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Alzheimer's Disease (AD) is a complex disease and the leading cause of dementia in older people. We aimed to uncover aspects of AD's pathogenesis that may contribute to drug repurposing efforts by integrating DNA methylation and genetic data. Implementing the network-based tool, a dense module search of genome-wide association studies (dmGWAS), we integrated a large-scale GWAS dataset with DNA methylation data to identify gene network modules associated with AD. Our analysis yielded 286 significant gene network modules...

Midwifery is undergoing increasing complexity attributed to global epidemiological, socio-economic and technological shifts. Coupled with a shortage of workforce and the imperative for cost-effectiveness and high-quality care, there is an ongoing international discourse and establishment of new care models and specialized roles, notably Advanced Midwifery Practice (AMP). While countries like the UK and Ireland have embraced AMP roles, Switzerland lags behind with only a few pioneering roles. The absence of regulatory frameworks for AMP within the Swiss legal and healthcare system, hinders the evolution of APM roles necessary to address contemporary needs in perinatal healthcare provision...

BACKGROUND: The immune status of a patient's tumor microenvironment (TME) may guide therapeutic interventions with cancer immunotherapy and help identify potential resistance mechanisms. Currently, patients' immune status is mostly classified based on CD8+tumor-infiltrating lymphocytes. An unmet need exists for comparable and reliable precision immunophenotyping tools that would facilitate clinical treatment-relevant decision-making and the understanding of how to overcome resistance mechanisms...

Numerous long non-coding RNAs (lncRNAs) were shown to have a functional impact on cellular processes such as human epidermal homeostasis. However, the mechanism of action for many lncRNAs remains unclear to date. Here, we report that lncRNA LINC00941 regulates keratinocyte differentiation on an epigenetic level through association with the NuRD complex, one of the major chromatin remodelers in cells. We find that LINC00941 interacts with NuRD-associated MTA2 and CHD4 in human primary keratinocytes. LINC00941 perturbation changes MTA2/NuRD occupancy at bivalent chromatin domains in close proximity to transcriptional regulator genes, including the EGR3 gene coding for a transcription factor regulating epidermal differentiation...

No abstract text is available yet for this article.

Large granular lymphocytic (LGL) leukaemia is a rare chronic lymphoproliferative disorder characterized by an expansion of cytotoxic T or NK cells. Despite a usually indolent evolution, most patients will require a treatment over the course of the disease because of cytopenia or symptomatic associated autoimmune disorders. First-line treatment is based on immunosuppressive agents, namely cyclophosphamide, methotrexate and ciclosporin. However, relapses are frequent, and there is no consensus on the management of relapsed/refractory patients...

OBJECTIVE: This study aimed to determine the diagnostic performance of contrasted magnetic resonance cholangiography for detecting bile duct lesions following cholecystectomy. MATERIALS AND METHODS: A retrospective case series study was conducted that included patients over 18 years of age with suspected bile duct injury after cholecystectomy, who underwent contrasted magnetic resonance cholangiography, and who also had endoscopic retrograde cholangiopancreatography, surgery, or subsequent clinical follow-up...

In this paper, the relocation decisions of manufacturing plants across the NUTS-3 regions of the German economy are investigated. A relocation decision concerns whether a plant (an incumbent) moves its location from one region to another over a given time period or whether it remains in the same region. This decision is distinct from a location decision (of a start-up). To analyze the relocations of plants, the rich information of the official German regional statistics as well as the official German firm statistics that are maintained by the German Federal Statistical Office and the Statistical Offices of the Federal States is exploited for the first time...

A 47-year-old male patient was referred to a level 1 trauma center with refractory acute respiratory distress syndrome, bilateral lung contusions, and flail chest after initial management for injuries sustained 5 days prior from an 8-m fall from a tower crane. Surgical stabilization of the rib fractures was achieved under extracorporeal membrane oxygenation support, with successful decannulation 4 days after surgery. The patient was discharged after 42 days and following multidisciplinary interventions...

The insular cortex, or insula, is a large brain region involved in the detection of thirst and the regulation of water intake. However, our understanding of the topographical, circuit, and molecular mechanisms for controlling water intake within the insula remains parcellated. We found that type-1 cannabinoid (CB1 ) receptors in the insular cortex cells participate in the regulation of water intake and deconstructed the circuit mechanisms of this control. Topographically, we revealed that the activity of excitatory neurons in both the anterior insula (aIC) and posterior insula (pIC) increases in response to water intake, yet only the specific removal of CB1 receptors in the pIC decreases water intake...

Congenital cryptorchidism, also known as undescended testis, is the condition where one or both testes are not in place in the scrotum at birth and is one of the most common birth defects in boys. Temporal trends and geographic variation in the prevalence of cryptorchidism from 1% to 9% have been reported in prospective cohort studies. The testes develop in the abdominal cavity and descend to the scrotum in two phases, which should be completed by gestational week 35. Thus, the risk of cryptorchidism is higher in preterm boys...

Shoulder dislocations remain the most frequent of joint dislocations, with anterior displacement of the humeral head being the direction of dislocation seen most often (97%). Recently, the Dutch clinical guideline on shoulder dislocations has been revised on the basis of predetermined bottlenecks in clinical practice. In this paper, the guideline is translated to clinical practice by means of two fictional cases, in which the novel recommendations are incorporated. The following topics were systematically assessed based on the best available scientific evidence: primary diagnostics, reduction techniques, painmedication/ sedation surrounding reduction and the need for physiotherapy, stabilization surgery and immobilization...

BACKGROUND: Pathogenic germline variants in the mismatch repair (MMR) genes are associated with an increased risk of prostate cancer (PCa). Since 2010 we have recommended MMR carriers annual PSA testing from the age of 40. Prospective studies of the outcome of long-term PSA screening are lacking. This study aimed to investigate the incidence and characteristics of PCa in Norwegian MMR carriers attending annual PSA screening (PSA threshold >3.0 ng/mL) to evaluate whether our recommendations should be continued...

International and national conservation policies almost exclusively focus on conserving species in their historic native ranges, thus excluding species that have been introduced by people and some of those that have extended their ranges on their own accord. Given that many of such migrants are threatened in their native ranges, conservation goals that explicitly exclude these populations may overlook opportunities to prevent extinctions and respond dynamically to rapidly changing environmental and climatic conditions...

No abstract text is available yet for this article.

Power can increase overconfidence and illusory thinking. We investigated whether power is also related to the illusion of explanatory depth (IOED), people's tendency to think they understand the world in more detail, coherence, and depth than they actually do. Abstract thinking was reported as a reason for the IOED, and according to the social distance theory of power, power increases abstract thinking. We linked these literatures and tested construal style as a mediator. Further, predispositions can moderate effects of power and we considered narcissism as a candidate because narcissism leads to overconfidence and may thus increase the IOED especially in combination with high power...

INTRODUCTION: The current standard treatment for endometrial cancer is a laparoscopic hysterectomy with adnexectomies and bilateral sentinel node resection. A retroperitoneal vNOTES sentinel node resection has several theoretical potential advantages. These include being less invasive, leaving no visible scars, operating without Trendelenburg, and therefore offering the anesthetic advantage of easier ventilation in obese patients and following the natural lymph node trajectory from caudally to cranially and therefore a lower risk of missing the sentinel node...

BACKGROUND: Prognostic indicators for equine multinodular pulmonary fibrosis (EMPF), an interstitial fibrosing lung disease, are poorly described. HYPOTHESIS/OBJECTIVES: Describe diagnostic findings and outcome predictors for EMPF. ANIMALS: Forty-six adult horses with EMPF. METHODS: Retrospective multicenter case series from 2009 to 2019. Radiographic (n = 27) and ultrasonographic studies (n = 19) from EMPF horses and bronchoalveolar lavage fluid (BALF) cytology from 6 EMPF and 13 asthma cases were independently reviewed and blinded to diagnosis and outcome...

BACKGROUND: As part of the new Flanders Quality Model (FlaQuM) towards sustainable quality management systems, a co-creation roadmap with six primary drivers and 19 building blocks that guides healthcare organisations has been developed. Currently, no assessment tool is available to monitor hospitals' quality management systems implementation according to this co-creation roadmap. Therefore, we aimed to measure the maturity of the implementation of the FlaQuM co-creation roadmap in hospitals...

Collagen VI-related dystrophies (COL6-RDs) are a group of severe, congenital-onset muscular dystrophies for which there is no effective causative treatment. Dominant-negative mutations are common in COL6A1 , COL6A2 , and COL6A 3 genes, encoding the collagen α1, α2, and α3 (VI) chains. They act by incorporating into the hierarchical assembly of the three α (VI) chains and consequently produce a dysfunctional collagen VI extracellular matrix, while haploinsufficiency for any of the COL6 genes is not associated with disease...