bluuebunny/crossref_metadata_2025 huggingface dataset:
MÍMESIS E LINGUAGEM DIALÓGICA
Authors: Pereira Luís Eduardo Santos , Marchezan Renata Coelho
Published: July 2020

O presente trabalho busca discutir o papel da mímesis na relação com a linguagem. Para tanto, serão discutidas as condições de enunciabilidade na Grécia antiga que propiciaram a formulação do conceito em meio a um embate cultural de mudança histórica, quando se passa da palavra mítica e monológica dos deuses para seu destronamento à palavra dialogal nas discussões públicas. Momento de travessia para uma conformação mais analítica sobre a realidade. Desse modo, e sem querer esgotar qualquer discussão, mas lançando uma sugestão de debate, este estudo passa por questões ligadas às vozes míticas no pensamento analítico e científico e o mesmo em sentido contrário, para pensar, a partir de uma relação entre o Círculo de Bakhtin, o pensamento de Cassirer e as reflexões de Adorno e Horkheimer, a constituição simbólica da cultura e a formação da consciência como linguagem, ao mesmo tempo social e singular. A hipótese de trabalho é de que a linguagem na sua dimensão artística – portanto, caracterizada também pela capacidade de representar semelhanças, de agir mimeticamente – é um campo de percepção de epistemologias que resolve dialeticamente a relação entre o particular e o geral, o subjetivo e o objetivo, o inteligível e o sensível.
The effect of anti-cancer and anti-tuberculosis treatments in lung cancer patients with active tuberculosis: a retrospective analysis
Authors: CHAI MEI , Shi Qingming
Published: July 2020

Background Lung tuberculosis (TB) and lung cancer have a complex relationship. Data concerning TB treatment in lung cancer patients are still incomplete. The aim of this study was to investigate the effects of anti-cancer and anti-tuberculosis treatments in lung cancer patients with active lung TB. Methods In a retrospective cohort study, lung cancer patients with active lung TB were identified between January 2013 and December 2016. Age- and sex-matched lung cancer patients without tuberculosis were selected as control subjects. Anti-cancer and anti-tuberculosis treatments were administered according to the national guidelines. The clinical courses and responses of lung cancer patients with and without active lung TB were examined and compared.Results A total of 31 consecutive lung cancer patients were diagnosed with active lung TB. Fifty-one lung cancer patients without TB were enrolled as control subjects. Most patients in the two groups were elderly, had advanced non-small cell lung cancer and had tumor burdens. The anti-cancer treatment completion rate and response rate were not different between two group (87.1% in TB treatment patients vs. 92.2% in lung cancer patients; 77.4% in TB treatment patients vs. 88.2% in lung cancer patients, respectively). The anti-tuberculosis treatment completion rate and success rate was 87.1% and 80.7%. The median survival times were not different between two groups (52 weeks in TB treatment patients vs. 57 weeks in lung cancer patients). The change in Karnofsky performance score was also not different between two groups. The most common side effect in TB treatment patients was liver injury (61.3%). The most serious side effect in TB treatment patients was leukocyte deficiency (9.7% in Grade 3). Both of side effects mentioned above were not different between two groups. Conclusion Both anti-cancer and anti-tuberculosis treatments can be safely and effectively administered in lung cancer patients with active lung TB. Attention should be paid to the risk of tuberculosis in lung cancer patients in TB high-burden countries.
Dysbiosis, gut barrier dysfunction and inflammation in dementia: A pilot study
Authors: Stadlbauer Vanessa , Engertsberger Lara , Komarova Irina , Feldbacher Nicole , Leber Bettina , Pichler Gerald , Fink Nicole , Scarpatetti Monika , Schippinger Walter , Schmidt Reinhold , Horvath Angela
Published: July 2020

Background: Dementia is an increasing public health threat worldwide. The pathogenesis of dementia has not been fully elucidated yet. Inflammatory processes are hypothesized to play an important role as a driver for cognitive decline but the origin of inflammation is not clear. We hypothesize that disturbances in gut microbiome composition, gut barrier dysfunction, bacterial translocation and resulting inflammation are associated with cognitive dysfunction in dementia. Methods: To test this hypothesis, a cohort of 23 patients with dementia and 18 age and sex matched controls without cognitive impairments were studied. Gut microbiome composition, gut barrier dysfunction, bacterial translocation and inflammation were assessed from stool and serum samples. Malnutrition was assessed by Mini Nutritional Assessment Short Form (MNA-SF), detailed information on drug use was collected. Microbiome composition was assessed by 16s rRNA sequencing, QIIME 2 and Calypso 7.14 tools. Results: Dementia was associated with dysbiosis characterized by differences in beta diversity and changes in taxonomic composition. Gut permeability was increased as evidenced by increased serum diamine oxidase (DAO) levels and systemic inflammation was confirmed by increased soluble cluster of differentiation 14 levels (sCD14). BMI and statin use had the strongest impact on microbiome composition. Conclusion: Dementia is associated with changes in gut microbiome composition and increased biomarkers of gut permeability and inflammation. Lachnospiraceae NK4A136 group as potential butyrate producer was reduced in dementia. Malnutrition and drug intake were factors, that impact on microbiome composition. Increasing butyrate producing bacteria and targeting malnutrition may be promising therapeutic targets in dementia.
Use of technology for public health surveillance reporting: opportunities, challenges and lessons learnt from Kenya
Authors: Njeru Ian , Kareko David , Kisangau Ngina , Langat Daniel , Liku Nzisa , Owiso George , Dolan Samantha , Rabinowitz Peter , Macharia Daniel , Ekechi Chinyere , Widdowson Marc-Alain
Published: July 2020

Background: Effective public health surveillance systems are crucial for early detection and response to outbreaks. In 2016, Kenya transitioned its surveillance system from a standalone web-based surveillance system to the more sustainable and integrated District Health Information System 2 (DHIS2). As part of Global Health Security Agenda (GHSA) initiatives in Kenya, training on use of the new system was conducted among surveillance officers. We evaluated the surveillance indicators during the transition period in order to assess the impact of this training on surveillance metrics and identify challenges affecting reporting rates. Methods: From February to May 2017, we analysed surveillance data for 13 intervention and 13 comparison counties. An intervention county was defined as one that had received refresher training on DHIS2 while a comparison county was one that had not received training. We evaluated the impact of the training by analysing completeness and timeliness of reporting 15 weeks before and 12 weeks after the training. A chi-square test of independence was used to compare the reporting rates between the two groups. A structured questionnaire was administered to the training participants to assess the challenges affecting surveillance reporting. Results: The average completeness of reporting for the intervention counties increased from 45% to 62%, i.e. by 17 percentage points (95% CI 16.14 -17.86) compared to an increase from 49% to 52% for the comparison group, i.e. by 3 percentage points (95% CI 2.23 -3.77). The timeliness of reporting increased from 30% to 51%, i.e. by 21 percentage points (95% CI 20.16 - 21.84) for the intervention group, compared to an increase from 31% to 38% for the comparison group, i.e.by 7 percentage points (95% CI 6.27-7.73). Major challenges for the low reporting rates included lack of budget support from government, lack of airtime for reporting, health workers strike, health facilities not sending surveillance data, use of wrong denominator to calculate reporting rates and surveillance officers having other competing tasks. Conclusions: Training plays an important role in improving public health surveillance reporting. However, to improve surveillance reporting rates to the desired national targets, other challenges affecting reporting must be identified and addressed accordingly.
MiR-23a induced the activation of CDC42/PAK1 pathway and cell cycle arrest in human cov434 cells by targeting FGD4
Authors: Lin Ji , Huang Huijuan , Lin Liheng , Li Weiwei , Huang Jianfen
Published: July 2020

Background: MiRNAs play important roles in the development of ovarian cancer, activation of primitive follicles, follicular development, oocyte maturation and ovulation. In the present study, we investigated the specific role of miR-23a in cov434 cells. Results: Downregulation of miR-23a was observed in serum of PCOS patients compared with the healthy control, suggesting the inhibitory effect of miR-23a in PCOS. MiR-23a was positively correlated with Body Mass Index (BMI) and negatively correlated with Luteinizing hormone (LH), Testostrone (T), Glucose (Glu) and Insulin (INS) of PCOS patients. MiR-23a mimic inhibited the proliferation and promoted apoptosis of human cov434 cells. In addition, flow cytometry assay confirmed that miR-23a blocked cell cycle on G0/G1 phase. MiR-23a inhibitor showed opposite results. Furthermore, double luciferase reporter assay proved that miR-23a could bind to the 3’UTR of FGD4 directly through sites predicted on Target Scan. FGD4 level was significantly suppressed by miR-23a mimic, but was significantly enhanced by miR-23a inhibitor. We further proved that miR-23a increased the expression of activated CDC42 (GTP bround) and p-PAK-1, suggesting that miR-23a induced cell cycle arrest through CDC42/PAK1 pathway. Conclusions: In conclusion, our study reveals that miR-23a participates in the regulation of proliferation and apoptosis of cov434 cells through target FGD4, and may play a role in the pathophysiology of PCOS.
Mouse skeletal muscles infected with Plasmodium berghei and Plasmodium chabaudi reveal a crosstalk between lipid mediators and gene expression
Authors: Marrelli Mauro Toledo , Wang Zhiying , Huang Jian , Brotto Marco
Published: July 2020

Background Malaria is one of the most prevalent infectious disease in the world with 3.2 billion humans at risk. Malaria causes splenomegaly and damage in other organs including skeletal muscles. Skeletal muscles comprise nearly 50% of the human body and are largely responsible for the regulation and modulation of overall metabolism. It is essential to understand how malaria damages muscles in order to develop effective preventive measures and/or treatments. Using a pre-clinical animal model, the potential molecular mechanisms of Plasmodium infection affecting skeletal muscles of mice were investigated. Methods Mouse Signal Transduction Pathway Finder PCR Array was used to monitor gene expression changes of 10 essential signaling pathways in skeletal muscles from mice infected with Plasmodium berghei and Plasmodium chabaudi. Then, a new targeted-lipidomic approach using liquid chromatography with tandem mass spectrometry (LC-MS/MS) to profile 158 lipid signalling mediators (LMs), mostly eicosanoids derived from arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), was applied. Finally, 16 key LMs directly associated with inflammation, oxidative stress, and tissue healing in skeletal muscles, were quantified. Results The results showed that the expression of key genes altered by Plasmodium infection is associated with inflammation, oxidative stress, and atrophy. In support to gene profiling results, lipidomics revealed higher concentrations of LMs in skeletal muscles directly related to inflammatory responses, while on the levels of LMs crucial in resolving inflammation and tissue repair reduced significantly. Conclusion The results provide new insights into the molecular mechanisms of malaria-induced muscle damage and revealed a potential mechanism modulating inflammation in malarial muscles. These pre-clinical studies should help with future clinical studies in humans aimed at monitoring of disease progression and development of specific interventions for the prevention and mitigation of long-term chronic effects on skeletal muscle function.
Reclassification of tumor size for solitary HBV-related hepatocellular carcinoma by minimum p value method: a large retrospective study
Authors: Liu Hongzhi , Yang Yuan , Chen Chuanchun , Wang Lei , Huang Qizhen , Zeng Jianxing , Lin Kongying , Zeng Yongyi , Guo Pengfei , Zhou Weiping , Liu Jingfeng
Published: July 2020

Background and Objectives Tumor size is one of the most important issues for hepatocellular carcinoma (HCC) treatment and prognosis but the classification of it still controversial. The aim of this study was to screen appropriate cutoffs for size of solitary hepatitis B virus (HBV) related HCC.Methods A cohort of 1760 patients with solitary HBV-related HCC undergoing curative liver resection were divided into 11 groups based on tumor size in 1-cm interval. The minimum p value method was used to screen the appropriate size cutoff according to overall survival (OS). If multiple cutoffs meet the above standard, univariate analysis will be performed by using the Cox proportional hazards regression model, and hazard ratio (HR) will be considered as a criterion to assess the difference in survival.Results There are 8 dichotomy, 8 trichotomy and no inquartation cutoffs were screened when classifying tumor sizes in accordance with OS. The HR values of tumor size at these trichotomy cutoffs for OS were compared, the highest HR value is 2.79 when size cutoff is 3/9cm. Then, we reclassified patients into three new classifications: ≤ 3cm (n = 422), > 3 and ≤ 9cm (n = 1072), and > 9cm (n = 266). The comparison of clinicopathologic characteristics among these three classifications showed that the increase of tumor size was associated with the increase of α-fetoprotein (AFP), microvascular invasion (MVI), tumor differentiation, and liver cirrhosis. And the comparison of the OS among three classifications showed statistical differences. Conclusions This study suggested that size criteria of 3cm and 9cm in solitary HBV-related HCC patients were appropriate based on biological characteristics and prognostic significance.
Aspects of the development of Ixodes anatis under different environmental conditions in the laboratory and in the field
Authors: Bansal Natasha , Pomroy William , Heath Allen C , Castro Isabel
Published: July 2020

Background Numerous laboratory and few field-based studies have explored the influence of microclimates on developmental times of different stages of various species of ixodid ticks and found that most of these species develop quicker and survive better at temperatures between 18 and 26°C and relative humidity between 75% and 94%. Ixodes anatis Chilton, 1904, or kiwi tick, is an endophilic, nidicolous species endemic to North Island brown kiwi (Apteryx mantelli, NIBK) and the tokoeka (Apteryx australis). Little is known about the environmental conditions that are ideal for the development of the kiwi tick. Our aims in this study were to determine and compare the conditions of temperature and RH that ensured the best survival, and the shortest interstadial periods for the kiwi tick, in the laboratory and outdoors inside artificial kiwi burrows.Methods We collected free walking engorged ticks off wild kiwi hosts and placed them in the laboratory at various fixed temperature and humidity regimes. We also placed sets of different stages of these ticks in artificial kiwi burrows and in both cases, recorded the times taken for the ticks to moult to the next stage.Results We found that larvae and nymphs both showed optimum development between 10-20°C, which is lower than many other species of ixodid ticks. However, larvae moulted quicker and survived better when saturation deficits were <1-2 mmHg (RH>94%) while for nymphs the optimum saturation deficits were 1-10 mmHg.Conclusions We believe that the kiwi tick has adapted to stable, but relatively cool and humid conditions in the burrows reflecting the evolutionary consequences of its association with the kiwi.
Inter-scanner reproducibility of brain volumetry: influence of automated brain segmentation software
Authors: Liu Sirui , Hou Bou , Zhang Yiwei , Lin Tianye , Fan Xiaoyuan , You Hui , Feng Feng
Published: July 2020

Background: The inter-scanner reproducibility of brain volumetry is important in multi-site neuroimaging studies, where the reliability of automated brain segmentation (ABS) tools plays an important role. This study aimed to evaluate the influence of ABS tools on the consistency and reproducibility of the quantified brain volumetry from different scanners. Methods: We included fifteen healthy volunteers who were scanned with 3D isotropic brain T1-weighted sequence on three different 3.0 Tesla MRI scanners (GE, Siemens and Philips). For each individual, the time span between image acquisitions on different scanners was limited to one hour. All the T1-weighted images were processed with FreeSurfer v6.0, FSL v5.0 and AccuBrain ® with default settings to obtain volumetry of brain tissues (e.g. gray matter) and substructures (e.g. basal ganglia structures) if available. Cofficient of variation (CV) was calculated to test inter-scanner variability in brain volumetry of various structures as quantified by these ABS tools. Results: The mean inter-scanner CV values per brain structure among three MRI scanners ranged from 6.946% to 12.29% (mean, 9.577%) for FreeSurfer, 7.245% to 20.98% (mean, 12.60%) for FSL and 1.348% to 8.800% (mean value, 3.546%) for AccuBrain @ . In addition, AccuBrain ® and FreeSurfer achieved the lowest mean values of region-specific CV between GE and Siemens scanners (from 0.818% to 5.958% for AccuBrain ® , and from 0.903% to 7.977% for FreeSurfer), while FSL-FIRST had the lowest mean values of region-specific CV between GE and Philips scanners (from 2.603% to 16.310%). AccuBrain ® also had the lowest mean values of region-specific CV between Siemens and Philips (from 1.138% to 6.615%). Conclusion: There is a large discrepancy in the inter-scanner reproducibility of brain volumetry when using different processing software. Image acquisition protocols and selection of ABS tool for brain volumetry quantification have impact on the robustness of results in multi-site studies.
Pericardial fat and its influence on cardiac diastolic function
Authors: de Wit-Verheggen Vera , Altintas Sibel , Spee Romy , Mihl Casper , Kuijk Sander van , Wildberger Joachim , Schrauwen-Hinderling Vera , Kietselaer Bas , de Weijer Tineke van
Published: July 2020

Background Pericardial fat (PF) has been suggested to directly act on cardiomyocytes, leading to diastolic dysfunction. The aim of this study was to investigate whether a higher PF volume is associated with a lower diastolic function in healthy subjects.Methods 254 adults (40-70 years, BMI 18-35 kg/m2, normal left ventricular ejection fraction), with (a)typical chest pain (otherwise healthy) from the cardiology outpatient clinic were retrospectively included in this study. All patients underwent a coronary computed tomographic angiography for the measurement of pericardial fat volume, as well as a transthoracic echocardiography for the assessment of diastolic function parameters. To assess the independent association of PF and diastolic function parameters, multivariable linear regression analysis was performed. To maximize differences in PF volume, the group was divided in low (lowest quartile of both sexes) and high (highest quartile of both sexes) PF volume. Multivariable binary logistic analysis was used to study the associations within the groups between PF and diastolic function, adjusted for age, BMI, and sex.Results Significant associations for all four diastolic parameters with the PF volume were found after adjusting for BMI, age, and sex. In addition, subjects with high pericardial fat had a reduced left atrial volume index (p=0.02), lower E/e (p<0.01) and E/A (p=0.01), reduced e’ lateral (p<0.01), reduced e’ septal p=0.03), compared to subjects with low pericardial fat.Conclusion These findings confirm that pericardial fat volume, even in healthy subjects with normal cardiac function, is associated with diastolic function. Our results suggest that the mechanical effects of PF may limit the distensibility of the heart and thereby directly contribute to diastolic dysfunction.Trial registration NCT01671930
The role of the Oncostatin M/ OSM receptor β axis in activating dermal microvascular endothelial cells in Systemic Sclerosis
Authors: Marden Grace , Wan Qianqian , Wilks James , Nevin Katherine , Feeney Maria , Wisniacki Nicolas , Trojanowski Marcin , Bujor Andreea , Stawski Lukasz , Trojanowska Maria
Published: July 2020

Background: Scleroderma (SSc) is a rare autoimmune disease characterized by vascular impairment and progressive fibrosis of the skin and other organs. Oncostatin M, a member of the IL-6 family, is elevated in SSc serum and was recognized as a significant player in various stages of fibrosis. The goal of this study was to assess the contribution of the OSM/OSMRβ pathway to endothelial cell (EC) injury and activation in SSc. Methods: IHC and IF were used to assess the distribution of OSM and OSMRβ in SSc (n=14) and healthy control (n=7) skin biopsies. Cell culture experiments were performed in human dermal microvascular endothelial cells (HDMECs) and included mRNA and protein analysis, and cell migration and proliferation assays. Ex vivo skin organoid culture was used to evaluate the effect of OSM on perivascular fibrosis.Results: OSMRβ protein was elevated in dermal ECs and in fibroblasts of SSc patients. Treatments of HDMECs with OSM or IL-6 +sIL-6R have demonstrated that both cytokines similarly stimulated proinflammatory genes and genes related to endothelial-to mesenchymal transition ((EndMT). OSM was more effective than IL-6+sIL-6R in inducing cell migration, while both treatments similarly induced cell proliferation. The effects of OSM were mediated via OSMRβ and STAT3, while the LIFR did not contribute to these responses. Both, OSM and IL-6+sIL-6R induced profibrotic gene expression in HDMECs, as well as expansion of the perivascular PDGFRβ+ cells in the ex vivo human skin culture system. Additional studies in HDMECs showed that siRNA-mediated downregulation of FLI1 and its close homolog ERG resulted in increased expression of OSMRβ in HDMECs.Conclusions: This work provides new insights into the role of the OSM/OSMRβ axis in activation/injury of dermal ECs and supports the involvement of this pathway in SSc vascular disease.
Determinants of deranged thyroid function parameters in children admitted for management of diabetic ketoacidosis/diabetic ketosis
Authors: Shao Peng , Guo Shujuan , Li Guimei , Qin Daogang , Li Sen , Ying Luan
Published: July 2020

Background: Sick euthyroid syndrome is frequent in children admitted with diabetic ketoacidosis/diabetic ketosis (DKA/DK). This study evaluates the interplay of various metabolic factors with occurrence of deranged thyroid function tests in children admitted for management of DKA/DK.Methods: 98 DKA and 96 DK children patients were selected from hospital records, among which individuals on thyroxine replacement, with overt hypothyroidism or positive anti-thyroperoxidase (TPO) antibody were excluded. Tests for liver function, renal function, lipid profile, serum osmolarity, thyroid function, c-peptide levels, and glycosylated hemoglobin were done for all. Children were divided into euthyroid (n=88) and euthyroid sick syndrome（ESS）groups (n=106).Results: The ESS group had a higher level of white blood cell count (WBC), plasma glucose (PG), beta-hydroxybutyric acid (β-HB), triglyceride (TG), anion gap (AG), glycosylated hemoglobin (HbA1c) and a lower level of HCO3-, prealbumin (PA), and albumin (ALB) compared with the euthyroid group (P<0.05). Free T3 (FT3) levels were significantly correlated to β-HB, HCO3-, AG, PA, and HbA1c (r=-0.642, 0.681, -0.377, 0.581, -0.309, respectively; P<0.01). Free T4 （FT4） levels were significantly correlated to β-HB, HCO3-, and ALB levels (r=-0.489, 0.338, 0.529, respectively; P<0.01). TSH levels were significantly affected by HCO3– only (r=-0.28; P<0.01). HCO3– level was the most important factor deciding euthyroid or ESS on logistic regression analysis (OR=0.844, P=0.004, 95%CI=0.751­-0.948).Conclusions: Lower levels of free thyroid hormones and occurrence of ESS were associated with a higher degree of acidosis in children with DKA/DK.
Ferritin modifies the relationship between inflammation and arterial stiffness in hypertensive patients with different glucose tolerance
Authors: Sciacqua Angela , Ventura Ettore , Tripepi Giovanni , Cassano Velia , D'Arrigo Graziella , Roumeliotis Stefanos , Maio Raffaele , Miceli Sofia , Perticone Maria , Andreozzi Francesco , Sesti Giorgio , Perticone Francesco
Published: July 2020

Backgroud: Ferritin, a crucial element for iron homeostasis, is associated with chronic diseases characterized by subclinical inflammation such as essential arterial hypertension and type 2 diabetes mellitus (T2DM), showing a prognostic value in different clinical settings. We investigated whether ferritin is associated with arterial stiffness (AS), an early indicator of atherosclerosis, and if it could act as effect modifier on the relationship between inflammation and AS in hypertensive patients with different glucose tolerance.Methods: We enrolled 462 newly diagnosed untreated hypertensive (HT) patients. All subjects underwent an oral glucose tolerance test. Insulin sensitivity was assessed by MATSUDA index and ferritin levels were estimated by immunoradiometric assay. AS was defined by carotid-femoral pulse wave velocity (PWV). Results: Out of 462 patients, 271 showed normal glucose tolerance (HT/NGT), 146 impaired glucose tolerance (HT/IGT) and 45 were diabetic (HT/T2DM). Iron levels significantly decreased and transferrin and ferritin significantly increased from the first to the third group. PWV values were significantly higher in HT/IGT and HT/T2DM patients. PWV was related directly with ferritin, high sensitivity C reactive protein (hs-CRP), transferrin, and inversely with MATSUDA index. Ferritin resulted the strongest determinant of PWV explaining a 14.9% of its variation; moreover it was a strong modifier of the relationship between hs-CRP and PWV. The estimated augmentation in PWV portended by a fixed increase in hs-CRP, was higher across increasing values of ferritin.Conclusion: Ferritin represents an independent risk factor of arterial stiffness in our study population and a strong effect modifier on the relationship between inflammation and PWV. However, further studies are needed to fully elucidate the potential role of this biomarker in human atherosclerosis.
Identification of a 4-lncRNA Signature Predicting Prognosis of Patients with Non-Small Cell Lung Cancer: a Multicenter Study in China
Authors: Wang Rui-Qi , Long Xiao-Ran , Ge Chun-Lei , Zhang Mei-Yin , Huang Long , Zhou Ning-Ning , Hu Yi , Li Rui-Lei , Li Zhen , Chen Dong-Ni , Zhang Lan-Jun , Wen Zhe-Sheng , Mai Shi-Juan , WANG HUI-YUN
Published: July 2020

Background: Previous findings have indicated that the tumor, nodes, and metastases (TNM) staging system is sub-optimal in terms of predicting survival outcomes in patients with non-small lung carcinoma (NSCLC).Thus, the aims to identify a long non-coding RNA (lncRNA) signature for predicting survival in patients with NSCLC and to provide additional prognostic information in combination with the TNM system.Methods: Patients with NSCLC were recruited from a hospital and divided into a discovery cohort (n=194) and validation cohort (n=172), and detected using a custom lncRNA microarray. Lung tissues obtained from patients at a different hospital (n = 73, independent validation cohort) were examined via qRT-PCR. Differentially expressed lncRNAs were determined with the Significance Analysis of Microarrays program and used to identify those associated with survival in the discovery cohort. These prognostic lncRNAs were employed to construct a prognostic signature with a risk-score method. Then, the utility of the prognostic signature was confirmed using the validation cohort and the independent cohort. Results: In the discovery cohort, we identified 305 lncRNAs that were differentially expressed between the NSCLC tissues and matched, adjacent normal lung tissues, of which 15 are associated with survival; a 4-lncRNA prognostic signature was identified from the 15 survival lncRNAs, which was significantly correlated with survivals of NSCLC patients. This signature was further validated in the validation cohort and independent cohort. Moreover, multivariate Cox analysis demonstrates that the 4-LncRNA signature is an independent survival predictor. Then we established a new risk-score model by combining 4-lncRNA signature and TNM stage. The receiver operating characteristics (ROC) curve indicates that the prognostic value of the combined model is significantly higher than that of the TNM stage alone, in all the cohorts. Conclusions: In this study, we identified a 4-lncRNA signature that can potentially serve as a powerful prognosis biomarker and can provide additional survival information to the traditional TNM staging system.
Strict bladder filling and rectal emptying during prostate SBRT - does it make a dosimetric or clinical difference?
Authors: Byun David Jaihun , Gorovets Daniel J. , Jacobs Lauren M. , Happersett Laura , Zhang Pengpeng , Pei Xin , Burleson Sarah , Zhang Zhigang , Hunt Margie , McBride Sean , Kollmeier Marisa A. , Zelefsky Michael J.
Published: July 2020

Background: To evaluate inter-fractional variations in bladder and rectum during prostate stereotactic body radiation therapy (SBRT) and determine dosimetric and clinical consequences. Methods: Eighty-five patients with 510 computed tomography (CT) images were analyzed. Median prescription dose was 40 Gy in 5 fractions. Patients were instructed to maintain a full bladder and empty rectum prior to simulation and each treatment. A single reviewer delineated organs at risk (OARs) on the simulation (Sim-CT) and Cone Beam CTs (CBCT) for analyses. Results: Bladder and rectum volume reductions were observed throughout the course of SBRT, with largest mean reductions of 86.9 mL (19.0%) for bladder and 6.4 mL (8.7%) for rectum noted at fraction #5 compared to Sim-CT (P<0.01). Higher initial Sim-CT bladder volumes were predictive for greater reduction in absolute bladder volume during treatment (ρ=-0.69; P<0.01). Over the course of SBRT, there was a small but significant increase in bladder mean dose (+4.5±12.8%; P<0.01) but no significant change in the D2cc (+0.8±4.0%; P=0.28). The mean bladder trigone displacement was in the anterior direction (+4.02±6.59 mm) with a corresponding decrease in mean trigone dose (-3.6±9.6%; P<0.01) and D2cc (-6.2±15.6%; P<0.01). There was a small but significant increase in mean rectal dose (+7.0±12.9%, P<0.01) but a decrease in rectal D2cc (-2.2±10.1%; P=0.04). No significant correlations were found between relative bladder volume changes, bladder trigone displacements, or rectum volume changes with rates of genitourinary or rectal toxicities. Conclusions: Despite smaller than expected bladder and rectal volumes at the time of treatment compared to the planning scans, dosimetric impact was minimal and not predictive of detrimental clinical outcomes. These results cast doubt on the need for excessively strict bladder filling and rectal emptying protocols in the context of image guided prostate SBRT and prospective studies are needed to determine its necessity.
Extracellular vesicles from human mesenchymal stem cells expedite chondrogenesis in 3D human degenerative disc cell cultures
Authors: Hingert Daphne , Ekström Karin , Aldridge Jonathan , Crescitelli Rosella , Brisby Helena
Published: July 2020

Background: Extracellular vesicles (EVs) from human mesenchymal stem cells (hMSCs) are known to be mediators of intercellular communication and has been suggested as possible therapeutic agents in many diseases. Their potential use in intervertebral disc (IVD) degeneration associated with low back pain (LBP) is yet to be explored. Since LBP affects more than 85% of the western population resulting in high socioeconomic consequences there is a demand for exploring new and possibly mini-invasive treatment alternatives. In this study, the effect of hMSCs derived small EVs (sEVs) on degenerated disc cells (DCs) isolated from patients with degenerative discs and chronic LBP was investigated in a 3D in vitro model. Methods: hMSCs were isolated from bone marrow aspirate and EVs were isolated from conditioned media of the hMSCs by differential centrifugation and filtration. 3D pellet cultures of DCs were stimulated with the EVs at 5x1010 vesicles/mL concentration for 28 days and compared to control. The pellets were harvested at day 7, 14, and 28 and evaluated for cell proliferation, viability, ECM production, apoptotic activity, chondrogenesis and cytokine secretions.Results: The findings demonstrated that treatment with sEVs from hMSCs resulted in more than 50% increase in cell proliferation and decrease in cellular apoptosis in degenerated DCs from this patient group. ECM production was also observed as early as in day 7 and was more than three times higher in the sEVs treated DC pellets compared to control cultures. Further, sEVs treatment suppressed secretion of MMP-1 in the DCs. Conclusion: hMSC derived sEVs improved cell viability and expedited chondrogenesis in DCs from degenerated IVDs. These findings open up for new tissue regeneration treatment strategies to be developed for degenerative disorders of the spine.
Circ_0002232 Acts as a Potential Biomarker for AML and Reveals a Potential ceRNA Network of Circ_0002232/miR-92a-3p/PTEN
Authors: Deng zhaoqun , Su Xiao-yu , Zhu Xin , Zhao Qian , Ke Jin-ming , Wu De-long , Yi Yun-yun , Yi Jing , Lin Jiang , Qian Jun , Deng Zhao-qun
Published: July 2020

Background: PTEN, known as a classical tumor suppressor, has been reported to be down-expressed in acute myeloid leukemia (AML) and affected the progression of AML patients. CircRNAs, an emerging type of non-coding RNAs, could act as competing endogenous RNAs (ceRNAs) and has been reported to regulate the expression of PTEN through sponging miRNA in many solid tumors. But there are rarely studies focused on the role of circ-PTEN in AML. Our research was aimed to investigate the expression level of circ_0002232, one of circular RNAs of PTEN, reveal the clinical significance and potential ceRNA interaction network in AML of it.Methods: Circ_0002232 expression in 117 AML patients and 48 controls was detected by using Real-time quantitative PCR. The diagnostic value of circ_0002232 expression was evaluated by receiver operating characteristic curve. Kaplan-Meier curves were used to analyse the impact of circ_0002232 for overall survival. CeRNA network of circ_0002232 was predicted by using interaction prediction websites.Results: Compared with controls, circ_0002232 was notably low-expressed in AML (P<0.001). According to the result of receiver operating characteristic curve, circ_0002232 expression could distinguish AML patients from controls (P<0.001). There were significant differences in patients’ age (P=0.002), FAB classifications (P=0.025), white blood cell count (P=0.034) and platelet count (P=0.047) between low-expressed circ_0002232 group and high-expressed circ_00022332 group. Moreover, there was a positive correlation between circ_0002232 expression and patients’ age (Pearson r=0.256, P=0.0053). Interestingly, we found that patients in low-expressed circ_0002232 group had better overall survival both in whole AML (P=0.019) and non-APL AML (P=0.044). Remarkably, the expression of circ_0002232 was positively correlated with PTEN (Pearson r=0.769, P<0.001). Furthermore, there was a negative correlation in AML between circ_0002232 and miR-92a-3p (Pearson r=-0.262, P=0.032), miR-92a-3p and PTEN (Pearson r=-0.358, P=0.019). Interaction prediction websites revealed that circ_0002232 might regulate the expression of PTEN through sponging miR-92a-3p and affect the process of AML.Conclusions: Circ_0002232, one of circRNAs of PTEN, was remarkably down-regulated in AML and could act as a promising biomarker for the diagnosis of AML. In addition, there might be a potential ceRNA interaction network of circ_0002232/miR-92a-3p/PTEN in AML.
The correlation of intraoperative hypotension and postoperative cognitive impairment: a meta-analysis of randomized controlled trials
Authors: Feng Xiaojin , Hu Jialing , Hua Fuzhou , Zhang Jing , Zhang Lieliang , Xu Guohai
Published: July 2020

Background: There is no consensus on whether intraoperative hypotension is associated with postoperative cognitive impairment. Hence, we performed a meta-analysis to evaluate the correlation of intraoperative hypotension and the incidence of postoperative delirium (POD) or postoperative cognitive dysfunction (POCD).Methods: We searched PubMed, Embase, and Cochrane Library databases to find randomized controlled trials (RCTs) in which reported the relationship between intraoperative hypotension and POD or POCD. The retrieval time is up to January 2020, without language restrictions. Quality assessment of the eligible studies was conducted by two researchers independently with the Cochrane evaluation system.Results: We analyzed five eligible RCTs. Based on the relative mean arterial pressure (MAP), participants were divided into low-target and high-target groups. For the incidence of POD, there were two studies with 99 participants in the low-target group and 94 participants in the high-target pressure group. For the incidence of POCD, there were four studies involved 360 participants in the low-target group and 341 participants in the high-target group, with a study assessed both POD and POCD. No significant difference between the low-target and the high-target group was observed in the incidence of POD (RR = 3.30, 95% CI 0.80 to 13.54, P = 0.10), or POCD (RR = 1.26, 95% CI 0.76 to 2.08, P = 0.37). Furthermore, it also demonstrates that intraoperative hypotension prolonged the length of ICU stay, but did not increased the mortality, the length of hospital stay, and mechanical ventilation (MV) time.Conclusions: There is no significant correlation between intraoperative hypotension and the incidence of POD or POCD. Keywords: Intraoperative hypotension, Postoperative delirium, Postoperative cognitive dysfunction, Meta-analysis
The protective effect of 3% diquafosol on meibomian gland morphology in glaucoma patients treated with prostaglandin analogs: a 12-month follow-up study
Authors: Guo Yue , Ha Jun Young , Piao Helong , Sung Mi Sun , Park Sang Woo
Published: July 2020

Background: To determine if 3% diquafosol (DQS) can preserve the meibomian gland morphology in glaucoma patients treated with prostaglandin analogs (PGA) for a 12-month follow-up period.Methods: This study included 84 eyes of 46 normal tension glaucoma (NTG) patients who were treated with either preservative-containing PGA (PC-PGA; 16 patients, 28 eyes), preservative-free PGA (PF-PGA; 21 patients, 39 eyes), or a combination of PC-PGA and 3% DQS (PC-PGA+DQS; 9 patients, 17 eyes). The meibography of the upper eyelid was acquired using Keratograph® 5M at baseline and at each follow-up (1, 3, 6, 9, and 12 months). Meibomian gland loss (MGL) was quantitatively analyzed by using ImageJ software. Results: In the PC-PGA group, MGL increased significantly from baseline to month 9 and month 12, whereas no significant changes were observed in the PF-PGA and PC-PGA+DQS groups during the entire 12 months. All groups showed similar MGL at each follow-up time from baseline to six months. However, MGL in the PC-PGA group was significantly higher than those in the PF-PGA and PC-PGA+DQS groups at the 9 and 12 months.Conclusions: Combining 3% DQS with PC-PGA was as effective as PF-PGA in preserving the meibomian gland morphology for at least 12 months. Our results suggest that 3% DQS may be a promising strategy for managing glaucoma patients with a high risk of developing meibomian gland dysfunction due to preservative-containing topical medications.
SARS-CoV-2 Origins and Evolution: Insights from Coronaviruses Recombination and Phylogenetic Analysis
Authors: Murahwa Alltalents Tutsirayi , Onywera Harris , Nindo Fredrick
Published: July 2020

Background: It is imperative in the midst of a global epidemic to investigate the origins of the infectious agent especially when it has reached parts of the world with either ailing economies or pre-existing political turmoil consistent with non-functional health systems. Methods: To explore the possibility of cross species infection, genomic recombination and the emergence of novel coronaviruses in the near future we carried out recombination and phylogenetic analysis to determine the spatio-temporal evolution and origins of the current SARS-CoV-2 virus. Results: Our findings prove using two robust recombination tools, RDPv4.100 and SimPlot3.5.1 analysis that SARS-CoV-2 is a recombinant of pangolin and bat RaTG13 sequences as been previously shown elsewhere. We also report one novel recombination event between two SARS-CoV-2 sequences (SARS-CoV-2 sequence, MT188341, SARS-CoV-2 sequence, MT293183). Bearing in mind that the prerequisite for recombination is the occurrence two viral sequences in the same reservoir, biological niche or host at the same time we postulate either co-infection with the two viral sequences, or superinfection, both scenarios have not been reported elsewhere. Conclusion: The possibility of recombination between the SARS-CoV-2 sequences poses the likelihood of the emergence of new and maybe more or less virulent “strains” of the virus. We believe that the future of science lies in our ability to be able to use computational based methods to predict the genetic sequences of infectious agents of the next epidemics. The addition of more SARS-CoV-2 sequences has a bearing on the understanding of the origin, evolution and clinical outcome prediction of given viral genomes. More SARS-CoV-2 sequences are needed to elucidate our understanding of this family of viruses.
Integrated bioinformatics analysis and screening hub genes in papillary thyroid cancer
Authors: Fan Rong , Dong Lijin , Li Ping , Wang Xiaoming , Chen Xuewei
Published: July 2020

Background

With the increasing incidence, papillary thyroid cancer (PTC) is receiving more and more attention, but the pathogenesis of which is still not completely elucidated. The purpose of this study was to explore key biomarkers and new therapeutic targets in PTC.
Methods

GEO2R and Venn online software were used for differential gene screening analysis. Hub genes were screened via STRING and Cytoscape, following Gene Ontology and KEGG enrichment analysis. Finally, survival analysis and expression validation were performed via UALCAN online software and immunohistochemistry.
Results

We screened 334 consistently differentially expressed genes (DEGs), composed of 136 upregulated genes and 198 downregulated genes. Gene ontology enrichment analysis suggested that DEGs mainly enriched in the cancer-related pathways and functions. PPI network visualization was performed to select 17 upregulated and 13 downregulated DEGs. Finally, the expression verification and overall survival analysis conducted in the Gene Expression Profiling Interactive Analysis Tool (GEPIA) and UALCAN showed that LPAR5, TFPI and ENTPD1 were related to the development of PTC and the prognosis of PTC patients, and the expression of LPAR5 was verified by tissue chip.
Conclusions

In summary, the hub genes and pathways identified in the present study not only provided new biomarkers for PTC, but also will be useful for elucidating the pathogenesis of PTC.
QT interval monitoring with handheld heart rhythm ECG device in COVID-19 patients.
Authors: Minguito-Carazo Carlos , Echarte-Morales Julio , Benito-González Tomás , Castillo-García Samuel Del , Rodríguez-Santamarta Miguel , Sánchez-Muñoz Enrique , González-Maniega Clea , Bergel-García Ruben , Menéndez-Suárez Paula , Prieto-González Silvia , Palacios-Echavarren Carmen , Borrego-Rodríguez Javier , Flores-Vergara Guisela , Iglesias-Garriz Ignacio , Fernández-Vázquez Felipe
Published: July 2020

Objectives: To evaluate the feasibility of QTc monitoring with a smart device in COVID-19 patients receiving QTc-interfering therapies.Background: QTc prolongation is an adverse effect of COVID-19 therapies. The use of a handheld device in this scenario has not been addressed.Methods: Prospective study of consecutive COVID-19 patients treated with hydroxychloroquine ± azithromycin ± lopinavir-ritonavir. ECG monitoring was performed with 12-lead ECG or with KardiaMobile-6L. Both registries were also sequentially obtained in a cohort of healthy patients. We evaluated differences in QTc in COVID-19 patients between 3 different monitoring strategies: 12-lead ECG at baseline and follow-up (A), 12-lead ECG at baseline and follow-up with the smart device (B), and fully monitored with handheld 6-lead ECG (group C). Time needed to obtain an ECG registry was also documented.Results: 182 COVID-19 patients were included (A: 119(65.4%); B: 50(27.5%); C: 13(7.1%). QTc peak during hospitalization did significantly increase in all groups. No differences were observed between the 3 monitoring strategies in QTc prolongation (p=0.864). In the control group, all but one ECG registry with the smart device allowed QTc measurement and mean QTc did not differ between both techniques (p=0.612), displaying a moderate reliability (ICC 0.56 [0.19-0.76]). Time of ECG registry was significantly longer for the 12-lead ECG than for handheld device in both cohorts (p<0.001).Conclusion: QTc monitoring with KardiaMobile-6L in COVID-19 patients was feasible. Time of ECG registration was significantly lower with the smart device, which may offer an important advantage for prevention of virus dissemination among healthcare providers.
T-S Fuzzy Systems Optimization Identification Based on FCM and PSO
Authors: Ren Yaxue , Liu Fucai , Lv Jingfeng , Meng Aiwen , Wen Yintang
Published: July 2020

The division of fuzzy space is very important in the identification of premise parameters and the Gaussian membership function is applied to the premise fuzzy set. However, the two parameters of Gaussian membership function, center and width, are not easy to be determined. In this paper, a novel T-S fuzzy model optimal identification method of optimizing two parameters of Gaussian function based on Fuzzy c-means (FCM) and particle swarm optimization (PSO) algorithm is presented. Firstly, we use FCM algorithm to determine the Gaussian center for rough adjustment. Then, under the condition that the center of Gaussian function is fixed, the PSO algorithm is used to optimize another adjustable parameter, the width of the Gaussian membership function, to achieve fine tuning, so as to complete the identification of prerequisite parameters of fuzzy model. In addition, the recursive least squares (RLS) algorithm is used to identify the conclusion parameters. Finally, the effectiveness of this method for T-S fuzzy model identification is verified by simulation examples, and the higher identification accuracy can be obtained by using the novel identification method described compared with other identification methods.