bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mediastinal lymph node enlargement in idiopathic pulmonary fibrosis: relationships with disease progression and pulmonary function trends
Authors: Sgalla Giacomo , Larici Anna Rita , Golfi Nicoletta , Calvello Mariarosaria , Farchione Alessandra , Ciello Annemilia Del , Varone Francesco , Iovene Bruno , Manfredi Riccardo , Richeldi Luca 
Published: September 2020

Abstract
Background and objectives
Evidence of mediastinal Lymph Node Enlargement (LNE) on CT scan is a common finding in idiopathic pulmonary fibrosis (IPF). We sought to investigate whether the involvement of mediastinal lymph nodes is associated with accelerated disease progression, and explored the changes occurring in mediastinal lymph nodes during the radiological follow up of these patients.

Methods
This retrospective study included IPF patients referred to a single ILD centre in Italy. A consensus-based assessment of mediastinal LNE on chest CT scan was performed by two thoracic radiologists. Kaplan-Meier curves and multivariate Cox proportional hazards regression were used to assess hazard ratios for mortality and disease progression (defined as categorical FVC decline ≥10%). The annualized rates of change in functional parameters for each patient were calculated using mixed linear models.

Results
152 IPF patients were included in the analysis, of whom 135 (89%) received antifibrotic treatment for IPF during the study follow up. Patients having evidence of 3 or more enlarged mediastinal lymph nodes on baseline CT scan showed increased rates of mortality (HR 5.03, 95% CI 1.86-13.62, p≤0.001) and significant disease progression (HR 2.99, 95% CI 1.22-7.33, p=0.17) as compared to patients without LNE, after adjusting for GAP stage. Among 62 patients with LNE who underwent a follow up CT scan of the chest and received antifibrotic treatment, 57 (92%) maintained evidence mediastinal LNE over time.

Conclusions
Diffuse mediastinal lymph node involvement predicts clinically meaningful functional deterioration in patients with IPF.
Hyperhomocysteinemia and Dyslipidemia in point mutation G307S of cystathionine β-synthase-deficient rabbit generated using CRISPR/Cas9
Authors: Zhang Ting , Lu Rui , Chen Yibing , Yuan Yuguo , Song Shaozheng , Yan Kunning , Zha Yiwen , Zhuang Wenwen , Cheng Yong , Liang Jingyan 
Published: September 2020

Abstract
Background: Congenital hyper-homocysteinemia (HHcy) is caused by a defective cystathionine β-synthase (CBS) gene, and is frequently associated with dyslipdemia. The aim of this study was to further elucidate the effect of mutated CBS gene on circulating lipids using a rabbit model harboring a homozygous G307S point mutation in CBS. Methods: CRISPR/Cas9 system was used to edit the CBS gene in rabbit embryos. The founder rabbits were sequenced, and their plasma homocysteine (Hcy) and lipid profile were analyzed. Results: Six CBS-knockout (CBS-KO) founder lines with biallelic modifications were obtained. Mutation in CBS caused significant growth retardation and high mortality rates within 6 weeks after birth. In addition, the 6-week old CBS-KO rabbits showed higher plasma levels of Hcy, triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) compared to the age-matched wild-type (WT) controls. Histological analysis of the mutants showed accumulation of micro-vesicular cytoplasmic lipid droplets in the hepatocytes. However, gastric infusion of vitamin B and betaine complex significantly decreased the plasma levels of TG, TC and LDL-C in the CBS-KO rabbits, and alleviated hepatic steatosis compared to the untreated animals. Conclusion: A CBSG307S rabbit model was generated that exhibited severe dyslipidemia when fed on a normal diet, indicating that G307S mutation in the CBS gene is a causative factor for dyslipidemia.
Recommendations for hemodynamic Monitoring for Critically Ill Children – Expert Consensus Statement issued by the Cardiovascular Dynamics Section of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC)
Authors: Singh Yogen , Villaescusa Javier Urbano , Cruz Eduardo M. da , Tibby Shane M , Bottari Gabriella , Saxena Rohit , Guillén Marga , Herce Jesus Lopez , Nardo Matteo Di , Cecchetti Corrado , Brierley Joe , de Boode Willem , Lemson Joris 
Published: September 2020

Abstract
Background: Cardiovascular instability is common in critically-ill children. There is scarcity of published high-quality studies to develop meaningful evidence-based hemodynamic monitoring guidelines and hence, with the exception of management of shock, currently there are no published guidelines for hemodynamic monitoring in children. The European Society of Paediatric and Neonatal Intensive Care (ESPNIC) Cardiovascular Dynamics section aimed to provide expert consensus recommendations on hemodynamic monitoring in critically ill children.Methods: Creation of a panel of experts in cardiovascular hemodynamic assessment and hemodynamic monitoring and review of relevant literature - a literature search was performed, and recommendations were developed through discussions managed following a Quaker-based consensus technique and evaluating appropriateness using a modified blind RAND/UCLA voting method. The AGREE statement was followed to prepare this document.Results: Of 100 suggested recommendations across 12 subgroups concerning hemodynamic monitoring in critically ill children, 72 reached “strong agreement”, 20 “weak agreement” and 2 had “no agreement”. Six statements were considered as redundant after rephrasing of statements following first round of voting. The agreed 72 recommendations were then coalesced into 36 detailing four key areas of hemodynamic monitoring in the main manuscript. Due to lack of published evidence to develop evidence-based guidelines, most of the recommendations are based upon expert consensus.Conclusions: These expert consensus-based recommendation may be used to guide clinical practice for hemodynamic monitoring in critically-ill children and they may serve as a basis for highlighting gaps in the knowledge base to guide further research in hemodynamic monitoring.
Ammonia Induced Microglial Activation Modulates Connexin 43 and Aquaporin 4 Expression in Astrocyte-microglia Co-culture Model
Authors: Ismail Fatme Seval , Faustmann Timo Jendrik , Tsvetanova Anamariya , Moinfar Zahra , Faustmann Pedro M. 
Published: September 2020

Abstract
Background Hepatic encephalopathy (HE) is a neurological complication resulting from acute or chronic liver disease. Hyperammonemia leading to astrocyte swelling and cerebral edema in combination with neuroinflammation including microglia activation, mainly contribute to the pathogenesis of HE. However, little is known about microglia and their inflammatory response, as well as their influence on astrocytic channels and astrocyte swelling under hyperammonemia.Objective To investigate the effects of ammonia on the microglial activation, glial viability, connexin 43 (Cx43) and aquaporin 4 (AQP4) expression in astrocytes in in vitro astrocyte-microglia co-culture model.Methods Primary rat glial cocultures of astrocytes containing 5% (M5, representing "physiological" conditions) or 30% (M30, representing "pathological" conditions) of microglia were incubated with 3 mM, 5 mM, 10 mM and 20 mM ammonium chloride (NH4Cl) for 6 h and 24 h in order to mimic the conditions of HE. An MTT assay was performed to measure the viability, proliferation and cytotoxicity of cells. The microglial phenotypes were analysed by immunocytochemistry. The expression of Cx43 and AQP4 were quantified by immunoblot analysis.Results A significant reduction of glial viability was observed in M30 co-cultures after incubation with 20 mM NH4Cl for 6 h, whereas in M5 co-cultures the viability remained unchanged. Microglial activation was detected by immunocytochemistry after incubation with 3 mM, 5 mM and 10 mM NH4Cl for 6 h and 24 h in M5 as well as in M30 co-cultures. The Cx43 expression was increased significantly in M30 co-cultures after 6 h incubation with 5 mM NH4Cl. The AQP4 expression was increased significantly in M5 co-cultures treated with 10 mM NH4Cl for 6 h.Conclusions Our findings showed a significant microglial activation, decrease of viability and increase in Cx43 and AQP4 expression after NH4Cl incubation in astrocyte-microglia co-culture model. Based on previous in vitro studies suggesting that microglia activation influences astrocytic networks, it can be assumed that the microglial activation under hyperammonemia can modulate the Cx43 and AQP4 expression in astrocytes in a dynamic way and this can contribute to astrocytic dysfunction in HE.
Chromosome segregation in B. subtilis is highly heterogeneous
Authors: Najjar Nina El , Graumann Peter 
Published: September 2020

Abstract
Objective: The bacterial cell cycle comprises initiation of replication and ensuing elongation, concomitant chromosome segregation (in some organisms with a delay termed cohesion), and finally cell division. By quantifying the number of origin and terminus regions in exponentially growing Bacillus subtilis cells, and after induction of DNA damage, we aimed at determining cell cycle parameters at different growth rates at a single cell level.Results: B. subtilis cells are mostly mero-oligoploid during fast growth and diploid during slow growth. However, we found that the number of replication origins and of termini is highly heterogeneous within the cell population at two different growth rates, and that even at slow growth, a majority of cells attempts to maintain more than a single chromosome at all times of the cell cycle. Heterogeneity of chromosome copy numbers may reflect different subpopulations having diverging growth rates even during exponential growth conditions. Cells continued to initiate replication and segregate chromosomes after induction of DNA damage, as judged by an increase in origin numbers per cell, showing that replication and segregation are relatively robust against cell cycle perturbation.
Ca2+-activated mitochondrial biogenesis and functions improve stem cell fate in Rg3-treated human mesenchymal stem cells
Authors: Hong Taeui , Kim Moon Young , Ly Dat Da , Park Su Jung , Eom Young Woo , Park Kyu-Sang , Baik Soon Koo 
Published: September 2020

Abstract
Although mitochondrial functions are essential for cell survival, their critical roles in stem cell fate, including proliferation, differentiation, and senescence, remain elusive. Ginsenoside Rg3 exhibits various biological activities and reportedly increases mitochondrial biogenesis and respiration. Herein, we observed that Rg3 increased proliferation and suppressed senescence of human bone marrow-derived mesenchymal stem cells. Osteogenic, but not adipogenic, differentiation was facilitated by Rg3 treatment. Rg3 suppressed reactive oxygen species production and upregulated mitochondrial biogenesis and antioxidant enzymes, including superoxide dismutase. Consistently, Rg3 strongly augmented basal and ATP synthesis-linked respiration with high spare respiratory capacity. Rg3 treatment elevated cytosolic Ca2+ concentration contributing to mitochondrial activation. Reduction of intracellular or extracellular Ca2+ levels strongly inhibited Rg3-induced activation of mitochondrial respiration and biogenesis. Taken together, Rg3 enhances capabilities of mitochondrial and antioxidant functions mainly through a Ca2+-dependent pathway, which improves the proliferation and differentiation potentials and prevents the senescence of human mesenchymal stem cells.
Development and Evaluation of Two-Parameter Linear Free Energy Models for the Prediction of Human Skin Permeability Coefficient of Neutral Organic Chemicals
Authors: Naseem Sana , Zushi Yasuyuki , Nabi Deedar 
Published: September 2020

Abstract
The experimental values of skin permeability coefficients, required for dermal exposure assessment, are not readily available for many chemicals. The existing estimation approaches are either less accurate or require many parameters that are not readily available. Furthermore, current estimation methods are not easy to apply to complex environmental mixtures. We present two models to estimate the skin permeability coefficients of neutral organic chemicals. The first model, referred to here as the 2-parameter partitioning model (PPM), exploits a linear free energy relationship (LFER) of skin permeability coefficient with a linear combination of partition coefficients for octanol-water and air-water systems. The second model is based on the retention time information of nonpolar analytes on comprehensive two-dimensional gas chromatography (GC×GC). The PPM successfully explained variability in the skin permeability data (n = 175) with R2 = 0.82 and root mean square error (RMSE) = 0.47 log unit. In comparison, the US-EPA’s model DERMWIN exhibited an RMSE of 0.78 log unit. The Zhang model a 5-parameter LFER equation based on experimental Abraham solute descriptors (ASDs) performed slightly better with an RMSE value of 0.44 log unit. However, the Zhang model is limited by the scarcity of experimental ASDs. The GC×GC model successfully explained the variance in skin permeability data of nonpolar chemicals (n = 79) with R2 = 0.90 and RMSE = 0.23 log unit. The PPM can easily be implemented in US-EPA’s Estimation Program Interface Suite (EPI Suite™). The GC×GC model can be applied to the complex mixtures of nonpolar chemicals.
Acute exercise in mice transiently remodels the hepatic lipidome in an intensity-dependent manner
Authors: Henderson Gregory C , Tenorio Valeria Martinez , Tuazon Marc A 
Published: September 2020

Abstract
Background: The content of triacylglycerol (TAG) in the liver is known to rapidly increase after a single bout of exercise followed by recovery to sedentary levels. The response of other hepatic lipids, and acyl chain composition of lipid classes, would provide a deeper understanding of the response of hepatic lipid metabolism to acute exercise. Methods: Female mice performed a single bout of continuous exercise (CE), high-intensity interval exercise (HIIE), or no exercise (CON). The total content of various lipids in the liver, and fatty acids within lipid classes, were measured in tissues collected 3 h after exercise (Day 1) and the day following exercise (Day 2). Results: The total concentration of TAG rose on Day 1 after exercise ( P < 0.05), with a greater elevation in HIIE than CE ( P < 0.05), followed by a decline toward CON levels on Day 2. The total concentration of other measured lipid classes was not significantly altered by exercise. However, n-6 polyunsaturated fatty acid relative abundance in diacylglycerol (DAG) was increased by HIIE ( P < 0.05). In CON liver, TAG content was positively correlated with DAG and phosphatidylethanolamine ( P < 0.05), while these statistical associations were disrupted in exercised mice on Day 1. Conclusions: The response of lipid metabolism to exercise involves the coordination of metabolism between various tissues, and the lipid metabolism response to acute exercise places a metabolic burden upon the liver. The present findings describe how the liver copes with this metabolic challenge. The flexibility of the TAG pool size in the liver, and other remodeling of the hepatic lipidome, may be fundamental components of the physiological response to intense exercise.
Genome-wide Association Analysis of Adaptation to Oxygen Stress in Nile Tilapia (Oreochromis Niloticus)
Authors: Yu Xiaofei , Megens Hendrik-Jan , Mengistu Samuel B. , Bastiaansen John W.M. , Mulder Han A. , Benzie John A.H. , Groenen Martien A.M. , Komen Hans 
Published: September 2020

Abstract
Background: Tilapia is one of the most abundant species in aquaculture. Hypoxia is known to depress growth rate, but the genetic mechanism by which this occurs is unknown. In this study, two groups consisting of 3140 fish that were raised in either aerated (normoxia) or non-aerated pond (nocturnal hypoxia). During grow out, fish were sampled five times to determine individual body weight (BW) gains. We applied a genome-wide association study to identify SNPs and genes associated with the hypoxic and normoxic environments in the 17th generation of a Genetically Improved Farmed tilapia population. Results: In the hypoxic environment, 36 SNPs associated with at least one of the five body weight measurements (BW1 till BW5), of which six, located between 19.48 Mb and 21.04 Mb on Linkage group (LG) 8, were significant for body weight in the early growth stage (BW1 to BW2). Further significant associations were found for BW in the later growth stage (BW3 to BW5), located on LG1 and LG8. Analysis of genes within the candidate genomic region suggested that MAPK and VEGF signalling were significantly involved in the later growth stage under the hypoxic environment. Well-known hypoxia-regulated genes such as igf1rb, rora, efna3 and aurk were also associated with growth in the later stage in the hypoxic environment. Conversely, 13 linkage groups containing 29 unique significant and suggestive SNPs were found across the whole growth period under the normoxic environment. A meta-analysis showed that 33 SNPs were significantly associated with BW across the two environments, indicating a shared effect independent of hypoxic or normoxic environment. Functional pathways involved in nervous system development and organ growth in the early stage, and oocyte maturation in the later stage.Conclusions: There are clear genotype-growth associations in both normoxic and hypoxic environments, although genome architecture involved changed over the growing period, indicating a transition in metabolism along the way. The involvement of pathways important in hypoxia especially at the later growth stage indicates a genotype-by-environment interaction, in which MAPK and VEGF signalling are important components.
Comprehensive Analysis of Prognostic lncRNAs, miRNAs, and mRNAs Forming a Competing Endogenous RNA Network in LGG
Authors: Ding Yiming , Liu Hanjie , Zhang Chuanbao , Bao Zhaoshi , Yu Shuqing 
Published: September 2020

Abstract
Background: Messenger RNA(mRNA) and Long non coding RNA (lncRNA) targets can interact through the ability to compete for microRNA binding. However, the roles of cancer specific lncRNAs in lncRNA-related ceRNA network of low grade glioma (LGG) are still unclear.Methods: This study obtained two types of RNAs sequencing data in Solid Tissue Normal and LGG Primary Tumor from TCGA database. We used a computational method to analyse the relation between mRNAs, lncRNAs and miRNAs. The function enrichment of Go item and KEGG pathway were analyzed to predict the biological process and pathway of the screened gene. Kaplan‐Meier survival analysis was used to evaluate the association with the expression levels of mRNAs, lncRNAs, and micRNAs and the overall survival of the patients. the ceRNA network of mRNA-lncRNA-miRNA was constructed with the version of cycloscape 3.5.1.Results: 2555 DEmRNA, 218 DElncRNA. 192 DEmiRNAs were screened by using the R package. We analyzed the function enrichment of Go item and KEGG pathway of mRNAs and lncRNAs in ceRNA network. The main 10 BP items, 10 CC items, 10 MF items and 48 KEGG pathways were selected.55 survival related lncRNAs, 50 survival related miRNAs and top 10 survival most related mRNAs in LGG. Finally, 59 miRNAs, 235 mRNAs and 17 lncRNAs, a total of 313 nodes and 1046 edges, constructed the ceRNA network of mRNA-lncRNA-miRNA.Conclusions: This study is advantageous to deeply understand the biological mechanism of ceRNA and to clarify the pathogenesis of LGG.
Coaxial Drainage Versus Standard Chest Tube After Pulmonary Lobectomy: A Randomized Controlled Study
Authors: Bassi Massimiliano , Mottola Emilia , Mantovani Sara , Amore Davide , Pagini Andreina , Diso Daniele , Poggi Camilla , Vannucci Jacopo , Giacomo Tiziano De , Rendina Erino Angelo , Venuta Federico , Anile Marco 
Published: September 2020

Abstract
Background

Chest tubes are routinely inserted after major thoracic surgery procedures and usually two drainages are placed. The aim of this study is to assess the efficacy of Smart Drain Coaxial drainage compared with two standard chest tubes in patients undergoing pulmonary lobectomy.
Methods

Ninety-eight patients (57 males and 41 females, mean age 68.3 ± 7.4 years) with lung cancer undergoing pulmonary lobectomy were randomized in two groups: 50 patients received one upper 28 Fr and one lower 32 Fr standard chest tube (ST group) and 48 patients received one 28 Fr Smart Drain Coaxial chest tube (CT group). Hospitalization, quantity of fluid output, air leaks, chest radiograph findings, pain control and costs were assessed.
Results

We performed 33 right upper lobectomies (17 ST, 16 CT), 25 right lower (15 ST, 10 CT), 20 left upper (8 ST, 12 CT) and 19 left lower (10 ST, 9 CT). The CT group showed a significantly shorter hospitalization (7.3 vs 6.1 days, p = 0.03), a significantly lower pain in postoperative day 1 (p = 0.015) and a lower use of analgesic drugs (p = 0.05). Pleural effusion drainage was lower in CT group both in first postoperative day (464 ± 143 ml vs 408 ± 141 ml, p = 0.05) and average of first three days (374 ± 96 ml vs 324 ± 95 ml, p = 0.01). No differences in terms of fluid retention, pneumothorax, subcutaneous emphysema and complications after chest tubes removal were found.
Conclusion

Smart Drain Coaxial chest tube seems an effective option after pulmonary lobectomy. The CT group showed lower hospitalization and use of analgesic drugs and thus a reduction of costs.
An Online Automatic Corona Diagnose System Based on Chest X-ray Images
Authors: Gougeh Reza Amini 
Published: September 2020

Abstract
An outbreak of SARS-CoV-2 shocked healthcare systems around the world. It began in December 2019 in Wuhan, China, and spread out in over 120 countries in less than three months. Imaging technologies helped in COVID-19 fast and reliable diagnosis. CT-Scan and X-ray imaging are popular methods. This study is focused on X-ray imaging, concerning limitations in small cities to access CT-Scan and its costs. Using deep learning models helps to diagnose precisely and quickly. We aimed to design an online system based on deep learning, which reports lung engagement with the disease, patient status, and therapeutic guidelines. Our objective was to relieve pressure on radiologists and minimize the interval between imaging and diagnosing. VGG19, VGG16, InceptionV3, and ResNet50 were evaluated to be considered as the main code of the online diagnosing system. VGG16, with 98.92% accuracy, achieved the best score. VGG19 performed quite similarly to VGG16. VGG19, InceptionV3 and ResNet50 obtained 98.90, 71.79 and 28.27 subsequently.
A Strategy for Scleroglucan Production in Sclerotium Rolfsii: Lowering pH in Fermentation Process by Manipulating Oxalate Metabolic Pathway With CRISPR/Cas9 Tool
Authors: Bai Tianlong , Wang Teng , Li Yan , Gao Na L , Zhang Lixin , Chen Wei-Hua , Yin Xiushan 
Published: September 2020

Abstract
Background: Sclerotium rolfsii is a potent producer of many secondary metabolites, one of which like scleroglucan is an exopolysaccharide (EPS) appreciated as a multipurpose compound applicable in many industrial fields. Results: We chose AAT1 gene in oxalate metabolic pathway as target of CRISPR/Cas9. When the AAT1 gene is disrupted, oxalate was not converted to α-ketoglutarate (AKG), but accumulated. So AAT1-mutant serves to lower the pH (pH 3-4) to increase the production of the pH-sensitive metabolite scleroglucan to be 21.03 g l-1 with productivity reached 0.25 g/(L·h).Conclusions: We established a platform for gene editing to rapidly generate and select mutants, and provide a new beneficial strain of S. rolfsii as a scleroglucan hyper-producer which could also reduce the cost of controlling optimum pH condition in fermentation industry.