Predicting immunogenicity of COVID-19 vaccines in hemodialysis patients with renal disease.

Individuals who are diagnosed with chronic kidney disease, particularly those receiving maintenance hemodialysis treatment, face a greater likelihood of suffering from severe symptoms and fatality due to COVID-19. This study aimed to explore the optimal vaccination approach for these individuals. The study used data analysis tasks such as data preprocessing, cleaning, and exploration, and machine learning models including linear regression, random forest, XGBoost, gradient boosting, AdaBoost, decision trees, Lasso, and ridge regression were used to construct the predictive model. The study found that the Lasso model performed the best overall in predicting anti-S IgG antibodies levels in response to COVID-19 vaccines for people with kidney failure with MAE of 8.81, RMSE of 19.59, and R2 value of 0.93. The adjusted R2 value for the Lasso model was also 0.93, indicating that the model's ability to explain the variance in the data was not affected by the number of predictors in the model. The Random Forest model best predicted the duration of immunogenicity, with R2 and adjusted R2 values of 0.71 and 0.69, respectively. The ensemble model that includes all eight models, i.e., Ridge, Lasso, Linear Regression, Random Forest, AdaBoost, Gradient Boosting, XGBoost, and Decision Tree, has the best performance with the lowest MAE, the lowest RMSE, the highest R2, and the highest adjusted R2 values of 3.91, 5.00, 0.73, and 0.72, respectively. However, further research is required to validate these models and extend their application to different populations and vaccine types, as well as considering other factors that may affect immune response to COVID-19 vaccines. These findings can be helpful in improving vaccination strategies and promoting public health.

Tumor mutational burden for the prediction of PD-(L)1 blockade efficacy in cancer: challenges and opportunities.

Tumor mutational burden (TMB) is a biomarker that measures the number of somatic mutations in a tumor's genome. TMB has emerged as a predictor of response to immune checkpoint inhibitors (ICIs) in various cancer types, and several studies have shown that patients with high TMB have better outcomes when treated with programmed death-ligand 1-based therapies. Recently, the Food and Drug Administration has approved TMB as a companion diagnostic for the use of pembrolizumab in solid tumors. However, despite its potential, the use of TMB as a biomarker for immunotherapy efficacy is limited by several factors. Here we review the limitations of TMB in predicting immunotherapy outcomes in patients with cancer and discuss potential strategies to optimize its use in the clinic.

The association between a rotator cuff tendon tear and a tear of the long head of the biceps tendon: Chart review study.

Rotator cuff (RC) and long head of the biceps tendon (LHBT) tears are common shoulder problems presented to the orthopedic clinic. The aim of this study was to assess the association between RC and LHBT tears among a Saudi population sample. A total of 243 patients who were diagnosed with shoulder pain due to RC or LHBT tear between 2016 and 2018 using a magnetic resonance imaging scan were included in this study. Females comprised 66% of the sample, and 59% (n = 143) of the shoulders were on the right side. The mean age of the patients was 58 ± 11 years, ranging from 23 to 88 years. A significant association was detected between the LHBT and RC tears (P < 0.001). Out of 26 cases showing RC and LHBT tears, 81% had a full thickness tear, whereas 19% had a partial tear. The LHBT tears were presented significantly in 48% of cases with at least two completely torn RC compared to 10% in cases with one completely torn RC (P < 0.001). The LHBT tear was significantly observed in shoulders with RC tears including the tendons of subscapularis, supraspinatus, and infraspinatus, but not the teres minor (P < 0.001). Both types of tears were presented significantly in senior patients aged more than 65 years compared to younger patients (P < 0.01). Thus, the LHBT should be assessed carefully in shoulders with more than one RC tear or in chronic cases.

Knowledge of Sickle Cell Disease Among Medical Students at Al-Baha University, Saudi Arabia: A Cross-Sectional Study.

BACKGROUND: Sickle cell disease (SCD) presents a major health challenge in Saudi Arabia due to its high prevalence. The important role of medical students as future healthcare leaders necessitates high awareness and knowledge about the disease. AIM: To assess SCD awareness among Al-Baha University medical students, and to evaluate its relation to gender and academic level. METHODS: A cross-sectional study was conducted, including 105 medical students from the first to sixth year at Al-Baha University. Data collection utilized an online self-administered questionnaire, covering demographic characteristics and assessing SCD knowledge. Fisher's exact and Pearson Chi-squared tests were employed to analyze associations between gender, academic level, and SCD awareness. RESULTS: The majority of male participants 52 (89.6%) and all females 47 (100%) demonstrated awareness of SCD. Clinical year enrollment (68.6%) correlated with heightened awareness across various aspects of SCD compared to the preclinical year. Most participants were in clinical years (68.6%), and 94.3% of them had knowledge about SCD. Approximately, 75 (71%) of participants correctly identified features of sickle cell crisis, 83 (79%) reported the accurate cause of SCD, and 75 (71%) cited the appropriate preventive measures. Only 15 (14%) demonstrated knowledge of correct management of SCD. Contrarily, 84 (80%) were aware of SCD complications, 66 (63%) recognized different SCD types, 67 (64%) felt adequately informed about SCD, and 34 (32%) were involved in SCD counseling. Male participants exhibited greater awareness of SCD features than females. Notably, involvement in SCD counseling was more prevalent among students of clinical years. CONCLUSION: This study underscores the need for targeted educational initiatives, particularly among preclinical year students to enhance SCD awareness among students. We also emphasize the role of clinical education in fostering a comprehensive understanding of SCD, with increased participation in counseling programs.

Rapid screening of bacteriostatic and bactericidal antimicrobial agents against Escherichia coli by combining machine learning (artificial intelligence) and UV-VIS spectroscopy.

Antibiotics are compounds that have a particular mode of action upon the microorganism they are targeting. However, discovering and developing new antibiotics is a challenging and timely process. Antibiotic development process can take up to 10-15 years and over $1billion to develop a single new therapeutic product. Rapid screening tools to understand the mode of action of the new antimicrobial agent are considered one of the main bottle necks in the antimicrobial agent development process. Classical approaches require multifarious microbiological methods and they do not capture important biochemical and organism therapeutic-interaction mechanisms. This work aims to provide a rapid antibiotic-antimicrobial biochemical diagnostic tool to reduce the timeframes of therapeutic development, while also generating new biochemical insight into an antimicrobial-therapeutic screening assay in a complex matrix. The work evaluates the effect of antimicrobial action through "traditional" microbiological analysis techniques with a high-throughput rapid analysis method using UV-VIS spectroscopy and chemometrics. Bacteriostatic activity from tetracycline and bactericidal activity from amoxicillin were evaluated on a system using non-resistant Escherichia coli O157:H7 by confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), and UV-VIS spectroscopy (high-throughput analysis). The data were analysed using principal component analysis (PCA) and support vector machine (SVM) classification. The rapid diagnostic technique could easily identify differences between bacteriostatic and bactericidal mechanisms and was considerably quicker than the "traditional" methods tested.

Demographic and Clinical Predictors of Disease Severity in Patients With Multiple Sclerosis: A Retrospective Cross-Sectional Analysis.

OBJECTIVES: Multiple sclerosis (MS) is a disease of the central nervous system (CNS). Several factors, including sex, body mass index (BMI), disease duration, and age of onset, have been identified as predictors of disease severity. This study investigated the association between the aforementioned factors and MS severity, measured by the number of hospital visits and admissions, length of stay, and frequency of methylprednisolone use. METHODS: This retrospective cross-sectional analysis used data obtained from BESTCare at the King Abdulaziz Medical City (KAMC). A total of 272 patients with MS and their demographic and clinical characteristics were included. RESULTS: The study population consisted of 68.75% (n = 187) females and 31.25% (n = 85) males. The regression analyses indicated that disease duration was a significant predictor of the number of hospital visits and admissions (p < 0.01). The study found a significant association between BMI (unstandardized beta (B) = -0.25, 95% confidence interval (CI) = -0.47, -0.02, p = 0.033), age at diagnosis (unstandardized beta (B) = 0.15, 95% CI = 0.001, 0.31, p = 0.048), and length of hospital stay. Additionally, there was a significant correlation between disease duration and the number of methylprednisolone doses (unstandardized beta (B) = 0.45, 95% CI = 0.01, 0.89, p = 0.045). CONCLUSION: Disease duration was found to be a significant predictor of hospital visits, admissions, and methylprednisolone use, while sex and BMI did not contribute to the variation in these outcomes. However, BMI and age of onset were significantly associated with length of hospital stay.

Effect of dapagliflozin against NAFLD and dyslipidemia in type 2 diabetic albino rats: possible underlying mechanisms.

OBJECTIVE: The aim was to investigate the effect of dapagliflozin on non-alcoholic fatty liver disease and dyslipidemia in type 2 diabetic rats by studying the histopathological structure of the liver and detecting possible underlying mechanisms for this impact by evaluating the potential anti-inflammatory action of dapagliflozin. MATERIALS AND METHODS: 100 albino rats were used in this work and divided into five equal groups: group I (Control group), group II (Control diabetic group), group III (was administered dapagliflozin, 0.75 mg/kg, p.o.), group IV (was administered dapagliflozin, 1.5 mg/kg, p.o.), and group V (was administered dapagliflozin, 3 mg/kg, p.o.). RESULTS: In our study, the total body weight, liver weight, liver index, blood glucose level, insulin level, insulin resistance, total cholesterol, triglycerides, liver enzymes, IL-1 ß, and MDA were significantly higher in the control diabetic group than the normal group. The dapagliflozin reduced all the above variables significantly in a dose-dependent manner compared to the control diabetic group (p-value = 0.001 for all). CONCLUSIONS: Dapagliflozin may be a promising novel treatment strategy for treating T2DM-related non-alcoholic fatty liver disease (NAFLD), and dyslipidemia where it possesses anti-oxidative, anti-inflammatory and anti-dyslipidemic effects.

Metabolic control and incidence of hypoglycaemia, hospitalisation and complications among Saudi patients with type 2 diabetes initiating second-line therapy: an analysis of the Saudi Arabia data from the DISCOVER Observational Study programme.

OBJECTIVES: The aim of the global DISCOVERing Treatment Reality of Type 2 Diabetes in Real World Settings (DISCOVER) Study was to provide a comprehensive real world assessment of the treatment pattern changes for patients with type 2 diabetes. The aim of this analysis was to assess the metabolic control and the annual incidence of hypoglycaemia, hospitalisation and complications among Saudi patients with type 2 diabetes initiating second-line therapy. DESIGN: This study is part of the observational, longitudinal, prospective multinational DISCOVER Study. SETTING: Governmental and private health sectors from different regions within Saudi Arabia. PARTICIPANTS: The study recruited 519 patients with type 2 diabetes aged ≥18 years who were switching to second-line therapy. Patients who were already using insulin/injectable agents, patients with type 1 diabetes, pregnant women, and patients undergoing dialysis or with a history of renal transplantation were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: Metabolic control among patients with type 2 diabetes mellitus; fear of hypoglycaemia; quality of life; and the incidence of complications, hypoglycaemic events and/or hospitalisations. Data were analysed using descriptive statistics. RESULTS: A total of 519 patients were recruited with a mean age of 52.4±11 years. Of these participants, 54.7% were male and 45.3% were female. The incidence of hypoglycaemia was 56.72/1000 patient-years. The Hypoglycemia Fear Survey II showed a significant increase in patient worry related to hypoglycaemia from 6.4±11.9 at baseline to (p=0.0446) at the 36-month follow-up. The incidence of hospitalisation was 30.81/1000 patient-years. There was a moderate improvement in glycaemic control, represented as an HbA1c reduction from 8.8% at baseline to 8.2% at the 36-month follow-up. The incidence of macroangiopathy was 24.51/1000 patient-years and the incidence of microvascular complications such as retinopathy and albuminuria was 47.00/1000 patient-years and 221.71/1000 patient-years, respectively. The mean score of fear of hypoglycaemia showed an increase with 13.0±21.5 at baseline to 16.1±22.2 at the 36-month follow-up. When assessing the patients' quality of life, there was an improvement in the mental component score from 47.4±9.1 at baseline to 53.0±6.7 at the 36-month follow-up. CONCLUSIONS: Treatment intensification decisions should be made individually, weighing the benefit of good glycaemic control against the risk of hypoglycaemia. TRIAL REGISTRATION NUMBER: NCT02322762 and NCT02226822.

Place and the Structuring of Cross-Sector Partnerships: The Moral and Material Conflicts Over Healthcare and Homelessness.

Local places, such as communities, cities, and towns, host many cross-cross sector partnerships, many geared primarily toward alleviating local social and environmental issues. Yet, existing literatures focus predominantly on largescale systemic impact and global challenges such as climate change, paying scant attention to the role of local, geographically bounded dynamics in shaping these partnerships. In this article, I conceptualize places as geographic locations imbued with specific meaning systems and material resources to unpack how local embeddedness shape the structure of cross-sector partnerships. Specifically, I investigate how place-based conflict, arising from tensions between the moral and material aspects of a partnership, can shape formalized aspects of organizational structure. These include the scope of operations, partners' roles, and shared resources. I unpack these relationships using a case study of Occupy Medical, a local partnership between the civic society and the local government in Eugene, Oregon, tackling the problem of providing healthcare to the homeless and other marginalized and disenfranchised communities. The analysis covers the nine-year period of 2011-2020 and spans three major restructurings of the organization, the latest prompted by the onset of the COVID-19 pandemic in March 2020. I theorize two forms of structural arrangements for cross-sector partnerships, confined and leveraged, and further elaborate on the role of cross-sector partnerships in crises response on the local level.

Declined Humoral Immunity of Kidney Transplant Recipients to SARS-CoV-2 Vaccines.

Background: Kidney transplant recipients (KTRs) commonly suffer from impaired immunity. KTRs' compromised immune response to COVID-19 vaccines indicates urgent revision of immunisation policies. Methods: A cross-sectional study was conducted in Madinah, Saudi Arabia of 84 KTRs who had received at least one dose of a COVID-19 vaccine. ELISA was used to evaluate anti-spike SARS-CoV-2 IgG and IgM antibody levels in blood samples obtained one month and seven months after vaccination. Univariate and multivariate analyses were performed to identify associations between seropositive status and factors such as the number of vaccine doses, transplant age, and immunosuppressive therapies. Results: The mean age of KTRs was 44.3 ± 14.7 years. The IgG antibody seropositivity rate (n=66, 78.5%) was significantly higher than the seronegativity rate (n=18, 21.4%) in the whole cohort (p<0.001). In KTRs seroconverting after one month (n=66), anti-SARS-CoV-2 IgG levels declined significantly between one month (median [IQR]:3 [3-3]) and seven months (2.4 [1.7-2.6]) after vaccination (p<0.01). In KTRs with hypertension, IgG levels significantly decreased between one and seven months after vaccination (p<0.01). IgG levels also decreased significantly in KTRs with a transplant of >10 years (p=0.02). Maintenance immunosuppressive regimens (triple immunosuppressive therapy and steroid-based and antimetabolite-based regimens) led to a significant decrease in IgG levels between the first and second sample (p<0.01). KTRs receiving three vaccine doses showed higher antibody levels than those receiving a single dose or two doses, but the levels decreased significantly between one (median [IQR]: 3 [3-3]) and seven months (2.4 [1.9-2.6]) after vaccination (p<0.01). Conclusion: KTRs' humoral response after SARS-CoV-2 vaccination is dramatically inhibited and wanes. Antibody levels show a significant decline over time in KTRs with hypertension; receiving triple immunosuppressive therapy or steroid-based or antimetabolite-based regimens; receiving mixed mRNA and viral vector vaccines; and with a transplant of >10 years.

Molecular markers of metastatic disease in KRAS-mutant lung adenocarcinoma.

BACKGROUND: Prior studies characterized the association of molecular alterations with treatment-specific outcomes in KRAS-mutant (KRASMUT) lung adenocarcinoma (LUAD). Less is known about the prognostic role of molecular alterations and their associations with metastatic disease. PATIENTS AND METHODS: We analyzed clinicogenomic data from 1817 patients with KRASMUT LUAD sequenced at the Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering Cancer Center (MSKCC). Patients with metastatic (M1) and nonmetastatic (M0) disease were compared. Transcriptomic data from The Cancer Genome Atlas (TCGA) were investigated to characterize the biology of differential associations with clinical outcomes. Organ-specific metastasis was associated with overall survival (OS). RESULTS: KEAP1 (DFCI: OR = 2.3, q = 0.04; MSKCC: OR = 2.2, q = 0.00027) and SMARCA4 mutations (DFCI: OR = 2.5, q = 0.06; MSKCC: OR = 2.6, q = 0.0021) were enriched in M1 versus M0 tumors. On integrative modeling, NRF2 activation was the genomic feature most associated with OS. KEAP1 mutations were enriched in M1 versus M0 tumors independent of STK11 status (KEAP1MUT/STK11WT: DFCI OR = 3.0, P = 0.0064; MSKCC OR = 2.0, P = 0.041; KEAP1MUT/STK11MUT: DFCI OR = 2.3, P = 0.0063; MSKCC OR = 2.5, P = 3.6 × 10-05); STK11 mutations without KEAP1 loss were not associated with stage (KEAP1WT/STK11MUT: DFCI OR = 0.97, P = 1.0; MSKCC OR = 1.2, P = 0.33) or outcome. KEAP1/KRAS-mutated tumors with and without STK11 mutations exhibited high functional STK11 loss. The negative effects of KEAP1 were compounded in the presence of bone (HR = 2.3, P = 4.4 × 10-14) and negated in the presence of lymph node metastasis (HR = 1.0, P = 0.91). CONCLUSIONS: Mutations in KEAP1 and SMARCA4, but not STK11, were associated with metastatic disease and poor OS. Functional STK11 loss, however, may contribute to poor outcomes in KEAP1MUT tumors. Integrating molecular data with clinical and metastatic-site annotations can more accurately risk stratify patients.

Separation, reserve estimation and radioactivity responsibility of the economic heavy minerals of East El- Arish black sand, North Sinai, Egypt.

Multi-heavy mineral separation techniques like density, magnetic, and electromagnetic techniques are followed by picking, grain counting, and mineralogical examinations conducted with an environmental scanning electron microscope (ESEM). These techniques have been applied to several drill hole (well) composite samples representing beach sand and dunes of East El-Arish area, North Sinai, Egypt. The results explain the remarkable enrichment in total heavy minerals (THM) of beach sand (4.4%) compared to sand dunes (2.6%): this is due to the natural concentration of the currents of the Mediterranean Sea. After characterizing the heavy minerals in terms of the abundance of each mineral species, the mean values of content relative to total economic heavy minerals (TEHM) were determined as 70.03% ilmenite, 3.81% leucoxene, 3.03% magnetite, 8.7% garnet, 10.6% zircon, 3.13% rutile, 0.37% monazite, and 0.31% titanite in the sand dune samples. The total economic heavy minerals in the beach samples were 64.08% ilmenite, 1.6% leucoxene, 2.84% magnetite, 18.16% garnet, 10.4% zircon, 2.18% rutile, 0.61% monazite, and 0.13% titanite. Monazite, thorite, zircon, and apatite are the main radioactive minerals in the study area. The combination of two specific characteristics of the studied monazite (relatively high Th-U content and high frequency) makes monazite the main contributor to radioactivity of the study area.

Hyperlipidemia and Hypertension Are Associated With Intracerebral Hemorrhage Incidence: A Retrospective Study.

Introduction Stroke places a huge burden on the socioeconomic systems. Hemorrhagic stroke (HS) is the second most common type of stroke and the second leading cause of disability and death. The updated data on the prevalence of intracerebral hemorrhage (ICH) stroke and related physiological risk factors in Saudi Arabia were limited. The aim of this study was to identify the prevalence of ICH stroke and the related physiological risk factors. Methods This was a retrospective, hospital-based, and chart review study that utilized the BESTCare system at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. Patients who attended the neurology department (inpatient/outpatient) between 2015 and 2020 were studied. The statistical tool JMP (JMP Inc., Cary, NC, USA) was used for data entry and analysis. Results Patient data (N = 1,870, 58.6 ± 13.87 years old) were screened for comorbidities, hypertension (66.1%), diabetes mellitus (DM) (57.7%), hyperlipidemia (28.4%), and history of an old stroke (22.3%). Ischemic stroke (IS) was more dominant than ICH stroke with ratios of 94.5% (n = 1767) versus 5.5% (n = 103), respectively. The prevalence of ICH stroke among the patients (n = 103) was 10.6%, 20.3%, 24.2%, and 28.1% in the age groups of <40, 41-50, 51-60, and 61-70 years old, respectively. There was a significant gender effect on the distribution of both IS and ICH (p = 0.003). ICH strokes were more prevalent in males than in females. Body mass index (BMI) has no significant effect on the prevalence of IS and ICH stroke (p = 0.081). ICH stroke was significantly associated with DM (p = 0.032), hypertension (p = 0.01), and hyperlipidemia (p = 0.002). Regression analyses show that only hypertension (positive association) and hyperlipidemia (negative association) were significantly associated with the incidence of ICH stroke. Conclusion IS was more prevalent than ICH stroke. ICH strokes were more prevalent in males than in females. Also, hypertension was the most common factor leading to ICH stroke, unlike hyperlipidemia, which was revealed to be protective against ICH stroke.

Clonal KEAP1 mutations with loss of heterozygosity share reduced immunotherapy efficacy and low immune cell infiltration in lung adenocarcinoma.

BACKGROUND: KEAP1 mutations have been associated with reduced survival in lung adenocarcinoma (LUAD) patients treated with immune checkpoint inhibitors (ICIs), particularly in the presence of STK11/KRAS alterations. We hypothesized that, beyond co-occurring genomic events, clonality prediction may help identify deleterious KEAP1 mutations and their counterparts with retained sensitivity to ICIs. PATIENTS AND METHODS: Beta-binomial modelling of sequencing read counts was used to infer KEAP1 clonal inactivation by combined somatic mutation and loss of heterozygosity (KEAP1 C-LOH) versus partial inactivation [KEAP1 clonal diploid-subclonal (KEAP1 CD-SC)] in the Memorial Sloan Kettering Cancer Center (MSK) MetTropism cohort (N = 2550). Clonality/LOH prediction was compared to a streamlined clinical classifier that relies on variant allele frequencies (VAFs) and tumor purity (TP) (VAF/TP ratio). The impact of this classification on survival outcomes was tested in two independent cohorts of LUAD patients treated with immunotherapy (MSK/Rome N = 237; DFCI N = 461). Immune-related features were studied by exploiting RNA-sequencing data (TCGA) and multiplexed immunofluorescence (DFCI mIF cohort). RESULTS: Clonality/LOH inference in the MSK MetTropism cohort overlapped with a clinical classification model defined by the VAF/TP ratio. In the ICI-treated MSK/Rome discovery cohort, predicted KEAP1 C-LOH mutations were associated with shorter progression-free survival (PFS) and overall survival (OS) compared to KEAP1 wild-type cases (PFS log-rank P = 0.001; OS log-rank P < 0.001). Similar results were obtained in the DFCI validation cohort (PFS log-rank P = 0.006; OS log-rank P = 0.014). In both cohorts, we did not observe any significant difference in survival outcomes when comparing KEAP1 CD-SC and wild-type tumors. Immune deconvolution and multiplexed immunofluorescence revealed that KEAP1 C-LOH and KEAP1 CD-SC differed for immune-related features. CONCLUSIONS: KEAP1 C-LOH mutations are associated with an immune-excluded phenotype and worse clinical outcomes among advanced LUAD patients treated with ICIs. By contrast, survival outcomes of patients whose tumors harbored KEAP1 CD-SC mutations were similar to those with KEAP1 wild-type LUADs.

Longitudinal assessment of the quality of life and patterns of antidiabetic medication use in patients with type 2 diabetes, Saudi Arabia perspective, DISCOVER study.

OBJECTIVES: Patients with type 2 diabetes nowadays have a wide range of new antidiabetic medications with better efficacy and safety. Physicians' attitude toward selecting antidiabetic medications to reach targeted glycemic control and better quality of life (QOL) has not been studied prospectively. The global DISCOVER study aims to comprehensively provide a real-world assessment of the treatment pattern changes for patients with type 2 diabetes, in addition to QOL assessment. The Kingdom of Saudi Arabia was one of the countries participating in the DISCOVER study program. METHODS: This study is a part of the prospective, longitudinal multinational DISCOVER study conducted in 38 countries including Saudi Arabia, a country facing an epidemic of type 2 diabetes, recruited 519 adult patients with type 2 diabetes with a mean age of 52.4 ± 11 years, where, they were followed up for three years period, where 477 patients completed the follow-up period. The clinical, biochemical, and patient lifestyle data were assessed periodically during the study period. DISCOVER study is registered with ClinicalTrials.gov identifiers: NCT02322762. RESULTS: The most frequently used antidiabetic medications (ADMs) initially and during the follow-up were biguanides (metformin) and sulfonylureas (gliclazide, glibenclamide, glimepiride, glipizide, and glyclopyramide). Insulin (premix Insulin, basal insulin, and basal/bolus insulin) and dipeptidyl peptidase-4 (DPP-4) inhibitors (sitagliptin, vildagliptin, saxagliptin, and linagliptin) were the most frequent second and alternative of therapy. Other medications namely thiazolidinediones (TZds) (pioglitazone and rosiglitazone), incretins (exenatide and liraglutide), and Sodium-glucose co-transporter-2 (SGLT-2) inhibitors (canagliflozin) were used at a lesser rate. Drug availability, efficacy, and safety were the main determinants for choosing antidiabetic medications. The physical component score of the QOL had shown a significant decrease, while the mental component score has demonstrated an increase in QOL using SF36v2 Survey. CONCLUSIONS: There is an increasing trend of using of newly available ADMs, mainly DPP-4 inhibitors. The major limitation of ADMs use is related to efficacy, availability, and safety. This warrant taking all the measures to overcome these limitations through adopting a multidisciplinary team approach for close monitoring of the patients and any unfavorable side effects. Additionally, global insurance coverage for all patients with type 2 diabetes could be a solution for the drug availability factor.

New Insight into the Possible Roles of L-Carnitine in a Rat Model of Multiple Sclerosis.

OBJECTIVE: We investigated the effect of L-carnitine (LC) on cuprizone (Cup) demyelinating rat model and its possible underlying mechanisms. METHODS: Thirty male Sprague-Dawley (SD) rats were randomly allocated to three groups: the normal control group; the Cup group, in which Cup was administrated at a dose of 450 mg/kg per day orally via gastric gavage for 5 weeks; and the Cup + LC group, which received the same dose of Cup as the Cup group, except that the rats were treated additionally with LC 100 mg/kg/day orally for 5 weeks. The nerve conduction (NCV) in isolated sciatic nerves was measured; then, the sciatic nerves were isolated for H&E staining and electron microscope examination. The expression of myelin basic protein (MBP), IL-1ß, p53, iNOS, and NF-KB by immunohistochemistry was detected in the isolated nerves. A PCR assay was also performed to detect the expression of antioxidant genes Nrf2 and HO-1. In addition, the level of IL-17 was measured by ELISA. RESULTS: There was a significant reduction in NCV in the Cup group compared to normal rats (p < 0.001), which was significantly improved in the LC group (p < 0.001). EM and histopathological examination revealed significant demyelination and deterioration of the sciatic nerve fibers, with significant improvement in the LC group. The level of IL-17 as well as the expression of IL-1ß, p53, iNOS, and NF-KB were significantly increased, with significant reduction expression of MBP in the sciatic nerves (p < 0.01), and LC treatment significantly improved the studied parameters (p < 0.01). CONCLUSION: The current study demonstrates a neuroprotective effect of LC in a Cup-induced demyelinating rat model. This effect might be due to its anti-inflammatory and antioxidant actions.

The Relation Between Body Mass Index and Musculoskeletal Injury.

Background The nature and extent of the relation between body mass index (BMI) score and the risk of Musculoskeletal (MSK) injury are still unclear, with few studies investigating. So, the purpose of this study was to assess the association between BMI scores and MSK injury and to see if the site of MSK injury is affected by a specific BMI score. In addition, the risk of MSK injuries was compared among different adult age groups. Methods The study population included all patients above 18 years old with musculoskeletal injuries between January 2009 and December 2019 at King Abdulaziz Medical City (KAMC). The estimated sample size was 377. The study subjects were distributed according to their BMI into four categories (underweight, normal weight, overweight, and obese). Also, they were divided according to their age into young adults, middle age, and older adults. Each MSK injury was identified by its location as upper extremity, axial skeleton, or lower extremity.  Results Only gender and age were significantly related to the site of injury, with P-values (0.018) and (0.001), respectively. As for the BMI category, its relation with the site of injury was nonsignificant (P-value: 0.092). The younger age group (≤ 35) has a significantly higher chance to be injured in the upper extremities compared with the older adults (≥ 56) (P-value = 0.014). While the axial skeleton (especially the lower back) was the most common site of injury in obese, overweight, and underweight categories, patients with normal BMI have lower extremities as their most common site of injury.  Conclusion Although a higher BMI is associated with an increased risk of MSK injury, the difference in the BMI score seems to not effect the site of injury. By contrast, both gender and age group have a significant relationship with the site of MSK injury.

The Chaotic Behavior of the Spread of Infection during the COVID-19 Pandemic in Japan.

In December 2019, China reported a new virus identified as SARS-CoV-2, causing COVID-19, which soon spread to other countries and led to a global pandemic. Although many countries imposed strict actions to control the spread of the virus, the COVID-19 pandemic resulted in unprecedented economic and social consequences in 2020 and early 2021. To understand the dynamics of the spread of the virus, we evaluated its chaotic behavior in Japan. A 0-1 test was applied to the time-series data of daily COVID-19 cases from January 26, 2020 to August 5, 2021 (3 days before the end of the Tokyo Olympic Games). Additionally, the influence of hosting the Olympic Games in Tokyo was assessed in data including the post-Olympic period until October 8, 2021. Even with these extended time period data, although the time-series data for the daily infections across Japan were not found to be chaotic, more than 76.6% and 55.3% of the prefectures in Japan showed chaotic behavior in the pre- and post-Olympic Games periods, respectively. Notably, Tokyo and Kanagawa, the two most populous cities in Japan, did not show chaotic behavior in their time-series data of daily COVID-19 confirmed cases. Overall, the prefectures with the largest population centers showed non-chaotic behavior, whereas the prefectures with smaller populations showed chaotic behavior. This phenomenon was observed in both of the analyzed time periods (pre- and post-Olympic Games); therefore, more attention should be paid to prefectures with smaller populations, in which controlling and preventing the current pandemic is more difficult.

Phase Ib study of eprenetapopt (APR-246) in combination with pembrolizumab in patients with advanced or metastatic solid tumors.

BACKGROUND: We conducted a phase I, multicenter, open-label, dose-finding, and expansion study to determine the safety and preliminary efficacy of eprenetapopt (APR-246) combined with pembrolizumab in patients with advanced/metastatic solid tumors (ClinicalTrials.gov NCT04383938). PATIENTS AND METHODS: For dose-finding, requirements were non-central nervous system primary solid tumor, intolerant to/progressed after ≥1 line of treatment, and eligible for pembrolizumab; for expansion: (i) gastric/gastroesophageal junction tumor, intolerant to/progressed after first-line treatment, and no prior anti-programmed cell death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy; (ii) bladder/urothelial tumor, intolerant to/progressed after first-line cisplatin-based chemotherapy, and no prior anti-PD-1/PD-L1 therapy; (iii) non-small-cell lung cancer (NSCLC) with previous anti-PD-1/PD-L1 therapy. Patients received eprenetapopt 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle. Primary endpoints were dose-limiting toxicity (DLT), adverse events (AEs), and recommended phase II dose (RP2D) of eprenetapopt. RESULTS: Forty patients were enrolled (median age 66 years; range 27-85) and 37 received eprenetapopt plus pembrolizumab. No DLTs were reported and the RP2D for eprenetapopt in combination was 4.5 g/day IV on days 1-4. The most common eprenetapopt-related AEs were dizziness (35.1%), nausea (32.4%), and vomiting (29.7%). AEs leading to eprenetapopt discontinuation occurred in 2/37 patients (5.4%). In efficacy-assessable patients (n = 29), one achieved complete response (urothelial cancer), two achieved partial responses (NSCLC, urothelial cancer), and six patients had stable disease. CONCLUSIONS: The eprenetapopt plus pembrolizumab combination was well tolerated with an acceptable safety profile and showed clinical activity in patients with solid tumors.

Correlation of iron levels with glycemia and microvascular complications among type II diabetes mellitus patients in Najran university hospital.

Background: Diabetes is influenced by changes in the body's iron levels. Because iron deficiency anemia is common in diabetes, this study examines the link between iron, glycemic control, and complication in patients with type 2 diabetes mellitus (T2DM). Methods: The study is a cross-sectional study conducted from October 2019 to June 2020 at Najran university hospital in the Najran area, Saudi Arabia. All T2DM patients (N = 201) during the study were recruited by simple random sampling. A checklist was completed to extract the study variables from each patient's medical record. Results: There is a positive poor correlation between hemoglobin (Hb) and diabetic foot (r = 0.186, P < 0.05), but not with other diabetic microvascular complications (i.e., retinopathy, nephropathy, and peripheral neuropathy) or glycemic indicators fasting blood sugar, random blood sugar and hemoglobin A1C (i.e., FBS, RBS, and HbA1C). No link is found between ferritin and glycemic indicators or diabetic microvascular complications. Conclusion: The study suggests that particular attention be paid to regular monitoring of iron levels before modifying the treatment plans for type 2 diabetes mellitus (T2DM) patients. It raises critical inquiry about the reality of iron role in diabetes mellitus either in pathogenesis or treatment. It recommends accurately assessing body iron status with careful interpretation for better clinical judgment, encouraging large-scale and long-term epidemiological as well as interventional trials examining the effect of lowering iron in controlling glycemia.