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Abstract Recent developments have highlighted the critical role that computer-aided diagnosis (CAD) systems play in analyzing whole-slide digital histopathology images for detecting gastric cancer (GC). We present a novel framework for gastric histology classification and segmentation (GHCS) that offers modest yet meaningful improvements over existing CAD models for GC classification and segmentation. Our methodology achieves marginal improvements over conventional deep learning (DL) and machine learning (ML) models by adaptively focusing on pertinent characteristics of images. This contributes significantly to our study, highlighting that the proposed model, which performs well on normalized images, is robust in certain respects, particularly in handling variability and generalizing to different datasets. We anticipate that this robustness will lead to better results across various datasets. An expectation-maximizing Naïve Bayes classifier that uses an updated Gaussian Mixture Model is at the heart of the suggested GHCS framework. The effectiveness of our classifier is demonstrated by experimental validation on two publicly available datasets, which produced exceptional classification accuracies of 98.87% and 97.28% on validation sets and 98.47% and 97.31% on test sets. Our framework shows a slight but consistent improvement over previously existing techniques in gastric histopathology image classification tasks, as demonstrated by comparative analysis. This may be attributed to its ability to capture critical features of gastric histopathology images better. Furthermore, using an improved Fuzzy c-means method, our study produces good results in GC histopathology picture segmentation, outperforming state-of-the-art segmentation models with a Dice coefficient of 65.21% and a Jaccard index of 60.24%. The model’s interpretability is complemented by Grad-CAM visualizations, which help understand the decision-making process and increase the model’s trustworthiness for end-users, especially clinicians.

Abstract Terahertz (THz) spectral region from 0.1 to 3 THz is envisaged to hold immense potential in the next generation of wireless technologies. Recently, research has focused on this terahertz gap, because of its unprecedented channel capacities. At the physical layer, the design complexities and fabrication of THz devices, especially antennas are the prime bottlenecks to realize its full potential. This article introduces a cost-effective, easy-to-fabricate, and reproducible sub-THz antenna design based on a single-layer planar printed circuit board technology. The antenna incorporates carefully designed quasi-cross slots and applied machine learning-assisted global optimization techniques to achieve the desired performance metrics. The antenna performance is elucidated through numerical simulations and verified through a rigorous in-house THz experimental framework around 100–110 GHz. The proposed antenna offers a peak gain of 13.90 dBi with less than 1 dB variation within the entire band of 100–110 GHz. The antenna holds the potential to achieve terabits per second data rates and futuristic high-resolution short-range THz imaging applications.

Platelets are small anucleated cell fragments that ensure the stopping of bleeding. In blood metastasis of cancer, Platelets are essential. One of the most important aspects of cancer metastasis is the interaction between platelets and circulating tumor cells. Platelets are involved in cancer spread and constitute a hazardous collation with the cancer cells. There are various factors involved in hemostasis and thrombosis, which can be activated by several cancer-related stimuli, including extracellular matrix (ECM), adenosine diphosphate (ADP), and Toll-like receptors (TLRs). Furthermore, it has been previously published that platelets build up inside the main tumors, producing growth factors that encourage tumor growth and angiogenesis. Additionally, tumor cells can interact with platelets through aggregation, further protecting cancer cells. Platelets interact both functionally and physically with different types of tumor cells via integrin and other surface receptors. Platelet integrin’s primary function is to maintain platelet adhesion and aggregation at vascular damage sites. Pharmacological treatments that target integrin have been shown to effectively inhibit experimental metastasis. This review paper summarized the recent advances and progress of mechanisms in platelet activation and its interaction with cancer cells in metastasis.

Abstract The escalation of global urbanization and industrial expansion has resulted in an increase in the emission of harmful substances into the atmosphere. Evaluating the effectiveness of titanium dioxide (TiO2) in photocatalytic degradation through traditional methods is resource-intensive and complex due to the detailed photocatalyst structures and the wide range of contaminants. Therefore in this study, recent advancements in machine learning (ML) are used to offer data-driven approach using thirteen machine learning techniques namely XG Boost (XGB), decision tree (DT), lasso Regression (LR2), support vector regression (SVR), adaBoost (AB), voting Regressor (VR), CatBoost (CB), K-Nearest Neighbors (KNN), gradient boost (GB), random Forest (RF), artificial neural network (ANN), ridge regression (RR), linear regression (LR1) to address the problem of estimation of TiO2 photocatalytic degradation rate of air contaminants. The models are developed using literature data and different methodical tools are used to evaluate the developed ML models. XGB, DT and LR2 models have high R2 values of 0.93, 0.926 and 0.926 in training and 0.936, 0.924 and 0.924 in test phase. While ANN, RR and LR models have lowest R2 values of 0.70, 0.56 and 0.40 in training and 0.62, 0.63 and 0.31 in test phase respectively. XGB, DT and LR2 have low MAE and RMSE values of 0.450 min-1/cm2, 0.494 min-1/cm2 and 0.49 min-1/cm2 for RMSE and 0.263 min-1/cm2, 0.285 min-1/cm2 and 0.29 min-1/cm2 for MAE in test stage. XGB, DT, and LR2 have 93% percent errors within 20% error range in training phase. XGB has 92% and DT, and LR2 have 94% errors with 20% range in test phase. XGB, DT, LR2 models remained the highest performing models and XGB is the most robust and effective in predictions. Feature importances reveal the role of input parameters in prediction made by developed ML models. Dosage, humidity, UV light intensity remain important experimental factors. This study will impact positively in providing efficient models to estimate photocatalytic degradation rate of air contaminants using TiO2.

Abstract Objective Pregnancy is a complex phenomenon accompanied by biological, physiological and psychosocial changes for a mother. It is also regarded as a stressful life event where a woman’s role, identity and interpersonal relationships are restructured. The present study from Pakistan explores the association of sleep quality and poor sleeping habits with prenatal stress using Pittsburgh Sleep quality Index. Results There were a total of 516 women (mean age = 29.82 years), with more than half reporting poor sleep quality. Ethnically, a majority (395, 76.6%) were natives of the Punjab province while rest were non-natives. A high percentage of respondents reported poor subjective sleep quality (22.1%), sleep latency (44.1%), habitual sleep efficiency (27.5%), sleep disturbance (30.1%), use of medications (7.1%) and daytime dysfunction (29.5%). According to logistic regression analysis, respondents with poor sleep quality were 2.24 (95% CI = 1.55–3.22, P

Background: Hepatitis C virus is one of the significant causes of morbidity and mortality in the World. Surprisingly, despite national screening campaigns, new cases of HCV are still on the rise. Methods and Results: A total of 5914 healthy blood donors was included in this study after informed consent. Anti-HCV ELISA was used to check presence of antigen in participant’s plasma.using Monlisa HCV Antigen-Antibody Ultra kit. Final confirmation was done by using real time PCR considered as a gold standard. Results: 0.5% of anti-HCV ELISA negative samples showed presence of antigen in plasma, when checked through core Ag detection method. Conclusion: Our result suggested that HCV core antigen detection and/or combo testing are far safer screening methods for the detection of HCV and the use of these methods can avoid/reduce further spread of this deadly disease.

Abstract The objective was to determine the postoperative hypersensitivity of two-step Total-etch as compared to one-step Universal adhesives followed by composite restorations on 100 patients by applying Total-etch on one tooth and Universal adhesive on another tooth. The bonds and teeth were randomly selected. Postoperative hypersensitivity was recorded by visual analog scale before, immediately after, and 24 h after the restoration using cold stimulus. The Mann–Whitney test was applied for statistical comparison of postoperative hypersensitivity between the two bonds as well as for any significant difference in genders with each bond. No significant difference was found between postoperative hypersensitivity of the two adhesives before (p-value = 0.57), immediately after (p-value = 0.604), and 24 h after (p-value = 0.728) the restoration. Males showed more hypersensitivity with Total-etch as compared to females before (p-value = 0.037), immediately after (p-value = 0.047), and 24 h after the restoration (p-value = 0.022). No significant difference was found between gender and Universal adhesive at all three stages (p-value > 0.05). The results suggest no significant difference in postoperative hypersensitivity between the two materials when good sample size and proper technique were observed along with the removal of bias like different patients having different pain perceptions and multiple operators having different operating skills. Males showed more hypersensitivity to Total-etch. Trial registration number: Australian New Zealand Clinical Trials. Registry number: ACTRN12622001213730. (Retrospectively registered: 09/09/2022).

Abstract Francisella tularensis (Ft) poses a significant threat to both animal and human populations, given its potential as a bioweapon. Current research on the classification of this pathogen and its relationship with soil physical–chemical characteristics often relies on traditional statistical methods. In this study, we leverage advanced machine learning models to enhance the prediction of epidemiological models for soil-based microbes. Our model employs a two-stage feature ranking process to identify crucial soil attributes and hyperparameter optimization for accurate pathogen classification using a unique soil attribute dataset. Optimization involves various classification algorithms, including Support Vector Machines (SVM), Ensemble Models (EM), and Neural Networks (NN), utilizing Bayesian and Random search techniques. Results indicate the significance of soil features such as clay, nitrogen, soluble salts, silt, organic matter, and zinc , while identifying the least significant ones as potassium, calcium, copper, sodium, iron, and phosphorus. Bayesian optimization yields the best results, achieving an accuracy of 86.5% for SVM, 81.8% for EM, and 83.8% for NN. Notably, SVM emerges as the top-performing classifier, with an accuracy of 86.5% for both Bayesian and Random Search optimizations. The insights gained from employing machine learning techniques enhance our understanding of the environmental factors influencing Ft’s persistence in soil. This, in turn, reduces the risk of false classifications, contributing to better pandemic control and mitigating socio-economic impacts on communities.

Objective: To compare the complications among patients undergoing three-port versus four-port laparoscopic cholecystectomy at our tertiary care hospital. Study Design: Comparative cross-sectional study. Place and Duration of Study: Department of Surgery, Combined Military Hospital, Quetta Pakistan, from Feb to Oct 2021. Methodology: Study was conducted on 200 patients who underwent laparoscopic cholecystectomy for any benign gall bladder pathology during the study period. Patients were randomly divided into two groups. Group-A underwent a three-port laparoscopic cholecystectomy, while Group-B underwent a four-port laparoscopic cholecystectomy. Post-operative pain, surgical site infection, duration of hospital stay, and conversion to open method were compared in both groups. Results: Out of 100 patients included in the final analysis, 33 were male, and 67 were female. The mean age of patients who underwent laparoscopic surgery for benign gall bladder pathologies in our study was 42.95±9.47 years. 43(43%) underwent three ports, while 57(57%) underwent four port laparoscopic cholecystectomy. Duration of hospital stay was statistically significantly less in patients with three-port laparoscopic surgery than in patients undergoing four-port laparoscopic cholecystectomy (p-value

Objective: To reduce the number of discarded red cell concentration units by 30 per cent in the hospital blood bank. Study Design: Cross-sectional study (Clinical Audit). Place and Duration of Study: Blood Bank, Najran Armed Forces Hospital, Kingdom of Saudi Arabia, from Jan 2019 to Jun 2020. Methodology: Data on discarded blood units was collected from January to June 2019 and January to June 2020 through nonprobability convenient sampling. All blood donations made during this period were included except therapeutic phlebotomy units. Changes in the blood bank process and procedures were made from July to December 2019. Discard of red cell concentrates from Jan to Jun 2019 and Jan to Jun 2020 was compared. Net Cost Savings were calculated using the Impact Analysis Calculator. Results: The total number of discarded Red Cell Concentrates was 174(41.1%) of the 423 donated units from Jan to Jun 2019. After making changes in inventory management and post-implementation these changes in the blood bank, 84(29.1%) of 288 RCC units were discarded from Jan to Jun 2020 (p-value of 0.02). The net cost savings was SAR 72750. Conclusion: Interventions in blood bank inventory management can prevent the loss of life-saving blood products and result in cost and resource savings.

Abstract Mammalian sperm cells are highly vulnerable to lipid peroxidation by free radicals. Antioxidants such as vitamin E, and vitamin C neutralize the activity of free radicals and protect the sperm from reactive oxygen species. The present study was conducted to investigate the effects of vitamin C, vitamin E, and their combination in a Tris-based extender on the semen quality of Kail Ram. Semen samples from five mature Kail rams were collected in this study. The semen samples were diluted by Tris-glucose-egg yolk. Diluted semen samples were divided into four parts. The first part was added with 1 mg/ml of vitamin C, the second part was added with 1 mg/ml of vitamin E and the third part was added with both vitamin C and E, in combination with a dose of 1 mg/ml. The fourth part was considered as control without any addition. The diluted semen samples were cooled gradually and preserved at 5˚C for three days. Sperms in chilled diluted semen samples were examined for motility, viability, and plasma membrane integrity every 24 h for three days (72 h). Present study results showed significant (P

Abstract Customer churn, a phenomenon that causes large financial losses when customers leave a business, makes it difficult for modern organizations to retain customers. When dissatisfied customers find their present company's services inadequate, they frequently migrate to another service provider. Machine learning and deep learning (ML/DL) approaches have already been used to successfully identify customer churn. In some circumstances, however, ML/DL-based algorithms lacks in delivering promising results for detecting client churn. Previous research on estimating customer churn revealed unexpected forecasts when utilizing machine learning classifiers and traditional feature encoding methodologies. Deep neural networks were also used in these efforts to extract features without taking into account the sequence information. In view of these issues, the current study provides an effective method for predicting customer churn based on a hybrid deep learning model termed BiLSTM-CNN. The goal is to effectively estimate customer churn using benchmark data and increase the churn prediction process's accuracy. The experimental results show that when trained, tested, and validated on the benchmark dataset, the proposed BiLSTM-CNN model attained a remarkable accuracy of 81%.

Abstract Amyloid beta (Aβ) aggregation and tau hyper phosphorylation (p-tau) are key molecular factors in Alzheimer’s disease (AD). The abnormal formation and accumulation of Aβ and p-tau lead to the formation of amyloid plaques and neurofibrillary tangles (NFTs) which ultimately leads to neuroinflammation and neurodegeneration. β- and γ-secretases produce Aβ peptides via the amyloidogenic pathway, and several kinases are involved in tau phosphorylation. Exosomes, a recently developed method of intercellular communication, derived from neuronal stem cells (NSC-exos), are intriguing therapeutic options for AD. Exosomes have ability to cross the BBB hence highly recommended for brain related diseases and disorders. In the current study, we examined how NSC-exos could protect human neuroblastoma cells SH-SY5Y (ATCC CRL-2266). NSC-exos were derived from Human neural stem cells (ATCC-BYS012) by ultracentrifugation and the therapeutic effects of the NSC-exos were then investigated in vitro. NSC-exos controlled the associated molecular processes to drastically lower Aβ and p-tau. A dose dependent reduction in β- and γ-secretase, acetylcholinesterase, GSK3β, CDK5, and activated α-secretase activities was also seen. We further showed that BACE1, PSEN1, CDK5, and GSK-3β mRNA expression was suppressed and downregulated, while ADAM10 mRNA was increased. NSC- Exos downregulate NF-B/ERK/JNK-related signaling pathways in activated glial cells HMC3 (ATCC-CRL-3304) and reduce inflammatory mediators such iNOS, IL-1β, TNF-α, and IL-6, which are associated with neuronal inflammation. The NSC-exos therapy ameliorated the neurodegeneration of human neuroblastoma cells SH-SY5Y by enhancing viability. Overall, these findings support that exosomes produced from stem cells can be a neuro-protective therapy to alleviate AD pathology.

Excessive utilization of nanoparticles renders it necessary to produce safer and more secure nanoparticles while preserving their efficacy. In this study, Psidium guajava L. pulp extract-mediated silver nanoparticles (AgNPs) were synthesized, characterized, and further evaluated regarding their antioxidant potential. The green synthesized silver nanoparticles (G-AgNPs) showed a higher level of radical scavenging activity (RSA) (25.85%), hydrogen peroxide scavenging activity (34.34%), and ferric reducing power (0.28). The comparison of the control group (G1) with the various treatment groups (G2–G6) revealed that the levels of catalase (CAT), superoxide dismutase (SOD), and glutathione-S-transferase (GST) were significantly different (P < 0.05). The levels of blood urea, uric acid, blood urea nitrogen (BUN), serum glutamic pyruvic transaminase (SGTP), serum creatinine, serum glutamic-oxaloacetic transaminase (SGOT), alkaline phosphatase, total bilirubin, and serum electrolytes were also evaluated. The results of clinical biochemistry also strengthened our hypothesis that G-AgNPs are less toxic than C-AgNPs. Finally, the histopathology of liver, kidney, and intestinal tissues indicated that green-synthesized AgNPs are relatively safer.

Background: Adhesive Capsulitis (AC) of the shoulder or Frozen Shoulder (FS) is the most common disabling shoulder condition which has serious functional implications in daily life. FS affects 2 to 3 percent of the population. In Pakistan, fewer studies have been performed in the past describing the common risk factors linked to AC. Objective: The objectives of the study are to assess the risk factors e.g diabetes, thyroid disease, stroke, trauma, hyperlipidemia, rheumatoid and tuberculosis present in patients with AC, and whether the levels of HbA1c have a role in AC. Study type, settings & duration: This descriptive study was carried out at Shifa Foundation Falahi Clinic and Pain and Medical Clinic at Shifa International Hospital, Islamabad between June 2018 and January 2021. Methodology:Non probability convenience sampling technique was used. Consecutive patients more than 18 years old with shoulder pain or stiffness were identified and informed consent was obtained. A detailed survey using a questionnaire was used. Descriptive statistics were performed. Mean and standard deviation was calculated for age. The SPSS version 23 was used for data analysis. Frequency analysis of risk factors was performed. Further statistical analysis was done by applying chi-square test to assess the relationship between HbA1c levels(control of Diabetes Mellitus) and adhesive capsulitis. Results:Data of 304 patients with mean age of 54±9 years. Frequency analysis showed 86 (28.3%) were males and 218 (71.7%) were females. The most common risk factor was diabetes 41.6% followed by hyperlipidemia 28.6%, shoulder trauma 14.8%, hypothyroidism 12.5%. High HbA1c levels were found in 78% of diabetic patients and it was strongly associated with AC (p-value

Introduction: Trigeminal neuralgia is a condition of craniofacial pain which is characterized by sudden, excruciating, and brief pain in the sensory distribution of one or more branches of the fifth cranial nerve resulting in decreased quality of life of the affected patient. In patient’s refractory to pharmacological or conservative treatment, the surgical procedure of choice is microvascular decompression. The aim of our study was to determine the outcome of retro mastoid suboccipital microvascular decompression technique for the trigeminal neuralgia. Material & Methods: This case series study was conducted in Department of Neurosurgery Prime Teaching Hospital and Irfan General Hospital Peshawar from January 2020 to January 2022. Consent from the ethical committee and patients were taken. All patients of trigeminal neuralgia were included. Those patients having mass lesion were excluded. All information were put in proforma. Results were analysed by SPSS version 20. Results: Total sample size of our study was 58 patients. Majority of the patients were female (n 34 59%). Mean age of the patients was 44+ 5 years (range 25-60 years). The common level of pain distribution was in maxillary and mandibular branches V2-V3, 39(67.8%). The most common aetiology of trigeminal neuralgia was superior cerebellar artery loop in 41(70.7%) patients. Surgical outcome in terms of pain relief was in 49 (84.5 %) patients, after 6-8 months follow-up, The most common complication of surgery was CSF leak in 3(5.2%) patients, followed by post operative Sub arachnoid haemorrhage in 1(1.8%) patient, mortality was reported in 2 (3.4%) patients. Conclusion: The results of our study concluded that microvascular decompression surgery is effective in reducing pain, improving patient satisfaction in trigeminal neuralgia patients who are refractory to conservative treatment options such as carbamazepine’s. The procedure also has some complications such as cerebrospinal fluid leakage and sub arachnoid haemorrhage.

Introduction: LSG is the gold standard sole bariatric procedure for morbid obesity. Small (2cm) and large (6cm) distance of resection margin from pylorus are both being used for neogastric sleeve formation however what is optimal distance remains controversial. Aims & Objectives: To assess excess weight loss results and complication rate with 6cm and 2cm distance of staple line from pylorus during a prolonged surveillance period. Place and Duration of Study: This retrospective cohort study was conducted at Fatima Memorial Hospital from Dec 2013 to Dec 2022 spanning 9 years. Material & Methods: Medical records of 50 morbidly obese patients aged 41- 50 yrs were segregated into two groups of 25 each based on the LSG procedure conducted. Group 1 had LSG with 6cm resection margin from pylorus while group 2 had a staple line distance of 2cm from pylorus for neogastric sleeve formation. The patients were subsequently followed up for excess weight loss (EXL) and BMI at 6 months, 1 year, 2 years, 3 years & 4-year interval. Data was entered and analyzed using SPSS version 21.P value ? 0.05 was considered significant. Results: EWL in Group 1 & 2 was 39.2± 6.77kg & 41.9± 4.35kg at 6 months,73.64± 6.49kg & 71.06± 7.77kg at 1 year, 65.52± 5.53kg & 63.92± 7.07kg at 2 years,58.16± 4.97kg & 57.28± 5.75kg at 3 years and 55.48± 3.39kg & 55.36± 3.72kg for 4 years were, not significant statistically. BMI in group 1 & 2 were 39.47± 5.11 & 35.88± 4.40 at 6 months, 29.22± 2.68 & 29.12± 2.00 at 1 year, 25.44± 1.96 & 24.73± 2.86 at 2 years, 22.84± 1.79 & 22.40±2.20 at 3 years and 21.66± 1.32, 21.67± 1.62 at 4 years were found to be statistically insignificant. Conclusion: With regards to extra weight loss, distance of resection margin from pylorus of 2cm or 6cm have identical effects but the latter has lowest complication incidence after 4 yrs of surveillance. Hence, a distance of 6cm is favoured to ensure safety of LSG for morbidly obese patients. And the findings of this study will help bariatric surgeons to improve technique of LSG in a safe and successful way for effective weight loss in morbidly obese patients.

Objective: To study the association of total leucocyte count and acute appendicitis among young patients undergoing emergency appendectomy. Study Design: Comparative cross-sectional study. Place and Duration of Study: Department of Surgery, Combined Military Hospital, Quetta Pakistan, from Mar to Oct 2021. Methodology: The study included one hundred patients diagnosed with acute appendicitis by a consultant surgeon undergoing an emergency appendectomy. The total leucocyte count was calculated for all the patients at the time of diagnosis. The treating surgeon confirmed acute appendicitis findings based on gross examination of the appendix at the time of surgery. The presence of acute appendicitis and other factors was associated with raised total leucocyte count in all the patients. Results: Out of 100 patients diagnosed with acute appendicitis, 59 were male, while 41 were female. The mean age of the study participants was 28.33±3.673 years. On gross examination, 79 had a confirmed diagnosis of acute appendicitis, while 21 did not have an inflamed appendix. 85 had raised total leucocyte count, while 15 patients had total leucocyte count in the normal range. Statistical analysis revealed that acute appendicitis on gross examination and raised C-reactive protein had a statistically significant correlation with raised total leucocyte count (p-value: 0.001). Conclusion: Total leucocyte count was significantly raised in patients who had confirmation of inflammation of the appendix at gross examination during the surgery. Raised total leucocyte count and C reactive protein should be given more weightage in diagnosing acute appendicitis and planning for an emergency appendectomy.

Non-cystic fibrosis (non-CF) bronchiectasis has emerged as a significant respiratory disease in developing countries. Given the variation in causes and clinical characteristics across different regions, it is necessary to conduct studies in regions with limited data such as low-middle income countries (LMIC). The aim of the study was to investigate the underlying causes, clinical presentation, etiology, lung function and imaging in patients with bronchiectasis who sought treatment at a tertiary care hospital in a LMIC. We conducted retrospective observational study at the Aga Khan University, Pakistan. Adult patients diagnosed with non-CF bronchiectasis on high-resolution computed tomography scan between 2000 and 2020 were included. We evaluated the etiology, clinical characteristics, microbiology, radiology and spirometric pattern of these patients. A total of 340 patients were included with 56.5% being female and 44.7% aged over 60 years. Among them, 157 (46.2%) had experienced symptoms for 1-5 years. The most common spirometric pattern observed was obstructive impairment (58.1%). Previous tuberculosis (TB) (52.94%) was the most common etiology followed by allergic bronchopulmonary aspergillosis (7.64%). Bilateral lung involvement on HRCT scan was found in 63.2% of patients. Pseudomonas aeruginosa was the most frequently identified organism (38.75%) among 240 patients with available specimens. Patients with P. aeruginosa infections had a significantly higher number of exacerbations (p=0.016). There was a significant difference (p

Abstract Coxiella burnetii (Cb) is a hardy, stealth bacterial pathogen lethal for humans and animals. Its tremendous resistance to the environment, ease of propagation, and incredibly low infectious dosage make it an attractive organism for biowarfare. Current research on the classification of Coxiella and features influencing its presence in the soil is generally confined to statistical techniques. Machine learning other than traditional approaches can help us better predict epidemiological modeling for this soil-based pathogen of public significance. We developed a two-phase feature-ranking technique for the pathogen on a new soil feature dataset. The feature ranking applies methods such as ReliefF (RLF), OneR (ONR), and correlation (CR) for the first phase and a combination of techniques utilizing weighted scores to determine the final soil attribute ranks in the second phase. Different classification methods such as Support Vector Machine (SVM), Linear Discriminant Analysis (LDA), Logistic Regression (LR), and Multi-Layer Perceptron (MLP) have been utilized for the classification of soil attribute dataset for Coxiella positive and negative soils. The feature-ranking methods established that potassium, chromium, cadmium, nitrogen, organic matter, and soluble salts are the most significant attributes. At the same time, manganese, clay, phosphorous, copper, and lead are the least contributing soil features for the prevalence of the bacteria. However, potassium is the most influential feature, and manganese is the least significant soil feature. The attribute ranking using RLF generates the most promising results among the ranking methods by generating an accuracy of 80.85% for MLP, 79.79% for LR, and 79.8% for LDA. Overall, SVM and MLP are the best-performing classifiers, where SVM yields an accuracy of 82.98% and 81.91% for attribute ranking by CR and RLF; and MLP generates an accuracy of 76.60% for ONR. Thus, machine models can help us better understand the environment, assisting in the prevalence of bacteria and decreasing the chances of false classification. Subsequently, this can assist in controlling epidemics and alleviating the devastating effect on the socio-economics of society.

Abstract Dampened immunity and impaired wound healing in diabetic patients may lead to diabetic foot ulcer disease, which is the leading cause of limb amputations and hospitalization. On the other hand, cancer is the most significant cause of mortality globally, accounting for over 10 million fatalities in 2020, or nearly one in every six deaths. Plants and herbs have been used to treat chronic diseases due to their essential pharmaceutical attributes, such as mitigating drug resistance, ameliorating systemic toxicities, reducing the need for synthetic chemotherapeutic agents,and strengthening the immune system. The present study has been designed to evaluate the effects of Tribulus terrestris on wound healing, cytotoxic and anti-inflammatory responses against HepG-2 liver cancer cell line. Two solvents (methanol and ethanol) were used for root extraction of T. terrestris. The wound healing potential of the extracts was studied on diabetic cell culture line by scratch assay. The anti-oxidant and cytotoxic potentials were evaluated by in vitro assays against HepG2 cell line. The methanolic root extract resulted in the coverage of robust radical scavenging or maximum inhibition of 66.72%,potent cytotoxic activity or reduced cell viability of 40.98%, and anti-diabetic activity having mighty α-glucosidase inhibition of 50.16% at a concentration of 80 μg/ml. Significant reduction in the levels of LDH leakage (56.38%), substantial ROS (48.45%) and SOD (72.13%) activities were recorededMoreover, gene expression analysis demonstrated the down-regulation of inflammatory markers (TNF-α, MMP-9, Bcl-2, and AFP) in HepG-2 cells when treated with T. terresteris methanolic extract as compared to stress. Furthermore, the down-regulation of inflammatory markers was validated through ELISA-mediated protein estimation of IL-1β and TNF-α. It is expected that this study will lay a foundation and lead to the development of efficient but low-cost, natural herbs extract-based dressing/ointment for diabetic patients and identify potential drug metabolites to treat out-of-whack inflammatory responses involved in cancer onset, progression, and metastasis.

Nocardiosis is an opportunistic infection that primarily targets the immunosuppressed. We investigate the differences in demographics and characteristics between immunosuppressed and immunocompetent patients with nocardiosis in a tertiary care hospital in Pakistan. Retrospective records were reviewed for patients diagnosed with pulmonary nocardiosis between 2010 and 2020. Immunosuppressed individuals were identified as those with autoimmune diseases, hematologic diseases and malignancies, HIV, immunosuppressant therapy, etc. Data collected included basic demographics, comorbid conditions, medication history, clinical presentation, radiological and microbiological data, and nocardiosis outcomes and complications. A total of 66 patients with nocardiosis were included in this study out of which 48 were immunosuppressed while 18 were immunocompetent. Both groups were compared for a number of variables including patient characteristics, underlying conditions, radiological findings, treatment regimen and outcomes. Immunosuppressed individuals were younger, and had higher rates of diabetes, chronic renal disease, chronic liver disease, higher platelet counts, surgical intervention, and longer hospital stays. Fever, dyspnea, and sputum production were the most common presentations. Nocardia asteroides was found to be the most common species of Nocardia overall. Nocardiosis presents differently in patients with immunosuppressed and immunocompetent patients consistent with previous studies. Nocardiosis should be considered in any patient presenting with treatment-resistant pulmonary or neurological symptoms.

Introduction: One of the most common urological emergency conditions is acute scrotum. Scrotal pain is commonly seen in early adults in the emergency departments with an association of different pathologies. The aim of this study was to determine the comparison of high-resolution sonography and colour Doppler flow imaging in patients presenting with acute scrotum. Material & Methods: A descriptive study was conducted at the Department of Radiology, Lady Reading Hospital, Peshawar, Pakistan. This study enrolled a purposive sample of emergency department patients presenting with acute scrotal pain. The pattern of blood flow, peak systolic velocity, resistive index, pulsatility index, mean and standard deviation were calculated for the continuous variables. Descriptive analyses were performed to investigate the distribution of data. Results: A total of 72 patients were enrolled in our study. The mean age of patients was recorded 36.33±11.66 years. The most common scrotal pathologies that associated with scrotal pain was hydrocele 31(38.8%), followed by varicocele 22(27.5%), testicular torsion 9(11.3%), cyst 8(10.0%), epididymo-orchitis 7(8.8%), pyocele 6(7.5%), orchitis 4(5.0%), increase scrotal wall thickness 3(3.8%), undescended testis 3(3.8%), inguinoscrotal hernia 1(1.3%), testicular atrophy 1(1.3%), rete testis 1(1.3%), hemangioma 1(1.3%), hematoma 1(1.3%), scrotal mass 1(1.3%), testicular microlithiasis 1(1.3%), and normal scrotal sonography 4(5.0%) of cases respectively. Conclusion: High-resolution ultrasonography along with colour and power Doppler should be used as 1st line imaging modality in patients presenting with acute scrotal pain.

Introduction: Hydronephrosis is a common complication of the kidney that is caused by obstruction to kidney ureters and bladder. The renal pelvis and pelvicalyceal system of the kidney become dilated. The obstruction may either be in the upper or lower urinary tract. Upper urinary tract obstruction includes ureteropelvic junction obstruction, renal stone, tumours, and vesicoureteric junction obstruction while lower tract includes benign prostatic hyperplasia, prostate tumours posterior urethral valves. Material & Methods: This cross-sectional study was conducted at the Department of Radiology Lady Reading Hospital Peshawar, Pakistan. The study duration was 9 months (September 2020 and May 2021). A total of 120 participants were presented with a history of flank and are suspicious for renal stone causing hydronephrosis. 30 patients were taken as control with no renal disease while 90 were cases having renal disease. Grading of hydronephrosis and Urine jet velocity was recorded by using real-time and spectral doppler ultrasound. Results: A total of 120 participants were included in this study. The mean jet velocity in the normal individuals was recorded as 50.37 ± 6.4 cm/s, however, in patients with mild, moderate, and severe hydronephrosis the mean jet velocity was recorded as 14.23 ± 10.47 cm/s, 7.32± 8.14 cm/s and, 1.5 ± 3.98 cm/s respectively. Conclusion: Urine jet velocity is a good indicator of ureteric obstruction in a patient with various grades of hydronephrosis. The velocity of the urine jet reduced significantly with increasing the severity of hydronephrosis.

Abstract Mahonia bealei is one of the important members of the genus Mahonia and Traditional Chinese Medicine (TCM). Several compounds isolated from this plant have exhibited useful biological activities. Polysaccharides, an important biomacromolecule have been underexplored in case of M. bealei. In this study, hot water extraction and ethanol precipitation were used for the extraction of polysaccharides from the stem of M. bealei, and then extract was purified using ultrafiltration membrane at 50,000 Da cut off value. Characterization of the purified M. bealei polysaccharide (MBP) was performed using Fourier Transform Infrared Spectroscopy (FT-IR), along with Scanning Electron Microscopy (SEM), X-ray crystallography XRD analysis and Thermal gravimetric analysis (TGA). The purified polysaccharide MBP was tested for antioxidant potential by determining its reducing power, besides determining the DPPH, ABTS, superoxide radical, and hydroxyl radical scavenging along with ferrous ion chelating activities. An increased antioxidant activity of the polysaccharide was reported with increase in concentration (0.5 to 5 mg/ml) for all the parameters. Antimicrobial potential was determined against gram positive and gram-negative bacteria. 20 µg/ml MBP was found appropriate with 12 h incubation period against Escherichia coli and Bacillus subtilis bacteria. We conclude that polysaccharides from M. bealei possess potential ability of biological importance; however, more studies are required for elucidation of their structure and useful activities.

Rotavirus is one of the main pathogens that causes severe diarrhea in children under the age of 5, primarily infecting the enterocytes of the small intestine. Currently, there are no specific drugs available for oral rehydration and antiviral therapy targeting rotavirus. However, metformin hydrochloride, a drug known for its antiviral properties, shows promise as it accumulates in the small intestine and modulates the intestinal microbiota. Therefore, we formulated a hypothesis that metformin hydrochloride could inhibit rotavirus replication in the intestine. To validate the anti-rotavirus effect of metformin hydrochloride, we conducted infection experiments using different models, ranging from in vitro cells and organoids to small intestines in vivo. The findings indicate that a concentration of 0.5 mM metformin hydrochloride significantly inhibits the expression of rotavirus mRNA and protein in Caco-2 cells, small intestinal organoids, and suckling mice models. Rotavirus infections lead to noticeable pathological changes, but treatment with metformin has been observed to mitigate the lesions caused by rotavirus infection in the treated group. Our study establishes that metformin hydrochloride can inhibit rotavirus replication, while also affirming the reliability of organoids as a virus model for in vitro research.

Objective: To analyse the clinicopathological spectrum of COVID-19 among 2000 patients. Study Design: Cross-sectional study. Place and Duration of Study: Combined Military Hospital, Abbottabad Pakistan, from Apr to Jun 2020. Methodology: The study included 2000 patients who came to CMH Abbottabad to seek medical attention during the first wave of the COVID-19 pandemic. Age, gender, contact history, history of foreign travel, clinical features, comorbid conditions and results of SARS-CoV-2 PCR were observed. Results: From 2000 cases, 1442(72%) were males, and 558(28%) were females. The mean age was 35.02±13.00 years, and 1275(63.8%) cases were from the 3rd to fourth decade of life. 900(45%) of the cases had a contact history with a COVID-19 patient, whereas only 4(0.2%) had a history of foreign travel. 1854(93.0%) of the cases were asymptomatic, whereas only 48(2.4%) presented with fever and cough, the most common symptoms. Only 26(1.3%) cases had associated comorbid conditions, and 263(13.0%) cases showed positive PCR results. The statistical association was found to be significant among age groups, gender, contact history and results of SARS-CoV-2 PCR,(p-value< 0.001). Conclusion: This study provides an overall view of the COVID-19 pandemic, which has grasped the globe within no time.Efficient preventive and control measures are mandatory, in addition to early identification and diagnosis, to overcome the infection.

BackgroundToxoplasma gondii is a zoonotic and foodborne intracellular parasite capable of inducing congenital infections, stillbirths and abortions in humans and animals, globally. The consumption of undercooked or raw mutton is "one of the vital risks" for acquiring toxoplasmosis: an asymptomatic condition in healthy persons, while life-threatening in immunodeficient individuals like "HIV/AIDS" patients.ObjectivesThe current study has multiple objectives: to optimize a newly ELISA kit for Sheep, to find out the seroprevalence of ovine toxoplasmosis of two ecological zones of the Punjab, Pakistan through LAT and newly Optimized Sheep ELISA kit, to do the comparison of efficacies of various tests (LAT with newly Optimized ELISA kit and newly Optimized ELISA kit with commercial ELISA kit) and to determine the different meteorological parameters as the risk factors for T. gondii infection in sheep.MethodsA cross-sectional study was conducted on 400 sheep sera, 200 were collected from sheep raised on open grazing system by local farmers in the adjoining areas of Civil Veterinary Dispensaries (CVDs) of range-ecological zone i.e. tehsil Kot Chutta (Dera Ghazi khan). Similarly, the remaining 200 were collected from agro-ecological zone i.e. tehsil Sharaqpur (Sheikhupura), to evaluate the comparative efficacy of LAT with optimized ELISA kit and newly optimized ELISA kit with commercial ELISA kit.FindingsThe newly ELISA kit optimized against a commercial ELISA kit was found to have 100% sensitivity, 97.6% specificity with 98% Positive Predictive Value, 100% Negative Predictive Value, Cut off value = 0.505, 28.28 LR+, 0.0104 LR-, and 2719.23 DOR. Seroprevalence of toxoplasmosis was detected significantly (P < 0.01; χ2) higher in Sharaqpur (44.5% by LAT; 35.5% by ELISA) as compared to that in Kot Chutta (39.5% by LAT; 31% by ELISA). The highest seroprevalence was seen in the sheep of the 1-2 years age group (P < 0.01; χ2), whereas the lowest in the oldest animals (≥ 4 years). Investigation of meteorological data of both the regions reveals that the zone with higher seroprevalence has relatively higher rainfall, higher humidity, lower environmental temperatures, and higher altitude as the critical factors, potentially behind the significant difference seen in seroprevalence level. The partial correlation of both tests (newly optimized ELISA kit and LAT) was 0.991 at maximum temperature in Sharaqpur while it was 0.981 in Kot Chutta.InterpretationA novel significant correlation was found between the meteorological parameters (relative humidity, minimum, maximum, and average temperatures) divided into yearly units of both the ecological zones, and year-wise seroprevalence (birth years of age-wise groups) of the corresponding regions. We hypothesize that such environmental conditions increase the risk of toxoplasmosis in grazing sheep, owing to a more favorable environment for coccidian oocyst survival. The ELISA kit optimized in this study will be helpful for the detection of seroprevalence of ovine toxoplasmosis in other ecological zones of Pakistan as well as of any other country in the world. More studies are recommended involving regions from other ecological zones of Pakistan to further explore the seroprevalence of ovine toxoplasmosis and to ratify the novel correlation of meteorological parameters with seroprevalence.

Prime objective of the current research was to develop a stable nimesulide emulgel with the help of arabinoxylan, a natural gelling agent extracted from Plantago ovata. The response surface methodology was used by a Design Expert 10 software to formulate and optimize the emulgel. The experimental design approach evaluated the impact of independent and dependent variables. Independent variables were different concentrations of arabinoxylan, span 80 and tween 20, whereas, dependent variables were viscosity, pH, and content uniformity. FTIR demonstrated the compatibility of nimesulide with the excipients. Stability study indicated no phase separation and no change in pH for formulation F1, F3 and F4. The negative values of zeta potential revealed the excellent stability of emulgel. Viscosity, spreadability and extrudability values were in desired range. Ex-vivo permeation study illustrated 86%, 55% and 66% release of the drug over a period of 24 h from the formulations F1, F3 and F4, respectively. Analgesic effect of the optimized emulgel was significantly higher in test group as compared to control and did not produce any sort of irritation. Therefore, it can be concluded that the newly developed emulgel based on arabinoxylan, as gelling agent, appear to be an effective drug delivery system.

Plant derived compounds have always been an important source of medicines and have received significant attention in recent years due to their diverse pharmacological properties. Millions of plant-based herbal or traditional medicines are used to cure various types of cancers especially due to activation of proliferative genes. The aim of the present study was to characterize the altered and attenuated gene expression of the selected growth factor namely Transforming growth factor Beta -1 (TGFβ1) and MYC in human hepatoma-derived (Huh7) liver cancer cell lines in response to extracts of Artemisia absinthium dissolved in selected organic solvents. Ethanolic, methanolic and acetone extract of different plant parts (leaf, stem and flowers) was used to access the antiproliferative activity by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. Quantitative Real-Time RT-PCR revealed that the transcript levels of TGFβ1 are induced in the samples treated with methanolic extract of Artemisia absinthium. Furthermore, reduced expression levels of MYC gene was noticed in cancerous cells suggesting antiproliferative properties of the plant. This study further highlights the resistance profile of various microbes by antimicrobial susceptibility test with plant extracts. In addition, antidiabetic effect of Artemisia absinthium have also shown positive results. Our study elucidates the potentials of Artemisia absinthium as a medicinal plant, and highlights the differential expression of genes involved in its mitogenic and anti-proliferative activity with a brief account of its pharmacological action.

Objective: To evaluate the various factors leading to conversion of laparoscopic cholecystectomy to open cholecystectomy. Study Design: Comparative cross-sectional study. Place and Duration of Study: Pak Emirates Military Hospital Rawalpindi, from May 2020 to Sep 2021. Methodology: This study was conducted on 200 patients who underwent laparoscopic cholecystectomy for any benign pathology during the study period. Data was collected for all the patients who required conversion of surgical procedure from laparoscopic to open cholecystectomy. Demographic and clinical risk factors were associated with conversion of procedure in the study participants. Results: Out of 200 patients included in the final analysis 67 (33.5%) were male and 133 (66.5%) were female. Mean age of patients put who underwent laparoscopic surgery for benign gall bladder pathologies in our study was 43.46 ± 8.337 years. Gall stones were the commonest clinical condition for which laparoscopic cholecystectomy was done. Out of 26 (13%) patients underwent conversion of laparoscopic to open surgery. It was revealed that frozen Calots triangle (p-value-0.033), empyema gall bladder (p-value-0.018) and previous abdominal surgeries (p-value-0.013) were significantly related to conversion of laparoscopic to open surgery Conclusion: Conversion rate of laparoscopic to open surgery for cholecystectomy was high in our study population. Patients who had previous abdominal surgeries or presence of frozen Calots triangle and empyema gall bladder were more at risk of conversion of surgery.

Background: Tuberculosis (TB) is the 10th leading cause of death globally and is leading cause of death from a single infectious disease. The objectives of our study were to determine the distribution of drug sensitive tuberculosis (DS-TB) by sex, age groups and type of disease in DS-TB population of District D.I.Khan, Pakistan. Materials Methods: This cross-sectional study was conducted in Department of Community Medicine, Gomal Medical College, D.I.Khan, Pakistan from January 5, 2021 to January 25, 2021. The data of 3,916 patients was retrieved from District Health Office, D.I.Khan for the period from January 1, 2019 to December 31, 2020. Sex, age groups and type of disease were categorical variables and analyzed by count and percentage with CI at 95%CL. Distribution of DR-TB by sex, age groups and type of disease was analyzed separately by chi-square goodness-of-fit test at alpha .05. Results: Out of 3,916 patients with DS-TB, women 2,110 (53.88%, 95% CI 52.32-55.44) were more than men 1,806 (46.12%, 95%CI 44.55-47.67), with most common age group of 15-44 years 1,948 (49.74%, 95%CI 48.17-51.31), and with more pulmonary 2,877 (73.47%, 95%CI 72.08-74.85%) than extrapulmonary 1,039 (26.53%, 95%CI 25.14-27.91) cases. Our observed prevalence of DS-TB in men was lower 46.12% than expected 51.72% and in women it was higher 53.88% than expected 48.28% (p.00001). Our observed distribution of DS-TB in different age groups was not similar to expected (p.00001). Our observed prevalence of pulmonary TB was lower 73.47% than expected 80.35% and in extrapulmonary TB it was higher 26.53% than expected 19.65% (p.00001). Conclusions: Drug sensitive tuberculosis was more common in women than men in DS-TB population of District D.I.Khan, Pakistan. It was highest in age group 15-44 years and higher for pulmonary TB than extrapulmonary TB. Our observed prevalence in men was lower than expected and in women it was higher than expected. Our observed prevalence for drug sensitive TB in various age groups was different than expected. Our observed prevalence for pulmonary TB was lower than expected and for extrapulmonary TB it was higher than expected.

Objective: To analyse histopathological findings in gastric biopsies of patients with dyspepsia using an updated Sydney System. Study Design: Retrospective longitudinal study. Place and Duration of Study: Histopathology Department, Najran Armed Forces Hospital (NAFH), Saudi Arabia, from Jan 2013 to Mar 2020. Methodology: A total of 408 cases whose gastric biopsies were included in the study, and their histological features were studied. Results: Among 408 patients included in the study, 191(46.8%) were males, and 217(53.2%) were females. The mean age was 37.0±15.0 years. A total of 343 patients showed gastritis, which was mild 152(44.3%), moderate 158(46.1%) and severe 33(9.6%), respectively. The activity was observed in 200(49.0%) patients. H.pylori infection was observed in 196(48.0%) patients and intestinal metaplasia in 9(2.2%) patients. Conclusion: Most of the cases with dyspepsia showed histological evidence of gastritis. However, a significant number of patients had no gastric mucosal abnormality. Therefore, adequate and timely treatment of H.pylori infection can significantly reduce related morbidity.

Background Primary congenital glaucoma (PCG) is the most common subtype of glaucoma caused by defects in the cytochrome P450 1B1 (CYP1B1) gene. It is developing among infants in more than 80% of cases who exhibit impairments in the anterior chamber angle and the trabecular meshwork. Thus, a comprehensive in silico approach was performed to evaluate the effect of high-risk deleterious missense variations in the CYP1B1 gene. Material and methods All the information for CYP1B1 missense variants was retrieved from the dbSNP database. Seven different tools, namely: SIFT, PolyPhen-2, PROVEAN, SNAP2, PANTHER, PhD-SNP, and Predict-SNP, were used for functional annotation, and two packages, which were I-Mutant 2.0 and MUpro, were used to predict the effect of the variants on protein stability. A phylogenetic conservation analysis using deleterious variants was performed by the ConSurf server. The 3D structures of the wild-type and mutants were generated using the I-TASSER tool, and a 50 ns molecular dynamic simulation (MDS) was executed using the GROMACS webserver to determine the stability of mutants compared to the native protein. Co-expression, protein-protein interaction (PPI), gene ontology (GO), and pathway analyses were additionally performed for the CYP1B1 in-depth study. Results All the retrieved data from the dbSNP database was subjected to functional, structural, and phylogenetic analysis. From the conducted analyses, a total of 19 high-risk variants (P52L, G61E, G90R, P118L, E173K, D291G, Y349D, G365W, G365R, R368H, R368C, D374N, N423Y, D430E, P442A, R444Q, F445L, R469W, and C470Y) were screened out that were considered to be deleterious to the CYP1B1 gene. The phylogenetic analysis revealed that the majority of the variants occurred in highly conserved regions. The MD simulation analysis exhibited that all mutants’ average root mean square deviation (RMSD) values were higher compared to the wild-type protein, which could potentially cause CYP1B1 protein dysfunction, leading to the severity of the disease. Moreover, it has been discovered that CYP1A1, VCAN, HSD17B1, HSD17B2, and AKR1C3 are highly co-expressed and interact with CYP1B1. Besides, the CYP1B1 protein is primarily involved in the metabolism of xenobiotics, chemical carcinogenesis, the retinal metabolic process, and steroid hormone biosynthesis pathways, demonstrating its multifaceted and important roles. Discussion This is the first comprehensive study that adds essential information to the ongoing efforts to understand the crucial role of genetic signatures in the development of PCG and will be useful for more targeted gene-disease association studies.

Abstract Due to urbanization and industrialization, there has been an increase in solid waste generation and has become a global concern and leakage of leachate from landfills contaminate the soil and groundwater and hence can have a severe impact on human health. The present study aimed to determine the composition of toxic metals (Cr, Mn, Cu, As) and heavy metals (Cd, Ba, Hg, Pb) in soil and water by an inductively coupled plasma optical emission spectrometer (ICP-OES). To ensure accuracy during the analysis of Cr, Mn, Cu, As, Cd, Ba, Hg, and Pb in real samples, certified reference material (CRM, SRM 2709a) of San Joaquin soil and water (SRM 1640a) were analyzed and results were presented in terms of % recovery studies. The mean concentration of all the metals in soil and water did not exceed the limit set by the European Community (EU), WHO, and US EPA except Cu where the permissible limit defined by the EU is 50–140 mg/kg in soil. The soil is uncontaminated to moderately contaminated with respect to all metals except the Cu and Pb. Among the average daily dose (ADD) of soil, ADD ing and ADD inh for children had the maximum dose for all metals than adults while ADD derm was higher in adults. Hazard quotient (HQ) trend in both adults and children was found in order HQ ing > HQ derm > HQ inh of soil for all metals except Ba which followed HQ ing > HQ inh > HQ derm . Hazard index (HI) values of soil for Cr and Pb in children were 7 and 7.5 times higher than adults respectively. Lifetime cancer risk (LCR) value for Cr by different exposure pathways of soil was 5.361 × 10−4 for children which are at the lower borderline of risk for cancer.

Objective: To find out the correlation between the red blood cell and platelet indices in patients presenting with iron deficiency anemia at a tertiary care hospital of Pakistan. Study Design: Cross-sectional study. Place and Duration of Study: Department of Hematology, Combined Military Hospital Lahore, from Sep 2018 to Mar 2019. Methodology: The patients of age 1-70 years of either gender presenting with IDA were included in the study. The blood sample of patients were sent to laboratory to assess the red blood cell and platelet indices. SPSS-23 was used to analyze data. Results: Two hundred and seven patients fulfilling the inclusion criteria were included in this study. The mean age was 25.6 ±17.8years. Correlation was weak and insignificant between haemoglobin and packed cell volume (r=-0.385**, p

Six heteroleptic Cu(II) carboxylates (1–6) were prepared by reacting 2-chlorophenyl acetic acid (L1), 3-chlorophenyl acetic acid (L2), and substituted pyridine (2-cyanopyridine and 2-chlorocyanopyridine). The solid-state behavior of the complexes was described via vibrational spectroscopy (FT-IR), which revealed that the carboxylate moieties adopted different coordination modes around the Cu(II) center. A paddlewheel dinuclear structure with distorted square pyramidal geometry was elucidated from the crystal data for complexes 2 and 5 with substituted pyridine moieties at the axial positions. The presence of irreversible metal-centered oxidation reduction peaks confirms the electroactive nature of the complexes. A relatively higher binding affinity was observed for the interaction of SS-DNA with complexes 2–6 compared to L1 and L2. The findings of the DNA interaction study indicate an intercalative mode of interaction. The maximum inhibition against acetylcholinesterase enzyme was caused for complex 2 (IC50 = 2 µg/mL) compared to the standard drug Glutamine (IC50 = 2.10 µg/mL) while the maximum inhibition was found for butyrylcholinesterase enzyme by complex 4 (IC50 = 3 µg/mL) compared to the standard drug Glutamine (IC50 = 3.40 µg/mL). The findings of the enzymatic activity suggest that the under study compounds have potential for curing of Alzheimer’s disease. Similarly, complexes 2 and 4 possess the maximum inhibition as revealed from the free radical scavenging activity performed against DPPH and H2O2.

Golden snub-nosed monkeys (Rhinopithecus roxellanae) belong to Class A, the highest level of endangered primate species. Exploring the infection status of potential pathogens in golden snub-nosed monkeys is important for controlling associated diseases and protecting this species. The objective of this study was to investigate the seroprevalence for a number of potential pathogens and the prevalence of fecal adenovirus and rotavirus. A total of 283 fecal samples were collected from 100 golden snub-nosed monkeys in December 2014, June 2015, and January 2016; 26 blood samples were collected from 26 monkeys in June 2014, June 2015, January 2016 and November 2016 at Shennongjia National Reserve in Hubei, China. The infection of 11 potential viral diseases was examined serologically using an Indirect Enzyme-linked Immunosorbent Assay (iELISA) and Dot Immunobinding Assays (DIA), while the whole blood IFN-γ in vitro release assay was used to test tuberculosis (TB). In addition, fecal Adenovirus and Rotavirus were detected using Polymerase Chain Reaction (PCR). As a result, the Macacine herpesvirus-1 (MaHV-1), Golden snub-nosed monkey cytomegalovirus (GsmCMV), Simian foamy virus (SFV) and Hepatitis A virus (HAV) were detected with the seroprevalence of 57.7% (95% CI: 36.9, 76.6), 38.5% (95% CI: 20.2, 59.4), 26.9% (95% CI: 11.6, 47.8), and 7.7% (95% CI: 0.0, 84.2), respectively. Two fecal samples tested positive for Adenovirus (ADV) by PCR, with a prevalence of 0.7% (95% CI: 0.2, 2.5), and further, the amplification products were sequenced. Phylogenetic analysis revealed that they belonged to the HADV-G group. However, other pathogens, such as Coxsackievirus (CV), Measles virus (MeV), Rotavirus (RV), Simian immunodeficiency virus (SIV), Simian type D retroviruses (SRV), Simian-T-cell lymphotropic virus type 1 (STLV-1), Simian varicella virus (SVV), Simian virus 40 (SV40) and Mycobacterium tuberculosis complex (TB) were negative in all samples. In addition, a risk factor analysis indicated that the seroprevalence of MaHV-1 infection was significantly associated with old age (≥4 years). These results have important implications for understanding the health status and conservation of the endangered golden snub-nosed monkey population at Shennongjia Nature Reserve.

Objective: To share experience of 1000 patients who underwent functional endoscopic sinus surgery (FESS) in 4 different hospitals for various diseases over span of 9 years. Study Design: Prospective observational study. Place and Duration of Study: Sheikh Khalifa Hospital Muzaffarabad, Combined Military Hospital Sialkot, Pak Emirates Military Hospital Rawalpindi and CMH Quetta, from Jun 2009 to Jun 2018. Methodology: We included 1000 patients who underwent Functional endoscopic sinus surgery (FESS) in four different military hospitals, suffering with various diseases discussed later. Patients were operated after failure to get response to medical therapy. All the patients had preoperative endoscopic examination and CT-scan paranasal sinuses (PNS) done for disease assessment. Patients were examined post operatively at 1, 15 days and 2 months. All patients were documented for the level of satisfaction at end of 2 months post-operative period. Results: Most patients were suffering from rhino sinusitis 364 (36.4%). Bilateral ethmoidal polyps constituted the second largest group at 289 (28.9%) patients. About 837 (83.7%) of patients were completely free of symptom, 104 (10.4%) with partial improvement whereas, 59 (5.9%) patients did not report any improvement in symptoms. 899 (89.9%) of patients were discharged on their first post operation day meaning less hospital stay and quick recovery. Conclusion: Functional endoscopic sinus surgery (FESS) can be employed to treatment variety of common nasal diseases (chronic rhino-sinusitis, nasal polyps) & non-nasal diseases like cerebrospinal fluid (CSF) rhinorrhea & as approach to skull base. This method of treatment was quite effective in alleviating symptoms of patients.

Abstract Background The Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) outbreak originating in Wuhan, China, has raised global health concerns and the pandemic has now been reported on all inhabited continents. Hitherto, no antiviral drug is available to combat this viral outbreak. Methods Keeping in mind the urgency of the situation, the current study was designed to devise new strategies for drug discovery and/or repositioning against SARS-CoV-2. In the current study, RNA-dependent RNA polymerase (RdRp), which regulates viral replication, is proposed as a potential therapeutic target to inhibit viral infection. Results Evolutionary studies of whole-genome sequences of SARS-CoV-2 represent high similarity (> 90%) with other SARS viruses. Targeting the RdRp active sites, ASP760 and ASP761, by antiviral drugs could be a potential therapeutic option for inhibition of coronavirus RdRp, and thus viral replication. Target-based virtual screening and molecular docking results show that the antiviral Galidesivir and its structurally similar compounds have shown promise against SARS-CoV-2. Conclusions The anti-polymerase drugs predicted here—CID123624208 and CID11687749—may be considered for in vitro and in vivo clinical trials.

The recent advances in nanoscience and nanotechnology have enhanced the synthesis of various forms of nanomaterials for practical applications. Undoubtedly, these nanomaterials are not without attendant toxicities to humans, environment, and other organisms. Moreover, the toxicity of nanomaterials dominates the landscape of current toxicity concerns highlighted by the FDA. Titanium dioxide nanoparticles (TiO2 NPs) contribute a large proportion of synthesized nanomaterials mainly due to their excellent photocatalytic activities, mechanical and chemical stability, bio- and chemical inertness, corrosion resistance, thin film transparency, and low production cost. These fascinating properties of TiO2 NPs have been extensively exploited and dramatically increased their utility for various applications such as in nanomedicine for cancer theranostics, nanobiotechnology, environment, pharmacy, energy, food, cosmetics, and paper industries. Owing to the poor understanding of the impacts of NPs on humans, no clear regulation has been implemented for NPs among international authorities. Over time, the toxicity state of TiO2 NPs is typical of a double-edged sword. Hitherto, there is no restriction on the use of TiO2 NPs irrespective of the toxicity concerns raised by some researchers. This may have been dampened by the low-to-no toxicity reports from other researchers on these NPs. This review therefore looks into the recent toxicity reports from various studies conducted with/on TiO2 NPs as to ascertain their present-day safety. To elucidate this, we discussed the possible exposure routes to these NPs and their effects on the environment, plants, soil organisms, and aquatic species. We also provided insights on the toxicity mechanisms of TiO2 NPs and proposed future perspectives for improving their safe applications.

Abstract Objective Antenatal stress is highly prevalent globally and is associated with adverse physical and psychiatric morbidities and adverse neonatal outcomes. However, the burden of antenatal stress and its psychosocial predicators have not been explored in context of the Pakistani sociocultural environment. The present study explores the prevalence of antenatal stress and its association with gender of offspring, socioeconomic background, cultural beliefs, and access to healthcare in the province of Punjab, Pakistan. Results There was a total of 516 pregnant women. Antenatal stress was measured by the Perceived Stress Scale (PSS). The mean score of the respondents on the Perceived Stress Scale was 7.55 (3.43). A total of 218 (42.2%) respondents reported higher stress levels. Logistic regression analysis (backward method) yielded a significant model predicting high stress levels. According to it, low family income, unplanned pregnancy, increasing number of children, less autonomy in decision making, marital problems, harassment, desire to have a male offspring, and the history of birth complications, attended by midwives were associated with high stress levels.

[This corrects the article DOI: 10.1371/journal.pone.0247249.].

Emergence of multidrug resistant pathogens is increasing globally at an alarming rate with a need to discover novel and effective methods to cope infections due to these pathogens. Green nanoparticles have gained attention to be used as efficient therapeutic agents because of their safety and reliability. In the present study, we prepared zinc oxide nanoparticles (ZnO NPs) from aqueous leaf extract of Acacia arabica. The nanoparticles produced were characterized through UV-Visible spectroscopy, scanning electron microscopy, and X-ray diffraction. In vitro antibacterial susceptibility testing against foodborne pathogens was done by agar well diffusion, growth kinetics and broth microdilution assays. Effect of ZnO NPs on biofilm formation (both qualitatively and quantitatively) and exopolysaccharide (EPS) production was also determined. Antioxidant potential of green synthesized nanoparticles was detected by DPPH radical scavenging assay. The cytotoxicity studies of nanoparticles were also performed against HeLa cell lines. The results revealed that diameter of zones of inhibition against foodborne pathogens was found to be 16–30 nm, whereas the values of MIC and MBC ranged between 31.25–62.5 μg/ml. Growth kinetics revealed nanoparticles bactericidal potential after 3 hours incubation at 2 × MIC for E. coli while for S. aureus and S. enterica reached after 2 hours of incubation at 2 × MIC, 4 × MIC, and 8 × MIC. 32.5–71.0% inhibition was observed for biofilm formation. Almost 50.6–65.1% (wet weight) and 44.6–57.8% (dry weight) of EPS production was decreased after treatment with sub-inhibitory concentrations of nanoparticles. Radical scavenging potential of nanoparticles increased in a dose dependent manner and value ranged from 19.25 to 73.15%. Whereas cytotoxicity studies revealed non-toxic nature of nanoparticles at the concentrations tested. The present study suggests that green synthesized ZnO NPs can substitute chemical drugs against antibiotic resistant foodborne pathogens.

The COVID-19 pandemic has led to mortality and morbidity since December 2019. Many possible treatment options have been advised till date. The role of ivermectin in the treatment of COVID-19 disease remains controversial. The aim of our study was to evaluate the effect of ivermectin in hospitalized patients with non-severe and severe COVID-19 disease. We conducted a retrospective cohort study that compared outcomes in 2 groups of COVID-19 patients hospitalized at the largest tertiary care center of Pakistan. The study group was given ivermectin along with standard treatment of covid-19 disease; the comparison group was not. Data on mortality, inflammatory markers such as C-reactive protein (CRP) and ferritin, length of hospital stay and baseline characteristics were collected from Aga Khan University’s database from October 2020 till February 2021. Statistical analysis was done to determine the effectiveness of ivermectin in non-severe and severe COVID-19. Comparison of effectiveness of Ivermectin in both the genders was also conducted. The cohort included 188 patients out of which 90 were treated with ivermectin. Mortality and length of hospitalization was not found to be significantly different in the study group compared with the control group (5.6% vs 5.1%; p=0.87 and 5 days vs 4 days; p=0.27). Analysis of secondary outcomes did not yield statistically significant results, apart from ferritin levels which were significantly less in patients treated with ivermectin (547.1 vs 756.7; p=0.03). The ferritin and CRP levels in affected males were higher than in females on admission and discharge. Our findings suggest ivermectin does not significantly affect all-cause mortality, length of hospitalization and CRP levels in hospitalized COVID-19 patients. Large scale randomized controlled trials (RCTs) are required to further evaluate the role of ivermectin in covid-19 disease.

Hearing impairment (HI) is a heterogeneous condition that affects many individuals globally with different age groups. HI is a genetically and phenotypically heterogeneous disorder. Over the last several years, many genes/loci causing rare autosomal recessive and dominant forms of hearing impairments have been identified, involved in various aspects of ear development. In the current study, two affected individuals of a consanguineous family exhibiting autosomal recessive nonsyndromic hearing impairment (AR-NSHI) were clinically and genetically characterized. The single affected individual (IV-2) of the family was subjected to whole-exome sequencing (WES) accompanied by traditional Sanger sequencing. Clinical examinations using air conduction audiograms of both the affected individuals showed profound hearing loss across all frequencies. WES revealed a homozygous missense variant (c.44G>C) in the SIX5 gene located on chromosome 19q13.32. We report the first case of autosomal recessive NSHI due to a biallelic missense variant in the SIX5 gene. This report further supports the evidence that the SIX5 variant might cause profound HI and supports its vital role in auditory function. Identification of novel candidate genes might help in application of future gene therapy strategies that may be implemented for NSHI, such as gene replacement using cDNA, gene silencing using RNA interference, and gene editing using the CRISPR/Cas9 system.

Background: Outbreaks of small ruminant morbillivirus (SRMV) are regularly occurring in Pakistan despite vaccine availability. This study was designed to identify substitutions within the immunogenic structural and functional regions of the nucleocapsid, fusion, and hemagglutinin genes of SRMV and their comparison with vaccinal strains of Nigerian and Indian origin. Methods: Swabs and tissue samples were collected from diseased animals. RT-PCR was used to characterize selected genes encoded by viral RNA. The study’s N, F, and H protein sequences and vaccinal strains were analyzed for B and T cell epitope prediction using ABCpred, Bipred, and IEDB, respectively. Results: Significant substitutions were found on the C terminus of the nucleocapsid, within the fusion motif region of the fusion gene and in the immunoreactive region of the hemagglutinin gene. Conclusion: Our results emphasize the need for the development of effective vaccines that match the existing variants of SRMV strains circulating in Pakistan.

Terpenes are a group of natural products made up of molecules with the formula (C5H8)n that are typically found in plants. They are widely employed in the medicinal, flavor, and fragrance industries. The total synthesis of terpenes as well as their origin and biological potential are discussed in this review.

Treating tuberculosis (TB) is not the end of the disease because of the wide spectrum of post TB sequelae associated with the disease. There is insufficient data on post TB radiological sequelae. The aim of this study is to evaluate the post TB radiological sequelae on chest x-rays in patients who had completed the treatment for pulmonary and pleural TB at a tertiary care hospital of a high TB burden country. This is a retrospective cross-sectional study conducted on patients treated for pulmonary and pleural TB. Adult patients (18 years or above) with a clinical or microbiological diagnosis of pulmonary or pleural TB were included. Patients were classified on the basis of site of TB into pulmonary and pleural TB. Post-treatment radiological sequelae on chest x-ray were evaluated and divided into three main types i.e. fibrosis, bronchiectasis and pleural thickening. During the study period a total of 321 patients were included with a mean age of 44(SD±19) years. Only 17.13% (n=55) patients had normal chest x-rays at the end of treatment and 82.87% (n=266) patients had post-TB radiological sequelae with fibrosis being the most common followed by pleural thickening. The post TB radiological sequelae were high in patients who had diabetes mellitus (78.94%), AFB smear-positive (90.19%), AFB culture-positive (89.84%), Xpert MTB/Rif positive (88.40%) and with drug-resistant TB (100%). As a clinician, one should be aware of all the post TB sequelae so that early diagnosis and management can be facilitated.