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Abstract Sustainable development in urban areas requires a wide variety of current and theme-based information for efficient management and planning. In addition, researching the spatial distribution of earthquake (EQ) clusters is an important step in reducing seismic risks and EQ losses through better assessment of seismic hazards, therefore it is desirable to acquire an uncontaminated database of seismic activity. Quarry blasts (QBs) conducted over the mapped area have tainted the seismicity inventory in the northwestern region of Egypt, which is the focus of this paper. Separating these QBs from the EQs is hence preferable for accurate seismicity and risk assessments. Consequently, we present a highly effective ML model for cleaning up the seismicity database, allowing for the accurate delineation of EQ clusters using data from a single seismic station, “AYT”, which is part of the Egyptian National Seismic Network. The magnitudes $$\le 3$$ ≤ 3 that are very uncertain as EQs or QBs and need a significant amount of time to analyze are the primary focus of the model. In order to find the best way to classify EQs and QBs, the method looks at a number of ML models before settling on the best one using eight features. The results show that the suggested method, which uses the quadratic discrimination analysis model for discriminating, successfully separates EQs and QBs with a 99.4% success rate.

Abstract Suppression of fungal camptothecin (CPT) biosynthesis with the preservation and successive subculturing is the challenge that impedes fungi from the industrial application, so, screening for a novel fungal isolate with a conceivable stable producing potency of CPT was the main objective of this work. Catharanthus roseus with diverse contents of bioactive metabolites could have a plethora of novel endophytes with unique metabolic properties. Among the endophytes of C. roseus, Alternaria brassicicola EFBL-NV OR131587.1 was the highest CPT producer (96.5 μg/L). The structural identity of the putative CPT was verified by HPLC, FTIR, HNMR and LC–MS/MS, with a molecular mass 349 m/z, and molecular fragmentation patterns that typically identical to the authentic one. The purified A. brassicicola CPT has a strong antiproliferative activity towards UO-31 (0.75 μM) and MCF7 (3.2 μM), with selectivity index 30.8, and 7.1, respectively, in addition to resilient activity to inhibit Topo II (IC50 value 0.26 nM) than Topo 1 (IC50 value 3.2 nM). The purified CPT combat the wound healing of UO-31 cells by ~ 52%, stops their matrix formation, cell migration and metastasis. The purified CPT arrest the cellular division of the UO-31 at the S-phase, and inducing their cellular apoptosis by ~ 20.4 folds, compared to the control cells. Upon bioprocessing with the surface response methodology, the CPT yield by A. brassicicola was improved by ~ 3.3 folds, compared to control. The metabolic potency of synthesis of CPT by A. brassicicola was attenuated with the fungal storage and subculturing, losing ~ 50% of their CPT productivity by the 6th month of storage and 6th generation. Practically, the CPT productivity of the attenuated A. brassicicola was restored by addition of 1% surface sterilized leaves of C. roseus, ensuring the eliciting of cryptic gene cluster of A. brassicicola CPT via the plant microbiome-A. brassicicola interactions. So, for the first time, a novel endophytic isolate A. brassicicola, from C. roseus, was explored to have a relatively stable CPT biosynthetic machinery, with an affordable feasibility to restore their CPT productivity using C. roseus microbiome, in addition to the unique affinity of the extracted CPT to inhibit Topoisomerase I and II.

Abstract Background Coronavirus was primarily discovered in December 2019, causing pneumonia and severe acute respiratory syndrome. It was reported several neurological symptoms associated with COVID-19. Both the central and peripheral nervous systems could be affected which might result in a higher mortality rate in hospitalized patients. This study aimed to determine the spectrum of neurological clinical presentations among patients admitted to Fayoum University Hospital before, during, and after the COVID-19 era and to examine the influence of COVID-19 vaccines mandated by the Egyptian government on neurological disorders. Methods This is a historical cohort study that was conducted on patients admitted to the Neurology Department at Fayoum University Hospital before, during, and after COVID-19 outbreaks from January 1st, 2018, to July 31, 2022. All participants had undergone thorough history taking and neurological examination and the necessary investigations according to the suspected diagnosis. All hospitalized patients during the COVID-19 pandemic were positive for the virus, as determined by either a positive rapid antigen test or a positive real-time reverse transcription polymerase chain reaction (RT-PCR). Results It was shown that the patients hospitalized during the COVID-19 era were notably older, smokers, and diabetic in comparison to other groups. Cerebrovascular disorders were more prevalent in the COVID-19 pandemic. Surprisingly, compared to prior times, individuals with autoimmune-mediated neurological diseases had higher hospitalization rates than those with other neurological disorders. Patients who were not vaccinated reported more vascular complications than those who got them. However, patients who received vaccination exhibited significantly higher neurological complications as regards, exacerbation of paroxysmal disorders. Conclusion It was concluded that the frequency of hospitalizations with cerebrovascular disorders and autoimmune-mediated illnesses was significantly influenced during the pandemic era. Although COVID-19 vaccinations have potential adverse effects, they have played a crucial role in preventing serious neurological problems.

Abstract Attenuation of camptothecin (CPT) productivity by fungi with preservation and subculturing is the challenge that halts fungi to be an industrial platform of CPT production. Thus, screening for novel endophytic fungal isolates with metabolic stability for CPT production was the objective. Catharanthus roseus is one of the medicinal plants with diverse bioactive metabolites that could have a plethora of novel endophytes with unique metabolites. Among the endophytes of C. roseus, Aspergillus terreus EFBL-NV OR131583.1 had the most CPT producing potency (90.2 μg/l), the chemical identity of the putative CPT was verified by HPLC, FT-IR, NMR and LC–MS/MS. The putative A. terreus CPT had the same molecular mass (349 m/z), and molecular fragmentation patterns of the authentic one, as revealed from the MS/MS analyses. The purified CPT had a strong activity against MCF7 (5.27 μM) and UO-31 (2.2 μM), with a potential inhibition to Topo II (IC50 value 0.52 nM) than Topo 1 (IC50 value 6.9 nM). The CPT displayed a high wound healing activity to UO-31 cells, stopping their metastasis, matrix formation and cell immigration. The purified CPT had a potential inducing activity to the cellular apoptosis of UO-31 by ~ 17 folds, as well as, arresting their cellular division at the S-phase, compared to the control cells. Upon Plackett–Burman design, the yield of CPT by A. terreus was increased by ~ 2.6 folds, compared to control. The yield of CPT by A. terreus was sequentially suppressed with the fungal storage and subculturing, losing ~ 50% of their CPT productivity by 3rd month and 5th generation. However, the productivity of the attenuated A. terreus culture was completely restored by adding 1% surface sterilized leaves of C. roseus, and the CPT yield was increased over-the-first culture by ~ 3.2 folds (315.2 μg/l). The restoring of CPT productivity of A. terreus in response to indigenous microbiome of C. roseus, ensures the A. terreus-microbiome interactions, releasing a chemical signal that triggers the CPT productivity of A. terreus. This is the first reports exploring the potency of A. terreus, endophyte of C. roseus” to be a platform for industrial production of CPT, with an affordable sustainability with addition of C. roseus microbiome.

Abstract Hepatocellular carcinoma (HCC) is the third leading cause of cancer‐related death worldwide. Functionally uncharacterized genes are an attractive repository to explore candidate oncogenes. It is demonstrated that C21orf58 displays an oncogenic role in promoting cell growth, tumorigenesis and sorafenib resistance of HCC cells by abnormal activation of STAT3 signaling. Mechanistically, a novel manner to regulate STAT3 signaling that adaptor C21orf58 forms a ternary complex is reveal with N‐terminal domain of STAT3 and SH2 domain of JAK2, by which C21orf58 overactivates wild‐type STAT3 by facilitating its phosphorylation mediated by JAK2, and hyper‐activates of constitutively mutated STAT3 due to preferred binding with C21orf58 and JAK2. Moreover, it is validated that inhibition of C21orf58 with drug alminoprofen, selected by virtual screening, could effectively repress the viability and tumorigenesis of HCC cells. Therefore, it is identified that C21orf58 functions as an oncogenic adaptor, reveal a novel regulatory mechanism of JAK2/STAT3 signaling, explain the cause of abnormal activity of activated mutants of STAT3, and explore the attractive therapeutic potential by targeting C21orf58 in HCC.

This investigation concentrates on refining the accuracy of earthquake parameters as reported by various Saudi seismic networks, addressing the significant challenges arising from data discrepancies in earthquake location, depth, and magnitude estimations. The application of sophisticated machine learning techniques, particularly the Isolation Forest algorithm, has markedly enhanced the precision in the estimation of seismicity parameters by effectively identifying and eliminating outliers and discrepancies. A newly developed and refined seismicity catalog was employed to accurately determine key seismic parameters such as the magnitude of completeness (Mc), a-value, and b-value, thereby underlining their indispensable role in regional seismic hazard assessment. The research underscores the substantial impact of data inconsistencies on the evaluation of seismic hazards, thereby advocating for the advancement of research methodologies within the field of seismotectonics. The insights derived from this study significantly contribute to a more profound understanding of the seismotectonic processes in the region. These insights are crucial for the development of comprehensive seismic hazard assessments and the formulation of targeted earthquake preparedness strategies, thereby enhancing resilience against seismic risks in the region.

Fatma M Elsharkawy,1 Maha M Amin,2 Hesham A Shamsel-Din,3 Walaa Ibrahim,3 Ahmed B Ibrahim,3 Sinar Sayed2 1Regulatory Affairs Department, Al Andalous for Pharmaceutical Industries, Giza, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 3Labeled Compounds Department, Hot Labs Center, Egyptian Atomic Energy Authority, Cairo, 13759, EgyptCorrespondence: Sinar Sayed, Faculty of Pharmacy, Cairo University, Kasr El-Aini, Cairo, 11562, Egypt, Tel +2 01010421543, Email sinar.fouad@pharma.cu.edu.egPurpose: The research objective is to design intranasal brain targeted CLZ loaded lecithin based polymeric micelles (CLZ- LbPM) aiming to improve central systemic CLZ bioavailability.Methods: In our study, intranasal CLZ loaded lecithin based polymeric micelles (CLZ- LbPM) were formulated using soya phosphatidyl choline (SPC) and sodium deoxycholate (SDC) with different CLZ:SPC:SDC ratios via thin film hydration technique aiming to enhance drug solubility, bioavailability and nose to brain targeting efficiency. Optimization of the prepared CLZ-LbPM using Design-Expert® software was achieved showing that M6 which composed of (CLZ:SPC: SDC) in respective ratios of 1:3:10 was selected as the optimized formula. The optimized formula was subjected to further evaluation tests as, Differential Scanning Calorimetry (DSC), TEM, in vitro release profile, ex vivo intranasal permeation and in vivo biodistribution.Results: The optimized formula with the highest desirability exhibiting (0.845), small particle size (12.23± 4.76 nm), Zeta potential of (− 38 mV), percent entrapment efficiency of > 90% and percent drug loading of 6.47%. Ex vivo permeation test showed flux value of 27 μg/cm².h and the enhancement ratio was about 3 when compared to the drug suspension, without any histological alteration. The radioiodinated clozapine ([131I] iodo-CLZ) and radioiodinated optimized formula ([131I] iodo-CLZ-LbPM) were formulated in an excellent radioiodination yield more than 95%. In vivo biodistribution studies of [131I] iodo-CLZ-LbPM showed higher brain uptake (7.8%± 0.1%ID/g) for intranasal administration with rapid onset of action (at 0.25 h) than the intravenous formula. Its pharmacokinetic behavior showed relative bioavailability, direct transport percentage from nose to brain and drug targeting efficiency of 170.59%, 83.42% and 117% respectively.Conclusion: The intranasal self-assembling lecithin based mixed polymeric micelles could be an encouraging way for CLZ brain targeting.Graphical Abstract: Keywords: clozapine, soy lecithin, self-assembling polymeric micelles, intranasal route, brain targeting, radioiodinated clozapine, 131I

Abstract Background The thalamus is crucial in the development of idiopathic generalized epilepsy (IGE), which could lead to cognitive dysfunctions, according to data from neuropsychology and advanced neuroimaging investigations. This research aimed to measure the metabolic changes in the thalamus and to assess if could be contributed to cognitive impairment in IGE patients. Thirty IGE patients and thirty healthy volunteers with matched ages, genders, and educational levels participated in this cross-sectional case–control research. The IGE patients and controls were evaluated neuropsychologically using Intelligence Quotient (IQ) to assess general cognitive ability, Digit span for attention, Wechsler memory scale (WMS) for verbal memory, cube drawing test for visuospatial memory, Trail making test for executive functions, and Controlled Oral Word Association test (COWAT) for verbal fluency and quantitative multi-voxel MR spectroscopy (MRS) measurements of N-acetyl aspartate (NAA), choline (Cho), creatine (Cr), NAA/Cr, NAA/Cho and Cho/Cr ratios at 1.5 T scanner. The voxels were located over the right and left thalamus. Results The IGE patients showed worse cognitive performance in IQ, attention, executive function, and verbal and visuospatial memory domains compared to the controls. The IGE patients exhibited a significantly decrease NAA in the right thalamus (p = 0.004) and a lower NAA/Cr ratio in the left thalamus (p = 0.01). the mean thalamus NAA level exhibited a positive correlation with CDT (r = 0.45, p = P = 0.01), and WMS-R (r = 0.39, p = 0.03) and a negative correlation with trail-making A test (r = 0.42, P = 0.01). Conclusions it was concluded that IGE patients exhibited poor cognition which could be attributed to thalamic neurometabolic changes due to impaired thalamic cortical circuits.

Rice bran (RB) is distinguished by its chemical stability, insoluble in water, and local availability, in addition to the presence of ionizable functional groups which able to bind with the elements. Hence, this material was preferred to be utilized in this study as an operative biosorbent of altered hazardous ions such as Pb2+, Sr2+, and Eu3+ from simulated radioactive waste to attain a safe environment free from the risk of such waste. The kinetic studies illustrated that the sorption process obeys the pseudo-second-order model. From the isotherm studies, Langmuir is the most applicable isotherm model to the experimental data with monolayer sorption capacities of 1.26, 0.76, and 0.33 mmol/g for Sr2+, Eu3+, and Pb2+, respectively. The efficiency of RB was evaluated by applying it to a simulated radioactive waste containing multicomponent to study the interfering ions. When the sorption capacities of RB and other sorbents were compared, it became clear that RB had a significantly higher sorption capacity than most sorbents. The findings exposed that RB is a material with the potential for the treatment of radioactive waste and can be successfully applied in this regard.

Background Despite several improvements in surgical techniques, the intracorporeal division of the distal end of the rectum is still challenging, particularly when it is too deep in a narrow pelvis. Even though it helps avoid spillage, the double-stapling technique (DST) raises concerns regarding safety and anastomotic leakage if multiple stapler firings are essential to complete the rectal division. Objective To assess the feasibility of vertically dividing the rectum and its impact in reducing the number of reloads essential for that division in non-low rectal cancer patients undergoing total mesorectal excision (TME). Materials and Methods A retroprospective study. Results From January 2017 to November 2021, a total of 123 patients with sigmoid and rectal cancers were enrolled in the present study; their data were collected and analyzed, and 21 patients were excluded. The remaining sample of 102 subjects was composed of 47 male (46%) and 55 female (54%) patients with a median age of 54 years (range: 30 to 78 years). Only 1 reload was enough to complete the rectal division in 82 (80.39%) cases, and 2 reloads were used in the remaining 20 (19.61%) patients. Anastomotic leakage was clinically evident in 4 cases (3.9%). No statically significant difference was observed when firing one or two staplers. No 30-day mortality was recorded in this series. Conclusion Our early experience indicates that this type of division has a real advantage in terms of decreasing the number of reloads needed and, in turn, lowering the incidence of anastomotic leakage after partial mesorectal excision (PME) or TME when applied with proper patient selection.

This investigation displayed a superb catalytic performance toward the formic acid electro-oxidation reaction (FAOR) in an alkaline medium at a binary catalyst composed of Pt and Pd that were simultaneously electrodeposited onto a glassy carbon (GC) surface. Interestingly, the proposed PtPd/GC catalyst displayed a significant enhancement in the catalytic activity (by ca. 12 times higher direct (Ipd) to indirect (Ipind) current ratio concurrently with ca. -91 mV shift in the onset potential (Eonset) and stability (ca. 2.5 times higher current density after 3600 s of continuous electrolysis) toward FAOR if compared to the Pt/GC catalyst. The catalytic enhancement was thought to arise mostly from minimizing the CO adsorption, i.e., third body effect, at the Pt surface during FAOR.

A comprehensive geostatistical analysis was conducted on a dataset comprising 24,321 seismic events in the Red Sea region, spanning from 1997 to 2020. This analysis involved the creation of a new seismic activity database, incorporating data from both Egyptian and Saudi Seismic Networks. This enriched database provided a robust foundation for a detailed examination of the seismic patterns and activities in the region. Utilizing geographic information systems and various spatial analytic methods, it identifies seismic patterns and tectonic influences. The findings reveal significant seismic clustering along the Central Red Sea axis, indicative of active rifting between the Nubian and Arabian plates. The study demonstrates spatial autocorrelation in seismic activities, with high-high clusters marking zones of elevated seismicity. Kernel Density Estimator analyses highlight concentrated seismic activity in the Gulfs of Aqaba and Suez. Higher magnitude events are shown to localize in areas of greater tectonic stress, aligning with known geological features. This research provides critical insights into the seismic dynamics of the Red Sea, showcasing the effectiveness of geostatistical techniques in analyzing seismic data in tectonically active regions.

Developing a safe and effective vaccine against the hepatitis C virus (HCV) remains a top priority for global health. Despite recent advances in antiviral therapies, the high cost and limited accessibility of these treatments impede their widespread application, particularly in resource-limited settings. Therefore, the development of the HCV vaccine remains a necessity. This review article analyzes the current technologies, future prospects, strategies, HCV genomic targets, and the governmental role in HCV vaccine development. We discuss the current epidemiological landscape of HCV infection and the potential of HCV structural and non-structural protein antigens as vaccine targets. In addition, the involvement of government agencies and policymakers in supporting and facilitating the development of HCV vaccines is emphasized. We explore how vaccine development regulatory channels and frameworks affect research goals, funding, and public health policy. The significance of international and public-private partnerships in accelerating the development of an HCV vaccine is examined. Finally, the future directions for developing an HCV vaccine are discussed. In conclusion, the review highlights the urgent need for a preventive vaccine to fight the global HCV disease and the significance of collaborative efforts between scientists, politicians, and public health organizations to reach this important public health goal.

Lactate dehydrogenase (LDH, EC 1.1.1.27) is one of the vital glycolytic conditions, especially during anaerobic conditions. It is a significant diagnostic, prognostic, and monitoring biomarker parameter. A 950-bp DNA fragment containing the gene (LDH) encoding LDH was amplified from Bacillus cereus NRC1. The deduced amino acid sequence reveals that B. cereus LDH (Bc-LDH) is highly homologous to the LDHs of Bacillus organisms. All LDH enzymes have a significant degree of conservation in their active site and several additional domains with unidentified functions. The gene for LDH, which catalyzes lactate synthesis, was cloned, sequenced (accession number: LC706200.1), and expressed in Escherichia coli BL21 (DE3). In this investigation, Bc-LDH was purified to homogeneity with a specific activity of 22.7 units/mg protein and a molecular weight of 35 kDa. It works optimally at pH 8.0. The purified enzyme was inhibited by FeCl2, CuCl2, ZnCl2, and NiCl, whereas CoCl2 was found to boost the activity of Bc-LDH. The molecular docking of the 3D model of the Bc-LDH structure with a natural inhibitor, mangiferin, demonstrated excellent LDH inhibition, with a free binding energy of −10.2 kcal/mol. Moreover, mangiferin is a potent Bc-LDH inhibitor that inhibits Bc-LDH competitively and has one binding site with a Ki value of 0.075 mM. The LDH-mangiferin interaction exhibits a low RMSF value (>1.5 Å), indicating a stable contact at the residues. This study will pave the way for more studies to improve the understanding of mangiferin, which could be considered an intriguing candidate for creating novel and improved LDH inhibitors.

Reena Shah,1 Jasmit Shah,1 Nancy Kunyiha,1 Sayed K Ali,1 Shahin Sayed,2 Salim Surani,3 Mansoor Saleh4 1Department of Medicine, Aga Khan University, Nairobi, Kenya; 2Department of Pathology, Aga Khan University, Nairobi, Kenya; 3Department of Medicine & Pharmacology, Texas A&M University, College Station, TX, USA; 4Department of Hematology and Oncology, Aga Khan University, Nairobi, KenyaCorrespondence: Reena Shah, Department of Medicine, Aga Khan University, East Tower Block, 3 rd Parklands Avenue, P.O. Box 30270 – 00100, Nairobi, Kenya, Tel +254 735 338003, Email reena.shah@aku.eduIntroduction: The first documented case of COVID-19 in Kenya was recorded March of 2020. Co-morbidities including hypertension and diabetes have been associated with increased morbidity, hospitalization, and mortality among COVID-19 patients. This retrospective study describes the clinical characteristics, disease severity, and outcomes among the patient population at a tertiary hospital in Kenya.Methods: This was a retrospective descriptive study of COVID-19 patients who were admitted between March 2020 and December 2020 at the Aga Khan University Hospital in Nairobi, Kenya. Data collected include patient demographic and baseline characteristics. Differences between patients who were known to have diabetes and hypertension during admission were compared for statistical significance. Difference between those who survived and those who died were also compared for statistical significance.Results: A total of 913 records of patients were studied with a mean age of 51.2 years (SD = 16.7), 66.5% were male and 80.8% were of African origin. History of diabetes, hypertension, and HIV status were at 27.3%, 33.1%, and 2.3%, respectively. At presentation, 33.1% (302/913) of patients had known hypertension by history, and following admission, this proportion increased to 37.7% (344/913). At presentation, 27.3% (249/913) of patients had known diabetes. During hospital stay, 20.8% (190) more patients were found to have diabetes, raising the overall percent to 48.1% (439/913). When comparing diabetes and hypertension at baseline versus at the end of admission, diabetes increased by 20.8% (p < 0.001) and hypertension by 4.6% (p = 0.049). HIV co-infection was 2.3%, and no patient had tuberculosis.Conclusion: This study showed a high incidence of co-morbidities in patients infected with COVID-19. Diabetes was most common, followed by hypertension. All patients admitted with COVID-19 infection should routinely be tested for diabetes with HbA1c and have regular blood pressure monitoring in order to diagnose occult diabetes and hypertension. Adverse outcomes were found in patients with these co-morbidities and should be monitored and treated appropriately.Keywords: COVID-19, diabetes, hypertension, sub-Saharan Africa

Effective management and planning for sustainable urban regions’ development require up-to-date information. Natural hazard maps (NHMs) creation is critical for urban development. Urban areas along the western coast of Saudi Arabia are susceptible to natural disasters due to their hazard sources’ proximity, especially, with the lack of preparation. Yanbu’ Al-Bahr, a major Red Sea port, provides an excellent example. This research aims to combine NHMs into a single multi-hazard map, allowing acceptable site identification for urban development. To create a seismic hazard model of the rapidly growing Yanbu’ Al-Bahr region, spatial distributions of different hazard entities were assessed using the analytical hierarchy process (AHP). To create a multi-hazard map, six seismic hazard assessment maps were independently developed. Hazard attributes were assimilated into a geographic information system (GIS) platform to delineate seismic hazard zones and build a suitability map for urban development. Weight and rank values were determined during AHP and assigned to each layer and its corresponding classes. By overlaying all the weighted maps, a suitability map was created. This map depicts the research area’s prospective appropriateness for urban growth. Accordingly, the study area was classified into five hazard categories, namely, very-low (VL), low (L), moderate (M), high (H), and very high (VH). Therefore, the limited regions, most appropriate locations, and least suitable areas were identified. Accordingly, stakeholders can use the produced seismic hazard map as a platform for future land-use planning and environmental hazard management. Furthermore, the AHP-GIS model would deliver more precise findings in urban development site selection studies.

Daclatasvir dihydrochloride (DAC) is a drug used to treat hepatitis C virus (HCV) infection. In this study, an ionophore-based nanosphere emulsion was made of tricresyl phosphate (TCP) as the oil phase that is dispersed in water using Pluronic F-127 as an emulsifying agent. The nanospheres, consisting of the oil phase TCP, were doped with sodium tetraphenyl borate (Na-TPB) as a cation-exchanger and dibenzo-18-Crown-6 (DB18C6) as an ionophore (chelating agent) for DAC. The nanosphere emulsion was employed as a titrant in the complexometric titration of DAC (the analyte), and the DAC-selective electrode (ISE) was used as an indicator electrode to detect the endpoint. In the sample solution, DAC2+ ions diffused into the emulsified nanospheres, replaced Na+ from the ion exchanger (Na-TPB), and bonded to the ionophore (DB18C6). The DAC-selective nanospheres were successfully utilized to determine DAC in various samples, including standard solutions, commercial tablets (Daclavirocyrl®), serum, and urine. The method exhibited a linear dynamic range of 81.18 µg/mL to 81.18 pg/mL (10−4 to 10−10 M), achieved high recovery values ranging from 99.4% to 106.5%, and displayed excellent selectivity over similar interfering species (sofosbuvir and ledipasvir). The proposed method offers a new approach to determine the drug species (neutral, anionic, and cationic) without the requirement of water-soluble ligands or pH control.

In this study, the formic acid electro-oxidation reaction (FAEOR) was catalyzed on a Pd-Au co-electrodeposited binary catalyst. The kinetics of FAEOR were intensively impacted by changing the Pd2+:Au3+ molar ratio in the deposition medium. The Pd1-Au1 catalyst (for which the Pd2+:Au3+ molar ratio was 1:1) acquired the highest activity with a peak current density for the direct FAEOR (Ip) of 4.14 mA cm−2 (ca. 13- times higher than that (ca. 0.33 mA cm−2) of the pristine Pd1-Au0 catalyst). It also retained the highest stability that was denoted in fulfilling ca. 0.292 mA cm−2 (ca. 19-times higher than 0.015 mA cm−2 of the pristine Pd1-Au0 catalyst) after 3600 s of continuous electrolysis at 0.05 V. The CO stripping and impedance measurements confirmed, respectively, the geometrical and electronic enhancements in the proposed catalyst.

Gopala Koneru,1 Gaber El-Saber Batiha,2 Abdelazeem M Algammal,3 Mahmoud Mabrok,4,5 Sara Magdy,6 Shrouk Sayed,6 Mai E AbuElmagd,6 Reham Elnemr,6 Mahmoud M Saad,6 Noura H Abd Ellah,7 Amal Hosni,8 Khalid Muhammad,9,* Helal F Hetta10,11,* 1Department of Medicine, Division of Gastroenterology and Hepatology, Rutger New Jersey Medical School, Rutgers University, New Brunswick, NJ, 07103, USA; 2Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicines, Damanhour University, Damanhur, 22511, Egypt; 3Department of Bacteriology, Immunology, and Mycology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt; 4Department of Fish Diseases and Management, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt; 5Fish Infectious Diseases Research Unit (FID RU), Department of Veterinary Microbiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand; 6Faculty of Medicine, Assiut University, Assiut, 71515, Egypt; 7Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt; 8Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt; 9Department of Biology, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates; 10Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt; 11Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA*These authors contributed equally to this workCorrespondence: Khalid Muhammad; Helal F Hetta Email k.muhammad@uaeu.ac.ae; helalhetta@aun.edu.egAbstract: In late 2019, a new virulent coronavirus (CoV) emerged in Wuhan, China and was named as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This virus spread rapidly, causing the coronavirus disease-2019 (COVID-19) pandemic. Bacillus Calmette–Guérin (BCG) is a live attenuated tuberculosis (TB) vaccine, associated with induction of non-specific cross-protection against unrelated infections. This protection is a memory-like response in innate immune cells (trained immunity), which is caused by epigenetic reprogramming via histone modification in the regulatory elements of specific genes in monocytes. COVID-19 related epidemiological studies showed an inverse relationship between national BCG vaccination policies and COVID-19 incidence and death, suggesting that BCG may induce trained immunity that could confer some protection against SARS-CoV-2. As this pandemic has put most of Earth’s population under quarantine, repurposing of the old, well-characterized BCG may ensure some protection against COVID-19. This review focuses on BCG-related cross-protection and acquisition of trained immunity, as well as the correlation between BCG vaccination and COVID-19 incidence and mortality.Keywords: COVID-19, BCG vaccine, coronavirus, trained immunity, tuberculosis

Ground vibrations caused by blasting operations in cement canisters is among the main mining issues that cause significant disruptions to nearby buildings and infrastructure. This research was performed in a limestone quarry situated southeast of Helwan City, Egypt, to investigate the impact of ground motion vibration due to cement blast action in limestone rocks. To reduce the environmental impact of quarry blasting, continuous monitoring, and accurate medium's peak particle velocity (PPV) assessment are required. Recently, machine learning (ML) models are employed in diverse applications. The default hyperparameters of such models must be modified to fit the problem concerned. The hyperparameters optimization for ML models impacts the employed model's performance and efficiency. In this research, different regression models are implemented for predicting the PPV values. A dataset representing 1438 blast incidents in the Helwan area was built and utilized to evaluate the considered ML models. This dataset incorporates the relationship of the ground vibration amplitude to both the explosive charge weight per delay and distance from the blast. The predictive models' output performance has been evaluated using the root-mean-squared error (RMSE) and the coefficient of determination ($R^{2}$ ). The PPV dataset has been divided into training and testing data to produce statistically significant results and to make the dataset more representative to avoid overfitting. The utilized test PPV dataset acts as a proxy for any new PPV data prediction. There was evidence of higher performance in the developed Decision Trees model with the lowest RMSE and the highest $R^{2}$ on training and testing data. The decision tree is, therefore, an acceptable algorithm for the construction of a predictive PPV model for other quarry blasting areas with conditions identical to those in Helwan. Finally, comparative experimental results have shown that optimized models can predict PPV values with lower errors and greater prediction accuracy.

Investigations made to evaluate the site-effect characteristics and to develop a reliable site classification scheme have received paramount importance for the urban areas planning and reliable site-specific seismic hazard assessment. This paper presents a novel non-objective and data-driven approach for preliminary seismic site-specific classification maps using machine learning (ML) based on affinity propagation (AP) along with a selected set of representative horizontal to vertical spectral ratio (HVSR) curves inside King Saud University (KSU) campus, which is among the main areas in Saudi Arabia. Besides, the proposed model aims to overcome the clustering error due to the dependency of the interpreter’s experience. Measurements of the ambient vibrations were performed to cover the entire campus area by about 307 stations. Recording at each station lasted for 20 minute length and a sample rate of 128 Hz for each station to satisfy the criteria for reliable and unambiguous HVSR results. Frequency and amplification values were used for subsequent site classification by passing messages between data points. The obtained results illustrate that the microtremor spectral ratio can be a remarkably robust tool in determining site effects. Accordingly, the proposed methodology can assist the decision-makers to set the priorities of managing land uses, estimating the earthquake losses, conducting programs for reducing the vulnerability of existing structures, enforcing building codes, planning for emergency response and long-term recovery, and designing and implementing phases of new constructions.

Mankind is vulnerable to artificial seismic sources and accompanying explosions’ consequences. Recently, seismicity catalog contamination is among the main problems faced by seismologists. Since identifying artificial seismic sources is the first and always challenging stage, it is imperative to develop an automated control system that will discriminate tectonic from non-tectonic events. Detection and removal of the artificial seismic sources have become urgent. Early treatments and cleaning of contaminated seismicity catalogs are crucial to assist in accurate seismic hazard identification and enhance the planning of future urban developments. With the advancement of machine learning (ML) techniques, artificial seismic source detection accuracy has been improved. Today, there are different kinds of methods, ML techniques, and diverse processes like knowledge discovery are developed for discriminating artificial seismic sources and earthquakes. ML techniques offer various probabilistic and statistical methods that allow intelligent systems to learn from reoccurring experiences to detect and identify patterns from a dataset. This study aims to build an automated system that is able to detect the existence of artificial seismic sources in seismicity catalogs. More concretely, we classify seismic activity reports into two classes using classical and ensemble ML algorithms. Classical seismicity parameters or features are supplied to linear and nonlinear ML classifiers. The proposed scheme based on the four features (Latitude, Longitude, depth, and Magnitude) can enhance the performance. To assure the enhanced performance, we have examined the proposed scheme by both the accuracy of each model, ROC curves, Precision-Recall, and Calibration. The obtained results prove that the ensemble learning algorithms exhibit better results compared to other classical ML algorithms by having 98.14% testing accuracy.

Sadek Ahmed, Mohamed Aly Kassem,† Sinar Sayed Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt†Mohamed Kassem, passed away on August 21, 2020Correspondence: Sinar SayedFaculty of Pharmacy, Cairo University, Kasr El-Aini, Cairo 11562, EgyptTel +2 0 1010421543Email sinar.fouad@pharma.cu.edu.egPurpose: The goal of this research was to enhance the transdermal delivery of lornoxicam (LX), using nanovesicular carriers composed of the bile salt sodium deoxycholate (SDC), soybean phosphatidyl choline (SPC) and a permeation enhancer limonene.Methods: Thin-film hydration was the technique employed for the fabrication using a Box–Behnken design with three central points. The investigated factors were SPC molar concentration, SDC amount in mg and limonene percentage (%). The studied responses were percent entrapment efficiency (%EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and in vitro drug release (after 2, 10 h). In order to obtain the optimum formula, numerical optimization by Design-Expert® software was used. Electing the optimized bilosomal formula was based on boosting %EE, ZP (as absolute value) and in vitro drug release, taking in consideration diminishing PS and PDI. Further assessment of the selected formula was achieved by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), stability testing, ex vivo skin permeation and deposition. The in vivo pharmacodynamics activities of the optimized formula were examined on male rats and mice and compared to that of the oral market product.Results: The optimized bilosomal formula demonstrated to be nonirritant, with noticeably enhanced anti-inflammatory and antinociceptive activities. Superior in vivo permeation was proved by confocal laser scanning microscopy (CLSM).Conclusion: The outcomes demonstrated that bilosomes could improve transdermal delivery of lornoxicam.Keywords: lornoxicam, permeation enhancer, factorial design, confocal laser scanning microscopy, antinociceptive

A propitious binary catalyst composed of Pt and Cu which were electrodeposited simultaneously onto a glassy carbon (GC) substrate was recommended for the formic acid (FA) electro-oxidation reaction (FAOR); the principal anodic reaction in the direct FA fuel cells (DFAFCs). The simultaneous co-electrodeposition of Pt and Cu in the catalyst provided an opportunity to tune the geometric functionality of the catalyst to resist the adsorption of poisoning CO at the Pt surface that represented the major impediment for DFAFCs marketing. The catalytic activity of the catalyst toward FAOR was significantly influenced by the (Pt4+/Cu2+) molar ratio of the electrolyte during electrodeposition, which also affected the surface coverage of Pt and Cu in the catalyst. Interestingly, with a molar (Pt4+/Cu2+) ratio of (1:4), the catalyst sustained superior (3.58 compared to 0.65 obtained at the pristine Pt/GC catalyst) activity for FAOR, concurrently with up to four-times (0.73 compared to 0.18 obtained at the pristine Pt/GC catalyst) improvement in the catalytic tolerance against CO poisoning. This associated, surprisingly, a negative shift of ca. 336 mV in the onset potential of FAOR, in an indication for the competitiveness of the catalyst to minimize superfluous polarizations in DFAFCs. Furthermore, it offered a better (ended up with 20% loss in the activity) stability for continuous (1 h) electrolysis than pristine Pt/GC catalyst (the loss reached 35%). The impedance and CO stripping measurements together excluded the electronic element but confirmed the geometrical influence in the catalytic enhancement.

Background: Middle East respiratory syndrome coronavirus (MERS-CoV) was primarily detected in 2012 and still causing disease in human and camel. Camel and bats have been identified as a potential source of virus for disease spread to human. Although, significant information related to MERS-CoV disease, spread, infection, epidemiology, clinical features have been published, A little information is available on the sequence diversity of Spike protein gene. The Spike protein gene plays a significant role in virus attachment to host cells. Recently, the information about recombinant MERS-CoV has been published. So, this work was designed to identify the emergence of any another recombinant virus in Jeddah, Saudi Arabia. Methods: In this study samples were collected from both human and camels and the Spike protein gene was amplified and sequenced. The nucleotide and amino acid sequences of MERS-CoV Spike protein gene were used to analyze the recombination, genetic diversity and phylogenetic relationship with selected sequences from Saudi Arabia. Results: The nucleotide sequence identity ranged from 65.7% to 99.8% among all the samples collected from human and camels from various locations in the Kingdom. The lowest similarity (65.7%) was observed in samples from Madinah and Dammam. The phylogenetic relationship formed different clusters with multiple isolates from various locations. The sample collected from human in Jeddah hospital formed a closed cluster with human samples collected from Buraydah, while camel sample formed a closed cluster with Hufuf isolates. The phylogenetic tree by using Aminoacid sequences formed closed cluster with Dammam, Makkah and Duba isolates. The amino acid sequences variations were observed in 28/35 samples and two unique amino acid sequences variations were observed in all samples analyzed while total 19 nucleotides sequences variations were observed in the Spike protein gene. The minor recombination events were identified in eight different sequences at various hotspots in both human and camel samples using recombination detection programme. Conclusion: The generated information from this study is very valuable and it will be used to design and develop therapeutic compounds and vaccine to control the MERS-CoV disease spread in not only in the Kingdom but also globally. Keywords: Genetic diversity, MERS-CoV, Human, Camel, Saudi Arabia

The second leading cause of death in the world is cancer. Mitogen-activated protein kinase (MAPK) and extracellular signal-regulated protein kinase (ERK) 1 and 2 (MEK1/2) stand out among the different anticancer therapeutic targets. Many MEK1/2 inhibitors are approved and widely used as anticancer drugs. The class of natural compounds known as flavonoids is well-known for their therapeutic potential. In this study, we focus on discovering novel inhibitors of MEK2 from flavonoids using virtual screening, molecular docking analyses, pharmacokinetic prediction, and molecular dynamics (MD) simulations. A library of drug-like flavonoids containing 1289 chemical compounds prepared in-house was screened against the MEK2 allosteric site using molecular docking. The ten highest-scoring compounds based on docking binding affinity (highest score: −11.3 kcal/mol) were selected for further analysis. Lipinski’s rule of five was used to test their drug-likeness, followed by ADMET predictions to study their pharmacokinetic properties. The stability of the best-docked flavonoid complex with MEK2 was examined for a 150 ns MD simulation. The proposed flavonoids are suggested as potential inhibitors of MEK2 and drug candidates for cancer therapy.

Middle East respiratory syndrome coronavirus (MERS-CoV) is caused by a well-known coronavirus first identified in a hospitalized patient in the Kingdom of Saudi Arabia. MERS-CoV is a serious pathogen affecting both human and camel health globally, with camels being known carriers of viruses that spread to humans. In this work, MERS-CoV genomic sequences were retrieved and analyzed by multiple sequence alignment to design and predict siRNAs with online software. The siRNAs were designed from the orf1ab region of the virus genome because of its high sequence conservation and vital role in virus replication. The designed siRNAs were used for experimental evaluation in selected cell lines: Vero cells, HEK-293-T, and Huh-7. Virus inhibition was assessed according to the cycle threshold value during a quantitative real-time polymerase chain reaction. Out of 462 potential siRNAs, we filtered out 21 based on specific selection criteria without off-target effect. The selected siRNAs did not show any cellular toxicity in the tested cell lines at various concentrations. Based on our results, it was obvious that the combined use of siRNAs exhibited a reduction in MERS-CoV replication in the Vero, HEK-293-T, and Huh-7 cell lines, with the highest efficacy displayed in the Vero cells.

Quiescent faults may be capable of creating catastrophic earthquakes in locations with moderate and/or low seismic activity, such as Egypt. This study combines structural, remote sensing (RS), geophysical, and seismic activity data to examine and analyze the relationship between tectonic structures and seismotectonic activity in Egypt. In a new seismo-lineaments map of Egypt, tectonic lineaments of the Egyptian mainland were delineated and classified. The database contains 8000 lineaments that were divided into distinct geographical zones using statistical analysis and general features. Delineated lineaments were integrated with digitized geological and geophysical surface and subsurface faults and geographic information systems (GIS) processing techniques were applied to produce 4249 faults. The spatial distribution of seismic activity was determined to extract 1968 competent faults out of 4249 capable faults (i.e., greater than 10 km and suitably orientated concerning the existing stress field). Maximum expected magnitudes (Mmax) were calculated for distinct seismogenic locations in Egypt, taking into account the nature of the regional rupture. At the national scale, empirical scaling relations between fault lengths and earthquake magnitude were employed for all mapped faults in Egypt. The findings concerning the faults were highly consistent with traditional geological information. The results suggest that our technique for estimating the highest predicted magnitudes produces similar values and might be used to evaluate Egypt’s possible future seismic hazard. The results were compared to seismic databases. The similarity of our results with those reported in the catalogs lends confidence to the proposed scheme.

Infectious diseases are the disorders caused by organisms such as bacteria, viruses, fungi, or parasites. Although many of them are permentantly hazardous, a number of them live in and on our bodies and they are normally harmless or even helpful. Under certain circumstances, some organisms may cause diseases and these infectious diseases may be passed directly from person to person or via intermediate vectors including insects and other animals. Dengue virus and Streptococcus pneumoniae are the critical and common sources of infectious diseases. So, it is critical to understand the gene expression profiling and their inferred functions in comparison to the normal and virus infected conditions. Here, we have analyzed the gene expression profiling for dengue hemorrhagic fever, dengue fever, and normal human dataset. Similar to it, streptococcus pneumoniae infectious data were analyzed and both the outcomes were compared. Our study leads to the conclusion that the dengue hemorrhagic fever arises in result to potential change in the gene expression pattern, and the inferred functions obviously belong to the immune system, but also there are some additional potential pathways which are critical signaling pathways. In the case of pneumoniae infection, 19 pathways were enriched, almost all these pathways are associated with the immune system and 17 of the enriched pathways were common with dengue infection except platelet activation and antigen processing and presentation. In terms of the comparative study between dengue virus and Streptococcus pneumoniae infection, we conclude that cell adhesion molecules (CAMs), MAPK signaling pathway, natural killer cell mediated cytotoxicity, regulation of actin cytoskeleton, and cytokine-cytokine receptor interaction are commonly enriched in all the three cases of dengue infection and Streptococcus pneumoniae infection, focal adhesion was enriched between classical dengue fever — dengue hemorrhagic fever, dengue hemorrhagic fever—normal samples, and SP, and antigen processing and presentation and Leukocyte transendothelial migration were enriched in classical dengue fever —normal samples, dengue hemorrhagic fever—normal samples, and Streptococcus pneumoniae infection.

Hussain Darraj,1 Mohammed Badedi,1 Kirsten R Poore,2 Abdulrahman Hummadi,1 Abdullah Khawaji,1 Yahia Solan,3 Ibrahim Zakri,1 Abdullah Sabai,1 Majid Darraj,4 Dhayf Alrahman Mutawwam,1 Mohammed Daghreeri,1 Safaa Sayed,1 Wael Alaallah,1 Abdulaziz Alfadhly,5 Abdullah Alsabaani61Jazan Health Affairs, Ministry of Health, Jazan, Saudi Arabia; 2Institute of Development Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; 3Medical Affairs, Jazan University Hospital, Jazan University, Jazan, Saudi Arabia; 4Department of Internal Medicine, College of Medicine, Jazan University, Jazan, Saudi Arabia; 5Diabetic Center, Prince Mansour Military Hospital, Taif, Saudi Arabia; 6Department of Family and Community Medicine, College of Medicine, King Khalid University, Abha, Saudi ArabiaBackground: The prevalence of vitamin D deficiency (VDD) is predicted to be high in patients with type 2 diabetes mellitus (T2DM), but the exact figure is not known in Jazan, Saudi Arabia. Emerging data suggests that VDD plays a role in glycemic control. The aim of this study was to measure the prevalence of VDD among T2DM patients and to investigate its association with patients’ characteristics and glycemic control in Jazan.Methods: This is an analytical cross-sectional study which recruited 309 patients with T2DM randomly from primary health care centers in Jazan. Logistic regression analysis was conducted to determine the VDD predictors and to examine the association of VDD and glycemic control.Results: The VDD prevalence was found to be 60.8% in patients with T2DM. Age, gender, diabetic retinopathy (DR), dyslipidemia, glycemic control, and obesity were significantly associated with VDD, and all except obesity were independent predictors of VDD. There was a significant negative correlation between 25-hydroxyvitamin D and HbA1c. VDD was a significant independent predictor of poor glycemic control after adjustment for hypertension, DR, diabetic neuropathy, type of diabetes medication, diabetes duration, and education level.Conclusion: In this Saudi Arabian population, VDD is highly prevalent in people with T2DM and is associated with poor glycemic control. Health education targeting patients with T2DM and national strategies regarding vitamin D fortification are needed to prevent VDD in Saudi Arabia. Earlier VDD diagnosis by health care providers may help to improve the outcome for patients with T2DM. Establishing the causal association between VDD and glycemic control and clarifying the biological role of vitamin D in T2DM are important aims for future studies.Keywords: diabetes mellitus, T2DM, vitamin D deficiency, VDD, glycemic control, diabetes complication

Diseases caused by begomoviruses represent serious threat to crop cultivation globally. A field survey was conducted in June, 2018 and severe leaf curl disease symptoms were observed on Dahlia pinnata at Ballia, U.P. India. The association of begomovirus was identified by polymerase chain reaction (PCR). The viral components were amplified by Rolling circle amplification (RCA); and digested with BamH1 and ECoRV which released the 2.7 kb fragment. The betasatellites was amplified by using betasatellites specific primers. The fragments were cloned, sequenced, analyzed and submitted to GenBank under the accession numbers (MK122994-full-length) and (MK122995-betasatellites). The full genome had total 2780 nucleotides, whereas betasatellites had 1347 nucleotides. The nucleotide sequence of full genome showed the highest identity (99.5%- 98.4%) with Tomato leaf curl Patna virus (ToLCPaV); infecting Casia tora, tomato, and Xanthium strumarium. The lowest sequence identity (37.9%) was observed with Chickpea chlorotic dwarf virus infecting X. strumarium in Pakistan. The betasatellites sequence showed the highest identity (99.2%) with Tomato leaf curl Patna betasatellites from C. tora. Currently, the association of begomovirus is known for Tomato, C. tora and X. strumarium in eastern U.P. and Bihar. Based on these findings, the begomovirus was tentatively known as a strain of ToLCPaV and designated as ToLPaV-Dahlia. This is a preliminary investigation about the natural occurrence of begomovirus causing leaf curl disease on D. pinnata in India.

Objective: The new coronavirus disease 2019 (COVID-19) is a major health problem worldwide. The surveillance of seropositive individuals serves as an indicator to the extent of infection spread and provides an estimation of herd immunity status among population. Reports from different countries investigated this issue among healthcare workers (HCWs) who are “at risk” and “sources of risk” for COVID-19. This study aims to investigate the seroprevalence of COVID-19 among HCWs in one of the COVID-19 referral centers in Makkah, Saudi Arabia using three different serological methods. Methods: In-house developed enzyme-linked immunoassay (ELISA), commercially available electro-chemiluminescence immunoassay (ECLIA), and microneutralization (MN) assay were utilized to determine the seroprevalence rate among the study population. 204 HCWs participated in the study. Both physicians and nurses working in the COVID-19 and non COVID-19 areas were included. Twelve out of 204 were confirmed cases of COVID-19 with variable disease severity. Samples from recovered HCWs were collected four weeks post diagnosis. Results: The overall seroprevalence rate was 6.3% (13 out of 204) using the in-house ELISA and MN assay and it was 5.8% (12 out of 204) using the commercial ECLIA. Among HCWs undiagnosed with COVID-19, the seroprevalence was 2% (4 out 192). Notably, neutralizing antibodies were not detected in 3 (25%) out 12 confirmed cases of COVID-19. Conclusions: Our study, similar to the recent national multi-center study, showed a low seroprevalence of SARS-Cov-2 antibodies among HCWs. Concordance of results between the commercial electro-chemiluminescence immunoassay (ECLIA), in-house ELISA and MN assay was observed. The in-house ELISA is a promising tool for the serological diagnosis of SARS-CoV-2 infection. However, seroprevalence studies may underestimate the extent of COVID-19 infection as some cases with mild disease did not have detectable antibody responses.

Summary: Background: An estimated 5·1 million stillbirths and neonatal deaths occur annually. Household surveys, most notably the Demographic and Health Survey (DHS), run in more than 90 countries and are the main data source from the highest burden regions, but data-quality concerns remain. We aimed to compare two questionnaires: a full birth history module with additional questions on pregnancy losses (FBH+; the current DHS standard) and a full pregnancy history module (FPH), which collects information on all livebirths, stillbirths, miscarriages, and neonatal deaths. Methods: Women residing in five Health and Demographic Surveillance System sites within the INDEPTH Network (Bandim in Guinea-Bissau, Dabat in Ethiopia, IgangaMayuge in Uganda, Matlab in Bangladesh, and Kintampo in Ghana) were randomly assigned (individually) to be interviewed using either FBH+ or FPH between July 28, 2017, and Aug 13, 2018. The primary outcomes were stillbirths and neonatal deaths in the 5 years before the survey interview (measured by stillbirth rate [SBR] and neonatal mortality rate [NMR]) and mean time taken to complete the maternity history section of the questionnaire. We also assessed between-site heterogeneity. This study is registered with the Research Registry, 4720. Findings: 69 176 women were allocated to be interviewed by either FBH+ (n=34 805) or FPH (n=34 371). The mean time taken to complete FPH (10·5 min) was longer than for FBH+ (9·1 min; p

Abstract Background Clinically isolated syndrome (CIS) is the first neurologic episode of multiple sclerosis (MS). Clinical presentation, neurophysiological studies, and magnetic resonance imaging (MRI) are used to predict risk of conversion to MS. There is little information regarding the risk factors of CIS conversion to MS so far in the Egyptian patients. This study aimed to evaluate the predictors of early conversion of the Egyptian patients with CIS to MS. Methods A longitudinal prospective study was conducted on 43 Egyptian patients diagnosed as CIS according to the McDonald criteria (2010). The CIS patients underwent clinical assessment of disability using Expanded Disability Status Scale(EDSS), brain imaging by magnetic resonance imaging (MRI), and visual evoked potential (VEP) at baseline and after 1-year follow-up. Results Eight patients (19.6%) with CIS converted to clinically definite MS after 1 year. A logistic regression analysis revealed that the CIS patients with initial clinical presentation with optic neuritis and higher MRI brain lesion number were associated with early conversion to MS (p = 0.003, p = 0.002, respectively). The total MRI brain T2 lesion number that predicts early conversion to MS was four lesions with sensitivity (100%) and specificity (85.7%). Conclusions The patients with CIS that early presented with optic neuritis and higher MRI brain lesion number are at higher risk for conversion to clinically definite MS.

Ibrahim Elsayed,1,2 Sinar Sayed1 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman, United Arab Emirates Abstract: Ocular drug delivery systems suffer from rapid drainage, intractable corneal permeation and short dosing intervals. Transcorneal drug permeation could increase the drug availability and efficiency in the aqueous humor. The aim of this study was to develop and optimize nanostructured formulations to provide accurate doses, long contact time and enhanced drug permeation. Nanovesicles were designed based on Box–Behnken model and prepared using the thin film hydration technique. The formed nanodispersions were evaluated by measuring the particle size, polydispersity index, zeta potential, entrapment efficiency and gelation temperature. The obtained desirability values were utilized to develop an optimized nanostructured in situ gel and insert. The optimized formulations were imaged by transmission and scanning electron microscopes. In addition, rheological characters, in vitro drug diffusion, ex vivo and in vivo permeation and safety of the optimized formulation were investigated. The optimized insert formulation was found to have a relatively lower viscosity, higher diffusion, ex vivo and in vivo permeation, when compared to the optimized in situ gel. So, the lyophilized nanostructured insert could be considered as a promising carrier and transporter for drugs across the cornea with high biocompatibility and effectiveness. Keywords: thin-film hydration, in situ, insert, confocal, transcorneal, tenoxicam

Identified in 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and often fatal acute respiratory illness in humans. No approved prophylactic or therapeutic interventions are currently available. In this study, we developed chicken egg yolk antibodies (IgY Abs) specific to the MERS-CoV spike (S) protein and evaluated their neutralizing efficiency against MERS-CoV infection. S-specific IgY Abs were produced by injecting chickens with the purified recombinant S protein of MERS-CoV at a high titer (4.4 mg/mL per egg yolk) at week 7 post immunization. Western blotting and immune-dot blot assays demonstrated specific binding to the MERS-CoV S protein. In vitro neutralization of the generated IgY Abs against MERS-CoV was evaluated and showed a 50% neutralizing concentration of 51.42 μg/mL. In vivo testing using a human-transgenic mouse model showed a reduction of viral antigen positive cells in treated mice, compared to the adjuvant-only controls. Moreover, the lung cells of the treated mice showed significantly reduced inflammation, compared to the controls. Our results show efficient neutralization of MERS-CoV infection both in vitro and in vivo using S-specific IgY Abs. Clinical trials are needed to evaluate the efficiency of the IgY Abs in camels and humans.

A few months ago, the availability of a reliable and cost-effective testing capacity for COVID-19 was a concern for many countries. With the emergence and circulation of new SARS-CoV-2 variants, another layer of challenge can be added for COVID-19 testing at both molecular and serological levels. This is particularly important for the available tests principally designed to target the S gene/protein where multiple mutations have been reported. Herein, the SARS-CoV-2 NP recombinant protein was utilized to develop a simple and reliable COVID-19 NP human IgG ELISA. The optimized protocol was validated against a micro-neutralization (MN) assay, in-house S-based ELISA, and commercial chemiluminescence immunoassay (CLIA). The developed assay provides 100% sensitivity, 98.9% specificity, 98.9% agreement, and high overall accuracy with an area under curve equal to 0.9998 ± 0.0002 with a 95% confidence interval of 0.99 to 1.00. The optical density values of positive samples significantly correlated with their corresponding MN titers. The assay specifically detects IgG antibodies to the SARS-CoV-2 NP protein and does not cross-detect IgG to the viral S protein. Moreover, it does not cross-react with antibodies related to other coronaviruses (e.g., the Middle East respiratory syndrome coronavirus or human coronavirus HKU1). The availability of this reliable COVID-19 NP IgG ELISA protocol is highly valuable for its diagnostic and epidemiological applications.

The unusual cases of pneumonia outbreak were reported from Wuhan city in late December 2019. Serological testing provides a powerful tool for the identification of prior infection and for epidemiological studies. Pseudotype virus neutralization assays are widely used for many viruses and applications in the fields of serology. The accuracy of pseudotype neutralizing assay allows for its use in low biosafety lab and provides a safe and effective alternative to the use of wild-type viruses. In this study, we evaluated the performance of this assay compared to the standard microneutralization assay as a reference. The lentiviral pseudotype particles were generated harboring the Spike gene of SARS-CoV-2. The generated pseudotype particles assay was used to evaluate the activity of neutralizing antibodies in 300 human serum samples from a COVID-19 sero-epidemiological study. Testing of these samples resulted in 55 positive samples and 245 negative samples by pseudotype viral particles assay while microneutralization assay resulted in 64 positive and 236 negative by MN assay. Compared to the MN, the pseudotyped viral particles assay showed a sensitivity of 85.94% and a specificity of 100%. Based on the data generated from this study, the pseudotype-based neutralization assay showed a reliable performance for the detection of neutralizing antibodies against SARS-CoV-2 and can be used safely and efficiently as a diagnostic tool in a biosafety level 2 laboratory.

In response to the coronavirus disease 2019 (COVID-19), Saudi Arabia have imposed timely restrictions to minimize the infection spread, lower the risk for vulnerable groups, and reduce the pressure on healthcare services. The effectiveness of these measures has not been assessed comprehensively and, thereby, remains uncertain. Besides monitoring the number of COVID-19 cases diagnosed by molecular assays, the seroprevalence can serve as an indicator for the incidence rate among the general population. This study aimed to evaluate seroprevalence status of all healthy blood donors who attended one of the main largest hospital located in the western region of Saudi Arabia from 1 January to 31 May 2020. The study period covered two months prior to reporting the first COVID-19 case in the country on 2 March 2020. Importantly, it covered the period when “lock-down type” measures have been enforced. Samples were subjected to in-house enzyme-linked immunosorbent assay (ELISA), chemiluminescence immunoassay (CLIA), and microneutralization (MN). The sero statuses of all samples were confirmed negative, demonstrating the lack of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among blood donors during COVID-19 lockdown period. This study supports the hypothesis that COVID-19 restrictions have potential for limiting the extent of the infection.

The ongoing coronavirus disease 19 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a threat to human health. Despite this, many affected countries are now in the process of gradual lifting of COVID-19 restrictions that were initially implemented in response to the pandemic. The success of the so-called “exit strategy” requires continued surveillance of virus circulation in the community and evaluation of the prevalence of protective immunity among population. Serology tests are valuable tools for these purposes. Herein, SARS-CoV-2 full-length spike (S) recombinant protein was utilized to develop and optimize an indirect enzyme-linked immunoassay (ELISA) that enables a reliable detection of virus-specific IgG antibody in human sera. Importantly, the performance of this assay was evaluated utilizing micro-neutralization (MN) assay as a reference test. Our developed ELISA offers 100% sensitivity, 98.4% specificity, 98.8% agreement, and high overall accuracy. Moreover, the optical density (OD) values of positive samples significantly correlated with their MN titers. The assay specifically detects human IgG antibodies directed against SARS-CoV-2, but not those to Middle East respiratory syndrome coronavirus (MERS-CoV) or human coronavirus HKU1 (HCoV-HKU1). The availability of this in-house ELISA protocol would be valuable for various diagnostic and epidemiological applications.

This study focused on rhizobacteria to promote sustainable crop production in arid regions of Saudi Arabia. The study isolated 17 tightly root-adhering rhizobacteria from various plants at Hada Al Sham in Saudi Arabia. All 17 rhizobacterial isolates were confirmed as plant growth promoting rhizobacteria by classical biochemical tests. Using 16S rDNA gene sequence analyses, the strains were identified as Bacillus, Acinetobacter and Enterobacter. Subsequently, the strains were assessed for their ability to improve the physiology, nutrient uptake, growth, and yield of alfalfa plants grown under desert agriculture conditions. The field trials were conducted in a randomized complete block design. Inoculation of alfalfa with any of these 17 strains improved the relative water content; chlorophyll a; chlorophyll b; carotenoid contents; nitrogen (N), phosphorus, and potassium contents; plant height; leaf-to-stem ratio; and fresh and dry weight. Acinetobacter pittii JD-14 was most effective to increase fresh and dry weight of alfalfa by 41 and 34%, respectively, when compared to non-inoculated control plants. Nevertheless, all strains enhanced crop traits when compared to controls plants, indicating that these desert rhizobacterial strains could be used to develop an eco-friendly biofertilizer for alfalfa and possibly other crop plants to enhance sustainable production in arid regions.

This study attempts to develop empirical correlations between average penetration resistance ([Formula: see text]), averaged velocities over depth up to bedrock depth ([Formula: see text]) and 30 m ([Formula: see text]) for shallow depth sites (having bedrock at a depth less than 25 m). A total of 63 shallow sites were assessed for penetration resistance values up to the bedrock from Standard Penetration Tests (SPT) and dynamic soil property analysis, i.e., Shear Wave Velocity (VS) from Multichannel Analysis of Surface Waves. The study shows that 30 m averaged shear wave velocities are more than the average velocity up to bedrock depth in shallow bedrock sites because of inclusion of rock site velocity. Furthermore, averaged SPT-N([Formula: see text]) and average VS ([Formula: see text]) up to bedrock depth were correlated with the 30 m average([Formula: see text]) values. This is the first attempt in developing empirical relationships of this kind for seismic site classification. These correlations can be made useful for seismic site classification of sites in regions with Standard Penetration Test (NSPT) values and limited VS values. Further surface and bedrock motion recordings of 12 selected KiK-net shallow depth sites were collected and amplifications were estimated with the respective peak ground acceleration, spectral acceleration and thereby related to the average shear wave velocity up to bedrock and 30 m. The results show that the amplification is better correlated to the [Formula: see text] than [Formula: see text] for shallow depth sites, and more data can be added to strengthen this correlation.