Establishment of a clinical cancer genetics program for breast cancer in a resource-limited country; challenges and opportunities.

Breast cancer is the most common cancer among women worldwide, and its incidence rate is still increasing, especially among younger women. Nationally, it constitutes one-fifth of all cancer cases and almost 40% of all female cancers. With a median age of 51 years, breast cancer is diagnosed at least a decade earlier, and at more advanced stages compared to Western societies.

Circulating hsa-miR-320a and its regulatory network in type 1 diabetes mellitus.

Introduction: Increasing evidence from human and animal model studies indicates the significant role of microRNAs (miRNAs) in pancreatic beta cell function, insulin signaling, immune responses, and pathogenesis of type 1 diabetes (T1D).

Methods: We aimed, using next-generation sequencing, to screen miRNAs from peripheral blood mononuclear cells of eight independent Kuwaiti-Arab families with T1D affected siblings, consisting of 18 T1D patients and 18 unaffected members, characterized by no parent-to-child inheritance pattern.

Results: Our analysis revealed 20 miRNAs that are differentially expressed in T1D patients compared with healthy controls.

ERAMER: A novel in silico tool for prediction of ERAP1 enzyme trimming.

MHC class I pathway consists of four main steps: proteasomal cleavage in the cytosol in which precursor proteins are cleaved into smaller peptides, which are then transported into the endoplasmic reticulum by the transporter associated with antigen processing, TAP, for further processing (trimming) from the N-terminal region by an ER resident aminopeptidases 1 (ERAP1) enzyme, to generate optimal peptides (8-10 amino acids in length) to produce a stable MHCI-peptide complex, that get transited via the Golgi apparatus to the cell surface for presentation to the cellular immune system. Several studies reported specificities related to the ERAP1 trimming process, yet there is no in silico tool for the prediction of the trimming process of the ERAP1 enzyme. In this paper, we provide and implement a prediction model for the trimming process of the ERAP1 enzyme.

Impact of the SARS-CoV-2 pandemic on the overall respiratory viruses' transmission in a cancer care setting.

Introduction And Objective: The emergence of the COVID-19 pandemic raised questions about the interaction between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory viruses. The objective of this study is to validate the impact of the SARS-CoV-2 pandemic and its interventional measures on the respiratory viruses' transmission/infection rates.

Methods: A retrospective chart review was conducted for cancer patients who underwent laboratory-confirmed respiratory virus polymerase chain reaction (PCR) testing from January 2018 to June 2022.

The Proinflammatory Role of ANGPTL8 R59W Variant in Modulating Inflammation through NF-κB Signaling Pathway under TNFα Stimulation.

Background: Angiopoietin-like protein 8 (ANGPTL8) is known to regulate lipid metabolism and inflammation. It interacts with ANGPTL3 and ANGPTL4 to regulate lipoprotein lipase (LPL) activity and with IKK to modulate NF-κB activity. Further, a single nucleotide polymorphism (SNP) leading to the ANGPTL8 R59W variant associates with reduced low-density lipoprotein/high-density lipoprotein (LDL/HDL) and increased fasting blood glucose (FBG) in Hispanic and Arab individuals, respectively.

Linkage analysis using whole exome sequencing data implicates SLC17A1, SLC17A3, TATDN2 and TMEM131L in type 1 diabetes in Kuwaiti families.

Type 1 diabetes (T1D) is characterized by the progressive destruction of pancreatic β-cells, leading to insulin deficiency and lifelong dependency on exogenous insulin. Higher estimates of heritability rates in monozygotic twins, followed by dizygotic twins and sib-pairs, indicate the role of genetics in the pathogenesis of T1D. The incidence and prevalence of T1D are alarmingly high in Kuwait.

Factors that predict severity of infection and seroconversion in immunocompromised children and adolescents with COVID-19 infection.

Objectives: We aimed to study the outcomes, severity, and seroconversion post SARS-CoV-2 infection in immunocompromised children and adolescents treated at our center.

Method: For this observational study, all pediatric patients who had COVID-19 infection from Sep-22-2020 to Nov-10-2021were identified by reviewing our laboratory records. Their charts were reviewed to determine clinical severity and outcome.

Online Teaching Practicum in Malaysia in the Time of COVID-19 Pandemic.

When the teachers' training practicum was paralyzed during the COVID-19 pandemic, preservice teachers in Malaysia were required to adapt to the online practicum. This qualitative case study was conducted with 20 preservice teachers to investigate their online teaching practicum experiences. The study drew on the Engagement Theory and Disaster Management Cycle framework to further suggest teaching approaches that might be effective during a tragic situation.

Towards the Sustainability of English Language Teachers Professionalism Professional Development Programs: Extrinsic and Intrinsic Satisfactions.

With a great emphasis on understanding teacher satisfaction in designing and improving professional development programs (PDPs), this study investigated the intrinsic and extrinsic aspects of satisfaction among Malaysian English as a Second Language (ESL) primary school teachers after finishing their first-degree program. A mixed-methods design was employed by using both quantitative methods (by administering survey research) and qualitative methods (through the use of items of the semi-structured questionnaire). The survey questionnaire was adapted from OECD Teaching and Learning International Survey (TALIS) questionnaire to measure the level of intrinsic and extrinsic teacher satisfaction among the samples.

A Phenomenological Study of Educators' Experience After a Year of the COVID-19 Pandemic.

This phenomenological study investigated educators' lived experiences of teaching online in higher institutions in Malaysia. Data, which was generated through semi-structured interviews with 20 lecturers from three universities in the country, was analysed based on the thematic analysis approach guided by the Technological, Pedagogical, and Content Knowledge (TPACK)-self-efficacy framework. The findings revealed that after a year of teaching online, the potential of technology has been acknowledged by the educators after some trials and constraints were addressed.

Genetic and clinical characteristics of pediatric patients with familial hemophagocytic lymphohistiocytosis.

Background: Our study was designed to investigate the frequencies and distributions of familial hemophagocytic lymphohistiocytosis (FHL) associated genes in Saudi patients.

Methods: FHL associated gene screening was performed on 87 Saudi patients who were diagnosed with hemophagocytic lymphohistiocytosis (HLH) between 1995 and 2014. The clinical and biochemical profiles were also retrospectively captured and analyzed.

Unraveling a fine-scale high genetic heterogeneity and recent continental connections of an Arabian Peninsula population.

Recent studies have showed the diverse genetic architecture of the highly consanguineous populations inhabiting the Arabian Peninsula. Consanguinity coupled with heterogeneity is complex and makes it difficult to understand the bases of population-specific genetic diseases in the region. Therefore, comprehensive genetic characterization of the populations at the finest scale is warranted.

Genome-wide landscape establishes novel association signals for metabolic traits in the Arab population.

While the Arabian population has a high prevalence of metabolic disorders, it has not been included in global studies that identify genetic risk loci for metabolic traits. Determining the transferability of such largely Euro-centric established risk loci is essential to transfer the research tools/resources, and drug targets generated by global studies to a broad range of ethnic populations. Further, consideration of populations such as Arabs, that are characterized by consanguinity and a high level of inbreeding, can lead to identification of novel risk loci.

Variant rs17782313 Associates With Increased Levels of DNAJC27, Ghrelin, and Visfatin and Correlates With Obesity and Hypertension in a Kuwaiti Cohort.

Melanocortin 4 receptor (MC4R), a notable component of the melanocortin system, regulates appetite, body weight, and energy homeostasis. Genome-wide association studies have identified several variants associated with adiposity; of these, rs17782313, which is associated with increased body mass index (BMI) and overeating behavior, is of particular interest. Another gene associated with increased adiposity in global genome-wide association studies is , a heat shock protein known to be elevated in obesity.

Genome-wide association study identifies novel risk variants from RPS6KA1, CADPS, VARS, and DHX58 for fasting plasma glucose in Arab population.

Consanguineous populations of the Arabian Peninsula, which has seen an uncontrolled rise in type 2 diabetes incidence, are underrepresented in global studies on diabetes genetics. We performed a genome-wide association study on the quantitative trait of fasting plasma glucose (FPG) in unrelated Arab individuals from Kuwait (discovery-cohort:n = 1,353; replication-cohort:n = 1,196). Genome-wide genotyping in discovery phase was performed for 632,375 markers from Illumina HumanOmniExpress Beadchip; and top-associating markers were replicated using candidate genotyping.

Mitochondrial DNA D-loop sequencing reveals obesity variants in an Arab population.

The association of mitochondrial DNA (mtDNA) variations with obesity has been investigated in diverse populations across the world. However, such obesity-associated mtDNA examinations are rarely conducted in Arab populations. We re-sequenced mtDNA displacement loop (D-loop) region of 395 Arab individuals of Kuwait.

Caveolin-1 Variant Is Associated With the Metabolic Syndrome in Kuwaiti Children.

Caveolin-1 () variants have been suggested to be associated with obesity and related metabolic disorders, but information based on human studies is limited. In the present study, we aimed to investigate the potential association between the rs1997623 C/A variant and metabolic syndrome (MetS) in Kuwaiti children. DNA from saliva samples collected from 1313 Kuwaiti children (mean age: 12 years) were genotyped using the TaqMan SNP genotyping assay.

Assessment of coding region variants in Kuwaiti population: implications for medical genetics and population genomics.

Consanguineous populations of the Arabian Peninsula have been underrepresented in global efforts that catalogue human exome variability. We sequenced 291 whole exomes of unrelated, healthy native Arab individuals from Kuwait to a median coverage of 45X and characterised 170,508 single-nucleotide variants (SNVs), of which 21.7% were 'personal'.

Genome-wide association study identifies novel recessive genetic variants for high TGs in an Arab population.

Abnormal blood lipid levels are influenced by genetic and lifestyle/dietary factors. Although many genetic variants associated with blood lipid traits have been identified in Europeans, similar data in Middle Eastern populations are limited. We performed a genome-wide association study with Arab individuals (discovery cohort: 1,353; replication cohort: 1,176) from Kuwait to identify possible associations of genetic variants with high lipid levels.

Association of FTO rs9939609 with Obesity in the Kuwaiti Population: A Public Health Concern?

Objective: To investigate the effect of the common fat mass and obesity-associated (FTO) gene polymorphism rs9939609 on body mass index (BMI) in one of the most obese populations worldwide.

Subjects And Methods: Genotypic data for FTO rs9939609 were available for 1,034 unrelated Kuwaiti adults obtained from Kuwait's Dasman Diabetes Institute and Kuwait University. The association between the FTO polymorphism with BMI as continuous and categorical (normal BMI [< 25] vs.

Investigation of genetic variation and lifestyle determinants in vitamin D levels in Arab individuals.

Background: Differences in the concentrations of circulating 25-hydroxyvitamin D [25(OH)D] are associated with a wide range of health outcomes; however, most studies on genetic variants that impact 25(OH)D levels have been conducted in European populations. Here we aimed to identify common genetic variants that affect vitamin D concentrations in individuals of self-reported Arab ethnicity.

Methods: The study included 1151 Arab subjects living in Kuwait.

Exome sequencing for the differential diagnosis of ciliary chondrodysplasias: Example of a WDR35 mutation case and review of the literature.

Exome sequencing is becoming widely popular and affordable, making it one of the most desirable methods for the identification of rare genetic variants for clinical diagnosis. Here, we report the clinical application of whole exome sequencing for the ultimate diagnosis of a ciliary chondrodysplasia case presented with an initial clinical diagnosis of Asphyxiating Thoracic Dystrophy (ATD, Jeune Syndrome). We have identified a novel homozygous missense mutation in WDR35 (c.

Genetic variants associated with warfarin dosage in Kuwaiti population.

Assessing the distinct prevalence or absence of genetic variants associated with differential response to the anticoagulant medication of warfarin in different population groups is actively pursued by pharmacogenomics community. Populations from Arabian Peninsula are underrepresented in such studies. By way of examining exome- and genome-wide genotype data from 1395 Arab individuals in Kuwait, we report distinct occurrence of warfarin response-related variants rs12460590_A/CYP2A7, rs2108622_T/CYP4F2, rs2884737_C/VKORC1 and distinct absence of rs11150606_C/PRSS53 in Kuwaiti population.

The TCN2 variant of rs9606756 [Ile23Val] acts as risk loci for obesity-related traits and mediates by interacting with Apo-A1.

Objective: Despite alarming obesity levels in the Arabian Peninsula, its population lacks convincingly identified genetic determinants of obesity. A genome-wide association study was performed for obesity-related anthropometric traits in Arabs and to decipher mechanisms by which the variants mediate traits.

Methods: The Illumina HumanOmniExpress BeadChip was used to genotype 1,353 Arab individuals (largely with Class I obesity) from Kuwait.