bluuebunny/crossref_metadata_2025 huggingface dataset:
WRAP-based nanoparticles for siRNA delivery: A SAR study and a comparison with lipid-based transfection reagents.
Authors: Konate Karidia , Josse Emilie , Tasic Milana , Redjatti Karima , Aldrian Gudrun , Deshayes Sébastien , Boisguérin Prisca , Vives Eric
Published: December 2020

Recently, we designed novel amphipathic cell-penetrating peptides, called WRAP, able to transfer efficiently siRNA molecules into cells. In order to gain more information about the relationship between amino acid composition, nanoparticle formation and cellular internalization of these peptides composed of only three amino acids (leucine, arginine and tryptophan), we perform a structure activity relationship (SAR) study. First, we compared our WRAP1 and WRAP5 peptides with the C6M1 peptide also composed of the same three amino acids and showing similar behaviors in siRNA transfection. Afterwards, to further define the main determinants in the WRAP activity, we synthesized 13 new WRAP analogues harboring different modifications like the number and location of leucine and arginine residues, the relative location of tryptophan residues, as well as the role of the α-helix formation upon proline insertions within the native WRAP sequence. After having compare the ability of these peptides to form peptide-based nanoparticles (PBNs) or not using different biophysical methods (circular dichroism, dynamic light scattering, gel shift assay) and to induce a targeted gene silencing (luciferase assay) in cells, we were able to establish the main sequential requirements of the amino acid composition of the WRAP peptides to maintain a good siRNA transfection efficacy. In addition, upon measuring the WRAP-based siRNA transfection ability into cells compared to several non-peptide transfection agents available on the markets, we confirmed that WRAP peptides induced an equivalent level of targeted gene silencing but in most of the cases with significant lower cell toxicity as clearly shown in clonogenic assays.
Analysis of Tracheal Intubation in Out-of-Hospital Helicopter Emergency Medicine Recorded by Video Laryngoscopy.
Authors: Knapp Jürgen , Eberle Bettina , Bernhard Michael , Theiler Lorenz , Pietsch Urs , Albrecht Roland
Published: December 2020

Objective. Tracheal intubation remains the gold standard of airway management in emergency medicine and maximizing safety, intubation success and especially first-pass intubation success (FPS) in these situations is imperative.Methods. We conducted a prospective observational study on all twelve helicopter emergency medical service (HEMS) bases of the Swiss Air Rescue, between February 15, 2018, and February 14, 2019. All 428 patients on whom out-of-hospital advanced airway management was performed by the HEMS crew were included. The C-MAC video laryngoscope was used as primary device for tracheal intubation. Intubation procedures were recorded by the video laryngoscope and precise time points were recorded to verify the time necessary for each attempt and the overall procedure time until successful intubation. The videos were further analysed for problems and complications during airway management by an independent reviewer. Additionally, a questionnaire about the intubation procedure, basic characteristics of the patient, as well as circumstances and environmental factors, and the level of experience in airway management of the provider had to be filled out. Main outcome measures were FPS of tracheal intubation, overall success rate, overall intubation time, problems and complications of video laryngoscopy.Results. FPS rate was 87.6% and overall success rate 98.6%. Success rates, overall time to intubation, and subjective difficulty were not associated to the providers’ expertise in airway management. In patients undergoing CPR FPS was 84.8%, in trauma patients 86.4% and in non-trauma patients 93.3%. FPS in patients with difficult airway characteristics, facial trauma/burns or obesity ranges between 87 and 89%. Performing airway management indoors or inside an ambulance resulted in a significantly higher FPS of 91.1% compared to outdoor locations (p<0.001). Direct solar irradiation on the screen, fogging of the lens, and blood on the camera significantly impaired FPS. Several issues for further improvements in the use of video laryngoscopy in the out-of-hospital setting and for quality control in airway management were identified.Conclusion. Airway management using the C-MAC video laryngoscope with Macintosh blade in a group of operators with mixed experience showed high FPS and overall rates of intubation success. Video recording emergency intubations may improve education and quality control.
Nicardipine Versus Nitroglycerin for The Treatment of Hypertensive Acute Heart Failure Syndrome: A Single-Center Observational Study
Authors: Koroki Takatoshi , Abe Tomohiro , Ochiai Hidenobu
Published: December 2020

Background: Nitroglycerin is considered a first-line agent for hypertensive acute heart failure syndromes (AHFS). In this study, we compared the effectiveness of nicardipine and nitroglycerin in patients with hypertensive AHFS. Methods: We conducted a single-center, retrospective, observational study at the intensive care unit of a Japanese hospital. Patients diagnosed with AHFS and systolic blood pressure exceeding 140 mmHg on arrival between April 2013 and August 2019 were included. The outcomes were the time to optimal blood pressure control, duration of the continuous infusion of anti-hypertensive agents, duration of positive pressure ventilation, need for additional anti-hypertensive agents, length of hospital stay, and body weight changes. Outcomes were compared between the nicardipine and nitroglycerin groups. We also compared these outcomes between the groups after excluding patients who received renal replacement therapy. Results: Forty-five patients were enrolled (25 and 20 were treated with nitroglycerin and nicardipine, respectively). The nicardipine group had a shorter time to optimal blood pressure control (1.0 [interquartile range, 1.0–3.0] h vs. 0.5 [0.5–1.0] h), shorter duration of the continuous infusion of anti-hypertensive agents (65.5 [32.5–127.5] h vs. 31.0 [18.5–61.0] h), less frequent need for additional anti-hypertensive agents (0 patients vs. 10 patients [40.0%]), and shorter length of hospital stay (19.0 [10.0–33.0] days vs. 8.0 [5.0–12.3] days) than the nitroglycerin group. The duration of positive pressure ventilation and body weight changes were similar between the groups. These outcomes were similar after excluding patients who received renal replacement therapy. Conclusions: Nicardipine may be more effective than nitroglycerin for treating hypertensive AHFS.
Disentangling archaeal and bacterial biogeography and co-occurrence networks in subtropical mangrove sediments under Spartina alterniflora invasion
Authors: Chen Weidong , Wen Donghui
Published: December 2020

Background Mangrove ecosystems are vulnerable due to the exotic Spartina alterniflora invasion in China. Large knowledge gaps remain with regard to archaeal and bacterial communities assembly processes and microbial interactions under S. alterniflora invasion. Here, using 16S rRNA gene amplicon sequencing, we investigated the assembly processes and co-occurrence relationships of the archaeal and bacterial communities under S. alterniflora invasion along the coastlines of Fujian province, southeast China.Results We found that the overall archaeal and bacterial communities were driven predominantly by stochastic processes, and the relative role of stochasticity was stronger for bacteria than archaea. Co-occurrence network analysis showed that the network structure of bacteria was more complex than that of the archaea. Putative keystone taxa often had low relative abundances (conditionally rare taxa), suggesting conditionally rare taxa or low abundances taxa may significantly contribute to network stability. Moreover, we found that S. alterniflora invasion changed the microbial communities assembly and co-occurrence patterns, indicating that S. alterniflora affected the composition and stability of the microbial community.Conclusions This study provides the first comparison in the biogeography and co-occurrence patterns of both archaea and bacteria in mangrove ecosystem. And this is the first exploration about the effect of S. alterniflora invasion on archaeal and bacterial ecological processes and co-occurrence patterns. Our study considers that the control of S. alterniflora invasion is important for mangrove ecosystem function and service.
Six-month follow-up of functional status in discharged patients with coronavirus disease 2019
Authors: Du Houwei , Fang Shuang-fang , Wu Sang-ru , Chen Xiao-ling , Chen Jun-nian , Zhang Yi-xian , Huang Hua-yao , Lei Han-han , Chen Rong-hua , Pan Xiao-bin , Li Xiao-qing , Xia Pin-cang , Zheng Zhen-yang , Lin Hai-long , Chen Li-min , Liu Nan
Published: December 2020

Background The long-term functional outcome of discharged patients with coronavirus disease 2019 (COVID-19) remains unresolved. We aimed to describe a six-month follow-up of functional status of COVID-19 survivors.Methods We reviewed the data of COVID-19 patients who had been consecutively admitted to the Tumor Center of Union Hospital (Wuhan, China) between 15 February and 14 March 2020. We quantified a six-month functional outcome reflecting symptoms and disability in COVID-19 survivors using a post-COVID-19 functional status scale ranging from 0 to 5 (PCFS). We examined the risk factors for the incomplete functional status defined as a PCFS > 0 at a six-month follow-up after discharge.Results We included a total of 95 COVID-19 survivors with a median age of 62 (IQR 53-69) who had a complete functional status (PCFS grade 0) at baseline in this retrospective observational study. At six-month follow-up, 67 (70.5%) patients had a complete functional outcome (grade 0), 9 (9.5%) had a negligible limited function (grade 1), 12 (12.6%) had a mild limited function (grade 2), 7 (7.4%) had moderate limited function (grade 3). Univariable logistic regression analysis showed a significant association between the onset symptoms of muscle or joint pain and an increased risk of incomplete function (unadjusted OR 4.06, 95%CI 1.33 - 12.37). This association remained after adjustment for age and admission delay (adjusted OR 3.39, 95%CI 1.06 - 10.81, p = 0.039).Conclusions A small proportion of discharged COVID-19 patients may have an incomplete functional outcome at a six-month follow-up; intervention strategies are required.
Recovery of Olfactory and Gustatory Dysfunctions in COVID-19 Patients in Iran: A Prospective Cohort Study
Authors: Balajelini Mohammad Hosein Taziki , Vakili Mohammad Ali , Rajabi Abdolhalim , Mohammadi Masoud , Tabarraei Alijan , Hosseini Seyed Mehran
Published: December 2020

Background: Olfactory and gustatory dysfunctions (OD and GD) manifested unpredictably in COVID-19 patients. Considering the high prevalence of OD and GD and the importance of the sense of smell and taste in the quality of life, this study aimed to determine the association of some demographic and clinical factors with OD and GD recovery in COVID-19 patients in Iran.Methods: This prospective cohort study was performed on COVID-19 patients with OD and GD during the first and second peak of pandemic in Golestan province, Iran. We used a local health care registry system for data collection. All cases had positive RT-PCR test for SARS-CoV-19 in nose and nasopharynx swab samples. Variables included age, sex, ethnicity, geographical location, time of onset of symptoms, severity of OD and GD (complete or partial). The follow-up time for recovery from OD and GD was six months. Time to recovery for OD and GD was estimated by Kaplan-Meier considering complete recovery as an endpoint. Differences among groups were evaluated using log-rank test and Cox proportional-hazard models as appropriate in SPSS version 16.Results: A total of 242 patients completed the study. The mean age of patients was 39.12±11.89 years. There were 127 (52%) females. After six months, 239 (98.8%) patients had complete OD recovery and 80.9% and 83.56% of patients recovered within the first 30 days following the onset of OD or GD, respectively. The mean time of OD recovery was significantly higher (35.07±4.25 days) in cases infected in the first peak of pandemic than in the second peak (21.65±2.05 days) (p=0.004). This finding also was observed for the recovery time of GD (p=0.005). The mean recovery time of GD was significantly higher in women than men (35.55±4.33 vs. 23.20±2.46 days) (p=0.04). The age (less than 20 years), second peak of epidemic, and partial dysfunction were identified as significant predictors for recovery.Conclusions: COVID-19–related OD and GD had high rate of recovery in the first month from onset of symptoms. Age of patients, severity of OD/GD and infecting in second peak of epidemic might be related to the recovery of OD or GD in patients with COVID-19.
A guideline for screw fixation of coracoid process base fracture by 3D technology
Authors: Sun Zhongye , Li Hao , Wang Bei , Yan Jun , Han Liren , Han Shizhang , Yang Xiaofei , Zhao Bei
Published: December 2020

BackgroundFractures of the base of the coracoid process are relatively rare, but an increasing number of studies have reported using screws to fix basal coracoid process fractures. This study was performed to simulate the surgical procedure and obtain the ideal diameter, length, insertion point and angle of the screw through the method of 3-D axial perspective in Chinese patients.MethodsWe randomly collected the right scapula computed tomography (CT) scans of 100 adults. DICOM-formatted CT-scan images were imported into Mimics software. The 3D digital model of the right scapula was established. Two virtual cylinders representing two screws were placed from the top of the coracoid process to the neck of the scapula and across the base of the coracoid process to fix the basal coracoid process. The largest secure diameters and lengths of the virtual screws were measured. The positions of the insertion points and the directions of the screws were also researched.ResultsThe screw insertion safe zone can exhibit an irregular fusiform shape from the reconstructed scapula model. The mean maximum diameters of the medial and lateral screws were 7.08 ± 1.19 mm and 7.34 ± 1.11 mm, respectively. The mean maximum lengths of the medial and lateral screws were 43.11 ± 6.31 mm and 48.16 ± 6.94 mm, respectively. The screw insertion corridor with a diameter of at least 4.5 mm was found in anyone. We found gender-dependent differences for the mean maximum diameters and the maximum lengths of the two screws. The positions of the two insertion points were statistically significant in different genders.ConclusionsThe study provides a valuable guideline for the largest secure corridor of two screws that fixed the fracture at the base of the coracoid process. For the ideal screw placement, we suggest an individual preoperative 3D reconstruction simulation. Further biomechanical studies are needed to verify the function of the screws.
Medial Abrasion Syndrome: A Neglected Cause of Persistent Pain After Knee Arthroplasty
Authors: Lyu Shaw-Ruey , Hsu Chia-Chen , Hung Jung-Pin
Published: December 2020

Introduction: Persistent postoperative pain (PPOP) has detracted from some otherwise successful knee arthroplasties. This study investigated medial abrasion syndrome (MAS) as a cause of PPOP after knee arthroplasty. The surgical techniques and outcomes of incorporating this concept into the management of both primary arthroplasty cases and patients suffering from unknown causes of PPOP after arthroplasties were presented. Materials and Methods: In a one-year period, the author performed unicompartmental or total knee arthroplasty (the UKA or TKA group) that also eliminated medial abrasion phenomenon (MAP) on 196 knees of 150 patients at advanced stages of knee osteoarthritis (OA). During the same year, 16 knees of 16 patients with unknown causes of PPOP after knee arthroplasties were referred to the author for the arthroscopic medial release procedure (the AMR group) after being diagnosed as MAS. Subjective satisfaction, Knee Society Score (KSS), and Knee injury and Osteoarthritis Outcome Score (KOOS) evaluations were used for outcome study.Results: All 166 patients were followed for more than 3 years (mean: 3.7 years, 3.1-4.2) for outcome study. All knees receiving arthroplasty showed medial plicae with MAP at the time of surgery. Only 2 of them suffered from PPOP: one was a neglected tibial plateau fracture with residual varus deformity after UKA and the other was a late infection after TKA and received revision. The satisfactory rate was 98.8% in the UKA group, 99.1% in the TKA group, and 100% in the AMR group. The Knee Society scores and all subscales of KOOS were statistically improved in all groups.Conclusions: MAS is a cause of pain in patients who have received knee arthroplasties, and MAP should be eliminated to ensure a successful knee arthroplasty. PPOP after knee arthroplasty can be caused by MAS, which can be managed by AMR.
Genotype-Environment Interaction and Stability of Fiber Properties and Growth Traits in Triploid Hybrid Clones of Populus Tomentosa
Authors: Wu Jian , Zhou Qing , Sang Yaru , Kang Xiangyang , Zhang Pingdong
Published: December 2020

Background: Clones provide a sensitive method for evaluating genotypic stability and detecting genotype-environment (G × E) interactions because of non-additive genetic effects among clones and no genetic effect among ramets of an ortet. The experiments aimed at confirming and expanding the earlier findings, estimating stability parameters, and providing accurate estimates of clonal repeatabilities and genetic gains for an triploid breeding programme of Populus tomentosa Carr. Results: Six 5-year-old clonal trials established in Northern China were used to determine the clonal variation, clone × site interactions and the stability parameters of fiber properties of wood and growth traits. Three hundred sixty trees from ten hybrid clones were collected in the six sites. The clonal and site effects had a highly significant effect (P < 0.001) for all studied traits. The clone × site interactions had a highly significant effect (P < 0.001) on fiber length (FL), coarseness (C), and tree growth (tree height [H], diameter at breast height [DBH] and stem volume [SV]), and a moderate effect (P < 0.05) on fiber width (FW) and fiber length/width (FL/W). For FL and SV, most of the triploid hybrid clones had higher reaction norms to the improvement in growth conditions and higher phenotypic plasticity. The estimated clonal repeatability of FW (0.93) was slightly higher than for FL (0.89), FL/W (0.83), C (0.91), DBH (0.76), H (0.85), and SV (0.80). Three clonal testing sites were sufficient to estimate quantitative parameters of fiber properties. However, more than three clonal testing sites will help improve the accuracy of quantitative parameters of growth traits.Conclusions: Our results unraveled that accurate estimation of quantitative parameters for growth traits in triploid hybrid clones of Populus tomentosa required more clonal testing sites than fiber properties.
WITHDRAWN: Hypothalamic Myo-Inositol and Glucose concentrations, mood symptoms and fatigue in depression: a 3 Tesla chemical-shift-imaging in vivo proton magnetic resonance spectroscopy study
Authors: Pedraz-Petrozzi Bruno , Blecker Carlo , Sammer Gebhard
Published: December 2020

Background: Many studies have confirmed altered brain Myo-Inositol (mIns) and Glucose (Glc) concentrations in depression. Alterations in the mIns-concentrations may represent a glial dysfunction and are associated mostly with depression symptoms. In comparison, alterations in the Glc-concentrations could represent impaired glucose metabolism. Despite this information, studies that assess these metabolites in the hypothalamus are missing. Therefore, this study aims to investigate mIns- and Glc-concentrations in the hypothalamus of participants with depression concerning mood symptoms and fatigue.Methods: We performed an in vivo proton magnetic resonance spectroscopy – chemical shift imaging of the hypothalamus in 49 participants (25 with depression diagnosis or DE, 24 healthy controls or HC), evaluating mIns- and Glc-concentrations. Concerning information about symptoms, we recollected information on depression symptomatology (BDI-FSTOT) and fatigue (FIS-D). For statistical analysis, we run generalized linear models by using the Poisson regression model with count data.Results: The results showed reduced hypothalamic mIns-concentration for every DE participant with higher FIS-D and higher BDI-FSTOT values (OR = 0.022; p < 0.001; CI95 [0.004 to 0.09]). Besides, the results showed increased hypothalamic Glc-concentration for every participant of the DE group and with higher BDI-FSTOT values (OR = 4.827; p = 0.002; CI95 [1.826 to 13.749]).Conclusions: These results provide initial evidence of a glial dysfunction and impaired glucose metabolism in the hypothalamus associated with mood symptoms and fatigue. Future studies are needed to confirm these pathophysiologic mechanisms.
SPP1 Might Be a Novel Prognostic Biomarker for Patients With Malignancy: a Meta-analysis and Sequential Verification Based on Bioinformatic Analysis
Authors: Zheng Hao-ran , Jiang Ai-Min , Liu Na , Ding Qian-Qian , Zhao Fu-Mei , Fu Xiao , Liang Xuan , Tian Tao , Ruan Zhi-Ping , Yao Yu
Published: December 2020

Background: Several studies have investigated the relationship between secreted phosphoprotein 1 (SPP1) expression level and prognosis of various tumors, but the results are far from conclusive. Therefore, we performed the present meta-analysis to investigate the prognostic value of SPP1 in pan-cancer. Furthermore, a followed confirmation based on The Cancer Genome Atlas (TCGA) database was also performed to verify our results.Methods: We performed a systematic search from PubMed, Embase, Web of Science, and Cochrane Library databases and 19 articles, including 3403 patients and 9 types of tumors, were pooled in our meta-analysis. Overall survival (OS) and disease-free survival (DFS), which correlated with SPP1 expression, were considered as the primary outcome. Subgroup analyses, sensitivity analysis, and publication bias were used to investigate heterogeneity and reliability of the results. Furthermore, we also explored the relationship between SPP1 expression and clinical parameters of tumor patients. Finally, the results were verified with TCGA database and we further explored the relationship between SPP1 expression and tumor immuno-microenvironment (TIME), DNA methylation, and enriched gene pathway.Results: Our meta-analysis showed that high-expressed SPP1 was significantly related to poor OS and DFS in various cancers, especially in liver hepatocellular carcinoma (LIHC). Furthermore, we also identified that the high expression level of SPP1 was significantly correlated with tumor grade. The expression level of SPP1 in the majority of tumor types were much higher than the corresponding normal tissues analyzed from databases. Besides, we also observed that high-expressed SPP1 was related to poor OS and DFS in LIHC, which supported the conclusion of meta-analysis. In addition, high-expressed SPP1 is related to 6 immune cells in TIME and DNA methylation regulatory genes. Ultimately, the results of Gene Set Enrichment Analysis (GSEA) suggested that tumor-related gene sets, such as hypoxia and lipid metabolism, were significantly enriched in high-expressed SPP1 group.Conclusions: SPP1 is high-expressed in various tumor tissues and correlated with poor prognosis. SPP1 might promote cancer invasion and metastasis by affecting tumor grade, TIME, DNA methylation, hypoxia, and lipid metabolism. SPP1 is expected to become a new clinical indicator for tumor detection and prognosis, and provide a new idea for tumor targeted therapy.
Identification of Metabolic Reprogramming Related Gene Signature to Predict the Prognosis of Bladder Cancer Patients
Authors: Li Tinghao , Tong Hang , Yin Hubin , Cao Honghao , Zhu Junlong , Qin Zijia , Yin Siwen , He Weiyang
Published: December 2020

Background: Different kinds of metabolic reprogramming have been widely researched in multifarious cancer types and show up as a guaranteed prognostic predictor, while bladder cancer (BLCA) is most frequent urothelium carcinoma but with poor prognosis despite there are emerging treatments, for lack of reliable predicting biomarkers to early predict the prognosis and delayed treatment options for patients in the terminal stage. Our study aims to explore new prognostic factors related to metabolism in BLCA and make these genes up as novel risk stratification.Methods: We selected a large number of samples downloaded from TCGA (The Cancer Genome Atlas) to find out the possible glycolysis-related genes that correlated with differentiation from cancer sample to normal tissue, aimed to find out a more credible model. To make our signature more believable, we chose the clinical features information from GEO (Gene Expression Omnibus) database as external validation cohort.Results: Finally, we established a three glycolysis-related gene signature based on the expression of AK3, GALK1 and NUP205 to make a prediction on the prognosis of BLCA patients, which were also validated by external cohort and whole mixed cohort. As a result, we built a three glycolysis-related gene signature and found its prognosis value is more valuable in high malignancy patients, which may help physicians to make a more aggressive choice.
JKAMP Inhibits the Osteogenic Capacity of Adipose-derived Stem Cells in Diabetic Osteoporosis by Modulating the Wnt Signaling Pathway Through Intragenic DNA Methylation
Authors: Peng Shuanglin , Shi Sirong , Tao Gang , Li Yanjing , Xiao Dexuan , Wang Lang , He Qing , Cai Xiaoxiao , Xiao Jingang
Published: December 2020

Background: Diabetic osteoporosis (DOP) is a systemic metabolic bone disease caused by diabetes mellitus (DM). Adipose-derived stem cells (ASCs) play an important role in bone regeneration. Our previous study confirmed that ASCs from DOP mice (DOP-ASCs) have a lower osteogenesis potential compared with control ASCs (CON-ASCs). However, the cause of this poor osteogenesis has not been elucidated. Therefore, this study investigated the underlying mechanism of the decline in the osteogenic potential of DOP-ASCs from the perspective of epigenetics and explored methods to enhance their osteogenic capacity. Methods: The expression level of JNK1-associated membrane protein (JKAMP) and degree of DNA methylation in CON-ASCs and DOP-ASCs were measured by mRNA expression profiling and MeDIP sequencing, respectively. JKAMP small interfering RNA (siRNA) and a Jkamp overexpression plasmid were used to assess the role of JKAMP in osteogenic differentiation of CON-ASCs and DOP-ASCs. Immunofluorescence, qPCR, and western blotting were used to measure changes in expression of Wnt signaling pathway-related genes and osteogenesis-related molecules after osteogenesis induction. Alizarin red and ALP staining was used to confirm the osteogenic potential of stem cells. Bisulfite-specific PCR (BSP) was used to detect JKAMP methylation degree. Results: Expression of JKAMP and osteogenesis-related molecules (RUNX2 and OPN) in DOP-ASCs was decreased significantly in comparison with CON-ASCs. JKAMP silencing inhibited the Wnt signaling pathway and reduced the osteogenic ability of CON-ASCs. Overexpression of JKAMP in DOP-ASCs rescued the impaired osteogenic capacity caused by DOP. Moreover, JKAMP in DOP-ASCs contained intragenic DNA hypermethylated regions related to the downregulation of JKAMP expression. Conclusions: Intragenic DNA methylation inhibits the Wnt signaling pathway by suppressing expression of JKAMP and the osteogenic ability of DOP-ASCs. This study shows an epigenetic explanation for the reduced osteogenic ability of DOP-ASCs, and provides a potential therapeutic target to prevent and treat osteoporosis.
TIMELESS is a Potential Molecular Marker in Glioma: A Study Based on Multiple Databases and Methods
Authors: Liu Zhendong , Ren Zhishuai , Han Zhibin , Cheng Xingbo , Zhang Wang , Liu Binfeng , Wang Jialin , Gao Yanzheng
Published: December 2020

Background: In recent years, some studies have shown that TIMELESS, as an oncogene, is involved in the malignant progression of cancers. However, its relationship with the prognosis of glioma patients is rarely reported. Our purpose is to explore the role of TIMELESS in glioma. Main body: Based on 1814 glioma samples from multiple databases such as TCGA, CGGA, GEO, we use a variety of bioinformatics methods to verify the mechanism of action of TIMELESS in glioma from mRNA to protein, from appearance to mechanism analysis, from clinical features to prognosis. Then, use the CMap tool to predict potential drugs that inhibit the expression of TIMELESS. First, we found TIMELESS is highly expressed in glioma from the mRNA level to the protein level. Second, TIMELESS is an independent risk factor for prognosis and has a suitable clinical diagnosis value in glioma. It was also positively correlated with WHO grade, age, histology, and negatively correlated with IDH1 mutation and 1p19q codeletion. Third, Base excision, cell cycle, and mismatch repair pathway were activated by TIMELESS in glioma. At last, we predict small molecules that potentially inhibit TIMELESS such as 8-azaguanine, gw8510, 6-thioguanosine, and ursodeoxycholic acid. Conclusion: This study is the first comprehensive analysis of TIMELESS, revealing the relationship between the novel oncogene and the clinical characteristics of patients with glioma, and the mechanism leading to poor prognosis. It also provides a potential biomarker for the diagnosis and treatment of glioma. Our research hopes to reveal the pathological progress of glioma at the genetic level.
Analysis of Bayesian Optimization Algorithms for Big Data Classification Based on Map Reduce Framework
Authors: Banchhor Chitrakant , N Srinivasu
Published: December 2020

The process of big data handling refers the efficient management of storage and processing of very large volume of data. The data in a structured and an unstructured format require specific approach for overall handling.The classifiers analyzed in this paper are correlative naïve bayes classifier (CNB), Cuckoo Grey wolf CNB (CGCNB), Fuzzy CNB (FCNB), and Holoentropy CNB (HCNB). These classifiers are based on Bayesian principle and work accordingly. The CNB is developed by extending the standard naïve bayes classifier with applied correlation among the attributes so that it becomes a dependent hypothesis and it is named as a correlative naïve bayes classifier (CNB). The cuckoo search and grey wolf optimization algorithms are integrated with the CNB classifier and significant performance improvement is achieved. The resulting classifier is called as cuckoo grey wolf correlative naïve bayes classifier (CGCNB). The further performance improvements are achieved by incorporating fuzzy theory termed as fuzzy correlative naïve bayes classifier (FCNB) and holoentropy theory termed as Holoentropy correlative naïve bayes classifier (HCNB) respectively. FCNB and HCNB classifiers are comparatively analyzed with CNB and CGCNB and achieved noticeable performance by analyzing with accuracy, sensitivity and specificity analysis.
WITHDRAWN: Simultaneous Production of Bioemulsifier and Exopolysaccharides by Thermophilic Brevibacillus Borstelensis Using Response Surface Model, Genetic Algorithm and NSGA
Authors: Dhagat Swasti , Jujjavarapu Satya Eswari
Published: December 2020

Bioemulsifier and exopolysaccharides are two of the important biomolecules produced as secondary metabolites by many microorganisms. Bioemulsifiers emulsify hydrophobic substrates allowing their consumption by microorganisms whereas exopolysaccharides provide structural scaffold for the microorganisms to attach to any surface for biofilm formation. Both of these biomolecules have various applications in pharmaceutical and biomedical sectors and hence their production with high yield becomes important. A thermophilic bacterium, Brevibacillus borstelensis, has shown to produce bioemulsifier and exopolysaccharides simultaneously with limited yields. Central composite design-response surface methodology was employed as experimental design strategy to maximize the yields of both of these products with concentrations of glucose, monosodium glutamate, yeast extract and magnesium sulphate in the medium as process variables. The concentration of bioemulsifiers, exopolysaccharides and biomass were chosen as responses of the study. A set of 30 experiments were performed as a part of optimization study with 24 runs as non-centre points and 6 runs as centre points. The model obtained from central composite design was further optimized by genetic algorithm and naïve sorted genetic algorithm. The best results obtained from the three modelling and optimization tools were compared and the models were validated.
Socioeconomic Differentials in Trends in the Prevalence of Hypertension and Pre-hypertension and Hypertension Awareness, Treatment, and Control in Rural Southwestern China
Authors: Fan Luming , Wang Fang , Zhao Min , Cui Wen-Long , Cai Le
Published: December 2020

Background: This study examines the socioeconomic differentials in trends in the prevalence of hypertension and pre-hypertension and hypertension awareness, treatment, and control in rural Southwestern China.Methods: Two cross-sectional interviews and health examination surveys were administered in rural Yunnan Province, including 6,350 consenting participants in 2009 and 6,359 consenting participants in 2016 (aged ≥ 35 years). Participant demographics, socioeconomic status (SES), and ethnicity, along with information about hypertension awareness, treatment, and control, were collected using similar questionnaires in the two surveys. The participants’ blood pressure levels were also measured.Results: From 2009 to 2016, the prevalence of hypertension substantially increased from 28.4% to 39.5% (P < 0.01), and awareness and control rose from 42.2 and 25.8% to 53.1 (P < 0.01) and 30.6% (P < 0.05), respectively. Although people with a higher education level also had higher awareness and control rates than the lower education level ones, there were no conspicuous differences in the improvement of awareness and control between publics with different education levels over the 7 years studied. Increases were observed in both rates of awareness and control in people with a high level of income (P < 0.01). However, only the awareness rate increased in participants with a low level of income. Furthermore, the prevalence (P < 0.01) and treatment (P < 0.05) of hypertension were higher in the Han people than in ethnic minorities.Conclusions: Individual SES has clear associations with trends in the prevalence, awareness, and control of hypertension. Future interventions to improve hypertension prevention and control should be tailored to address individual SES.
Src is Essential for the Endosomal Delivery of the FGFR4 Signaling Complex in Hepatocellular Carcinoma
Authors: Shin Ji-Yon , Ahn Sung-Min
Published: December 2020

BackgroundHepatocytes usually express fibroblast growth factor receptor 4 (FGFR4), but not its ligand, fibroblast growth factor 19 (FGF19). A subtype of hepatocellular carcinoma (HCC) expresses FGF19, which activates the FGFR4 signaling pathway that induces cell proliferation. FGFR4 inhibitors that target this mechanism are under clinical development for the treatment of HCCs with FGF19 amplification or FGFR4 overexpression. Src plays an essential role in the FGFR1 and FGFR2 signaling pathways. However, it is yet to be understood whether Src has any role in the FGF19-FGFR4 pathway in HCCs. In this study, we aimed to elucidate the role of Src in the FGF19-FGFR4 axis in HCC.Methods3 HCC cell lines expressing both FGF19 and FGFR4 were selected. The expression of each protein was suppressed by siRNA treatment, and the activity-regulating relationship between FGFR4 and Src was investigated by westernblot. Co-immunoprecipitation was performed using the FGFR4 antibody to identify the endosomal complex formation and receptor endocytosis. The intracellular migration pathways of the endosomal complex were observed by immuno-fluorescence and nuclear co-immunoprecipitation. Dasatinib and BLU9931 were used for cytotoxicity comparison.ResultsFGFR4 modulates the activity of Src and Src modulates the expression of FGFR4, showing a mutual regulatory relationship. FGFR4 activated by FGF19 formed an endosomal complex with Src and STAT3 and moved to the nucleus. However, when Src was suppressed, the formation of the endosomal complex was not observed. FGFR4 was released from the complex transferred into the nucleus and the binding of Src and STAT3 was maintained. Dasatinib showed cytotoxic results comparable to BLU9931. The results of our study demonstrated that Src is essential for the nuclear transport of STAT3, as it induces the endosomal delivery of FGFR4 in FGF19-expressing HCC cell lines.ConclusionsWe found that Src is essential for the endosomal delivery of the FGFR4 signaling complex in HCC. Our findings provide a scientific rationale for repurposing Src inhibitors for the treatment of HCCs in which the FGFR4 pathway is activated.
Aortic Root Enlargement in patients with small aortic annulus undergoing double valve replacement. A retrospective Comparative cohort study
Authors: Mubarak Yasser Shaban , Abdeljawad Ahmed Abdel Rahman
Published: December 2020

Objectives
Small Aortic Annulus (AA) is big issue during Aortic Valve Replacement (AVR) necessitating replacement of inappropriate-sized prostheses especially during Double Valve Replacement (DVR). Despite that small aortic valve prostheses can lead to Prosthesis-Patient Mismatch (PPM), there remains reluctance to perform aortic root enlargement (ARE) procedures fearing from morbidity and mortality. We evaluate clinical and echocardiographic outcomes in patients with small AA undergoing DVR.
Methods
The study included 100 consecutive patients underwent DVR for combined rheumatic aortic and mitral valve diseases, between June 2016 and November 2020. Only (50) patients had ARE with DVR. ARE was performed using an autologous or bovine pericardium or Dacron patch by Nick′s or Manouguian procedures. The estimated post-operative end-points were mortality, effective orifice areas (EOA), mean aortic pressure gradient and valve-related complications. The least post-operative follow-up period was 6 months.
Results
The study included 30 male and 70 female patients with mean age of 45 ± 10 years, body surface area (BSA) of 1.6 ± 0.50 m2, aortic annulus diameter was 20 ± 0.4 mm, EOAi was 0.80 ± 0.50 cm2/m2, and aortic mean gradient (PG) 80 ± 40 mm Hg. During follow-up period, there was a mild paravalvular leak (1%) with, (1%) heart block, and residual mean PG on prosthetic aortic valve with all cases of DVR alone.
Conclusion
Enlargement of aortic root by Nick′s or Manouguian technique is safe and effective in patients with small aortic annulus undergoing double valve replacements.
Validation of the Arabic version of the EORTC Colorectal (CR29) module in Moroccan colorectal cancer patients
Authors: Alami Yacir El , Bachri Houda , Essangri Hajar , Benamer Said , Benkabbou Amine , Mohsine Raouf , Majbar Mohammed Anass , Souadka Amine
Published: December 2020

Purpose

Quality of life outcomes are a focal endpoint of cancer treatment strategies which can be evaluated through patient-related outcome measures (PROMs). We aim to validate the Moroccan Arabic version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Colorectal cancer patients (EORTC QLQ CR-29).
Methods

Following translation to Moroccan Arabic, the QLQ CR-29 was administered to patients treated for colorectal cancer (CRC) in the national institute of oncology. Psychometric properties were tested by measuring Cronbach’s alpha coefficient for reliability and Intraclass correlation coefficient(ICC) to examine test-retest reproducibility. The multitrait-scaling analysis was performed to demonstrate the validity of the instrument and the ability to discriminate between different patient groups was tested using known-groups comparison.
Results

In total, 221 patients were included in our study and 34 patients completed the questionnaire twice. The urinary Frequency scale and Stool Frequency scale had good internal consistency with alpha Cronbach coefficients of 0,79 and 0,83 respectively, whereas the coefficient was moderately lower for the Blood and Mucus in Stool scale (0,61) and the Body Image scale (0,67). The ICCs ranged from 0,88 to 1 indicating good to excellent reproducibility. In multitrait scaling analyses, the criterion for item convergent and divergent validity was satisfactory. The known-group comparison showed statistically significant differences between patients according to age, gender, stoma status, tumor location, and radiotherapy.
Conclusion

The Moroccan Arabic version of the EORTC QLQ-CR29 is a valid and reliable tool and can be used for research and clinical purposes in Moroccan CRC patients.
EEG characteristics of mechanically ventilated critically ill patients at high risk of delirium
Authors: Eskioglou E. , Iaquaniello C. , Alvarez V. , Rüegg S. , Schindler K. , Rossetti A. O. , Oddo M.
Published: December 2020

Background

Neurophysiological exploration of ICU delirium is limited. Here, we examined EEG characteristics of medical-surgical critically ill patients with new onset altered consciousness state at high risk for ICU delirium.
Methods

Pre-planned analysis of non-neurological mechanically ventilated medical-surgical ICU subjects, who underwent a prospective multicenter randomized, controlled EEG study (NCT03129438, April 2017-November 2018). EEG characteristics, according to the 2012 ACNS nomenclature, included background activity, rhythmic periodic patterns/epileptic activity, amplitude, frequency, stimulus-induced discharges, triphasic waves, reactivity and NREM sleep. We explored EEG findings in delirious vs. non-delirious patients, specifically focusing on presence of burst-suppression and rhythmic periodic patterns (ictal-interictal continuum), and epileptiform activity (ictal EEG).
Results

We analyzed 91 patients (median age, 66 years) who underwent EEG because of new onset altered consciousness state at a median 5 days from admission; 42 patients developed delirium (46%). Burst-suppression (10 vs. 0%, p = 0.02), rhythmic/periodic patterns (43% vs. 22%, p = 0.03) and epileptiform activity (7 vs. 0%, p = 0.05) were more frequent in delirious vs. non-delirious patients. The presence of at least one of these abnormal EEG findings (32/91 patients; 35%) was associated with a significant increase in the likelihood of delirium (42 vs. 15%, p = 0.006). Cumulative dose of sedatives and analgesics, as well as all other EEG characteristics, did not differ significantly between the two groups.
Conclusion

In mechanically ventilated non-neurological critically ill patients with new onset alteration of consciousness, EEG showing burst-suppression and/or ictal-interictal continuum findings indicates a higher risk of ICU delirium, independently of sedation and analgesia.
Implications of Cardiac Markers in Risk-Stratification and Management for COVID-19 Patients
Authors: Li Pengping , Wu Wei , Zhang Tingting , Wang Ziyu , Li Jie , Zhu Mengyan , Liang Yuan , You Wenhua , Li Kening , Ding Rong , Huang Bin , Wu Lingxiang , Duan Weiwei , Han Yi , Li Xuesong , Tang Xin , Wang Xin , Wang Qianghu , Xia Xinyi , Ji Yong , chen hongshan
Published: December 2020

Background

COVID-19 has resulted in high mortality worldwide. Information regarding cardiac markers for precise risk-stratification is limited. We aim to discover a sensitive and reliable early-warning biomarker for optimizing management and improving the prognosis of COVID-19 patients.
Methods

A total of 2,954 consecutive COVID-19 patients who were receiving treatment from the Wuhan Huoshenshan Hospital in China from February 4 to April 10 were included in this selected retrospectively cohort. Serum levels of cardiac markers were collected after admission. Coronary artery disease diagnosis and survival status were also recorded. Single-cell RNA-sequencing of cells was performed to analyze SARS-CoV-2 receptor expression.
Results

Among 2,954 COVID-19 patients in the final analysis, the median age was 60 years (50–68 years), 1,461 (49.5%) were female, and 1,515 (51.3%) were severe/critical. Compared to mild/moderate (1,439, 48.7%) patients, severe/critical patients showed significantly higher levels of cardiac markers within the first week after admission. In severe/critical COVID-19 patients, those with abnormal serum levels of brain natriuretic peptide (42 [24.6%] vs 7 [1.1%]), hs-TNI (38 [48.1%] vs 6 [1.0%]), α- HBDH (55 [10.4%] vs 2 [0.2%]), CK-MB (45 [36.3%] vs 12 [0.9%]), and LDH (56 [12.5%] vs 1 [0.1%]) had a significantly higher mortality rate compared to patients with normal levels. The same trend was observed in the ICU admission rate. Severe/critical COVID-19 patients with pre-existing coronary artery disease (165/1,155 [10.9%]) had more cases of abnormal brain natriuretic peptide (52 [46.5%] vs 119 [16.5%]), hs-TNI (24 [26.7%] vs 9.6 [%], α- HBDH (86 [55.5%] vs 443 [34.4%]), CK-MB (27 [17.4%] vs 97 [7.5%]), and LDH (65 [41.9%] vs 382 [29.7%]), when compared with those without coronary artery disease. There was enhanced SARS-CoV-2 receptor expression in coronary artery disease compared with healthy controls. From regression analysis, patients with elevated BNP levels were at a higher risk of death (hazards ratio, 1.001 [95% CI, 1.0003–1.002]).
Conclusions

COVID-19 patients with pre-existing coronary artery disease represented a higher abnormal percentage of cardiac markers, accompanied by high mortality and ICU admission rate. Brain natriuretic peptide is an effective biomarker for risk assessment in COVID-19 patients with or without pre-existing CAD.