bluuebunny/crossref_metadata_2025_split huggingface dataset:
Charactering tumor microenvironment reveals stromal‐related transcription factors promote tumor carcinogenesis in gastric cancer
Authors: Liu Haining , Ni Shujuan , Wang Hanbo , Zhang Qiongyan , Weng Weiwei 
Published: May 2020

AbstractTranscription factors represent the crucial role of controlling gene transcription in cancer development and progression. However, their functions in gastric cancer have not been thoroughly characterized. For this study, we comprehensively evaluated the correlation between infiltration patterns of tumor microenvironment (TME) cells and TFs expression in the cohort of stomach adenocarcinoma (STAD) from TCGA database. We integrally explored differential expression panel and prognostic value of candidate TFs in TCGA‐STAD cohort. Notably, we found a key transcription factor named HEYL, which its expression level was correlated with stromal component transformation of TME. HEYL was regularly high expressed in gastric cancer and correlated with patients’ poor prognosis. Knockdown of HEYL prominently abrogated the tendency of cell proliferation, migration, and progression in gastric cancer. Consistently, overexpression of HEYL strikingly accelerated the gastric carcinoma development through activating oncogenic signaling pathways and transcriptional activation of cadherin 11 (CDH11). Our findings not only identified the close relationship between TFs and TME phenotype, but also emphasized the crucial importance of TFs, especially HEYL, which could be identified as a candidate biomarker to evaluate prognostic risk and therapeutic effect in gastric cancer.
Characteristics of non‐culprit plaques in acute coronary syndrome patients with calcified plaque at the culprit lesion
Authors: Kim Hyung Oh , Kim Chong Jin , Cho Jin‐Man , Soeda Tsunenari , Kurihara Osamu , Russo Michele , Araki Makoto , Lee Hang , Minami Yoshiyasu , Jang Ik‐Kyung 
Published: May 2020

AbstractObjectivesTo investigate the non‐culprit plaques (NCPs) characteristics in acute coronary syndrome (ACS) patients with calcified plaques (CP).BackgroundRecently, a new in vivo classification of calcified culprit plaques in patients with ACS was proposed. Characteristics of NCPs in this group of patients are unknown.MethodsA total of 692 NCPs from 492 ACS patients were retrospectively compared based on the culprit plaque phenotype: 71 from CP patients, 383 from plaque rupture (PR) patients, 238 from plaque erosion (PE) patients.ResultsNCPs of CP patients had greater maximal calcium thickness, wider calcium arc, longer calcium length, and greater calcium index, compared to PR or PE patients (CP vs. PR: all p < .001, CP vs. PE: all p < .001). Thin‐cap fibroatheroma was less prevalent (p = .023), fibrous cap was thicker (p = .035), and mean lipid arc was narrower in CP than in PR (p < .001).ConclusionsIn conclusion, NCPs of CP patients had greater calcium burden and less vulnerability. This information may help to better understand the underlying mechanisms of ACS and to develop strategy for tailored management.
Function‐integrative Lightweight Engineering – Design Methods and Applications
Authors: Modler Niels , Winkler Anja , Filippatos Angelos , Weck Daniel , Dannemann Martin 
Published: May 2020

AbstractFunction‐integrative lightweight engineering represents an essential element in modern design methods. Currently, there is a great need for the incorporation of sensors, actuators and electronics in novel, demand‐oriented components. In contrast to a subsequent, mostly adhesive bonding, structural integration offers numerous advantages, for example in terms of space requirements and robustness. This paper demonstrates the potential of integrated sensors for various industrial sectors based on selected examples from mechanical engineering, aviation, mobility, sports, and medical technology.
Validation of the Functional Assessment of Cancer Therapy–Leukemia instrument in patients with acute myeloid leukemia who are not candidates for intensive therapy
Authors: Peipert John Devin , Yount Susan E. , Efficace Fabio , Loefgren Christina , Pierson Renee , He Jianming , Cella David 
Published: May 2020

BackgroundThe objective of this study was to validate the Functional Assessment of Cancer Therapy–Leukemia (FACT‐Leu) in patients with acute myeloid leukemia (AML) who are not candidates for intensive therapy.MethodsA sample of 317 patients with AML who were not eligible for intensive chemotherapy completed the FACT‐Leu and EuroQol 5‐Dimension (EQ‐5D) measures (Utility Index and Visual Analogue Scale) every 28 days until the end of treatment. Internal consistency reliability was estimated with Cronbach's α. Concurrent validity was examined with correlations between FACT‐Leu and EQ‐5D scales, and known‐groups validity was examined by determining whether FACT‐Leu scales distinguished between Eastern Cooperative Oncology Group (ECOG) performance status ratings (PSRs) and between maximum adverse event toxicities at the baseline. This study examined responsiveness to change by anchoring change in the FACT‐Leu scales to a 0.10 change in the EQ‐5D Health Utility Index.ResultsCronbach's α usually exceeded the threshold for good (≥0.80) or excellent reliability (≥0.90). Correlations between FACT‐Leu and EQ‐5D scales were moderate (r > 0.50) or high (r > 0.70). FACT‐Leu scales distinguished between ECOG PSR groups with large effect sizes for an ECOG PSR of 0 versus an ECOG PSR of 2 (0.50 ≤ d < 0.80). In addition, Functional Assessment of Cancer Therapy–General, Additional Concerns, FACT‐Leu Total, and Trial Outcomes Index scales distinguished between patients with grade 3 or lower maximum adverse event toxicities and those with maximum adverse event toxicities higher than grade 3, but effect sizes were small (d < 0.50). Finally, FACT‐Leu scale coefficients for a 0.10 change in the 5‐level version of the EQ‐5D HUI ranged between −0.01 and 4.30.ConclusionsThe FACT‐Leu is a suitable outcome measure for AML clinical trials among patients not eligible for intensive therapy, and it may have value for clinical monitoring.
A Randomized, Double‐Blind, Parallel‐Group, Phase 1 Clinical Trial Comparing the Pharmacokinetic, Safety, and Immunogenicity of the Biosimilar HS016 and the Originator Adalimumab in Chinese Healthy Male Subjects
Authors: Cao Guoying , Yu Jicheng , Wu Jufang , Wang Jingjing , Xue Yu , Yang Xiaoli , Zhang Jing 
Published: May 2020

AbstractA comparison of the immunogenicity, safety, and pharmacokinetic properties of HS016 and its originator, adalimumab, was conducted in Chinese healthy male subjects. This was a phase 1 single‐center, randomized, parallel‐group double‐blind clinical trial. Chinese healthy male subjects (1:1) allocated to HS016 and adalimumab groups were treated with single subcutaneous injections (40 mg/0.8 mL). The pharmacokinetic equivalence of HS016 and adalimumab was assessed by (1) the area under the plasma concentration‐time curve (AUC) from time 0 to the last detectable drug concentration (AUC0‐t), (2) the AUC from time 0 extrapolated to infinity (AUC0‐∞), and (3) the maximum plasma concentration (Cmax). Other pharmacokinetic parameters (time to Cmax, apparent clearance, and half‐life), safety, and immunogenicity were also evaluated. A total of 136 subjects were randomly divided into HS016 (n = 68) or adalimumab (n = 68) groups. The geometric means of AUC0‐t, AUC0‐∞, and Cmax were similar for HS016 and adalimumab. The 90%CIs of AUC0‐t (87.2% to 106.1%), AUC0‐∞ (87.4% to 108.4%), and Cmax (98.6% to 113.6%) were all within the prespecified bioequivalence criteria (80% to 125%). The incidence of treatment‐emergent adverse events (TEAEs) was similar in both groups, with most TEAEs being mild; only 3 (4.4%) subjects in the HS016 group experienced moderate TEAEs. No significant differences in the time to Cmax, apparent clearance, half‐life, and immunogenicity were detected. The pharmacokinetic profile of HS016 was equivalent to that of the originator, adalimumab, with similar safety and immunogenicity profiles. HS016 may be considered for assessment in the treatment of patients with ankylosing spondylitis.
Generating a Cost‐Effective, Weekend‐Free Chemically Defined Human Induced Pluripotent Stem Cell (hiPSC) Culture Medium
Authors: Fonoudi Hananeh , Lyra‐Leite Davi M. , Javed Hoor A. , Burridge Paul W. 
Published: May 2020

AbstractWe have previously developed a cost‐effective chemically defined medium formula for weekend‐free culture of human induced pluripotent stem cells (hiPSCs), costing ∼3% of the price of commercial medium. This medium, which we termed B8, is specifically optimized for robust and fast growth of hiPSCs and for a weekend‐free medium change regimen. We demonstrated that this medium is suitable for reprogramming of somatic cells into hiPSCs and for differentiation into a variety of lineages. Here, we provide a protocol for simple generation of the most cost‐effective variant of this medium, along with a protocol for making Matrigel‐coated plates and culturing, passaging, cryopreserving, and thawing hiPSCs. © 2020 Wiley Periodicals LLC.Basic Protocol 1: Preparation of a highly optimized, robust, and cost‐effective human induced pluripotent stem cell culture mediumBasic Protocol 2: Weekend‐free maintenance and passaging of human induced pluripotent stem cells in B8 medium
Association study between HTR2A rs6313 polymorphism and early response to risperidone and olanzapine in schizophrenia patients
Authors: Maffioletti Elisabetta , Valsecchi Paolo , Minelli Alessandra , Magri Chiara , Bonvicini Cristian , Barlati Stefano , Sacchetti Emilio , Vita Antonio , Gennarelli Massimo 
Published: May 2020

AbstractAntipsychotic drugs are the preferred choice for schizophrenia treatment; however, response is highly variable. In the context of the search for predictors of antipsychotic treatment effectiveness, the evaluation of response within 2 weeks has been indicated to predict long‐term outcome. Moreover, a focus on symptomatological domains could be helpful to better characterize antipsychotic response, identifying more specific predictors. Pharmacogenetic studies have indicated a role for rs6313 in the serotonin receptor gene HTR2A in affecting response to antipsychotics, with heterogeneous results. With the aim to test for the first time the application of a dimensional approach for the evaluation of early response, we carried out a genetic association study between rs6313 and antipsychotic response in two groups of schizophrenia patients in monotherapy with risperidone (n = 121) and olanzapine (n = 100). Patients were evaluated at the baseline and after 1 and 2 weeks of treatment. When comparing early responders versus early nonresponders, no association was detected for the two drugs separately, whereas by taking into consideration the two drugs together it was observed that carriers of the T allele had a higher response probability compared to noncarriers. Considering 2‐week improvements, changes in PANSS total scores, subscores and in PANSS Emsley's symptomatological dimensions were associated with rs6313 for both risperidone and olanzapine. Moreover, the repeated measures analysis indicated an association of rs6313 with the disorganized thought dimension for risperidone, and with the depressive and anxiety dimensions for olanzapine. These data add support to the hypothesis that the HTR2A gene is involved in antipsychotic treatment outcome.
60 specific eDNA qPCR assays to detect invasive, threatened, and exploited freshwater vertebrates and invertebrates in Eastern Canada
Authors: Hernandez Cecilia , Bougas Bérénice , Perreault‐Payette Alysse , Simard Anouk , Côté Guillaume , Bernatchez Louis 
Published: May 2020

AbstractPractical applications of environmental DNA (eDNA) are in exponential expansion, especially for the assessment and monitoring of freshwater metazoans. Because eDNA sampling and analysis is noninvasive, it improves the detection of threatened, invasive, and exploited species for which monitoring may be challenging. Species detection efforts using a combination of eDNA and qPCR have been highly successful and, as a result, their use in species monitoring is expanding rapidly. We developed qPCR primers and probes in order to monitor many invasive, threatened, or exploited aquatic species as part of various monitoring eDNA projects in the province of Québec, Canada. Here, we present a total of 60 species‐specific qPCR assays (including PCR protocols, primers, and TaqMan probes sequences) developed for the detection of 45 fishes, six amphibians, five reptiles, two mollusks, and two crustaceans. These comprised nine and 27 species, respectively, listed as invasive and threatened in Eastern Canada. These resources should be of broad usefulness not only for monitoring studies based in Québec but throughout the geographic range of the targeted species in North America.
Study on induced stress of hydraulic fracturing in fractured‐porous elastic media
Authors: Hu Yongquan , Wang Qiang , Zhao Jinzhou , Chen Shengnan , Zhang Guiyi , Wang Sukai , Wang Zhiyong , Fu Chenghao 
Published: May 2020

AbstractThe study on induced stress of hydraulic fracturing is an important part of hydraulic fracturing design, temporary plugging and steering fracturing design, and completion design in oil and gas development. Based on fracture continuum method (FCM), cohesive unit method, and finite volume method (FVM), the propagation behavior of multiple hydraulic fractures (HFs) in fractured‐porous media reservoir is simulated from the perspective of fluid and geological stress coupling. The influence of natural fractures (NFs) on stress distribution and stress inversion sensitive factors are studied. NFs in the model are equivalent to physical models controlled by tension and shear bonds. The proposed model can deal with any number of NFs, which greatly improves the computational efficiency of the model. Then PKN analytic solution and Abaqus software results were used to verify the correctness of our model. The results show that the NF will make the reservoir stress show strong heterogeneity after fracturing, and the prominent feature is the regional stress mutation. The sudden change of stress shows the sudden increase or decrease in stress; with the increase in the initial stress difference, the stress inversion becomes more difficult. When the stress difference exceeds 3 MPa, the stress inversion area is almost 0. The stress interference increases with the decrease in cluster spacing. The stress inversion region between HFs decreases, while the external stress inversion region increases; Biot coefficient has great influence on stress and stress inversion. With the decrease in Biot coefficient, stress inversion region will decrease obviously. When the Biot coefficient is 0.4, there is no stress inversion area in the whole reservoir. Poisson's ratio has little influence on stress inversion. When Poisson's ratio changes between 0.1 and 0.3, the change range of stress is within 1 MPa, and the stress inversion area is almost unchanged. Our results can be helpful for understanding the stress distribution after hydraulic fracturing in fractured‐porous media.
Protective and Detrimental Roles of p38α Mitogen‐Activated Protein Kinase in Different Stages of Nonalcoholic Fatty Liver Disease
Authors: Hwang Seonghwan , Wang Xiaolin , Rodrigues Robim M. , Ma Jing , He Yong , Seo Wonhyo , Park Seol Hee , Kim Seung‐Jin , Feng Dechun , Gao Bin 
Published: May 2020

Background and Aims
Neutrophil infiltration is a hallmark of nonalcoholic steatohepatitis (NASH), but how this occurs during the progression from steatosis to NASH remains obscure. Human NASH features hepatic neutrophil infiltration and up‐regulation of major neutrophil‐recruiting chemokines (e.g., chemokine [C‐X‐C motif] ligand 1 [CXCL1] and interleukin [IL]‐8). However, mice fed a high‐fat diet (HFD) only develop fatty liver without significant neutrophil infiltration or elevation of chemokines. The aim of this study was to determine why mice are resistant to NASH development and the involvement of p38 mitogen‐activated protein kinase (p38) activated by neutrophil‐derived oxidative stress in the pathogenesis of NASH.

Approach and Results
Inflamed human hepatocytes attracted neutrophils more effectively than inflamed mouse hepatocytes because of the greater induction of CXCL1 and IL‐8 in human hepatocytes. Hepatic overexpression of Cxcl1 and/or IL‐8 promoted steatosis‐to‐NASH progression in HFD‐fed mice by inducing liver inflammation, injury, and p38 activation. Pharmacological inhibition of p38α/β or hepatocyte‐specific deletion of p38a (a predominant form in the liver) attenuated liver injury and fibrosis in the HFD
+Cxcl1
‐induced NASH model that is associated with strong hepatic p38α activation. In contrast, hepatocyte‐specific deletion of p38a in HFD‐induced fatty liver where p38α activation is relatively weak exacerbated steatosis and liver injury. Mechanistically, weak p38α activation in fatty liver up‐regulated the genes involved in fatty acid β‐oxidation through peroxisome proliferator‐activated receptor alpha phosphorylation, thereby reducing steatosis. Conversely, strong p38α activation in NASH promoted caspase‐3 cleavage, CCAAT‐enhancer‐binding proteins homologous protein expression, and B cell lymphoma 2 phosphorylation, thereby exacerbating hepatocyte death.

Conclusions
Genetic ablation of hepatic p38a increases simple steatosis but ameliorates oxidative stress‐driven NASH, indicating that p38α plays distinct roles depending on the disease stages, which may set the stage for investigating p38α as a therapeutic target for the treatment of NASH.
Spectral relaxation method analysis of Casson nanofluid flow over stretching cylinder with variable thermal conductivity and Cattaneo–Christov heat flux model
Authors: Tulu Ayele , Ibrahim Wubshet 
Published: May 2020

AbstractThis article deals with non‐Newtonian Casson nanofluid flow and heat transfer over stretching cylinder in a porous medium. The mode of heat transfer is presented considering temperature‐dependent thermal conductivity by integrating the Cattaneo–Christov heat flux and mass flux models. Boundary layer theory is applied to develop the governing partial differential equations from the physical problem. Employing proper similarity transformation, the governing boundary layer equations are transformed into dimensionless system of nonlinear ordinary differential equations. Then, the resulting problem is numerically solved by means of spectral relaxation method. The convergence analysis of the proposed numerical scheme is presented via a table, which confirms almost the 10th order of approximation is enough for the convergence of the skin friction coefficient, local heat transfer, and mass transfer rates. The effects of various embedded parameters on velocity, temperature, and concentration profiles as well as skin friction coefficient, surface heat and mass transfer rates are examined through graphs and tables. The findings reveal that the growth of permeability and velocity slip parameters appears to decelerate the velocity distributions of fluid. Thermal boundary layer thickness tends to develop with greater values of permeability and Brownian motion parameters. Also, the local heat transfer rate is less with Fourier's law of heat conduction than Cattaneo–Christov heat flux model. Furthermore, the validity and accuracy of the present result is checked with the available literature, and very sound agreement has been obtained.
Numerical study of natural convection and acoustic waves using the lattice Boltzmann method
Authors: Benhamou Jaouad , Jami Mohammed , Mezrhab Ahmed , Botton Valéry , Henry Daniel 
Published: May 2020

AbstractIn this paper, the lattice Boltzmann method is used to study the acoustic waves propagation inside a differentially heated square enclosure filled with air. The waves are generated by a point sound source located at the center of this cavity. The main aim of this simulation is to simulate the interaction between the thermal convection and the propagation of these acoustic waves. The results have been validated with those obtained in the literature and show that the effect of natural convection on the acoustic waves propagation is almost negligible for low Rayleigh numbers (Ra ≤ 104), which begins to appear when the Rayleigh number begins to become important (Ra ≥ 105) and it becomes considerable for large Rayleigh numbers (Ra ≥ 106) where the thermal convection is important.
Progressive plasmacytoid variant bladder cancer with retroperitoneal dissemination: An autopsy case report
Authors: Kohada Yuki , Kaiho Yasuhiro , Ito Jun , Mikami Jotaro , Anan Go , Asano Katsutoshi , Yaegashi Toru , Murakami Kazuhiro , Nakamura Yasuhiro , Sato Makoto 
Published: May 2020

IntroductionPlasmacytoid urothelial carcinoma is a rare and aggressive variant of bladder cancer.Case presentationA 75‐year‐old woman presented with plasmacytoid urothelial carcinoma with retroperitoneal dissemination was treated with chemotherapy. After an unsuccessful first‐line chemotherapy with gemcitabine and cisplatin, we assessed circulating tumor cells; one such cell was found to be positive for programmed death‐ligand 1. The patient received second‐line chemotherapy with pembrolizumab. However, the tumor extended to the retroperitoneal organs, and the patient eventually died. Autopsy revealed a widespread diffuse scirrhous infiltration of the carcinoma into the retroperitoneum. However, distant metastasis was not observed.ConclusionThe evaluation of circulating tumor cells and autopsy revealed a disease state of progressive plasmacytoid urothelial carcinoma treated with pembrolizumab.
Response to Bistrian BR. Parenteral Fish‐Oil Emulsions in Critically Ill COVID‐19 Emulsions
Authors: Torrinhas Raquel S. , Calder Philip C. , Waitzberg Dan L. 
Published: May 2020

AbstractIn this letter we discuss the proposition of Bristian BR (2020) to use the intravenous administration of fish‐oil emulsions in critically ill patients with Coronavirus Disease 2019 (COVID‐19). We consider that immune‐modulatory properties of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, rapidly provided in high amounts by fish‐oil emulsions, may be important to change the course of COVID‐19's death pathway. Prescriptions should be based on body weight (eg, 0.2‐g pure fish‐oil lipid emulsion/kg body weight/d) and also should consider combining the parenteral administration of fish‐oil emulsions with low oral aspirin intake to trigger resolvin synthesis from EPA and DHA.