Are medical school preclinical tests biased for sex and race? A differential item functioning analysis.

Background: A common practice in assessment development, fundamental for fairness and consequently the validity of test score interpretations and uses, is to ascertain whether test items function equally across test-taker groups. Accordingly, we conducted differential item functioning (DIF) analysis, a psychometric procedure for detecting potential item bias, for three preclinical medical school foundational courses based on students' sex and race.

Methods: The sample included 520, 519, and 344 medical students for anatomy, histology, and physiology, respectively, collected from 2018 to 2020.

Updates in the Surgical Management of Pancreatic Ductal Adenocarcinoma.

Surgical management of pancreas cancer is complex, including the timing of surgery, surgical approach, intraoperative techniques, and postoperative management, which are reviewed in detail in this manuscript. Ultimately, referral to a high-volume pancreatic surgeon or pancreatic surgery center is critical to ensuring appropriate short-term and long-term outcomes.

Risk Factors and Mechanisms for Diabetes in Pancreatitis.

Diabetes (DM) can occur as a complication of acute, acute recurrent, or chronic pancreatitis, affecting more than 30% of adults with chronic pancreatitis. Data on the pathophysiology and management are limited, especially in pediatric population. Proposed mechanisms include insulin deficiency, insulin resistance, decreased pancreatic polypeptide, and possible beta-cell autoimmunity (in a small subset).

Updates in the Management of Chronic Pancreatitis: Navigating Through Recent Advances.

This article provides an up-to-date review of the management of chronic pancreatitis, highlighting advancements in medical therapy, nutritional support, endoscopic and surgical approaches, and emerging treatments. Nutritional management accentuates addressing malabsorption and nutrient deficiencies. Advances in endoscopy and parenchyma-sparing surgical techniques have opened new avenues for improved patient outcomes, with total pancreatectomy and islet autotransplantation offering the only definitive solution for selected patients.

Updates in the Diagnosis of Chronic Pancreatitis: Current Approaches and New Possibilities.

This review provides a comprehensive update on the diagnostic approaches to chronic pancreatitis (CP), emphasizing recent advancements in imaging techniques, biomarker research, and multivariable scoring systems. Despite substantial progress in these areas, current diagnostic algorithms have limitations, particularly for early and non-calcific CP. Traditional criteria have focused on classic diagnostic signs, but "minimal change" CP is increasingly recognized through advanced imaging and function tests.

New PPARα Agonist A190-Loaded Microemulsion for Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect of anticancer agents with limited effective preventive or therapeutic interventions. Although fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, has demonstrated neuroprotective and analgesic properties, its clinical utility is hindered by low receptor affinity, poor subtype selectivity, and suboptimal bioavailability. A190, a highly selective and potent nonfibrate PPARα agonist, offers a promising alternative but is limited by poor aqueous solubility, resulting in reduced oral bioavailability and therapeutic efficacy.

Organ-specific microenvironments drive divergent T cell evolution in acute graft-versus-host disease.

Tissue-specific T cell immune responses play a critical role in maintaining organ health but can also drive immune pathology during both autoimmunity and alloimmunity. The mechanisms controlling intratissue T cell programming remain unclear. Here, we leveraged a nonhuman primate model of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation to probe the biological underpinnings of tissue-specific alloimmune disease using a comprehensive systems immunology approach including multiparameter flow cytometry, population-based transcriptional profiling, and multiplexed single-cell RNA sequencing and TCR sequencing.

Electronically Nonadiabatic Quenching of Excited States of O by Collisions with O Atoms.

The kinetics of electronically inelastic quenching of O(Δ) and O(Σ) by collisions with O(P) have been investigated using mixed quantum-classical trajectories governed by adiabatic potential energy surfaces and state couplings generated from a recently developed diabatic potential energy matrix (DPEM) for the 14 lowest-energy A' states of O. Using the coherent switching with decay of mixing (CSDM) method, dynamics calculations were performed both with 14 coupled electronic states and with 8 coupled electronical states, and similar results were obtained. The calculated thermal quenching rate coefficients are generally small, but they increase with temperature.

Optimizing Sedation Strategies in the Cardiac ICU: Induction, Maintenance and Weaning.

Purpose Of Review: We aim to summarize the available literature guiding tailored sedation practices for specific conditions encountered in the Cardiovascular Intensive Care Unit (CICU).

Recent Findings: Data specific for the CICU population is lacking. Preclinical data and observational studies guide sedation approaches for specific pathologies that we have used to generate a guideline for sedative choice for various scenarios.

Correcting scale distortion in RNA sequencing data.

RNA sequencing (RNA-seq) is the conventional genome-scale approach used to capture the expression levels of all detectable genes in a biological sample. This is now regularly used for population-based studies designed to identify genetic determinants of various diseases. Naturally, the accuracy of these tests should be verified and improved if possible.

"The biggest challenge is there's never a routine": a qualitative study of the time burdens of cancer care at home.

Purpose: As cancer care is increasingly delivered in the home, more tasks and responsibilities fall on patients and their informal care partners. These time costs can present significant mental, physical, and financial burdens, and are undercounted in current measures of time toxicity that only consider care received in formal healthcare settings.

Methods: Semi-structured qualitative interviews were conducted with patients with gastrointestinal cancer and informal care partners at a single tertiary cancer center between March and October 2023.

Effect of formulation composition on trastuzumab stability.

For monoclonal antibody drug products as for other biologics, while the innovator drug products first becomes commercially available, they are often followed by one or more biosimilar products. These biosimilars often differ from the innovator product, as well as from each other, in their formulation composition. However, the impact of the formulation composition on the stability of the active pharmaceutical ingredient subjected to different 'stresses' is still not understood.

Electro-oxidative Deoxyfluorination of Arenes with NEt·3HF.

This report describes the design, development, and optimization of an electrochemical deoxyfluorination of arenes using a tetrafluoropyridine-derived leaving group. NEt·3HF serves as the fluoride source, and the reactions are conducted using either constant potential or constant current electrolysis in an undivided electrochemical cell. Mechanistic studies support a net oxidative pathway, in which initial single-electron oxidation generates a radical cation intermediate that is trapped by fluoride.

Developmental maturation of millimeter-scale functional networks across brain areas.

Processing sensory information, generating perceptions, and shaping behavior engages neural networks in brain areas with highly varied representations, ranging from unimodal sensory cortices to higher-order association areas. In early development, these areas share a common distributed and modular functional organization, but it is not known whether this undergoes a common developmental trajectory, or whether such organization persists only in some brain areas. Here, we examine the development of network organization across diverse cortical regions in ferrets using in vivo wide field calcium imaging of spontaneous activity.

Octupolar Vortex Crystal and Toroidal Moment in Twisted Bilayer MnPSe.

Experimental detection of antiferromagnetic order in two-dimensional materials is a challenging task. Identifying multidomain antiferromagnetic textures via the current techniques is even more difficult. Therefore, we investigate the higher-order multipole moments in twisted bilayer MnPSe.

Radiotherapeutics, clonal hematopoiesis, and risk of hematologic malignancies: The good, the bad, the ugly.

While radiotherapeutics have demonstrated significant clinical benefit across multiple cancer types including thyroid cancer, neuroendocrine tumors, and prostate cancer, hematological toxicities can be frequent and challenging. It remains unknown to what extent the hematologic toxicity is driven by clonal processes that preexist and are selected for by treatment induced selection pressures. In this review, we discuss the background leading to the adoption of radiotherapeutics in the treatment of solid tumor malignancies, the risk of hematologic toxicities and myeloid neoplasms and the evidence pointing to potential precursor lesions that may predispose patients to hematologic toxicities.

Spin-Orbit Coupling and Admixture Coefficients in SA-CASSCF and MS-CASPT2, and Triplet Excitation Yield Simulated via Trajectory Surface Hopping and Calibrated SA-CASSCF in 1,2-Dioxetane Derivatives.

The energy gaps, spin-orbit coupling (SOC), and admixture coefficients over a series of the configurations are evaluated by the SA-CASSCF/6-31G, SA-CASSCF/6-31G*, SA-CASSCF/ANO-RCC-VDZP, and MS-CASPT2/ANO-RCC-VDZP to reveal the extent of the inaccuracy of the SA-CASSCF. By comparing the mean absolute errors for the energy gaps and the admixture coefficient magnitudes (ACMs) measured between the SA-CASSCF/6-31G, SA-CASSCF/6-31G*, or SA-CASSCF/ANO-RCC-VDZP and the MS-CASPT2/ANO-RCC-VDZP, the SA-CASSCF/6-31G is selected as the electronic structure method in the nonadiabatic molecular dynamics simulation. The major components of the ACMs of the SA-CASSCF/6-31G and MS-CASPT2/ANO-RCC-VDZP are identified and compared; we find that the ACMs are underestimated by the SA-CASSCF/6-31G, which is verified by the reasonable triplet quantum yield simulated by the trajectory surface hopping and the calibrated SA-CASSCF/6-31G.

A forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance.

Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo and applied this to sonic hedgehog (SHH) medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver.

Alginate Hydrogel Beads with a Leakproof Gold Shell for Ultrasound-Triggered Release.

Focused ultrasound has advantages as an external stimulus for drug delivery as it is non-invasive, has high precision and can penetrate deep into tissues. Here, we report a gold-plated alginate (ALG) hydrogel system that retains highly water-soluble small-molecule fluorescein for sharp off/on release after ultrasound exposure. The ALG is crosslinked into beads with calcium chloride and layered with a polycation to adjust the surface charge for the adsorption of catalytic platinum nanoparticles (Pt NPs).

p97 Inhibitors Possessing Antiviral Activity Against SARS-CoV-2 and Low Cytotoxicity.

p97 (also known as valosin-containing protein, VCP) is a member of the AAA+ ATPase family and is intimately associated with protein quality control and homeostasis regulation. Therefore, pharmaceutical inhibition of p97 has been actively pursued as an anticancer strategy. Recently, p97 has emerged as an important pro-viral host factor and p97 inhibitors are being evaluated as potential antiviral agents.

Machine Learning Models for the Early Real-Time Prediction of Deterioration in Intensive Care Units-A Novel Approach to the Early Identification of High-Risk Patients.

Predictive machine learning models have made use of a variety of scoring systems to identify clinical deterioration in ICU patients. However, most of these scores include variables that are dependent on medical staff examining the patient. We present the development of a real-time prediction model using clinical variables that are digital and automatically generated for the early detection of patients at risk of deterioration.

Purine but Not Pyrimidine De Novo Nucleotide Biosynthesis Inhibitors Strongly Enhance the Antiviral Effect of Corresponding Nucleobases Against Dengue Virus.

Every year, dengue virus affects hundreds of millions of individuals worldwide. To date, there is no specific medication to treat dengue virus infections. Nucleobases, the base of a nucleoside without ribose, are understudied as potential treatments for viral infections.

Cell Type Specific Suppression of Hyper-Recombination by Human RAD18 Is Linked to Proliferating Cell Nuclear Antigen K164 Ubiquitination.

RAD18 is a conserved eukaryotic E3 ubiquitin ligase that promotes genome stability through multiple pathways. One of these is gap-filling DNA synthesis at active replication forks and in post-replicative DNA. RAD18 also regulates homologous recombination (HR) repair of DNA breaks; however, the current literature describing the contribution of RAD18 to HR in mammalian systems has not reached a consensus.