Tamuzimod in patients with moderately-to-severely active ulcerative colitis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 induction trial.

Background: Tamuzimod (VTX002) is a selective sphingosine 1-phosphate receptor 1 modulator in development for ulcerative colitis. We aimed to assess the safety and efficacy of tamuzimod in patients with moderately-to-severely active ulcerative colitis.

Methods: This double-blind, randomised, placebo-controlled, phase 2 induction trial was conducted at 122 centres across 15 countries in Asia, Europe, and North America.

A single-nuclei transcriptome census of the Arabidopsis maturing root identifies that MYB67 controls phellem cell maturation.

The periderm provides a protective barrier in many seed plant species. The development of the suberized phellem, which forms the outermost layer of this important tissue, has become a trait of interest for enhancing both plant resilience to stresses and plant-mediated CO sequestration in soils. Despite its importance, very few genes driving phellem development are known.

Design and implementation of an action plan for justice, equity, diversity, and inclusion within the Clinical Genome Resource.

How might members of a large, multi-institutional research and resource consortium foster justice, equity, diversity, and inclusion as central to its mission, goals, governance, and culture? These four principles, often referred to as JEDI, can be aspirational-but to be operationalized, they must be supported by concrete actions, investments, and a persistent long-term commitment to the principles themselves, which often requires self-reflection and course correction. We present here the iterative design process implemented across the Clinical Genome Resource (ClinGen) that led to the development of an action plan to operationalize JEDI principles across three major domains, with specific deliverables and commitments dedicated to each. Active involvement of consortium leadership, buy-in from its members at all levels, and support from NIH program staff at pivotal stages were essential to the success of this effort.

Functional optimality underpins the repeated evolution of the extreme "saber-tooth" morphology.

"Saber teeth"-elongate, blade-like canines-are a classic example of convergence, having evolved repeatedly throughout mammalian history. Within canine teeth, there is a trade-off between the aspects of shape that improve food fracture and those that increase tooth strength. Optimal morphologies strike a balance between these antagonistic functional criteria.

Addressing Financial Toxicity From a Global Perspective: How to Advance Shared-Learning to Facilitate Change?

Financial Toxicity is a global issue requiring international efforts, but importantly, where to next?

Outcomes After Thoracoscopic and Open Repair of Esophageal Atresia With Tracheoesophageal Fistula at US Children's Hospitals.

Background: Thoracoscopic repair of esophageal atresia with tracheoesophageal fistula (EA/TEF) has been reported to have superior outcomes to the open approach. We sought to evaluate adoption of thoracoscopic repair at US children's hospitals and compare outcomes to open repair.

Methods: The Pediatric Health Information System database was used to identify patients with EA/TEF who underwent repair between 2016 and 2023.

Mid-life anti-inflammatory metabolites are inversely associated with long-term cardiovascular disease events.

Background: Preclinical data have shown that low levels of metabolites with anti-inflammatory properties may impact metabolic disease processes. However, the association between mid-life levels of such metabolites and long-term ASCVD risk is not known.

Methods: We characterised the plasma metabolomic profile (1228 metabolites) of 1852 participants (58.

A subgroup of multiple system atrophy with rapid decline in vital capacity.

Introduction: Patients with neurodegenerative disorders resulting in progressive dysphagia often require gastrostomy. Pulmonary function tests (PFTs) are crucial in presurgical evaluation; however, reports on pulmonary function in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are limited.

Materials And Methods: This single-center, retrospective study analyzed the PFT records from patients with MSA and PSP admitted between January 2012 and October 2023.

A first-in-human phase 1/2 dose-escalation study of MAK683 (EED inhibitor) in patients with advanced malignancies.

Purpose: MAK683, a first-in-class and highly selective allosteric inhibitor of the embryonic ectoderm development subunit of polycomb repressive complex 2, has shown sustained antitumor activity in tumor xenograft models. This first-in-human phase 1/2 study evaluated the safety, pharmacokinetics (PK), and clinical activity of single-agent MAK683 in advanced malignancies.

Methods: MAK683 was administered fasted once daily or twice daily continuously in 28-day treatment cycles.

Sociodemographic differences in modes of cannabis use among pregnant individuals in Northern California.

Background: The potential risks of prenatal cannabis use may vary depending on how cannabis is administered, but little is known about modes of prenatal cannabis use. This study characterized prevalence and sociodemographic correlates of modes of prenatal cannabis use in California.

Methods: This cross-sectional study included patients with pregnancies between January 1, 2021 and December 31, 2022 in a large healthcare system (3507 pregnancies [3454 individuals]) who self-reported prenatal cannabis use and mode of use (smoke, vape, edibles, dabs, and topicals) during universal screening at entrance to prenatal care.

A reproducibility study on invasion in small pulmonary adenocarcinoma according to the WHO and a modified classification, supported by biomarkers.

Objectives: Evaluating invasion in non-mucinous adenocarcinoma (NMA) of the lung is crucial for accurate pT-staging. This study compares the World Health Organization (WHO) with a recently modified NMA classification.

Materials And Methods: A retrospective case-control study was conducted on small NMA pT1N0M0 cases with a 5-year follow-up.

The Availability of Paternity Leave in US Surgical Residencies: A Study of Program Websites.

Introduction: As family dynamics evolve, an increasing number of male residents are embracing parenthood during their training. Consequently, paternity leave has emerged as a crucial consideration. The aim of this study was to determine the gap in public availability of paternity leave policies in surgical residency programs across the United States.

Partially temporally constrained modeling of speeding crash-injury severities on freeways and non-freeways before, during, and after the stay-at-home order.

Speeding crashes remain high injury severities after the stay-at-home order in California, highlighting a need for further investigation into the fundamental cause of this increment. To systematically explore the temporal impacts of the stay-at-home order on speeding behaviors and the corresponding crash-injury outcomes, this study utilizes California-reported single-vehicle speeding crashes on freeways (access-controlled) and non-freeways (non-access-controlled) before, during, and after the order. Significant injury factors and in-depth heterogeneity across observations are identified by random parameter logit models with heterogeneity in means and variances.

Activity of Platinum Chemotherapy in Men With Prostate Cancer With and Without DNA Damage Repair Mutations.

Introduction: Alterations in homologous recombination repair (HRR) genes occur in 20%-30% of men with metastatic castration-resistant prostate cancer (mCRPC) which may increase sensitivity to platinum chemotherapy. Specifically, exceptional responses to platinum chemotherapy have been reported among patients with BRCA mutations. This study aimed to evaluate the efficacy of platinum chemotherapy in patients with mCRPC with and without HRR.

Outcomes associated with local treatment of nasal planum squamous cell carcinoma in dogs: 89 cases (2003-2020).

Objective: To describe the clinical characteristics, treatments, complications, and outcomes in dogs with nasal planum squamous cell carcinoma (SCC) undergoing local treatment.

Methods: A retrospective, multi-institutional study was performed. Medical records were searched to identify dogs diagnosed with nasal planum SCC.

Primary intrarenal hemangioma - A series of 39 cases.

Intrarenal hemangiomas lack concise clinicopathologic information, due to the predominance of single case reports and inclusion of other vascular neoplasms and hemangiomas of perirenal, hilar, and renal vein origin. Herein, in this multi-institutional study we evaluate clinicopathologic features of 39 intrarenal hemangiomas. The median age was 62 years (range = 27-94 years; 2:1 male to female ratio), with left-sided predominance (left = 21, right = 13; one case was bilateral).

A conifer metabolite corrects episodic ataxia type 1 by voltage sensor-mediated ligand activation of Kv1.1.

Loss-of-function sequence variants in , which encodes the voltage-gated potassium channel Kv1.1, cause Episodic Ataxia Type 1 (EA1) and epilepsy. Due to a paucity of drugs that directly rescue mutant Kv1.

Visibility, Physical Work Environment, and Stress in ICU Nurses.

Objective: Relationships among coworker and patient visibility, reactions to physical work environment, and work stress in ICU nurses are explored.

Background: Millions of dollars are invested annually in the building or remodeling of ICUs, yet there is a gap in understanding relationships between the physical layout of nursing units and work stress.

Methods: Using a cross-sectional, correlational, exploratory, predictive design, relationships among variables were studied in a diverse sample of ICU nurses.

Practical Steps Supporting Professional Publications for Leadership and Teams.

Disseminating research or evidence-based practice is not straightforward. As more clinical nurses, executive nurse leaders, nurse scientists, and faculty contribute to new knowledge, there is an increasing need to support the processes to publish and disseminate manuscripts to advance healthcare. Nurse administrators and leaders are key influencers and supporters to bolster expertise and resources to publish.

The changing relationship between racial identity and skin color in Brazil.

In recent years, Brazil's non-White (Brown and Black) population became a numerical majority for the first time since the 19th century. Although we know this change was mostly due to racial reclassification, we do not know how such changes are related to skin color, the primary marker of race in Brazil. Using data from six Latin American Public Opinion Project (LAPOP), or America's Barometer, surveys from 2010 to 2023, we examine how changes in racial self-identification (White, Brown, or Black) are related to respondent skin color (light, medium, or dark).

Synapse-specific catecholaminergic modulation of neuronal glutamate release.

Norepinephrine in vertebrates and its invertebrate analog, octopamine, regulate the activity of neural circuits. We find that, when hungry, larvae switch activity in type II octopaminergic motor neurons (MNs) to high-frequency bursts, which coincide with locomotion-driving bursts in type I glutamatergic MNs that converge on the same muscles. Optical quantal analysis across hundreds of synapses simultaneously reveals that octopamine potentiates glutamate release by tonic type Ib MNs, but not phasic type Is MNs, and occurs via the G-coupled octopamine receptor (OAMB).

Dissecting the cellular architecture and genetic circuitry of the soybean seed.

Seeds are complex structures composed of three regions, embryo, endosperm, and seed coat, with each further divided into subregions that consist of tissues, cell layers, and cell types. Although the seed is well characterized anatomically, much less is known about the genetic circuitry that dictates its spatial complexity. To address this issue, we profiled mRNAs from anatomically distinct seed subregions at several developmental stages.