bluuebunny/crossref_metadata_2025 huggingface dataset:
circEPS15 Overexpression in Hepatocellular Carcinoma Modulates Tumor Invasion and Migration
Authors: Tian Maolin , Li Gang , Jiang Bin , Abuduhaibaier Sadula , Xiu Dianrong , Yuan Chunhui , Bing Yuntao
Published: August 2020

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Recent evidence indicates that circular RNAs (circRNAs) play important roles in tissue development, gene regulation, and carcinogenesis. However, whether circRNAs are involved in HCC progression and encode functional proteins remains largely unknown.Methods: Circular RNA microarrays were performed using three pathologically diagnosed HCC samples and their paired adjacent normal liver tissues. Cell invasion, migration, cell cycle, and apoptosis after circRNA overexpression were measured using a transwell culture system, a wound healing assay, and flow cytometry . Full-length, mutated, and truncated sequences of circEPS15 with a FLAG tag were inserted inside a circular expression vector. Western blotting was used to confirm circEPS15 expression and the requirement of internal ribosomal entry site (IRES) elements within the circRNA. The miRNA and mRNA expression profiles were obtained by analyzing data retrieved from The Cancer Genome Atlas (TCGA) database. We then constructed a ceRNA network of mRNAs, miRNAs, and circEPS15. Using tissue samples from own patients, we also verified certain analytical results with quantitative real-time PCR (qRT-PCR).Results: The expression of circEPS15 was downregulated in HCC tissues, and the survival curves showed that low circEPS15 levels were associated with poor overall survival in HCC patients. Overexpression of circEPS15 suppressed tumor invasion and migration by inhibiting the TJP1/CDH2/VIM signaling pathway and retarded cell cycle progression, but it had no effect on cell apoptosis. ceRNA analysis and qRT-PCR showed that there might be a circRNA (circEPS15)-miRNA (miR-24-3p)-mRNA (CIDEA) network in HCC. The spanning junction open reading frame in circEPS15 driven by IRES encoded a novel protein.Conclusions: Endogenous circEPS15 plays a novel role in repressing HCC through the ceRNA network and encoding a functional protein.
An Ultra-low Magnetic Field Thermal Demagnetizer for High-precision Paleomagnetism
Authors: Qin Huafeng , Zhao Xiang , Liu Shuangchi , Paterson Greig , Jiang Zhaoxia , Cai Shuhui , Li Jinhua , Liu Qingsong , Zhu Rixiang
Published: August 2020

Thermal demagnetization furnaces are widely used paleomagnetic facilities for progressive removal of naturally acquired magnetic remanence or the imparting of well controlled laboratory magnetization. An ideal thermal demagnetizer should maintain “zero” magnetic field in the sample chamber during thermal treatments. However, magnetic field noises, including the residual magnetic fields of the construction material and the induced fields caused by the alternating current (AC) in the heating element are always present, which often greatly contaminate the paleoamgnetic results at the elevated temperatures or for the magnetically weak samples. Here, we designed a new structure of heating wire named named straight core solenoid to develop a new demagnetization furnace with ultra-low magnetic field noise. Simulation and practical measurement show that the heating current magnetic field can be greatly reduced by using the new technology. Thermal demagnetization experiments demonstrate that the new demagnetizer can yield low noise results even for weakly magnetic samples.
To Include, or Not Include, that is the Question: An Empirical Analysis of Dealing with Patients who are Lost to Follow-up when Developing Prognostic Models Using a Cohort Design
Authors: Reps Jenna M , Rijnbeek Peter , Cuthbert Alana , Ryan Patrick B , Pratt Nicole , Schuemie Martijn J
Published: August 2020

Background: Researchers developing prediction models are faced with numerous design choices that may impact model performance. One of the main decisions is how to include patients who are lost to follow-up. In this paper we perform a large-scale empirical evaluation investigating the impact of this decision. In addition, we aim to provide guidelines for how to deal with loss to follow-up. Methods: We generate a synthetic dataset with complete follow-up and simulate loss to follow-up based either on random selection or on selection based on comorbidity. We investigate four simple strategies for developing models using data containing some patients with loss to follow-up. Three strategies employ a binary classifier with data that: i) include all patients (including those lost to follow-up), ii) exclude all patients lost to follow-up or iii) only exclude patients lost to follow-up who do not have the outcome before being lost to follow-up. The fourth strategy uses a survival model with data that include all patients. In addition to our synthetic data study, we empirically evaluate the discrimination and calibration performance of these strategies across 21 prediction problems using real-world data. Results: The synthetic data study results show that excluding patients lost to follow-up can introduce bias when loss to follow-up is common and does not occur at random. However, when loss to follow-up was completely at random, the choice of addressing it had negligible impact on the model performance. Our empirical results showed that the four design choices investigated to deal with loss to follow-up resulted in comparable performance when the time-at-risk was 1-year, but demonstrated differential bias when we looking into 3-year time-at-risk. Removing patients who are lost to follow-up before the outcome but keeping patients who are loss to follow-up after the outcome can bias a model and should be avoided. Conclusion: Based on this study we therefore recommend i) developing models using data that includes patients that are lost to follow-up and ii) evaluate the discrimination and calibration of models twice: on a test set including patients lost to follow-up and a test set excluding patients lost to follow-up.
Rhenium N-heterocyclic Carbene Complexes Block Growth of Aggressive Cancers by Inhibiting FGFR- and SRC-Mediated Signalling
Authors: Domenichini Alice , Casari Ilaria , Simpson Peter V , Desai Nima Maheshkumar , Chen Lingfeng , Dustin Christopher , Edmands Jeanne S , Vliet Albert van der , Mohammadi Moosa , Massi Massimiliano , Falasca Marco
Published: August 2020

Background: Platinum-based anticancer drugs have been at the frontline of cancer therapy for the last 40 years, and are used in more than half of all treatments for different cancer types. However, they are not universally effective, and patients often suffer severe side effects because of their lack of cellular selectivity. There is therefore a compelling need to investigate the anticancer activity of alternative metal complexes. Here we describe the potential anticancer activity of rhenium-based complexes with preclinical efficacy in different types of solid malignancies.Methods: Kinase profile assay of rhenium complexes. Toxicology studies using zebrafish. Analysis of the growth of pancreatic cancer cell line-derived xenografts generated in zebrafish and in mice upon exposure to rhenium compounds.Results: We describe rhenium complexes which block cancer proliferation in vitro by inhibiting the signalling cascade induced by FGFR and Src. Initially, we tested the toxicity of rhenium complexes in vivo using a zebrafish model and identified one compound that displays anticancer activity with low toxicity even in the high micromolar range. Notably, the rhenium complex has anticancer activity in very aggressive cancers such as pancreatic ductal adenocarcinoma and neuroblastoma. We demonstrate the potential efficacy of this complex via a significant reduction in cancer growth in mouse xenografts.Conclusions: Our findings provide a basis for the development of rhenium-based chemotherapy agents with enhanced selectivity and limited side effects compared to standard platinum-based drugs.
NOX1 Inhibition Attenuates the Development of a Pro-Tumorigenic Environment in Experimental Hepatocellular Carcinoma
Authors: Vandierendonck Astrid , Degroote Helena , Vanderborght Bart , Devisscher Lindsey , Vlierberghe Hans Van
Published: August 2020

Background The poor prognosis of advanced HCC and limited efficacy of current systemic treatments emphasize the need for new or combined targeted therapies. The development of HCC is a multistage process in which liver injury appears in a complex microenvironment associated with oxidative stress. NOX enzymes are the main source of ROS during hepatocarcinogenesis and NOX1 in particular has shown correlation with poor prognosis of HCC patients. This study evaluates the effect of pharmacological NOX1 inhibition on the development and progression of HCC and its effect on the tumor microenvironment.Methods The in vitro cytotoxic effects of the NOX1 inhibitor GKT771 (Genkyotex) on human Huh7 and Hep3B and murine Hepa1-6 HCC cell lines, and murine macrophages were evaluated via MTT, LDH activity and CaspGlo® assays. In order to induce in vivo HCC, male SV129 wild-type mice received weekly IP injections of diethylnitrosamine (DEN) (35 mg/kg) for 20-25 weeks. Mice were treated with vehicle or GKT771 (30 mg/kg) via oral gavage. Treatment duration and frequency (daily or twice daily) varied in the preventive and therapeutic studies. mRNA transcript levels in the tumor and liver tissue were determined by RT-qPCR. Fibrosis was visualized by Sirius Red staining and quantified by the Metavir​ score. Results A concentration-dependent reduction in cellular activity of the human HCC cell lines without cytotoxicity was observed. GKT771 treatment reduced LPS-induced pro-inflammatory bone-marrow derived macrophage polarization. DEN injections resulted in 100% tumor formation and the induction of HCC markers which could be reduced by twice daily dosing of GKT771 at early onset of advanced HCC. DEN-induced HCC resulted in an upregulation of pro-inflammatory, angiogenic and fibrotic markers which was less pronounced in GKT771 treated mice in all treatment regimens. In line, liver fibrosis was induced in HCC mice and this to a lesser extend upon GKT771 treatment.Conclusion NOX1 inhibition showed to be safe and well tolerated and was able to attenuate the induction of a pro-inflammatory, angiogenic and pro-fibrotic microenvironment suggesting that this might be a promising adjuvant therapeutic strategy in the treatment of advanced HCC.
HPAC Pretreatment Facilitates Enzymatic Hydrolysis of Softwood
Authors: Lee Dae-Seok , Lee Yoon-Gyo , Cho Eun Jin , Song Younho , Bae Hyeun-Jong
Published: August 2020

Background: Woody plants with high glucose content are alternative bioresources for the production of biofuels and biochemicals. Various pretreatment methods may be used to reduce the effects of retardation factors such as lignin interference and cellulose structural recalcitrance on the degradation of the lignocellulose material of woody plants. Results: Here, a hydrogen peroxide-acetic acid (HPAC) pretreatment was used to reduce the lignin content of several types of woody plants, and the effect of the cellulose structural recalcitrance on the enzymatic hydrolysis was analyzed. The cellulose structural recalcitrance and the degradation patterns of the wood fibers in the xylem tissues of Quercus acutissima (hardwood) resulted in greater retardation in the enzymatic saccharification than those in the tracheids of Pinus densiflora (softwood). In addition to the HPAC pretreatment, application of supplementary enzymes (7.5 FPU cellulose for 24 hours) further increased the hydrolysis rate of P. densiflora from 61.42% to 91.94% whereas the same effect was not observed for Q. acutissima. Also, it was observed that endoxylanase synergism significantly affects the hydrolysis of P. densiflora. However, this synergistic effect was lower for other supplementary enzymes. The maximum concentration of the reducing sugars produced from 10% softwood was 89.17 g L-1 in 36 hours of hydrolysis with 15 FPU cellulase and other supplementary enzymes. Approximately 80 mg mL-1 of reducing sugars was produced with the addition of 7.5 FPU cellulase and other supplementary enzymes after 36hours, achieving rapid saccharification. Conclusion: HPAC pretreatment thus removed the interference of lignin, reduced structural recalcitrance of cellulose in the P. densiflora, and thereby enabled rapid saccharification of the woody plants including a high concentration of insoluble substrates with only low amounts of cellulase. HPAC pretreatment may thus be a viable as an alternative for the cost-efficient production of biofuels or biochemicals from softwood plant tissues.
COVID-19 and Radiation Oncology: a 2-phase planning in a mono-institutional experience in Central Italy
Authors: Caravatta Luciana , Rosa Consuelo , Sciascio Maria Bernadette Di , Scaringi Andrea Tavella , Pilla Angelo Di , Ursini Lucia Anna , Taraborrelli Maria , Vinciguerra Annamaria , Augurio Antonietta , Tommaso Monica Di , Trignani Marianna , Nuzzo Marianna , Falco Maria Daniela , Nicola Andrea De , Adorante Nico , Patani Fabiola , Centofanti Giuseppe , Gasparini Lucrezia , Fasciolo David , Guglielmo Fiorella Cristina Di , Bonfiglio Cecilia , Borgia Marzia , Caravaggio Gabriella , Marcucci Stefano , Turchi Consalvo , Mancinelli Domenico , Sartori Stephanie , Schael Thomas , Muraglia Angelo , Caputi Sergio , D’Amario Claudio , Verì Nicoletta , Genovesi Domenico
Published: August 2020

Background: COVID-19 in Italy has led to a reorganization of hospital activities with risks of cancer treatments discontinuity. We report a management model in the two phases of the COVID-19 emergency, lockdown phase I and post-lockdown phase II.Methods: Actions were planned in the two phases: workloads of the visits and radiotherapy planning, dedicated routes, measures for triage areas, management of suspected and positive COVID-19 cases, personal protective equipment, environments andintra-institutional meetings and tumor boards management.Results: Comparing our radiotherapy activity in the period March 9- May 4, 2019 with the same period of 2020 in full phase I of the COVID-19 emergency, no changes were observed.First radiotherapy visits, Simulation Computed Tomography and Linear Accelerators treatments were 123, 137 and 151 in 2019 respect to 121, 135 and 170 in 2020.There were no cases of COVID-19 positivity recorded either in patients or in healthcare professionals who were all negative to the buffers performed.Conclusions: The model planned in our experience in both phases has guaranteed continuity of radiotherapy treatments without workload reduction nor treatment interruption ensuring safety of cancer patients, environments and staff.
Modeling and Spatialization of Biomass and Carbon Stock Using Lidar Metrics in Tropical Dry Forest, Brazil: Preliminary Results
Authors: Lima Robson Borges de , Oliveira Cinthia Pereira de , Ferreira Rinaldo Luiz Caraciolo , Silva José Antônio Aleixo da , Silva Emanuel Araújo , Silva Anderson Francisco da , Lucena Josias Divino Silva de , Santos Nattan Adler Tavares dos , Lopes Iran Jorge Corrêa , Pessoa Mayara Maria de Lima , Melo Cybelle Laís Souto-Maior Sales de
Published: August 2020

Background: In recent years, with the growing environmental concern regarding climate change, there has been a search for efficient alternatives in indirect methods for studies on the quantification of biomass and forest carbon stock. In this article, we seek to obtain pioneering and preliminary results of estimates of biomass and carbon using data from conventional forest inventory and LiDAR technology in a dry tropical forest in Brazil. We used data from conventional forest inventory in two areas together with data from the LiDAR overflight, generating local biomass estimates from a developed local equation and the carbon levels obtained from local species. With data from LiDAR technology, we extracted the metrics from the point cloud and were used as an independent variable. For the construction of the biomass and carbon allometric models per hectare, we approach three types of models for data analysis: Multiple linear regression with Principal Components - PCA, Conventional multiple linear regression and Multiple linear regression with Stepwise, the generated equations were analyzed by comparisons of statistical criteria (R²aj and RMSE). After selecting the best equation, we generate the carbon estimates by area by assessing the plot level.Results: The best fit TAGB and TAGC model was the multiple linear regression with Stepwise, concluding, then, that LiDAR data can be used to estimate biomass and total carbon in dry tropical forest, proven by an adjustment considered in the models employed, with a significant correlation between the LiDAR metrics.Conclusions: Our preliminary results provide important information about the spatial distribution of TAGB and TAGC in the study area, which can be used to manage the reserve for optimal carbon sequestration.
Effective Elimination of Lymphoma Cells in Stromal Microenvironment by Double Impact on ROS and ATP Metabolism Using Auranofin
Authors: Yang Mengqi , Liu Panpan , Chen Huanting , Yang Jing , Wen Shijun , Hu Yumin , Lu Wenhua , Chen Ping , Hou Guoxin , Jiang Weiye , Jiang Wenqi , Liu Jinyun , Huang Peng
Published: August 2020

Background

Protection of cancer cells by the stromal microenvironment is an important drug-resistant mechanism in vivo, and poses a major challenge in cancer treatment. Based on our recent findings that auranofin (AF), an anti-rheumatic drug known to inhibit thioredoxin reductases (TrxR), was effective against several cancer models in vivo, this study tested the ability of AF to eliminate cancer cells in the tumor stromal microenvironment and investigated the underlying mechanisms.
Methods

Cytotoxic effect of AF on 33 cancer cell lines in vitro was determined by MTS assay to identify AF- sensitive cancer cells. Further cytotoxic effect of AF on the identified cancer cells was determined by flow cytometry analysis in stromal co-culture system. Mitochondrial bioenergetics assays using the Seahorse XF24 analyzer, mass spectrometry analyses, and enzyme activity assays were used in the mechanistic study. For in vivo study, lymphoma xenograft models were utilized to evaluate the in vivo therapeutic activity of AF in mice.
Results

We unexpectedly found that AF exhibited higher therapeutic activity against lymphoma cells in stromal microenvironment compared to lymphoma cell treated with AF without stromal cells. Mechanistic study showed that AF impacted energy metabolism by inhibiting the glycolytic enzyme GAPDH and suppressing mitochondrial electron transport complex II, leading to ATP depletion. Surprisingly, inhibition of TrxR seemed not critical for its anticancer activity, as genetic silencing of TrxR1 and TrxR2 did not significantly affect cell viability. Co-culture of lymphoma cells with stromal cells enhanced the expression of TrxR1, which became an ROS-generating molecule when interacting with AF. The AF-induced ATP depletion plus ROS generation together effectively killed the cancer cells in stromal microenvironment, and significantly suppressed tumor growth in mice bearing mantle cell lymphoma xenografts.
Conclusions

Our study reveals a novel mechanism by which AF eliminates cancer cells in tumor microenvironment by impacting cancer metabolism and promoting ROS generation, and suggests a possibility to repurpose this anti-rheumatic drug for treatment of lymphoma and overcome drug resistance in stromal microenvironment.
Hsa_circ_0004831 Serves as a Blood-Based Prognostic Biomarker for Colorectal Cancer and its Potentially circRNA-miRNA-mRNA Regulatory Network Construction
Authors: Xing Linlin , Xia Mengyan , Jiao Xin , Fan Ling
Published: August 2020

Background: Colorectal cancer (CRC) is a common malignant tumor with unsatisfactory overall prognosis. CircRNAs could be promosing prognostic biomarkers in cancers, and play important role in the process of tumorigenesis and progression. Here, we explored the role of hsa_circ_0004831 in blood extracellular vesicles and its prognostic value in CRC. Methods: The circRNA and mRNA expression level matrix in extracellular vesicles of CRC and normal samples were obtained from the exoRBase database. The corresponding miRNA expression level matrix in extracellular vesicles was downloaded from the BBCancer database. Differentially expressed circRNAs, miRNAs and mRNAs were identified using the limma package of R software at the cut-off criteria of fold change (FC) > 2 and adj. p < 0.05. RT-qPCR assay was conducted to measure hsa_circ_0004831 expression level in CRC blood samples. A circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 was constructed based on competitive endogenous RNA mechanism and differentially expressed genes. The mRNAs co-expressed with hsa_circ_0004831 were screened at the cut-off criteria of pearson |R| > 0.3 and p < 0.05. Gene set enrichment analysis (GSEA) based on co-expressed mRNAs was used to explore the potential molecular function of hsa_circ_0004831. Results: Differentially expressed circRNAs, miRNAs and mRNAs were identified and hsa_circ_0004831 had a FC value of 3.92 in CRC blood extracellular vesicles. The RT-qPCR assay showed that the hsa_circ_0004831 was up-regulated in CRC blood samples. The overall survival analysis found that high expression of hsa_circ_0004831 was linked with poorer prognosis. Finally, a circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 was constructed based on down-regulated miR-4326 and 12 up-regulated mRNAs. GSEA indicated that mRNAs co-expressed with hsa_circ_0004831 were involved in EMT, WNT and p53 signaling pathways.Conclusions: The study confirmed the up-regulation of hsa_circ_0004831 in CRC, and it may act as a vital prognostic biomarker. The circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 could be used to uncover the tumorigenesis and progression of CRC.
SFRP1 Decline in Non-Small Cell Lung Cancer (NSCLC) and its Importance in Prognoses
Authors: Zhao Yue , Kong Xiangjun , Wang Hongbing
Published: August 2020

Background: In the present study, we sought to detect the expression of secreted fizzled-related protein-1 (SFRP1) and investigate its role in the progression and prognosis of patients with non-small cell lung cancer (NSCLC). Methods: The expression of SFRP1 at both mRNA and protein level were examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Immunohistochemistry analysis, respectively. The relationship between SFRP1 expression and clinical factors of patients with NSCLC was analyzed by chi-square test. Transwell assay was conducted to determine the influences of SFRP1 on migratory and invasive of NSCLC cells. Kaplan-Meier analysis was used to describe the overall survival of NSCLC patients. Cox regression analysis was conducted to estimate the prognostic value of SFRP1 in NSCLC.Results: The expression of SFRP1 was down-regulated in NSCLC tissues compared to that in adjacent normal controls both at mRNA and protein level (P<0.05). And the low SFRP1 expression was related to the distant metastasis, vascular invasion and TNM stage. The overexpression of SFRP1 in vitro significantly inhibited the migration and invasion of NSCLC cells. The overall survival of patients with high SFRP1 expression was was proved to be longer than those with low expression (log rank test, P<0.001). In addition, univariate and multivariate analyses suggested that SFRP1 was an independent prognostic molecule marker for NSCLC patients. Conclusion: Taken together, our findings indicated that the decreased of SFRP1 could influence the cell migration and invasion as well as be regarded as an independent prognostic marker in NSCLC.
Development an Immune-Associated LncRNA Prognostic Index for Papillary Thyroid Cancer
Authors: Mao Min , Huang Rong-zhi , Yu Zhu , Zheng Jie , Liang Hai-qi , Li Cheng , Zeng Rong-zhi , Li Jie-hua
Published: August 2020

BACKGROUND: Papillary thyroid cancer (PTC) is the most common pathological type of thyroid cancer and its incidence is still on the rise worldwide. Our study aimed to provide an understanding of papillary thyroid cancer in immunological aspects and prompt its clinical diagnosis and treatment.METHODS: We obtained RNA-FPKM data and clinical data of papillary thyroid cancer (PTC) samples from the TCGA data portal. Immune-related genes (IRGs) were selected from Molecular Signatures Database v7.0. The immune-related lncRNAs were identified by constructing DELs-IRGs co-expression networks. Cox regression and Kaplan-Meier methods were used to construct immune-related lncRNAs prognosis index (IRLPI) and analyze the impact of IRLPI on overall survival. Gene Set Enrichment Analysis (GSEA) was performed by clusterProfiler R package to explore the potential molecular mechanism in TCGA dataset. The relationship between immune cell types and IRLPI were explored by using Pearson correlation analysis.RESULTS: A total of 478 primary PTC samples were collected for the analysis. 162 immune-related lncRNAs were identified in immune-lncRNAs co-expression network. And 7 lncRNAs were extracted to develop the IRLPI. Patients with high-IRLPI showed poor survival probability (P =0.00052) and IRLPI was identified as an independent prognostic factor (HR: 2.329, 95%CI: 1.481-2.664, p =2.54e-4). ROC curve declared a promising prognosis ability of IRLPI. PCA proved that IRLPI reflected different immune environment and biological processes. GSEA indicated that immune system development is the main different biological process between high- and low-IRLPI group. Furthermore, IRLPI was proved that it related with multiple immune cells and immune responses by Pearson correlation analysis.CONCLUSION: Our results showed that immune-related lncRNAs prognosis index (IRLPI) could serve as a potential prognostic model in papillary thyroid cancer and play an important role in the immunotherapies and surveillance of PTC.
β-Lactamase-Mediated Resistance in MDR-Pseudomonas Aeruginosa from Qatar
Authors: Ahmed Mazen A. Sid , Khan Faisal Ahmad , Sultan Ali A. , Söderquist Bo , Ibrahim Emad Bashir , Jass Jana , Omrani Ali S.
Published: August 2020

Background: Anti-pseudomonal b-lactam antibiotics are of paramount importance in the management of Pseudomonas aeruginosa infections. The distribution of b-lactam resistance genes in P. aeruginosa is often closely related to the distribution of certain high-risk international clones. In the present study whole-genome sequencing (WGS) was used to identify the predominant sequence types (STs) and b-lactamase genes in clinical isolates of multidrug-resistant (MDR)-P. aeruginosa from QatarMethods: Microbiological identification and susceptibility tests were performed by automated BD PhoenixTM system and manual Liofilchem MIC Test Strips. Seventy-five MDR-P. aeruginosa isolates were subsequently processed for WGS. Results: Among 75 MDR-P. aeruginosa isolates; the largest proportions of susceptibility were to ceftazidime-avibactam (n=36, 48%), followed by ceftolozane-tazobactam (30, 40%), ceftazidime (n=21, 28%) and aztreonam (n=16, 21.33%). Almost all isolates possessed Class C and Class D b-lactamases (n=72, 96% each), while metallo-β-lactamases were detected in 20 (26.67%) isolates. Eight (40%) metallo-β-lactamases producers were susceptible to aztreonam and did not produce any concomitant extended-spectrum b-lactamases. The most frequent sequence types identified were ST235 (n=16, 21.33%), ST357 (n=8, 10.67%), ST389 and ST1284 (6, 8% each). Nearly all ST235 (15/16; 93.75%) were resistant to all tested b-lactams.Conclusion: MDR-P. aeruginosa isolates from Qatar are highly resistant to antipseudomonal b-lactams. Global high-risk STs are predominant in Qatar and their associated multi-resistant phenotypes are a cause for considerable concern. The molecular epidemiology trends of P. aeruginosa should be surveillance at national levels to track their trends and institute the appropriate control strategies.
Understanding Patient Outcomes to Develop a Multimobidity Adapted Patient-reported Outcomes Measure: A Qualitative Description of Patient and Provider Perspectives.
Authors: Sasseville Maxime , Chouinard Maud-Chrisitne , Fortin Martin
Published: August 2020

Background: Understanding the outcomes of multimorbidity-adapted interventions from the perspective of patients and providers is essential to research and practice in this population, but is currently lacking. The purpose of this study was to describe the outcomes of patient-centred interventions for people with multimorbidity from the patients’ and providers’ perspectives.Methods: This study followed a qualitative descriptive design. Nine patients with multimorbidity and 18 healthcare professionals (nurses, general practitioners, nutritionists, and physical and respiratory therapists), participating in a multimorbidity-adapted intervention in primary care were recruited. Data was collected using semi-structured interviews with 12 open-ended questions. Triangulation of disciplines among interviewers, research team debriefing, data saturation assessment and iterative data collection and analysis ensured a rigorous research process.Results: Outcome constructs described by participants covered a wide range of themes and were grouped into seven outcome domains: Health Management, Functional Status, Physical Symptoms, Psychosocial Health, Health-oriented Behaviours, General Health and Health Services. The description of constructs by stakeholders provides valuable insight on how outcomes are experienced and worded by patients in that context.Conclusion: Stakeholders described a wide range of outcome constructs, which were relevant to and observable by patients and were in line with the clinical reality. The description provides a portrait of multimorbidity-adapted intervention outcomes that are significant for the selection and development of clinical research outcome measures.
Femoral artery cannulation combined with axillary artery cannulation is safe for Stanford type A aortic dissection
Authors: Huang Ling-chen , Xu Qi-chen , Chen Dao-zhong , Dai Xiao-fu , Chen Liang-wan
Published: August 2020

Background
The optimal cannulation strategy in surgery for Stanford type A aortic dissection is critical to the patients’ survival, but remains controversial. Different cannulation strategies have their own advantages and drawbacks during cardiopulmonary bypass. Our center used femoral and axillary artery cannulation for Stanford type A aortic dissection. The purpose of this study was to review and clarify the clinic outcome of femoral artery cannulation combined with axillary artery cannulation for the treatment of type A aortic dissection.
Methods
We performed a retrospective study that included 327 patients who were surgically treated for type A aortic dissection in our institution from January 2017 to June 2019.Using femoral and axillary artery cannulation to establish cardiopulmonary bypass in patients with type A aortic dissection. The demographics data and surgical data, clinical results of the patients were calculated.
Results
Femoral artery combined with axillary artery cannulation was technically successful in 327 patients. The cardiopulmonary bypass time was 141.60 ± 34.89 minutes, and the selective antegrade cerebral perfusion time was 14.94 ± 2.76 minutes. The early mortality was 3.06%. The incidence of permanent neurologic dysfunction was 0.92%. Sixteen patients had post-operative renal insufficiency and five patients with liver failure. Two patients ended up with paraplegia.
Conclusion
Femoral artery combined with axillary artery cannulation for type A aortic dissection can significantly reduce the occurrence of malperfusion syndrome and nervous system complications, especially for cerebral protection.
Did the COVID-19 Pandemic Have Immediate Impacts on Japanese Children? Evidence of the Socio-Emotional Behavior and Digital Skills
Authors: Moriguchi Yusuke , Sakata Chifumi , Meng Xianwei , Todo Naoya
Published: August 2020

Background: A novel coronavirus, SARS-CoV-2, has spread widely throughout the world. To reduce the spread of infection, children are prevented from going to school and have fewer opportunities for in-person communication. Although the pandemic has affected the everyday lives of children, its impact on their development is unknown. This cross-sectional study compared Japanese children’s socio-emotional behaviors and skills for operating digital devices before and during the pandemic.Methods: Parents completed a web-based questionnaire before and during the pandemic for children aged 0-9. Children’s socio-emotional development in the context of everyday life was assessed using the Strengths and Difficulties Questionnaire (SDQ). Children’s basic touch interaction skills to operate digital devices and skills to use functions of digital devices were also measured.Results: The results indicated that during the pandemic, children were more prosocial, experienced more problems in their peer relationships, and had better digital skills, but no differences were found in emotional symptoms; conduct problems; and hyperactivity between, before, and during the pandemic. The differences in digital skills were explained by the duration of children’s media use.Conclusions: Overall, our results suggest that the pandemic may have an immediate impact on children’s socio-emotional behaviors and digital skills.Trial registration: Registration type: OSF Preregistration.Date registered: April 27, 2020.Registration from osf.io/tfh4k.(https://osf.io/c7p6b)
4-week eicosapentaenoic acid-rich fish oil supplementation partially protects muscular damage following eccentric contractions
Authors: Tsuchiya Yosuke , Ueda Hisashi , Yanagimoto Kenichi , Kato Ayaka , Ochi Eisuke
Published: August 2020

Background
We previously showed that the 8-week supplementation of fish oil attenuates muscle damage. However, the effect of a shorter period of fish oil supplementation is unclear. The present study investigates the effect of supplementation of fish oil in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for 4 weeks on muscular damage caused by eccentric contractions (ECCs) of the elbow flexors.
Methods
Twenty-two untrained men were recruited in this double-blind, placebo-controlled, parallel design study and the subjects were randomly assigned to the EPA and DHA group (EPA, n = 11) and placebo group (PL, n = 11). They consumed either EPA 600 mg and DHA 260 mg per day or placebo supplement for 4 weeks prior to exercise. Subjects performed 60 ECCs at 100% maximal voluntary contraction (MVC) using a dumbbell. Changes in MVC torque, range of motion (ROM), upper arm circumference, muscle soreness, echo intensity, muscle thickness, serum creatine kinase (CK), and interleukin-6 (IL-6) were assessed before exercise; immediately after exercise; and 1, 2, 3, and 5 days after exercise.
Results
ROM was significantly higher in the EPA group than in the PL group immediately after performing ECCs (p < 0.05). No differences between groups were observed in terms of MVC torque, upper arm circumference, muscle soreness, echo intensity, and thickness. A significant difference was observed in serum CK 3 days after ECCs (p < 0.05).
Conclusion
We concluded that shorter period EPA and DHA supplementation benefits joint flexibility and protection of muscle fiber following ECCs.
Selective Bacterial Community Enrichment Between the Pitcher Plants Sarracenia Minor and Sarracenia Flava
Authors: Stasulli Nikolas M. , Yourstone Scott M. , Weinstein Ilon , Ademski Elizabeth , Shank Elizabeth A.
Published: August 2020

BackgroundThe interconnected and overlapping habitats present in natural ecosystems remain a challenge in determining the forces driving microbial community composition. The cup-like leaf structures of some carnivorous plants, including the family Sarraceniaceae, are self-contained ecological habitats that represent systems for exploring such microbial ecology questions. We investigated whether Sarracenia minor and Sarracenia flava, when sampled at the same geographic location and time, cultivate unique microbiota; an indication of biotic selection of microbes due to eliminating many of the environmental variable present in other studies comparing samples harvested over several time points. ResultsDNA was extracted from the decomposing detritus trapped in the base of each Sarracenia leaf pitcher. We profiled a portion of the 16S rRNA gene across the bacterial community members present in this detritus using Illumina MiSeq technology. We identified a surprising amount of diversity within each pitcher, but also discovered that the two Sarracenia species each contained distinct, enriched microbial community members. This suggests a non-random establishment of microbial communities within these two Sarracenia species.ConclusionsOverall, our results indicate that microbial selection is occurring within the pitchers of these two closely related plant species, which is not due to factors such as geographic location, weather, or prey availability. This suggests that specific features of S. minor and S. flava may play a role in fostering specific insect-decomposing microbiomes. These naturally occurring microbial ecosystems can be developed to answer important questions about microbial community succession, disruption, and member contributions to the community. This study will help further establish carnivorous pitcher plants as a model system for studying confined, naturally occurring bacterial communities.
Trophic States Regulate Assembly Processes and Network Structures of Picophytoplankton Communities in Subtropical Coastal Ecosystems
Authors: Chen Xing , Zhao Huaxian , Jiang Gonglingxia , Tang Jinli , Xu Qiangsheng , Chen Si , Li Xiaoli , Zou Shuqi , Dong Ke , Hou Weiguo , Pan Lianghao , Li Nan
Published: August 2020

Background: Long-term coastal eutrophication especially in semi-enclosed marine areas is driven by increased amounts of nutrients derived from anthropogenic activities. Given that accelerating nutrients may constitute a strong environmental filter, understanding the diversity, assembly process and co-occurrence pattern of picophytoplankton communities in response to increasing coastal eutrophication is clearly of great importance. Results: We investigated picophytoplankton community changes using rbcL gene amplicon sequencing. The results exhibited that the alpha diversity (ANOVA, p < 0.001) and beta diversity (ANOSIM, p < 0.001) were significantly different among eutrophic states. Further, phylogenetic based β-nearest taxon distance analyses revealed that stochastic processes mainly provided 69.26% contribution to picophytoplankton community assembly, whereas deterministic processes dominated community assembly in a heavy eutrophic state. Integrated co-occurrence networks modularly responded to eutrophic states and revealed that keystone taxa mainly belonged to the oligo eutrophic group, which may play fundamental roles in network persistence. Importantly, increased environmental disturbances, such as nitrogen and phosphorus nutrients, could alter picophytoplankton community structure and disrupt ecological processes. Conclusion: Stochastic and deterministic processes simultaneously influenced the assembly of picophytoplankton communities in the subtropical coastal ecosystems. Eutrophic disturbances alert the assembly processes and network structures of picophytoplankton community. Our findings promote the understanding of fundamental ecological processes along eutrophic gradients in subtropical coastal ecosystems.
Social Listening – Revealing Parkinson’s Disease over Day and Night
Authors: Zhang Hui , Meng Fanwen , Li Xingyu , Ning Yali , Cai Meng
Published: August 2020

Background: Nocturnal symptoms in Parkinson’s disease and their related burdens on patients are often treated after management of daytime manifestations. In order to better understand the unmet needs of nocturnal symptoms management, we sought to analyze the characteristics of nocturnal symptoms and the burden of nocturnal-occurring motor and non-motor symptoms from patients’ perspectives.Methods: We used a contemporary Social Listening big-data technique to analyze large amounts of Parkinson’s disease symptoms in patient-doctor and patient-patient dialogues available from social media platforms in China. Frequency of nocturnal symptoms as a proportion of total dialogues per year and their relative negative sentiment were analyzed. As a contrast, overall symptoms (occurring at day or night) were also analyzed. Results: We found that share of voice for overall motor symptoms did not increase from 2016 to 2018 (79%, p = 0.5), but share of voice for non-motor symptoms was 69% in 2018, growing by 7% (p < 0.01), and motor complications was 9%, growing by 6% (p < 0.01), respectively. For nocturnal symptoms, 45% of the analyzed PD population reported nocturnal symptoms in 2018, growing by 6% from 2016 (p < 0.01). Share of voice for nocturnal-occurring motor symptoms was higher than non-motor symptoms. Non-motor symptoms evoked higher negative sentiment no matter whether they occurred during the day or night. For symptoms that can occur at either day or night, each nocturnal symptom was rated with a higher negative sentiment score than the same symptom during the day, regardless of the type of symptom (motor, non-motor, or motor complication).Conclusions: The growing share of voice and the greater negative sentiment of nocturnal symptoms from patients’ perspectives suggest that management of nocturnal symptoms is an unmet need of patients with Parkinson’s disease. A greater emphasis on detecting nocturnal symptoms and treating them with 24-hour care is encouraged.
Efficacy and Outcomes of Lianhuaqingwen Capsule for Coronavirus Disease 2019: A Retrospective Propensity Score Matching Analysis
Authors: liu zhiyong , Du Yongsheng , Liu Jiankun , Wei Xiaolong , Zheng Feiyang , LI Raomei , Zhang Shurong
Published: August 2020

Background: Coronavirus disease 2019 (COVID-19) has outbroken in Wuhan, China, in December, 2019, and became a global pandemic.No effective antiviral agents were approved for COVID-19. In this study, we aim to evaluate the efficacy and outcomes of Lianhuaqingwen (LH) capsulein patients with COVID-19.Methods:In this retrospective cohort study, we included 147 hospitalized patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)infection between February 4th and April 15th, 2020, in Wuhan Huoshen shan hospital. Patients were grouped as usual treatment alone or combination with LH capsules. Propensity score matching analysis were performed between two groups. Primary outcomes were mortality and duration of hospitalization time. Secondary outcomes included the recovery rate of chest radiological manifestations and abnormal laboratory examinations.Results: In two groups, 40 pairs patients were matched for analysis. The baseline information and clinical characteristics were comparable. 73 (91.25%) of all 80 patients were older than 50 years old. All patients in LH treatment group and 38 (95%) in usual treatment group were surviving respectively (P = 0.494). The hospitalization time of patients in LH treatment group was significantly shorter than usual treatment group (17.85±6.612vs.20.72±5.01 days, P = 0.032). After treatment, the rate of lung lesions detected by chest computerized tomography (CT) was lower in LH treatment group (30% vs. 55.0%, P = 0.024).Conclusion: LH capsules were associated with the improved clinical effects, and might be recommended in the treatment practices of COVID-19 patients. Moreover, further evaluation of LH capsules in large population randomized controlled trial is needed.
Diagnostic performance of distinct metabolic features in the plasma of patients with silicosis
Authors: Xue Changjiang , Wu Na , Fan Yali , Ma Jing , Ye Qiao
Published: August 2020

Background Silicosis is a progressive pneumoconiosis characterized by interstitial fibrosis following exposure to silica dust. This study aimed to identify potential noninvasive metabolic biomarkers for the diagnosis and monitoring of this condition by pilot and validation analyses of patients with silicosis in metabolomics studies.Methods Patients with silicosis, dust-exposed workers (DEWs) without silicosis and age-matched healthy controls were recruited in a case-control study. Plasma samples were collected, and metabolomics analyses by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) were conducted. Distinct metabolic features (DMFs) among the groups were identified in the pilot study and were validated in the validation study. The enriched signalling pathways of these DMFs were determined. The ability of DMFs to discriminate among the groups in the validation study was analysed through receiver operating characteristic (ROC) curves. The correlations between DMFs and clinical features were also explored.Results Twenty-nine DMFs and 9 DMFs were detected in the plasma of the DEW and silicosis groups, respectively, compared with the control group; these features showed the same trend in the pilot study and the validation study. Sphingolipid metabolism was the major metabolic pathway in the DEWs, and arginine and proline metabolism was associated with silicosis. Twenty DMFs in the DEWs and 3 DMFs in the patients with silicosis showed a discriminatory ability with ROC curve analysis. The abundance of kynurenine was higher in Stage III silicosis than in Stage I or Stage II silicosis. L-arginine and kynurenine were both negatively correlated with the percentage of forced vital capacity predicted in silicosis.Conclusions Distinct metabolic features of plasma samples related to sphingolipid metabolism and arginine and proline metabolism were identified in the DEW and silicosis groups, respectively. L-arginine and kynurenine may have a predictive role in the diagnosis and severity of silicosis.
Comparative Transcriptomic Analysis of Antimony Resistant and Susceptible Leishmania Infantum Lines
Authors: Andrade Juvana Moreira , Gonçalves Leilane Oliveira , Liarte Daniel Barbosa , Lima Davi Alvarenga , Guimarães Frederico Gonçalves , Resende Daniela , Santi Ana Maria Murta , de Oliveira Luciana Marcia , Velloso João Paulo Linhares , Delfino Renato Guimarães , Pescher Pascale , Späth Gerald F. , Ruiz Jeronimo Conceição , Murta Silvane Maria Fonseca
Published: August 2020

Background: One of the major challenges for leishmaniasis treatment is the emergence of parasites resistant to antimony. In order to study differentially expressed genes associated with drug resistance we performed a comparative transcriptomic analysis between wild-type and potassium antimonyl tartrate (SbIII)-resistant Leishmania infantum lines using high-throughput RNA sequencing.Methods: All the cDNA libraries were constructed from promastigote forms of each line, sequenced and analyzed using STAR for mapping the reads against the reference genome (L. infantum JPCM5) and DESeq2 for differential expression statistical analyses. All the genes were functionally annotated using sequence similarity search.Results: The analytical pipeline considering an adjusted p-value lower than 0.05 and fold change greater than 2.0 identified 933 transcripts differentially expressed (DE) between wild-type and SbIII-resistant L. infantum lines. Out of 933 DE transcripts, 504 presented functional annotation and 429 were assigned as hypothetical proteins. A total of 837 transcripts were upregulated and 96 were downregulated in the SbIII-resistant L. infantum line. Using this DE dataset, the proteins were further grouped in functional classes according to Gene Ontology database. The functional enrichment analysis for biological process showed that the upregulated transcripts in the SbIII-resistant line are associated with protein phosphorylation, microtubule-based movement, ubiquitination, host-parasite interaction, cellular process and other categories. The downregulated transcripts in the SbIII-resistant line are assigned in the GO categories: ribonucleoprotein complex, ribosome biogenesis, rRNA processing, nucleosome assembly and translation.Conclusions: The transcriptomic profile of L. infantum showed a robust set of genes from different metabolic pathways associated with antimony resistance phenotype in this parasite. Our results address the complex and multifactorial antimony resistance mechanism of Leishmania, identifying several potential genes for resistance markers and drug targets against leishmaniasis.