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.

Divergent evolution of a thermospermine-dependent regulatory pathway in land plants.

Plants adapted to life on land by developing diverse anatomical features across lineages. The molecular basis of these innovations often involves the emergence of new genes or establishing new connections between conserved elements, though evidence for evolutionary genetic circuit rewiring remains scarce. Here, we show that the thermospermine-dependent pathway regulating vascular cell proliferation in Arabidopsis thaliana operates as two distinct modules with different functions in the bryophyte Marchantia polymorpha.

Balancing limited resources in actin network competition.

In cells, multiple actin networks coexist in a dynamic manner. These networks compete for a common pool of actin monomers and actin-binding proteins. Interestingly, all of these networks manage to coexist despite the strong competition for resources.

Development and Validation of a Simplified Financial Toxicity Screening Tool for Use in Clinical Practice.

Purpose: Cancer-related financial toxicity occurs frequently and is a key driver of inequities in access to care and disparities in treatment outcomes. Current practices to screen for financial toxicity are inconsistent because of the lack of a validated and clinically integrated screening tool. This analysis aimed to create and assess an abbreviated version of the validated Comprehensive Score for Financial Toxicity (COST) tool, a measure of financial toxicity used for research purposes, which could easily be added into often-lengthy clinical screening workflows.

Cost Conversations to Mitigate the Effects of Financial Toxicity in Oncology: Current State, Opportunities, and Barriers.

The direct and indirect financial burden of cancer care, from medication costs to lost wages, results in financial toxicity for patients. Despite the growing recognition of financial toxicity as a problem for patients, there are few solutions available at the point of care. Structured cost conversations between oncologists and patients to help identify financial toxicity and intervene early when it is recognized have been posited as a patient facing intervention.

Financial Toxicity in Older Adults With Cancer and Their Caregivers.

With advances in cancer treatment, long-term survival rates have improved in recent decades, resulting in extended life expectancies for many patients. This progress brings substantial challenges, however, particularly in terms of the costs associated with cancer care. The financial burden, often considerable, poses difficulties for older adults with cancer and their caregivers.

Social and Legal Needs in Patients and Families With Cancer: Interaction With Patient-Level Financial Toxicity.

Adverse financial burden and its effect on patients resulting from the costs associated with cancer care, both direct and indirect, is known as financial toxicity. This review explores the interplay between financial toxicity and key social and legal needs in cancer care. Drawing from the WHO's framework and the ASCO's policy statement on social determinants of health, we propose a conceptual model that discusses five key needs-housing insecurity, food insecurity, transportation and access barriers, employment disruptions, and psychosocial needs-which interact with, and are affected by financial toxicity, and adversely influence patients' well-being and adherence to treatment.

Physician-dominated conversations: An analysis of illness understanding discussions among patients with advanced cancer.

Context: Effective communication between patients and oncologists is crucial, particularly around illness understanding. When this communication is asymmetric or imbalanced, it can hinder shared decision-making and lead to suboptimal clinical outcomes.

Objectives: We sought to describe physician-patient speech imbalances ("asymmetry") in illness understanding portions of discussions between oncologists and advanced cancer patients and explore potential trends related to patient characteristics.

Early bedtime routines and behavioral outcomes among children from low-income families: Mediating role of emotion regulation.

The establishment of early bedtime routine is essential for children's emotion and behavioral outcomes. Less is known, however, about the longitudinal effects and mechanisms predicting behavioral outcomes through early bedtime routine and emotion regulation in school-age children from low-income families. Thus, the present study examined emotion regulation at age three as a potential mediator in the longitudinal links between early bedtime routine and behavioral outcomes among racially diverse school age children from low-income families.

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 relationship of medical and recreational cannabis laws with opioid misuse and opioid use disorder in the USA: Does it depend on prior history of cannabis use?

Background: Wider availability of cannabis through medical and recreational legalization (MCL alone and RCL+MCL) has been hypothesized to contribute to reductions in opioid use, misuse, and related harms. We examined whether state adoption of cannabis laws was associated with changes in opioid outcomes overall and stratified by cannabis use.

Methods: Using National Survey on Drug Use and Health (NSDUH) data from 2015 to 2019, we estimated cannabis law associations with opioid (prescription opioid misuse and/or heroin use) misuse and use disorder.

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.

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).

Intraoperative Anesthetic Care During Emergent/Urgent Craniotomy or Craniectomy for Intracranial Hypertension or Herniation: A Systematic Review.

This systematic review aimed to identify and describe best practice for the intraoperative anesthetic management of patients undergoing emergent/urgent decompressive craniotomy or craniectomy for any indication. The PubMed, Scopus, EMBASE, and Cochrane databases were searched for articles related to urgent/emergent craniotomy/craniectomy for intracranial hypertension or brain herniation. Only articles focusing on intraoperative anesthetic management were included; those investigating surgical or intensive care unit management were excluded.

Geometrically modulated contact forces enable hula hoop levitation.

Mechanical systems with moving points of contact-including rolling, sliding, and impacts-are common in engineering applications and everyday experiences. The challenges in analyzing such systems are compounded when an object dynamically explores the complex surface shape of a moving structure, as arises in familiar but poorly understood contexts such as hula hooping. We study this activity as a unique form of mechanical levitation against gravity and identify the conditions required for the stable suspension of an object rolling around a gyrating body.

Protein dynamics underlies strong temperature dependence of heat receptors.

Ion channels are generally allosteric proteins, involving specialized stimulus sensor domains conformationally linked to the gate to drive channel opening. Temperature receptors are a group of ion channels from the transient receptor potential family. They exhibit an unprecedentedly strong temperature dependence and are responsible for temperature sensing in mammals.

Modular DNA origami-based electrochemical detection of DNA and proteins.

The diversity and heterogeneity of biomarkers has made the development of general methods for single-step quantification of analytes difficult. For individual biomarkers, electrochemical methods that detect a conformational change in an affinity binder upon analyte binding have shown promise. However, because the conformational change must operate within a nanometer-scale working distance, an entirely new sensor, with a unique conformational change, must be developed for each analyte.

Binding mode-guided development of high-performance antibodies targeting site-specific posttranslational modifications.

Posttranslational modifications (PTMs) of proteins play critical roles in regulating many cellular events. Antibodies targeting site-specific PTMs are essential tools for detecting and enriching PTMs at sites of interest. However, fundamental difficulties in molecular recognition of both PTM and surrounding peptide sequence have hindered the efficient generation of highly sequence-specific anti-PTM antibodies.

Structural basis of nearest-neighbor cooperativity in the ring-shaped gene regulatory protein TRAP from protein engineering and cryo-EM.

The homo-dodecameric ring-shaped RNA binding attenuation protein (TRAP) from binds up to twelve tryptophan ligands (Trp) and becomes activated to bind a specific sequence in the 5' leader region of the operon mRNA, thereby downregulating biosynthesis of Trp. Thermodynamic measurements of Trp binding have revealed a range of cooperative behavior for different TRAP variants, even if the averaged apparent affinities for Trp have been found to be similar. Proximity between the ligand binding sites, and the ligand-coupled disorder-to-order transition has implicated nearest-neighbor interactions in cooperativity.

Hydroxychloroquine prevents resistance and potentiates the antitumor effect of SHP2 inhibition in NF1-associated malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas and the primary cause of mortality in patients with neurofibromatosis type 1 (NF1). These malignancies develop within preexisting benign lesions called plexiform neurofibromas (PNs). PNs are solely driven by biallelic loss eliciting RAS pathway activation, and they respond favorably to MEK inhibitor therapy.

How and why funders support engaged research.

Research that better aligns policy, practice, and research communities is gaining momentum around the world. This includes engaged research strategies that bring partners, and their diverse perspectives and kinds of knowledge, together to shape research agendas with on-the-ground-needs and to create dynamic problem-solving processes. These approaches aim to generate more equitable and effective solutions to societal challenges.

Comparing integrative ventilatory and renal acid-base acclimatization in lowlanders and Tibetan highlanders during ascent to 4,300 m.

With over 14 million people living above 3,500 m, the study of acclimatization and adaptation to high altitude in human populations is of increasing importance, where exposure to high altitude (HA) imposes a blood oxygenation and acid-base challenge. A sustained and augmented hypoxic ventilatory response protects oxygenation through ventilatory acclimatization, but elicits hypocapnia and respiratory alkalosis. A subsequent renally mediated compensatory metabolic acidosis corrects pH toward baseline values, with a high degree of interindividual variability.

Pöschl Reformations Created from High-Resolution Noncontrast Enhanced CT Head Exams Can Be Used to Detect and Classify Superior Semicircular Canal Abnormalities.

Objective: To compare the diagnostic capability of Pöschl reformations created from temporal bone CT (TBCT) and high-resolution noncontrast CT head exams (HR-NECTH) to detect and classify superior semicircular canal (SSC) abnormalities.

Study Design: Retrospective case review.

Setting: Tertiary referral center.