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.

Hormone therapy enhances anti-PD1 efficacy in premenopausal estrogen receptor-positive and HER2-negative advanced breast cancer.

The efficacy of immunotherapy for estrogen receptor-positive/HER2-negative (ER+/HER2-) metastatic breast cancer (MBC) has not been proven. We conduct a phase 1b/2 trial to assess the efficacy of combining pembrolizumab (anti-PD1 antibody), exemestane (nonsteroidal aromatase inhibitor), and leuprolide (gonadotropin-releasing hormone agonist) for 15 patients with premenopausal ER+/HER2- MBC who had failed one to two lines of hormone therapy (HT) without chemotherapy. The primary endpoint of progression-free survival rate at 8 months (i.

Activation of Imprinted Gene Promotes Cardiac Fibrosis After Ischemic Injury.

Background: Cardiac fibrosis, characterized by excessive extracellular matrix (ECM) deposition in the myocardium, is an important target for heart disease treatments. (paternally expressed gene 3) is an imprinted gene expressed from the paternal allele, and de novo purine biosynthesis (DNPB) is a crucial pathway for nucleotide synthesis. However, the roles of PW1 and DNPB in ECM production by cardiac fibroblasts during myocardial ischemia are not yet understood.

Dexmedetomidine Regulates Macrophage Phenotype Remodeling Through AMPK/SIRT1 to Alleviate Inflammatory Mediators and Lung Injury.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality in the intensive care unit (ICU) and can cause excessive inflammation. Dexmedetomidine (DEX) is a drug that exerts anti-inflammatory effects. Identifying the anti-inflammatory mechanism of DEX in the context of ALI/ARDS possesses potential significance for the prevention and treatment of ARDS.

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.

Histogram analysis of advanced diffusion-weighted MRI models for evaluating the grade and proliferative activity of meningiomas.

Rationale And Objectives: To explore the value of diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), and mean apparent propagator (MAP) magnetic resonance imaging histogram analysis in evaluating the grade and proliferative activity of meningiomas.

Materials And Methods: A total of 134 meningioma patients were prospectively included and underwent magnetic resonance diffusion imaging. The whole-tumor histogram parameters were extracted from multiple functional maps.

Neuroprotective Effects of Rapid Local Ischemic Postconditioning in Successful Endovascular Thrombectomy Patients.

Background: We aim to assess the efficacy of rapid local ischemic postconditioning (RL-IPostC) following successful reperfusion in patients with acute ischemic stroke with anterior circulation large vessel occlusion who underwent endovascular thrombectomy.

Methods: We conducted an ambidirectional cohort study with 78 prospectively enrolled patients with RL-IPostC and endovascular thrombectomy and 129 retrospectively enrolled patients with endovascular thrombectomy. The RL-IPostC procedure involved 5 cycles of 15-s balloon inflation and deflation in the ipsilateral internal carotid artery.

Effects of Extracted Pulse Proteins on Lipid Targets for Cardiovascular Risk Reduction: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Many clinical practice guidelines recommend dietary pulses for the prevention and management of cardiovascular disease and diabetes. The impact of extracted pulse proteins remains unclear. We therefore conducted a systematic review and meta-analysis of randomized controlled trials of the effect of extracted pulse proteins on therapeutic lipid targets.

Progression Patterns and Risk Factors of Axial Elongation in Young Adults With Nonpathologic High Myopia: Three-Year Large Longitudinal Cohort Follow-Up.

Purpose: To investigate the progression patterns and risk factors of axial elongation in young adults with nonpathologic high myopia.

Design: Prospective, clinical observational cohort study with 2- to 4-year follow-up.

Methods: A total of 1043 eyes of 563 participants (3515 medical records) aged 18 to 50 years with nonpathologic high myopia (axial length [AL] ≥ 26 mm; myopic maculopathy < diffuse chorioretinal atrophy; without posterior staphyloma) were included from 1546 participants (6318 medical records).

Cataract Surgery and Incidence of Retinal Vascular Occlusion: Population-Based Cohort Study Using a Target Trial Emulation Framework.

Background: Previous studies suggested an association between cataract surgery and retinal vascular occlusion. However, the association may be attributable to detection bias because postoperative monitoring may be more frequent for those who receive cataract surgery than for those who do not.

Design: Population-based cohort study using target trial emulation framework.

Discovery of a mu-opioid receptor modulator that in combination with morphinan antagonists induces analgesia.

Morphinan antagonists, which block opioid effects at mu-opioid receptors, have been studied for their analgesic potential. Previous studies have suggested that these antagonists elicit analgesia with fewer adverse effects in the presence of the mutant mu-opioid receptor (MOR; S196A). However, introducing a mutant receptor for medical applications represents significant challenges.

CKB Promotes Mitochondrial ATP Production by Suppressing Permeability Transition Pore.

Creatine kinases are essential for maintaining cellular energy balance by facilitating the reversible transfer of a phosphoryl group from ATP to creatine, however, their role in mitochondrial ATP production remains unknown. This study shows creatine kinases, including CKMT1A, CKMT1B, and CKB, are highly expressed in cells relying on the mitochondrial F1F0 ATP synthase for survival. Interestingly, silencing CKB, but not CKMT1A or CKMT1B, leads to a loss of sensitivity to the inhibition of F1F0 ATP synthase in these cells.

Smooth Muscle Ythdf2 Abrogation Ameliorates Pulmonary Vascular Remodeling by Regulating Myadm Transcript Stability.

Background: The N6-methyladenosine (mA) modification of RNA and its regulators have important roles in the pathogenesis of pulmonary hypertension (PH). (YTH N6-methyladenosine RNA binding protein 2) is best known for its role in degrading mA-modified mRNAs such as mRNA, which leads to alternative activation of macrophages in PH. Recent studies have also linked to the proliferation of pulmonary artery smooth muscle cells (PASMCs).

Efficacy of Voluntary Medical Male Circumcision to Prevent HIV Infection Among Men Who Have Sex With Men : A Randomized Controlled Trial.

Background: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this.

Objective: To assess the efficacy of VMMC in preventing incident HIV infection among MSM.

Protocol to develop a moisture-desorptive passive cooling system for electronics thermal management.

Passive thermal management with zero-energy consumption and high compactness has drawn increasing attention. Here, we present a protocol to develop a hygroscopic salt-loaded heat sink with a moisture-permeable membrane encapsulation technique for electronics cooling. We describe steps for preparing lithium bromide solution and heat sink with anti-corrosion graphene coating.

Long-term Risks of Cirrhosis and Hepatocellular Carcinoma Across Steatotic Liver Disease Subtypes.

Introduction: The prospective study aimed to investigate the long-term associated risks of cirrhosis and hepatocellular carcinoma (HCC) across various subtypes of steatotic liver disease (SLD).

Methods: We enrolled 332,175 adults who participated in a health screening program between 1997 and 2013. Participants were categorized into various subtypes, including metabolic dysfunction-associated SLD (MASLD), MASLD with excessive alcohol consumption (MetALD), and alcohol-related liver disease (ALD), based on ultrasonography findings, alcohol consumption patterns, and cardiometabolic risk factors.

Diagnostic Performance of Carotid Ring Sign on CT-Angiography in Internal Carotid True Occlusion.

Background: To differentiate between pseudo occlusion (PO) and true occlusion (TO) of internal carotid artery (ICA) is important in thrombectomy treatment planning for patients with acute ischemic stroke. Although delayed contrast filling has been differentiated carotid PO from TO, its application has been limited by the implementations of multiphasic computed tomography angiography. In this study, we hypothesized that carotid ring sign, which is readily acquired from single-phasic CTA, can sufficiently differentiate carotid TO from PO.

Hypermethylation Loci of ZNF671, IRF8, and OTX1 as Potential Urine-Based Predictive Biomarkers for Bladder Cancer.

Bladder cancer (BCa) is a significant health issue and poses a healthcare burden on patients, highlighting the importance of an effective detection method. Here, we developed a urine DNA methylation diagnostic panel for distinguishing between BCa and non-BCa. In the discovery stage, an analysis of the TCGA database was conducted to identify BCa-specific DNA hypermethylation markers.

Intravenous Alteplase Versus Best Medical Therapy for Patients With Minor Stroke: A Systematic Review and Meta-Analysis.

Background: The efficacy of thrombolysis (IVT) in minor stroke (National Institutes of Health Stroke Scale score, 0-5) remains inconclusive. The aim of this study is to compare the effectiveness and safety of IVT with best medical therapy (BMT) by means of a systematic review and meta-analysis of randomized controlled trials and observational studies.

Methods: We searched the PubMed, Embase, Cochrane Library, and Web of Science databases to obtain articles related to IVT in minor stroke from inception until August 10, 2023.