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Background: There is an urgent need to identify new biomarkers for early diagnosis and development of therapeutic strategies for diabetes mellitus (DM) patients who have invasive breast cancer (BC). We previously reported the increased activated form of 70 kDa ribosomal protein S6 kinase 1 (phospho-p70S6K1) in a triple-negative BC (TNBC) cell line MDA-MB-231 exposed to glycated albumin (GA) and in invasive ductal carcinoma tissues from T2DM patients, compared to untreated cells and their non-diabetic counterparts, respectively. Objective: We aimed to explore the function of p70S6K1 in GA-promoted TNBC progression. Methods: By employing small interference (si)RNA technology or blocking its kinase activity using its specific pharmacological inhibitor, we monitored cell invasion using Transwell® inserts and the expression levels of activated signaling proteins and cancer-related proteins using Western blot. Results: In silico analysis revealed that high mRNA levels of p70S6K1 were associated with an unfavorable prognosis and progression to advanced stages of TNBC in DM patients. The downregulation/blockade of p70S6K1 inhibited GA-promoted MDA-MB-231 cell invasion and the phosphorylation of protein S6 and ERK1/2, the p70S6K1 downstream effector, and the key oncogenic signaling protein, respectively. The suppression of the expression of GA-upregulated cancer proteins, including enolase-2, capping protein CapG, galectin-3, and cathepsin D, was observed after p70S6K1 downregulation/blockade. Further in silico validation analyses revealed increased gene expression of galectin-3 in DM TNBC patients, resulting in poor overall survival and disease-free survival. Conclusions: Targeting p70S6K1 may present a valuable therapeutic strategy, while galectin-3 could serve as a potential prognostic biomarker for invasive BC progression in DM patients.

Background Biotin–thiamine‐responsive basal ganglia disease (BTBGD) is an autosomal recessive neurometabolic disorder mostly presented in children. The disorder is described as having subacute encephalopathy with confusion, dystonia, and dysarthria triggered by febrile illness that leads to neuroregression and death if untreated. Using biotin and thiamine at an early stage of the disease can lead to significant improvement. Methods BTBGD is a treatable disease if diagnosed at an early age and has been frequently reported in Saudi population. Keeping this in mind, the current study screened 3000 Saudi newborns for the SLC19A3 gene mutations using target sequencing, aiming to determine the carrier frequency in Saudi Population and whether BTBGD is a good candidate to be included in the newborn‐screened disorders. Results Using targeted gene sequencing, DNA from 3000 newborns Saudi was screened for the SLC19A3 gene mutations using standard methods. Screening of the SLC19A3 gene revealed a previously reported heterozygous missense mutation (c.1264A>G (p.Thr422Ala) in six unrelated newborns. No probands having homozygous pathogenic mutations were found in the studied cohort. The variant has been frequently reported previously in homozygous state in Saudi population, making it a hot spot mutation. The current study showed that the carrier frequency of SLC19A3 gene mutation is 1 of 500 in Saudi newborns. Conclusion For the first time in the literature, we determined the carrier frequency of SLC19A3 gene mutation in Saudi population. The estimated prevalence is too rare in Saudi population (at least one in million); therefore, the data are not in favor of including such very rare disorders in newborn screening program at population level. However, a larger cohort is needed for a more accurate estimate.

Background Loss-of-Function (LoF) variants in human genes are important due to their impact on clinical phenotypes and frequent occurrence in the genomes of healthy individuals. The association of LoF variants with complex diseases and traits may lead to the discovery and validation of novel therapeutic targets. Current approaches predict high-confidence LoF variants without identifying the specific genes or the number of copies they affect. Moreover, there is a lack of methods for detecting knockout genes caused by compound heterozygous (CH) LoF variants. Results We have developed the Loss-of-Function ToolKit (LoFTK), which allows efficient and automated prediction of LoF variants from genotyped, imputed and sequenced genomes. LoFTK enables the identification of genes that are inactive in one or two copies and provides summary statistics for downstream analyses. LoFTK can identify CH LoF variants, which result in LoF genes with two copies lost. Using data from parents and offspring we show that 96% of CH LoF genes predicted by LoFTK in the offspring have the respective alleles donated by each parent. Conclusions LoFTK is a command-line based tool that provides a reliable computational workflow for predicting LoF variants from genotyped and sequenced genomes, identifying genes that are inactive in 1 or 2 copies. LoFTK is an open software and is freely available to non-commercial users at https://github.com/CirculatoryHealth/LoFTK .

Despite the effectiveness of warfarin in extended anticoagulation, its narrow therapeutic index requires frequent dose adjustments and careful patient monitoring. Thus, we aimed to evaluate the outcomes of clinical pharmacists’ intervention in warfarin therapy management in terms of International Normalized Ratio (INR) control, reduction of bleeding, and hospitalization in a tertiary care hospital. An observational retrospective cohort study was conducted on 96 patients taking warfarin therapy in a clinical pharmacist-led anticoagulation clinic. We observed that 39.6% of patients required dose adjustments at their first and second visits. However, dose adjustments during the third, fourth, and fifth weeks were required at 31.1%, 20.8%, and 4.2%, respectively, to achieve INR levels. We also observed that 36.46% of the patients attained the target INR at baseline, which was increased over the first week to the fifth week to 57.29%, 61.46%, 61.46%, 68.75%, and 85.42%, respectively. No one reported the ADR between the third and fifth weeks. Based on our findings, the study strongly suggests that pharmacists’ interventions can improve the health-related quality of life of patients undergoing warfarin therapy. Thus, competent pharmacy personnel must be a priority in both usual patient care and critical care among primary care networks.

Background: Stress urinary incontinence (SUI) is a prevalent condition among women in Saudi Arabia, characterized by involuntary urine leakage during physical activities that increase abdominal pressure, such as coughing or sneezing. This systematic review and meta-analysis aimed to evaluate the prevalence of SUI and identify its key risk factors. Methods: A comprehensive search of PubMed, Scopus, and Web of Science was conducted for studies published up to July 2024, following PRISMA 2020 guidelines. Results: Ten observational studies involving 18,245 participants met the inclusion criteria, and study quality was assessed using the Newcastle–Ottawa Scale. A random-effects model was employed for meta-analysis, with subgroup and sensitivity analyses performed to address heterogeneity. The pooled prevalence of SUI was 26% (95% CI: 14–41%, I2 = 99%, p < 0.001), with rates ranging from 3.3% to 50%. Subgroup analysis showed a prevalence of 17% (95% CI: 1–42%, I2 = 99%, p < 0.001) in the general population and 33% (95% CI: 19–48%, I2 = 99%, p < 0.001) in specific groups, such as postpartum women and those with low back pain. Significant risk factors included age, obesity, high parity, and chronic conditions like diabetes. Despite high heterogeneity, sensitivity analyses confirmed the robustness of these findings. Conclusions: The findings underscore the need for public health strategies focused on weight management, pelvic floor rehabilitation, and increased awareness about SUI. Effective preventive measures could significantly reduce the burden of SUI and improve the quality of life for women in Saudi Arabia.

Background This study aimed to document the occurrence of the Egyptian fruit bat Rousettus aegyptiacus in King Salman Bin Abdulaziz Royal Nature Reserve (KSRNR), Hail region, Saudi Arabia, where its presence had not previously been confirmed. Methods Field surveys were conducted in the Hail region, and direct observations were documented using photographic evidence. Bats roosting in a natural crevice were photographed and assessed for colony size. Results More than 50 individuals, including adults and juveniles, were observed roosting in a rock crevice. The photographic documentation confirms the presence of a stable colony of R. aegyptiacus in this area, extending the known distribution of the species into a previously unrecorded region of Saudi Arabia. Conclusions These findings provide the first photographic record of R. aegyptiacus in KSRNR and highlight the species’ ecological adaptation to arid habitats. The results emphasize the need for targeted surveys and long-term monitoring to better understand the distribution and conservation of this species in desert environments.

Background This study aimed to document the occurrence of the Egyptian fruit bat Rousettus aegyptiacus in King Salman Bin Abdulaziz Royal Nature Reserve (KSRNR), Hail region, Saudi Arabia, where its presence had not previously been confirmed. Methods Field surveys were conducted in the Hail region, and direct observations were documented using photographic and video evidence. The colony was visually counted in the field during a single daytime visit from an estimated distance of 15 meters. Results More than 50 individuals, including adults and juveniles, were observed roosting in a rock crevice. The photographic documentation confirms the presence of a colony of R. aegyptiacus in this area, extending the known distribution of the species into a previously unrecorded region of Saudi Arabia. Conclusions These findings provide the first photographic record of R. aegyptiacus in KSRNR and highlight the species’ ecological use of arid rock crevices. The results emphasize the need for targeted surveys and long-term monitoring to better understand the distribution and conservation of this species in desert environments.

B-lineage acute lymphocytic leukemia (B-ALL) is characterized by different genetic aberrations at a chromosomal and gene level which are very crucial for diagnosis, prognosis and risk assessment of the disease. However, there is still controversial arguments in regard to disease outcomes in specific genetic abnormalities, e.g., 9p-deletion. Moreover, in absence of cytogenetic abnormalities it is difficult to predict B-ALL progression. Here, we use the advantage of Next-generation sequencing (NGS) technology to study the mutation landscape of 12 patients with B-ALL using Comprehensive Cancer Panel (CCP) which covers the most common mutated cancer genes. Our results describe new mutations in CSF3R gene including S661N, S557G, and Q170X which might be associated with disease progression.

This study investigates the impact of diabetes mellitus on the success rates and complications associated with dental implants, a significant advancement in restorative dentistry. Diabetes, characterized by chronic hyperglycemia and metabolic dysfunction, poses unique challenges for dental implant therapy, particularly concerning wound healing, osseointegration, and infection control. The literature indicates that while well-controlled diabetic patients can achieve comparable implant success rates to non-diabetic individuals, those with poorly managed diabetes face increased risks of implant failure due to compromised vascular integrity, impaired immune response, and extended healing times. The osseointegration process, critical for the stability of dental implants, may be delayed in diabetic patients, with studies suggesting that healing times can be prolonged by up to 50%. Key risk factors include glycemic control, duration of diabetes, age, and overall oral hygiene practices, with elevated HbA1c levels serving as a crucial biomarker for predicting adverse outcomes. Complications such as infections and peri-implantitis are more prevalent among diabetic patients, underscoring the necessity for meticulous preoperative assessments and interdisciplinary management involving dental professionals and endocrinologists. This research highlights the importance of understanding the intricate relationship between diabetes and dental implant success, advocating for tailored treatment strategies that address the specific needs of diabetic patients to enhance their oral health outcomes and overall quality of life. By elucidating the complexities surrounding diabetes and dental implants, this study aims to inform clinical practices and improve patient care in restorative dentistry.

Acute gastrointestinal bleeding (GIB) is a critical medical emergency that poses significant risks to patient morbidity and mortality. It can arise from various etiologies, including peptic ulcers, diverticular disease, malignancies, and vascular anomalies. The management of acute GIB has evolved considerably, with interventional radiology (IR) emerging as a vital component in both diagnosis and treatment. This review explores the role of interventional radiology in the management of acute GIB, emphasizing its diagnostic capabilities and therapeutic interventions. Diagnostic angiography is a cornerstone of IR, allowing for the real-time visualization of the vascular supply to the gastrointestinal tract. This technique is particularly beneficial in cases where the source of bleeding is not readily apparent through conventional imaging methods. The ability to identify active bleeding enables targeted therapeutic interventions, such as embolization. Therapeutic embolization involves the selective occlusion of bleeding vessels using various embolic agents, including coils, particles, and liquid agents. This minimally invasive approach has demonstrated high success rates in controlling hemorrhage, with reported efficacy ranging from 70% to 90%. In addition to embolization, stenting is another important IR technique, particularly in cases involving malignant obstruction or strictures. Endovascular stents can restore patency in obstructed vessels, improving blood flow and reducing the risk of further bleeding. The use of stenting has been associated with enhanced patient outcomes, including decreased need for surgical intervention and shorter hospital stays. Despite the advantages of interventional radiology, potential complications such as vessel injury and non-target embolization must be considered. A multidisciplinary approach involving gastroenterologists, surgeons, and interventional radiologists is essential for optimizing patient care. As the field of interventional radiology continues to advance, ongoing research and technological innovations promise to further enhance the management of acute gastrointestinal bleeding, ultimately improving patient safety and outcomes. This review underscores the critical role of interventional radiology in the comprehensive management of acute GIB, highlighting its potential to transform patient care in this challenging clinical scenario.