Search results for: viral mutation

Authors: Yasser Ahmed Mahmoud Ali Helal

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The use of CAD (Computer Aided Design) technology is ubiquitous in the architecture, engineering and construction (AEC) industry. This has led to its inclusion in the curriculum of architecture schools in Nigeria as an important part of the training module. This article examines the ethical issues involved in implementing CAD (Computer Aided Design) content into the architectural education curriculum. Using existing literature, this study begins with the benefits of integrating CAD into architectural education and the responsibilities of different stakeholders in the implementation process. It also examines issues related to the negative use of information technology and the perceived negative impact of CAD use on design creativity. Using a survey method, data from the architecture department of University was collected to serve as a case study on how the issues raised were being addressed. The article draws conclusions on what ensures successful ethical implementation. Millions of people around the world suffer from hepatitis C, one of the world's deadliest diseases. Interferon (IFN) is treatment options for patients with hepatitis C, but these treatments have their side effects. Our research focused on developing an oral small molecule drug that targets hepatitis C virus (HCV) proteins and has fewer side effects. Our current study aims to develop a drug based on a small molecule antiviral drug specific for the hepatitis C virus (HCV). Drug development using laboratory experiments is not only expensive, but also time-consuming to conduct these experiments. Instead, in this in silicon study, we used computational techniques to propose a specific antiviral drug for the protein domains of found in the hepatitis C virus. This study used homology modeling and abs initio modeling to generate the 3D structure of the proteins, then identifying pockets in the proteins. Acceptable lagans for pocket drugs have been developed using the de novo drug design method. Pocket geometry is taken into account when designing ligands. Among the various lagans generated, a new specific for each of the HCV protein domains has been proposed.

Keywords: drug design, anti-viral drug, in-silicon drug design, hepatitis C virus (HCV) CAD (Computer Aided Design), CAD education, education improvement, small-size contractor automatic pharmacy, PLC, control system, management system, communication

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Authors: Sarah Holdren, Laura Crook, Anne Drapkin Lyerly

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Objective: The COVID-19 Pandemic has drawn new attention to long-existing bioethical questions around pregnancy, childbirth, and parenthood. Due to the increased risk of severe COVID-19, pregnant individuals may experience anxiety regarding medical decision-making. Especially in the case of hospital births, questions around the ethics of bringing healthy pregnant individuals into a high-risk environment for viral transmission illuminate gaps in the American maternal and child healthcare system. Limited research has sought to understand the experiences of those who gave birth outside hospitals during this time. This study aims to understand pregnant individuals’ conceptualization of risk during the COVID-19 pandemic. Methods: Individuals who gave birth after March 2020 were recruited through advertisements on social media. Participants completed a 1-hour semi-structured interview and a demographic questionnaire. Interviews were transcribed and coded by members of the research team using thematic narrative analysis. Results: A total of 18 participants were interviewed and completed the demographic questionnaire. The language of risk was utilized in birth narratives in three different ways, which highlighted the multileveled and nuanced ways in which risk is understood and mitigated by pregnant and birthing individuals. These included: 1. The risk of contracting COVID-19 before, during, and after birth, 2. The risk of birth complications requiring medical interventions dependent on selected birthing space (home, birthing center, hospital), and 3. The overall risk of creating life in the middle of a pandemic. The risk of contracting COVID-19 and risk of birth complications were often weighed in paradoxical ways throughout each individual’s pregnancy, while phrases such as “pandemic baby” and “apocalypse” appeared throughout narratives and highlighted the broader implications of pregnancy and childbirth during this momentous time. Conclusions: Healthcare professionals should consider the variety of ways that pregnant and birthing individuals understand the risk when counseling patients on healthcare decisions, especially during times of healthcare crisis such as COVID-19. Future work should look to understand how the language of risk fits into a broader understanding of the human experience of growing life in times of crisis.

Keywords: maternal and child health, thematic narrative analysis, COVID-19, risk mitigation

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Authors: Yori Gidron, Maartje Mol, Norbert Foudraine, Frits Van Osch, Joop Van Den Bergh, Moshe Farchi, Maud Straus

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Background: The worldwide pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-COV2), which began in 2019, also known as Covid-19, has infected over 136 million people and tragically took the lives of over 2.9 million people worldwide. Many of the complications and deaths are predicted by the inflammatory “cytokine storm.” One way to progress in the prevention of death is by finding a predictive and protective factor that inhibits inflammation, on the one hand, and which also increases anti-viral immunity on the other hand. The vagal nerve does precisely both actions. This study examined whether vagal nerve activity, indexed by heart-rate variability (HRV), predicts survival in patients with Covid-19. Method: We performed a pseudo-prospective study, where we retroactively obtained ECGs of 271 Covid-19 patients arriving at a large regional hospital in The Netherlands. HRV was indexed by the standard deviation of the intervals between normal heartbeats (SDNN). We examined patients’ survival at 3 weeks and took into account multiple confounders and known prognostic factors (e.g., age, heart disease, diabetes, hypertension). Results: Patients’ mean age was 68 (range: 25-95) and nearly 22% of the patients had died by 3 weeks. Their mean SDNN (17.47msec) was far below the norm (50msec). Importantly, relatively higher HRV significantly predicted a higher chance of survival, after statistically controlling for patients’ age, cardiac diseases, hypertension and diabetes (relative risk, H.R, and 95% confidence interval (95%CI): H.R = 0.49, 95%CI: 0.26 – 0.95, p < 0.05). However, since HRV declines rapidly with age and since age is a profound predictor in Covid-19, we split the sample by median age (40). Subsequently, we found that higher HRV significantly predicted greater survival in patients older than 70 (H.R = 0.35, 95%CI: 0.16 – 0.78, p = 0.01), but HRV did not predict survival in patients below age 70 years (H.R = 1.11, 95%CI: 0.37 – 3.28, p > 0.05). Conclusions: To the best of our knowledge, this is the first study showing that higher vagal nerve activity, as indexed by HRV, is an independent predictor of higher chances for survival in Covid-19. The results are in line with the protective role of the vagal nerve in diseases and extend this to a severe infectious illness. Studies should replicate these findings and then test in controlled trials whether activating the vagus nerve may prevent mortality in Covid-19.

Keywords: Covid-19, heart-rate Variability, prognosis, survival, vagal nerve

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Authors: Recep Kesli, Cengiz Demir, Riza Durmaz, Zekiye Bakkaloglu, Aysegul Bukulmez

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Objective: Acute diarrhea disease in children is a major cause of morbidity worldwide and is a leading cause of mortality, and it is the most common agent responsible for acute gastroenteritis in developing countries. With hospitalized children suffering from acute enteric disease up to 50% of the analyzed specimen were positive for rotavirus. Further molecular surveillance could provide a sound basis for improving the response to epidemic gastroenteritis and could provide data needed for the introduction of vaccination programmes in the country. The aim of this study was to investigate the prevalence of viral etiology of the gastroenteritis in children aged 0-6 years with acute gastroenteritis and to determine predominant genotypes of rotaviruses in the province of Afyonkarahisar, Turkey. Methods: An epidemiological study on rotavirus was carried out during 2016. Fecal samples obtained from the 144 rotavirus positive children with 0-6 years of ages and applied to the Pediatric Diseases Outpatient of ANS Research and Practice Hospital, Afyon Kocatepe University with the complaint of diarrhea. Bacterial agents causing gastroenteritis were excluded by using bacteriological culture methods and finally, no growth observed. Rotavirus antigen was examined by both the immunochromatographic (One Step Rotavirus and Adenovirus Combo Test, China) and ELISA (Premier Rotaclone, USA) methods in stool samples. Rotavirus RNA was detected by using one step real-time reverse transcription-polymerase chain reaction (RT-PCR). G and P genotypes were determined using RT-PCR with consensus primers of VP7 and VP4 genes, followed by semi nested type-specific multiplex PCR. Results: Of the total 144 rotavirus antigen-positive samples with RT-PCR, 4 (2,8%) were rejected, 95 (66%) were examined, and 45 (31,2%) have not been examined for PCR yet. Ninety-one (95,8%) of the 95 examined samples were found to be rotavirus positive with RT-PCR. Rotavirus subgenotyping distributions in G, P and G/P genotype groups were determined as; G1:45%, G2:27%, G3:13%, G9:13%, G4:1% and G12:1% for G genotype, and P[4]:33%, P[8]:66%, P[10]:1% for P genotype, and G1P[8]:%37, G2P[4]:%21, G3P[8]:%10, G4P[8]:%1, G9P[8]:%8, G2P[8]:%3 for G/P genotype . Not common genotype combination were %20 in G/P genotype. Conclusions: This study subscribes to the global agreement of the molecular epidemiology of rotavirus which will be useful in guiding the alternative and application of rotavirus vaccines or effective control and interception. Determining the diversity and rates of rotavirus genotypes will definitely provide guidelines for developing the most suitable vaccine.

Keywords: gastroenteritis, genotyping, rotavirus, RT-PCR

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Authors: Samuel E. Okere, Anthony E. Ataga

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Introduction: This paper evaluated the mineral compositions, disease resistance elicitors in Pleurotus ostratus (POWESMS), and Pleurotus tuber-regium water extract spent mushroom substrate (PTWESMS) on the growth, yield, and management of cassava mosaic disease. Materials and Methods: The cassava plantlet (tms 98/0505) were generated through meristem tip culture at the Tissue Culture Laboratory, National Root Crop Research Institute, Umudike before they were transferred to the screen house, University of Port Harcourt Research Farm. The minerals and elicitors contained in the two spent mushroom substrates were evaluated using standard procedures. The treatments for this investigation comprised cassava plants treated with POWESMS, PTWESMS, and untreated cassava as control, which were inoculated with viral inoculum seven days after treatment application. The experiment was laid out in a completely randomized block design with 3 replicates. The data generated were subjected to analysis of variance (ANOVA). Means were separated using Fishers Least Significant Difference at p=0.05. Results: The results obtained revealed that POWESMS contained 19.3, 0.52, and 0.1g/200g substrate of carbohydrate polymers, glycoproteins, and lipid molecules elicitors respectively while it also contained 3.17, 212.1, 17.9,21.8, 58.8 and 111.0 mg/100g substrate for N, P, K, Na, Mg and Ca respectively. Further, PTWESMS contain 1.6, 0.04, and 0.2g/200g of the substrate as carbohydrate polymers, glycoprotein, and lipid respectively; the minerals contained in this substrate were 3.4, 204.8, 8.9, 24.2, 32.2 and 105.5 mg respectively for N, P, K, Na, and Ca. There were also significant differences in the mean values of the number of storage roots, root length, fresh root weight, fresh weight plant biomass, root girth, and whole plant dry biomass, but no significant difference was recorded for harvest index. The result also revealed significant differences in mean values of disease severity index evaluated at 4, 8, 12, 16, 20, 24, and 28 weeks after inoculation (WAI). Conclusion: The aqueous extract of these spent mushrooms substrate have shown outstanding prospect in managing cassava mosaic disease and also improvement in growth and yield of cassava due to the high level of the minerals and elicitors they contain when compared with the control. However, more work is recommended, especially in understanding the mechanism of this induced resistance.

Keywords: characterization, elicitors, mosaic, mushroom

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Authors: Abdoulie K. Ceesay

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Within the sequence of the whole genome, it is known that 99.9% of the human genome is similar, whilst our difference lies in just 0.1%. Among these minor dissimilarities, the most common type of genetic variations that occurs in a population is SNP, which arises due to nucleotide substitution in a protein sequence that leads to protein destabilization, alteration in dynamics, and other physio-chemical properties’ distortions. While causing variations, they are equally responsible for our difference in the way we respond to a treatment or a disease, including various cancer types. There are two types of SNPs; synonymous single nucleotide polymorphism (sSNP) and non-synonymous single nucleotide polymorphism (nsSNP). sSNP occur in the gene coding region without causing a change in the encoded amino acid, while nsSNP is deleterious due to its replacement of a nucleotide residue in the gene sequence that results in a change in the encoded amino acid. Predicting the effects of cancer related nsSNPs on protein stability, function, and dynamics is important due to the significance of phenotype-genotype association of cancer. In this thesis, Data of 5 oncogenes (ONGs) (AKT1, ALK, ERBB2, KRAS, BRAF) and 5 tumor suppressor genes (TSGs) (ESR1, CASP8, TET2, PALB2, PTEN) were retrieved from ClinVar. Five common in silico tools; Polyphen, Provean, Mutation Assessor, Suspect, and FATHMM, were used to predict and categorize nsSNPs as deleterious, benign, or neutral. To understand the impact of each variation on the phenotype, Maestro, PremPS, Cupsat, and mCSM-NA in silico structural prediction tools were used. This study comprises of in-depth analysis of 10 cancer gene variants downloaded from Clinvar. Various analysis of the genes was conducted to derive a meaningful conclusion from the data. Research done indicated that pathogenic variants are more common among ONGs. Our research also shows that pathogenic and destabilizing variants are more common among ONGs than TSGs. Moreover, our data indicated that ALK(409) and BRAF(86) has higher benign count among ONGs; whilst among TSGs, PALB2(1308) and PTEN(318) genes have higher benign counts. Looking at the individual cancer genes predisposition or frequencies of causing cancer according to our research data, KRAS(76%), BRAF(55%), and ERBB2(36%) among ONGs; and PTEN(29%) and ESR1(17%) among TSGs have higher tendencies of causing cancer. Obtained results can shed light to the future research in order to pave new frontiers in cancer therapies.

Keywords: tumor suppressor genes (TSGs), oncogenes (ONGs), non synonymous single nucleotide polymorphism (nsSNP), single nucleotide polymorphism (SNP)

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Authors: Sabin Aslam, Sultan Habibullah Khan, James G. Thomson, Abhaya M. Dandekar

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Losses due to viral diseases are posing a serious threat to crop production. A quick breakdown of resistance to viruses like Cotton Leaf Curl Virus (CLCuV) demands the application of a proficient technology to engineer durable resistance. Gene stacking has recently emerged as a potential approach for integrating multiple genes in crop plants. In the present study, recombinase technology has been used for site-specific gene stacking. A target vector (pG-Rec) was designed for engineering a predetermined specific site in the plant genome whereby genes can be stacked repeatedly. Using Agrobacterium-mediated transformation, the pG-Rec was transformed into Coker-312 along with Nicotiana tabacum L. cv. Xanthi and Nicotiana benthamiana. The transgene analysis of target lines was conducted through junction PCR. The transgene positive target lines were used for further transformations to site-specifically stack two genes of interest using Bxb1 and PhiC31 recombinases. In the first instance, Cas9 driven by multiplex gRNAs (for Rep gene of CLCuV) was site-specifically integrated into the target lines and determined by the junction PCR and real-time PCR. The resulting plants were subsequently used to stack the second gene of interest (AVP3 gene from Arabidopsis for enhancing cotton plant growth). The addition of the genes is simultaneously achieved with the removal of marker genes for recycling with the next round of gene stacking. Consequently, transgenic marker-free plants were produced with two genes stacked at the specific site. These transgenic plants can be potential germplasm to introduce resistance against various strains of cotton leaf curl virus (CLCuV) and abiotic stresses. The results of the research demonstrate gene stacking in crop plants, a technology that can be used to introduce multiple genes sequentially at predefined genomic sites. The current climate change scenario highlights the use of such technologies so that gigantic environmental issues can be tackled by several traits in a single step. After evaluating virus resistance in the resulting plants, the lines can be a primer to initiate stacking of further genes in Cotton for other traits as well as molecular breeding with elite cotton lines.

Keywords: cotton, CRISPR/Cas9, gene stacking, genome editing, recombinases

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Authors: Marissa Dallara, Amalia Ardeljan, Lexi Frankel, Nadia Obaed, Naureen Rashid, Omar Rashid

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Human Cytomegalovirus (HCMV) is a ubiquitous virus that remains latent in approximately 60% of individuals in developed countries. Viral load is kept at a minimum due to a robust immune response that is produced in most individuals who remain asymptomatic. HCMV has been recently implicated in cancer research because it may impose oncomodulatory effects on tumor cells of which it infects, which could have an impact on the progression of cancer. HCMV has been implicated in increased pathogenicity of certain cancers such as gliomas, but in contrast, it can also exhibit anti-tumor activity. HCMV seropositivity has been recorded in tumor cells, but this may also have implications in decreased pathogenesis of certain forms of cancer such as leukemia as well as increased pathogenesis in others. This study aimed to investigate the correlation between cytomegalovirus and the incidence of breast cancer. Methods The data used in this project was extracted from a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to analyze the patients infected versus patients not infection with cytomegalovirus using ICD-10, ICD-9 codes. Permission to utilize the database was given by Holy Cross Health, Fort Lauderdale, for the purpose of academic research. Data analysis was conducted using standard statistical methods. Results The query was analyzed for dates ranging from January 2010 to December 2019, which resulted in 14,309 patients in both the infected and control groups, respectively. The two groups were matched by age range and CCI score. The incidence of breast cancer was 1.642% and 235 patients in the cytomegalovirus group compared to 4.752% and 680 patients in the control group. The difference was statistically significant by a p-value of less than 2.2x 10^-16 with an odds ratio of 0.43 (0.4 to 0.48) with a 95% confidence interval. Investigation into the effects of HCMV treatment modalities, including Valganciclovir, Cidofovir, and Foscarnet, on breast cancer in both groups was conducted, but the numbers were insufficient to yield any statistically significant correlations. Conclusion This study demonstrates a statistically significant correlation between cytomegalovirus and a reduced incidence of breast cancer. If HCMV can exert anti-tumor effects on breast cancer and inhibit growth, it could potentially be used to formulate immunotherapy that targets various types of breast cancer. Further evaluation is warranted to assess the implications of cytomegalovirus in reducing the incidence of breast cancer.

Keywords: human cytomegalovirus, breast cancer, immunotherapy, anti-tumor

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Authors: Y. Z. Gad

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Disorders of Sex Development (DSD) are defined as congenital conditions in which development of chromosomal, gonadal or anatomical sex is atypical. The DSD are relatively prevalent in Egypt. In spite of that, the relative rarity of the individual disease types or their molecular pathologies frequently resulted in reporting on single or few cases. This augmented the challenging nature of phenotype-genotype correlation in this disease group and its utilization in the management of such medical emergency. Through critical assessment of the published DSD reports, the current review aims at analyzing the clinical characteristics of the various DSD forms in relation to the underlying molecular pathologies. A systematic literature search was done in Pubmed, using relevant keywords (Egypt versus DSD, genital ambiguity or ambiguous genitalia, the old terms of 'intersex, hermaphroditism and pseudohermaphroditism', and a list of the DSD entities and their related genes). The search yielded 24 reports of molecular data in Egyptian patients presenting with ambiguous genitalia. However, only 21 publications fulfilled the criteria of inclusion of detailed clinical descriptions and definitive molecular diagnoses of individual patients. Curation of the data yielded a total of 53 cases that were ascertained from 40 families. Fifty-one patients present with ambiguous genitalia only while 2 had multiple congenital anomalies. Parental consanguinity was noted in 60% of cases. Sex of rearing at initial presentation was female in 75% and 60% in 46,XY and 46,XX DSD cases, respectively. The external genital phenotype in 2/3 of the 46,XY DSD cases showed moderate undermasculinization [Quigley scores 3 & 4] and 1/3 had severe presentations [scores 5 & 6]. For 46,XX subjects, 1 had severe virilization of the external genitalia while 8 had moderate phenotype. Hormonal data were inconclusive or contradictory to final diagnosis in a forth of cases. Collectively, 31 families [31/40, 77.5%] with 46,XY DSD had molecular defects in the genes, 5 alpha reductase 2 (SRD5A2) [12/31], 17 beta-hydroxysteroid dehydrogenase 3 [8/31], androgen receptor [7/31], Steroidogenic factor 1 [2/31], luteinizing hormone receptor [1/31], and fibroblast growth factor receptor 1 [1/31]. In a multiethnic study, 9 families afflicted with 46,XX DSD due to 11 beta hydroxylase (CYP11B1) deficiency were documented. Two recurrent mutations, G34R and N160D, in SRD5A2 were present, respectively, in 42 and 17% of cases. Similarly, 4 recurrent mutations resulted in 89% of the CYP11B1 presentations. In conclusion, this analysis highlights the importance of autosomal recessive inheritance and inbreeding among DSD presentations, the importance of founder effect in at least 2 disorders, the difficulties in relating the genotype with the indeterminate genital phenotype, the under-reporting of some DSD subtypes, and the notion that the reported mutational profiles among Egyptian DSD cases are relatively different from those reported in other ethnic groups.

Keywords: disorders of sex development, genital ambiguity, mutation, molecular diagnosis, Egypt

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Authors: Asghar Arif

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Lung cancer has been recognized as one of the greatest common cancers, causing the annual mortality rate of about 1.2 million people in the world. Lung cancer is the most prevalent cancer in men and the third-most common cancer among women (after breast and digestive cancers).Recent evidences have shown the inflammatory process as one of the potential factors of cancer. Tuberculosis (TB), pneumonia, and chronic bronchitis are among the most important inflammation-inducing factors in the lungs, among which TB has a more profound role in the emergence of cancer.TB is one of the important mortality factors throughout the world, and 205,000 death cases are reported annually due to this disease. Chronic inflammation and fibrosis due to TB can induce genetic mutation and alternations. Parenchyma tissue of lung is involved in both diseases of TB and lung cancer, and continuous cough in lung cancer, morphological vascular variations, lymphocytosis processes, and generation of immune system mediators such as interleukins, are all among the factors leading to the hypothesis regarding the role of TB in lung cancer Some reports have shown that the induction of necrosis and apoptosis or TB reactivation, especially in patients with immune-deficiency, may result in increasing IL-17 and TNF_α, which will either decrease P53 activity or increase the expression of Bcl-2, decrease Bax-T, and cause the inhibition of caspase-3 expression due to decreasing the expression of mitochondria cytochrome oxidase. It has been also indicated that following the injection of BCG vaccine, the host immune system will be reinforced, and in particular, the rates of gamma interferon, nitric oxide, and interleukin-2 are increased. Therefore, CD4 + lymphocyte function will be improved, and the person will be immune against cancer.Numerous prospective studies have so far been conducted on the role of TB in lung cancer, and it seems that this disease is effective in that particular cancer.One of the main challenges of lung cancer is its correct and timely diagnosis. Unfortunately, clinical symptoms (such as continuous cough, hemoptysis, weight loss, fever, chest pain, dyspnea, and loss of appetite) and radiological images are similar in TB and lung cancer. Therefore, anti-TB drugs are routinely prescribed for the patients in the countries with high prevalence of TB, like Pakistan. Regarding the similarity in clinical symptoms and radiological findings of lung cancer, proper diagnosis is necessary for TB and respiratory infections due to nontuberculousmycobacteria (NTM). Some of the drug resistive TB cases are, in fact, lung cancer or NTM lung infections. Acid-fast staining and histological study of phlegm and bronchial washing, culturing and polymerase chain reaction TB are among the most important solutions for differential diagnosis of these diseases. Briefly, it is assumed that TB is one of the risk factors for cancer. Numerous studies have been conducted in this regard throughout the world, and it has been observed that there is a significant relationship between previous TB infection and lung cancer. However, to prove this hypothesis, further and more extensive studies are required. In addition, as the clinical symptoms and radiological findings of TB, lung cancer, and non-TB mycobacteria lung infections are similar, they can be misdiagnosed as TB.

Keywords: TB and lung cancer, TB people, TB servivers, TB and HIV aids

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Authors: Josiane N. Muller, Allan K. R. Galardo, Tatiane A. Barbosa, Evan P. Ferro, Wellington M. Dos Santos, Ana Paula S. A. Correa, Edinaldo C. Rego, Jose B. P. Lima

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The susceptibility status of an insect population to any larvicide depends on several factors such includes genetic constitution, environmental conditions and others. The mosquito Aedes aegypti is the primary vector of three important viral diseases, Zika, Dengue, and Chikungunya. The frequent outbreaks of those diseases in different parts of Brazil demonstrate the importance of testing the susceptibility of vectors in different environments. Since the control of this mosquito leads to the control of disease, alternatives for vector control that value the different Brazilian environmental conditions are needed for effective actions. The aim of this study was to evaluate a new commercial formulation of Bacillus thuringiensis israelenses (DengueTech: Brazilian innovative technology) in the Brazilian Legal Amazon considering the climate conditions. Semi-field tests were conducted in the Institute of Scientific and Technological Research of the State of Amapa in two different environments, one in a shaded area and the other exposed to sunlight. The mosquito larvae were exposed to larvicide concentration and a control; each group was tested in three containers of 40 liters each. To assess persistence 50 third instar larvae of Aedes aegypti laboratory lineages (Rockefeller) and 50 larvae of Aedes aegypti collected in the municipality of Macapa, Brazil’s Amapa state, were added weekly and after 24 hours the mortality was assessed. In total 16 tests were performed, where 12 were done with replacement of water (1/5 of the volume, three times per week). The effectiveness of the product was determined through mortality of ≥ 80%, as recommend by the World Health Organization. The results demonstrated that high-water temperatures (26-35 °C) on the containers influenced the residual time of the product, where the maximum effect achieved was 21 days in the shaded area; and no effectiveness of 60 days was found in any of the tests, as expected according to the larvicide company. The test with and without water replacement did not present significant differences in the mortality rate. Considering the different environments and climate, these results stimulate the need to test larvicide and its effectiveness in specific environmental settings in order to identify the parameters required for better results. Thus, we see the importance of semi-field researches considering the local climate conditions for a successful control of Aedes aegypti.

Keywords: Aedes aegypti, bioassay, larvicida, vector control

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Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade

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Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".

Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency

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Authors: Samuel Munaf, Kevin Swingler, Franz Brülisauer, Anthony O’Hare, George Gunn, Aaron Reeves

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Background: Avian influenza, more commonly known as Bird flu, is a viral zoonotic respiratory disease stemming from various species of poultry, including pets and migratory birds. Researchers have purported that the accessibility of health information online, in addition to the low-cost data collection methods the internet provides, has revolutionized the methods in which epidemiological and disease surveillance data is utilized. This paper examines the feasibility of using internet data sources, such as Twitter and livestock forums, for the early detection of the avian flu outbreak, through the use of text mining algorithms and social network analysis. Methods: Social media mining was conducted on Twitter between the period of 01/01/2021 to 31/12/2021 via the Twitter API in Python. The results were filtered firstly by hashtags (#avianflu, #birdflu), word occurrences (avian flu, bird flu, H5N1), and then refined further by location to include only those results from within the UK. Analysis was conducted on this text in a time-series manner to determine keyword frequencies and topic modeling to uncover insights in the text prior to a confirmed outbreak. Further analysis was performed by examining clinical signs (e.g., swollen head, blue comb, dullness) within the time series prior to the confirmed avian flu outbreak by the Animal and Plant Health Agency (APHA). Results: The increased search results in Google and avian flu-related tweets showed a correlation in time with the confirmed cases. Topic modeling uncovered clusters of word occurrences relating to livestock biosecurity, disposal of dead birds, and prevention measures. Conclusions: Text mining social media data can prove to be useful in relation to analysing discussed topics for epidemiological surveillance purposes, especially given the lack of applied research in the veterinary domain. The small sample size of tweets for certain weekly time periods makes it difficult to provide statistically plausible results, in addition to a great amount of textual noise in the data.

Keywords: veterinary epidemiology, disease surveillance, infodemiology, infoveillance, avian influenza, social media

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Authors: Ashutosh Biswas, Poonam Coushic, Kalpana Baruah, Paras Singla, A. C. Dhariwal, Pawana Murthy

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Burden of Dengue in Northern India Ashutosh Biswas, Poonam Coushic, Kalpana Baruah, Paras Singla, AC Dhariwal, Pawana Murthy. All India Institute of Medical Sciences, NVBDCP,WHO New Delhi, India Aim: This study was conducted to estimate the burden of dengue in capital region of India. Methodology:Seropositivity of Dengue for IgM Ab, NS1 Ag and IgG Ab were performed among the blood donors’ samples from blood bank, those who were coming to donate blood for the requirement of blood for the admitted patients in hospital. Blood samplles were collected through out the year to estimate seroprevalance of dengue with or without outbreak season. All the subjects were asymptomatic at the time of blood donation. Results: A total of 1558 donors were screened for the study. On the basis of inclusion/ exclusion criteria, we enrolled 1531subjects for the study.Twenty seven donors were excluded from the study, out of which 6 were detected HIV +ve, 11 were positive for HBsAg and 10 were found positive for HCV.Mean age was 30.51 ± 7.75 years.Of 1531subjects, 18 (1.18%) had a past history of typhoid fever, 28 (1.83%) had chikungunya fever, 9 (0.59%) had malaria and 43 subjects (2.81%) had a past history of symptomatic dengue infection.About 2.22% (34) of subjects were found to have sero-positive for NS1 Ag with a peak point prevalence of 7.14% in the month of October and sero-positive of IgM Ab was observed about 5.49% (84)with a peak point prevalence of 14.29% in the month of October. Sero-prevalnce of IgGwas detected in about 64.21% (983) of subjects. Conclusion: Acute asymptomatic dengue (NS1 Ag+ve) was observed in 7.14%, as the subjects were having no symptoms at the time of sampling. This group of subjects poses a potential public health threat for transmitting dengue infection through blood transfusion (TTI) in the community as evident by presence of active viral infection due to NS1Ag +VE. Therefore a policy may be implemented in the blood bank for testing NS1 Ag to look for active dengue infection for preventing dengue transmission through blood transfusion (TTI). Acute or Subacute dengue infection ( IgM Ab+ve) was observed from 5.49% to 14.29% which is a peak point prevalence in the month of October. About 64.21% of the population were immunized by natural dengue infection ( IgG Ab+ve) in theNorthern province of India. This might be helpful for implementing the dengue vaccine in a region. Blood samples in blood banks should be tested for dengue before transfusion to any other person to prevent transfusion transmitted dengue infection as we estimated upto 7.14% positivity of NS1 Ag in our study which indicates presence of dengue virus in blood donors’ samples.

Keywords: Dengue Burden, Seroprevalance, Asymptomatic dengue, Dengue transmission through blood transfusion

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Authors: A. H. Taghdisi, M. Mirmohammadi, S. Kamali

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Evening primrose (Oenothera biennis L.) is a biennial and herbaceous and one of the most important species of medicinal plants in the world. due to the production of unsaturated fatty acids such as linoleic acid, alpha-linolenic acid, etc. in its seeds and roots, and compounds such as kaempferol in its leaves, Evening primrose has important medicinal efficiency such as reducing premenstrual problems, acceleration of wound healing, inhibiting platelet aggregation, sedation of cardiovascular diseases, and treatment of viral infections. The sap of the plant is used to treat warts, and the plant itself is used as a charm against mental and spiritual diseases and poisonous animals. Its leaves have significant antibacterial activity against yellow staphylococci. It is also used in the treatment of poisoning, especially the toxication caused by the consumption of alcoholic beverages, in the treatment of arteriosclerosis and diseases caused by liver cell insufficiency. Low germination and production speed are the problems of evening primrose growth and propagation. In the present study, extracts were obtained from four components (flowers, stems, seeds, leaves) of the evening primrose plant using the Soxhlet apparatus. To measure the antibacterial properties against MDR bacteria, microbial methods, including dilution, cultivation on a plate containing nutrient agar culture medium, and disc diffusion in agar, were performed using Staphylococcus aureus and Escherichia coli bacteria on all four extracts. The maximum antibacterial activity related to the dilution method was obtained in all extracts. In the plate culture method, antibacterial activity was obtained for all extracts in the nutrient agar medium. The maximum diameter of the non-growth halo was obtained in the disc diffusion method in agar in the leaf extract. The statistical analysis of the microbial part was done by one-way ANOVA test (SPSS). By comparing the amount of omega-3 in extracts of Iranian and foreign oils available in the market and the extracts extracted from evening primrose plant samples with gas chromatography, it is shown that the stem extract had the most omega-3 (oleic acid) and compared to the extract of the mentioned oils, it had the highest amount of omega-3 overall. Also, the amount of omega-3 in the extract of Iranian oils was much higher than in the extract of foreign oils. It should be noted that the extract of foreign oils had a more complete composition of omega-3 than the extract of Iranian oils.

Keywords: antibacterial activity, MDR bacteria, evening primrose, omega-3

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Authors: Esshili Awatef, Manitz Marie-Pierre, Eßlinger Manuela, Gerhardt Alexandra, Plümper Jennifer, Wachholz Simone, Friebe Astrid, Juckel Georg

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Maternal immune activation (MIA) resulting from maternal viral infection during pregnancy is a known risk factor for schizophrenia. The neural mechanisms by which maternal infections increase the risk for schizophrenia remain unknown, although the prevailing hypothesis argues that an activation of the maternal immune system induces changes in the maternal-fetal environment that might interact with fetal brain development. It may lead to an activation of fetal microglia inducing long-lasting functional changes of these cells. Based on post-mortem analysis showing an increased number of activated microglial cells in patients with schizophrenia, it can be hypothesized that these cells contribute to disease pathogenesis and may actively be involved in gray matter loss observed in such patients. In the present study, we hypothesize that prenatal treatment with the inflammatory agent Poly(I:C) during embryogenesis at contributes to microglial activation in the offspring, which may, therefore, represent a contributing factor to the pathogenesis of schizophrenia and underlines the need for new pharmacological treatment options. Pregnant rats were treated with intraperitoneal injections a single dose of Poly(I:C) or saline on gestation day 17. Brains of control and Poly(I:C) offspring, were removed and into 20-μm-thick coronal sections were cut by using a Cryostat. Brain slices were fixed and immunostained with ba1 antibody. Subsequently, Iba1-immunoreactivity was detected using a secondary antibody, goat anti-rabbit. The sections were viewed and photographed under microscope. The immunohistochemical analysis revealed increases in microglia cell number in the prefrontal cortex, in offspring of poly(I:C) treated-rats as compared to the controls injected with NaCl. However, no significant differences were observed in microglia activation in the cerebellum among the groups. Prenatal immune challenge with Poly(I:C) was able to induce long-lasting changes in the offspring brains. This lead to a higher activation of microglia cells in the prefrontal cortex, a brain region critical for many higher brain functions, including working memory and cognitive flexibility. which might be implicated in possible changes in cortical neuropil architecture in schizophrenia. Further studies will be needed to clarify the association between microglial cells activation and schizophrenia-related behavioral alterations.

Keywords: Microglia, neuroinflammation, PolyI:C, schizophrenia

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Authors: L. D. Upegui, Isabel Alvarez-Solorza, Karina Garduno-Ulloa, Maren Boecker

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Introduction: The increasing prevalence rate of resistant and multiresistant bacterial strains to antibiotics is a threat to public health and requires a rapid multifunctional answer. Individuals that are affected by resistant strains present a higher morbidity and mortality than individuals that are infected with the same species of bacteria but with sensitive strains. There have been identified risk factors that are related to the misuse and overuse of antibiotics, like socio-demographic characteristics and psychological aspects of the individuals that have not been explored objectively due to a lack of valid and reliable instruments for their measurement. Objective: To validate a questionnaire for the evaluation of the levels of knowledge related to the use of antibiotics in a Mexican population. Materials and Methods: Analytical cross-sectional observational study. The questionnaire consists of 12 items to evaluated knowledge (1=no, 2=not sure, 3=yes) regarding the use of antibiotics, with higher scores corresponding to a higher level of knowledge. Data are collected in a sample of students. Data collection is still ongoing. In this abstract preliminary results of 30 respondents are reported which were collected during pilot-testing. The validation of the instrument was done using the Rasch model. Fit to the Rasch model was tested checking overall fit to the model, unidimensionality, local independence and evaluating the presence of Differential Item Functioning (DIF) by age and gender. The software Rumm2030 and the SPSS were used for the analyses. Results: The participants of the pilot-testing presented an average age of 32 years ± 12.6 and 53% were women. The preliminary results indicated that the items showed good fit to the Rasch model (chi-squared=12.8 p=0.3795). Unidimensionality (number of significant t-tests of 3%) could be proven, the items were locally independent, and no DIF was observed. Knowledge was the smallest regarding statements on the role of antibiotics in treating infections, e.g., most of the respondents did not know that antibiotics would not work against viral infections (70%) and that they could also cause side effects (87%). The knowledge score ranged from 0 to 100 points with a transformed measurement (mean of knowledge 27.1 ± 4.8). Conclusions: The instrument showed good psychometric proprieties. The low scores of knowledge about antibiotics suggest that misinterpretations on the use of these medicaments were prevalent, which could influence the production of antibiotic resistance. The application of this questionnaire will allow the objective identification of 'Hight risk groups', which will be the target population for future educational campaigns, to reduce the knowledge gaps on the general population as an effort against antibiotic resistance.

Keywords: antibiotics, knowledge, misuse, overuse, questionnaire, Rasch model, validation

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Authors: Satendra Pal Singh, Dalip Kr. Kakru, Jyoti Mishra, Rajesh Thakur, Tarana Sarwat

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COVID-19 is still an intrigue as far as morbidity or mortality is concerned. The rate of recovery varies from person to person, & it depends upon the accessibility of the healthcare system and the roles played by the physicians and caregivers. It is envisaged that with the passage of time, people would become immune to this virus, and those who are vulnerable would sustain themselves with the help of vaccines. The proposed study deals with the severeness of COVID-19 is associated with some specific biomarkers linked to correlate age and gender. We will be assessing the overall homeostasis of the persons who were affected by the coronavirus infection and also of those who recovered from it. Some people show more severe effects, while others show very mild symptoms, however, they show low CT values. Thus far, it is unclear why the new strain of Covid has different effects on different people in terms of age, gender, and ABO blood typing. According to data, the fatality rate with heart disease was 10.5 percent, 7.3 percent were diabetic, and 6 percent who are already infected from other comorbidities. However, some COVID-19 cases are worse than others & it is not fully explainable as of date. Overall data show that the ABO blood group is effective or prone to the risk of SARS-COV2 infection, while another study also shows the phenotypic effects of the blood group related to covid. It is an accepted fact that females have more strong immune systems than males, which may be related to the fact that females have two ‘X’ chromosomes, which might contain a more effective immunity booster gene on the X chromosome, and are capable to protect the female. Also specific sex hormones also induce a better immune response in a specific gender. This calls for in-depth analysis to be able to gain insight into this dilemma. COVID-19 is still not fully characterized, and thus we are not very familiar with its biology, mode of infection, susceptibility, and overall viral load in the human body. How many virus particles are needed to infect a person? How, then, comorbidity contribute to coronavirus infection? Since the emergence of this virus in 2020, a large number of papers have been published, and seemingly, vaccines have been prepared. But still, a large number of questions remain unanswered. The proneness of humans for infection by covid-19 needs to be established to be able to develop a better strategy to fight this virus. Our study will be on the Impact of demography on the Severity of covid-19 infection & at the same time, will look into gender-specific sensitivity of Covid-19 and the Operational variation of different biochemical markers in Covid-19 positive patients. Besides, we will be studying the co-relation, if any, of COVID severity & ABO Blood group type and the occurrence of the most common blood group type amongst positive patience.

Keywords: coronavirus, ABO blood group, age, gender

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Authors: Ismail Bamidele Afolabi, Abdulmujeeb Babatunde Aremu, Lawal Abdurraheem Maidoki, Nnodimele Onuigbo Atulomah

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Background: Hepatitis B virus infection remains a significant global public health challenge with infectivity as well as the potential for transmission more than 50 to 100 times that of HIV. Annually, global HBV-related mortality is linked primarily to cirrhosis and liver carcinoma. The ever-increasing endemicity of HBV among children under-5-years, owing to vertical transmission and its lingering chronicity in developing countries, will hamper the global efforts concertedly endorsed towards eliminating viral hepatitis as a global public health threat by 2030. Objective: This study assessed information motivation behavioral skills model constructs as predictors of HBV infection prevention practices among consenting expectant mothers attending antenatal care in Central Uganda as a focal point of intervention towards breaking materno-foetal transmission of HBV. Methods: A cross-sectional study with a quantitative data collection approach based on the constructs of the IMB model was used to capture data on the study variables among 385 randomly selected pregnant women between September and October 2020. Data derived from the quantitative instrument were transformed into weighted aggregate scores using SPSS version 26. ANOVA and regression analysis were done to ascertain the study hypotheses with a significance level set as (p ≤ 0.05). Results: Relatively 60% of the respondents were aged between 18 and 28. Expectant mothers with secondary education (42.3%) were predominant. Furthermore, an average but inadequate knowledge (X ̅=5.97±6.61; B=0.57; p<.001), incorrect perception (X ̅=17.10±18.31; B=0.97; p=.014), and good behavioral skills (X ̅=12.39±13.37; B=0.56; p<.001) for adopting prevention practices all statistically predicted the unsatisfactory level of prevention practices (X ̅=15.03±16.20) among the study respondents as measured on rating scales of 12, 33, 21 and 30 respectively. Conclusion: Evidence from this study corroborates the imperativeness of IMB constructs in reducing the burden of HBV infection in developing countries. Therefore, the inadequate HBV knowledge and misperception among obstetric populations necessitate personalized health education during antenatal visits and subsequent health campaigns in order to inform better prevention practices and, in turn, reduce the lingering chronicity of HBV infection in developing countries.

Keywords: behavioral skills, HBV infection, knowledge, perception, pregnant women, prevention practices

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Authors: Steven G. Sclan

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Background: Since December 2019, the world has been afflicted by the spread of the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2), which is responsible for the condition referred to as Covid-19. The illness has had a cataclysmic impact on the political, social, economic, and overall well-being of the population of the entire globe. While Covid-19 has had a substantial universal fatality impact, it may have an even greater effect on the socioeconomic, medical well-being, and healthcare planning for remaining societies. Significance: As these numbers illustrate, many more persons survive the infection than die from it, and many of those patients have noted ongoing, persistent symptoms after successfully enduring the acute phase of the illness. Recognition and understanding of these symptoms are crucial for developing and arranging efficacious models of care for all patients (whether or not having been hospitalized) surviving acute covid illness and plagued by post-acute symptoms. Furthermore, regarding Covid infection in children (< 18 y/o), although it may be that Covid “+” children are not major vectors of infective transmission, it now appears that many more children than initially thought are carrying the virus without accompanying obvious symptomatic expression. It seems reasonable to wonder whether viral effects occur in children – those children who are Covid “+” and now asymptomatic – and if, over time, they might also experience similar symptoms. An even more significant question is whether Covid “+” asymptomatic children might manifest increased multiple health problems as they grow – i.e., developmental complications (e.g., physical/medical, metabolic, neurobehavioral, etc.) – in comparison to children who had been consistently Covid “ - ” during the pandemic. Topics Addressed and Theoretical Importance: This review is important because of the description of both quantitative and qualitative methods for clinical and biomedical research. Topics reviewed will consider the importance of well-designed, comprehensive (i.e., quantitative and qualitative methods) longitudinal studies of Post Covid-19 symptoms in both adults and children. Also reviewed will be general characteristics of longitudinal studies and a presentation of a model for a proposed study. Also discussed will be the benefit of longitudinal studies for the development of efficacious interventions and for the establishment of cogent, practical, and efficacious community healthcare service planning for post-acute covid patients. Conclusion: Results of multi-dimensional, longitudinal studies will have important theoretical implications. These studies will help to improve our understanding of the pathophysiology of long COVID and will aid in the identification of potential targets for treatment. Such studies can also provide valuable insights into the long-term impact of COVID-19 on public health and socioeconomics.

Keywords: COVID-19, post-COVID-19, long COVID, longitudinal research, quantitative research, qualitative research

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Authors: R. Pussinen, V. Jankovic, U. Herzberg, M. Cerrada-Gimenez, T. Huhtala, A. Nurmi, T. Ahtoniemi

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Targeted over-expression of human α-synuclein using viral-vector mediated gene delivery into the substantia nigra of rats and non-human primates has been reported to lead to dopaminergic cell loss and the formation of α-synuclein aggregates reminiscent of Lewy bodies. We have previously shown how AAV-mediated expression of α-synuclein is seen in the chronic phenotype of the rats over 16 week follow-up period. In the context of these findings, we attempted to further characterize this long term PD related functional and motor deficits as well as neurochemical and neuropathological changes in AAV-mediated α-synuclein transfection model in rats during chronic follow-up period. Different titers of recombinant AAV expressing human α-synuclein (A53T) were stereotaxically injected unilaterally into substantia nigra of Wistar rats. Rats were allowed to recover for 3 weeks prior to initial baseline behavioral testing with rotational asymmetry test, stepping test and cylinder test. A similar behavioral test battery was applied again at weeks 5, 9,12 and 15. In addition to traditionally used rat PD model tests, MotoRater test system, a high speed kinematic gait performance monitoring was applied during the follow-up period. Evaluation focused on animal gait between groups. Tremor analysis was performed on weeks 9, 12 and 15. In addition to behavioral end-points, neurochemical evaluation of dopamine and its metabolites were evaluated in striatum. Furthermore, integrity of the dopamine active transport (DAT) system was evaluated by using 123I- β-CIT and SPECT/CT imaging on weeks 3, 8 and 12 after AAV- α-synuclein transfection. Histopathology was examined from end-point samples at 3 or 12 weeks after AAV- α-synuclein transfection to evaluate dopaminergic cell viability and microglial (Iba-1) activation status in substantia nigra by using stereological analysis techniques. This study focused on the characterization and validation of previously published AAV- α-synuclein transfection model in rats but with the addition of novel end-points. We present the long term phenotype of AAV- α-synuclein transfected rats with traditionally used behavioral tests but also by using novel fine motor analysis techniques and tremor analysis which provide new insight to unilateral effects of AAV α-synuclein transfection. We also present data about neurochemical and neuropathological end-points for the dopaminergic system in the model and how well they correlate with behavioral phenotype.

Keywords: adeno-associated virus, alphasynuclein, animal model, Parkinson’s disease

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Authors: Christi Jackson, Chuka Onaga

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Introduction: We report a case of delayed diagnosis of extra-pulmonary INH-mono-resistant Tuberculosis (TB) in a South African patient with drug-resistant HIV. Case Presentation: A 36-year old male was initiated on 1st line (NNRTI-based) anti-retroviral therapy (ART) in September 2009 and switched to 2nd line (PI-based) ART in 2011, according to local guidelines. He was following up at the outpatient wellness unit of a public hospital, where he was diagnosed with Protease Inhibitor resistant HIV in March 2016. He had an HIV viral load (HIVVL) of 737000 copies/mL, CD4-count of 10 cells/µL and presented with complaints of productive cough, weight loss, chronic diarrhoea and a septic buttock wound. Several investigations were done on sputum, stool and pus samples but all were negative for TB. The patient was treated with antibiotics and the cough and the buttock wound improved. He was subsequently started on a 3rd-line ART regimen of Darunavir, Ritonavir, Etravirine, Raltegravir, Tenofovir and Emtricitabine in May 2016. He continued losing weight, became too weak to stand unsupported and started complaining of abdominal pain. Further investigations were done in September 2016, including a urine specimen for Line Probe Assay (LPA), which showed M. tuberculosis sensitive to Rifampicin but resistant to INH. A lymph node biopsy also showed histological confirmation of TB. Management and outcome: He was started on Rifabutin, Pyrazinamide and Ethambutol in September 2016, and Etravirine was discontinued. After 6 months on ART and 2 months on TB treatment, his HIVVL had dropped to 286 copies/mL, CD4 improved to 179 cells/µL and he showed clinical improvement. Pharmacy supply of his individualised drugs was unreliable and presented some challenges to continuity of treatment. He successfully completed his treatment in June 2017 while still maintaining virological suppression. Discussion: Several laboratory-related factors delayed the diagnosis of TB, including the unavailability of urine-lipoarabinomannan (LAM) and urine-GeneXpert (GXP) tests at this facility. Once the diagnosis was made, it presented a treatment dilemma due to the expected drug-drug interactions between his 3rd-line ART regimen and his INH-resistant TB regimen, and specialist input was required. Conclusion: TB is more difficult to diagnose in patients with severe immunosuppression, therefore additional tests like urine-LAM and urine-GXP can be helpful in expediting the diagnosis in these cases. Patients with non-standard drug regimens should always be discussed with a specialist in order to avoid potentially harmful drug-drug interactions.

Keywords: drug-resistance, HIV, line probe assay, tuberculosis

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Authors: Mathula Thangarajh

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Duchenne muscular dystrophy (DMD) is a severe form of X-linked muscular dystrophy caused by mutations in the dystrophin gene resulting in progressive skeletal muscle weakness. Boys with DMD also have significant cognitive disabilities. The intelligence quotient of boys with DMD, compared to peers, is approximately one standard deviation below average. Detailed neuropsychological testing has demonstrated that boys with DMD have a global developmental impairment, with verbal memory and visuospatial skills most significantly affected. Furthermore, the total brain volume and gray matter volume are lower in children with DMD compared to age-matched controls. These results are suggestive of a significant structural and functional compromise to the developing brain as a result of absent dystrophin protein expression. There is also some genetic evidence to suggest that mutations in the 3’ end of the DMD gene are associated with more severe neurocognitive problems. Our working hypothesis is that (i) boys with DMD do not make gains in neurodevelopmental skills compared to typically developing children and (ii) women carriers of DMD mutations may have subclinical cognitive deficits. We also hypothesize that there may be an intergenerational vulnerability of cognition, with boys of DMD-carrier mothers being more affected cognitively than boys of non-DMD-carrier mothers. The objectives of this study are: 1. Assess the neurodevelopment in boys with DMD at 4-time points and perform baseline neuroradiological assessment, 2. Assess cognition in biological mothers of DMD participants at baseline, 3. Assess possible correlation between DMD mutation and cognitive measures. This study also explores functional brain abnormalities in people with DMD by exploring how regional and global connectivity of the brain underlies executive function deficits in DMD. Such research can contribute to a better holistic understanding of the cognition alterations due to DMD and could potentially allow clinicians to create better-tailored treatment plans for the DMD population. There are four study visits for each participant (baseline, 2-4 weeks, 1 year, 18 months). At each visit, the participant completes the NIH Toolbox Cognition Battery, a validated psychometric measure that is recommended by NIH Common Data Elements for use in DMD. Visits 1, 3, and 4 also involve the administration of the BRIEF-2, ABAS-3, PROMIS/NeuroQoL, PedsQL Neuromuscular module 3.0, Draw a Clock Test, and an optional fMRI scan with the N-back matching task. We expect to enroll 52 children with DMD, 52 mothers of children with DMD, and 30 healthy control boys. This study began in 2020 during the height of the COVID-19 pandemic. Due to this, there were subsequent delays in recruitment because of travel restrictions. However, we have persevered and continued to recruit new participants for the study. We partnered with the Muscular Dystrophy Association (MDA) and helped advertise the study to interested families. Since then, we have had families from across the country contact us about their interest in the study. We plan to continue to enroll a diverse population of DMD participants to contribute toward a better understanding of Duchenne Muscular Dystrophy.

Keywords: neurology, Duchenne muscular dystrophy, muscular dystrophy, cognition, neurodevelopment, x-linked disorder, DMD, DMD gene

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Authors: David Tennison

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In the wake of the Covid-19 pandemic, a new chronic illness emerged onto the global stage: Long Covid. Long Covid presents with several symptoms commonly seen in other poorly-understood illnesses, such as fibromyalgia (FM) and myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). However, while Long Covid has swiftly become a recognised illness, FM and ME/CFS are still seen as contested, which impacts patient care and healthcare experiences. This study aims to examine what the differences are between Long Covid and FM; and if the Long Covid case can provide guidance for how to address the healthcare challenge of contested illnesses. To address this question, this study performed comprehensive research into the history of FM; our current biomedical understanding of it; and available healthcare interventions (within the context of the UK NHS). Analysis was undertaken of the stigma and stereotypes around FM, and a comparison made between FM and the emerging Long Covid literature, along with the healthcare response to Long Covid. This study finds that healthcare for chronic contested illnesses in the UK is vastly insufficient - in terms of pharmaceutical and holistic interventions, and the provision of secondary care options. Interestingly, for Long Covid, many of the treatment suggestions are pulled directly from those used for contested illnesses. The key difference is in terms of funding and momentum – Long Covid has generated exponentially more interest and research in a short time than there has been in the last few decades of contested illness research. This stands to help people with FM and ME/CFS – for example, research has recently been funded into “brain fog”, a previously elusive and misunderstood symptom. FM is culturally regarded as a “women’s disease” and FM stigma stems from notions of “hysteria”. A key finding is that the idea of FM affecting women disproportionally is not reflected in modern population studies. Emerging data on Long Covid also suggests a slight leaning towards more female patients, however it is less feminised, potentially due to it emerging in the global historical moment of the pandemic. Another key difference is that FM is rated as an extremely low-prestige illness by healthcare professionals, while it was in large part due to the advocacy of affected healthcare professionals that Long Covid was so quickly recognised by science and medicine. In conclusion, Long Covid (and the risk of future pandemics and post-viral illnesses) highlight a crucial need for implementing new, and reinforcing existing, care networks for chronic illnesses. The difference in how contested illnesses like FM, and new ones like Long Covid are treated have a lot to do with the historical moment in which they emerge – but cultural stereotypes, from within and without medicine, need updating. Particularly as they contribute to disease stigma that causes genuine harm to patients. However, widespread understanding and acceptance of Long Covid could help fight contested illness stigma, and the attention, funding and research into Long Covid may actually help raise the profile of contested illnesses and uncover answers about their symptomatology.

Keywords: long COVID, fibromyalgia, myalgic encephalomyelitis, chronic fatigue syndrome, NHS, healthcare, contested illnesses, chronic illnesses, COVID-19 pandemic

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Authors: Sophio Kobauri, Temur Kantaria, Nina Kulikova, David Tugushi, Ramaz Katsarava

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The elaboration of effective drug delivery vehicles is still topical nowadays since targeted drug delivery is one of the most important challenges of the modern nanomedicine. The last decade has witnessed enormous research focused on synthetic cationic polymers (CPs) due to their flexible properties, in particular as non-viral gene delivery systems, facile synthesis, robustness, not oncogenic and proven gene delivery efficiency. However, the toxicity is still an obstacle to the application in pharmacotherapy. For overcoming the problem, creation of new cationic compounds including the polymeric nano-size particles – nano-containers (NCs) loading with different pharmaceuticals and biologicals is still relevant. In this regard, a variety of NCs-based drug delivery systems have been developed. We have found that amino acid-based biodegradable polymers called as pseudo-proteins (PPs), which can be cleared from the body after the fulfillment of their function are highly suitable for designing pharmaceutical NCs. Among them, one of the most promising are NCs made of biodegradable Cationic PPs (CPPs). For preparing new cationic NCs (CNCs), we used CPPs composed of positively charged amino acid L-arginine (R). The CNCs were fabricated by two approaches using: (1) R-based homo-CPPs; (2) Blends of R-based CPPs with regular (neutral) PPs. According to the first approach NCs we prepared from CPPs 8R3 (composed of R, sebacic acid and 1,3-propanediol) and 8R6 (composed of R, sebacic acid and 1,6-hexanediol). The NCs prepared from these CPPs were 72-101 nm in size with zeta potential within +30 ÷ +35 mV at a concentration 6 mg/mL. According to the second approach, CPPs 8R6 was blended in organic phase with neutral PPs 8L6 (composed of leucine, sebacic acid and 1,6-hexanediol). The NCs prepared from the blends were 130-140 nm in size with zeta potential within +20 ÷ +28 mV depending on 8R6/8L6 ratio. The stability studies of fabricated NCs showed that no substantial change of the particle size and distribution and no big particles’ formation is observed after three months storage. In vitro biocompatibility study of the obtained NPs with four different stable cell lines: A549 (human), U-937 (human), RAW264.7 (murine), Hepa 1-6 (murine) showed both type cathionic NCs are biocompatible. The obtained data allow concluding that the obtained CNCs are promising for the application as biodegradable drug delivery vehicles. This work was supported by the joint grant from the Science and Technology Center in Ukraine and Shota Rustaveli National Science Foundation of Georgia #6298 'New biodegradable cationic polymers composed of arginine and spermine-versatile biomaterials for various biomedical applications'.

Keywords: biodegradable polymers, cationic pseudo-proteins, nano-containers, drug delivery vehicles

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Authors: Tatyana Savchuk, Yelena Grinvald, Mohamed Ali, Ramune Sepetiene, Dinara Sadvakassova, Saniya Saussakova, Kuralay Zhangazieva, Dulat Imashpayev

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Introduction. The problem of viral hepatitis B (HBV) takes a vital place in the global health system. The existing risk of HBV transmission through blood transfusions is associated with transfusion of blood taken from infected individuals during the “serological window” period or from patients with latent HBV infection, the marker of which is anti-HBcore. In the absence of information about other markers of hepatitis B, the presence of anti-HBcore suggests that a person may be actively infected or has suffered hepatitis B in the past and has immunity. Aim. To study the risk factors influencing the positive anti-HBcore indicators among the donor population. Materials and Methods. The study was conducted in 2021 in the Scientific and Production Center of Transfusiology of the Ministry of Healthcare in Kazakhstan. The samples taken from blood donors were tested for anti-HBcore, by CLIA on the Architect i2000SR (ABBOTT). A special questionnaire was developed for the blood donors’ socio-demographic characteristics. Statistical analysis was conducted by the R software (version 4.1.1, USA, 2021). Results.5709 people aged 18 to 66 years were included in the study, the proportion of men and women was 68.17% and 31.83%, respectively. The average age of the participants was 35.7 years. A weighted multivariable mixed effects logistic regression analysis showed that age (p<0.001), ethnicity (p<0.05), and marital status (p<0.05) were statistically associated with anti-HBcore positivity. In particular, analysis adjusting for gender, nationality, education, marital status, family history of hepatitis, blood transfusion, injections, and surgical interventions, with a one-year increase in age (adjOR=1.06, 95%CI:1.05-1.07), showed an 6% growth in odds of having anti-HBcore positive results. Those who were russian ethnicity (adjOR=0.65, 95%CI:0.46-0.93) and representatives of other nationality groups (adjOR=0.56, 95%CI:0.37-0.85) had lower odds of having anti-HBcore when compared to Kazakhs when controlling for other covariant variables. Among singles, the odds of having a positive anti-HBcore were lower by 29% (adjOR = 0.71, 95%CI:0.57-0.89) compared to married participants when adjusting for other variables. Conclusions.Kazakhstan is one of the countries with medium endemicity of HBV prevalence (2%-7%). Results of the study demonstrated the possibility to form a profile of risk factors (age, nationality, marital status). Taking into account the data, it is recommended to increase attention to donor questionnaires by adding leading questions and to improve preventive measures to prevent HBV. Funding. This research was supported by a grant from Abbott Laboratories.

Keywords: anti-HBcore, blood donor, donation, hepatitis B virus, occult hepatitis

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Authors: Khaled Alabduljabbar

Abstract:

Background: Benign, isolated, recurrent sixth nerve palsy is very rare in children. Here we report a case of recurrent abducens nerve palsy with no obvious etiology. It is a diagnosis of exclusion. A recurrent benign form of 6th nerve palsy, a rarer still palsy, has been described in the literature, and it is of most likely secondary to inflammatory causes, e.g, following viral and bacterial infections. Purpose: To present a case of 14 months old girl with recurrent attacks of isolated left sixth cranial nerve palsy following upper respiratory tract infection. Observation: The patient presented to opthalmology clinic with sudden onset of inward deviation (esotropia) of the left eye with a compensatory left face turn one week following signs of upper respiratory tract infection. Ophthalmological examination revealed large angle esotropia of the left eye in primary position, with complete limitation of abduction of the left eye, no palpebral fissure changes, and abnormal position of the head (left face turn). Visual acuity was normal, and no significant refractive error on cycloplegic refraction for her age. Fundus examination was normal with no evidence of papilledema. There was no relative afferent pupillary defect (RAPD) and no anisocoria. Past medical history and family history were unremarkable, with no history of convulsion attacks or head trauma. Additional workout include CBC. Erythrocyte sedimentation rate, Urgent magnetic resonance imaging (MRI), and angiography of the brain were performed and demonstrated the absence of intracranial and orbital lesions. Referral to pediatric neurologist was also done and concluded no significant finding. The patient showed improvement of the left sixth cranial nerve palsy and left face turn over a period of two months. Seven months since the first attack, she experienced a recurrent attack of left eye esotropia with left face turn concurrent with URTI. The rest of eye examination was again unremarkable. CT scan and MRI scan of brain and orbit were performed and showed only signs of sinusitis with no intracranial pathology. The palsy resolved spontaneously within two months. A third episode of left 6th nerve palsy occurred 6 months later, whichrecovered over one month. Examination and neuroimagingwere unremarkable. A diagnosis of benign recurrent left 6th cranial nerve palsy was made. Conclusion: Benign sixth cranial nerve palsy is always a diagnosis of exclusion given the more serious and life-threatening alternative causes. It seems to have a good prognosis with only supportive measures. The likelihood of benign 6th cranial nerve palsy to resolve completely and spontaneously is high. Observation for at least 6 months without intervention is advisable.

Keywords: 6th nerve pasy, abducens nerve pasy, recurrent nerve palsy, cranial nerve palsy

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Authors: Siddhant Sethi, Yasuharu Takashima, Shigetaka Nakamura, Kenzo Fujimoto

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Site-directed mutagenesis is a renowned technique to introduce specific mutations in the genome. To achieve site-directed mutagenesis, many chemical and enzymatic approaches have been reported in the past like disulphite induced genome editing, CRISPR-Cas9, TALEN etc. The chemical methods are invasive whereas the enzymatic approaches are time-consuming and expensive. Most of these techniques are unusable in the cellular application due to their toxicity and other limitations. Photo-chemical cytosine deamination, introduced in 2010, is one of the major technique for enzyme-free single-point mutation of cytosine to uracil in DNA and RNA, wherein, 3-cyanovinylcarbazole nucleoside (CNVK) containing oligodeoxyribonucleotide (ODN) having CNVK at -1 position to that of target cytosine is reversibly crosslinked to target DNA strand using 366 nm and then incubated at 90ºC to accommodate deamination. This technique is superior to enzymatic methods of site-directed mutagenesis but has a disadvantage that it requires the use of high temperature for the deamination step which restricts its applicability in the in vivo applications. This study has been focused on improving the technique by reducing the temperature required for deamination. Firstly, the photo-cross-linker, CNVK has been modified by replacing cyano group attached to vinyl group with methyl ester (OMeVK), amide (NH2VK), and carboxylic acid (OHVK) to observe the acceleration in the deamination of target cytosine cross-linked to vinylcarbazole derivative. Among the derivatives, OHVK has shown 2 times acceleration in deamination reaction as compared to CNVK, while the other two derivatives have shown deceleration towards deamination reaction. The trend of rate of deamination reaction follows the same order as that of hydrophilicity of the vinylcarbazole derivatives. OHVK being most hydrophilic has shown highest acceleration while OMeVK is least hydrophilic has proven to be least active for deamination. Secondly, in the related study, the counter-base of the target cytosine, guanine has been replaced by inosine, 2-aminopurine, nebularine, and 5-nitroindole having distinct hydrogen bonding patterns with target cytosine. Among the ODNs with these counter bases, ODN with inosine has shown 12 fold acceleration towards deamination of cytosine cross-linked to CNVK at physiological conditions as compared to guanosine. Whereas, when 2-aminopurine, nebularine, and 5-nitroindole were used, no deamination reaction took place. It can be concluded that inosine has potential to be used as the counter base of target cytosine for the CNVK mediated photo-cross-linking induced deamination of cytosine. The increase in rate of deamination reaction has been attributed to pattern and number of hydrogen bonding between the cytosine and counter base. One of the important factor is presence of hydrogen bond between exo-cyclic amino group of cytosine and the counter base. These results will be useful for development of more efficient technique for site-directed mutagenesis for C → U transformations in the DNA/RNA which might be used in the living system for treatment of various genetic disorders and genome engineering for making designer and non-native proteins.

Keywords: C to U transformation, DNA editing, genome engineering, ultra-fast photo-cross-linking

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Authors: Hongmei Wang, Ziyun Xiang, Ying liu, Li Yu, Dongsheng Yue

Abstract:

Intro: The COVID-19 (Corona Virus Disease 2019) has greatly changed the global economic, political and financial ecology. The mutation of the coronavirus in the UK in December 2020 has brought new panic to the world. Deep learning was performed on Chest Computed tomography (CT) of COVID-19 and Influenza and describes their characteristics. The predominant features of COVID-19 pneumonia was ground-glass opacification, followed by consolidation. Lesion density: most lesions appear as ground-glass shadows, and some lesions coexist with solid lesions. Lesion distribution: the focus is mainly on the dorsal side of the periphery of the lung, with the lower lobe of the lungs as the focus, and it is often close to the pleura. Other features it has are grid-like shadows in ground glass lesions, thickening signs of diseased vessels, air bronchi signs and halo signs. The severe disease involves whole bilateral lungs, showing white lung signs, air bronchograms can be seen, and there can be a small amount of pleural effusion in the bilateral chest cavity. At the same time, this year's flu season could be near its peak after surging throughout the United States for months. Chest CT for Influenza infection is characterized by focal ground glass shadows in the lungs, with or without patchy consolidation, and bronchiole air bronchograms are visible in the concentration. There are patchy ground-glass shadows, consolidation, air bronchus signs, mosaic lung perfusion, etc. The lesions are mostly fused, which is prominent near the hilar and two lungs. Grid-like shadows and small patchy ground-glass shadows are visible. Deep neural networks have great potential in image analysis and diagnosis that traditional machine learning algorithms do not. Method: Aiming at the two major infectious diseases COVID-19 and influenza, which are currently circulating in the world, the chest CT of patients with two infectious diseases is classified and diagnosed using deep learning algorithms. The residual network is proposed to solve the problem of network degradation when there are too many hidden layers in a deep neural network (DNN). The proposed deep residual system (ResNet) is a milestone in the history of the Convolutional neural network (CNN) images, which solves the problem of difficult training of deep CNN models. Many visual tasks can get excellent results through fine-tuning ResNet. The pre-trained convolutional neural network ResNet is introduced as a feature extractor, eliminating the need to design complex models and time-consuming training. Fastai is based on Pytorch, packaging best practices for in-depth learning strategies, and finding the best way to handle diagnoses issues. Based on the one-cycle approach of the Fastai algorithm, the classification diagnosis of lung CT for two infectious diseases is realized, and a higher recognition rate is obtained. Results: A deep learning model was developed to efficiently identify the differences between COVID-19 and influenza using chest CT.

Keywords: COVID-19, Fastai, influenza, transfer network

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Authors: Neda Jebellie

Abstract:

New information and communication technologies (ICT) not only has revolutionized the world of communication but has also strongly impacted the state of international terrorism. Using the potential of social media, the new wave of terrorism easily can recruit new jihadi members, spread their violent ideology and garner financial support. IS (Islamic State) as the most dangerous terrorist group has already conquered a great deal of social media space and has deployed sophisticated web-based strategies to promote its extremist doctrine. In this respect the vastly popular social media are the perfect tools for IS to establish its virtual Caliphate (e-caliphate) and e-Ommah (e-citizen).Using social media to release violent videos of beheading journalists, burning their hostages alive and mass killing of prisoners are IS strategies to terrorize and subjugate its enemies. Several Twitter and Facebook accounts which are IS affiliations have targeted young generation of Muslims all around the world. In fact IS terrorists use modern resources of communication not only to share information and conduct operations but also justify their violent acts. The strict Wahhabi doctrine of ISIS is based on a fundamental interpretation of Islam in which religious war against non Muslims (Jihad) and killing infidels (Qatal) have been praised and recommended. Via social media IS disseminates its propaganda to inspire sympathizers across the globe. Combating this new wave of terrorism which is exploiting new communication technologies is the most significant challenge for authorities. Before the rise of internet and social media governments had to control only mosques and religious gathering such as Friday sermons(Jamaah Pray) to prevent spreading extremism among Muslims community in their country. ICT and new communication technologies have heighten the challenge of dealing with Islamic radicalism and have amplified its threat .According to the official reports even some of the governments such as UK have created a special force of Facebook warriors to engage in unconventional warfare in digital age. In compare with other terrorist groups, IS has effectively grasped social media potential. Their horrifying released videos on YouTube easily got viral and were re-twitted and shared by thousands of social media users. While some of the social media such as Twitter and Facebook have shut down many accounts alleged to IS but new ones create immediately so only blocking their websites and suspending their accounts cannot solve the problem as terrorists recreate new accounts. To combat cyber terrorism focusing on disseminating counter narrative strategies can be a solution. Creating websites and providing online materials to propagate peaceful and moderate interpretation of Islam can provide a cogent alternative to extremist views.

Keywords: IS-islamic state, cyber terrorism, social media, terrorism, information, communication technologies

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