bluuebunny/crossref_metadata_2025_split huggingface dataset:
YAP1 Withdrawal in Hepatoblastoma Drives Therapeutic Differentiation of Tumor Cells to Functional Hepatocyte‐Like Cells
Authors: Smith Jordan L. , Rodríguez Tomás C. , Mou Haiwei , Kwan Suet‐Yan , Pratt Henry , Zhang Xiao‐Ou , Cao Yueying , Liang Shunqing , Ozata Deniz M. , Yu Tianxiong , Yin Qiangzong , Hazeltine Max , Weng Zhiping , Sontheimer Erik J. , Xue Wen 
Published: May 2020

Background and Aims
Despite surgical and chemotherapeutic advances, the 5‐year survival rate for stage IV hepatoblastoma (HB), the predominant pediatric liver tumor, remains at 27%. Yes‐associated protein 1 (YAP1) and β‐catenin co‐activation occurs in 80% of children’s HB; however, a lack of conditional genetic models precludes tumor maintenance exploration. Thus, the need for a targeted therapy remains unmet. Given the predominance of YAP1 and β‐catenin activation in HB, we sought to evaluate YAP1 as a therapeutic target in HB.

Approach and Results
We engineered the conditional HB murine model using hydrodynamic injection to deliver transposon plasmids encoding inducible YAP1S127A, constitutive β‐cateninDelN90, and a luciferase reporter to murine liver. Tumor regression was evaluated using bioluminescent imaging, tumor landscape characterized using RNA and ATAC sequencing, and DNA footprinting. Here we show that YAP1S127A withdrawal mediates more than 90% tumor regression with survival for 230+ days in mice. YAP1S127A withdrawal promotes apoptosis in a subset of tumor cells, and in remaining cells induces a cell fate switch that drives therapeutic differentiation of HB tumors into Ki‐67‐negative hepatocyte‐like HB cells (“HbHeps”) with hepatocyte‐like morphology and mature hepatocyte gene expression. YAP1S127A withdrawal drives the formation of hbHeps by modulating liver differentiation transcription factor occupancy. Indeed, tumor‐derived hbHeps, consistent with their reprogrammed transcriptional landscape, regain partial hepatocyte function and rescue liver damage in mice.

Conclusions
YAP1S127A withdrawal, without silencing oncogenic β‐catenin, significantly regresses hepatoblastoma, providing in vivo data to support YAP1 as a therapeutic target for HB. YAP1S127A withdrawal alone sufficiently drives long‐term regression in HB, as it promotes cell death in a subset of tumor cells and modulates transcription factor occupancy to reverse the fate of residual tumor cells to mimic functional hepatocytes.
Study on drivers' visual perception characteristics during the take‐over of vehicle control in automated driving
Authors: Niu Jianwei , Xu Haixin , Sun Yipin , Qin Hua 
Published: May 2020

AbstractA high degree of automated driving distracts drivers more easily, resulting in slow recognition of critical events during driving and slow responses to emergencies. Automated driving and manual switching processes are also prone to erroneous decisions. We conducted a simulated automated driving experiment to study participants' visual perception characteristics during the take‐over of vehicle control. The present study used dynamic videos to imitate the driving situations when drivers returned their gaze from the distractive source to the road. We collected the drivers' eye movement data to analyze the search strategy and physiological characteristics of the drivers after the take‐over reminder. The results showed that the instant information search method of the drivers was scanning of the driving scene. When the degree of distraction deepened and the hazard level of scenes increased, the pupil diameter of the drivers increased and the fixation duration became longer. These findings can help to design take‐over warnings and support more intelligent automated driving systems to judge whether measures should be taken to interfere with the driver's operation to avoid collisions. Furthermore, the drivers' fixation point distribution focused on the left side and the lower side of the scene. We suggest that the take‐over warning is displayed in the head‐up display. This study provides a better understanding of drivers' visual perception characteristics when drivers' eyesight returns from other distractors to the driving scene and a good theoretical basis for the design of hazard warning information for automated driving.
Radiation aspects on magneto‐Carreau nanoliquid flow over a bidirectionally stretchable surface with variable thermal conditions
Authors: Ahmad Iftikhar , Faisal Muhammad , Javed Tariq 
Published: May 2020

AbstractInspired by spectacular applications of nonlinear resources in the field of nanotechnology, we formulate a mathematical relation for unsteady radiative flow of a magneto‐Carreau nanoliquid as the consequence of a bidirectionally stretchable surface using the Buongiorno model. Practically, this newly mentioned approach is more genuine where we account for the fact that the surface temperature and surface heat flux are adjusted themselves on the boundaries, accordingly. With the utilization of this approach, industrial and engineering quantities of interest are investigated in a more effective manner. A suitable combination of variables is used to alter the partial differential equations into ordinary differential equations and then computationally solved by employing the Keller box method. The great significance of the involved constraints on the Carreau nanomaterial velocity components, temperature, and concentration fields is depicted graphically and elucidated in detail. The foremost outcomes for drag forces, surface temperature gradient, and concentration gradient for the Carreau nanomaterial are anticipated and arranged through tables. For endorsement of the present solution, the attained outcomes are linked with formerly published work in a particular case and found in marvelous agreement. It is observed that an escalating amount of radiative parameter Rd enhances the temperature of the Carreau nanomaterial. Moreover, the amounts of heat and mass fluxes are significantly improved by increasing the temperature of the surface.
Analysis of visualization techniques of bottom heated lid–driven square cavity
Authors: Narayana Vekamulla , Rani Hari Ponnamma 
Published: May 2020

AbstractIn the present study, an attempt is made to explore the flow visualization techniques inside the bottom heated lid–driven square cavity. The governing equations along with boundary conditions are solved numerically. The convection differencing schemes namely, upwind difference, quadratic upstream interpolation for convective kinetics, Superbee, and self‐filtered central differencing schemes are discussed and are used to simulate the flow using message passing interface (MPI) code. An attempt has been made to analyze the flow behavior inside the cavity using streamlines, isotherms energy streamlines, and field synergy by varying the Reynolds number (Re) and Richardson number (Ri). The simulated results (100≤ Re ≤ 1000 and 0.001≤ Ri ≤ 10) are validated with previous results in literature. It is observed that the computational cost for all the differencing schemes gets reduced tremendously when the MPI code is implemented. Flow becomes quasi‐two‐dimensional for Ri < 1. Overall, Nusselt number increases mildly with cavity inclination for the forced convection–dominated case (Ri = 0.1) while it increases much more rapidly with inclination for natural convection–dominated case (Ri = 10).
Unsteady problem of magnetohydrodynamic heat plus mass transfer convective flow over a moveable plate with effects of thermophoresis and thermal radiation
Authors: Ayegbusi Florence D. , Onwubuoya Cletus , Falodun Bidemi O. 
Published: May 2020

AbstractThis paper investigates the problem of unsteady magnetohydrodynamic heat plus mass transfer convective flow over a moveable vertical plate with the influence of thermophoresis and thermal radiation. The physical problem is governed by a set of partial differential equations. These sets of equations are coupled and are nonlinear. They were transformed into a dimensionless form of equations by introducing appropriate nondimensional quantities. An iterative method called the spectral relaxation method was used to linearize and decouple the set of dimensionless equations. Results were presented both in graphs and tables. It was found out that thermophoresis parameter has a significant effect on velocity and concentration fields. The thermal radiation is seen to have a significant effect on velocity and temperature fields. The skin friction is seen to increase the moment thermal Grashof number is increased. The model of Newtonian fluid flow over a moveable vertical plate is considered. The plate was considered moving toward the ‐direction and the radiative heat flux is only with respect to . This study considered effects of viscous dissipation, thermophoresis, and radiation on heat plus mass transfer. This, to the best of our knowledge, has not been considered in the literature.
Impact of aligned MHD flow with inclined outer velocity for a casson nanofluid over a stretching sheet
Authors: Devi Renu , Poply Vikas , Manimala  
Published: May 2020

AbstractThe scope of the introduced study focuses on the analysis of heat as well as flow transportation in an oblique Casson nanofluid in the presence of an aligned magnetic field. The fluid is supposed to impinge obliquely on a sheet that stretches in both directions of the x‐axis with heat generation. The moulded partial differential equations computed numerically with the shooting procedure by adopting the Runge Kutta Fehlberg method. The change in the behaviour of the emerging fluid parameters are described graphically and their results are shows in tables. The outcomes disclosed that the fluid velocity declined for Casson fluid parameter and the aligned angle of the magnetic field. In addition, with the increase in the Casson fluid parameter and aligned angle of magnetic field, the fluid temperature and concentration rise. The outcomes of this study may be beneficial to control the rate of heat and mass transportation as well as controlling fluid velocity in industry to obtain a final product of the desired quality.
Assessment of thermal characteristics of square wavy plates
Authors: Hussain Shafqat , Kalendar Abdulrahim , Rafique Muhammad Zeeshan , Oosthuizen Patrick H. 
Published: May 2020

AbstractIn this paper, the thermal characteristics and air flow behavior over heated square plate of wavy configurations are assessed. Two cases of heated wavy configurations were considered, one having an elliptical and other with the sinusoidal cross‐sectional shape to augment heat transfer rate over the plate. To explore the impact of wavy configurations of plate on convective heat transfer, the Rayleigh numbers in the range of 104 to 1013 were considered. The steady‐state two‐dimensional momentum and energy equations were solved using a validated numerical model. The numerical results in terms of Nusselt numbers, Rayleigh numbers, aspect ratio (AR), and flow/temperature distribution over the plate are presented. The variations in the heat transfer coefficient and temperature contours with Rayleigh number and AR of waves were concentrated for both the elliptical and sinusoidal configurations of the plate. The results obtained indicate that the enhancement in heat transfer rate from the heated plate depends on the Rayleigh number, the AR of waves, plate configuration, and the Prandtl number.
Monitoring of water surface temperature of Eurasian large lakes usingMODISland surface temperature product
Authors: Du Jia , Jacinthe Pierre‐Andre , Zhou Haohao , Xiang Xiaoyun , Zhao Boyu , Wang Min , Song Kaishan 
Published: May 2020

AbstractIn this study, data from MODIS land surface temperature product level 3 (MOD11A2) were used to investigate the spatiotemporal variation of Eurasian lakes water surface temperature (LSWT) from 2001 to 2015, and to examine the most influencing factors of that variation. The temperature of most lakes in the dry climate zone and in the equatorial climatic zone varied from 17 to 31°C and from 23 to 27°C, respectively. LSWTs in the warm temperate and cold climatic zones were in the range of 20 to 27°C and −0.6 and 17°C, respectively. The average day time LSWT in the polar climate zone was −0.71°C in the summer. Lakes in high latitude and in the Tibetan Plateau displayed low LSWT, ranging from −11 to 26°C during the night time. Large spatial variations of diurnal temperature difference (DTD) were observed in lakes across Eurasia. However, variations in DTDs were small in lakes located in high latitude and in tropical rainforest regions. The shallow lakes showed a rapid response of LSWT to solar and atmospheric forcing, while in the large and deep lakes, that response was sluggish. Results of this study demonstrated the applicability of remote sensing and MODIS LST products to capture the spatial–temporal variability of LSWT across continental scales, in particular for the vast wilderness areas and protected environment in high latitude regions of the world. The approach can be used in future studies examining processes and factors controlling large scale variability of LSWT.
Blockade of p38 kinase impedes the mobilization of protumorigenic myeloid populations to impact breast cancer metastasis
Authors: Zonneville Justin , Colligan Sean , Grant Sydney , Miller Alexandra , Wallace Paul , Abrams Scott I. , Bakin Andrei V. 
Published: May 2020

AbstractPatients with metastatic breast cancer (MBC) have limited therapeutic options and novel treatments are critically needed. Prior research implicates tumor‐induced mobilization of myeloid cell populations in metastatic progression, as well as being an unfavorable outcome in MBC; however, the underlying mechanisms for these relationships remain unknown. Here, we provide evidence for a novel mechanism by which p38 promotes metastasis. Using triple‐negative breast cancer models, we showed that a selective inhibitor of p38 (p38i) significantly reduced tumor growth, angiogenesis, and lung metastasis. Importantly, p38i decreased the accumulation of myeloid populations, namely, myeloid‐derived suppressor cells (MDSCs) and CD163+ tumor‐associated macrophages (TAMs). p38 controlled the expression of tumor‐derived chemokines/cytokines that facilitated the recruitment of protumor myeloid populations. Depletion of MDSCs was accompanied by reduced TAM infiltration and phenocopied the antimetastatic effects of p38i. Reciprocally, p38i increased tumor infiltration by cytotoxic CD8+ T cells. Furthermore, the CD163+/CD8+ expression ratio inversely correlated with metastasis‐free survival in breast cancer, suggesting that targeting p38 may improve clinical outcomes. Overall, our study highlights a previously unknown p38‐driven pathway as a therapeutic target in MBC.
CD8+ T‐cell senescence and skewed lymphocyte subsets in young Dyskeratosis Congenita patients with PARN and DKC1 mutations
Authors: Zeng Ting , Lv Ge , Chen Xuemei , Yang Lu , Zhou Lina , Dou Ying , Tang Xuemei , Yang Jun , An Yunfei , Zhao Xiaodong 
Published: May 2020

AbstractBackgroundDyskeratosis congenita (DC) is a syndrome resulting from defective telomere maintenance. Immunodeficiency associated with DC can cause significant morbidity and lead to premature mortality, but the immunological characteristics and molecular hallmark of DC patients, especially young patients, have not been described in detail.MethodsWe summarize the clinical data of two juvenile patients with DC. Gene mutations were identified by whole‐exome and direct sequencing. Swiss‐PdbViewer was used to predict the pathogenicity of identified mutations. The relative telomere length was determined by QPCR, and a comprehensive analysis of lymphocyte subsets and CD57 expression was performed by flow cytometry.ResultsBoth patients showed typical features of DC without severe infection. In addition, patient 1 (P1) was diagnosed with Hoyeraal‐Hreidarsson syndrome due to cerebellar hypoplasia. Gene sequencing showed P1 had a compound heterozygous mutation (c.204G > T and c.178‐245del) in PARN and P2 had a novel hemizygous mutation in DKC1 (c.1051A > G). Lymphocyte subset analysis showed B and NK cytopenia, an inverted CD4:CD8 ratio, and decreased naïve CD4 and CD8 cells. A significant increase in CD21low B cells and skewed numbers of helper T cells (Th), regulatory T cells (Treg), follicular regulatory T cells (Tfr), and follicular helper T cells (Tfh) were also detected. Short telomere lengths, increased CD57 expression, and an expansion of CD8 effector memory T cells re‐expressing CD45RA (TEMRA) were also found in both patients.ConclusionUnique immunologic abnormalities, CD8 T‐cell senescence, and shortened telomere together as a hallmark occur in young DC patients before progression to severe disease.
Far away, so close: The role of self‐differentiation in psychopathology among spouses of ex‐POWs and comparable combatants
Authors: Kapel Lev‐Ari Rony , Solomon Zahava , Horesh Danny 
Published: May 2020

AbstractObjectiveWar captivity entails severe posttraumatic implications for ex‐prisoners of war (POWs) and their partners. This study examines the role of self‐differentiation in secondary traumatization and dyadic adjustment among ex‐POWs' spouses.MethodsA total of 106 spouses of Israeli ex‐POWs and 56 matched spouses of ex‐combatants completed self‐report questionnaires assessing secondary posttraumatic stress disorder symptoms (SPS), self‐differentiation (fusion, cut‐off, balanced), general psychiatric distress (GPD), and dyadic adjustment.ResultsEx‐POWs' spouses reported lower dyadic adjustment and higher levels of SPS, GPD, and fusion and cut‐off differentiation, compared to ex‐combatants' spouses. A “mixed” differentiation style characterized by high levels of both fusion and cut‐off was associated with particularly high distress levels. Fusion differentiation moderated the association between SPS/GPD and dyadic adjustment.ConclusionSelf‐differentiation plays an important role in posttraumatic spousal relationships. Women showing unstable differentiation may be particularly vulnerable when living with a veteran. Treatments for posttraumatic couples should target dysregulated interpersonal distance and promote adaptive differentiation.
Emerging landscape of circular RNAs as biomarkers and pivotal regulators in osteosarcoma
Authors: Tu Chao , He Jieyu , Qi Lin , Ren Xiaolei , Zhang Chenghao , Duan Zhixi , Yang Kexin , Wang Wanchun , Lu Qiong , Li Zhihong 
Published: May 2020

AbstractOsteosarcoma represents the most prevailing primary bone tumor and the third most common cancer in children and adolescents worldwide. Among noncoding RNAs, circular RNAs (circRNAs) refer to a unique class in the shape of a covalently closed continuous loop with neither 5′ caps nor 3′‐polyadenylated tails, which are generated through back‐splicing. Recently, with the development of whole‐genome and transcriptome sequencing technologies, a growing number of circRNAs have been found aberrantly expressed in multiple diseases, including osteosarcoma. circRNA are capable of various biological functions including miRNA sponge, mediating alternatives, regulating genes at posttranscriptional levels, and interacting with proteins, indicating a pivotal role of circRNA in cancer initiation, progression, chemoresistance, and immune response. Moreover, circRNAs have been thrust into the spotlight as potential biomarkers and therapeutic targets in osteosarcoma. Herein, we briefly summarize the origin and biogenesis of circRNA with current knowledge of circRNA in tumorigenesis of osteosarcoma, aiming to elucidate the specific role and clinical implication of circRNAs in osteosarcoma.
Identification of a four immune‐related genes signature based on an immunogenomic landscape analysis of clear cell renal cell carcinoma
Authors: Gao Xin , Yang Jinlian , Chen Yinyi 
Published: May 2020

AbstractRenal clear cell carcinoma (ccRCC) is the most common type of renal cell carcinoma, which has strong immunogenicity. A comprehensive study of the role of immune‐related genes (IRGs) in ccRCC is of great significance in finding ccRCC treatment targets and improving patient prognosis. In this study, we comprehensively analyzed the expression of IRGs in ccRCC based on The Cancer Genome Atlas datasets. The mechanism of differentially expressed IRGs in ccRCC was analyzed by bioinformatics. In addition, Cox regression analysis was used to screen prognostic related IRGs from differentially expressed IRGs. We also identified a four IRGs signature consisting of four IRGs (CXCL2, SEMA3G, PDGFD, and UCN) through lasso regression and multivariate Cox regression analysis. Further analysis results showed that the four IRGs signature could effectively predict the prognosis of patients with ccRCC, and its predictive power is independent of other clinical factors. In addition, the correlation analysis of immune cell infiltration showed that this four IRGs signature could effectively reflect the level of immune cell infiltration of ccRCC. We also found that the expression of immune checkpoint genes CTLA‐4, LAG3, and PD‐1 in the high‐risk group was higher than that in the low‐risk group. Our research revealed the role of IRGs in ccRCC, and developed a four IRGs signature that could be used to evaluate the prognosis of patients with ccRCC, which will help to develop personalized treatment strategies for patients with ccRCC and improve their prognosis. In addition, these four IRGs may be effective therapeutic targets for ccRCC.
A retrospective analysis of venous thromboembolism trends in chemotherapy‐induced anemia: Red blood cell transfusion versus erythrocyte stimulating agent administration
Authors: Bryer Emily J. , Kallan Michael J. , Chiu Ting‐Shan , Scheuba Katharina M. , Henry David H. 
Published: May 2020

AbstractBackgroundPatients receiving a variety of chemotherapy regimens often develop chemotherapy‐induced anemia (CIA), which contributes to poor outcomes including increased mortality. Prompt and effective treatment of CIA is essential to prevent fewer chemotherapy dose delays and reductions. Optimal therapy of CIA is controversial and involves the solitary and combined use of intravenous iron, red blood cell (RBC) transfusions, and erythropoietin stimulating agents (ESAs). Despite the baseline coagulopathies present in patients with malignancy, administration of both RBC transfusions and ESAs is associated with venous thromboembolism (VTE). It remains unknown whether the risk of VTE in patients with CIA is greater among patients who receive RBC transfusions or ESAs.MethodsA retrospective study analyzed 10,269 University of Pennsylvania Health System patients with malignancies of various type, stage, and histopathology who developed CIA between 2008 and 2017. Using multivariate Cox regression, we determined adjusted hazard ratios (and corresponding 95% confidence intervals) of VTE development after adjusting for RBC and ESA intervention (all during the 90 days following CIA diagnosis).ResultsAmong the 10,269 patients with CIA, 2,642 (25.7%) developed a VTE within the 90‐day period. VTE risk following RBC transfusion (HR = 1.37, 95% CI 1.24‐1.50, P < .001) was more than twice as common as VTE risk following ESA administration (HR = 0.53, 95% CI 0.40‐0.69, P < .001).ConclusionWhile both RBC transfusion and ESA are independently associated with VTE, our data suggest a greater risk of VTE development with RBC transfusion as compared with ESA.