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Patients with glycogen storage disease type 1a (GSD-1a) primarily present with life-threatening hypoglycemia and display severe liver disease characterized by hepatomegaly. Despite strict dietary management, long-term complications still occur, such as liver tumor development. Variations in residual glucose-6-phosphatase (G6PC1) activity likely contribute to phenotypic heterogeneity in biochemical symptoms and complications between patients. However, lack of insight into the relationship between G6PC1 activity and symptoms/complications and poor understanding of the underlying disease mechanisms pose major challenges to provide optimal health care and quality of life for GSD-1a patients. Currently available GSD-1a animal models are not suitable to systematically investigate the relationship between hepatic G6PC activity and phenotypic heterogeneity or the contribution of gene-gene interactions (GGIs) in the liver. To meet these needs, we generated and characterized a hepatocyte-specific GSD-1a mouse modelents for GSD-1a and other genetic liver diseases. In conclusion, we show that somatic CRISPR/Cas9-mediated gene editing allows for the modeling of a spectrum of hepatocyte-borne GSD-1a disease symptoms in mice and to efficiently study GGIs in the liver. This approach opens perspectives for translational research and will likely contribute to personalized treatments for GSD-1a and other genetic liver diseases.Biologicals are crucial targeted therapeutic agents in oncological, immunological, and inflammatory diseases, and their use in clinical practice is broadening. In recent years, the spread of Personalized Precision Medicine has facilitated a proliferation of new treatment options, especially biologicals. Consequently, biologicals are now among the drugs that most frequently cause hypersensitivity reactions (HSRs). Patients can develop HSRs to these agents during the first-lifetime exposure or after repeated exposure, and these HSRs can be potentially life-threatening or limit therapeutic options. Despite the relatively high prevalence, the underlying mechanisms of these HSRs remain obscure, and the optimal management pathways are still a matter of discussion. In this Position Paper, the authors will provide evidence-based recommendations for diagnosing and managing HSRs to biologicals. Additionally, the document defines unmet needs as an opportunity to shape future research.In this article, we analyzed pedigree information on males from 12 bovine breeds born in France between 2015 and 2019. We report an overall small number of paternal lineages with, for example, a minimal number of ancestors accounting for 95% of the Y-chromosome pool of their breed ranging from only 2 to 15 individuals. Then, we mined whole-genome sequence data from 811 sires (2 ≤ n ≤ 510 per breed) and built a median-joining network using 1411 SNPs. Most branches were breed-specific and in agreement with the geographic and genetic relatedness of these populations. The within-breed haplotype diversity was lower than expected based on genealogical information, which supports the existence of major male founder effects predating pedigree recording. In addition, we observed de novo mutation events among the descendants of the same ancestors, which are of interest to define paternal sub-lineages. Our results pave the way to future studies on the estimation of the effects of Y-chromosome haplotypes on male reproductive performances and on the conservation of Y-chromosome diversity. Psoriasis is a chronic inflammatory skin disease requiring prolonged treatment. New biologic therapies require long-term evaluation to assess durability of their efficacy and safety profile over time. To evaluate long-term efficacy and safety of risankizumab (RZB) for the treatment of psoriasis. LIMMitless is an ongoing, phase3, open-label extension study evaluating long-term efficacy and safety of RZB in adults with moderate-to-severe plaque psoriasis following multiple phase2/3 studies. This analysis assessed efficacy through 172 weeks of continuous RZB treatment by examining the proportion of patients achieving ≥90%or 100% improvement in Psoriasis Area and Severity Index (PASI90 and PASI100), static Physician's Global Assessment of clear or almost clear (sPGA0/1), and Dermatology Life Quality Index of no effect on quality of life (DLQI 0/1). Safety was assessed by recording adverse events (AEs) through the data cutoff date. Of 955 patients randomized to RZB150mg in the base studies, 897patients continued into LIMMitless; 799 patients were still receiving treatment in LIMMitless at the time of data cutoff for this analysis. After 172 weeks of continuous RZB treatment, 85·5% of patients achieved PASI90, 54·4% achieved PASI100, 85·2%achieved sPGA0/1, and 78·4% achieved DLQI0/1 using modified non-responder imputation. Rates of AEs leading to discontinuation and AEs of safety interest were low with long-term treatment and comparable to those identified in the base studies. Overall, long-term continuous RZB was well tolerated and showed high and durable efficacy over 172 weeks. Overall, long-term continuous RZB was well tolerated and showed high and durable efficacy over 172 weeks.Frontal Fibrosing Alopecia (FFA) and Fibrosing Alopecia in a Pattern Distribution (FAPD) are forms of primary cicatricial alopecia, classified as subtypes of lichen planopilaris (LPP).1, 2 FAPD and FFA may present with clinical overlap and similar histopathology and dermoscopy features.1 Parietal scalp involvement with frontal hair line recession can obscure the clincial deliniation between FAPD and FFA. https://www.selleckchem.com/products/nms-p937-nms1286937.html The aim of this study is to establish whether FAPD can be differentiated from FFA by histopathological analysis. Long-term growth has been poorly investigated in boys and girls born to parents receiving fertility treatment. This study aimed to investigate the growth of children born following fertility treatment up to adulthood hypothesizing comparable growth in children born to parents receiving fertility treatment or to subfertile parents conceiving spontaneously to that in children spontaneously conceived by fertile parents. In this historical long-term follow-up study the study population consisted of 4151 singletons born at term in the Aarhus Birth Cohort between 1990 and 1992. Parental lifestyle and sociodemographic characteristics together with multiple measurements of weight and height were collected up to 20years of age (6.1% of children contributed with at least one measurement for height or weight at age 20years). The main outcome was difference in z-score for height (m) and weight (kg) between children conceived spontaneously (reference) and children conceived following fertility treatment, children conceived spontaneously by subfertile parents, or unplanned.
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