Pharmacological blocking of microfibrillar-associated protein 4 reduces retinal neoangiogenesis and vascular leakage.

Neovascular age-related macular degeneration and diabetic macular edema are leading causes of vision-loss evoked by retinal neovascularization and vascular leakage. The glycoprotein microfibrillar-associated protein 4 (MFAP4) is an integrin αβ ligand present in the extracellular matrix. Single-cell transcriptomics reveal MFAP4 expression in cell-types in close proximity to vascular endothelial cells including choroidal vascular mural cells and retinal astrocytes and Müller cells.

A Comprehensive Atlas of AAV Tropism in the Mouse.

Gene therapy with Adeno-Associated Virus (AAV) vectors requires knowledge of their tropism within the body. Here we analyze the tropism of ten naturally occurring AAV serotypes (AAV3B, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAVrh8, AAVrh10 and AAVrh74) following systemic delivery into male and female mice. A transgene expressing ZsGreen and Cre recombinase was used to identify transduction in a cell-dependent manner based on fluorescence.

Neonatal Familiar Cleidocranial Dysplasia: A Case Report.

BACKGROUND Cleidocranial dysplasia (CCD) is a rare (1: 1 000 000) autosomal dominant congenital skeletal dysplasia characterized by widely patent calvarial sutures, clavicular hypoplasia, supernumerary teeth, and short stature. Only a minority of the cases are diagnosed early after birth. We present another case of proven CCD presenting with typical neonatal phenotype to promote awareness of this rare disorder.

Suppression of METTL3 expression attenuated matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal modulation of the extracellular matrix in pelvic organ prolapse.

Background: Fibrosis of the connective tissue in the vaginal wall predominates in pelvic organ prolapse (POP), which is characterized by excessive fibroblast-to-myofibroblast differentiation and abnormal deposition of the extracellular matrix (ECM). Our study aimed to investigate the effect of ECM stiffness on vaginal fibroblasts and to explore the role of methyltransferase 3 (METTL3) in the development of POP.

Methods: Polyacrylamide hydrogels were applied to create an ECM microenvironment with variable stiffness to evaluate the effects of ECM stiffness on the proliferation, differentiation, and expression of ECM components in vaginal fibroblasts.

Negative association between 15 obesity- and lipid-related indices and testosterone in adult males: a population based cross-sectional study.

Background: An association exists between obesity and reduced testosterone levels in males. The propose of this research is to reveal the correlation between 15 indices linked to obesity and lipid levels with the concentration of serum testosterone, and incidence of testosterone deficiency (TD) among adult American men.

Methods: The study utilized information gathered from the National Health and Nutrition Examination Survey (NHANES) carried out from 2011 to 2016.

A Nomogram utilizing ECG P-wave parameters to predict recurrence risk following catheter ablation in paroxysmal atrial fibrillation.

Objective: The objective of this study is to assess the predictive utility of perioperative P-wave parameters in patients with paroxysmal atrial fibrillation (PAF) undergoing catheter ablation, and to develop a predictive model using these parameters.

Methods: A total of 213 patients with PAF undergoing catheter ablation were retrospectively analyzed. P-wave parameters were measured within 3 days preoperatively and on the day postoperatively to determine their predictive significance for postoperative PAF recurrence.

Sperm DNA fragmentation index: limited effectiveness on predicting embryo quality in assisted reproduction technology treatments.

Purpose: Prior sperm DNA fragmentation index (DFI) thresholds for diagnosing male infertility and predicting assisted reproduction technology (ART) outcomes fluctuated between 15 and 30%, with no agreed standard. This study aimed to evaluate the impact of the sperm DFI on early embryonic development during ART treatments and establish appropriate DFI cut-off values.

Methods: Retrospectively analyzed 913 couple's ART cycles from 2021 to 2022, encompassing 1,476 IVF and 295 ICSI cycles, following strict criteria.

Association between the hemoglobin A1c/High-density lipoprotein cholesterol ratio and stroke incidence: a prospective nationwide cohort study in China.

Background: Stroke has emerged as an escalating public health challenge among middle-aged and older individuals in China, closely linked to glycolipid metabolic abnormalities. The Hemoglobin A1c/High-Density Lipoprotein Cholesterol (HbA1c/HDL-C) ratio, an integrated marker of glycolipid homeostasis, may serve as a novel predictor of stroke risk.

Methods: Our investigation utilized data from the China Health and Retirement Longitudinal Study cohort (2011-2018).

The effects of unified pooling arrangement on health inequity in China: a DID-RIF approach.

Background: To address the health inequity caused by decentralized management, China has introduced a provincial pooling system for urban employees' basic medical insurance. This paper proposes a research framework to evaluate similar policies in different contexts. This paper adopts a mixed-methods approach to more comprehensively and precisely capture the causal effects of the policy.

Repression of PFKFB3 sensitizes ovarian cancer to PARP inhibitors by impairing homologous recombination repair.

Background: Ovarian cancer (OC), particularly high-grade serous ovarian carcinoma (HGSOC), is the leading cause of mortality from gynecological malignancies worldwide. Despite the initial effectiveness of treatment, acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPis) represents a major challenge for the clinical management of HGSOC, highlighting the necessity for the development of novel therapeutic strategies. This study investigated the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a pivotal regulator of glycolysis, in PARPi resistance and explored its potential as a therapeutic target to overcome PARPi resistance.

Peroral Endoscopic myotomy (POEM) in pediatric achalasia: a retrospective cohort on institutional experience and quality of life.

Background: Achalasia is a rare esophageal motility disorder with an estimated annual incidence of 1-5/100.000 and a mean age at diagnosis > 50 years of age. Only a fraction of the patients has an onset during childhood (estimated incidence of 0.

Specialized pediatric palliative care in Italy: where are we going? The Palliped 2022-2023 study.

Background: The PalliPed project is a nationwide, observational, cross-sectional study designed with the aim of providing a constantly updated national database for the census and monitoring of specialized pediatric palliative care (PPC) activities in Italy. This paper presents the results of the first monitoring phase of the PalliPed project, which was developed through the PalliPed 2022-2023 study, to update current knowledge on the provision of specialized PPC services in Italy.

Methods: Italian specialized PPC centers/facilities were invited to participate and asked to complete a self-reporting, ad-hoc, online survey regarding their clinical activity in 2022-2023, in the revision of the data initially collected in the first PalliPed study of 2021.

Delineation of reduced CTV2 on the basis of the characteristics and distribution of cervical lymph node metastasis in nasopharyngeal carcinoma.

Introduction: The core objective of this study was to precisely locate metastatic lymph nodes, identify potential areas in nasopharyngeal carcinoma patients that may not require radiotherapy, and propose a hypothesis for reduced target volume radiotherapy on the basis of these findings. Ultimately, we reassessed the differences in dosimetry of organs at risk (OARs) between reduced target volume (reduced CTV2) radiotherapy and standard radiotherapy.

Methods And Materials: A total of 209 patients participated in the study.

Correlations between spinopelvic parameters and health-related quality of life in degenerative lumbar scoliosis patients before and after long -level fusion surgery.

Background: For degenerative lumbar scoliosis (DLS), prior studies mainly focused on the preoperative relationship between spinopelvic parameters and health-related quality of life (HRQoL), lacking an exhaustive evaluation of the postoperative situation. Therefore, the postoperative parameters most closely bonded with clinical outcomes has not yet been well-defined in DLS patients. The objective of this study was to comprehensively assess the correlation between radiographic parameters and HRQoL before and after surgery, and to identified the most valuable spinopelvic parameters for postoperative curative effect.

Reverse-engineering the FLT3-PI3K/AKT axis to enhance TILs function and improve prognosis in ovarian and cervical cancers.

Background: Ovarian cancers (OC) and cervical cancers (CC) have poor survival rates. Tumor-infiltrating lymphocytes (TILs) play a pivotal role in prognosis, but shared immune mechanisms remain elusive.

Methods: We integrated single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to explore immune regulation in OC and CC, focusing on the PI3K/AKT pathway and FLT3 as key modulators.

Neutrophil-to-lymphocyte ratio and short-term mortality in patients having anti-MDA5-positive dermatomyositis with interstitial lung disease: a retrospective study.

Background: In this study, we aimed to explore the association between baseline and early changes in the neutrophil-to-lymphocyte ratio (NLR) and the 30-day mortality rate in patients having anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis with interstitial lung disease (DM-ILD).

Methods: Overall, 263 patients with anti-MDA5 DM-ILD from four centers in China were analyzed. Multivariate logistic regression analysis was used to evaluate the impact of baseline NLR on the 30-day mortality rate in patients with anti-MDA5-positive DM-ILD.

Improving preparedness for time critical prehospital care: a descriptive study of the first responder system in Central Norway.

Background: First responders exist in several countries and have been a prehospital emergency medical resource in Norwegian municipalities since 2010. However, the Norwegian system has not yet been studied. The aim of this study was to describe the first responder system in Central Norway and how it is used as a supplement to emergency medical services (EMS).

Efficacy and safety of SHEN26, a novel oral small molecular RdRp inhibitor for COVID-19 treatment: a multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial.

Background: SHEN26 (ATV014) is an oral RNA-dependent RNA polymerase (RdRp) inhibitor with potential anti-SARS-CoV-2 activity. Safety, tolerability, and pharmacokinetic characteristics were verified in a Phase I study. This phase II study aimed to verify the efficacy and safety of SHEN26 in COVID-19 patients.

Posteromedial opening wedge high tibial osteotomy has favourable outcomes in simultaneous medial meniscus posterior root repair and varus medial knee osteoarthritis patients without concomitant root tear.

Purpose: To evaluate the radiological and clinical outcomes in two patient groups: first, varus aligned medial meniscus posterior root tear (MMPRT) patients who underwent posteromedial open wedge high tibial osteotomy (PMOWHTO) and simultaneous root repair; second, patients with varus medial knee osteoarthritis without MMPRT who underwent PMOWHTO.

Methods: Patients had MMPRT repair concomitant with PMOWHTO and varus medial knee osteoarthritis without concomitant root tear patients who underwent PMOWHTO and were reviewed. Radiographic parameters, medial meniscus extrusion (MME) and Knee Society Scores [KSSs, including the following subscores: knee score (KS) and knee function score (KFS)] were evaluated.

Evaluating programmatic reactive focal drug administration impact on malaria incidence in northern Senegal: an interrupted time series analysis.

Background: The World Health Organization conditionally recommends reactive drug administration to reduce malaria transmission in settings approaching elimination. However, few studies have evaluated the impact of reactive focal drug administration (rFDA) in sub-Saharan Africa, and none have evaluated it under programmatic conditions. In 2016, Senegal's national malaria control programme introduced rFDA, the presumptive treatment of compound members of a person with confirmed malaria, and reactive mass focal drug administration (rMFDA), an expanded effort including neighbouring compounds during an outbreak, in 10 low transmission districts in the north of the country.

Temporary ectopic banking as a treatment option for mangled thumb: a case report.

Background: Management of the extensive soft tissue injuries remains a significant challenge in orthopedic and plastic reconstructive surgery. Since the thumb is responsible for 40% of the functions of the hand, saving and reconstructing a mangled thumb is essential for the patient's future.

Case Presentation: This case report describes the management of a severe occupational thumb injury in a 25-year-old white Persian male who sustained an occupational injury to his left thumb, resulting in extensive burn, crush injury to the distal and proximal phalanx, and severe soft tissue damage to the first metacarpal, thenar, and palmar areas.

Syndemic, mental health and living with dependent persons in Latin America and Spain: a study with a gender perspective.

Objective: To analyze the sociostructural determinants associated with mental health problems during the lockdown period among populations residing in Brazil, Chile, Ecuador, Mexico, Peru, and Spain who lived with minors or dependents, approached from a gender perspective.

Methods: A cross-sectional study was conducted in six participating countries via an adapted, self-managed online survey. People living with minors and/or dependents were selected.

Fluoride-induced testicular and ovarian toxicity: evidence from animal studies.

Fluoride (F), as a natural element found in a wide range of sources such as water and certain foods, has been proven to be beneficial in preventing dental caries, but concerns have been raised regarding its potential deleterious effects on overall health. Sodium fluoride (NaF), another form of F, has the ability to accumulate in reproductive organs and interfere with hormonal regulation and oxidative stress pathways, contributing to reproductive toxicity. While the exact mechanisms of F-induced reproductive toxicity are not fully understood, this review aims to elucidate the mechanisms involved in testicular and ovarian injury.

Semaglutide and laparoscopic sleeve gastrectomy in an adolescent with congenital adrenal hyperplasia due to 21-hydroxylase: a case report.

Background: Classic congenital adrenal hyperplasia, primarily due to 21-hydroxylase deficiency, leads to impaired cortisol and aldosterone production and excess adrenal androgens. Lifelong glucocorticoid therapy is required, often necessitating supraphysiological doses in youth to manage androgen excess and growth acceleration. These patients experience higher obesity rates, hypertension, and glucose metabolism issues, complicating long-term health management.