Strangeebsen0442

Urinary stone disease is a widespread disease with tremendous impact on those affected and on societies around the globe. Nevertheless, clinical and health care research in this area seem to lag far behind cardiovascular diseases or cancer. This may be due to the lack of an immediate deadly threat from the disease and therefore less public and professional interest. However, the patients suffer from recurring, sometimes intense pain and often must be treated in hospital. Long-term morbidity includes doubled rates of chronic kidney disease and arterial hypertension after at least one stone-related event. Observational studies, more specifically, registries and other electronic data sets have been proposed as a means of filling critical gaps in evidence. We propose a nationwide digital and fully automated registry as part of the German Ministry for Education and Research (BMBF) call for the "establishment of model registries".

RECUR builds on the technical infrastructure of Germany's Medical Informatics Inides advanced diagnostic algorithms and treatment pathways. The registry will help us identify those patients who will most benefit from specific interventions to prevent recurrences. The RECUR study protocol and the registry's technical architecture including full digitalization and automation of almost all registry-associated proceedings can be transferred to future registries.

This study is registered at the German Clinical Trial Register (Deutsches Register Klinischer Studien), DRKS-ID DRKS00026923 , date of registration January, 11

2022.

This study is registered at the German Clinical Trial Register (Deutsches Register Klinischer Studien), DRKS-ID DRKS00026923 , date of registration January, 11th 2022.

SP140 is a bromodomain-containing protein expressed predominantly in immune cells. Genetic polymorphisms and epigenetic modifications in the SP140 locus have been linked to Crohn's disease (CD), suggesting a role in inflammation.

We report the development of the first small molecule SP140 inhibitor (GSK761) and utilize this to elucidate SP140 function in macrophages. We show that SP140 is highly expressed in CD mucosal macrophages and in in vitro-generated inflammatory macrophages. SP140 inhibition through GSK761 reduced monocyte-to-inflammatory macrophage differentiation and lipopolysaccharide (LPS)-induced inflammatory activation, while inducing the generation of CD206

regulatory macrophages that were shown to associate with a therapeutic response to anti-TNF in CD patients. SP140 preferentially occupies transcriptional start sites in inflammatory macrophages, with enrichment at gene loci encoding pro-inflammatory cytokines/chemokines and inflammatory pathways. GSK761 specifically reduces SP140 chromatin binding and thereby expression of SP140-regulated genes. GSK761 inhibits the expression of cytokines, including TNF, by CD14

macrophages isolated from CD intestinal mucosa.

This study identifies SP140 as a druggable epigenetic therapeutic target for CD.

This study identifies SP140 as a druggable epigenetic therapeutic target for CD.

One of the most significant challenges of implementing a multi-provider bundled payment contract is to determine an appropriate, casemix-adjusted total bundle price. The most frequently used approach is to leverage historic care utilization based on claims data. However, those claims data may not accurately reflect appropriate care (e.g. due to supplier induced demand and moral hazard effects). This study aims to examine variation in claims-based costs of post-discharge primary care physical therapy (PT) utilization after total knee and hip arthroplasties (TKA/THA) for osteoarthritis patients.

This retrospective cohort study used multilevel linear regression analyses to predict the factors that explain the variation in the utilization of post-discharge PT after TKA or THA for osteoarthritis patients, based on the historic (2015-2018) claims data of a large Dutch health insurer. The factors were structured as predisposing, enabling or need factors according to the behavioral model of Andersen.

The 15,309acts and the desired changes in care delivery it aims to support.

This study shows that if enabling factors (such as supplementary insurance coverage or co-payments) are not taken into account in risk-adjustment of the bundle price, they may cause historic claims-based pricing methods to over- or underestimate appropriate post-discharge primary care PT use, which would result in a bundle price that is either too high or too low. Not adjusting bundle prices for all relevant casemix factors is a risk because it can hamper the successful implementation of bundled payment contracts and the desired changes in care delivery it aims to support.

Venous thromboembolism has been a major public health problem and caused a heavy disease burden. Venous thromboembolism clinical decision support system was proved to have a positive influence on the prevention and management of venous thromboembolism. As the direct users, nurses' acceptance of this system is of great importance to support the successful implementation of it. However, there are few relevant studies to investigate nurses' acceptance and the associated factors are still unclear.

To investigate the determinant factors of nurses' acceptance of venous thromboembolism clinical decision support system with the modified Unified Theory of Acceptance and Use of Technology.

We designed a questionnaire based on the modified Unified Theory of Acceptance and Use of Technology and then a cross-sectional survey was conducted among nurses in a tertiary hospital in Nanjing, China. Statistically, a Structural Equation Modeling -Partial Least Squares path modeling approach was applied to examine the researpectancy was considered as the top priority. It highlights the importance of optimizing system performance to fit the users' needs. Generally, the findings in our research provide clinical technology designers and administrators with valuable information to better meet users' requirements and promote the implementation of venous thromboembolism clinical decision support system.

The research enhances our understanding of the determinants of nurses' acceptance of venous thromboembolism clinical decision support system. Among these factors, performance expectancy was considered as the top priority. It highlights the importance of optimizing system performance to fit the users' needs. Generally, the findings in our research provide clinical technology designers and administrators with valuable information to better meet users' requirements and promote the implementation of venous thromboembolism clinical decision support system.Bioactive materials have been extensively developed for the adjuvant therapy of cancer. MSDC0160 However, few materials can meet the requirements for the postoperative resection of hepatocellular carcinoma (HCC) due to massive bleeding and high recurrence. In particular, combination therapy for HCC has been highly recommended in clinical practice, including surgical resection, interventional therapy, ablation therapy and chemotherapy. Herein, an injectable magnetic colloidal gel (MCG) was developed by controllable electrostatic attraction between clinically available magnetic montmorillonites and amphoteric gelatin nanoparticles. The optimized MCG exhibited an effective magnetic heating effect, remarkable rheological properties, and high gel network stability, realizing the synergistic treatment of postoperative HCC by stimuli-responsive drug delivery, hemostasis and magnetic hyperthermia. Furthermore, a minimal invasive MCG-induced interventional magnetic hyperthermia therapy (MHT) under ultrasound guidance was realized on hepatic tumor rabbits, providing an alternative therapeutics to treat the postoperative recurrence. Overall, MCG is a clinically available injectable formulation for adjuvant therapy after HCC surgical resection.

This study was to report a novel CREBBP mutation and phenotype in a child with Rubinstein-Taybi syndrome.

Case report of a 9-year-old boy.

We described the patient's clinical manifestations in detail, and found that in addition to the typical systemic manifestations of the syndrome, the outstanding manifestation of the child was severe intellectual deficiency and prominent ocular abnormalities. Whole-exome sequencing and sanger sequencing were performed on the patient and his parents, a large intragenic deletion, covering the exon 1 region and part of the intron 1 region of the TRAP1 gene, and the entire region from intron 27 to exon 30 of the CREBBP gene (chr163745393-3783894) was identified on the patient. This mutation affected the CREBBP histone acetyltransferase (HAT) domain.

This findings in our patient add to the spectrum of genetic variants described in Rubinstein-Taybi syndrome and present a RSTS patient with various ocular anomalies including early onset glaucoma.

This findings in our patient add to the spectrum of genetic variants described in Rubinstein-Taybi syndrome and present a RSTS patient with various ocular anomalies including early onset glaucoma.Population frequency has been one of the most widely used criteria to help assign pathogenicity to newly described mitochondrial DNA variants. However, after sequencing this molecule in thousands of healthy individuals, it has been observed that a very large number of genetic variants have a very low population frequency, which has raised doubts about the utility of this criterion. By analyzing the genetic variation of mitochondrial DNA-encoded genes for oxidative phosphorylation subunits in 195,983 individuals from HelixMTdb that were not sequenced based on any medical phenotype, we show that rare variants are deleterious and, along with other criteria, population frequency is still a useful criterion to assign pathogenicity to newly described variants.

Disappointing clinical efficacy of standard treatment has been proven in refractory metastatic osteosarcoma, and the emerging anti-angiogenic regimens are still in the infantile stage. Thus, there is an urgent need to develop novel therapeutic approach for osteosarcoma lung metastasis.

circFIRRE was selected from RNA-sequencing of 4 matched osteosarcoma and adjacent samples. The expression of circFIRRE was verified in clinical osteosarcoma samples and cell lines via quantitative real-time polymerase chain reaction (RT-qPCR). The effect of circFIRRE was investigated in cell lines in vitro models, ex vivo models and in vivo xenograft tumor models, including proliferation, invasion, migration, metastasis and angiogenesis. Signaling regulatory mechanism was evaluated by RT-qPCR, Western blot, RNA pull-down and dual-luciferase reporter assays.

In this article, a novel circular RNA, circFIRRE (hsa_circ_0001944) was screened out and identified from RNA-sequencing, and was upregulated in both osteosarcoma cell lines and tissues. Clinically, aberrantly upregulated circFIRRE portended higher metastatic risk and worse prognosis in osteosarcoma patients. Functionally, in vitro, ex vivo and in vivo experiments demonstrated that circFIRRE could drive primary osteosarcoma progression and lung metastasis by inducing both tumor cells and blood vessels, we call as "tumorigenic-angiogenic coupling". Mechanistically, upregulated circFIRRE was induced by transcription factor YY1, and partially boosted the mRNA and protein level of LUZP1 by sponging miR-486-3p and miR-1225-5p.

We identified circFIRRE as a master regulator in the tumorigenesis and angiogenesis of osteosarcoma, which could be purposed as a novel prognostic biomarker and therapeutic target for refractory osteosarcoma.

We identified circFIRRE as a master regulator in the tumorigenesis and angiogenesis of osteosarcoma, which could be purposed as a novel prognostic biomarker and therapeutic target for refractory osteosarcoma.