Long-Term Treatment With Ocrelizumab in Patients With Early-Stage Relapsing MS: Nine-Year Data From the OPERA Studies Open-Label Extension.

Background And Objectives: Patients with multiple sclerosis (MS) may demonstrate better disease control when treatment is initiated on high-efficacy disease-modifying therapies (DMTs) from onset. This subgroup analysis assessed the long-term efficacy and safety profile of the high-efficacy DMT ocrelizumab (OCR) as first-line therapy for early-stage relapsing MS (RMS).

Methods: Post hoc exploratory analyses of efficacy and safety were performed in a subgroup of treatment-naive patients with RMS who received ≥1 dose of OCR in the multicenter OPERA I/II (NCT01247324/NCT01412333) studies.

Myristoylated Neuronal Calcium Sensor-1 captures the ciliary vesicle at distal appendages.

The primary cilium is a microtubule-based organelle that cycles through assembly and disassembly. In many cell types, formation of the cilium is initiated by recruitment of ciliary vesicles to the distal appendage of the mother centriole. However, the distal appendage mechanism that directly captures ciliary vesicles is yet to be identified.

A hierarchical pathway for assembly of the distal appendages that organize primary cilia.

Distal appendages are nine-fold symmetric blade-like structures attached to the distal end of the mother centriole. These structures are critical for formation of the primary cilium, by regulating at least four critical steps: ciliary vesicle recruitment, recruitment and initiation of intraflagellar transport (IFT), and removal of CP110. While specific proteins that localize to the distal appendages have been identified, how exactly each protein functions to achieve the multiple roles of the distal appendages is poorly understood.

Emergent Carotid Stenting During Thrombectomy in Tandem Occlusions Secondary to Dissection: A STOP-CAD Secondary Study.

The optimal endovascular management of cervical carotid dissection causing tandem occlusion remains uncertain. We investigated the impact of emergent carotid stenting during endovascular treatment (EVT) for acute ischemic stroke (AIS) in patients with tandem occlusion secondary to cervical carotid artery dissection. This was a secondary analysis of patients treated with EVT for AIS due to occlusive carotid artery dissection and tandem occlusion included in the retrospective international Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection (STOP-CAD) study.

Impact of Anti-Fatigue Floor Mat on Surgical Staff Comfort Levels in Head and Neck Surgery Cases.

Objective: Musculoskeletal symptoms are common among surgical staff and can have long-term implications on health and wellbeing. The purpose of this study is to evaluate the impact of anti-fatigue floor mat on the comfort level of surgical teams during head and neck surgeries lasting ≥ 3 h.

Methods: Over 4 months, we prospectively randomized 34 major (≥ 3 h) head and neck procedures to the use or not of an anti-fatigue floor mat.

Impact of pulmonary artery catheterization in patients with acute myocardial infarction cardiogenic shock.

Acute myocardial infarction (AMI) remains one of the most common causes for cardiogenic shock (CS), with high inpatient mortality (40-50 %). Studies have reported the use of pulmonary artery catheters (PACs) in decompensated heart failure, but contemporary data on their use to guide management of AMI-CS and in different SCAI stages of CS are lacking. We investigated the association of PACs and clinical outcomes in AMI-CS.

A family-based behavioral group obesity randomized control feasibility trial across a clinical trials network: a focus on contact hours.

Objective: This ancillary study's purpose is to describe the relationship between dose of treatment and body mass index (BMI) outcomes in a tele-behavioral health program delivered in the IDeA States Pediatric Clinical Trials Network to children and their families living in rural communities.

Methods: Participants randomized to the intervention were able to receive 26 contact hours (15 hr of group sessions and 11 hr of individual sessions) of material focused on nutrition, physical activity, and behavioral caregiver training delivered via interactive televideo. Dose of the intervention received by child/caregiver dyads (n = 52) from rural areas was measured as contact hours.

Health System, Community-Based, or Usual Dementia Care for Persons With Dementia and Caregivers: The D-CARE Randomized Clinical Trial.

Importance: The effectiveness of different approaches to dementia care is unknown.

Objective: To determine the effectiveness of health system-based, community-based dementia care, and usual care for persons with dementia and for caregiver outcomes.

Design, Setting, And Participants: Randomized clinical trial of community-dwelling persons living with dementia and their caregivers conducted at 4 sites in the US (enrollment June 2019-January 2023; final follow-up, August 2023).

Characterization of extended-spectrum beta-lactamase-producing from recreational water in Athens, GA, using an undergraduate laboratory module.

We present a laboratory module that uses isolation of antibiotic-resistant bacteria from locally collected stream water samples to introduce undergraduate students to basic microbiological culture-based and molecular techniques. This module also educates them on the global public health threat of antibiotic-resistant organisms. Through eight laboratory sessions, students are involved in quality testing of water sources from their neighborhoods, followed by isolation of extended-spectrum beta-lactamase-producing .

Second-line treatment patterns and outcomes in advanced HCC after progression on atezolizumab/bevacizumab.

Background & Aims: Atezolizumab/bevacizumab (A/B) is now a standard first-line treatment for advanced hepatocellular carcinoma (HCC), but the optimal second-line regimen is not known. We evaluated real-world treatment patterns and outcomes to investigate factors associated with post-progression survival (PPS).

Methods: In this multicenter, international, retrospective study, we examined clinical characteristics and outcomes of patients with advanced HCC who progressed on first-line A/B.

Detecting Deception and Ensuring Data Integrity in a Nationwide mHealth Randomized Controlled Trial: Factorial Design Survey Study.

Background: Social behavioral research studies have increasingly shifted to remote recruitment and enrollment procedures. This shifting landscape necessitates evolving best practices to help mitigate the negative impacts of deceptive attempts (eg, fake profiles and bots) at enrolling in behavioral research.

Objective: This study aimed to develop and implement robust deception detection procedures during the enrollment period of a remotely conducted randomized controlled trial.

Attitudes towards healthy eating and its determinants among older adults in a deprived region of Hungary: implications for the National Healthy Aging Program.

A healthy diet is a key determinant of successful aging. However, the psychological, social, and physiological changes associated with ageing often disrupt dietary behaviours. Hungary has one of the highest rates of chronic age-related diseases in the European Union, exacerbated by unhealthy dietary patterns and rapid population aging.

Effects of methylphenidate on sensitivity to reinforcement delay, magnitude, and probability: Implications for impulsive and risky choice.

Under rapid-acquisition, concurrent-chains choice procedures, psychomotor stimulants typically decrease the sensitivity of responding to changes in separate dimensions of reinforcement. Across two experiments, pigeons chose between outcomes that differed in terms of reinforcement delay and magnitude (the dimensions involved in delay discounting or "impulsive" choice; Experiment 1) or reinforcement probability and magnitude (the dimensions involved in probability discounting or "risky" choice; Experiment 2). Outcomes associated with each terminal link were varied independently and pseudorandomly across sessions such that in dominated sessions one terminal link was favorable in terms of both dimensions (sooner, larger in Experiment 1 and more likely, larger in Experiment 2) and in trade-off sessions each terminal link was favorable in terms of a different dimension.

The Effects of Nitric Oxide on Choroidal Gene Expression.

Purpose: Nitric oxide (NO) is recognized as an important biological mediator that controls several physiological functions, and evidence is now emerging that this molecule may play a significant role in the postnatal control of ocular growth and myopia development. We therefore sought to understand the role that nitric oxide plays in visually-guided ocular growth in order to gain insight into the underlying mechanisms of this process.

Methods: Choroids were incubated in organ culture in the presence of the NO donor, PAPA- NONOate (1.

"Do all bisexuals have this power?": An exploratory study of "crippling nicotine addiction," identity, and other emergent themes in vaping messages on QueerTok.

Nicotine and tobacco use disproportionally affects sexual and gender minority (SGM) populations in the United States. Social media narratives may contribute to these disparities. This qualitative study delineated perceptions and experiences depicted in SGM-related videos about nicotine vaping on TikTok.

MAFLD: Exploring the Systemic Effects Beyond Liver.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a growing global health concern which is driven by the increasing prevalence of diabetes and obesity. MAFLD is characterized by excessive fat accumulation in the liver, which encompasses a range of conditions, from simple hepatic steatosis to more severe forms. This condition is associated with various complications, including chronic kidney disease (CKD), Cardiovascular Disease (CVD), liver cirrhosis, and even malignancy.

Infection prevention in the immunocompromised traveler due to conditions other than transplantation: a review.

This narrative review explores the risks related to infection in immunocompromised travelers due to conditions other than transplantation, and evaluates the evidence behind current prophylactic strategies, including immunizations, antimicrobials, and non-pharmacological interventions, to prevent various infection and how the current evidence applies to this special patient population, from the perspective of a US-based traveler.

Maternal Western Diet Programmes Bile Acid Dysregulation and Hepatic Fibrosis in Fetal and Juvenile Macaques.

Background And Aims: Maternal obesity increases the risk of the paediatric form of metabolic dysfunction-associated steatotic liver disease (MASLD), affecting up to 30% of youth, but the developmental origins remain poorly understood.

Methods: Using a Japanese macaque model, we investigated the impact of maternal Western-style diet (mWSD) or chow diet followed by postweaning WSD (pwWSD) or chow diet focusing on bile acid (BA) homeostasis and hepatic fibrosis in livers from third-trimester fetuses and 3-year-old juvenile offspring.

Results: Juveniles exposed to mWSD had increased hepatic collagen I/III content and stellate cell activation in portal regions.

The Brain's Aging Resting State Functional Connectivity.

Resting state networks (RSNs) of the brain are characterized as correlated spontaneous time-varying fluctuations in the absence of goal-directed tasks. These networks can be local or large-scale spanning the brain. The study of the spatiotemporal properties of such networks has helped understand the brain's fundamental functional organization under healthy and diseased states.

Herpesvirus Infections After Chimeric Antigen Receptor T-Cell Therapy and Bispecific Antibodies: A Review.

In this narrative review, we explore the burden and risk factors of various herpesvirus infections in patients receiving chimeric antigen receptor T-cell (CAR-T) therapy or bispecific antibodies (BsAb) for the treatment of hematologic malignancies. Antiviral prophylaxis for herpes simplex/varicella zoster viruses became part of the standard of care in this patient population. Breakthrough infections may rarely occur, and the optimal duration of prophylaxis as well as the timing of recombinant zoster immunization remain to be explored.

Clinical and Genomic Features of Androgen Indifferent Prostate Cancer.

Androgen-indifferent prostate cancer (AIPC) is increasingly common and particularly lethal. Data describing these tumors are sparse, and AIPC remains a poorly understood malignancy. Utilizing the Oncology Research Information Exchange Network (ORIEN) database, we enriched for tumors with features of AIPC using previously described characteristics.

Evolutionary and Structural Insights into the RNA Polymerase I A34 Protein Family: A Focus on Intrinsic Disorder and Phase Separation.

Background: Eukaryotic RNA polymerase I consists of 12 or 11 core subunits and three dissociable subunits, Rrn3, A34, and A49. The A34 and A49 subunits exist as a heterodimer. In silico analysis of the A34 family of transcription factors demonstrates a commonly shared domain structure despite a lack of sequence conservation, as well as N-terminal and C-terminal disordered regions.

SORL1-Mediated EGFR and FGFR4 Regulation Enhances Chemoresistance in Ovarian Cancer.

Recurrent tumors that are resistant to conventional chemotherapy are a major challenge of ovarian cancer treatment. A better understanding of the underlying molecular mechanisms of chemoresistance is critical for developing more effective targeted therapies for ovarian cancer. In this study, we analyzed the transcriptomic profiles of thirteen pairs of matching primary and recurrent ovarian cancers to identify genes that were upregulated in the recurrent tumors.