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Warisha Zahid,1,* Nida Farooqui,2,* Nida Zahid,3,* Khalid Ahmed,2 Muhammad Faraz Anwar,4 Syed Rizwan-ul-Hasan,5 Azhar R Hussain,2 Antonio Sarría-Santamera,6 Syed Hani Abidi2,6 1Department of Community Health Sciences, Aga Khan University, Karachi, Pakistan; 2Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan; 3Department of Surgery, Aga Khan University, Karachi, Pakistan; 4Department of Biochemistry, Bahria University Medical and Dental College, Karachi, Pakistan; 5Department of Computer Science, DHA Suffa University, Karachi, Pakistan; 6Department of Biomedical Sciences, Nazarbayev University School of Medicine, Astana, Kazakhstan*These authors contributed equally to this workCorrespondence: Syed Hani Abidi, Department of Biomedical Sciences, Nazarbayev University School of Medicine, Astana, Kazakhstan, Email m.haniabidi@gmail.comIntroduction: Expression and certain SNPs of interferon lambda 3 and 4 (IFNL3 and 4) have been associated with variable outcomes in COVID-19 patients in different regions, suggesting population-specific differences in the disease outcome. This study examined the association of INFL3 and INFL4 SNPs (rs12979860 and rs368234815, respectively) and nasopharyngeal expression with COVID-19 disease severity in Pakistani patients.Methods: For this study, 117 retrospectively collected nasopharyngeal swab samples were used from individuals with mild and severe COVID-19 disease. qPCR assays were used to determine the viral loads and mRNA expression of IFNL3 and 4 through the Ct and delta Ct methods, respectively. Due to funding limitations, only one SNP each in INFL3 and INFL4 (found to be most significant through literature search) was analyzed using tetra-arm PCR and RFLP-PCR strategies, respectively. The Mann–Whitney U-test was applied to evaluate the statistical differences in the expression of IFNL3/4 genes in the mild and severe groups, while for SNPs, a Chi-square test was employed. A multivariate Cox regression test was performed to assess the relationship of different variables with COVID-19 severity.Results: Comparative analysis of SNPs between mild and severe groups showed only the difference in SNP of the IFNL4 gene to be statistically significant (p = 0.001). Similarly, nasopharyngeal expression of IFNL3 and IFNL4 genes, respectively, was found to be 3.48-fold less and 3.48-fold higher in the severe group as compared to the mild group. Multivariate analysis revealed SNP in the IFNL4 gene and age to have a significant association with COVID-19 severity.Conclusion: Despite the small sample size, IFNL4 gene SNP and patient age were associated with COVID-19 severity. Age, IFNL3/IFNL4 mRNA expression in the nasopharyngeal milieu, and the presence of SNP in the IFNL4 (rs368234815) gene in COVID-19 patients may be biomarkers for infection severity and help improve SARS-CoV-2 infection management.Keywords: COVID-19 severity, single nucleotide polymorphisms, interferon lambda, IFNL4, IFNL3

Abstract Aphids are one of the major insect pests of greenhouses and field crops worldwide. Several species of entomopathogenic fungi (EPF), including Lecanicillium spp. Beauveria bassiana, Isaria fumosorosea and Metarhizium anisopliae, have been developed commercially to control aphid species. However, there are no commercial products based on EPF that have been registered in Iraq. This study, therefore, was conducted to evaluate the virulence of four isolates of EPF, including, B. bassiana, Lecanicillium lecanii, M. anisopliae and Chaetomium globosum to select the highly virulent ones against the greenhouse aphids. Although the isolate of L. lecanii had the highest virulence against all tested aphid species in the laboratory bioassay, Myzus persicae Sulz and Aphis gossypii Gloy were more susceptible than Aphis fabae and Macrosiphum euphorbiae to infection with L. lecanii. Mortality caused by L. lecanii 7 days post-treatment with 108 conidia ml−1 was 100%. Further experiments in the greenhouses showed that L. lecanii significantly reduced the density of both M. persicae and A. gossypii 5 days after fungal applications. This isolate shows a promise for development of an alternative control agent against M. persicae and A. gossypii in Iraq.

Purpose: Measurement of the number of circulating tumor cells (CTCs) in the bloodstream has been shown to have prognostic significance in treating breast carcinoma. This pilot study was formulated to determine if stage IV non-small cell lung carcinomas similarly shed malignant cells into the circulation and if their presence has prognostic significance. Methods: Patients with stage IV non-small cell lung carcinomas were tested once for CTCs in 7.5 ml of their blood prior to receiving any treatments. A proprietary blood collection kit produced by Veridex LLC (Raritan, NJ), which manufactures the instrument that performs the immunomagnetic CELLSEARCH® CTC assay, was used. Tumor measurements were determined in three dimensions by the same radiologist using computerized axial tomography. The three-dimensional sum was used to represent tumor size. Survival from the date of the pretreatment CTC assay was monitored and recorded. Data were analyzed statistically using NCSS8 statistical software (NCSS LLC, Kaysville, UT). Results: Of 19 evaluable patients, 10 had no detectable CTCs. There was no relation between intrapulmonary primary tumor size and the number of CTCs, nor between tumor size and survival. Survival was not affected by gender or age at entry into the trial. The mean survival of those with no detectable CTCs was 536 ± 91.1 days versus 239 ± 96.0 days for those with 1 or more detectable CTCs, a statistically significant advantage (P=0.034) favoring those without CTCs. Conclusions: Patients with a CTC score of 0 survived significantly longer than those with a CTC score of ≥ 1. Survival was not correlated with gender, age or primary tumor size. Recovery of CTCs potentially provides a noninvasive source of tumor cells for genomic profiling, which may enable development of a custom treatment plan for the individual patient. Further investigations are warranted and needed.

Tumor hypoxia is associated with adverse outcome in many malignancies. The goal of this study was to determine if elevated expression of carbonic anhydrase IX (CAIX), a biomarker of hypoxia, predicts for recurrence in early-stage cervical cancer. The charts of all patients with early-stage cervical cancer, primarily FIGO IB, treated by radical hysterectomy at our institution from 1988–2001 were reviewed. Adequate pathologic specimens from patients who recurred or who had at least three years follow-up and remained disease-free were stained for CAIX. An immunohistochemical score (IHC) was generated from the extent/intensity of staining. Outcome, as measured by freedom from recurrence (FFR), distant metastases (FFDM) and local recurrence (FFLR), was analyzed as a function of age, IHC, lymph node status (LN) and histology.Forty-two relapsing patients and 76 non-relapsing patients were evaluated. In univariate analysis, +LN, though not IHC or histology, was a significant predictor of any recurrence. Both +LN and higher IHC were associated with decreased FFDM but not FFLR. Patients with both +LN and elevated IHC more frequently exhibited distant metastases as first site of failure (5-year FFDM 50%) than patients with only +LN, elevated IHC or neither feature (70, 85 and 95%, respectively, p = 0.0004). In multivariable analysis, only +LN was significantly associated with poorer FFDM (hazard ratio 4.6, p = 0.0015) though there was a strong trend with elevated CAIX expression (p = 0.069). Elevated CAIX expression is associated with more frequent distant metastases in early-stage cervical cancer, suggesting that patients with this characteristic may benefit from more aggressive treatment.

Resistance of hypoxic solid tumor niches to chemotherapy and radiotherapy remains a major scientific challenge that calls for conceptually new approaches. Here we exploit a hitherto unrecognized ability of sickled erythrocytes (SSRBCs) but not normal RBCs (NLRBCs) to selectively target hypoxic tumor vascular microenviroment and induce diffuse vaso-occlusion. Within minutes after injection SSRBCs, but not NLRBCs, home and adhere to hypoxic 4T1 tumor vasculature with hemoglobin saturation levels at or below 10% that are distributed over 70% of the tumor space. The bound SSRBCs thereupon form microaggregates that obstruct/occlude up to 88% of tumor microvessels. Importantly, SSRBCs, but not normal RBCs, combined with exogenous prooxidant zinc protoporphyrin (ZnPP) induce a potent tumoricidal response via a mutual potentiating mechanism. In a clonogenic tumor cell survival assay, SSRBC surrogate hemin, along with H(2)O(2) and ZnPP demonstrate a similar mutual potentiation and tumoricidal effect. In contrast to existing treatments directed only to the hypoxic tumor cell, the present approach targets the hypoxic tumor vascular environment and induces injury to both tumor microvessels and tumor cells using intrinsic SSRBC-derived oxidants and locally generated ROS. Thus, the SSRBC appears to be a potent new tool for treatment of hypoxic solid tumors, which are notable for their resistance to existing cancer treatments.

Tumor hypoxia is associated with adverse outcome in many malignancies. The goal of this study was to determine if elevated expression of carbonic anhydrase IX (CAIX), a biomarker of hypoxia, predicts for recurrence in early-stage cervical cancer. The charts of all patients with early-stage cervical cancer, primarily FIGO IB, treated by radical hysterectomy at our institution from 1988–2001 were reviewed. Adequate pathologic specimens from patients who recurred or who had at least three years follow-up and remained disease-free were stained for CAIX. An immunohistochemical score (IHC) was generated from the extent/intensity of staining. Outcome, as measured by freedom from recurrence (FFR), distant metastases (FFDM) and local recurrence (FFLR), was analyzed as a function of age, IHC, lymph node status (LN) and histology. Forty-two relapsing patients and 76 non-relapsing patients were evaluated. In univariate analysis, +LN, though not IHC or histology, was a significant predictor of any recurrence. Both +LN and higher IHC were associated with decreased FFDM but not FFLR. Patients with both +LN and elevated IHC more frequently exhibited distant metastases as first site of failure (5-year FFDM 50%) than patients with only +LN, elevated IHC or neither feature (70, 85 and 95%, respectively, p = 0.0004). In multivariable analysis, only +LN was significantly associated with poorer FFDM (hazard ratio 4.6, p = 0.0015) though there was a strong trend with elevated CAIX expression (p = 0.069). Elevated CAIX expression is associated with more frequent distant metastases in early-stage cervical cancer, suggesting that patients with this characteristic may benefit from more aggressive treatment.

The induction of tumor angiogenesis, a pathologic process critical for tumor progression, is mediated by multiple regulatory factors released by tumor and host cells. We investigated the role of the hematopoietic cytokine erythropoietin as an angiogenic factor that modulates tumor progression.Fluorescently-labeled rodent mammary carcinoma cells were injected into dorsal skin-fold window chambers in mice, an angiogenesis model that allows direct, non-invasive, serial visualization and real-time assessment of tumor cells and neovascularization simultaneously using intravital microscopy and computerized image analysis during the initial stages of tumorigenesis. Erythropoietin or its antagonist proteins were co-injected with tumor cells into window chambers. In vivo growth of cells engineered to stably express a constitutively active erythropoietin receptor EPOR-R129C or the erythropoietin antagonist R103A-EPO were analyzed in window chambers and in the mammary fat pads of athymic nude mice. Co-injection of erythropoietin with tumor cells or expression of EPOR-R129C in tumor cells significantly stimulated tumor neovascularization and growth in window chambers. Co-injection of erythropoietin antagonist proteins (soluble EPOR or anti-EPO antibody) with tumor cells or stable expression of antagonist R103A-EPO protein secreted from tumor cells inhibited angiogenesis and impaired tumor growth. In orthotopic tumor xenograft studies, EPOR-R129C expression significantly promoted tumor growth associated with increased expression of Ki67 proliferation antigen, enhanced microvessel density, decreased tumor hypoxia, and increased phosphorylation of extracellular-regulated kinases ERK1/2. R103A-EPO antagonist expression in mammary carcinoma cells was associated with near-complete disruption of primary tumor formation in the mammary fat pad.These data indicate that erythropoietin is an important angiogenic factor that regulates the induction of tumor cell-induced neovascularization and growth during the initial stages of tumorigenesis. The suppression of tumor angiogenesis and progression by erythropoietin blockade suggests that erythropoietin may constitute a potential target for the therapeutic modulation of angiogenesis in cancer.

Background: The United Arab Emirates (UAE) has experienced rapid economic growth in the last few decades, resulting in swift urbanization and an influx of foreign labor. This has facilitated an advanced, yet sedentary lifestyle characterized by increased reliance on technology, unhealthy dietary habits, and a reduction in physical activity levels. These factors significantly contributed to the rise in the prevalence of obesity. Objective: To determine the prevalence of obesity, it’s associated factors, and complications among adults presenting to the primary care clinic at Hatta Hospital, located in the Hatta area UAE. Materials and Methods: This cross-sectional study enrolled adult Emirati patients aged between 18-55 year. The study duration was from January 2022 to August 2022 Body Mass Index (BMI) was categorized based on the World Health Organization’s threshold. Patients’ socio-demographic and clinical data was obtained and recorded. Results: A total of 600 Emirati patients were included in this study, with a median age of 33 (IQR=25-45) years. Gender distribution was kept almost equal with 50.5% male and 49.5% female participants. The median BMI among the participants was 28.2 (IQR=24.3- 32.5) kg/m2 . The prevalence of underweight, normal weight, overweight, and obesity was found as 4.3%, 23.5%, 33.7% and 38.5% respectively. After adjusting the co-variants in the multivariable model, lower education levels were found to be significantly associated with higher odds of obesity. Conversely, being single and adhering to a healthy lifestyle was associated with lower odds of obesity in the multivariable model. Conclusion: The present study identified that 38.5% of the adult population attending Hatta Hospital family medicine clinics were obese and 33.7% were overweight. Conclusively, 72.2% of the adult population of the Hatta area have a BMI above normal, indicating a very high prevalence of obesity and overweight cases. Furthermore, a significant association of obesity was found with lower education levels, being married, having unhealthy dietary habits, and insufficient physical activity

Herein, we evaluated the effects of gonadotropin hormone-releasing hormone (GnRH) administration 84 h after medroxyprogesterone acetate (MAP) sponge removal on follicular growth, ovulation timing, and pregnancy per artificial insemination (AI) in cosynchronized postpartum Nili Ravi buffaloes. In this study, 58 Nili Ravi postpartum buffaloes (DIM = 103 ± 1.64) were randomly divided into two treatment groups (n = 29/treatment): GnRH-TAI-84 and TAI-84. All buffaloes were administered a MAP sponge for seven days. Upon MAP sponge removal, all the subjects received prostaglandin F2α (PGF2α) and Timed AI (TAI) was performed 84 h after sponge removal. In the GnRH-TAI-84 group, the buffaloes received GnRH alongside insemination, whereas in the TAI-84 group, the buffaloes were inseminated without GnRH administration. Follicle diameter and blood estradiol levels were measured every 6 h from 72–108 h after MAP sponge removal. The animals were checked for pregnancy using ultrasonography 40 days after AI. Animals subjected to the GnRH-TAI-84 protocol had a higher follicular growth rate and preovulatory follicle size than those in the TAI-84 group. The follicular diameter was also larger in animals that received GnRH-TAI-84 than in those that received TAI-84 90 and 96 h after MAP sponge removal. Buffaloes in the GnRH-TAI-84 group had lower estradiol concentrations at 90, 96, 102, and 108 h than those in the TAI-84 group. Ovulation in GnRH-TAI-84 buffaloes occurred 11 h earlier than that in buffaloes from the TAI-84 group. A shorter interval between AI and ovulation in GnRH-TAI-84 buffaloes (14 h vs. 25 h) led to greater pregnancies per AI (62% vs. 17%) compared to buffaloes from the TAI-84 group.

Thermal performance of peristaltic pump are significant to enhance the efficiency of the system. Heat transfer analysis for peristalsis of hybrid nanofluid through a curved duct is investigated here. Effect of radially varying magnetic field, Joule heating and heat generation/absorption are taken into consideration. Viscous dissipation and thermal radiation effects are considered to improve the heat transfer rate. Thermal and viscous characteristics are varying according to temperature. Velocity slip and temperature jump constraints are employed to solve the problem. The solution of resulting system are obtained under the lubrication technique. Curvature effect are also discussed to observe variation in the flow rate. NDSolve is built in shooting technique that are used in Mathematica software to find the solution. Numerical results for pertinent non-dimensional parameters are presented graphically. Heat transfer characteristics are represented through table. Results revealed that the inclusion of nanomaterials in liquid improves the cooling process and perturbs the flow rate. Comparative analysis indicates that heat transfer rate are 4 % higher in the case of copper nanomaterial as compare to iron oxide nanomaterial. The results of present study has relevance with cancer therapy, heart surgery and drug delivery processes.

Plant-based natural compounds are widely used to treat various ailments owing to their readily availability and minimal adverse effects. This study aimed to perform qualitative and quantitative biochemical profiling and assess the in vitro anti-diabetic, anti-Alzheimer, and anti-cancer activities of various apricot (Prunus armeniaca) cultivars. High-performance liquid chromatography (HPLC) was utilized to determine the concentrations of bioactive compounds across 10 distinct apricot cultivars. Initial phytochemical screening revealed a significant content of secondary metabolites. Subsequently, methanolic extracts from these cultivars were evaluated for their therapeutic potential against several human cancer cell lines, including prostate cancer (PC-3), lung cancer (A-549), breast cancer (MCF-7), cervical cancer (HELA), and kidney cancer (HEK). Notably, the breast cancer cell line MCF-7 showed a pronounced inhibition rate post-treatment with the apricot extracts. Correlation analysis exhibited phenols are highly correlated with flavonoids (r = 0.92), DPPH (r = 0.95), and alpha-amylase (%) inhibition (r = 0.96), and showed a significant correlation with other parameters. Principal Component Analysis (PCA) revealed that PC1 explained 43.31 % of the variance, while PC2 explained 12.88 %, together explaining 80.033 % of the total variance. PC1 was identified as the dominant axis, indicating the primary pattern of variation among the variables. Hierarchical Cluster Analysis (HCA) divided the cultivars into 2 main clusters, with cluster 2 further subdivided into various sub-clusters and sub-sub-clusters. This analysis highlighted distinct genetic similarities and differences among the apricot cultivars. Among the tested cultivars, ‘Irani’ and ‘Tilton’ were found to contain the highest levels of bioactive constituents. This research marks the first comprehensive examination of the impacts of these two apricot cultivars. The findings from this study provide a robust scientific foundation for the future isolation and purification of therapeutic compounds, potentially leading to their application in pharmaceuticals or dietary supplements. This research contributes significantly to the understanding of the pharmacological properties of apricot cultivars and establishes a basis for further investigation into their clinical benefits.