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With SCAview, we present a prompt and comprehensive tool that enables scientists to browse large datasets of the most common spinocerebellar ataxias intuitively and without technical effort. Basic concept is a visualization of data, with a graphical handling and filtering to select and define subgroups and their comparison. Several plot types to visualize all data points resulting from the selected attributes are provided. The underlying synthetic cohort is based on clinical data from five different European and US longitudinal multicenter cohorts in spinocerebellar ataxia type 1, 2, 3, and 6 (SCA1, 2, 3, and 6) comprising > 1400 patients with overall > 5500 visits. First, we developed a common data model to integrate the clinical, demographic, and characterizing data of each source cohort. Second, the available datasets from each cohort were mapped onto the data model. Third, we created a synthetic cohort based on the cleaned dataset. With SCAview, we demonstrate the feasibility of mapping cohort data from different sources onto a common data model. The resulting browser-based visualization tool with a thoroughly graphical handling of the data offers researchers the unique possibility to visualize relationships and distributions of clinical data, to define subgroups and to further investigate them without any technical effort. Access to SCAview can be requested via the Ataxia Global Initiative and is free of charge.

Data in the literature on the use of ceftazidime-avibactam (CAZ-AVI) in carbapenem-resistant Klebsiella pneumoniae bloodstream infections (CRKP-BSIs) are limited especially in OXA-48 (Oxacillinase-48) predominant regions. Our study aimed to evaluate the effect of CAZ-AVI use on outcomes in CRKP-BSIs in Turkey, where OXA-48 is endemic. A multicenter retrospective observational study was conducted between January 2017 and September 2021. The effects of clinical and treatment characteristics on 30-day mortality and relapse in CRKP-BSIs were analyzed. Predictors of outcomes were detected using a Cox regression model. The study enrolled 106 adults with CAZ-AVI-sensitive CRKP-BSIs who received CAZ-AVI for at least 72 h. Patients who received CAZ-AVI as initial therapy had lower mortality rates when compared to those who switched from last resort regimens [14.3% ( n  = 3/21) vs. 37.7% ( n  = 32/85), p  = 0.04]. In multivariate analysis, older age and severe neutropenia were detected to be associated with higher mortality, significantly. Initiation of CAZ-AVI on the day of blood culture was obtained, was found to be significantly associated with lower mortality (HR: 0.25, CI: 0.07–0.84, p  = 0.025). CAZ-AVI monotherapy is an important treatment option for CRKP-BSIs in OXA-48 endemic areas. Early initiation of CAZ-AVI should be preferred rather than switching from a last-resort regimen as it profoundly improves the survival rates.

The objective of our study was to evaluate the predictive ability of a multi-trait genomic prediction model that accounts for interactions between marker effects to estimate heritability and genetic correlations of traits including 305-day milk yield, milk fat percentage, milk protein percentage, milk lactose percentage, and milk dry matter percentage in the Polish Holstein Friesian cow population. For this aim, 14,742 SNP genotype records for 586 Polish Holstein Friesian dairy cows from Poland were used. Single-Trait-ssGBLUP (ST) and Multi-Trait-ssGBLUP (MT) methods were used for estimation. We examined 305-day milk yield (MY, kg), milk fat percentage (MF, %), milk protein percentage (MP, %), milk lactose percentage (ML, %), and milk dry matter percentage (MDM, %). The results showed that the highest marker effect rank correlation was found between milk fat percentage and milk dry matter. The weakest marker effect rank correlation was found between ML and all other traits. Obtained accuracies of this study were between 0.770 and 0.882, and 0.773 and 0.876 for MT and ST, respectively, which were acceptable values. All estimated bias values were positive, which is proof of underestimation. The highest heritability value was obtained for MP (0.3029) and the lowest heritability value was calculated for ML (0.2171). Estimated heritability values were low for milk yield and milk composition as expected. The strongest genetic correlation was estimated between MDM and MF (0.4990) and the weakest genetic correlation was estimated between MY and ML (0.001). The genetic relations with milk yield were negative and can be ignored as they were not significant. In conclusion, multi-trait genomic prediction can be more beneficial than single-trait genomic prediction.

The development of chronic obstructive pulmonary disease (COPD) pathogenesis remains unclear, but emerging evidence supports a crucial role for inducible bronchus‐associated lymphoid tissue (iBALT) in disease progression. Mechanisms underlying iBALT generation, particularly during chronic CS exposure, remain to be defined. Oxysterol metabolism of cholesterol is crucial to immune cell localization in secondary lymphoid tissue. Here, we demonstrate that oxysterols also critically regulate iBALT generation and the immune pathogenesis of COPD. In both COPD patients and cigarette smoke (CS)‐exposed mice, we identified significantly upregulated CH25H and CYP7B1 expression in airway epithelial cells, regulating CS‐induced B‐cell migration and iBALT formation. Mice deficient in CH25H or the oxysterol receptor EBI2 exhibited decreased iBALT and subsequent CS‐induced emphysema. Further, inhibition of the oxysterol pathway using clotrimazole resolved iBALT formation and attenuated CS‐induced emphysema in vivo therapeutically. Collectively, our studies are the first to mechanistically interrogate oxysterol‐dependent iBALT formation in the pathogenesis of COPD, and identify a novel therapeutic target for the treatment of COPD and potentially other diseases driven by the generation of tertiary lymphoid organs. Synopsis COPD is the third leading cause of death worldwide with limited therapy. iBALT is a crucial contributor to COPD pathogenesis. Local airway production of oxysterols is crucial for iBALT formation without affecting B and T cell activation, whose inhibition offers new therapeutic potential. Oxysterol metabolizing enzymes CH25H and CYP7B1 are upregulated in airway epithelial cells of COPD patients and cigarette smoke‐exposed mice. Mice deficient in CH25H or the oxysterol receptor EBI2 failed to generate iBALT in their lungs and critically were protected against emphysema development following chronic cigarette smoke exposure. B cells failed to migrate ex vivo towards CS‐stimulated airways from Ch25h −/− mice or mice in which oxysterol synthesis genetically and pharmacologically had been blocked. Therapeutically, the CYP7B1 inhibitor clotrimazole resolved iBALT formation and attenuated cigarette smoke‐induced COPD in a murine model suggesting a novel therapeutic option for COPD patients. Graphical Abstract COPD is the third leading cause of death worldwide with limited therapy. iBALT is a crucial contributor to COPD pathogenesis. Local airway production of oxysterols is crucial for iBALT formation without affecting B and T cell activation, whose inhibition offers new therapeutic potential.

Patients with solitary kidneys (SKs) are at risk of hypertension (HT) and associated end‐organ damage. The authors aimed to evaluate whether children with congenital SKs (CSKs) have higher office, ambulatory, or central blood pressure (BP), increased arterial stiffness or left ventricular mass index, or any risk for arrhythmia. With this purpose, patients with CSK and healthy controls being followed up between January 2018 and June 2019 were enrolled in the study. Demographic, biochemical, and office blood pressure (BP) data were recorded. Then, ambulatory blood pressure monitoring (ABPM) and measurements of central BP (cBP), pulse wave velocity (PWV), and augmentation index (AIx@75) were obtained. Ventricular repolarization parameters were acquired by 12‐lead electrocardiography. Left ventricular mass index (LVMI) and abdominal aortic stiffness parameters including strain, pressure strain elastic modulus (Ep), and normalized Ep (Ep*) were calculated with echocardiographic measurements. Finally, 36 children with CSK and 36 healthy controls were included. Serum creatinine, uric acid, total cholesterol levels, ABPM parameters, cBP levels, and PWV values were significantly higher, and eGFR levels were significantly lower in the CSK group. VR parameters, abdominal aortic stiffness indices, and LVMI were similar between the groups. CSK increased the risk of HT in ABPM (HTABPM) by 6 times. PWV was significantly correlated with Ep and Ep* in cases with CSK. Determination of cBP and PWV along with 24‐hour ABPM would be a useful tool in children with CSK.

Hybrid hydrogels from protein–polymer conjugates are biomaterials formed via the chemical bonding of a protein molecule with a polymer molecule. Protein–polymer conjugates offer a variety of biological properties by combining the mechanical strength of polymers and the bioactive functionality of proteins. These properties allow these conjugates to be used as biocompatible components in biomedical applications. Protein–polymer conjugation is a vital bioengineering strategy in many fields, such as drug delivery, tissue engineering, and cancer therapy. Protein–polymer conjugations aim to create materials with new and unique properties by combining the properties of different molecular components. There are various ways of creating protein–polymer conjugates. PEGylation is one of the most common conjugation techniques where a protein is conjugated with Polyethylene Glycol. However, some limitations of PEGylation (like polydispersity and low biodegradability) have prompted researchers to devise novel synthesis techniques like PEGylation, where synthetic polypeptides are used as the polymer component. This review will illustrate the properties of protein–polymer conjugates, their synthesis methods, and their various biomedical applications.