Autosomal dominant ApoA4 mutations present as tubulointerstitial kidney disease with medullary amyloidosis.

Sporadic cases of apolipoprotein A-IV medullary amyloidosis have been reported. Here we describe five families found to have autosomal dominant medullary amyloidosis due to two different pathogenic APOA4 variants. A large family with autosomal dominant chronic kidney disease (CKD) and bland urinary sediment underwent whole genome sequencing with identification of a chr11:116692578 G>C (hg19) variant encoding the missense mutation p.

Neglected SARS-CoV-2 variants and potential concerns for molecular diagnostics: a framework for nucleic acid amplification test target site quality assurance.

Molecular tests like polymerase chain reaction were widely used during the COVID-19 pandemic but as the pandemic evolved, so did SARS-CoV-2. This virus acquired mutations, prompting concerns that mutations could compromise molecular test results and be falsely negative. While some manufacturers may have in-house programs for monitoring mutations that could impact their assay performance, it is important to promptly report mutations in circulating viral strains that could adversely impact a diagnostic test result.

The DataHarmonizer: a tool for faster data harmonization, validation, aggregation and analysis of pathogen genomics contextual information.

Pathogen genomics is a critical tool for public health surveillance, infection control, outbreak investigations as well as research. In order to make use of pathogen genomics data, they must be interpreted using contextual data (metadata). Contextual data include sample metadata, laboratory methods, patient demographics, clinical outcomes and epidemiological information.

Factors contributing to a coronavirus disease 2019 (COVID-19) outbreak on a mixed medical-surgical unit in a Canadian acute-care hospital.

Objective: To identify preventable factors that contribute to the cross transmission of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) to patients in healthcare facilities.

Design: A case-control study was conducted among inpatients on a coronavirus disease 2019 (COVID-19) outbreak unit.

Setting: This study was conducted in a medical-surgical unit of a tertiary-care hospital in Nova Scotia in May 2021.

RB1-deficient squamous cell carcinoma: the proposed source of combined Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine (NE) carcinoma arising from integration of Merkel cell polyomavirus (MCPyV) DNA into a host cell or from ultraviolet light-induced genetic damage (proportions vary geographically). Tumors in the latter group include those with "pure" NE phenotype and those "combined" with other elements, most often squamous cell carcinoma (SCC). We performed comprehensive genomic profiling (CGP) of MCPyV+ and MCPyV- (pure and combined) tumors, to better understand their mutational profiles and shed light on their pathogenesis.

Gastrointestinal stromal tumors caused by novel germline variants in SDHB and KIT: a report of two cases and literature review.

Gastrointestinal stromal tumors (GISTs) are usually caused by somatic mutations, but there are rare germline variants that predispose patients to the development of one or, more commonly, multiple GISTs. We present 2 cases of multifocal GISTs related to previously unreported germline variants. The first case is a 28-year-old female who developed multiple gastric GISTs with widespread abdominal metastases that were resistant to imatinib.

Relationship between p63 and p53 expression in Merkel cell carcinoma and corresponding abnormalities in TP63 and TP53: a study and a proposal.

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine carcinoma. Oncogenesis occurs via Merkel cell polyomavirus-mediated (MCPyV+) and/or ultraviolet radiation-associated (MCPyV-) pathways. Advanced clinical stage and an MCPyV- status are important adverse prognostic indicators.

Familial Optic Disc Pits in 2 Father-Son Pairs: Clinical Features and Genetic Analysis.

Congenital optic disc pits (ODPs) are well-circumscribed depressions within the optic disc. Thought to arise from anomalous closure of the optic fissure during embryonic development, they are now considered to lie on a broader spectrum of congenital optic disc anomaly (CODA). An increasing number of reports describe clustering of these cases within families, suggesting that inherited genetic elements play a role in disease predisposition.

Humanized zebrafish enhance human hematopoietic stem cell survival and promote acute myeloid leukemia clonal diversity.

Xenograft models are invaluable tools in establishing the current paradigms of hematopoiesis and leukemogenesis. The zebrafish has emerged as a robust alternative xenograft model but, like mice, lack specific cytokines that mimic the microenvironment found in human patients. To address this critical gap, we generated the first humanized zebrafish that express human hematopoietic-specific cytokines (GM-CSF, SCF, and SDF1α).

Low-depth sequencing for copy number abnormalities in multiple myeloma supersedes fluorescent in situ hybridization in scope and resolution.

Multiple myeloma (MM) is an incurable hematological malignancy that relies on cytogenetic determination of copy number abnormalities (CNAs) for prognosis and management. Low-depth whole genome sequencing (LD-WGS) is a cost-effective alternative to targeted genomics for CNA detection, but its value has yet to be explored in MM. DNA from CD138+ cells from MM patients were sequenced using an Illumina NextSeq at <1x depth (ultralow-depth).

ACTH-Secreting Neuroendocrine Carcinoma of the Cecum: Case Report and Review of the Literature.

Background: Approximately 30% of neuroendocrine tumors (NETs) present with secretory syndromes or develop one during the course of the disease. Cushing syndrome caused by a gastrointestinal tract NET is rare, with limited published information. We describe a patient with florid Cushing syndrome due to ectopic adrenocorticotropic hormone (ACTH) from a NET of colonic origin.

Characterization of genome-wide copy number aberrations in colonic mixed adenoneuroendocrine carcinoma and neuroendocrine carcinoma reveals recurrent amplification of PTGER4 and MYC genes.

Colonic mixed adenoneuroendocrine carcinoma (MANEC) is an aggressive neoplasm with worse prognosis compared with adenocarcinoma. To gain a better understanding of the molecular features of colonic MANEC, we characterized the genome-wide copy number aberrations of 14 MANECs and 5 neuroendocrine carcinomas using the OncoScan FFPE (Affymetrix, Santa Clara, CA) assay. Compared with 269 colonic adenocarcinomas, 19 of 42 chromosomal arms of MANEC exhibited a similar frequency of major aberrant events as adenocarcinomas, and 13 chromosomal arms exhibited a higher frequency of copy number gains.

PML nuclear bodies contribute to the basal expression of the mTOR inhibitor DDIT4.

The promyelocytic leukemia (PML) protein is an essential component of PML nuclear bodies (PML NBs) frequently lost in cancer. PML NBs coordinate chromosomal regions via modification of nuclear proteins that in turn may regulate genes in the vicinity of these bodies. However, few PML NB-associated genes have been identified.

Outbreak of Norovirus GII.P17-GII.17 in the Canadian Province of Nova Scotia.

Background. Norovirus is the leading cause of viral gastroenteritis, with GII.4 being the most common circulating genotype.

Glycine and Folate Ameliorate Models of Congenital Sideroblastic Anemia.

Sideroblastic anemias are acquired or inherited anemias that result in a decreased ability to synthesize hemoglobin in red blood cells and result in the presence of iron deposits in the mitochondria of red blood cell precursors. A common subtype of congenital sideroblastic anemia is due to autosomal recessive mutations in the SLC25A38 gene. The current treatment for SLC25A38 congenital sideroblastic anemia is chronic blood transfusion coupled with iron chelation.

vitisFlower®: Development and Testing of a Novel Android-Smartphone Application for Assessing the Number of Grapevine Flowers per Inflorescence Using Artificial Vision Techniques.

Grapevine flowering and fruit set greatly determine crop yield. This paper presents a new smartphone application for automatically counting, non-invasively and directly in the vineyard, the flower number in grapevine inflorescence photos by implementing artificial vision techniques. The application, called vitisFlower(®), firstly guides the user to appropriately take an inflorescence photo using the smartphone's camera.

CRISPR multitargeter: a web tool to find common and unique CRISPR single guide RNA targets in a set of similar sequences.

Genome engineering has been revolutionized by the discovery of clustered regularly interspaced palindromic repeats (CRISPR) and CRISPR-associated system genes (Cas) in bacteria. The type IIB Streptococcus pyogenes CRISPR/Cas9 system functions in many species and additional types of CRISPR/Cas systems are under development. In the type II system, expression of CRISPR single guide RNA (sgRNA) targeting a defined sequence and Cas9 generates a sequence-specific nuclease inducing small deletions or insertions.

Germline mutations in MAP3K6 are associated with familial gastric cancer.

Gastric cancer is among the leading causes of cancer-related deaths worldwide. While heritable forms of gastric cancer are relatively rare, identifying the genes responsible for such cases can inform diagnosis and treatment for both hereditary and sporadic cases of gastric cancer. Mutations in the E-cadherin gene, CDH1, account for 40% of the most common form of familial gastric cancer (FGC), hereditary diffuse gastric cancer (HDGC).

Molecular evolution and functional divergence of X-intrinsic protein genes in plants.

X-intrinsic proteins (XIPs) are a novel class of major intrinsic proteins found in diverse organisms. Recently, XIP genes have been reported to be involved in the transport of a wide range of hydrophobic solutes; however, the evolutionary forces driving their structural and functional divergence in plants are poorly understood. In the present study, comprehensive bioinformatics analyses were performed to gain insight into the molecular and evolutionary mechanisms driving this structural and functional diversification.