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.

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 Role of Sulfatides in Liver Health and Disease.

Sulfatides or 3-O-sulfogalactosylceramide are negatively charged sulfated glycosphingolipids abundant in the brain and kidneys and play crucial roles in nerve impulse conduction and urinary pH regulation. Sulfatides are present in the liver, specifically in the biliary tract. Sulfatides are self-lipid antigens presented by cholangiocytes to activate cluster of differentiation 1d (CD1d)-restricted type II natural killer T (NKT) cells.

Contribution of Nuclear Fragmentation to Dose and RBE in Carbon-Ion Radiotherapy.

Variable relative biological effectiveness (RBE) of carbon radiotherapy may be calculated using several models, including the microdosimetric kinetic model (MKM), stochastic MKM (SMKM), repair-misrepair-fixation (RMF) model, and local effect model I (LEM), which have not been thoroughly compared. In this work, we compared how these four models handle carbon beam fragmentation, providing insight into where model differences arise. Monoenergetic and spread-out Bragg peak carbon beams incident on a water phantom were simulated using Monte Carlo.

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.

Behavior Changes in Quinpirole Obsessive-Compulsive Disorder Rats Treated with 6-Hydroxydopamine and the Corresponding Dopaminergic Compulsive Loop Mechanism.

Background: Recent studies suggest that the anterior limb of the internal capsule may be an area of convergence for multiple compulsion loops. In this study, the role of different dopaminergic compulsion loops in the mechanism of obsessive-compulsive disorder (OCD) was investigated by selectively damaging dopaminergic neurons or fibers in the corresponding targets with 6-hydroxydopamine (6-OHDA) and depicting the anatomical map of various compulsion loops located in the anterior limb of the internal capsule.

Methods: A total of 52 male Sprague Dawley (SD) rats were exposed to either saline (1 mL/kg, NS group, n = 6) or quinpirole (QNP, dopamine D2-agonist, 0.

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.

Efficacy of Orthognathic Surgery in OSAS Patients: A Systematic Review and Meta-Analysis.

Background: Obstructive sleep apnea syndrome (OSAS) is a prevalent condition characterised by repeated episodes of partial or complete obstruction of the upper airway during sleep, leading to disrupted sleep and associated morbidities. Orthognathic surgery (OGS) has been proposed as a treatment option for OSAS, aimed at anatomically repositioning the maxillofacial structures to alleviate airway obstruction. This systematic review and meta-analysis aimed to evaluate the efficacy of OGS in reducing apnea-hypopnea index (AHI) and Epworth Sleepiness Scale (ESS) scores among OSAS patients.

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.

Comparative Analyses of Antiviral Potencies of Second-Generation Integrase Strand Transfer Inhibitors (INSTIs) and the Developmental Compound 4d Against a Panel of Integrase Quadruple Mutants.

Second-generation integrase strand transfer inhibitors (INSTIs) are strongly recommended for people living with HIV-1 (PLWH). The emergence of resistance to second-generation INSTIs has been infrequent and has not yet been a major issue in high-income countries. However, the delayed rollouts of these INSTIs in low- to middle-income countries during the COVID-19 pandemic combined with increased transmission of drug-resistant mutants worldwide are leading to an increase in INSTI resistance.

Gene Therapy for Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is a devastating, aggressive primary brain tumor with poor patient outcomes and a five-year survival of less than 10%. Significant limitations to effective GBM treatment include poor drug delivery across the blood-brain barrier, drug resistance, and complex genetic tumor alterations. Gene therapy uses a mechanism different from other GBM therapies to reduce tumor growth and enhance antitumor immunity.

The Genes of Nigerian Marek's Disease Virus (MDV) Field Isolates Contain Mutations Common to Both European and US High Virulence Strains.

Background: Marek's disease (MD) is a pathology affecting chickens caused by Marek's disease virus (MDV), an acute transforming alphaherpesvirus of the genus . MD is characterized by paralysis, immune suppression, and the rapid formation of T-cell (primarily CD4+) lymphomas. Over the last 50 years, losses due to MDV infection have been controlled worldwide through vaccination; however, these live-attenuated vaccines are non-sterilizing and potentially contributed to the virulence evolution of MDV field strains.

Investigations of Long-Acting Formulations in Children, Adolescents, and Pregnant Women: A Systematic Review.

Long-acting and extended-release drug delivery strategies have greatly improved treatment for a variety of medical conditions. Special populations, specifically infants, children, young people, and pregnant and postpartum women, could greatly benefit from access to these strategies but are often excluded from clinical trials. We conducted a systematic review of all clinical studies involving the use of a long-acting intramuscular injection or implant in infants, children, young people, and pregnant and postpartum people.

Pharmacokinetic Evaluation of Neutral Sphinghomyelinase2 (nSMase2) Inhibitor Prodrugs in Mice and Dogs.

: Extracellular vesicles (EVs) can carry pathological cargo, contributing to disease progression. The enzyme neutral sphingomyelinase 2 (nSMase2) plays a critical role in EV biogenesis, making it a promising therapeutic target. Our lab previously identified a potent and selective inhibitor of nSMase2, named DPTIP (IC = 30 nM).

Global Transcriptomic Analysis of Inbred Lines Reveal Candidate Genes for Response to Maize Lethal Necrosis.

Maize lethal necrosis (MLN) is a significant threat to food security in Sub-Saharan Africa (SSA), with limited commercial inbred lines displaying tolerance. This study analyzed the transcriptomes of four commercially used maize inbred lines and a non-adapted inbred line, all with varying response levels to MLN. RNA-Seq revealed differentially expressed genes in response to infection by maize chlorotic mottle virus (MCMV) and sugarcane mosaic virus (SCMV), the causative agents of MLN.

On the Biosynthesis of Bioactive Tryptamines in Black Cohosh ( L.).

Botanical dietary supplements are widely used, but issues of authenticity, consistency, safety, and efficacy that complicate their poorly understood mechanism of action have prompted questions and concerns in the popular and scientific literature. Black cohosh ( L., syn.

Seasonal Pattern of Endo-β-Mannanase Activity During Germination of , Exhibiting Morphophysiological Dormancy.

Morphophysiological dormancy (MPD) is considered one of the most primitive dormancy classes among seed plants. While extensive studies have examined the occurrence of endo-β-mannanase in seeds with physiological dormancy (PD) or non-dormancy, little is known about the activity of this enzyme in seeds with MPD. This study aimed to investigate the temporal and spatial patterns of endo-β-mannanase activity during dormancy break and germination.

Freeze-Drying for the Reduction of Fruit and Vegetable Chain Losses: A Sustainable Solution to Produce Potential Health-Promoting Food Applications.

Freeze-drying fresh vegetables and fruits may not only prevent post-harvest losses but also provide a concentrated source of nutrients and phytochemicals. This study focused on the phenolic composition of different freeze-dried products derived from horticultural crop remains (HCRs) in the vegetable and fruit production chain. These products may be considered as a potential health-promoting solution for preventing post-harvest fruit spoiling and losses.

Exploring Gender Differences in the Effects of Diet and Physical Activity on Metabolic Parameters.

Background: Gender differences in metabolic response to lifestyle interventions remain poorly explored. This study aimed to evaluate the impact of a six-month Mediterranean diet (MD) intervention combined with regular physical activity on metabolic parameters in overweight adults.

Methods: A prospective cohort study was conducted in an obesity clinic in Rome, Italy, involving overweight adults (BMI ≥ 25 kg/m) motivated to improve their lifestyle.

Specific Nutrients Mediate the Association of Food Insecurity and Sleep Regularity Index (SRI) in U.S. Adults: NHANES 2011-2014.

Background/objectives: Food-insecure individuals are at risk for poor health outcomes, including substandard sleep health. A possible association of food insecurity with sleep regularity has not been explored, and factors contributing to the relationship between food insecurity and sleep are not well understood. This cross-sectional study explored the relationship between food insecurity and sleep regularity and identified specific nutrients that mediated the association.

Dietary Intake, Mediterranean and Nordic Diet Adherence in Alzheimer's Disease and Dementia: A Systematic Review.

Background/objectives: Dementia is not a single disease but an umbrella term that encompasses a range of symptoms, such as memory loss and cognitive impairments, which are severe enough to disrupt daily life. One of the most common forms of dementia is Alzheimer's Disease (AD), a complex neurodegenerative condition influenced by both genetic and environmental factors. Recent research has highlighted diet as a potential modifiable risk factor for AD.

Examining the Influence of Omega-3 Fatty Acids on Performance, Recovery, and Injury Management for Health Optimization: A Systematic Review Focused on Military Service Members.

Background/objectives: Omega-3 fatty acids (-3), recognized for their anti-inflammatory and brain health benefits, are being studied to enhance cognitive function, aid physical recovery, and reduce injury rates among military service members (SMs). Given the unique demands faced by this tactical population, this systematic review aims to evaluate the evidence of -3 to support physical and mental resilience and overall performance.

Methods: This review was conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and includes articles that assessed -3 status or implemented -3 interventions in relation to physical and cognitive performance, recovery, and injury outcomes (2006 to 2024).

Associations of Maternal Prenatal Zinc Consumption with Infant Brain Tissue Organization and Neurodevelopmental Outcomes.

Background/objectives: While studies in rat pups suggest that early zinc exposure is critical for optimal brain structure and function, associations of prenatal zinc intake with measures of brain development in infants are unknown. This study aimed to assess the associations of maternal zinc intake during pregnancy with MRI measures of brain tissue microstructure and neurodevelopmental outcomes, as well as to determine whether MRI measures of the brain mediated the relationship between maternal zinc intake and neurodevelopmental indices.

Methods: Forty-one adolescent mothers were recruited for a longitudinal study during pregnancy.

Adherence to the Mediterranean Diet and the Risk of Head and Neck Cancer: A Systematic Review and Meta-Analysis of Case-Control Studies.

Background/objectives: Head and neck cancer (HNC) is the seventh most common cancer worldwide, with rising incidence rates and significant mortality. While tobacco use, alcohol consumption, and viral infections are established risk factors, the role of dietary patterns, particularly adherence to the Mediterranean diet (MD), in HNC prevention has gained increasing attention. The aim of the current systematic review and meta-analysis is to investigate the association between adherence to the MD and the risk of HNC.