SPIRIT-DEFINE explanation and elaboration: recommendations for enhancing quality and impact of early phase dose-finding clinical trials protocols.

Unlabelled: Transparent and accurate reporting in early phase dose-finding (EPDF) clinical trials is crucial for informing subsequent larger trials. The SPIRIT statement, designed for trial protocol content, does not adequately cover the distinctive features of EPDF trials. Recent findings indicate that the protocol contents in past EPDF trials frequently lacked completeness and clarity.

CONSORT-DEFINE explanation and elaboration: recommendations for enhancing reporting quality and impact of early phase dose-finding clinical trials.

Unlabelled: Early phase dose-finding (EPDF) trials are key in the development of novel therapies, with their findings directly informing subsequent clinical development phases and providing valuable insights for reverse translation. Comprehensive and transparent reporting of these studies is critical for their accurate and critical interpretation, which may improve and expedite therapeutic development. However, quality of reporting of design characteristics and results from EPDF trials is often variable and incomplete.

Multi-center benchmarking of cervical spinal cord RF coils for 7 T MRI: A traveling spines study.

Purpose: The depth within the body, small diameter, long length, and varying tissue surrounding the spinal cord impose specific considerations when designing radiofrequency coils. The optimal coil configuration for 7 T cervical spinal cord MRI is unknown and, currently, there are very few coil options. The purpose of this work was (1) to establish a quality control protocol for evaluating 7 T cervical spinal cord coils and (2) to use that protocol to evaluate the performance of 4 different coil designs.

Amyotrophic lateral sclerosis caused by FUS mutations: advances with broad implications.

Autosomal dominant mutations in the gene encoding the DNA and RNA binding protein FUS are a cause of amyotrophic lateral sclerosis (ALS), and about 0·3-0·9% of patients with ALS are FUS mutation carriers. FUS-mutation-associated ALS (FUS-ALS) is characterised by early onset and rapid progression, compared with other forms of ALS. However, different pathogenic mutations in FUS can result in markedly different age at symptom onset and rate of disease progression.

Task activation results in regional C-lactate signal increase in the human brain.

Hyperpolarized-C magnetic resonance imaging (HP-C MRI) was used to image changes in C-lactate signal during a visual stimulus condition in comparison to an eyes-closed control condition. Whole-brain C-pyruvate, C-lactate and C-bicarbonate production was imaged in healthy volunteers (N = 6, ages 24-33) for the two conditions using two separate hyperpolarized C-pyruvate injections. BOLD-fMRI scans were used to delineate regions of functional activation.

Plant Compounds Inhibit the Growth of W12 Cervical Precancer Cells Containing Episomal or Integrant HPV DNA; Tanshinone IIA Synergizes with Curcumin in Cervical Cancer Cells.

This study explores the effects of plant compounds on human papillomavirus (HPV)-induced W12 cervical precancer cells and bioelectric signaling. The aim is to identify effective phytochemicals, both individually and in combination, that can prevent and treat HPV infection and HPV associated cervical cancer. Phytochemicals were tested using growth inhibition, combination, gene expression, RT PCR, and molecular docking assays.

Differentiation of Early Sacroiliitis Using Machine-Learning- Supported Texture Analysis.

We wished to compare the diagnostic performance of texture analysis (TA) against that of a visual qualitative assessment in identifying early sacroiliitis (nr-axSpA). A total of 92 participants were retrospectively included at our university hospital institution, comprising 30 controls and 62 patients with axSpA, including 32 with nr-axSpA and 30 with r-axSpA, who underwent MR examination of the sacroiliac joints. MRI at 3T of the lumbar spine and the sacroiliac joint was performed using oblique T1-weighted (W), fluid-sensitive, fat-saturated (Fs) T2WI images.

Paediatric strategy forum for medicinal product development in diffuse midline gliomas in children and adolescents ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

Fewer than 10 % of children with diffuse midline glioma (DMG) survive 2 years from diagnosis. Radiation therapy remains the cornerstone of treatment and there are no medicinal products with regulatory approval. Although the biology of DMG is better characterized, this has not yet translated into effective treatments.

Safety and Efficacy in Mitral Regurgitation Management with the MitraClip G4 System: Insights from a Single-Center Study.

Background: Mitral regurgitation (MR) is a common valvular disorder linked to high morbidity and mortality. For patients unsuitable for surgery, transcatheter mitral edge-to-edge repair (TEER) with the MitraClip G4 system offers an alternative. This study aims to evaluate procedural, echocardiographic, functional, and quality of life (QoL) outcomes in patients who underwent TEER with the MitraClip G4 system, along with possible predictors of New York Heart Association (NYHA) class I at 30 days and at 1 year.

Risk factors affecting polygenic score performance across diverse cohorts.

Apart from ancestry, personal or environmental covariates may contribute to differences in polygenic score (PGS) performance. We analyzed the effects of covariate stratification and interaction on body mass index (BMI) PGS (PGS) across four cohorts of European (N = 491,111) and African (N = 21,612) ancestry. Stratifying on binary covariates and quintiles for continuous covariates, 18/62 covariates had significant and replicable R differences among strata.

Prescriptions (Rx) for Prevention: Clinical Tools for Integrating Environmental Health into Pediatric Clinical Care.

The integration of environmental health (EH) into routine clinical care for children is in its early stages. The vision of pediatric EH is that all clinicians caring for children are aware of and able to help connect families to needed resources to reduce harmful environmental exposures and increase health-enhancing ones. Environmental exposures include air pollution, substandard housing, lead, mercury, pesticides, consumer products chemicals, drinking water contaminants, industrial facility emissions and, increasingly, climate change-related extreme weather and heat events.

Myosin-based nucleation of actin filaments contributes to stereocilia development critical for hearing.

Assembly of actin-based stereocilia is critical for cochlear hair cells to detect sound. To tune their mechanosensivity, stereocilia form bundles composed of graded rows of ascending height, necessitating the precise control of actin polymerization. Myosin 15 (MYO15A) drives hair bundle development by delivering critical proteins to growing stereocilia that regulate actin polymerization via an unknown mechanism.

MRI-assessed Dynamic Hyperinflation Induced by Tachypnea in Chronic Obstructive Pulmonary Disease: The SPIROMICS-HF Study.

Purpose To assess the repeatability of real-time cine pulmonary MRI measures of metronome-paced tachypnea (MPT)-induced dynamic hyperinflation and its relationship with chronic obstructive pulmonary disease (COPD) severity. Materials and Methods SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) (ClinicalTrials.gov identifier no.

Outcomes of a transapical edge-to-edge repair system in secondary mitral regurgitation.

Objectives: The ValveClamp system (Hanyu Medical Technology) is a novel transcatheter edge-to-edge repair (TEER) system designed for ease of operation; however, there is a lack of data on its application in secondary mitral regurgitation (SMR). The authors report the mid-term outcomes of TEER using the ValveClamp system in SMR.

Methods: The study prospectively analyzed consecutive severe SMR patients who underwent transapical ValveClamp implantation at 10 Chinese centers.

Predicting Robotic Hysterectomy Incision Time: Optimizing Surgical Scheduling with Machine Learning.

Background And Objectives: Operating rooms (ORs) are critical for hospital revenue and cost management, with utilization efficiency directly affecting financial outcomes. Traditional surgical scheduling often results in suboptimal OR use. We aim to build a machine learning (ML) model to predict incision times for robotic-assisted hysterectomies, enhancing scheduling accuracy and hospital finances.

A Topical Formulation Containing Ferment for Managing Barrier Damage After Mild-Moderate Skin Disruption from Cosmetic Dermatologic Procedures.

Objective: The primary objective of these studies was to evaluate the potential of a serum containing Macrocystis pyrifera ferment (MPF-Serum) to both strengthen the barrier of intact skin and enhance barrier recovery after a non-ablative laser procedure or glycolic acid chemical peel.

Methods: Two whole-face clinical trials and three split-face, randomized, controlled clinical trials were conducted in women aged 31 to 65 years. The effect of MPF-Serum on barrier integrity and strength was assessed by transepidermal water loss measurement before and after controlled tape-stripping experiments and in-clinic 70% glycolic acid peel and non-ablative laser procedures.

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.

Advances in the understanding and therapeutic manipulation of cancer immune responsiveness: a Society for Immunotherapy of Cancer (SITC) review.

Cancer immunotherapy-including immune checkpoint inhibition (ICI) and adoptive cell therapy (ACT)-has become a standard, potentially curative treatment for a subset of advanced solid and liquid tumors. However, most patients with cancer do not benefit from the rapidly evolving improvements in the understanding of principal mechanisms determining cancer immune responsiveness (CIR); including patient-specific genetically determined and acquired factors, as well as intrinsic cancer cell biology. Though CIR is multifactorial, fundamental concepts are emerging that should be considered for the design of novel therapeutic strategies and related clinical studies.

Surgical Management of Fibrosing Mediastinitis Presenting as Superior Vena Cava Syndrome.

Fibrosing mediastinitis is a rare chronic inflammatory condition characterized by excessive fibrotic process in the mediastinum. Although various infectious processes are more common causes, it can also be related to several malignancies. We report a case of a 28-year-old woman with fibrosing mediastinitis related to an aggressive primary gray-zone lymphoma causing complete occlusion of the superior vena cava (SVC) and the innominate veins.

The impact of mental health disorders on outcomes following total ankle arthroplasty: A systematic review.

Background: The purpose of this systematic review was to evaluate the impact of mental health disorders (MHDs) on the clinical and functional outcomes following total ankle arthroplasty (TAA) for the treatment of end-stage ankle arthritis.

Methods: A systematic review of the EMBASE, MEDLINE, and Cochrane Library databases was conducted in April 2024 following PRISMA guidelines. Data collected included patient demographics, clinical outcomes, complications, and failures.

Examining Healthy Lifestyles as a Mediator of the Association Between Socially Determined Vulnerabilities and Incident Heart Failure.

Background: Increased burden of socially determined vulnerabilities (SDV), which include nonmedical conditions that contribute to patient health, is associated with incident heart failure (HF). Mediators of this association have not been examined. We aimed to determine if a healthy lifestyle mediates the association between SDV and HF.

Valvular Heart Disease-Related Mortality Between Middle- and High-Income Countries During 2000 to 2019.

Background: Valvular heart disease (VHD) management has evolved rapidly in recent decades, but disparities in health care access persist among countries with varying socioeconomic backgrounds.

Objectives: The purpose of this study was to investigate global mortality trends from VHD and assess the difference between middle- and high-income countries.

Methods: We obtained mortality data from the World Health Organization Mortality Database for VHD and its subgroups (rheumatic valvular disease [RVD], infective endocarditis [IE], aortic stenosis [AS], and mitral regurgitation [MR]) from 2000 to 2019.

Brain aging rejuvenation factors in adults with genetic and sporadic neurodegenerative disease.

The largest risk factor for dementia is age. Heterochronic blood exchange studies have uncovered age-related blood factors that demonstrate 'pro-aging' or 'pro-youthful' effects on the mouse brain. The clinical relevance and combined effects of these factors for humans is unclear.

A conceptual model for advanced/metastatic gastric or gastroesophageal junction cancer: a review of qualitative studies and results from patient interviews.

Background: Despite approvals of new first-line immunotherapies for advanced/metastatic gastric cancer/gastroesophageal junction cancer (aGC/GEJC), patients' median survival is around 14 months and their health-related quality of life (HRQoL) is affected by disease-related symptoms and treatment-related side effects. Using a targeted literature review (TLR) and patient interviews, this study identified disease- and treatment-related concepts that are important to patients with aGC/GEJC and their HRQoL.

Methods: A TLR was conducted to identify primary qualitative studies from 2018 to 2021 on patients' experiences with aGC/GEJC.