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Abstract Background Wilson disease (WD) is an inherited disorder of copper metabolism commonly involving the liver, cornea, and brain. Its incidence is increasing day by day worldwide. Early diagnosis and prompt treatment are the key for best outcome. Material and methods A cross-sectional descriptive study was done from January 2014 to December 2019. Sixty children of both genders between 3 and 18 years were diagnosed by clinical and laboratory profile meeting selected criteria. Results Mean age was 8.42 ± 2.6 years and male female ratio was 1.5:1. Consanguinity of marriage was found in 38.3% cases. Seventy percent of cases were hepatic, 16.7% were neuropsychiatric, 5.0% were hepatic with neuropsychiatric, and 8.3% cases were manifested asymptomatically. Asymptomatic and hepatic WD were reported between 3 and 10 years and most of the neuropsychiatric and hepatic with neuropsychiatric manifested after 10 years of age. More than 50% cases improved, a little more than 20% children died, 18.4% were unchanged and 6.6% were hepatic added neuropsychiatric manifestations. Most of the asymptomatic (100%) and hepatic (61.9%) cases improved. High mortality was found with 76.9% cases of acute liver failure (ALF), 7.7% case of chronic liver disease (CLD) and 25% cases of CLD with portal hypertension (CLD and PH). Most of the neuropsychiatric cases (90.0%), and approximately two-third (66.6%) of hepatic with neuropsychiatric cases remained unchanged. Neuropsychiatric manifestations were added in 15.4% cases of CLD and 25% cases of CLD with PH patient. The treatment was well tolerated in 66% children without any side effects. Low WBC (6.3%) and platelet count (4.3%), vomiting (6.3%), anorexia (4.3%), loss of taste (4.3%), rash (4.3%), and proteinuria (2.1%) were found in few cases. Conclusion Majority of the children were presented with hepatic manifestations. More than half of patients with WD treated by D-penicillamine (DP) were improved. Significant mortality was found in acute liver failure whereas neuropsychiatric presentations had persistent abnormalities. No major side effects of DP was observed in most of the cases. Early diagnosis and prompt treatment were crucial for better outcome.

IntroductionHeparins, naturally occurring glycosaminoglycans, are widely used for thrombosis prevention. Upon application as anticoagulants in cancer patients, heparins were found to possess additional antitumor activities. Ectonucleotidases have recently been proposed as novel targets for cancer immunotherapy.Methods and resultsIn the present study, we discovered that heparin and its derivatives act as potent, selective, allosteric inhibitors of the poorly investigated ectonucleotidase NPP1 (nucleotide pyrophosphatase/phosphodiesterase-1, CD203a). Structure-activity relationships indicated that NPP1 inhibition could be separated from the compounds’ antithrombotic effect. Moreover, unfractionated heparin (UFH) and different low molecular weight heparins (LMWHs) inhibited extracellular adenosine production by the NPP1-expressing glioma cell line U87 at therapeutically relevant concentrations. As a consequence, heparins inhibited the ability of U87 cell supernatants to induce CD4+ T cell differentiation into immunosuppressive Treg cells.DiscussionNPP1 inhibition likely contributes to the anti-cancer effects of heparins, and their specific optimization may lead to improved therapeutics for the immunotherapy of cancer.

Information and communication technology has gradually become one of the most important pillars of the economy. In addition to economic growth, environmental pollution is a product of information and communication technologies (ICTs) as well. However, whether and how ICTs may affect these systems is unclear. Based on a more comprehensive measurement of ICTs, the current study has investigated the impact of ICTs, education, and economic performance on environmental sustainability from 2000 to 2019 across 93 countries categorized as low-income, middle-income, and high-income. Contrary to preceding studies, this research has used advanced econometric techniques to counter heterogeneities and dependencies in the data and, thus, has produced more trustworthy and efficient results. The finding obtained from the Bias-corrected method of the moment’s estimator and Driscoll and Kraal’s standard error techniques are consistent. According to the results, ICTs have a heterogenous effect on environmental sustainability across low-, middle- and high-income countries. Further results have revealed that education plays a significant role in maintaining environmental sustainability across middle—and high-income groups but does not seem to do so for lower—income groups. Environmental education for all should be part of the policy measures to tackle climate change across all income groups.

BACKGROUND: Blood proteins are frequently measured in serum or plasma, because they provide a wealth of information. Differences in the ex vivo processing of serum and plasma raise concerns that proteomic health and disease signatures derived from serum or plasma differ in content and quality. However, little is known about their respective power to predict feto-maternal health outcomes. Predictive power is a sentinel characteristic to determine the clinical use of biosignatures. OBJECTIVE: This study aimed to compare the power of serum and plasma proteomic signatures to predict a physiological pregnancy outcome. STUDY DESIGN: Paired serum and plasma samples from 73 women were obtained from biorepositories of a multinational prospective cohort study on pregnancy outcomes. Gestational age at the time of sampling was the predicted outcome, because the proteomic signatures have been validated for such a prediction. Multivariate and cross-validated models were independently derived for serum and plasma proteins. RESULTS: A total of 1116 proteins were measured in 88 paired samples from 73 women with a highly multiplexed platform using proximity extension technology (Olink Proteomics Inc, Watertown, MA). The plasma proteomic signature showed a higher predictive power (R=0.64; confidence interval, 0.42–0.79; P=3.5×10-6) than the serum signature (R=0.45; confidence interval, 0.18–0.66; P=2.2×10-3). The serum signature was validated in plasma with a similar predictive power (R=0.58; confidence interval, 0.34–0.75; P=4.8×10-5), whereas the plasma signature was validated in serum with reduced predictive power (R=0.53; confidence interval, 0.27–0.72; P=2.6×10-4). Signature proteins largely overlapped in the serum and plasma, but the strength of association with gestational age was weaker for serum proteins. CONCLUSION: Findings suggest that serum proteomics are less informative than plasma proteomics. They are compatible with the view that the partial ex-vivo degradation and modification of serum proteins during sample processing are an underlying reason. The rationale for collecting and analyzing serum and plasma samples should be carefully considered when deriving proteomic biosignatures to ascertain that specimens of the highest scientific and clinical yield are processed. Findings suggest that plasma is the preferred matrix.

As technology is spreading very fast across the world, people from different countries have started using portable devices like phones, tablets, or laptops. People belonging to different countries and cultures are using smartphones. Most smart apps are not available in multiple languages, users are bounded to use apps in the language in which the app is developed. Developing a multilingual app and taking input in multiple languages is still a headache for developers. This research aims to develop a multilingual keyboard package for flutter apps. By using this package developers can easily add a multilingual keyboard to their apps. For now, the package only supports English, Urdu, and Sindhi languages. Along with language keyboards, we have added some special characters and a numeric keyboard as well. The keyboard interface is highly customizable, developers can customize the keyboard interface as per their preferences, and they can change different properties of keyboards including, key text color, key background color, keyboard background color, and shadows. Developers can reduce end-user efforts by adding this keyboard package to their apps. End-users can interact with the app in their native language without any extra effort of downloading third-party keyboards. This package allows users to enter text in multiple languages in the same or different input fields. After the publication of this package, we conducted a survey, in which questions like the performance, accuracy, and interface of the keyboards have been asked of developers. In the survey, we asked for the developer's suggestions and feedback about keyboards, and other languages they want us to add to the package.

Purpose: High-precision radiation therapy is crucial for cancer treatment. Currently, the delivered dose can only be verified via simulations with phantoms, and an in-tumor, online dose verification is still unavailable. An innovative detection method called x-ray–induced acoustic computed tomography (XACT) has recently shown the potential for imaging the delivered radiation dose within the tumor. Prior XACT imaging systems have required tens to hundreds of signal averages to achieve high-quality dose images within the patient, which reduces its real-time capability. Here, we demonstrate that XACT dose images can be reproduced from a single x-ray pulse (4 µs) with sub-mGy sensitivity from a clinical linear accelerator. Methods and Materials: By immersing an acoustic transducer in a homogeneous medium, it is possible to detect pressure waves generated by the pulsed radiation from a clinical linear accelerator. After rotating the collimator, signals of different angles are obtained to perform a tomographic reconstruction of the dose field. Using 2-stage amplification with further bandpass filtering increases the signal-to-noise ratio (SNR). Results: Acoustic peak SNR and voltage values were recorded for singular and dual-amplifying stages. The SNR for single-pulse mode was able to satisfy the Rose criterion, and the collected signals were able to reconstruct 2-dimensional images from the 2 homogeneous media. Conclusions: By overcoming the low SNR and requirement of signal averaging, single-pulse XACT imaging holds great potential for personalized dose monitoring from each individual pulse during radiation therapy.

In this work we present a single scale wavelet-Galerkin method (WGM) for obtaining the linear dynamic response of single degree of freedom (SDOF) and multi-degree of freedom (MDOF) systems, the equation of motion is discretized using a polynomial extrapolation-based time stepping scheme. The aim of the study is to investigate the accuracy of the dynamic response resulting from the application of the proposed method and to explore the Daubechies wavelet types that can be used for unconditional stability. In our work we solve only for the scaling function coefficients of the displacement response, the scaling function coefficients of the velocity and the acceleration responses are obtained from the solved scaling function coefficients of the displacement function and the pertaining connection coefficients. The classical central differences method (CCDM) is used to generate consistent values of the velocity and the acceleration response to replace the distorted ones at the edges of the time interval. Stability analysis shows that the method using D6 wavelets is unconditionally stable for the practical range of the product of the time step and the frequency of vibration. An application of a SDOF system with initial conditions shows that for D6 wavelets the calculated responses at an adequate approximation level correspond well with those obtained using Newmark’s average acceleration method (AAM). The method is also applied to a MDOF system without performing a modal analysis, the resulting dynamic response is found to be accurate enough to be compared to that of the mode superposition method used by the STAAD pro program.

Objective: To determine the Carcinoembryonic Antigen Levels among patients with epithelial carcinoma presenting at a tertiary care hospital. Study Design: Prospective longitudinal study. Place and Duration of Study: Department of Medical Oncology, Jinnah Postgraduate Medical Centre, Karachi Pakistan, from May 2019 to May 2020. Methodology: Two hundred six patients presenting with a confirmed diagnosis of epithelial carcinoma, aged more than 15 years and of either gender were enrolled in the study. The CEA levels in all the patients were measured using an ELISA kit. The CEA levels were classified as 0-3.0 ng/mL, 3.1-5.0 ng/mL, 5.1-10 ng/mL and >10ng/mL. Results: The mean age of the cancer patients was estimated as 47.30±14.10 years. Most patients had rectum carcinoma 28(13.59%), followed by CA sigmoid 25(12.14%), respectively. The median CEA level was estimated as 5.80ng/mL ranging from 0.82 to 1000 ng/mL. About 76 patients had CEA level >10ng/mL (36.9%), 55 had CEA level 0-3.0 ng/mL (26.7%), 43 had CEA level 3.1-5.0ng/mL (20.9%), and 32 had CEA level 5.1-10.0ng/mL (15.5%). A statistically significant difference in proportions of CEA levels was found for histological type (p=0.001), type of cancer (p=0.001) and number of Mets (p=0.003). Conclusion: Rectal cancer profoundly expressed carcinoembryonic antigen levels, followed by sigmoid, colon, and ovarian cancer. Moreover, there is a significant association among carcinoembryonic antigen levels, histology, type and metastasis of cancer.

Objective: To determine the severity of High-Resolution Computed Tomography Chest findings of COVID-19 patients having co-morbid in comparison to those without co-morbid. Study Design: Comparative cross sectional study. Place and Duration of the Study: Radiology Department Combined Military Hospital, Multan Pakistan, from Mar to Sep 2020. Methodology: Data was collected through the medical record system of positive COVID-19 tests. Patients were divided into patients with no co-morbidities and others having co-morbidities. Two radiologists interpreted High-Resolution Computed Tomography chests independently to assess the disease severity in these two Groups. Co-morbidities included diabetes mellitus, hypertension, chronic renal disease, heart disease, Chronic Obstructive Pulmonary Disease and liver diseases. Results: A total of 200 patients were included. Out of 121 male patients, 85 had co-morbidities (71 had moderate to severe lung involvement; 14 had mild lung involvement); while 36 had no co-morbidities (5 had moderate to severe lung involvement; 31 had mild lung involvement). Out of 79 female patients, 47 had co-morbidities (15 had moderate to severe lung involvement; 32 had mild lung involvement); while 32 had no co-morbidities (3 had moderate to severe lung involvement; 29 had mild lung involvement). Conclusion: The severity of lung involvement was remarkably higher in patients with associated co-morbidities compared to no co-morbidities. Older age male patients having co-morbidities pose a risk factor for the severity of disease progression as compared to younger age female patients having no co-morbidities

Abstract Background Bangladesh introduced the 10-valent pneumococcal conjugate vaccine (PCV10) for children aged

Yomna M El-Meligui,1 Naglaa M Hassan,1 Amira B Kassem,2 Nora A Gouda,3 Marwa Mohanad,4 Manal A Hamouda,5 Ahmad Salahuddin6 1Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt; 2Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt; 3Cancer Epidemiology and Biostatistics Department, National Cancer Institute, Cairo University, Cairo, Egypt; 4Biochemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza, Egypt; 5Clinical Pharmacy Department, Faculty of Pharmacy, Menoufia University, Shibin El Kom, Egypt; 6Biochemistry Department, Faculty of Pharmacy, Damanhour University, Damanhour, EgyptCorrespondence: Amira B Kassem, Email amira.kassem@pharm.dmu.edu.egIntroduction: Acute myeloid leukemia (AML) is the most common type of leukemia among adults and is characterized by various genetic abnormalities. HOXB4 and PRDM16 are promising markers of AML. Our objective is to assess the potential roles of HOXB4 and PRDM16 as prognostic and predictive markers in newly diagnosed AML patients and determine the correlation between their expressions and other prognostic markers as FLT3-ITD, NPM1 exon 12 mutations, response to treatment, and patient’s survival.Methods: This study included 83 de novo AML adult patients. All patients were subjected to clinical, morphological, cytochemical, and molecular analysis to detect HOXB4 and PRDM16 gene expressions and FLT3-ITD, NPM1 exon 12 mutations.Results: The results showed that a low expression of HOXB4 was found in 31.3% of AML patients, whereas a high expression of PRDM16 was evident in 33.8% of AML patients. FLT3-ITD mutations were detected in 6 patients (7.2%), while NPM1 exon 12 mutations were detected in 7 patients (19.4%) out of 36 patients with intermediate genetic risk. Out of the 50 patients who achieved complete remission (CR), relapse occurred in 16% of the cases. Low expression of HOXB4 and high expression of PRDM1 6 were associated with CR of 32% and 28%, respectively, and a short overall survival (OS) and disease-free survival (DFS).Conclusion: Further larger study should be conducted to verify that high PRDM16 and low HOXB4 gene expressions could be used as a poor prognostic predictor for AML. The correlation between PRDM16 and HOXB4 gene expressions and FLT3-ITD and NPM1 exon 12 mutations might have a role on CR, relapse, OS, and, however, this should be clarified in analysis with a larger number of samples.Keywords: AML, HOXB4, PRDM16, NPM1 exon 12, FLT3-ITD

Plant-based nanoformulation is one of the novel approaches for therapeutic benefits. This research synthesized a silver nanoparticle from the polyherbal combination of four plants/seeds (Momordica charantia, Trigonella foenum-graecum, Nigella sativa, and Ocimum sanctum) and investigated its antidiabetic effects in streptozotocin-induced Wistar albino rat model. The polyherbal extract (PH) was extracted by the Soxhlet-solvent extraction method and the resulting crude extract was undergone for silver nanoparticle synthesis. The PH extract was subjected to a four-week intervention in fructose-fed streptozotocin-induced Wistar Albino rats’ models and in vitro antioxidative tests. Experimental animals (age: 6–7 weeks, male, body weight: 200–220 g), were divided into five groups including normal control (NC), reference control (RC), diabetic control (DC), and treatment groups PH200, PH100, and PHAgNP20. After three weeks of intervention, body weight, weekly blood glucose level, oral glucose tolerance test, AST, ALT, alkaline phosphatase, total cholesterol, triglycerides, uric acid, urea, and creatinine level of PH200 were found to be significantly (P

Objective: To compare the loss of proteins with high and low flux hemodialysis membranes. Study Design: Cross-sectional analytical study. Place and Duration of Study: Department of Nephrology, Pak Emirates Military Hospital, Rawalpindi Pakistan, from Nov 2019 to Feb 2020. Methodology: This study was conducted on patients with end-stage renal disease on maintenance haemodialysis. We excluded patients on haemodialysis for less than one month, those with poor compliance to hemodialysis, those undergoing hemodialysis for less than four hours per session and unwilling patients. Patients were divided into two groups: one was dialyzed with high flux membranes, whereas low flux membranes were used for the other group. Dialysate samples were collected during the first hour and then during the last hour of each haemodialysis session to estimate protein losses in each group. Results: Data were recorded during 133 hemodialysis sessions, the patients underwent. There were 22 patients, including 12 (54.55%) males, having a mean age of 46.45±13.99 years. Most patients (17, 77.27%) were on twice-a-week dialysis, whereas the rest were dialyzed thrice weekly. Protein loss was 0.45± 0.23g/L with low flux membranes and 1.20±0.60g/L with high flux membranes. This difference was statistically significant (p=

Nyamplung (Calophyllum Inophyllum) is an environmentally friendly alternative fuel that can be used to replace the consumption of fossil fuels. The purpose of this experiment was to analyze the effect of magnetic fields on the premixed flame of biodiesel from Calophyllum Inophyllum, the experiments were carried out on a bunsen burner. Fuel evaporation uses a temperature of 473 K and the equivalent ratio used is between ϕ 0.7; 0.8; 0.9; 1.0; 1.1 and 1.2. This experiment used a modified magnet that has magnetic force in 11.000 gausses with magnetic variations N-S, S-N, N-N, and S-S. Experiments revealed that magnetic fields have a significant effect to increase the value of laminar flame speed on magnetic variations point at S-S 3.8%; N-N 4.8%; S-N 17.09%, and the highest laminar flame speed were at point N-S 20.7%. The enhancement value of laminar flame speed indicated more optimum combustion processes. The magnetic fields can influence the O2, and H2O and change the orientation of the hydrocarbons which makes it easier for O2 and fuel to carry out the oxidation process, resulting in more optimal combustion.

This study discusses Fazlur Rahman's thoughts which are focused on: (1) the concept of modernization of Islamic education; (2) the variety of modernization of Islamic education; and (3) the implications of his thought on Islamic education in the modern era. This type of research is library research using a philosophical and historical approach. The primary data sources in this study were books written directly by Fazlur Rahman, as well as books relevant to the discussion, while the secondary data in this study were relevant literature materials produced by other thinkers who discussed Fazlur Rahman. The method of data collection in this study used the documentation method and then analyzed using. content analysis techniques. The results show that the concept of modernization of Islamic education according to Fazlur Rahman is that education is the starting point for reform. Any reform model in Islam will never happen without the involvement of education in it. Furthermore, according to Fazlur Rahman, education should be held by prioritizing the freedom of students, because without creative nature, it is difficult for students to develop. The variety of modernization of Islamic education initiated by Fazlur Rahman includes five aspects: educational objectives, education system, educators, students, and educational facilities. The implication of this research is that the modernization of Islamic education leads to the importance of democratizing Islamic education by respecting human potential.

The aim of this paper is to consider a general non-stationary optimization problem whose objective function need not be smooth in general and only approximation sequences are known instead of exact values of the functions. We apply a two-step technique where approximate solutions of a sequence of a generalized mixed variational inequality problem (GMVIP) are inserted in the iterative method of a selective coordinate-wise decomposition descent method. Its convergence is achieved under coercivity-type assumptions.

In this article, we introduce two new rough set models based on the concept of double fuzzy relations. These models are called optimistic and pessimistic multi-granulation double fuzzy rough sets. We discuss their properties and explore the relationship between these new models and double fuzzy rough sets. Our study focuses on the lower and upper approximations of these models, which generalize the conventional rough set model. In addition, we suggest that the development of the multi-granulation double fuzzy rough set model is significant for the generalization of the rough set model.

Efficient truck flow is essential for the efficient operation of a factory and the distribution of its products. This study demonstrated methods to improve truck loading times and overall efficiency at a major sugar manufacturing facility in the Middle East. The objective was to reduce truck waiting times at loading units and increase capacity. The data were collected through questionnaires, observations, and interviews with stakeholders. A simulation software was employed to analyze truck activity at loading stations at the factory. Multi-criteria decision making (MCDM) tools, AHP and TOPSIS, addressed five primary criteria and nine sub-criteria to assist in identifying, evaluating, and ranking feasible solutions. The study suggested different utilization of the various factory loading platforms at different times of the day. The findings from this study emphasize the importance of simulation-based approaches supplemented with decision-making processes to improve efficiency in sugar manufacturing facilities that may have broader applications in the factories of other industries. The study highlights remarkable improvements in operational efficiency, as seen in Alternative 4 substantial 27.9% enhancement, resulting in cost savings and time efficiency. By implementing these findings, factories can enhance their truck flow management system, reduce waiting times, increase capacity utilization, optimize resource allocation, and improve overall efficiency.

In the current study, we described the synthesis of ten new 5-(3-Bromophenyl)-N-aryl-4H-1,2,4-triazol-3-amine analogs (4a–j), as well as their characterization, anticancer activity, molecular docking studies, ADME, and toxicity prediction. The title compounds (4a–j) were prepared in three steps, starting from substituted anilines in a satisfactory yield, followed by their characterization via spectroscopic techniques. The National Cancer Institute (NCI US) protocol was followed to test the compounds’ (4a–j) anticancer activity against nine panels of 58 cancer cell lines at a concentration of 10−5 M, and growth percent (GP) as well as percent growth inhibition (PGI) were calculated. Some of the compounds demonstrated significant anticancer activity against a few cancer cell lines. The CNS cancer cell line SNB-75, which showed a PGI of 41.25 percent, was discovered to be the most sensitive cancer cell line to the tested compound 4e. The mean GP of compound 4i was found to be the most promising among the series of compounds. The five cancer cell lines that were found to be the most susceptible to compound 4i were SNB-75, UO-31, CCRF-CEM, EKVX, and OVCAR-5; these five cell lines showed PGIs of 38.94, 30.14, 26.92, 26.61, and 23.12 percent, respectively, at 10−5 M. The inhibition of tubulin is one of the primary molecular targets of many anticancer agents; hence, the compounds (4a–j) were further subjected to molecular docking studies looking at the tubulin–combretastatin A-4 binding site (PDB ID: 5LYJ) of tubulin. The binding affinities were found to be efficient, ranging from −6.502 to −8.341 kcal/mol, with two major electrostatic interactions observed: H-bond and halogen bond. Ligand 4i had a binding affinity of −8.149 kcal/mol with the tubulin–combretastatin A-4 binding site and displayed a H-bond interaction with the residue Asn258. The ADME and toxicity prediction studies for each compound were carried out using SwissADME and ProTox-II software. None of the compounds’ ADME predictions showed that they violated Lipinski’s rule of five. All of the compounds were also predicted to have LD50 values between 440 and 500 mg/kg, putting them all in class IV toxicity, according to the toxicity prediction. The current discovery could potentially open up the opportunity for further developments in cancer.

Intestinal parasitic infections pose a grave threat to human health, particularly in tropical and subtropical regions. The traditional manual microscopy system of intestinal parasite detection remains the gold standard procedure for diagnosing parasite cysts or eggs. This approach is costly, time-consuming (30 min per sample), highly tedious, and requires a specialist. However, computer vision, based on deep learning, has made great strides in recent years. Despite the significant advances in deep convolutional neural network-based architectures, little research has been conducted to explore these techniques’ potential in parasitology, specifically for intestinal parasites. This research presents a novel proposal for state-of-the-art transfer learning architecture for the detection and classification of intestinal parasite eggs from images. The ultimate goal is to ensure prompt treatment for patients while also alleviating the burden on experts. Our approach comprised two main stages: image pre-processing and augmentation in the first stage, and YOLOv5 algorithms for detection and classification in the second stage, followed by performance comparison based on different parameters. Remarkably, our algorithms achieved a mean average precision of approximately 97% and a detection time of only 8.5 ms per sample for a dataset of 5393 intestinal parasite images. This innovative approach holds tremendous potential to form a solid theoretical basis for real-time detection and classification in routine clinical examinations, addressing the increasing demand and accelerating the diagnostic process. Our research contributes to the development of cutting-edge technologies for the efficient and accurate detection of intestinal parasite eggs, advancing the field of medical imaging and diagnosis.

Human African trypanosomiasis (HAT) is a neglected tropical disease that is caused by flagellated parasites of the genus Trypanosoma. HAT imposes a significant socio-economic burden on many countries in sub-Saharan Africa and its control is hampered by several drawbacks ranging from the ineffectiveness of drugs, complex dosing regimens, drug resistance, and lack of a vaccine. Despite more than a century of research and investigations, the development of a vaccine to tackle HAT is still challenging due to the complex biology of the pathogens. Advancements in computational modeling coupled with the availability of an unprecedented amount of omics data from different organisms have allowed the design of new generation vaccines that offer better antigenicity and safety profile. One of such new generation approaches is a multi-epitope vaccine (MEV) designed from a collection of antigenic peptides. A MEV can stimulate both cellular and humoral immune responses as well as avoiding possible allergenic reactions. Herein, we take advantage of this approach to design a MEV from conserved hypothetical plasma membrane proteins of Trypanosoma brucei gambiense, the trypanosome subspecies that is responsible for the west and central African forms of HAT. The designed MEV is 402 amino acids long (41.5 kDa). It is predicted to be antigenic, non-toxic, to assume a stable 3D conformation, and to interact with a key immune receptor. In addition, immune simulation foresaw adequate immune stimulation by the putative antigen and a lasting memory. Therefore, the designed chimeric vaccine represents a potential candidate that could be used to target HAT.

Objective: To assess the role of unenhanced multidetector computed tomography (CT) of kidneys, ureters and bladder (KUB) in the initial imaging of suspected acute renal colic. Study Design: Retrospective longitudinal study. Place and Duration of Study: Combined Military Hospital, Kharian Pakistan, from Jan 2020 to Jan 2021. Methodology: One hundred and thirty-eight cases of suspected acute renal colic underwent CT-KUB. The demographic,radiological, clinical, and follow-up data were recorded for each patient. Results: There were 88(51.8%) males and 82(48.2%) females in the present study, with a mean age of 50.86±18.57 years. Out of 170 patients, only 138(81.17%) were indicated with acute findings, whereas 32(18.82%) individuals showed no acute findings.The mean stone size was found to be 4.77±0.98mm. Most of the stones had a location near the pelvic brim (n=47; 34.15%). Conclusion: The use of CT KUB should be encouraged for the evaluation of renal colic. Keywords: Acute renal colic, Computed tomography (CT), Computed tomography of Kidneys, ureter and bladder (CT-KUB).

Introduction With the ratification of the Sustainable Development Goals, there is an increased emphasis on early childhood development (ECD) and well-being. The WHO led Global Scales for Early Development (GSED) project aims to provide population and programmatic level measures of ECD for 0–3 years that are valid, reliable and have psychometrically stable performance across geographical, cultural and language contexts. This paper reports on the creation of two measures: (1) the GSED Short Form (GSED-SF)—a caregiver reported measure for population-evaluation—self-administered with no training required and (2) the GSED Long Form (GSED-LF)—a directly administered/observed measure for programmatic evaluation—administered by a trained professional.Methods We selected 807 psychometrically best-performing items using a Rasch measurement model from an ECD measurement databank which comprised 66 075 children assessed on 2211 items from 18 ECD measures in 32 countries. From 766 of these items, in-depth subject matter expert judgements were gathered to inform final item selection. Specifically collected were data on (1) conceptual matches between pairs of items originating from different measures, (2) developmental domain(s) measured by each item and (3) perceptions of feasibility of administration of each item in diverse contexts. Prototypes were finalised through a combination of psychometric performance evaluation and expert consensus to optimally identify items.Results We created the GSED-SF (139 items) and GSED-LF (157 items) for tablet-based and paper-based assessments, with an optimal set of items that fit the Rasch model, met subject matter expert criteria, avoided conceptual overlap, covered multiple domains of child development and were feasible to implement across diverse settings.Conclusions State-of-the-art quantitative and qualitative procedures were used to select of theoretically relevant and globally feasible items representing child development for children aged 0–3 years. GSED-SF and GSED-LF will be piloted and validated in children across diverse cultural, demographic, social and language contexts for global use.

The goal of this paper is further to study a kind of generalized vector inverse quasi-variational inequality problems and to obtain error bounds in terms of the residual gap function, the regularized gap function, and the global gap function by utilizing the relaxed monotonicity and Hausdorff Lipschitz continuity. These error bounds provide effective estimated distances between an arbitrary feasible point and the solution set of generalized vector inverse quasi-variational inequality problems.

Objective: To determine the diagnostic accuracy of MRI in diagnosing placenta accrete with post-operative histopathological findings considered a gold standard. Study Design: Cross-sectional study. Place and Duration of study: Combined Military Hospital, Kharian Pakistan, from Jan to Dec 2020. Methodology: In total, 119 individuals suspected of placenta accreta were evaluated with the help of magnetic resonance imaging (MRI). However, confirmation for 71 patients was obtained based on clinical criteria at the time of delivery. Results: The mean age of women was 28.67±5.64 years, and the mean gestational age for the foetus was 33.14±1.74 weeks. The present study showed that MRI has 90(141%) sensitivity, 91(66%) specificity, 94(11%) positive predictive value (PPV), and 86(27%) negative predictive value (NPV) and diagnostic accuracy of 90(75%) for diagnosing placental accreta. Conclusion: It is concluded that the use of MRI should be encouraged as an efficient and primary diagnostic tool for placenta accreta.

Abstract This work presents a gallium nitride (GaN) high electron mobility transistor (HEMT)–based cascaded multistage power amplifier (MPA) in class‐AB for L‐band radar applications. The purpose of this endeavour is to develop an MPA using GaN HEMT devices to achieve optimised parameters such as high gain, high power, better efficiency, and linearity in a compact size. In an MPA design with multiple stages, oscillations are common owing to unwanted high gain at the lower frequency range. To overcome this issue, we introduced interstage harmonic termination networks as a novel approach to suppress high gain at low frequencies, which are prone to oscillations. The proposed cascaded MPA provides the maximum radio‐frequency output power of 89 W and a power gain of 52 dB with an associated power‐added efficiency of 51%. Second and third harmonic levels are −32.5 and −37 dBc, respectively. Two‐tone measurements are performed with a frequency separation of 10 MHz, and an intermodulation level of less than −33 dBc is achieved.

Alimentary tract duplications may be symptomatic or may be discovered incidentally. They are named for the organ with which they are associated.1 Congenital gastrointestinal (GI) tract duplication cysts are commonly located in the ileum (53%), mediastinum (18%), colon (13%), stomach (7%), duodenum (6%), rectum (4%), or oesophagus (2%)2. A single theory is insufficient to explain all types of duplications.3 Children may present with symptoms like vomiting, abdominal pain, lumps, or weight loss.4 The presence of ectopic gastric mucosa and the potential for malignancy remain matters of concern.2 Surgical management is essential for these rare cysts.5 We encountered a Bangladeshi boy with a gastric duplication cyst (GDC) that was pre-operatively diagnosed as a pancreatic cyst. A variety of imaging modalities failed to indicate GDC before the operation. Here we present the clinical course of the case and discuss the difficulties and problems in diagnosing GDC.

Abstract Background Babies born early and/or small for gestational age in Low and Middle-income countries (LMICs) contribute substantially to global neonatal and infant mortality. Tracking this metric is critical at a population level for informed policy, advocacy, resources allocation and program evaluation and at an individual level for targeted care. Early prenatal ultrasound examination is not available in these settings, gestational age (GA) is estimated using new-born assessment, last menstrual period (LMP) recalls and birth weight, which are unreliable. Algorithms in developed settings, using metabolic screen data, provided GA estimates within 1–2 weeks of ultrasonography-based GA. We sought to leverage machine learning algorithms to improve accuracy and applicability of this approach to LMICs settings. Methods This study uses data from AMANHI-ACT, a prospective pregnancy cohorts in Asia and Africa where early pregnancy ultrasonography estimated GA and birth weight are available and metabolite screening data in a subset of 1318 new-borns were also available. We utilized this opportunity to develop machine learning (ML) algorithms. Random Forest Regressor was used where data was randomly split into model-building and model-testing dataset. Mean absolute error (MAE) and root mean square error (RMSE) were used to evaluate performance. Bootstrap procedures were used to estimate confidence intervals (CI) for RMSE and MAE. For pre-term birth identification ROC analysis with bootstrap and exact estimation of CI for area under curve (AUC) were performed. Results Overall model estimated GA had MAE of 5.2 days (95% CI 4.6–6.8), which was similar to performance in SGA, MAE 5.3 days (95% CI 4.6–6.2). GA was correctly estimated to within 1 week for 85.21% (95% CI 72.31–94.65). For preterm birth classification, AUC in ROC analysis was 98.1% (95% CI 96.0–99.0; p

Introduction Manual counting of respiratory rate (RR) in children is challenging for health workers and can result in misdiagnosis of pneumonia. Some novel RR counting devices automate the counting of RR and classification of fast breathing. The absence of an appropriate reference standard to evaluate the performance of these devices is a challenge. If good quality videos could be captured, with RR interpretation from these videos systematically conducted by an expert panel, it could act as a reference standard. This study is designed to develop a video expert panel (VEP) as a reference standard to evaluate RR counting for identifying pneumonia in children.Methods and analysis Using a cross-sectional design, we will enrol children aged 0–59 months presenting with suspected pneumonia at different levels of health facilities in Dhaka and Sylhet, Bangladesh. We will videorecord a physician/health worker counting RR manually and also using an automated RR counter (Children’s Automated Respiration Monitor) from each child. We will establish a standard operating procedure for capturing quality videos, make a set of reference videos, and train and standardise the VEP members using the reference videos. After that, we will assess the performance of the VEP as a reference standard to evaluate RR counting. We will calculate the mean difference and proportions of agreement within±2 breaths per minute and create Bland-Altman plots with limits of agreement between VEP members.Ethics and dissemination The study protocol was approved by the National Research Ethics Committee of Bangladesh Medical Research Council, Bangladesh (registration number: 39315022021) and Edinburgh Medical School Research Ethics Committee (EMREC), Edinburgh, UK (REC Reference: 21-EMREC-040). Dissemination of the study findings will be through conference presentations and publications in peer-reviewed scientific journals.

Summary: Background: After considerable debate, there is now unequivocal evidence that use of antenatal corticosteroids improves outcomes in preterm neonates when used in women at risk of early preterm birth in reasonably equipped hospitals in low-resource countries. We aimed to evaluate the cost-effectiveness of dexamethasone administration in the management of preterm birth in a cohort of pregnant women from five low-resource countries. Methods: We performed a cost-effectiveness analysis using data from 2828 women (and 3051 babies) who participated in the WHO ACTION-I trial, a multicentre, randomised, placebo-controlled trial that assessed the safety and efficacy of dexamethasone in pregnant women at risk of early preterm birth in 29 hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan. We used a decision tree model to assess the cost-effectiveness of dexamethasone treatment compared with no intervention from a health-care sector perspective. Outcome data were taken from the primary results of the trial and primary data on cost were collected in 28 hospitals. The primary cost-effectiveness outcome was cost per neonatal death or the cost per disability-adjusted life-years (DALYs) averted, or costs saved per 1000 woman–baby units if the intervention was found to be cost-saving. Findings: Administration of dexamethasone averted 38 neonatal deaths per 1000 woman–baby units and 1132 DALYs per 1000 woman–baby units. Compared with no intervention, use of antenatal corticosteroids was cost-saving in all five countries, ranging from a saving of US$1778 per 1000 woman–baby units (95% uncertainty interval [UI] –13 878 to 9483) in Nigeria, to $20 531 per 1000 woman–baby units (–46 387 to 4897) in Pakistan, to $36 870 per 1000 woman–baby units (–61 569 to –15 672) in Bangladesh, to $38 303 per 1000 woman–baby units (–64 183 to –10 753) in India, and to $53 681 per 1000 woman–baby units (–113 822 to 2394) in Kenya. Findings remained consistent following sensitivity analyses. In all five countries, dexamethasone was more effective and cost less compared with no treatment. Interpretation: Antenatal dexamethasone for early preterm birth was cost-saving when used in hospitals in low-resource countries. Decision makers in low-resource settings can be confident that use of antenatal dexamethasone for early preterm birth is cost-effective, and often cost-saving when used in reasonably equipped hospitals in low-resource countries. Funding: Bill & Melinda Gates Foundation and WHO.

We report herein the synthesis, docking studies and biological evaluation of a series of new 4-chloro-2-((5-aryl-1,3,4-oxadiazol-2-yl)amino)phenol analogues (6a-h). The new compounds were designed based on the oxadiazole-linked aryl core of tubulin inhibitors of IMC-038525 and IMC-094332, prepared in five steps and further characterized via spectral analyses. The anticancer activity of the compounds was assessed against several cancer cell lines belonging to nine different panels as per National Cancer Institute (NCI US) protocol. 4-Chloro-2-((5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazol-2-yl)amino)phenol (6h) demonstrated significant anticancer activity against SNB-19 (PGI = 65.12), NCI-H460 (PGI = 55.61), and SNB-75 (PGI = 54.68) at 10 µM. The compounds were subjected to molecular docking studies against the active site of the tubulin–combretastatin A4 complex (PDB ID: 5LYJ); they displayed efficient binding and ligand 4h (with docking score = −8.030 kcal/mol) lay within the hydrophobic cavity surrounded by important residues Leu252, Ala250, Leu248, Leu242, Cys241, Val238, Ile318, Ala317, and Ala316. Furthermore, the antibacterial activity of some of the compounds was found to be promising. 4-Chloro-2-((5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl)amino)phenol (6c) displayed the most promising antibacterial activity against both Gram-negative as well as Gram-positive bacteria with MICs of 8 µg/mL and a zone of inhibition ranging from 17.0 ± 0.40 to 17.0 ± 0.15 mm at 200 µg/mL; however, the standard drug ciprofloxacin exhibited antibacterial activity with MIC values of 4 µg/mL.

In this paper, a radiating element consisting of a modified circular patch is proposed for MIMO arrays for 5G millimeter-wave applications. The radiating elements in the proposed 2 × 2 MIMO antenna array are orthogonally configured relative to each other to mitigate mutual coupling that would otherwise degrade the performance of the MIMO system. The MIMO array was fabricated on Rogers RT/Duroid high-frequency substrate with a dielectric constant of 2.2, a thickness of 0.8 mm, and a loss tangent of 0.0009. The individual antenna in the array has a measured impedance bandwidth of 1.6 GHz from 27.25 to 28.85 GHz for S11 ≤ −10 dB, and the MIMO array has a gain of 7.2 dBi at 28 GHz with inter radiator isolation greater than 26 dB. The gain of the MIMO array was increased by introducing frequency-selective surface (FSS) consisting of 7 × 7 array of unit cells comprising rectangular C-shaped resonators, with one embedded inside the other with a central crisscross slotted patch. With the FSS, the gain of the MIMO array increased to 8.6 dBi at 28 GHz. The radiation from the array is directional and perpendicular to the plain of the MIMO array. Owing to the low coupling between the radiating elements in the MIMO array, its Envelope Correlation Coefficient (ECC) is less than 0.002, and its diversity gain (DG) is better than 9.99 dB in the 5G operating band centered at 28 GHz between 26.5 GHz and 29.5 GHz.

This research investigated the antihypertensive effects of tamarind products and compared their potentials based on an animal model’s data verified by molecular docking, multitarget interactions, and dynamic simulation assays. GC-MS-characterized tamarind products were administered to cholesterol-induced hypertensive albino rat models. The two-week-intervened animals were dissected to collect their serum and organs and respectively subjected to analyses of their hypertension-linked markers and tissue architectures. The lead biometabolites of tamarinds interacted with eight target receptors in the molecular docking and dynamic simulation studies and with multitarget in the network pharmacological analyses. The results show that the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), C-reactive protein (CRP), troponin I, and lipid profiles were maximally reinstated by the phenolic-enriched ripened sour tamarind extract compared to the sweet one, but the seed extracts had a smaller influence. Among the tamarind’s biometabolites, ϒ-sitosterol was found to be the best ligand to interact with the guanylate cyclase receptor, displaying the best drug-likeliness with the highest binding energy, −9.3 Kcal. A multitargeted interaction-based degree algorithm and a phylogenetic tree of pathways showed that the NR3C1, REN, PPARG, and CYP11B1 hub genes were consistently modulated by ϒ-sitosterol to reduce hypertension and related risk factors. The dynamic simulation study showed that the P-RMSD values of ϒ-sitosterol–guanylate cyclase were stable between 75.00 and 100.00 ns at the binding pocket. The findings demonstrate that ripened sour tamarind extract may be a prospective antihypertensive nutraceutical or supplement target affirmed through advanced preclinical and clinical studies.

Background An important mechanism, by which cancer cells achieve immune escape, is the release of extracellular adenosine into their microenvironment. Adenosine activates adenosine A2A and A2B receptors on immune cells constituting one of the strongest immunosuppressive mediators. In addition, extracellular adenosine promotes angiogenesis, tumor cell proliferation, and metastasis. Cancer cells upregulate ectonucleotidases, most importantly CD39 and CD73, which catalyze the hydrolysis of extracellular ATP to AMP (CD39) and further to adenosine (CD73). Inhibition of CD39 is thus expected to be an effective strategy for the (immuno)therapy of cancer. However, suitable small molecule inhibitors for CD39 are not available. Our aim was to identify drug-like CD39 inhibitors and evaluate them in vitro.Methods We pursued a repurposing approach by screening a self-compiled collection of approved, mostly ATP-competitive protein kinase inhibitors, on human CD39. The best hit compound was further characterized and evaluated in various orthogonal assays and enzyme preparations, and on human immune and cancer cells.Results The tyrosine kinase inhibitor ceritinib, a potent anticancer drug used for the treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer, was found to strongly inhibit CD39 showing selectivity versus other ectonucleotidases. The drug displays a non-competitive, allosteric mechanism of CD39 inhibition exhibiting potency in the low micromolar range, which is independent of substrate (ATP) concentration. We could show that ceritinib inhibits ATP dephosphorylation in peripheral blood mononuclear cells in a dose-dependent manner, resulting in a significant increase in ATP concentrations and preventing adenosine formation from ATP. Importantly, ceritinib (1–10 µM) substantially inhibited ATP hydrolysis in triple negative breast cancer and melanoma cells with high native expression of CD39.Conclusions CD39 inhibition might contribute to the effects of the powerful anticancer drug ceritinib. Ceritinib is a novel CD39 inhibitor with high metabolic stability and optimized physicochemical properties; according to our knowledge, it is the first brain-permeant CD39 inhibitor. Our discovery will provide the basis (i) to develop more potent and balanced dual CD39/ALK inhibitors, and (ii) to optimize the ceritinib scaffold towards interaction with CD39 to obtain potent and selective drug-like CD39 inhibitors for future in vivo studies.

O-GlcNAcylation is a reversible post-translational modification that regulates numerous cellular processes, including embryonic development as well as immune responses. However, its role in inflammation remains ambiguous. This study was designed to examine the role of O-GlcNAcylation in rheumatoid arthritis (RA) and its regulation using human RA patient-derived synovial fibroblasts (RASFs). The efficacy of penta-O-galloyl-beta-D-glucose (PGG), a potent anti-inflammatory molecule, in regulating inflammatory processes in human RASFs was also evaluated. Human synovial tissues and RASFs exhibited higher expression of O-GlcNAcylation compared to their non-diseased counterparts. Pretreatment of RASFs with Thiamet G, an inhibitor of O-GlcNAcase, markedly increased the O-GlcNAc-modified proteins and concomitantly inhibited the IL-1β-induced IL-6 and IL-8 production in human RASFs in vitro. Pretreatment of human RASFs with PGG (0.5-10 µM) abrogated IL-1β-induced IL-6 and IL-8 production in a dose-dependent manner. Immunoprecipitation analysis showed that PGG inhibited O-GlcNAcylation of TAB1 to reduce its association with TGF β-activated kinase 1 (TAK1) and its autophosphorylation, an essential signaling step in IL-1β-induced signaling pathways. Molecular docking in silico studies shows that PGG occupies the C174 position, an ATP-binding site in the kinase domain to inhibit TAK1 kinase activity. Oral administration of PGG (25 mg/kg/day) for 10 days from disease onset significantly ameliorated rat adjuvant-induced (AIA) in rats. PGG treatment reduced the phosphorylation of TAK1 in the treated joints compared to AIA joints, which correlated with the reduced disease severity and suppressed levels of serum IL-1β, GM-CSF, TNF-α, and RANKL. These findings suggest O-GlcNAcylation as a potential therapeutic target and provide the rationale for testing PGG or structurally similar molecule for their therapeutic efficacy.

PurposeThe goal of this study is to investigate treatment planning of total marrow irradiation (TMI) using intensity-modulated spot-scanning proton therapy (IMPT). The dosimetric parameters of the intensity-modulated proton plans were evaluated and compared with the corresponding TMI plans generated with volumetric modulated arc therapy (VMAT) using photon beams.MethodsIntensity-modulated proton plans for TMI were created using the Monte Carlo dose-calculation algorithm in the Raystation 11A treatment planning system with spot-scanning proton beams from the MEVION S250i Hyperscan system. Treatment plans were generated with four isocenters placed along the longitudinal direction, each with a set of five beams for a total of 20 beams. VMAT-TMI plans were generated with the Eclipse-V15 analytical anisotropic algorithm (AAA) using a Varian Trilogy machine. Three planning target volumes (PTVs) for the bones, ribs, and spleen were covered by 12 Gy. The dose conformity index, D80, D50, and D10, for PTVs and organs at risk (OARs) for the IMPT plans were quantified and compared with the corresponding VMAT plans.ResultsThe mean dose for most of the OARs was reduced substantially (5% and more) in the IMPT plans for TMI in comparison with VMAT plans except for the esophagus and thyroid, which experienced an increase in dose. This dose reduction is due to the fast dose falloff of the distal Bragg peak in the proton plans. The conformity index was found to be similar (0.78 vs 0.75) for the photon and proton plans. IMPT plans provided superior superficial dose coverage for the skull and ribs in comparison with VMAT because of increased entrance dose deposition by the proton beams.ConclusionTreatment plans for TMI generated with IMPT were superior to VMAT plans mainly due to a large reduction in the OAR dose. Although the current IMPT-TMI technique is not clinically practical due to the long overall treatment time, this study presents an enticing alternative to conventional TMI with photons by providing superior dose coverage of the targets, increased sparing of the OARs, and enhanced radiobiological effects associated with proton therapy.

Background: Systematic assessment of childhood asthma is challenging in low- and middle-income country (LMIC) settings due to the lack of standardised and validated methodologies. We describe the contextual challenges and adaptation strategies in the implementation of a community-based asthma assessment in four resource-constrained settings in Bangladesh, India, and Pakistan. Method: We followed a group of children of age 6–8 years for 12 months to record their respiratory health outcomes. The study participants were enrolled at four study sites of the ‘Aetiology of Neonatal Infection in South Asia (ANISA)’ study. We standardised the research methods for the sites, trained field staff for uniform data collection and provided a ‘Child Card’ to the caregiver to record the illness history of the participants. We visited the children on three different occasions to collect data on respiratory-related illnesses. The lung function of the children was assessed in the outreach clinics using portable spirometers before and after 6-minute exercise, and capillary blood was examined under light microscopes to determine eosinophil levels. Results: We enrolled 1512 children, 95.5% (1476/1512) of them completed the follow-up, and 81.5% (1232/1512) participants attended the lung function assessment tests. Pre- and post-exercise spirometry was performed successfully in 88.6% (1091/1232) and 85.7% (1056/1232) of children who attempted these tests. Limited access to health care services, shortage of skilled human resources, and cultural diversity were the main challenges in adopting uniform procedures across all sites. Designing the study implementation plan based on the local contexts and providing extensive training of the healthcare workers helped us to overcome these challenges. Conclusion: This study can be seen as a large-scale feasibility assessment of applying spirometry and exercise challenge tests in community settings of LMICs and provides confidence to build capacity to evaluate children’s respiratory outcomes in future translational research studies.

Yomna M El-Meligui,1 Heba E Abd Elrhman,2 Ahmad Salahuddin,3 Manal Ali Hamouda,4 Amira B Kassem5 1Department of Clinical Pathology, National Cancer Institute, Cairo University, Cairo, Egypt; 2Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 3Biochemistry Department, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt; 4Clinical Pharmacy Department, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt; 5Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Damanhour University, Damanhour, EgyptCorrespondence: Amira B Kassem Email amira.kassem@pharm.dmu.edu.egIntroduction: Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. HLA-DR and CD117 (c-Kit) are important diagnostic markers of AML. Our objective is to determine the prognostic significance of HLA-DR and CD117 expressions in newly diagnosed AML patients and determine the correlation between HLA-DR and CD117 expressions and other prognostic markers such as cytogenetic abnormalities, FLT3-ITD, response to treatment, and patient’s survival.Methods: This study included 100 newly diagnosed AML patients. All patients were subjected to clinical, morphological, cytochemical, cytogenetic analysis, molecular genetic analysis to detect FLT3-ITD, and Flowcytometric detection of HLA-DR, CD117, and CD 34.Results: The results showed that HLA-DR expression was found in 75 patients (77.3%), while CD117 expression was found in 63 patients (64.9%). Patients with HLA-DR expression showed significantly higher mean Hb concentration, significantly higher platelet count, associated with AML-FAB subtypes (M0, M1, and M2), CD34 expression, and favorable cytogenetic group. M3 subtype was significantly associated with HLA-DR-ve. While patients with CD117 expression showed significantly lower platelets count. Double positive patients (HLA-DR+ve/CD117+ve) showed significant association with the intermediate cytogenetic group, while double-negative patients (HLA-DR-ve/CD117-ve) were associated with the favorable and intermediate cytogenetic group and either positive (HLA-DR+ve /CD117-ve or HLA-DR-ve/CD117+ve) associated with poor cytogenetic groups. FLT3-ITD expression had significantly worse overall survival.Conclusion: The current study suggested that the expression of CD117 and HLA-DR may be a prognostic marker in AML, as they are associated with M0, M1, and M2 FAB subtypes; moreover, patients with combined HLA-DR and CD117 positive expression are associated with CD34 expression and intermediate cytogenetic group.Keywords: acute myeloid leukemia, HLA-DR, CD117, CD34, FLT3-ITD, response, cytogenetic

Purpose: To investigate dosimetric implications of biodegradable Biozorb (BZ) markers for proton accelerated partial breast irradiation (APBI) plans. Materials and Methods: Six different BZs were placed within in-house breast phantoms to acquire computed tomography (CT) images. A contour correction method with proper mass density overriding for BZ titanium clip and surrounding tissue was applied to minimize inaccuracies found in the CT images in the RayStation planning system. Each breast phantom was irradiated by a monoenergetic proton beam (103.23 MeV and 8×8 cm2) using a pencil-beam scanning proton therapy system. For a range perturbation study, doses were measured at 5 depths below the breast phantoms by using an ionization chamber and compared to the RayStation calculations with 3 scenarios for the clip density: the density correction method (S1: 1.6 g/cm3), raw CT (S2), and titanium density (S3: 4.54 g/cm3). For the local dose perturbation study, the radiographic EDR2 film was placed at 0 and 2 cm below the phantoms and compared to the RayStation calculations. Clinical effects of the perturbations were retrospectively examined with 10 APBI plans for the 3 scenarios (approved by our institutional review board). Results: In the range perturbation study, the S1 simulation showed a good agreement with the chamber measurements, while excess pullbacks of 1~2 mm were found in the S2 and S3 simulations. The film study showed local dose shadowing and perturbation by the clips that RayStation could not predict. In the plan study, no significant differences in the plan quality were found among the 3 scenarios. However, substantial range pullbacks were observed for S3. Conclusion: The density correction method could minimize the dose and range difference between measurement and RayStation prediction. It should be avoided to simply override the known physical density of the BZ clips for treatment planning owing to overestimation of the range pullback.

Md Dilshad Manzar,1 Ahmad H Alghadir,2 Shahnawaz Anwer,2,3 Mazen Alqahtani,4 Mohammed Salahuddin,5,6 Habtamu Acho Addo,5 Wakuma Wakene Jifar,7 Nofaa Ali Alasmee8 1Department of Nursing, College of Applied Medical Sciences, Majmaah University, Majmaah, 11952, Saudi Arabia; 2Rehabilitation Research Chair, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia; 3Department of Building and Real Estate, Hong Kong Polytechnic University, Kowloon, Hong Kong Special Administrative Region; 4Department of Physiotherapy, College of Applied Medical Sciences, Majmaah University, Majmaah 11952, Saudi Arabia; 5Department of Pharmacy, College of Medicine and Health Sciences, Mizan-Tepi University (Mizan Campus), Mizan-Aman, Ethiopia; 6Pharmacology Division, Department of BioMolecular Sciences, University of Mississippi, Oxford, MS, USA; 7Department of Pharmacy, College of Health Science, Mettu University, Metu, Ethiopia; 8Faculty of Nursing, King Abdulaziz University, Jeddah, Saudi ArabiaCorrespondence: Shahnawaz Anwer Email shahnawaz.anwer@connect.polyu.hkBackground: Few studies have investigated the psychometric validation of the General Anxiety Disorders-7 Scale (GAD-7) using appropriate data assumptions. This study examined the reliability, factorial validity, divergent validity, and item analysis of the GAD-7 using categorical data methods in a sample of Ethiopian young adults.Methods: A sample of 270 students in the age group (18– 20 years) was recruited during February-May of 2017 in this cross-sectional study using simple random sampling. The participants completed a tool for socio-demographic details, the GAD-7, and the Perceived Stress Scale-10 (PSS-10).Results: The cumulative variance rule (> 40%), the scree test, Kaiser’s criteria (Eigenvalues > 1), and the parallel analysis found a 1-factor model for the GAD-7 (factor loadings, 0.38 to 0.63). Fit indices suggested a 1-factor model: the tests applied included the weighted root mean square residual (0.030), comparative fit index (1.000), the goodness of fit index (1.00), root mean square error of approximation (0.037) and the non-normed fit index (1.00). McDonald’s Omega (0.772) implied that the scores had adequate internal consistency. Divergent validity was supported by significant but weak correlations that were found between the GAD-7 and PSS-10 scores (r = 0.11 to 0.25, p< 0.05).Conclusion: The psychometric validity of the GAD-7 in Ethiopian university attending young adults was supported by the categorical data method.Keywords: anxiety, Africa, stress, McDonald’s omega, factor analysis

The current technological world is growing rapidly and each aspect of life is being transformed toward automation for human comfort and reliability. With autonomous vehicle technology, the communication gap between the driver and the traditional vehicle is being reduced through multiple technologies and methods. In this regard, state-of-the-art methods have proposed several approaches for advanced driver assistance systems (ADAS) to meet the requirement of a level-5 autonomous vehicle. Consequently, this work explores the role of textual cues present in the outer environment for finding the desired locations and assisting the driver where to stop. Firstly, the driver inputs the keywords of the desired location to assist the proposed system. Secondly, the system will start sensing the textual cues present in the outer environment through natural language processing techniques. Thirdly, the system keeps matching the similar keywords input by the driver and the outer environment using similarity learning. Whenever the system finds a location having any similar keyword in the outer environment, the system informs the driver, slows down, and applies the brake to stop. The experimental results on four benchmark datasets show the efficiency and accuracy of the proposed system for finding the desired locations by sensing textual cues in autonomous vehicles.

In this work, we used reflexive Banach spaces to study the differential variational—hemivariational inequality problems with constraints. We established a sequence of perturbed differential variational–hemivariational inequality problems with perturbed constraints and penalty coefficients. Then, for each perturbed inequality, we proved the unique solvability and convergence of the solutions to the problems. Following that, we proposed a mathematical model for a viscoelastic rod in unilateral contact equilibrium, where the unknowns were the displacement field and the history of the deformation. We used the abstract penalty method in the analysis of this inequality and provided the corresponding mechanical interpretations.

A 21-year-old male presented with a 2-week history of nausea and non-bloody, non-bilious vomiting, accompanied by diffuse chronic myalgia. The patient endorsed headaches, dizziness, and diplopia that had started one day prior to admission. The patient had consumed a meat-only diet for the prior year. The patient was found to have a high anion gap metabolic acidosis with a superimposed normal anion gap metabolic acidosis in the setting of a several-month history of ingesting multiple naturopathic substances as well as recent use of disulfiram for management of his chronic myalgia. Magnetic resonance imaging (MRI) of the brain demonstrated symmetric hyperintensity involving bilateral thalami, periventricular regions, putamina, pons and medulla, with sparing of the mammillary bodies, consistent with Wernicke’s encephalopathy (WE). The patient was treated with intravenous thiamine, a balanced nutritional diet, and hydration. Over the ensuing four days, his metabolic derangements resolved and a repeat MRI demonstrated significantly decreased FLAIR signal abnormality.

Md Dilshad Manzar,1 Mohammed Salahuddin,2,3 Seithikurippu R Pandi-Perumal,4 Ahmed S Bahammam5,6 1Department of Nursing, College of Applied Medical Sciences, Majmaah University, Al Majmaah 11952, Saudi Arabia; 2Department of Pharmacy, College of Medicine and Health Sciences, Mizan-Tepi University (Mizan Campus), Mizan-Aman, Ethiopia; 3Pharmacology Division, Department of BioMolecular Sciences, University of Mississippi, Oxford, MS, USA; 4Somnogen Canada Inc, Toronto, ON, Canada; 5The University Sleep Disorders Center, College of Medicine, King Saud University, Riyadh 11324, Saudi Arabia; 6National Plan for Science and Technology, College of Medicine, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Md Dilshad ManzarDepartment of Nursing, College of Applied Medical Sciences, Majmaah University, Al Majmaah 11952, Saudi ArabiaTel +966-551923468Email m.manzar@mu.edu.saBackground: High perceived stress and anxiety disorders are usually comorbid with each other, with stress often sequentially preceding the development of anxiety. While prior findings showed a causal role of sleep problems in anxiety, no study has assessed the role of insomnia as a mediator in the relationship between stress and anxiety.Methods: A cross-sectional study on university students (n = 475, age = 21.1+2.6 years) was conducted over 3 months. Participants completed self-report measures of Leeds Sleep Evaluation Questionnaire-Mizan (LSEQ-M), Perceived Stress Scale-10 (PSS-10), generalized anxiety disorder-7 scale (GAD-7), and a sociodemographic tool. The mediation effect model given by Baron and Kelly was used to determine the relationship.Results: The prevalence of insomnia and anxiety disorder was 43.6% and 21.9%, respectively. Stress was significantly associated with LSEQ-M (insomnia measure) (b = − .44, SE = 0.16, p< 0.01), and high levels of anxiety (b = 0.25, SE = 0.03, p < 0.01). The indirect effect of stress on anxiety through LSEQ-M (insomnia measure) was significant (95% confidence interval [0.01, 0.04]). However, the indirect effect of anxiety on stress through LSEQ-M (insomnia measure) was non-significant (95% confidence interval [− .01, 0.04]).Conclusions: Students having higher perceived stress levels and comorbid insomnia were also likely to have a higher anxiety level.Keywords: stress, anxiety, insomnia, mediator