Since leaving Africa, human populations have gone through a series of range expansions. While the genomic signatures of these expansions are well detectable on a continental scale, the genomic consequences of small-scale expansions over shorter time spans are more challenging to disentangle. The medieval migration of the Walser people from their homeland in ssouthern Switzerland (Upper Valais) into other regions of the Alps is a good example of such a comparatively recent geographic and demographic expansion in humans.
View Article and Find Full Text PDFThe androgen receptor (AR) is central in prostate tissue identity and differentiation, and controls normal growth-suppressive, prostate-specific gene expression. It also drives prostate tumorigenesis when hijacked for oncogenic transcription. The execution of growth-suppressive AR transcriptional programs in prostate cancer (PCa) and the potential for reactivation remain unclear.
View Article and Find Full Text PDFIntroduction: The management of anemia in chronic kidney disease (CKD-An) presents significant challenges for nephrologists due to variable responsiveness to erythropoietin-stimulating agents (ESAs), hemoglobin (Hb) cycling, and multiple clinical factors affecting erythropoiesis. The Anemia Control Model (ACM) is a decision support system designed to personalize anemia treatment, which has shown improvements in achieving Hb targets, reducing ESA doses, and maintaining Hb stability. This study aimed to evaluate the association between ACM-guided anemia management with hospitalizations and survival in a large cohort of hemodialysis patients.
View Article and Find Full Text PDFWe describe the design, synthesis, and structure-activity relationship (SAR) of heterobifunctional RET ligand-directed degraders (LDDs) derived from three different second-generation RET inhibitors. These LDDs are composed of a target binding motif (TBM) that binds to the RET protein, a linker, and a cereblon binding motif (CBM) as the E3 ligase recognition unit. This led to the identification of a series of pyrazolopyridine-based heterobifunctional LDDs, as exemplified by compound .
View Article and Find Full Text PDFBackground: Vaccine hesitancy is a concerning public health issue, further amplified during the COVID-19 pandemic. Social media is an important player in this context, promoting the dissemination of both information and misinformation. Qualitative studies analyzing the meaning of social media contents in correlation with epidemiological data are scarce, and could aid our understanding of social media's impact on vaccine hesitancy.
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