bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abdominal subcutaneous fat quantification in obese patients from limited field-of-view MRI data
Authors: Michel Sophia , Linder Nicolas , Eggebrecht Tobias , Schaudinn Alexander , Blüher Matthias , Dietrich Arne , Denecke Timm , Busse Harald 
Published: November 2020

AbstractDifferent types of adipose tissue can be accurately localized and quantified by tomographic imaging techniques (MRI or CT). One common shortcoming for the abdominal subcutaneous adipose tissue (ASAT) of obese subjects is the technically restricted imaging field of view (FOV). This work derives equations for the conversion between six surrogate measures and fully segmented ASAT volume and discusses the predictive power of these image-based quantities. Clinical (gender, age, anthropometry) and MRI data (1.5 T, two-point Dixon sequence) of 193 overweight and obese patients (116 female, 77 male) from a single research center for obesity were analyzed retrospectively. Six surrogate measures of fully segmented ASAT volume (VASAT) were considered: two simple ASAT lengths, two partial areas (Ap-FH, Ap-ASIS) and two partial volumes (Vp-FH, Vp-ASIS) limited by either the femoral heads (FH) or the anterior superior iliac spine (ASIS). Least-squares regression between each measure and VASAT provided slope and intercept for the computation of estimated ASAT volumes (V~ASAT). Goodness of fit was evaluated by coefficient of determination (R2) and standard deviation of percent differences (sd%) between V~ASAT and VASAT. Best agreement was observed for partial volume Vp-FH (sd% = 14.4% and R2 = 0.78), followed by Vp-ASIS (sd% = 18.1% and R2 = 0.69) and AWFASIS (sd% = 23.9% and R2 = 0.54), with minor gender differences only. Other estimates from simple lengths and partial areas were moderate only (sd% > 23.0% and R2 < 0.50). Gender differences in R2 generally ranged between 0.02 (dven) and 0.29 (Ap-FH). The common FOV restriction for MRI volumetry of ASAT in obese subjects can best be overcome by estimating VASAT from Vp-FH using the equation derived here. The very simple AWFASIS can be used with reservation.
Identification and characterization of the proteolytic flagellin from the common freshwater bacterium Hylemonella gracilis
Authors: Eckhard Ulrich , Blöchl Constantin , Jenkins Benjamin G. L. , Mansfield Michael J. , Huber Christian G. , Doxey Andrew C. , Brandstetter Hans 
Published: November 2020

AbstractFlagellins are the protein components of bacterial flagella and assemble in up to 20,000 copies to form extracellular flagellar filaments. An unusual family of flagellins was recently discovered that contains a unique metalloprotease domain within its surface-exposed hypervariable region. To date, these proteolytic flagellins (also termed flagellinolysins) have only been characterized in the Gram-positive organism Clostridium haemolyticum, where flagellinolysin was shown to be proteolytically active and capable of cleaving extracellular protein substrates. The biological function of flagellinolysin and its activity in other organisms, however, remain unclear. Here, using molecular biochemistry and proteomics, we have performed an initial characterization of a novel flagellinolysin identified from Hylemonella gracilis, a Gram-negative organism originally isolated from pond water. We demonstrate that H. gracilis flagellinolysin (HgrFlaMP) is an active calcium-dependent zinc metallopeptidase and characterize its cleavage specificity profile using both trypsin and GluC-derived peptide libraries and protein substrates. Based on high-throughput degradomic assays, HgrFlaMP cleaved 784 unique peptides and displayed a cleavage site specificity similar to flagellinolysin from C. haemolyticum. Additionally, by using a set of six protein substrates, we identified 206 protein-embedded cleavage sites, further refining the substrate preference of HgrFlaMP, which is dominated by large hydrophobic amino acids in P1′, and small hydrophobic or medium-sized polar residues on the amino-terminal side of the scissile bond. Intriguingly, recombinant HgrFlaMP was also capable of cleaving full-length flagellins from another species, suggesting its potential involvement in interbacterial interactions. Our study reports the first experimentally characterized proteolytic flagellin in a Gram-negative organism, and provides new insights into flagellum-mediated enzymatic activity.
Antifibrotic therapy by sustained release of low molecular weight heparin from poly(lactic-co-glycolic acid) microparticles on bleomycin-induced pulmonary fibrosis in mice
Authors: Saito Takashi , Kotani Takuya , Suzuki Koichi 
Published: November 2020

AbstractHeparin and low molecular weight heparin (LMWH) have recently been considered useful treatment tools for inflammation. Heparin has antifibrotic activity, mediated by cellular secretion of hepatocyte growth factor (HGF). HGF has antifibrotic properties demonstrated in experimental models of lung, kidney, heart, skin, and liver fibrosis. The ability of LMWH for HGF secretion is similar to that of normal heparin. Poly (lactic-co-glycolic acid) (PLGA) is widely used for sustained drug release, because of its biocompatibility and low toxicity. LMWH-loaded PLGA microparticles are prepared by a conventional water-in-oil-in-water emulsion method. Interstitial pneumonia is a life-threatening pathological condition that causes respiratory failure when it progresses. In the present study, we investigated the therapeutic effect of LMWH-loaded PLGA microparticles in a mouse model of bleomycin-induced lung fibrosis. The ratios of fibrotic area to total area were significantly lower in mice administered LMWH-loaded microparticles than in mice administered bleomycin alone. The microparticle administration did not further enhance the gene expression for inflammatory cytokines. In a cell culture study, HGF secretion by mouse and human lung fibroblasts was significantly increased by LMWH addition. We conclude that LMWH showed anti-inflammatory activity, through the effects of LMWH-loaded PLGA microparticles on cells at sites of inflammation.
Temperature-dependent optical and vibrational properties of PtSe2 thin films
Authors: Gulo Desman P. , Yeh Han , Chang Wen-Hao , Liu Hsiang-Lin 
Published: November 2020

AbstractPtSe2 has received substantial research attention because of its intriguing physical properties and potential practical applications. In this paper, we investigated the optical properties of bilayer and multilayer PtSe2 thin films through spectroscopic ellipsometry over a spectral range of 0.73–6.42 eV and at temperatures between 4.5 and 500 K. At room temperature, the spectra of refractive index exhibited several anomalous dispersion features below 1000 nm and approached a constant value in the near-infrared frequency range. The thermo-optic coefficients of bilayer and multilayer PtSe2 thin films were (4.31 ± 0.04) × 10−4/K and (–9.20 ± 0.03) × 10−4/K at a wavelength of 1200 nm. Analysis of the optical absorption spectrum at room temperature confirmed that bilayer PtSe2 thin films had an indirect band gap of approximately 0.75 ± 0.01 eV, whereas multilayer PtSe2 thin films exhibited semimetal behavior. The band gap of bilayer PtSe2 thin films increased to 0.83 ± 0.01 eV at 4.5 K because of the suppression of electron–phonon interactions. Furthermore, the frequency shifts of Raman-active Eg and A1g phonon modes of both thin films in the temperature range between 10 and 500 K accorded with the predictions of the anharmonic model. These results provide basic information for the technological development of PtSe2-based optoelectronic and photonic devices at various temperatures.
Human perinatal stem cell derived extracellular matrix enables rapid maturation of hiPSC-CM structural and functional phenotypes
Authors: Block Travis , Creech Jeffery , da Rocha Andre Monteiro , Marinkovic Milos , Ponce-Balbuena Daniela , Jiménez-Vázquez Eric N. , Griffey Sy , Herron Todd J. 
Published: November 2020

AbstractThe immature phenotype of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) is a major limitation to the use of these valuable cells for pre-clinical toxicity testing and for disease modeling. Here we tested the hypothesis that human perinatal stem cell derived extracellular matrix (ECM) promotes hiPSC-CM maturation to a greater extent than mouse cell derived ECM. We refer to the human ECM as Matrix Plus (Matrix Plus) and compare effects to commercially available mouse ECM (Matrigel). hiPSC-CMs cultured on Matrix Plus mature functionally and structurally seven days after thaw from cryopreservation. Mature hiPSC-CMs showed rod-shaped morphology, highly organized sarcomeres, elevated cTnI expression and mitochondrial distribution and function like adult cardiomyocytes. Matrix Plus also promoted mature hiPSC-CM electrophysiological function and monolayers’ response to hERG ion channel specific blocker was Torsades de Pointes (TdP) reentrant arrhythmia activations in 100% of tested monolayers. Importantly, Matrix Plus enabled high throughput cardiotoxicity screening using mature human cardiomyocytes with validation utilizing reference compounds recommended for the evolving Comprehensive In Vitro Proarrhythmia Assay (CiPA) coordinated by the Health and Environmental Sciences Institute (HESI). Matrix Plus offers a solution to the commonly encountered problem of hiPSC-CM immaturity that has hindered implementation of these human based cell assays for pre-clinical drug discovery.
Implications of historical height loss for prevalent vertebral fracture, spinal osteoarthritis, and gastroesophageal reflux disease
Authors: Nakano Masaki , Nakamura Yukio , Suzuki Takako , Kobayashi Tsukasa , Takahashi Jun , Shiraki Masataka 
Published: November 2020

AbstractWe recently uncovered an association between spinal osteoarthritis and height loss that was independent of incident vertebral fracture. However, the optimal cut-off value of historical height loss (HHL) for discriminating spinal osteoarthritis has not been reported. This cross-sectional study aimed to evaluate the implications of HHL for prevalent vertebral fracture, spinal osteoarthritis, and other co-morbidities in postmenopausal women from the Nagano Cohort Study. In total, 942 Japanese postmenopausal outpatients (mean age: 66.7 years) were investigated. HHL was estimated by arm span – body height difference. Multiple logistic regression analysis revealed significant independent associations of HHL with prevalent vertebral fracture (odds ratio [OR] 1.89; 95% confidence interval [CI] 1.55–2.29), spinal osteoarthritis (OR 1.57; 95% CI 1.31–1.88), and gastroesophageal reflux disease (GERD) (OR 1.75; 95% CI 1.34–2.28) after adjustment for other confounders. Receiver operating characteristic curve analysis of HHL was conducted to discriminate the prevalence of co-morbidities. The optimal cut-off value as defined by the Youden index for prevalent vertebral fracture, spinal osteoarthritis, and GERD was 4.95 cm (area under the curve [AUC] 0.740; 95% CI 0.704–0.776), 2.75 cm (AUC 0.701; 95% CI 0.667–0.735), and 5.35 cm (AUC 0.692; 95% CI 0.629–0.754), respectively. Better understanding of the above relationships and proposed cut-off values will be useful for improving the diagnosis, care management, and quality of life in elderly patients.
Hydroxyurea treatment is associated with reduced degree of oxidative perturbation in children and adolescents with sickle cell anemia
Authors: Vinhaes Caian L. , Teixeira Rozana S. , Monteiro-Júnior Jay A. S. , Tibúrcio Rafael , Cubillos-Angulo Juan M. , Arriaga María B. , Sabarin Adrielle G. , de Souza Amâncio J. , Silva Jacqueline J. , Lyra Isa M. , Ladeia Ana Marice , Andrade Bruno B. 
Published: November 2020

AbstractSickle cell anemia (SCA) is the most common inherited hemolytic anemia worldwide. Here, we performed an exploratory study to investigate the systemic oxidative stress in children and adolescents with SCA. Additionally, we evaluated the potential impact of hydroxyurea therapy on the status of oxidative stress in a case–control study from Brazil. To do so, a panel containing 9 oxidative stress markers was measured in plasma samples from a cohort of 47 SCA cases and 40 healthy children and adolescents. Among the SCA patients, 42.5% were undertaking hydroxyurea. Multidimensional analysis was employed to describe disease phenotypes. Our results demonstrated that SCA is associated with increased levels of oxidative stress markers, suggesting the existence of an unbalanced inflammatory response in peripheral blood. Subsequent analyses revealed that hydroxyurea therapy was associated with diminished oxidative imbalance in SCA patients. Our findings reinforce the idea that SCA is associated with a substantial dysregulation of oxidative responses which may be dampened by treatment with hydroxyurea. If validated by larger prospective studies, our observations argue that reduction of oxidative stress may be a main mechanism through which hydroxyurea therapy attenuates the tissue damage and can contribute to improved clinical outcomes in SCA.
Prognostic significance of the Controlling Nutritional Status (CONUT) score in predicting postoperative complications in patients with Crohn’s disease
Authors: Dong Xue , Tang Shasha , Liu Wei , Qi Weilin , Ye Linna , Yang Xiaoyan , Ge Xiaolong , Zhou Wei 
Published: November 2020

AbstractPreoperative immune-nutritional status is correlated with postoperative outcomes. The Controlling Nutritional Status (CONUT) score is a useful tool for predicting the postoperative outcomes of cancer surgery. This study aimed to evaluate whether the CONUT score could predict postoperative complications in Crohn’s disease (CD) patients. In total, 202 CD patients were eligible. Univariate and multivariate analyses were performed to identify risk factors for postoperative complications. Receiver operating characteristic (ROC) curves were generated to examine the cutoff value for predictors of postoperative complications. Among all the patients, 66 developed postoperative complications. The cut-off value of the CONUT score was 3.5 for complications. Eighty-one patients had a low CONUT score (< 3.5), and 121 patients had a high CONUT score (> 3.5). There was a significant difference in postoperative complications between the groups with low and high CONUT score (17.3% vs. 43.0%, p < 0.001). Patients with high CONUT score had low body mass index (BMI), more mild postoperative complications (p = 0.001) and a longer postoperative stay (p = 0.002). Postoperative complications were correlated with BMI, preoperative albumin, the preoperative CONUT score, and preoperative infliximab use. Then, the preoperative CONUT score was an independent risk factor for complications (OR 3.507, 95% CI 1.522–8.079, p = 0.003). ROC analysis showed that the CONUT score was a better predictor of postoperative complications in CD patients than albumin and the prognostic nutritional index. Thus, a preoperative CONUT score cut-off value of more than 3.5 could help to identify patients with a high possibility of malnutrition and postoperative complications.
Inhibition of red blood cell development by arsenic-induced disruption of GATA-1
Authors: Zhou Xixi , Medina Sebastian , Bolt Alicia M. , Zhang Haikun , Wan Guanghua , Xu Huan , Lauer Fredine T. , Wang Shu Chun , Burchiel Scott W. , Liu Ke Jian 
Published: November 2020

AbstractAnemia is a hematological disorder that adversely affects the health of millions of people worldwide. Although many variables influence the development and exacerbation of anemia, one major contributing factor is the impairment of erythropoiesis. Normal erythropoiesis is highly regulated by the zinc finger transcription factor GATA-1. Disruption of the zinc finger motifs in GATA-1, such as produced by germline mutations, compromises the function of this critical transcription factor and causes dyserythropoietic anemia. Herein, we utilize a combination of in vitro and in vivo studies to provide evidence that arsenic, a widespread environmental toxicant, inhibits erythropoiesis likely through replacing zinc within the zinc fingers of the critical transcription factor GATA-1. We found that arsenic interacts with the N- and C-terminal zinc finger motifs of GATA-1, causing zinc loss and inhibition of DNA and protein binding activities, leading to dyserythropoiesis and an imbalance of hematopoietic differentiation. For the first time, we show that exposures to a prevalent environmental contaminant compromises the function of a key regulatory factor in erythropoiesis, producing effects functionally similar to inherited GATA-1 mutations. These findings highlight a novel molecular mechanism by which arsenic exposure may cause anemia and provide critical insights into potential prevention and intervention for arsenic-related anemias.
Differential type I interferon response and primary airway neutrophil extracellular trap release in children with acute respiratory distress syndrome
Authors: Grunwell Jocelyn R. , Stephenson Susan T. , Mohammad Ahmad F. , Jones Kaitlin , Mason Carrie , Opolka Cydney , Fitzpatrick Anne M. 
Published: November 2020

AbstractAcute respiratory distress syndrome (ARDS) is a heterogeneous condition characterized by the recruitment of large numbers of neutrophils into the lungs. Neutrophils isolated from the blood of adults with ARDS have elevated expression of interferon (IFN) stimulated genes (ISGs) associated with decreased capacity of neutrophils to kill Staphylococcus aureus and worse clinical outcomes. Neutrophil extracellular traps (NETs) are elevated in adults with ARDS. Whether pediatric ARDS (PARDS) is similarly associated with altered neutrophil expression of ISGs and neutrophil extracellular trap release is not known. Tracheal aspirate fluid and cells were collected within 72 h from seventy-seven intubated children. Primary airway neutrophils were analyzed for differential ISG expression by PCR, STAT1 phosphorylation and markers of degranulation and activation by flow cytometry. Airway fluid was analyzed for the release of NETs by myeloperoxidase-DNA complexes using an ELISA. Higher STAT1 phosphorylation, markers of neutrophil degranulation, activation and NET release were found in children with versus without PARDS. Higher NETs were detected in the airways of children with ventilator-free days less than 20 days. Increased airway cell IFN signaling, neutrophil activation, and NET production is associated with PARDS. Higher levels of airway NETs are associated with fewer ventilator-free days.
Comparison and verification of turbulence Reynolds-averaged Navier–Stokes closures to model spatially varied flows
Authors: Chipongo Kudzai , Khiadani Mehdi , Sookhak Lari Kaveh 
Published: November 2020

AbstractThe robustness and accuracy of Reynolds-averaged Navier–Stokes (RANS) models was investigated for complex turbulent flow in an open channel receiving lateral inflow, also known as spatially varied flow with increasing discharge (SVF). The three RANS turbulence models tested include realizable k–ε, shear stress transport k–ω and Reynolds stress model based on their prominence to model jets in crossflows. Results were compared to experimental laser Doppler velocimetry measurements from a previous study. RANS results in the uniform flow region and farther from the jet centreline were more accurate than within the lateral inflow region. On the leeward side of the jet, RANS models failed to capture the downward velocity vectors resulting in major deviations in vertical velocity. Among RANS models minor variations were noted at impingement and near the water surface. Regardless of inadequately predicting complex characteristics of SVF, RANS models matched experimental water surface profiles and proved more superior to the theoretical approach currently used for design purposes.
Regulatory (FoxP3+) T cells and TGF-β predict the response to anti-PD-1 immunotherapy in patients with non-small cell lung cancer
Authors: Koh Jiae , Hur Joon Young , Lee Kyoung Young , Kim Mi Soon , Heo Jae Yeong , Ku Bo Mi , Sun Jong-Mu , Lee Se-Hoon , Ahn Jin Seok , Park Keunchil , Ahn Myung-Ju 
Published: November 2020

AbstractAntitumor immune responses induced by immune checkpoint inhibitors anti-PD-1 or anti-PD-L1 have been used as therapeutic strategies in advanced non-small cell lung cancer (NSCLC) patients over the last decade. Favorable antitumor activity to immune checkpoint inhibitors is correlated with high PD-L1 expression, increased tumor-infiltrating lymphocytes, and decreased suppressive immune cells including Treg cells, myeloid-derived suppressor cells, or tumor-associated macrophages in various cancer types. In this study, we investigated the potential correlation between clinical outcomes and peripheral blood immune cell profiles, specifically focused on FoxP3+Treg cells, collected at baseline and one week after anti-PD-1 therapy in two independent cohorts of patients with NSCLC: a discovery cohort of 83 patients and a validation cohort of 49 patients. High frequencies of circulating Treg cells one week after anti-PD-1 therapy were correlated with a high response rate, longer progression-free survival, and overall survival. Furthermore, high levels of TGF-β and Treg cells were associated with favorable clinical outcomes. Our results suggest that higher levels of FoxP3+Treg cells and TGF-β can predict a favorable response to anti-PD-1 immunotherapy in patients with advanced NSCLC.
Evolution from adherent to suspension: systems biology of HEK293 cell line development
Authors: Malm Magdalena , Saghaleyni Rasool , Lundqvist Magnus , Giudici Marco , Chotteau Veronique , Field Ray , Varley Paul G. , Hatton Diane , Grassi Luigi , Svensson Thomas , Nielsen Jens , Rockberg Johan 
Published: November 2020

AbstractThe need for new safe and efficacious therapies has led to an increased focus on biologics produced in mammalian cells. The human cell line HEK293 has bio-synthetic potential for human-like production attributes and is currently used for manufacturing of several therapeutic proteins and viral vectors. Despite the increased popularity of this strain we still have limited knowledge on the genetic composition of its derivatives. Here we present a genomic, transcriptomic and metabolic gene analysis of six of the most widely used HEK293 cell lines. Changes in gene copy and expression between industrial progeny cell lines and the original HEK293 were associated with cellular component organization, cell motility and cell adhesion. Changes in gene expression between adherent and suspension derivatives highlighted switching in cholesterol biosynthesis and expression of five key genes (RARG, ID1, ZIC1, LOX and DHRS3), a pattern validated in 63 human adherent or suspension cell lines of other origin.