Dissecting the Binding Affinity of Anti-SARS-CoV-2 Compounds to Human Transmembrane Protease, Serine 2: A Computational Study.

The human transmembrane protease, serine 2 (TMPRSS2), essential for SARS-CoV-2 entry, is a key antiviral target. Here, we computationally profiled the TMPRSS2-binding affinities of 15 antiviral compounds. Molecular dynamics (MD) simulations for the docked complexes revealed that three compounds exited the substrate-binding cavity (SBC), suggesting noncompetitive inhibition.

Luminescence Properties of Hoechst 33258 in Polyvinyl Alcohol Films.

We report a comprehensive investigation of the photophysical properties of Hoechst 33258 (HOE) embedded in polyvinyl alcohol (PVA) films. HOE displays a bright, highly polarized, blue fluorescence emission centered at 430 nm, indicating effective immobilization within the polymer matrix of PVA. Its fluorescence quantum yield is notably high (~0.

Neoadjuvant Chemotherapy for T3 Tumors in the Era of Precision Medicine-Biology Is Still King.

Clinical T3 (cT3) breast cancer (BC) presents a challenge for achieving cosmetically acceptable breast conservation, and neoadjuvant chemotherapy (NAC) is commonly used for cytoreduction in these high-risk cancers. MammaPrint risk-of-recurrence and BluePrint molecular subtyping genomic signatures have demonstrated high accuracy in predicting chemotherapy benefits. Here, we examined the utility of MammaPrint/BluePrint for predicting pathological Complete Response (pCR) rates to NAC among 404 patients diagnosed with cT3 early-stage BC.

Targeting Metabolic and Epigenetic Vulnerabilities in Glioblastoma with SN-38 and Rabusertib Combination Therapy.

Glioblastoma (GBM), the most prevalent primary malignant brain tumor, remains challenging to treat due to extensive inter- and intra-tumor heterogeneity. This variability demands combination treatments to improve therapeutic outcomes. A significant obstacle in treating GBM is the expression of O-methylguanine-DNA methyltransferase, a DNA repair enzyme that reduces the efficacy of the standard alkylating agent, temozolomide, in about 50% of patients.

Surgical Outcomes and Associated Morbidity of Active and Expectant Management of Second-Trimester Placenta Accreta Spectrum (PAS).

Management of second-trimester placenta accreta spectrum (PAS) is currently center-dependent with minimal evidence-based practices. This study aims to analyze outcomes of hysterectomy as second-trimester active management (AM) versus cesarean hysterectomy as expectant management (EM) in cases of PAS with intraoperative and postoperative outcomes. This study is a retrospective case-control study of patients with a pathology-confirmed diagnosis of PAS managed at a single center over 16 years (2005-2020).

Research Progress and Clinical Translation Potential of Coronary Atherosclerosis Diagnostic Markers from a Genomic Perspective.

Coronary atherosclerosis (CAD) is characterized by arterial intima lipid deposition, chronic inflammation, and fibrous tissue proliferation, leading to arterial wall thickening and lumen narrowing. As the primary cause of coronary heart disease and acute coronary syndrome, CAD significantly impacts global health. Recent genetic studies have demonstrated CAD's polygenic and multifactorial nature, providing molecular insights for early diagnosis and risk assessment.

Management and Outcome of Invasive Clindamycin-Resistant MRSA Community-Associated Infections in Children.

Background: Clindamycin resistance among community-associated methicillin-resistant (CA-MRSA) complicates the management of a challenging infection. Little data exist to guide clinicians in the management of invasive clindamycin-resistant CA-MRSA infections in children and studies using oral regimens such as trimethoprim-sulfamethoxazole (TMP-SMX) and linezolid for treatment of these infections are limited. We sought to reevaluate antibiotic management among invasive CA-MRSA at a tertiary children's hospital.

Age-Related Changes in Gut Health and Behavioral Biomarkers in a Beagle Dog Population.

The gut and the gut microbiome communicate with the nervous system through the gut-brain axis via neuroimmune and neuroendocrine mechanisms. Despite existing research, studies exploring this link in aging dogs are limited. This study aims to examine multiple blood and fecal biomarkers of intestinal health, along with various behavioral indicators based on saliva, blood, observations, and activity, in different age populations (junior: <2 y.

A Review of Neoadjuvant Therapy for Localized and Locally Advanced Renal Cell Carcinoma.

The introduction of vascular endothelial growth factor receptor-tyrosine kinases (VEGFR-TKIs) and immune checkpoint inhibitors (IOs) have drastically altered the treatment landscape for kidney cancer, with doublet combination immunotherapy (IO/IO or IO/VEGFR-TKI) now set as the standard front-line treatment for advanced renal cell carcinoma (RCC). However, the roles of VEGFR-TKIs and IOs in the neoadjuvant setting for locoregional/locally advanced RCC remain undefined, where the goals may be primary tumor downsizing/downstaging and potentially eradicating micrometastatic disease. This review will examine VEGFR-TKI monotherapy, IO monotherapy, and VEGFR-TKI/IO combination regimens in a preoperative setting with a focus on the efficacy, toxicity, surgical, and long-term implications.

The Clinical Utility of a Next-Generation Sequencing-Based Approach to Detecting Circulating HPV DNA in Patients with Advanced Anal Cancer.

Background: To extend the practicality of liquid biopsy beyond the historical HPV circulating tumor DNA (ctDNA) assays, we evaluated the clinical relevance of a novel next-generation sequencing HPV ctDNA assay in patients with locally advanced and metastatic squamous cell cancer of the anal canal (mSCCA).

Methods: ctDNA isolated from the plasma of patients with mSCCA was sequenced using a 1.4 Mb hybrid-capture target-enrichment panel covering the whole genome sequences of all 193 HPV types.

Activation of Genes by Nuclear Receptor/Specificity Protein (Sp) Interactions in Cancer.

The human nuclear receptor (NR) superfamily consists of 48 genes that are ligand-activated transcription factors that play a key role in maintaining cellular homeostasis and in pathophysiology. NRs are important drug targets for both cancer and non-cancer endpoints as ligands for these receptors can act as agonists, antagonists or inverse agonists to modulate gene expression. With two exceptions, the classical mechanism of action of NRs involves their interactions as monomers, dimers or heterodimers with their cognate response elements (cis-elements) in target gene promoters.

DNA Methylation Profile in Buffy Coat Identifies Methylation Differences Between Cirrhosis with and Without Hepatocellular Carcinoma.

Background/objectives: Cirrhosis is the precursor to most cases of hepatocellular carcinoma (HCC). Understanding the mechanisms leading to the transition from cirrhosis to HCC and identifying key biomarkers is crucial to developing effective screening strategies and reducing HCC-related mortality. DNA methylation is associated with gene inactivation and plays an important role in physiological and pathological processes; however, its role in cirrhosis progression to HCC is unknown.

Spatial Distribution of Tumor Cells in Clear Cell Renal Cell Carcinoma Is Associated with Metastasis and a Matrisome Gene Expression Signature.

Predicting the behavior of clear cell renal cell carcinoma (ccRCC) is challenging using standard-of-care histopathologic examination. Indeed, pathologic RCC tumor grading, based on nuclear morphology, performs poorly in predicting outcomes of patients with International Society of Urological Pathology/World Health Organization grade 2 and 3 tumors, which account for most ccRCCs. We applied spatial point process modeling of H&E-stained images of patients with grade 2 and grade 3 ccRCCs ( = 72) to find optimum separation into two groups.

A Multidisciplinary Approach to Diagnosing Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): Practical Recommendations and Insights from Countries of the Gulf Cooperation Council.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive orphan hematopoietic malignancy characterized by cutaneous and systemic hematologic involvement. BPDCN is frequently misidentified, but early, accurate diagnosis is critical to extending patient survival using tagraxofusp, a first-in-class CD123-targeted therapy, and increasing their chances of receiving a potentially curative stem cell transplantation. Cases of BPDCN in countries of the Gulf Cooperation Council are lower than the extrapolated incidence from other geographic locations due to lack of awareness of key diagnostic features, lack of consensus on the minimal phenotype for diagnosis, and lack of local immunohistochemistry testing facilities, contributing to underdiagnosis in this region.

An Updated Systematic Review and Network Meta-Analysis of First-Line Triplet vs. Doublet Therapies for Metastatic Hormone-Sensitive Prostate Cancer.

: The addition of androgen receptor pathway inhibitors (ARPIs) to androgen deprivation therapy (ADT), with or without docetaxel (Doc), is currently recommended for metastatic, hormone-sensitive prostate cancer (mHSPC). Recently, the ARANOTE trial evaluated the efficacy and safety of Darolutamide + ADT in this setting. We aimed to update a network meta-analysis (NMA) of these combination therapies.

Genetic Variations in Gene Contribute to Renal Cell Carcinoma Susceptibility: A Genotype-Phenotype Correlation Study.

Background: This study aimed to investigate the polymorphic genotypes of rs937282, rs937283, rs2279744, and rs769412, as well as the combined effects of genotypes and environmental factors on RCC susceptibility.

Methods: A total of 135 RCC patients and 590 controls were recruited for genotyping using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Quantitative PCR was performed to assess MDM2 mRNA levels among 30 healthy individuals and 22 RCC patients.

SSTR2-Targeted Theranostics in Hepatocellular Carcinoma.

Background: While the clinical use of radiolabeled somatostatin analogs is well established in neuroendocrine tumors, there is growing interest in expanding their application to other somatostatin receptor 2 (SSTR2)-expressing cancers. This study investigates the potential utility of SSTR2-targeted theranostics in hepatocellular carcinoma (HCC).

Methods: SSTR2 expression in HCC cell lines and clinical samples was evaluated using qRT-PCR, Western blot analysis, and a public dataset.

Artificial Intelligence in Pediatric Electrocardiography: A Comprehensive Review.

Artificial intelligence (AI) is revolutionizing healthcare by offering innovative solutions for diagnosis, treatment, and patient management. Only recently has the field of pediatric cardiology begun to explore the use of deep learning methods to analyze electrocardiogram (ECG) data, aiming to enhance diagnostic accuracy, expedite workflows, and improve patient outcomes. This review examines the current state of AI-enhanced ECG interpretation in pediatric cardiology applications, drawing insights from adult AI-ECG research given the progress in this field.

Artificial Intelligence in Fetal and Pediatric Echocardiography.

Echocardiography is the main modality in diagnosing acquired and congenital heart disease (CHD) in fetal and pediatric patients. However, operator variability, complex image interpretation, and lack of experienced sonographers and cardiologists in certain regions are the main limitations existing in fetal and pediatric echocardiography. Advances in artificial intelligence (AI), including machine learning (ML) and deep learning (DL), offer significant potential to overcome these challenges by automating image acquisition, image segmentation, CHD detection, and measurements.

Rat Sarcoma Virus Family Genes in Acute Myeloid Leukemia: Pathogenetic and Clinical Implications.

Acute myeloid leukemias (AMLs) comprise a group of genetically heterogeneous hematological malignancies that result in the abnormal growth of leukemic cells and halt the maturation process of normal hematopoietic stem cells. Despite using molecular and cytogenetic risk classification to guide treatment decisions, most AML patients survive for less than five years. A deeper comprehension of the disease's biology and the use of new, targeted therapy approaches could potentially increase cure rates.

Direct-Acting Oral Anticoagulants in the Management of Cerebral Venous Sinus Thrombosis-Where Do We Stand?

Background: Cerebral venous sinus thrombosis (CVT) is a rare cause of stroke, constituting 0.5-3% of all strokes with an extremely varied spectrum of presentation, predisposing factors, neuroimaging findings, and eventual outcomes. A high index of suspicion is needed because timely diagnosis can significantly alter the natural course of the disease, reduce acute complications, and improve long-term outcomes.

A Narrative Review of Prognostic Gene Signatures in Oral Squamous Cell Carcinoma Using LASSO Cox Regression.

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies of the head and neck squamous cell carcinoma (HNSCC). HNSCC is recognized as the eighth most commonly occurring cancer globally in men. It is essential to distinguish between cancers arising in the head and neck regions due to significant differences in their etiologies, treatment approaches, and prognoses.

Circulating Isthmin-1 Levels and Their Relationship with Diabetes and Metabolic Diseases in Kuwaiti Adults.

Obesity and type 2 diabetes (T2D) are associated with significant alterations in various metabolic biomarkers. Isthmin-1 (Ism1) has recently emerged as a potential marker of metabolic health and was shown in animal studies to associate with metabolic-associated fatty liver disease (MAFLD). In this study, we aimed to investigate the circulatory levels of Ism1 in individuals with obesity compared to non-obese individuals and evaluate their association with insulin resistance, MAFLD, and T2D.

Transcriptomic Profile Analysis of Brain Tissue in the Absence of Functional TRPM8 Calcium Channel.

Transient Receptor Potential Melastatin 8 (TRPM8) is a non-selective, Ca-permeable cation channel involved in thermoregulation and other physiological processes, such as basal tear secretion, cell differentiation, and insulin homeostasis. The activation and deactivation of TRPM8 occur through genetic modifications, channel interactions, and signaling cascades. Recent evidence suggests a significant role of TRPM8 in the hypothalamus and amygdala related to pain sensation and sexual behavior.

Prolonged Cardiopulmonary Bypass Time-Induced Endothelial Dysfunction via Glypican-1 Shedding, Inflammation, and Matrix Metalloproteinase 9 in Patients Undergoing Cardiac Surgery.

Objectives: A prolonged cardiopulmonary bypass (CPB) time of over 180 min is linked to poorer outcomes and higher mortality in cardiac surgery. This study examines how glypican-1 shedding, matrix metallopeptidase 9 (MMP9), and the pro-inflammatory cytokine IL-1β may contribute to endothelial dysfunction in patients undergoing on-pump surgery with an extended CPB.

Methods: Fifty-one patients undergoing cardiac surgical procedures were divided into two groups based on the intraoperative CPB duration: (i) normal CPB (<180 min, = 23) and (ii) prolonged CPB (>180 min, = 28).