bluuebunny/crossref_metadata_2025 huggingface dataset:
Selection of basal medium for culturing human umbilical cord mesenchymal stem cells in combination with human platelet lysate
Authors: Wang Lingjuan , Liu Chunxiang , Lu Huiying , YAN JUN , Zhang Yi
Published: July 2020

Background

Different basal media have very different effects on cell growth, proliferation and differentiation potential of cultured human umbilical cord mesenchymal stem cell (hUC-MSC). This issue has not gotten enough research. The goal of this study is to select high safety and low cost basal media for hUC-MSC, which performs best in combination with commercial human platelet lysate product for cell proliferation and differentiation functions, especially suitable for high-passage hUC-MSC cultures.
Methods

Three different basal media were combined with 5% UltraGROGAdvanced to culture P0 to P8 passage hUC-MSC. Cell morphology, cell expansion ratio, proliferation, differentiation and cell surface markers were examined and analyzed in order to draw conclusions.
Results

When observing the same passage under different culture systems, the number of cells obtained in MSCBM and α-MEM were higher than that cultured in IMDM (0.01 < P < 0.05). The results between MSCBM and α-MEM were not significantly different (P > 0.05). Combining growth curve measurement and cell doubling time calculation, it was found that the cell proliferation functions of the three culture media were ranked as MSCBM, α-MEM and IMDM from high to low. The P8 cells cultured in different media all yield good clonal formation, and also all differentiated well. The number of cells differentiated into osteoblasts and chondrocytes cultured in different media was not significantly different (P > 0.05), while the number of adipocyte differentiation in MSCBM and α-MEM cultures were significantly higher than that of IMDM culture (0.01 < P < 0.05). The cells in all cultures uniformly express high levels of MSC surface markers CD73, CD90, CD105, and negatively express CD34, CD45.
Conclusions

Taking all indicators into consideration, we conclude that the culture system of MSMBM supplemented with 5% UltraGROGAdvanced is the best for culturing hUC-MSC withα-MEM follows right after. This study revealed the importance of basal media in MSC cultures, and offer guidance on their selective use.
Tumor marker based survival analysis for patients with pseudomyxoma peritonei of appendiceal origin: A retrospective cohort study
Authors: Bai Mingjian , Wang Shilong , Ma Ruiqing , Cai Ying , Lu Yiyan , Hou Nianzong , Liang Guowei , Xu Hongbin , Zhang Man
Published: July 2020

Background Pseudomyxoma peritonei (PMP) is a rare disease, the prognosis of overall survival (OS) is affected by many factors, present study aim to screen independent prediction indicators for PMP and establish prediction model for OS rates in PMP.Methods 119 PMP patients received cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in our center for the first time were included between 01/06/2013 and 22/11/2019 . The log-rank test was used to compare the OS rate among groups, subsequently, variables with P<0.10 were subjected to multivariate Cox model for screening independent prediction indicators. Finally, the prediction models for OS in PMP will be established.Results Univariate analysis showed that Barthel Index Score, albumin, D-dimer, CEA, CA125, CA19-9, CA724, CA242, PCI, degree of radical surgery, histopathological grade were signiﬁcant predictors for OS in PMP. At multivariate analysis, sex, D-dimer, CA125, CA19-9, and degree of radical surgery were independently associated with OS rate in PMP. ROC analysis was performed to calculate discrimination ability of prediction model and the area under curves (AUC) was 0.902 (95%CI: 0.823-0.954). Finally, nomogram was plotted by the independent predictive factors for PMP.Conclusions Several factors (sex, degree of radical surgery, D-dimer, preoperative CA125 and CA19-9) have independent prognostic value for survival in PMP, the tumor based prediction model has better prediction value, more researches are need to verify and improve the prediction model.
Prevalence and factors related to inappropriate referrals during intrapartum care – a mixed method study
Authors: Desta Binyam Fekadu , Dolamo Bethabile L.
Published: July 2020

Background: Complications during delivery are responsible for half of all maternal deaths, one-third of stillbirths and a quarter of neonatal deaths. The care necessitates emergency care, and it is a known fact that reductions in maternal mortality and morbidity are not possible without an effective referral system. This study is aimed at measuring the prevalence of inappropriate referrals and identifying factors that contribute to it. Methods: The study employed a sequential explanatory mixed research design. In the first phase, a retrospective cross-sectional quantitative study was done, 718 medical records were reviewed. The second phase involved a qualitative study of 26 key informants being interviewed. Results: Three quarters of cases, (74.23%; n=533), who visited the selected hospitals could have been managed at the health center level. Sixty-five percent of them, (n=436), sought care at the hospital level with no referral from the lower level. Further analysis of the data showed no major difference as to the appropriateness of hospital level care in relation to age of mothers, previous medical and obstetrics history as well as danger signs at admission. On the other hand, number of parities, (chi-square = 9.3; P-value = 0.010), frequency of ANC, (chi-square = 6.7; p-value = 0.037) and the institution where ANC was sought, (chi-square = 12.9; p-value = 0.005) were found to be associated with appropriateness of the case for hospital level care. Further inventory of the referred cases revealed that 33.2% of referred cases were appropriate for hospital level care. In addition, the qualitative study identified three major themes in relation to appropriateness of referrals: capability of identifying appropriate cases for referral, proper initiation of the referral process determining the outcome and functional cross-facility support platforms for better collaboration and coordination between facilities. Conclusion: Referral, which is the coordination between facilities, requires readiness of the facilities at both ends as well as a transportation system. The governance system should also be strengthened to ensure the emergency management system in the country is effective.
Comparison of different lipid extraction methods for different tissue types of Arabidopsis thaliana
Authors: Kehelpannala Cheka , Rupasinghe Thusitha Wasantha Thilaka , Hennessy Thomas , Bradley David , Ebert Berit , Roessner Ute
Published: July 2020

Background: The plant lipidome is highly complex, and the composition of lipids in different tissues as well as their specific functions in plant development, growth and stress responses have yet to be fully elucidated. To do this, efficient lipid extraction protocols which deliver target compounds in solution at concentrations adequate for subsequent detection, quantitation and analysis through spectroscopic methods are required. To date, numerous methods are used to extract lipids from plant tissues. However, a comprehensive analysis of the efficiency and reproducibility of these methods to extract multiple lipid classes from diverse tissues of a plant has not been undertaken. Results: In this study, we report the comparison of four different lipid extraction procedures in order to determine the most effective lipid extraction protocol to extract lipids from different tissues of the model plant Arabidopsis thaliana . Conclusion: While particular methods were best suited to extract different lipid classes from diverse Arabidopsis tissues, overall a single-step extraction method with a 24 h extraction period, which uses a mixture of chloroform, isopropanol, methanol and water, was the most efficient, reproducible and the least labor-intensive to extract a broad range of lipids for untargeted lipidomic analysis of Arabidopsis tissues. This method extracted a broad range of lipids from leaves, stems, siliques, roots, seeds, seedlings and flowers of Arabidopsis. In addition, appropriate methods for targeted lipid analysis of specific lipids from particular Arabidopsis tissues were also identified.
Influence of Socioeconomic Status on Oral Disease Burden: A Population-Based Study
Authors: de Lucena Edson Hilan Gomes , Silva Rênnis , Barbosa Maria , Araújo Elza , Pereira Antônio , Cavalcanti Yuri
Published: July 2020

Background : Dental caries is associated with Biological, behavioral, socioeconomic, and environmental factors; however, socioeconomic status is a distal determinant of dental caries development that modulates exposure to risk and protective factors. This study aimed to analyze the factors associated with the distribution and concentration of oral diseases in a population-based study in Brazil. Methods : This is a quantitative, analytical, cross-sectional study based on secondary data from the SB São Paulo 2015 epidemiological survey. A total of 17,560 subjects were included. The concentration of oral disease in the population was estimated by the oral disease burden (ODB) variable. The ODB consists of four components: dental caries; tooth loss; need for dental prosthesis and periodontal condition. Thus, the total score on the ODB could vary between 0 and 4, with the highest score indicating the worst possible situation. ODB was analyzed in multivariate negative binomial regression, and multivariate binary logistic regression analysis. The following demographic data were included as independent variables: age group, skin color, socioeconomic data, and family income. Results : ODB was present in 86.9% of the sample. Negative multivariate binomial regression showed a statistically significant relationship (p<0.005) between ODB and all variables analyzed (skin color, family income, education, OIDP results and age range). The adjusted multivariate binary logistic regression showed that the individuals most likely to have at least one component of ODB were nonwhite (25.5%), had a family income of up to R$ 1,500.00 / month (19.6%), had only completed primary education (19.1%), and reported that their oral health had an impact on their daily activities (57.6%). Elderly individuals were two times more likely than adolescents to have an ODB component. Conclusions : ODB is associated with factors related to social inequality. Adults and elderly individuals had the highest cumulative number of ODB components.
Assessment of The Nerve Ending Distributions on Dartos Fascia in Children with Concealed Penises
Authors: Huang WenFang , Tang DaXing , Gu WeiZhong
Published: July 2020

Background: The role of nerve ending distribution indartos fascia in the pathogenesis of concealed penis (CP) is still unclear. Our aim is to compare the histological structure of dartos fascia of both normal and CP tissue to evaluate the importance of nerve ending distribution. Methods: After degloving, tissue specimens of dartos fascia located at 3-, 6-, 9-, and 12- o’clock of the penile shaft were harvested from the CP.Therelatively normal tissues at the periphery after resection of black moles or hemangioma in other parts were considered as control. The distribution of nerve plexuses between these groups was compared using standard hematoxylin and eosin (H&E) staining and S-100 immunohistochemical staining. Results: The number of nerve plexuses for all cases of CP was abundant but significantly fewer in the normal group. In CP, the number of nerve plexuses in superficial fascia collected at 6 o’clock position of penile shaft was the most abundant among different positions. Conclusions: Abundant nerve plexuses were presented indartos fascia in children with CP, especially at the 6 o’clock position,suggesting surgery performed at the preputial frenulum should avoid damage of dartos fascia to preserve the erectile and sexual function of penis in puberty.
Optimized sequential method assisting design and implementation of electro-pneumatic/hydraulic circuit
Authors: Marques Vinicius Abrão da Silva , Rodrigues Felipe Nascimento Cerqueira , Tavares José Jean-Paul Z. de S.
Published: July 2020

Electro-pneumatic circuits returned to be an important topic of research after the need of ventilator due COVID-19. Not only for this type of device but to assist economy restarting, the electro-pneumatic/hydraulic systems will be one of the industrial automation cornerstones after COVID pandemic. Programmable Logic Controllers (PLC) are one of the main components of these circuits and the standard of industrial automation; however, its application is highly dependent on programmers skills. Usually, electro-pneumatic/hydraulic solutions rely on sequential circuits. Different methods are found in the literature to design that systems, but they involve complex analyzes and intuitive strategies in cases that the actuators extend and retract more than once within the cycle of movements, and within simultaneous movements. As consequence, the resulting circuits mostly require a large number of valves and electronic components in order to be implemented. The objective of this work is to describe a novel method that can be applied in the design and implementation of optimized circuits using PLC's, eliminating intuitive solutions. Examples are presented to illustrate the theoretical procedures and experimental tests performed to validate the method. The results prove the generality of this work, the simplicity of its implementation, and introduce a bridge between design and implementation of electro-pneumatics and electro/hydraulics circuits with PLC's.
Effect of Electroacupuncture on gut Microbiota in Participants with Knee Osteoarthritis
Authors: Wang Tianqi , Wang Tian-Qi , Yang Jing-Wen , Shi Guang-Xia , Wang Li-Qiong , Li Ling-Ru , Hu Hui , Liu Zhi-Shun , Wang Jun , Yuan Yong , Jia Wen-Rui , Li Hua , Wang Xin-Wei , Wu Bin , Liu Cun-Zhi
Published: July 2020

Objective A close relationship between knee osteoarthritis and gut microbiota disorders has recently been described. Herein, we aim to investigate the effect of electroacupuncture on gut microbiota in participants with knee osteoarthritis.Methods We conducted a study of 60 participants with KOA and 30 matched healthy controls. Sixty participants with KOA were allocated to either electroacupuncture (EA) group (n=30) or sham acupuncture (SA) group (n=30). EA group was treated by five obligatory acupoints and three adjunct acupoints. Eight non-acupoints that were separated from conventional acupoints or meridians were used for the SA group. Both groups received 24 sessions within eight weeks. Faecal microbial analyses were carried out after collecting stools at T0 and T8 weeks, and microbiomes were analyzed by 16S ribosomal RNA gene sequencing. Results There was a significant structure difference of gut microbiota between KOA participants and healthy controls (HCs). Difference was observed in β-diversity analysis. Thirteen genera separated KOA from HCs, out of which Escherichia-Shigella, Streptococcus and Eubacterium_hallii group were increased in KOA participants, while Bacteroides, Blautia, Bifidobacterium, Faecalibacterium, Subdoligranulum, Prevotella, Lactobacillus, Ruminococcus, Agathobacter and Megamonas were decreased. After treatment, the amount of Streptococcus and Escherichia-Shigella in EA group had statistically decreased while Ruminococcus increased compared with SA group (all P<0.05). EA group decreased more in WOMAC pain, WOMAC total score (all P<0.05) and NRS score (P=0.002) than those in SA group at eight weeks. Adverse events were low and similarly distributed between groups. Ruminococcus and the total score of WOMAC was negatively correlated (P=0.044). Streptococcus was positively correlated with WOMAC total score (P=0.044) and Escherichia-Shigella was positively correlated with NRS score (P=0.024).Conclusion This study presents a comprehensive landscape of gut microbiota in KOA. EA could reduce pain by regulating the intestinal flora of KOA participants. Dysbiosis was found in the gut microbiome in KOA and partially relieved by electroacupuncture. Our study suggests that gut microbiota could be a potential therapeutic target and diagnostic biomarker for KOA.
Increased Expression of UBE2T Predicting Poor Survival of Ovarian Cancer: Based on Comprehensive Analysis of UBE2s, Clinical Samples And the GEO Database
Authors: Zou Ruoyao , Xu Haoya , Li Feifei , Wang Shengke , Zhu Liancheng
Published: July 2020

Background：Ubiquitin-conjugating enzymes E2 (UBE2) have been reported in the microenvironment of various malignant tumors, but their correlation with ovarian cancer remains elusive. Methods: The Oncomine, GEPIA, Kaplan-Meier Plotter, cBioPortal, and STRING databases were used to systematically analyze the expression pattern, prognostic value, genetic variation, and biological function of 12 members of the UBE2 gene family in ovarian cancer. UBE2T exhibited the greatest correlation with ovarian cancer and was thus further examined. Gene set enrichment analysis (GSEA), as well as analyses of function and pathway enrichment, somatic mutations, copy number variation, and methylation were performed, and the correlation with immune cell infiltration was examined to explore the mechanism underlying aberrant UBE2T expression. Finally, the expression and prognostic value of UBE2T in ovarian cancer were verified by immunohistochemical evaluation of 131 clinical ovarian samples and the Gene Expression Omnibus (GEO) database (GSE51088, GSE73614, and GSE63885 datasets) analysis.Results: The mRNA levels of UBE2C, UBE2N, UBE2S, and UBE2T were significantly upregulated in ovarian cancer compared with those in normal ovarian tissue. In patients with ovarian serous carcinoma, UBE2A, UBE2B, UBE2C, UBE2G, and UBE2T upregulation and UBE2R2 downregulation were associated with poor overall survival. Moreover, UBE2A, UBE2N, and UBE2T upregulation and UBE2G and UBE2R2 downregulation were associated with poor progression-free survival. Immunohistochemistry revealed that UBE2T was significantly upregulated in ovarian malignant tumors compared with that in borderline tumors, benign tumors, and normal ovarian tissues, and its high expression was associated with poor prognosis. The Cox model showed that UBE2T upregulation was an independent risk factor affecting the prognosis of ovarian cancer (hazard ratio: 4.095, P=0.029). The above results were verified in the GEO database. In addition, UBE2T was associated with specific immune cells and mainly involved in cell cycle-related events. Genomic analysis showed that TP53 and TTN mutations were associated with UBE2T expression. Gene copy number amplification and hypomethylation may be responsible for UBE2T upregulation in ovarian cancer. Conclusions: UBE2 family members may play a role in the development of ovarian cancer. Specifically, UBE2T could serve as a new prognostic marker and therapeutic target for this disease.
Predictors associated with neurological recovery after anterior decompression with fusion for degenerative cervical myelopathy
Authors: Inose Hiroyuki , Hirai Takashi , Yoshii Toshitaka , Kimura Atsushi , Takeshita Katsushi , Inoue Hirokazu , Maekawa Asato , Endo Kenji , Furuya Takeo , Nakamura Akira , Mori Kanji , Kanbara Shunsuke , Imagama Shiro , Seki Shoji , Matsunaga Shunji , Okawa Atsushi
Published: July 2020

Background
Anterior decompression with fusion (ADF) has often been performed for degenerative cervical myelopathy (DCM) in patients with poor cervical spine alignment and/or anterior cord compression. However, it is difficult to preoperatively predict the extent to which patients will experience postoperative neurological improvement. We aimed to identify predictors associated with neurological recovery after ADF in a retrospective study of prospectively collected data.
Methods
We prospectively enrolled patients who were scheduled for ADF for DCM. The associations of baseline variables with recovery rate were investigated using a multiple linear regression model.
Results
In total, 36 patients completed the 1-year follow-up. Regarding clinical outcomes, the Japanese Orthopedic Association score for the assessment of cervical myelopathy, European Quality of Life Five Dimensions Scale, Neck Disability Index, and Physical Component Summary of the SF-36 (PCS) scores improved postoperatively. The recovery rate was significantly correlated with the sagittal vertical axis (SVA) and T1 pelvic angle. Univariate regression analyses showed that the SVA and PCS score were significantly associated with recovery rate. Lastly, multiple regression analysis identified the independent predictors of recovery rate after ADF as thoracic kyphosis (TK), PCS, and SVA. According to this prediction model, the following equation was obtained: recovery rate = − 8.26 + 1.17 × (TK) – 0.45 × (SVA) + 0.85 × (PCS).
Conclusion
Patients with lower TK, lower PCS score, and higher SVA were more likely to have poor neurological recovery after ADF. Therefore, DCM patients with these predictors who undergo ADF might be cautioned about poor recovery and be required to provide adequate informed consent.
Intensive Care Unit Acquired Hypernatremia after Major Surgery is Associated with Urine Concentrating Defect: An Observational Study
Authors: Deetjen Philipp , Jaschinski Ulrich , Heller Axel
Published: July 2020

Background: Although intensive care acquired hypernatremia is a common event, limited knowledge exists about the pathogenesis of this disorder. The present study attempts to show that patients undergoing major surgery develop hypernatremia in the presence of both high salt and volume load and concentration disorder of the kidney with insufficient sodium excretion.Methods: In a retrospective study, all patients who were admitted to a 40-bed tertiary surgical intensive care unit of a university hospital from July 2019 to December 2019 with major surgery were examined. Hypernatremia was defined as a sodium value exceeding 145 mmol/l. In addition to the analysis of all patients, complete water and salt balances were performed in a smaller subgroup with 142 patients.Results: 23.9% of patients undergoing major surgery developed hypernatremia, whereby hypernatremia was associated with increased mortality. Patients with hypernatremia showed a renal concentration defect with decreased urine sodium concentration (65 (IQR: 44.8-90) mmol/l vs 78 (IQR: 46-107) mmol/l, p = 0.007) and decreased urine osmolality (514 (IQR: 465-605) mmol/l vs 602 (IQR: 467-740) mmol/l, p < 0.001). In the subgroup of patients with complete sodium and water balance, a positive salt and water balance was observed. After propensity score matching, we found a significantly increased electrolyte free water clearance (1020 ±1740 ml vs -560 ±1620 ml, p <0.001) in the hypernatremia group, together with an inadequately lower total sodium urine excretion (401 ±303 mmol vs 593 ±400 mmol, p = 0.02). Conclusion: The present study shows that postoperative hypernatremia is associated with an imbalance between perioperative salt and water load and renal sodium and water handling with inadequately low renal sodium excretion and inadequately high renal water excretion. The underlying renal concentration disorder may be explained by a defect in a natriuretic-ureotelic response a recently described renal urea-mediated water conservation mechanism after salt exposure.
The Effects of Anesthesiologist Experience on Postoperative Hoarseness After Double-Lumen Endotracheal Tube Intubation: A Single-Center Propensity Score-Matched Analysis
Authors: Kamimura Yuji , Nakanishi Toshiyuki , Sato(Boku) Aiji , Osaga Satoshi , Kako Eisuke , Sobue Kazuya
Published: July 2020

Background: Postoperative hoarseness after general anesthesia is associated with patient discomfort and dissatisfaction. A recent large retrospective study showed that single-lumen endotracheal tube intubation by a trainee did not alter the incidence of postoperative pharyngeal symptoms compared with that by a senior anesthesiologist. However, little is known about the relationship between anesthesiologist experience and hoarseness after double-lumen endotracheal tube intubation. We tested the hypothesis that double-lumen endotracheal tube intubation by a trainee increases the incidence of postoperative hoarseness compared with that by a senior anesthesiologist.Methods: This retrospective observational study included patients who underwent lung resection from April 2015 to March 2018 in a university hospital. Patients underwent double-lumen endotracheal tube intubation with a Macintosh laryngoscope. We divided the patients into two groups: one group comprising patients whose tracheas were intubated by a trainee anesthesiologist and the other comprising those whose tracheas were intubated by a senior anesthesiologist. The primary outcome was the incidence of postoperative hoarseness 24 h after surgery. We collected data on postoperative hoarseness using a checklist of postanesthetic adverse events. One-to-one propensity score matching was performed. P values of <0.05 were considered statistically significant.Results: There were 256 eligible patients; 153 patients underwent intubation by trainee anesthesiologists, and the remaining 103 patients underwent intubation by senior anesthesiologists. The one-to-one propensity score matching generated 96 pairs of patients for the groups. The incidence of postoperative hoarseness 24 h after the surgery was significantly higher in patients whose tracheas were intubated by a trainee anesthesiologist than in those whose tracheas were intubated by a senior anesthesiologist (9.4% vs. 2.1%, respectively; P = 0.03).Conclusions: Double-lumen endotracheal tube intubation by trainee anesthesiologists increased the incidence of postoperative hoarseness 24 h after the surgery compared with intubation by senior anesthesiologists.
Short term perinatal outcome and their correlates among retained second twins, 15 years' retrospective study from northern Tanzania
Authors: Masoli Zakaria Abdi , Maro Eusebious , Masenga Gileard , Shayo Benjamin C , Mchome Bariki
Published: July 2020

Background : Second twin delivery has been associated with poor perinatal outcome such as birth asphyxia ,neonatal ICU admission and perinatal death in comparison to the first twin. There is limited information on the perinatal outcome of second twin in Tanzania. This study aimed at determining the perinatal outcome associated with second twin delivery in a tertiary hospital in Northern Tanzania.Methods: A retrospective cross-sectional study was conducted in a Tanzanian northern zone tertiary health facility using existing maternal linked data from medical birth registry. Women with twin deliveries from 2000 to 2015 were recruited. Adverse perinatal outcomes associated with second twin deliveries were estimated using multivariable logistic regression models. A p-value of < 0.05 was considered statistically significant. Results : Retention rate of second twin was 18.6% (n=265). Out of the 265 retained second twins, 54.7% were referral cases, majority of which came from district hospitals. Retained second twins had 1.54 ( 95% CI 1.08-2.20) and 2.49( 95% CI 1.14-5.48) higher odds of lower Apgar scores in the 5 th minute and perinatal death when compared to non-retained twins respectively. Referral cases had poor outcome compared to non-referrals. Retained twin who had caesarean section had lower odds of low Apgar scores in the 5 th minute, perinatal death and Neonatal intensive care admission although this was not statistically significant but clinically significant. Conclusion : Rate of retained second twin is high in this setting, most of which are referral cases. The retained second twin is associated with higher risk for perinatal death and low Apgar score in the 5 th minute. Timely delivery by caesarean section has lower chances of perinatal death, Neonatal intensive care admission and low Apgar scores. Therefore, early diagnosis and/or referral of twin pregnancy coupled with timely and appropriate intervention for delivery of the retained second twin will contribute to reduction in perinatal morbidity and mortality.
Plasma exosomes derived from patients with end-stage renal disease and renal transplant recipients have different effects on vascular calcification
Authors: lin xiao , Zhu Ting , Xu Feng , Zhong Jia-Yu , Li Fuxingzi , Shan Su-Kang , Wu Feng , Guo Bei , Zheng Ming-Hui , Wang Yi , Xu Qiu-Shuang , Liao Xiao-Bo , Xie Xu-Biao , Yuan Ling-Qing
Published: July 2020

Background

End-stage renal disease (ESRD) patients usually develop extensive and progressive vascular calcification, and lots of calcification inhibitors as well as pro-calcifying factors are involved in the process. However, the mechanisms of vascular calcification in ESRD patients are still ill-defined.
Methods

The participants in the study were selected at the Second Xiangya Hospital, Central South University, and the plasma exosomes derived from ESRD patients (ESRD-Ex), renal transplant recipients (RTR-Ex), and the normal health control group (Nor-Ex) were isolated by ExoQuick-TC kit. Transmission electron microscopy and molecular size analysis were used to assess the morphology and size of exosomes. Alizarin Red S staining was carried out to detect calcification of vascular smooth muscle cells (VSMCs). Protein levels of Fetuin-A, matrix gla protein (MGP), Annexin-A2, bone morphogenetic protein (BMP-2), and receptor activator for nuclear factor-κ B ligand (Rankl) were measured by Western Blot analysis and the contents of that were detected using ELISA. Coronary artery calcification scores (CACS) were quantified via Agaston and analysed by Siemens CaScoring software.
Results

Compared with Nor-Ex, the ESRD-Ex promoted calcification of VSMCs significantly, and RTR-Ex could attenuate VSMCs calcification. Moreover, the protein concentration of ESRD-Ex was significantly higher than Nor-Ex and RTR-Ex, and the content of both MGP and Fetuin-A, the calcification inhibitors, were prominently lower in ESRD-Ex than those in Nor-Ex. The content of Annexin-A2, one of the calcification promoters, was significantly higher in ESRD-Ex and RTR-Ex than that in Nor-Ex. But, BMP-2 and Rankl had no significant difference among the three groups. In addition, the content of Fetuin-A in RTR-Ex was higher than that in ESRD-Ex, though it was still lower than in Nor-Ex. Furthermore, the content of both plasma Fetuin-A and MGP were negatively while that of Annexin-A2 was negatively correlated to CACS.
Conclusions

These results indicated that ESRD-Ex significantly promoted VSMCs calcification while renal transplantation could partially attenuate the effect of exosomes. Fetuin-A and MGP were decreased but Annexin-A2 was increased in ESRD-Ex, and renal transplantation could increase the level of Fetuin-A rather than MGP.
Implementing time-domain 1H-Nuclear Magnetic Resonance relaxometry to investigate recovery and stability of vegetative oil in bioenergy crops following feedstock preprocessing
Authors: Maitra Shraddha , Dien Bruce , Long Stephen P. , Singh Vijay
Published: July 2020

Background The bioenergy crops energycane, miscanthus and, sorghum are being genetically modified using state of the art synthetic biotechnology techniques to accumulate energy-rich molecules such as triacylglycerides (TAGs) in their vegetative cells to enhance their utility for biofuel production. Typically, measuring and analyzing vegetative lipid contents at each step of feedstock preprocessing requires tedious sample preparation and extraction with an organic solvent. In the present study, proton nuclear magnetic resonance ( 1 H-NMR) spectroscopy was successfully adapted for non-invasive and rapid quantification of vegetative oil in untreated and pretreated cellulosic biomass. Results We show that the establishment of a precise and specific NMR calibration for each biomass with a distinct oil composition is key for accurate quantification of vegetative oil. The values obtained with 1 H-NMR were validated using a conventional solvent extraction method and cross-referenced values were within 10% deviation. 1 H-NMR relaxation time distribution provided insight into the proton environment associated with the vegetative oil in the biomass. T1T2 correlation spectra resolved two distinct populations of proton molecules based on their ‘molecular tumbling’ rate. The population of protons with short and long relaxation times was characterized as bound and free oil in the biomass sample, respectively. Besides, we show that biomass pretreated with two-staged hydrothermal and mechanical pretreatment can be directly used for NMR analysis unlike dilute acid and alkaline pretreated biomass which needs an additional step for neutralization of sample. Conclusion Time-domain 1 H-NMR provides a chemical-free and one-step analysis of in situ vegetative oil in transgenic cellulosic biomass. T1T2 correlation spectra facilitated the resolution of the influence of various pretreatment procedures typical of cellulosic bioprocessing on the chemical composition of molecular and local 1 H population in each sample, hence yield information on the stability and oil recovery subsequent to each step of feedstock preprocessing.
Clinical characteristics of 134 convalescent patients with COVID-19 in Guizhou, China
Authors: Zhang Siqin , Liu Lin , Yang Bin , Li Rou , Luo Jianhua , Huang Jing , Long Yanjun , Huang Ying , Zhou Jianping , Zha Yan , Zhang Xiangyan
Published: July 2020

Background: Previous studies have focused on the clinical characteristics of hospitalized patients with the novel 2019 coronavirus disease (COVID-19). Limited data are available for convalescent patients. This study aimed to evaluate the clinical characteristics of discharged COVID-19 patients.Methods: In this retrospective study, we extracted data for 134 convalescent patients with COVID-19 in Guizhou Provincial Staff Hospital from February 15 to March 31, 2020. Cases were analyzed on the basis of demographic, clinical, and laboratory data as well as radiological features. Results: Of 134 convalescent patients with COVID-19, 19 (14.2%) were severe cases, while 115 (85.8%) were non-severe cases. The median patient age was 33 years (IQR, 21.8 to 46.3), and the cohort included 69 men and 65 women. Compared with non-severe cases, severe patients were older and had more chronic comorbidities, especially hypertension, diabetes, and thyroid disease (P<0.05). Leukopenia was present in 32.1% of the convalescent patients and lymphocytopenia was present in 6.7%, both of which were more common in severe patients. 48 (35.8%) of discharged patients had elevated levels of alanine aminotransferase, which was more common in adults than in children (40.2% vs 13.6%, P=0.018). A normal chest CT was found in 61 (45.5%) patients during rehabilitation. Severe patients had more ground-glass opacity, bilateral patchy shadowing, and fibrosis. No significant differences were observed in the positive rate of IgG and/or IgM antibodies between severe and non-severe patients.Conclusion: Leukopenia, lymphopenia, ground-glass opacity, and fibrosis are common in discharged severe COVID-19 patients, and liver injury is common in discharged adult patients. We suggest physicians develop follow-up treatment plans based on the different clinical characteristics of convalescent patients.
Long noncoding RNA MEG3 blocks telomerase activity in human liver cancer stem cells epigenetically
Authors: Jiang Xiaoxue , wang Liyan , xie sijie , Chen Yingjie , Song Shuting , Lu Yanan , Lu Dongdong
Published: July 2020

Background: MEG3 is abnormally down-regulated in most tumors and inhibits tumorigenesis. Methods: Gene infection, Western blotting and tumorigenesis test in vitro and in vivo were performed to analyze the signaling pathway. Results: MEG3 increased the loading of P300 and RNA polymerase II onto the promoter regions of P53. Notably, MEG3 increased the methylation of histone H3 at lysine 27 through increasing the interplay between PRC2 and histone H3. Furthermore, MEG3 inhibited the expression of TERT by increasing the H3K27me3 and decreasing the loading of RNA pol Ⅱ in TERT promoter regions. Moreover, MEG3 inhibit the activity of telomerase by reducing the binding of TERT to TERC competitively. In addition, MEG3 also increased the TERRA through reducing DNA methyltransferase DNMT3b binding to the promoter regions of TERRA competitively. Therefore, the interaction between TERC and TERT was competitively attenuated by increasing the interaction between TERRA and TERT, which inhibited the activity of telomerase in hLCSCs.In particular, MEG3 shortened the length of telomere by blocking the formation of complex maintaining telomere length(POT1-Exo1-TRF2-SNM1B) and decreasing the binding of the complex to telomere competitively, which was caused by increasing the interplay between P53 and HULC in hLCSCs.Strikingly, MEG3 inhibited the growth in vitro and in vivo of hLCSCs by reducing the activity of telomerase and attenuating telomeric repeat binding factor 2(TRF2). Conclusions: our results demonstrated MEG3 inhibits the occurrence of human liver cancer and these findings provide an important insight into the prevention and treatment of human liver cancer.
“Brought to Life through Imagery” – Animated Graphic Novels to Promote Empathic, Patient-Centred Care in Postgraduate Medical Learners
Authors: Sutherland Travis , Choi Dorothy , Yu Catherine
Published: July 2020

Background: Empathy levels decline through medical training. This has been associated with poor patient and physician outcomes, and strategies to combat this decline are increasingly recognized as critical aspects of medical education. The aim of this study was to qualitatively determine factors associated with empathy decline, and to assess the impact of a comics/graphic novel-based curriculum on enhancing empathy and a patient-centered approach to care in post-graduate medical learners. Methods: Fourth and fifth year residents in the Adult and Pediatric Endocrinology and Metabolism Program at the University of Toronto were recruited from the 2017 cohort of the Empathy, Humanism & Comics course. Participants completed a 12-month curriculum, viewing a total of four animated graphic novels over six sessions. At the end of the course participants were interviewed either individually or in a focus group. A coding framework of emerging themes was developed based on consensus between the three authors using a qualitative descriptive approach and the constant-comparison method.Results: Analysis of coded interview data revealed four themes. 1. The curriculum accurately reflected and addressed issues in real world medical practice; 2. The comics curriculum facilitated holistic development; 3. Participants appreciated the comics as an educational medium; 4. Participant feedback on the curriculum. The importance of empathy was noted, while participants acknowledged their own empathy decline and increased burnout. Stressors included increasing responsibility, long work hours, and competing work-life responsibilities. They felt the sessions developed resilience, an appreciation for the patient perspective, and communication skills. They appreciated the comics as a novel and engaging educational modality. Feedback on the effectiveness and relevancy of the curriculum was variable.Conclusions: Residents appreciated sharing difficult experiences and seeking support. They acknowledged the curriculum as a commitment to wellness and felt it reduced burnout and improved empathy. The comics were viewed as an effective reminder of the patient perspective. Variable curriculum feedback highlights the challenge in designing a course for adult learners. Future investigations may include the development and incorporation of similar curricula in other post-graduate residency training programs.
Bioinformatics Analysis IdentifiesThrombospondin-1 and its related micro RNAs as biomarkers for Hepatocellular carcinoma
Authors: xuan Wei , Song Dandan , Ren Yunjia , Li Ming
Published: July 2020

Hepatocellular carcinoma (HCC) has a poor prognosis, while the diagnosis biomarkers or treatment targets for HCC are still lacking. Recently, mining strategies on public access databases has been successfully used to discover novel and sensitive biomarkers. In this study, bioinformatics analysis of the genomic and transcriptome data of HCC PBMC samples obtained from the Gene Expression Omnibus datasets. The analysis results showed that thrombospondin-1 (THBS-1) was dysregulated in HCC, and might be as biomarkers as it is a secretory protein and found to participate in liver dysfunction including HCC development. THBS-1 related micro RNAs are identified by bioinformatics analysis and tested as biomarkers as they are altered in many tumors and stable in circulation. The results showed that plasma THBS-1 and miR-194 were down-regulated in HCC patients and their correlations were positive. Whereas plasma level of miR-338-3p was significantly increased in the HCC patients and negatively correlated with THBS-1 and they showed a highly significant diagnostic value in discriminating HCC. In addition, THBS-1 and miR-338-3p combination displayed higher predictive power than them alone, and addition of miR-338-3p might enhance predictive power of AFP for HCC. Our data showed that THBS-1 and miR-338-3p displayed a highly significant diagnostic value in discriminating between HCC patients and control subjects. Addition of miR-338-3p might enhance the predictive potency of AFP for HCC.
Efficacy of Definite Concurrent Chemoradiotherapy for Patients with Limited-Disease Small-Cell Lung Cancer: A Retrospective, Nationwide, Population-Based Cohort Study
Authors: Ko Yoon Ho , Kim Seoree , Hong Ji Hyung , Sung Soo-Yoon , Kim Yeo Hyung , Chun Sang Hoon , Lee Hyun Woo , Lee Jung Soo
Published: July 2020

Background: Small-cell lung cancer (SCLC) is a highly proliferative, rapidly growing tumor with a poor prognosis, even in cases of limited disease (LD). Timely and accurate high-intensity therapy is necessary. For concurrent chemoradiotherapy (CCRT), etoposide/platinum (EP)-based regimens are recommended, although irinotecan/platinum (IP)-based regimens are also effective with radiotherapy. This large-scale, retrospective, nationwide cohort study aimed to analyze the efficacy of CCRT in patients with LD-SCLC.Methods: Population data registered between January 2008 and December 2018 were extracted from the Health Insurance Review and Assessment Service of Korea database. Survival outcomes of 4,446 LD-SCLC patients who received CCRT were analyzed.Results: Patients who received EP-CCRT (n = 4,187) showed better progression-free survival (PFS: 11.2 months) and overall survival (OS: 22.2 months) than did those who received IP-CCRT (n = 259; PFS: 9.6 months, P = 0.0477; OS: 16.4 months, P <0.0001). When CCRT failed, dual-agent chemotherapy (n = 925; OS: 9.1 months) provided a better survival benefit than did single-agent chemotherapy (n = 815; OS: 7.5 months). IP-based chemotherapy resulted in better OS (9.6 months) than did EP-based chemotherapy (7.1 months, P = 0.0170) in platinum-resistant relapsed patients; the opposite was observed for platinum-sensitive relapsed patients (OS: EP, 17.2 months; IP, 6.6 months; P <0.0001). Cox proportional hazards regression analysis demonstrated that age, EP-CCRT, and hypercholesterolemia retained significant associations with OS after adjustment for all variables.Conclusion: In the Korean population, the effects of EP-CCRT on OS and PFS are significantly more favorable than those of IP-CCRT.
Evaluation of Immunophenotypic Markers and Clinico-Hematological Profile in Chronic Lymphocytic Leukemia: Implications for Prognosis
Authors: Bagheri Marziye , Vosoughi Tina , Hosseinzadeh Mehran , Saki Najmaldin
Published: July 2020

Objective: Chronic lymphocytic leukemia (CLL) is an adult leukemia presented with clonal accumulation of lymphocytes. Immunophenotypic changes can be effective in predicting clinical course, the survival of patients, and determining first-line treatment. This is a study of the association between immunophenotypic markers expression with complete blood cell count (CBC) values and clinical parameters. Results: Peripheral blood samples were collected from 35 new CLL patients. The expression of immunophenotypic markers and CBC were evaluated. Platelet counts and hemoglobin concentration had a significant, negative association with Rai staging, modified Rai staging, Binet staging systems (all p< 0.001 in both parameters), and splenomegaly (p = 0.001 and 0.007, respectively). The platelet/lymphocyte ratio (PLR) had a significant, negative association with Rai staging (p = 0.014), modified Rai staging (p = 0.024), Binet staging systems (p = 0.027), and splenomegaly (p = 0.033). However, CD38, CD25, and double-positive CD56/CD117 expression, as group3 of innate lymphocyte cells (ILC3s), had no significant association with clinical parameters. In regression analysis, that ILC3s has a negative correlation with neutrophil/lymphocyte ratio (r = -0.340, p = 0.046). Given that there is a negative association between PLR and advanced clinical stages, it seems that PLR may have prognostic value in CLL.
CERTL Reduces C16 Ceramide, Amyloid-β Levels and Inflammation in a Model of Alzheimer's Disease
Authors: Crivelli Simone Mwenda , Luo Qian , Stevens Jo , Giovagnoni Caterina , Kruining Daan van , Bode Gerard , Hoedt Sandra den , Hobo Barbara , Scheithauer Anna-Lena , Walter Jochen , Mulder Monique T , Exley Christopher , Mielke Michelle M. , De Vries Helga E , Wouters Kristiaan , Hove Daniel L.A. van den , Berkes Dusan , Ledesma María Dolores , Verhaagen Joost , Losen Mario , Bieberich Erhard , Martinez-Martinez Pilar
Published: July 2020

Background: Deregulation of ceramide and sphingomyelin levels have been suggested to contribute to the pathogenesis of Alzheimer’s disease (AD). Ceramide transfer proteins (CERTs) are ceramide carriers, crucial for ceramide and sphingomyelin balance in cells. Extracellular forms of CERTs co-localize with amyloid-β (Aβ) plaques in AD brains. To date, the significance of these observations for the pathophysiology of AD remains uncertain.Methods: The plasmid expressing CERTL, the long isoform of CERTs, was used to study the interaction of CERTL with amyloid precursor protein (APP) by co-immunoprecipitation and immunofluorescence in HEK cells. The recombinant CERTL protein was employed to study interaction of CERTL with amyloid-β (Aβ), Aβ aggregation process in presence of CERTL, and the resulting changes in Aβ toxicity in neuroblastoma cells. CERTL was overexpressed in neurons by adeno associated virus (AAV) in a familial mouse model of familial AD (5xFAD). Ten weeks after transduction animal were challenged with behavior tests for memory, anxiety and locomotion. At week twelve brains were investigated for sphingolipid levels by mass spectrometry, plaques and neuroinflammation by immunohistochemistry, gene expression and/or immunoassay.Results: Here, we report that CERTL, binds to APP, modifies Aβ aggregation and reduces Aβ neurotoxicity in vitro. Furthermore, we show that intracortical injection of AAV, mediating the expression of CERTL, decreases levels of ceramide d18:1/16:0 and increases sphingomyelin levels in the brain of male transgenic mice, modelling familial AD (5xFAD). CERTL in vivo over-expression has a mild effect on animal locomotion and decreases Aβ formation and modulates microglia by decreasing their pro-inflammatory phenotype.Conclusion: Our results demonstrate a crucial role of CERTL in regulating ceramide levels in the brain, in amyloid plaque formation and neuroinflammation, thereby opening research avenues for therapeutic targets of AD and other neurodegenerative diseases.