Design, Synthesis and Anti-Inflammatory Evaluation of 3-Substituted 5-Amidobenzoate Derivatives as Novel P2Y Receptor Antagonists via Structure-Guided Molecular Hybridization.

The P2YR is activated by UDP and UDP glucose and is involved in many human inflammatory diseases. Based on the molecular docking analysis of currently reported P2YR antagonists and the crystallographic overlap study between PPTN and compound , a series of 3-substituted 5-amidobenzoate derivatives were designed, synthesized, and identified as promising P2YR antagonists. The optimal compound (methyl 3-(1-benzo[]imidazol-2-yl)-5-(2-(-tolyl) acetamido)benzoate, IC = 0.

Noncoding variants and sulcal patterns in congenital heart disease: Machine learning to predict functional impact.

Neurodevelopmental impairments associated with congenital heart disease (CHD) may arise from perturbations in brain developmental pathways, including the formation of sulcal patterns. While genetic factors contribute to sulcal features, the association of noncoding variants (ncDNVs) with sulcal patterns in people with CHD remains poorly understood. Leveraging deep learning models, we examined the predicted impact of ncDNVs on gene regulatory signals.

Risk of residual/recurrent cervical diseases in HPV-positive women post-conization depends on HPV integration status.

Background: It is crucial to identify post-operative patients with HPV infection who are at high risk for residual/recurrent disease. This study aimed to evaluate the association between HPV integration and clinical outcomes in HPV-positive women after cervical conization, as well as to identify HPV integration breakpoints.

Methods: This retrospective study analyzed data of 791 women who underwent cervical conization for cervical intraepithelial neoplasia grades 2-3 (CIN2-3) between September 2019 and September 2023, sourced from the Fujian and Hubei cervical lesion screening cohorts.

Raynaud Syndrome Associated with Medication for Attention-Deficit/Hyperactivity Disorder: A Systematic Review.

Background: Raynaud syndrome (RS) is a peripheral vasculopathy characterised be impaired acral perfusion typically manifesting as skin discolouration with pallor, cyanosis and/or erythema, and increased sensitivity to cold. RS may be primary or secondary to systemic disease, lifestyle and environmental factors or medication. RS has been reported with medication to treat ADHD, but we found no recent comprehensive overview of the literature.

Free-breathing multi-parametric SASHA (mSASHA) mapping provides reliable non-contrast myocardial characterization in a pediatric and adult congenital population.

Parametric mapping has become a standard of care technique for the non-invasive assessment of myocardial edema and fibrosis. Conventional MOLLI-based T1 mapping is susceptible to many confounding effects particularly in the pediatric population. The requirement for compliant breath holds is a major limitation for younger or more ill patients.

Real-world usage and effectiveness of recombinant factor IX Fc in haemophilia B from the B-SURE study in France.

Background: More real-world data are needed to complement existing phase III studies on the efficacy and safety of recombinant factor IX Fc fusion protein (rFIXFc) in people with haemophilia B.

Objectives: We report final data from the B-SURE study, evaluating the real-world usage and effectiveness of rFIXFc in France.

Methods: Previously treated patients (all ages/severities) received on-demand or prophylactic rFIXFc during B-SURE.

Efficacy of 4-dimensional hysterosalpingo-contrast sonography and X-ray hysterosalpingography in infertility.

Objective: To assess and compare efficacy of 4-dimensional hysterosalpingo-contrast sonography (4D-HyCoSy) and X-ray hysterosalpingography (HSG) for fallopian tube examination.

Methods: Clinical data of patients with suspected tubal infertility, who underwent examinations in Qingdao Women and Children's Hospital from September 2021 to December 2023, were retrospectively analyzed. Of them, 40 patients received laparoscopy and dye test+ 4D-HyCoSy (4D-HyCoSy group), and 36 patients received laparoscopy and dye test +HSG (HSG group).

The dilemma of X-linked agammaglobulinemia carriers.

Background: Many patients with X-linked agammaglobulinemia (XLA) nowadays have reached adulthood, as well as their sisters, possibly carriers of a deleterious Bruton tyrosine kinase variant. Studies on motherhood outcomes in families with XLA are lacking.

Objective: We sought to investigate adherence to carrier status screening, interest in preconception and prenatal genetic counseling, and reproductive decisions in relatives with XLA.

Profiling and bioinformatics analyses of circular RNAs in myocardial ischemia/reperfusion injury model in mice.

Background: Myocardial ischemia/reperfusion (I/R) injury, which is associated with high morbidity and mortality, is a main cause of unexpected myocardial injury after acute myocardial infarction. However, the underlying mechanism remains unclear. Circular RNAs (circRNAs), which are formed from protein-coding genes, can sequester microRNAs or proteins, modulate transcription and interfere with splicing.

Once a day administration of R(+) propranolol is sufficient to block vasculogenesis in a xenograft model of infantile hemangioma.

Objectives: Infantile hemangioma (IH) is a benign vascular tumor that occurs in 5% of infants, predominantly in female and preterm neonates. Propranolol is the mainstay of treatment for IH. Given the short half-life of propranolol regarding β-adrenergic receptor inhibition as well as its side effects, propranolol is administered to infants 2-3 times daily with 1 mg/kg/dose.

A OHCs-Targeted Strategy for PEDF Delivery in Noise-Induced Hearing Loss.

Noise-induced hearing loss (NIHL) results from prolonged exposure to intense noise, causing damage to sensory outer hair cells (OHCs) and spiral ganglion neurons (SGNs). The blood labyrinth barrier (BLB) hinders systemic drug delivery to the inner ear. This study applied a retro-auricular round window membrane (RWM) method to bypass the BLB, enabling the transport of macromolecular proteins into the inner ear.

Simultaneous determination of busulfan, fludarabine, phenytoin, and posaconazole in plasma from patients undergoing hematopoietic stem cell transplantation.

A simple, fast, sample-saving, and sensitive liquid chromatography-tandem mass spectrometry method was established with a linear range adjusted by in-source collision-induced dissociation. Notably, this could simultaneously determine busulfan, fludarabine, phenytoin, and posaconazole in plasma from children, each having unique physical and chemical properties. The procedure necessitated only 20 μL of plasma and involved a simple protein precipitation process.

Clinical characteristics, complications and satisfaction of megameatus intact prepuce (MIP) hypospadias variant: a 15 year retrospective study.

Background: To analyze the clinical characteristics, complications and patients satisfaction of MIP hypospadias variant.

Methods: A retrospective analysis was performed for 31 patients with MIP admitted to our hospital from January 2008 to February 2023. All enrolled patients underwent telephone follow-up and a survey was conducted on the satisfaction of patients and their families.

CircKIAA0182 Enhances Lung Cancer Progression and Chemoresistance through Interaction with YBX1.

Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a leading cause of cancer-related mortality. Resistance to platinum-based chemotherapy, such as cisplatin, significantly limits treatment efficacy. Circular RNAs (circRNAs) have emerged as key regulators of cancer progression and chemotherapy resistance due to their stable structure, which protects them from degradation.

Metabolic Sequelae and Quality of Life in Early Post-Treatment Period in Adolescents with Hodgkin Lymphoma.

: The long-term consequences of intensive treatment for Hodgkin lymphoma (HL), including metabolic syndrome (MetS) and cardiovascular diseases, but also deteriorated quality of life (QoL), are present in many survivors of childhood HL. : Adolescents and young adults diagnosed with HL who continued the follow-up after successful treatment for HL were included. Anthropometric parameters, body composition, laboratory data, blood pressure values, compliance to the Mediterranean diet (MD), QoL and lifestyle habits were evaluated at the follow-up.

Paternal Depression and Anxiety During the COVID-19 Pandemic.

The COVID-19 pandemic significantly impacted the lives of families worldwide. Findings suggest a substantial impact of the COVID-19 pandemic on maternal mental health. Yet, much less is known about the impact of COVID-19 on paternal mental health.

Peripheral blood miRNAs are associated with airflow below threshold in children with asthma.

Background: MicroRNAs (miRNAs) are crucial post-transcriptional regulators involved in inflammatory diseases, such as asthma. Poor lung function and airflow issues in childhood are linked to the development of chronic obstructive pulmonary disease (COPD) in adulthood.

Methods: We analyzed small RNA-Seq data from 365 peripheral whole blood samples from the Genetics of Asthma in Costa Rica Study (GACRS) for association with airflow levels measured by FEV1/FVC.

Development of the PRECIOUS Short-Form (PRECIOUS-SF) quality of care measure for children with serious illnesses.

Background: Rising number of children with complex medical conditions necessitate regular healthcare quality evaluation to achieve optimal outcomes. To address the need for a periodic and quick assessment of quality of care in serious childhood illnesses, we developed a short version of previously validated 45-item PaRental Experience with care for Children with serIOUS illnesses (PRECIOUS) measure.

Methodology: PRECIOUS was administered by parents of children living with serious illnesses at two time-points (baseline and two weeks) in an online survey.

Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease.

Obesity strongly increases the risk of cardiometabolic diseases, yet the underlying mediators of this relationship are not fully understood. Given that obesity strongly influences circulating protein levels, we investigated proteins mediating the effects of obesity on coronary artery disease, stroke and type 2 diabetes. By integrating two-step proteome-wide Mendelian randomization, colocalization, epigenomics and single-cell RNA sequencing, we identified five mediators and prioritized collagen type VI α3 (COL6A3).

V3+ extends the V3 framework to ensure user-centricity and scalability of sensor-based digital health technologies.

We propose the addition of usability validation to the extended V3 framework, now "V3+", and describe a pragmatic approach to ensuring that sensor-based digital health technologies can be used optimally at scale by diverse users. Alongside the original V3 components (verification; analytical validation; clinical validation), usability validation will ensure user-centricity of digital measurement tools, paving the way for more inclusive, reliable, and trustworthy digital measures within clinical research and clinical care.

Comparative proteomic landscapes elucidate human preimplantation development and failure.

Understanding mammalian preimplantation development, particularly in humans, at the proteomic level remains limited. Here, we applied our comprehensive solution of ultrasensitive proteomic technology to measure the proteomic profiles of oocytes and early embryos and identified nearly 8,000 proteins in humans and over 6,300 proteins in mice. We observed distinct proteomic dynamics before and around zygotic genome activation (ZGA) between the two species.

Thoracic Electric Impedance Tomography Detects Lung Volume Changes in Amyotrophic Lateral Sclerosis.

Introduction/aims: Spirometry is the conventional means to measure lung function in amyotrophic lateral sclerosis (ALS), but is dependent on patient effort and bulbar strength. We aimed to use electric impedance tomography (EIT), an emerging non-invasive imaging modality, to measure dynamic lung volume changes.

Methods: Twenty-one patients with ALS underwent sitting and supine spirometry for forced vital capacity (FVC), and sitting and supine EIT.