bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamical systems methods and statender diagnostic of interacting vacuum energy models
Authors: Panotopoulos Grigoris , Rincón Ángel , Otalora Giovanni , Videla Nelson 
Published: March 2020

AbstractWe study three interacting dark energy models within the framework of four-dimensional General Relativity and a spatially flat Universe. In particular, we first consider two vacuum models where dark energy interacts with dark matter, while relativistic matter as well as baryons are treated as non-interacting fluid components. Secondly, we investigate a third model where the gravitational coupling is assumed to be a slowly-varying function of the Hubble rate and dark energy and dark matter interact as well. We compute the statefinders parameters versus red-shift as well as the critical points and their nature applying dynamical systems methods. In the case of only an interaction term, our main findings indicate that (i) significant differences between the models are observed as we increase the strength of the interaction term, and (ii) all the models present an unique attractor corresponding to acceleration. On the other hand, when we allow for a variable gravitational coupling, we find that (i) the deviation from the concordance model depends of both the strength of gravitational coupling parameter and the interaction term, and (ii) there is an unique attractor corresponding to acceleration.
Targeting Mutant PPM1D Sensitizes Diffuse Intrinsic Pontine Glioma Cells to the PARP Inhibitor Olaparib
Authors: Wang Zhaohui , Xu Cheng , Diplas Bill H. , Moure Casey J. , Chen Chin-Pu Jason , Chen Lee H. , Du Changzheng , Zhu Huishan , Greer Paula K. , Zhang Liwei , He Yiping , Waitkus Matthew S. , Yan Hai 
Published: March 2020

AbstractDiffuse intrinsic pontine glioma (DIPG) is an invariably fatal brain tumor occurring predominantly in children. Up to 90% of pediatric DIPGs harbor a somatic heterozygous mutation resulting in the replacement of lysine 27 with methionine (K27M) in genes encoding histone H3.3 (H3F3A, 65%) or H3.1 (HIST1H3B, 25%). Several studies have also identified recurrent truncating mutations in the gene encoding protein phosphatase 1D, PPM1D, in 9%–23% of DIPGs. Here, we sought to investigate the therapeutic potential of targeting PPM1D, alone or in combination with inhibitors targeting specific components of DNA damage response pathways in patient-derived DIPG cell lines. We found that GSK2830371, an allosteric PPM1D inhibitor, suppressed the proliferation of PPM1D-mutant, but not PPM1D wild-type DIPG cells. We further observed that PPM1D inhibition sensitized PPM1D-mutant DIPG cells to PARP inhibitor (PARPi) treatment. Mechanistically, combined PPM1D and PARP inhibition show synergistic effects on suppressing a p53-dependent RAD51 expression and the formation of RAD51 nuclear foci, possibly leading to impaired homologous recombination (HR)-mediated DNA repair in PPM1D-mutant DIPG cells. Collectively, our findings reveal the potential role of the PPM1D–p53 signaling axis in the regulation of HR-mediated DNA repair and provide preclinical evidence demonstrating that combined inhibition of PPM1D and PARP1/2 may be a promising therapeutic combination for targeting PPM1D-mutant DIPG tumors.Implications:The findings support the use of PARPi in combination with PPM1D inhibition against PPM1D-mutant DIPGs.
Aquaporin-9, Mediated by IGF2, Suppresses Liver Cancer Stem Cell Properties via Augmenting ROS/β-Catenin/FOXO3a Signaling
Authors: Zheng Xi , Li Chuanfei , Yu Keqi , Shi Shasha , Chen Hongyu , Qian Yanzhi , Mei Zhechuan 
Published: March 2020

Abstract

Liver cancer stem cells (LCSCs) play a critical role in hepatocellular carcinoma (HCC) by virtue of their aggressive behavior and association with poor prognoses. Aquaporin-9 (AQP9) is a transmembrane protein that transports water and reportedly transports H2O2. Recent studies have shown that AQP9 expression has a negative effect on HCC cell invasion by inhibiting the epithelial-to-mesenchymal transition. However, the role of AQP9 in LCSCs remains obscure. We performed spheroid formation assay and flow cytometric analysis to investigate LCSCs stemness. CD133+ and CD133− cells were isolated by flow cytometry. Real-time quantitative PCR (qRT-PCR), Western blot analysis, and immunofluorescence assay were used to estimate gene expression. The protein association of β-catenin with TCF4 and the interaction of β-catenin with FOXO3a were detected by immunoprecipitation (IP). Here, we found that AQP9 was preferentially decreased in LCSCs. Upregulated AQP9 significantly suppressed LCSCs stemness. In contrast, the inhibition of AQP9 had the opposite effect. Mechanistically, AQP9 was shown to be downregulated by insulin-like growth factor 2 (IGF2), which was widely reported to contribute to maintaining CSCs stemness. Furthermore, AQP9 overexpression was found to result in reactive oxygen species (ROS) accumulation, which inhibited β-catenin activity by attenuating the interaction of β-catenin with TCF4 while concurrently enhancing the association of β-catenin with FOXO3a, ultimately inhibiting LCSCs stemness. Our study implies that stimulation of the AQP9 signaling axis may be a novel preventive and/or therapeutic approach for eliminating LCSCs.

Implications:
Our findings demonstrate that AQP9 signaling axis may be a novel preventive and/or therapeutic approach for eliminating LCSCs.
Human NKp44+ Group 3 Innate Lymphoid Cells Associate with Tumor-Associated Tertiary Lymphoid Structures in Colorectal Cancer
Authors: Ikeda Atsuyo , Ogino Takayuki , Kayama Hisako , Okuzaki Daisuke , Nishimura Junichi , Fujino Shiki , Miyoshi Norikatsu , Takahashi Hidekazu , Uemura Mamoru , Matsuda Chu , Yamamoto Hirofumi , Takeda Kiyoshi , Mizushima Tsunekazu , Mori Masaki , Doki Yuichiro 
Published: March 2020

Abstract
Innate lymphoid cells (ILC) are responsible for mucosal tissue homeostasis and are involved in the progression and suppression of several types of cancer. However, the effects of ILCs on colorectal cancer are poorly understood. We characterized human ILCs in normal colon and colorectal cancer tissue, investigating their role in the tumor immune microenvironment. Normal mucosa and tumor tissues were obtained from patients with colorectal cancer, and the cells were isolated by enzymatic digestion. NKp44+ ILC3s with high expression of tertiary lymphoid structure (TLS) formation–related genes, including LTA, LTB, and TNF, accumulated in the normal colonic mucosa and T1/T2 tumors. However, the number of NKp44+ ILC3s was significantly reduced in T3/T4 tumors compared with normal colonic mucosa and T1/T2 tumors. NKp44+ ILC3s present in T3/T4 tumors had decreased expression of TLS formation–related genes, whereas stromal cells had decreased expression of CXCL13, CCL19, and CCL21. The decreasing number of NKp44+ ILC3s during tumor progression correlated with the TLS density in tumors. Thus, our results indicate that NKp44+ ILC3s infiltrate colorectal cancer tissue, but the number of cells decreases in T3/T4 tumors with associated decreases in TLS induction.
Gene Expression Profiling of Mediastinal Gray Zone Lymphoma and Its Relationship to Primary Mediastinal B-cell Lymphoma and Classical Hodgkin Lymphoma
Authors: Pittaluga Stefania , Nicolae Alina , Wright George W. , Melani Christopher , Roschewski Mark , Steinberg Seth , Huang DaWei , Staudt Louis M. , Jaffe Elaine S. , Wilson Wyndham H. 
Published: March 2020

Abstract

Mediastinal gray zone lymphoma (MGZL) has immunopathologic features between classical Hodgkin lymphoma (cHL) and primary mediastinal thymic B-cell lymphoma (PMBL), leading to uncertainty regarding its biological relationship to these entities. We performed gene expression profiling from patients with MGZL (20), cHL (18), and PMBL (17) and show MGZL clusters between cHL and PMBL. Expression signatures reveal germinal B-cell and IFN regulatory factor 4 (IRF4) signatures were relatively low in MGZL and cHL compared with PMBL, indicating downregulation of the B-cell program in MGZL, a hallmark of cHL. T-cell and macrophage signatures were higher in MGZL and cHL compared with PMBL, consistent with infiltrating immune cells, which are found in cHL. The NFκB signature was higher in MGZL than PMBL, and like cHL, MGZL and PMBL express NFκB inducing kinase (NIK), indicating noncanonical signaling. These findings indicate that while MGZL has distinctive clustering, it is biologically closer to cHL.

Significance:
We performed comparative gene expression analysis of MGZL, cHL, and PMBL and show most MGZL cases are biologically closer to cHL. MGZL has significantly higher tumor cell density than cHL and greater NFκB activation compared with PMBL, which may explain its greater treatment resistance compared with cHL and PMBL.
This article is highlighted in the In This Issue feature, p. 127
Blood Pressure Drop Rate After Standing Up Is Associated With Frailty and Number of Falls in Geriatric Outpatients
Authors: Mol Arjen , Slangen Lois Robin Nicolle , Trappenburg Marijke C. , Reijnierse Esmee M. , van Wezel Richard J. A. , Meskers Carel G. M. , Maier Andrea B. 
Published: March 2020

Background
The relationship between orthostatic hypotension and clinical outcome in older adults is poorly understood. Blood pressure drop rate (ie, speed of blood pressure drop) may particularly reflect the imposed challenge to the baroreflex and the associated clinical outcome (ie, frailty and number of falls). This study aimed to compare orthostatic blood pressure drop rate and drop magnitude with regard to their association with frailty and number of falls.

Methods and Results

Blood pressure was measured continuously during a standardized active stand task in 168 patients (mean age 81.4±7.0; 55.4% female) who visited a geriatric outpatient clinic for cognitive or mobility problems. The association of orthostatic blood pressure drop rate, blood pressure drop magnitude, and baroreflex sensitivity (ie, increase in heart rate divided by systolic blood pressure drop magnitude) with frailty (Fried criteria and 4 frailty markers) and self‐reported number of falls was assessed using linear regression models, adjusting for age and sex. Systolic blood pressure drop rate had the strongest association with frailty according to the 4 frailty markers (β 0.30; 95%
CI
, 0.11–0.49;
P
=0.003) and number of falls (β 1.09; 95%
CI
, 0.19–1.20;
P
=0.018); diastolic blood pressure drop magnitude was most strongly associated with frailty according to the Fried criteria (β 0.37; 95%
CI
, 0.15–0.60;
P
<0.001). Baroreflex sensitivity was associated with neither frailty nor number of falls.

Conclusions
Orthostatic blood pressure drop rate was associated with frailty and falls and may reflect the challenge to the baroreflex rather than drop magnitude.
Decoupling Between Diastolic Pulmonary Artery and Pulmonary Capillary Wedge Pressures Is Associated With Right Ventricular Dysfunction and Hemocompatibility‐Related Adverse Events in Patients With Left Ventricular Assist Devices
Authors: Imamura Teruhiko , Narang Nikhil , Kim Gene , Raikhelkar Jayant , Chung Ben , Nguyen Ann , Holzhauser Luise , Rodgers Daniel , Kalantari Sara , Smith Bryan , Ota Takeyoshi , Song Tae , Juricek Colleen , Burkhoff Daniel , Jeevanandam Valluvan , Sayer Gabriel , Uriel Nir 
Published: March 2020

Background
Decoupling between diastolic pulmonary artery pressure and pulmonary capillary wedge pressure is an index of pulmonary vascular damage. This study assessed the impact of decoupling on right heart function and hemocompatibility‐related adverse events.

Methods and Results

In this prospective study, patients underwent invasive hemodynamic tests following left ventricular assist device implantation. Decoupling was defined as a difference of >5 mm Hg between diastolic pulmonary artery pressure and pulmonary capillary wedge pressure. Among 92 patients with left ventricular assist devices (median age, 61 years; 57% male), 44 patients (48%) had decoupling. Right heart function and size by echocardiographic assessment worsened during a 1‐year observational period in the decoupling group as compared with the control group (
P
<0.05). The decoupling group had significantly lower 1‐year freedom from any hemocompatibility‐related adverse events (49% versus 79%;
P
=0.005), as well as a higher hemocompatibility score (2.14 versus 0.67;
P
=0.004). The scoring system depicts the severity of hemocompatibility‐related adverse events using 4 escalating tiers. Increased tier I scores (1–2 gastrointestinal bleedings or medically managed pump thrombosis;
P
=0.027) and tier IIIB scores (disabling stroke or hemocompatibility‐related adverse event–related death;
P
=0.041) occurred more frequently in the decoupling group.

Conclusions
The presence of decoupling between diastolic pulmonary artery pressure and pulmonary capillary wedge pressure was associated with worsening of right heart function and hemocompatibility‐related adverse events in patients with left ventricular assist devices.
Spectral Modeling of Ice-Induced Wave Decay
Authors: Liu Qingxiang , Rogers W. Erick , Babanin Alexander , Li Jingkai , Guan Changlong 
Published: March 2020

AbstractThree dissipative (two viscoelastic and one viscous) ice models are implemented in the spectral wave model WAVEWATCH III to estimate the ice-induced wave attenuation rate. These models are then explored and intercompared through hindcasts of two field cases: one in the autumn Beaufort Sea in 2015 and the other in the Antarctic marginal ice zone (MIZ) in 2012. The capability of these dissipative models, along with their limitations and applicability to operational forecasts, are analyzed and discussed. The sensitivity of the simulated wave height to different source terms—the ice-induced wave decay Sice and other physical processes Sother (e.g., wind input, nonlinear four-wave interactions)—is also investigated. For the Antarctic MIZ experiment, Sother is found to be remarkably less than Sice and thus contributes little to the simulated significant wave height Hs. The saturation of dHs/dx at large wave heights in this case, as reported by a previous study, is well reproduced by the three dissipative ice models with or without the utilization of Sother in the ice-infested seas. A clear downward trend in the peak frequency fp is found as Hs increases. As fp decreases, the dominant wave components of a wave spectrum will experience reduced damping by sea ice, and finally result in the flattening of dHs/dx for Hs > 3 m in this specific case. Nonetheless, Sother should not be disregarded within a more general modeling perspective, as our simulations suggest Sother could be comparable to Sice in the Beaufort Sea case where wave and ice conditions are remarkably different.
LncRNA CASC11 was downregulated in coronary artery disease and inhibits transforming growth factor-β1
Authors: Chen Junhua , Dang Jianli 
Published: March 2020

Objective To investigate the involvement of long non-coding RNA (lncRNA) Cancer Susceptibility 11 (CASC11) in patients with coronary artery disease (CAD). Methods This case–control study enrolled patients with CAD and age- and sex-matched healthy control subjects. The plasma levels of lncRNA CASC11 and transforming growth factor-beta 1 (TGF-β1) were measured. Diagnostic values of lncRNA CASC11 and TGF-β1 for CAD were determined using receiver operating characteristic curve analysis. Correlations between plasma levels of lncRNA CASC11 and TGF-β1 were analysed using linear regression. Results The study enrolled 82 patients with CAD and 82 healthy controls. Plasma levels of lncRNA CASC11 were downregulated in patients with CAD, while plasma TGF-β1 levels were upregulated in patients with CAD, compared with healthy controls. Plasma levels of lncRNA CASC11 and TGF-β1 distinguished patients with CAD from healthy controls and were inversely correlated in both groups. LncRNA CASC11 over-expression mediated the downregulation of TGF-β1 in human primary coronary artery endothelial cells, while TGF-β1 over-expression showed no significant effects on lncRNA CASC11 levels. An 8-year follow-up study showed that low lncRNA CASC11 levels were closely correlated with a higher mortality rate in patients with CAD. Conclusion LncRNA CASC11 is downregulated in CAD and inhibits TGF-β1.
Association between mean corpuscular volume and severity of coronary artery disease in the Northern Chinese population: a cross-sectional study
Authors: Wang Huaiyu , Yang Guang , Zhao Juan , Wang Mengchang 
Published: March 2020

Objective This study was performed to explore the relationship between the mean corpuscular volume (MCV) and the severity of coronary artery disease (CAD) in the Northern Chinese population. Methods In total, 1326 patients who underwent coronary angiography from July 2015 to February 2017 were retrospectively enrolled in this cross-sectional study. Coronary artery stenosis was evaluated by the Gensini score. Linear regression analysis was performed to investigate the association between the severity of CAD and the MCV. Results Patients within the fourth quartile of the Gensini score had a significantly higher MCV than those within the third, second, and first quartiles (94.1 ± 6.7 vs. 93.2 ± 6.4 vs. 92.8 ± 5.1 vs. 92.6 ± 6.2, respectively). After adjustment for potential confounding factors, the multivariate linear regression analysis showed that the MCV was significantly associated with the severity of CAD. Additionally, the red blood cell distribution width (RDW) and red blood cell count were significantly associated with the severity of CAD. Conclusions These results suggest that the MCV, RDW, and red blood cell count are correlated with and may serve as biomarkers for the severity of CAD.
Bacillus Calmette-Guérin (BCG) stimulates changes in dendritic cell surface marker expression in vitamin D-deficient mice
Authors: Yang Huifeng , Zhan Yang , Wu Haotian , Xiang Liangbi 
Published: March 2020

Objective Vitamin D (VD) deficiency increases susceptibility to tuberculosis and is an important immunomodulator. Dendritic cells (DCs) are important antigen-presenting cells that play a critical role during tuberculosis infection, and Mycobacterium tuberculosis modulates DC responses. The underlying mechanism is poorly understood. Our aim was to study changes in DC surface markers in VD deficient mice administered Bacillus Calmette-Guérin (BCG). Methods We divided C57BL/6 mice into a normal group and a VD deficient group. Two groups of mouse bone marrow-derived cells were isolated and cultured with granulocyte-macrophage colony-stimulating factor (20 ng/mL) and interleukin-4 (10 ng/mL) for 6 days. On day 7, BCG (0, 1 or 2 mg/mL) was administered to both groups for 24 hours. Non-adherent cells were harvested to assess DC phenotypic changes induced by different concentrations of BCG. Results Expression levels of CD80, MHC-I, MHC-II and CD86 on the surfaces of DCs from VD deficient mice were lower than those in DCs from normal mice. By contrast, the expression level of CD11c on DCs was higher in VD deficient mice than in normal mice. Changes in all factors were concentration-dependent. Conclusions These findings indicate that BCG reduced DC surface marker expression to modulate immune responses during M. tuberculosis infection.
Effect of Sex and Ankle Brace Design on Knee Biomechanics During a Single-Leg Cut
Authors: Ihmels Wyatt D. , Seymore Kayla D. , Brown Tyler N. 
Published: March 2020

Background: Despite success at preventing ankle sprain, prophylactics that restrict ankle plantarflexion motion may produce deleterious knee biomechanics and increase injury risk. Purpose: To determine if ankle prophylactics that restrict plantar- and dorsiflexion motion produce changes in knee biomechanics during a single-leg cut and whether those changes differ between sexes. Study Design: Controlled laboratory study. Methods: A total of 17 male and 17 female participants performed a single-leg cut with 4 conditions: Ankle Roll Guard (ARG), lace-up brace, nonelastic tape, and an unbraced control. Peak stance knee flexion, abduction, and internal rotation joint angle and moment; total knee reaction moment (TKM) and its components (sagittal, frontal, and transverse); and ankle plantarflexion and inversion range of motion (ROM) and peak stance joint moments were tested with a repeated measures analysis of variance to determine the main effect and interaction of condition and sex. Results: Brace and tape restricted plantarflexion ROM as compared with ARG and control (all P < .001). With the brace, women had increased peak knee abduction angle versus ARG ( P = .012) and control ( P = .009), and men had decreased peak knee internal rotation moment as compared with ARG ( P = .032), control ( P = .006), and tape ( P = .003). Although the restrictive tape decreased inversion ROM when compared with ARG ( P = .004) and brace ( P = .017), it did not change knee biomechanics. Neither brace nor tape produced significant changes in TKM or components, yet sagittal TKM increased with ARG versus control ( P = .016). Women exhibited less ankle inversion ROM ( P = .003) and moment ( P = .049) than men, while men exhibited significantly greater frontal TKM ( P = .022) and knee internal rotation moment with the ARG ( P = .029), control ( P = .007), and tape ( P = .016). Conclusion: Prophylactics that restrict ankle plantarflexion motion may elicit knee biomechanical changes during a single-leg cut, but these changes may depend on prophylactic design and user’s sex and may increase women’s injury risk. Clinical Relevance: Sex-specific ankle prophylactic designs may be warranted to reduce knee injury during sports.
Systematic review and meta-analysis of femtosecond laser–enabled keratoplasty versus conventional penetrating keratoplasty
Authors: Liu Yang , Li Xiaojun , Li Wenjie , Jiu Xudong , Tian Mannan 
Published: March 2020

Purpose: The aim of this meta-analysis is to compare femtosecond laser–enabled keratoplasty with conventional penetrating keratoplasty regarding postoperative astigmatism, visual functions, graft rejection, graft failure, and complications. Methods: Eligible studies were retrieved from five mainstream electronic databases, including PubMed, Embase, Ovid MEDLINE, Cochrane Library, and ClinicalTrial.gov. Postoperative topographic astigmatism was set as the primary outcome, and best-corrected visual acuity, spherical equivalent, endothelial cell density, graft rejection, graft failure, and complications were chosen as the secondary outcomes. Standard mean difference and risk ratio were the size effects for continuous data and binomial data, respectively. The data were pooled through either the random-effects model or the fixed-effects model based on data heterogeneity. Moreover, subgroup analyses were conducted when the heterogeneity occurred distinctly (I2 > 50%). Results: A total of seven comparative studies were included. The pooled standard mean difference (−0.32, 95% confidence interval: −0.74 to 0.10) showed that femtosecond laser–enabled keratoplasty was not superior over conventional penetrating keratoplasty to decrease postoperative topographic astigmatism (p = 0.14). However, best-corrected visual acuity after femtosecond laser–enabled keratoplasty was significantly better than that after conventional penetrating keratoplasty (p = 0.00, standard mean difference: −0.23, 95% confidence interval: −0.37 to −0.10). Furthermore, endothelial cell density after femtosecond laser–enabled keratoplasty was preserved significantly better (p = 0.03, standard mean difference: 0.63, 95% confidence interval: 0.07–1.20). Moreover, spherical equivalent, graft rejection, graft failure, and complications represented no distinct differences between femtosecond laser–enabled keratoplasty and conventional penetrating keratoplasty (p > 0.05). Conclusion: Femtosecond laser–enabled keratoplasty may not be superior over conventional penetrating keratoplasty in decreasing postoperative topographic astigmatism, but might have advantages to achieve best-corrected visual acuity and endothelial cell density preservation. In addition, the two techniques seem to be comparable regarding spherical equivalent, graft rejection/failure, and complications.