Search results for: pooled sera

Authors: Septiany Trisnaningtyas

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Purpose: This research aims to examine the factors affecting the profitability of pharmaceutical company during the Covid-19 Pandemic in Indonesia. A sharp decline in the number of patients coming to the hospital for treatment during the pandemic has an impact on the growth of the pharmaceutical sector and brought major changes in financial position and business performance. Pharmaceutical companies that provide products related to the Covid-19 pandemic can survive and continue to grow. This study investigates the factors affecting the profitability of pharmaceutical company during the Covid-19 Pandemic in Indonesia associated with the number of Covid-19 cases. Design/methodology/approach: This study uses panel-data regression models to evaluate the influence of the number of Covid-19 confirmed cases on profitability of ninelisted pharmaceuticalcompanies in Indonesia. This research is based on four independent variables that were empirically examined for their relationship with profitability. These variables are liquidity (current ratio), growth rate (sales growth), firm size (total sales), and market power (the Lerner index). Covid-19 case is used as moderating variable. Data of nine pharmaceutical companies listed on the Indonesia Stock Exchange covering the period of 2018–2021 were extracted from companies’ quarterly annual reports. Findings: In the period during Covid-19, company growth (sales growth) and market power (lerner index) have a positive and significant relationship to ROA and ROE. Total of confirmed Covid-19 cases has a positive and significant relationship to ROA and is proven to have a moderating effect between company’s growth (sales growth) to ROA and ROE and market power (Lerner index) to ROA. Research limitations/implications: Due to data availability, this study only includes data from nine listed pharmaceutical companies in Indonesian Stock exchange and quarterly annual reportscovering the period of 2018-2021. Originality/value: This study focuses onpharmaceutical companies in Indonesia during Covid-19 pandemic. Previous study analyzes the data from pharmaceutical companies’ annual reports since 2014 and focus on universal health coverage (national health insurance) implementation from the Indonesian government. This study analyzes the data using fixed effect panel-data regression models to evaluate the influence of Covid-19 confirmed cases on profitability. Pooled ordinary least squares regression and fixed effects were used to analyze the data in previous study. This study also investigate the moderating effect of Covid-19 confirmed cases to profitability in relevant with the pandemic situation.

Keywords: profitability, indonesia, pharmaceutical, Covid-19

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Authors: Ahlam Ali, Katrina Lappin, Jaine Blayney, Ken Mills

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Leukaemia is the most frequently (30%) occurring type of paediatric cancer. Of these, approximately 80% are acute lymphoblastic leukaemia (ALL) with acute myeloid leukaemia (AML) cases making up the remaining 20% alongside other leukaemias. Unfortunately, children with AML do not have promising prognosis with only 60% surviving 5 years or longer. It has been highlighted recently the need for age-specific therapies for AML patients, with paediatric AML cases having a different mutational landscape compared with AML diagnosed in adult patients. Drug Repurposing is a recognized strategy in drug discovery and development where an already approved drug is used for diseases other than originally indicated. We aim to identify novel combination therapies with the promise of providing alternative more effective and less toxic induction therapy options. Our in-silico analysis highlighted ‘cell death and survival’ as an aberrant, potentially targetable pathway in paediatric AML patients. On this basis, 83 apoptotic inducing compounds were screened. A preliminary single agent screen was also performed to eliminate potentially toxic chemicals, then drugs were constructed into a pooled library with 10 drugs per well over 160 wells, with 45 possible pairs and 120 triples in each well. Seven cell lines were used during this study to represent the clonality of AML in paediatric patients (Kasumi-1, CMK, CMS, MV11-14, PL21, THP1, MOLM-13). Cytotoxicity was assessed up to 72 hours using CellTox™ Green reagent. Fluorescence readings were normalized to a DMSO control. Z-Score was assigned to each well based on the mean and standard deviation of all the data. Combinations with a Z-Score <2 were eliminated and the remaining wells were taken forward for further analysis. A well was considered ‘successful’ if each drug individually demonstrated a Z-Score <2, while the combination exhibited a Z-Score >2. Each of the ten compounds in one well (155) had minimal or no effect as single agents on cell viability however, a combination of two or more of the compounds resulted in a substantial increase in cell death, therefore the ten compounds were de-convoluted to identify a possible synergistic pair/triple combinations. The screen identified two possible ‘novel’ drug pairing, with BCL2 inhibitor ABT-737, combined with either a CDK inhibitor Purvalanol A, or AKT/ PI3K inhibitor LY294002. (ABT-737- 100 nM+ Purvalanol A- 1 µM) (ABT-737- 100 nM+ LY294002- 2 µM). Three possible triple combinations were identified (LY2409881+Akti-1/2+Purvalanol A, SU9516+Akti-1/2+Purvalanol A, and ABT-737+LY2409881+Purvalanol A), which will be taken forward for examining their efficacy at varying concentrations and dosing schedules, across multiple paediatric AML cell lines for optimisation of maximum synergy. We believe that our combination screening approach has potential for future use with a larger cohort of drugs including FDA approved compounds and patient material.

Keywords: AML, drug repurposing, ABT-737, apoptosis

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Authors: Vladimir Berezin, Andrey Bogoyavlenskiy, Pavel Alexyuk, Madina Alexyuk, Aizhan Turmagambetova, Irina Zaitseva, Nadezhda Sokolova, Elmira Omirtaeva

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Introduction: Triterpene saponins of plant origin are one of the most promising candidates for elaboration of novel adjuvants. Due to the combination of immunostimulating activity and the capacity interact with amphipathic molecules with formation of highly immunogenic nanocomplexes, triterpene saponins could serve as a good adjuvant/delivery system for vaccine use. In the research presented adjuvants on the base of nanocomplexes contained triterpene saponins isolated from Glycyrrhiza glabra and Saponaria officinalis plants indigenous to Kazakhstan were elaborated for influenza vaccine use. Methods: Purified triterpene saponins 'Glabilox' and 'SO1' with low toxicity and high immunostimulatory activity were isolated from plants Glycyrrhiza glabra L. and Saponaria officinalis L. by high-performance liquid chromatography (HPLC) and identified using electrospray ionization mass spectrometry (ESI-MS). Influenza virus A/St-Petersburg/5/09 (H1N1) propagated in 9-days old chicken embryos was concentrated and purified by centrifugation in sucrose gradient. Nanocomplexes contained lipids, and triterpene saponins Glabilox or SO1 were prepared by dialysis technique. Immunostimulating activity of experimental vaccine preparations was studied in vaccination/challenge experiments in mice. Results: Humoral and cellular immune responses and protection against influenza virus infection were examined after single subcutaneous and intranasal immunization. Mice were immunized subunit influenza vaccine (HA+NA) or whole virus inactivated influenza vaccine in doses 3.0/5.0/10.0 µg antigen/animal mixed with adjuvant in dose 15.0 µg/animal. Sera were taken 14-21 days following single immunization and mice challenged by A/St-Petersburg/5/09 influenza virus in dose 100 EID₅₀. Study of experimental influenza vaccine preparations in animal immunization experiments has shown that subcutaneous and intranasal immunization with subunit influenza vaccine mixed with nanocomplexes contained Glabilox or SO1 saponins stimulated high levels of humoral immune response (IgM, IgA, IgG1, IgG2a, and IgG2b antibody) and cellular immune response (IL-2, IL-4, IL-10, and IFN-γ cytokines) and resulted 80-90% protection against lethal influenza infection. Also, single intranasal and single subcutaneous immunization with whole virus inactivated influenza vaccine mixed with nanoparticulated adjuvants stimulated high levels of humoral and cellular immune responses and provided 100% protection against lethal influenza infection. Conclusion: The results of study have shown that nanocomplexes contained purified triterpene saponins Glabilox and SO1 isolated from plants indigenous to Kazakhstan can stimulate a broad spectrum of humoral and cellular immune responses and induce protection against lethal influenza infection. Both elaborated adjuvants are promising for incorporation to influenza vaccine intended for subcutaneous and intranasal routes of immunization.

Keywords: influenza vaccine, adjuvants, triterpene saponins, immunostimulating activity

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Authors: Yasmeen Jamal Alabdallat, Almutazballlah Bassam Qablan, Hamza Al-Salhi, Salameh Alarood, Ibraheem Alkhawaldeh, Obada Abunar, Adam Abdallah

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Obstructive sleep apnea (OSA) is a disorder caused by the repeated collapse of the upper airway during sleep. It is the most common cause of sleep-related breathing disorder, as OSA can cause loud snoring, daytime fatigue, or more severe problems such as high blood pressure, cardiovascular disease, coronary artery disease, insulin-resistant diabetes, and depression. The hypoglossal nerve stimulator (HNS) is an implantable medical device that reduces the occurrence of obstructive sleep apnea by electrically stimulating the hypoglossal nerve in rhythm with the patient's breathing, causing the tongue to move. This stimulation helps keep the patient's airways clear while they sleep. This systematic review and meta-analysis aimed to assess the clinical outcome of hypoglossal nerve stimulation as a treatment of obstructive sleep apnea. A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials was conducted from inception until August 2022. Studies assessing the following clinical outcomes (Apnea-Hypopnea Index (AHI), Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), Oxygen Desaturation Indices (ODI), (Oxygen Saturation (SaO2)) were pooled in the meta-analysis using Review Manager Software. We assessed the quality of studies according to the Cochrane risk-of-bias tool for randomized trials (RoB2), Risk of Bias In Non-randomized Studies - of Interventions (ROBINS-I), and a modified version of NOS for the non-comparative cohort studies.13 Studies (Six Clinical Trials and Seven prospective cohort studies) with a total of 817 patients were included in the meta-analysis. The results of AHI were reported in 11 studies examining OSA 696 patients. We found that there was a significant improvement in the AHI after 12 months of HNS (MD = 18.2 with 95% CI, (16.7 to 19.7; I2 = 0%); P < 0.00001). Further, 12 studies reported the results of ESS after 12 months of intervention with a significant improvement in the range of sleepiness among the examined 757 OSA patients (MD = 5.3 with 95% CI, (4.75 to 5.86; I2 = 65%); P < 0.0001). Moreover, nine studies involving 699 participants reported the results of FOSQ after 12 months of HNS with a significant reported improvement (MD = -3.09 with 95% CI, (-3.41 to 2.77; I2 = 0%); P < 0.00001). In addition, ten studies reported the results of ODI with a significant improvement after 12 months of HNS among the 817 examined patients (MD = 14.8 with 95% CI, (13.25 to 16.32; I2 = 0%); P < 000001). The Hypoglossal Nerve Stimulation showed a significant positive impact on obstructive sleep apnea patients after 12 months of therapy in terms of apnea-hypopnea index, oxygen desaturation indices, manifestations of the behavioral morbidity associated with obstructive sleep apnea, and functional status resulting from sleepiness.

Keywords: apnea, meta-analysis, hypoglossal, stimulation

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Authors: Kathrina Aseanne Acapulco-Gomez, Shayne Julieane Morales, Tzar Francis Verame

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Mean platelet volume (MPV) is the most accurate measure of the size of platelets and is routinely measured by most automated hematological analyzers. Several studies have shown associations between MPV and cardiovascular risks and outcomes. Although its measurement may provide useful data, MPV remains to be a diagnostic tool that is yet to be included in routine clinical decision making. The aim of this systematic review and meta-analysis is to determine summary estimates of the diagnostic accuracy of mean platelet volume for the diagnosis of myocardial infarction among adult patients with angina and/or its equivalents in terms of sensitivity, specificity, diagnostic odds ratio, and likelihood ratios, and to determine the difference of the mean MPV values between those with MI and those in the non-MI controls. The primary search was done through search in electronic databases PubMed, Cochrane Review CENTRAL, HERDIN (Health Research and Development Information Network), Google Scholar, Philippine Journal of Pathology, and Philippine College of Physicians Philippine Journal of Internal Medicine. The reference list of original reports was also searched. Cross-sectional, cohort, and case-control articles studying the diagnostic performance of mean platelet volume in the diagnosis of acute myocardial infarction in adult patients were included in the study. Studies were included if: (1) CBC was taken upon presentation to the ER or upon admission (within 24 hours of symptom onset); (2) myocardial infarction was diagnosed with serum markers, ECG, or according to accepted guidelines by the Cardiology societies (American Heart Association (AHA), American College of Cardiology (ACC), European Society of Cardiology (ESC); and, (3) if outcomes were measured as significant difference AND/OR sensitivity and specificity. The authors independently screened for inclusion of all the identified potential studies as a result of the search. Eligible studies were appraised using well-defined criteria. Any disagreement between the reviewers was resolved through discussion and consensus. The overall mean MPV value of those with MI (9.702 fl; 95% CI 9.07 – 10.33) was higher than in those of the non-MI control group (8.85 fl; 95% CI 8.23 – 9.46). Interpretation of the calculated t-value of 2.0827 showed that there was a significant difference in the mean MPV values of those with MI and those of the non-MI controls. The summary sensitivity (Se) and specificity (Sp) for MPV were 0.66 (95% CI; 0.59 - 0.73) and 0.60 (95% CI; 0.43 – 0.75), respectively. The pooled diagnostic odds ratio (DOR) was 2.92 (95% CI; 1.90 – 4.50). The positive likelihood ratio of MPV in the diagnosis of myocardial infarction was 1.65 (95% CI; 1.20 – 22.27), and the negative likelihood ratio was 0.56 (95% CI; 0.50 – 0.64). The intended role for MPV in the diagnostic pathway of myocardial infarction would perhaps be best as a triage tool. With a DOR of 2.92, MPV values can discriminate between those who have MI and those without. For a patient with angina presenting with elevated MPV values, it is 1.65 times more likely that he has MI. Thus, it is implied that the decision to treat a patient with angina or its equivalents as a case of MI could be supported by an elevated MPV value.

Keywords: mean platelet volume, MPV, myocardial infarction, angina, chest pain

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Authors: Parul Kulshreshtha, Subrata Sinha, Rakesh Bhatnagar

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This study was conducted by taking B. anthracis as a model pathogen. On infecting a host, B. anthracis secretes three proteins, namely, protective antigen (PA, 83kDa), edema factor (EF, 89 kDa) and lethal factor (LF, 90 kDa). These three proteins are the components of two anthrax toxins. PA binds to the cell surface receptors, namely, tumor endothelial marker (TEM) 8 and capillary morphogenesis protein (CMG) 2. TEM8 and CMG2 interact with LDL-receptor related protein (LRP) 6 for endocytosis of EF and LF. On entering the cell, EF acts as a calmodulin-dependent adenylate cyclase that causes a prolonged increase of cytosolic cyclic adenosine monophosphate (cAMP). LF is a metalloprotease that cleaves most isoforms of mitogen-activated protein kinase kinases (MAPKK/MEK) close to their N-terminus. By secreting these two toxins, B.anthracis ascertains death of the host. Once the systemic levels of the toxins rise, antibiotics alone cannot save the host. Therefore, toxin-specific inhibitors have to be developed. In this wake, monoclonal antibodies have been developed for the neutralization of toxic effects of anthrax toxins. We created hybridomas by using spleen of mice that were actively immunized with rLFn (recombinant N-terminal domain of lethal factor of B. anthracis) to obtain anti-toxin antibodies. Later on, separate group of mice were immunized with rLFn to obtain a polyclonal control for passive immunization studies of monoclonal antibodies. This led to the identification of one cohort of rLFn-immunized mice that harboured disease-enhancing polyclonal antibodies. At the same time, the monoclonal antibodies from all the hybridomas were being tested. Two hybridomas secreted monoclonal antibodies (H8 and H10) that were cross-reactive with EF (edema factor) and LF (lethal factor), while the other two hybridomas secreted LF-specific antibodies (H7 and H11). The protective efficacy of H7, H8, H10 and H11 was investigated. H7, H8 and H10 were found to be protective. H11 was found to have disease enhancing characteristics in-vitro and in mouse model of challenge with B. anthracis. In this study the disease enhancing character of H11 monoclonal antibody and anti-rLFn polyclonal sera was investigated. Combination of H11 with protective monoclonal antibodies (H8 and H10) reduced its disease enhancing nature both in-vitro and in-vivo. But combination of H11 with LETscFv (an scFv with VH and VL identical to H10 but lacking Fc region) could not abrogate the disease-enhancing character of H11 mAb. Therefore it was concluded that for suppression of disease enhancement, Fc portion was absolutely essential for interaction of H10 with H11. Our study indicates that the protective potential of an antibody depends equally on its idiotype/ antigen specificity and its isotype. A number of monoclonal and engineered antibodies are being explored as immunotherapeutics but it is absolutely essential to characterize each one for their individual and combined protective potential. Although new in the sphere of toxin-based diseases, it is extremely important to characterize the disease-enhancing nature of polyclonal as well as monoclonal antibodies. This is because several anti-viral therapeutics and vaccines have failed in the face of this phenomenon. The passive –immunotherapy thus needs to be well formulated to avoid any contraindications.

Keywords: immunotherapy, polyclonal, monoclonal, antibody-dependent disease enhancement

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Authors: Peter J. Fusco, Dave M. Mathew, Chris Mathew, Kenneth H. Levy, Kathryn S. Varghese, Stephanie Salazar-Restrepo, Serena M. Mathew, Sofia Khaja, Eamon Vega, Mia Polizzi, Alyssa Mullane, Adham Ahmed

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Background: Laparoscopic (LS) removal of neuroblastomas in children has been reported to offer favorable outcomes compared to the conventional open thoracotomy (OT) procedure. Critical perioperative measures such as blood loss, operative time, length of stay, and time to postoperative chemotherapy have all supported laparoscopic use rather than its more invasive counterpart. Herein, a pairwise meta-analysis was performed comparing perioperative outcomes between LS and OT in thoracoabdominal neuroblastoma cases. Methods: A comprehensive literature search was performed on PubMed, Ovid EMBASE, and Scopus databases to identify studies comparing the outcomes of pediatric patients with thoracoabdominal neuroblastomas undergoing resection via OT or LS. After deduplication, 4,227 studies were identified and subjected to initial title screening with exclusion and inclusion criteria to ensure relevance. When studies contained overlapping cohorts, only the larger series were included. Primary outcomes include estimated blood loss (EBL), hospital length of stay (LOS), and mortality, while secondary outcomes were tumor recurrence, post-operative complications, and operation length. The “meta” and “metafor” packages were used in R, version 4.0.2, to pool risk ratios (RR) or standardized mean differences (SMD) in addition to their 95% confidence intervals in the random effects model via the Mantel-Haenszel method. Heterogeneity between studies was assessed using the I² test, while publication bias was assessed via funnel plot. Results: The pooled analysis included 209 patients from 5 studies (141 OT, 68 LS). Of the included studies, 2 originated from the United States, 1 from Toronto, 1 from China, and 1was from a Japanese center. Mean age between study cohorts ranged from 2.4 to 5.3 years old, with female patients occupying between 30.8% to 50% of the study populations. No statistically significant difference was found between the two groups for LOS (SMD -1.02; p=0.083), mortality (RR 0.30; p=0.251), recurrence(RR 0.31; p=0.162), post-operative complications (RR 0.73; p=0.732), or operation length (SMD -0.07; p=0.648). Of note, LS appeared to be protective in the analysis for EBL, although it did not reach statistical significance (SMD -0.4174; p= 0.051). Conclusion: Despite promising literature assessing LS removal of pediatric neuroblastomas, results showed it was non-superior to OT for any explored perioperative outcomes. Given the limited comparative data on the subject, it is evident that randomized trials are necessary to further the efficacy of the conclusions reached.

Keywords: laparoscopy, neuroblastoma, thoracoabdominal, thoracotomy

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Authors: Piotr Tylec, Alicja Dudek, Grzegorz Torbicz, Magdalena Mizera, Natalia Gajewska, Michael Su, Tanawat Vongsurbchart, Tomasz Stefura, Magdalena Pisarska, Mateusz Rubinkiewicz, Piotr Malczak, Piotr Major, Michal Pedziwiatr

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Introduction: Quality of life after bariatric surgery is an important factor when evaluating the final result of the treatment. Considering the vast surgical options, we tried to globally compare available methods in terms of quality of following the surgery. The aim of the study is to compare the quality of life a year after bariatric intervention using network meta-analysis methods. Material and Methods: We performed a systematic review according to PRISMA guidelines with Bayesian network meta-analysis. Inclusion criteria were: studies comparing at least two methods of weight loss treatment of which at least one is surgical, assessment of the quality of life one year after surgery by validated questionnaires. Primary outcomes were quality of life one year after bariatric procedure. The following aspects of quality of life were analyzed: physical, emotional, general health, vitality, role physical, social, mental, and bodily pain. All questionnaires were standardized and pooled to a single scale. Lifestyle intervention was considered as a referenced point. Results: An initial reference search yielded 5636 articles. 18 studies were evaluated. In comparison of total score of quality of life, we observed that laparoscopic sleeve gastrectomy (LSG) (median (M): 3.606, Credible Interval 97.5% (CrI): 1.039; 6.191), laparoscopic Roux en-Y gastric by-pass (LRYGB) (M: 4.973, CrI: 2.627; 7.317) and open Roux en-Y gastric by-pass (RYGB) (M: 9.735, CrI: 6.708; 12.760) had better results than other bariatric intervention in relation to lifestyle interventions. In the analysis of the physical aspects of quality of life, we notice better results in LSG (M: 3.348, CrI: 0.548; 6.147) and in LRYGB procedure (M: 5.070, CrI: 2.896; 7.208) than control intervention, and worst results in open RYGB (M: -9.212, CrI: -11.610; -6.844). Analyzing emotional aspects, we found better results than control intervention in LSG, in LRYGB, in open RYGB, and laparoscopic gastric plication. In general health better results were in LSG (M: 9.144, CrI: 4.704; 13.470), in LRYGB (M: 6.451, CrI: 10.240; 13.830) and in single-anastomosis gastric by-pass (M: 8.671, CrI: 1.986; 15.310), and worst results in open RYGB (M: -4.048, CrI: -7.984; -0.305). In social and vital aspects of quality of life, better results were observed in LSG and LRYGB than control intervention. We did not find any differences between bariatric interventions in physical role, mental and bodily aspects of quality of life. Conclusion: The network meta-analysis revealed that better quality of life in total score one year after bariatric interventions were after LSG, LRYGB, open RYGB. In physical and general health aspects worst quality of life was in open RYGB procedure. Other interventions did not significantly affect the quality of life after a year compared to dietary intervention.

Keywords: bariatric surgery, network meta-analysis, quality of life, one year follow-up

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Authors: Gunta Resevica, Nikita Zrelovs, Ivars Silamikelis, Ieva Kalnciema, Helvijs Niedra, Gunārs Lācis, Toms Bartulsons, Inga Moročko-Bičevska, Arturs Stalažs, Kristīne Drevinska, Andris Zeltins, Ina Balke

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Newly discovered viruses provide novel knowledge for basic phytovirus research, serve as tools for biotechnology and can be helpful in identification of epidemic outbreaks. Blackcurrant-associated rhabdovirus (BCaRV) have been discovered in USA germplasm collection samples from Russia and France. As it was reported in one accession originating from France it is unclear whether the material was already infected when it entered in the USA or it became infected while in collection in the USA. Due to that BCaRV was definite as non-EU viruses. According to ICTV classification BCaRV is representative of Blackcurrant betanucleorhabdovirus specie in genus Betanucleorhabdovirus (family Rhabdoviridae). Nevertheless, BCaRV impact on the host, transmission mechanisms and vectors are still unknown. In RNA-seq data pool from Ribes plants resistance gene study by high throughput sequencing (HTS) we observed differences between sample group gene transcript heat maps. Additional analysis of the whole data pool (total 393660492 of 150 bp long read pairs) by rnaSPAdes v 3.13.1 resulted into 14424 bases long contig with an average coverage of 684x with shared 99.5% identity to the previously reported first complete genome of BCaRV (MF543022.1) using EMBOSS Needle. This finding proved BCaRV presence in EU and indicated that it might be relevant pathogen. In this study leaf tissue from twelve asymptomatic blackcurrant cv. Mara Eglite plants (negatively tested for blackcurrant reversion virus (BRV)) from Dobele, Latvia (56°36'31.9"N, 23°18'13.6"E) was collected and used for total RNA isolation with RNeasy Plant Mini Kit with minor modifications, followed by plant rRNA removal by a RiboMinus Plant Kit for RNA-Seq. HTS libraries were prepared using MGI Easy RNA Directional Library Prep Set for 16 reactions to obtain 150 bp pair-end reads. Libraries were pooled, circularized and cleaned and sequenced on DNBSEQ-G400 using PE150 flow cell. Additionally, all samples were tested by RT-PCR, and amplicons were directly sequenced by Sanger-based method. The contig representing the genome of BCaRV isolate Mara Eglite was deposited at European Nucleotide Archive under accession number OU015520. Those findings indicate a second evidence on the presence of this particular virus in the EU and further research on BCaRV prevalence in Ribes from other geographical areas should be performed. As there are no information on BCaRV impact on the host this should be investigated, regarding the fact that mixed infections with BRV and nucleorhabdoviruses are reported.

Keywords: BCaRV, Betanucleorhabdovirus, Ribes, RNA-seq

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Authors: Jaeyoung Lee, Minji Je

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Objectives: In adolescence, adolescents are curious about sex, but sexual experience before becoming an adult can cause the risk of high probability of sexually transmitted infection. Therefore, it is very important to prevent sexually transmitted infections so that adolescents can grow in healthy and upright way. Adolescent females, especially, have sexual behavior distinguished from that of male adolescents. Protecting female adolescents’ reproductive health is even more important since it is directly related to the childbirth of the next generation. This study, thus, investigated the predictors of sexually transmitted infection in adolescent females with sexual experiences based on the National Health Statistics in Korea. Methods: This study was conducted based on the National Health Statistics in Korea. The 11th Korea Youth Behavior Web-based Survey in 2016 was conducted in the type of anonymous self-reported survey in order to find out the health behavior of adolescents. The target recruitment group was middle and high school students nationwide as of April 2016, and 65,528 students from a total of 800 middle and high schools participated. The study was conducted in 537 female high school students (Grades 10–12) among them. The collected data were analyzed as complex sampling design using SPSS statistics 22. The strata, cluster, weight, and finite population correction provided by Korea Center for Disease Control & Prevention (KCDC) were reflected to constitute complex sample design files, which were used in the statistical analysis. The analysis methods included Rao-Scott chi-square test, complex samples general linear model, and complex samples multiple logistic regression analysis. Results: Out of 537 female adolescents, 11.9% (53 adolescents) had experiences of venereal infection. The predictors for venereal infection of the subjects were ‘age at first intercourse’ and ‘sexual intercourse after drinking’. The sexually transmitted infection of the subjects was decreased by 0.31 times (p=.006, 95%CI=0.13-0.71) for middle school students and 0.13 times (p<.001, 95%CI=0.05-0.32) for high school students whereas the age of the first sexual experience was under elementary school age. In addition, the sexually transmitted infection of the subjects was 3.54 times (p < .001, 95%CI=1.76-7.14) increased when they have experience of sexual relation after drinking alcohol, compared to those without the experience of sexual relation after drinking alcohol. Conclusions: The female adolescents had high probability of sexually transmitted infection if their age for the first sexual experience was low. Therefore, the female adolescents who start sexual experience earlier shall have practical sex education appropriate for their developmental stage. In addition, since the sexually transmitted infection increases, if they have sexual relations after drinking alcohol, the consideration for prevention of alcohol use or intervention of sex education shall be required. When health education intervention is conducted for health promotion for female adolescents in the future, it is necessary to reflect the result of this study.

Keywords: adolescent, coitus, female, sexually transmitted diseases

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Authors: A. Delimitsou, C. Gouedard, E. Konstanta, A. Koletis, S. Patera, E. Manou, K. Spaho, S. Murray

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Background: There remains a lack of International Standard Control Reference materials for Next Generation Sequencing-based approaches or device calibration. We have designed and validated dsDNA biomimetic reference materials for targeted such approaches incorporating proprietary motifs (patent pending) for device/test calibration. They enable internal single-sample calibration, alleviating sample comparisons to pooled historical population-based data assembly or statistical modelling approaches. We have validated such an approach for BRCA Copy Number Variation analytics using iQRS™-CNVSUITE versus Mixed Ligation-dependent Probe Amplification. Methods: Standard BRCA Copy Number Variation analysis was compared between mixed ligation-dependent probe amplification and next generation sequencing using a cohort of 198 breast/ovarian cancer patients. Next generation sequencing based copy number variation analysis of samples spiked with iQRS™ dsDNA biomimetics were analysed using proprietary CNVSUITE software. Mixed ligation-dependent probe amplification analyses were performed on an ABI-3130 Sequencer and analysed with Coffalyser software. Results: Concordance of BRCA – copy number variation events for mixed ligation-dependent probe amplification and CNVSUITE indicated an overall sensitivity of 99.88% and specificity of 100% for iQRS™-CNVSUITE. The negative predictive value of iQRS-CNVSUITE™ for BRCA was 100%, allowing for accurate exclusion of any event. The positive predictive value was 99.88%, with no discrepancy between mixed ligation-dependent probe amplification and iQRS™-CNVSUITE. For device calibration purposes, precision was 100%, spiking of patient DNA demonstrated linearity to 1% (±2.5%) and range from 100 copies. Traditional training was supplemented by predefining the calibrator to sample cut-off (lock-down) for amplicon gain or loss based upon a relative ratio threshold, following training of iQRS™-CNVSUITE using spiked iQRS™ calibrator and control mocks. BRCA copy number variation analysis using iQRS™-CNVSUITE™ was successfully validated and ISO15189 accredited and now enters CE-IVD performance evaluation. Conclusions: The inclusion of a reference control competitor (iQRS™ dsDNA mimetic) to next generation sequencing-based sequencing offers a more robust sample-independent approach for the assessment of copy number variation events compared to mixed ligation-dependent probe amplification. The approach simplifies data analyses, improves independent sample data analyses, and allows for direct comparison to an internal reference control for sample-specific quantification. Our iQRS™ biomimetic reference materials allow for single sample copy number variation analytics and further decentralisation of diagnostics to single patient sample assessment.

Keywords: validation, diagnostics, oncology, copy number variation, reference material, calibration

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Authors: Kaori Narita, Juan de Dios Tena Horrillo, Claudio Detotto

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Decisions on replacement of leaders are of significance and high prevalence in any organization, and concerns many of its stakeholders, whether it is a leader in a political party or a CEO of a firm, as indicated by high media coverage of such events. This merits an investigation into the consequences and implications of a leadership change on the performances and behavior of organizations and their workers. Sport economics provides a fruitful field to explore these issues due to the high frequencies of managerial changes in professional sports clubs and the transparency and regularity of observations of team performance and players’ abilities. Much of the existing research on managerial change focuses on how this affects the performance of an organization. However, there is scarcely attention paid to the consequences of such events on the behavior of individuals within the organization. Changes in behavior and attitudes of a group of workers due to a managerial change could be of great interest in management science, psychology, and operational research. On the other hand, these changes cannot be observed in the final outcome of the organization, as this is affected by many other unobserved shocks, for example, the stress level of workers with the need to deal with a difficult situation. To fill this gap, this study shows the first attempt to evaluate the impact of managerial change on players’ behaviors such as attack intensity, aggressiveness, and efforts. The data used in this study is from the top tier Italian football league (“Serie A”), where an average of 13 within season replacements of head coaches were observed over the period of seasons from 2000/2001 to 2017/18. The preliminary estimation employs Pooled Ordinary Least Square (POLS) and club-season Fixed Effect (FE) in order to assess the marginal effect of having a new manager on the number of shots, corners and red/yellow cards after controlling for a home-field advantage, ex ante abilities and current positions in the league of a team and their opponent. The results from this preliminary estimation suggest that the teams do not show a significant difference in their behaviors before and after the managerial change. To build on these preliminary results, other methods, including propensity score matching and non-linear model estimates, will be used. Moreover, the study will further investigate these issues by considering other measurements of attack intensity, aggressiveness, and efforts, such as possessions, a number of fouls and the athletic performance of players, respectively. Finally, the study is going to investigate whether these results vary over the characteristics of a new head coach, for example, their age and experience as a manager and a player. Thus far, this study suggests that certain behaviours of individuals in an organisation are not immediately affected by a change in leadership. To confirm this preliminary finding and lead to a more solid conclusion, further investigation will be conducted in the aforementioned manner, and the results will be elaborated in the conference.

Keywords: behaviour, effort, manager characteristics, managerial change, sport economics

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Authors: Manal M. Kame, Zeinab A. Demerdash, Hanan G. El-Baz, Salwa M. Hassan, Faten M. Salah, Wafaa Mansour, Olfat Hammam

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Cord blood (CB) derived Unrestricted Somatic Stem Cells (USSCs) with their multipotentiality hold great promise in liver regeneration. This work aims at evaluation of the therapeutic potentiality of USSCs in two experimental models of chronic liver injury induced either by S. mansoni infection in balb/c mice or CCL4 injection in hamsters. Isolation, propagation, and characterization of USSCs from CB samples were performed. USSCs were induced to differentiate into osteoblasts, adipocytes and hepatocyte-like cells. Cells of the third passage were transplanted in two models of liver fibrosis: (1) Twenty hamsters were induced to liver fibrosis by repeated i. p. injection of 100 μl CCl4 /hamster for 8 weeks. This model was designed as; 10 hamsters with liver fibrosis and treated with i.h. injection of 3x106 USSCs (USSCs transplanted group), 10 hamsters with liver fibrosis (pathological control group), and 10 hamsters with healthy livers (normal control group). (2) Murine chronics S.mansoni model: twenty mice were induced to liver fibrosis with S. mansoni ceracariae (60 cercariae/ mouse) using the tail immersion method and left for 12 weeks. This model was designed as; 10 mice with liver fibrosis were transplanted with i. v. injection of 1×106 USCCs (USSCs transplanted group). Other 2 groups were designed as in hamsters model. Animals were sacrificed 12 weeks after USSCs transplantation, and their liver sections were examined for detection of human hepatocyte-like cells by immunohistochemistry staining. Moreover, liver sections were examined for fibrosis level, and fibrotic indices were calculated. Sera of sacrificed animals were tested for liver functions. CB USSCs, with fibroblast-like morphology, expressed high levels of CD44, CD90, CD73 and CD105 and were negative for CD34, CD45, and HLA-DR. USSCs showed high expression of transcripts for Oct4 and Sox2 and were in vitro differentiated into osteoblasts, adipocytes. In both animal models, in vitro induced hepatocyte-like cells were confirmed by cytoplasmic expression of glycogen, alpha-fetoprotein, and cytokeratin18. Livers of USSCs transplanted group showed engraftment with human hepatocyte-like cells as proved by cytoplasmic expression of human alpha-fetoprotein, cytokeratin18, and OV6. In addition, livers of this group showed less fibrosis than the pathological control group. Liver functions in the form of serum AST & ALT level and serum total bilirubin level were significantly lowered in USSCs transplanted group than pathological control group (p < 0.001). Moreover, the fibrotic index was significantly lower (p< 0.001) in USSCs transplanted group than pathological control group. In addition liver sections, of i. v. injection of 1×106 USCCs of mice, stained with either H&E or sirius red showed diminished granuloma size and a relative decrease in hepatic fibrosis. Our experimental liver fibrosis models transplanted with CB-USSCs showed liver engraftment with human hepatocyte-like cells as well as signs of liver regeneration in the form of improvement in liver function assays and fibrosis level. These data provide hope that human CB- derived USSCs are introduced as multipotent stem cells with great potentiality in regenerative medicine & strengthens the concept of cellular therapy for the treatment of liver fibrosis.

Keywords: cord blood, liver fibrosis, stem cells, transplantation

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Authors: Zikun Li, Regine Talleyrand

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Negative body image is one of the most common causes of eating disorders, and it is not only happening to women. Regardless of the increasing attention that researchers and practitioners have been paying to the male population and their body image concerns, men of color have yet to be fully represented or studied. Given the consensus that the sociocultural experiences of people of color may play a significant role in their health and well-being, this study focused on assessing the mechanism through which sociocultural factors may influence men of color’s perceptions of body image. In particular, this study focused on untangling how interpersonal and media pressure, as well as ethnic-racial identities and perceptions, would impact body dissatisfaction in terms of muscularity, body fat, and height in men of color and how this mechanism is moderated across different ethnic-racial groups. The structural equation modeling approach was therefore applied to achieve the research goal. With the sample size of 181 self-identified Black, Indigenous, and People of Color male participants aged 20-50 (M=33.33, SD=6.9) through surveying on Amazon’s MTurk platform, the proposed model achieved a modestly acceptable model fit with the pooled sample, X2(836) = 1412.184, CFI = 0.900, RMSEA = 0.062 [0.056, 0.067]. And SRMR = 0.088, And it explained 89.5% of the variance in body dissatisfaction. The results showed that of all the direct effects on body dissatisfaction, interpersonal appearance pressure exhibited the strongest effect (β = 0.410***), followed by media appearance pressure (β = 0.272**) and self-hatred feeling (β = 0.245**). The ethnic-racial related factors (i.e., stereotype endorsement, ethnic-racial salience, and nationalistic assimilation) statistically influenced body dissatisfaction through the mediators of media appearance pressure and/or self-hatred feeling. Furthermore, the moderation analysis between Black/African American men and non-Black/African American men revealed the substantial differences in how ethnic/racial identity impacts one’s perception of body image, and the Black/African American men were found to be influenced by sociocultural factors at a higher level, compared with their counterparts. The impacts of demographic characteristics (i.e., SES, weight, height) on body dissatisfaction were also examined. Instead of considering interpersonal appearance pressure and media pressure as two subscales under one construct, this study considered them as two separate and distinct sociocultural factors. The good model fit to the data indicates this rationality and encourages scholars to reconsider the impacts of two sources of social pressures on body dissatisfaction. In addition, this study also provided empirical evidence of the moderation effect existing within the population of men of color, which reveals the heterogeneity existing across different ethnic-racial groups and implies the necessity to study individual ethnic-racial groups so as to better understand the mechanism of sociocultural influences on men of color’s body dissatisfaction. These findings strengthened the current understanding of the body image concerns exciting among men of color and meanwhile provided empirical evidence for practitioners to provide tailored health prevention and treatment options for this growing population in the United States.

Keywords: men of color, body image concerns, sociocultural factors, structural equation modeling

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Authors: Katharina Lapin, Debashis Sanyal

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Worldwide urban areas are growing. Urbanization has a great impact on social and economic development and ecosystem services. This global trend of urbanization also has significant impact on habitat and biodiversity. The impact of urbanization on the biodiversity of cities in Europe and North America is well studied, while there is a lack of data from cities in currently fast growing urban areas. Indian cities are expanding. The scientific community and the governmental authorities are facing the ongoing urbanization process as an opportunity for the environment. This case study supports the evaluation of urban biodiversity of the city Raipur in the North-West of India. The aim of this study is to assess the overview of the environmental and ecological implications of urbanization. The collected data and analysis was used to discuss the challenges for the sustainable city development. Vascular plants were chosen as an appropriate indicator for the assessment of local biodiversity changes. On the one hand, the vegetation cover is sensible to anthropogenic influence, and in the other hand, the local species composition is comparable to changes at the regional and national scale, using the plant index of India. Further information of abiotic situation can be gathered with the determination of indicator species. In order to calculate the influence of urbanization on the native plant diversity, the Shannon diversity index H´ was chosen. The Pielou`s pooled quadrate method was used for estimating diversity when a random sample is not expected. It was used to calculate the Pilou´s index of evenness. The estimated species coverage was used for calculating the H´ and J. Pearson correlation was performed to test the relationship between urbanization pattern and plant diversity. Further, a SWOT analysis was used in for analyzing internal and external factors impinging on a decision making process. The city of Raipur (21.25°N 81.63°E) has a population of 1,010,087 inhabitants living in an urban area of 226km², in the district of the Indian state of Chhattisgarh. Within the last decade, the urban area of Raipur increased. The results show that various novel ecosystems exist in the urban area of Raipur. The high amount of native flora is mainly to find at the shore of urban lakes and along the river Karun. These areas of high Biodiversity Index are to protect as urban biodiversity hot spots. The governmental authorities are well informed about the environmental challenges for the sustainable development of the city. Together with the scientific community of the Technical University of Raipur many engineering solutions are discussed for implementation of the future. The case study helped to point out the importance environmental measures that support the ecosystem services of green infrastructure. The fast process of urbanization is difficult to control. Uncontrolled creation of urban housing leads to difficulties in unsustainable use of natural resources. This is the major threat for the urban biodiversity.

Keywords: India, novel ecosystems, plant diversity, urban ecology

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Authors: Harriet Koshie Lamptey, Richard Boateng

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Mobile learning (m-learning) is a novel approach to knowledge acquisition and dissemination and is gaining global attention. Steady progress in wireless technologies and the portability of communication devices continue to broaden the scope and use of mobiles. With the convergence of Web functionality onto mobile platforms and the affordability and availability of mobile technology, m-learning has the potential of being the next prevalent channel of education in both formal and informal settings. There is substantive literature on developed countries but the state in developing countries (DCs) however appears vague. This paper is a synthesis of extant literature on mobile learning in DCs. The research interest is based on the fact that in DCs, mobile communication and internet connectivity are popular. However, its use in education is under explored. There are some reviews on the state, conceptualizations, trends and teacher education, but to the authors’ knowledge, no study has focused on mobile learning adoption and integration issues. This study examines issues and gaps associated with its adoption and integration in DCs higher education institutions. A qualitative build-up of literature was conducted using articles pooled from electronic databases (Google Scholar and ERIC). To enable criteria for inclusion and incorporate diverse study perspectives, search terms used were m-learning, DCs, higher education institutions, challenges, benefits, impact, gaps and issues. The synthesis revealed that though mobile technology has diffused globally, its pedagogical pursuit in DCs remains quite low. The absence of a mobile Web and the difficulty of resource conversion into mobile format due to lack of funding and technical competence is a stumbling block. Again, the lack of established design and implementation rules to guide the development of m-learning platforms in DCs is a hindrance. The absence of access restrictions on devices poses security threats to institutional systems. Negative perceptions that devices are taking over faculty roles lead to resistance in some situations. Resistance to change can be a hindrance to the acceptance and success of new systems. Lack of interest for m-learning is also attributed to lower technological literacy levels of the underprivileged masses. Scholarly works on m-learning in DCs is yet to mature. Most technological innovations are handed down from developed countries, and this constantly creates a lag for DCs. Lack of theoretical grounding was also identified which reduces the objectivity of study reports. The socio-cultural terrain of DCs results in societies with different views and needs that have been identified as a hindrance to research. Institutional commitment decisions, adequate funding for the necessary infrastructural development as well as multiple stakeholder participation is important for project success. Evidence suggests that while adoption decisions are readily made, successful integration of the concept for its full benefits to be realized is often neglected. Recommendations to findings were made to provide possible remedies to identified issues.

Keywords: developing countries, higher education institutions, mobile learning, literature review

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Authors: Dalia Ambrazaitienė, Monika Vilkienė, Danute Karcauskienė, Gintaras Siaudinis

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The soil is a complex ecosystem that is part of our biosphere. The ability of soil to provide ecosystem services is dependent on microbial diversity. T Tillage is one of the major factors that affect soil properties. The no-till systems or shallow ploughless tillage are opposite of traditional deep ploughing, no-tillage systems, for instance, increase soil organic matter by reducing mineralization rates and stimulating litter concentrations of the top soil layer, whereas deep ploughing increases the biological activity of arable soil layer and reduces the incidence of weeds. The role of soil organisms is central to soil processes. Although the number of microbial species in soil is still being debated, the metagenomic approach to estimate microbial diversity predicted about 2000 – 18 000 bacterial genomes in 1 g of soil. Despite the key role of bacteria in soil processes, there is still lack of information about the bacterial diversity of soils as affected by tillage practices. This study focused on metagenomic analysis of bacterial diversity in long-term experimental plots of Dystric Epihypogleyic Albeluvisols in western part of Lithuania. The experiment was set up in 2013 and had a split-plot design where the whole-plot treatments were laid out in a randomized design with three replicates. The whole-plot treatments consisted of two tillage methods - deep ploughing (22-25 cm) (DP), ploughless tillage (7-10 cm) (PT). Three subsamples (0-20 cm) were collected on October 22, 2015 for each of the three replicates. Subsamples from the DP and PT systems were pooled together wise to make two composition samples, one representing deep ploughing (DP) and the other ploughless tillage (PT). Genomic DNA from soil sample was extracted from approximately 200 mg field-moist soil by using the D6005 Fungal/Bacterial Miniprep set (Zymo Research®) following the manufacturer’s instructions. To determine bacterial diversity and community composition, we employed a culture – independent approach of high-throughput pyrosequencing of the 16S rRNA gene. Metagenomic sequencing was made with Illumina MiSeq platform in Base Clear Company. The microbial component of soil plays a crucial role in cycling of nutrients in biosphere. Our study was a preliminary attempt at observing bacterial diversity in soil under two common but contrasting tillage practices. The number of sequenced reads obtained for PT (161 917) was higher than DP (131 194). The 10 most abundant genus in soil sample were the same (Arthrobacter, Candidatus Saccharibacteria, Actinobacteria, Acidobacterium, Mycobacterium, Bacillus, Alphaproteobacteria, Longilinea, Gemmatimonas, Solirubrobacter), just the percent of community part was different. In DP the Arthrobacter and Acidobacterium consist respectively 8.4 % and 2.5%, meanwhile in PT just 5.8% and 2.1% of all community. The Nocardioides and Terrabacter were observed just in PT. This work was supported by the project VP1-3.1-ŠMM-01-V-03-001 NKPDOKT and National Science Program: The effect of long-term, different-intensity management of resources on the soils of different genesis and on other components of the agro-ecosystems [grant number SIT-9/2015] funded by the Research Council of Lithuania.

Keywords: deep ploughing, metagenomics, ploughless tillage, soil community analysis

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Authors: Leo Nnamdi Ozurumba-Dwight

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Messenger ribooxynucleic acid (mRNA) molecules are compositional, protein-based. These proteins, encoding mRNA molecules (which collectively connote the transcriptome), when analyzed by RNA sequencing (RNAseq), unveils the nature of gene expression in the RNA. The obtained gene expression provides clues of cellular traits and their dynamics in presentations. These can be studied in relation to function and responses. RNAseq is a practical concept in Genomics as it enables detection and quantitative analysis of mRNA molecules. Single cell and spatial transcriptomics both present varying avenues for expositions in genomic characteristics of single cells and pooled cells in disease conditions such as cancer, auto-immune diseases, hematopoietic based diseases, among others, from investigated biological tissue samples. Single cell transcriptomics helps conduct a direct assessment of each building unit of tissues (the cell) during diagnosis and molecular gene expressional studies. A typical technique to achieve this is through the use of a single-cell RNA sequencer (scRNAseq), which helps in conducting high throughput genomic expressional studies. However, this technique generates expressional gene data for several cells which lack presentations on the cells’ positional coordinates within the tissue. As science is developmental, the use of complimentary pre-established tissue reference maps using molecular and bioinformatics techniques has innovatively sprung-forth and is now used to resolve this set back to produce both levels of data in one shot of scRNAseq analysis. This is an emerging conceptual approach in methodology for integrative and progressively dependable transcriptomics analysis. This can support in-situ fashioned analysis for better understanding of tissue functional organization, unveil new biomarkers for early-stage detection of diseases, biomarkers for therapeutic targets in drug development, and exposit nature of cell-to-cell interactions. Also, these are vital genomic signatures and characterizations of clinical applications. Over the past decades, RNAseq has generated a wide array of information that is igniting bespoke breakthroughs and innovations in Biomedicine. On the other side, spatial transcriptomics is tissue level based and utilized to study biological specimens having heterogeneous features. It exposits the gross identity of investigated mammalian tissues, which can then be used to study cell differentiation, track cell line trajectory patterns and behavior, and regulatory homeostasis in disease states. Also, it requires referenced positional analysis to make up of genomic signatures that will be sassed from the single cells in the tissue sample. Given these two presented approaches to RNA transcriptomics study in varying quantities of cell lines, with avenues for appropriate resolutions, both approaches have made the study of gene expression from mRNA molecules interesting, progressive, developmental, and helping to tackle health challenges head-on.

Keywords: transcriptomics, RNA sequencing, single cell, spatial, gene expression.

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Authors: John D. Sanderson

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The popularity of American cinema worldwide has contributed to the development of sociolects related to specific film genres in other cultural contexts by means of screen translation, in many cases eluding norms of usage in the target language, a process whose result has come to be known as 'dubbese'. A consequence for the reception in countries where local audiovisual fiction consumption is far lower than American imported productions is that this linguistic construct is preferred, even though it differs from common everyday speech. The iconography of film genres such as science-fiction, western or sword-and-sandal films, for instance, generates linguistic expectations in international audiences who will accept more easily the sociolects assimilated by the continuous reception of American productions, even if the themes, locations, characters, etc., portrayed on screen may belong in origin to other cultures. And the non-normative language (e.g., calques, semantic loans) used in the preferred mode of linguistic transfer, whether it is translation for dubbing or subtitling, has diachronically evolved in many cases into a status of canonized sociolect, not only accepted but also required, by foreign audiences of American films. However, a remarkable step forward is taken when this typology of artificial linguistic constructs starts being used creatively by nationals of these target cultural contexts. In the case of Spain, the success of American sitcoms such as Friends in the 1990s led Spanish television scriptwriters to include in national productions lexical and syntactical indirect borrowings (Anglicisms not formally identifiable as such because they include elements from their own language) in order to target audiences of the former. However, this commercial strategy had already taken place decades earlier when Spain became a favored location for the shooting of foreign films in the early 1960s. The international popularity of the then newly developed sub-genre known as Spaghetti-Western encouraged Spanish investors to produce their own movies, and local scriptwriters made use of the dubbese developed nationally since the advent of sound in film instead of using normative language. As a result, direct Anglicisms, as well as lexical and syntactical borrowings made up the creative writing of these Spanish productions, which also became commercially successful. Interestingly enough, some of these films were even marketed in English-speaking countries as original westerns (some of the names of actors and directors were anglified to that purpose) dubbed into English. The analysis of these 'back translations' will also foreground some semantic distortions that arose in the process. In order to perform the research on these issues, a wide corpus of American films has been used, which chronologically range from Stagecoach (John Ford, 1939) to Django Unchained (Quentin Tarantino, 2012), together with a shorter corpus of Spanish films produced during the golden age of Spaghetti Westerns, from una tumba para el sheriff (Mario Caiano; in English lone and angry man, William Hawkins) to tu fosa será la exacta, amigo (Juan Bosch, 1972; in English my horse, my gun, your widow, John Wood). The methodology of analysis and the conclusions reached could be applied to other genres and other cultural contexts.

Keywords: dubbing, film genre, screen translation, sociolect

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Authors: Abdou Elhendy

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Numerous study have shown the efficacy of the percutaneous intervention (PCI) and coronary stenting in improving left ventricular function and relieving exertional angina. Furthermore, PCI remains the main line of therapy in acute myocardial infarction. Improvement of procedural techniques and new devices have resulted in an increased number of PCI in those with difficult and extensive lesions, multivessel disease as well as total occlusion. Immediate and late outcome may be compromised by acute thrombosis or the development of fibro-intimal hyperplasia. In addition, progression of coronary artery disease proximal or distal to the stent as well as in non-stented arteries is not uncommon. As a result, complications can occur, such as acute myocardial infarction, worsened heart failure or recurrence of angina. In a stent, restenosis can occur without symptoms or with atypical complaints rendering the clinical diagnosis difficult. Routine invasive angiography is not appropriate as a follow up tool due to associated risk and cost and the limited functional assessment. Exercise and pharmacologic stress testing are increasingly used to evaluate the myocardial function, perfusion and adequacy of revascularization. Information obtained by these techniques provide important clues regarding presence and severity of compromise in myocardial blood flow. Stress echocardiography can be performed in conjunction with exercise or dobutamine infusion. The diagnostic accuracy has been moderate, but the results provide excellent prognostic stratification. Adding myocardial contrast agents can improve imaging quality and allows assessment of both function and perfusion. Stress radionuclide myocardial perfusion imaging is an alternative to evaluate these patients. The extent and severity of wall motion and perfusion abnormalities observed during exercise or pharmacologic stress are predictors of survival and risk of cardiac events. According to current guidelines, stress echocardiography and radionuclide imaging are considered to have appropriate indication among patients after PCI who have cardiac symptoms and those who underwent incomplete revascularization. Stress testing is not recommended in asymptomatic patients, particularly early after revascularization, Coronary CT angiography is increasingly used and provides high sensitive for the diagnosis of coronary artery stenosis. Average sensitivity and specificity for the diagnosis of in stent stenosis in pooled data are 79% and 81%, respectively. Limitations include blooming artifacts and low feasibility in patients with small stents or thick struts. Anatomical and functional cardiac imaging modalities are corner stone for the assessment of patients after PCI and provide salient diagnostic and prognostic information. Current imaging techniques cans serve as gate keeper for coronary angiography, thus limiting the risk of invasive procedures to those who are likely to benefit from subsequent revascularization. The determination of which modality to apply requires careful identification of merits and limitation of each technique as well as the unique characteristic of each individual patient.

Keywords: coronary artery disease, stress testing, cardiac imaging, restenosis

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Authors: Asif Ali, Daud Salim Faruquie

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With the advancement of knowledge about the utility and impact of sustainability, its feasibility has been explored into different walks of life. Scientists, however; have established their knowledge in four areas viz environmental, economic, social and cultural, popularly termed as four pillars of sustainability. Aspects of environmental and economic sustainability have been rigorously researched and practiced and huge volume of strong evidence of effectiveness has been founded for these two sub-areas. For the social and cultural aspects of sustainability, dependable evidence of effectiveness is still to be instituted as the researchers and practitioners are developing and experimenting methods across the globe. Therefore, the present research aimed to identify globally used practices of social and cultural sustainability and through evidence synthesis assess their outcomes to determine the effectiveness of those practices. A PICO format steered the methodology which included all populations, popular sustainability practices including walkability/cycle tracks, social/recreational spaces, privacy, health & human services and barrier free built environment, comparators included ‘Before’ and ‘After’, ‘With’ and ‘Without’, ‘More’ and ‘Less’ and outcomes included Social well-being, cultural co-existence, quality of life, ethics and morality, social capital, sense of place, education, health, recreation and leisure, and holistic development. Search of literature included major electronic databases, search websites, organizational resources, directory of open access journals and subscribed journals. Grey literature, however, was not included. Inclusion criteria filtered studies on the basis of research designs such as total randomization, quasi-randomization, cluster randomization, observational or single studies and certain types of analysis. Studies with combined outcomes were considered but studies focusing only on environmental and/or economic outcomes were rejected. Data extraction, critical appraisal and evidence synthesis was carried out using customized tabulation, reference manager and CASP tool. Partial meta-analysis was carried out and calculation of pooled effects and forest plotting were done. As many as 13 studies finally included for final synthesis explained the impact of targeted practices on health, behavioural and social dimensions. Objectivity in the measurement of health outcomes facilitated quantitative synthesis of studies which highlighted the impact of sustainability methods on physical activity, Body Mass Index, perinatal outcomes and child health. Studies synthesized qualitatively (and also quantitatively) showed outcomes such as routines, family relations, citizenship, trust in relationships, social inclusion, neighbourhood social capital, wellbeing, habitability and family’s social processes. The synthesized evidence indicates slight effectiveness and efficacy of social and cultural sustainability on the targeted outcomes. Further synthesis revealed that such results of this study are due weak research designs and disintegrated implementations. If architects and other practitioners deliver their interventions in collaboration with research bodies and policy makers, a stronger evidence-base in this area could be generated.

Keywords: built environment, cultural sustainability, social sustainability, sustainable architecture

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Authors: Mary-Ann N. Jallad, Dalal F. Jaber, Alexander M. Abdelnoor

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Introduction: Current evidence confirms that both innate and adaptive immune systems are capable of recognizing and abolishing malignant cells. The emergence of cancerous tumors in patients is, therefore, an indication that certain cancer cells can resist elimination by the immune system through a process known as “immune evasion”. In fact, cancer cells often exploit regulatory mechanisms to escape immunity. Such mechanisms normally exist to control the immune responses and prohibit exaggerated or autoimmune reactions. Recently, immunotherapies have shown promising yet limited results. Therefore this study investigates several immunotherapeutic combinations and devises a triple immunotherapy which harnesses the innate and acquired immune responses towards the annihilation of malignant cells through overcoming their ability of immune evasion, consequently hampering malignant progression and eliminating established tumors. The aims of the study are to rule out acute/chronic toxic effects of the proposed treatment combinations, to assess the effect of these combinations on tumor growth and survival rates, and to investigate potential mechanisms underlying the phenotypic results through analyzing serum levels of anti-tumor cytokines, angiogenic factors and tumor progression indicator, and the tumor-infiltrating immune-cells populations. Methodology: For toxicity analysis, cancer-free C57BL/6 mice are randomized into 9 groups: Group 1 untreated, group 2 treated with sterile saline (solvent of used treatments), group 3 treated with Monophosphoryl-lipid-A, group 4 with anti-CTLA4-antibodies, group 5 with 1-Methyl-Tryptophan (Indolamine-Dioxygenase-1 inhibitor), group 6 with both MPLA and anti-CTLA4-antibodies, group 7 with both MPLA and 1-MT, group 8 with both anti-CTLA4-antibodies and 1-MT, and group 9 with all three: MPLA, anti-CTLA4-antibodies and 1-MT. Mice are monitored throughout the treatment period and for three following months. At that point, histological sections from their main organs are assessed. For tumor progression and survival analysis, a murine melanoma model is generated by injecting analogous mice with B16F10 melanoma cells. These mice are segregated into the listed nine groups. Their tumor size and survival are monitored. For a depiction of underlying mechanisms, melanoma-bearing mice from each group are sacrificed at several time-points. Sera are tested to assess the levels of Interleukin-12 (IL-12), Vascular-Endothelial-Growth Factor (VEGF), and S100B. Furthermore, tumors are excised for analysis of infiltrated immune cell populations including T-cells, macrophages, natural killer cells and immune-regulatory cells. Results: Toxicity analysis shows that all treated groups present no signs of neither acute nor chronic toxicity. Their appearance and weights were comparable to those of control groups throughout the treatment period and for the following 3 months. Moreover, histological sections from their hearts, kidneys, lungs, and livers were normal. Work is ongoing for completion of the remaining study aims. Conclusion: Toxicity was the major concern for the success of the proposed comprehensive combinational therapy. Data generated so far ruled out any acute or chronic toxic effects. Consequently, ongoing work is quite promising and may significantly contribute to the development of more effective immunotherapeutic strategies for the treatment of cancer patients.

Keywords: cancer immunotherapy, check-point blockade, combination therapy, melanoma

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Authors: Maddalena Arigoni, Maria Luisa Ratto, Raffaele A. Calogero, Luca Alessandri

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The presence of tumor heterogeneity, where distinct cancer cells exhibit diverse morphological and phenotypic profiles, including gene expression, metabolism, and proliferation, poses challenges for molecular prognostic markers and patient classification for targeted therapies. Understanding the causes and progression of cancer requires research efforts aimed at characterizing heterogeneity, which can be facilitated by evolving single-cell sequencing technologies. However, analyzing single-cell data necessitates computational methods that often lack objective validation. Therefore, the establishment of benchmarking datasets is necessary to provide a controlled environment for validating bioinformatics tools in the field of single-cell oncology. Benchmarking bioinformatics tools for single-cell experiments can be costly due to the high expense involved. Therefore, datasets used for benchmarking are typically sourced from publicly available experiments, which often lack a comprehensive cell annotation. This limitation can affect the accuracy and effectiveness of such experiments as benchmarking tools. To address this issue, we introduce omics benchmark experiments designed to evaluate bioinformatics tools to depict the heterogeneity in single-cell tumor experiments. We conducted single-cell RNA sequencing on six lung cancer tumor cell lines that display resistant clones upon treatment of EGFR mutated tumors and are characterized by driver genes, namely ROS1, ALK, HER2, MET, KRAS, and BRAF. These driver genes are associated with downstream networks controlled by EGFR mutations, such as JAK-STAT, PI3K-AKT-mTOR, and MEK-ERK. The experiment also featured an EGFR-mutated cell line. Using 10XGenomics platform with cellplex technology, we analyzed the seven cell lines together with a pseudo-immunological microenvironment consisting of PBMC cells labeled with the Biolegend TotalSeq™-B Human Universal Cocktail (CITEseq). This technology allowed for independent labeling of each cell line and single-cell analysis of the pooled seven cell lines and the pseudo-microenvironment. The data generated from the aforementioned experiments are available as part of an online tool, which allows users to define cell heterogeneity and generates count tables as an output. The tool provides the cell line derivation for each cell and cell annotations for the pseudo-microenvironment based on CITEseq data by an experienced immunologist. Additionally, we created a range of pseudo-tumor tissues using different ratios of the aforementioned cells embedded in matrigel. These tissues were analyzed using 10XGenomics (FFPE samples) and Curio Bioscience (fresh frozen samples) platforms for spatial transcriptomics, further expanding the scope of our benchmark experiments. The benchmark experiments we conducted provide a unique opportunity to evaluate the performance of bioinformatics tools for detecting and characterizing tumor heterogeneity at the single-cell level. Overall, our experiments provide a controlled and standardized environment for assessing the accuracy and robustness of bioinformatics tools for studying tumor heterogeneity at the single-cell level, which can ultimately lead to more precise and effective cancer diagnosis and treatment.

Keywords: single cell omics, benchmark, spatial transcriptomics, CITEseq

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Authors: Arifur Rahman, Ardeshir Amirkhani, Honghua Hu, Mark Molloy, Karen Vickery

Abstract:

Introduction and Objectives: Staphylococcus aureus and coagulase-negative staphylococci comprises approximately 65% of infections associated with medical devices and are well known for their biofilm formatting ability. Biofilm-related infections are extremely difficult to eradicate owing to their high tolerance to antibiotics and host immune defences. Currently, there is no efficient method for early biofilm detection. A better understanding to enable detection of biofilm specific proteins in vitro and in vivo can be achieved by studying planktonic and different growth phases of biofilms using a proteome analysis approach. Our goal was to construct a reference map of planktonic and biofilm associated proteins of S. aureus. Methods: S. aureus reference strain (ATCC 25923) was used to grow 24 hours planktonic, 3-day wet biofilm (3DWB), and 12-day wet biofilm (12DWB). Bacteria were grown in tryptic soy broth (TSB) liquid medium. Planktonic growth was used late logarithmic bacteria, and the Centres for Disease Control (CDC) biofilm reactor was used to grow 3 days, and 12-day hydrated biofilms, respectively. Samples were subjected to reduction, alkylation and digestion steps prior to Multiplex labelling using Tandem Mass Tag (TMT) 10-plex reagent (Thermo Fisher Scientific). The labelled samples were pooled and fractionated by high pH RP-HPLC which followed by loading of the fractions on a nanoflow UPLC system (Eksigent UPLC system, AB SCIEX). Mass spectrometry (MS) data were collected on an Orbitrap Elite (Thermo Fisher Scientific) Mass Spectrometer. Protein identification and relative quantitation of protein levels were performed using Proteome Discoverer (version 1.3, Thermo Fisher Scientific). After the extraction of protein ratios with Proteome Discoverer, additional processing, and statistical analysis was done using the TMTPrePro R package. Results and Discussion: The present study showed that a considerable proteomic difference exists among planktonic and biofilms from S. aureus. We identified 1636 total extracellular secreted proteins, of which 350 and 137 proteins of 3DWB and 12DWB showed significant abundance variation from planktonic preparation, respectively. Of these, simultaneous up-regulation in between 3DWB and 12DWB proteins such as extracellular matrix-binding protein ebh, enolase, transketolase, triosephosphate isomerase, chaperonin, peptidase, pyruvate kinase, hydrolase, aminotransferase, ribosomal protein, acetyl-CoA acetyltransferase, DNA gyrase subunit A, glycine glycyltransferase and others we found in this biofilm producer. On the contrary, simultaneous down-regulation in between 3DWB and 12DWB proteins such as alpha and delta-hemolysin, lipoteichoic acid synthase, enterotoxin I, serine protease, lipase, clumping factor B, regulatory protein Spx, phosphoglucomutase, and others also we found in this biofilm producer. In addition, we also identified a big percentage of hypothetical proteins including unique proteins. Therefore, a comprehensive knowledge of planktonic and biofilm associated proteins identified by S. aureus will provide a basis for future studies on the development of vaccines and diagnostic biomarkers. Conclusions: In this study, we constructed an initial reference map of planktonic and various growth phase of biofilm associated proteins which might be helpful to diagnose biofilm associated infections.

Keywords: bacterial biofilms, CDC bioreactor, S. aureus, mass spectrometry, TMT

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