Measurement Equivalence of Standard and Zoom-Enabled Electronic Clinical Outcome Assessments: Implications for Patient Accessibility in Clinical Trials.

Objectives: Diversity and inclusion in clinical trials remains an important topic, particularly for participants with disabilities such as vision impairment. With advances in smartphone and tablet technologies and their increasing use in clinical trials, accessibility features, such as pinch to zoom, are now at our fingertips. However, implementing such accessibility features when collecting electronic clinical outcomes assessments (eCOA) does not come without risks and must be designed with careful consideration and scientifically tested to ensure no impact to data integrity.

The Impact of Peer-Led Learning Groups on First-Year Medical Students.

Active learning and peer instruction contribute to positive learning outcomes. We developed a 25-week, question-based program for first-year medical students (MS1). Senior students developed weekly question and answer sets.

Strategic naps in automated driving - Sleep architecture predicts sleep inertia better than nap duration.

At higher levels of driving automation, drivers can nap during parts of the trip but must take over control in others. Awakening from a nap is marked by sleep inertia which is tackled by the NASA nap paradigm in aviation: Strategic on-flight naps are restricted to 40 min to avoid deep sleep and therefore sleep inertia. For future automated driving, there are currently no such strategies for addressing sleep inertia.

Carbocyclic setmelanotide analogs maintain biochemical potency at melanocortin 4 receptors.

The melanocortin 4 receptor (MC4R) plays a critical role in satiety and energy homeostasis, and its dysregulation is implicated in numerous hyperphagic and obese disease states. Setmelanotide, a disulfide-based cyclic peptide, can rescue MC4R activity and treat obesities caused by genetic defects in MC4R signaling. But this peptide has moderate blood-brain barrier penetrance and metabolic stability, which can limit its efficacy in practice.

Temozolomide and the PARP Inhibitor Niraparib Enhance Expression of Natural Killer Group 2D Ligand ULBP1 and Gamma-Delta T Cell Cytotoxicity in Glioblastoma.

Glioblastoma (GBM) is an immunologically cold tumor, but several immunotherapy-based strategies show promise, including the administration of ex vivo expanded and activated cytotoxic gamma delta T cells. Cytotoxicity is partially mediated through interactions with natural killer group 2D ligands (NKG2DL) on tumor cells. We sought to determine whether the addition of the blood-brain barrier penetrant PARP inhibitor niraparib to the standard of care DNA alkylator temozolomide (TMZ) could upregulate NKG2DL, thereby improving immune cell recognition.

Unlocking flavin photoacid catalysis through electrophotochemistry.

Molecular flavins are one of the most versatile photocatalysts. They can coordinate single and multiple electron transfer processes, gift hydrogen atoms, form reversible covalent linkages that support group transfer mechanisms, and impart photonic energy to ground state molecules, priming them for downstream reactions. But one mechanism that has not featured extensively is the ability of flavins to act as photoacids.

Attentional warnings caused by driver monitoring systems: How often do they appear and how well are they understood?

The present study investigated the effects of a driver monitoring system that triggers attention warnings in case distraction is detected. Based on the EuroNCAP protocol, distraction could either be long glances away from the forward roadway (≥3s) or visual attention time sharing (>10 cumulative seconds within a 30 s time interval). In a series of manual driving simulator drives, 30 participants completed both driving related tasks (e.

Combination Immunotherapy with Vaccine and Oncolytic HSV Virotherapy Is Time Dependent.

Oncolytic virotherapy or immunovirotherapy is a strategy that utilizes viruses to selectively infect and kill tumor cells while also stimulating an immune response against the tumor. Early clinical trials in both pediatric and adult patients using oncolytic herpes simplex viruses (oHSV) have demonstrated safety and promising efficacy; however, combinatorial strategies designed to enhance oncolysis while also promoting durable T-cell responses for sustaining disease remission are likely required. We hypothesized that combining the direct tumor cell killing and innate immune stimulation by oHSV with a vaccine that promotes T cell-mediated immunity may lead to more durable tumor regression.

Spectral and Electrochemical Properties of Common Photocatalysts in Water: A Compendium for Aqueous Photoredox Catalysis.

Electrochemical potentials of photocatalysts are solvent dependent. One of the largest discrepancies is observed when water is used in place of organic solvents as the reaction media. Unfortunately, the redox potentials for many photocatalysts in water have not been determined, at least under one unifying set of conditions, and this greatly hinders the rational design of sustainable and biocompatible photoredox reactions.

Signature reversion of three disease-associated gene signatures prioritizes cancer drug repurposing candidates.

Drug repurposing is promising because approving a drug for a new indication requires fewer resources than approving a new drug. Signature reversion detects drug perturbations most inversely related to the disease-associated gene signature to identify drugs that may reverse that signature. We assessed the performance and biological relevance of three approaches for constructing disease-associated gene signatures (i.

Test procedure for the evaluation of partially automated driving HMI including driver monitoring systems in driving simulation.

The proposed test procedure presents an approach for the evaluation of the usability of partial automated driving HMI including driver monitoring systems in driving simulation. This procedure is based on a definition of requirements that a Level 2 HMI and its included driver monitoring system must fulfill in order to guarantee that the drivers understand their responsibilities of continuously monitoring the driving environment and the status of the partial automated driving system. These requirements are used to define the evaluation criteria that have to be validated in the test as well as the use cases in which these criteria can be assessed.

A tutorial on automatic post-stratification and weighting in conventional and regression-based norming of psychometric tests.

Norm scores are an essential source of information in individual diagnostics. Given the scope of the decisions this information may entail, establishing high-quality, representative norms is of tremendous importance in test construction. Representativeness is difficult to establish, though, especially with limited resources and when multiple stratification variables and their joint probabilities come into play.

Reducing the Bias of Norm Scores in Non-Representative Samples: Weighting as an Adjunct to Continuous Norming Methods.

We investigated whether the accuracy of normed test scores derived from non-demographically representative samples can be improved by combining continuous norming methods with compensatory weighting of test results. To this end, we introduce , a method from social sciences, to psychometrics. In a simulated reference population, we modeled a latent cognitive ability with a typical developmental gradient, along with three demographic variables that were correlated to varying degrees with the latent ability.

Immunotherapy for Pediatric Brain and Spine Tumors: Current State and Future Directions.

Background: Brain tumors are the most common solid tumors and the leading cause of cancer-related deaths in children. Incidence in the USA has been on the rise for the last 2 decades. While therapeutic advances in diagnosis and treatment have improved survival and quality of life in many children, prognosis remains poor and current treatments have significant long-term sequelae.

Peptide cycles: From -SS- to -CC- via a Late-Stage "Snip-and-Stitch".

One way to improve the therapeutic potential of peptides is through cyclization. This is commonly done using a disulfide bond between two cysteine residues in the peptide. However, disulfide bonds are susceptible to reductive cleavage, and this can deactivate the peptide and endanger endogenous proteins through covalent modification.

Safety and Efficacy of Intraventricular Immunovirotherapy with Oncolytic HSV-1 for CNS Cancers.

Purpose: Oncolytic virotherapy with herpes simplex virus-1 (HSV) has shown promise for the treatment of pediatric and adult brain tumors; however, completed and ongoing clinical trials have utilized intratumoral/peritumoral oncolytic HSV (oHSV) inoculation due to intraventricular/intrathecal toxicity concerns. Intratumoral delivery requires an invasive neurosurgical procedure, limits repeat injections, and precludes direct targeting of metastatic and leptomeningeal disease. To address these limitations, we determined causes of toxicity from intraventricular oHSV and established methods for mitigating toxicity to treat disseminated brain tumors in mice.

Standard clinical approaches and emerging modalities for glioblastoma imaging.

Glioblastoma (GBM) is the most common primary adult intracranial malignancy and carries a dismal prognosis despite an aggressive multimodal treatment regimen that consists of surgical resection, radiation, and adjuvant chemotherapy. Radiographic evaluation, largely informed by magnetic resonance imaging (MRI), is a critical component of initial diagnosis, surgical planning, and post-treatment monitoring. However, conventional MRI does not provide information regarding tumor microvasculature, necrosis, or neoangiogenesis.

Clinical advances in oncolytic virotherapy for pediatric brain tumors.

Malignant brain tumors constitute nearly one-third of cancer diagnoses in children and have recently surpassed hematologic malignancies as the most lethal neoplasm in the pediatric population. Outcomes for children with brain tumors are unacceptably poor and current standards of care-surgical resection, chemotherapy, and radiation-are associated with significant long-term morbidity. Oncolytic virotherapy has emerged as a promising immunotherapy for the treatment of brain tumors.

Targeting oncometabolism to maximize immunotherapy in malignant brain tumors.

Brain tumors result in significant morbidity and mortality in both children and adults. Recent data indicate that immunotherapies may offer a survival benefit after standard of care has failed for malignant brain tumors. Modest results from several late phase clinical trials, however, underscore the need for more refined, comprehensive strategies that incorporate new mechanistic and pharmacologic knowledge.

The psychological impact of COVID-19 on ear, nose and throat (ENT) specialists.

Introduction: Ear, nose and throat (ENT) specialists are a high-risk group for COVID-19. Although the implications of SARS-CoV-2 infection on physical health are well-documented, the psychological impact is frequently overlooked.

Aims: The aim of this study was to gauge the psychological impact of COVID-19 on ENT specialists in Ireland.

The impact of edema and fiber crossing on diffusion MRI metrics assessed in an ex vivo nerve phantom: Multi-tensor model vs. diffusion orientation distribution function.

Diffusion tensor imaging (DTI) has been employed for over 2 decades to noninvasively quantify central nervous system diseases/injuries. However, DTI is an inadequate simplification of diffusion modeling in the presence of coexisting inflammation, edema and crossing nerve fibers. We employed a tissue phantom using fixed mouse trigeminal nerves coated with various amounts of agarose gel to mimic crossing fibers in the presence of vasogenic edema.

Diffusion Histology Imaging Combining Diffusion Basis Spectrum Imaging (DBSI) and Machine Learning Improves Detection and Classification of Glioblastoma Pathology.

Purpose: Glioblastoma (GBM) is one of the deadliest cancers with no cure. While conventional MRI has been widely adopted to examine GBM clinically, accurate neuroimaging assessment of tumor histopathology for improved diagnosis, surgical planning, and treatment evaluation remains an unmet need in the clinical management of GBMs.

Experimental Design: We employ a novel diffusion histology imaging (DHI) approach, combining diffusion basis spectrum imaging (DBSI) and machine learning, to detect, differentiate, and quantify areas of high cellularity, tumor necrosis, and tumor infiltration in GBM.