bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthetic Monoclonal Antibody Designed for Novel SARS-nCoV-2 Spike-S1 Protein Antigenic Targeted Epitope of Receptor Binding Domain Inhibit to Prevent Viral Entry
Authors: Abduljaleel Zainularifeen , Al-Allaf Faisal A.
Published: September 2020

Severe acute respiratory syndrome (SARS) is developing disease caused by novel coronavirus (COVID19). This situation has urgently prompted many pharma and R&D research companies and public research health sectors to concentrate their efforts on research for effective therapeutics. SARS-nCoV-2 as a spike (S) protein was a targeted for the development of monoclonal antibody and therapeutics for the prevention and treatment. We developed monoclonal antibody by deep mutational scanning to characterize the effects of mutations in an antibody variable fragment on its based on expression levels, specificity, stability, and affinity for antigenic specific epitope to the Spike-S-RBD. Further to make this antibody multipoint core mutations to improve contacts between specific Fv light and heavy chains to the targeted antigen of RBD. This antibody combined enhancing mutations yielding with higher binding affinity and substantially improved stability in between RBD and antibody. Overall, this antibody may well prevent into the cell interaction with RBD-hACE2 to viral entry and prevention. SARS-nCoV-Spike-S monoclonal antibodies potently inhibited SARS-nCoV-2-Spike-S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited based upon vaccination.
Logistics of an Advanced Therapy Medicinal Product During Covid-19 Pandemic in Italy: Successful Delivery of Mesenchymal Stromal Cells in Dry Ice
Authors: Astori Giuseppe , Bernardi Martina , Bozza Angela , Catanzaro Daniela , Chieregato Katia , Merlo Anna , Santimaria Monica , Barbazza Roberto , Amodeo Giuseppe , Ciccocioppo Rachele , Elice Francesca , Ruggeri Marco
Published: September 2020

Background: During the coronavirus disease-2019 (COVID-19) pandemic, Italian hospitals faced the most daunting challenges of their recent history, and only essential therapeutic interventions were feasible. From March to April 2020, the Laboratory of Advanced Cellular Therapies (Vicenza, Italy) received requests to treat a patient with severe COVID-19 and a patient with acute graft-versus-host disease with umbilical cord-derived mesenchymal stromal cells (UC-MSCs). Access to clinics was restricted due to the risk of contagion. Transport of UC-MSCs in liquid nitrogen was unmanageable, leaving shipment in dry ice as the only option. Methods: We assessed effects of the transition from liquid nitrogen to dry ice on cell viability; apoptosis; phenotype; proliferation; immunomodulation; and clonogenesis; and validated dry ice-based transport of UC-MSCs to clinics. Results: Our results showed no differences in cell functionality related to the two storage conditions, and demonstrated the preservation of immunomodulatory and clonogenic potentials in dry ice. UC-MSCs were successfully delivered to points-of-care, enabling favourable clinical outcomes.Conclusions: This experience underscores the flexibility of a public cell factory in its adaptation of the logistics of an advanced therapy medicinal product during a public health crisis. Alternative supply chains should be evaluated for other cell products to guarantee delivery during catastrophes.
Prevalence and Associated Factors for Alcohol Use Disorder Among Tuberculosis Patients: A Systematic Review and Meta-analysis.
Authors: Necho Mogesie , Tsehay Mekonnen , Seid Muhammed , Zenebe Yosef , Belete Asmare , Gelaye Habitam , Muche Amare
Published: September 2020

Background: Alcohol use disorders (AUD) in tuberculosis patients are complicated with the poor compliance to anti-tuberculosis treatment and poor tuberculosis treatment outcomes. However, aggregate data concerning this problem is not available. Therefore, this study aimed at its inception to fill the above gap by generating an average prevalence of AUD and associated factors in tuberculosis patients.Method: Our electronic search was conducted in the databases of Scopus, PubMed, and EMBASE, African Index Medicus, and psych-info. Besides, the reference list of selected articles was looked manually to have further eligible articles. The random-effects model was employed during the analysis. MS-Excel was used to extract data and stata-11 to determine the average prevalence of AUD among tuberculosis patients. A sub-group analysis and sensitivity analysis were also run. A visual inspection of the funnel plots and an Eggers publication bias plot test were checked for the presence of publication bias.Result: A search of the electronic and manual system resulted in 1965 articles. However, after the massive screening, only 27 articles that studied 30654 tuberculosis patients met the inclusion criteria. The average estimated prevalence of AUD in tuberculosis patients was 30% (95% CI: 24.00, 35.00). This was with a slight heterogeneity (I2 = 57%, p-value = 0.000). The prevalence of AUD in tuberculosis patients was higher in Asia and Europe; 37% than the prevalence in the US and Africa; 24%. Besides, the average prevalence of AUD was 39%, 30%, 30%, and 20% in studies with case-control, cohort, cross-sectional and experimental in design respectively. Also, the prevalence of AUD was higher studies with the assessment tool not reported (36%) than studies assessed with AUDIT. AUD was also relatively higher in studies with a mean age of ≥ 40 years (42%) than studies with a mean age < 40 years (24%) and mean age not reported (27%).Conclusion: There existed a high prevalence of AUD in tuberculosis patients and this varies across continents, design of studies, mean age of the participants, and assessment tool used. This will be of paramount importance for public health intervention in the area.
A scoring model to predict the prognosis of patients with poor-grade aneurysmal subarachnoid hemorrhage
Authors: Shen Jie , Yu Jianbo , Huang Sicong , Mungur Rajneesh , Huang Kaiyuan , Pan Xinfa , Yu Guofeng , Xie Zhikai , Zhou Lihui , Liu Zongchi , Cheng Dexin , Pan Jianwei , Zhan Renya
Published: September 2020

Background

Patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH), defined as World Federation of Neurosurgical Societies (WFNS) grade IV-V has high rates of disability and mortality. The objective of this research is to prognosticate outcomes of poor-grade aSAH accurately.
Methods

A total of 147 poor-grade aSAH patients in our center were enrolled. Risk variables identified by multivariate logistic regression were used to devise the scoring model (total score of 0–9 points). The score values were estimated according to β coefficients. A cohort of 68 patients from another institute was used to validate the model.
Results

Multivariate analysis revealed that modified Fisher grade above II (odds ratio [OR], 2.972; p = 0.034), age ≥ 65 years (OR, 3.534; p = 0.006), conservative treatment (OR, 5.078; p = 0.019), WFNS Grade V (OR, 2.638; p = 0.029), delayed cerebral ischemia (OR, 3.170; p = 0.016), shunt-dependent hydrocephalus (OR, 3.202; p = 0.032) and cerebral herniation (OR, 7.337; p < 0.001) were significant predictors of poor prognosis (modified Rankin Scale [mRS] ≥ 3). By integration of above factors, a scoring system was constructed and divided poor-grade aSAH patients into three categories: low risk (0–1 point), intermediate risk (2–3 points) and high risk (4–9 points), with risk of poor prognosis being 11%, 52% and 87% respectively (P < 0.001). The area under the curve in derivation cohort was 0.844 (p < 0.001; 95% CI, 0.778–0.909). AUC in validation cohort was 0.831 (p < 0.001; 95% CI, 0.732–0.929).
Conclusions

The new scoring model could improve prognostication of prognosis and help decision-making for subsequent complement treatment.
COVID-19 Related Mental Health Burdens: Impact of Educational Level and Relationship Status Among Low Income Earners of Western Uganda
Authors: Lemuel Ann Monima , Usman Ibe Michael , Kasozi Kenneth Iceland , Aigbogun Eric Osamudiamwen , Bassey Victor Archibong , Ifie Josiah , Ssebuufu Robinson , Afodun Adam Moyosore , Terkimbi Swase Dominic , Mbiydzenyuy Ngala Elvis , Adeoye Azeez , Aruwa Joshua Ojodale , Saidi Odoma , Ssempijja Fred , Ayuba John Tabakwot , Onohuean Hope , Kembabazi Stellamaris , Pius Theophilus , Nankya Viola , Matama Kevin , Henry Rachael , Yusuf Helen , Welburn Susan Christina
Published: September 2020

Background: The imposed COVID-19 lockdown is taking a toll mental health, with low-income earners considered particularly affected. The study aimed to investigate level of education and relationship status on awareness of mental healthcare and explore how these factors influence mental health among low income earners in Western Uganda.Methods: A cross sectional descriptive study was undertaken among low-income earners in South Western Uganda. Data were collected from two hundred and fifty-three (253) participants using a structured closed ended questionnaire. Anxiety, anger and depression were assessed using a modified generalized anxiety disorder (GAD-7), Spielberger’s State-Trait Anger Expression Inventory-2 (STAXI-2) and Beck Depression Inventory (BDI) item tools respectively.Result: Most respondents were single male individuals with secondary level. Respondents with tertiary level of education and those with partners had higher score (71.7% and 70.28% respectively) for awareness on mental healthcare. Respondents with primary education level and individuals that were single had higher score (46.98% and 43.72% respectively) for anxiety. Respondents with primary education level and those living with partners had higher mean score (56.44% and 56.21% respectively) for anger. Respondents with no formal education and those who had lost partners had higher mean score (32.11% and 30.50% respectively) for depression. Individuals without formal educational and primary education were observed to have a negative correlation (r2 = 47.4 and 6.4% respectively) with awareness on mental healthcare, and the no formal group had positive correlation with anger and depression (r2 =1.9 and 0.3% respectively), while other groups were negatively correlated (r2 =10.1%). The group of single individuals had a negative correlation with awareness on mental healthcare, anger and depression (r2 =1.9, 0.8 and 0.3% respectively), and a positive correlation with anxiety (r2 =3.9%).Conclusion: It is evident that education and relationship status influence awareness on mental healthcare and mental health state among low income earners in Western Uganda. Therefore, we advocate for new approaches in mental healthcare awareness programs equipped with robust strategy, which will focus on improving optimal mental health among these set of people.
Massive MIMO, mmWave and mmWave-Massive MIMO Communications: Performance Assessment with Beamforming Techniques
Authors: Engda Tewelgn Kebede , Wondie Yihenew , Steinbrunn Johannes
Published: September 2020

A considerable amount of enabling technologies are being explored in the era of fifth generation (5G) mobile system. The dream is to build a wireless network that substantially improves the existing mobile networks in all performance metrics. To address this 5G design targets, massive MIMO (multiple input multiple output) and mmWave (millimeter wave) communication are also candidate technologies. Luckily, in many respects these two technologies share a symbiotic integration. Accordingly, a logical step is to integrate mmWave communications and massive MIMO to form mmWave-massive MIMO which substantially increases user throughput, improve spectral and energy efficiencies, increase the capacity of mobile networks and achieve high multiplexing gains. Thus, this work analyses the concepts, performances, comparison and discussion of these technologies called: massive MIMO, mmWave Communications and mmWave-massive MIMO systems jointly. Besides, outcomes of extensive researches, emerging trends together with their respective benefits, challenges, proposed solutions and their comparative analysis is addressed. The performance of hybrid analog-digital beamforming architecture with a fully digital and analog beamforming techniques are also analyzed. Analytical and simulation results show that the low-complexity hybrid analog-digital precoding achieves all round comparable precoding gains for mmWave-Massive MIMO technology.
Elevated Expression of lncRNA MEG3 Induces Endothelial Dysfunction on HUVECs of IVF Born Offspring via Epigenetic Regulation
Authors: Jiang Ying , Zhu Hong , Chen Hong , Yang Meng-Meng , Yu Yi-Chen , He Sai-Nan , Xu Ye-Tao , Liu Fang , Sagnelli Matthew , Zhu Yi-Min , Luo Qiong
Published: September 2020

Background: The cardiovascular dysfunction in children born after in vitro fertilization (IVF) has been of great concern, in our study, we aim to explore potential molecular mechanism for such long-term outcomes. Methods：Real-time qPCR was used to test long non-coding RNA MEG3 and endothelium-derived factors, endothelial nitric oxide synthase (eNOS), endothelin-1(ET1), vascular endothelial growth factor (VEGF). Primary HUVEC after caesarean section was treated with different estradiol concentrations in vitro. Besides, knockdown of MEG3 on HUVEC provided further evidence between MEG3 expression and alteration of NO, ET1, VEGF. Then, by using pyrosequencing, we detected MEG3 promoter methylation status.Results: We found that the expression level of MEG3 was higher in human umbilical vein endothelial cells (HUVECs) of IVF offspring than that in spontaneously born offspring. Furthermore, we found decreased expression of eNOS, VEGF, elevated expression of ET1 in HUVECs from IVF offspring compared to spontaneously born offspring. We further confirmed the results from in-vivo experiments by demonstrating that high-estradiol intrauterine environments lead to abnormal expression of MEG3 and endothelium-derived factors. Meanwhile, silencing MEG3 expression decreased ET1 expression, and increased nitrite, nitrate, VEGF secretion, which could correct the effect we observed in-vivo. With pyrosequencing technology, we found that elevated expression of MEG3 in IVF offspring derived HUVECs was the result of hypomethylation of the MEG3 promoter. Conclusions: Our results demonstrated that higher expression of MEG3 in IVF-born HUVECs, accompanied by lower secretion of eNOS, VEGF, and higher secretion of ET1, which is closely related with endothelial dysfunction, which together provide a potential mechanism addressing high-risk of hypertension in IVF offspring.
Anemoside B4 ameliorates TNBS-induced colitis involved suppressing the S100A9/NF-κB signaling pathway
Authors: Zhang Yong , Zha Zhengxia , Shen Wenhua , Li Dan , Kang Naixin , Chen Zhong , Liu Yanli , Xu Guoqiang , Xu Qiongming
Published: September 2020

Background
Despite the increased morbidity of ulcerative colitis (UC) in the developing countries, available treatments remain unsatisfactory. Therefore, it is urgent to discover more effective therapeutic strategies. Pulsatilla chinensis was widely used for the treatment of inflamed intestinal diseases including UC for thousands of years in China. However, it is unclear which compound in P. chinensis is responsible for the therapeutic effect. Our previous study reported that anemoside B4, the most abundant triterpenoid saponin isolated from P. chinensis, exerts anti-inflammatory and antioxidant effects.
Methods
Here, we used the 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rat model to evaluate the therapeutic effect of anemoside B4. Blood samples of colitis rat were collected for hematology analysis. The effects of anemoside B4 on inflammation-associated mediators were investigated by Enzyme-linked immunosorbent assay (ELISA) and hematoxylin and eosin staining (HE) staining. Cell proliferation or apoptosis was measured by immunofluorescence technique. The mechanisms of anemoside B4 was investigated using label-free quantitative proteomics. The level of proteins was quantified by western blotting. mRNA expression was quantified by quantitative real-time RT-PCR.
Results
The results showed that anemoside B4 ameliorated TNBS-induced colitis symptoms, including tissue damage, inflammatory cell infiltration, and pro-inflammatory cytokine production, apoptosis and slowed proliferation in the colon. Quantitative proteomic analyses discovered that 56 proteins were significantly altered by anemoside B4 in the TNBS-induced rats. These proteins were mainly clustered in tricarboxylic acid cycle (TCA) cycle and respiratory electron transport chain. Among the altered proteins, S100A9 is one of the most significantly downregulated proteins and associated with NF-κB and MAPK signaling pathways in the pathogenesis of UC. Further experiments revealed that anemoside B4 suppresses the expression of S100A9 and its downstream genes including TLR4, NF-κB, and p-JNK in colon. In vitro, S100A9 protein could active NF-κB signaling pathway in human intestinal epithelial Caco-2 cells. However, anemoside B4 could inhibit the NF-κB signaling pathway induced by S100A9 protein. Besides, it also inhibited active of NF-κB signaling pathway stimulated by LPS or IL-6.
Conclusions
Our results demonstrate that anemoside B4 prevents TNBS-induced colitis involved inhibiting the NF-κB signaling pathway through inactivating S100A9 suggesting that anemoside B4 is a promising therapeutic candidate for colitis.
An Inverse Association of Weight and the Occurrence of Asymptomatic Gallbladder Stone Disease in Hypercholesterolemia Patients in Northwest China: A Case-Control Study.
Authors: Sheng Binwu , Zhao Qingbin , Ma Mao , Zhang Jianqin
Published: September 2020

Background Despite the fact that the majority of gallstones formed in the gallbladder are mainly composed of cholesterol, as they are formed from cholesterol-supersaturated bile, there is still no consensus regarding the contribution of blood serum lipids in the pathogenesis of gallbladder stone disease (GSD). Here, we aimed to investigate the relationship between hypercholesterolemia and the risk of new-onset asymptomatic GSD, and to determine the prevalence of factors associated with new-onset asymptomatic GSD in patients with hypercholesterolemia.Methods In this case-control study, we enrolled 927 Chinese patients with new-onset asymptomatic gallstone disease and 845 healthy controls starting in August 2012. Patients were matched for age, gender, race, occupation, systolic blood pressure, diastolic blood pressure, and fasting blood glucose levels (FBG). Body mass index, nonalcoholic fatty liver disease (NAFLD) and serum lipids indexes were compared and the relationships between BMI, blood lipid and gallbladder stone hazards were examined by using logistic multivariate regression models.Results The result showed a significant higher morbidity with GSD in hypercholesterolemia than non-hypercholesterolemia patients (X2=17.211, P<0.001). Of hypercholesterolemia patients, LDL-c (OR=1.493, P=0.029) and NAFLD (OR=2.723, P=0.022) were significant risk factors for GSD, while male sex (OR=0.244, P=0.033), weight (OR=0.961, P=0.022), HDL-c (OR=0.305, P<0.001), and FBG (OR=0.687, P=0.034) significantly negatively correlated with GSD in univariate analysis. Multivariate logistic regression indicated weakly positive correlations with NAFLD (OR=3.284, P=0.054), and significant negative correlations with weight (OR=0.930, P=0.018), HDL-c (OR=0.144, P<0.001), and GSD. Conclusion Hypercholesterolemia acts as an independent risk factor for new-onset asymptomatic GSD, while obesity and NAFLD are synergistic factors. Interestingly, we are the first to report that elevated weight was inversely associated with GSD in patients with hypercholesterolemia.
Circulating ErbB3/HER3 Levels are Associated with Increased Risk of Hypertension with Overweight: A Cross-Sectional Study
Authors: Zhu Lijun , Fang Zhengmei , Jin Yuelong , Chang Weiwei , Huang Mengyun , Chen Yan , Yao Yingshui
Published: September 2020

Background: Hypertension and overweight are both independent risk factors for cardiovascular disease，and being overweight can more likely to develop high blood pressure. Recent research has shown that ErbB3/HER3 played a considerable role in the development of cardiovascular disease. However, ErbB3 levels effects in the hypertensive overweight patients are unknown. This study aimed to assess the association between ErbB3 levels and hypertension with overweight in Chinese population. Methods: 128 Chinese adults aged 33-79 years, both sexes, underwent evaluation of height and weight, blood pressure, biochemical indicators and ErbB3 levels. Plasma ErbB3 levels was assessed by the Enzyme-linked immunosorbent assay (ELISA), and body mass index (BMI) was calculated as body weight divided by height squared. Participants were allocated in three groups according to blood pressure and BMI: healthy control group (CNT; n = 31; normotensive and nonoverweight), hypertension group (HT; n = 33; hypertension and nonoverweight) and hypertension with overweight group (HTO; n = 64; hypertension and overweight). A 2-tailed P<0.05 was defined to be statistically significant. Results: The difference in mean of ErbB3 levels in three groups was not significant, but had a linear decrease in males, in CNT (1.13±0.36), HT (1.03±0.36) and HTO (0.84±0.26) ng/ml, with P was 0.007. In drinking population, the ErbB3 was significantly reduced in the HTO group as compared with the CNT and HT groups (0.76±0.23 versus 1.18±0.37 and 1.20±0.30, respectively). ErbB3 levels was negatively correlated with DBP in males(r=-0.293, P=0.012), in smoking populations (r=-0.47, P=0.004) and drinking populations (r=-0.387, P=0.008). Besides, BMI in males and in drinking populations and UA in males presented negatively correlations with ErbB3 (p＜0.05). The multivariate conditional logistic regression showed that plasma ErbB3 levels was associated with reduced risk for HTO in males (OR 0.054; 95% CI: 0.007-0.412) and drink group(OR 0.002; 95% CI: 0.000-0.101). Conclusions：The apparent association between lower ErbB3 levels and overweight hypertensive patients suggested that ErbB3 may contribute to the pathogenesis to hypertension with overweight, with BMI, gender, and drinking all potentially modulating the process.Keywords: ErbB3; Hypertension; Overweight; Body mass index.
The Impact of COVID-19 pandemic Lockdown on the utilization of acute surgical care, retrospective, multicenter analysis
Authors: Presl Jaroslav , Varga Martin , Mittermaier Christof , Mitterwallner Stefan , Weitzendorfer Michael , Borhanian Kurosch , Heuberger Andreas , Weiss Helmut , Emmanuel Klaus , Rahden Burkhard von , Koch Oliver Owen
Published: September 2020

Background: The emergency general surgery encompasses the care of critically ill patients, with a potentially high mortality if delayed. As some medical disciplines have reported a strong decrease of emergencies during the COVID-19 pandemic, remains the effect of the Lockdown on the general surgery emergencies unclear. Methods:This study is a retrospective, multicentre analysis of the general surgery emergency operations performed during the 2020 Lockdown and in the same period of 2019 in three centers covering the surgical care of the area Salzburg-North, Austria. Results: In total 165 emergency surgeries were performed in the study period of 2020 compared to 287 in Year 2019. This is a significant decrease of 122 (42.5%) emergency surgeries during the COVID-19 Lockdown (p=0.005). The average length of hospital stay in the 2019 was in median 4 days and was reduced to 3 days during the Lockdown. Appendectomy remained the most performed emergency surgery for the both periods but the operations count reduced to less than a half with 72 cases in 2019 and 33 cases in 2020 (p=0.118). Considering the ration of appendectomy vs all emergency surgeries, it represented 25 % in 2019 and 20% in 2020. The emergency colon surgery observed the strongest decrease of 75% from 17 cases in 2019 to 4 in 2020. In addition, the emergency abdominal wall hernia, cholecystectomies for acute cholecystitis, small surgeries and proctological emergencies recorded drops of 70%, 39%, 33% and 47% respectively. A strongest reduction in frequency of 6 of 13 main categories of emergency surgeries was reported from Center 1, which was the only COVID designed Center (“Hot” hospital) in the examined region.Conclusions:The emergency general surgery is an essential service that continues to run under any circumstances. Our data showed that the COVID-19 related restriction and the fear of being infected with COVID-19 in the hospital result in a significant decrease of the utilization of acute surgical care. Policies and modern alternatives are needed to ensure continued access to specialized services to prevent patients from harm.
Active Behavior of Triple-negative Breast Cancer With Adipose Tissue Invasion: A Single Center and Retrospective Review
Authors: Yamaguchi Junzo , Moriuchi Hiroki , Ueda Takashi , Kawashita Yujo , Hazeyama Takanori , Tateishi Masaki , Aoki Shigehisa , Uchihashi Kazuyoshi , Nakamura Mikio
Published: September 2020

Background: Interactions between adipocyte and breast cancer (BC) cells have yet to be fully elucidated. Here we investigated the prognostic impact of marginal adipose tissue invasion in both luminal breast cancer (HR+/HER2-) and triple-negative breast cancer (TNBC) (HR-/HER2-). Methods: A total of 735 patients with early-stage invasive BC (1999-2014) were retrospectively registered. Median length of patient follow-up was 8.9 years. Survival curves were calculated using a Kaplan-Meier cumulative survival plot. The prognostic difference between two groups were assessed by the univariate Cox-proportional hazard regression model.Results: Patients with adipose tissue invasion (n = 614) had a significantly poorer prognosis than those without adipose tissue invasion (n = 121) in overall survival (OS) (hazard ratio, 2.1; 95% Confidence interval [CI], 1.1 to 4.0; P = 0.025). While a poorer prognosis was observed in TNBC (n = 137) than in luminal BC patients (n = 496) (hazard ratio, 0.45; 95% CI, 0.30 to 0.68, P < 0.001), this aggressive nature of TNBC was noted in node-positive disease (hazard ratio, 0.3; 95% CI, 0.18 to 0.5, P < 0.001) but not in node-negative disease (hazard ratio, 0.78; 95% CI, 0.39 to 1.55, P = 0.472), and also noted in adipose tissue invasion-positive patients (hazard ratio, 0.4; 95% CI, 0.26 to 0.6, P < 0.001) but not in adipose tissue invasion-negative patients (hazard ratio, 0.73; 95% CI, 0.16 to 3.24, P = 0.675). In addition, although patients suffering from TNBC with adipose tissue invasion had a poorer outcome than those without adipose tissue invasion (hazard ratio, 3.63; 95% CI, 1.11 to 11.84; P = 0.033), the difference was not observed in luminal BC (hazard ratio, 1.75; 95% CI, 0.64 to 4.82; P = 0.277). Conclusions: Adipose tissue invasion was correlated with poor survival in TNBC. Cancer cell invasion into local fat may be a first step on cancer progression and systemic disease in TNBC.
Long non-coding RNAs responsive to blast fungus infection in rice
Authors: Wang Lanlan , Jin Jing-Jing , Li Li-Hua , Qu Shao-Hong
Published: September 2020

Background
Long non-coding RNAs (LncRNAs) have emerged as important regulators in many physiological processes in plant. By high-throughput RNA-sequencing, many pathogen-associated lncRNAs were mapped in various plants, and some of them were proved to be involved in plant defense responses. The rice blast disease caused by Magnaporthe oryzae (M. oryzae ) is one of the most destructive diseases in rice. However, M. oryzae-induced lncRNAs in rice is yet to be studied.
Findings:
We investigated rice lncRNAs that were associated with the rice blast fungus. Totally 83 lncRNAs were up-regulated after blast fungus infection and 78 were down-regulated. Of them, the natural antisense transcripts (NATs) were the most abundant. The expression of some lncRNAs has similar pattern with their host genes or neighboring genes, suggesting a cis function of them in regulating gene transcription level. The deferentially expressed (DE) lncRNAs and genes co-expression analysis revealed some lncRNAs were associated with genes known to be involved in pathogen resistance, and these genes were enriched in terpenoid biosynthesis and defense response by Gene Ontology (GO) enrichment analysis. Interestingly, one of up-regulated DE-intronic RNA was derived from a jasmonate (JA) biosynthetic gene, lipoxygenase RLL (LOX-RLL). Levels of JAs were significantly increased after blast fungus infection. Given that JA is known to regulate blast resistance in rice, we suggested that lncRNA may be involved in JA-mediated rice resistance to blast fungus.
Conclusions
This study identified blast fungus-responsive lncRNAs in rice, which provides another layer of candidates that regulate rice and blast fungus interactions.
Prognostic Models for Knee Osteoarthritis: A Protocol for Systematic Review, Critical Appraisal and Meta-Analysis
Authors: Zhong Jingyu , Si Liping , Zhang Guangcheng , Huo Jiayu , Xing Yue , Hu Yangfan , Zhang Huan , Yao Weiwu
Published: September 2020

Background: Osteoarthritis is the most common degenerative joint disease diagnosed in clinical practice. It is associated with significant socioeconomic burden and poor quality of life, a large proportion of which is due to knee osteoarthritis (KOA), mainly driven by total knee arthroplasty (TKA). As the difficulty of being detected early and deficiency of disease-modifying drug, the focus of KOA is shifting to disease prevention and the treatment to delay its rapid progression. Thus, the prognostic prediction models are called for, to stratify individuals to guide clinical decision making. The aim of our review is to identify and characterize reported multivariable prognostic models for KOA which concern about three clinical concerns: (1) the risk of developing KOA in general population; (2) the risk of receiving TKA in KOA patients; and (3) the outcome of TKA in KOA patients who plan to receive TKA.Methods: Studies will be identified by searching seven electronic databases. Title and abstract screening and full-text review will be accomplished by two independent reviewers. Data extraction instrument and critical appraisal instrument will be developed before formal assessment, and will be modified during a training phase in advance. Study reporting transparency, methodological quality, and risk of bias will be assessed according to Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement, CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS) and Prediction model Risk Of Bias ASsessment Tool (PROBAST). Prognostic prediction models will be summarized qualitatively. Quantitative metrics on predictive performance of these models will be synthesized with meta-analyses if appropriate.Discussion: Our systematic review will collate evidence from prognostic prediction models that can be used through the whole process of KOA. The review may identify models which are capable of allowing personalized preventative and therapeutic interventions to be precisely targeted at those individuals who are at the highest risk. To accomplish the prediction models to cross the translational gaps between an exploratory research method and a valued addition to precision medicine workflows, research recommendations relating to model development, validation or impact assessment will be made.Systematic review registration: PROSPERO (registered, waiting for assessment, ID 203543)
Exosomes from Adipose Tissue-Derived Mesenchymal Stem Cells Ameliorate Histone-Induced Acute Lung Injury by Activating the PI3K/Akt Pathway in Endothelial Cells.
Authors: Mizuta Yukie , Akahoshi Tomohiko , Guo Jie , Zhang Shuo , Narahara Sayoko , Kawano Takahito , Murata Masaharu , Tokuda Kentaro , Eto Masatoshi , Hashizume Makoto , Yamaura Ken
Published: September 2020

BackgroundMesenchymal stem cells (MSCs), including adipose-derived mesenchymal stem cells (ADSCs), have been shown to attenuate organ damage in acute respiratory distress syndrome (ARDS) and sepsis; however, the underlying mechanisms have not been fully understood. In this study, we aimed to explore the potential roles and molecular mechanisms of action of ADSCs in histone-induced endothelial damage. MethodsMale C57BL/6N mice were intravenously injected with ADSCs, followed by histones or a vehicle. The mice in each group were assessed for survival, pulmonary vascular permeability, and histological changes. A co-culture model with primary human umbilical vein endothelial cells (HUVECs) exposed to histones was used to clarify the paracrine effect of ADSCs. Overexpression and inhibition of miR-126 ADSCs were also examined as causative factors for endothelial protection.ResultsThe administration of ADSCs markedly improved survival, inhibited histone-mediated lung hemorrhage and edema, and attenuated vascular hyper-permeability in mice. ADSCs were engrafted in the injured lung and attenuated histone-induced endothelial cell apoptosis. ADSCs showed endothelial protection (via a paracrine effect) and Akt phosphorylation in the histone-exposed HUVECs. Notably, increased Akt phosphorylation by ADSCs was mostly mediated by exosomes in histone-induced cytotoxicity and lung damage. Moreover, inhibition of miR-126, which is known to be present in exosomes, in ADSCs did not increase Akt phosphorylation in histone-exposed HUVECs. ConclusionADSC-derived exosomes may exert protective effects on endothelial cells via activation of the PI3K/Akt pathway.
Improving the fermentability of pre-hydrolysis liquor to produce ethanol and xylonic acid by removing fermentation inhibitors using polystyrene divinylbenzene resin
Authors: Huang Caoxing , Lin Wenqian , Shi Yuxuan , Zheng Yayue , Yong Qiang
Published: September 2020

Background
The existences of soluble lignin, furfural and HMF in industrial pre-hydrolysis liquor (PHL) can inhibit its bioconversion into bioethanol and other bio-chemicals. Although various technologies have been carried out to remove these inhibitors, a undesirable sugars removal is also happened during the process. Hence, polystyrene divinylbenzene (PS-DVB) resin was used as adsorptive material to simultaneously remove fermentation inhibitors while retain sugars with higher yield for improving the fermentability of PHL after acid-hydrolysis (A-PHL) treatment. The fermentability of treated PHL was evaluated by the bioconversion into ethanol and xylosic acid (XA).
Results
Results showed that an highest xylose concentration (101.1 g/L) in PHL could be obtained by acid-hydrolysis at 100 oC for 80 min with 4% acid, while concentration of fermentation inhibitors (furfural, HMF and lignin) could also be significantly improved. After treating, not only 97% of lignin, 92% of furfural, and 97% of HMF were removed from solution, but also 96% of xylose was retained for subsequent fermentation. With resin treatment, the fermentability of A-PHL could be improved by 162–282% for ethanol production from A-PHL with 30–50 g/L xylose and by 18–828% for XA production from A-PHL with 90–150 g/L xylose.
Conclusions
These results confirmed that PS-DVB resin can remove inhibitors from PHL before producing value-added products by bioconversion. In addition, the work will ideally provide a concept by which pulping facilities could go about producing value-added chemicals from existing waste streams.
Role of Food Choice for Breast Cancer Prevention in Developing Societies: A Case Control Study in North Cyprus
Authors: Danladi Ceasar Dubor , Serakinci Nedime
Published: September 2020

Background: Breast cancer incidence is increasing in developing societies. The Mediterranean eating regimen has been suggested to play a preventive role in reducing breast cancer risk.Objective: This study investigated the preventive role of fruits and vegetables, eggs, fish, olives and olive oil and fresh potatoes consumption similar to western Mediterranean diets on breast cancer development in the women of North Cyprus.Methods: This case-control study was carried out in Dr. Burhan Nalbantoglu Devlet Hastanesi, Lefkosa, North Cyprus. The study group were 305 women with confirmed cases of breast cancer and control group were 302 women without breast cancer. Due consent to participate was obtained. Information on dietary intake was collected, which included age, menopausal status, breast density, age at menarche and dietary consumption of fresh potatoes, fruits and vegetables, olives and olive oil, fish and eggs. logistic regression model was used to analyze the link between the dietary intake and breast cancer risk. Results: Consumption of fruits and vegetables, Olives and olive oil 5 or more servings per day and fish 2 servings per week showed an OR=0.09(0.04,0.18), 0.06(0.03,016) and 0.04(0.02,0.10) respectively, with the 3-6 eggs per week and 4 or more servings of fresh potatoes per week OR=0.10(0.54,0.20) and 0.15(0.08,0.28) respectively.Conclusion: The consumption of olives and olive oil 5 or more times, and fish 2 or 1 times weekly played a more significant role in reducing the risk of breast cancer in women. Investigating at a larger scale in the study population is yet to be done.
COVID-19 mortality risk factors in older people in a long-term care center
Authors: Heras Eva , Garibaldi Pablo , Boix Maite , Valero Oliver , Castillo Jorge , Curbelo Yurisan , Gonzalez Elso , Mendoza Obilagilio , Anglada Maria , Miralles Joan Carles , Lllull Petra , Llovera Ricard , Pique Josep M.
Published: September 2020

Objectives: Despite high rates of COVID-19 infection and increased related mortality have been reported among older adults admitted in long-term care facilities, a limited amount of information is available about the natural course of this pandemic and prognostic factors in this population. In the current study, we aimed to investigate the epidemiologic, demographics, clinical, or therapeutic factors that may predict the prognosis in a cohort of COVID-19 infected elderly in a nursing home.Methods: We conducted a retrospective analysis of all COVID-19 confirmed institutionalized elderly in a nursing home transformed into a reference intermediate healthcare facility from March 15 to June 5, 2020. Epidemiological, demographic, and frailty status before infection, and clinical, laboratory, treatment, and outcome data during infection were collected. We used bivariate analysis and multivariate logistic regression to identify risk factors for mortality.Results: The analysis comprised all 100 COVID-19 confirmed cases during the study period. The median age was 85 years; 62% were female. The case fatality rate was 20%. In the bivariate analysis, male gender, fever, respiratory symptoms, severe cognitive decline, a low Barthel index, and lymphocytopenia were significantly associated with mortality. Multivariate logistic regression analysis identified male gender, low Barthel index, no pharmacological treatment, and lymphocytopenia as independent risk factors associated with mortality.Conclusions and Implications: Male gender, low Barthel index, no pharmacological treatment and lymphocytopenia are independent risk factors for COVID-19 mortality in institutionalized elderly patients in long-term care nursing homes. Treatment with hydroxychloroquine and azithromycin was associated with lower mortality in these patients.
Polyparasitism in School-Aged Children Living in the Schistosomiasis Endemic Focus of Muyuka-Cameroon after >8 Years of Sustained Control Measures: A Cross Sectional Study
Authors: Sumbele Irene Ule Ngole , Otia Ofon Vitalis , Bopda Orelien Sylvain Mtopi , Ebai Calvin Bisong , Kimbi Helen KuoKuo , Nkuo-Akenji Theresa
Published: September 2020

Background: Despite the ubiquity of polyparasitism, its health impacts have been inadequately studied. The aim of this study was to determine the prevalence and determinants of polyparasitism with Schistosoma haematobium, Plasmodium and soil-transmitted helminths (STH) following sustained control measures, as well as evaluate the outcomes and the clinical correlates of infection in school-aged children (SAC) living in the schistosomiasis endemic focus of Muyuka-Cameroon.Methods: Microhaematuria in urine sample was detected using reagent strip and S. haematobium ova by filtration/microscopy methods. Plasmodium in blood sample was detected using Giemsa stained blood films and complete blood count was obtained using an auto-haematology analyser. STH in stool sample was detected by the Kato-Katz method. Categorical and continuous variables were compared as required, Kappa value estimated and the adjusted odds ratio (AOR) in the multivariate analysis was used to evaluate association of the risk factors with infection.Results: Out of the 638 SAC examined, single infection was prevalent in 33.4% while polyparasitism was 19.9%. Prevalence of S. haematobium + Plasmodium was 7.8%; S. haematobium + STH was 0.8%; Plasmodium + STH was 0.8% while, S. haematobium + Plasmodium + STH was 0.9%. Higher preponderance of S. haematobium + Plasmodium infection occurred in females, those from Likoko, did not use potable water, practiced bathing in stream and carried out open defecation than their equivalents. However, being female (AOR = 2.38, P = 0.009) was the only significant risk factor identified. Anaemia was a common morbidity (74.3%) with a slight agreement with microscopy in predicting S. haematobium and Plasmodium infections. The sensitivity and specificity of haematuria (13.0%) in predicting S. haematobium infection was 46.5% and 100% with a moderate agreement with microscopy. Co-infection with S haematobium and malaria parasite was significantly associated with 3-fold odds of history of fever in the last three days.Conclusions: Polyparasitism is a public health problem in the Ikata-Likoko area in Muyuka with females most at risk. Anaemia prevalence is exacerbated in co- and triple-infections and together with a history of fever are of value in predicting polyparasitism.
In silico dynamics of COVID-19 phenotypes for optimizing clinical management
Authors: Voutouri Chrysovalantis , Nikmaneshi Mohammad Reza , Hardin C. Corey , Patel Ankit B. , Verma Ashish , Khandekar Melin J. , Dutta Sayon , Stylianopoulos Triantafyllos , Munn Lance L. , Jain Rakesh K.
Published: September 2020

Understanding the underlying mechanisms of COVID-19 progression and the impact of various pharmaceutical interventions is crucial for the clinical management of the disease. We developed a comprehensive mathematical framework based on the known mechanisms of the SARS-CoV-2 virus infection, incorporating the renin-angiotensin system and ACE2, which the virus exploits for cellular entry, key elements of the innate and adaptive immune responses, the role of inflammatory cytokines and the coagulation cascade for thrombus formation. The model predicts the evolution of viral load, immune cells, cytokines, thrombosis, and oxygen saturation based on patient baseline condition and the presence of co-morbidities. Model predictions were validated with clinical data from healthy people and COVID-19 patients, and the results were used to gain insight into identified risk factors of disease progression including older age, co-morbidities such as obesity, diabetes, and hypertension, and dysregulated immune response 1,2. We then simulated treatment with various drug classes to identify optimal therapeutic protocols. We found that the outcome of any treatment depends on the sustained response rate of activated CD8+ T cells and sufficient control of the innate immune response. Furthermore, the best treatment –or combination of treatments – depends on the pre-infection health status of the patient. Our mathematical framework provides important insight into SARS-CoV-2 pathogenesis and could be used as the basis for personalized, optimal management of COVID-19. Chrysovalantis Voutouri and Mohammad Reza Nikmaneshi contributed equally to this work
Elucidation of Molecular and Hormonal Background of Early Growth Cessation and Endodormancy Induction in Two Contrasting Populus Hybrid Cultivars
Authors: Boldizsár Ákos , Soltész Alexandra , Tanino Karen , Kalapos Balázs , Marozsán-Tóth Zsuzsa , Monostori István , Dobrev Petre I , Vankova Radomira , Galiba Gábor
Published: September 2020

Background Over the life cycle of perennial trees, the dormant state enables the avoidance of abiotic stress conditions. The growth cycle can be partitioned into induction, maintenance and release and is controlled by complex interactions between many endogenous and environmental factors. While phytohormones have long been linked with dormancy, there is increasing evidence of regulation by DAM and CBF genes. To reveal whether the expression kinetics of CBFs and their target PtDAM1 is related to growth cessation and endodormancy induction in Populus, two hybrid poplar cultivars were studied.Results Growth cessation, dormancy status and expression of six PtCBFs and PtDAM1 were analyzed. The ‘Okanese’ hybrid cultivar ceased growth rapidly, was able to reach endodormancy, and exhibited a significant increase of several PtCBF transcripts in the buds on the 10th day. The ‘Walker’ cultivar had delayed growth cessation, was unable to enter endodormancy, and showed much lower CBF expression in buds. Expression of PtDAM1 peaked on the 10th day only in the buds of ‘Okanese’. Besides, in the leaves of the two cultivars, PtDAM1 was not expressed while the CBFs expression pattern was reversed. Leaf phytohormones in both cultivars followed similar profiles during growth cessation but differentiated based on cytokinins which were largely reduced, while the Ox-IAA and iP7G increased in ‘Okanese’ compared to ‘Walker’. Surprisingly, ABA concentration was reduced in leaves of both cultivars. However, the metabolic deactivation product of ABA, phaseic acid, exhibited an early peak on the first day in ‘Okanese’.Conclusions Our results indicate that PtCBFs and PtDAM1 have differential kinetics and spatial localization which may be related to early growth cessation and endodormancy induction under the regime of low night temperature and short photoperiod in poplar. Unlike buds, PtCBFs and PtDAM1 expression levels in leaves were not associated with early growth cessation and dormancy induction under these conditions. Our study provides new evidence that the degradation of auxin and cytokinins in leaves may be an important regulatory point in a CBF-DAM induced endodormancy. Further investigation of other PtDAMs in bud tissue and a study of both growth-inhibiting and the degradation of growth-promoting phytohormones is warranted.
Quantum quench dynamics in the transverse-field Ising model: A numerical expansion in linked rectangular clusters
Authors: Richter Jonas , Heitmann Tjark , Steinigeweg Robin
Published: September 2020

We study quantum quenches in the transverse-field
Ising model defined on different lattice
geometries such as chains, two- and three-leg ladders,
and two-dimensional square lattices.
Starting from fully polarized initial
states, we consider the dynamics of
the transverse and the longitudinal
magnetization for quenches to weak, strong, and critical
values of the transverse field. To this end, we rely on an efficient
combination of numerical linked cluster
expansions (NLCEs) and a forward propagation of pure states in
real time.
As a main result, we demonstrate that NLCEs comprising solely
rectangular clusters
provide a promising approach to study
the real-time dynamics of two-dimensional quantum many-body systems directly in
the thermodynamic limit. By comparing to existing data from the
literature, we unveil that NLCEs yield converged results on time scales
which are competitive to other state-of-the-art numerical methods.