bluuebunny/crossref_metadata_2025 huggingface dataset:
Breed differences in placental development during late gestation between Chinese Meishan and White crossbred gilts in response to intrauterine crowding
Authors: Miles Jeremy , Vallet Jeffrey L.
Published: September 2020

Background: The porcine placenta plays a critical role on uterine capacity, fetal growth, and survival as well as postnatal piglet growth and survival. The objective of this study was to evaluate placental development during late gestation between Chinese Meishan (MS) and White crossbred (WC) gilts following intrauterine crowding. To induce uterine crowding, MS (n = 7) and WC (n = 5) gilts were unilaterally hysterectomized-ovariectomized, bred to sires from their same breed, and the remaining uterine tract was collected at day 100 of gestation. Gross placental morphology and areolae density as well as histological morphology (i.e., folded bilayer and placental stroma) were analyzed using computer-assisted morphometry from placentas of the smallest and largest fetuses within each litter. All data were analyzed using MIXED model procedures for ANOVA. Results: Fetal and placental weight were not different (P > 0.10) between MS and WC pregnancies. In contrast, within-litter fetal weight variation and allometric growth relationship between fetal and placental weights were decreased (P < 0.08) in MS gilts compared to WC gilts indicating greater fetal sparing within MS gilts. There was a breed by fetal size interaction (P < 0.01) for areolae density in which placentas from large MS fetuses had greater areolae density compared to small MS fetuses, but the density of areolae was greater from MS fetuses compared to WC fetuses, irrespective of fetal size. The width of the folded bilayer was greater (P < 0.01) in placentas from WC gilts compared to MS gilts, irrespective of fetal size. Placentas from small fetuses had greater (P < 0.01) folded bilayer width compared to large fetuses, irrespective of breed. The placental stromal width was greater (P < 0.01) in placentas from large fetuses compared to small, irrespective of breed. However, the difference between stromal width in placentas between divergent-sized littermates was greater (P = 0.05) in WC gilts compared to MS gilts, suggesting limited response to intrauterine crowding in MS gilts. Conclusions: These results demonstrate altered placental development during late gestation in MS pregnancies compared to WC pregnancies corresponding to different mechanisms for responding to intrauterine crowding between breeds.
Direct evidence of preventive effect of severe diarrhea in calf by milk replacer-based probiotic feeding
Authors: Kayasaki Fumi , Okagawa: Tomohiro , Konnai Satoru , Kohara Junko , Sajiki Yamato , Watari Kei , Otgontuya Ganbaatar , Goto Shinya , Nakamura Hayato , Shimakura Honami , Minato Erina , Kobayashi Atsuhi , Kubota Manabu , Terasaki Nobuhiro , Takeda Akira , Noda Haruka , Honma Mitsuru , Maekawa Naoya , Murata Shiro , Ohashi Kazuhiko
Published: September 2020

Background Diarrhea is one of the major causes of death in calves directly linked to economic loss in cattle industry. Fermented milk has been widely used for calf feeding to reduce the diarrhea in clinical settings. However, the fermentation of raw milk has many difficulties, such as unstable fermentation due to large variances of nutrient composition in raw milk and contamination with coliform. Practical use of fermented milk replacer (FMR) has a strong potential to overcome these difficulties. However, the clinical efficacy of FMR on calf diarrhea is still unclear. Result In this study, we developed a stable condition of fermentation for FMR and verified the preventive effects of FMR feeding on calf diarrhea by an experimental infection model of bovine rotavirus (BRV) in newborn calf and a field study in dairy farms with calf diarrhea. Additionally, the clinical efficacy of lactic acid bacteria (LAB)-supplemented milk replacer (LAB-MR) was also evaluated in the experimental infection model. In the experimental infection model, control calves fed a milk replacer showed severe watery diarrhea after BRV challenge. Two out of three control calves were died after rapid decline of milk intake. In contrast, calves fed FMR or high-concentrated LAB-MR showed diarrhea, but the water content of feces was low and stable. In addition, the amount of milk intake decreased temporarily, but recovered immediately in the FMR- or LAB-MR-fed calves. Histopathological analysis of intestinal tracts revealed mucosal lesions were slighter in the FMR- or LAB-MR-fed calves than in the control calves. In a field study of FMR feeding in dairy farms with mixed infection with BRV and Cryptosporidium parvum, the incidence of enteritis and mortality of calf by enteritis were significantly reduced by the allocation of FMR. Additionally, the FMR-fed calves exhibited shorter duration of treatment, fewer consultations, and lower cost of medical care for enteritis compared with control calves. Conclusion These results suggest that feeding of milk replacer-based probiotics to calves reduces severity of diarrhea and tissue damage to intestinal tracts caused by BRV infection and provides significant clinical benefits for the prevention and treatment of calf diarrhea.
Nicotinamide, a vitamin B3 ameliorates depressive behaviors independent of SIRT1 activity in mice
Authors: Liu Zhuxi , Li Caiqin , Fan Xuelian , Kuang Yifang , Zhang Xu , Chen Lei , Song Jinjing , Zhou Ying , Takahashi Eiki , He Guang , Li Weidong
Published: September 2020

Sirtuins 1 (SIRT1), is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase and a candidate gene for depression. Nicotinamide (NAM), a form of vitamin B3, is reported as a potential inhibitor of SIRT1. Our previous study found that the 24-hour restraint stress could induce long-term depressive-like phenotypes in mice. These mice displayed increased SIRT1 activity. Here, we studied whether NAM was capable of attenuating depressive behaviors through inhibiting SIRT1 activity. Surprisingly, the application of NAM significantly reversed the depressive behaviors but increased SIRT1 activity further. In contrast, the level of ATP was reduced in the restraint model for depression, and recovered by the administration of NAM. Furthermore, Sirt1−/− mice exhibited antidepressant behaviors and increased ATP levels. These data suggest that ATP plays an important role in depression pathogenesis, and NAM could be a potential treatment method for depression by regulating ATP independent of Sirt1 activity.
High Expression Level of miR-1260 Family in the Peripheral Blood of Patients with Ovarian Carcinoma
Authors: Ghafour Arash Adamnejad , Odemis Demet Akdeniz , Tuncer Seref Bugra , Kurt Busra , Sarali Mukaddes Avsar , Kılıc Seda , Erdogan Ozge Sukruoglu , Celik Betul , Saip Pinar , Yazici Hulya
Published: September 2020

The most common gynecologic cancers detected in women in Turkey are uterine cancer, ovarian cancer, and cervical cancer. These data reported that a mean of 3800 individuals were diagnosed with uterine cancer, 2790 were diagnosed with ovarian cancer, and 1950 were diagnosed with cervical cancer, and 400 individuals were diagnosed with other gynecologic cancers each year in Turkey. A mean of 14.270 individuals were detected to have been diagnosed with gynecologic cancers each year in the United States of America(USA). Ovarian cancer treatment is generally composed of chemotherapy, and surgery. In general, chemotherapy is administered after surgery. The identification of the molecular pathogenesis of ovarian cancer, and discovery of new moleculer biomarkers which facilitate the ovarian cancer treatment are required for an effective ovarian cancer treatment in clinics. miRNAs are reported to be the possible biologic indicators for various cancer types. We aimed to investigate 2 miRNAs which were suggested to have effect in ovarian cancer in our (previous)monozygotic twin study from miR-1260 microRNA family whose association with ovarian cancer yet has not been reported in the literature. We investigated the expression levels of miR-1260a, and miR-1260b miRNAs, in the peripheral blood lymphocytes of 150 familial and sporadic ovarian cancer patients, and of 100 healthy individuals of the control group who were matched for age, sex, and ethnicity with the patient group, and investigated their possible property of being a biologic indicator for ovarian cancer. The expression results of ovarian cancer patients were evaluated by comparison of the results of the control group in the study. The expression levels of miR-1260a, and miR-1260b in ovarian cancer patients were found highly increased compared with the levels in the control group. miR-1260a expression level in ovarian cancer patients was detected to have increased approximately 17 fold compared with the control group, and miR-1260b expression level in ovarian cancer patients was detected to have increased approximately 33 fold compared with the levels in the control group. The String Analyses showed that the miR-1260a was associated with the ribosomal protein family which was known to be effective in the translation stage of cell and that miR-1260b was associated with CHEK2 protein which was a member of the serine/threonine-protein kinase family. It should be investigated for larger cohorts in benign ovarian diseases and in different stages of patients receiving ovarian cancer treatment whether these two molecules are a noninvasive biomarker and therapeutic target to be used especially in the early diagnosis and prognosis of ovarian cancer in future.
Elevated serum galectin-1 concentrations are associated with increased risks of mortality and acute kidney injury in critically ill patients
Authors: Chou Ruey-Hsing , Tsai Chuan-Tsai , Lu Ya-Wen , Guo Jiun-Yu , Lu Chi-Ting , Tsai Yi-Lin , Wu Cheng-Hsueh , Lin Shing-Jong , Lien Ru-Yu , Lu Shu-Fen , Yang Shang-Feng , Huang Po-Hsun
Published: September 2020

Background: Galectin-1 (Gal-1), a member of the β-galactoside binding protein family, is associated with inflammation and chronic kidney disease. However, the effect of Gal-1 on mortality and acute kidney injury (AKI) in critically ill patients remains unclear.Methods: From May 2018 to March 2020, 350 patients admitted to the medical intensive care unit (ICU) of Taipei Veterans General Hospital, a tertiary medical center, were enrolled in this study. Forty-one patients receiving long-term renal replacement therapy were excluded. Serum Gal-1 levels were determined within 24 h of ICU admission. The patients were divided into three equally sized groups according to their serum Gal-1 levels (low, serum Gal-1 < 39 ng/ml; median, 39–70 ng/ml; high, >71 ng/ml). All patients were followed for 90 days or until death.Results: Mortality in the ICU and at 90 days was greater among patients with elevated serum Gal-1 levels. In analyses adjusted for the body mass index, malignancy, sepsis, Sequential Organ Failure Assessment (SOFA) score, and serum lactate level, the serum Gal-1 level remained an independent predictor of 90-day mortality [median vs. low: adjusted hazard ratio (aHR) 2.11, 95% confidence interval (CI) 1.24–3.60, p = 0.006; high vs. low: aHR 3.21, 95% CI 1.90–5.42, p < 0.001]. Higher serum Gal-1 levels were also associated with a higher incidence of AKI within 48 h after ICU admission, independent of the SOFA score and renal function (median vs. low: aHR 2.77, 95% CI 1.21–6.34, p = 0.016; high vs. low: aHR 2.88, 95% CI 1.20–6.88, p = 0.017). The results were consistent among different subgroups with high and low Gal-1 levels.Conclusion: Serum Gal-1 elevation at the time of ICU admission were associated with an increased risk of mortality at 90 days, and an increased incidence of AKI within 48 h after ICU admission.
Equivalence and switching between biosimilars and reference molecules in rheumatoid arthritis: protocol for two systematic reviews and meta-analyses
Authors: Ascef Bruna de Oliveira , Almeida Matheus Oliveira , Ribeiro Ana Cristina de Medeiros , de Andrade Danieli Castro Oliveira , Júnior Haliton Alves de Oliveira , Pereira Tiago da Veiga , de Soárez Patrícia Coelho
Published: September 2020

Background Biologic drugs such as adalimumab, etanercept, and infliximab represent major first-line and second-line treatments for rheumatoid arthritis (RA) patients. However, their high cost poses a massive burden on healthcare systems worldwide. The expiration of patents for these biologics has driven to the production of biosimilar drugs, which are potentially less costly and remarkably similar, albeit not identical to the reference molecules. These two systematic reviews aim to investigate the efficacy and safety profile of biosimilars compared to biologics (systematic review 1) and the impact of switching between biosimilar drugs and reference biologics on the management of RA patients (systematic review 2).Methods Electronic searches will be performed through MEDLINE (via Pubmed), EMBASE, LILACS, and CENTRAL (from inception to September 2020). Risk of bias assessments will be carried out with the Cochrane risk of bias tool, supplemented with specific domains from equivalence trials. Random-effects models will be fitted to obtain summary estimates using either relative risk or standardized mean difference as a metric. Between-trial heterogeneity will be tested and quantified with the Q-test and I2 metric, respectively, whereas assessment of small-study bias will be examined through contour-enhanced funnel plots and Egger and Harbord's tests. Meta-regression models will be fitted when appropriate. The primary outcome will be the rate of treatment success according to the American College of Rheumatology 20 (ACR20) and the co-primary outcome will be the Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index). Conclusions will be based on equivalence hypothesis testing using predefined margins of equivalence elicited from a group of experienced rheumatologists and prior studies. The overall certainty of evidence will be assessed based on the GRADE system.Discussion The two systematic reviews described here, to the best of our knowledge, are the first ones proposing a comprehensive, clinician-oriented approach to assess the equivalence and the impact of switching between biosimilars and biologics on the management of patients with RA. The results will elucidate the efficacy, safety, immunogenicity of biosimilars, and the clinical consequences of substituting biologics with biosimilars in the management of RA. Systematic Review Registration Protocol synopses were previously registered on PROSPERO (CRD42019137152 and CRD42019137155).
Pulmonary fibrosis and its related factors in discharged patients with new coronavirus pneumonia: A cohort study of 90-150 days follow-up after onset
Authors: Li Xiaohe , Shen Chenguang , Wang Lifei , Majumder Sumit , Zhang Die , Deen M. Jamal , Li Yanjie , Qing Ling , Zhang Ying , Chen Chuming , Zou Rongrong , Lan Jianfeng , Huang Ling , Peng Cheng , Zeng Lijiao , Liang Yanhua , Cao Mengli , Yang Yang , Yang Minghui , Tan Guoyu , Tang Shenghong , Liu Lei , Yuan Jing , Liu Yingxia
Published: September 2020

Background: Thousands of the Coronavirus Disease 2019 (COVID-19) patients have been discharged from hospitals, long-term follow-up studies are required to evaluate the prevalence of post-COVID-19 fibrosis.Methods: This study involves 462 laboratory confirmed patients with COVID-19 who were admitted to Shenzhen Third People’s Hospital from January 11, 2020 to April 26, 2020. A total of 457 patients underwent thin-section chest CT scans during the hospitalization or after discharge to identify the pulmonary lesion. A total of 289 patients were followed up from 90 days to 150 days after the onset of the disease.Results: Parenchymal bands, irregular interfaces, meshwork and traction bronchiectasis were the most common CT features in all COVID-19 patients. 86.87%, 74.40%, 79.56%, 68.12% and 62.03% patients developed with pulmonary fibrosis and 4.53%, 19.61%, 18.02%, 38.30% and 48.98% patients reversed pulmonary fibrosis during the 0-30, 31-60, 61-90, 91-120 and >120 days after onset, respectively. It was observed that Age, BMI, Fever, and Highest PCT were predictive factors for sustaining fibrosis even after 90 days from onset. A predictive model of the persistence with pulmonary fibrosis was developed based-on the Logistic Regression method with an accuracy, PPV, NPV, Sensitivity and Specificity of the model of 76%, 71%, 79%, 67%, and 82%, respectively. Only a fraction of COVID-19 patients suffered with abnormal lung function after 90 days from onset, and the ratio of abnormal lung function did not differ on a statistically significant level between the fibrotic and non-fibrotic groups.Conclusions: Long-term pulmonary fibrosis was more likely to develop in patients with older age, high BMI, severe/critical condition, fever, long time to turn the viral RNA negative, pre-existing disease and delay to admission. Fibrosis developed in COVID-19 patients could be reversed in about a half of the patients after 120 days from onset. The pulmonary function of most of COVID-19 patients with pulmonary fibrosis could turn to normal condition after three months from onset. An effective prediction model with an average Area Under the Curve (AUC) of 0.84 was established to predict the persistence of pulmonary fibrosis in COVID-19 patients for early diagnosis.
Differential and paradoxical roles of new-generation antidepressants in primary astrocytic inflammation
Authors: He Jia-Hui , Liu Rong-Pei , Peng Yi-Man , Guo Qing , Zhu Lan-Bing , Hu Bei-Lei , Fan Hui-Hui , Zhang Xiong , Zhu Jian-Hong
Published: September 2020

Background: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are commonly used new-generation drugs for depression. Depressive symptoms are thought to be closely related to neuroinflammation. In this study, we used up-to-date protocols of culture and stimulation and aimed to understand how astrocytes respond to the antidepressants. Methods: Primary astrocytes were isolated and cultured using neurobasal-based serum free medium. The cells were treated with a cytokine mixture comprising complement component 1q, tumor necrosis factor α and interleukin 1α with or without pretreatments of antidepressants. Cell viability, phenotypes, inflammatory responses and the underlying mechanisms were analyzed. Results: All the SSRIs, including paroxetine, fluoxetine, sertraline, citalopram, and fluvoxamine, show a visible cytotoxicity within the range of applied doses, and a paradoxical effect on astrocytic inflammatory responses as manifested by the promotion of inducible nitric oxide synthase (iNOS) and/or nitric oxide (NO) and the inhibition of interleukin 6 (IL-6) and/or interleukin 1β (IL-1β). The SNRI venlafaxine was the least toxic to astrocytes and inhibited the production of IL-6 and IL-1β but with no impact on iNOS and NO. All the drugs had no regulation on the polarization of astrocytic A1 and A2 types. Mechanisms associated with the antidepressants in astrocytic inflammation route via inhibition of JNK1 activation and STAT3 basal activity. ﻿Conclusions: The study demonstrated that the antidepressants possess differential cytotoxicity to astrocytes and function differently, also paradoxically for the SSRIs, to astrocytic inflammation. Our results provide novel pieces into understanding the differential efficacy and tolerability of the antidepressants in treating patients in the context of astrocytes.
A method of Ga removal from a specimen fabricated on MEMS-based chip for in-situ transmission electron microscopy
Authors: Kwon Yena , An Byeong-Seon , Shin Yeon-Ju , Yang Cheol-Woong
Published: September 2020

In-situ transmission electron microscopy (TEM) holders, which are widely used in recent years, employ a chip-type specimen stage. To prepare the specimen on the microelectromechanical system (MEMS)-based chip, focused ion beam (FIB) and ex-situ lift-out (EXLO) techniques has been widely used. However, thin foil specimens prepared using the FIB inevitably contain the contamination induced by Ga+ ions. In particular, when the specimen is heated for real time observation, it is observed that Ga+ ions influence the reaction or aggregate in the protection layer. An effective method of removing the Ga residue is demonstrated using Ar+ ion milling within FIB. In the case of lifting the thin foil specimen from the trench by the EXLO technique, Ga still remained even if Ar+ ion milling was conducted. To avoid this problem, the thin foil specimen was attached to FIB lift-out grid, performing Ar+ ion milling, and then transferred to a MEMS chip using EXLO technique. The removal of the Ga residue was confirmed using energy dispersive spectroscopy (EDS).
Serial SARS-CoV-2 Seropravelence Studies in Delhi July-August 2020: Indications of Pre-existing Cross-reactive Antibodies and Implications for Disease Progression
Authors: Dey Smarajit
Published: September 2020

Two seropravelence studies were undertaken in Delhi, the city-state capital of India, in July-August 2020, exactly one month apart, to test for SARS-CoV-2 antibodies. Virus-tested (mostly RT-PCR) caseloads corresponding to these surveys, as of 13 days earlier to ensure antibody generation, were compared. The survey conducted June 26-July 10 (sample size 21387) showed 23.48% seropravelence, (extrapolated to 4.48 mn of Delhi population of 19.1 mn), which was 79-times higher than corresponding virus-tested positives totaling 56746. Survey conducted August 1-7 (15311 samples) showed 29.1% antibody-positive (5.56 mn population), and was 44x of virus-tested positive total of 125096. Pointing out that all serological surveys world-over have shown antibody-positives to be higher than virus-test positives by multiples 7x to 80x, this study seeks to examine why the multiple should decline so drastically in one month, from 79x to 44x. Statistical adjustments were performed for Sampling Error and Sensitivity/Specificity of the diagnostic kits. Indigenously developed COVID KAVACH ELISA tests for IgG antibodies to the SARS-CoV-2 virus were used for the surveys. Significantly, statistical adjustments were also done to account for the Testing Volumes and (Spot) Positivity rates at the two different times. [Spot Positivity is defined in the study and is the closest estimate of current or fresh positivity.] After all statistical revisions, the antibody-positive to virus-test positive multiples stood at 53x and 37x for the two surveys. Calculating across the two sets of data, and other sensitivity analysis, the study indicates that there is a significant proportion of pre-existing cross-reactive antibodies (possibly to the HCoV viruses), that are seropositive in SARS-CoV-2 antibody tests, to the extent of 16%-19% of the population. The study also infers that there is an Amplification Factor of 15 in the Delhi serostudies: ie, each virus-test positive represents 14 more who are possibly asymptomatic and untested. The study forecasts a seropravelence 31%-34% for the 3rd serial serosurvey scheduled in September, whose results expected 22nd September. Limitations of the study are discussed, notably the absence of any research paper on the survey techniques, antibody testing controversies, and the statistical adjustment for Testing Volumes. The study discusses how Chain-of-Transmission protocols and Decreasing Susceptible Population work in unison to slow down a pandemic, and analyses the disease progression graph of Delhi in that context. The implications of 16%-19% pre-existing antibodies on disease progression in Delhi are discussed.
The efficacy of intensive therapy and anaesthesiology virtual distance learning among fifth-year medical students during the COVID-19 pandemic: a cross-sectional study
Authors: Kovács Enikő , Kállai András , Fritúz Gábor , Iványi Zsolt , Mikó Vivien , Valkó Luca , Hauser Balázs , Gál János
Published: September 2020

Background: The coronavirus disease (COVID-19) brought several challenges in medical education. The aim of our study was to investigate whether virtual trainings (VT) organized during the COVID-19 pandemic at our university were effective in replacing in-person bed-side education in intensive therapy and anaesthesiology among fifth-year medical students, both from students' and instructors' perspectives. Methods: This was a cross-sectional study consisting of three parts: a 20-item students' questionnaire filled out by students participating in VT, a 22-item instructors' questionnaire filled out by instructors taking part in virtual education and a 20-item knowledge test completed by students participating in VT, as well as by students visiting bed-side trainings (BT) during the same semester, before COVID-19 pandemic. The questionnaires focused on effectiveness, content, self-preparedness, technical background and interactivity of VT. Instructors' and students' responses given to the common questions, as well as the knowledge test results were compared. Mann-Whitney U test was used for group comparisons and binary logistic regression was performed to analyse the influence of previous health-care experience on students' feeling of self-preparedness. Results: 113 students (68% response rate) and 29 instructors (97% response rate) filled out the questionnaires. The majority of students found our VT useful and effective; however, a considerable number of participants felt disadvantaged by taking a virtual course instead of bed-side learning sessions and would recommend to keep virtual distance learning methods combined with BT. Instructors found VT overall effective and deemed the transfer of their knowledge satisfactory; however, they described worse interactivity and contact with students during virtual sessions compared to in-person teaching. Instructors showed a clearer consensus that VT should not replace BT in the future, while students’ answers were more divided in this regard. Previous health-care experience did not influence students' feeling of self-preparedness. One hundred and twenty-seven students (56 after VT and 71 after BT) completed the end-of-semester knowledge test. Students participating in VT performed better than students visiting BT (median score VT:83.5 vs BT:77.3; p=0.015). Conclusions: The new curriculum incorporating virtual practice sessions was effective in maintaining continuous education of intensive therapy and anaesthesiology among fifth-year medical students during the COVID-19 outbreak.
Whole Genome Sequence Analysis of SARS-CoV-2 Strains Circulating in Malaysia During First Wave and Early Second Wave of Infections.
Authors: Zawawi Zarina Mohd , Suppiah Jeyanthi , Kalyanasundram Jeevanathan , Azizan Muhammad Afif , Mat-Sharani Shuhaila , Hisham Hamidah Akmal , Ping Tan Lu , Wahid Manisya Zauri Ab , Rashid Tengku Rogayah Tengku Abdul , Zain Rozainanee Mohd , Ahmad Norazah , Thayan Ravindran
Published: September 2020

Background: Since December 2019, the outbreak of COVID-19 has raised a great public health concern globally. Here, we report the whole genome sequencing analysis of SARS-CoV-2 strains in Malaysia isolated from six patients diagnosed with COVID-19.Methods: The SARS-CoV-2 viral RNA extracted from clinical specimens and isolates were subjected to whole genome sequencing using NextSeq 500 platform. The sequencing data were assembled to full genome sequences using Megahit and phylogenetic tree was constructed using Mega X software.Results: Six full genome sequences of SARS-CoV-2 comprising of strains from 1st wave (25th January 2020) and 2nd wave (27th February 2020) infection were obtained. Downstream analysis demonstrated diversity among the Malaysian strains with several synonymous and non-synonymous mutations in four of the six cases, affecting the genes M, orf1ab, and S of the SARS-CoV-2 virus. The phylogenetic analysis revealed viral genome sequences of Malaysian SARS-CoV-2 strains clustered under the ancestral Type B.Conclusion: This study comprehended the SARS-CoV-2 virus evolution during its circulation in Malaysia. Continuous monitoring and analysis of the whole genome sequences of confirmed cases would be crucial to further understand the genetic evolution of the virus.
Sensitive Detection and Quantification of SARS-CoV-2 by Multiplex Droplet Digital RT-PCR
Authors: Kock Remco de , Baselmans Mieke , Scharnhorst Volkher , Deiman Birgit
Published: September 2020

Purpose. We aimed to develop a one-step droplet digital RT-PCR (RT-ddPCR) multiplex assay that allows for sensitive detection of SARS-CoV-2 RNA with respect to human derived RNA and could be used for triage and monitoring of Covid-19 patients. Methods. A one step RT-ddPCR multiplex assay was developed for simultaneous detection of SARS-CoV-2 E, RdRp and N viral RNA, and human Rpp30 DNA and GUSB mRNA, for internal nucleic acid (NA) extraction and RT-PCR control. Dilution series of viral RNA transcripts were prepared in water and total NA extract of Covid-19 negative patients. As reference assay, an E-GUSB duplex RT-PCR was used. Results. Assay sensitivity of the RT-PCR assay drastically decreased when SARS-CoV-2 copies were detected in a background of total NA extract compared to water, while the sensitivity of the RT-ddPCR was not affected by the total NA background. GUSB mRNA detection was used to set validity criteria to assure viral RNA and RT-PCR assay quality. In a background of at least 100 GUSB mRNA copies, 5 copies of viral RNA are reliably detectable and 10 copies viral RNA copies are reliably quantifiable. Conclusion. The present study describes a robust and sensitive one-step RT-ddPCR multiplex assay for reliable detection and quantification of SARS-CoV-2 RNA. By determining the fractional abundance of viral RNA with respect to a human housekeeping gene, viral loads from different samples can be compared, what could be used to investigate the infectiveness and to monitor Covid-19 patients.
Predicting Performance of Briquette Made from Millet Bran: A Neural Network Approach
Authors: Kumar Gaurav , Thampi B.S. Gireeshkumaran , Mondal Pranab Kumar
Published: September 2020

Millet bran possesses good fuel quality and can be successfully used as a professional feedstock for producing solid biofuel.  In this paper, a framework for developing an Artificial Neural Network (ANN) to estimate the performance of millet bran briquettes is presented by using experimental data to train, test, and validate the ANN. With the capacity of the developed multi-layer ANN, the effects of moisture content, temperature, and applied pressure on the density, durability, and impact resistance are predicted. Different cases considering three parameters as inputs to the ANN, namely, moisture content, temperature, and applied pressure were analyzed. The outputs of the ANN are the density, durability, and impact resistance for each of the input parameters separately. By comparing with the experimental values, it is shown that the ANN-based method can predict the data well with a Mean Square Error (MSE) value ~ 0.2%. Further, Multiple Linear Regression (MLR) model is used to check the efficiency of ANN prediction from which it is shown that the proposed ANN-based method provides useful guidance for the prediction of the physical parameters efficiently, with the least deviation and high accuracy.
Antioxidant and Antimicrobial Properties of Ocimum sanctum and Cymbopogon nardus
Authors: Ogbonna Ruth Amarachi , Ramanathan Rahini , Ping Ng Shee
Published: September 2020

Plant extracts have gained popularity recently, for their importance as potential antioxidative and antimicrobial agents. These properties have been attributed to their phytochemical content. The extraction solvent and the plant part are among the factors that influence the yield of these phytochemicals This study was therefore undertaken to investigate the antimicrobial and antioxidant activities of extracts of the leaf and stem of Ocimum sanctum (holy basil) and Cymbopogon nardus (citronella grass); two commonly occurring plants in South East Asia. The extracts were obtained by solvent extraction using water, methanol and ethanol. The percentage yield, antimicrobial activity, antioxidant activity and high-performance liquid chromatography (HPLC) analysis was investigated. The organic extracts yielded a higher percentage recovery of phytochemicals compared to the water extracts.  HPLC analysis revealed the presence of chlorogenic acid in all extracts; rutin only in the leaf extracts and the citronella grass leaf extract contained both rutin and gallic acid. Antimicrobial assays were performed using the agar well diffusion method with tetracycline as positive control. Basil extracts exerted a greater inhibitory growth on both S. aureus and E. coli. S. aureus was found to be more susceptible to the presence of plant extracts. Water extracts did not display any zones of inhibition. The DPPH (2,2-diphenyl-1-picrylhydrazyl) assay was used to study the antioxidant effect with Vitamin C (0.1mg/ml) as positive control. The results indicated that the Basil leaf extracts possessed greater antioxidant potential compared to the stem. The study concludes that organic extracts of O. sanctum and C. nardus possess pharmaceutical properties.
The integration of Management Accounting Practices as an innovative strategy towards sustaining small businesses operating in eThekwini metropolitan, South Africa
Authors: Portia Msomi Mbali , Ngibe Musawenkosi , Loraine Bingwa Luyanda
Published: September 2020

The adoption of Management Accounting Practices (MAPs) has been acclaimed for providing positive administrative and strategic influence on large organizations, and are understood to play an integral part in decision-making. However, SMEs are operating in a turbulent environment, they are now challenged to effectively utilize the embedded MAPs to strengthen their strategic business approaches to maintain their sustainability and survival. Therefore, this study seeks to explore the challenges of integrating the adopted MAPs as an innovative strategy towards sustaining small businesses. The research sample consisted of 120 manufacturing SMEs operating in eThekwini metropolitan South Africa. A nonprobability convenience sampling technique and a quantitative questionnaire were utilized to identify and collect the data from the sampled population. The results of the study indicated that amongst other critical factors, lack of education and training of owner/manager and shortage of skills were the contributory factors influencing the integration of MAPs as an innovative strategy towards SMEs’ sustainability. The study results further revealed that there are a variety of other challenges hindering SMEs from utilizing MAPs as an innovative strategic tool and those were the enterprise age and years in operation, lack of government business incubation and technology adoption. These contributory factors were identified as necessary aspects that SMEs needed to align and iron out before integrating MAPs as an innovative strategic tool.
Carbohydrate-Binding Agents: Potential of Repurposing for COVID-19 Therapy
Authors: Gupta Rajesh Kumar , Apte Girish R. , Lokhande Kiran Bharat , Mishra Satyendra , Pal Jayanta K.
Published: September 2020

:

With the emergence of the novel severe acute respiratory syndrome coronavirus-2
(SARS-CoV-2), the whole world is suffering from atypical pneumonia, which resulted in more
than 559,047 deaths worldwide. In this time of crisis and urgency, the only hope comes from new
candidate vaccines and potential antivirals. However, formulating new vaccines and synthesizing
new antivirals are a laborious task. Therefore, considering the high infection rate and mortality due
to COVID-19, utilization of previous information, and repurposing of existing drugs against valid
viral targets have emerged as a novel drug discovery approach in this challenging time. The transmembrane
spike (S) glycoprotein of coronaviruses (CoVs), which facilitates the virus’s entry into
the host cells, exists in a homotrimeric form and is covered with N-linked glycans. S glycoprotein
is known as the main target of antibodies having neutralizing potency and is also considered as an
attractive target for therapeutic or vaccine development. Similarly, targeting of N-linked glycans of
S glycoprotein envelope of CoV via carbohydrate-binding agents (CBAs) could serve as an attractive
therapeutic approach for developing novel antivirals. CBAs from natural sources like lectins
from plants, marine algae and prokaryotes and lectin mimics like Pradimicin-A (PRM-A) have
shown antiviral activities against CoV and other enveloped viruses. However, the potential use of
CBAs specifically lectins was limited due to unfavorable responses like immunogenicity, mitogenicity,
hemagglutination, inflammatory activity, cellular toxicity, etc. Here, we reviewed the current
scenario of CBAs as antivirals against CoVs, presented strategies to improve the efficacy of
CBAs against CoVs; and studied the molecular interactions between CBAs (lectins and PRM-A)
with Man9 by molecular docking for potential repurposing against CoVs in general, and SARSCoV-
2, in particular.
A Study on the Effect and Mechanism of Xiaoaiping (XAP) Injection and S-1 Combination Therapy in Inhibiting the Invasion and Metastasis of Human GC Cells
Authors: Wen Peiyu , Wang Haibo , Ni Tengyang , Dai Xiaojun , Chu Zewen , Ma Shuang , Xiang Liangliang , Zhou Zhen , Qian Yayun , Sunagawa Masataka , Liu Yanqing
Published: September 2020

Background:

This study aimed to determine the effect and mechanism of Xiaoaiping (XAP) injection
combined with S-1 in inhibiting the invasion and metastasis of human GC cells.

Methods:

BGC-823 and MGC-803 cells were incubated in vitro, and the effects of treatment on the cytotoxicity
and proliferation of BGC-823 and MGC-803 cells were evaluated by MTT assay. Cell adhesion tests and Transwell
assays were used to detect the effects of Xiaoaiping injection combined with S-1 on the metastatic ability
of BGC-823 and MGC-803 cells. The expression of VEGF, Metalloproteinases (MMPs) and proteins related to
the Epithelial-Mesenchymal Transition (EMT) were detected by Western blotting. Meanwhile, a tumour model
was established in nude mice, and the effect of XAP combined with S-1 on BGC-823 cells in vivo was studied.

Results:

Compared with the single drug group, the combination of XAP with S-1 increased the inhibition rate
(P<0.05). The adhesion test showed that the combination group significantly inhibited the adhesion of BGC-823
and MGC-803 cells (P<0.05). The combination of XAP with S-1 reduced the migration and invasion potential
of human GC BGC-823 and MGC-803 cells. Western blotting showed that the expression of VEGF, MMP-9, Ncadherin
and vimentin was decreased and E-cadherin expression was increased in the combination group compared
with these expression values in either the XAP or S-1 alone group (P<0.05). In vivo, we found that XAP
combined with S-1 had a significant inhibitory effect on the growth of tumours compared with XAP or S-1
alone. Immunohistochemistry showed that XAP combined with S-1 was able to enhance the levels of E-cadherin
and downregulate N-cadherin and vimentin.

Conclusion:

The combination of XAP with S-1 can enhance the inhibitory effect of a single drug on proliferation,
invasion and metastasis. The mechanism may be related to the decrease in the expression of VEGF and
MMP-9 proteins and the effect on EMT.
The Chemosensitizing Role of Metformin in Anti-Cancer Therapy
Authors: Tang Zhimin , Tang Nan , Jiang Shanshan , Bai Yangjinming , Guan Chenxi , Zhang Wansi , Fan Shipan , Huang Yonghong , Lin Hui , Ying Ying
Published: September 2020

Chemoresistance, which leads to the failure of chemotherapy and further tumor recurrence, presents
the largest hurdle for the success of anti-cancer therapy. In recent years, metformin, a widely used first-line
antidiabetic drug, has attracted increasing attention for its anti-cancer effects. A growing body of evidence indicates
that metformin can sensitize tumor responses to different chemotherapeutic drugs, such as hormone modulating
drugs, anti-metabolite drugs, antibiotics, and DNA-damaging drugs via selective targeting of Cancer Stem
Cells (CSCs), improving the hypoxic microenvironment, and by suppressing tumor metastasis and inflammation.
In addition, metformin may regulate metabolic programming, induce apoptosis, reverse Epithelial to Mesenchymal
Transition (EMT), and Multidrug Resistance (MDR). In this review, we summarize the chemosensitization
effects of metformin and focus primarily on its molecular mechanisms in enhancing the sensitivity of
multiple chemotherapeutic drugs, through targeting of mTOR, ERK/P70S6K, NF-κB/HIF-1α, and Mitogen-
Activated Protein Kinase (MAPK) signaling pathways, as well as by down-regulating the expression of CSC
genes and Pyruvate Kinase isoenzyme M2 (PKM2). Through a comprehensive understanding of the molecular
mechanisms of chemosensitization provided in this review, the rationale for the use of metformin in clinical
combination medications can be more systematically and thoroughly explored for wider adoption against numerous
cancer types.
Designing Specific HSP70 Substrate Binding Domain Inhibitor for Perturbing Protein Folding Pathways to Inhibit Cancer Mechanism
Authors: Coşkun Kübra A. , Koca İrfan , Gümüş Mehmet , Tutar Yusuf
Published: September 2020

Background:

HSP70 is a survival factor for tumor cells in transformation and in tumor progression as well as
in anti-apoptotic response.

Objective:

Several inhibitors targeting HSP70 ATPase function displayed off-target affect but PES which targets HSP70
substrate binding domain prevents tumor cell survival prominently. However, PES may not bind HSP70 in the absence of
nucleotide. This research aimed to design a unique inhibitor molecule that work both in the presence and absence of
nucleotides to amplify inhibition.

Methods:

A set of chimeric coumarine-pyrazole derivatives determined by in silico techniques and synthesized to
elucidate their inhibitory effects. Cell viability experiments displayed KBR1307 as the most efficient inhibitor. A set of
characterization experiments performed, and results compared to that of PES agent. Binding constant, ATP hydrolysis
rate, and percent aggregation determined in the presence and absence of inhibitors.

Results:

In silico docking experiments showed that only KBR1307 binds the HSP70 substrate binding domain
and interacts with cochaperone interface. Binding experiments indicated that KBR1307 binds HSP70 both in the
presence and absence of nucleotides, but PES does not. Both inhibitors significantly lower HSP70 ATPase activity
and substrate protein disaggregation activity. However, KBR1307 displays a lower IC50 value at the MCF-7 cell
line compared to PES. Both inhibitors do not alter HSP70 secondary structure composition and overall stability.

Conclusion:

KBR1307 effectively inhibits HSP70 compared to PES and provides promising template for novel anticancer
drug development.
Antiproliferative and Genotoxic Action of an Underexploited Organoteluran Derivative on Sarcoma 180 Cells
Authors: do Nascimento Maria L.L. Barreto , dos Reis Antonielly Campinho , Santos José V.O. , Negreiros Helber A. , da Silva Felipe C. Carneiro , Ferreira Paulo M.P. , Gonçalves Juan C.R. , Dittz Dalton , Braz Débora C. , Nunes Adriana M.V. , Cunha Rodrigo L.O.R. , Melo-Cavalcante Ana A.C. , de Castro e Sousa João Marcelo
Published: September 2020

Background:

The search for novel metallic chemical compounds with toxicogenic effects has been of
great importance for more efficient cancer treatment.

Objective:

The study evaluated the cytotoxic, genotoxic and mutagenic activity of organoteluran RF07 in the
S-180 cell line.

Methods:

The bioassays used were cell viability with 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium
bromide (MTT) test, evaluation of apoptosis and necrosis using fluorescence and flow cytometry, cytokinesisblock
micronucleus test and comet assay. The compound was tested at 1; 2.5 and 5μM.

Results:

The results showed the cytotoxicity of RF07 at concentrations of 2.5, 5, 10 and 20μM when compared
to the negative control. For genotoxicity tests, RF07 showed effects in all concentrations assessed by increased
index and frequencies of damage and mutagenic alterations. The compound was also cytotoxic due to the significant
decrease in the nuclear division index, with significant values of apoptosis and necrosis. The results of
fluorescence and flow cytometry showed apoptosis as the main type of cell death caused by RF07 at 5μM,
which is thought to avoid an aggressive immune response of the organism.

Conclusion:

In addition to cytotoxic and genotoxic effects, RF07 creates good perspectives for future antitumor
formulations.
Establishment of Quality Standards for Raw Material of Cyanthillium cinereum (L.) H. Rob
Authors: Charoonratana Tossaton , Pongnuruk Ketkanok , Puttarak Panupong
Published: September 2020

Introduction:

Cyanthillium cinereum has long been used in Thai traditional medicine.
However, the standard information of C. cinereum raw material has not been established.

Objective:

This study aimed to present the standard information of C. cinereum raw material.

Material and methods:

The microscopic and macroscopic characteristics, the physicochemical
analysis, and assays for bioactive contents of 24 samples of C. cinereum from different locations
were evaluated to determine the standard information of the plant material.

Results:

The result showed the microscopic characteristic of pollens in all powder samples. No nicotine
content in C. cinereum extract was observed with LC-MS; apigenin and luteolin were instead
selected as markers. The observed average contents of apigenin and luteolin were 0.238 and
1.059 mg/g, respectively, using HPLC-UV. Nitrite and nitrate components in C. cinereum, which
induced flavor aversion leading to smoking cessation, were determined. The average nitrite and nitrate
content were 0.004 and 0.526 mg/kg in ethanol extract and 0.014 and 1.645 mg/kg in the water
extract, respectively. The results did not substantiate the concern for high potassium content in
C. cinereum materials for cardiovascular and renal patients where only traces were observed in all
samples (3.113 and 20.898 mg/kg in ethanol and water extracts, respectively).

Conclusion:

The results can be used to establish the specification of C. cinereum, which will be
useful for quality control of the raw material. This new information is crucial and can be utilized extensively
prior to herbal product preparation.
A Novel Approach for Extraction of Distinguishing Emotions for Semantic
Granularity Level Sentiment Analysis in Multilingual Context
Authors: Naik Midde V. , D Vasumathi , Kumar A.P. Siva
Published: September 2020

Introduction:

Extraction of distinguishing semantic level emotions posed in multi-languages over social media
is an essential task in the field of sentiment analysis or opinion mining. The extraction of emotions expressed in Dravidian
or local languages combining with multi-languages over social media has become an essential challenge in the field of big
data sentiment analysis.

Methods:

In the proposed approach, an innovative framework to recognize the sentiments of users in multi-languages or
Dravidian languages text data using scientific linguistic theories has been defined. The proposed method used machine
learning techniques such as naïve Bayes, support vector machine for fine-grained classification of multilingual text with
help of lexicon-based features groups.

Results:

The results obtained by the experiments conducted on collected benchmark datasets in the proposed approach are
outperformed and better in comparison with corpus-based and world level, phrase-level sentiment analysis for multilanguages text.

Conclusion:

Machine learning technnique SVM has outperformed for sentiment and emotion extraction.