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Breast cancer (BC) is a growing global public health concern, affecting millions of women worldwide. Gulf Cooperation Council (GCC) countries are no exception to this trend. Mortality rates in GCC nations are still high despite improvements in BC treatment. This article examines the changing picture of BC incidence, prevalence, and mortality in the GCC region from 1990 to 2019 and predictions up to 2030. Using data from the Global Burden of Disease study, we analyzed BC incidence, prevalence, and mortality rates per 100,000 individuals across different age groups and countries. The study reveals a significant rise in Age-Standardized Incidence Rates (ASIR) for breast cancer among females in Saudi Arabia from 1990 to 2019, with Oman experiencing the highest increase and Kuwait the highest decrease. Bahrain also saw a significant increase in male Age-standardized death rate (ASDR), despite all other countries experiencing a decrease. Also, the data demonstrated a statistically significant positive correlation between ASIR and Human Development Index (HDI), evident across all countries. Metabolic risk and tobacco use were identified as primary contributors. A ten-year BC prediction predicts a significant increase in female cases, with Saudi Arabia expected to experience the highest rise. This study underscores the urgent need for improved BC awareness, early detection through screening programs, enhanced access to quality healthcare services, and the addressing of sociocultural barriers in the GCC countries.

The incidence of early-onset colorectal cancer (EO-CRC) has been consistently rising leading to a significant cancer burden among younger adults in Asian and Middle Eastern high-income countries. The study aims to investigate the survival outcomes of EO-CRC among high-income Asian and Middle Eastern populations from 1990 to 2019 using the mortality-to-incidence ratio, with a focus on examining the differences in gender. This is a systematic analysis of the Global Burden of Disease (GBD) 2019 study. We include individuals aged 15 to 49 years old in high-income Asian and the Middle Eastern countries. The colorectal cancer mortality-to-incidence ratio (MIR) was calculated for both genders by dividing the age-specific mortality rate per 100,000 for colorectal cancer by the age-specific incidence rate per 100,000 for each nation in the sample for a given year. An overall decline in male and female MIR was observed from 1990 to 2019 in Asian and Middle Eastern countries. Ten out of thirteen Asian and Middle Eastern countries had a higher female MIR compared to their male counterparts. The global male MIR was found to be significantly higher than that of female (p-value 0.008, coefficient estimate: 1.51). In Middle Eastern countries, Saudi Arabia had a significantly higher female MIR compared to their male counterparts (p < 0.0001, coefficient estimate: 12.65). This research addresses the knowledge gap concerning gender-based differences in EO-CRC survival outcomes in high-income Asian and Middle Eastern countries, providing insights into the factors influencing these disparities in these regions. Policymakers should focus on developing targeted prevention and treatment programs for women, and addressing cultural and social barriers that may prevent women from seeking timely medical care.

Many tissues contain adult mesenchymal stem cells (MSCs), which may be used in tissue regeneration therapies. However, the MSC availability in most tissues is limited which demands expansion in vitro following isolation. Like many developing cells, the state of MSCs is affected by the surrounding microenvironment, and mimicking this natural microenvironment that supports multipotent or differentiated state in vivo is essential to understand for the successful use of MSC in regenerative therapies. Many researchers are, therefore, optimizing cell culture conditions in vitro by altering growth factors, extracellular matrices, chemicals, oxygen tension, and surrounding pH to enhance stem cells self-renewal or differentiation. Insulin-like growth factors (IGFs) system has been demonstrated to play an important role in stem cell biology to either promote proliferation and self-renewal or enhance differentiation onset and outcome, depending on the cell culture conditions. In this review, we will describe the importance of IGFs, IGF-1 and IGF-2, in development and in the MSC niche and how they affect the pluripotency or differentiation towards multiple lineages of the three germ layers.

Background: The rise in vaping use across high-income countries is driven partly by marketing, advertising, and flavors promoted by e-cigarette producer firms. The current study aim is to examine the potential variation in the relative research volume on vaping products between countries with highest level of tobacco banning internet advertising and those with no ban on tobacco internet advertising. Method: We used weekly relative search volume (RSV) data produced by Google Trends (GT). A total of eight countries included in the study, Saudi Arabia, United Arab Emirates, United States, Ireland, New Zealand, Canada, United Kingdom, and Australia. The countries were regrouped into ban in internet advertising countries, and the no bans in internet advertising countries. Results: The trend test indicates a statistically significant upward trend in GT vaping search volume across all the included countries. However, the percentage increase of search volume for the ads no ban group was higher than ban group. There is a statistically significant difference in median between the two group, (P < 0.0007), (median, 6.25 [IQR, 0.103] for the ban in internet advertising countries vs (median 7.5 Interquartile Ranges (IQR), [0.542] for the no bans on internet advertising countries. Conclusion: Countries with stringent bans on online tobacco advertising have shown lower levels of vaping-related search interest, indicating the potential effectiveness of such regulations. Our research underscores the importance of emphasizing comprehensive bans on tobacco advertising and sales online could help mitigate the upward trend in vaping interest.

Background Human iPSCs' derivation and use in clinical studies are transforming medicine. Yet, there is a high cost and long waiting time associated with autologous iPS-based cellular therapy, and the genetic engineering of hypo-immunogenic iPS cell lines is hampered with numerous hurdles. Therefore, it is increasingly interesting to create cell stocks based on HLA haplotype distribution in a given population. This study aimed to assess the potential of HLA-based iPS banking for the Saudi population. Methods In this study, we interrogated the HLA database of the Saudi Stem Cell Donor Registry (SSCDR), containing high-resolution HLA genotype data from 64,315 registered Saudi donors at the time of analysis. This database was considered to be a representative sample of the Saudi population. The most frequent HLA haplotypes in the Saudi population were determined, and an in-house developed iterative algorithm was used to identify their HLA matching percentages in the SSCDR database and cumulative coverage. Subsequently, to develop a clinically relevant protocol for iPSCs generation, and to illustrate the applicability of the concept of HLA-based banking for cell therapy purposes, the first HLA-based iPS cell line in Saudi Arabia was generated. Clinically relevant methods were employed to generate the two iPS clones from a homozygous donor for the most prevalent HLA haplotype in the Saudi population. The generated lines were then assessed for pluripotency markers, and their ability to differentiate into all three germ layers, beating cardiomyocytes, and neural progenitors was examined. Additionally, the genetic stability of the HLA-iPS cell lines was verified by comparing the mutational burden in the clones and the original blood sample, using whole-genome sequencing. The standards set by the American College of Medical Genetics and Genomics (ACMG) were used to determine the clinical significance of identified variants. Results The analysis revealed that the establishment of only 13 iPSC lines would match 30% of the Saudi population, 39 lines would attain 50% coverage, and 596 lines would be necessary for over 90% coverage. The proof-of-concept HLA-iPSCs, which cover 6.1% of the Saudi population, successfully demonstrated pluripotency and the ability to differentiate into various cell types including beating cardiomyocytes and neuronal progenitors. The comprehensive genetic analysis corroborated that all identified variants in the derived iPSCs were inherently present in the original donor sample and were classified as benign according to the standards set by the ACMG. Conclusions Our study sets a road map for introducing iPS-based cell therapy in the Kingdom of Saudi Arabia. It underscores the pragmatic approach of HLA-based iPSC banking which circumvents the limitations of autologous iPS-based cellular therapies. The successful generation and validation of iPSC lines based on the most prevalent HLA haplotype in the Saudi population signify a promising step toward broadening the accessibility and applicability of stem cell therapies and regenerative medicine in Saudi Arabia.

Breast cancer is the most common cancer among women worldwide. High-income countries have a greater incidence and mortality rate of breast cancer than low-income countries. As a result, raising awareness about breast cancer is crucial in increasing the chances of early detection and treatment. Social media has evolved into an essential tool for Breast Cancer Awareness Month campaigns, allowing people to share their breast cancer stories and experiences while also providing a venue for education and support. The aim of this study was to assess the level of public interest in searches linked to breast cancer among a sample of high-income nations with a sizable internet user base from 2012 to 2022. We also sought to compare the proportional search volume for breast cancer during Breast Cancer Awareness Month with that during other months of the year. Google Trends was used to retrieve data on internet user search behaviors in the context of breast cancer from 2012 to 2022. Seven countries were evaluated in this study: Australia, Canada, Ireland, New Zealand, the United Kingdom, Saudi Arabia, and the United States, in addition to global data. Breast cancer relative search volume trends were analyzed annually, monthly, and weekly from 2012 to 2022. The annual percent change (APC) was calculated for each country and worldwide. Monthly and weekly data were used to identify potential trends. A fluctuating pattern in APC rates was observed, with a notable increase in 2018 and a significant decrease in 2020, particularly in Saudi Arabia. Monthly analysis revealed a consistent peak in search volume during October (Breast Cancer Awareness Month) each year. Weekly trends over a 20-year period indicated significant decreases in Australia, Canada, New Zealand, and the United States, while increases were noted in Ireland. Heatmap analysis further highlighted a consistent elevation in median search volume during October across all countries. These findings underscore the impact of Breast Cancer Awareness Month and suggest potential influences of governmental COVID-19 pandemic control measures in 2020 on internet search behavior.

Insulin-like growth factors (IGFs) are critical components of the stem cell niche, as they regulate proliferation and differentiation of stem cells into different lineages, including skeletal muscle. We have previously reported that insulin-like growth factor binding protein-6 (IGFBP-6), which has high affinity for IGF-2, alters the differentiation process of placental mesenchymal stem cells (PMSCs) into skeletal muscle. In this study, we determined the roles of IGF-1 and IGF-2 and their interactions with IGFBP-6. We showed that IGF-1 increased IGFBP-6 levels within 24 hours but decreased after 3 days, while IGF-2 maintained higher levels of IGFBP-6 throughout myogenesis. IGF-1 increased IGFBP-6 in the early phase as a requirement for muscle commitment. In contrast, IGF-2 enhanced muscle differentiation as shown by the expression of muscle differentiation markers MyoD, MyoG, and MHC. IGF-1 and IGF-2 had different effects on muscle differentiation with IGF-1 promoting early commitment to muscle and IGF-2 promoting complete muscle differentiation. We also showed that PMSCs acquired increasing capacity to synthesize IGF-2 during muscle differentiation, and the capacity increased as the differentiation progressed suggesting an autocrine and/or paracrine effect. Additionally, we demonstrated that IGFBP-6 could enhance the muscle differentiation process in the absence of IGF-2.

Sickle cell disease (SCD) is a major chronic hematologic disorder in Saudi Arabia associated with recurrent vaso-occlusive crises (VOCs), acute pain episodes, and heavy reliance on emergency department (ED) visits. Despite improvements in survival, longitudinal data on ED utilization patterns and their determinants remain limited in the region. Therefore, the aim of this study is to assess temporal trends and predictors of ED utilization among patients with SCD across multiple tertiary centers in Saudi Arabia between 2016 and 2021. This multicenter retrospective cohort study analyzed data from the National Guard Health Affairs (NGHA) electronic health record (EHR) system across five hospitals (Riyadh, Jeddah, Madinah, Dammam, and Al-Ahsa). The study included all patients with a confirmed SCD diagnosis (ICD-10 code D57) and at least one ED visit during the study period. After applying the eligibility criteria, 691 patients were included. Demographics, comorbidities, hospital region, and prescribed ED medications, including opioids, non-steroidal anti-inflammatory drugs (NSAIDs), neuropathic agents, and benzodiazepines. The primary outcome was annual ED visits per patient. Multivariable negative binomial regression estimated incidence rate ratios (IRRs) with 95% confidence intervals (CIs), adjusted for demographics, comorbidities, and clustering by hospital site. The cohort [mean (SD) age, 26.5 (13.6) years; 350 (50.7%) men] showed a sharp rise in ED visits from 9.2 visits in 2016 to 38.8 in 2021 (relative increase, + 76.3%; < 0.001). Hospital admissions also rose from 6.3 to 13.6 ( < 0.001). In 2021, the mean ED visit rate [38.83 (2) ± 10.59] exceeded the threshold for high ED utilization > 33. Male gender (IRR, 1.52; 95% CI, 1.28-1.81; < 0.001), older age (per 10 years: IRR, 1.27; 95% CI, 1.08-1.50; = 0.006), and asthma (IRR, 1.29; 95% CI, 1.04-1.60; = 0.02) predicted higher ED utilization. Opioids were prescribed in 96.5% of visits, mostly for single-day use (93.5%). ED utilization among patients with SCD from the NGHA hospitals in Saudi Arabia rose substantially between 2016 and 2021, reflecting both clinical severity and system-level care gaps. Our findings highlight the need for standardized pain protocols, comprehensive outpatient services, and Vision 2030-aligned transformations to reduce preventable ED dependence.

The most prevalent form of epileptic encephalopathy is Dravet syndrome (DRVT), which is triggered by the pathogenic variant SCN1A in 80% of cases. iPSCs with different SCN1A mutations have been constructed by several groups to model DRVT syndrome. However, no studies involving DRVT-iPSCs with rare genetic variants have been conducted. Here, we established two DRVT-iPSC lines harboring a homozygous mutation in the CPLX1 gene and heterozygous mutation in SCN9A gene. Therefore, the derivation of these iPSC lines provides a unique cellular platform to dissect the molecular mechanisms underlying the cellular dysfunctions consequent to CPLX1 and SCN9A mutations.

As mesenchymal stem cells (MSCs) are being investigated for regenerative therapies to be used in the clinic, delineating the roles of the IGF system in MSC growth and differentiation, in vitro, is vital in developing these cellular therapies to treat degenerative diseases. Muscle differentiation is a multistep process, starting with commitment to the muscle lineage and ending with the formation of multinucleated fibers. Insulin-like growth factor binding protein-6 (IGFBP-6), relative to other IGFBPs, has high affinity for IGF-2. However, the role of IGFBP-6 in muscle development has not been clearly defined. Our previous studies showed that in vitro extracellular IGFBP-6 increased myogenesis in early stages and could enhance the muscle differentiation process in the absence of IGF-2. In this study, we identified the signal transduction mechanisms of IGFBP-6 on muscle differentiation by placental mesenchymal stem cells (PMSCs). We showed that muscle differentiation required activation of both AKT and MAPK pathways. Interestingly, we demonstrated that IGFBP-6 could compensate for IGF-2 loss and help enhance the muscle differentiation process by triggering predominantly the MAPK pathway independent of activating either IGF-1R or the insulin receptor (IR). These findings indicate the complex interactions between IGFBP-6 and IGFs in PMSC differentiation into the skeletal muscle and that the IGF signaling axis, specifically involving IGFBP-6, is important in muscle differentiation. Moreover, although the major role of IGFBP-6 is IGF-2 inhibition, it is not necessarily the case that IGFBP-6 is the main modulator of IGF-2.