α-Cyclodextrin supplementation improves endurance exercise performance and reduces post-exercise fatigue in human males: a randomized, double-blind, placebo-controlled, parallel-group study.

α-Cyclodextrin (αCD), a cyclic hexasaccharide composed of six glucose units, is not digested in the small intestine but is completely fermented by gut microbes. Recently, we have reported that αCD supplementation for nonathlete men improved their 10 km biking times. However, the beneficial effects of αCD on exercise are not yet fully understood.

Gut microbiome signatures of vegan, vegetarian and omnivore diets and associated health outcomes across 21,561 individuals.

As plant-based diets gain traction, interest in their impacts on the gut microbiome is growing. However, little is known about diet-pattern-specific metagenomic profiles across populations. Here we considered 21,561 individuals spanning 5 independent, multinational, human cohorts to map how differences in diet pattern (omnivore, vegetarian and vegan) are reflected in gut microbiomes.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

SARS-CoV-2 Productively Infects Human Hepatocytes and Induces Cell Death.

SARS-CoV-2 infection is accompanied by elevated liver enzymes, and patients with pre-existing liver conditions experience more severe disease. While it was known that SARS-CoV-2 infects human hepatocytes, our study determines the mechanism of infection, demonstrates viral replication and spread, and highlights direct hepatocyte damage. Viral replication was readily detectable upon infection of primary human hepatocytes and hepatoma cells with the ancestral SARS-CoV-2, Delta, and Omicron variants.

Personalized, autologous neoantigen-specific T cell therapy in metastatic melanoma: a phase 1 trial.

New treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy. We designed BNT221, a personalized, neoantigen-specific autologous T cell product derived from peripheral blood, and tested this in a 3 + 3 dose-finding study with two dose levels (DLs) in patients with locally advanced or metastatic melanoma, disease progression after ICB, measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1) and, where appropriate, BRAF-targeted therapy.

Why some coalitions benefit from historical myths more than others.

Behavioural ecologies in themselves can create variation in fitness interdependencies among individuals, and hence modulate the functionality of invoking historical myths. We develop this possibility for the case where coalitions form to attack and exploit enemies, or to defend and protect against hostile out-groups. We propose that invoking historical myths are functional and observed especially when groups aggressively expand.

Epidemiology and Characteristics of Meniscal Tears in Patients With Combined ACL and Medial Collateral Ligament Injuries Versus Isolated ACL Tears: A Case-Control Study From the Francophone Arthroscopic Society.

Background: The co-occurrence of anterior cruciate ligament (ACL) rupture with medial collateral ligament (MCL) rupture is a compound injury that can be associated with meniscal tears.

Purpose: To report the characteristics of meniscal tears in knees with isolated ACL versus combined ACL and MCL injuries, analyzing their frequency, distribution by site, and lesion type.

Study Design: Cross-sectional study; Level of evidence, 3.

Real-World Outcomes After Switch From Aflibercept to Faricimab in Eyes With Diabetic Macular Edema.

Purpose: To assess the anatomic and functional outcomes in eyes with diabetic macular edema (DME) switched from intravitreal aflibercept to faricimab in a real-world setting.

Methods: Retrospective, interventional consecutive case series. Patients with DME were switched from aflibercept to faricimab and categorized based on central subfield thickness (CST) 4 weeks after last aflibercept injection into responding DME (rDME, CST reduction >20% or CST ≤ 250 µm) and nonresponding DME (nrDME, CST unchanged or increased).

Unsupervised inter-domain transformation for virtually stained high-resolution mid-infrared photoacoustic microscopy using explainable deep learning.

Mid-infrared photoacoustic microscopy can capture biochemical information without staining. However, the long mid-infrared optical wavelengths make the spatial resolution of photoacoustic microscopy significantly poorer than that of conventional confocal fluorescence microscopy. Here, we demonstrate an explainable deep learning-based unsupervised inter-domain transformation of low-resolution unlabeled mid-infrared photoacoustic microscopy images into confocal-like virtually fluorescence-stained high-resolution images.

Total synthesis and target identification of marine cyclopiane diterpenes.

Marine cyclopianes are a family of diterpenoid with novel carbon skeleton and diverse biological activities. Herein, we report our synthetic and chemical proteomics studies of cyclopiane diterpenes which culminate in the asymmetric total synthesis of conidiogenones C, K and 12β-hydroxy conidiogenone C, and identification of Immunity-related GTPase family M protein 1 (IRGM1) as a cellular target. Our asymmetric synthesis commences from Wieland-Miescher ketone and features a sequential intramolecular Pauson-Khand reaction and gold-catalyzed Nazarov cyclization to rapidly construct the 6-5-5-5 tetracyclic skeleton.

Evaluation of an assistive exosuit for alleviating neck and shoulder muscle fatigue during prolonged flexed neck posture.

Introduction: Neck pain affects 203 million people globally and is prevalent in various settings due to factors like poor posture, lack of exercise, and occupational hazards. Therefore, addressing ergonomic issues with solutions like a wearable robotic device is crucial. This research presents a novel assistive exosuit, characterized by its slim and lightweight structure and intuitive control without the use of hands, designed to mitigate muscle fatigue in the neck and shoulders during prolonged flexed neck posture.

Yes, We Can! Ensuring That our Graduating Resident's Procedural Skills Meet the Needs of Their Patients.

Objectives: There is a burgeoning discrepancy between the procedural competency of graduating diagnostic radiology residents and the needs of our patient population. The causes of this mismatch and opportunities for improvement are explored by the APDR Procedural Competency of Graduating DR Residents Task Force.

Materials And Methods: The APDR convened a task force consisting of diverse broad stakeholder viewpoints, drawing from organized radiology, academic and private practices.

Neural markers of error processing relate to task performance, but not to substance-related risks and problems and externalizing problems in adolescence and emerging adulthood.

Detecting errors and adapting behavior accordingly constitutes an integral aspect of cognition. Previous studies have linked neural correlates of error processing (e.g.

First Clinical Application of Aztreonam-Avibactam in Treating Carbapenem-Resistant Enterobacterales: Insights from Therapeutic Drug Monitoring and Pharmacokinetic Simulations.

: A novel fixed combination of aztreonam (ATM) and avibactam (AVI) offers promising potential to treat infections with carbapenem-resistant (CRE) producing metallo-β-lactamases (MBL). This study aimed to assess the accuracy of population pharmacokinetic (PK) models for ATM-AVI in predicting in vivo concentrations in a critically ill patient with CRE infection during its first clinical use. : A 70-year-old male with septic shock due to hospital-acquired pneumonia (HAP) caused by MBL-producing was treated with ATM-AVI.

Role of Altmetric Attention Scores in Evaluating the Influence of Spine Surgery Research.

Study Design: Retrospective cohort.

Objective: To analyze the annual trends in the most prevalent topics, journals, and geographic regions of the top 100 spine surgery articles, as determined by altmetric attention scores (AASs). We also describe the relationship between AAS and traditional article metrics.

Long-Term Risk of Acute Myocardial Infarction in Patients With a Transient Ischemic Attack: A Danish Nationwide Cohort Study.

Background: Sparse information regarding the long-term risk of acute myocardial infarction (MI) following a transient ischemic attack (TIA) emphasizes further research to guide preventive strategies and risk stratification in patients with a TIA.

Methods: We conducted a nationwide cohort study to investigate the 5-year risk of MI and all-cause mortality in patients with a first-time TIA. Patients with a first-time TIA were identified in the Danish Stroke Registry (2013-2020), matched on age, sex, and calendar year (1:4) with the general population and (1:1) with patients with first-time ischemic stroke.

Gadopiclenol: A q = 2 Gadolinium-Based MRI Contrast Agent Combining High Stability and Efficacy.

Objectives: Gadopiclenol is a q = 2 pyclen gadolinium-based contrast agent (GBCA) recently approved by the Food and Drug Administration, European Medicines Agency, and other European countries. The aim of this report is to demonstrate its stability in multiple stressed in vitro conditions and in vivo, in rat kidney, while maintaining its higher relaxivity compared with conventional GBCAs on the market.

Materials And Methods: Both gadopiclenol and its chemical precursor Pi828-Gd were characterized and compared with q = 1 gadolinium (Gd) complexes.

Prognostic Relevance of Relative Ellipsoid Zone Reflectivity for Ellipsoid Zone Loss in Macular Telangiectasia Type 2.

Purpose: The relative ellipsoid zone reflectivity (rEZR) is an innovative biomarker for photoreceptor alterations and showed association with disease staging in macular telangiectasia type 2 (MacTel). However, its prognostic relevance for the ellipsoid zone (EZ) loss is unclear.

Methods: Longitudinal spectral-domain optical coherence tomography (SD-OCT) imaging of patients with MacTel from an observational natural history study was used for en face determination of manifest EZ loss.

Penalizing underage alcohol use is associated with lower mortality for young drivers: Use/lose laws and their association with motor vehicle collision mortality.

Background: Motor vehicle collisions (MVC) continue to be a leading cause of mortality for youth in the United States. Since 2010, seven states have revoked mandatory laws that suspended licenses for underage alcohol use, also known as use/lose laws. This study analyzed whether each state's policy change was associated with increased youth MVC mortality.

In-depth analysis of active compounds targeting tropomyosin-related kinase A via constructed lipid raft @capillary monolith affinity chromatography.

In order to enrich the selection of biological ligands, realize the miniaturization analysis, and broaden the application of monolith materials for active ingredients screening and separating, we sough to construct a lipid raft @capillary monolith microcolumn affinity chromatography model. Single factor experiments and various characterization methods, including scanning electron microscopy (SEM) and thermogravimetric analysis, were employed to investigate the polymerization of the monolith column under different material ratios to determine optimal preparation conditions. Subsequently, the lipid raft from U251 cells was integrated with the monolith materials based on epoxy-based covalent crosslinking principle and characterized through SEM and immunofluorescence methods.

Optimizing regulatory frameworks for gene therapies in rare diseases: Challenges and solutions.

The advent of genetic medicines and advanced diagnostics has revolutionized the treatment landscape for rare diseases and, with over 10,000 identified conditions affecting millions globally, has the potential to improve many lives. Despite this progress, only 5% of rare diseases have FDA-approved therapies, highlighting a significant unmet need. This article examines the critical need for optimizing the regulatory environment to support the development and approval of gene therapies for rare and ultrarare diseases, which often face unique challenges due to their complexity in the midst of a rapidly evolving field.

Patient-Derived Xenografts of Triple-Negative Breast Cancer Enable Deconvolution and Prediction of Chemotherapy Responses.

Combination chemotherapy remains essential for clinical management of triple-negative breast cancer (TNBC). Consequently, responses to individual agents cannot be easily delineated at the single patient level, even though some patients might not require all drugs in the combination. Herein, we conduct multi-omic analyses of orthotopic TNBC patient-derived xenografts (PDXs) treated with single agent carboplatin, docetaxel, or the combination.

Lower socioeconomic status is correlated with worse outcomes after arthroscopic rotator cuff repair.

Background: Socioeconomic status has been recognized as a crucial social determinant of health influencing patient outcomes. Area Deprivation Index (ADI) is a validated measure of an area's socioeconomic status. Limited data exists on the impact of ADI and clinical outcomes and complications following rotator cuff repair (RCR).

Transcriptional profile of the rat cardiovascular system at single-cell resolution.

We sought to characterize cellular composition across the cardiovascular system of the healthy Wistar rat, an important model in preclinical cardiovascular research. We performed single-nucleus RNA sequencing (snRNA-seq) in 78 samples in 10 distinct regions, including the four chambers of the heart, ventricular septum, sinoatrial node, atrioventricular node, aorta, pulmonary artery, and pulmonary veins, which produced 505,835 nuclei. We identified 26 distinct cell types and additional subtypes, with different cellular composition across cardiac regions and tissue-specific transcription for each cell type.