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Abstract Background This study delves into the complex interplay among prostate-specific antigen, alkaline phosphatase, and the temporal dynamics of tumor shrinkage in prostate cancer. By investigating the longitudinal trajectories and time-to-prostate cancer tumor shrinkage, we aim to untangle the intricate patterns of these biomarkers. This understanding is pivotal for gaining profound insights into the multifaceted aspects of prostate cancer progression. The joint model approach serves as a comprehensive framework, facilitating the elucidation of intricate interactions among these pivotal elements within the context of prostate cancer . Methods A new joint model under a shared parameters strategy is proposed for mixed bivariate longitudinal biomarkers and event time data, for obtaining accurate estimates in the presence of missing covariate data. The primary innovation of our model resides in its effective management of covariates with missing observations. Built upon established frameworks, our joint model extends its capabilities by integrating mixed longitudinal responses and accounting for missingness in covariates, thus confronting this particular challenge. We posit that these enhancements bolster the model’s utility and dependability in real-world contexts characterized by prevalent missing data. The main objective of this research is to provide a model-based approach to get full information from prostate cancer data collected with patients’ baseline characteristics ( $$Age$$ Age , body mass index ( $$BMI$$ BMI ), $$Gleason Score$$ GleasonScore , $$Grade$$ Grade , and $$Drug$$ Drug ) and two longitudinal endogenous covariates ( $$Platelets$$ Platelets and $$Bilirubin$$ Bilirubin ). Results The results reveal a clear association between prostate-specific antigen and alkaline phosphatase biomarkers in the context of time-to-prostate cancer tumor shrinkage. This underscores the interconnected dynamics of these key indicators in gauging disease progression. Conclusions The analysis of the prostate cancer dataset, incorporating a joint evaluation of mixed longitudinal prostate-specific antigen and alkaline phosphatase biomarkers alongside tumor status, has provided valuable insights into disease progression. The results demonstrate the effectiveness of the proposed joint model, as evidenced by accurate estimates. The shared variables associated with both longitudinal biomarkers and event times consistently deviate from zero, highlighting the robustness and reliability of the model in capturing the complex dynamics of prostate cancer progression. This approach holds promise for enhancing our understanding and predictive capabilities in the clinical assessment of prostate cancer.

Aim: To estimate the working length of teeth using conventional tactile technique, radiovisiography technique, Apex locator, and confirmation of working length by cone beam computed tomography technique. Materials and Methods: Forty patients with the age group between 20 and 50 years with irreversible pulpitis were included in this study. After taking a preoperative radiograph, the procedure was started. The cavity wall buildup was done using composite in the cases needed and then rubber dam application was done. The working length of mesiobuccal and mesiolingual canal was taken using cone beam computed tomography and this was considered as the standard value. Then using tactile method, length of the canal was measured using radiovisiographic software followed by apexlocator. Result: The Apex locator has showed best result as compared to tactile and radiovisiography. Conclusion: Apex locator values were closest to cone beam computed tomography working length measurement values and electronic apexlocator can be used efficiently as an alternative method for working length determination. The quality of various techniques according to ranks of working length determination was found to be Cone beam computed tomography (CBCT) > Apexloc > Radiovisiography (RVG) > Tactile. Thus, Apex locator can be used as an alternative to cone beam computed tomography for working length determination.

Background: Artificial intelligence (AI) implies a machine’s overall capacity to carry out tasks that require human intelligence. AI’s active role in medical and dental practices has resulted in the advancement of patient care systems with enhancement in the healthcare industry. This research aimed to assess dental students’ awareness and perception of the use of AI and its potential application in the prospects of dentistry. Methods: This cross-sectional, survey-based research was carried out using an electronic questionnaire at Altamash Institute of Dental Medicine Karachi, from July to August 2022. With convenience sampling, a total of 160 students were selected, questionnaire was divided into three sections demographic details, general awareness, and perception of students for AI. They were directed to rate their responses for each statement on a 5-point Likert scale. Using SPSS version 26, the data was evaluated for descriptive and inferential statistics. Results: The majority of the students 128 (80%), were aware of AI, with about 105 (65.6%) of them recognizing its use in dentistry. The mean of responses for awareness (1.86) and perception (2.01) sections falls in the range of “agree” (1.81-2.60) to the statements. There was no significant difference present regarding gender and all four years of BDS education for the concept and utilization of AI. Conclusion: Dental students are well aware of the advantages and utilization of AI tools in dentistry, with a strong perception that some aspect of AI should be added to the undergraduate dental curriculum and clinical training.

AbstractAcceptance sampling plans are commonly utilized for planning, process control, and implementation of industrial data sets. In addition to this, they also provide a solution for process quality control. They could be used for executing a decision for acceptance or rejection of a lot. A good acceptance sampling plan can be formulated depending on the requirements of the project. Usually, the plan should follow a defined lifetime distribution. Hence, the appropriate plan would not only determine the plan parameters but would also be cost and time efficient. In this article, an attribute multiple dependent repetitive group sampling (MDRGS) plan is developed assuming that the lifetime of the product follows the Marshall-Olkin logistic-exponential (MOLE) distribution. The parameters of plan are examined by considering a two-point approach. The suggested plan is contrasted with the single sampling and repeated group sampling plans. Finally, the implementation of the proposed plan is discussed using industrial as well as simulated data sets. It is concluded that the proposed plan reduces the sampling inspection cost and time as compared to existing acceptance sampling plans.

Abstract This study focuses on the issue of lots resubmission in inspection processes, which often arises when the initial inspection of a lot is suspected, marked as held, or not accepted. To address this problem, a novel variables sampling plan based on the coefficient of variation is proposed. The objective is to determine the sampling plan parameters that minimize the average sample number while satisfying the two-points of operating characteristic curve. Practical considerations are taken into account by providing tabulated values for the inspection sample size and acceptance criteria of the proposed plan. These tables incorporate various combinations of quality levels, considering commonly used producer's risk and consumer's risk. Furthermore, a comparative analysis between the proposed plan and a single sampling plan is conducted to highlight the advantages of the new approach. To illustrate the practical implementation of the proposed plan, an example is presented.

It is well-known that smoking tobacco harms the respiratory system and can lead to various health problems. Regarding COVID-19, a respiratory illness caused by the novel coronavirus SARS-CoV-2, smoking may have implications for both the risk of infection and the severity of the disease. Several studies have explored the association between smoking and COVID-19. However, findings have been somewhat inconsistent and vary from region to region for sample size. This article aims to study the prevalence of COVID-19 among those affected with their ongoing smoking history by computing pooled estimates of the published research. Fixed effect meta-analysis by following the guidelines of PRISMA has been carried out on 34 studies. The patients with confirmed RT-PCR and CT-scan were included, a total of 13,368; The studies' quality assessment was performed according to the Appraisal Checklist recommended by the Joanna Briggs Institute. The effect sizes of the published research are presented in the form of pooled estimates with their respective confidence intervals. Forest plots are used to represent the effect size graphically. Current smokers' effect sizes are 0.12 (CI = 0.11–0.12); for non-smokers, it is estimated to be 0.88 (CI = 0.88–0.89). The heterogeneity statistic I2 describes 0% of the total variation, meaning no heterogeneity among studies exists. A higher prevalence of COVID-19 among non-smokers is observed than the smokers.

In this study, we solved the Schrödinger wave equation by using effective potential in an artificial neural network (ANN) for the mass spectrum of different charmonium states, including ηc, ψ2, χ2, and χ4. The ANN approach provides an efficient, more general, and continuous solution-approximating strategy, thus eliminating the possibility of skipping any region of interest in mass spectroscopy. The close consistency of ANN results with the already-reported results from numerical and theoretical approaches and experimental ones shows the reliability and accuracy of the ANN approach.

AbstractRural poverty is often discussed in combination with spatial inequality where rural poor face worse problems with diverse remedies in comparison to urban poor. The present study aims to find out area-level effects and possible determinants of rural poverty based on data from the Rural Household Panel Survey of Pakistan Round-1 (2012). The multilevel binary logistic model is used to integrate concurrent individual and district-level variables to explore area-level effects on poverty. A two-level multilevel model is used for the analysis of the poverty status of 4804 respondents nested in 19 districts. Individual-level variables included in the model are education, socioeconomic status, and spending behaviour. It is found that approximately 60% of individuals of the overall population were found poor, and district-level effect accounts for 7% variations in poverty. A particularly significant ratio of poor is found for people who attained deeni madrassa/religious education or no education at all. Poverty existence is significantly associated with spending behavior and socioeconomic status. The persons with relatively middle/high socioeconomic status and successful educational achievement but a lacking attitude toward spending money are considered poor.

Abstract In Statistical Process Control, many techniques exist for monitoring the stability of a process over time. In this work, we study the relationship of the response variable with explanatory variables in the form of linear profiles for detecting changes in slope and intercept of the linear quality profiles. We used the transformation of explanatory variables approach used for make the regression estimates independent of each other to have zero average. A comparative study of three phase-II methods using DEWMA statistics in monitoring and capturing undesirable deviations in the slope, intercept, and variability is also studied by applying different proposed run rules schemes i.e., R1/1, R2/3, R3/3. Monte Carlo simulations were carried out on R-Software for finding the results of proposed schemes by taking various levels of shifts for intercept, slope, and standard deviation in identifying the false alarm rate of a process. The simulation results based on the average run length criterion show that the proposed run rule schemes improve the detection ability of the control structure. Among all the proposed schemes R2/3 is found to be the best one because of its quick detection ability of false alarm rate. The proposed scheme also shows superiority in comparison to other schemes. The simulation results are further justified with a real data application.

Abstract Background It is currently under discussion whether Learner Handovers (LH) are beneficial, disadvantageous, or useful in Health Professions Education. Research has not been conducted to determine the extent of existing informal learner handover (ILH) through faculty discussions. In addition to providing stakeholders with added context, examining the nature of ILH may also provide insight into the bias associated with Learner Handover. Methods Transcripts from a series of semi-structured Focus Group Discussions (FGDs) and interviews (from January to March 2022) were iteratively reviewed to identify relevant patterns and correlations. The study involved the voluntary participation of 16 active clinical dental faculty members with a variety of designations. We did not discard any opinions. Results It was found that ILH had a mild impact on students' training. ILH effects can be categorized into four key areas: (1) faculty behavior with students, (2) faculty expectations from students, 3) teaching approach, and 4) faculty feedback practices. Furthermore, five additional factors were identified as having a greater influence on ILH practices. Conclusions In clinical dental training, ILH has a minor effect on faculty-student interactions. Faculty perceptions and ILH are strongly influenced by other factors contributing to the student's 'academic reputation. As a result, student-faculty interactions are never free of prior influences, so stakeholders need to take them into consideration when creating a formal LH.

Abstract Marshall Olkin Exponentiated Dagum distribution (MOED) with four shape parameters and one scale parameter is proposed. Alternative expressions are derived for the newly proposed distribution to sort out lengthy calculations. Various properties of MOED are derived, including the measure of central tendency, the measure of dispersion, hazard rate and survival rate are also derived for the MOED. Moreover, the network properties are also derived, including moments, moment generating function, quantile function, median, and mean deviation random number generator. Estimation of parameters is done through MLE (Maximum likelihood estimation) method, and to assess the value of the proposed distribution, the performance of the parameter’s estimates is studied through Monte Carlo Simulation. Three real-life data sets are used to evaluate the application and to scrutinize the performance of MOED as compared to the Marshall Olkin Dagum (MOD) distribution, Exponentiated Dagum (ED) distribution, Dagum (D) distribution, Burr III distribution, Kumaraswamy Burr III (KBurr III) distribution, Kumaraswamy Log Logistic (KLL) distribution and Log Logistic (LL) distribution. Four information criteria are used to examine the performance of the MOED with other special cases. The results showed that the newly proposed distribution performs better than the compared distributions.

This research work appertains to the acceptance sampling plan under the neutrosophic statistical interval method (ASP-NSIM) based on gamma distribution (GD), Burr type XII distribution (BXIID) and the Birnbaum-Saunders distribution (BSD). The plan parameters will be determined using the neutrosophic non-linear optimization problem. We will provide numerous tables for the three distributions using various values of shape parameters and degree of indeterminacy. The efficiency of the proposed ASP-NSIM will be discussed over the existing sampling plan in terms of sample size. The application of the proposed ASP-NSIM will be given with the aid of industrial data.

Objectives: To identify the use of different emotion regulation strategies by medical trainees, and to determine the frequency and the predominant pattern of emotional response in emotion-triggering situations. Method: The descriptive cross-sectional study was conducted at 2 public and 1 private medical college in Lahore, Pakistan, from March to September 2019, and comprised postgraduate medical trainees of either gender from all clinical disciplines from years 1-4. Data was collected using a questionnaire based on the Gross theory of emotional regulation and the Situational model of emotion. Emotion regulation strategies included situation selection, situation modification, cognitive change, attention deployment, and response modulation. Data was analysed using SPSS 25. Results: Of the 377 trainees approached, 308(81.69%) participated; 206(67%) females and 102(33%) males. The overall mean age was 27.8+2.91 years. The majority of the trainees were from the Obstetrics and Gynaecology department 133(43.2%) and were in the first year of their training 116(37.7%). The most frequent emotion-triggering situation identified was prolonged working hours 292(95%), and the major emotional response was quietness in 5 out of ten situations (50%). The trainees used greater emotion regulation strategies in sad situations 3.49±1.79 (p

Introduction: There is a steady increase in colorectal cancer (CRC) incidences worldwide; at diagnosis, about 20 percent of cases show metastases. The transforming growth factor-beta (TGF-β) signaling pathway is one of the critical pathways that influence the expression of cadherins allowing the epithelial-to-mesenchymal transition (EMT), which is involved in the progression of the normal colorectal epithelium to adenoma and metastatic carcinoma. The current study aimed to investigate the impact of a novel coordination complex of platinum (salicylaldiminato) PT(II) complex with dimethyl propylene linkage (PT-complex) on TGF-β and EMT markers involved in the invasion and migration of the human HT-29 and SW620 CRC cell lines.Methods: Functional study and wound healing assay showed PT-complex significantly reduced cell motility and the migration and invasion of CRC cell lines compared to the untreated control. Western blot performed in the presence and absence of TGF-β demonstrated that PT-complex significantly regulated the TGF-β-mediated altered expressions of EMT markers.Results and Discussion: PT-complex attenuated the migration and invasion by upregulating the protein expression of EMT-suppressing factor E-cadherin and suppressing EMT-inducing factors such as N-Cadherin and Vimentin. Moreover, PT-complex significantly suppressed the activation of SMAD3 in both CRC cell lines. Further, the microarray data analysis revealed differential expression of genes related to invasion and migration. In conclusion, besides displaying antiproliferative activity, the PT complex can decrease the metastasis of CRC cell lines by modulating TGF-β-regulated EMT markers. These findings provide new insight into TGF-β/SMAD signaling as the molecular mechanism involved in the antitumoral properties of novel PT-complex.

Aim: Evaluation of the efficacy of different obturating techniques and assessment of the presence of voids in different regions of the canal. Materials and Methods: Sixty permanent single-rooted teeth with complete, mature root apices without any anatomic variation having straight patent root canals were included in the present study. Access cavity preparation followed by biomechanical preparation was done. Samples were divided into three groups—Group A: Single cone obturation, Group B: GuttaFlow 2, and Group C: GuttaCore, and obturation was carried out. The samples after obturation were stored at 370°C and 100% humidity in an incubator for 7 days to give adequate time for obturating materials to set. Cone beam computed tomography was performed with i-cat Cb 500 machine. The voids were checked on the root canal wall. The statistical analysis was done and the data after the statistical analysis was presented. Result: GuttaCore obturators presented a lesser volume of voids followed by GuttaFlow 2 than the single cone techniques. Conclusion: All the obturation techniques presented an inadequacy of obturation when the pre- and post-obturated volume of the root canal space was calculated. However, no statistically significant obturated volume differences were found between single cone and GuttaFlow 2 or between GuttaFlow 2 and GuttaCore system.

Ninety-five amateur cricketers of age, 15-35 years with confirmed acute or chronic ankle sprain, selected from four different cities of the Punjab, Pakistan were evaluated through Star Excursion Balance Test (SEBT), Single Leg Balance test (SLB) and subject to a set of progressively increasing exercises on ground and in water as well known as MixedBag rehab exercises which consisted of Hydro, Isometric, Isotonic and proprioception protocols. Another group of same level cricketer (n = 40) served as control. Comparisons of pre and post-exercise values showed significant increase (p < 0.001) in Lateral direction reach and Posteromedial direction while the rest of the six directions showed non-significant results. MixedBag Rehab Group showed an overall improvement of 14.3 % and 9.2 % with an increase (cm) of 9.6 and 6.3 for the non-injured and injured leg respectively. However, the range of improvement in percentage for all eight directions lies between 5.5-6.3 and 7.7-11.8 for the non-injured and injured leg, respectively. Similarly, the difference between pre and post-exercise difference of two positions of non-injured leg and injured leg in seconds were 2.9, 12.1 and 4.1, 27.7. The results indicated that MixedBag exercises improved isometric and isotonic muscular strength, proprioception and stability that ultimately helped to recover, regaining strength and reinstall proprioception. After completing the MixedBag Rehab plan, the subjects were followed for four months to check the recurrence and it was found that the recurrence of Control Injured Group and MixedBag Rehab Group was 17.5 % and 7.5 %, respectively.

Abstract Background Operating Room (OR) is a high-pressure setting where multiple complex surgical, educational, and administrative facets interplay. Contrary to resident training, the dynamics of undergraduate medical students’ learning process is highly demanding, opportunistic, unstandardized, and suboptimal owing to many reasons. Upon reviewing the existing published literature regarding the medical students’ experience in the OR setting, it was clear that this field is still to date, unstructured, and ambiguous, with many grey areas that need to be worked on. To achieve an optimized and enhanced theatre experience, it is of immense importance to recognize the recurrent themes affecting medical students within this setting and deduce ways to overcome these challenges. This study explores and prioritizes factors influencing OR-based student learning quality and develops guidelines for structured clinical encounters within the OR setting. Methods The study involved an extensive literature review and thematic analysis to generate themes and subthemes, which were subjected to a modified Delphi technique where students and teachers participated to identify, debate, and produce a consensus on the relative value of these factors. Finally, expert-validated guidelines were developed for OR curricular designs. Results Operating theater-based student learning is multifactorial. Structured learning through optimized course planning, content selection, assessment, and administration are decisive in determining the quality of OR learning experience. The teacher’s interest, attitude, and students’ desire and preparedness to learn play a central role in OR-based student learning, suggesting an enhanced need for adequate faculty training. Similarly, emotional, socio-environmental, and organizational factors can influence students’ learning in a significant way. A new model for undergraduate student learning in OR has been proposed based on these factors and the stakeholders’ interplay. In this model, the teacher’s role is responsible despite OR learning being student- led. Guidelines for the OR curricular designs have been developed. Conclusion Structured learning process within the OR setting can lead to optimized lesson planning, content selection, assessment, and administration for a more meaningful and enriched OR learning experience.

Thiosemicarbazones have received noteworthy attention due to their numerous pharmacological activities. Various thiosemicarbazone derivatives have been reported to play a key role as potential chemotherapeutic agents for the management of cancer. Herein, we aimed to establish the anticancer efficacy of novel thiosemicarbazone derivative C4 against colon cancer in vitro. The MTT viability assay identified C4 as a promising anticancer compound in a panel of cancer cell lines with the most potent activity against colon cancer cells. Further, anticancer potential of C4 was evaluated against HT-29 and SW620 colon cancer cell lines considering the factors like cell adhesion and migration, oxidative stress, cell cycle arrest, and apoptosis. Our results showed that C4 significantly inhibited the migration and adhesion of colon cancer cells. C4 significantly increased the intracellular reactive oxygen species (ROS) and induced apoptotic cell death. Cell cycle analysis revealed that C4 interfered in the cell cycle distribution and arrested the cells at the G2/M phase of the cell cycle. Consistent with these results C4 also down-regulated the Bcl-XL and Bcl-2 and up-regulated the caspase-3 expression. These findings introduced C4 as the potential anticancer agent against colon cancer.

Background The MUC1-C protein evolved in mammals to protect barrier tissues from loss of homeostasis; however, MUC1-C promotes oncogenesis in association with chronic inflammation. Aberrant expression of MUC1-C in cancers has been linked to depletion and dysfunction of T cells in the tumor microenvironment. In contrast, there is no known involvement of MUC1-C in the regulation of natural killer (NK) cell function.Methods Targeting MUC1-C genetically and pharmacologically in cancer cells was performed to assess effects on intracellular and cell surface expression of the MHC class I chain-related polypeptide A (MICA) and MICB ligands. The MICA/B promoters were analyzed for H3K27 and DNA methylation. Shedding of MICA/B was determined by ELISA. MUC1-C interactions with ERp5 and RAB27A were assessed by coimmunoprecipitation and direct binding studies. Exosomes were isolated for analysis of secretion. Purified NK cells were assayed for killing of cancer cell targets.Results Our studies demonstrate that MUC1-C represses expression of the MICA and MICB ligands that activate the NK group 2D receptor. We show that the inflammatory MUC1-C→NF-κB pathway drives enhancer of zeste homolog 2-mediated and DNMT-mediated methylation of the MICA and MICB promoter regions. Targeting MUC1-C genetically and pharmacologically with the GO-203 inhibitor induced intracellular and cell surface MICA/B expression but not MICA/B cleavage. Mechanistically, MUC1-C regulates the ERp5 thiol oxidoreductase that is necessary for MICA/B protease digestion and shedding. In addition, MUC1-C interacts with the RAB27A protein, which is required for exosome formation and secretion. As a result, targeting MUC1-C markedly inhibited secretion of exosomes expressing MICA/B. In concert with these results, we show that targeting MUC1-C promotes NK cell-mediated killing.Conclusions These findings uncover pleotropic mechanisms by which MUC1-C confers evasion of cancer cells to NK cell recognition and destruction.

Quality control (QC) is a systematic approach to ensuring that products and services meet customer requirements. It is an essential part of manufacturing and industry, as it helps to improve product quality, customer satisfaction, and profitability. Quality practitioners generally apply control charts to monitor the industrial process, among many other statistical process control tools, and to detect changes. New developments in control charting schemes for high-quality monitoring are the need of the hour. In this paper, we have enhanced the performance of the mixed homogeneously weighted moving average (HWMA)-cumulative sum (CUSUM) control chart by using the auxiliary information-based (AIB) regression estimator and named it MHCAIB. The proposed MHCAIB chart provided an unbiased and more efficient estimator of the process location. The various measures of the run length are used to judge the performance of the proposed MHCAIB and to compare it with existing AIB charts like CUSUMAIB, EWMAAIB, MECAIB (mixed AIB EWMA-CUSUM), and HWMAAIB. The Run length (RL) based performance comparisons indicate that the MHCAIB chart performs relatively better in monitoring small to moderate shifts over its competitor's charts. It is shown that the chart's performance improves with the increase in correlation between the study variable and the auxiliary variable. An illustrative application of the proposed MHCAIB chart is also provided to show its implementation in practical situations.

Social exchange theory (SET) is one of the most influential theories in social sciences, which has implications across various fields. Despite its usefulness being a typical social transaction, there is a need to look at it from the lens of psychological transactions to further its evolution and to identify future directions. After generally reviewing 3,649 articles from the Social Science Citation Index and Scopus, a total of 46 articles were selected for final review using a comprehensive systematic review approach. We have highlighted the need for further research in psychological transactions, reciprocity principles, exchange relations, and the impact of various factors on the exchange process. Among other exchange rules (social, economic, and psychological) and transactions (social, economic, and psychological), this research provides an elevation platform for the less explored exchange rules in psychological transactions. Among other theories in the social sciences, social exchange theory is a theory that shadows many other theories under its umbrella.

Objective: To ascertain the immunogenicity and short-term safety of inactivated SARS-CoV-2 Vaccine (Vero Cell), BBIBPCorV (Sinopharm) in our setup. Study Design: Cross-sectional study. Place and Duration of Study: Combined Military Hospital Sialkot Pakistan, from Feb to Apr 2021. Methodology: A total of 227 health care workers (HCWs) between 18 to 59 years of age were included in the study. Two doses of Inactivated SARS-CoV-2 Vaccine (Vero Cell), BBIBP-CorV were administered to all individuals 21 days apart and they were monitored for any vaccine-related adverse reactions for 7 days after each dose. Neutralizing antibodies (NAbs) in study subjects were detected in three samples i.e. before 1st dose of vaccine, 21 days after 1st dose and 14 days after 2nd dose by Elecsys Anti- SARS-CoV-2 S (Roche Diagnostics). Results: Mean age of individuals in the study was 36.70 ± 18.08 years and most individuals were in the 31-45 years age group. Fatigue and drowsiness were the most common adverse effects experienced by study subjects after 1st and 2nd dose of the vaccine followed by malaise and headache. Only 42 (39%) individuals developed positive neutralizing antibody titers in a sample taken 21 days after 1st dose while all individuals except one (99%) developed positive neutralizing antibody titers in a sample taken 2 weeks after 2nd vaccine dose. Conclusion: Inactivated SARS-CoV-2 Vaccine (Vero Cell), BBIBP-CorV is safe and well-tolerated with very few adverse reactions. Immunogenicity was well achieved as the seroconversion rate was 99% two weeks after 2nd dose of the vaccine.

Hypertensive crises is still a major public health problem, causing end organ damage like myocardial infarction, stroke, and renal failure. Labetalol and nitroglycerine are among the two most commonly used medicine to control the blood pressure, but there is no head to head comparison between these two medicines. This was a prospective randomized non-blinded study which included 50 patients of hypertensive crises, out which 25 patients received intravenous labetalol and 25 patients received intravenous nitroglycerine. We found that labetalol controlled the blood pressure more rapidly in comparison to nitroglycerine, without causing any extra side effect.

Abstract Background Kruskal-Wallis H test from the bank of classical statistics tests is a well-known nonparametric alternative to a one-way analysis of variance. The test is extensively used in decision-making problems where one has to compare the equality of several means when the observations are in exact form. The test is helpless when the data is in an interval form and has some indeterminacy. Methods The interval-valued data often contain uncertainty and imprecision and often arise from situations that contain vagueness and ambiguity. In this research, a modified form of the Kruskal-Wallis H test has been proposed for indeterminacy data. A comprehensive theoretical methodology with an application and implementation of the test has been proposed in the research. Results The proposed test is applied on a Covid-19 data set for application purposes. The study results suggested that the proposed modified Kruskal-Wallis H test is more suitable in interval-valued data situations. The application of this new neutrosophic Kruskal-Wallis test on the Covid-19 data set showed that the proposed test provides more relevant and adequate results. The data representing the daily ICU occupancy by the Covid-19 patients were recorded for both determinate and indeterminate parts. The existing nonparametric Kruskal-Wallis H test under Classical Statistics would have given misleading results. The proposed test showed that at a 1% level of significance, there is a statistically significant difference among the average daily ICU occupancy by corona-positive patients of different age groups. Conclusions The findings of the results suggested that our proposed modified form of the Kruskal-Wallis is appropriate in place of the classical form of the test in the presence of the neutrosophic environment.

Abstract Water pollution is one of the most dangerous problems which is commonly ignored in our country. Pakistan ranks very low in the world, regarding drinkable water. Both surface and underground water are contaminated with toxic metals and pesticides and arsenic (μg/L) were found to be 50. The quality parameters set by the WHO are persistently violated. The water quality is seriously affected by improper disposal of industrial, domestic waste and agrochemicals. These pollutants are responsible alone, or along with other factors for a variety of health problems. This article discusses drinking water being supplied in Sahiwal (Pakistan) to students living in the hostel along with an emphasis on the major pollutants, their effects and consequent health problems. The data presented in this article have been collected in Sahiwal. The water samples were collected from the main supply and the blood samples were of the consumers of that water.

The current study aims to determine the impact of diversity and intra-team trust on conflict within the health sector of Pakistan. This study also measures the moderating role of trust in the relationship between diversity and conflict among team members. Data was collected using personally administered questionnaires from 61 teams, including 377 respondents working in 4 public sector hospitals in Pakistan, which were selected using a simple random sampling technique. The results revealed that diversity (as a composite) positively influences task conflict, while its two components—surface-level diversity and deep-level diversity—are associated positively with task conflict. Moreover, the results also lead to an exciting finding that trust among team members could reduce the positive influence of diversity on team members’ conflict. The implications for theory and practitioners are presented along with the avenues for future research directions.

Student learning within the Operating Room (OR) is complex and challenging, especially for medical students who heavily rely upon structured learning plans. Medical students’ OR-based surgical learning experience is heterogenous, unstandardized, and inadequate for many reasons. There is a growing need to evaluate the learning modalities and models that we currently use for medical graduates’ OR-based learning process, create a balance between structured and opportunistic learning encounters and incorporate previously identified factors that have been known to influence the quality of OR-based learning positively. In continuation with our previous work on OR-based learning, here we argue for a structured OR-based learning plan that embodies appropriate learning models and teaching methodologies and focuses on a comprehensive plan that justifies a local needs analysis and addresses factors influencing the quality of OR-based student learning to produce enhanced learning outcomes.

This research is an extension of classical statistics distribution theory as the theory did not deal with the problems having ambiguity, impreciseness, or indeterminacy. An important life-time distribution called Beta distribution from classical statistics is proposed by considering the indeterminate environment and named the new proposed distribution as neutrosophic beta distribution. Various distributional properties like mean, variance, moment generating function, r-th moment order statistics that includes smallest order statistics, largest order statistics, joint order statistics, and median order statistics are derived. The parameters of the proposed distribution are estimated via maximum likelihood method. Proposed distribution is applied on two real data sets and goodness of fit is assessed through AIC and BIC criteria’s. The estimates of the proposed distribution suggested a better fit than the classical form of Beta distribution and recommended to use when the data in the interval form follows a Beta distribution and have some sort of indeterminacy.

Mitochondrial anti-apoptotic Bcl2 and BclxL proteins, are overexpressed in multiple tumour types, and has been involved in the progression and survival of malignant cells. Therefore, inhibition of such proteins has become a validated and attractive target for anticancer drug discovery. In this manner, the present studies developed a series of novel isatin–indole conjugates (7a-j and 9a-e) as potential anticancer Bcl2 and BclxL inhibitors. The progression of the two examined colorectal cancer cell lines was significantly inhibited by all of the prepared compounds with IC50 ranges 132–611 nM compared to IC50 = 4.6 µM for 5FU, against HT-29 and IC50 ranges 37–468 nM compared to IC50 = 1.5 µM for 5FU, against SW-620. Thereafter, compounds 7c and 7g were selected for further investigations. Interestingly, both compounds exhibited selective cytotoxicity against both cell lines with high safety to normal fibroblast (HFF-1). In addition, both compounds 7c and 7g induced apoptosis and inhibited Bcl2 and BclxL expression in a dose-dependent manner. Collectively, the high potency and selective cytotoxicity suggested that conjugates 7c and 7g could be a starting point for further optimisation to develop novel pro-apoptotic and antitumor agents towards colon cancer.

In the current work, a new set of carbohydrazide linked benzofuran-isatin conjugates (5a–e and 7a–i) was designed and synthesised. The anticancer activity for compounds (5b–d, 7a, 7b, 7d and 7g) was measured against NCI-55 human cancer cell lines. Compound 5d was the most efficient, and thus subjected to the five-dose screen where it showed excellent broad activity against almost all tested cancer subpanels. Furthermore, all conjugates (5a–e and 7a–i) showed a good anti-proliferative activity towards colorectal cancer SW-620 and HT-29 cell lines, with an excellent inhibitory effect for compounds 5a and 5d (IC50 = 8.7 and 9.4 µM (5a), and 6.5 and 9.8 µM for (5d), respectively). Both compounds displayed selective cytotoxicity with good safety profile. In addition, both compounds provoked apoptosis in a dose dependent manner in SW-620 cells. Also, they significantly inhibited the anti-apoptotic Bcl2 protein expression and increased the cleaved PARP level that resulted in SW-620 cells apoptosis.

Background: Emergence of carbapenem resistance (CR) is a health concern of pertinent importance. Epidemiological surveillance of CR at global and indigenous level (Pakistan) can help to improve infection control and establish pharmacovigilance programs. This study evaluates the prevalence of clinically significant CR isolates, and its genetic variant distribution among geographical regions of Pakistan. Methods: A meta-analysis was conducted to present the current rate of CR infections and prevalence of Metallo-β-lactamases (MBLs). The proposed subject was researched using electronic databases to identify the available literature. Thereafter, relevant data was extracted and statistical analysis was performed using STATA version 14. Results: A total of 110 relevant studies were identified with 19 meeting the inclusion criteria for the meta-analysis of CR, while 22 for MBLs. Pooled rate for carbapenem resistance was determined to be 0.28 (95% CI: 0.26–0.31) with overall significant heterogeneity (I2 = 99.61%, P

Objective: To compare the effect of individual versus team competitiongamification on trainees’ engagement in journal club. Methods: The quasi-experimental study was conducted at two tertiary care hospitals in Lahore, Pakistan, from December, 2019 to May, 2020, and comprised all plastic surgery residents in training years 3-5who had attended non-gamified journal club sessions. They were divided into two groups. Initially, two journal club sessions were run in a gamified manner. Group 1had an individual competition whereas group 2 had a team competition. In the second phase, the group orientation was reversed. Engagement scores were measured using the student engagement survey toolat baseline, at the completion of the first part, and at end of the intervention. Data was analysed using SPSS 22. Results: Of the 44 participants, 23(52.3%) were in group 1 and 21(47.7%) in group 2. Overall, there were 27(61%) females and 17(39%) males. The mean age of the sample was 31+/-2 years. Gamification resulted in significant increase in the level of residents’ engagement in journal club activities compared to the baseline scores(p0.05). Conclusion: Gamification designs used in the journal club activity increased student engagement level compared to the pre-intervention score, but gamification design was not a significant factor in this regard. Key Words: Journal club, Gamification, Game designs, Student engagement. Continue

Abstract Background Colorectal cancer (CRC) is a heterogeneous tumor having various genetic alterations. The current treatment options had limited impact on disease free survival due to therapeutic resistance. Novel anticancer agents are needed to treat CRC specifically metastatic colorectal cancer. A novel coordination complex of platinum, (salicylaldiminato)Pt(II) complex with dimethylpropylene linkage (PT) exhibited potential anti-cancer activity. In this study, we explored the molecular mechanism of PT-induced cell death in colorectal cancer. Methods Colony formation was evaluated using the clonogenic assay. Apoptosis, cell cycle analysis, reactive oxygen species, mitochondrial membrane potential and caspase-3/− 7 were assessed by flow cytometry. Glutathione level was detected by colorimetric assay. PT-induced alteration in pro-apoptotic/ anti-apoptotic proteins and other signaling pathways were investigated using western blotting. P38 downregulation was performed using siRNA. Results In the present study, we explored the molecular mechanism of PT-mediated inhibition of cell proliferation in colorectal cancer cells. PT significantly inhibited the colony formation in human colorectal cancer cell lines (HT-29, SW480 and SW620) by inducing apoptosis and necrosis. This platinum complex was shown to significantly increase the reactive oxygen species (ROS) generation, depletion of glutathione and reduced mitochondrial membrane potential in colorectal cancer cells. Exposure to PT resulted in the downregulation of anti-apoptotic proteins (Bcl2, BclxL, XIAP) and alteration in Cyclins expression. Furthermore, PT increased cytochrome c release into cytosol and enhanced PARP cleavage leading to activation of intrinsic apoptotic pathway. Moreover, pre-treatment with ROS scavenger N-acetylcysteine (NAC) attenuated apoptosis suggesting that PT-induced apoptosis was driven by oxidative stress. Additionally, we show that PT-induced apoptosis was mediated by activating p38 MAPK and inhibiting AKT pathways. This was demonstrated by using chemical inhibitor and siRNA against p38 kinase which blocked the cytochrome c release and apoptosis in colorectal cancer cells. Conclusion Collectively, our data demonstrates that the platinum complex (PT) exerts its anti-proliferative effect on CRC by ROS-mediated apoptosis and activating p38 MAPK pathway. Thus, our findings reveal a novel mechanism of action for PT on colorectal cancer cells and may have therapeutic implication.

TGFβ has a role in cancer immunosuppression but the exact mechanisms haven’t been fully elucidated. Here, using mouse models deficient in TGFβ-signaling, the authors show that loss of ALK5 in CD8 + T cells enhances their tumour trafficking and cytotoxicity suggesting that ALK5 inhibitors may have clinical utility.

Abstract Background Colorectal carcinoma is one of the most deadly cancers that requests effective and safe chemotherapy. Evaluation of natural product-based anticancer drugs as adjuvant treatment with fewer side effects is largely unexplored research fields. Herbal melanin (HM) is an extract of the seed coats of Nigella sativa that modulates an inflammatory response through toll-like receptor 4 (TLR4). This TLR4 receptor is also involved in the modulation of apoptosis. We therefore explored the anticancer potential of HM and specifically its effect on the molecular mechanisms underlying adenocarcinoma and metastatic colorectal cancer (mCRC) cell death in vitro. Methods Cell viability was evaluated using the MTT assay. Cellular reactive oxygen species (ROS), glutathione levels, and apoptotic status were assessed using fluorometric and colorimetric detection methods. HM-induced apoptotic and other signaling pathways were investigated using Western blot technology and mitochondrial transition pore assay kit. TLR4 receptor downregulation and blockade were performed using siRNA technology and neutralizing antibody, respectively. Results Our results showed that HM inhibited the proliferation of the colorectal adenocarcinoma HT29 and mCRC SW620 cell lines. Furthermore, HM enhanced ROS production and decreased glutathione levels. HM-induced apoptosis was associated with mitochondrial outer membrane permeability and cytochrome c release, inhibition of the Bcl2 family proteins, and activation of caspase-3/-7. In addition, HM modulated MAPK pathways by activating the JNK pathway and by inhibiting ERK phosphorylation. TLR4 receptor downregulation enhanced HM-induced apoptosis while TLR4 receptor blockade partially alleviated HM-inhibited ERK phosphorylation. Conclusion Altogether, these findings indicate that HM exerts pro-apoptotic effects and inhibits MAPK pathway through TLR4 in mCRC and colorectal adenocarcinoma cells, suggesting HM as a promising natural-based drug for the treatment of colorectal cancer.

Speaker diarization system identifies the speaker homogenous regions in those set of recordings where multiple speakers are present. It answers the question `who spoke when?'. The data set for speaker diarization usually consists of telephone, meetings, TV/ talk shows, broadcast news and other multi-speaker recordings. In this paper, we present the performance of our proposed multimodal speaker diarization system under noisy conditions. Two types of noises comprising additive white Gaussian noise (AWGN) and realistic environmental noise is used to evaluate the system. To mitigate the effect of noise, we propose to add an LSTM based speech enhancement block in our diarization pipeline. This block is trained on synthesized data set with more than 100 noise types to enhance the noisy speech. The enhanced speech is further used in multimodal speaker diarization system which utilizes a pre-trained audio-visual synchronization model to find the active speaker. High confidence active speaker segments are then used to train the speaker specific clusters on the enhanced speech. A subset of AMI corpus consisting of 5.4 h of recordings is used in this analysis. For AWGN, the LSTM model performance improvement is comparable with Wiener filter while in case of realistic environmental noise, the LSTM model improves significantly as compared to Wiener filter in terms of diarization error rate (DER).

To address the printed circuit board shop scheduling problem, a dynamic based on multi-indicator bottleneck degree is proposed to formulate this complex flexible job shop scheduling problem (FJSP). Then, a bottleneck degree-based migrating birds optimization algorithm (MBO) is proposed to tackle this NP-hard problem. Specifically, a multi-indicator assessment model is first developed to obtain the bottleneck degree, and then a two-layer code-decoding structure based on the variable domain structure and the addition of the improved migratory bird algorithm with competitive mechanisms are employed to improve the effectiveness. Finally, the computational experiments demonstrate that the proposed dynamic scheduling approach based on bottleneck degrees and improved migrating bird algorithms can obtain promising results and it outperforms several other algorithms.

Purpose: Changing community needs and disease patterns are the major stimulator for change in medical curriculum throughout the world. The process of change depends on many factors that come under the umbrella of organizational readiness for its successful implementation. Inappropriate planning and low levels of organizational readiness for change will result in failure of change process. Methodology: A quantitative study design was chosen for this study. Medical school’s organizational readiness questionnaire (MORC) was used to collect data. The questionnaire consists of 53 items further categorized into three scales and twelve subscales. The questionnaire was distributed among faculty members of four medical colleges of Punjab, collected data was coded and descriptive and inferential statistics were applied for analysis using SPSS. Analysis revealed that all four medical colleges were having good organizational readiness to adopt change. Findings: The results of descriptive analysis showed, that majority of the respondents (47%) were agreed that their medical school, is in preparatory phase, 29%respondents showed that their institute is in more than two years of implementation phase of curriculum change, 23.8% agreed that in their medical school is in first two years of implementation phase. Implication: MORC is a reliable instrument for assessing institutional preparedness for curriculum change.

Background: Root resorption is an unwanted phenomenon occurring in a substantial population proportion these days. Hence, the current study was conducted to evaluate root resorption in endodontically treated teeth following fixed orthodontic treatment. Materials and Methods: A total of 100 patients were enrolled. Only those patients were enrolled that were scheduled to undergo fixed orthodontic therapy. Pretreatment examination was done in all the patients, and their radiographs were obtained. Both orthopantomograms and peri-apical radiographs were taken. All the patients were recalled on follow-up, and radiographic examination was again carried out. Pretreatment radiographs and follow-up radiographs were compared. The incidence of root resorption was documented. The data were entered in an Excel sheet (Microsoft office version 2007) and analyzed using IBM SPSS software version 20. Results: Root resorption was present in 30 patients. Among these 30 patients, 20 were male, whereas 10 were female. In 19 patients, root resorption was present in the maxillary arch, whereas in 11 patients, it was seen in the mandibular arch. The most common tooth involved with root resorption was premolars, followed by anteriors and molars. Conclusion: The risk of root resorption is higher in endodontically treated teeth under the influence of orthodontic forces.

Background: Midfacial hypoplasia is a common feature in patients with combined cleft lip and palate. The current study was done to assess the effect of facemask (FM) therapy in patients with unilateral cleft palate. Materials and Methods: A total of 16 patients with unilateral complete cleft lip and palate were treated with maxillary transversal discrepancy with rapid maxillary expansion (RME) followed by FM therapy. After the completion of the RME treatment, the same appliance was used for protraction. Radiographs were taken after removing the RME appliance (T1) and at the end of the FM treatment after removing the appliance (T2). Results: There were 5 males and 11 females. SNA was 73.1° and 79.4°, SNB was 75.2° and 72.4°, ANB was −3.21° and 2.90°, SN-PP was 11.2° and 10.4°, Co-A was 84.3 mm and 87.5 mm, A-HR was 55.2 mm and 57.8 mm, A-VR was 62.4 mm and 64.7 mm, and SN-MP was 38.2 mm and 41.5 mm before and after treatment, respectively. Conclusion: FM proved to be beneficial in causing significant improvement in patients having combined cleft lip and palate.

Objective: To determine perception of faculty regarding social accountability of a private medical college. Study Design: Qualitative case study. Place and Duration of Study: The study was done at Islamic International Medical College of Riphah University Pakistan, from Jan 2017 to Jan 2018. Material and Methods: Purposive sampling was done to collect data from 21 faculty members after informed consent. Interviews were done using open ended semi-structured questions to the point of saturation. The interview questions were based on Conceptualization, Processes and Usability Model (CPU). Triangulation for reliability was achieved by using multiple interviewees and co-investigator for data collection. The interviews were audio recorded and thematic analysis was done using NVivo software. Results: Six themes emerged from data analysis. Subthemes for each theme were grouped with frequency of responses. Theme of social accountability included type of student produced, productivity and impact on population as subthemes. Second theme, major health issues of Pakistan had curriculum, expert input and vision as subthemes. Theme “inculcation of community health problems” included priority given to community health problems, educational program, health outcomes. Theme “predetermined competencies” comprised of stakeholders, and prospectus subthemes. Fifth theme “underprivileged students and admission process” considered railway employees, preventive aspect and student’s society as subthemes. Finally, motivation to work, role of college and future employment were the subthemes for “exposure to underserved population”. Conclusion: Concept of social accountability is new to the faculty. A comparison between private and public sector needs to be drawn. If Social Accountability is to be taken up seriously by the medical education institutes across Pakistan, so they can contribute actively toward delivery of healthcare which is equitable, relevant, costeffective and quality-driven, and which has a demonstrable impact on the health indicators of the communities it serves, then a major revision of the teaching and training programs needs to ensue. There must be a national consensus on the conceptual framework driving curricular change, with the end-object not being production of under-graduate medical doctors but, rather, a demonstrable and measurable impact on actual health outcomes of the society.

To promote online businesses and sales, e-commerce industry focuses to fulfill users' demands by giving them top set of recommendations which are ranked through different ranking measures.Deep learning based auto-encoder models have further improved the performance of recommender systems. A state-of-the-art collaborative denoising auto-encoder (CDAE) models user-item interactions as a corrupted version of users rating inputs. However, this architecture still lacks users' ratings-trend information which is an important parameter to recommend top-N items to users. In this paper, building upon CDAE characteristics, we propose a novel users rating-trend based collaborative denoising auto-encoder (UT-CDAE) which determines user-item correlations by evaluating rating-trend(High or Low) of a user towards a set of items. This inclusion of a user's rating-trend provides additional regularization flexibility which helps to predict improved top-N recommendations. The correctness of the suggested method is verified through different ranking evaluation metrics i.e., (mean reciprocal rank, mean average precision and normalized discounted gain), for various input corruption values, learning rates and regularization parameters.Experiments on standard ML-100K and ML-1M datasets show that suggested model has improved performance overstate-of-the-art denoising auto-encodermodels.

Some new 3H-quinazolin-4-one derivatives were synthesised and screened for anticancer, antiphospholipases, antiproteases, and antimetabolic syndrome activities. Compound 15d was more potent in reducing the cell viabilities of HT-29 and SW620 cells lines to 38%, 36.7%, compared to 5-FU which demonstrated cell viabilities of 65.9 and 42.7% respectively. The IC50 values of 15d were ∼20 µg/ml. Assessment of apoptotic activity revealed that 15d decreased the cell viability by down regulating Bcl2 and BclxL. Moreover, compounds, 8j, 8d/15a/15e, 5b, and 8f displayed lowered IC50 values than oleanolic acid against proinflammatory isoforms of hGV, hG-X, NmPLA2, and AmPLA2. In addition, 8d, 8h, 8j, 15a, 15b, 15e, and 15f showed better anti-α-amylase than quercetin, whereas 8g, 8h, and 8i showed higher anti-α-glucosidase activity than allopurinol. Thus, these compounds can be considered as potential antidiabetic agents. Finally, none of the compounds showed higher antiproteases or xanthine oxidase activities than the used reference drugs.

The Sign test is a famous nonparametric test from classical statistics used to assess the one or two sample averages. The test is practical when the sample size is small, or the distributional assumption under a parametric test does not satisfy. One of the limitations of the Sign test is the exact form of the data, and the existing methodology of the test does not cover the interval-valued data. The interval-valued data often comes from the fuzzy logic where the experiment's information is not sure and possesses some kind of vagueness, uncertainty or indeterminacy. This research proposed a modified version of the Sign test by considering the indeterminate state and the exact form of the data-the newly proposed sign test methodology is designed for both one-sample and two-sample hypothesis testing problems. The performance of the proposed modified versions of the Sign test is evaluated through two real-life data examples comprised of covid-19 reproduction rate and covid-positive daily occupancy in ICU in Pakistan. The findings of the study suggested that our proposed methodologies are suitable in nonparametric decision-making problems with an interval-valued data. Therefore, applying the new neutrosophic sign test is explicitly recommended in biomedical sciences, engineering, and other statistical fields under an indeterminate environment.

Many problems in real life exist that are full of confusion, vagueness, and ambiguity. The quantification of such issues in a scientific way is the need of time. The negative binomial distribution is an important discrete probability distribution from the account of classical probability distribution theory. The distribution was used to study the chance of kth success in n trials before n − 1 failures for crisp data. The literature lacks in dealing with the situations for interval-valued data under negative binomial distribution. In this research, the neutrosophic negative binomial distribution is proposed to generalize the classical negative binomial distribution. The generalized proposed distribution considers the indeterminacy and crisp form from interval-valued. Several properties of the proposed distribution, such as moment generating function, characteristic function, and probability generating function, are also derived. Furthermore, the derivation of reliability analysis properties such as survival, hazard rate, reversed hazard rate, cumulative hazard rate, mills ratio, and odds ratio are also presented. In addition, order statistics for the proposed distribution, including wth, joint, median, minimum, and maximum order statistics are part of the paper. The proposed distribution is discussed from the real data applications perspective by considering the different case studies. This research opens the way to deal with the problems that follow conventional conveyances and include nonprecisely determined details simultaneously.

In decision-making problems, the researchers' application of parametric tests is the first choice due to their wide applicability, reliability, and validity. The common parametric tests require the validation of the normality assumption even for large sample sizes in some cases. Jarque-Bera test is among one of the methods available in the literature used to serve the purpose. One of the Jarque-Bera test restrictions is the computational limitations available only for the data in exact form. The operational procedure of the test is helpless for the interval-valued data. The interval-valued data generally occurs in situations under fuzzy logic or indeterminate state of the outcome variable and is often called neutrosophic form. The present research modifies the existing statistic of the Jarque-Bera test for the interval-valued data. The modified design and operational procedure of the newly proposed Jarque-Bera test will be useful to assess the normality of a data set under the neutrosophic environment. The proposed neutrosophic Jarque-Bera test is applied and compared with its existing form with the help of a numerical example of real gold mines data generated under the fuzzy environment. The study's findings suggested that the proposed test is effective, informative, and suitable to be applied in indeterminacy compared to the existing Jarque-Bera test.

Objective: Intestinal anastomosis is among the most commonly performed major abdominal procedures; however, leaks are an ongoing problem. The aim of this study was to investigate the effect of Insulin-like Growth Factor (IGF-1) on colonic healing under hypoxia. Methods: Thirty-two Sprague–Dawley male rats underwent laparotomy with colonic transection and anastomosis. Rats were divided into four groups—Group A: normoxic (FiO2 21%) with saline [2 mg/kg, Intraperitoneally (IP)] at days 0, 2, 4, and 6; Group B: hypoxic (FiO2 11%) with saline injection; Group C: normoxic with IGF-1 injection at a dose of 2 mg/kg at days 0, 2, 4, and 6; Group D: hypoxic with IGF-1 treatment. On day 7, all animals were sacrificed, and intestine weight and bursting pressure were measured; anastomotic tissues were analyzed for mRNA level of collagen I and Matrix Metalloproteinase-13 (MMP-13) and cytokines analysis by enzyme-linked immunosorbent assay. Results: There was significant increase in intestinal length in normoxic group treated with IGF-1 as compared to control (129.9 cm vs. 99.38 cm, p < 0.05); the length increased significantly in hypoxic group treated with IGF as compared to hypoxic control (123.1 cm vs. 82.25, p < 0.01). In the normoxic groups, a 6.7% decrease in mean body weight was found; however, the normoxic IGF-1 group sustained a weight gain of 0.5% (p < 0.01). The average weight decreased in the hypoxic control group (28.3%) and in the hypoxic IGF-1 treated group (16.6%, p < 0.05). Anastomotic bursting pressure increased significantly (p < 0.05) after IGF-1 treatment. Collagen I and MMP-13 mRNA expressions increased significantly (p < 0.001) in the IGF-1 treated group. Interleukin-10 and tumor necrosis factor alpha levels decreased under hypoxia with IGF-1 (p < 0.05). Vascular endothelial growth factor (p < 0.001), transforming growth factor beta (p < 0.05), and IGF-1 (p < 0.001) were significantly elevated in response to IGF-1. Conclusion: IGF-1 stimulates the healing of colonic anastomosis under hypoxia. Factors promoting neoangiogenesis, collagen deposition, and paracrine expression were increased after IGF-1 treatment resulting in wound healing.

Abstract Background South-Asia is known as a hub for multidrug-resistant (MDR) bacteria. Unfortunately, proper surveillance and documentation of MDR pathogens is lacking in Pakistan. The alarming increase in the prevalence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is a serious problem. From this perspective, we analysed published data regarding ESBL-producing Enterobacteriaceae in different regions of Pakistan. Methods A meta-analysis was performed to determine the prevalence of ESBL-producing Enterobacteriaceae in Pakistan. A Web-based search was conducted in electronic databases, including PubMed, Scopus and PakMedi Net (for non-indexed Pakistani journals). Articles published (in either indexed or non-indexed journals) between January 2002 and July 2016 were included in the study. Relevant data were extracted, and statistical analysis was performed using the Metaprop command of STATA version 14.1. Results A total of 68 studies were identified from the electronic data base search, and 55 of these studies met our inclusion criteria. Pakistan’s overall pooled proportion of ESBL-producers was 0.40 (95% CI: 0.34–0.47). The overall heterogeneity was significant (I2 = 99.75%, p

Cerium oxide nanocrystals (CeO2-NCs) exhibit superoxide dismutase and catalase mimetic activities. Based on these catalytic activities, CeO2-NCs have been suggested to have the potential to treat various diseases. The crystalline size of these materials is an important factor that influences the performance of CeO2-NCs. Previous reports have shown that several metal-based nanocrystals, including CeO2-NCs, can induce cytotoxicity in cancer cells. However, the underlying mechanisms have remained unclear. To characterize the anticancer activities of CeO2-NCs, several assays related to the mechanism of cytotoxicity and induction of apoptosis has been performed. Here, we have carried out a systematic study to characterize CeO2-NCs phase purity (X-ray diffraction), morphology (electron microscopy), and optical features (optical absorption, Raman scattering, and photoluminescence) to better establish their potential as anticancer drugs. Our study revealed anticancer effects of CeO2-NCs in HT29 and SW620 colorectal cancer cell lines with half-maximal inhibitory concentration (IC50) values of 2.26 and 121.18 μg ml–1, respectively. Reductions in cell viability indicated the cytotoxic potential of CeO2-NCs in HT29 cells based on inverted and florescence microscopy assessments. The mechanism of cytotoxicity confirmed by estimating possible changes in the expression levels of Bcl2, BclxL, Bax, PARP, cytochrome c, and β-actin (control) proteins in HT29 cells. Down-regulation of Bcl2 and BclxL and up-regulation of Bax, PARP, and cytochrome c proteins suggested the significant involvement of CeO2-NCs exposure in the induction of apoptosis. Furthermore, biocompatibility assay showed minimum effect of CeO2-NCs on human red blood cells.