bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circ_0000215 Increases the Expression of CXCR2 and Promoted the Progression of Glioma Cells by Sponging miR-495-3p
Authors: Mutalifu Nurehemaiti , Du Peng , Zhang Jingjing , Akbar Halik , Yan Baofeng , Alimu Sulaiman , Tong Lingxiao , Luan Xinping 
Published: October 2020

Background: In recent years, accumulating studies have found that circular RNA (circRNA) exerts a great effect on tumor progression. Circ_0000215, a novel circRNA, remains largely unknown in terms of its effect and mechanism in glioma. Method: Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to detect the expressions of circ_0000215, miR-495-3p and CXCR2 in human glial cell line HEB and glioma cell lines (A172, U251, U87, SHG-44, LN-18), human glioma tissues and adjacent healthy tissues. Gain- and loss-assays of circ_0000215 were conducted. Cell proliferation ability was detected via the CCK8 assay, and cell invasion ability was examined by Transwell assay. CXCR2 expression was evaluated via RT-PCR and Western blot. Moreover, bioinformatics was applied to analyze the targeting molecules of circ_0000215 and CXCR2. Verification of the relationship between these molecules were supported through the dual-luciferase reporter gene and RNA immunocoprecipitation (RIP) assay. Results: Circ_0000215 and CXCR2 were remarkably upregulated in glioma tissues and cells. Overexpression of circ_0000215 notably promoted the proliferation, invasion and epithelial-mesenchymal transition (EMT) but inhibited apoptosis of glioma cells, while knocking down circ_0000215 had the opposite effects. Additionally, miR-495-3p, a sponge RNA of circ_0000215, inhibited the growth, invasion and EMT of glioma cells. Mechanistically, miR-495-3p targeted CXCR2 and negatively regulated CXCR2/PI3K/Akt pathway. However, the effects of miR-495-3p were all dampened by overexpression of circ_0000215. Conclusion: These data demonstrated that circ_0000215 functions as a competitive endogenous RNA by sponging miR-495-3p, thus accelerating glioma progression through CXCR2 axis.
Internal Lipid Profile and Body Lipid Profile in Relation to Cognition: A Cross-Sectional Study in Southern China
Authors: Liu Lian , Huang Xiao , Feng Liang , Wu Yanqing 
Published: October 2020

Aim: There are currently no established, clinically relevant, non-invasive markers of cognitive impairment, except for age and APOE genotype. Methods: A cross-sectional study of 1,296 participants from Nanchang, China, has been conducted. We collected data from Mini–Mental State Examination (MMSE) scores, internal lipid profiles and body lipid profiles, age and other factors that may have an effect on cognitive impairment. Results: Internal lipid profiles (OR = 1.03 [95%CI, 1.00-1.06], P = 0.024), body lipid profiles (OR = 1.05 [95%CI, 1.01-1.09], P = 0.014), and age (OR = 1.03 [95%CI, 1.01-1.05], P < 0.001) were all positively correlated with cognitive impairment. Conclusions: Cognitive impairment was more frequent in female patients with high internal lipid profiles or body lipid profiles, and these characteristics were related to age and education.
Preliminary six-month outcomes of LIMBSAVE (treatment of critical Limb IscheMia with infragenicular Bypass adopting in situ SAphenous VEin technique) registry
Authors: Troisi Nicola , Blasis Giovanni De , Salvini Mauro , Michelagnoli Stefano , Setacci Carlo ,   LIMBSAVE registry Collaborative Group
Published: October 2020

Objectives Guidelines recommend open bypass surgery for long occlusions of infrainguinal arteries. In situ saphenous vein bypass is a standardized technique. The aim of this study was to report preliminary six-month outcomes of a national, multicenter, observational, prospective registry based on the examination of treatment of critical Limb IscheMia with infragenicular Bypass adopting the in situ SAphenous VEin technique (LIMBSAVE). Methods From January 2018 until October 2019, 428 patients from 41 centers were enrolled in the LIMBSAVE registry. Data were prospectively collected in a dedicated database, including demographics, preoperative risk factors, clinical and diagnostic preoperative assessments, intraoperative measures (including safety and effectiveness of the valvulotome during the surgical procedures), and 30-day follow-up data. Furthermore, estimated six-month outcomes according to Kaplan–Meier curves in terms of primary patency, primary assisted patency, secondary patency, and limb salvage were evaluated. Results Patients were predominantly male ( n = 332, 77.6%) with a mean age of 73.3 years (range 39–95). Technical success, defined as bypass pulse after use of the valvulotome, was obtained in all cases. The proximal anastomosis could be reached by the valvulotome in all cases. The mean number of valvulotome uses was 2.5 (range 1–5). No vein perforation was reported. In nine cases (2.1%), a vein lesion with intramural hemorrhage occurred. The mean length of hospital stay was 11.1 days (range 1–60). At 30-day follow-up, the overall bypass patency rate was 97.4%, and the rate of open or endo reinterventions for failing bypass was 5.4%. At six-month follow-up, the estimated primary patency, primary assisted patency, secondary patency, and limb salvage were 78.1%, 86.2%, 92.1%, and 94.7%, respectively. Conclusions Preliminary intraprocedural outcomes of the LIMBSAVE registry show that the in situ technique with the valvulotome is safe and effective in disrupting valves and obtaining pulsatility in the saphenous vein. The complication rate related to the use of the valvulotome is low. The six-month preliminary outcomes in terms of overall patency and limb salvage are promising. Further examinations and continuous follow-up are needed to evaluate long-term outcomes.
Predicting Diabetic Neuropathy Risk Level Using Artificial Neural Network and Clinical Parameters of Subjects With Diabetes
Authors: Dubey Venketesh N. , Dave Jugal M. , Beavis John , Coppini David V. 
Published: October 2020

Background: A risk assessment tool has been developed for automated estimation of level of neuropathy based on the clinical characteristics of patients. The smart tool is based on risk factors for diabetic neuropathy, which utilizes vibration perception threshold (VPT) and a set of clinical variables as potential predictors. Methods: Significant risk factors included age, height, weight, urine albumin-to-creatinine ratio, glycated hemoglobin, total cholesterol, and duration of diabetes. The continuous-scale VPT was recorded using a neurothesiometer and classified into three categories based on the clinical thresholds in volts (V): low risk (0-20.99 V), medium risk (21-30.99 V), and high risk (≥31 V). Results: The initial study had shown that by just using patient data ( n = 5088) an accuracy of 54% was achievable. Having established the effectiveness of the “classical” method, a special Neural Network based on a Proportional Odds Model was developed, which provided the highest level of prediction accuracy (>70%) using the simulated patient data ( n = 4158). Conclusion: In the absence of any assessment devices or trained personnel, it is possible to establish with reasonable accuracy a diagnosis of diabetic neuropathy by means of the clinical parameters of the patient alone.
Biomechanical Comparison of a Novel Method of Tricortical Kirschner Wire Fixation of Distal Chevron Osteotomies of the First Metatarsal Versus Traditional Kirschner Wire and Versus Screw Fixation
Authors: Chen Jie , Black Natalie R. , Morris Randall , Panchbhavi Vinod K. 
Published: October 2020

Introduction: Traditional Kirschner wire (K-wire) stabilization of first metatarsal distal chevron osteotomy involves 1 cortex of fixation; however, unicortical fixation is associated with a high complication rate, including pin migration. A method of K-wire fixation utilizing 3 cortices may be biomechanically superior and potentially equivalent to single-screw fixation. Methods: Cadaveric specimens fixed with tricortical K-wires were tested in both the physiologic and cantilever conditions against specimens fixed with unicortical K-wires (N = 8) and single screws (N = 9) utilizing matched-pair comparison groups. Differences in physiologic and cantilever fixed/intact stiffness ratio and cantilever failure load were determined. Results: The tricortical fixation specimens had a significantly higher stiffness ratio in cantilever loading than the unicortical fixation specimens (60.50% tricortical, 34.17% unicortical, P = .02) but not in physiologic load (15.34% tricortical, 25.75% unicortical, P = .23). In cantilever failure loading, the tricortical fixation specimens had a significantly higher load to failure than the unicortical fixation specimens (132.81 N tricortical, 58.58 N unicortical, P < .01). Stiffness ratio under physiologic load, cantilever load, and ultimate load to failure were not significantly different between tricortical K-wire and screw-fixation groups. Conclusion: Tricortical K-wire fixation for distal chevron osteotomies is biomechanically superior to traditional unicortical K-wire fixation, and equivalent to single-screw fixation. Levels of Evidence: Level V: Cadaver study
Long-term single-cell passaging of human iPSC fully supports pluripotency and high-efficient trilineage differentiation capacity
Authors: Cruvinel Estela , Ogusuku Isabella , Cerioni Rosanna , Rodrigues Sirlene , Gonçalves Jéssica , Góes Maria Elisa , Alvim Juliana Morais , Silva Anderson Carlos , Lino Vanesca de Souza , Boccardo Enrique , Goulart Ernesto , Pereira Alexandre , Dariolli Rafael , Valadares Marcos , Biagi Diogo 
Published: October 2020

Objectives: To establish a straightforward single-cell passaging cultivation method that enables high-quality maintenance of human induced pluripotent stem cells without the appearance of karyotypic abnormalities or loss of pluripotency. Methods: Cells were kept in culture for over 50 passages, following a structured chronogram of passage and monitoring cell growth by population doubling time calculation and cell confluence. Standard procedures for human induced pluripotent stem cells monitoring as embryonic body formation, karyotyping and pluripotency markers expression were evaluated in order to assess the cellular state in long-term culture. Cells that underwent these tests were then subjected to differentiation into keratinocytes, cardiomyocytes and definitive endoderm to evaluate its differentiation capacity. Results: Human induced pluripotent stem cells clones maintained its pluripotent capability as well as chromosomal integrity and were able to generate derivatives from the three germ layers at high passages by embryoid body formation and high-efficient direct differentiation into keratinocytes, cardiomyocytes and definitive endoderm. Conclusions: Our findings support the routine of human induced pluripotent stem cells single-cell passaging as a reliable procedure even after long-term cultivation, providing healthy human induced pluripotent stem cells to be used in drug discovery, toxicity, and disease modeling as well as for therapeutic approaches.
Caval foramen hernia in a cat
Authors: Siow Jia Wen , Hoon QiCai Jason , Jenkins Elizabeth , Heblinski Nikola , Makara Mariano 
Published: October 2020

Case summary A 3-year-old neutered female domestic shorthair cat presented for a 2-week history of hyporexia, lethargy and weight loss. Aspartate aminotransferase, alanine aminotransferase and cholesterol were mildly elevated. Thoracic radiographs identified a lobulated soft tissue opacity in the caudal thorax to the right of midline, with the border effacing the caudal vena cava and broad-based towards the diaphragm. The broad base was suggestive of diaphragmatic hernia, with the other radiographic features and location suggestive of caval foramen hernia. Ultrasound confirmed diaphragmatic hernia with liver herniation. CT showed the herniation of multiple liver lobes and the gallbladder through a defect at the caval foramen. Herniorrhaphy was performed via ventral midline coeliotomy. Following this procedure, the cat’s clinical signs resolved and its weight has been regained. Relevance and novel information To our knowledge, this is the first report of successful caval foramen herniorrhaphy in a cat. Caval foramen hernia is a type of congenital diaphragmatic hernia. The authors suggest that its embryopathology involves defective septum transversum development. The case was detected during the standard diagnostic investigation of non-specific clinical signs. Its radiographic findings may easily be mistaken for a pulmonary mass. Although not seen in our case, caval foramen hernia is commonly associated with caudal vena cava obstruction, which can potentially result in Budd–Chiari-like syndrome.
Mitochondrial antiviral signaling protein is crucial for the development of pulmonary fibrosis
Authors: Kim Sang-Hun , Lee Jung Yeon , Yoon Chang Min , Shin Hyeon Jun , Lee Sei Won , Rosas Ivan , Herzog Erica , Dela Cruz Charles S. , Kaminski Naftali , Kang Min-Jong 
Published: October 2020

Danger signals, or damage-associated molecular patterns (DAMPs), instigate mitochondrial innate immune responses wherein mitochondrial antiviral signaling protein (MAVS) functions as a key platform molecule to mediate them. The role of MAVS in the pathogenesis of idiopathic pulmonary fibrosis (IPF), however, has not yet been identified. Whether MAVS signalling can be modulated by currently existing drugs has also not been explored.We used an established model of pulmonary fibrosis to demonstrate that MAVS is a critical mediator of multiple DAMP signalling pathways and the consequent lung fibrosis after bleomycin-induced injuryin vivo.After bleomycin injury, MAVS expression was mainly observed in macrophages. Multimeric MAVS aggregation, a key event of MAVS signalling activation, was significantly increased and persisted in bleomycin-injured lungs. A proapoptotic BH3 mimetic, ABT-263, attenuated the expression of MAVS and its signalling and, consequently, the development of experimental pulmonary fibrosis. In contrast, the therapeutic effects of nintedanib and pirfenidone, two drugs approved for IPF treatment, were not related to the modulation of MAVS or its signalling. Multimeric MAVS aggregation was significantly increased in lungs from IPF patients as well.MAVS may play an important role in the development of pulmonary fibrosis, and targeting MAVS with BH3 mimetics may provide a novel and much needed therapeutic strategy for IPF.
Clinical phenotypes of extrapulmonary sarcoidosis: an analysis of a French, multi-ethnic, multicentre cohort
Authors: Lhote Raphael , Annesi-Maesano Isabella , Nunes Hilario , Launay David , Borie Raphael , Sacré Karim , Schleinitz Nicolas , Hamidou Mohamed , Mahevas Matthieu , Devilliers Hervé , Bonniaud Philippe , Lhote François , Haroche Julien , Rufat Pierre , Amoura Zahir , Valeyre Dominique , Cohen Aubart Fleur 
Published: October 2020

Sarcoidosis is a rare disease of unknown cause with wide heterogeneity in clinical features and outcomes. We aimed to explore sarcoidosis phenotypes and their clinical relevance with particular attention to extrapulmonary subgroups.The Epidemiology of Sarcoidosis (EpiSarc) study is a French retrospective multicentre study. Sarcoidosis patients were identified through national hospitalisation records using appropriate codes from 11 hospital centres between 2013 and 2016 according to a standardised protocol. Medical charts were reviewed. The phenotypes of sarcoidosis were defined using a hierarchical cluster analysis.A total of 1237 patients were included (562 men and 675 women). The mean age at sarcoidosis diagnosis was 43.5±13 years. Hierarchical cluster analysis identified five distinct phenotypes according to organ involvement and disease type and symptoms: 1) erythema nodosum, joint involvement and hilar lymph nodes (n=180); 2) eye, neurological, digestive and kidney involvement (n=137); 3) pulmonary involvement with fibrosis and heart involvement (n=630); 4) lupus pernio and a high percentage of severe involvement (n=41); and 5) hepatosplenic, peripheral lymph node and bone involvement (n=249). Phenotype 1 was associated with being European/Caucasian and female and with non-manual work, phenotype 2 with being European/Caucasian, and phenotypes 3 and 5 with being non-European/Caucasian. The labour worker proportion was significantly lower in phenotype 5 than in the other phenotypes.This multicentre study confirms the existence of distinct phenotypes of sarcoidosis, with a non-random distribution of organ involvement. These phenotypes differ according to sex, geographical origin and socioprofessional category.
Pharmacological and nonpharmacological interventions to improve symptom control, functional exercise capacity and quality of life in interstitial lung disease: an evidence synthesis
Authors: Bajwah Sabrina , Colquitt Jill , Loveman Emma , Bausewein Claudia , Almond Howard , Oluyase Adejoke , Dzingina Mendy , Maddocks Matthew , Higginson Irene J. , Wells Athol 
Published: October 2020

We assessed efficacy and effectiveness of pharmacological and nonpharmacological interventions in improving symptom control, functional exercise capacity and quality of life (QoL) in people living with fibrotic interstitial lung disease (ILD).We summarised evidence from three previous reviews (to June 2014) and conducted an updated search of nine databases and grey literature (2011–2019) (registration: CRD42017065933) for prospective studies of interventions aimed to alleviate symptoms, improve QoL or functional exercise capacity in fibrotic ILD. Data were synthesised through narrative synthesis or meta-analysed as appropriate.Forty-seven studies with 2527 participants were included. From 22 pharmacological studies of 11 different interventions (n=1683), the most tested interventions were bosentan and sildenafil. From 25 nonpharmacological studies, the most tested intervention was for pulmonary rehabilitation/exercise training (PR) (22 studies, n=748). There was an improvement in 6-min walk distance immediately following PR (six studies; n=200, mean difference (MD) (95% CI) 39.9 m (18.2 to 61.5)), but not longer term (3 or 6 months, four studies; n=147, MD 5.3 m (−12.9 to 23.4). Multiple, varied outcome measures were used (e.g.37 studies assessing dyspnoea used 10 different scales with a lack of reporting of rate of deterioration in outcomes). Evidence gap mapping highlighted the most and least researched symptoms, as dyspnoea and cough, respectively.This evidence synthesis highlights overwhelmingly that the most researched symptom is dyspnoea and the strongest evidence base is for short-term PR. The least researched symptom was cough. Research going forward must focus on prioritising and standardising meaningful outcomes and focussing interventions on neglected symptoms.
Adherence to disease-specific drug treatment among patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension
Authors: Kjellström Barbro , Sandqvist Anna , Hjalmarsson Clara , Nisell Magnus , Näsman Per , Ivarsson Bodil 
Published: October 2020

BackgroundPulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) require lifelong treatment. The aim of the present study was to investigate adherence to disease-specific treatment in patients with PAH or CTEPH.MethodsThe study comprised an adult population diagnosed with PAH (n=384) or CTEPH (n=187) alive in 2016–2017. The study utilised three registries: the Swedish PAH registry, the National Board of Health and Welfare, and Statistics Sweden. Withdrawals from pharmacies of disease-specific oral treatments were studied. Adherence was assessed as: 1) Number of days covered defined as the difference between the total number of daily dosages dispensed and the total number of days covered; and 2) Manual assessment by two persons that independently reviewed each patient's prescription fill history to detect anomalies or patterns of deteriorating or improving adherence over time.ResultsThe mean age was 61±16 years, 61% were female and mean time since diagnosis was 4.6 years. Adherence was 62% using the Number of days covered method and 66% by the Manual assessment method. Drug-specific adherence varied from 91% for riociguat to 60% for sildenafil. Good adherence was associated with shorter time since diagnosis in patients with PAH and with lower number of concomitant other chronic treatments in patients with CTEPH. Age, sex, socioeconomic status or number of pulmonary hypertension (PH) treatments were not associated with adherence.ConclusionAdherence to oral disease-specific treatment was 60–66% and associated with time since diagnosis and number of concomitant chronic treatments. Sex, age or socioeconomic factors did not affect adherence.
Preclinical evaluation of the epithelial sodium channel inhibitor BI 1265162 for treatment of cystic fibrosis
Authors: Nickolaus Peter , Jung Birgit , Sabater Juan , Constant Samuel , Gupta Abhya 
Published: October 2020

BackgroundEpithelial sodium channel (ENaC) is an important regulator of airway surface liquid volume; ENaC is hyperactivated in cystic fibrosis (CF). ENaC inhibition is a potential therapeutic target for CF. Here, we reportin vitroandin vivoresults for BI 1265162, an inhaled ENaC inhibitor currently in Phase II clinical development, administeredviathe Respimat® Soft Mist™ inhaler.MethodsIn vitroinhibition of sodium ion (Na+) transport by BI 1265162 was tested in mouse renal collecting duct cells (M1) and human bronchial epithelial cells (NCI-H441); inhibition of water transport was measured using M1 cells.In vivoinhibition of liquid absorption from rat airway epithelium and acceleration of mucociliary clearance (MCC) in sheep lungs were assessed. Fully differentiated normal and CF human epithelium was used to measure the effect of BI 1265162 with or without ivacaftor and lumacaftor on water transport and MCC.ResultsBI 1265162 dose-dependently inhibited Na+transport and decreased water resorption in cell line models. BI 1265162 reduced liquid absorption in rat lungs and increased MCC in sheep. No effects on renal function were seen in the animal models. BI 1265162 alone and in combination with CF transmembrane conductance regulator (CFTR) modulators decreased water transport and increased MCC in both normal and CF airway human epithelial models and also increased the effects of CFTR modulators in CF epithelium to reach the effect size seen in healthy epithelium with ivacaftor/lumacaftor alone.ConclusionThese results demonstrate the potential of BI 1265162 as a mutation agnostic, ENaC-inhibitor-based therapy for CF.