Cannabidiol abrogates cue-induced anxiety associated with normalization of mitochondria-specific transcripts and linoleic acid in the nucleus accumbens shell.

Anxiety disorders are one of the top contributors to psychiatric burden worldwide. Recent years have seen a dramatic rise in the potential anxiolytic properties ascribed to cannabidiol (CBD), a non-intoxicating constituent of the Cannabis Sativa plant. This has led to several clinical trials underway to examine the therapeutic potential of CBD for anxiety disorders.

Unraveling the dynamics of B7-H3-targeting therapeutic antibodies in cancer through PET imaging and antibody pharmacokinetics.

B7-H3, an immunomodulatory protein overexpressed in many cancers, is associated with tumor aggressiveness and poor prognosis, making it a crucial target for imaging to elucidate its role in cancer progression and guide therapeutic interventions. This study employed PET imaging to investigate the in vivo delivery and pharmacokinetics of two anti-B7-H3 antibodies, Ab-1 and Ab-2, in mouse xenograft models with varying B7-H3 expression levels. The antibodies were radiolabeled with [Zr]Zr and evaluated through PET imaging, biodistribution studies, and in vitro assays to assess binding, tumor uptake, and retention.

A phase 1 trial of prizloncabtagene autoleucel, a CD19/CD20 CAR T-cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma.

Prizloncabtagene autoleucel (prizlon-cel), a novel bispecific chimeric antigen receptor (CAR) T-cell, targets and eliminates CD19/CD20 positive tumor cells. This phase 1, open-label study investigated the safety and efficacy of prizlon-cel in patients with relapsed/refractory B-cell non-Hodgkin Lymphoma (r/r B-NHL). Patients with CD19 and/or CD20-positive r/r B-NHL received a 3-day lymphodepletion (cyclophosphamide: 300 mg/m2/d; fludarabine: 30 mg/m2/d) followed by an intravenous dose of prizlon-cel.

Opioid Prescriptions for Low Back Pain among Military-Connected Older Adults Across Multiple Care Systems.

Background: Untreated low back pain (LBP) in older adults can lead to disability and development of chronicity. Due to the potential development of medical comorbidities and negative risks associated with pharmacological use, chronic LBP management for older adults requires a responsive approach.

Methods: The objective of this study is to evaluate the probability of (1) opioid prescription receipt and (2) opioid-sedative coprescription, in a sample of military-service-connected patients enrolled in the Veterans Health Administration (VHA) or TRICARE, ages 30-85 years, receiving care in three systems: VHA, Military Health System (MHS), and nonfederal (civilian) healthcare facilities.

Hypomorphic RAG2 Deficiency Promotes Selection of Self-Reactive B Cells.

Reduced function or hypomorphic variants in recombination-activating genes (RAG) 1 or 2 result in a broad clinical phenotype including common variable immunodeficiency (CVID) and even adult-onset disease. Milder RAG variants are less characterized. Here we describe the longitudinal course of a milder combined RAG deficiency in 3 of 7 siblings sharing the same RAG2 mutations over a 50-year study.

Impact of Financial Toxicity on the Health-Related Quality of Life and Financial Well-Being of Cancer Patients and Survivors: A Comparative Study of the United Kingdom and United States.

Background: This study investigated and compared the impact of financial toxicity (FT) on the health-related quality of life (HRQoL) and financial well-being of cancer patients and survivors in the United Kingdom (UK) and United States (US).

Methods: UK & US participants (n = 600) completed an online questionnaire that consisted of a validated FT instrument (COmprehensive Score for financial Toxicity-COST), a standardised HRQoL instrument (EQ-5D-5L) and questions related to their financial well-being. Tobit regression models and descriptive statistics plus χ tests were used to analyse the association between FT and (i) HRQoL whilst controlling for sociodemographic characteristics; and (ii) financial well-being.

Data-integration with pseudoweights and survey-calibration: application to developing US-representative lung cancer risk models for use in screening.

Accurate cancer risk estimation is crucial to clinical decision-making, such as identifying high-risk people for screening. However, most existing cancer risk models incorporate data from epidemiologic studies, which usually cannot represent the target population. While population-based health surveys are ideal for making inference to the target population, they typically do not collect time-to-cancer incidence data.

Tolvaptan and Autosomal Dominant Polycystic Kidney Disease Progression in Individuals Aged 18-35 Years: A Pooled Database Analysis.

Rational & Objective: Data are limited regarding the long-term efficacy of tolvaptan in adults aged 18-35 years with autosomal dominant polycystic kidney disease (ADPKD) at increased risk of rapid progression. We assessed the effects of tolvaptan within a larger population of younger adults and over longer follow-up than individual clinical trials could provide.

Study Design: Pooled database study.

Genomic and phenotypic correlates of mosaic loss of chromosome Y in blood.

Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole-genome sequencing (WGS) of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program.

Development of the Lee Symptom Scale-Skin Sclerosis for chronic GVHD-associated sclerosis.

Sclerosis is a highly morbid manifestation of chronic GVHD (cGVHD), associated with distressing symptoms and significant long-term disability. A patient-reported outcome measure (PRO) for cGVHD-associated sclerosis is essential to advance therapeutic trials. We aimed to develop a PRO for adults with cGVHD-associated sclerosis and evaluate and refine its content validity.

Phase 1b/2a safety study of lemborexant as an adjunctive treatment for insomnia to buprenorphine-naloxone for opioid use disorder: A randomized controlled trial.

Background: Evidence supports the common incidence of sleep disturbance in opioid use disorder (OUD) as a potential marker of disrupted orexin system functioning. This study evaluated the initial safety and tolerability of a challenge dose of lemborexant, a dual orexin antagonist, as an adjunct to buprenorphine/naloxone.

Methods: Patients (18-65 years old) with OUD receiving sublingual buprenorphine/naloxone, with a Pittsburgh Sleep Quality Index total score of 6 or higher, were recruited from outpatient clinics.

Structure and Dynamics of Monoclonal Antibody Domains Using Spins, Scattering, and Simulations.

Antibody-based pharmaceuticals are the leading biologic drug platform (> $75B/year). Despite a wealth of information collected on them, there is still a lack of knowledge on their inter-domain structural distributions, which impedes innovation and development. To address this measurement gap, we have developed a new methodology to derive biomolecular structure ensembles from distance distribution measurements via a library of tagged proteins bound to an unlabeled and otherwise unmodified target biologic.

Conformational dynamics and multi-modal interaction of Paxillin with the Focal Adhesion Targeting Domain.

Paxillin (PXN) and focal adhesion kinase (FAK) are two major components of the focal adhesion complex, a multiprotein structure linking the intracellular cytoskeleton to the cell exterior. PXN interacts directly with the C-terminal targeting domain of FAK (FAT) via its intrinsically disordered N-terminal domain. This interaction is necessary and sufficient for localizing FAK to focal adhesions.

Increasing Representativeness in the Cohort Using Inverse Probability Weighting.

Large-scale population biobanks rely on volunteer participants, which may introduce biases that compromise the external validity of epidemiological studies. We characterized the volunteer participant bias for the Research Program cohort and developed a set of inverse probability (IP) weights that can be used to mitigate this bias. The cohort is older, more female, more educated, more likely to be covered by health insurance, less White, less likely to drink or smoke, and less healthy compared to the US population.

Genomic ascertainment to quantify prevalence and cancer risk in adults with pathogenic and likely pathogenic germline variants in RASopathy genes.

Purpose: Genomic ascertainment of electronic health record-linked exome data in two large biobanks was used to quantify germline pathogenic/likely pathogenic (P/LP) variant prevalence, cancer prevalence, and survival in adults with non- RAS/mitogen-activated protein kinase genes (RASopathies).

Patients And Methods: Germline RASopathy variants were examined from adult participants in UK Biobank (UKBB; n=469,802), Geisinger MyCode (n=167,050) and Mount Sinai Bio (n=30,470). Variants were classified as per American College of Medical Genetics/Association for Molecular Pathology criteria and reviewed by a RASopathy variant expert.

Genetic regulation of splicing contributes to reduced or elevated cancer risk by altering cellular longevity and replicative potential.

The chromosome 5p15.33 region, which encodes telomerase reverse transcriptase (TERT), harbors multiple germline variants identified by genome-wide association studies (GWAS) as risk for some cancers but protective for others. We characterized a variable number tandem repeat within intron 6 (VNTR6-1, 38-bp repeat unit) and observed a strong association between VNTR6-1 alleles (Short: 24-27 repeats, Long: 40.

What Matters in Psoriatic Arthritis: A Comparison of Patient and Clinician Perspectives.

Objective: This study aimed to expand the understanding of the patient with psoriatic arthritis (PsA) experience and to compare/contrast patient and clinician prioritization of PsA dimensions.

Methods: We conducted four patients with PsA focus groups across three US rheumatology practices using mixed methods to identify attributes of PsA important to patients. Combination with extant attributes of PsA identified by a steering committee created a comprehensive list of attributes.

Outcomes of Extremely Preterm Infants Exposed to Prolonged Prelabor Rupture of Membranes before 24 Weeks of Gestation.

Background: Preterm prelabor rupture of membranes (PPROM) before or around the limit of fetal viability is associated with serious maternal and neonatal complications including chorioamnionitis, extremely preterm birth, and pulmonary hypoplasia.

Objectives: To describe contemporary outcomes of extremely preterm infants born after prolonged periviable PPROM, and to identify perinatal factors associated with survival and survival without severe neurodevelopmental impairment (NDI).

Study Design: Among actively treated infants born alive at <27 weeks' gestational age (GA) in centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from 2012 to 2018, the outcomes of survival and survival without severe NDI at 22-26 months' corrected age were compared between infants exposed to prolonged (≥120 hours) periviable (<24 weeks' GA) PPROM and unexposed infants born after rupture of membranes ≤18 hours before delivery or at delivery, adjusting for birth GA, sex, multiple gestation, antenatal steroids, small for gestational age (SGA), insurance, and center.

Effect of mass drug administration on malaria incidence in southeast Senegal during 2020-22: a two-arm, open-label, cluster-randomised controlled trial.

Background: In Africa, the scale-up of malaria-control interventions has reduced malaria burden, but progress towards elimination has stalled. Mass drug administration (MDA) is promising as a transmission-reducing strategy, but evidence from low-to-moderate transmission settings is needed. We aimed to assess the safety, coverage, and effect of three cycles of MDA with dihydroartemisinin-piperaquine plus single, low-dose primaquine on Plasmodium falciparum incidence and prevalence in southeast Senegal.

Making the Case for an International Childhood Cancer Data Partnership.

Childhood cancers are a heterogeneous group of rare diseases, accounting for less than 2% of all cancers diagnosed worldwide. Most countries, therefore, do not have enough cases to provide robust information on epidemiology, treatment, and late effects, especially for rarer types of cancer. Thus, only through a concerted effort to share data internationally will we be able to answer research questions that could not otherwise be answered.

Safety and immunogenicity of ascending doses of influenza A(H7N9) inactivated vaccine with or without MF59®.

Introduction: While it remains impossible to predict the timing of the next influenza pandemic, novel avian influenza A viruses continue to be considered a significant threat.

Methods: A Phase II study was conducted in healthy adults aged 18-64 years to assess the safety and immunogenicity of two intramuscular doses of pre-pandemic 2017 influenza A(H7N9) inactivated vaccine administered 21 days apart. Participants were randomized (n = 105 in each of Arms 1-3) to receive 3.

Validation of a Cancer-Focused Information Seeking Experience (ISEE) Scale.

Background: Searching for health information is critical for maintaining one's health and reducing risk of disease, including cancer. However, some people are more likely to experience challenges in finding and comprehending health information; therefore, it is important to measure health information-seeking behavior. In order to add to prior research conducted with the scale, this study provides the first formal evaluation of the validity and reliability of the four-item, cancer-focused Information Seeking Experience (ISEE) scale in a cross-sectional, nationally representative health survey of U.

Lentivirus-mediated gene therapy for Fabry disease: 5-year End-of-Study results from the Canadian FACTs trial.

Background: Fabry disease is an X-linked lysosomal storage disorder due to a deficiency of α-galactosidase A (α-gal A) activity. Our goal was to correct the enzyme deficiency in Fabry patients by transferring the cDNA for α-gal A into their CD34+ hematopoietic stem/progenitor cells (HSPCs). Overexpression of α-gal A leads to secretion of the hydrolase; which can be taken up and used by uncorrected bystander cells.