Comparison of Standard Setting Procedures to Establish Defensible Passing Standards for Clinical Skills Assessment: Angoff, Borderline Group, Contrasting Groups and Patient Safety Methods.

Introduction: Standard setting methods for clinical skills assessments help establish cut scores that accurately reflect clinical performance expectations. However, these methods lead to varied cut scores, and guidance for method selection is limited. This study compares the application of four methods.

How I Approach Ethical Considerations for Pediatric Phase I CAR T-Cell Trials.

Phase I trials of chimeric antigen receptor (CAR) T cells have shown remarkable promise in pediatric B-cell malignancies. Such outcomes have shifted expectations for other phase I CAR T-cell trials to have high response rates. The juxtaposition of high expectations, uncertain outcomes, and potential for life-threatening toxicities raises unique ethical considerations.

Craniectomy and Cranioplasty Effects on Balance and Gait in Rehabilitation: A Retrospective Study.

Objective: To analyze changes in balance and gait in patients undergoing rehabilitation postcraniectomy and postcranioplasty, including comparison of outcomes across time periods, rate of change, and among diagnoses.

Design: Retrospective cohort study.

Setting: Inpatient rehabilitation.

Implementation of medication for opioid use disorder treatment during a natural disaster: The PROUD-LA study.

Background: The impacts of climate change-related extreme weather events (EWEs) on Medication for Opioid Use Disorders (MOUD) implementation for Medicaid beneficiaries are relatively unknown. Such information is critical to disaster planning and other implementation strategies. In this study we examined implementation determinants and strategies for MOUD during EWEs.

Systematic Development and Validity Evidence for a Checklist to Assess Bed Mobility Skills Among Physical Therapy Students.

Introduction: Assessments with strong validity evidence are necessary to accurately assess health professions students' performance of clinical skills. The aim of this study was to develop and validate a checklist assessment of physical therapy students' performance of bed mobility skills.

Methods: A checklist was developed using a 4-step process: 1) evidence review and preliminary checklist development, 2) Delphi review to reach consensus on content, 3) pilot testing and checklist editing, 4) final round of Delphi review.

A methodology for specific disruption of microtubule polymerization into dendritic spines.

Dendritic spines, the mushroom-shaped extensions along dendritic shafts of excitatory neurons, are critical for synaptic function and are one of the first neuronal structures disrupted in neurodevelopmental and neurodegenerative diseases. Microtubule (MT) polymerization into dendritic spines is an activity-dependent process capable of affecting spine shape and function. Studies have shown that MT polymerization into spines occurs specifically in spines undergoing plastic changes.

A Methodology for Specific Disruption of Microtubules in Dendritic Spines.

Dendritic spines, the mushroom-shaped extensions along dendritic shafts of excitatory neurons, are critical for synaptic function and are one of the first neuronal structures disrupted in neurodevelopmental and neurodegenerative diseases. Microtubule (MT) polymerization into dendritic spines is an activity-dependent process capable of affecting spine shape and function. Studies have shown that MT polymerization into spines occurs specifically in spines undergoing plastic changes.

Suitability of maize crop residue fermented by as feed for edible crickets: growth performance, micronutrient content, and iron bioavailability.

Small-scale farming of edible insects could help combat public health challenges such as protein energy malnutrition and anemia, but reliable low-cost feeds for insects are needed. In resource-limited contexts, where grains such as maize are prohibitively costly for use as insect feed, the feasibility of insect farming may depend on finding alternatives. Here, we explore the potential to modify plentiful maize crop residue with edible mushroom mycelium to generate a low-cost feed adjunct for the farmed two-spotted cricket, .

A comprehensive analysis of adverse events in the first 30 days of phase 1 pediatric CAR T-cell trials.

The tremendous success of chimeric antigen receptor (CAR) T cells in children and young adults (CAYAs) with relapsed/refractory B-cell acute lymphoblastic leukemia is tempered by toxicities such as cytokine release syndrome (CRS). Despite expansive information about CRS, profiling of specific end-organ toxicities secondary to CAR T-cell therapy in CAYAs is limited. This retrospective, single-center study sought to characterize end-organ specific adverse events (AEs) experienced by CAYAs during the first 30 days after CAR T-cell infusion.

Chimeric Antigen Receptor T Cells as Salvage Therapy for Post-Chimeric Antigen Receptor T Cell Failure.

Outcomes for post-chimeric antigen receptor (CAR) T cell therapy (CART) relapse are poor. The utilization of a unique CAR T cell construct for post-CART failure is increasing, but this approach is not well described. In this study, with CART-A the first unique CAR T cell construct received and CART-B the second, the primary objective was to characterize outcomes following CART-B.

The MC1R r allele does not increase melanoma risk in MITF E318K carriers.

Background: Population-wide screening for melanoma is not cost-effective, but genetic characterization could facilitate risk stratification and targeted screening. Common Melanocortin-1 receptor (MC1R) red hair colour (RHC) variants and Microphthalmia-associated transcription factor (MITF) E318K separately confer moderate melanoma susceptibility, but their interactive effects are relatively unexplored.

Objectives: To evaluate whether MC1R genotypes differentially affect melanoma risk in MITF E318K+ vs.

Association of germline variants in telomere maintenance genes ( and ) with spitzoid morphology in familial melanoma: A multi-center case series.

Background: Spitzoid morphology in familial melanoma has been associated with germline variants in , a telomere maintenance gene (TMG), suggesting a link between telomere biology and spitzoid differentiation.

Objective: To assess if familial melanoma cases associated with germline variants in TMG (, , , and ) commonly exhibit spitzoid morphology.

Methods: In this case series, melanomas were classified as having spitzoid morphology if at least 3 of 4 dermatopathologists reported this finding in ≥25% of tumor cells.

Efficacy of second CAR-T (CART2) infusion limited by poor CART expansion and antigen modulation.

Chimeric antigen receptor T-cells (CART) are active in relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL), but relapse remains a substantial challenge. Reinfusion with the same CART product (CART2) in patients with suboptimal response or antigen positive relapse following first infusion (CART1) represents a potential treatment strategy, though early experiences suggest limited efficacy of CART2 with CD19 targeting. We report on our experience with CART2 across a host of novel CAR T-cell trials.

A Single Transcript Knockdown-Replacement Strategy Employing 5' UTR Secondary Structures to Precisely Titrate Rescue Protein Translation.

One overarching goal of gene therapy is the replacement of faulty genes with functional ones. A significant hurdle is presented by the fact that under- or over-expression of a protein may cause disease as readily as coding mutations. There is a clear and present need for pipelines to translate experimentally validated gene therapy strategies to clinical application.

Bombesin-drug conjugates in targeted therapy for small cell lung cancer.

Small cell lung cancer (SCLC) is a aggressive form of primary lung neoplasm that often presents in elderly smokers. While stage I SCLC can be managed with surgery, extensive-stage disease is managed with chemotherapy using etoposide and cisplatin among other agents, and often complemented by radiation therapy to the chest and cranium. Recent advances in pharmacological research have yielded novel antibody and peptide-conjugated adjunctive chemotherapy, of which bombesin and bombesin receptors have played an important role due to their overexpression in SCLC and other lung cancers.

Case Report: Fatal Complications of BK Virus-Hemorrhagic Cystitis and Severe Cytokine Release Syndrome Following BK Virus-Specific T-Cells.

BK virus (BKV)-hemorrhagic cystitis (HC) is a well-known and rarely fatal complication of hematopoietic stem cell transplantation (HSCT). Treatment for BKV-HC is limited, but virus-specific T-cells (VST) represent a promising therapeutic option feasible for use posttransplant. We report on the case of a 16-year-old male with dedicator of cytokinesis 8 (DOCK8) deficiency who underwent haploidentical HSCT complicated by severe BKV-HC, catastrophic renal hemorrhage, and VST-associated cytokine release syndrome (CRS).

Characterization of extramedullary disease in B-ALL and response to CAR T-cell therapy.

Chimeric antigen receptor (CAR) T cells effectively eradicate medullary B-cell acute lymphoblastic leukemia (B-ALL) and can traffic to and clear central nervous system (CNS) involvement. CAR T-cell activity in non-CNS extramedullary disease (EMD) has not been well characterized. We systematically evaluated CAR T-cell kinetics, associated toxicities, and efficacy in B-ALL non-CNS EMD.

Birth cohort-specific trends of sun-related behaviors among individuals from an international consortium of melanoma-prone families.

Background: Individuals from melanoma-prone families have similar or reduced sun-protective behaviors compared to the general population. Studies on trends in sun-related behaviors have been temporally and geographically limited.

Methods: Individuals from an international consortium of melanoma-prone families (GenoMEL) were retrospectively asked about sunscreen use, sun exposure (time spent outside), sunburns, and sunbed use at several timepoints over their lifetime.

A Dermatologist's Guide to Implementation of Gene Expression Profiling in the Management of Melanoma.

With the advent of effective therapeutics, melanoma mortality rates have decreased, yet incidence rates are continuing to rise, making accurate prognostication for risk of recurrence increasingly important. Gene expression profiling (GEP) is a clinically available, objective metric that can be used in conjunction with traditional clinicopathological staging to help physicians stratify risk in melanoma patients. There is a gap in guidance from the American Joint Committee on Cancer (AJCC) and the National Comprehensive Cancer Network (NCCN) regarding how to utilize GEP in melanoma care.

FRAMe: Familial Risk Assessment of Melanoma-a risk prediction tool to guide CDKN2A germline mutation testing in Australian familial melanoma.

Germline mutations in CDKN2A greatly increase risk of developing cutaneous melanoma. We have constructed a risk prediction model, Familial Risk Assessment of Melanoma (FRAMe), for estimating the likelihood of carrying a heritable CDKN2A mutation among Australian families, where the prevalence of these mutations is low. Using logistic regression, we analysed characteristics of 299 Australian families recruited through the Sydney site of GenoMEL (international melanoma genetics consortium) with at least three cases of cutaneous melanoma (in situ and invasive) among first-degree blood relatives, for predictors of the presence of a pathogenic CDKN2A mutation.

Evaluation of the contribution of germline variants in BRCA1 and BRCA2 to uveal and cutaneous melanoma.

Germline mutations of BRCA1 and BRCA2 predispose individuals to a high risk of breast and ovarian cancer, and elevated risk of other cancers, including those of the pancreas and prostate. BRCA2 mutation carriers may have increased risk of uveal melanoma (UM) and cutaneous melanoma (CM), but associations with these cancers in BRCA1 mutation carriers have been mixed. Here, we further assessed whether UM and CM are associated with BRCA1 or BRCA2 by assessing the presence, segregation and reported/predicted pathogenicity of rare germline mutations (variant allele frequency < 0.

Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT.

Background: Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5%-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of families with melanoma and whether performance improvements can be achieved.

Methods: In total, 2116 familial melanoma cases were ascertained by the international GenoMEL Consortium.

Can working memory training work for ADHD? Development of central executive training and comparison with behavioral parent training.

Objective: Working memory deficits have been linked experimentally and developmentally with attention-deficit/hyperactivity disorder (ADHD)-related symptoms/impairments. Unfortunately, substantial evidence indicates that extant working memory training programs fail to improve these symptoms/impairments. We hypothesized that this discrepancy may reflect insufficient targeting, such that extant protocols do not adequately engage the specific working memory components linked with the disorder's behavioral/functional impairments.