Cardiovascular Events Associated with CDK4/6 Inhibitors: A Safety Meta-Analysis of Randomized Controlled Trials and a Pharmacovigilance Study of the FAERS Database.

Background: CDK4/6 inhibitors are highly valued, but the incidence of cardiovascular adverse events (CVAEs) associated with CDK4/6 inhibitors is not clear.

Objective: Our aim was therefore to assess the risk of developing CVAEs associated with CDK4/6 inhibitors, by conducting a systematic review and meta-analysis of randomized controlled trials (RCTs), along with a pharmacovigilance study of the FDA Adverse Event Reporting System (FAERS) database.

Methods: Eligible CVAEs were extracted from the ClinicalTrials.

Surgical technique for complicated preauricular sinus: Pilot study of double elliptical excision with coaptation suture.

Objectives: Preauricular sinus (PAS) is a congenital anomaly that can progress to complicated cases with granulation tissue around the PAS area due to skin inflammation. Treatment involves incision and drainage or continuous dressing; however, surgical treatment may be necessary. We evaluated a surgical method for the effective treatment of complicated PAS.

Development of potent antibody drug conjugates against ICAM1 cancer cells in preclinical models of cholangiocarcinoma.

As a highly lethal adenocarcinoma of the hepatobiliary system, outcomes for cholangiocarcinoma (CCA) patients remain prominently poor with a 5-year survival of <10% due to the lack of effective treatment modalities. Targeted therapeutics for CCA are limited and surgical resection of CCA frequently suffers from a high recurrence rate. Here we report two effective targeted therapeutics in this preclinical study for CCA.

Discordance of HER2 Expression and/or Amplification on Repeat Testing.

We sought to assess discordance of HER2 status in patients with HER2-amplified/expressing solid tumors who underwent reevaluation of HER2 status. Patients with metastatic solid tumors and HER2 expression by IHC or amplification by FISH/next-generation sequencing on local testing underwent central HER2 IHC/FISH testing with either archival or fresh biopsies and were evaluated for discordance in HER2 status. 70 patients (12 cancer types) underwent central HER2 reevaluation, including 57 (81.

Tinea Capitis in Children Younger than Two Years Old: A Retrospective Study and Treatment Recommendations.

Background: Tinea capitis (TC) is a dermatophytosis of the scalp and hair, which occurs less common in children younger than two years of age, and the data of TC in this age group are still unknown.

Objectives: We aimed to reveal the epidemiological, clinical and mycological characteristics of TC in children under two years old.

Methods: We retrospectively analyzed all reported cases of TC in children in their first two years of life from 1991 to 2022, by searching PubMed, Embase, Web of Science, CNKI, Wanfang and Weipu databases.

Development of intravenously administered synthetic RNA virus immunotherapy for the treatment of cancer.

The therapeutic effectiveness of oncolytic viruses (OVs) delivered intravenously is limited by the development of neutralizing antibody responses against the virus. To circumvent this limitation and to enable repeated systemic administration of OVs, here we develop Synthetic RNA viruses consisting of a viral RNA genome (vRNA) formulated within lipid nanoparticles. For two Synthetic RNA virus drug candidates, Seneca Valley virus (SVV) and Coxsackievirus A21, we demonstrate vRNA delivery and replication, virus assembly, spread and lysis of tumor cells leading to potent anti-tumor efficacy, even in the presence of OV neutralizing antibodies in the bloodstream.

Quantitative immunopeptidomics reveals a tumor stroma-specific target for T cell therapy.

T cell receptor (TCR)-based immunotherapy has emerged as a promising therapeutic approach for the treatment of patients with solid cancers. Identifying peptide-human leukocyte antigen (pHLA) complexes highly presented on tumors and rarely expressed on healthy tissue in combination with high-affinity TCRs that when introduced into T cells can redirect T cells to eliminate tumor but not healthy tissue is a key requirement for safe and efficacious TCR-based therapies. To discover promising shared tumor antigens that could be targeted via TCR-based adoptive T cell therapy, we employed population-scale immunopeptidomics using quantitative mass spectrometry across ~1500 tumor and normal tissue samples.

ADAM9-Responsive Mesoporous Silica Nanoparticles for Targeted Drug Delivery in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) has the worst survival rate of all cancers. This poor prognosis results from the lack of efficient systemic treatment regimens, demanding high-dose chemotherapy that causes severe side effects. To overcome dose-dependent toxicities, we explored the efficacy of targeted drug delivery using a protease-dependent drug-release system.

Anti-Fatigue Effect of a Dietary Supplement from the Fermented By-Products of Taiwan Tilapia Aquatic Waste and Oligosaccharide Complex.

The Taiwan Tilapia is an important aquaculture product in Taiwan. The aquatic by-products generated during Tilapia processing, such as fish bones and skin, are rich in minerals and protein. We aimed to explore the effect of a dietary supplement, comprising a mixture of fermented Tilapia by-products and oligosaccharides as the raw materials, combined with physical training on exercise performance and fatigue.

DKK3 (Dickkopf 3) Alters Atherosclerotic Plaque Phenotype Involving Vascular Progenitor and Fibroblast Differentiation Into Smooth Muscle Cells.

Objective: DKK3 (dickkopf 3), a 36-kD secreted glycoprotein, has been shown to be involved in the differentiation of partially reprogrammed cells and embryonic stem cells to smooth muscle cells (SMCs), but little is known about its involvement in vascular disease. This study aims to assess the effects of DKK3 on atherosclerotic plaque composition.

Approach And Results: In the present study, we used a murine model of atherosclerosis () in conjunction with and performed tandem stenosis of the carotid artery to evaluate atherosclerotic plaque development.

Intratumoural heterogeneity generated by Notch signalling promotes small-cell lung cancer.

The Notch signalling pathway mediates cell fate decisions and is tumour suppressive or oncogenic depending on the context. During lung development, Notch pathway activation inhibits the differentiation of precursor cells to a neuroendocrine fate. In small-cell lung cancer, an aggressive neuroendocrine lung cancer, loss-of-function mutations in NOTCH genes and the inhibitory effects of ectopic Notch activation indicate that Notch signalling is tumour suppressive.

A sequence variant associating with educational attainment also affects childhood cognition.

Only a few common variants in the sequence of the genome have been shown to impact cognitive traits. Here we demonstrate that polygenic scores of educational attainment predict specific aspects of childhood cognition, as measured with IQ. Recently, three sequence variants were shown to associate with educational attainment, a confluence phenotype of genetic and environmental factors contributing to academic success.

Next-generation sequencing-based detection of circulating tumour DNA After allogeneic stem cell transplantation for lymphoma.

Next-generation sequencing (NGS)-based circulating tumour DNA (ctDNA) detection is a promising monitoring tool for lymphoid malignancies. We evaluated whether the presence of ctDNA was associated with outcome after allogeneic haematopoietic stem cell transplantation (HSCT) in lymphoma patients. We studied 88 patients drawn from a phase 3 clinical trial of reduced-intensity conditioning HSCT in lymphoma.

Discovery of D1 Dopamine Receptor Positive Allosteric Modulators: Characterization of Pharmacology and Identification of Residues that Regulate Species Selectivity.

The present studies represent the first published report of a dopamine D1 positive allosteric modulator (PAM). D1 receptors have been proposed as a therapeutic target for the treatment of cognitive deficits associated with schizophrenia. However, the clinical utility of orthosteric agonist compounds is limited by cardiovascular side effects, poor pharmacokinetics, lack of D1 selectivity, and an inverted dose response.

Cinnamon extract lowers glucose, insulin and cholesterol in people with elevated serum glucose.

Cinnamon ( ròu guì) has insulin potentiating activity, and proanthocyanidins from cinnamon prevent formation of advanced glycation end products. Some human studies were equivocal, but several have shown beneficial effects of cinnamon supplementation on circulating glucose, lipids, and/or insulin. This placebo-controlled double-blind trial tested the effects of a dried water extract of cinnamon () on circulating glucose, lipids, insulin, and insulin resistance.

Megakaryocytic leukemia 1 directs a histone H3 lysine 4 methyltransferase complex to regulate hypoxic pulmonary hypertension.

Enhanced interaction between vascular endothelial cells and circulating leukocytes, as a result of transcriptional activation of cell adhesion molecules (CAM), helps establish a proinflammatory milieu contributing to the pathogenesis of chronic hypoxia-induced pulmonary hypertension. The molecular switch that dictates CAM transactivation is not clearly defined. Our goal was to determine the involvement of the transcriptional modulator megakaryocytic leukemia 1 (MKL1), also known as myocardin-related transcription factor A (MRTF-A), in CAM transactivation and the underlying mechanism.

Effects of hormonal contraceptive use on HIV acquisition and transmission among HIV-discordant couples.

Background: The risk of HIV associated with hormonal contraceptives is controversial. We assessed hormonal contraceptive use and HIV incidence in HIV-discordant couples in Rakai, Uganda.

Methods: HIV-discordant couples were retrospectively identified from a cohort between 1999 and 2009.

Aberrant whole-brain functional connectivity and intelligence structure in children with primary nocturnal enuresis.

Aim: To assess the potential relationship between intelligence structure abnormalities and whole-brain functional connectivity in children with primary nocturnal enuresis (PNE) with resting-state functional magnetic resonance imaging (fMRI) to provide insights into the association between these two seemingly unrelated conditions.

Methods: Intelligence testing and fMRI data were obtained from 133 right-handed children, including 67 PNE children (M/F, 39:28; age, 10.5 ± 1.

Phylogenetic analysis and comparison of eight strains of pigeon paramyxovirus type 1 (PPMV-1) isolated in China between 2010 and 2012.

Eight strains of pigeon paramyxovirus type 1 (PPMV-1) were isolated and identified in this study, from diseased pigeon flocks suspected to be infected with PPMV-1 in China between 2010 and 2012. These PPMV-1 isolates were purified using specific-pathogen-free (SPF) chicken embryo cells before full-length genomic sequencing. The complete genome of these isolates contained 15,192 nucleotides, similar to those of Newcastle disease virus (NDV) strains in genotypes V-XI, with the gene order 3'-NP-P-M-F-HN-L-5'.

Assessment of memory/attention impairment in children with primary nocturnal enuresis: a voxel-based morphometry study.

Aim: Assessment of memory/attention impairment and related exploration of the gray matter differential MR density variations between children with and without primary nocturnal enuresis (PNE) using voxel-based morphometry (VBM) methodology is the aim of the present study.

Methods: A total of 75 right-handed PNE children (M/F=39:36, average age 10.4±1.