-l-arabinose (L-Ara4N) headgroup, which renders polymyxins ineffective.

Phase I trial of hydroxychloroquine to enhance palbociclib and letrozole efficacy in ER+/HER2- breast cancer.

Endocrine therapy with CDK4/6 inhibitors is standard for estrogen receptor-positive, HER2-negative metastatic breast cancer (ER+/HER2- MBC), yet clinical resistance develops. Previously, we demonstrated that low doses of palbociclib activate autophagy, reversing initial G1 cell cycle arrest, while high concentrations induce off-target senescence. The autophagy inhibitor hydroxychloroquine (HCQ) induced on-target senescence at lower palbociclib doses.

Patient Characteristics, Management and Long-term Outcomes of Patients with Cardiogenic Shock at a Large Safety Net Hospital.

Data regarding cardiogenic shock (CS) from safety-net hospitals serving socioeconomically-disadvantaged patients are limited. In addition, little is known regarding long-term outcomes and management of heart failure-related CS (HF-CS), a population potentially especially vulnerable to adverse social determinants of health (SDOH). A single-center retrospective cohort study of patients with Stage C, D, or E CS at a public safety-net hospital between 2017-2023 was performed.

Impacto - A single-arm open-label pilot trial of a digital-based integrated smoking cessation program for Spanish-speaking Hispanic individuals who smoke: Development, feasibility, engagement, and clinical outcomes.

Introduction: Hispanic/Latinx (hereafter Hispanic) individuals who smoke have challenges in quitting and a disproportionate risk of smoking-related health problems when compared to the general population. The smoking inequalities among the Hispanic population are influenced by limited treatment access and chronic stress exposure (e.g.

The Full Range of Weight Status by Race and Ethnicity in Children with and without Autism: A Cross-sectional Study of US Children.

Objective: To identify and characterize how race and ethnicity influence the relationship between autism and weight status, across all categories of weight from underweight to severe obesity.

Study Design: We developed a propensity score-matched cross-sectional dataset of children with and without parent-reported autism in the National Survey of Children Health (NSCH, 2016-2022) and Adolescent Brain and Cognition Development Study (ABCD, 2016-2018). We included non-Hispanic Asian, non-Hispanic Black, non-Hispanic White, and Hispanic children aged 6 to 17 years.

Pulsed Field Ablation in the Elderly via a Pentaspline Multielectrode Catheter: Safety, Efficacy, and Comparison with Cryoballoon and Radiofrequency Devices.

Background: Catheter ablation is an effective treatment for atrial fibrillation (AF). Pulsed field ablation (PFA) has emerged as a novel energy modality, which relies on high-voltage electric fields to achieve cardiac tissue ablation. Data on its efficacy in the elderly are scarce.

Global metabolomic alterations associated with endocrine-disrupting chemicals among pregnant individuals and newborns.

Background: Gestational exposure to non-persistent endocrine-disrupting chemicals (EDCs) may be associated with adverse pregnancy outcomes. While many EDCs affect the endocrine system, their effects on endocrine-related metabolic pathways remain unclear. This study aims to explore the global metabolome changes associated with EDC biomarkers at delivery.

Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial.

Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC.

Clinically Meaningful Upstaging and Upgrading in Favorable Intermediate-Risk Radical Prostatectomy Patients.

Introduction: In NCCN favorable intermediate-risk (FIR) prostate cancer (PCa) patients treated with radical prostatectomy (RP), we tested the effect of upstaging and upgrading on cancer-specific mortality (CSM).

Methods: Within the SEER database (2010-2021), upstaging (≥pT3a or pN1) and upgrading (ISUP ≥3) rates in FIR RP patients were tabulated. Kaplan-Meier (KM) plots and multivariable Cox-regression models (CRMs) were fitted.

Assessing the performance of ChatGPT in medical ethical decision-making: a comparative study with USMLE-based scenarios.

Introduction: The integration of artificial intelligence (AI) into healthcare introduces innovative possibilities but raises ethical, legal and professional concerns. Assessing the performance of AI in core components of the United States Medical Licensing Examination (USMLE), such as communication skills, ethics, empathy and professionalism, is crucial. This study evaluates how well ChatGPT versions 3.

AGA Clinical Practice Guideline on the Prevention and Treatment of Hepatitis B Virus Reactivation in At-Risk Individuals.

Background & Aims: Hepatitis B reactivation (HBVr) can occur due to a variety of immune-modulating exposures, including multiple drug classes and disease states. Antiviral prophylaxis can be effective in mitigating the risk of HBVr. In select cases, clinical monitoring without antiviral prophylaxis is sufficient for managing the risk of HBVr.

Arterial Stiffness and Subsequent Incidence of CKD and Kidney Function Decline in a Large Longitudinal Community Cohort: The Atherosclerosis in Communities (ARIC) Study.

Rationale & Objective: Arterial stiffness is associated with prevalent chronic kidney disease (CKD). Whether arterial stiffness is prospectively associated with incident CKD is inconclusive.

Study Design: Longitudinal cohort study.

Racial and ethnic enrollment disparities in clinical trials leading to FDA approvals for gynecologic malignancies.

Background: Black women and other minorities have higher age adjusted incidence risk for cervical and endometrial cancer than White women. However, the extent of racial and ethnic disparities in clinical trial enrollment among studies performed mainly in North America and Europe for gynecologic malignancy is unknown.

Objective: This study analyzed enrollment rates by race/ethnicity in trials that led to Food and Drug Administration (FDA) approvals for gynecological cancers from 2010 to 2024.

Discordance in acute gastrointestinal toxicity between synchrotron-based proton and linac-based electron ultra-high dose rate irradiation.

Purpose: Proton FLASH has been investigated using cyclotron and synchrocyclotron beamlines but not synchrotron beamlines. We evaluated the impact of dose rate (ultra-high [UHDR] vs. conventional [CONV]) and beam configuration (shoot-through [ST] vs.

Polysomnography in a Private Tertiary Hospital in Tanzania: Subjects' Characteristics and Sleep Disorders.

Background And Objectives: Huge clinical and research gaps exist concerning the epidemiology, natural history, availability, and accessibility of care for sleep disorders in sub-Saharan Africa (SSA). This study aimed to profile the characteristics of patients referred for polysomnography and the frequencies of sleep disorders encountered at the new sleep laboratory in Dar es Salaam, Tanzania.

Materials And Methods: This retrospective hospital-based descriptive observational study was conducted at the Aga Khan Hospital Dar es Salaam.

Improving Cooking Skills, Lifestyle Behaviors, and Clinical Outcomes for Adults at Risk for Cardiometabolic Disease: Protocol for a Randomized Teaching Kitchen Multisite Trial (TK-MT).

Background/objectives: This protocol describes a study to investigate the feasibility and preliminary efficacy of a novel Teaching Kitchen Multisite Trial (TK-MT) for adults with cardiometabolic abnormalities. The TK-MT protocol describes a hybrid lifestyle intervention combining in-person and virtual instruction in culinary skills, nutrition education, movement, and mindfulness with community support and behavior change strategies. This 18-month-long randomized controlled trial aims to evaluate the feasibility of implementing a 12-month, 24 class program, assess preliminary study efficacy, and identify barriers and facilitators to implementation.

Exploring Zinc C295 as a Dual HIV-1 Integrase Inhibitor: From Strand Transfer to 3'-Processing Suppression.

: The global AIDS pandemic highlights the urgent need for novel antiretroviral therapies (ART). In our previous work, Zinc C295 was identified as a potent HIV-1 integrase strand transfer (ST) inhibitor. This study explores its potential to also inhibit 3'-processing (3'P), thereby establishing its dual-targeting capability.

Pathogen Detection and Resistome Analysis in Healthy Shelter Dogs Using Whole Metagenome Sequencing.

According to the Humane Society, 25 to 40 percent of pet dogs in the United States are adopted from animal shelters. Shelter dogs can harbor bacterial, viral, fungal, and protozoal pathogens, posing risks to canine and human health. These bacterial pathogens may also carry antibiotic resistance genes (ARGs), serving as a reservoir for antimicrobial resistance (AMR) transmission.

Conjugation of Short-Chain Fatty Acids to Bicyclic-Amines for Analysis by Liquid Chromatography Tandem Mass Spectroscopy.

Conjugation of short-chain fatty acids (SDFAs) to amines containing ring structures allows for better measurement by liquid chromatography tandem mass spectroscopy (LC-MS/MS). However, collision-induced dissociation (CID) results in breaking the conjugate back to the original SCFA and amine. We therefore set out to find an amine that would remain on the SCFA after CID and create a unique daughter for selectivity of measurement.

Hydrogen-Bonded Di(hydroperoxy)alkane Adducts of the Type CyP=O·(HOO)CHR (R = Alkyl).

Five representatives of a novel type of di(hydroperoxy)alkane adducts of phosphine oxides have been synthesized and fully characterized, including their solubility in organic solvents. The phosphine oxide CyPO () has been used in combination with the corresponding aldehydes to create the adducts CyPO·(HOO)CHCH (), CyPO·(HOO)CHCHCH (), CyPO·(HOO)CH(CH)CH (), CyPO·(HOO)CH(CH)CH (), and CyPO·(HOO)CH(CH)CH (). All adducts crystallize easily and contain the peroxide and phosphine oxide hydrogen-bonded in 1:1 ratios.

Modeling, Design, and Laboratory Testing of a Passive Friction Seismic Metamaterial Base Isolator (PFSMBI).

This paper focuses on the theoretical and analytical modeling of a novel seismic isolator termed the Passive Friction Mechanical Metamaterial Seismic Isolator (PFSMBI) system, which is designed for seismic hazard mitigation in multi-story buildings. The PFSMBI system consists of a lattice structure composed of a series of identical small cells interconnected by layers made of viscoelastic materials. The main function of the lattice is to shift the fundamental natural frequency of the building away from the dominant frequency of earthquake excitations by creating low-frequency bandgaps (FBGs) below 20 Hz.

The Clinical Utility of a Next-Generation Sequencing-Based Approach to Detecting Circulating HPV DNA in Patients with Advanced Anal Cancer.

Background: To extend the practicality of liquid biopsy beyond the historical HPV circulating tumor DNA (ctDNA) assays, we evaluated the clinical relevance of a novel next-generation sequencing HPV ctDNA assay in patients with locally advanced and metastatic squamous cell cancer of the anal canal (mSCCA).

Methods: ctDNA isolated from the plasma of patients with mSCCA was sequenced using a 1.4 Mb hybrid-capture target-enrichment panel covering the whole genome sequences of all 193 HPV types.