Sex-Specific Clinical and Genetic Factors Associated With Adverse Outcomes in Hypertrophic Cardiomyopathy.

Background: Females with hypertrophic cardiomyopathy present at a more advanced stage of the disease and have a higher risk of heart failure and death. The factors behind these differences are unclear. We aimed to investigate sex-related differences in clinical and genetic factors affecting adverse outcomes in the Sarcomeric Human Cardiomyopathy Registry.

A first-in-human study of JNJ-70218902, a bispecific T-cell-redirecting antibody against TMEFF2 in metastatic castration-resistant prostate cancer.

Background: Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis, necessitating the investigation of novel treatments and targets. This study evaluated JNJ-70218902 (JNJ-902), a T-cell redirector targeting transmembrane protein with epidermal growth factor-like and 2 follistatin-like domains 2 (TMEFF2) and cluster of differentiation 3, in mCRPC.

Patients And Methods: Patients who had measurable/evaluable mCRPC after at least one novel androgen receptor-targeted therapy or chemotherapy were eligible.

Integration of Deep Learning and Sub-regional Radiomics Improves the Prediction of Pathological Complete Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Patients.

Rationale And Objectives: The precise prediction of response to neoadjuvant chemoradiotherapy is crucial for tailoring perioperative treatment in patients diagnosed with locally advanced rectal cancer (LARC). This retrospective study aims to develop and validate a model that integrates deep learning and sub-regional radiomics from MRI imaging to predict pathological complete response (pCR) in patients with LARC.

Materials And Methods: We retrospectively enrolled 768 eligible participants from three independent hospitals who had received neoadjuvant chemoradiotherapy followed by radical surgery.

Dietary-Lifestyle Patterns and Colorectal Cancer Risk: Global Cancer Update Programme (CUP Global) Systematic Literature Review.

Background: While healthy dietary and lifestyle factors have been individually linked to lower colorectal cancer (CRC) risks, recommendations for whole diet-lifestyle patterns remained unestablished due to limited studies and inconsistent pattern definitions.

Objective: This updated review synthesized literature on dietary-lifestyle patterns and CRC risk/mortality.

Methods: PubMed and Embase were searched through 31 March 2023 for randomized controlled trials and prospective cohort studies examining adulthood dietary patterns combined with modifiable lifestyle factors such as adiposity, smoking, alcohol consumption, physical activity, and/or others.

Biomechanical Outcomes of Glenoid Bone Graft Fixation Techniques: A Systematic Review.

Background: The Latarjet and other bony augmentation procedures are commonly used to treat anterior shoulder instability in the setting of significant glenoid bone loss. Although several fixation strategies have been reported, the biomechanical strength of these techniques remains poorly understood.

Purpose: To perform a systematic review of the biomechanical strength of glenoid bony augmentation procedures for anterior shoulder instability.

Maximizing the clinical utility and performance of cytology samples for comprehensive genetic profiling.

Comprehensive molecular profiling by next-generation sequencing has revolutionized tumor classification and biomarker evaluation. However, routine implementation is challenged by the scant nature of diagnostic material obtained through minimally invasive procedures. Here, we describe our long-term experience in profiling cytology samples with an in-depth assessment of the performance, quality metrics, biomarker identification capabilities, and potential pitfalls.

Incorporating Economic Evidence in Clinical Guidelines: A Framework From the Clinical Guidelines Committee of the American College of Physicians.

In recognition of accelerating health care spending and alignment with the American College of Physicians (ACP) principles of promoting high-value care, the ACP Clinical Guidelines Committee (CGC) developed a framework to standardize its approach to identifying, appraising, and considering economic evidence in the development of ACP clinical guidelines. This article presents the CGC's process for incorporating economic evidence, which encompasses cost-effectiveness analyses, economic outcomes in randomized controlled trials, and resource utilization (intervention cost) data. Economic evidence is one component of ACP recommendations.

Novel Naphthyridones Targeting Pannexin 1 for Colitis Management.

Pannexin 1 (PANX1) forms cell-surface channels capable of releasing signaling metabolites for diverse patho-physiological processes. While inhibiting dysregulated PANX1 has been proposed as a therapeutic strategy for many pathological conditions, including inflammatory bowel disease (IBD), low efficacy, or poor specificity of classical PANX1 inhibitors introduces uncertainty for their applications in basic and translational research. Here, hit-to-lead optimization is performed and a naphthyridone, compound 12, is identified as a new PANX1 inhibitor with an IC of 0.

Multimodal Deep Learning Fusing Clinical and Radiomics Scores for Prediction of Early-Stage Lung Adenocarcinoma Lymph Node Metastasis.

Rationale And Objectives: To develop and validate a multimodal deep learning (DL) model based on computed tomography (CT) images and clinical knowledge to predict lymph node metastasis (LNM) in early lung adenocarcinoma.

Materials And Methods: A total of 724 pathologically confirmed early invasive lung adenocarcinoma patients were retrospectively included from two centers. Clinical and CT semantic features of the patients were collected, and 3D radiomics features were extracted from nonenhanced CT images.

Radiomics of Periprostatic Fat and Tumor Lesion Based on MRI Predicts the Pathological Upgrading of Prostate Cancer from Biopsy to Radical Prostatectomy.

Rationale And Objectives: To assess the predictive value of MRI-based radiomics of periprostatic fat (PPF) and tumor lesions for predicting Gleason score (GS) upgrading from biopsy to radical prostatectomy (RP) in prostate cancer (PCa).

Methods: A total of 314 patients with pathologically confirmed prostate cancer (PCa) after radical prostatectomy (RP) were included in the study. The patients were randomly assigned to the training cohort (n = 157) and the validating cohort (n = 157) in a 1:1 ratio.

Characterization and Safety Evaluation of Autoclaved Gut Commensal RV-01.

Gut commensals play important roles in maintaining the homeostasis of human health. Previous studies indicated that the abundance of in animal hosts was increased by the administration of prebiotics such as polysaccharides purified from iconic oriental medicinal fungi. Subsequently, was found to exert beneficial effects on the amelioration of multiple chronic inflammation-associated diseases.

Estimating the public economic gains in Taiwan from in vitro fertilization (IVF) subsidy changes implemented in 2021.

Study Question: What is the governmental fiscal impact of a new assisted reproduction subsidy scheme based on projected lifetime net taxes attributed to resulting live births in Taiwan?

Summary Answer: We estimate that the new fertility reimbursement scheme has generated favorable lifetime fiscal gains for the Taiwanese government, resulting in a return on investment (ROI) of NT$5.6 for every NT$1.0 spent based on those families receiving public subsidies for fertility care under the new scheme.

A programmable, open-source robot that scratches cultured tissues to investigate cell migration, healing, and tissue sculpting.

Despite the widespread popularity of the "scratch assay," where a pipette is dragged manually through cultured tissue to create a gap to study cell migration and healing, it carries significant drawbacks. Its heavy reliance on manual technique can complicate quantification, reduce throughput, and limit the versatility and reproducibility. We present an open-source, low-cost, accessible, robotic scratching platform that addresses all of the core issues.

Elevated Donor-Derived Cell-Free DNA Levels Are Associated With Reduced Myocardial Blood Flow but Not Angiographic Cardiac Allograft Vasculopathy: The EVIDENT Study.

Background: Cardiac allograft vasculopathy (CAV) leads to impaired myocardial blood flow (MBF), increasing the risk of cardiovascular death or retransplant among heart transplantation (HT) recipients. Data on elevation in donor-derived cell-free DNA (dd-cfDNA) and CAV in the absence of rejection are mixed. We sought to test the hypothesis that CAV with reduced MBF (RMBF) is associated with elevated dd-cfDNA.

β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain.

Loss of proteostasis is a hallmark of aging and Alzheimer disease (AD). We identify β-hydroxybutyrate (βHB), a ketone body, as a regulator of protein solubility. βHB primarily provides ATP substrate during periods of reduced glucose availability, and regulates other cellular processes through protein interactions.

Peli1 Deficiency in Macrophages Attenuates Pulmonary Hypertension by Enhancing Foxp1-Mediated Transcriptional Inhibition of IL-6.

Background: The infiltration of macrophages into the lungs is a common characteristic of perivascular inflammation, contributing to vascular remodeling in pulmonary hypertension (PH). Peli1 (pellino E3 ubiquitin-protein ligase 1) plays a critical role in regulating the production of proinflammatory cytokines and the polarization of macrophages in various diseases. However, the role of Peli1 in PH remains to be investigated.

Middle Meningeal Artery Embolization for Nonacute Subdural Hematoma.

Background: The effect of embolization of the middle meningeal artery in patients with subacute or chronic subdural hematoma is uncertain.

Methods: We performed a multicenter, open-label, randomized trial in China, involving patients with symptomatic nonacute subdural hematoma with mass effect. Patients were assigned to undergo burr-hole drainage or receive nonsurgical treatment at the surgeon's discretion, and patients in each group were then randomly assigned, in a 1:1 ratio, to undergo middle meningeal artery embolization with liquid embolic material or to receive usual care.

Releasing a sugar brake generates sweeter tomato without yield penalty.

In tomato, sugar content is highly correlated with consumer preferences, with most consumers preferring sweeter fruit. However, the sugar content of commercial varieties is generally low, as it is inversely correlated with fruit size, and growers prioritize yield over flavour quality. Here we identified two genes, tomato (Solanum lycopersicum) calcium-dependent protein kinase 27 (SlCDPK27; also known as SlCPK27) and its paralogue SlCDPK26, that control fruit sugar content.

A randomized, placebo-controlled first-in-human study of oral TQS-168 in healthy volunteers: Assessment of safety, tolerability, pharmacokinetics, pharmacodynamics, and food effect.

TQS-168, a first-in-class small-molecule inducer of peroxisome proliferator-activated receptor gamma coactivator 1-alpha gene expression, is in development for the treatment of amyotrophic lateral sclerosis. A single-ascending-dose (SAD) and multiple-ascending-dose (MAD) study of TQS-168 was carried out in healthy male subjects to investigate safety, tolerability, pharmacokinetics (PK), food effect, and preliminary pharmacodynamic effects (PD). Since solubility enhancement could be beneficial, assessment of three formulations was incorporated into the study using an integrated rapid manufacturing and clinical testing approach.

Modulating metal-centered dimerization of a lanthanide chaperone protein for separation of light lanthanides.

Elucidating details of biology's selective uptake and trafficking of rare earth elements, particularly the lanthanides, has the potential to inspire sustainable biomolecular separations of these essential metals for myriad modern technologies. Here, we biochemically and structurally characterize () LanD, a periplasmic protein from a bacterial gene cluster for lanthanide uptake. This protein provides only four ligands at its surface-exposed lanthanide-binding site, allowing for metal-centered protein dimerization that favors the largest lanthanide, La.

Observation of the decay.

Using proton-proton collision data corresponding to an integrated luminosity of collected by the CMS experiment at , the decay is observed for the first time, with a statistical significance exceeding 5 standard deviations. The relative branching fraction, with respect to the decay, is measured to be , where the first uncertainty is statistical, the second is systematic, and the third is related to the uncertainties in and .

Arthroscopy Patients in Medicare Population Became Sicker While Reimbursement Decreased From 2013 to 2020.

Purpose: To assess surgeon reimbursement for common arthroscopic procedures, including arthroscopic meniscal debridement and arthroscopic rotator cuff repair, in patients with differing risk profiles within the Medicare population.

Methods: A publicly available Medicare database was used to identify all cases of arthroscopic meniscal debridement and arthroscopic rotator cuff repair procedures billed to Medicare from 2013 to 2020. The surgeon reimbursement from Medicare was collected and adjusted for inflation.