Safety outcomes of ketamine for treatment-resistant depression in clinical settings and development of the ketamine side effect tool-revised (KSET-R).

Background: Ketamine and its derivates (e.g. esketamine) are increasingly used in clinical settings for treatment-resistant depression (TRD).

How Can One Metal Power Nucleic Acid Phosphodiester Bond Cleavage by a Nuclease? Multiscale Computational Studies Highlight a Diverse Mechanistic Landscape.

Despite the remarkable resistance of the nucleic acid phosphodiester backbone to degradation affording genetic stability, the P-O bond must be broken during DNA repair and RNA metabolism, among many other critical cellular processes. Nucleases are powerful enzymes that can enhance the uncatalyzed rate of phosphodiester bond cleavage by up to ∼10-fold. Despite the most well accepted hydrolysis mechanism involving two metals (M to activate a water nucleophile and M to stabilize the leaving group), experimental evidence suggests that some nucleases can use a single metal to facilitate the chemical step, a controversial concept in the literature.

Neoadjuvant Chemotherapy VI-RADS Scores for Assessing Muscle-invasive Bladder Cancer Response to Neoadjuvant Immunotherapy with Multiparametric MRI.

Background An accurate method of assessing the response of muscle-invasive bladder cancer (MIBC) to neoadjuvant treatment is needed for selecting candidates for bladder-sparing strategies. Purpose To evaluate the diagnostic accuracy and reproducibility of neoadjuvant chemotherapy Vesical Imaging Reporting and Data System (nacVI-RADS) scores and posttreatment Vesical Imaging Reporting and Data System (VI-RADS) scores when assessing MIBC response to neoadjuvant immunotherapy with multiparametric MRI (mpMRI). Materials and Methods A retrospective analysis of MRI scans was conducted in patients enrolled in the PURE-01 study (NCT02736266) from February 2017 to December 2019 who underwent pre- and postimmunotherapy mpMRI before radical cystectomy.

Computational exploration of M-sites with chemical order and disorder in M'M''B and M'M''B compounds.

Boron-based materials are highly desirable for their promising mechanical properties, rendering them ideal for various industrial applications. In this study, we take advantage of the two unique metal Wyckoff sites in the prototype structures VB (4 and 2) and CrB (16 and 4). These two sites were populated by two different metals, M' and M'', forming novel B-based ternary M'M''B and M'M''B compounds.

Encompassing view of spatial and single-cell RNA sequencing renews the role of the microvasculature in human atherosclerosis.

Atherosclerosis is a pervasive contributor to ischemic heart disease and stroke. Despite the advance of lipid-lowering therapies and anti-hypertensive agents, the residual risk of an atherosclerotic event remains high, and developing therapeutic strategies has proven challenging. This is due to the complexity of atherosclerosis with a spatial interplay of multiple cell types within the vascular wall.

Analysis of trends in the context of implant therapy in a university surgical specialty clinic: a 20-year retrospective study.

Objectives: To analyze the trends in the context of implant therapy in a 3-year patient population and compare it with data obtained over the last 20 years.

Materials And Methods: All adult subjects who received treatment in the context of implant therapy between 2020 and 2022 were included in this retrospective study. Data regarding patient demographics, indications and location of implant therapy, implant characteristics, surgical techniques, complications, and early implant failures were recorded and compared to data obtained in the years 2002-2004, 2008-2010, and 2014-2016.

Patterns and predictors of multiple sclerosis phenotype transition.

Currently, there are limited therapeutic options for patients with non-active secondary progressive multiple sclerosis. Therefore, real-world studies have investigated differences between patients with relapsing-remitting multiple sclerosis, non-active secondary progressive multiple sclerosis and active secondary progressive multiple sclerosis. Here, we explore patterns and predictors of transitioning between these phenotypes.

Biological Augmentation With Retro-Drilling Core Decompression in Early Stage of Femoral Head Avascular Necrosis.

Osteonecrosis of the femoral head can lead to end-stage osteoarthritis when left untreated. The incidence has been on the rise since the onset of the COVID-19 pandemic. Core decompression of the femoral head is usually the first line of surgical treatment when conservative options fail.

All Arthroscopic Osteochondral Autograft Transplantation for Medial Talar Dome Lesions Talus With Burring of the Anterior Lip of the Distal Tibia.

Osteochondral lesions of the talus are chondral lesions affecting the subchondral bone mostly due to acute ankle trauma, including either sprains or fractures. After failure of conservative treatment, operative treatment is necessary, with different surgical techniques described in the literature. We describe a single-step osteochondral autograft transfer to access the medial talar dome lesion that avoids the need for a medial malleolar osteotomy and therefore eliminates morbidity while reducing operative time.

Effects of a Digital Intervention to Improve DASH and Blood Pressure Among US Adults.

Background: Dietary Approaches to Stop Hypertension (DASH) is a recommended first-line treatment for adults with hypertension, yet adherence to DASH is low. To evaluate the efficacy of a digital health intervention (DHI), compared with attention control, on changes in DASH adherence and blood pressure among adults with hypertension.

Methods: Nourish was a 12-month, parallel, 2-arm, randomized controlled trial of a virtually delivered DHI.

Asymmetric intra and inter-hemispheric subcellular rat brain correlation of arginyl-aminopeptidase activity during development and aging.

The functional significance of brain asymmetry is still largely unknown. Studying the level of correlation of neuropeptide-degrading activities between subcellular fractions such as synaptosomal, of the left and right hemispheres of male rats during development and aging could provide relevant data on their functional role during these periods. The present study analyzes the level of correlation of a enkephalin- or angiotensin III-degrading activity, such as membrane-bound arginyl-aminopeptidase activity (M-B ArgAP) between the left versus right homogenate and/or synaptosomal subcellular fractions obtained and processed independently from both brain hemispheres during development and aging.

A position and wave spectra dataset of Marginal Ice Zone dynamics collected around Svalbard in 2022 and 2023.

Sea ice is a key element of the global Earth system, with a major impact on global climate and regional weather. Unfortunately, accurate sea ice modeling is challenging due to the diversity and complexity of underlying physics happening there, and a relative lack of ground truth observations. This is especially true for the Marginal Ice Zone (MIZ), which is the area where sea ice is affected by incoming ocean waves.

Impact of hyperkalaemia on renin-angiotensin-aldosterone (RAAS) inhibitor reduction or withdrawal following hospitalisation.

Background: Inhibitors of the renin-angiotensin-aldosterone system (RAAS), such as ACE inhibitors (ACEi), angiotensin-II receptor blockers and mineralocorticoid receptor antagonists, reduce morbidity and mortality in hypertension, congestive heart failure and chronic kidney disease. However, their use can lead to hyperkalaemia. We examined the proportions of RAAS inhibitor (RAASi) reduction or withdrawal, across GFR strata, following hospitalisation and the effect on patient mortality.

Optimization of a Mobile Transdiagnostic Emotion Regulation Intervention for University Students: A Micro-Randomized Trial.

Increasing mental health problems among university students highlight the need for scalable, effective solutions. We have developed a transdiagnostic mobile intervention called ROOM, promoting adaptive emotion regulation (ER) skills among university students. Understanding how the intervention works and optimising content and delivery is essential for creating an effective and adaptive system.

Inclisiran as a siRNA Inhibitor of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9); Past, Present, and Future.

Reducing low-density lipoprotein cholesterol (LDL-C) levels has been shown to reduce the risk of developing atherosclerotic cardiovascular disease (ASCVD). Statins are the foundation of LDL-C lowering therapy with other non-statin agents used in circumstances where goal LDL-C levels are not reached or owing to intolerance to adverse effects of statins. In 2003, the discovery of the role of the proprotein convertase subtilisin/kexin type 9 (PCSK9) system in promoting elevated LDL-C levels led to new avenues of drug development to achieve target LDL-C.

Biologically defined neuronal synuclein disease as a tool to advance drug development.

In a recent Viewpoint article (. 2024;81:789‒90), Okubadejo et al. raised concerns regarding two recent proposals for biological definitions and staging systems for synucleinopathies (the Neuronal Synuclein Disease Integrated Staging System and SynNeurGe system).

CySP3-96 enables scalable, streamlined, and low-cost sample preparation for cysteine chemoproteomic applications.

Cysteine chemoproteomic screening platforms are widely utilized for chemical probe and drug discovery campaigns. Chemoproteomic compound screens, which use a mass spectrometry-based proteomic readout, can interrogate the structure activity relationship (SAR) for thousands of proteins in parallel across the proteome. The versatility of chemoproteomic screens has been demonstrated across electrophilic, nucleophilic, and reversible classes of molecules.

Synthetic organizer cells guide development via spatial and biochemical instructions.

In vitro development relies primarily on treating progenitor cells with media-borne morphogens and thus lacks native-like spatial information. Here, we engineer morphogen-secreting organizer cells programmed to self-assemble, via cell adhesion, around mouse embryonic stem (ES) cells in defined architectures. By inducing the morphogen WNT3A and its antagonist DKK1 from organizer cells, we generated diverse morphogen gradients, varying in range and steepness.

Adaptive Platform Trials in Stroke.

Clinical trials of treatments for stroke have generally utilized 2-arm, randomized designs to evaluate a single intervention against a control. Running separate clinical trials, with each addressing a single therapeutic question, is resource intensive and slows evidence generation, especially in a field with rapidly expanding treatment options and evolving practices. Platform trials-randomized clinical trials designed to evaluate multiple interventions that may enter and exit the ongoing platform based on a master protocol-accelerate the investigation of multiple therapeutic options within a single infrastructure.

Dual Antiplatelet Treatment up to 72 Hours After Ischemic Stroke Stratified by Risk Profile: A Post Hoc Analysis.

Background: Risk profile of recurrence may influence the effect of antiplatelet therapy. This study aimed to evaluate the efficacy and safety of clopidogrel-aspirin initiated within 72 hours after symptom onset for acute mild stroke or high-risk transient ischemic attack stratified by risk profile.

Methods: This is a secondary post hoc analysis of the INSPIRES (Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis) randomized clinical trial that enrolled patients 35 to 80 years old with acute mild ischemic stroke or high-risk transient ischemic attack between 2018 and 2022.

High-Risk Embolic Sources on Cardiac Computed Tomography in Patients With Acute Ischemic Stroke: A Case-Control Study.

Background: Cardiac computed tomography (CT) is increasingly used to search for cardioembolic sources of acute ischemic stroke (AIS). We assessed the association between high-risk cardioembolic sources on cardiac CT and AIS.

Methods: We performed a case-control study using data from a prospective cohort including consecutive adult patients with suspected stroke who underwent cardiac CT acquired during the initial stroke imaging protocol between 2018 and 2020.

Unveiling the Potential of Natural Resources-Derived Therapeutics for Improved Malaria Management: Computational to Experimental Studies.

Malaria kills millions of people annually, and it is one of the major causes of preventable mortality in the world. Of the different plasmodium species that induce malaria, Plasmodium falciparum and Plasmodium vivax account for the most severe form of malarial disease in humans. This review focuses on understanding preventive measures, mutation-based disease evolution, malaria-related biomarkers, and potential plant bioactive components for the treatment and management of malaria.

3D extrusion bioprinting of microbial inks for biomedical applications.

In recent years, the field of 3D bioprinting has witnessed the intriguing development of a new type of bioink known as microbial inks. Bioinks, typically associated with mammalian cells, have been reimagined to involve microbes, enabling many new applications beyond tissue engineering and regenerative medicine. This review presents the latest advancements in microbial inks, including their definition, types, composition, salient characteristics, and biomedical applications.

Evaluation of pollution potential in swine manure across growth stages: Impact of dietary nutrients and management strategies.

Regulation of dietary nutrient fractions to control the release of labile manure pollutants in swine production remains a challenge. Feeding trials were conducted to assess the impact of dietary nutrient fractions on labile manure composition and pollution potential in pigs at different growth stages. The pigs were selected based on age (weaning = 60 days, feeding = 100 days, and finishing = 160 days), health, and average body weight (23.