BACKGROUND Accurate interpretation of rare genetic variants is a challenge for clinical translation. Updates in recommendations for rare variant classification require the reanalysis and reclassification. We aim to perform an exhaustive re-analysis of rare variants associated with inherited arrhythmogenic syndromes, which were classified ten years ago, to determine whether their classification aligns with current standards and research findings. METHODS In 2010, the rare variants identified through genetic analysis were classified following recommendations available at that time. Nowadays, the same variants have been reclassified following current American College of Medical Genetics and Genomics recommendations. FINDINGS Our cohort included 104 cases diagnosed with inherited arrhythmogenic syndromes and 17 post-mortem cases in which inherited arrhythmogenic syndromes was cause of death. 71.87% of variants change their classification. While 65.62% of variants were classified as likely pathogenic in 2010, after reanalysis, only 17.96% remain as likely pathogenic. In 2010, 18.75% of variants were classified as uncertain role but nowadays 60.15% of variants are classified of unknown significance. INTERPRETATION Reclassification occurred in more than 70% of rare variants associated with inherited arrhythmogenic syndromes. Our results support the periodical reclassification and personalized clinical translation of rare variants to improve diagnosis and adjust treatment. FUNDING Obra Social “La Caixa Foundation” (ID 100010434, LCF/PR/GN16/50290001 and LCF/PR/GN19/50320002), Fondo Investigacion Sanitaria (FIS PI16/01203 and FIS, PI17/01690), Sociedad Española de Cardiología, and “Fundacio Privada Daniel Bravo Andreu”. BACKGROUND Metastatic prostate cancer is a clonally heterogeneous disease state characterized by progressive somatic perturbations. The aim of this study was to identify cell free DNA- (cfDNA-) based alterations and their associations with outcomes in progressive metastatic prostate cancer. METHODS In this longitudinal prospective cohort study plasma cfDNA/circulating tumor DNA (ctDNA) was analyzed before, during, and after androgen deprivation therapy (ADT) in 4 independent patient groups ranging from untreated metastatic hormone sensitive prostate cancer (mHSPC) to metastatic castrate resistant prostate cancer (mCRPC). Next generation sequencing was performed on ctDNA and germline DNA to characterize alterations and associations with clinical outcomes were determined for each group. FINDINGS cfDNA yields were different in progressive mHSPC and mCRPC states (P  less then  .001). In mHSPC, a higher than median ctDNA fraction was predictive of shorter time to ADT failure (HR, 2.29 [95% CI, 1.13-4.65]; Log-Rank P  =  .02). cfDNA, ctDNA taken with volume of metastatic disease in mHSPC and with alkaline phosphatase levels prognosticated survival better than clinical factors alone in mHSPC and mCRPC states (Log Rank P = 0.03). ctDNA-based AR, APC mutations were increased in mCRPC compared to mHSPC (P  less then  ·05).TP53 mutations, RB1 loss, and AR gene amplifications correlated with poorer survival in mCRPC. Mutations in multiple DNA repair genes (ATM, BRCA1, BRCA2, CHEK2) were associated with time to ADT treatment failure and survival in mHSPC. INTERPRETATION ctDNA fraction can further refine clinical prognostic factors in metastatic prostate cancer. Somatic ctDNA alterations have potential prognostic, predictive, and therapeutic implications in metastatic prostate cancer management. FUNDING Several funding sources have supported this study. A full list is provided in the Acknowledgments. No funding was received from Predicine, Inc. during the conduct of the study. BACKGROUND Untreated HIV infection leads to alterations in HIV-specific CD4+ T cells including increased expression of co-inhibitory receptors (IRs) and skewing toward a T follicular helper cell (Tfh) signature. However, which changes are maintained after suppression of viral replication with antiretroviral therapy (ART) is poorly known. METHODS We analyzed blood CD4+ T cells specific to HIV and comparative viral antigens in ART-treated people using a cytokine-independent activation-induced marker assay alone or in combination with functional readouts. FINDINGS In intra-individual comparisons, HIV-specific CD4+ T cells were characterized by a larger fraction of circulating Tfh (cTfh) cells than CMV- and HBV-specific cells and preferentially expressed multiple IRs and showed elevated production of the Tfh cytokines CXCL13 and IL-21. In addition, HIV-specific cTfh exhibited a predominant Th1-like phenotype and function when compared to cTfh of other specificities, contrasting with a reduction in Th1-functions in HIV-specific non-cTfh. Using longitudinal samples, we demonstrate that this distinct HIV-specific cTfh profile was induced during chronic untreated HIV infection, persisted on ART and correlated with the translation-competent HIV reservoir but not with the total HIV DNA reservoir. INTERPRETATION Expansion and altered features of HIV-specific cTfh cells are maintained during ART and may be driven by persistent HIV antigen expression. FUNDING This work was supported by the National Institutes of Health (NIH), the Canadian Institutes of Health Research (CIHR) and the FRQS AIDS and Infectious Diseases Network. BACKGROUND Maturation of ultrasound myocardial tissue characterization may have far-reaching implications as a widely available alternative to cardiac magnetic resonance (CMR) for risk stratification in left ventricular (LV) remodeling. selleck screening library METHODS We extracted 328 texture-based features of myocardium from still ultrasound images. After we explored the phenotypes of myocardial textures using unsupervised similarity networks, global LV remodeling parameters were predicted using supervised machine learning models. Separately, we also developed supervised models for predicting the presence of myocardial fibrosis using another cohort who underwent cardiac magnetic resonance (CMR). For the prediction, patients were divided into a training and test set (8020). FINDINGS Texture-based tissue feature extraction was feasible in 97% of total 534 patients. Interpatient similarity analysis delineated two patient groups based on the texture features one group had more advanced LV remodeling parameters compared to the other group.