Effect of Target-Mediated Disposition on Iptacopan Clinical Pharmacokinetics in Participants with Normal or Impaired Hepatic Function.

Iptacopan, a first-in-class complement factor B inhibitor acting proximally in the alternative complement pathway, has been shown to be safe and effective for patients with complement-mediated diseases. Iptacopan selectively binds with high affinity to factor B, a soluble, plasma-based, hepatically produced protein. Factor B is abundant in the circulation but can be saturated at the iptacopan clinical dose of 200 mg twice daily.

Loading monocytes with magnetic nanoparticles enables their magnetic control without toxicity.

Background: With the help of superparamagnetic iron oxide nanoparticles (SPIONs), cells can be magnetically directed so that they can be accumulated at target sites. This principle can be used to make monocytes magnetically steerable in order to improve tumor accumulation, e.g.

Baseline Drug Clearance Predicts Outcomes in Children With Inflammatory Bowel Disease Treated With Vedolizumab: Results From the VedoKids Prospective Multicentre Study.

Background: The pharmacokinetics of biologic agents can differ between children and adults with inflammatory bowel disease (IBD), often necessitating modified paediatric dosing strategies.

Aims: To define the exposure-response relationship of vedolizumab in the paediatric IBD VedoKids cohort including the effect of baseline clearance on deep biochemical remission (normal C-reactive protein [CRP]/erythrocyte sedimentation rate [ESR] and steroid-free remission) at 30 weeks, and to use population pharmacokinetic models to find the best matches between adult and paediatric pharmacokinetic profiles.

Methods: We sought a pharmacokinetic model on 312 serum vedolizumab concentrations from 129 children, assisted by a published adult model as a Bayesian prior.

Maintenance treatment with vedolizumab in paediatric inflammatory bowel disease (VEDOKIDS): 54-week outcomes of a multicentre, prospective, cohort study.

Background: Infliximab and adalimumab are the only biologics thus far approved for paediatric patients with inflammatory bowel disease (IBD), so other biologics, such as vedolizumab, are prescribed off-label. Despite its frequent use, prospective data for vedolizumab treatment in children are available only for short-term induction outcomes. We aimed to evaluate the long-term efficacy and safety of maintenance therapy with vedolizumab in paediatric patients with IBD.

Loading of CAR-T cells with magnetic nanoparticles for controlled targeting suppresses inflammatory cytokine release and switches tumor cell death mechanism.

Therapies against hematological malignancies using chimeric antigen receptors (CAR)-T cells have shown great potential; however, therapeutic success in solid tumors has been constrained due to limited tumor trafficking and infiltration, as well as the scarcity of cancer-specific solid tumor antigens. Therefore, the enrichment of tumor-antigen specific CAR-T cells in the desired region is critical for improving therapy efficacy and reducing systemic on-target/off-tumor side effects. Here, we functionalized human CAR-T cells with superparamagnetic iron oxide nanoparticles (SPIONs), making them magnetically controllable for site-directed targeting.

Development of Receptor Desolvation Scoring and Covalent Sampling in DOCK 6: Methods Evaluated on a RAS Test Set.

Molecular docking methods are widely used in drug discovery efforts. RAS proteins are important cancer drug targets, and are useful systems for evaluating docking methods, including accounting for solvation effects and covalent small molecule binding. Water often plays a key role in small molecule binding to RAS proteins, and many inhibitors─including FDA-approved drugs─covalently bind to oncogenic RAS proteins.

Efficacy, Safety, and Immunogenicity of the MATISSE (Maternal Immunization Study for Safety and Efficacy) Maternal Respiratory Syncytial Virus Prefusion F Protein Vaccine Trial.

Objective: To evaluate descriptive efficacy data, exploratory immunogenicity data, and safety follow-up through study completion from the global, phase 3 MATISSE (Maternal Immunization Study for Safety and Efficacy) maternal vaccination trial of bivalent respiratory syncytial virus (RSV) prefusion F protein vaccine (RSVpreF).

Methods: MATISSE was a phase 3, randomized, double-blinded, placebo-controlled trial. Healthy pregnant participants aged 49 years or younger at 24-36 weeks of gestation were randomized (1:1) to receive a single RSVpreF 120 micrograms or placebo dose.

The role of healthcare professionals' communication in trial participation decisions: a qualitative investigation of recruitment consultations and patient interviews across three RCTs.

Background: Although the challenges of recruiting to randomised controlled trials (RCTs) are well documented, few studies have focused on the impact that the communication between recruiters and patients has on patients' participation decisions. Recruiters are thought to influence patient decision-making, but the mechanisms by which this occurs are unclear. The aim of this research was to investigate how patients interpret and use the information conveyed to them by healthcare professionals (HCPs) in trial participation decisions.

Adaptation of the German language version of the QUAlity of life assessment of spina bifida for adults (QUALAS-A-G).

Introduction: Spina bifida (SB) affects almost all activities in daily life and therefore also health-related quality of life (HRQOL). To assess the HRQOL of adults with SB, a self-reported QUAlity of Life Assessment of Spina bifida in Adults (QUALAS-A) was validated in English. The purpose of this study was to develop and validate a German version of QUALAS-A.

Adipose tissue biology and effect of weight loss in women with lipedema.

Lipedema is a lipodystrophic disease that is typically characterized by a marked increase in lower-body subcutaneous adipose tissue that is purported to have increased inflammation and fibrosis, impaired microvascular/lymphatic circulation and to be resistant to reduction by weight loss therapy. However, these outcomes have not been adequately studied. We evaluated body composition, insulin sensitivity, metabolic health and adipose tissue biology in women with obesity and lipedema (Obese-LIP) before and after moderate (~9%) diet-induced weight loss.

Teneurin C-Terminal Associated Peptide (TCAP)-1 Attenuates Restraint Stress-Induced Corticosterone Increases in Male Mice and Rats.

Hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis response can result in anxiety and other neuropsychiatric disorders and effective therapeutics are needed to mitigate this maladaptive response. Here we examined the effects of Teneurin C-terminal Associated Peptide (TCAP)-1, a peptide known to inhibit corticotropin releasing factor (CRF)-mediated stress, on the physiological expression of stress, and whether the effects of TCAP-1 were dependent on the route of administration. We first examined whether subcutaneous administration of TCAP-1 influenced tube restraint stress-induced corticosterone (CORT) increases in both male mice and rats.

Pure open versus robotic radical cystectomy with intracorporeal urinary diversion: a propensity matched analysis.

Objective: To compare surgical parameters and short-term outcomes between open radical cystectomy (ORC) and robotic radical cystectomy with total intracorporeal urinary diversion (icRARC).

Methods: Among the study period, 133 patients who underwent ORC and pelvic node dissection for bladder cancer (group 1) were matched and compared to 61 patients who underwent icRARC during the same period (group 2). The groups were matched 1:1 according to their propensity scores adjusted on their baseline demographics and disease characteristics.

Characteristics of Young Children Associated with Diagnostic Utility of the Autism Diagnostic Observation Schedule: A DBPNet Study.

Objective: The aim of this study is to identify characteristics of children for whom a developmental-behavioral pediatrician's (DBP) diagnostic impressions of autism spectrum disorder (ASD) or non-ASD were changed by Autism Diagnostic Observation Schedule (ADOS) results.

Method: A prospective study of children 1½ to <6 years consecutively referred to 8 sites for possible ASD. Cognitive/developmental, language, and adaptive testing varied, as each site followed its usual clinical approach.

Effectiveness of BNT162b2 and CoronaVac against COVID-19-related severe outcomes among children and adolescents: A Brazilian nationwide cohort study.

Introduction: Nationwide databases from large countries may provide real-world evidence about COVID-19 vaccine effectiveness (VE). This study sought to assess the VE of BNT162b2 and CoronaVac against COVID-19-related severe outcomes in school-aged children and adolescents during the Omicron wave of the COVID-19 pandemic in Brazil.

Methods: A nationwide population-based cohort study compared the incidence risk ratios (IRRs) of hospitalization due to COVID-19-associated severe acute respiratory syndrome (SARS), need for invasive ventilatory support, and death among school-aged children (age 5 to 11 years) and adolescents (age 12 to 17 years), stratified by vaccination status (none, one, or two doses), in 2022.

Systemic inhibition of purine biosynthesis prevents weight gain and improves metabolic health by increasing thermogenesis and decreasing food intake.

Objective: Obesity is a major health concern, largely because it contributes to type 2 diabetes mellitus (T2DM), cardiovascular disease, and various malignancies. Increase in circulating amino acids and lipids, in part due to adipose dysfunction, have been shown to drive obesity-mediated diseases. Similarly, elevated purines and uric acid, a degradation product of purine metabolism, are found in the bloodstream and in adipose tissue.

Does Sleep Moderate the Effects of Exercise Training or Complex Mental and Social Activities on Cognitive Function in Adults With Chronic Stroke? Secondary Analysis of a Randomized Trial.

Background: Exercise (EX) or cognitive and social enrichment (ENRICH) are 2 strategies for promoting cognition poststroke. Whether sleep moderates the effects of EX or ENRICH on cognition in adults with chronic stroke is unknown.

Methods: A 3-arm parallel randomized clinical trial among community-dwelling adults aged 55+ years with chronic stroke (ie, ≥12 months since stroke).

Defining unique structural features in the MAFA and MAFB transcription factors that control Insulin gene activity.

MAFA and MAFB are related basic-leucine-zipper domain-containing transcription factors which have important overlapping and distinct regulatory roles in a variety of cellular contexts, including hormone production in pancreatic islet cells. Here, we first examined how mutating conserved MAF protein-DNA contact sites obtained from X-ray crystal structure analysis impacted their DNA-binding and Insulin enhancer-driven activity. While most of these interactions were essential and their disruption severely compromised activity, we identified that regions outside of these contact sites also contributed to transcriptional activity.

Building social equity and person-centred innovation into the end TB response.

Reducing systemic inequities in testing, access to care, social protection - and in the scientific process - is essential to end TB. Incorporating social science methods and expertise on inequity into the mainstream TB response would help ensure that political commitments to equity move beyond symbolic gestures. We convened a meeting between TB social scientists, people with lived experience, civil society and community members to discuss equity within the global TB response.

Sex-Based Differences in Pulmonary Function and Cardiopulmonary Response 30 Months Post-COVID-19: A Brazilian Multicentric Study.

: (I) to verify if there are sex differences in respiratory function, respiratory muscle strength, and effort limitation in individuals recovered from severe acute COVID-19 30 months after the initial infection, and (II) to evaluate the influence of length of stay on cardiorespiratory capacity among men and women. : Cross-sectional observational multicentric study with participants from five Brazilian states (São Paulo, Amazonas, Minas Gerais, Bahia, and Brasília). We assessed lung function and respiratory muscle strength by maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and cardiorespiratory fitness by cardiopulmonary exercise test (CPET).

Azatriangulene-Based Conductive C═C Linked Covalent Organic Frameworks with Near-Infrared Emission.

Two near-infrared (NIR) emissive π-conjugated covalent organic frameworks (COFs) pTANG1 and pTANG2 are synthesized using Knoevenagel condensation of trioxaazatriangulenetricarbaldehyde (TATANG) with benzene- and biphenyldiacetonitriles, respectively. The morphology of the COFs is affected by the size of TATANG precursor crystals. Donor-acceptor interactions in these COFs result in small bandgaps (≈1.