Highly mutable pathogens generate viral diversity that impacts virulence, transmissibility, treatment, and thwarts acquired immunity. We previously described C19-SPAR-Seq, a high-throughput, next-generation sequencing platform to detect SARS-CoV-2 that we here deployed to systematically profile variant dynamics of SARS-CoV-2 for over 3 years in a large, North American urban environment (Toronto, Canada). Sequencing of the ACE2 receptor binding motif and polybasic furin cleavage site of the Spike gene in over 70,000 patients revealed that population sweeps of canonical variants of concern (VOCs) occurred in repeating wavelets.
View Article and Find Full Text PDFBackground The prevalence of obesity has increased over the years, resulting in multiple physical and psychological health issues that impact the quality of human life. Numerous Western studies have linked obesity and depression, but few studies have investigated this correlation among the Saudi population. Hence, this study assesses the correlation between obesity and depression among the general population of Saudi Arabia.
View Article and Find Full Text PDFAims: To determine the acceptability and identify potential concerns and barriers of using a hypothetical smartphone application (app) for home monitoring (HM) of visual function among patients with diabetes.
Methods: Quantitative, cross-sectional study using a self-administered questionnaire. Patients diagnosed with diabetes aged between 20 and 70 years were included.
Functionally characterizing the genetic alterations that drive pancreatic cancer is a prerequisite for precision medicine. Here, we perform somatic CRISPR/Cas9 mutagenesis screens to assess the transforming potential of 125 recurrently mutated pancreatic cancer genes, which revealed USP15 and SCAF1 as pancreatic tumor suppressors. Mechanistically, we find that USP15 functions in a haploinsufficient manner and that loss of USP15 or SCAF1 leads to reduced inflammatory TNFα, TGF-β and IL6 responses and increased sensitivity to PARP inhibition and Gemcitabine.
View Article and Find Full Text PDFBrenner tumors are relatively uncommon surface epithelial tumors of the ovary, accounting for less than 2% of all ovarian tumors. They may be of benign, borderline, or malignant nature as classified by the World Health Organization. Definitive diagnosis is made by histopathological examination after surgical excision, as it does not have pathognomonic imaging features.
View Article and Find Full Text PDFMutational signatures represent a genomic footprint of endogenous and exogenous mutational processes through tumor evolution. However, their functional impact on the proteome remains incompletely understood. We analyzed the protein-coding impact of single-base substitution (SBS) signatures in 12,341 cancer genomes from 18 cancer types.
View Article and Find Full Text PDFIt is widely assumed that all normal somatic cells can equally perform homologous recombination (HR) and non-homologous end joining in the DNA damage response (DDR). Here, we show that the DDR in normal mammary gland inherently depends on the epithelial cell lineage identity. Bioinformatics, post-irradiation DNA damage repair kinetics, and clonogenic assays demonstrated luminal lineage exhibiting a more pronounced DDR and HR repair compared to the basal lineage.
View Article and Find Full Text PDFKikuchi's disease is an idiopathic self-limiting condition first reported in Japan in 1972. However, hemophagocytic lympho-histiocytosis is a condition that occurs due to overstimulation of the immune system. The presence of the two conditions is rare, and the clinical observation of this unusual clinical syndrome is worth reporting.
View Article and Find Full Text PDFBackground: Computer vision syndrome (CVS) can be described as ocular-related symptoms that result from prolonged exposure and use of computers, smartphones, tablets, and other devices with digital displays. The main objective of this study was to investigate the prevalence of CVS among school-age children, the associated signs, risk factors, and the association between the disease before and during the COVID-19 pandemic in the Jazan region of Saudi Arabia. Methods: The study employed a descriptive cross-sectional research design.
View Article and Find Full Text PDFUnlabelled: Systematically investigating the scores of genes mutated in cancer and discerning disease drivers from inconsequential bystanders is a prerequisite for precision medicine but remains challenging. Here, we developed a somatic CRISPR/Cas9 mutagenesis screen to study 215 recurrent "long-tail" breast cancer genes, which revealed epigenetic regulation as a major tumor-suppressive mechanism. We report that components of the BAP1 and COMPASS-like complexes, including KMT2C/D, KDM6A, BAP1, and ASXL1/2 ("EpiDrivers"), cooperate with PIK3CAH1047R to transform mouse and human breast epithelial cells.
View Article and Find Full Text PDFQuantum bandgap buffer layers can improve sunlight absorption in the short wavelength region, hence improving the performance of CIGS solar cells. In this study, we use numerical modelling to determine the impact of various buffer layers' electrical characteristics on the performance of CIGS thin film photovoltaic devices, particularly, carrier concentration and the quantum effect. As well AgS buffer layer has been experimentally examined to fulfilment its effect in term of bulk and quantum bandgap.
View Article and Find Full Text PDFBackground: Breast cancer is a highly heterogeneous disease with multiple drivers and complex regulatory networks. Periostin (Postn) is a matricellular protein involved in a plethora of cancer types and other diseases. Postn has been shown to be involved in various processes of tumor development, such as angiogenesis, invasion, cell survival and metastasis.
View Article and Find Full Text PDFBackground: The role of fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in indolent lymphoma has been minimally studied.
Objective: This study aims to assess the value of FDG-PET/CT in predicting the prognosis of indolent lymphoma.
Methods: We prospectively recruited 42 patients with indolent lymphoma.
Background: Approximately 5-10% of HER2-positive breast cancers can be defined by low expression of the Ste20-like kinase, SLK, and high expression of SOX10. Our lab has observed that genetic deletion of SLK results in the induction of Sox10 and significantly accelerates tumor initiation in a HER2-induced mammary tumor model. However, the mechanism responsible for the induction of SOX10 gene expression in this context remains unknown.
View Article and Find Full Text PDFOver the past 20 years, the Ste20-like kinase (SLK; also known as STK2) has emerged as a central regulator of cytoskeletal dynamics. Reorganization of the cytoskeleton is necessary for a plethora of biological processes including apoptosis, proliferation, migration, tissue repair and signaling. Several studies have also uncovered a role for SLK in disease progression and cancer.
View Article and Find Full Text PDFTrismus is a post-radiotherapy complication that affects survivors of head and neck cancers. It is described as the reduction of mouth opening to less than 35 mm. The condition is a progressive process; hence early intervention is crucial to prevent further damage and weakness to the elevator muscles of the mandible.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Cell Res
February 2021
Duchenne's muscular dystrophy (DMD) is a severe muscle wasting disorder characterized by the loss of dystrophin expression, muscle necrosis, inflammation and fibrosis. Ongoing muscle regeneration is impaired by persistent cytokine stress, further decreasing muscle function. Patients with DMD rarely survive beyond their early 20s, with cardiac and respiratory dysfunction being the primary cause of death.
View Article and Find Full Text PDFHER2 is overexpressed in 20-30% of all breast cancers and is associated with an invasive disease and poor clinical outcome. The Ste20-like kinase (SLK) is activated downstream of HER2/Neu and is required for efficient epithelial-to-mesenchymal transition, cell cycle progression, and migration in the mammary epithelium. Here we show that loss of SLK in a murine model of HER2/Neu-positive breast cancers significantly accelerates tumor onset and decreases overall survival.
View Article and Find Full Text PDFWorldwide, food waste is one of the prime issues threatening food security and the Kingdom of Saudi Arabia (KSA) is not an exception. With 427 kg of food wasted per capita per year, the country ranks among the top food wasters. Ironically, the Kingdom has limited arable lands and scarce water resources to support mass-scale agriculture and to feed its increasing population, KSA relies heavily on imports and subsidized food to meet needs.
View Article and Find Full Text PDFWe have extended our previous survey of the association of mitochondrial prevalence in particular tissues with ascites susceptibility in broilers. We previously reported that in breast muscle of 22 week old susceptible line male birds had significantly higher mtDNA copy number relative to nuclear copy number (mtDNA/nucDNA), compared to resistant line male birds. The higher copy number correlated with higher expression of PPARGC1A mRNA gene.
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