Licensure Actions Against Psychiatric Clinicians: A Cohort Analysis of National Practitioner Database Reports.

Objective: To examine trends and predictors of administrative actions against psychiatric clinicians' licenses between 2002 and 2022.

Methods: Data from the National Practitioner Data Bank (NPDB) identified 6400 disciplinary actions against psychiatric clinicians' licenses. Linear trend models assessed the trends of disciplinary actions across mental/physical health, licensing/legal issues, and unprofessional conduct.

Functional characterization of eQTLs and asthma risk loci with scATAC-seq across immune cell types and contexts.

cis-regulatory elements (CREs) control gene transcription dynamics across cell types and in response to the environment. In asthma, multiple immune cell types play an important role in the inflammatory process. Genetic variants in CREs can also affect gene expression response dynamics and contribute to asthma risk.

Burdens of type 2 diabetes and cardiovascular disease attributable to sugar-sweetened beverages in 184 countries.

The consumption of sugar-sweetened beverages (SSBs) is associated with type 2 diabetes (T2D) and cardiovascular diseases (CVD). However, an updated and comprehensive assessment of the global burden attributable to SSBs remains scarce. Here we estimated SSB-attributable T2D and CVD burdens across 184 countries in 1990 and 2020 globally, regionally and nationally, incorporating data from the Global Dietary Database, jointly stratified by age, sex, educational attainment and urbanicity.

Personalized, autologous neoantigen-specific T cell therapy in metastatic melanoma: a phase 1 trial.

New treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy. We designed BNT221, a personalized, neoantigen-specific autologous T cell product derived from peripheral blood, and tested this in a 3 + 3 dose-finding study with two dose levels (DLs) in patients with locally advanced or metastatic melanoma, disease progression after ICB, measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1) and, where appropriate, BRAF-targeted therapy.

Targeting chromosomally unstable tumors with a selective KIF18A inhibitor.

Chromosome instability is a prevalent vulnerability of cancer cells that has yet to be fully exploited therapeutically. To identify genes uniquely essential to chromosomally unstable cells, we mined the Cancer Dependency Map for genes essential in tumor cells with high levels of copy number aberrations. We identify and validate KIF18A, a mitotic kinesin, as a vulnerability of chromosomally unstable cancer cells.

Sustained growth-promoting effects of vosoritide in children with achondroplasia from an ongoing phase 3 extension study.

Background: Vosoritide is a C-type natriuretic peptide analog that addresses an underlying pathway causing reduced bone growth in achondroplasia. Understanding the vosoritide treatment effect requires evaluation over an extended duration and comparison with outcomes in untreated children.

Methods: After completing ≥6 months of a baseline observational growth study and 52 weeks in a double-blind, placebo-controlled study (ClinicalTrials.

Test-Retest Reliability of Two Computationally-Characterised Affective Bias Tasks.

Affective biases are commonly seen in disorders such as depression and anxiety, where individuals may show attention towards and preferential processing of negative or threatening stimuli. Affective biases have been shown to change with effective intervention: randomized controlled trials into these biases and the mechanisms that underpin them may allow greater understanding of how interventions can be improved and their success be maximized. For such trials to be informative, we must have reliable ways of measuring affective bias over time, so we can detect how and whether they are altered by interventions: the test-retest reliability of our measures puts an upper bound on our ability to detect any changes.

Nascent matrix deposition supports alveolar organoid formation from aggregates in synthetic hydrogels.

Human induced pluripotent stem cell (iPSC)-derived alveolar organoids have emerged as a system to model the alveolar epithelium in homeostasis and disease. However, alveolar organoids are typically grown in Matrigel, a mouse sarcoma-derived basement membrane matrix that offers poor control over matrix properties, prompting the development of synthetic hydrogels as a Matrigel alternative. Here, we develop a two-step culture method that involves pre-aggregation of organoids in hydrogel-based microwells followed by embedding in a synthetic hydrogel that supports alveolar organoid growth, while also offering considerable control over organoid and hydrogel properties.

Feasibility of Simon 2-Stage Futility Trials in Early Parkinson Disease: Analysis of the PRECEPT and DATATOP Trial Datasets.

Background And Objectives: Disease-modifying treatments (DMTs) are a major unmet need in Parkinson disease (PD). To date, trials investigating DMT candidates in PD most often used a randomized controlled trial (RCT) design. Unfortunately, RCTs to date have not led to a breakthrough, in part because of the large sample sizes and length of follow-up required.

Crimean-Congo hemorrhagic fever virus replicon particle vaccine is safe and elicits functional, non-neutralizing anti-nucleoprotein antibodies and T cell activation in rhesus macaques.

Advancement of vaccine candidates that demonstrate protective efficacy in screening studies necessitates detailed safety and immunogenicity investigations in pre-clinical models. A non-spreading Crimean-Congo hemorrhagic fever virus (CCHFV) viral replicon particle (VRP) vaccine was developed for single-dose administration to protect against disease. To date, several studies have supported safety, immunogenicity, and efficacy of the CCHF VRP in multiple highly sensitive murine models of lethal disease, but the VRP had yet to be evaluated in large animals.

Elovanoids, a Novel Class of Lipid Mediators, Are Neuroprotective in a Traumatic Brain Injury Model in Rats.

Background: In the United States, traumatic brain injury (TBI) contributes significantly to mortality and morbidity. Elovanoids (ELVs), a novel class of homeostatic lipid mediators we recently discovered and characterized, have demonstrated neuroprotection in experimental stroke models but have never been tested after TBI.

Methods: A moderate fluid-percussion injury (FPI) model was used on male rats that were treated with ELVs by intravenous (IV) or intranasal (IN) delivery.

Environmental Life Cycle Assessment of a U.S. Hospital-based Radiology Practice.

Background Climate change, driven primarily by human-induced greenhouse gas (GHG) emissions, poses major risks to human health. Health care contributes 8.5% of GHG emissions in the United States.

Integrated molecular and functional characterization of the intrinsic apoptotic machinery identifies therapeutic vulnerabilities in glioma.

Genomic profiling often fails to predict therapeutic outcomes in cancer. This failure is, in part, due to a myriad of genetic alterations and the plasticity of cancer signaling networks. Functional profiling, which ascertains signaling dynamics, is an alternative method to anticipate drug responses.

Improving precision of vaccine efficacy evaluation using immune correlate data in time-to-event models.

Understanding potential differences in vaccine-induced protection between demographic subgroups is key for vaccine development. Vaccine efficacy evaluation across these subgroups in phase 2b or 3 clinical trials presents challenges due to lack of precision: such trials are typically designed to demonstrate overall efficacy rather than to differentiate its value between subgroups. This study proposes a method for estimating vaccine efficacy using immunogenicity (instead of vaccination status) as a predictor in time-to-event models.

Health-Related Behaviors and Risk of Common Age-Related Brain Diseases Across Severities of Genetic Risk.

Background And Objectives: The 21-point Brain Care Score (BCS) is an index that ranks behaviors and clinical measurements with the aim of encouraging lifestyle adjustments to lower the incidence of age-related brain disease, including stroke, late-life depression (LLD), and dementia. A higher BCS at baseline is associated with a lower risk of these outcomes. We aimed to investigate whether the associations between BCS and stroke, LLD, and dementia risks are independent of genetic predisposition for these conditions and quantify the effect of healthy lifestyle across genetic risk distributions for these outcomes.

Introducing synthetic thermostable RNase inhibitors to single-cell RNA-seq.

Single-cell RNA-sequencing (scRNAseq) is revolutionizing biomedicine, propelled by advances in methodology, ease of use, and cost reduction of library preparation. Over the past decade, there have been remarkable technical improvements in most aspects of single-cell transcriptomics. Yet, little to no progress has been made in advancing RNase inhibition despite maintained RNA integrity being critical during cell collection, storage, and cDNA library generation.

Editorial Commentary: Meniscal Posterior Root to Bone Postoperative Healing Appears Incomplete at 24 Weeks in a Goat Model.

The goal of many orthopaedic surgeries is to mechanically stabilize the tissue long enough for biological healing to occur. The healed tissue should be able to bear the load before the mechanical device (screw, suture, anchor, etc.) eventually fails.

Multiplexed Assays of Variant Effect and Automated Patch Clamping Improve -LQTS Variant Classification and Cardiac Event Risk Stratification.

Background: Long QT syndrome is a lethal arrhythmia syndrome, frequently caused by rare loss-of-function variants in the potassium channel encoded by . Variant classification is difficult, often because of lack of functional data. Moreover, variant-based risk stratification is also complicated by heterogenous clinical data and incomplete penetrance.

Phase 3 Trial of Cabozantinib to Treat Advanced Neuroendocrine Tumors.

Background: Treatment options for patients with advanced neuroendocrine tumors are limited. The efficacy of cabozantinib in the treatment of previously treated, progressive extrapancreatic or pancreatic neuroendocrine tumors is unclear.

Methods: We enrolled two independent cohorts of patients - those with extrapancreatic neuroendocrine tumors and those with pancreatic neuroendocrine tumors - who had received peptide receptor radionuclide therapy or targeted therapy or both.

In sepsis or septic shock, prolonged vs. intermittent infusion of β-lactam antibiotics reduces mortality at 90 d.

Abdul-Aziz MH, Hammond NE, Brett SJ, et al. JAMA. 12 June 2024.

In sepsis, continuous and intermittent infusion of β-lactam antibiotics did not differ for mortality at 90 d.

Dulhunty JM, Brett SJ, De Waele JJ, et al; BLING III Study Investigators. JAMA. 12 June 2024.