β3 accelerates microtubule plus end maturation through a divergent lateral interface.

β-tubulin isotypes exhibit similar sequences but different activities, suggesting that limited sequence divergence is functionally important. We investigated this hypothesis for TUBB3/β3, a β-tubulin linked to aggressive cancers and chemoresistance in humans. We created mutant yeast strains with β-tubulin alleles that mimic variant residues in β3 and find that residues at the lateral interface are sufficient to alter microtubule dynamics and response to microtubule targeting agents.

Restorative Neurostimulation Therapy Compared to Optimal Medical Management: A Randomized Evaluation (RESTORE) for the Treatment of Chronic Mechanical Low Back Pain due to Multifidus Dysfunction.

Introduction: Many interventional strategies are commonly used to treat chronic low back pain (CLBP), though few are specifically intended to target the distinct underlying pathomechanisms causing low back pain. Restorative neurostimulation has been suggested as a specific treatment for mechanical CLBP resulting from multifidus dysfunction. In this randomized controlled trial, we report outcomes from a cohort of patients with CLBP associated with multifidus dysfunction treated with restorative neurostimulation compared to those randomized to a control group receiving optimal medical management (OMM) over 1 year.

Ocrelizumab dose selection for treatment of pediatric relapsing-remitting multiple sclerosis: results of the OPERETTA I study.

Background: The presented study identified the appropriate ocrelizumab dosing regimen for patients with pediatric-onset multiple sclerosis (POMS).

Methods: Patients with POMS aged 10-17 years were enrolled into cohort 1 (body weight [BW] < 40 kg, ocrelizumab 300 mg) and cohort 2 (BW ≥ 40 kg, ocrelizumab 600 mg) during a 24-week dose-exploration period (DEP), followed by an optional ocrelizumab (given every 24 weeks) extension period.

Primary Endpoints: pharmacokinetics, pharmacodynamics (CD19 B-cell count); secondary endpoint: safety; exploratory endpoints: MRI activity, protocol-defined relapses, Expanded Disability Status Scale (EDSS) score change.

Sexual minority stressors and disordered eating behaviors in daily life: a daily diary study of sexual minority cisgender female couples.

Young cisgender sexual minority women (e.g. lesbian, queer) in the U.

General Kernel Machine Methods for Multi-Omics Integration and Genome-Wide Association Testing With Related Individuals.

Integrating multi-omics data may help researchers understand the genetic underpinnings of complex traits and diseases. However, the best ways to integrate multi-omics data and use them to address pressing scientific questions remain a challenge. One important and topical problem is how to assess the aggregate effect of multiple genomic data types (e.

Assessing Clinical Improvement of Infants Hospitalized for Respiratory Syncytial Virus-Related Critical Illness.

Background: Pediatric respiratory syncytial virus (RSV)-related acute lower respiratory tract infection (LRTI) commonly requires hospitalization. The Clinical Progression Scale Pediatrics (CPS-Ped) measures level of respiratory support and degree of hypoxia across a range of disease severity, but it has not been applied in infants hospitalized with severe RSV-LRTI.

Methods: We analyzed data from a prospective surveillance registry of infants hospitalized for RSV-related complications across 39 U.

Ecosystem Drivers of Freshwater Mercury Bioaccumulation Are Context-Dependent: Insights from Continental-Scale Modeling.

Significant variation in mercury (Hg) bioaccumulation is observed across the diversity of freshwater ecosystems in North America. While there is support for the major drivers of Hg bioaccumulation, the relative influence of different external factors can vary widely among waterbodies, which makes predicting Hg risk across large spatial scales particularly challenging. We modeled Hg bioaccumulation by coupling Hg concentrations in more than 21,000 dragonflies collected across the United States from 2008 to 2021 with a suite of chemical (e.

Fibrotic and Emphysematous Murine Lung Mechanics Under Negative-Pressure Ventilation.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and the progressive nature heightens the calamity of the disease. Despite countless existing COPD studies, lung mechanics are often reported under positive-pressure ventilation (PPV) and implications and extrapolations made from these studies pose serious restrictions as recent works have divulged disparate elastic and energetic results between PPV and more physiological negative-pressure counterparts (NPV). This non-equivalence of PPV and NPV needs to be investigated under diseased states to augment our understanding of disease mechanics.

Thermotropic reentrant isotropy and induced smectic antiferroelectricity in the ferroelectric nematic realm: comparing RM734 and DIO.

The current intense study of ferroelectric nematic liquid crystals was initiated by the observation of the same ferroelectric nematic phase in two independently discovered organic, rod-shaped, mesogenic compounds, RM734 and DIO. We recently reported that the compound RM734 also exhibits a monotropic, low-temperature, apolar phase having reentrant isotropic symmetry (the I phase), the formation of which is facilitated to a remarkable degree by doping with small (below 1%) amounts of the ionic liquid BMIM-PF. Here we report similar phenomenology in DIO, showing that this reentrant isotropic behavior is not only a property of RM734 but is rather a more general, material-independent feature of ferroelectric nematic mesogens.

Intracellular tenofovir-diphosphate concentrations in HIV pre-exposure prophylaxis users who underwent bariatric surgery.

Objective: To measure concentrations of tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) among individuals taking tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC) or tenofovir alafenamide plus emtricitabine (TAF/FTC) who were scheduled to undergo or had already undergone bariatric surgery.

Methods: We enrolled pre-exposure prophylaxis (PrEP) users attending clinics in Toronto or Ottawa who were undergoing or had undergone bariatric surgery. After participants completed a minimum of 7 days of consecutive PrEP dosing, we collected DBS samples immediately before they administered their next daily dose of PrEP.

Navigating Children's Risky Play: A Comparative Analysis of Saudi Mothers and Fathers.

Despite documented benefits for development, children are engaging in considerably fewer risky play activities. Research on parent gender and children's risky play is inconsistent. Gender and cultural context shape how individuals perceive and tolerate children's risky play.

Perspectives, Experiences, and Opportunities of Academic Surgeons in the Era of Healthcare Corporatization.

Objective: To characterize contemporary surgeons' viewpoints and perspectives on the academic mission during healthcare corporatization.

Summary Background Data: Academic surgery, traditionally driven by the tripartite missions of excellence in clinical care, scientific research, and education, faces increasing challenges from a corporatized healthcare environment. While previous studies have addressed the financial aspects of corporatization, a comprehensive evaluation of academic surgeons' attitudes and experiences remains lacking.

An Unexpected Activity of a Minor Cannabinoid: Cannabicyclol (CBL) Is a Potent Positive Allosteric Modulator of Serotonin 5-HT Receptor.

Cannabicyclol ((±)-CBL), a minor phytocannabinoid, is largely unexplored, with its biological activity previously undocumented. We studied its conversion from cannabichromene (CBC) using various acidic catalysts. Montmorillonite (K30) in chloroform at room temperature had the highest yield (60%) with minimal byproducts.

Exploring the perceptions and cultural differences surrounding mindfulness among early childhood education informal caregivers: A qualitative study.

Background: Early childhood education (ECE) caregivers experience high levels of stress and increased physical and emotional work demands. Promoting mindfulness practices may be an acceptable and feasible strategy to bolster mental health and well-being. The present study's goals were to explore the 1) perceptions and 2) cultural differences surrounding mindfulness practices and mental health among Spanish-speaking Hispanic (SSH), English-speaking Hispanic (ESH), and English-speaking non-Hispanic (ESNH) informal ECE caregivers.

Cathepsin-D and outcomes in peripartum cardiomyopathy: Results from IPAC.

Objective: Evaluate the relationship of cathepsin-D (CD) on disease severity and clinical outcomes for women with peripartum cardiomyopathy.

Background: Cathepsin-D is a protease released during oxidative stress that cleaves prolactin (PRL) generating a 16 kDa fragment that is pro-apoptotic, anti-angiogenic, and has been implicated in the pathogenesis of peripartum cardiomyopathy (PPCM).

Methods: In 99 women with newly diagnosed PPCM enrolled in the Investigation in Pregnancy Associated Cardiomyopathy (IPAC) study, CD levels were assessed by ELISA from serum obtained at study entry.

The impact of highly effective modulator therapy on sinusitis and dysosmia in young children with cystic fibrosis: a prospective study protocol.

Background: Chronic rhinosinusitis (CRS) and olfactory dysfunction (OD) are prevalent disease complications in people with cystic fibrosis. These understudied comorbidities significantly impact quality of life. The impact of highly effective modulator therapy (HEMT) in young children with cystic fibrosis (YCwCF) on these disease complications is unknown.

Pivotal Trial Toward Effectiveness of Self-administered OCT in Neovascular Age-related Macular Degeneration. Report 2-Artificial Intelligence Analytics.

Purpose: To validate the performance of the Notal OCT Analyzer (NOA) in processing self-administered OCT images from an OCT system designed for home use (home OCT [HOCT]) as part of a pivotal study aimed at achieving de novo United States Food and Drug Admininstration marketing authorization.

Design: A prospective quantitative cross-sectional artificial intelligence study.

Participants: The study enrolled adults aged ≥55 years diagnosed with neovascular age-related macular degeneration (nAMD) in ≥1 eligible eye with a best-corrected visual acuity of 20/320 or better.

The Albright-Losee Low Profile Pivot Shift Test for ACL Deficiency.

Background: Recognizing ACL injuries on the field and in the office can be very challenging in awake and apprehensive patients. Despite high specificity, many published "pivot-shift" techniques have limited acceptance mainly because of unsatisfactory sensitivity. We describe in detail, four specific modifications and provide a critical review of our clinical experiences to empower the new user's readiness to master a novel screening procedure for ACL disruption.

Chronic Health Conditions in the Workplace: Work Stressors and Supportive Supervision, Work Design, and Programs.

A large and growing number of workers are managing chronic physical and mental health conditions while working, necessitating attention from both researchers and leaders and practitioners in organizations. Much of the current discourse around research and practice in this area is focused on prevention of chronic disease and rehabilitation of disability to help workers return to work. Less commonly attended to are workplace factors that can support the quality of working life and the longevity of working life for workers with chronic health conditions.

Impact of antiparasitic therapy on cardiovascular outcomes in chronic Chagas disease. A systematic review and meta-analysis.

Background: Endemic in more than 20 countries, Chagas disease affects 6.3 million people worldwide, leading to 28,000 new infections and 7700 deaths each year. Previous meta-analyses on antiparasitic treatment need updates to encompass recent studies and to assess key clinically meaningful endpoints.

A Comprehensive Assessment of the Marginal Abatement Costs of CO of Co-Optima Multi-Mode Vehicles.

The Co-Optimization of Fuels and Engines (Co-Optima) is a research and development consortia funded by the U.S. Department of Energy, which has engaged partners from national laboratories, universities, and industry to conduct multidisciplinary research at the intersection of biofuels and combustion sciences.

Translation and assessment of encultured meaning of the Multi-Dimensional Scale of Perceived Social Support in Diné bizaad (Navajo) using community-based participatory action research methods.

Introduction: Perceived social support is a psychological construct that is used to describe the 'perception of adequacy' of the support being provided by a person's social network. Higher perceived social support has been linked to multiple benefits across numerous studies over the past several decades and among multiple populations. The Multidimensional Scale of Perceived Social Support (MSPSS) is a 12-item scale to assess the construct of perceived social support.