Localized Reconstruction of Multimodal Distance Distribution from DEER Data of Biopolymers.

Pulsed Dipolar ESR Spectroscopy (PDS) is a uniquely powerful technique to characterize the structural property of intrinsically disordered proteins (IDPs) and polymers and the conformational evolution of IDPs and polymers, e.g. during assembly, by offering the probability distribution of segment end-to-end distances.

Rapid Analysis of DEER Signals Including Short Distances.

Double electron electron resonance (DEER) spectroscopy is an important technique to measure distance distributions () for studying protein structures and protein-protein interactions. DEER data analysis can at times become challenging due to the lack of a detailed analytical signal expression or numerical methods with rapid computation time. We have derived an analytical expression κ, which includes both the pseudo-secular dipolar coupling (PSDC) and the finite pulse effects, especially important for shorter distances.

MRI Denoising Using Pixel-Wise Threshold Selection.

Magnetic resonance imaging (MRI) has emerged as a promising technique for non-invasive medical imaging. The primary challenge in MRI is the trade-off between image visual quality and acquisition time. Current MRI image denoising algorithms employ global thresholding to denoise the whole image, which leads to inadequate denoising or image distortion.

Large Language Model Influence on Management Reasoning: A Randomized Controlled Trial.

Importance: Large language model (LLM) artificial intelligence (AI) systems have shown promise in diagnostic reasoning, but their utility in management reasoning with no clear right answers is unknown.

Objective: To determine whether LLM assistance improves physician performance on open-ended management reasoning tasks compared to conventional resources.

Design: Prospective, randomized controlled trial conducted from 30 November 2023 to 21 April 2024.

Novel requirements for HAP2/GCS1-mediated gamete fusion in .

The ancestral gamete fusion protein, HAP2/GCS1, plays an essential role in fertilization in a broad range of taxa. To identify factors that may regulate HAP2/GCS1 activity, we screened mutants of the ciliate for behaviors that mimic knockout phenotypes in this species. Using this approach, we identified two new genes, and , whose products are necessary for membrane pore formation following mating type recognition and adherence.

Ying and Yang of Ceramide in the Vascular Endothelium.

Ceramides, a group of biologically active sphingolipids, have been described as the new cholesterol given strong evidence linking high plasma ceramide with endothelial damage, risk for early adverse cardiovascular events, and development of cardiometabolic disease. This relationship has sparked great interest in investigating therapeutic targets with the goal of suppressing ceramide formation. However, the growing data challenge this paradigm of ceramide as solely eliciting detrimental effects to the cardiovascular system.

Is the peripheral microcirculation a window into the human coronary microvasculature?

An increasing body of evidence suggests a pivotal role for the microvasculature in the development of cardiovascular disease. A dysfunctional coronary microvascular network, specifically within endothelial cells-the inner most cell layer of vessels-is considered a strong, independent risk factor for future major adverse cardiac events. However, challenges exist with evaluating this critical vascular bed, as many of the currently available techniques are highly invasive and cost prohibitive.

Noninvasive assessment of human microvascular function in health and disease using incident dark-field microscopy.

Reduced peripheral microvascular reactivity is associated with an increased risk for major adverse cardiac events (MACEs). Tools for noninvasive assessment of peripheral microvascular function are limited, and existing technology is poorly validated in both healthy populations and patients with cardiovascular disease (CVD). Here, we used a handheld incident dark-field imaging tool (CytoCam) to test the hypothesis that, compared with healthy individuals (no risk factors for CVD), subjects formally diagnosed with coronary artery disease (CAD) or those with ≥2 risk factors for CAD (at risk) would exhibit impaired peripheral microvascular reactivity.

Inhibitory control of locomotor statistics in walking .

In order to forage for food, many animals regulate not only specific limb movements but the statistics of locomotor behavior over time, switching between long-range dispersal and localized search depending on resource availability. How pre-motor circuits regulate such locomotor statistics is not clear. Here we analyze and model locomotor statistics in walking , and their modulation by attractive food odor.

Assessing ChatGPT 4.0's test performance and clinical diagnostic accuracy on USMLE STEP 2 CK and clinical case reports.

While there is data assessing the test performance of artificial intelligence (AI) chatbots, including the Generative Pre-trained Transformer 4.0 (GPT 4) chatbot (ChatGPT 4.0), there is scarce data on its diagnostic accuracy of clinical cases.

An analysis of double-quantum coherence ESR in an N-spin system: Analytical expressions and predictions.

Electron spin resonance pulsed dipolar spectroscopy (PDS) has become popular in protein 3D structure analysis. PDS studies yield distance distributions between a pair or multiple pairs of spin probes attached to protein molecules, which can be used directly in structural studies or as constraints in theoretical predictions. Double-quantum coherence (DQC) is a highly sensitive and accurate PDS technique to study protein structures in the solid state and under physiologically relevant conditions.

A Predictive Algorithm for Discriminating Myeloid Malignancies and Leukemoid Reactions.

Background: Adults presenting with a neutrophil-predominant leukocytosis (white cell count >50,000/μL) often necessitate urgent medical management. These patients are diagnosed with either acute presentations of chronic myeloid malignancies or leukemoid reactions, yet accurate models to distinguish between these entities do not exist. We used demographic and lab data to build a machine learning model capable of discriminating between these diagnoses.

Rethinking the consultation paradigm: Validity evidence for a new framework, a multimethods study.

Background: In-hospital consultation is essential for patient care. We previously proposed a framework of seven specific consultation types to classify consult requests to improve communication, workflow, and provider satisfaction.

Methods: This multimethods study's aim was to evaluate the applicability of the consult classification framework to real internal medicine (IM) consults.

Rewiring Endothelial Sphingolipid Metabolism to Favor S1P Over Ceramide Protects From Coronary Atherosclerosis.

Background: Growing evidence correlated changes in bioactive sphingolipids, particularly S1P (sphingosine-1-phosphate) and ceramides, with coronary artery diseases. Furthermore, specific plasma ceramide species can predict major cardiovascular events. Dysfunction of the endothelium lining lesion-prone areas plays a pivotal role in atherosclerosis.

Necessary Role of Ceramides in the Human Microvascular Endothelium During Health and Disease.

Background: Elevated plasma ceramides and microvascular dysfunction both independently predict adverse cardiac events. Despite the known detrimental effects of ceramide on the microvasculature, evidence suggests that activation of the shear-sensitive, ceramide-forming enzyme NSmase (neutral sphingomyelinase) elicits formation of vasoprotective nitric oxide (NO). Here, we explore a novel hypothesis that acute ceramide formation through NSmase is necessary for maintaining NO signaling within the human microvascular endothelium.

Novel interactive text-messaging curriculum for endocrinology board review.

Background: The ABIM certification exam is one of the measures to ensure that physicians have the clinical skills for good care delivery. The 5-year average pass rate for ABIM Endocrinology exam is 82%. The pass rate significantly decreased to a nadir of 74% in 2021 and 2022, lowest of all medicine subspecialties.

Addressing the decline in graduate students' mental well-being.

At the American Physiology Summit 2023 session entitled, "Mental Health for Graduate Students," numerous students expressed struggling with poor mental well-being primarily because of negative experiences during their graduate training. In fact, studies show that up to 50% of graduate students report symptoms of depression, anxiety, or burnout during their training, and poor mental well-being is a major contributor to students' decision to leave academia. Most of the current solutions focus on treatment or wellness strategies; while these are important and necessary, the training environment or culture that often contributes to worsening well-being continues to persist.

Differentiating Unimodal and Multimodal Distributions in Pulsed Dipolar Spectroscopy Using Wavelet Transforms.

Site directed spin labeling has enabled protein structure determination using electron spin resonance (ESR) pulsed dipolar spectroscopy (PDS). Small details in a distance distribution can be key to understanding important protein structure-function relationships. A major challenge has been to differentiate unimodal and overlapped multimodal distance distributions.

Thermal Degradation of Thaumatin at Low pH and Its Prevention Using Alkyl Gallates.

Thaumatin, a potent sweet tasting protein extracted from the Katemfe Plant, is emerging as a natural alternative to synthetic non-nutritive sweeteners and flavor enhancer. As a food additive, its stability within the food matrix during thermal processing is of great interest to the food industry. When heated under neutral or basic conditions, thaumatin was found to lose its sweetness due to protein aggregation caused by sulfhydryl catalyzed disulfide bond interchange.

Necessary Role of Acute Ceramide Formation in The Human Microvascular Endothelium During Health and Disease.

Background: Elevated plasma ceramides independently predict adverse cardiac events and we have previously shown that exposure to exogenous ceramide induces microvascular endothelial dysfunction in arterioles from otherwise healthy adults (0-1 risk factors for heart disease). However, evidence also suggests that activation of the shear-sensitive, ceramide forming enzyme neutral sphingomyelinase (NSmase) enhances vasoprotective nitric oxide (NO) production. Here we explore a novel hypothesis that acute ceramide formation through NSmase is necessary for maintaining NO signaling within the human microvascular endothelium.

Structural insights into perilipin 3 membrane association in response to diacylglycerol accumulation.

Lipid droplets (LDs) are dynamic organelles that contain an oil core mainly composed of triglycerides (TAG) that is surrounded by a phospholipid monolayer and LD-associated proteins called perilipins (PLINs). During LD biogenesis, perilipin 3 (PLIN3) is recruited to nascent LDs as they emerge from the endoplasmic reticulum. Here, we analyze how lipid composition affects PLIN3 recruitment to membrane bilayers and LDs, and the structural changes that occur upon membrane binding.