Thyroid cancer incidences in the United Arab Emirates: a retrospective study on association with age and gender [version 1; peer review: 1 approved]

Background: Thyroid cancer is the ninth most common malignancy worldwide, but the third most common malignancy in the United Arab Emirates (UAE) . To our knowledge, this is the first UAE nationwide study aimed at presenting incidence rates of thyroid cancer at the national level of UAE based upon data from the national cancer registry and GLOBOCAN. Methods: Between 2011 and 2017, a total of 2036 thyroid cancer cases from UAE patients were registered, of which 75.3% were female and 24.7% male patients. Results: The results showed 6.6% increase in thyroid cancer cases in the UAE from 2011 to 2017 (p < 0.001) with a rise of approximately 400 cases per year from 2011 to 2040. Age standardized rate calculations showed increase in prevalence from 1.18 in 2011 to 4.32 in 2017 but decreases in incidence from 1.05 in 2011 to 0.15 in 2017. This trend is confirmed by the predictive model showing increase in incidence from 0.15 in 2017 to 0.64 by 2040. Gender was shown to be significantly associated with thyroid cancer. The female to male ratio was significantly higher in Emirati patients (4.86:1) (p < 0.001) than expat patients (2.47:1) (p < 0.01). Interestingly, expat patients contributed to the majority of thyroid cancer cases despite having lower female to male ratio. The age at diagnosis was significantly associated with thyroid cancer (p = 0.03) with the highest frequency diagnosed at 35-39 years of age. Globally, data from the predictive model showed that Asia had the highest rate of increase per year and UAE the lowest. Conclusions: The slight increase in thyroid cancer prevalence and incidence, together with the different female to male ratio and diagnosis at younger age warrants further investigation at the molecular level from UAE thyroid cancer patients to elucidate the molecular basis of thyroid cancer

Thyroid cancer incidence in the United Arab Emirates: a retrospective study on association with age and gender [version 2; peer review: 2 approved, 1 approved with reservations]

Background: Thyroid cancer is the ninth most common malignancy worldwide, but the third most common malignancy in the United Arab Emirates (UAE). To our knowledge, this is the first UAE nationwide study aimed at presenting incidence rates of thyroid cancer at the national level of UAE based upon data from the national cancer registry and GLOBOCAN. Methods: Between 2011 and 2017, a total of 2036 thyroid cancer cases from UAE patients were registered, of which 75.3% were female and 24.7% male patients. Results: The results showed 6.6% increase in thyroid cancer cases in the UAE from 2011 to 2017 (p < 0.001) with a rise of approximately 400 cases per year from 2011 to 2040. Age standardized rate calculations showed increase in prevalence from 1.18 in 2011 to 4.32 in 2017 but decreases in incidence from 1.05 in 2011 to 0.15 in 2017. This trend is confirmed by the predictive model showing increase in incidence from 0.15 in 2017 to 0.64 by 2040. Gender was shown to be significantly associated with thyroid cancer. The female to male ratio was significantly higher in Emirati patients (4.86:1) (p < 0.001) than expat patients (2.47:1) (p < 0.01). Interestingly, expat patients contributed to the majority of thyroid cancer cases despite having lower female to male ratio. The age at diagnosis was significantly associated with thyroid cancer (p = 0.03) with the highest frequency diagnosed at 35-39 years of age. Globally, data from the predictive model showed that Asia had the highest rate of increase per year and UAE the lowest. Conclusions: The slight increase in thyroid cancer prevalence and incidence, together with the different female to male ratio and diagnosis at younger age warrants further investigation at the molecular level from UAE thyroid cancer patients to elucidate the molecular basis of thyroid cancer

Prediction of COVID-19 Hospital Length of Stay and Risk of Death Using Artificial Intelligence-Based Modeling

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious virus with overwhelming demand on healthcare systems, which require advanced predictive analytics to strategize COVID-19 management in a more effective and efficient manner. We analyzed clinical data of 2017 COVID-19 cases reported in the Dubai health authority and developed predictive models to predict the patient's length of hospital stay and risk of death. A decision tree (DT) model to predict COVID-19 length of stay was developed based on patient clinical information. The model showed very good performance with a coefficient of determination R2 of 49.8% and a median absolute deviation of 2.85 days. Furthermore, another DT-based model was constructed to predict COVID-19 risk of death. The model showed excellent performance with sensitivity and specificity of 96.5 and 87.8%, respectively, and overall prediction accuracy of 96%. Further validation using unsupervised learning methods showed similar separation patterns, and a receiver operator characteristic approach suggested stable and robust DT model performance. The results show that a high risk of death of 78.2% is indicated for intubated COVID-19 patients who have not used anticoagulant medications. Fortunately, intubated patients who are using anticoagulant and dexamethasone medications with an international normalized ratio of <1.69 have zero risk of death from COVID-19. In conclusion, we constructed artificial intelligence–based models to accurately predict the length of hospital stay and risk of death in COVID-19 cases. These smart models will arm physicians on the front line to enhance management strategies to save lives

Efficacy of photochemical internalisation using disulfonated chlorin and porphyrin photosensitisers: An in vitro study in 2D and 3D prostate cancer models

This study shows the therapeutic outcome of Photochemical Internalisation (PCI) in prostate cancer in vitro surpasses that of Photodynamic Therapy (PDT) and could improve prostate PDT in the clinic, whilst avoiding chemotherapeutics side effects. In addition, the study assesses the potential of PCI with two different photosensitisers (TPCS2a and TPPS2a) in prostate cancer cells (human PC3 and rat MatLyLu) using standard 2D monolayer culture and 3D biomimetic model. Photosensitisers were used alone for photodynamic therapy (PDT) or with the cytotoxin saporin (PCI). TPPS2a and TPCS2a were shown to be located in discrete cytoplasmic vesicles before light treatment and redistribute into the cytosol upon light excitation. PC3 cells exhibit a higher uptake than MatLyLu cells for both photosensitisers. In the 2D model, PCI resulted in greater cell death than PDT alone in both cell lines. In 3D model, morphological changes were also observed. Saporin-based toxicity was negligible in PC3 cells, but pronounced in MatLyLu cells (IC50 = 18 nM). In conclusion, the study showed that tumour features such as tumour cell growth rate or interaction with drugs determine therapeutic conditions for optimal photochemical treatment in metastatic prostate cancer

The FGF-21 genetic variants rs838133 and rs838145 are associated with high salt intake in the Emirati population

Food predilection is linked to variants in the hepatokine “Fibroblast Growth Factor-21” gene (FGF21); with rs838133 linked to the sweet tooth in Caucasians. The effect of FGF21 variants on food intake is still unclear in other populations. A cohort of 196 healthy Emirati subjects was investigated [age: 30.34 ± 9.75yrs (44.4% males)]. The FGF21 rs838133 and rs838145 were genotyped. The daily intake was calculated based on a 61-item food frequency questionnaire. Multivariate analysis was performed using in house R script that implements two-way unsupervised hierarchical clustering to detect the association of the studied single-nucleotide polymorphisms (SNPs) and related SNPs in linkage disequilibrium, using data from the 1000 genome project. Both SNPs were in Hardy-Weinberg Equilaribium (HWE). BMI positively correlated with age (p = 0.002), but not with caloric intake. Salt intake was significantly higher in subjects homozygous (A: rs838133) and (G:rs838145),(p = 0.03 and 0.01, respectively). An interaction was observed between both SNPs; significantly associated with high salt intake. Using publicly available data, both SNPs fall within a region transmitted in Iberians which has a profile closely similar to Caucasians, but far from Chinese population. In conclusion, the minor alleles of FGF21 rs838145 and rs838133 are associated with high salt intake in Emiratis and may suggest neuro-metabolic link to dietary preference across different populations

An Integrative Phenotype-Genotype Approach Using Phenotypic Characteristics from the UAE National Diabetes Study Identifies HSD17B12 as a Candidate Gene for Obesity and Type 2 Diabetes

The United Arab Emirates National Diabetes and Lifestyle Study (UAEDIAB) has identified obesity, hypertension, obstructive sleep apnea, and dyslipidemia as common phenotypic characteristics correlated with diabetes mellitus status. As these phenotypes are usually linked with genetic variants, we hypothesized that these phenotypes share single nucleotide polymorphism (SNP)-clusters that can be used to identify causal genes for diabetes. We explored the National Human Genome Research Institute-European Bioinformatics Institute Catalog of Published Genome-Wide Association Studies (NHGRI-EBI GWAS) to list SNPs with documented association with the UAEDIAB-phenotypes as well as diabetes. The shared chromosomal regions affected by SNPs were identified, intersected, and searched for Enriched Ontology Clustering. The potential SNP-clusters were validated using targeted DNA next-generation sequencing (NGS) in two Emirati diabetic patients. RNA sequencing from human pancreatic islets was used to study the expression of identified genes in diabetic and non-diabetic donors. Eight chromosomal regions containing 46 SNPs were identified in at least four out of the five UAEDIAB-phenotypes. A list of 34 genes was shown to be affected by those SNPs. Targeted NGS from two Emirati patients confirmed that the identified genes have similar SNP-clusters. ASAH1, LRP4, FES, and HSD17B12 genes showed the highest SNPs rate among the identified genes. RNA-seq analysis revealed high expression levels of HSD17B12 in human islets and to be upregulated in type 2 diabetes (T2D) donors. Our integrative phenotype-genotype approach is a novel, simple, and powerful tool to identify clinically relevant potential biomarkers in diabetes. HSD17B12 is a novel candidate gene for pancreatic β-cell function

Systems Immunology Analysis Reveals the Contribution of Pulmonary and Extrapulmonary Tissues to the Immunopathogenesis of Severe COVID-19 Patients

As one of the current global health conundrums, COVID-19 pandemic caused a dramatic increase of cases exceeding 79 million and 1.7 million deaths worldwide. Severe presentation of COVID-19 is characterized by cytokine storm and chronic inflammation resulting in multi-organ dysfunction. Currently, it is unclear whether extrapulmonary tissues contribute to the cytokine storm mediated-disease exacerbation. In this study, we applied systems immunology analysis to investigate the immunomodulatory effects of SARS-CoV-2 infection in lung, liver, kidney, and heart tissues and the potential contribution of these tissues to cytokines production. Notably, genes associated with neutrophil-mediated immune response (e.g. CXCL1) were particularly upregulated in lung, whereas genes associated with eosinophil-mediated immune response (e.g. CCL11) were particularly upregulated in heart tissue. In contrast, immune responses mediated by monocytes, dendritic cells, T-cells and B-cells were almost similarly dysregulated in all tissue types. Focused analysis of 14 cytokines classically upregulated in COVID-19 patients revealed that only some of these cytokines are dysregulated in lung tissue, whereas the other cytokines are upregulated in extrapulmonary tissues (e.g. IL6 and IL2RA). Investigations of potential mechanisms by which SARS-CoV-2 modulates the immune response and cytokine production revealed a marked dysregulation of NF-κB signaling particularly CBM complex and the NF-κB inhibitor BCL3. Moreover, overexpression of mucin family genes (e.g. MUC3A, MUC4, MUC5B, MUC16, and MUC17) and HSP90AB1 suggest that the exacerbated inflammation activated pulmonary and extrapulmonary tissues remodeling. In addition, we identified multiple sets of immune response associated genes upregulated in a tissue-specific manner (DCLRE1C, CHI3L1, and PARP14 in lung; APOA4, NFASC, WIPF3, and CD34 in liver; LILRA5, ISG20, S100A12, and HLX in kidney; and ASS1 and PTPN1 in heart). Altogether, these findings suggest that the cytokines storm triggered by SARS-CoV-2 infection is potentially the result of dysregulated cytokine production by inflamed pulmonary and extrapulmonary (e.g. liver, kidney, and heart) tissues

Multiple early introductions of SARS-CoV-2 into a global travel hub in the Middle East

International travel played a significant role in the early global spread of SARS-CoV-2. Understanding transmission patterns from different regions of the world will further inform global dynamics of the pandemic. Using data from Dubai in the United Arab Emirates (UAE), a major international travel hub in the Middle East, we establish SARS-CoV-2 full genome sequences from the index and early COVID-19 patients in the UAE. The genome sequences are analysed in the context of virus introductions, chain of transmissions, and possible links to earlier strains from other regions of the world. Phylogenetic analysis showed multiple spatiotemporal introductions of SARS-CoV-2 into the UAE from Asia, Europe, and the Middle East during the early phase of the pandemic. We also provide evidence for early community-based transmission and catalogue new mutations in SARS-CoV-2 strains in the UAE. Our findings contribute to the understanding of the global transmission network of SARS-CoV-2

Mutational Profile and Pathological Features of a Case of Interleukin-10 and RGS1-Positive Spindle Cell Variant Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma with spindle cell morphology is a rare variant. We present the case of a 74-year-old male who initially presented with a right supraclavicular (lymph) node enlargement. Histological analysis showed a proliferation of spindle-shaped cells with narrow cytoplasms. An immunohistochemical panel was used to exclude other tumors, such as melanoma, carcinoma, and sarcoma. The lymphoma was characterized by a cell-of-origin subtype of germinal center B-cell-like (GCB) based on Hans’ classifier (CD10-negative, BCL6-positive, and MUM1-negative); EBER negativity, and the absence of BCL2, BCL6, and MYC rearrangements. Mutational profiling using a custom panel of 168 genes associated with aggressive B-cell lymphomas confirmed mutations in ACTB, ARID1B, DUSP2, DTX1, HLA-B, PTEN, and TNFRSF14. Based on the LymphGen 1.0 classification tool, this case had an ST2 subtype prediction. The immune microenvironment was characterized by moderate infiltration of M2-like tumor-associated macrophages (TMAs) with positivity of CD163, CSF1R, CD85A (LILRB3), and PD-L1; moderate PD-1 positive T cells, and low FOXP3 regulatory T lymphocytes (Tregs). Immunohistochemical expression of PTX3 and TNFRSF14 was absent. Interestingly, the lymphoma cells were positive for HLA-DP-DR, IL-10, and RGS1, which are markers associated with poor prognosis in DLBCL. The patient was treated with R-CHOP therapy, and achieved a metabolically complete response