Belzutifan plus cabozantinib as first-line treatment for patients with advanced clear-cell renal cell carcinoma (LITESPARK-003): an open-label, single-arm, phase 2 study.

Background: Belzutifan, a first-in-class HIF-2α inhibitor, has shown antitumour activity as monotherapy and in combination with cabozantinib in patients with previously treated advanced kidney cancer. The phase 2 LITESPARK-003 study was designed to determine the antitumour activity and safety of belzutifan in combination with cabozantinib in patients with advanced clear-cell renal cell carcinoma that was previously untreated (cohort 1) or previously treated with immunotherapy (cohort 2). Here, we report results from cohort 1 of this clinical trial.

Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials.

Background: The goal of cystic fibrosis transmembrane conductance regulator (CFTR) modulators is to reach normal CFTR function in people with cystic fibrosis. Vanzacaftor-tezacaftor-deutivacaftor restored CFTR function in vitro and in phase 2 trials in participants aged 18 years and older resulting in improvements in CFTR function, as measured by sweat chloride concentrations and lung function as measured by spirometry. We aimed to evaluate the efficacy and safety of vanzacaftor-tezacaftor-deutivacaftor compared with standard of care elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older.

Longitudinal patterns in smoking abstinence in trials of e-cigarettes for smoking cessation: secondary analysis of data from a systematic review, with meta-analyses.

Introduction: We set out to better understand patterns of smoking abstinence and relapse in trials of e-cigarettes for smoking cessation.

Methods: Secondary analysis of studies from a Cochrane review. Studies had to test any type of e-cigarette intervention for smoking cessation.

Consensus review and considerations on TMS to treat depression: A comprehensive update endorsed by the National Network of Depression Centers, the Clinical TMS Society, and the International Federation of Clinical Neurophysiology.

This article updates the prior 2018 consensus statement by the National Network of Depression Centers (NNDC) on the use of transcranial magnetic stimulation (TMS) in the treatment of depression, incorporating recent research and clinical developments. Publications on TMS and depression between September 2016 and April 2024 were identified using methods informed by PRISMA guidelines. The NNDC Neuromodulation Work Group met monthly between October 2022 and April 2024 to define important clinical topics and review pertinent literature.

Multiple environmental tracers combined with a constrained Bayesian isotope mixing model to elucidate nitrate and sulfate contamination in a coastal groundwater system.

Several groundwater quality investigations have been conducted in coastal regions that are commonly exposed to multiple anthropogenic stressors. Nonetheless, such studies remain challenging because they require focused-diagnostic approaches for a comprehensive understanding of groundwater contamination. Therefore, this study integrates a multi-tracer approach to acquire comprehensive information allowing for an improved understanding of the origins of groundwater contamination, the relative contribution of contaminants, and their biogeochemical cycling within a coastal groundwater system.

Using What Matters Most to improve health care delivery for individuals and populations of veterans experiencing homelessness and substance use disorders.

Objectives: To understand ways in which the Personal Health Inventory (PHI), a tool to prompt reflection on what matters most and status in 8 components of health and well-being, can be used to inform care of homeless veterans entering a Mental Health Residential Rehabilitation Treatment Program, at individual and programmatic levels.

Methods: Mixed method study was conducted at one residential treatment program. Quantitative data was collected from the PHI (n=64) and was analyzed using descriptive statistics.

Self-reported longitudinal COVID-19 vaccination reactogenicity profiles in persons with multiple sclerosis.

Background: Preventing severe COVID-19 associated outcomes continues to be a priority for persons with multiple sclerosis (PwMS). We previously reported in an interim analysis that short-term reactions to the first and second SARS-CoV-2 vaccines experienced by PwMS were mostly self-limiting and similar to reactions experienced by the general population.

Objectives: First, to report short-term reactogenicity experienced by PwMS in relation to the first through fourth SARS-CoV-2 vaccines.

Assessment of the effect of non-ionic surfactant alkylphenol ethoxylates on the penetration of pesticides in fresh produce.

Understanding the penetration behaviour of pesticide active ingredient (AI) in the presence of adjuvants is important in managing application efficacy and minimizing residues. This study investigates the impact of non-ionic surfactant alkylphenol ethoxylates (APEOs) on the penetration of two pesticides, systemic thiabendazole and non-systemic phosmet, in apple and spinach. Surface-enhanced Raman Spectroscopy (SERS) was employed using two different detection methods, namely XZ depth mapping and XY area mapping, in conjunction with liquid Chromatography with tandem mass spectrometry (LC-MS/MS) to investigate the penetration of various pesticide formulations over time.

Protocol for capturing a full transcriptome from single preimplantation embryos using So-Smart-seq.

Strand-optimized Smart-seq (So-Smart-seq) can capture a comprehensive transcriptome from low-input samples. This technique detects both polyadenylated and non-polyadenylated RNAs, inclusive of repetitive RNAs, while excluding highly abundant ribosomal RNAs. So-Smart-seq preserves strand information and minimizes 5' to 3' coverage bias.

Evidence-Based Medicine in Otolaryngology Part 17: A Qualitative Research Primer.

As qualitative data analysis becomes more frequently applied within the fields of medicine and surgery, it is beneficial to expand our knowledge of the utility, methodology, and interpretation of these techniques. While qualitative research serves a distinct purpose and differs from quantitative research, both can be approached with diligence, with careful techniques that are similarly maintained and respected. In advance of this installment in the Evidence-Based Medicine in Otolaryngology series, we presented a comparison between qualitative and quantitative methods.

Nextflow4MS-DIAL: A Reproducible Nextflow-Based Workflow for Liquid Chromatography-Mass Spectrometry Metabolomics Data Processing.

Reproducibility in untargeted metabolomics data processing remains a significant challenge due to software limitations and the complex series of steps required. To address these issues, we developed Nextflow4MS-DIAL, a reproducible workflow for liquid chromatography-mass spectrometry (LC-MS) metabolomics data processing, validated with publicly available data from MetaboLights (MTBLS733). Nextflow4MS-DIAL automates LC-MS data processing to minimize human errors from manual data handling.

In-vitro and in-vivo assessment of biocompatibility and efficacy of ostrich eggshell membrane combined with platelet-rich plasma in Achilles tendon regeneration.

Tendon injuries present significant medical, social, and economic challenges globally. Despite advancements in tendon injury repair techniques, outcomes remain suboptimal due to inferior tissue quality and functionality. Tissue engineering offers a promising avenue for tendon regeneration, with biocompatible scaffolds playing a crucial role.

3-year Outcomes of Botulinum Toxin versus Strabismus Surgery for the Treatment of Acute Acquired Comitant Esotropia in Children.

Introduction: Botulinum toxin is an alternative to conventional strabismus surgery for treatment for acute, acquired, comitant esotropia (AACE). Previous studies suggest that the two treatment approaches may be equally effective for 6 months. The purpose of our study was to determine whether botulinum toxin remains as effective as strabismus surgery for 36 months after treatment.

A Guide to Pediatric Antibiotic Allergy Testing: A Report from the United States Drug Allergy Registry.

Pediatric antibiotic labels are common, and unnecessary antibiotic avoidance is associated with negative personal and public health outcomes; as a result, there is an increasing emphasis on the importance of pediatric antibiotic allergy evaluations. Different testing strategies have been advised, including skin testing and challenge testing with varied doses and duration. Established consensus testing protocols are lacking.

Sleep deprivation affects pain sensitivity by increasing oxidative stress and apoptosis in the medial prefrontal cortex of rats via the HDAC2-NRF2 pathway.

Sleep is crucial for sustaining normal physiological functions, and sleep deprivation has been associated with increased pain sensitivity. The histone deacetylases (HDACs) are known to significantly regulate in regulating neuropathic pain, but their involvement in nociceptive hypersensitivity during sleep deprivation is still not fully understood. Utilizing a modified multi-platform water environment technique to establish a sleep deprivation model.

A systematic review and meta-analysis of endovascular treatment of carotid blowout syndrome.

Unlabelled: Carotid Blowout Syndrome (CBS) is a rare and life-threatening condition that necessitates prompt intervention to prevent fatal hemorrhage. This study compares the outcomes of two primary endovascular approaches: reconstructive interventions, which aim to preserve carotid artery function using stents or balloon angioplasty, and deconstructive interventions, which involve vessel occlusion to halt bleeding. A systematic review and meta-analysis were performed by searching multiple databases for relevant studies published from January 2000 to August 2023.

Intraoperative FiO and risk of impaired postoperative oxygenation in lung resection: A propensity score-weighted analysis.

Study Objective: To assess whether, in a lung resection cohort with a low probability of confounding by indication, higher FiO is associated with an increased risk of impaired postoperative oxygenation - a clinical manifestation of lung injury/dysfunction.

Design: Pre-specified registry-based retrospective cohort study.

Setting: Two large academic hospitals in the United States.

Relationship of Time to First Therapy and Survival Outcomes of Neoadjuvant Chemotherapy Versus Upfront Surgery Approach in Resectable Pancreatic Ductal Adenocarcinoma.

Introduction: Evidence demonstrating overall survival benefit of neoadjuvant chemotherapy (NAC) followed by surgical resection over upfront surgical resection for resectable pancreatic ductal adenocarcinoma (PDAC) has been mixed. The time to first therapy (TTFT) variable has not been studied as a contributing factor.

Methods: A nationwide retrospective analysis using the National Cancer Database to evaluate patients with clinical stage T1 and T2 PDACs from 2010 to 2020.

Urinary Kidney Injury Biomarker Profiles in Healthy Individuals and After Nephrotoxic and Ischemic Injury.

Two observational studies were conducted to support an initiative to qualify translational kidney safety biomarkers as clinical drug development tools that identify tubular injury prior to changes in estimated glomerular filtration rate (eGFR). Normal healthy volunteers provided three morning spot urine collections over 4 weeks. Patients undergoing surgical resection and intrathoracic cisplatin for malignant pleural mesothelioma provided urine samples pre- and postoperatively at 4, 8, and 12 hours and daily for 6 days.

Toward a Science of Emergence: Definitions, Prototypes, Principles and Applications.

Emergence as a phenomenon is embedded and expressed in the natural world, and in social systems. Introduced nearly 150 years ago in a philosophical context, it has since been applied in nearly every natural and social science. However all of these uses are not congruent, as the range of emergences in this Special Issue reflect as well; this has limited the accumulation of knowledge about emergence, as well as its development as a discipline.

Introduction to Emergence in Social Systems.

The articles in this special issue examine the contributions of Jeffrey A. Goldstein to the understanding of emergence as a formal group of processes. Applications include work teams, organizations, ecologies of organizations, and societies.