bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of VEGF-C and its association with clinicopathological features among patients with gastric cancer undergoing gastric surgery at Tongji medical hospital, China.
Authors: MAWALLA BRIAN , Luo Xiaoxiao , Xianglin Yuan
Published: March 2020

Objectives: Gastric cancer shows epidemiological variability according to geographic locations, these differences have been demonstrated both regionally and within countries. There is no baseline protocol regarding using VEGF-C as tumor marker in local setting therefore it was necessary to conduct this study, the current study conducted to analyze the correlation exists between VEGF-C and clinicopathological parameters in patients with gastric cancer undergoing a surgical procedure at Tongji medical hospital. Results: 161samples analyzed were from Chinese patients who had undergone either palliative or curative surgical procedure between October 2015 and September 2017 at Tongji medical hospital. I mmunohistochemistry was method was used to analyses presence of VEGF-C in tissues. Among 161 gastric cancer patients, 101 (62.7%) gastric samples showed strong VEGF-C expression and 60 (37.3%) gastric samples showed weak VEGF-C expression. Using multivariate logistic regression analysis, tumor grade, invasion of lymph nodes and TNM staging were statistically significantly found to associate with strong expression of VEGF-C. VEGF-C strong expression was significantly seen more in adenocarcinoma of gastric cancer, and Therefore, VEGF-C may be used as a biological marker for assessing the biological characteristics of gastric.
Unraveling the Molecular Heterogeneity in type 2 Diabetes: A Potential Subtype Discovery Study Followed by Metabolic Modeling
Authors: Khoshnejat Maryam , Kavousi Kaveh , Moghaddam Ali Mohammad Banaei , Moosavi-Movahedi Ali Akbar
Published: March 2020

Background: Type 2 diabetes mellitus (T2DM) is a complex multifactorial disease with a high prevalence in the world. Insulin resistance and impaired insulin secretion are the two major abnormalities in the pathogenesis of T2DM. Skeletal muscle is responsible for over 75% of the glucose uptake thus plays a critical role in T2DM. Here, we attempt to provide a better understanding of abnormalities in this tissue. Methods: We have explored the muscle gene expression pattern in healthy and newly-diagnosed T2DM individuals using supervised and unsupervised classification along with the discovery of potential subtypes of type 2 diabetes. Results: A machine-learning technique applied to identify a pattern of gene expression that could potentially discriminates between normoglycemic and diabetic groups. A gene set comprises of 26 genes identified which was able to discriminate healthy from diabetic individuals with the 94% accuracy after 10-fold stratified cross-validation. In addition, three distinct potential subtypes with different dysregulated genes and metabolic pathways identified in diabetic patients. Conclusion: This study implies that it seems the disease has triggered through different cellular/molecular mechanisms. Therefore, subtyping of T2DM patients in combination with real clinical profiles of patients will provide a better understanding of abnormalities in each group and lead to the recommendation of the appropriate precision therapy for each subtype in the future.
Hospitalization and Definitive Radiotherapy in Lung Cancer: Incidence, Risk Factors and Survival Impact
Authors: Hazell Sarah Z. , Mai Nicholas , Fu Wei , Hu Chen , Friedes Cole , Negron Alex , Voong Khinh Ranh , Feliciano Josephine L. , Han Peijin , Myers Samantha , McNutt Todd R. , Hales Russell K.
Published: March 2020

Background: Unplanned hospitalization during cancer treatment is costly, can disrupt treatment, and affect patient quality of life. However, incidence and risks factors for hospitalization during lung cancer radiotherapy are not well characterized. Methods: Patients treated with definitive intent radiation (≥45 Gy) for lung cancer between 2008 and 2018 at a tertiary academic institution were identified. In addition to patient, tumor, and treatment related characteristics, specific baseline frailty markers (Charlson comorbidity index, ECOG, patient reported weight loss, BMI, hemoglobin, creatinine, albumin) were recorded. All cancer-related hospitalizations during or within 30 days of completing radiation were identified. Associations between baseline variables and any hospitalization, number of hospitalizations, and overall survival were identified using multivariable linear regression and multivariable Cox proportional-hazards models, respectively. Results: Of 270 patients included: median age was 66.6 years (31-88), 50.4% of patients were male (n=136), 62% were Caucasian (n=168). Cancer-related hospitalization incidence was 17% (n=47), of which 21% of patients hospitalized (n=10/47) had >1 hospitalization. On multivariable analysis, each 1 g/dL baseline drop in albumin was associated with a 2.4 times higher risk of any hospitalization (95% confidence interval (CI) 1.2-5.0, P =0.01), and baseline hemoglobin ≤10 was associated with, on average, 2.7 more hospitalizations than having pre-treatment hemoglobin >10 (95% CI 1.3-5.4, P =0.01). After controlling for baseline variables, cancer-related hospitalization was associated with 1.8 times increased risk of all-cause death (95% CI: 1.02-3.1, P =0.04).Conclusions: Our data show baseline factors can predict those who may be at increased risk for hospitalization, which was independently associated with increased mortality. Taken together, these data support the need for developing further studies aimed at early and aggressive interventions to decrease hospitalizations during treatment.
Effect of the Short-Segment Internal Fixation with Intermediate Inclined-Angle polyaxial Screw at the Fractured Vertebrae on the Treatment of Denis type B Thoracolumbar Fracture
Authors: Xiong Chengjie , Huang Biwang , Wei Tanjun , Kang Hui , Xu Feng
Published: March 2020

Backgroud Short-segment internal fixation with straight-forward monoaxial screw (SSIF-SFM) and long-segment internal fixation (LSIF) are two major surgical options for thoracolumbar (TL) fracture, however, limitations of both surgical options l are obvious. SSIF with inclined-angle polyxial screw (SSIF-IAP) have been developed to take advantage of their benefits and minimize their adverse effects . Methods 69 consecutive patients (47 males and 22 females; average 34.5 years ) who met the criteria for inclusion were enrolled in this study . Sagittal Cobb’s angle (SCA), anterior vertebral body height (AVBH), vertebral body index (VBI) and spinal canal encroachment (SCE) were measured and assessed . Functional recovery Visual Analogue Scale (VAS) and Oswestry disability index (ODI) were also evaluated. Results The value of incision length, mean blood loss, duration of operation and hospital stay in the SSIF–IAP group and SSIF-SFM group were significantly lower than those in the LSIF group. The AVBH and VBI in the SSIF–IA P group and LSIF group were significantly more improved than those in the SSIF–SFM group at 6 months and the latest follow-ups (p < 0.05). The correction losses of AVBH and VBI ( calculated by the reduction of AVBH and VBI) in the SSIF-IAP group and LSIF group were also significantly lower than those in the SSIF–SFM group at 6 months and the latest follow-ups (P<0.05). There was no significant difference of SCE among three groups. The VAS and ODI in the SSIF–IAP group and SSIF-SFM group were significantly lower than those in the LSIF group at 6 months and the latest follow-ups (P<0.05). Conclusion SSIF-IAP can achieve comparable treatment outcomes compared with LSIF, but it was less invasive compared with LSIF . The SSIF–IA was an effective and reliable operative technique for patients with Denis type B TL fracture.
Combined ANN/ EVOP Factorial Design Approach for Media Screening for Cost-effective Production of Alkaline Proteases from Rhizopus oryzae (SN5) / NCIM-1447 under SSF
Authors: Negi Sangeeta , Jain Sapna , Kumar Anand
Published: March 2020

In order to achieve high yield of fungal protease in a very cost effective way and to meet its increased market demand, current study deals with the screening of various agro-wastes as carbon source for the production of protease from Rhizopus oryzae (SN5) / NCIM-1447 under solid state fermentation. Substrates and culture parameters such as wheat bran, soybean meal, black-gram husk, rice husk, mixture of wheat bran, soybean meal, nitrogen sources, pH, temperature and incubation time were first optimized with one factor at time strategy and then EVOP factorial and yield of alkaline protease was achieved 412.8 U/gds at 28 o C and pH=6 after 72 hours of fermentation taking wheat bran and soybean as a substrate in 4:1 ratio. Further Artificial Neural Networks (ANN), was trained with data of EVOP and yield of protease was enhanced up to 422.6 U/gds with wheat bran: soyabean in ratio of 70:30, pH 6.2 at 30°C. The evolved process and Rhizopus oryzae (SN5)/ NCIM-1447 strain would be promising for protease production at industrial scale at low cost.
The effect of simulation-based training in non-physician anesthetists in Tigray region, Ethiopia
Authors: Etanaa Naod Bulti , Benwu Kore Menjie , Gebremedhin Hagos Gebregzabiher , Desta Haftom Berhane
Published: March 2020

Objective : In Ethiopia simulation-based anesthesia education is a new way of teaching method which started in Mekelle University as of January, 2019. Hence, the purpose of this study is to evaluate whether simulation-based training improves non-physician anesthetists’ knowledge and attitude on maternal and neonatal anesthesia cares or not. Results : Out of 50 study subjects, 66% had a working experience of less than 5 years.. Knowledge score improved significantly from 49.78% and 66.22% in pretest and posttest results respectively. The posttest result was significantly improved (P< 0.001) for all knowledge questions. The respondents were asked about a negative statement and a positive statement about the need to have effective closed lope communication, maternal resuscitation and neonatal resuscitation. The attitude score improved from 72.45% to 79.11% in pretest and posttest respectively. From the 9 questions the attitudinal mean score for pretest was 6.52 and posttest 7.12. The null hypothesis of equal knowledge and attitude was rejected, t (49) = -5.54, p < 0.001 and t (49) = -2.25, p < 0.03 respectively.
Comparative effectiveness of post-discharge strategies for hospitalized smokers: Study protocol for the Helping Hand 4 randomized controlled trial
Authors: Rigotti Nancy A , Schnitzer Kristina , Davis Esa M , Regan Susan , Chang Yuchiao , Kelly Jennifer H.K. , Notier Anna E , Gillam Karen , Douaihy Antoine , Levy Douglas E , Singer Daniel E , Tindle Hilary A
Published: March 2020

Background. Tobacco smoking remains the leading preventable cause of death in the U.S. A hospital admission provides smokers with a unique opportunity to stop smoking because it requires temporary tobacco abstinence while illness may enhance motivation to quit. Hospital interventions must continue post-discharge to increase tobacco abstinence long-term, but how best to accomplish this remains unclear. Building on two previous randomized controlled trials, each of which tested smoking cessation interventions that began in hospital and continued after discharge, this trial compares two interventions that provide sustained smoking cessation treatment after hospital discharge with the goal of improving long-term smoking cessation rates among hospitalized smokers. Methods. Helping Hand 4 is a three-site randomized controlled trial that compares the effectiveness of two active interventions for producing validated past 7-day tobacco abstinence 6 months after hospital discharge. Smokers who are admitted to three hospitals receive a standard in-hospital smoking intervention, and plan to quit smoking after discharge are recruited and randomly assigned to two interventions that begin at discharge, Personalized Tobacco Care Management (PTCM) or Quitline eReferral. Each lasts 3 months. At discharge, PTCM provides 8 weeks of free nicotine replacement (NRT; a participant’s choice of patch, gum, lozenge, or a combination) and then proactive smoking cessation support using an automated communication platform and live contact with a tobacco treatment specialist who is based in the health care system. In the eReferral condition, a direct referral is made from the hospital electronic health record to a community-based resource, the state’s telephone quitline. The quitline provides up to 8 weeks of free NRT and offers behavioral support via a series of phone calls from a trained coach. Outcomes are assessed at 1, 3, and 6 months after discharge. The study hypothesis is that PTCM will produce higher quit rates than eReferral. Discussion. HH4 is a pragmatic trial that aims to evaluate interventions in real-world conditions. This project will give hospital systems critical evidence-based tools for meeting National Hospital Quality Measures for tobacco treatment and maximizing their ability to improve cessation rates and overall health for the millions of smokers hospitalized annually in the U.S.
EST-SSR markers identification based on RNA-sequencing and application in Schisandra chinensis
Authors: Shi Guangli , Wang Zhenxing , Sun Dan , Zhang Susu , Guo Jianhui , Ai Jun
Published: March 2020

Background: Schisandra chinensis, a climbing woody vine, is the best-known and representative genus of the Schisandraceae family which is an important plant in Chinese herbal medicine; however, the application of molecular breeding is restricted by the few genetic markers for this species. Results: In this study, we performed transcriptome sequencing of S. chinensis using the Illumina HiSeq platform to establish a library of expressed sequence tag-simple sequence repeat (EST-SSR) markers. A total of 59,786 unigenes were obtained and 6254 putative SSR sites were detected with a frequency of 10.46%. The predominant type of repeat motif was dinucleotide (35.71%), followed by trinucleotide (13.22%), hexanucleotide (0.50%), tetranucleotide (0.06%), and pentanucleotide (0.22%). We randomly selected 50 EST-SSR primer pairs and used 14 of these for genetic diversity analysis in 42 S. chinensis genotypes. All 42 accessions were successfully identified and formed four major clusters, indicating that the SSR markers can be used for genetic diversity analysis and genetic linkage map construction. In addition, using the polymorphic bands associated with 10 markers as DNA fingerprints, we generated a manual cultivar identification diagram that can distinguish between the 42 accessions, with different individuals identifiable based on polymorphic band patterns. Conclusion: S. chinensis transcriptome data is an effective resource for developing SSR markers. These results can provide a basis for the identification of S. chinensis accessions and construction of genetic linkage maps as part of future selective breeding and conservation efforts for this valuable plant.
How does the various sectors of the financial market influence growth around the globe?
Authors: Dwumfour Richard Adjei , Ntow-Gyamfi Matthew
Published: March 2020

We explore the links between financial markets, institutional quality and economic growth. We document that the unconditional effect of finance on growth is ambiguous. This variation is caused by regional bloc, income level and legal origin differences. Our results suggest that, for financial development (banking sector, insurance sector, stock market) to elicit positive effect on growth, there needs to be an effective institutional framework in place. However, in cases where finance in itself elicits positive effect on growth, further tightening of the institutional framework could be harmful to growth; hence, must be done with caution. Policy implications are discussed.
Uganda’s Increasing Dependence On Development Partner Support For Immunization – A Five Year Resource Tracking Study (2012 – 2016)
Authors: Kamya Carol , Abewe Christabel , Waiswa Peter , Asiimwe Gilbert , Namugaya Faith , Opio Charles , Lagony Stephen , Charlotte Muheki
Published: March 2020

Background There are persistent weaknesses in obtaining accurate reliable and complete data on local and external investments in immunization and yet these are critical to estimate costs, resource needs and gaps so as to aid country financing, planning and resource mobilization. This study aimed to measure and describe the financial envelope for immunization activities and conduct an expenditure analysis at district level. Methods The Systems of Health Accounts (SHA) 2011 methodology was used to quantify and map out the resource envelope for immunization. Data were collected at national and district levels from public and external sources of immunization through key informant interviews coupled with document reviews. Data were coded (SHA), categorized and disaggregated to allow for greater detail on the types of immunization activities. Financing methodology used was largely drawn from Guthrie et al, 2015. Results Over a five-year period, funding for immunization has increased fourfold from US$20.4 million in 2012 to US$ 85.6 million in 2016. The increase in the resource envelope is attributed to the lift of the ban of Gavi funding to Uganda as well as new vaccine introduction. Gavi, the Vaccine Alliance became the biggest contributor (59%) in 2015 and 2016 with 66% of the funds managed by National Medical Stores. Eighty percent of the resources are spent on facility-based routine immunization which includes expenditure on human resources and immunization outreaches. At district level, the overall proportion of total funding to immunization was 15% of their Primary Health Care (PHC) Grant. The bulk (82%) of the PHC funds were spent on supervision to lower health centers (transport and distribution of vaccines) while majority (51%) development partner funds were spent on routine immunization activities (vaccine collection and per-diems/allowances to support outreaches). Conclusion The increasing dependence on development partner support raises issues around sustainability alongside other challenges like misalignment and displacement This warrants an increase in financial commitment to immunization by Government of Uganda, prioritization of resources for immunization at district level, and also operationalization of the existing financial sustainability plan for immunization.
Systematic analysis of the Capsicum ERF transcription factor family uncovers new insights into the regulation of species-specific metabolites
Authors: Song Jiali , Chen Changming , Zhang Shuanglin , Wang Juntao , Huang Zhubin , Liu Renjian , Cao Bihao , Zhu Zhangsheng , Lei Jianjun
Published: March 2020

Background: ERF transcription factors (TFs) belong to the Apetala2/Ethylene responsive Factor (AP2/ERF) TF family and play a vital role in plant growth and development processes. Capsorubin and capsaicinoids have relatively high economic and nutritional value, and they are specifically found in Capsicum. However, there is little understanding of how ERFs participate in the regulatory networks of capsorubin and capsaicinoids biosynthesis. Results: In this study, a total of 142 ERFs were identified in the Capsicum annuum genome. Subsequent phylogenetic analysis allowed us to divide ERFs into DREB (dehydration responsive element binding proteins) and ERF subfamilies, and further classify them into 11 groups with several subgroups. Expression analysis of biosynthetic pathway genes and CaERFs facilitated the identification of candidate genes related to the regulation of capsorubin and capsaicinoids biosynthesis; the candidates were focused in cluster C9 and cluster C10, as well as cluster L3 and cluster L4, respectively. The expression patterns of CaERF82, CaERF97, CaERF66, CaERF107 and CaERF101, which were found in cluster C9 and cluster C10, were consistent with those of accumulating of carotenoids (β-carotene, zeaxanthin and capsorubin) in the pericarp. In cluster L3 and cluster L4, the expression patterns of CaERF102, CaERF53, CaERF111 and CaERF92 were similar to those of the accumulating capsaicinoids. Furthermore, CaERF92, CaERF102 and CaERF111 were found to be potentially involved in temperature-mediated capsaicinoids biosynthesis. Conclusion: This study will provide an extremely useful foundation for the study of candidate ERFs in the regulation of carotenoids and capsaicinoids biosynthesis in peppers.
Site to site detection and analysis of C-to-U RNA editing in rice mitochondria-encoded ORFs
Authors: Zheng Peng , Huang Yuqing , Chen Hao , Du Hao , Tu Jumin
Published: March 2020

Background Cytidine to uridine (C-to-U) RNA editing is an important type of substitutional RNA editing. In plants, C-to-U modification is almost omnipresent in chloroplasts and mitochondria, where it mainly serves to restore evolutionarily conserved amino acids by changing the codon information. The important roles that C-to-U RNA editing plays in organelle biogenesis, adaptation to environmental changes, and signal transduction have been confirmed in different plant species. In rice mitochondria, 491 C-to-U editing sites have been identified previously, and case studies have elucidated the function of several C-to-U editing sites in rice, but the functional consequence of most C-to-U alteration need to be investigated further. Results Here, we totally identified 539 C-to-U editing sites in rice mitochondria-encoded ORFs, 87.2% of these editing sites were observed on the first or the second base of a codon, resulting in the alteration of encoded amino acid. Moreover, we found some novel editing sites and several inaccurately annotated sites which may be functionally important, with the support of the highly conserved amino acids encoded by these edited codons. Finally, we annotated all 539 C-to-U RNA editing sites in their biological context. Conclusions We detected 539 C-to-U editing sites in rice mitochondria-encoded ORFs and annotated them with more precise information, which will facilitate our investigation on the function of C-to-U editing events in rice.
Prevalence of depression among women with obstetric fistula: A systematic review and meta-analysis Berhanu Boru Bifftu [BBB] 1*and Yonas Deressa Guracho [YDG]2
Authors: Biftu Berhanu Boru , Guracho Yonas Deressa
Published: March 2020

Objective Obstetric fistula is one of the most devastating birth injuries, affecting up to 3.5 million women. Depression is the priority mental disorders affecting up to 98% the patient living with obstetric fistula and adversely affects their quality of life. Inconsistent reported prevalence of depression and dearth of comprehensive meta-analysis need an up to date evidence for decision makers. Thus, the purpose of this meta-analysis was to determine the pooled prevalence of depression among women with obstetric fistula. Methods Databases including PubMed, Cochrane Library and SCOPUS were searched. Heterogeneity across the studies was assessed by Cochrane chi-square (χ2) and quantified by I 2 statistics test. Funnel plots and Egger’s test were used to determine publication bias. Sensitivity test and subgroup analysis were also performed. The pooled prevalence of depression was calculated using random effects model and Dersimonian and Laird method. Results Fifteen eligible studies were included in the study. The pooled prevalence of depression was found to be 72% (95% CI; 60%-83%). We found evidence of significant heterogeneity (I 2 =95.64% and p < 0.001). Sensitivity test showed none of the point estimates was outside of the overall 95%CI. No evidence of publication bias egger’s test (p =0.654). Conclusion Around three fourth of women with obstetric fistula experienced depression. Thus, authors’ suggest the need of special attention to mange co-morbid depression among women with obstetric fistula, such as an integrated mental health care.
Ultrasound diaphragm excursion and noninvasive ventilation in critically ill patients: a horse to bet on?
Authors: Barbariol Federico , Guadagnin Giovanni Maria , Deana Cristian
Published: March 2020

BACKGROUND Diaphragmatic dysfunction is seen in up to 60% of critically ill patients with respiratory failure, and it is associated with worse outcomes. The functionality of the diaphragm can be studied with simple and codified bedside ultrasound evaluation. Diaphragm excursion (echographic measurement of the inspiratory displacement of the hemidiaphragm) is one of the most studied parameters. The aim of this study was to assess the prevalence of diaphragmatic dysfunction in critically ill non-intubated patients admitted to a general intensive care unit with acute respiratory failure. Response to non-invasive ventilation (NIV) was evaluated in patients with diaphragm dysfunction, as was whether the ultrasound assessment of the diaphragm excursion may be employed as a predictor of NIV failure. METHODS We collected data, including ultrasound diaphragm excursion, at 2 time points: at T0 (at the time of recruitment, just before starting NIV) and at T1 (after one hour of NIV). RESULTS A total of 47 patients were enrolled. Prevalence of diaphragm dysfunction was 42.5% (95% CI 28, 3 - 57,8). Surgical patients showed a higher incidence (relative risk of 1.97) than medical patients. Mean DE was not significantly different between NIV responders (1,35 ± 0.78 cm) and non-responders (1.21 ± 0.85 cm, p 0,6). Patients with diaphragmatic dysfunction responded positively to NIV in 60% (95% CI 36.0 - 80.9%) of cases, while patients without diaphragmatic dysfunction responded positively to the NIV trial in 70.4% (95% CI 49.8 - 86.2%) of cases (p = 0.54). Taking the use of ultrasound diaphragm excursion as a potential predictor of NIV response, the corresponding ROC curve had an area under the curve of 0.53; the best balance between sensitivity (58.1%) and specificity (62.5%) was obtained with a cut-off diaphragm excursion of 1.37 cm. CONCLUSIONS Diaphragm dysfunction is particularly frequent in critically ill patients with respiratory failure. The functionality of the diaphragm can be effectively and easily tested by bedside ultrasound examination, and its measurement should be considered in every patient with respiratory failure. Overall, our results point towards tentative evidence of a trend of a different response to NIV in patients with vs without diaphragmatic dysfunction.
RNA sequencing reveals BMP4 as a basis for the dual-target treatment of diabetic retinopathy
Authors: Dong Lijie , Zhang Zhe , Liu Xun , Wang Qiong , Hong Yaru , Liu Juping , Li Xiaorong
Published: March 2020

Backgroud: Diabetic retinopathy, currently considered a neurovascular disease, has become the major cause of blindness. Continuously high glucose levels are regarded as a risk factor for DR. Intravitreal injection of anti-VEGF drugs is a classic treatment for DR; however, anti-VEGF drugs can exacerbate fibrosis and eventually lead to retinal detachment.Methods: We explored changes in gene expression in high-glucose-induced vascular endothelial cells using RNA sequencing technology, utilized transcriptome signatures to explore the pathogenesis of DR and identified new treatments that can provide dual-target intervention for angiogenesis and fibrosis. We identified BMP4 and SMAD9 among 449 differentially expressed genes from RNA-seq data and investigated the expression of these two genes in the blood of diabetes patients and in STZ-induced rat retinas. Moreover, considering that DR is a multifactorial and multicellular disease, we used H2O2, AGEs, CoCl2, 4HNE and hypoxia to induce three human retinal cell types (Müller, RPE and HRCECs) to simulate the pathogenesis of DR and then verified the overexpression of these two genes in the cell models. We further tested the effects of BMP4 on retinal cells. Results: The results demonstrated that BMP4 and SMAD9 were highly expressed in both in vivo and in vitro models, while BMP4 could significantly upregulate the expression of SMAD9 and promote the expression of VEGF and fibrosis factors.Conclusions: This study is the first to analyze the mechanism by which high glucose levels affect retinal vascular endothelial cells through RNA transcriptome sequencing and indicates that BMP4 may be a potential target for the dual-target treatment (anti-VEGF and antifibrosis) of DR.
Serum soluble programmed death ligand-1 is correlated with HBsAg level and nucleos(t)ide analogue therapy in chronic hepatitis B
Authors: Ke Ruo Man , Ouyang Li Juan , Li Wen Fang , Huang Ming Xing , Peng Xiao Mou
Published: March 2020

Background The restoration of immune responses is thought as a complementary approach to the nucleos(t)ide analogue (NUC) therapy of chronic HBV infection. The antiviral immunity is negatively regulated by the programmed cell death-1/programmed death ligand-1 (PD-1/PD-L1) axis. Here, the soluble form of PD-L1 (sPD-L1) that represents the amount of PD-L1 expression cells was used as an indicator to investigate the involvement of this axis in chronic HBV infection, especially in the setting of NUC therapy. Methods A total of 273 adult patients with chronic HBV infection, regardless of the treatment, and 86 healthy controls were consecutively enrolled. Serum sPD-L1 was measured using an ELISA assay. Its correlations with clinical/virological characteristics were analyzed. Results Serum sPD-L1 levels in patients with chronic HBV infection (median 425.2 IQR 245.8-558.6 pg/mL) were significantly higher than those in healthy controls (median 81.69 IQR 54.62-121.1 pg/mL). Among patients at various disease phases, those with immune-tolerant CHB had the lowest sPD-L1 levels (median 205.3 IQR 92.27-340.7 pg/mL). These results indicated that serum sPD-L1 was significantly increased in a manner of two steps from health to infection and from immunotolerance to immunoactivation in chronic HBV infection. Furthermore, the serum sPD-L1 in immune-active CHB was correlated with HBsAg positively, HBV DNA negatively and liver damage marginally. Interestingly, the increased serum sPD-L1 levels were strongly associated with the treatment of NUCs, especially in HBeAg-positive immune-active CHB. Conclusions Serum sPD-L1 might be a meaningful indicator to monitor the immune status and disease progression in chronic HBV infection. The correlations of the increased sPD-L1 with HBsAg and NUC treatment suggest that the activated PD-1/PD-L1 axis may explain the rarity of HBsAg seroconversion of NUC therapy and the clinically available checkpoint inhibitors may serve as partners for NUCs to improve their anti-HBV efficacy in the future
Multi-Omic integration after carbon monoxide toxicity in a child reveals gene transcripts related to Parkinson and Multiple Sclerosis
Authors: Leimanis Mara , Prokop Jeremy W. , Nedveck Derek , Darin Christina , Lydic Todd A. , Bupp Caleb , DeRoos Steven , Rajasekaran Surender
Published: March 2020

Background This report highlights the unique transcriptomic and lipidomic changes noted in a 4-year-old African American female patient exposed to a house fire. She required admission to the pediatric Intensive care unit due to organ failure that resulted from CO and cyanide toxicity. Patient was neurologically intact initially but later developed neurological symptoms consistent with Parkinsonism, a transient state resembling Parkinson’s Disease. Results An integrative omics-based approach was used to examine both gene expression and the lipidome of the patient which was then compared to 4 control patients. Total blood RNA from a PaxGene®collection system was correlated to plasma-based metabolomics measured over three time points and correlated with the clinical condition of the patient. We see significant elevation of the Parkinson’s associated gene ( SELENOT ) on day one. This gene plays a crucial role in the protection of dopaminergic neurons against oxidative stress in Parkinson's disease. The Multiple Sclerosis linked gene DDX39B which mediates ATP hydrolysis during pre-mRNA splicing was increased on day 8. We noted increased UGCG gene expression which correlated with increased ceramide lipids on lipidome analysis. The elevated ratio of hexosylceramide to its ceramide precursor is indicative of an elevated UGCG mediated ceramide glucosyltransferase activity. This correlation of clinical symptoms with both increased gene activity and lipid dyshomeostasis is unique, highlighting the potential of personalized omics. ConclusionsIn clinical practice, the ability to predict and quantify neurological injury using gene expression has the potential to make meaningful changes to management. This report shows the potential for real time transcriptomics and metabolomics to modify not only initial therapy, but the eventual physical rehabilitation of patients exposed to neurotoxins.
A novel ultra-sensitive urine based FGFR3 mutation assay for diagnosis and recurrence detection of non-muscle-invasive bladder cancer (NMIBC) – Design of the Urodiag® Kit
Authors: ROPERCH Jean-Pierre , HENNION Claude
Published: March 2020

Background We have recently developed a highly accurate urine-based test, named Urodiag ® , associating FGFR3 mutation and DNA methylation assays for recurrence surveillance in patients with low-, intermediate-, and high-risk NMIBC. Previously, the detection of four FGFR3 mutations (G372C, R248C, S249C and Y375C) required the amplification steps and the PCR products were analyzed by capillary electrophoresis (Allele Specific-PCR, AS-PCR), which was expensive and time-consuming. Here, we present the development a novel ultra-sensitive multiplex PCR assay as called “Mutated Allele Specific Oligonucleotide-PCR (MASO-PCR)”, generating cost-effective, simple, fast and clinically applicable assay for the detection of FGFR3 mutations in voided urine. Methods Comparative clinical performances of MASO-PCR and AS-PCR technologies were performed from 263 urine DNA samples (87 FGFR3 mutated and 176 FGFR3 wild type). In the development of Urodiag ® Kit, we studied the stability and reproducibility of each all-in-one PCR master mix (single reaction mixture including all the necessary PCR components) for MASO-PCR and QM-MSPCR (Quantitative Multiplex Methylation-Specific PCR to co-amplify SEPTIN9, HS3ST2 and SLIT2 methylated genes) assays. Results Complete concordance (100%) was observed between the MASO-PCR and AS-PCR results. Each PCR master mix displayed excellent reproducibility and stability after 12 months of storage at -20°C, with intra-assay standard deviations lower than 0.3 Ct and coefficient of variations (CV) lower than 1%. The limit of detection (LoD) of MASO-PCR was 5% mutant detection in a 95% of wild-type background. The limit of quantification (LoQ) of QM-MSPCR was 10 pg of bisulfite-converted DNA. Conclusions We developed and clinically validated the MASO-PCR assay, generating cost-effective, simple, fast and clinically applicable assay for the detection of FGFR3 mutations in urine. We also designed the Urodiag ® Kit, which includes the MASO-PCR and QM-MSPCR assays. Adapted to routine clinical laboratory (simplicity, accuracy), the kit will be a great help to urologists for recurrence surveillance in patients at low-, intermediate- and high-risk NMIBC. Reducing the number of unnecessary cystoscopies, it will have extremely beneficial effects for patients (painless) and for the healthcare systems (low cost).
Development of A Novel Competing Risk Survival Predicting Model for Esophagogastric Junction Adenocarcinoma: a SEER population-based study
Authors: Wang Tongbo , Wu Yan , Zhou Hong , Wu Chaorui , Zhang Xiaojie , Chen Yingtai , Zhao Dongbing
Published: March 2020

Background: Adenocarcinoma in Esophagogastric Junction (AEG) is a severe gastrointestinal malignancy with a unique clinicopathological feature. To develop a competing risk nomogram for AEG patients and compared it with new 8th traditional tumor-node-metastasis (TNM) staging system.Methods: Based on AEG patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2010, we used the univariate and multivariate analysis to filter clinical factors and then built the competing risk nomogram to predicting the AEG cause-specific survival. We measured the clinical accuracy by comparing to the 8th TNM stage with receiver operating characteristic (ROC) curve, Brier score, and decision curve analysis (DCA).Results: Total of 1755 patients were included into this study. This nomogram was based on five variables: Number of examined lymph nodes, grade, invasion, metastatic LNs and age. The nomogram model was greater than traditional TNM staging with ROC curve (1-year AUC:0.747 vs. 0.641, 3-year AUC: 0.761 vs. 0.679, 5-year AUC: 0.759 vs. 0.682, 7-year AUC: 0.749 vs. 0.673, P<0.001), Brier score (3-year: 0.198 vs. 0.217, P=0.012; 5-year: 0.198 vs. 0.216, P=0.008; 7-year: 0.199 vs. 0.215, P=0.014) and DCA.Conclusions: Based on the SEER database with AEG patients, the competing risk nomogram showed the greater accurate individualized prediction of the survival compared with traditional TNM classification.
Microwave Ablation-Aided Curettage for Treatment of Aggressive Benign Bone Tumors in the Extremities: Preliminary Report and Technical Points
Authors: Cong Lin , Chen Yu
Published: March 2020

The authors have requested that this preprint be removed from Research Square.
Risk factors of the suprasternal lymph node metastasis in papillary thyroid carcinoma with clinical lateral cervical lymph node metastasis
Authors: Kwon Hyun-Keun , Cheon Yong-Il , Shin Sung-Chan , Sung Eui-Suk , Lee Jin-Choon , Kim In-Ju , Lee Byung-Joo
Published: March 2020

Background: Metastatic lymph nodes are occasionally found in the suprasternal lymph nodes in patients with papillary thyroid cancer (PTC), but there are few studies on these lymph nodes. Therefore, we investigated the frequency and risk factors of suprasternal lymph node metastasis in PTC patients with lateral cervical lymph node metastasis.Methods: A total of 85 patients with cN1b PTC underwent total thyroidectomy with elective lateral neck dissection including the suprasternal lymph nodes. We analyzed the correlation between suprasternal lymph node metastasis and sex, age, tumor characteristics, and cervical lymph node metastasis status.Results: Eleven patients (12.9%) had pathological suprasternal lymph node metastasis. Suprasternal lymph node metastasis was associated with tumors located in the inferior pole and level IV lymph node metastasis.Conclusion: In cN1b PTC patients, especially those with inferior pole tumors and level IV nodal metastasis, the suprasternal lymph node should be routinely dissected.
Induced extracellular production of viniferins in grapevine cell culture medium by elicitation with methyl jasmonate and stevioside
Authors: Jeong Yu Jeong , Park Su Hyun , Park Sung-Chul , Kim Soyoung , Kim Tae Hee , Lee Jiyoung , Kim Suk Weon , Ryu Young Bae , Jeong Jae Cheol , Kim Cha Young
Published: March 2020

We report the high production of stilbenes, including resveratrol and viniferins, in grapevine (Vitis labruscana L.) cell cultures through elicitation with methyl jasmonate (MJ) and stevioside (STE). Methyl-β-cyclodextrin (CD-M) is widely used as a solubilizer for resveratrol production. For the first time, we used STE as a solubilizer for stilbene production in plant cell cultures. MJ was most effective in activating VvSTS expression and stimulating stilbene biosynthesis and induced accumulation of trans-piceid in the cells. High levels of trans-resveratrol and δ-viniferin production were observed in the culture medium when CD-M and STE, respectively, were used as solubilizers, but neither were significantly elevated within the cells. Maximum production of trans-resveratrol (12.2 mg/L) and δ-viniferin (892.2 mg/L) was observed 5 days after elicitation of cells with MJ and STE in shake flask cultures. Notably, predominant production of δ-viniferin and trans-resveratrol was observed in shake and static flask culture medium, respectively. Furthermore, stilbene compounds of resveratrol, e-viniferin, and δ-viniferin were mainly produced in a 3 L bioreactor culture following elicitation of cells with MJ and STE. These results provide new strategies for conditional, high-level production of resveratrol and viniferins in cell cultures by utilizing the solubilizing properties of STE or CD-M.
Identification of a gene from Streptomyces rimosus M527 negatively affecting antibiotic biosynthesis and morphological differentiation
Authors: Ma Zheng , Song Zhangqing , Xu Jie , Bechthold Andreas , Yu Xiaoping
Published: March 2020

Background: The polyene macrolide rimocidin, produced by Streptomyces rimosus M527, was found to be highly effective against a broad range of fungal plant pathogens. Current understanding of the regulatory mechanism of rimocidin biosynthesis and morphological differentiation in S. rimosus M527 is limited. NsdA is considered as a negative regulator involved in morphological differentiation and biosynthesis of secondary metabolites in some Streptomyces.Results: In this study, nsdAsr was cloned from S. rimosus M527. The role of nsdAsr in rimocidin biosynthesis and morphological differentiation was investigated by gene deletion, complementation, and over-expression. A ΔnsdAsr mutant was obtained using CRISPR/Cas9. The mutant produced more rimocidin (46%) and generated more spores than the wild-type strain. Over-expression of nsdAsr led to a decrease in rimocidin production and impairment of sporulation. Quantitative reverse transcription-PCR (qRT-PCR) analysis revealed that transcription of rim genes responsible for rimocidin biosynthesis was up-regulated in the ΔnsdAsr mutant but down-regulated in the nsdAsr over-expression strain. Similar effects have been described for Streptomyces coelicolor M145 and the industrial toyocamycin-producing strain Streptomyces diastatochromogenes 1628.Conclusion: NsdAsr is identified as a negative regulator of sporluation and antibiotic biosynthesis as well as the transcription of biosynthetic genes both in its host S. rimosus M527 and in model strain S. coelicolor and industrial producer strain S. diastatochromogenes 1628. This work will provide further information for understanding regulatory mechanisms controlling rimocidin biosynthesis in S. rimosus M527.
Knowledge, Attitude, Motivation and Planning of Breastfeeding; A cross Sectional Study among Jordanian Women.
Authors: khasawneh wasim , Kheirallah Khalid , Mazin Mai , Abdulnabi Sanaa
Published: March 2020

Background Antenatal women’s attitude and planning for breastfeeding are affected by their awareness and the support they receive. These are key factors that contribute to the trend variation in breastfeeding practice. This study aims to assess knowledge, attitude, support, and planning of breastfeeding among Jordanian women. Methods A face-to-face cross sectional semi-structured questionnaire survey was conducted among healthy women in the antenatal clinic and postpartum ward at three hospitals in Northern Jordan during the period August 2019 to December 2019. Data was collected about demographics, knowledge and attitude, support and counseling, and feeding planning. Factors associated with planning to breastfeed were reported. Results 660 women completed the survey questionnaires. 78% were knowledgeable about breastfeeding benefits and aware of WHO recommendations. 72% had a positive attitude towards breastfeeding. More than half received support from their husbands to breastfeed their infants, while less than 20% received any counseling from their obstetric physicians. 97% reported their intention to breastfeed, and more than half indicated their willing to exclusively breastfeed. With Multilogistic regression model, predictors of EBF planning include primiparty (AOR 1.79 95% C.I 1.1, 3.25), positive attitude (AOR 1.80 95% C.I 1.05, 3.1) and positive husband’s support (AOR 1.92 95% C.I. 1.18, 3.15). Barriers include women’s employment (AOR 0.43 95% C.I. 0.26, 0.70) and low birth weight (AOR 0.46 95% C.I. 0.25, 0.84) Conclusion Jordanian women are highly knowledgeable about breastfeeding benefits, and they exhibit a positive attitude towards breastfeeding resulting in a very high percentage intending to breastfeed their infants. Limited counseling about breastfeeding by obstetric physicians is a major gap in antenatal care. Assigning a specific time allotment for antenatal or postnatal counseling and support is expected to promote breastfeeding practice in our population.
SV40T reprograms Schwann cells into stem-like cells that can re-differentiate into terminal nerve cells.
Authors: Li Rui-Fang , Nan Guo-Xin , Wang Dan , Gao Chang , Yang Juan , He Tong-Chuan , Zhang Zhong-lin
Published: March 2020

Background : The effects of Simian virus 40 T antigen (SV40T) on various kinds of cells are different. Previous researchers failed to use SV40T immortalized nerve cells. However, they argued that SV40T caused nerve cell transformation. No one further study what is the specific effect of SV40T on nerve cells. We transfected Schwann cells (SCs) that did not have differentiation ability with MPH 86 plasmid containing SV40T in order to explore the effects of SV40T on Schwann cells. Methods : SCs were transfected with MPH 86 plasmid carrying the SV40T gene and cultured in different media, as well as co-cultured with neural stem cells (NSCs). In our study, SCs overexpressing SV40T were defined as SV40T-SCs. The proliferation of these cells was detected by WST-1, and the expression of different biomarkers was analyzed by qPCR and immunohistochemistry. Results: SV40T induced the characteristics of NSCs, such as the ability to grow in suspension, form spheroid colonies and proliferate rapidly, in the SCs, which were reversed by knocking out SV40T by the Flip-adenovirus . In addition, SV40T up-regulated the neurocrest markers Nestin, Pax3 and Slug, and down-regulated S100b as well as the late differentiation markers MBP, GFAP and Olig1/2. These cells also expressed NSC markers like Nestin, Sox2, CD133 and SSEA-1, as well as early development markers of embryonic stem cells (ESCs) like BMP4, c-Myc, OCT4 and Gbx2. Co-culturing with NSCs induced differentiation of the SV40T-SCs into neuronal and glial cells. Conclusions: SV40T reprograms Schwann cells to stem-like cells at the stage of neural crest cells that can differentiate to terminal nerve cells.
Different age pattern of COVID-19 cases in Hong Kong and Singapore by March 4, 2020
Authors: Zhu Shuying , Tao Jun , Gao Huizhi , He Daihai
Published: March 2020

Objective Coronavirus disease 2019 (COVID-19) now poses a huge threat to global public health and economics. It was found that elderly is more vulnerable to the infection. In this work, we compare the age structure of confirmed COVID-19 cases in Hong Kong SAR China and Singapore by March 4, 2020. Results We find significant difference in age patterns of confirmed cases in these two localities. We highlight the potential importance of population age structure in confirmed cases, which should be considered in evaluation of the effectiveness of control effort in different localities.