bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebral blood flow regulation and cognitive function in women with posttraumatic stress disorder
Authors: Ogoh Shigehiko , Yoo Jeung-Ki , Badrov Mark B. , Parker Rosemary S. , Anderson Elizabeth H. , Wiblin Jessica L. , North Carol S. , Suris Alina , Fu Qi 
Published: August 2018

Posttraumatic stress disorder (PTSD) is associated with structural and functional alterations in a number of interacting brain regions, but the physiological mechanism for the high risk of cerebrovascular disease or impairment in brain function remains unknown. Women are more likely to develop PTSD after a trauma than men. We hypothesized that cerebral blood flow (CBF) regulation is impaired in women with PTSD, and it is associated with impairment in cognitive function. To test our hypothesis, we examined dynamic cerebral autoregulation (CA) and cognitive function by using a transfer function analysis between arterial pressure and middle cerebral artery blood velocity and the Stroop Color and Word test (SCWT), respectively. We did not observe any different responses in these hemodynamic variables between women with PTSD ( n = 15) and healthy counterparts (all women; n = 8). Cognitive function was impaired in women with PTSD; specifically, reaction time for the neutral task of SCWT was longer in women with PTSD compared with healthy counterparts ( P = 0.011), but this cognitive dysfunction was not affected by orthostatic stress. On the other hand, transfer function phase, gain, and coherence were not different between groups in either the supine or head-up tilt (60°) position, or even during the cognitive challenge, indicating that dynamic CA was well maintained in women with PTSD. In addition, there was no relationship between cognitive function and dynamic CA. These findings suggest that PTSD-related cognitive dysfunction may not be due to compromised CBF regulation. NEW & NOTEWORTHY Cognitive function was impaired; however, dynamic cerebral autoregulation (CA) as an index of cerebral blood flow regulation was not impaired during supine and 60° head-up tilt in women with PTSD compared with healthy females. In addition, there was no relationship between cognitive function and dynamic CA. These findings suggest that the mechanism of PTSD-related cognitive dysfunction may not be due to CBF regulation.
Spinal protein phosphatase 1 constrains respiratory plasticity after sustained hypoxia
Authors: Huxtable Adrianne G. , Peterson Timothy J. , Ouellette Jonathan N. , Watters Jyoti J. , Mitchell Gordon S. 
Published: August 2018

Plasticity is an important aspect of the neural control of breathing. One well-studied form of respiratory plasticity is phrenic long-term facilitation (pLTF) induced by acute intermittent but not sustained hypoxia. Okadaic acid-sensitive protein phosphatases (PPs) differentially regulate phrenic nerve activity with intermittent vs. sustained hypoxia, at least partially accounting for pLTF pattern sensitivity. However, okadaic acid inhibits multiple serine/threonine phosphatases, and the relevant phosphatase (PP1, PP2A, PP5) for pLTF pattern sensitivity has not been identified. Here, we demonstrate that sustained hypoxia (25 min, 9–10.5% O2) elicits phrenic motor facilitation in rats pretreated with bilateral intrapleural injections of small interfering RNAs (siRNAs; Accell-modified to preferentially transfect neurons, 3.33 μM, 3 days) targeting PP1 mRNA (48 ± 14% change from baseline, n = 6) but not PP2A (14 ± 9% baseline, n = 6) or nontargeting siRNAs (4 ± 10% baseline, n = 7). In time control rats (no hypoxia) treated with siRNAs ( n = 6), no facilitation was evident (−9 ± 9% baseline). siRNAs had no effect on the hypoxic phrenic response. Immunohistochemistry revealed PP1 and PP2A protein in identified phrenic motoneurons. Although PP1 and PP2A siRNAs significantly decreased PP1 and PP2A mRNA in PC12 cell cultures, we were not able to verify “knockdown” in vivo after siRNA treatment. On the other hand, PP1 and PP2A siRNAs significantly decreased PP1 and PP2A mRNA in PC12 cell cultures, verifying the intended siRNA effects. In conclusion, PP1 (not PP2A) is the relevant okadaic acid-sensitive phosphatase constraining phrenic motor facilitation after sustained hypoxia and likely contributing to pLTF pattern sensitivity.NEW & NOTEWORTHY This study demonstrates that the relevant okadaic acid-sensitive Ser/Thr protein phosphatase (PP) constraining facilitation after sustained hypoxia is PP1 and not PP2A. It suggests that PP1 may be critical in the pattern sensitivity of hypoxia-induced phrenic motor plasticity.
Systematic Analysis of Compounds Specifically Targeting Telomeres and Telomerase for Clinical Implications in Cancer Therapy
Authors: Lee Hee-Sheung , Carmena Mar , Liskovykh Mikhail , Peat Emma , Kim Jung-Hyun , Oshimura Mitsuo , Masumoto Hiroshi , Teulade-Fichou Marie-Paule , Pommier Yves , Earnshaw William C. , Larionov Vladimir , Kouprina Natalay 
Published: August 2018

Abstract
The targeting of telomerase and telomere maintenance mechanisms represents a promising therapeutic approach for various types of cancer. In this work, we designed a new protocol to screen for and rank the efficacy of compounds specifically targeting telomeres and telomerase. This approach used two isogenic cell lines containing a circular human artificial chromosome (HAC, lacking telomeres) and a linear HAC (containing telomeres) marked with the EGFP transgene; compounds that target telomerase or telomeres should preferentially induce loss of the linear HAC but not the circular HAC. Our assay allowed quantification of chromosome loss by routine flow cytometry. We applied this dual-HAC assay to rank a set of known and newly developed compounds, including G-quadruplex (G4) ligands. Among the latter group, two compounds, Cu-ttpy and Pt-ttpy, induced a high rate of linear HAC loss with no significant effect on the mitotic stability of a circular HAC. Analysis of the mitotic phenotypes induced by these drugs revealed an elevated rate of chromatin bridges in late mitosis and cytokinesis as well as UFB (ultrafine bridges). Chromosome loss after Pt-ttpy or Cu-ttpy treatment correlated with the induction of telomere-associated DNA damage. Overall, this platform enables identification and ranking of compounds that greatly increase chromosome mis-segregation rates as a result of telomere dysfunction and may expedite the development of new therapeutic strategies for cancer treatment.
Significance: An assay provides a unique opportunity to screen thousands of chemical compounds for their ability to inactivate replication of telomeric ends in cancer cells and holds potential to lay the foundation for the discovery of new treatments for cancer. Cancer Res; 78(21); 6282–96. ©2018 AACR.
Development, Function, and Clinical Significance of Plasmacytoid Dendritic Cells in Chronic Myeloid Leukemia
Authors: Inselmann Sabrina , Wang Ying , Saussele Susanne , Fritz Lea , Schütz Christin , Huber Magdalena , Liebler Simone , Ernst Thomas , Cai Dali , Botschek Sarah , Brendel Cornelia , Calogero Raffaele A. , Pavlinic Dinko , Benes Vladimir , Liu Edison T. , Neubauer Andreas , Hochhaus Andreas , Burchert Andreas 
Published: August 2018

Abstract
Plasmacytoid dendritic cells (pDC) are the main producers of a key T-cell–stimulatory cytokine, IFNα, and critical regulators of antiviral immunity. Chronic myeloid leukemia (CML) is caused by BCR-ABL, which is an oncogenic tyrosine kinase that can be effectively inhibited with ABL-selective tyrosine kinase inhibitors (TKI). BCR-ABL–induced suppression of the transcription factor interferon regulatory factor 8 was previously proposed to block pDC development and compromise immune surveillance in CML. Here, we demonstrate that pDCs in newly diagnosed CML (CML-pDC) develop quantitatively normal and are frequently positive for the costimulatory antigen CD86. They originate from low-level BCR-ABL–expressing precursors. CML-pDCs also retain their competence to maturate and to secrete IFN. RNA sequencing reveals a strong inflammatory gene expression signature in CML-pDCs. Patients with high CML-pDC counts at diagnosis achieve inferior rates of deep molecular remission (MR) under nilotinib, unless nilotinib therapy is combined with IFN, which strongly suppresses circulating pDC counts. Although most pDCs are BCR-ABL–negative in MR, a substantial proportion of BCR-ABL+ CML-pDCs persists under TKI treatment. This could be of relevance, because CML-pDCs elicit CD8+ T cells, which protect wild-type mice from CML. Together, pDCs are identified as novel functional DC population in CML, regulating antileukemic immunity and treatment outcome in CML.
Significance: CML-pDC originates from low-level BCR-ABL expressing stem cells into a functional immunogenic DC-population regulating antileukemic immunity and treatment outcome in CML. Cancer Res; 78(21); 6223–34. ©2018 AACR.
Augmentation of Nab-Paclitaxel Chemotherapy Response by Mechanistically Diverse Antiangiogenic Agents in Preclinical Gastric Cancer Models
Authors: Awasthi Niranjan , Schwarz Margaret A. , Zhang Changhua , Schwarz Roderich E. 
Published: August 2018

Abstract
Gastric adenocarcinoma (GAC) remains the third most common cause of cancer-related deaths worldwide. Systemic chemotherapy is commonly recommended as a fundamental treatment for metastatic GAC; however, standard treatment has not been established yet. Angiogenesis plays a crucial role in the progression and metastasis of GAC. We evaluated therapeutic benefits of mechanistically diverse antiangiogenic agents in combination with nab-paclitaxel, a next-generation taxane, in preclinical models of GAC. Murine survival studies were performed in peritoneal dissemination models, whereas tumor growth studies were performed in subcutaneous GAC cell-derived or patient-derived xenografts. The mechanistic evaluation involved IHC and Immunoblot analysis in tumor samples. Nab-paclitaxel increased animal survival that was further improved by the addition of antiangiogenic agents ramucirumab (or its murine version DC101), cabozantinib and nintedanib. Nab-paclitaxel combination with nintedanib was most effective in improving animal survival, always greater than 300% over control. In cell-derived subcutaneous xenografts, nab-paclitaxel reduced tumor growth while all three antiangiogenic agents enhanced this effect, with nintedanib demonstrating the greatest inhibition. Furthermore, in GAC patient-derived xenografts the combination of nab-paclitaxel and nintedanib reduced tumor growth over single agents alone. Tumor tissue analysis revealed that ramucirumab and cabozantinib only reduced tumor vasculature, whereas nintedanib in addition significantly reduced tumor cell proliferation and increased apoptosis. Effects of nab-paclitaxel, a promising chemotherapeutic agent for GAC, can be enhanced by new-generation antiangiogenic agents, especially nintedanib. The data suggest that nab-paclitaxel combinations with multitargeted antiangiogenic agents carry promising potential for improving clinical GAC therapy. Mol Cancer Ther; 17(11); 2353–64. ©2018 AACR.
Mutational Landscape of Ovarian Adult Granulosa Cell Tumors from Whole Exome and Targeted TERT Promoter Sequencing
Authors: Alexiadis Maria , Rowley Simone M. , Chu Simon , Leung Dilys T.H. , Stewart Colin J.R. , Amarasinghe Kaushalya C. , Campbell Ian G. , Fuller Peter J. 
Published: August 2018

Abstract

Adult granulosa cell tumor (aGCT), the most common malignant ovarian sex cord-stromal tumor, is characterized by the forkhead transcription factor FOXL2 p.C134W somatic mutation. Late recurrences are relatively common but the molecular mechanisms of relapse or aggressive behavior are not known. The mutational landscape of FOXL2 p.C134W mutation–positive tumors (n = 22) was determined using whole-exome sequencing (WES). An average of 64 coding and essential splice-site variants were identified per tumor. As the TERT promoter region is poorly covered by the WES, targeted sequencing identified the TERT -124C&gt;T promoter mutation as the only recurrent mutation (∼40% of cases). Pathway analysis suggested an association with DNA replication/repair and the EGFR family canonical pathways. Copy number analysis confirmed that gains of chromosomes 12 and 14 occur in approximately 30% of aGCT and loss of chromosome 22 occurs in approximately 40% of cases. In summary, exome-wide analysis of the mutational landscape of aGCT revealed that, except for the TERT promoter mutation, recurrence and/or aggressive behavior is not defined by activation or loss of specific genes.

Implications:
This study found that although aGCTs are defined by the presence of a common FOXL2 gene mutation, recurrence and/or aggressive behavior cannot be attributed to subsequent mutation of specific gene(s) or pathways; however, there is a high frequency of the TERT -124C&gt;T promoter mutation, which is associated with more aggressive disease.
Virtuous Governance and the Chinese Way
Authors: Fang Zhaohui , Gandolfo Stefano 
Published: August 2018

AbstractLucian W. Pye, the renowned American Sinologist, argues that power/authority in Chinese culture follows a paternalistic structure, that the distinction in Chinese society between public and private has historically been in a state of tension, and therefore that Chinese governance has always emphasized central power over local self-governance, suppressed cultural pluralism, and rebuffed multipolar structures of power. Even though the inherent tension identified by Pye certainly exists, the thesis that Chinese culture has a deeply ingrained authoritarian orientation is simply incorrect. In order to resolve the tension between the public and private realms, Chinese thinkers—from the various strands of legalist thought to the Confucian notion of “kingly governance”—have premised the division of power on the priority of preserving centralized power. In other words, diffusion of power has been premised on the idea of an already collectivized authority. Therefore, the power structure that defines Chinese culture has certainly not been the polycentric one that Pye implicitly values, but neither has it been the centralist, authoritarian structure that he abhors. Rather, it has been the Confucian model premised on the values of governance through ritual and moral virtue. Insights from cultural psychology help explain ethical governance—that is, rule by an ethical meritocracy—in Chinese society and culture.
Climate Dependence in Empirical Parameters of Subgrid-Scale Parameterizations using the Fluctuation–Dissipation Theorem
Authors: Pieroth Martin , Dolaptchiev Stamen I. , Zacharuk Matthias , Heppelmann Tobias , Gritsun Andrey , Achatz Ulrich 
Published: August 2018

Abstract
Many subgrid-scale (SGS) parameterizations in climate models contain empirical parameters and are thus data dependent. In particular, it is not guaranteed that the SGS parameterization still helps the model to produce the correct climate projection in the presence of an external perturbation (e.g., because of climate change). Therefore, a climate dependence of tuning parameters is proposed, using the fluctuation–dissipation theorem (FDT). The FDT provides an estimation of the changes in the statistics of a system, caused by a small external forcing. These estimations are then used to update the SGS parameterization. This procedure is tested for a toy atmosphere given by a quasigeostrophic three-layer model (QG3LM). We construct a low-order climate model for this toy atmosphere, based on a reduced number of its empirical orthogonal functions (EOFs), equipped with either an empirical deterministic or an empirical stochastic SGS parameterization. External forcings are considered that are either a local anomalous heat source in the extratropics or a global dynamical forcing represented by individual EOF patterns. A quasi-Gaussian variant of the FDT is able to successfully update the SGS parameterization leading to an improvement in both amplitude and correlation between the low-order climate model and the QG3LM, in case of a perturbed system. The stochastic closure exhibits nearly no improvement compared to the deterministic parameterization. The application of a more sophisticated non-Gaussian FDT algorithm (i.e., the blended short-time/quasi-Gaussian FDT) yields only marginal improvement over the simple quasi-Gaussian FDT.
Implementation of a Geometrically Informed and Energetically Constrained Mesoscale Eddy Parameterization in an Ocean Circulation Model
Authors: Mak J. , Maddison J. R. , Marshall D. P. , Munday D. R. 
Published: August 2018

AbstractThe global stratification and circulation, as well as their sensitivities to changes in forcing, depend crucially on the representation of the mesoscale eddy field in a numerical ocean circulation model. Here, a geometrically informed and energetically constrained parameterization framework for mesoscale eddies—termed Geometry and Energetics of Ocean Mesoscale Eddies and Their Rectified Impact on Climate (GEOMETRIC)—is proposed and implemented in three-dimensional channel and sector models. The GEOMETRIC framework closes eddy buoyancy fluxes according to the standard Gent–McWilliams scheme but with the eddy transfer coefficient constrained by the depth-integrated eddy energy field, provided through a prognostic eddy energy budget evolving with the mean state. It is found that coarse-resolution models employing GEOMETRIC display broad agreement in the sensitivity of the circumpolar transport, meridional overturning circulation, and depth-integrated eddy energy pattern to surface wind stress as compared with analogous reference calculations at eddy-permitting resolutions. Notably, eddy saturation—the insensitivity of the time-mean circumpolar transport to changes in wind forcing—is found in the coarse-resolution sector model. In contrast, differences in the sensitivity of the depth-integrated eddy energy are found in model calculations in the channel experiments that vary the eddy energy dissipation, attributed to the simple prognostic eddy energy equation employed. Further improvements to the GEOMETRIC framework require a shift in focus from how to close for eddy buoyancy fluxes to the representation of eddy energetics.
Pre-diagnosis consumption of preserved vegetables and prognosis of invasive oesophageal squamous cell carcinoma: a prospective cohort study in one high-risk area in China
Authors: Shi Feng , Yan Fengcai , Jin Mulan , Chang Hong , Zhou Quan , Zhao Lin , Hu Zhiping , Song Qingkun , Li Jun , He Yongming , Qu Chenxu 
Published: August 2018

Objective To investigate the prognostic effect of pre-diagnosis preserved vegetable consumption on oesophageal squamous cell carcinoma (ESCC) in Yanting County, China. Methods This prospective cohort study enrolled consecutive patients with ESCC. The pre-diagnosis diet consumption data were collected using a food frequency questionnaire at baseline. Preserved vegetable consumption was categorized into two groups: < 1/week and ≥1/week. Kaplan–Meier survival curve analysis with a log-rank test and a Cox proportional hazard regression model analysis were undertaken to compare the two consumption groups. Results The study enrolled 185 patients (121 males and 64 females) with ESCC. Patients consuming preserved vegetables ≥1/week had a median survival time of 41 months, but patients consuming preserved vegetables <1/week did not achieve a median survival time. The adjusted hazard ratio (HR) for an intake of ≥1/week was 1.58 (95% confidence interval [CI] 1.01, 2.47). Among ‘ever smokers’, the HR increased to 2.04 (95% CI 1.10, 3.77) and among ‘ever alcohol drinkers’, the HR increased to 2.50 (95% CI 1.33, 4.73). Among ‘never smokers’ or ‘never alcohol drinkers’, no significant association was observed. Conclusion A high consumption of preserved vegetables was associated with a poorer prognosis among patients with ESCC.
Fall prevention knowledge and practice patterns among home healthcare professionals in southern Saudi Arabia: an observational study
Authors: Asiri Faisal , ALMohiza Mohammad A. , Faia Aseeri Mohammad , Mehtab Alam Mohammed , Ataalla Sabri M. , Alqahtani Mazen , Alshahrani Adel 
Published: August 2018

Objectives To determine the knowledge of falls risk factors among home healthcare (HHC) professionals and the practice patterns of HHC professionals regarding falls prevention. Methods A modified version of a survey designed and validated for use in home healthcare settings was distributed to HHC professionals for self-completion. Responses were collected and analysed using descriptive methods. Results Out of 80 surveys distributed to 23 HHC centres, 52 returned surveys were included for analyses (completed by physicians, physical therapists [PTs] and nurses). In terms of practice patterns, 82.7% of participants always asked older adults if they have a history of falls, 81% always identified falls risk factors, 73% documented risk factors for falling and 71% always provided interventions to address falls risk factors. Environmental hazards were the most common risk factor identified by HHC professionals. Approximately one quarter of nurses felt they had little knowledge of falls risk factors. Conclusion Over 70% of HHC professionals acknowledged the importance of falls, and over 80% of participants displayed knowledge of falls prevention factors. As HHC professionals most likely to encounter patients requiring intervention for falls prevention, physical therapists may benefit from training programmes to help identify important falls risk factors.
Vitamin D in acutely ill patients
Authors: Kostoglou-Athanassiou Ifigenia , Pantazi Eleni , Kontogiannis Sofoklis , Kousouris Dimitrios , Mavropoulos Iordanis , Athanassiou Panagiotis 
Published: August 2018

Objective To investigate 25(OH)D3 levels and their relationship to survival in a cohort of acutely ill patients on admission to an intensive care unit. Methods This study enrolled acutely ill patients at admission to an intensive care unit and a group of sex- and age-matched healthy control subjects. The 25(OH)D3 levels were measured using an enzyme immunoassay. C-reactive protein and procalcitonin levels were also measured using immunoassays. Results A total of 50 acutely ill patients and 50 healthy control subjects were enrolled in the study. The mean ± SEM 25(OH)D3 levels were significantly lower in the acutely ill patients compared with the control group (11.74 ± 0.88 ng/ml versus 24.66 ± 1.60 ng/ml, respectively). The 25(OH)D3 levels were not related to survival. An inverse relationship was observed between 25(OH)D3 levels and C-reactive protein levels. A weak inverse relationship was also observed between 25(OH)D3 levels and procalcitonin levels. Conclusions The 25(OH)D3 levels were decreased in acutely ill patients admitted to an intensive care unit compared with healthy control subjects. 25(OH)D3 levels may be inversely related to C-reactive protein and procalcitonin levels.