Response Trajectories and Temporal Trends of Viloxazine Treatment for Young People With ADHD: A Meta-Analysis.

Importance: Viloxazine is a novel nonstimulant medication approved for the treatment of attention-deficit/hyperactivity disorder (ADHD).

Objectives: To investigate the whether viloxazine is associated with effective and acceptable outcomes when treating children and adolescents with ADHD and to evaluate these outcomes' associations with viloxazine doses and duration of treatment.

Data Sources: The MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, PsycINFO, and ClinicalTrial.

Evaluation of a Tailored Patient Navigation Program for Improving Multitarget Stool DNA Test Adherence.

Background: Multitarget stool DNA (mt-sDNA) is an increasingly utilized noninvasive option for colorectal cancer screening; however, its impact is limited by imperfect test adherence. Tailored patient navigation (TPN) improves adherence for other cancer screening tests, but its role in mt-sDNA is not known.

Aim: Determine whether TPN improves mt-sDNA completion and reduces sample could not be processed (SCNBP) result rates.

Immune persistence and booster response of a quadrivalent meningococcal conjugate vaccine (MenACYW-TT) 5 years after primary vaccination of adults at ≥56 years of age.

Stage I of this study (NCT04142242) demonstrated the safety and immunogenicity of a booster dose of a licensed quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) and immune persistence 3 and 6-7 years after priming in older adults who received either quadrivalent meningococcal polysaccharide vaccine (MPSV4) or MenACYW-TT at ≥56 years of age. Stage II, reported here, assessed the antibody persistence after MenACYW-TT versus MPSV4 priming and the safety and immunogenicity of a booster dose of MenACYW-TT in older adults 5 years after primary vaccination with either MPSV4 or MenACYW-TT. A serum bactericidal assay (hSBA) was used to measure functional antibodies against each serogroup immediately before MenACYW-TT booster vaccination and on day (D) 30 post-booster.

Efficacy and safety of novel multiple-chain DAP-CAR-T cells targeting mesothelin in ovarian cancer and mesothelioma: a single-arm, open-label and first-in-human study.

Background: Despite remarkable achievements in applying chimeric antigen receptor (CAR)-T cells to treat hematological malignancies, they remain much less effective against solid tumors, facing several challenges affecting their clinical use. We previously showed that multichain DNAX-activating protein (DAP) CAR structures could enhance the safety and efficacy of CAR-T cells when used against solid tumors. In particular, mesothelin (MSLN)-targeted CAR-T cell therapy has therapeutic potential in MSLN-positive solid tumors, including ovarian cancer and mesothelioma.

STK19 positions TFIIH for cell-free transcription-coupled DNA repair.

In transcription-coupled nucleotide excision repair (TC-NER), stalled RNA polymerase II (RNA Pol II) binds CSB and CRL4, which cooperate with UVSSA and ELOF1 to recruit TFIIH. To explore the mechanism of TC-NER, we recapitulated this reaction in vitro. When a plasmid containing a site-specific lesion is transcribed in frog egg extract, error-free repair is observed that depends on CSB, CRL4, UVSSA, and ELOF1.

Tirzepatide for Obesity Treatment and Diabetes Prevention.

Background: Obesity is chronic disease and causal precursor to myriad other conditions, including type 2 diabetes. In an earlier analysis of the SURMOUNT-1 trial, tirzepatide was shown to provide substantial and sustained reductions in body weight in persons with obesity over a 72-week period. Here, we report the 3-year safety outcomes with tirzepatide and its efficacy in reducing weight and delaying progression to type 2 diabetes in persons with both obesity and prediabetes.

Non-serious adverse events in patients with ulcerative colitis receiving etrasimod: an analysis of the phase II OASIS and phase III ELEVATE UC 52 and ELEVATE UC 12 clinical trials.

Background: Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P) receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). It is known that non-serious treatment-emergent adverse events (TEAEs) may not lead to UC drug discontinuation but can affect treatment tolerability.

Objectives: This post hoc analysis evaluated the incidence of specific, common, non-serious TEAEs reported in the etrasimod UC clinical programme and the characteristics of affected patients.

Safety and immunogenicity of a pentavalent meningococcal conjugate vaccine versus a quadrivalent meningococcal conjugate vaccine in adults in India: an observer-blind, randomised, active-controlled, phase 2/3 study.

Background: Meningococcal disease remains an important public health problem globally. We assessed the non-inferiority and the lot-to-lot consistency of a pentavalent meningococcal ACYWX conjugate vaccine (NmCV-5; Serum Institute of India, Pune, India) versus a quadrivalent meningococcal ACWY conjugate vaccine (MenACWY-D) in healthy adults.

Methods: In this observer-blind, randomised, active-controlled, phase 2/3 study, healthy adults aged 18-85 years were recruited from nine hospitals across seven cities in India.

Randomized trial showing persistence of hSBA titers elicited by a pentavalent meningococcal MenABCWY vaccine for up to 4 years following a primary series and safety and immunogenicity of a booster dose.

Background: Vaccination against 5 prominent meningococcal serogroups (A/B/C/W/Y) is necessary for broad disease protection. We report immunopersistence through 4 years after a 2-dose (6-month interval) pentavalent MenABCWY primary vaccine series and safety and immunogenicity of a booster administered 4 years after primary vaccination.

Methods: This randomized, active-controlled, observer-blinded study was conducted in the United States and Europe.

Effects of Extracted Pulse Proteins on Lipid Targets for Cardiovascular Risk Reduction: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Many clinical practice guidelines recommend dietary pulses for the prevention and management of cardiovascular disease and diabetes. The impact of extracted pulse proteins remains unclear. We therefore conducted a systematic review and meta-analysis of randomized controlled trials of the effect of extracted pulse proteins on therapeutic lipid targets.

Health Benefits Beyond the Scale: The Role of Diet and Nutrition During Weight Loss Programmes.

Introduction: Obesity management strategies such as caloric restriction, very-low-calorie diets (VLCDs), and meal replacements can lead to moderate short-term weight loss. However, many patients face significant challenges in maintaining these results. Personalized interventions, including behavioral counseling and physical activity, have been shown to improve long-term adherence and success.

Physiologically based pharmacokinetic modeling of drug-drug interactions between ritonavir-boosted atazanavir and rifampicin in pregnancy.

Ritonavir-boosted atazanavir (ATV/r) and rifampicin are mainstays of second-line antiretroviral and multiple anti-TB regimens, respectively. Rifampicin induces CYP3A4, a major enzyme involved in atazanavir metabolism, causing a drug-drug interaction (DDI) which might be exaggerated in pregnancy. Having demonstrated that increasing the dose of ATV/r from once daily (OD) to twice daily (BD) in non-pregnant adults can safely overcome this DDI, we developed a pregnancy physiologically based pharmacokinetic (PBPK) model to explore the impact of pregnancy.

CRISPRi/a screens in human iPSC-cardiomyocytes identify glycolytic activation as a druggable target for doxorubicin-induced cardiotoxicity.

Doxorubicin is limited in its therapeutic utility due to its life-threatening cardiovascular side effects. Here, we present an integrated drug discovery pipeline combining human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs), CRISPR interference and activation (CRISPRi/a) bidirectional pooled screens, and a small-molecule screening to identify therapeutic targets mitigating doxorubicin-induced cardiotoxicity (DIC) without compromising its oncological effects. The screens revealed several previously unreported candidate genes contributing to DIC, including carbonic anhydrase 12 (CA12).

Protocol to study electrophysiological properties of hPSC-derived 3D cardiac organoids using MEA and sharp electrode techniques.

Continuing advancements in human pluripotent stem cell (hPSC)-derived complex three-dimensional (3D) cardiac tissues require the development of novel technologies or adaptation of existing technologies to understand the physiology of the derived 3D cardiac tissues. In this protocol, we describe the use of multielectrode array (MEA) and sharp electrode electrophysiology techniques to investigate the electrical properties of 3D cardiac organoids. This protocol deciphers the electrical behavior of 3D cardiac organoids at both the single-cell level and tissue level.

Quadrivalent Conjugate Vaccine and Invasive Meningococcal Disease in US Adolescents and Young Adults.

Importance: Beginning in 2005, the US implemented routine immunization of adolescents with a quadrivalent conjugate vaccine (MenACWY) for the prevention of invasive meningococcal disease (IMD).

Objectives: To assess whether MenACWY immunization was associated with a reduced IMD burden among the US adolescent population and how the downward trajectory of IMD that began in the mid-1990s might have evolved in the absence of vaccination efforts.

Design, Setting, And Participants: In this decision analytical study, a bayesian hierarchical Poisson regression model was developed to investigate the potential trajectory of IMD among US adolescents and young adults without vaccination and evaluate the direct association of vaccination with IMD burden.

Combining Biology-based and MRI Data-driven Modeling to Predict Response to Neoadjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer.

Purpose To combine deep learning and biology-based modeling to predict the response of locally advanced, triple-negative breast cancer before initiating neoadjuvant chemotherapy (NAC). Materials and Methods In this retrospective study, a biology-based mathematical model of tumor response to NAC was constructed and calibrated on a patient-specific basis using imaging data from patients enrolled in the MD Anderson A Robust TNBC Evaluation FraMework to Improve Survival trial (ARTEMIS; ClinicalTrials.gov registration no.

A Multimodal Deep Learning Nomogram for the Identification of Clinically Significant Prostate Cancer in Patients with Gray-Zone PSA Levels: Comparison with Clinical and Radiomics Models.

Rationale And Objectives: To establish a multimodal deep learning nomogram for predicting clinically significant prostate cancer in patients with gray-zone PSA levels.

Methods: This retrospective study enrolled 303 patients with pathological results between January 2018 and December 2022. Clinical variables and the PI-RADS v2.