Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated.

An accessible workflow for high-sensitivity proteomics using parallel accumulation-serial fragmentation (PASEF).

Deep and accurate proteome analysis is crucial for understanding cellular processes and disease mechanisms; however, it is challenging to implement in routine settings. In this protocol, we combine a robust chromatographic platform with a high-performance mass spectrometric setup to enable routine yet in-depth proteome coverage for a broad community. This entails tip-based sample preparation and pre-formed gradients (Evosep One) combined with a trapped ion mobility time-of-flight mass spectrometer (timsTOF, Bruker).

The Role of Social Deficits in the Link Between Social Gambling Motives and Problem Gambling.

In comparison to other motives for gambling, social motives (e.g., gambling for social interaction) are often suggested to be the least problematic and, in some cases, even a protective factor for problem gambling.

Exploring treatment-driven subclonal evolution of prognostic triple biomarkers: Dual gene fusions and chimeric RNA variants in novel subtypes of acute myeloid leukemia patients with KMT2A rearrangement.

Chromosomal rearrangements (CR) initiate leukemogenesis in approximately 50 % of acute myeloid leukemia (AML) patients; however, limited targeted therapies exist due to a lack of accurate molecular and genetic biomarkers of refractory mechanisms during treatment. Here, we investigated the pathological landscape of treatment resistance and relapse in 16 CR-AML patients by monitoring cytogenetic, RNAseq, and genome-wide changes among newly diagnosed, refractory, and relapsed AML. First, in FISH-diagnosed KMT2A (MLL gene, 11q23)/AFDN (AF6, 6q27)-rearrangement, RNA-sequencing identified an unknown CCDC32 (15q15.

Study protocol for a multi-center stepped-wedge cluster randomized trial to explore the usability and outcomes among young people living with HIV in Kiambu and Kirinyaga counties of Kenya, using an online health portal.

While the incidence of Human Immunodeficiency Virus (HIV) infection is decreasing in most age groups worldwide, it is rising among adolescents and young adults, who also face a higher rate of HIV-related deaths. This tech-savvy demographic may benefit from an online patient portal designed to enhance patient activation-empowering them to manage their health independently. However, the effectiveness of such digital health interventions on young HIV patients in Kenya remains uncertain.

A case of simultaneous bilateral pulmonary resection for arteriovenous pulmonary malformation.

Pulmonary arteriovenous malformation (PAVM) is a congenital vascular pathology, which is caused by the presence of a direct connection between the branches of the artery and the veins of the lungs, and the discharge of unoxygenated blood into the arterial bed. Arteriovenous malformations are characterized by a wide variety of clinical manifestations and, in some cases, may be accompanied with severe circulatory disorders.

Short-Term Warm-Water Immersion for Improving Whole-Body Heat Loss in Older Men.

Purpose: Exercise-induced heat acclimation can mitigate age-related reductions in heat-loss capacity, though performing repeated bouts of strenuous exercise in the heat may be untenable for many older adults. While short-term passive heat acclimation (e.g.

Comparison of Pain Assessment Tools and Numeric Rating Scale Thresholds for Analgesic Administration in the Postanaesthetic Care Unit.

Purpose: The aim of this study was to assess the correlation between the Visual Analog Scale (VAS), Numeric Rating Scale (NRS), and Verbal Rating Scale (VRS). Additionally, the study aimed to determine NRS threshold values for both mild analgesic administration (= without risk of nausea and vomiting [NV] side effects) and strong analgesic administration (= with risk of NV side effects) in the postanaesthetic care unit (PACU).

Design: Prospective, observational study design.

Neuropsychiatric symptoms predict rate of change in executive function in Alzheimer's disease and related dementias.

Objective: Neuropsychiatric symptoms (NPS) are considered diagnostic and prognostic indicators of dementia and are attributable to neurodegenerative processes. Little is known about the prognostic value of early NPS on executive functioning (EF) decline in Alzheimer's disease and related dementias (ADRD). We examined whether baseline NPS predicted the rate of executive function (EF) decline among older adults with ADRD.

Bilateral hip exoskeleton assistance enables faster walking in individuals with chronic stroke-related gait impairments.

Millions of individuals surviving a stroke have lifelong gait impairments that reduce their personal independence and quality of life. Reduced walking speed is one of the major problems limiting community mobility and reintegration. Previous studies have shown positive effect of robot-assisted gait training utilizing hip exoskeletons for individuals with gait impairments due to a stroke, leading to increased walking speed in post-treatment compared to pre-treatment assessments.

A Warm Water Immersion Intervention for Symptoms of PTSD in Military Veterans: A Qualitative Descriptive Study.

Background: Post-Traumatic Stress Disorder (PTSD) is a substantial problem for Veterans and active members of armed forces across the globe, resulting in debilitating mental and physical comorbidities. Evidence-based treatments have demonstrated some success; however, many Veterans remain symptomatic mandating the urgent need for innovative treatment strategies.

Purpose: The purpose of this study was to explore the lived experience of military Veterans with PTSD symptoms who participated in a therapeutic warm water immersion intervention aimed at reducing their symptoms.

Local delivery of mesenchymal stem cell-extruded nanovesicles through a bio-responsive scaffold for acute spinal cord injury treatment.

Intense inflammatory responses and elevated levels of reactive oxygen species (ROS) extremely exacerbate the pathological process of spinal cord injury (SCI). Mesenchymal stem cell (MSC)-derived extracellular vesicles (EV) can mitigate SCI-related inflammation but their production yield remains limited. Alternatively, MSC-extruded nanovesicles (NV) inherit the therapeutic potential from MSCs and have a markedly higher yield than EV.

Enteric neuronal substrates underlying spontaneous and evoked neurogenic contractions in mouse colon.

Background And Aims: Gastrointestinal motility persists when peripheral cholinergic signaling is blocked genetically or pharmacologically, and a recent study suggests nitric oxide drives propagating neurogenic contractions.

Methods: To determine the neuronal substrates that underlie these contractions, we measured contractile-associated movements together with calcium responses of cholinergic or nitrergic myenteric neurons in un-paralyzed ex vivo preparations of whole mouse colon. We chose to look at these two subpopulations because they encompass nearly all myenteric neurons.

Twenty-four-hour pattern of children with febrile seizures presenting to a United States Pediatric Emergency Department.

Background: Febrile seizure (FS) is the most common convulsive disorder in children. Understanding its time-of-day pattern can provide insight into mechanisms and prevention.

Purpose: We explored clock-time variation of FS presentations of children to a US pediatric emergency department (PED) in comparison to two control cohorts: one (n = 5719) like-aged children presenting solely with fever, i.

Tissue remodeling during high-altitude pulmonary edema in rats: Biochemical and histomorphological analysis.

High altitude characterized by the low partial pressure of the oxygen is a life-threatening condition that contributes to the development of acute pulmonary edema and hypoxic lung injury. In this study, we aimed to investigate the contribution of some inflammatory and oxidative stress markers along with antioxidant system enzymes in the pathogenesis of HAPE (high-altitude pulmonary edema) formation. We incorporated the study on 42 male rats to unravel the role of mast cells (MCs) and TNF-α in the lung after the effect of acute hypobaric hypoxia.

In Vivo Nanodiamond Quantum Sensing of Free Radicals in Caenorhabditis elegans Models.

Free radicals are believed to play a secondary role in the cell death cascade associated with various diseases. In Huntington's disease (HD), the aggregation of polyglutamine (PolyQ) not only contributes to the disease but also elevates free radical levels. However, measuring free radicals is difficult due to their short lifespan and limited diffusion range.

Rapid, in Situ Neutralization of Nitrogen- and Silicon-Vacancy Centers in Diamond Using Above-Band Gap Optical Excitation.

The charge state of a quantum point defect in a solid-state host strongly determines its optical and spin characteristics. Consequently, techniques for controlling the charge state are required to realize technologies for quantum networking and sensing. In this work, we demonstrate the use of deep-ultraviolet (DUV) radiation to dynamically neutralize nitrogen- (NV) and silicon-vacancy (SiV) centers.

Contextualizing the Upper Paleolithic of the Armenian Highlands: New data from Solak-1, central Armenia.

As a potential corridor connecting Southwest Asia with western and northern Europe, the Armenian Highlands and southern Caucasus hold great potential for increasing our understanding of Upper Paleolithic behavioral and cultural variability. However, given the dearth of Upper Paleolithic sites, we lack the data necessary to answer basic questions regarding the timing and nature of the Upper Paleolithic in this region. Solak-1 is an open-air site located along the upper Hrazdan Valley (1635 m above sea level) in central Armenia.

Dynamics of fungal endophytic communities in bilberry (Vaccinium myrtillus L.) fruits through development is shaped by host phenolic compounds.

The physical and chemical properties of wild berry fruits change dramatically during development, and the ripe berries host species-specific endophytic communities. However, the development of fungal endophytic communities during berry ripening is unknown. We studied bilberries (Vaccinium myrtillus L.

Sustainable corrosion prevention of mild steel in acidic media with herb extract.

Mild steel provides strength to various building and industrial materials but it is badly affected by corrosion. In the present study, we investigate the efficacy of , a plant-based green corrosion inhibitor to minimize mild steel corrosion in a 1 M HSO solution. Weight loss, surface coverage, inhibition efficiency, and corrosion rate measurements were evaluated for various inhibitor concentrations and time intervals.