Ultrasound and genetic findings in a case series of fetuses presenting vertebral defects.

Purpose: This study aimed to summarize the ultrasound and genetic features in a case series of fetuses presenting vertebral defects, to provide useful information for prenatal counseling and prognostic evaluation.

Methods: Fetuses with vertebral anomalies by a second or third trimester ultrasound screening between January 2020 and April 2024 at a single center were included in the study. Chromosome microarray analysis (CMA) as a first-line diagnostic test was performed.

A molecular dynamics protocol for rapid prediction of EGFR overactivation and its application to the rare mutations S768I, S768N, D761N.

Hyperactivation caused by mutations in the Epidermal Growth Factor Receptor (EGFR) kinase domain is implicated in various diseases, including cancer. However, the structural mechanisms underlying overactivation in many EGFR mutations remain poorly understood, and exploring these mechanisms through conventional experiments or simulations is often labor- and cost-intensive. Here, we establish a Molecular Dynamics (MD) protocol capable of rapidly revealing EGFR mutant modes of action using multiple short simulations.

Prenatal Characterization of Houge-Janssens Syndrome Type 2: A Case Report and Systematic Review of Fetal Phenotypes Associated With PPP2R1A Mutations.

Background: Houge-Janssens syndrome type 2 (HJS2, OMIM 616362) is a rare neurodevelopmental disorder caused by pathogenic variants in PPP2R1A, typically characterized postnatally by hypotonia, developmental delay, intellectual disability, and distinctive craniofacial features.

Methods: We describe a 28-year-old pregnant woman referred for increased nuchal translucency (4.4 mm) and high risk on first trimester screening.

A Comparative Study of Medium-Coverage Genome Sequencing and SNP Array Technology in Identifying Chromosomal Abnormalities to Advance Prenatal and Postnatal Diagnosis.

This study compared the performance of 5-fold genome sequencing (GS) with single nucleotide polymorphism (SNP) array technology in detecting chromosomal abnormalities, particularly in the context of prenatal and postnatal diagnostics. A total of 42 samples, previously analyzed by SNP array, were re-examined using 5-fold GS to evaluate the detection of clinically significant copy number variations (CNVs), mosaicism, and absence of heterozygosity (AOH). The results revealed a 100% concordance between the two methods for the identification of clinically relevant CNVs, with both technologies detecting similar CNV size ranges.

A novel cinnamic acid derivative for hepatocellular carcinoma therapy by degrading METTL16 protein.

The RNA methyltransferase methyltransferaselike protein 16 (METTL16) is upregulated in a large proportion of hepatocellular carcinoma (HCC), and its high expression is associated with poor clinical outcomes. METTL16 deletion inhibits HCC growth in vitro and in vivo. Referencing the structure of cinnamic acid, here we designed and synthesized a novel series of small molecular compounds, and found through bioactivity screening that compound 15a effectively reduced METTL16 level and modulated oncogenic PI3K/AKT pathway signaling.

The effect of continuous positive airway pressure therapy on atrial fibrillation in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) stands as an autonomous risk factor for a broad spectrum of cardiovascular diseases, particularly atrial fibrillation (AF), which is closely associated with heightened morbidity and mortality rates. The intricate pathophysiological pathways linking OSA to AF encompass chronic intermittent hypoxia, disruptions in the autonomic nervous system, inflammatory responses, and alterations in ion channel function. Continuous positive airway pressure (CPAP) therapy emerges as the frontline treatment for moderate to severe OSA, effectively alleviating symptomatic manifestations and potentially mitigating cardiovascular risks.

Usp11 maintained the survival of marginal zone B cells under ionizing radiation by deubiquitinating DLL1 and JAG2.

Efficacy of radiation therapy is compromised by hematopoietic and immune impairments, with elusive underlying causes. This study aimed to elucidate Usp11's role in radiation-induced injuries and uncover related mechanisms. Utilized ARS mouse model to observe survival rates of Usp11 (KO) mice post-TBI (Total Body Irradiation).

Oncogenic non-V600 mutations evade the regulatory machinery of RAF including the Cdc37/Hsp90 chaperone and the 14-3-3 scaffold.

The Ser/Thr kinase RAF, particularly BRAF isoform is a dominant target of oncogenic mutations and many mutations have been identified in various cancers. However, how these mutations except V600E evade the regulatory machinery of RAF protein and hence trigger its oncogenicity remains unclear. In this study, we used mutagenesis, peptide affinity assay, immunoprecipitation, immunoblot, and complementary split luciferase assay as well as mouse xenograft tumour model to investigate how the function of RAF is cooperatively regulated by Cdc37/Hsp90 chaperones and 14-3-3 scaffolds and how this regulatory machinery is evaded by prevalent non-V600 mutations.

Temporal variations in QTc interval during and after COVID-19 infection: a retrospective study.

Objective: The aim of this study was to investigate the dynamic changes in QTc interval duration among patients with COVID-19 infection before, during, and after infection, in order to assess the short- and potential long-term impact of COVID-19 on cardiac electrophysiology.

Methods: A retrospective analysis was conducted on 303 inpatients diagnosed with COVID-19 who visited a tertiary Grade A hospital in China between August 2022 and December 2023. Inclusion criteria required patients to have at least two electrocardiogram (ECG) recordings at three specific time points: before COVID-19 infection, during acute infection, and after recovery (more than one month post-infection).

Unsupervised attribute reduction based on variable precision weighted neighborhood dependency.

Neighborhood rough set (NRS) have been successfully applied to attribute reduction (AR). However, most current methods of AR based on NRS are supervised or semi-supervised. This limits their ability to process data without decision information.

Therapeutic vulnerabilities and pan-cancer landscape of BRAF class III mutations in epithelial solid tumors.

Background: Kinase-impaired class III BRAF mutations have recently received attention as a possible prognostic factor and therapeutic target. Class III BRAF variants differ from class I and class II mutations in terms of mechanism of pathway activation and therapeutic vulnerabilities. Genomic landscape analyses of tumors in large real-world cohorts represent a great opportunity to further characterize tumor-related molecular events and treatment vulnerabilities, however, such data is not yet available for tumors with BRAF class III mutations.

Fabrication of a high-sensitivity electrochemical immunosensor by the oriented immobilization of engineered nanobody on nanofibrous membrane.

A new type of label-free electrochemical immunosensor for the high-sensitivity determination of parathion was developed based on the oriented immobilization of nanobody (VHH9) on a gold nanoparticle-loaded polyvinyl alcohol/citric acid nanofiber membrane-modified electrode. The morphology characterization and assembly process of the modified materials were investigated using scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). Under the optimum conditions, the label-free electrochemical immunosensor for parathion exhibited a linear range of 0.

Preparation and sensing performance of wet-spun fabric triboelectric nanogenerator for energy harvesting.

Flexible, wearable triboelectric nanogenerators (TENGs) monitoring human movement and health signals have received more attention recently. In particular, developing a flexible TENG combining stress, strain, electrical output performance and durability becomes the current research focus. Herein, a highly stretchable, self-powered coaxial yarn TENGs were manufactured using a low-cost, efficient continuous wet-spinning method.

Species turnover and functional nestedness constitute the geographic patterns of stream diatoms in the Three Parallel Rivers region, China.

Unraveling biodiversity patterns and their driving processes is paramount in ecology and biogeography. However, there remains a limited understanding regarding the underlying mechanisms of community assembly, particularly in alpine streams where significant elevation gradients and habitat heterogeneity exist. We investigated the patterns and drivers of beta diversity, explicitly focusing on taxonomic and functional diversity, in the three parallel rivers region in China.

Historical sedimentary and evolutionary characteristics of POPs and EDCs in typical regions of the three Gorges reservoir, China.

The historical sedimentary and evolutionary characteristics of persistent organic pollutants and endocrine disruptors in typical regions of the Three Gorges Reservoir are scarcely studied. Herein, the 96-year data on contaminated sediment history were reconstructed using Caesium 137 isotope dating. Polychlorinated biphenyl concentrations in the involved sediment cores ranged from non-detected (ND) to 11.

Exceptional Response to MEK Inhibition in a Patient With RAF1-Mutant Myxofibrosarcoma: Case Report and Mechanistic Overview.

Complete response to Trametinib in a heavily-pretreated sarcoma: RAF1 as a predictor of MEKi Response

Sleep CLIP: A Multimodal Sleep Staging Model Based on Sleep Signals and Sleep Staging Labels.

Since the release of the contrastive language-image pre-training (CLIP) model designed by the OpenAI team, it has been applied in several fields owing to its high accuracy. Sleep staging is an important method of diagnosing sleep disorders, and the completion of sleep staging tasks with high accuracy has always remained the main goal of sleep staging algorithm designers. This study is aimed at designing a multimodal model based on the CLIP model that is more suitable for sleep staging tasks using sleep signals and labels.

BRAF(V600E) mutation together with loss of Trp53 or pTEN drives the origination of hairy cell leukemia from B-lymphocytes.

Hairy cell leukemia (HCL) is a B-lymphoma induced by BRAF(V600E) mutation. However, introducing BRAF(V600E) in B-lymphocytes fails to induce hematological malignancy, suggesting that BRAF(V600E) needs concurrent mutations to drive HCL ontogeny. To resolve this issue, here we surveyed human HCL genomic sequencing data.

Exploiting metabolic vulnerabilities in breast cancers with NF1 loss.

Auf der Maur et al. identify neurofibromin 1 (NF1) loss as a mechanism of resistance to PI3K inhibitor in breast cancer cells. NF1 loss leads to enhanced glycolysis, which may be targeted with the antioxidant N-acetyl cysteine (NAC).

Case report: Detection of fetal trisomy 9 mosaicism by multiple genetic testing methods: Report of two cases.

Chromosomal mosaicism remains a perpetual diagnostic and clinical dilemma. In the present study, we detected two prenatal trisomy 9 mosaic syndrome cases by using multiple genetic testing methods. The non-invasive prenatal testing (NIPT) results suggested trisomy 9 in two fetuses.

Drug resistance in targeted cancer therapies with RAF inhibitors.

Hyperactive RAS/RAF/MEK/ERK signaling has a well-defined role in cancer biology. Targeting this pathway results in complete or partial regression of most cancers. In recent years, cancer genomic studies have revealed that genetic alterations that aberrantly activate the RAS/RAF/MEK/ERK signaling mainly occur on RAF or upstream, which motivated the extensive development of RAF inhibitors for cancer therapy.

Sleep staging classification based on a new parallel fusion method of multiple sources signals.

In the field of medical informatics, sleep staging is a challenging and time consuming task undertaken by sleep experts. The conventional method for sleep staging is to analyze Polysomnograms (PSGs) recorded in a sleep lab, but the sleep monitoring with polysomnography (PSG) severely degrades the sleep quality. Despite recent significant progress in the development of automatic sleep staging methods, building a good model still remains a big challenge for sleep studies due to the data-variability and data-inefficiency issues.

Whole Exome Sequencing Analysis in Fetal Skeletal Dysplasia Detected by Ultrasonography: An Analysis of 38 Cases.

Skeletal dysplasias (SDs) are a heterogeneous group of genetic disorders that primarily affect bone and cartilage. This study aims to identify the genetic causes for fetal SDs, and evaluates the diagnostic yield of prenatal whole-exome sequencing (WES) for this disorder. WES was performed on 38 fetuses with sonographically identified SDs and normal results of karyotype and single nucleotide polymorphism (SNP) analysis.

Case Report: Novel Variants Cause Cornelia de Lange Syndrome in Chinese Patients.

Cornelia de Lange syndrome (CdLS) is a genetic disorder characterized by multisystemic malformations. Mutation in the gene accounts for nearly 60% of the cases. This study reports the clinical and genetic findings of three cases of CdLS from unrelated Chinese families.

The stability of R-spine defines RAF inhibitor resistance: A comprehensive analysis of oncogenic BRAF mutants with in-frame insertion of αC-β4 loop.

Although targeting BRAF mutants with RAF inhibitors has achieved promising outcomes in cancer therapy, drug resistance remains a remarkable challenge, and underlying molecular mechanisms are not fully understood. Here, we characterized a previously unknown group of oncogenic BRAF mutants with in-frame insertions (LLR or VLR) of αC-β4 loop. Using structure modeling and molecular dynamics simulation, we found that these insertions formed a large hydrophobic network that stabilizes R-spine and thus triggers the catalytic activity of BRAF.