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Introduction: Early diagnosis of Hepatocellular Carcinoma (HCC) by imaging and biochemical tests would be valuable in controlling morbidity and mortality associated with this most common primary hepatic malignancy which is the third leading cause of global cancer-related deaths. Objective: To determine an association between the level of serum Alpha Fetoprotein (AFP) and the size of the tumor in Hepatocellular Carcinoma (HCC).Materials & Methods: This cross-sectional descriptive study was conducted in Rehman Medical Institute, Peshawar, Pakistan from January 2018 till December 2019. Data were gathered from the medical records of Endoscopy Unit of Rehman Medical Institute. Patients were separated into three groups on the basis of serum AFP levels: Group I had standard levels of AFP (400 IU/ml). Patients were also separated into three groups on the basis of tumor; in Group A tumor size was less than 3 cm, in Group B it was between 3 and 5 cm, and in Group C the size was greater than 5 cm. For categorical variables, the Chi-square and Z test for proportions were applied; the Wilcoxon Rank-Sum (Mann-Whitney) test was used to evaluate the variation in the two categories, and the Kruskal-Wallis Rank test was used to evaluate the difference between categories. A p value ≤0.05 was taken as significant. Descriptive statistics were obtained by SPSS 24. Result: A total of 136 patients were evaluated according to AFP levels. The male to female ratio was 2.31:1. The mean presenting age was 59.36 ± 9.85 years while the mean tumor size was 6.93 ± 4.39 cm. Regarding AFP groups, there were 50(36.76%), in Group I, 31(22.79%) in Group II and 38(27.94%) in Group III. As per the Child Pugh classification, Class A, B and C were 69.85%, 16.18% and 0% respectively.Conclusion: Serum alpha fetoprotein was significantly associated with HCC tumor size. Alpha fetoprotein level can be a helpful marker to detect HCC and to differentiate between its initial and late stages. Monitoring AFP levels could be useful to diagnose recurring disease for patients with tumors that produce AFP.Keywords: Serum Alpha Fetoprotein; Hepatocellular Carcinoma; Tumor size.

Introduction: Research has implicated an exaggerated or self-directed immune response as a factor in determining patient outcome in COVID-19. Initial reports identify lymphopenia as having a predictive role in COVID-19 related disease severity.Objective: To document the occurrence of lymphopenia in COVID-19 patients and explore its association with demographic factors and disease course.Materials & Methods: This cross sectional, observational study was conducted at Rehman Medical Institute, Peshawar from May, 2020 to August, 2020. All patients admitted to the hospital with COVID-19 diagnosis were included. Relevant information including demographics, disease severity, laboratory findings & outcomes were noted in a predesigned Performa. The data were analyzed on SPSS 22 for descriptive and comparative statistics; p≤0.05 denoted significance.Results: A total of 216 patients were included, of whom 172 (79.6%) were males. The mean age was 54.61 ± 14.35 years. Classic lymphopenia was found in 67 (31.5%), 66 (31.0%) had borderline lymphopenia, and 80 (37.6%) had no lymphopenia. Of the classic lymphopenia group, 14 (20.9%) had mild disease, 21 (31.3%) had moderate disease, 18 (26.9%) had severe disease & 14 (20.9%) had critical disease. In patients with borderline lymphopenia 31 (47.0%) had mild disease, 17 (25.8%) moderate disease, 14 (21.2%) had severe disease and 04 (6.1%) had critical disease. In patients with no lymphopenia, 32 (40.0%) had mild, 32 (40.0%) had moderate, 14 (17.5%) had severe & 02 (2.5%) had critical disease. Mortality associated with classical lymphopenia was 37.3% (n=25) whereas 43.3% (n=29) patients recovered. Male gender, disease severity and outcome were statistically linked to lymphopenia; no statistical significance was observed with age.Conclusion: A statistically significant association of lymphopenia with severe/critical disease and adverse outcomes was noted.Keywords: Lymphopenia, COVID-19, Pandemic.

Introduction: Endoscopic Retrograde Cholangio-pancreatography (ERCP), being a useful though technically demanding diagnostic and therapeutic procedure to evaluate and treat diseases of biliary and pancreatic ducts is dependent in large part for its success on the skill of the operator. Objective: To determine the indications, procedures performed and success rate of ERCP at a tertiary care center of Peshawar. Materials & Methods: A descriptive cross-sectional study was carried out at the Endoscopy Unit of Rehman Medical Institute (RMI) from January 2020 to April 2020 using universal sampling technique. All ERCP procedures done in the endoscopy unit from January 2019 to December 2019 were included in the study regardless of their age, gender, ethnicity or presenting complains. Any ERCP that did not have complete data were excluded from the study. Data were collected in a structured Performa. Data were analyzed in Microsoft Excel for descriptive statistics. Results: A total of 161 ERCP procedures were performed during the study duration, of which 84(52.2%) were in males while 77(47.82%) were in females; the mean age was 54.82 ± 15.83 years. Biliary Stent placement (51.6%) was the most commonly performed procedure followed by Biliary Stone extraction (22.4%). Failed ERCP accounted for 30(18.6%) cases. The main indication for ERCP was Obstructive Jaundice (65.8%) followed by Common Bile duct (CBD) stones (42.9%). The least common indication was Dilated Intrahepatic Duct (1.86%). Only 4 cases of minor bleeding were observed during the procedure which were controlled during the procedures. No major complications have been seen on follow-up. Conclusion: Obstructive Jaundice is major contributor to ERCP’s being performed. It is a relatively safe procedure in the hands of an experienced operator. Keywords: Obstructive Jaundice; Retrograde Cholangiopancreatography; Gallstones; Pancreatic Duct.

Background: Among the many non-invasive techniques performed on patients with Hepatitis B Virus (HBV) related fibrosis, the most appropriate results have been obtained using Transient Elastography (FibroScan) to measure liver stiffness. The accurate diagnosis of fibrosis related to HBV is essential for prognostic and therapeutic decisions and offset the limitations of liver biopsy. Objective: To evaluate Transient Elastography (FibroScan) for detecting and staging hepatic fibrosis by comparing it with hepatic histopathology in patients with Hepatitis B at a tertiary care hospital of Peshawar. Materials & Methods: A descriptive study was done in March-April 2020 at Rehman Medical Institute, Peshawar, based on retrospective data from May 2016 to March 2020 on 145 HBV positive patients with various stages of hepatic fibrosis who had undergone non-invasive FibroScan during their first visit. Routine demographic, clinical and laboratory parameters were analyzed to predict the existence or absence of advanced fibrosis. At the end of the evaluation, the samples were categorized as F0 (No fibrosis), F1 (Initial fibrosis without septa), F2 (Fibrosis with septa), F3 (Advanced fibrosis) and F4 (Severe fibrosis with cirrhosis, C1). Descriptive data analysis was done by SPSS 17.0. Results: Out of 145 included patients of chronic hepatitis B, 110 were males and 35 were females. At initial stages the existing laboratory tools diagnosed chronic HBV-infected patients correctly, with minor fibrosis and cirrhosis. Independent indicators of liver fibrosis included platelet count, age, AST, ALT values and albumin; 80% of the patients were not affected by the disease, which means F0 was 80%. Yet some patients had fibrosis at different stages F1, F2, F3, F4 and C1. The FibroScan assessment revealed that out of 145 patients, only 11% patients were at stage F1 whereas the diagnostic value for F2, F3, F4, and C1 are ≤3% with F2=3%, F3=1%, F4=2%, and C1=2%. Conclusion: FibroScan is an effective method to detect HBV-related fibrosis and cirrhosis; it provided accurate distinction between various stages of fibrosis in Hepatitis B patients. Keywords: Cirrhosis, Liver; Hepatitis B; Liver Fibrosis; Carcinoma, Hepatocellular.

Newcastle disease virus (NDV) causes a highly contagious and devastating disease in poultry. ND causes heavy economic losses to the global poultry industry by decreasing the growth rate, decrease in egg production high morbidity and mortality. Although significant advances have been made in the vaccine development, outbreaks are reported in vaccinated birds. In this study, we report the damage caused by NDV infection in the pancreatic tissues of vaccinated and specific-pathogen-free chickens. The histopathological examination of the pancreas showed severe damage in the form of partial depletion of zymogen granules, acinar cell vacuolization, necrosis, apoptosis, congestion in the large and small vessels, sloughing of epithelial cells of the pancreatic duct, and mild perivascular edema. Increased plasma levels of corticosterone and somatostatin were observed in NDV-infected chicken at three- and five- days post infection (DPI). A slight decrease in the plasma concentrations of insulin was noticed at 5 DPI. Significant changes were not observed in the plasma levels of glucagon. Furthermore, NDV infection decreased the activity and mRNA expression of amylase, lipase, and trypsin from the pancreas. Taken together, our findings highlight that NDV induces extensive tissue damage in the pancreas, decreases the activity and expression of pancreatic enzymes, and increases plasma corticosterone and somatostatin. These findings provide new insights that a defective pancreas may be one of the reasons for decreased growth performance after NDV infection in chickens.

Metagenomic analysis of mosquito-borne and mosquito-specific viruses is useful to understand the viral diversity and for the surveillance of pathogens of medical and veterinary importance. Yunnan province is located at the southwest of China and has rich abundance of mosquitoes. Arbovirus surveillance is not conducted regularly in this province particularly at animal farms, which have public health as well as veterinary importance. Here, we have analyzed 10 pools of mosquitoes belonging to Culex tritaeniorhyncus, Aedes aegypti, Anopheles sinensis, and Armigeres subalbatus species, collected from different animal farms located at Yunnan province of China by using metagenomic next-generation sequencing technique. The generated viral metagenomic data reveal that the viral community matched by the reads was highly diverse and varied in abundance among animal farms, which contained more than 19 viral taxonomic families, specific to vertebrates, invertebrates, fungi, plants, protozoa, and bacteria. Additionally, a large number of viral reads were related to viruses that are non-classified. The viral reads related to animal viruses included parvoviruses, anelloviruses, circoviruses, flaviviruses, rhabdoviruses, and seadornaviruses, which might be taken by mosquitoes from viremic animal hosts during blood feeding. Notably, the presence of viral reads matched with Japanese encephalitis virus, Getah virus, and porcine parvoviruses in mosquitoes collected from different geographic sites suggested a potential circulation of these viruses in their vertebrate hosts. Overall, this study provides a comprehensive knowledge of diverse viral populations present at animal farms of Yunnan province of China, which might be a potential source of diseases for humans and domestic animals.

Understanding the proteolytic processing of polyprotein mediated by NS2B-NS3 protease contributes to the exploration of the mechanisms underlying infection of Japanese encephalitis virus (JEV), a zoonotic flavivirus. In this study, eukaryotic and prokaryotic cell models were employed to identify the cleavage sites mediated by viral NS2B-NS3 protease in JEV polyprotein. Artificial green fluorescent protein (GFP) substrates that contained the predicted cleavage site sequences of JEV polyprotein were expressed in swine testicle (ST) cells in the presence and absence of JEV infection, or co-expressed in E. coli with the recombinant NS2B-NS3 protease that was generated by fusing the N-terminal protease domain of NS3 to the central hydrophilic domain of NS2B. The cleavage of GFP substrates was examined by western blot. Among twelve artificial GFP substrates containing the cleavage site sequences predictively processed by host cell and/or NS2B-NS3 proteases, all sites were found to be cleaved by host cell proteases with different efficiencies. The sites at internal C, NS2A/NS2B, NS2B/NS3 and NS3/NS4A junctions, but not the sites at internal NS3, internal NS4A and NS4B/NS5 junctions were identified to be cleaved by JEV NS2B-NS3 protease. These data provide insight into the proteolytic processing of polyprotein, which is useful for understanding JEV replication and pathogenesis.

A total of 548 mosquitoes were collected from different animal farms located near to highly populated cities in Xinjiang and were subjected to metagenomic next-generation sequencing (mNGS). The mNGS data demonstrated that 18,842 (XJ1 strain) and 1,077 (XJ2 strain) of Japanese encephalitis virus (JEV)-related reads were detected in XJ1 and XJ2 mosquito samples collected from Wushi and Wensu counties of Aksu area, which accounted for 0.032% and 0.006% of the total clean reads generated from XJ1 and XJ2 samples, respectively. The Bayesian molecular phylogenetic analysis suggested that XJ1 and XJ2 strains belonged to JEV genotype III and were clustered with JEV strains isolated in China. Notably, Bayesian molecular time line phylogeny revealed that XJ1 strain shared its MRCA with JEV GSS strain about 67 YA, suggesting that XJ1 strain likely originated from linages closely related to GSS strain and spread to Xinjiang later. Overall, these findings suggest that Xinjiang was probably not free from JEV, and thus, a further surveillance of JEV is required in Xinjiang.

The phenotypic and genotypic characteristics of a live-attenuated genotype I (GI) strain (SD12-F120) of Japanese encephalitis virus (JEV) were compared with its virulent parental SD12 strain to gain an insight into the genetic changes acquired during the attenuation process. SD12-F120 formed smaller plaque on BHK-21 cells and showed reduced replication in mouse brains compared with SD12. Mice inoculated with SD12-F120 via either intraperitoneal or intracerebral route showed no clinical symptoms, indicating a highly attenuated phenotype in terms of both neuroinvasiveness and neurovirulence. SD12-F120 harbored 29 nucleotide variations compared with SD12, of which 20 were considered silent nucleotide mutations, while nine resulted in eight amino acid substitutions. Comparison of the amino acid variations of SD12-F120 vs SD12 pair with those from other four isogenic pairs of the attenuated and their virulent parental strains revealed that the variations at E138 and E176 positions of E protein were identified in four and three pairs, respectively, while the remaining amino acid variations were almost unique to their respective strain pairs. These observations suggest that the genetic changes acquired during the attenuation process were likely to be strain-specific and that the mechanisms associated with JEV attenuation/virulence are complicated.

This study examines point and non-point sources of air pollution and particulate matter and their associated socioeconomic and health impacts in South Asian countries, primarily India, China, and Pakistan. The legislative frameworks, policy gaps, and targeted solutions are also scrutinized. The major cities in these countries have surpassed the permissible limits defined by WHO for sulfur dioxide, carbon monoxide, particulate matter, and nitrogen dioxide. As a result, they are facing widespread health problems, disabilities, and causalities at extreme events. Populations in these countries are comparatively more prone to air pollution effects because they spend more time in the open air, increasing their likelihood of exposure to air pollutants. The elevated level of air pollutants and their long-term exposure increases the susceptibility to several chronic/acute diseases, i.e., obstructive pulmonary diseases, acute respiratory distress, chronic bronchitis, and emphysema. More in-depth spatial-temporal air pollution monitoring studies in China, India, and Pakistan are recommended. The study findings suggest that policymakers at the local, national, and regional levels should devise targeted policies by considering all the relevant parameters, including the country's economic status, local meteorological conditions, industrial interests, public lifestyle, and national literacy rate. This approach will also help design and implement more efficient policies which are less likely to fail when brought into practice.

Karyopherin α4 (KPNA4) is an adaptor molecule that mediates type I interferon (IFN) production by facilitating the nuclear translocation of IFN transcription factors. Here, we cloned the duck KPNA4 (duKPNA4) gene and analyzed its involvement in type I IFN expression as well as antiviral response against Japanese encephalitis virus (JEV). The full-length duKPNA4 gene encoded a 520-amino acid protein that shared 97.3–98.7% sequence similarity with its orthologues in chickens, humans and mice. The duKPNA4 was extensively expressed in various duck tissues at the mRNA level. Analysis of the subcellular localization of duKPNA4 by immunofluorescence assays indicated that the duKPNA4 was primarily distributed in both the cytoplasm and nucleus in primary duck embryonic fibroblasts (DEFs). However, it translocated from the cytoplasm to the nucleus in response to poly(I:C) stimulation or JEV infection. The duKPNA4 interacted with duck IFN regulatory factor 7 and facilitated its nuclear translocation, thereby up-regulating the expression of IFN-α and IFN-β in DEFs in the presence of poly(I:C) stimulation. Exogenous expression of duKPNA4 significantly elevated the expression of IFN-α and IFN-β induced by JEV infection and inhibited JEV replication in DEFs. These data demonstrate the importance of duKPNA4 in type I IFN signaling as well as the antiviral response against JEV replication., Highlights • duKPNA4 elevates type I IFN expression. • duKPNA4 promotes the nuclear translocation of duIRF7. • duKPNA4 inhibits JEV replication.

Japanese Encephalitis virus (JEV) is a zoonotic flavivirus that is the most significant etiological agent of childhood viral neurological infections. However, no specific antiviral drug is currently available to treat JEV infections. The JEV envelope (E) protein is a class II viral fusion protein that mediates host cell entry, making interference with the interaction between the E protein of JEV and its cognate receptors an attractive strategy for anti-JEV drug development. In this study, we identified a peptide derived from a phage display peptide library against the E protein of JEV, designated P1, that potentially inhibits in vitro and in vivo JEV infections. P1 inhibits JEV infection in BHK-21 cells with 50% inhibitory capacity at a concentration of 35.9 μM. The time-of-addition assay indicates that JEV replication is significantly inhibited during pre-infection and co-infection of P1 with JEV while post-infection treatments with P1 have very little impact on JEV proliferation, showing that P1 inhibits JEV infection at early stages and indicating the potential prophylactic effect of P1. We adapted an in vitro BiFC assay system and demonstrated that P1 interacts with JEV E proteins and blocks their entry into cells. We also evaluated the therapeutic efficacy of P1 in a lethal JEV mouse model exhibiting systemic and brain infections. Interestingly, P1 treatment protected C57BL/6 mice against mortality, markedly reduced the viral loads in blood and brain, and diminished the histopathological lesions in the brain cells. In addition to controlling systemic infection, P1 has a very low level of cytotoxicity and acts in a sequence-specific manner, as scrambled peptide sP1 does not show any antiviral activity. In conclusion, our in vitro and in vivo experimental findings show that P1 possesses antiviral activity against JEV infections, is safe to use, and has potential for further development as an antiviral treatment against JEV infections.

Japanese Encephalitis virus (JEV) is a zoonotic flavivirus that represents the most significant etiology of childhood viral neurological infections throughout the Asia. During the last 20 years, JEV genotype dominance has shifted from genotype III (GIII) to genotype I (GI). To date, the exact mechanism of this displacement is still not known. Culex (Cx.) mosquitoes are the most common species in China and play an essential role in maintaining JEV enzootic transmission cycle. In this study, we used Cx. pipiens mosquitoes from China as an in vivo mosquito model to explore if mosquitoes played a potential role in JEV genotype shift. We exposed female Cx. pipiens mosquitoes orally to either GI or GIII JEV strains. Midgut, whole mosquitoes, secondary organs, and salivary glands of JEV-infected mosquitoes were collected at 7 and 14 days of post infection (dpi) and subjected to measure the infection rate, replication kinetics, dissemination rate and transmission potential of the infected JEV strains in Cx. pipiens mosquitoes by 50% tissue culture infective dose assay. We found that Cx. pipiens mosquito was competent vector for both GI and GIII JEV infection, with similar infection rates and growth kinetics. After the establishment of infection, Cx. pipiens mosquitoes disseminated both JEV genotypes to secondary organs at similar rates of dissemination. A few GI-infected mosquito salivary glands (16.2%) were positive for GI virus, whereas GIII virus was undetectable in GIII-infected mosquito salivary glands at 7 dpi. However, 29.4% (5/17) and 36.3% (8/22) were positive for GI- and GIII-infected mosquito salivary glands at 14 dpi, respectively, showing an increase in JEV positive rate. No statistical difference in the transmission rate between GI- and GIII-infected mosquitoes was detected. Our experiment data demonstrated that GI and GIII viruses have similar infectivity in Cx. pipiens mosquitoes, suggesting that Cx. pipiens mosquitoes from China may not play a critical role in JEV genotype shift. Although the current data were obtained solely from Cx. pipiens mosquitoes, it is likely that the conclusion drawn could be extrapolated to the role of mosquitoes in JEV genotype shift., Author summary Japanese encephalitis virus (JEV) causes encephalitis and reproductive disorder in humans and pigs respectively, causing a serious impact on public health and pig industry. In nature JEV life cycle include both vertebrates (birds and pigs) as well as invertebrates (mosquitoes). Phylogenetic studies confirmed that JEV has five geographically and epidemiologically distinct genotypes (GI-V). Genotype III (GIII) was an endemic strain in Asia, but recently genotype I (GI) has displaced GIII as the most frequently isolated virus genotype. It is unclear if mosquitoes play a role in this genotype shift or not. Both genotypes are endemic in China and primarily transmitted by different species of Culex (Cx.) mosquitoes. Cx. Mosquitoes are the most common species in China and their role in this genotype shift was not studied previously. In the present study, we used Cx. pipiens mosquitoes from China as an in vivo mosquito model and challenged with GI and GIII JEV strains to explore if mosquitoes played a potential role in JEV genotype shift. Our investigation showed that GI and GIII viruses had similar infectivity in Cx. pipiens mosquitoes which highlighted that Cx. pipiens mosquitoes from China may not play a critical role in the genotype shift. Although the current data were obtained solely from Cx. pipiens mosquitoes, it is likely that the conclusion drawn could be extrapolated to the role of mosquitoes in JEV genotype shift.

A pneumonia-like disease of unknown origin caused a catastrophe in Wuhan city, China. This disease spread to 215 countries affecting a wide range of people. World health organization (WHO) called it a pandemic and it was officially named as Severe Acute Respiratory Syndrome Corona virus 2 (SARS CoV-2), also known as Corona virus disease (COVID-19). This pandemic compelled countries to enforce a socio-economic lockdown to prevent its widespread. This paper focuses on how the particulate matter pollution was reduced during the lockdown period (23 March to April 15, 2020) as compared to before lockdown. Both ground-based and satellite observations were used to identify the improvement in air quality of Pakistan with primary focus on four major cities of Lahore, Islamabad, Karachi and Peshawar. Both datasets have shown a substantial reduction in PM2.5 pollution levels (ranging from 13% to 33% in case of satellite observations, while 23%-58% in ground-based observations) across Pakistan. Result shows a higher rate of COVID-19 spread in major cities of Pakistan with poor air quality conditions. Yet more research is needed in order to establish linkage between COVID-19 spread and air pollution. However, it can be partially attributed to both higher rate of population density and frequent exposure of population to enhanced levels of PM2.5 concentrations before lockdown period.

This study, for the first time, aims to evaluate the situation of air quality in Pakistan critically; through a detailed assessment of sources, policies, and key challenges to identify the plausible way forward. Air pollution and particulate matter have merged as a global challenge in recent years because of its growing health and socio-economic risks. The intensity and impacts of these risks have become more pronounced, especially in developing countries like Pakistan that lack adequate warning, protection, and management systems. Various epidemiological studies have linked poor air quality with different health disorders and increasing death rates. In Pakistan, mortality rates as a result of exposure to increased levels of air pollutants, especially particulate matter, are alarming. According to the World Bank's estimates, Pakistan's annual burden of disease from outdoor air pollution is responsible for around 22,000 premature adult deaths and 163,432 DALYs (disability-adjusted life years) lost. The concentration of major air pollutants in Pakistan, such as NOx, O3, and SO2 have also been increasing significantly over the last two decades. Several studies are also reporting multiple instances of air quality around the major cities of Pakistan being consistently exceeding the national guidelines. During teh year 2019 PM2.5 cocnentrations in the city of Lahore revealed that almost every single day was in exceedance of the WHO and national air quality standards. Although the substantial effects of these rising pollutant concentrations in Pakistan have been stated in a few studies, however, the total extent, nature of contributing factors, and consequences remain inadequately understood. This study aims to use data available from monitoring stations, satellites, and literature to highlight the gaps in our understanding and emphasize the critical challenges associated with poor air quality faced in Pakistan. Topmost is the lack of air quality monitoring systems followed by poor initiatives by policymakers and enforcement agencies. A way forward while addressing these key challenges is also discussed, which focuses on the development of flexible monitoring, new technologies, and monitoring approaches in addition to communications among the various public, private agencies, and all relevant stakeholders.

The SD12-F120 is a live-attenuated genotype I strain of Japanese encephalitis virus (JEV) and was obtained by serial passage of wild-type strain SD12 on BHK-21 cells combined with multiple plaque purification and virulence selection in mice. The large scale production and vast clinical trials always demand ideal safety and efficacy profile of live-attenuated vaccines. In the present study, SD12-F120VC has undergone serial passaging of P1-P30 in WHO qualified Vero cells to assess the potential effect of adaptation to growth on Vero cells. The series of experiments showed that vaccine SD12-F120VC (Vero cell adapted) variants have consistently increased in peak virus titer compared to early passages and have good adaptation to growth in Vero cells. The animal experiments showed that Vero cell adapted SD12-F120VC variants have attenuation phenotype in suckling mice and the plaque morphology for all SD12-F120VC variants was small. Vaccination of mice with SD12-F120VC vaccine produced complete protection for homologous SD12 genotype I strain, but failed to give the complete protection of vaccinated mice against the challenge of heterologous N28 genotype III strain. In response to immunization of SD12-F120VC in mice, the neutralizing antibodies titer against homologous SD12-F120VC and SD12 (GI) was higher than heterologous N28 (GIII) strain. The prM protein has 6 amino acid substitutions, of which 5 amino acid changes were confined at the start of the pr domain in the ∼40 amino acids, and some mutations in the pr domain of prM might contribute to Vero cell adaptation. Our findings in this study are important for validation, evaluation and quality control study of live attenuated flaviviruses vaccines and show that Vero cells are a suitable substrate for the production of a safe and stable live-attenuated JEV vaccine.

Long non-coding RNAs (lncRNAs) are a class of non-protein-coding RNA molecules, which are involved in various biological processes, including chromatin modification, cell differentiation, pre-mRNA transcription and splicing, protein translation, etc. During the last decade, increasing evidence has suggested the involvement of lncRNAs in both immune and antiviral responses as positive or negative regulators. The immunity-associated lncRNAs modulate diverse and multilayered immune checkpoints, including activation or repression of innate immune signaling components, such as interleukin (IL)-8, IL-10, retinoic acid inducible gene I, toll-like receptors 1, 3, and 8, and interferon (IFN) regulatory factor 7, transcriptional regulation of various IFN-stimulated genes, and initiation of the cell apoptosis pathways. Additionally, some virus-encoded lncRNAs facilitate viral replication through individually or synergistically inhibiting the host antiviral responses or regulating multiple steps of the virus life cycle. Moreover, some viruses are reported to hijack host-encoded lncRNAs to establish persistent infections. Based on these amazing discoveries, lncRNAs are an emerging hotspot in host–virus interactions. In this review, we summarized the current findings of the host- or virus-encoded lncRNAs and the underlying mechanisms, discussed their impacts on immune responses and viral replication, and highlighted their critical roles in host–virus interactions.

Objectives\ud The objective of this research is to find the factors associated with tinnitus masker from the literature, and by using the large amount of audiology data available from a large NHS (National Health Services, UK) hearing aid clinic. The factors evaluated were hearing impairment, age, gender, hearing aid type, mould and clinical comments. \ud \ud Design\ud The research includes literature survey for factors associated with tinnitus masker, and performs the analysis of audiology data using statistical and data mining techniques. \ud \ud Setting\ud This research uses a large audiology data but it also faced the problem of limited data for tinnitus. \ud \ud Participants\ud It uses 1,316 records for tinnitus and other diagnoses, and 10,437 records of clinical comments from a hearing aid clinic. \ud \ud Primary and secondary outcome measures\ud The research is looking for variables associated with tinnitus masker, and in future, these variables can be combined into a single model to develop a decision support system to predict about tinnitus masker for a patient. \ud \ud Results\ud The results demonstrated that tinnitus maskers are more likely to be fit to individuals with milder forms of hearing loss, and the factors age, gender, type of hearing aid and mould were all found significantly associated with tinnitus masker. In particular, those patients having Age

The purpose of this research is to mine a large set of heterogeneous audiology data to create a decision support system (DSS) to choose between two hearing aid types (ITE\ud and BTE aid). This research is based on the data analysis of audiology data using various statistical and data mining techniques. It uses the data of a large NHS (National Health Services, UK) facility. It uses 180,000 records (covering more than 23,000 different patients) from a hearing aid clinic. The developed system uses an unconventional method to predict hearing aid type for a patient and it can be used as a second opinion by audiologists for complex cases. After modifying the system to take account of the feedback from a professional audiologist, the success rates obtained were in the ranges 63 to 66 percent. In this research an automatic system was developed to choose between an ITE or a BTE hearing aid type with an explanation facility that can be used as a second opinion by audiologist in cases where the choice of an ITE or a BTE hearing aid is not clear cut. This analysis of audiology data and DSS will provide supplementary information for audiology experts and hearing aid dispensers. This type of system may also be of interest to manufacturers of hearing technologies in using as a ready means for their telephone customer services staff to check data, discovering data in audiology records will also be good for general awareness about the suitability of hearing aid type.

Presented is a comparative study of two machine learning models (MLP Neural Network and Bayesian Network) as part of a decision support system for prescribing ITE (in the ear) and BTE (behind the ear) aids for people with hearing difficulties. The models are developed/trained and evaluated on a large set of patient records from major NHS audiology centre in England. The two main questions which the models aim to address are: 1) What type of hearing aid (ITE/BTE) should be prescribed to the patient? and 2) Which factors influence the choice of ITE as opposed to BTE hearing aids? The models developed here were evaluated against actual prescriptions given by the doctors and showed relatively high classification rates with the MLP network achieving slightly better results.

Background This paper describes the analysis of a database of over 180,000 patient records, collected from over 23,000 patients, by the hearing aid clinic at James Cook University Hospital in Middlesbrough, UK. These records consist of audiograms (graphs of the faintest sounds audible to the patient at six different pitches), categorical data (such as age, gender, diagnosis and hearing aid type) and brief free text notes made by the technicians. This data is mined to determine which factors contribute to the decision to fit a BTE (worn behind the ear) hearing aid as opposed to an ITE (worn in the ear) hearing aid. Methods From PCA (principal component analysis) four main audiogram types are determined, and are related to the type of hearing aid chosen. The effects of age, gender, diagnosis, masker, mould and individual audiogram frequencies are combined into a single model by means of logistic regression. Some significant keywords are also discovered in the free text fields by using the chi-squared (χ2) test, which can also be used in the model. The final model can act a decision support tool to help decide whether an individual patient should be offered a BTE or an ITE hearing aid. Results The final model was tested using 5-fold cross validation, and was able to replicate the decisions of audiologists whether to fit an ITE or a BTE hearing aid with precision in the range 0.79 to 0.87. Conclusions A decision support system was produced to predict the type of hearing aid which should be prescribed, with an explanation facility explaining how that decision was arrived at. This system should prove useful in providing a "second opinion" for audiologists.

In this chapter, we have used the chi-squared test and Yule’s Q measure to discover associations in tables of patient audiology data. These records are examples of heterogeneous medical records, since they contain audiograms, textual notes and typical relational fields. In our first experiment we used the chi-squared measure to discover associations between the different fields of audiology data such as patient gender and patient age with diagnosis and the type of hearing aid worn. Then, in our second experiment we used Yule’s Q to discover the strength and direction of the significant associations found by the chi-squared measure. Finally, we examined the likelihood ratio used in Bayesian evidence evaluation. We discuss our findings in the context of producing an audiology decision support system.