Association of SGLT2 Inhibitor Initiation and PSA Response in Prostate Cancer.

Introduction: Non-castrating therapies are an unmet clinical need for patients with advanced prostate cancer. To maximize quality of life and prioritize cardiovascular health, we investigated SGLT2 inhibitors as a non-castrating therapy in patients with prostate cancer.

Materials And Methods: We conducted a retrospective analysis of patients with either local or biochemically recurrent prostate cancer who initiated therapy with an SGLT2 inhibitor without concurrent androgen deprivation therapy.

CHMP2B promotes CHMP7 mediated nuclear pore complex injury in sporadic ALS.

Alterations to the composition and function of neuronal nuclear pore complexes (NPCs) have been documented in multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis (ALS). Moreover, recent work has suggested that injury to the NPC can at least in part contribute to TDP-43 loss of function and mislocalization, a pathological hallmark of ALS and related neurodegenerative diseases. Collectively, these studies highlight a role for disruptions in NPC homeostasis and surveillance as a significant pathophysiologic event in neurodegeneration.

Blood-brain barrier breakdown in brain ischemia: Insights from MRI perfusion imaging.

Brain ischemia is a major cause of neurological dysfunction and mortality worldwide. It occurs not only acutely, such as in acute ischemic stroke (AIS), but also in chronic conditions like cerebral small vessel disease (cSVD). Any other conditions resulting in brain hypoperfusion can also lead to ischemia.

Evolving Food Allergy Clinical Trials to Become More Patient-Centered.

The current FDA paradigm may not fully capture important patient-centered outcomes or measure a primary outcome that is truly meaningful to patients. Patient reported outcome measures (PROMs) are standardized tools measuring the patient's experience in food allergy clinical trials, which can help support shared decision-making (SDM) and further our understanding of treatment impact. Food allergy PROMs include quality of life (QoL), health state utility (HSU), severity, and self-efficacy measures.

The effects of plasma exchange and glucocorticoids on early kidney function among patients with ANCA-associated vasculitis in the PEXIVAS trial.

Therapeutic plasma exchange (PLEX) is an adjunctive treatment for patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and kidney involvement. Little is known about the effect of PLEX on early changes in kidney function. This post-hoc analysis of the PEXIVAS trial investigated the effects of PLEX on changes in kidney function within 12 months.

Health System Purchasing Professionals' Approaches to Considering Equity in Procurement.

Background: Continuing data on racial bias in pulse oximeters and artificial intelligence has sparked calls for health systems to drive innovation against racial bias in healthcare device and artificial intelligence markets by incorporating equity concerns explicitly into purchasing decisions.

Research Question: How do healthcare purchasing professionals integrate equity concerns into purchasing decision-making?

Study Design And Methods: Between 8/2023-3/2024, we conducted semi-structured interviews via videoconferencing with healthcare purchasing professionals about purchasing processes for pulse oximeters and other devices-and whether and where equity concerns arise in decision-making. An abductive approach was used to analyze perspectives on how equity and disparity concerns are currently integrated into healthcare purchasing decision-making.

Thermosensitive, injectable, antibacterial glabridin liposome/chitosan dual network hydrogel for diabetic wound healing.

Thermosensitive hydrogels show great potential in healing diabetic wounds, but they are still challenged by the long healing time, risk of infectivity, and accumulation of melanin. Herein, a dual network hydrogel is designed, which consists of chlorogenic acid (CA) modified chitosan (CS) (CA@CS), poly(N-isopropylacrylamide) (PNIPAm), and glabridin liposomes (GL). The gelation transition temperature of the hydrogel is 32-34 °C, which thus endows it with superior injectability at ambient temperature.

PTSP-BERT: Predict the thermal stability of proteins using sequence-based bidirectional representations from transformer-embedded features.

Thermophilic proteins, mesophiles proteins and psychrophilic proteins have wide industrial applications, as enzymes with different optimal temperatures are often needed for different purposes. Convenient methods are needed to determine the optimal temperatures for proteins; however, laboratory methods for this purpose are time-consuming and laborious, and existing machine learning methods can only perform binary classification of thermophilic and non-thermophilic proteins, or psychrophilic and non-psychrophilic proteins. Here, we developed a deep learning model, PSTP-BERT, based on protein sequences that can directly perform Three classes identification of thermophilic, mesophilic, and psychrophilic proteins.

Endoscopic Papillary Large Balloon Dilatation With or Without Endoscopic Sphincterotomy in the Treatment of Common Bile Duct Stones.

Purpose Of Review: Endoscopic papillary large balloon dilation (EPLBD) has been proved to have better efficacy and safety in removing common bile duct stones. Conventional endoscopic sphincterotomy (EST) is usually performed before EPLBD. However, EPLBD without EST has recently reported short-term outcomes similar to those of EPLBD with EST.

Breaking the Myth of Enzymatic Azoreduction.

Flavin-dependent azoreductases have been applied to a wide range of tasks from decolorizing numerous azo dyes to releasing azo-conjugated prodrugs. A general narrative reiterated in much of the literature suggests that this enzyme promotes sequential reduction of both the azo-containing substrate and its corresponding hydrazo product to release the aryl amine components while consuming two equivalents of NAD(P)H. Indeed, such aryl amines can be formed by incubation of certain azo compounds with azoreductases, but the nature of the substrates capable of this apparent azo bond lysis remained unknown.

De-escalating and discontinuing disease-modifying therapies in multiple sclerosis.

The development of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) has been highly successful in recent decades. It is now widely accepted that early initiation of DMTs after disease onset is associated with a better long-term prognosis. However, the question of when and how to de-escalate or discontinue DMTs remains open and critical.

Physician, know thyself: Applying brand management principles to professional identity in academic medicine.

Context: A career in medicine is a journey of countless opportunities, challenges and choices. Determining the "right" decision for any given career choice ultimately must come from within; thus, a clear understanding of a physician's core professional identity is critical. Existing conceptualizations of professional identity within medicine focus primarily on medical training; however, it is clear that professional identity evolves throughout one's career.

Raman Imaging of Targeted Drug Delivery with DNA-Based Nano-Optical Devices.

Raman spectroscopy (RS) has emerged as a novel optical imaging modality by identifying molecular species through their bond vibrations, offering high specificity and sensitivity in molecule detection. However, its application in intracellular molecular probing has been limited due to challenges in combining vibrational tags with functional probes. DNA nanostructures, known for their high programmability, have been instrumental in fields like biomedicine and nanofabrication.

Effectiveness of tofacitinib versus tumor necrosis factor inhibitors and in those receiving tofacitinib as different lines of therapy in patients with rheumatoid arthritis: results from the United States CorEvitas Rheumatoid Arthritis Registry.

Objectives: To compare effectiveness of tofacitinib versus tumor necrosis factor inhibitors (TNFi), and across tofacitinib lines of therapy, in patients with rheumatoid arthritis (RA), using US CorEvitas RA Registry data.

Methods: Analysis included patients with RA initiating tofacitinib or TNFi with a 12-month follow-up visit between November 2012-February 2021. Primary (Clinical Disease Activity Index-defined low disease activity [CDAI-LDA: CDAI ≤ 10]) and secondary (clinical/disease activity/patient-reported) effectiveness outcomes were assessed at month 12.

Quantitative Systems Pharmacology Modeling in Immuno-Oncology: Hypothesis Testing, Dose Optimization, and Efficacy Prediction.

Despite an increasing number of clinical trials, cancer is one of the leading causes of death worldwide in the past decade. Among all complex diseases, clinical trials in oncology have among the lowest success rates, in part due to the high intra- and inter-tumoral heterogeneity. There are more than a thousand cancer drugs and treatment combinations being investigated in ongoing clinical trials for various cancer subtypes, germline mutations, metastasis, etc.

Seven years of chronic fertilization affects how plant functional types respond to drought, but not plant production.

Nitrogen deposition continues to change grassland plant community composition particularly in more mesic systems; however, whether these altered plant communities will respond differently to other global change factors remains to be seen. Here, we explore how nutrient-altered tallgrass prairie responds to drought. Seven years of nutrient treatments (control, nitrogen (N), phosphorus (P), and N + P) resulted in significantly different plant communities.

The long and short of hyperdivergent regions.

The increasing prevalence of genome sequencing and assembly has uncovered evidence of hyperdivergent genomic regions - loci with excess genetic diversity - in species across the tree of life. Hyperdivergent regions are often enriched for genes that mediate environmental responses, such as immunity, parasitism, and sensory perception. Especially in self-fertilizing species where the majority of the genome is homozygous, the existence of hyperdivergent regions might imply the historical action of evolutionary forces such as introgression and/or balancing selection.

Safety and immunogenicity of an acellular pertussis vaccine containing genetically detoxified pertussis toxin administered to pregnant women living with and without HIV and their newborns (WoMANPOWER): a randomised controlled trial in Uganda.

Background: Immunisation in pregnancy against pertussis can reduce severe disease in infancy. There are few data on the safety and immunogenicity of vaccines given to pregnant women living with HIV and their infants. We aimed to describe the safety and immunogenicity of a tetanus-diphtheria-acellular pertussis (TdaP) vaccine containing genetically detoxified pertussis toxin given to pregnant women living with HIV and the effect of the vaccine on infant whole-cell pertussis vaccine responses.

Progress in reducing socioeconomic inequalities in the use of modern contraceptives in 48 focus countries as part of the FP2030 initiative between 1990 and 2020: a population-based analysis.

Background: Despite increases in modern contraception use, socioeconomic inequalities in family planning persist. In this study, we aimed to measure progress in reducing socioeconomic inequalities in modern contraceptive prevalence rate (mCPR) and demand for family planning satisfied by modern methods (mDFPS) in 48 countries as part of the Family Planning 2030 (FP2030) initiative between 1990 and 2020 for which Demographic and Health Survey data were available.

Methods: We analysed two rounds of Demographic and Health Survey data per country.

To Acquire or Not to Acquire: Evaluating Compressive Sensing for Raman Spectroscopy in Biology.

Raman spectroscopy has revolutionized the field of chemical biology by providing detailed chemical and compositional information with minimal sample preparation. Despite its advantages, the technique suffers from low throughput due to the weak Raman effect, necessitating long acquisition times and expensive equipment. This limitation is particularly acute in time-sensitive applications like bioprocess monitoring and dynamic studies.

The Society of Thoracic Surgeons Expert Consensus Statements on a Framework for a Standardized National Robotic Curriculum for Thoracic Surgery Trainees.

Objective: With robotic technology's rapid growth and integration, an urgent need to bridge the educational gap in thoracic surgical training has emerged. This document, a result of consensus among a group of experts in the practice and training of robotic surgery from the Society of Thoracic Surgeons (STS), aims to provide a framework for a standardized national robotic curriculum for thoracic surgery trainees.

Methods: The STS Task Force on Robotic Thoracic Surgery and Workforce on E-learning and Educational Innovation assembled an expert group with the input of the Thoracic Surgery Director's Association (TSDA).