Pivotal trial characteristics and types of endpoints used to support Food and Drug Administration rare disease drug approvals between 2013 and 2022.

Background/aims: Rare disease drug development faces unique challenges, such as genotypic and phenotypic heterogeneity within small patient populations and a lack of established outcome measures for conditions without previously successful drug development programs. These challenges complicate the process of selecting the appropriate trial endpoints and conducting clinical trials in rare diseases. In this descriptive study, we examined novel drug approvals for non-oncologic rare diseases by the U.

2024 White Paper on Recent Issues in Bioanalysis: Evolution of Immunogenicity Assessment beyond ADA/NAb; Regulated Genomic/NGS Assays; Hypersensitivity Reactions; Minimum Noise Reduction; False Positive Range; Modernized Vaccine Approaches; NAb/TAb Correlation - Recommendations on Advanced Strategies for Molecular Assays and Immunogenicity of Gene Therapy, Cell Therapy, Vaccine; Biotherapeutics Immunogenicity Assessment & Clinical Relevance - Regulatory Agencies' Input on Immunogenicity/Technologies of Biotherapeutics, Gene, Cell & Vaccine Therapies).

The 18 Workshop on Recent Issues in Bioanalysis (18 WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

Adaptive promising zone design for sequential parallel comparison design with continuous outcomes.

Introduction: The sequential parallel comparison design has emerged as a valuable tool in clinical trials with high placebo response rates. To further enhance its efficiency and effectiveness, adaptive strategies, such as sample size adjustment and allocation ratio modification can be employed.

Methods: We compared the performance of Jennison and Turnbull's method and the Promising Zone approach for sample size adjustment in a two-phase sequential parallel comparison design study.

2024 White paper on recent issues in bioanalysis: Impact of LDT in US and IVDR in EU; AI/ML for High Parameter Flow Cytometry; The rise of Olink Technology; CDx for AAV Gene Therapies; Integrative Bioanalysis by Multiple Platforms; Super Sensitive ADA/NAb LBA ( - Recommendations on Advanced Strategies for Biomarkers, IVD/CDx Assays (BAV), Cell Based Assays (CBA), and Ligand-Binding Assays (LBA) - Regulatory Agencies' Input on Biomarkers, IVD/CDx, and Biomarker Assay Validation).

The 18th Workshop on Recent Issues in Bioanalysis (18th WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

The relationship of cultural variables to attitudes toward prescription drug usage among Iranian/Persian Americans.

The present study examined the effects of cultural factors(ethnic identity, acculturation, perceived discrimination, and religiosity), derived from the Multicultural Assessment-Intervention Process (MAIP) model, on attitudes toward prescription drug use among Iranian/Persian Americans across the United States. The study consisted of a final sample of 454 Iranian/Persian American adult participants. The results indicated that Iranian/Persian American attitudes toward prescription drug use are impacted by demographic and cultural factors.

ERK1/2 Inhibition Alleviates Diabetic Cardiomyopathy by Suppressing Fatty Acid Metabolism.

Background: Diabetes mellitus is associated with morphological and functional impairment of the heart primarily due to lipid toxicity caused by increased fatty acid metabolism. Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) have been implicated in the metabolism of fatty acids in the liver and skeletal muscles. However, their role in the heart in diabetes remains unclear.

Ignoring Gender-Based Immunometabolic Reprograming, a Risky Business in Immune-Based Precision Medicine.

Immunology advances have increased our understanding of autoimmune, auto-inflammatory, immunodeficiency, infectious, and other immune-mediated inflammatory diseases (IMIDs). Furthermore, evidence is growing for the immune involvement in aging, metabolic and neurodegenerative diseases, and different cancers. However, further research has indicated sex/gender-based immune differences, which further increase higher incidences of various autoimmune diseases (AIDs), such as systemic lupus erythematosus (SLE), myasthenia gravis, and rheumatoid arthritis (RA) in females.

HIF-1α and VEGF Immunophenotypes as Potential Biomarkers in the Prognosis and Evaluation of Treatment Efficacy of Atherosclerosis: A Systematic Review of the Literature.

Background: Hypoxia-inducible factor 1 alpha (HIF-1α) and its related vascular endothelial growth factor (VEGF) may play a significant role in atherosclerosis and their targeting is a strategic approach that may affect multiple pathways influencing disease progression. This study aimed to perform a systematic review to reveal current evidence on the role of HIF-1α and VEGF immunophenotypes with other prognostic markers as potential biomarkers of atherosclerosis prognosis and treatment efficacy.

Methods: We performed a systematic review of the current literature to explore the role of HIF-1α and VEGF protein expression along with the relation to the prognosis and therapeutic strategies of atherosclerosis.

Impact of Vitamin D on Skin Aging, and Age-Related Dermatological Conditions.

Human skin is a physical and biochemical barrier that protects the internal body from the external environment. Throughout a person's life, the skin undergoes both intrinsic and extrinsic aging, leading to microscopic and macroscopic changes in its morphology. In addition, the repair processes slow with aging, making the older population more susceptible to skin diseases.

Analysis of "Dose Accuracy and Reliability of a Connected Insulin Pen System".

In an article in the , Backfish and coauthors examined the dose accuracy and reliability of the Tempo Pen and Tempo Smart Button connected insulin pen system. This study sponsored by Eli Lilly and Company found that this system met the International Organization for Standardization 11608-1:2014 requirements for dose accuracy at a range of doses, as well as the data transfer requirements after all injections. While these results are very encouraging, they were based on simulated human factors data while data from a human factors validation study where individuals successfully dialed and administered correct doses was not reported.

Frequent Alcohol Use of Adolescents in Low-Income Families: Application of the Multiple Disadvantage Model.

Background: This study investigated relationships between low-income adolescent drinkers' frequent alcohol use and five factors: social disorganization, social structural, social integration, mental health, and access to healthcare.

Objective: A sample of 1,256 low-income adolescent drinkers and caregivers were extracted from the Future of Families and Child Wellbeing Study.

Results: Logistic regression yielded results showing adolescent drinkers' weekly drinking to be associated positively with Hispanic adolescents, drinking peers, adolescents' depression/anxiety, and caregiver's daily drinking.

Design and early progress of the Comparison of Anticoagulation and anti-Platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA) trial.

Background: The usual antithrombotic treatment for symptomatic intracranial atherosclerotic stenosis (ICAS) consists of dual treatment with clopidogrel and aspirin for 90 days followed by aspirin alone but the risk of recurrent stroke remains high up to 12 months. The Comparison of Anticoagulation and anti-Platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA) trial was designed to determine whether other combinations of dual antithrombotic therapy are superior to clopidogrel and aspirin.

Methods: CAPTIVA is an ongoing, prospective, double-blinded, three-arm clinical trial at over 100 sites in the United States and Canada that will randomize 1683 high-risk subjects with a symptomatic infarct attributed to 70-99% stenosis of a major intracranial artery to 12 months of treatment with (1) ticagrelor (180 mg loading dose, then 90 mg twice daily), (2) low-dose rivaroxaban (2.

Comparison of Interportal and Periportal Capsulotomies and Axial Distraction Resistance During Hip Arthroscopy: An In Vivo Propensity-Matched Cohort Study.

Background: Intraoperative hip capsule management is increasingly recognized as an important component of hip arthroscopy for the prevention of capsular-related instability. The periportal capsulotomy, relative to the interportal capsulotomy, has been proposed as a minimally invasive technique for decreasing postarthroscopy hip instability; however, the biomechanical effects of this technique are not well established.

Purpose/hypothesis: This study aimed to provide a biomechanical characterization of interportal and periportal capsulotomies, helping inform surgeon choice of capsulotomy type and repair, potentially guiding clinical practice in hip arthroscopy.

Assembly and Annotation of the Tetraploid Salsola tragus (Russian thistle) Genome.

This report presents two phased chromosome-scale genome assemblies of allotetraploid Salsola tragus (2n=4x=36) and fills the current genomics resource gap for this species. Flow cytometry estimated 1C genome size was 1.319 Gbp.

Use of the Adaptive Behaviour Dementia Questionnaire in a Down Syndrome Specialty Clinic.

Objective: To study the use of a dementia screening tool in our clinic cohort of adults with Down syndrome.

Study Design: A retrospective chart review of patients with Down syndrome was conducted to follow the use of the Adaptive Behaviour Dementia Questionnaire (ABDQ) in a dementia screening protocol. The ABDQ results for patients aged 40 years and older at a Down syndrome specialty clinic program were assessed.

The Impact of Optical Undersampling on the Ca Signal Resolution in Ca Imaging of Spontaneous Neuronal Activity.

Background: In neuroscience, Ca imaging is a prevalent technique used to infer neuronal electrical activity, often relying on optical signals recorded at low sampling rates (3 to 30 Hz) across multiple neurons simultaneously. This study investigated whether increasing the sampling rate preserves critical information that may be missed at slower acquisition speeds.

Methods: Primary neuronal cultures were prepared from the cortex of newborn pups.

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.

Multicenter screening for ADHD among school-age pediatric patients with type 1 diabetes - study protocol.

Purpose: Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental condition that affects approximately 5% of the pediatric population, with increased prevalence among those with type 1 diabetes (T1D). Reports suggest that unrecognized and untreated ADHD impairs T1D control and that ADHD may be underdiagnosed in the Polish population. The International Society for Pediatric and Adolescent Diabetes recommends neurodevelopmental assessments in children with T1D, but specific guidelines on procedures and implementation are lacking.

An Iterative Design Method for Advancing Air Traffic Control and Management Training Through Immersive VFR 3D Map Visualization.

OCCUPATIONAL APPLICATIONSInnovative tools that align with modern learners' preferences are essential for training in safety-critical professions like Air Traffic Control/Management. This study evaluated a Virtual Reality Visual Flight Rules 3D Map Visualization Tool designed to meet the Federal Aviation Administration's (FAA) modernization goals. The tool immerses trainee in contextually accurate environments, enhancing engagement and self-paced learning.

Association between body mass index, obesity, and vulvar cancer recurrence.

Objective: The objective of this paper is to study the association between obesity and tumor recurrence in patients with vulvar cancer.

Methods: This is a retrospective study including vulvar cancer patients from 2003 to 2022. Our primary outcome was progression-free survival (PFS) stratified by status of obesity, defined as body mass index (BMI) >30.

Evaluation of the Pediatric Regional Anesthesia Time-Out Checklist: A Simulation Study.

Introduction: The Society for Pediatric Anesthesia Quality and Safety Committee developed the Pediatric Regional Anesthesia Time-Out Checklist, consisting of 14 safety items intended to be reviewed by an anesthesia team prior to a regional anesthetic. Primarily, we hypothesized that use of this Checklist would increase the number of safety items performed compared with no checklist, evaluating the usefulness of this tool. Secondarily, we hypothesized that, after checklist training, subjects would show better clinical judgment by electing to perform a regional anesthetic in scenarios in which no programmed error existed and electing to not perform a regional anesthetic in scenarios in which a programmed error did exist.

Premature Coronary Artery Disease Presenting as STEMI in a Teenager.

An 18-year-old teenager with significant atherosclerotic cardiovascular disease (ASCVD) risk factors developed acute chest pain. His electrocardiogram showed inferior ST-segment elevations. Emergent coronary angiogram revealed complete thrombotic occlusion of the right coronary artery.

A Comprehensive Weightbearing Computed Tomography Study on Patients With Hallux Valgus: Exploring Multiplanar Deformity Interrelationships.

Background: Hallux valgus (HV) is a complex, multiplanar deformity. In this study, we examined the interrelationships between various components of this deformity using weightbearing computed tomography (WBCT). We hypothesized that the severity of traditional axial plane deformities would correlate with malpositioning of the metatarsosesamoid complex, first-ray coronal rotational deformity, and malalignment of the hindfoot and midfoot.