Nucleotide Transformer: building and evaluating robust foundation models for human genomics.

The prediction of molecular phenotypes from DNA sequences remains a longstanding challenge in genomics, often driven by limited annotated data and the inability to transfer learnings between tasks. Here, we present an extensive study of foundation models pre-trained on DNA sequences, named Nucleotide Transformer, ranging from 50 million up to 2.5 billion parameters and integrating information from 3,202 human genomes and 850 genomes from diverse species.

Self-perceived role and knowledge of community pharmacists in organ donation.

Background: Although a majority of North Americans is in favor of organ donation, registration remains challenging. Community pharmacists are highly accessible frontline health care professionals that could contribute to a new common registration donation consent system.

Aim: The objective of the study was to assess self-perceived professional role and organ donation knowledge of community pharmacists in Quebec.

Refractory Dabigatran-Induced Hemorrhage Despite Multiple Idarucizumab Administration and Renal Replacement Therapy.

Purpose: This case report describes a patient with dabigatran accumulation due to acute kidney injury on chronic kidney disease, requiring multiple administration of idarucizumab along with renal replacement therapy because of rebound effect causing numerous episodes of bleeding.

Summary: An 86-year-old man on dabigatran etexilate 110 mg twice daily for stroke prevention with atrial fibrillation was admitted to the hospital for bowel obstruction and severe acute kidney injury on chronic kidney disease. The patient had an abnormal coagulation profile and no history of bleeding.

Publisher Correction: Melting conditions in the modern Tibetan crust since the Miocene.

The original PDF version of this Article contained an error in which Fig. 3 and its legend were omitted and Equations 5 and 6 contained errors.This has been corrected in the PDF version of the Article.

Melting conditions in the modern Tibetan crust since the Miocene.

Abundant granitic rocks exposed in ancient mountain belts suggest that crustal melting plays a major role in orogenic processes. However, complex field relations and superposition of multiple tectonic events make it difficult to determine the role of melting in orogenesis. In contrast, geophysical measurements image present-day crustal conditions but cannot discriminate between partial melt and aqueous fluids.

Paraxial mesoderm contributes stromal cells to the developing kidney.

The development of most, if not all, tubular organs is dependent on signaling between epithelial and stromal progenitor populations. Most often, these lineages derive from different germ layers that are specified during gastrulation, well in advance of organ condensation. Thus, one of the first stages of organogenesis is the integration of distinct progenitor populations into a single embryonic rudiment.

Tailbud-derived mesenchyme promotes urinary tract segmentation via BMP4 signaling.

Urinary tract morphogenesis requires the sub-division of the ureteric bud (UB) into the intra-renal collecting system and ureter, two tissues with unique structural and functional properties. In this report we investigate the cellular and molecular mechanisms that mediate their differentiation. Fate mapping experiments in the developing chick indicate that the UB is surrounded by two distinct mesenchymal populations: nephrogenic mesenchyme derived from the intermediate mesoderm and tailbud-derived mesoderm, which is selectively associated with the domain of the UB that differentiates into the ureter.

Overexpression of PKD1 causes polycystic kidney disease.

The pathogenetic mechanisms underlying autosomal dominant polycystic kidney disease (ADPKD) remain to be elucidated. While there is evidence that Pkd1 gene haploinsufficiency and loss of heterozygosity can cause cyst formation in mice, paradoxically high levels of Pkd1 expression have been detected in the kidneys of ADPKD patients. To determine whether Pkd1 gain of function can be a pathogenetic process, a Pkd1 bacterial artificial chromosome (Pkd1-BAC) was modified by homologous recombination to solely target a sustained Pkd1 expression preferentially to the adult kidney.

c-myc-induced apoptosis in polycystic kidney disease is independent of FasL/Fas interaction.

Apoptosis is a critical early cellular event in the development of polycystic kidney disease (PKD) in humans and mice. In the SBM transgenic model of PKD, both apoptosis and proliferation are c-myc driven and are independent of p53 and Bcl-2 pathways. On the basis of recent evidence implicating the FasL/Fas pathway in c-myc-induced apoptosis, we investigated the potential interaction of these pathways in vivo.