Unveiling the Anti-Angiogenic Potential of Small-Molecule (Kinase) Inhibitors for Application in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation leading to joint damage and systemic complications. Angiogenesis promotes inflammation and contributes to RA progression. This study evaluated potential anti-angiogenic effects of several compounds including small-molecule kinase inhibitors, such as sunitinib (pan-kinase inhibitor), tofacitinib (JAK-inhibitor), NIKi (NF-κB-inducing kinase inhibitor), and the integrin-targeting peptide fluciclatide, using a scratch assay and 3D spheroid-based models of angiogenesis.

Reproducibility and Consistency of Isolation Protocols for Fibroblasts, Smooth Muscle Cells, and Epithelial Cells from the Human Vagina.

(1) Background: For the reconstruction of a human vagina, various surgical procedures are available that are often associated with complications due to their failure to mimic the physiology of the human vagina. We recently developed a vascularized, organ-specific matrix from healthy human vaginal wall tissue with suitable biomechanical properties. A superior graft would require further extensive colonization with autologous vaginal cells to reduce complications upon implantation.

The role of germline and somatic mutations in predicting cancer-associated thrombosis: a narrative review.

Purpose Of Review: Patients with cancer have an increased risk of venous thromboembolism (VTE). Guidelines suggest to use risk assessment tools to guide decisions about thromboprophylaxis, but current tools have modest discriminatory ability. Genetic information from the germline or tumor has the potential to improve VTE prediction.

Directed Evolution of AAV9 for Efficient Gene Expression in Cardiomyocytes and .

Adeno-associated viral (AAV) vectors are increasingly used for preclinical and clinical cardiac gene therapy approaches. However, gene transfer to cardiomyocytes poses a challenge due to differences between AAV serotypes in terms of expression efficiency and . For example, AAV9 vectors work well in rodent heart muscle cells but not in cultivated neonatal rat ventricular cardiomyocytes (NRVCMs), necessitating the use of AAV6 vectors for studies.

Somatic mutations and DNA methylation identify a subgroup of poor prognosis within lower-risk myelodysplastic syndromes.

Lower risk (LR) myelodysplastic syndromes (MDS) are heterogeneous hematopoietic stem and progenitor disorders caused by the accumulation of somatic mutations in various genes including epigenetic regulators that may produce convergent DNA methylation patterns driving specific gene expression profiles. The integration of genomic, epigenomic, and transcriptomic profiling has the potential to spotlight distinct LR-MDS categories on the basis of pathophysiological mechanisms. We performed a comprehensive study of somatic mutations and DNA methylation in a large and clinically well-annotated cohort of treatment-naive patients with LR-MDS at diagnosis from the EUMDS registry (ClinicalTrials.

Systematic optimization and evaluation of a Dutch sexual health intervention: Role model stories for chlamydia prevention, testing, and treatment.

Background: The rapidly evolving nature of eHealth necessitates regular optimization and subsequent evaluation. Within the Dutch sexual health intervention Sense.info, we utilized a mixed-methods cyclic evaluation process to assess and optimize the potential impact of the chlamydia page.

Expert Consensus Methods In The Humanities: An Exploration of their Potential.

Background: Despite the significant role of consensus and dissensus in knowledge production, formal approaches to consensus are notably less common in the humanities compared to their frequent application in natural, social, and life sciences. This article therefore explores the potential of expert consensus methods in humanities-related research.

Methods: In order to do so, an interdisciplinary team of both sciences researchers experienced in consensus methods and researchers familiar with the domain of the humanities and epistemology, conducted a literary review and exchanged their expertise in multiple brainstorm sessions.

Neurobehavioural Exploration of Breath-counting & Breath-awareness in Novice Indian Meditators: A Naturalised Ānāpānasati-based Paradigmatic Approach.

Background: Neural activity and subjective experiences indicate that breath-awareness practices, which focus on mindful observation of breath, promote tranquil calm and thoughtless awareness.

Purpose: This study explores the impact of tristage Ānāpānasati-based breath meditation on electroencephalography (EEG) oscillations and self-reported mindfulness states in novice meditators following a period of effortful cognition.

Methods: Eighty-nine novice meditators (82 males; Mean Age = 24.

Single-cell sequencing of human Langerhans cells identifies altered gene expression profiles in patients with atopic dermatitis.

Atopic dermatitis (AD) is characterized by dysregulated T cell immunity and skin microbiome dysbiosis with predominance of Staphylococcus aureus, which is associated with exacerbating AD skin inflammation. Specific glycosylation patterns of S. aureus cell wall structures amplify skin inflammation through interaction with Langerhans cells (LCs).

Root-cause analysis of mortality after pancreatic resection in a nationwide cohort.

Background: This study evaluates leading causes of in-hospital mortality after pancreatic resection nationwide to determine areas for improvement.

Methods: This observational cohort study included all in-hospital mortality after pancreatic resection in the Netherlands (2014-2019). Each fatality was considered to be caused by local complications (i.

Unlocking the signaling potential of GPI-anchored proteins through lipolytic cleavage.

Glycosylphosphatidylinositol (GPI)-anchored proteins (APs) regulate numerous biological processes through interaction with signaling effectors at the cell surface. As a unique feature, GPI-APs can be released from their anchors by multi-pass GPI-specific phospholipases (types A2, C, and D) to impact signaling networks, phenotype, and cell fate; however, many questions remain outstanding. Here, we discuss and expand our current understanding of the distinct GPI-specific phospholipases, their substrates, effector pathways, and emerging physiological roles, with a focus on the six-transmembrane ecto-phospholipases GDE2 (GDPD5) and GDE3 (GDPD2).

Intrapatient 16α-[F]Fluoro-17β-Estradiol PET Heterogeneity as a Prognostic Factor for Endocrine Therapy Response and Survival in Patients with Estrogen Receptor-Positive Metastatic Breast Cancer.

Intrapatient heterogeneity of estrogen receptor (ER) expression on 16α-[F]fluoro-17β-estradiol ([F]FES) PET is related to outcome in patients with ER-positive metastatic breast cancer (MBC), but a validated and practical method to support clinical decision-making is lacking. Therefore, the [F]FES PET heterogeneity score (i.e.

The blood transcriptional response in patients developing intensive care unit-acquired pneumonia.

Introduction: Immune response dysregulation has been implicated in the development of intensive care unit (ICU)-acquired pneumonia. We aimed to determine differences in the longitudinal blood transcriptional response between patients who develop ICU-acquired pneumonia (cases) and those who do not (controls).

Methods: We performed a case-cohort study in mechanically ventilated trauma and surgery patients with ICU stays >2 days, enrolled in 30 hospitals across Europe.

Therapeutic quality of exercise interventions for chronic low back pain: a meta-research study using i-CONTENT tool.

Objective: To assess the therapeutic quality of exercise interventions delivered in chronic low back pain (cLBP) trials using the international Consensus on Therapeutic Exercise aNd Training (i-CONTENT) tool and its inter-rater agreement.

Methods: We performed a meta-research study, starting from the trials' arms included in the published Cochrane review (2021) 'Exercise therapy for chronic low back pain'. Two pairs of independent reviewers applied the i-CONTENT tool, a standardised tool designed to ensure the quality of exercise therapy intervention, in a random sample of 100 different exercise arms.

The lncRNA DSCR9 is modulated in pulmonary arterial hypertension endothelial cell models and is associated with alterations in the nitric oxide pathway.

Long non-coding RNA (lncRNA) may be involved in dysfunction of pulmonary artery endothelial cells (PAEC) and, thus, in pulmonary arterial hypertension (PAH) pathobiology. We screened the RNA expression profile of commercial human PAEC (hPAEC) exposed to increased hydrostatic pressure, and found that the lncRNA Down syndrome critical region 9 (DSCR9) was the most regulated transcript (log2FC 1.89 vs control).

Intravascular lithotripsy in calcified left main coronary artery: Procedural success and 1-year clinical outcomes.

Background: Intravascular lithotripsy (IVL) has an excellent efficacy and safety profile in the treatment of calcified coronary lesions during percutaneous coronary intervention (PCI). However, data regarding its use on left main (LM) lesions are still limited.

Objective: We aimed to analyze the technical success and 1-year clinical outcomes in calcified LM lesions treated with IVL.

A health economic evaluation of the multinational, randomized controlled CONVINCE trial - cost-utility of high-dose online hemodiafiltration compared to high-flux hemodialysis.

High-flux hemodialysis (HD) and high-dose hemodiafiltration (HDF) are established treatments for patients with kidney failure. Since HDF has been associated with improved survival rates compared to HD, we evaluated the cost-effectiveness of HDF compared to HD. Cost-utility analyses were performed from a societal perspective alongside the multinational randomized controlled CONVINCE trial.

Thermal ablation versus surgical resection of small-size colorectal liver metastases (COLLISION): an international, randomised, controlled, phase 3 non-inferiority trial.

Background: For patients with small-size colorectal liver metastases, growing evidence suggests thermal ablation to be associated with fewer adverse events and faster recovery than resection while also challenging resection in terms of local control and overall survival. This study assessed the potential non-inferiority of thermal ablation compared with surgical resection in patients with small-size resectable colorectal liver metastases.

Methods: Adult patients (aged ≥18 years) from 14 centres in the Netherlands, Belgium, and Italy with ten or fewer small-size (≤3 cm) colorectal liver metastases, no extrahepatic metastases, and an Eastern Cooperative Oncology Group performance status of 0-2, were stratified per centre, and according to their disease burden, into low, intermediate, and high disease burden subgroups and randomly assigned 1:1 to receive either thermal ablation (experimental group) or surgical resection (control group) of all target colorectal liver metastases using the web-based module Castor electronic data capture with variable block sizes of 4, 6, and 8.

Semaglutide in obesity-related heart failure with preserved ejection fraction and type 2 diabetes across baseline HbA levels (STEP-HFpEF DM): a prespecified analysis of heart failure and metabolic outcomes from a randomised, placebo-controlled trial.

Background: About half of patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF) have type 2 diabetes. In the STEP-HFpEF DM trial of adults with obesity-related HFpEF and type 2 diabetes, subcutaneous once weekly semaglutide 2·4 mg conferred improvements in heart failure-related symptoms and physical limitations, bodyweight, and other heart failure outcomes. We aimed to determine whether these effects of semaglutide differ according to baseline HbA.

Incidence and survival of European adolescents and young adults diagnosed with sarcomas: EUROCARE-6 results.

Background: Epidemiological data for sarcoma in adolescents and young adults (AYAs) and across age groups are limited. We aim to: 1) update sarcoma incidence, survival, and changes over time in European AYAs; 2) provide an updated comparison of sarcoma survival in AYAs versus children and mature adults.

Methods: We calculated crude incidence rates (IR) per 100,000 European population per year from 2006 to 2013.

Loneliness is positively associated with populist radical right support.

Objectives: The mental and physical health consequences of loneliness are well documented. However, loneliness's socio-political ramifications have been largely unexplored. We theorize that loneliness, due to its physiologically dysregulating impact on the nervous system, facilitates greater susceptibility towards populist radical right parties.

Supporting parents to reduce children's anxiety: A meta-analysis of interventions and their theoretical components.

Parent-focused interventions hold promise for reducing child anxiety, but their content varies greatly, and little is known on the intervention content. We estimated the effects of parent-focused interventions on child anxiety and the most effective combinations of theoretical components. We searched PsycINFO, Medline, and Web of Science in October 2022 for randomized trials on parent-focused interventions to reduce children's anxiety.