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.

Preclinical development of a standardized extract of Ilex paraguariensis A.St.-Hil for the treatment of obesity and metabolic syndrome.

Obesity is a global epidemic often associated with serious medical complications such as diabetes, hypertension and metabolic dysfunction-associated steatohepatitis. Considering the multifactorial nature of these diseases, medicinal plants could be a valuable therapeutic strategy as their phytoconstituents interact with multiple and relevant biological targets. In this context, Ilex paraguariensis emerges as a potential alternative to treat obesity and associated metabolic diseases since several studies have demonstrated its anti-inflammatory, anti-obesity and anti-diabetic effects.

Motion-Compensated Multishot Pancreatic Diffusion-Weighted Imaging With Deep Learning-Based Denoising.

Objectives: Pancreatic diffusion-weighted imaging (DWI) has numerous clinical applications, but conventional single-shot methods suffer from off resonance-induced artifacts like distortion and blurring while cardiovascular motion-induced phase inconsistency leads to quantitative errors and signal loss, limiting its utility. Multishot DWI (msDWI) offers reduced image distortion and blurring relative to single-shot methods but increases sensitivity to motion artifacts. Motion-compensated diffusion-encoding gradients (MCGs) reduce motion artifacts and could improve motion robustness of msDWI but come with the cost of extended echo time, further reducing signal.

Association between choroidal microvasculature in the eye and Alzheimer's disease risk in cognitively healthy mid-life adults: A pilot study.

Introduction: We explored associations between measurements of the ocular choroid microvasculature and Alzheimer's disease (AD) risk.

Methods: We measured the choroidal vasculature appearing in optical coherence tomography (OCT) scans of 69 healthy, mid-life individuals in the PREVENT Dementia cohort. The cohort was prospectively split into low-, medium-, and high-risk groups based on the presence of known risk factors (apolipoprotein E [] ε4 genotype and family history of dementia [FH]).

Association of Alzheimer's Disease Polygenic Risk Score with Concussion Severity and Recovery Metrics.

Background: Identification of genetic alleles associated with both Alzheimer's disease (AD) and concussion severity/recovery could help explain the association between concussion and elevated dementia risk. However, there has been little investigation into whether AD risk genes associate with concussion severity/recovery, and the limited findings are mixed.

Objective: We used AD polygenic risk scores (PRS) and APOE genotypes to investigate any such associations in the NCAA-DoD Grand Alliance CARE Consortium (CARE) dataset.

Taking time: Auditory statistical learning benefits from distributed exposure.

In an auditory statistical learning paradigm, listeners learn to partition a continuous stream of syllables by discovering the repeating syllable patterns that constitute the speech stream. Here, we ask whether auditory statistical learning benefits from spaced exposure compared with massed exposure. In a longitudinal online study on Prolific, we exposed 100 participants to the regularities in a spaced way (i.

Comparison of RT-qPCR With Branched DNA to Quantify a Lipid Nanoparticle-Encapsulated mRNA Therapeutic in Serum and Liver Tissue Samples From Nonclinical PK Studies.

While the branched DNA (bDNA) assay is an established bioanalytical method for measurement of lipid nanoparticle (LNP)-encapsulated messenger RNA (mRNA) pharmacokinetic parameters, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) has been considered as an alternative platform. RT-qPCR and bDNA platforms were compared for sensitivity, specificity, correlation, and overall assay performance using serum and tissue samples from 2 nonclinical mouse studies of a therapeutic mRNA candidate, LNP-PAH-mRNA, which encodes for human phenylalanine hydroxylase enzyme. Pharmacokinetic parameter noncompartmental analysis was completed using Phoenix WinNonlin.

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.

Efficacy and tolerability of neoadjuvant therapy with Talimogene laherparepvec in cutaneous basal cell carcinoma: a phase II trial (NeoBCC trial).

We present a single-arm, phase II, neoadjuvant trial with the oncolytic virus talimogene laherparepvec (T-VEC) in 18 patients with difficult-to-resect cutaneous basal cell carcinomas. The primary end point, defined as the proportion of patients, who after six cycles of T-VEC (13 weeks), become resectable without the need for plastic reconstructive surgery, was already achieved after stage I (9 of 18 patients; 50.0%); thus the study was discontinued for early success.

Case for Establishing a National Stroke Activation Fee in the United States: Learning From Trauma Centers.

There is a large burden of stroke in the United States, and extensive systems of care have been established to address it. The resources devoted to stroke centers are analogous to those of trauma centers, both sharing many strict requirements for certification, clinical preparedness, quality improvement, data management, and reporting. However, trauma programs partly defray these costs through a trauma activation billing code, a billable fee that is charged for activation of the trauma team under strict criteria.

Evaluation of a Deep Learning Denoising Algorithm for Dose Reduction in Whole-Body Photon-Counting CT Imaging: A Cadaveric Study.

Rationale And Objectives: Photon Counting CT (PCCT) offers advanced imaging capabilities with potential for substantial radiation dose reduction; however, achieving this without compromising image quality remains a challenge due to increased noise at lower doses. This study aims to evaluate the effectiveness of a deep learning (DL)-based denoising algorithm in maintaining diagnostic image quality in whole-body PCCT imaging at reduced radiation levels, using real intraindividual cadaveric scans.

Materials And Methods: Twenty-four cadaveric human bodies underwent whole-body CT scans on a PCCT scanner (NAEOTOM Alpha, Siemens Healthineers) at four different dose levels (100%, 50%, 25%, and 10% mAs).

Opposing roles of p38α-mediated phosphorylation and PRMT1-mediated arginine methylation in driving TDP-43 proteinopathy.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder typically characterized by insoluble inclusions of hyperphosphorylated TDP-43. The mechanisms underlying toxic TDP-43 accumulation are not understood. Persistent activation of p38 mitogen-activated protein kinase (MAPK) is implicated in ALS.

Outcomes of liposuction techniques for management of lipedema: a case series and narrative review.

Background And Objective: Lipedema is a commonly underdiagnosed chronic condition. This study aimed to evaluate liposuction techniques for lipedema by conducting a systematic review and presenting our experience. A case series study and a comprehensive review were conducted.

Cognitive and Alzheimer's disease biomarker effects of oral nicotinamide riboside (NR) supplementation in older adults with subjective cognitive decline and mild cognitive impairment.

Introduction: Age-associated depletion in nicotinamide adenine dinucleotide (NAD+) concentrations has been implicated in metabolic, cardiovascular, and neurodegenerative disorders. Supplementation with NAD+ precursors, such as nicotinamide riboside (NR), offers a potential therapeutic avenue against neurodegenerative pathologies in aging, Alzheimer's disease, and related dementias. A crossover, double-blind, randomized placebo (PBO) controlled trial was conducted to test the safety and efficacy of 8 weeks' active treatment with NR (1 g/day) on cognition and plasma AD biomarkers in older adults with subjective cognitive decline and mild cognitive impairment.

De novo designed proteins neutralize lethal snake venom toxins.

Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage and inhibition of nicotinic acetylcholine receptors, resulting in life-threatening neurotoxicity. At present, the only available treatments for snakebites consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs.

The course of physical fitness and nutritional status in patients following prehabilitation before esophageal cancer surgery: Results from the PRIOR study.

Introduction: This study evaluates the course of physical fitness and nutritional status during curative therapy for esophageal cancer, after implementation of a prehabilitation program. Additionally, the impact of baseline physical fitness level and severe postoperative complications on the course of individual patients were explored.

Materials And Methods: This multicenter, observational cohort study included patients with esophageal cancer following curative treatment.

Sex Differences in Natural History and Health Outcomes Among Individuals With Tic Disorders.

Objectives: To analyze sex differences in outcomes in Tourette syndrome (TS) and Persistent Motor or Vocal tic disorders (PMVT) in the Tourette Association of America International Consortium for Genetics (TAAICG) dataset.

Methods: The relationship between sex and clinical measures was explored in 2,403 participants (N = 2,109 with TS; N = 294 with PMVT) from the TAAICG dataset using generalized estimating equation regression models, and adjusted for age and family relationships.

Results: Female (vs male) participants with TS (25.

Clinical Pharmacokinetics of Psilocin After Psilocybin Administration: A Systematic Review and Post-Hoc Analysis.

Background And Objective: Psilocybin is currently being extensively studied as a potential therapeutic agent for multiple psychiatric disorders. Here, a systematic literature review of all published pharmacokinetic data on the pharmacologically active metabolite of psilocybin, psilocin, is presented.

Methods: The review includes clinical studies that reported pharmacokinetic data and/or parameters after psilocybin administration in humans.

Comments about the comparative bulk RNA sequencing between palmoplantar pustulosis and dyshidrotic palmoplantar eczema.

This correspondence discusses the recent findings by Straalen et al., highlighting molecular similarities and distinctions between palmoplantar pustulosis (PPP) and dyshidrotic palmoplantar eczema (DPE). The study emphasizes shared proinflammatory pathways and T-cell-related gene upregulation while detailing unique features such as neutrophil involvement in PPP and lipid antigen processing in DPE.

Vacancy-Mediated Increases in Brine-Salt Surface Energies.

Salt formations have been explored for the permanent isolation of spent nuclear fuel based on their high thermal conductivity, self-healing nature, and low hydraulic permeability to brine flow. Vacancy defect concentrations in salt complicate fracture mechanics not driven by dislocation dynamics and can influence the resulting surface structure. Classical molecular dynamic simulations were used to simulate tensile testing of salt crystals (halite) with vacancy defect concentrations of up to 0.

In vivo base editing extends lifespan of a humanized mouse model of prion disease.

Prion disease is a fatal neurodegenerative disease caused by the misfolding of prion protein (PrP) encoded by the PRNP gene. While there is currently no cure for the disease, depleting PrP in the brain is an established strategy to prevent or stall templated misfolding of PrP. Here we developed in vivo cytosine and adenine base strategies delivered by adeno-associated viruses to permanently modify the PRNP locus to achieve PrP knockdown in the mouse brain.