bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between participation in, intensity of, and time spent on leisure time physical activity and risk of inflammatory bowel disease among older adults (PA-IBD): A prospective cohort study
Authors: Rasmussen Nathalie Fogh , Bech Bodil Hammer , Rubin Katrine Hass , Andersen Vibeke
Published: July 2020

Background: Inflammatory bowel diseases (IBDs) are diseases of the immune system that share some genetic and lifestyle-related predisposing factors. Increasing incidences have been reported in all age groups. Based on experimental studies suggesting a role of physical activity on intestinal inflammation, this study aimed to investigate the association between leisure time physical activity and the risk of IBD in older adults. Methods: The study is a prospective cohort study using Danish registry data and questionnaire data from the Danish “Diet, Cancer and Health” cohort. The outcome IBD was defined as having at least two main diagnoses of Crohn’s disease or ulcerative colitis registered in the National Patient Registry from the period between December 1993 and May 1997 with an average follow-up of 25 years. Cox proportional hazard models were used to estimate hazard-ratios for IBD onset associated with being physically active and with levels of the metabolic equivalent of task (MET) hours/week of physical activity and hours/week spent on six types of physical activity. All analyses were adjusted for potential confounders. Furthermore, the analyses were stratified according to age-group, occupational physical activity, smoking, BMI and work status to test for effect modification. Results: In total, 54 645 men and women aged between 50-64 years were included, and of which there were 529 cases. When comparing physically active with inactive participants measured by MET hours/week there was no statistically significant difference in risk of IBD (0.89 [0.13; 6.27]), regardless of how participation was measured. Results did not indicate any dose-response effect when comparing quartile groups of MET hours/week (HR=0.97 [0.76 ; 1.22], HR=0.82 [0.64 ; 1.05] and HR=0.83 [0.65 ; 1.07] or whether five of the six types of activities were compared with the lowest quartile as reference. For do-it-yourself-work, the third quartile of hours/week was associated with a higher risk of IBD compared to the second quartile of hours/week (HR=1.44 [1.10 ; 1.90]. No effect modification was found. Conclusions: There was no association between physical activity and risk of IBD when comparing physically active with inactive participants. Neither did the results indicate any dose-response effect when comparing quartile groups of MET hours/week with the lowest quartile as reference. Do-it-yourself work, however, appeared to be associated with a higher risk of IBD when comparing the third quartile with the second quartile of hours/week. The study has clinical relevance by its contribution to the explanatory field of the causes of IBD. However, the study has some limitations, and further research is needed to clarify associations between physical activity and risk of IBD.
Comparative effectiveness of two methods for inducing osteoarthritis in a novel animal model, the Diannan small-ear pig1
Authors: Jia Di , He Yinghong , Cai Guofeng , Zheng Jiali , Yang Yuye , Li Yanlin
Published: July 2020

Background: Varieties of animals were used to study osteoarthritis pathogenesis. The Diannan small-ear pig, which is native to Yunnan, China, is thought to have an articular anatomy similar to that of humans and is more likely to be a source of pathological tissues than other animals. The aim of this study was determine whether this animal can serve as a more effective osteoarthritis model.[A1] Methods: Twenty-seven adult pigs were randomly divided into three groups and underwent the Hulth procedure, papain articular injection [A2] , and conventional breeding. After 4, 8, and 12 weeks, cartilage tissues from knee joint were extracted for general and histological observation, immunofluorescence, and biochemical analysis. [A3] Synovium was taken out for stromal cell-derived factor-1 analysis. Results: Histopathological observation showed obvious cartilage loss in two experimental groups, this cartilage loss was more severe in the chemical groups. Synovial stromal cell-derived factor1 levels increased over time in all groups. mRNA and protein levels of matrix metalloproteinase-3 were much higher in the chemical groups than in the other groups, whereas levels of collagen type II[A4] and aggrecan were significantly lower in the chemical groups than in the other groups. Immunofluorescence assays of collagen type II[A5] revealed an apparent reduction in this marker in the chemical groups compared with the other groups. Conclusions: These results indicated that the Diannan small-ear pig can be used as an effective osteoarthritis model. In addition, it is much more convenient and much faster to induce osteoarthritis by intra-articular injection of papain, which is a method worthy of being promoted.
Retrospective analysis for the LNM risk factors and effect of chemotherapy for the early colorectal cancer: A Chinese multicenter study
Authors: Zeng Chunyan , Xiong Dandan , Cheng Fei , Luo Qingtian , Wang Qiang , Huang Jun , Lan Guilian , Zhong Huan , Chen Youxiang
Published: July 2020

Background Estimating the risk of lymph node metastasis (LNM) is crucial for determining subsequent treatments following curative resection of early colorectal cancer (ECC). This multicenter study analyzed the risk factors of LNM and the effectiveness of postoperative chemotherapy in patients with ECC.Methods We retrospectively analyzed the data of 473 patients with ECC who underwent general surgery in five hospitals between January 2007 and October 2018. The correlations between LNM and sex, age, tumor size, tumor location, endoscopic morphology, pathology, depth of invasion and tumor budding (TB) were directly estimated based on postoperative pathology results. We also observed the overall survival (OS) and recurrence in ECC patients with and without LNM after matching according to baseline measures. Results In total, 473 ECC patients were observed, 288 patients were enrolled, and 17 patients had LNM (5.90%). The univariate analysis revealed that tumor size, pathology, and lymphovascular invasion were associated with LNM in ECC (P=0.026, 0.000, and 0.000, respectively), and the multivariate logistic regression confirmed that tumor size, pathology, and lymphovascular invasion were risk factors for LNM (P=0.021, 0.023, and 0.001, respectively). There were no significant differences in OS and recurrence between the ECC patients with and without LNM after matching based on baseline measures (P=0.158 and 0.346, respectively), and no significant difference was observed between chemotherapy and no chemotherapy in ECC patients without LNM after surgery (P=0.729 and 0.052).Conclusion Tumor size, pathology, and lymphovascular invasion are risk factors for predicting LNM in ECC patients. Adjuvant chemotherapy could improve OS and recurrence in patients with LNM but not always in ECC patients without LNM.
A high-throughput drug combination screen identifies an anti-glioma synergism between TH588 and PI3K inhibitors
Authors: Chen Zhen , Chen Chao , Zhou Tingting , Duan Chao , Wang Qianqian , Zhou Xiaohui , Zhang Xia , Wu Fangrong , Hua Yunfen , Lin Fan
Published: July 2020

Background: Glioblastoma multiforme (GBM) is the most common and lethal type of primary brain tumor. More than half of GBMs contain mutation(s) of PTEN/PI3K/AKT, making inhibitors targeting the PI3K pathway very attractive for clinical investigation. However, so far, PI3K/AKT/mTOR inhibitors have not achieved satisfactory therapeutic effects in clinical trials of GBM. In this study, we aimed to develop a high-throughput screening method for high-throughput identification of potential targeted agents that synergize with PI3K inhibitors in GBM.Methods: A Sensitivity Index (SI)-based drug combination screening method was established to evaluate the interactions between BKM120, a pan-PI3K inhibitor, and compounds from a library of 606 target-selective inhibitors. Proliferation, colony and 3D spheroid formation assays, western blotting, comet assay, γ-H2AX staining were used to evaluate the anti-glioma effects of the top-ranked candidates. The drug combination effects were analyzed by the Chou-Talalay method.Results: Six compounds were successfully identified from the drug screen, including three previously reported compounds that cause synergistic antitumor effects with PI3K/mTOR inhibitors. TH588, a putative MTH1 inhibitor exhibited significant synergy with BKM120 in suppressing the proliferation, colony formation and 3D spheroid formation of GBM cells. Further investigation revealed that both DNA damage and apoptosis were markedly enhanced upon combination treatment with TH588 and BKM120. Finally, activation of PI3K or overexpression of AKT compromised the anti-glioma efficacy of TH588.Conclusions: The screening method developed in this study demonstrated its usefulness in the rapid identification of synergistic drug combinations of PI3K inhibitors and targeted agents.
Peritumoral ductular reaction can be a prognostic factor for intrahepatic cholangiocellular carcinoma
Authors: Shen Zhenyang , Xiao Jingbo , Wang Junjun , Lu Lungen , Wan Xinjian , Cai Xiaobo
Published: July 2020

Background: Peritumoral ductular reaction (DR) was reported to be related to the prognosis of combined hepatocellular-cholangiocarcinoma and hepatocellular carcinoma. Non-mucin-producing intrahepatic cholangiocarcinoma (ICC) which may be derived from small bile duct cells or liver progenitor cells (LPCs) was known to us. However, whether peritumoral DR is also related to non-mucin-producing ICCs remains to be investigated. Methods: Forty-seven patients with non-mucin-producing ICC were eventually included in the study and clinicopathological variables were collected. Immunohistochemical analysis and immunofluorescence staining for cytokeratin 19, proliferating cell nuclear antigen, and α-smooth muscle actin were performed in tumor and peritumor liver tissues.Results: A significant correlation existed between peritumoral DR and local inflammation and fibrosis. (r = 0.357, 95% CI, 0.037-0.557; P = 0.008 and r = 0.742, 95% CI, 0.580-0.849; P < 0.001, respectively). Patients with obvious peritumoral DR had high recurrence rate (81.8% vs 56.0%, P = 0.058) and poor overall and disease-free survival time (P = 0.01 and P = 0.03, respectively) comparing with mild peritumoral DR. Compared with the mild peritumoral DR group, the proliferation activity of LPCs/ cholangiocytes was higher in obvious peritumoral DR, which, however, was not statistically significant. (0.43±0.29 vs 0.28±0.31, P = 0.172). Furthermore, the correlation analysis showed that the DR grade was positively related to the portal/septalα-SMA level (r = 0.359, P = 0.001).Conclusions: Peritumoral DR was associated with local inflammation and fibrosis. Patients with non-mucin-producing ICC having obvious peritumoral DR had a poor prognosis. Peritumoral DR could be a prognostic factor for ICC. However, the mechanism should be further investigated.
Cervical Spine Osteoradionecrosis or Bone Metastasis after Radiotherapy for Nasopharyngeal Carcinoma? The MRI-Based Radiomics for Characterization
Authors: Zhong Xi , Li Li , Jiang Huali , Yin Jinxue , Lu Bingui , Han Wen , Li Jiansheng , Zhang Jian
Published: July 2020

Background: To develop and validate a MRI-based radiomics nomogram for differentiation of cervical spine ORN from metastasis after radiotherapy (RT) in nasopharyngeal carcinoma (NPC).Methods: A radiomics nomogram was developed in a training set that comprised 46 NPC patients after RT with 95 cervical spine lesions (ORN, n = 51; metastasis, n = 44), and data was gathered from January 2008 to December 2012. 279 radiomics features were extracted from axial contrast-enhanced T1-weighted image (CE-T1WI), a radiomics signature was created by using the least absolute shrinkage and selection operator (LASSO) algorithmin, and a nomogram was developed based on the radiomics scores. The performance of the nomogram was determined in terms of its discrimination, calibration, and clinical utility. An independent validation set contained 25 consecutive patients with 47 lesions (ORN, n = 25; metastasis, n = 22) from January 2013 to December 2015. Results: The radiomics signature that comprised eight selected features was significantly associated with the differentiation of cervical spine ORN and metastasis. The nomogram model demonstrated good calibration and discrimination in the training set [AUC, 0.725; 95% confidence interval (CI), 0.622–0.828] and the validation set (AUC, 0.720; 95% CI, 0.573–0.867). Decision curve analysis indicated that the radiomics nomogram was clinically useful.Conclusions: MRI-based radiomics nomogram shows potential value to differentiate cervical spine ORN from metastasis after RT in NPC.
Genome-wide screening and characterization of genes involved in response to high dose of ciprofloxacin in Escherichia coli
Authors: Sun Rui , Zhang Chunmei , Zhao Xianqi , Han Xue , Zhao Qian , Jiang Peidong , Liu Xinyi , Zhang Wenli , Zhang Fengmin , Fu Yingmei
Published: July 2020

Background

Antibiotic resistance is an urgent threat to public health. Prior to the evolution of antibiotic resistance, bacteria frequently undergo response and tend to develop a state of adaption to the antibiotic. Ciprofloxacin is a broad-spectrum antibiotic by damaging DNA. With the widespread clinical application, the resistance of bacteria to ciprofloxacin continues to increase. This study aimed to investigate the transcriptome changes under the action of high concentration of ciprofloxacin in Escherichia coli.
Results

We identified 773 higher expressed differentially expressed genes (DEGs) and 645 lower expressed DEGs in ciprofloxacin treated cells. Enriched biological pathways reflected the up-regulation of biological process such as DNA damage and repair system, toxin/antitoxin systems, formaldehyde detoxification system, peptide biosynthetic process and cellular protein metabolic process. With KEGG pathway analysis, higher expressed DEGs of kdsA and waa operon were associated with “LPS biosynthesis”. rfbABC operon was related to “streptomycin biosynthesis” and “polyketide sugar unit biosynthesis ”. Lower expressed DEGs of thrABC and fliL operons were associated with “flagellum-dependent cell motility” and “bacterial-type flagellum” in GO terms, and enriched into “biosynthesis of amino acids” and “flagellar assembly” in KEGG pathways. After treatment of ciprofloxacin, bacterial lipopolysacchride (LPS) release was increased by two times, and the mRNA expression level of LPS synthesis genes, waaB, waaP and waaG were elevated (P < 0.05).
Conclusions

Characterization of the gene clusters by RNA-seq showed high dose of ciprofloxacin not only lead to damage of bacterial macromolecules and components, but also induce protective response against antibiotic action by up-regulating the SOS system, toxin/antitoxin system and formaldehyde detoxification system. Moreover, genes related to biosynthesis of LPS were also higher expressed by the treatment indicating that ciprofloxacin can enhance the production of endotoxin on the level of transcription. These results demonstrated that transient exposure of high dose ciprofloxacin is double edged. Cautions should be taken when administering the high dose antibiotic treatment for infectious diseases.
Assessment of the Effectiveness of Various Adult Mosquito Sampling Methods in a Thickly Populated Urban Slum Settlement - A study from Besant Nagar, Chennai, India
Authors: Ravishankaran Sangamithra , Asokan Aswin , A Johnson Amala Justin N , Thomas Shalu , Joshua Vasna , Mathai Manu Thomas , Eapen Alex
Published: July 2020

The authors have withdrawn this preprint due to author disagreement.
Downregulation of miR-342-3p/miR-342-5p in type 1 diabetes mellitus and vascular health; Case controlled study in peripheral blood mononuclear cells and plasma, CD45dimCD34+CD133+ cells, inflammatory markers, CXCR1/2 and PANEX2 mRNA combined with Ingenuity Pathway Analysis
Authors: Ray Sabina L , Coulson David J , Yeoh Megan LY , Bakhashab Sherin , Tamara Alice , Latief Jevi S , Weaver Jolanta U
Published: July 2020

The authors have withdrawn this preprint due to author disagreement.
Family planning practices of women working in the Cambodian garment industry: a qualitative study
Authors: Masuda Chisato , Oreglia Elisa , Sokhey Ly , McLaren Megan , Free Caroline , Tijamo Camille , Amra Ou , Velthoven Michelle Helena van , Williamson Amy , Smith Chris
Published: July 2020

Background: Women working in Cambodian garment factories have unmet needs for family planning (contraception and safe abortion) services, because of their background and living conditions. This study describes their experiences regarding abortion and contraception as part of a larger project to develop an intervention to support comprehensive post-abortion care.Methods: We conducted semi-structured interviews with women seeking abortion services at private health facilities. In addition, we interviewed the private providers of abortion and contraception services surrounding garment factories. Interviews lasted up to 60 minutes and were conducted in Khmer and later translated into English. A thematic analysis was undertaken, with medical abortion experiences coded according to the Cambodia comprehensive abortion care protocol.Results: We interviewed 16 women and 13 providers between August and November 2018. Most women reported being married and had at least one child. Among factory workers the major reported reasons for abortion were birth spacing and financial constraints. Family, friends, or co-workers were the major information resources regarding abortion and contraception, and their positive or negative experiences strongly influenced women’s attitude towards both. Medical abortion pills were not always provided with adequate instructions. Half of the participants had a manual vacuum aspiration procedure performed after medical abortion. While women knew the side effects of medical abortion, many did not know the adverse warning signs and the signs of abortion completion. Only three women started post abortion family planning, as most of the women expressed fear and hesitation due to concerns about side effects of modern contraception. Fear of infertility was particularly reported among young women without children. Conclusion: This research shows that in this setting not all women are receiving comprehensive abortion care and contraceptive counselling. Provision of accurate and adequate information about abortion methods and modern contraception was the dominant shortfall in abortion care. Future work to address this gap could involve the development of appropriate interventions and informative tools for women in the Cambodian garment industry such as through existing client contact-centres or social media, including creation of videos or posts on topics that come from clients questions.
Performance of Commercially Available Rapid Serological Assays for The Detection of SARS-CoV-2 Antibodies
Authors: Hashem Anwar M , Alhabbab Rowa Y Y Rowa Y , Algaissi Abdullah , Alfaleh Mohamed A , Hala Sharif , Abujamel Turki S , ElAssouli M-Zaki , AL-Somali Afrah A , Alofi Fadwa S , Khogeerk Asim A , Alkayyall Almohanad A , Mahmoud Ahmad B , Almontashiri Naif AM , Pain Arnab
Published: July 2020

Background: The Coronavirus Disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread globally. Although several commercial SARS-CoV-2 rapid serological assays have been developed, little is known about their performance and accuracy in detecting SARS-CoV-2 specific antibodies in COVID-19 patient samples. Method: We have evaluated the performance of seven commercially available rapid lateral flow immunoassay (LFIA) serological assays obtained from different manufacturers, and compared them to in-house developed and validated ELISA assays for the detection of SARS-CoV-2 specific IgG and IgM antibodies in COVID-19 patients. Results: While all evaluated LFIA assays showed high specificity, our data showed a significant variation in sensitivity of these assays in which it ranged from 0 to 54% for samples collected early during infection (3-7 days post symptoms onset) and from 54 to 88% for samples collected at later time points during infection (8-27 days post symptoms onset). Conclusion: Commercially available LFIA assays for detection of SARS-CoV-2 specific antibodies may be specific and show high degree of variation in their sensitivity. Further evaluations and validation of rapid serological assays is needed before being routinely used in detecting IgM and IgG in COVID-19 patients.
Tumor cell plasticity, heterogeneity and resistance in
crucial microenvironmental niches in glioma
Authors: Jung Erik , Osswald Matthias , Ratliff Miriam , Xie Ruifan , Weil Sophie , Kurz Felix , Sahm Felix , von Deimling Andreas , Heiland Sabine , Wick Wolfgang , Winkler Frank
Published: July 2020

Both the perivascular niche (PVN) and the integration into multicellular networks by tumor microtubes (TMs) have been associated with progression and resistance to therapies in glioblastoma, but their specific contribution remained unknown. By long-term tracking of tumor cell fate and dynamics in the live mouse brain, differential therapeutic responses in both niches could be determined. Both the PVN, a preferential location of long-term quiescent glioma cells, and network integration facilitated resistance against cytotoxic effects of radiotherapy and chemotherapy - independently of each other, but with additive effects. Perivascular glioblastoma cells were particularly able to actively repair damage to tumor regions. Population of the PVN and resistance in it depended on proficient NOTCH1 expression. In turn, NOTCH1 downregulation induced resistant multicellular networks by TM extension. Our findings identify NOTCH1 as a central switch between the PVN and network niche in glioma, and demonstrate robust cross-compensation when only one niche is targeted.
An effective scheme to determine surface energy and its relation with adsorption energy
Authors: Li Bo , Li Xin , Jiang Qing , Gao Wang
Published: July 2020

Surface energy is fundamental in controlling surface properties and surface-driven processes like heterogeneous catalysis, as adsorption energy is. It is thus crucial to establish an effective scheme to determine surface energy and its relation with adsorption energy. Herein, we propose a model to quantify the effects of materials’ intrinsic characteristics on the material-dependent property and anisotropy of surface energy, based on the period number and group number of bulk atoms, and the valence-electron number, electronegativity and coordination of surface atoms. Our scheme holds for elemental crystals in both solid and liquid phases, body-centered-tetragonal intermetallics, fluorite-structure intermetallics, face-centered-cubic intermetallics, Mg-based surface alloys and semiconductor compounds, which further identifies a quantitative relation between surface energy and adsorption energy and rationalizes the material-dependent error of first-principle methods in calculating the two quantities. This model is predictive with easily accessible parameters and thus allows the rapid screening of materials for targeted properties.
Quality-of-life after cholecystectomy in Kazakhstan and Sweden: comparative study based on the GIQLI questionnaire
Authors: Koishibayeva Leyla Meiramovna , Turgunov Yermek Meiramovich , Sandblom Gabriel , Koishibayev Zhandos Muratovich , Teleuov Murat Koishibayevich
Published: July 2020

Background: As severe morbidity rarely is the focus in gallstone surgery, health-related quality of life has evolved as the main outcome measure of the management of patients with gallstone disease. The lack of universally accepted guidelines on treatment of gallstone disease has also resulted in great regional differences in the preoperative evaluation and management of patients with gallstone disease.Objective: The aim of this study was to compare quality-of-life following gallstone surgery in cohorts from Kazakhstan and Sweden.Methods: A comparative study on quality-of-life (QoL) after cholecystectomy (CE) in two cohorts from Sweden and Kazakhstan using the Gastrointestinal Quality-of-Life Index (GIQLI) questionnaire. QoL measures of 259 patients in Kazakhstan and 448 patients in Sweden were compared taking into account surgical approach, mode of admission, and indication for surgery. Patients in both cohorts were requested to fill in the GIQLI questionnaire after surgery. Similar routines were applied to ensure high coverage in both countries. Results: The mean overall GIQLI score was higher for patients undergoing cholecystectomy in Sweden than those in Kazakhstan (p<0.01). The same was seen when stratifying for open or laparoscopic surgery (both p<0.05), absence of presence of acute cholecystitis (both p<0.05) and emergency admission (p<0.05), but not in case of planned admission (p=0.54).Conclusions: There were large differences in perceived QoL, even when taking indication for surgery and approach into account. These differences in may be explained by differences in attitudes to health status and treatment expectations. Standardized routines for evaluating the outcome after surgery are needed.
Air versus water chilling of chicken: a pilot study of quality, shelf-life, microbial ecology, and economics
Authors: Belk Aeriel D , Duarte Toni , Quinn Casey , Coil David A. , Belk Keith E. , Eisen Jonathan A. , Quinn Jason C. , Martin Jennifer N. , Yang Xiang , Metcalf Jessica L.
Published: July 2020

Background.
The United States’ large-scale poultry meat industry is energy and water intensive, and opportunities may exist to improve sustainability during the broiler chilling process. After harvest, the internal temperature of the chicken is rapidly cooled to inhibit bacterial growth that would otherwise compromise the safety of the product. This step is accomplished most commonly by water immersion chilling in the United States, while air chilling methods dominate other global markets. A comprehensive understanding of the differences between these chilling methods is lacking. Therefore, we assessed the meat quality, shelf-life, microbial ecology, and technoeconomic impacts of chilling methods on chicken broilers in a university meat laboratory setting.
Results.
We discovered that air-chilling (AC) methods resulted in superior chicken odor and shelf-life, especially prior to 14 days of dark storage. Moreover, we demonstrated that AC resulted in a more diverse microbiome that we hypothesize may delay the dominance of the spoilage organism Pseudomonas. Finally, a technoeconomic analysis highlighted potential economic advantages to AC when compared to water-chilling (WC) in facility locations where water costs are a more significant factor than energy costs.
Conclusions.
In this pilot study, AC chilling methods resulted in a superior product compared to WC methods and may have economic advantages in regions of the U.S. where water is expensive. As a next step, a similar experiment should be done in an industrial setting to confirm these results generated in a small-scale university lab facility.
Utility of routine haematological parameters and infectious biomarkers to assess the disease severity in COVID-19 positive patients, analysis and early trend from India
Authors: Singh Pomilla , Kumar Alok , Singh Shashank , Kelkar Anjali , Doshi Preeti , Nimbargi RC , Mani NS
Published: July 2020

Background and Objective- India has emerged as fifth worst hit nation by novel Corona virus pandemics in terms of total number of cases. Our literature on clinicopathological, hematopathological characterstics and trend is still miniscule. The study was conducted to assess utility of haematological parameters and infection biomarkers in identifying disease severity. Method- The test results for complete blood counts, Coagulation screen and inflammatory markers of covid 19 positive patients were recorded and analysed based on their admission to Intensive care units, High Dependency Units or Ward. Those parameters with significant differences between the groups werewere assessed by receiver operating curve and the best screening cut-off was selected. Results- 100 adults were analysed, area under the curve for total leukocyte count, Absolute neutrophil count, Neutrophil-to-Lymphocyte ratio was found >0.800, with p<0.05.The best cut off value obtained for TLC was 8100/cmm, with sensitivity and specificity of 91% and 62.5%; ANC – 6739/cmm, with 91.7% and 75% respectively; NLR - 6.9 with sensitivity and specificity 91.7% and 87.5% respectively. Haematological parameters of 33 paediatric patients studied separately and were well within normal physiological limits. Interpretation and conclusion- study suggests that in adults, using TLC, ANC and NLR, obtained from the basic preliminary workup may segregate patients requiring intensive care at the time of admission enabling risk stratification and guide intervention.
COVID-19 Transmission Dynamics and Final Epidemic Size
Authors: Duan Daifeng , Wang Cuiping , Yuan Yuan
Published: July 2020

We propose two kinds of compartment models to study the transmission dynamics of COVID-19 virus and to explore the potential impact of the interventions, to disentangle how transmission is affected in different age group. Starting with an SEAIQR model by combining the effect from exposure, asymptomatic and quarantine, then extending the model to an two groups with ages below and above 65 years old, and classify the infectious individuals according to their severity, we focus our analysis on each model with and without vital dynamics. In the models with vital dynamics, we study the dynamical properties including the global stability of the disease free equilibrium and the existence of endemic equilibrium, with respect to the basic reproduction number. Whereas in the models without vital dynamics, we address the final epidemic size rigorously, which is one of the common but difficult questions regarding an epidemic. Finally, using the data of COVID-19 confirmed cases in Canada and Newfoundland & Labrador province, we can parameterize the models to estimate the basic reproduction number and the final epidemic size of disease transmission.
WITHDRAWN: The Case Against Cantor’s Diagonal Argument
Authors: Jones Peter P.
Published: July 2020

We present the case against Cantor’s Diagonal Argument (CDA), exposing a number of fatal inconsistencies.
Analysis of the efficacy of HIV protease inhibitors against SARS-CoV-2’s main protease
Authors: mahdi mohamed , Mótyán János András , Szojka Zsófia Ilona , Golda Mária , Miczi Márió , Tőzsér József
Published: July 2020

Background
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in millions of infections worldwide. While the search for an effective antiviral is still ongoing, experimental therapies based on repurposing of available antivirals is being attempted, of which HIV protease inhibitors (PIs) have gained considerable interest. Inhibition profiling of the PIs directly against the viral protease has never been attempted in vitro, and while few studies reported an efficacy of lopinavir and ritonavir in SARS-CoV-2 context, the mechanism of action of the drugs remains to be validated.
Methods
We carried out an in-depth analysis of the efficacy of HIV PIs against the main protease of SARS-CoV-2 (Mpro) in cell culture and in vitro enzymatic assays, using a methodology that enabled us to focus solely on any potential inhibitory effects of the inhibitors against the viral protease.
Results
Lopinavir, ritonavir, darunavir, saquinavir, and atazanavir were able to inhibit the viral protease in cell culture, albeit in concentrations much higher than their achievable plasma levels, given their current drug formulations. While inhibition by lopinavir was attributed to its cytotoxicity, ritonavir was the most effective of the panel, with IC50 of 13.7 µM. Atazanavir on the other hand was the only PI to inhibit the viral protease both in cell culture and in our in vitro enzymatic assay.
Conclusion
Targeting of SARS-CoV-2 Mpro by some of the HIV PIs might be of limited clinical potential, given the high concentration of the drugs required to achieve significant inhibition. Therefore, given their weak inhibition of the viral protease, any potential beneficial effect of the PIs in COVID-19 context might perhaps be attributed to acting on other molecular target(s), rather than SARS-CoV-2 Mpro.
Decoding semi-automated title-abstract screening: a retrospective exploration of the review, study, and publication characteristics associated with accurate relevance predictions
Authors: Gates Allison , Gates Michelle , DaRosa Daniel , Elliott Sarah A. , Pillay Jennifer , Rahman Sholeh , Vandermeer Ben , Hartling Lisa
Published: July 2020

Background

We evaluated the benefits and risks of using the Abstrackr machine learning (ML) tool to semi-automate title-abstract screening, and explored whether Abstrackr’s predictions varied by review or study-level characteristics.

Methods

For 16 reviews we screened a 200-record training set in Abstrackr and downloaded the predicted relevance of the remaining records. We retrospectively simulated the liberal-accelerated screening approach: one reviewer screened the records predicted as relevant; a second reviewer screened those predicted as irrelevant and those excluded by the first reviewer. We estimated the time savings and proportion missed compared with dual independent screening. For reviews with pairwise meta-analyses, we evaluated changes to the pooled effects after removing the missed studies. We explored whether the tool’s predictions varied by review and study-level characteristics using Fisher’s Exact and unpaired t-tests.

Results

Using the ML-assisted liberal-accelerated approach, we wrongly excluded 0 to 3 (0 to 14%) records but saved a median (IQR) 26 (33) hours of screening time. Removing missed studies from meta-analyses did not alter the reviews’ conclusions. Of 802 records in the final reports, 87% were correctly predicted as relevant. The correctness of the predictions did not differ by review (systematic or rapid, P=0.37) or intervention type (simple or complex, P=0.47). The predictions were more often correct in reviews with multiple (89%) vs. single (83%) research questions (P=0.01), or that included only trials (95%) vs. multiple designs (86%) (P=0.003). At the study level, trials (91%), mixed methods (100%), and qualitative (93%) studies were more often correctly predicted as relevant compared with observational studies (79%) or reviews (83%) (P=0.0006). Studies at high or unclear (88%) vs. low risk of bias (80%) (P=0.039), and those published more recently (mean (SD) 2008 (7) vs. 2006 (10), P=0.02) were more often correctly predicted as relevant.

Conclusion

Our screening approach saved time and may be suitable in conditions where the limited risk of missing relevant records is acceptable. ML-assisted screening may be most trustworthy for reviews that seek to include only trials. Several of our findings are paradoxical, and require further study to fully understand the tasks to which ML-assisted screening is best suited.
Effect of Chromium Methionine Supplementation on the Lactation Performance, Hepatic Respiratory Rate and Antioxidative Capacity of Early-Lactating Dairy Cows
Authors: Wu Zezhong , Peng Wenchao , Liu Jianxin , Xu Guozhong , Wang Diming
Published: July 2020

Backgrounds: Chromium is an important trace element that may regulate dairy cow metabolism. The objective of this study was to investigate the effect of chromium methionine (Cr-Met) supplementation on lactation performance, hepatic respiratory rate and anti-oxidative capacity in early-lactating Holstein dairy cows. Results: Sixty-four multiparous cows were grouped into 16 blocks based on parity, days in milk and milk production, and four cows within a block then were assigned randomly to one of four dietary treatments with 0, 4, 8 or 16 g/d of Cr-Met per cow in addition to a basal diet. The experiment lasted for 14 weeks, with the first two weeks as adaptation period. Milk yield and composition were recorded weekly. Dry matter intake was measured every other week. The plasma variables were measured in weeks 4, 8 and 12 of the experiment. Supplementation of Cr-Met did not affect dry matter intake of early-lactating dairy cows. As the supplementation of Cr-Met increased, yields of milk, fat, lactose and energy corrected milk increased in a linear manner (P < 0.01). In terms of plasma variables, insulin concentration decreased in a linear manner with Cr-Met supplementation (P = 0.04). As for variables relative to hepatic respiration rate, concentrations of pyruvate and NADH in the plasma were increased in linear (P < 0.01) and quadratic manners (P < 0.01), and lactic dehydrogenase activity was linearly increased as the feeding levels of Cr-Met increased (P < 0.01). Moreover, plasma glutathione peroxidase and superoxide dismutase activity were increased in a linear manner (P < 0.01). Conclusion: The results suggest that Cr-Met supplementation improved lactation performance of early-lactating dairy cows through enhancing antioxidant capacity and hepatic cellular respiration.
Protocol for Comparing Two Training Approaches for Primary Care Professionals Implementing the Safe Environment for Every Kid (SEEK) Model
Authors: Dubowitz Howard , Saldana Lisa , Magder Lawrence , Palinkas Lawrence , Landsverk John , Belanger Rose , Nwosu Ugonna
Published: July 2020

Background: Child maltreatment (CM) is a major public health problem, affecting many lives, in the short-and long-term, and costing individuals, families and society dearly. There is a need for broad implementation of evidence-based preventive interventions, such as the Safe Environment for Every Kid (SEEK) model, developed for pediatric primary care. Primary care offers an excellent opportunity to help address prevalent psychosocial problems (e.g., parental depression) that are risk factors for CM. By addressing such problems, SEEK can strengthen families and support parents, promote children’s health, development and safety, help prevent CM, and benefit the health of the US population. This study will examine intervention strategies for optimizing SEEK’s adoption, implementation and sustainment, and its effectiveness in preventing CM. Despite strong evidence from two federally funded randomized controlled trials, SEEK has not been widely adopted. The goal of this study is to examine technology driven implementation strategies to scale-up SEEK - in pediatric and family medicine primary care settings. The aims are to: 1) evaluate the effectiveness of training strategies on SEEK’s implementation in primary care practices; 2) evaluate barriers and facilitators to successful implementation and sustainment of SEEK; and 3) examine the model’s effectiveness in preventing CM and the economic costs of implementing SEEK.Methods: This randomized Type III hybrid mixed methods design will examine how advances in medical training can bolster SEEK’s adoption and implementation in pediatric and family medicine practices in different regions of the U.S. These are independent online training and in-depth structured training via a Quality Improvement project, approved by the American Boards of Pediatrics and of Family Medicine. We will also evaluate SEEKonline, software that assists primary care practitioners implement the model, and a “Traditional” paper and pencil strategy for their impact on implementation. The study uses the EPIS framework and the Universal Stages of Implementation Completion, quantitative measures, qualitative interviews and data abstracted from electronic health records. Discussion: The knowledge gained should improve pediatric primary care to better address prevalent social determinants of health, benefiting many children and families. The outcomes should enhance the field of implementation science, and guide future interventions in primary care.Trial Registration: NCT03642327, Clinical Trials, registered 8/21/18, https://register.clinicaltrials.gov
COSMIN Risk of Bias tool to assess the quality of studies on reliability or measurement error of outcome measurement instruments: a Delphi study.
Authors: Mokkink Lidwine B. , Boers Maarten , Vleuten CPM van der , Bouter LM , Alonso Jordi , Patrick Donald L , de Vet HCW , Terwee CB
Published: July 2020

Background

Scores on an outcome measurement instrument depend on the type and settings of the instrument used, how instructions are given to patients, how professionals administer and score the instrument, etc. The impact of all these sources of variation on scores can be assessed in studies on reliability and measurement error, if properly designed and analyzed. The aim of this study was to develop standards to assess the quality of studies on reliability and measurement error of clinician-reported outcome measurement instruments, performance-based outcome measurement instrument, and laboratory values.

Methods

We conducted a 3-round Delphi study involving 52 panelists.

Results

Consensus was reached on how a comprehensive research question can be deduced from the design of a reliability study to determine how the results of a study inform us about the quality of the outcome measurement instrument at issue. Consensus was reached on components of outcome measurement instruments, i.e. the potential sources of variation. Next, we reached consensus on standards on design requirements (n=5), standards on preferred statistical methods for reliability (n=3) and measurement error (n=2), and their ratings on a four-point scale. There was one term for a component and one rating of one standard on which no consensus was reached, and therefore required a decision by the steering committee.

Conclusion

We developed a tool that enables researchers with and without thorough knowledge on measurement properties to assess the quality of a study on reliability and measurement error of outcome measurement instruments.
CD137 Agonist Induces Gastric Cancer Cell Apoptosis by Enhancing The Functions of CD8+ T Cells via NF-κB Signaling
Authors: Hu Ben-Shun , Tang Tian , Wu Tie-Long , Sheng Ying-Yue , Xue Yu-Zheng
Published: July 2020

Background: CD137 is identified as a target for tumor immunotherapy. However, the role of CD137 in gastric cancer (GC), especially in inducing GC cell apoptosis has not been studied yet. Methods: Foxp3+ and CD8+ T cells in GCs were investigated by immunohistochemistry (IHC). CD137 expression in GCs was detected by flow cytometry, IHC and immunofluorescence (IF). Peripheral blood mononuclear cells (PBMCs) and CD8+ T cells isolated from peripheral blood were stimulated with a CD137 agonist in vitro. CD8+ T cells proliferation and p65 expression were explored by flow cytometry. p65 nuclear translocation was analyzed by IF. IL-10, TGF-β, IFN-γ, Perforin and Granzyme B were detected by real-time quantitative PCR (real-time PCR). PBMCs and primary GC cells were cocultured and stimulated with the CD137 agonist in vitro. Apoptosis of the primary GC cells was detected by flow cytometry. Results: Our data demonstrated that GC tumors show characteristics of an immunosuppressive microenvironment. CD137 was predominantly expressed in CD8+ T cells in GCs and had a positive correlation with tumor cell differentiation. CD137 agonist promoted CD8+ T cells proliferation and increased the secretion of IFN-γ, Perforin and Granzyme B, which induced primary GC cell apoptosis. Mechanistically, this study found that CD137 agonist could induce NF-κB nuclear translocation in CD8+ T cells. ﻿Conclusion: Our results demonstrate that CD137 agonist can induce primary GC cell apoptosis by enhancing CD8+ T cells via activating NF-κB signaling.
Using circ-ANAPC7 as a novel type of biomarker in the monitoring of acute myeloid leukemia
Authors: Shen Ying , Jia Yachun , Zhang Ru , Chen Hongli , Wang Ting , He Aili , Yang Yun
Published: July 2020

Background
Circular RNAs (circRNAs) that occupy gene expression at the transcriptional or post-transcriptional level have great potential to be biomarker for types of cancers. We have screened one altered circRNA named circ-ANAPC7 in acute myeloid leukemia (AML) before. In this study, we aimed to validate its expression by enlarging sample size and illuminating the diagnostic and monitoring value of circ-ANAPC7 in AML.
Methods
Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was supposed to confirm the expression of circ-ANAPC7 of AML patients. We assessed the correlation of circ-ANAPC7 and clinical variables using Spearman correlation test. Receiver operating characteristic (ROC) curve was carried out to evaluate the diagnostic value.
Results
Circ-ANAPC7 was first found to be upregulated in AML, and its expression was correlated to WBC counts and blast percentage in bone marrow. ROC curve analysis revealed that circ-ANAPC7 has significant value of AML diagnosis (AUC = 0.915, P < 0.001). Furthermore, the expression level of circ-ANAPC7 was changed accompanied with disease condition transformation.
Conclusions
Circ-ANAPC7 could be used as a biomarker to monitor disease condition of AML.
Physiological characterization of a new thermotolerant yeast strain isolated during Brazilian ethanol production and its application in high temperature fermentation
Authors: Prado Cleiton Dias do , Mandrujano Gustavo Patricio Lorca , de Souza Jonas Paulino , Sgobbi Flavia Beatriz , Novaes Hosana Ribeiro , Silva João Pedro Maia Oliveira da , Alves Mateus Henrique Ribeiro , Eliodório Kevy Pontes , Cunha Gabriel Caetano de Gois e , Giudici Reinaldo , Procópio Dielle Pierotti , Basso Thiago Olitta , Malavazi Iran , Cunha Anderson
Published: July 2020

Background
The use of thermotolerant yeast strains can improve the efficiency of ethanol fermentation, allowing fermentation to occur at temperatures higher than 40 °C. This increment in temperature could benefit traditional bio-ethanol production and allow simultaneous saccharification and fermentation (SSF) of starch or lignocellulosic biomass.
Results
We identified and characterized the physiology of a new thermotolerant strain able to fermentate at 40 °C while producing high yields of ethanol. Our results showed that, in comparison to the industrial yeast CAT-1, our strain was more resistant to various stressors generated during the production of first- and second-generation ethanol, and it also was able to change the pattern of genes involved in sucrose assimilation (SUC2 and AGT1). The formation of secondary products of fermentation was different at 40ºC, with reduced expression of genes involved in the formation of glycerol (GPD2), acetate (ALD6 and ALD4), and acetyl-CoA (ACS2).
Conclusion
The LBGA-01 strain is a thermotolerant strain that modulates the production of key genes, changing metabolic pathways during high-temperature fermentation, and increasing its tolerance to the high concentration of ethanol, sugar, acetic lactic, acetic acid, furfural and HMF. This indicates that this strain can be used to improve first- and second-generation ethanol production in Brazil.