Impact of Genomic Classifiers on Risk Stratification and Treatment Intensity in Patients With Localized Prostate Cancer : A Systematic Review.

Background: Tissue-based genomic classifiers (GCs) have been developed to improve prostate cancer (PCa) risk assessment and treatment recommendations.

Purpose: To summarize the impact of the Decipher, Oncotype DX Genomic Prostate Score (GPS), and Prolaris GCs on risk stratification and patient-clinician decisions on treatment choice among patients with localized PCa considering first-line treatment.

Data Sources: MEDLINE, EMBASE, and Web of Science published from January 2010 to August 2024.

NNFit: A Self-Supervised Deep Learning Method for Accelerated Quantification of High- Resolution Short Echo Time MR Spectroscopy Datasets.

Purpose To develop and evaluate the performance of NNFit, a self-supervised deep-learning method for quantification of high-resolution short echo-time (TE) echo-planar spectroscopic imaging (EPSI) datasets, with the goal of addressing the computational bottleneck of conventional spectral quantification methods in the clinical workflow. Materials and Methods This retrospective study included 89 short-TE whole-brain EPSI/GRAPPA scans from clinical trials for glioblastoma (Trial 1, May 2014-October 2018) and major-depressive-disorder (Trial 2, 2022- 2023). The training dataset included 685k spectra from 20 participants (60 scans) in Trial 1.

Effectiveness of Synchronous Postdischarge Contacts on Health Care Use and Patient Satisfaction : A Systematic Review and Meta-analysis.

Background: Postdischarge contacts (PDCs) after hospitalization are common practice, but their effectiveness in reducing use of acute care after discharge remains unclear.

Purpose: To assess the effects of PDC on 30-day emergency department (ED) visits, 30-day hospital readmissions, and patient satisfaction.

Data Sources: MEDLINE, Embase, and CINAHL searched from 2012 to 25 May 2023.

Consuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer's disease in humans.

Background: Alzheimer's disease (AD) is a major neurodegenerative disorder with significant environmental factors, including diet and lifestyle, influencing its onset and progression. Although previous studies have suggested that certain diets may reduce the incidence of AD, the underlying mechanisms remain unclear.

Method: In this post-hoc analysis of a randomized crossover study of 20 elderly adults, we investigated the effects of a modified Mediterranean ketogenic diet (MMKD) on the plasma lipidome in the context of AD biomarkers, analyzing 784 lipid species across 47 classes using a targeted lipidomics platform.

Sex differences in mitochondrial free-carnitine levels in subjects at-risk and with Alzheimer's disease in two independent study cohorts.

A major challenge in the development of more effective therapeutic strategies for Alzheimer's disease (AD) is the identification of molecular mechanisms linked to specific pathophysiological features of the disease. Importantly AD has a two-fold higher incidence in women than men and a protracted prodromal phase characterized by amnestic mild-cognitive impairment (aMCI) suggesting that biological processes occurring early can initiate vulnerability to AD. Here, we used a sample of 125 subjects from two independent study cohorts to determine the levels in plasma (the most accessible specimen) of two essential mitochondrial markers acetyl-L-carnitine (LAC) and its derivative free-carnitine motivated by a mechanistic model in rodents in which targeting mitochondrial metabolism of LAC leads to the amelioration of cognitive function and boosts epigenetic mechanisms of gene expression.

Structure-guided design and synthesis of C22- and C32-modified FK520 analogs with enhanced activity against human pathogenic fungi.

Invasive fungal infections are a leading cause of death worldwide. Translating molecular insights into clinical benefits is challenging because fungal pathogens and their hosts share similar eukaryotic physiology. Consequently, current antifungal treatments have limited efficacy, may be poorly fungicidal in the host, can exhibit toxicity, and are increasingly compromised by emerging resistance.

Design of an equilibrative nucleoside transporter subtype 1 inhibitor for pain relief.

The current opioid crisis urgently calls for developing non-addictive pain medications. Progress has been slow, highlighting the need to uncover targets with unique mechanisms of action. Extracellular adenosine alleviates pain by activating the adenosine A1 receptor (A1R).

The Safety of Recently Approved Therapeutics in Age-Related Macular Degeneration.

Recent developments in treatments for both forms of advanced age-related macular degeneration (AMD) have led to the approval of multiple agents and modalities within the last few years. Five new medications for both neovascular AMD (nAMD) and geographic atrophy (GA) secondary to nonexudative AMD (neAMD) have been FDA-approved within the last 5 years, along with a new device designed for sustained drug delivery for nAMD. In nAMD, the newest agents approved by the FDA are brolucizumab (Novartis Pharmaceuticals, Basel, Switzerland), faricimab (F.

International workshop: what is needed to ensure outcome measures for Rett syndrome are fit-for-purpose for clinical trials? June 7, 2023, Nashville, USA.

Introduction: The clinical, research and advocacy communities for Rett syndrome are striving to achieve clinical trial readiness, including having fit-for-purpose clinical outcome assessments. This study aimed to (1) describe psychometric properties of clinical outcome assessment for Rett syndrome and (2) identify what is needed to ensure that fit-for-purpose clinical outcome assessments are available for clinical trials.

Methods: Clinical outcome assessments for the top 10 priority domains identified in the Voice of the Patient Report for Rett syndrome were compiled and available psychometric data were extracted.

Covered Stent Correction for Sinus Venosus Atrial Septal Defects, an Emerging Alternative to Surgical Repair: Results of an International Registry.

Background: Covered stent correction for a sinus venosus atrial septal defect (SVASD) was first performed in 2009. This innovative approach was initially viewed as experimental and was reserved for highly selected patients with unusual anatomic variants. In 2016, increasing numbers of procedures began to be performed, and in several centers, it is now offered as a standard of care option alongside surgical repair.

Advancing digital sensing in mental health research.

Digital sensing tools, like smartphones and wearables, offer transformative potential for mental health research by enabling scalable, longitudinal data collection. Realizing this promise requires overcoming significant challenges including limited data standards, underpowered studies, and a disconnect between research aims and community needs. This report, based on the 2023 Workshop on Advancing Digital Sensing Tools for Mental Health, articulates strategies to address these challenges to ensure rigorous, equitable, and impactful research.

Early life exposure to structural sexism and late-life memory trajectories among black and white women and men in the United States.

Introduction: We investigated whether early life exposure to state-level structural sexism influenced late-life memory trajectories among United Staes (U.S.) -born women and men and determined whether associations differed between racialized groups.

One-Year Follow-Up Is Sufficient Time for Patient-Reported Outcomes Following Rotator Cuff Repair: A Systematic Review and Meta-analysis.

Purpose: To perform a systematic review to determine whether there were clinically significant differences in patient-reported outcome measures from 1- to 2-year follow-up following rotator cuff repair (RCR).

Methods: A literature search of 3 databases was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized controlled trials (RCTs) reporting on patient-reported outcomes at the 1- and 2-year follow-up following RCR were included.

Optimal adaptive SMART designs with binary outcomes.

In a sequential multiple-assignment randomized trial (SMART), a sequence of treatments is given to a patient over multiple stages. In each stage, randomization may be done to allocate patients to different treatment groups. Even though SMART designs are getting popular among clinical researchers, the methodologies for adaptive randomization at different stages of a SMART are few and not sophisticated enough to handle the complexity of optimal allocation of treatments at every stage of a trial.

Evaluating Performance Among National Basketball Association Players After Jones Fractures: A Retrospective Cohort Study.

Background: In professional basketball, Jones fractures are among the most common cause of lower extremity stress injury. Despite its prevalence, there is a paucity of research on the impact of Jones fractures on athletic performance in the National Basketball Association (NBA).

Purpose: To determine the impact of Jones fractures on return to play and performance among NBA players when compared with preinjury values and healthy matched controls.

Does Tibial Plateau Slope and Depth Influence ACL Strain In Vivo?

Background: The anterior cruciate ligament (ACL) is loaded under tension when the tibia translates anteriorly relative to the femur. The shape of the articular surfaces of the tibiofemoral joint may influence the amount of anterior tibial translation under compressive loading. Thus, a steep lateral tibial plateau and a shallow medial plateau are thought to be risk factors for ACL injury.

Hand and Glove Sanitizing in Sterile Compounding, Part 1.

Selecting an appropriate sanitizer (i.e., "rub") for application to hands and gloves before and, if necessary, during sterile compounding is as important as is its consistent and judicious use.

Integrating Out-of-Pocket Costs Into Shared Decision-Making for Heart Failure With Reduced Ejection Fraction: A Stepped-Wedge Trial (POCKET-COST-HF).

Background: Guideline-directed medical therapy for heart failure (HF) with reduced ejection fraction can entail high out-of-pocket (OOP) costs, prompting concerns about financial toxicity and access. OOP costs are generally unavailable during encounters. This trial assessed the impact of providing patient-specific OOP costs to patients and clinicians.

Design and Evaluation of Pyridinyl Sulfonyl Piperazine LpxH Inhibitors with Potent Antibiotic Activity Against Enterobacterales.

Enterobacterales, a large order of Gram-negative bacteria, including and , are major causes of urinary tract and gastrointestinal infections, pneumonia, and other diseases in healthcare settings and communities. ESBL-producing Enterobacterales and carbapenem-resistant Enterobacterales can break down commonly used antibiotics, with some strains being resistant to all available antibiotics. This public health threat necessitates the development of novel antibiotics, ideally targeting new pathways in these bacteria.

Exploring facilitators and barriers to daily chlorhexidine gluconate bathing in adult patients undergoing hematopoietic stem cell transplantation.

Unlabelled: Hematopoietic cell transplantation (HCT) is a promising treatment for hematologic malignancies, but intensive conditioning leads to immunosuppression and susceptibility to healthcare-associated infections (HAI). Despite standard prevention measures, bloodstream infections (BSI) impact a significant percentage of immunocompromised HCT patients. Incidence of BSI can be mitigated by chlorhexidine gluconate (CHG) bathing-an underutilized infection-prevention strategy.

DNA Methylation Signatures of Cardiovascular Health Provide Insights into Diseases.

Background: The association of overall cardiovascular health (CVH) with changes in DNA methylation (DNAm) has not been well characterized.

Methods: We calculated the American Heart Association's Life's Essential 8 (LE8) score to reflect CVH in five cohorts with diverse ancestry backgrounds. Epigenome-wide association studies (EWAS) for LE8 score were conducted, followed by bioinformatic analyses.