bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nursing home hospital transfers in the terminally ill: night shift nurses matter!
Authors: Economos Guillaume , Tholly Francoise , Rhondali Wadih , Ruer Murielle , Tricou Colombe , Fawoubo Audrey , Perceau-Chambard Élise , Filbet Marilene 
Published: September 2019

BackgroundFrench demographic projection expects an increasing number of older, dependent patients in the next few years. A large proportion of this population lives in nursing homes and their transfer to hospitals at the end of life is an ongoing issue.ObjectiveThis study explored the factors influencing the transfer of patients living in nursing homes to hospital at the end of life.DesignWe used a mixed-methods questionnaire developed by an expert group and assessing different characteristics of the nursing homes.ParticipantsAll the nursing homes in the Rhône-Alpes area (n=680) were surveyed.ResultsWe obtained 466 (68%) answers. We found that a palliative care programme was present in 336 (72%) nursing homes. The majority had a coordinating physician 428 (82%) and a mean number of 6 nurses for 83 beds, with 83 (18%) having a night shift nurse. There was a mean number of 19 deaths per nursing home during the recorded year. The main cause of death was dementia (41%), cancer-related death (13%). Death occurred mostly in the nursing home (14 74%). Night shift nurse attendance was significantly associated with the place of death: 27 deaths occurred in nursing homes with a night shift nurse versus 12 in those without one (p<0001).ConclusionsThe location of the death of frail elderly patients is a major health issue that needs to be addressed. Our results suggests that the presence of a night shift nurse decreases the number of emergency transfers and deaths in the hospital.
Rilpivirine attenuates liver fibrosis through selective STAT1-mediated apoptosis in hepatic stellate cells
Authors: Martí-Rodrigo Alberto , Alegre Fernando , Moragrega Ángela B , García-García Francisco , Martí-Rodrigo Pablo , Fernández-Iglesias Anabel , Gracia-Sancho Jordi , Apostolova Nadezda , Esplugues Juan V , Blas-García Ana 
Published: September 2019

ObjectiveLiver fibrosis constitutes a major health problem worldwide due to its rapidly increasing prevalence and the lack of specific and effective treatments. Growing evidence suggests that signalling through cytokine-activated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways regulates liver fibrosis and regeneration. Rilpivirine (RPV) is a widely used anti-HIV drug not reported to produce hepatotoxicity. We aimed to describe the potential hepatoprotective effects of RPV in different models of chronic liver injury, focusing on JAK-STAT signalling regulation.DesignThe effects of RPV on hepatic steatosis, inflammation and fibrogenesis were studied in a nutritional mouse model of non-alcoholic fatty liver disease, carbon tetrachloride-induced fibrosis and bile duct ligation-induced fibrosis. Primary human hepatic stellate cells (hHSC) and human cell lines LX-2 and Hep3B were used to investigate the underlying molecular mechanisms.ResultsRPV exerted a clear anti-inflammatory and antifibrotic effect in all the in vivo models of liver injury employed, and enhanced STAT3-dependent proliferation in hepatocytes and apoptosis in HSC through selective STAT1 activation. These results were reproduced in vitro; RPV undermined STAT3 activation and triggered STAT1-mediated pathways and apoptosis in HSC. Interestingly, this selective pro-apoptotic effect completely disappeared when STAT1 was silenced. Conditioned medium experiments showed that HSC apoptosis activated STAT3 in hepatocytes in an interleukin-6-dependent mechanism.ConclusionRPV ameliorates liver fibrosis through selective STAT1-dependent induction of apoptosis in HSC, which exert paracrinal effects in hepatocytes, thus promoting liver regeneration. RPV’s actions may represent an effective strategy to treat chronic liver diseases of different aetiologies and help identify novel therapeutic targets.
Clinical trials of neurointervention : 2007–2018
Authors: Saber Hamidreza , Jadhav Ashutosh P , Rajah Gary B , Narayanan Sandra , Sheth Sunil A , Liebeskind David S , Somai Melek 
Published: September 2019

BackgroundClinicalTrials.gov is one of the largest trials’ registries in the world.ObjectiveTo leverage the ClinicalTrials.gov database to define the portfolio of clinical trials of neurointervention.MethodsWe restricted our extraction to interventional clinical trials submitted between 2007 and 2018, and included MeSH terms that are part of the nervous system (n=19 344) or cardiovascular disease (n=19 234) categories and included a list of neurointerventional terms. The characteristics of trials, geographic distribution, dissemination, and funding sources were explored using descriptive and regression models.ResultsA total of 206 neurointerventional clinical trials across 1691 medical centers were identified. Acute stroke was the most studied conditions (68, 33%), followed by aneurysms (63, 31%), carotid stenosis (48, 24%), intracranial atherosclerotic disease (7, 3.5%), cerebral venous thrombosis (6, 3%), arteriovenous malformation (4, 2%), idiopathic intracranial hypertension (3, 1.5%), and others (6, 3%). Overall, 59 (29%) trials were completed, 79 (37%) were active trials (28% recruiting), and 22 (11%) were terminated or suspended. Academic centers and industry were the most common primary funding source (63% and 29%, respectively), with no funding source reported in 16 (7.7%) trials. Among 77 completed or terminated trials, only 9 (11.7%) trials reported findings within 12 months. Median time to publication for trials funded by academia was 1.66 years (interquartile range (IQR) 0.7–2.1) versus 2.1 years (IQR 1.2–3.25) for industry-funded studies.ConclusionsA low dissemination rate for results and a high rate of study non-completion, as well as lack of geographic dispersion of trials appear to be major challenges in the field.
Efficacy and safety of rescue stenting following failed mechanical thrombectomy for anterior circulation large vessel occlusion: propensity score analysis
Authors: Peng Feng , Wan Junfang , Liu Wenhua , Huang Wenguo , Wang Li , Qiu Tao , Yang Shiquan , Shi Qiang , Zhang Shuai , Zeng Guoyong , Wang Yan , Ai Zhibin , Liu Yong , Hu Wei , Wen Changming , Shi Zhonghua , Pu Jie , Qiu Zhongmin , Wu Deping , Gong Zili , Shuai Jie , Yang Qingwu , Zi Wenjie , Li Fengli 
Published: September 2019

PurposeTo evaluate the effectiveness and safety of rescue stenting (RS) after failed mechanical thrombectomy (MT) for patients with large artery occlusion in the anterior circulation.MethodsConsecutive patients who experienced failed reperfusion and subsequently did or did not undergo RS at 16 comprehensive stroke centers were enrolled from January 2015 to June 2018. Propensity score matching was used to achieve baseline balance between the patient groups. Symptomatic intracranial hemorrhage (sICH) at 48 hours and the modified Rankin Scale scores and mortality at 3 months in the two groups were compared.ResultsA total of 90 patients with RS and 117 patients without RS after failed MT were enrolled. Propensity score matching analysis selected 132 matched patients. The good outcome rate was significantly higher in matched patients with RS than in those without RS (36.4% vs 19.7%, p=0.033), whereas the sICH (13.6% vs 21.2%, p=0.251) and mortality (31.9% vs 43.9%, p=0.151) were not significantly different between the groups.ConclusionsRS seems to be an effective safe choice for patients with large vessel occlusion of the anterior circulation who underwent failed MT.
Nutritional evaluation of seal by-products as an alternative protein source for use in monogastric animals
Authors: Anderson Derek M. , Priest Gina , Collins Stephanie A. , MacIsaac Janice L. 
Published: September 2019

Seal by-products (grey seal with the bone in, grey seal with the bone removed, and harp seal) were subjected to five different processing methods: high (100 °C) and low (45 °C) temperature oven-drying, freeze-drying (FD), silage by acid or natural fermentation. Growth performance of diets containing these seal by-products was evaluated in rats as a monogastric model species. With the exception of naturally fermented grey seal without bone, weight gains for rats fed the boneless grey seal products were highest of the seal products (24.65–30.04 g rat−1) and statistically similar to those of rats fed casein (32.15 g rat−1). An in vivo crude protein (CP) digestibility study was conducted using 12 adult white rats in metabolic cages that allowed separate collection of urine and feces. The 16% CP diets contained chromic oxide as an inert fecal marker at 0.5%. Total fecal and urine production, as well as feed and water intake, were recorded daily within the three experimental periods. Digestibility of CP was significantly higher for the naturally fermented grey seal without bone silage (94.0%) than casein (89.0%), whereas the other seal products were statistically similar (91.7%–92.7%). The CP content of FD grey seal was as high as 91.7% (FD). Seal by-products have the potential to be used as alternative high-protein feedstuffs in monogastric diets.
Aurora A–Selective Inhibitor LY3295668 Leads to Dominant Mitotic Arrest, Apoptosis in Cancer Cells, and Shows Potent Preclinical Antitumor Efficacy
Authors: Du Jian , Yan Lei , Torres Raquel , Gong Xueqian , Bian Huimin , Marugán Carlos , Boehnke Karsten , Baquero Carmen , Hui Yu-Hua , Chapman Sonya C. , Yang Yanzhu , Zeng Yi , Bogner Sarah M. , Foreman Robert T. , Capen Andrew , Donoho Gregory P. , Van Horn Robert D. , Barnard Darlene S. , Dempsey Jack A. , Beckmann Richard P. , Marshall Mark S. , Chio Li-Chun , Qian Yuewei , Webster Yue W. , Aggarwal Amit , Chu Shaoyou , Bhattachar Shobha , Stancato Louis F. , Dowless Michele S. , Iversen Phillip W. , Manro Jason R. , Walgren Jennie L. , Halstead Bartley W. , Dieter Matthew Z. , Martinez Ricardo , Bhagwat Shripad V. , Kreklau Emiko L. , Lallena Maria Jose , Ye Xiang S. , Patel Bharvin K.R. , Reinhard Christoph , Plowman Gregory D. , Barda David A. , Henry James R. , Buchanan Sean G. , Campbell Robert M. 
Published: September 2019

Abstract
Although Aurora A, B, and C kinases share high sequence similarity, especially within the kinase domain, they function distinctly in cell-cycle progression. Aurora A depletion primarily leads to mitotic spindle formation defects and consequently prometaphase arrest, whereas Aurora B/C inactivation primarily induces polyploidy from cytokinesis failure. Aurora B/C inactivation phenotypes are also epistatic to those of Aurora A, such that the concomitant inactivation of Aurora A and B, or all Aurora isoforms by nonisoform–selective Aurora inhibitors, demonstrates the Aurora B/C-dominant cytokinesis failure and polyploidy phenotypes. Several Aurora inhibitors are in clinical trials for T/B-cell lymphoma, multiple myeloma, leukemia, lung, and breast cancers. Here, we describe an Aurora A–selective inhibitor, LY3295668, which potently inhibits Aurora autophosphorylation and its kinase activity in vitro and in vivo, persistently arrests cancer cells in mitosis, and induces more profound apoptosis than Aurora B or Aurora A/B dual inhibitors without Aurora B inhibition–associated cytokinesis failure and aneuploidy. LY3295668 inhibits the growth of a broad panel of cancer cell lines, including small-cell lung and breast cancer cells. It demonstrates significant efficacy in small-cell lung cancer xenograft and patient-derived tumor preclinical models as a single agent and in combination with standard-of-care agents. LY3295668, as a highly Aurora A–selective inhibitor, may represent a preferred approach to the current pan-Aurora inhibitors as a cancer therapeutic agent.
A Novel Salicylanilide Derivative Induces Autophagy Cell Death in Castration-Resistant Prostate Cancer via ER Stress-Activated PERK Signaling Pathway
Authors: Hsieh Chia-Ling , Huang Hsu-Shan , Chen Kuan-Chou , Saka Teigi , Chiang Chih-Ying , Chung Leland W.K. , Sung Shian-Ying 
Published: September 2019

Abstract
Metastatic castration-resistant prostate cancer (CRPC) is currently incurable. Cancer growth and progression is intimately affected by its interaction with host microenvironment. Cotargeting of the stroma and prostate cancer is therefore an emerging therapeutic strategy for metastatic CRPC. Cancer-induced osteoclastogenesis is known to contribute to CRPC bone metastasis. This study is to extend pharmacologic value of our synthesized LCC03, a derivative of 5-(2′,4′-difluorophenyl)-salicylanilide that has previously testified for its osteoclastogenesis activity, by exploring its additional cytotoxic properties and underlying mechanism in CRPC cells. LCC03 was chemically synthesized and examined for cell growth inhibition in a serial of CRPC cell lines. We demonstrated that LCC03 dose-dependently suppressed proliferation and retarded cell-cycle progression in CRPC cells. The classical autophagy features, including autophagosome formation and LC3-II conversion, were dramatically shown in LCC03-treated CRPC cells, and it was associated with the suppressed AKT/mTOR signaling pathways, a major negative regulator of autophagy. Moreover, an expanded morphology of the endoplasmic reticulum (ER), increased expression of the ER stress markers GRP78 and PERK, and eIF2α phosphorylation were observed. Blockage of autophagy and PERK pathways using small molecule inhibitors or shRNA knockdown reversed LCC03-induced autophagy and cell death, thus indicating that the PERK–eIF2α pathway contributed to the LCC03-induced autophagy. Furthermore, treatment of tumor-bearing mice with intraperitoneal administered LCC03 suppressed the growth of CRPC xenografts in mouse bone without systemic toxicity. The dual action of 5-(2′,4′-difluorophenyl)-salicylanilide on targeting both the osteoclasts and the tumor cells strongly indicates that LCC03 is a promising anticancer candidate for preventing and treating metastatic CRPC.
Point of Care Clinical Risk Score to Improve the Negative Diagnostic Utility of an Agatston Score of Zero
Authors: Alshahrani Ali M. , Mahmood Hamza , Wells George A. , Hossain Alomgir , Rybicki Frank J. , Achenbach Stephan , Al-Mallah Mouaz H. , Andreini Daniele , Bax Jeroen J. , Berman Daniel S. , Budoff Matthew J. , Cademartiri Filippo , Callister Tracy Q. , Chang Hyuk-Jae , Chinnaiyan Kavitha , Cury Ricardo C. , DeLago Augustin , Feuchtner Gudrun , Hadamitzky Martin , Hausleiter Joerg , Kaufmann Philipp A. , Kim Yong-Jin , Leipsic Jonathon A. , Maffei Erica , Marques Hugo , Pontone Gianluca , Raff Gilbert , Rubinshtein Ronen , Shaw Leslee J. , Villines Todd C. , Lin Fay Y. , Min James K. , Chow Benjamin J. 
Published: September 2019

Background:
Coronary artery calcification is a marker of underlying atherosclerotic vascular disease. The absence of coronary artery calcification is associated with a low prevalence of obstructive coronary artery disease (CAD), but it cannot be ruled out completely. We sought to develop a clinical tool that can be added to Agatston score of zero to rule out obstructive CAD with high accuracy.

Methods:
We developed a clinical score retrospectively from a cohort of 4903 consecutive patients with an Agatston score of zero. Patients with prior diagnosis of CAD, coronary percutaneous coronary intervention, or surgical revascularization were excluded. Obstructive CAD was defined as any epicardial vessel diameter narrowing of ≥50%. The score was validated using an external cohort of 4290 patients with an Agatston score of zero from a multinational registry.

Results:
The score consisted of 7 variables: age, sex, typical chest pain, dyslipidemia, hypertension, family history, and diabetes mellitus. The model was robust with an area under the curve of 0.70 (95% CI, 0.65–0.76) in the derivation cohort and 0.69 (95% CI, 0.65–0.72) in the validation cohort. Patients were divided into 3 risk groups based on the score: low (≤6), intermediate (7–13), and high (≥14). Patients who score ≤6 have a negative likelihood ratio of 0.42 for obstructive CAD, whereas those who score ≥14 have a positive likelihood ratio of >5.5 for obstructive CAD. The outcome was ruled out in >98% of patients with a score ≤6 in the validation cohort.

Conclusions:
We developed a score that may be used to identify the likelihood of obstructive CAD in patients with an Agatston score of zero, which may be used to direct the need for additional testing. However, the results of this retrospective analysis are hypothesis generating and before clinical implementation should be validated in a trial with a prospectively collected data.
Development of a Misaligned Tropical Cyclone
Authors: Schecter David A. , Menelaou Konstantinos 
Published: September 2019

AbstractA cloud-resolving model is used to examine the virtually shear-free evolution of incipient tropical cyclones initialized with different degrees of misalignment between the lower- and middle-tropospheric centers of rotation. Increasing the initial displacement of rotational centers (the tilt) from a negligible value to several hundred kilometers extends the time scale of hurricane formation from 1 to 10 days. Hindered amplification of the maximum tangential velocity υm at the surface of a strongly perturbed system is related to an extended duration of misalignment resulting from incomplete early decay and subsequent transient growth of the tilt magnitude. The prolonged misalignment coincides with a prolonged period of asymmetric convection peaked far from the surface center of the vortex. A Sawyer–Eliassen model is used to analyze the disparity between azimuthal velocity tendencies of selected pre–tropical storm vortices with low and high degrees of misalignment. Although no single factor completely explains the difference of intensification rates, greater misalignment is linked to weaker positive azimuthal velocity forcing near υm by the component of the mean secondary circulation attributed to heating by microphysical cloud processes. Of note regarding the dynamics, enhanced tilt only modestly affects the growth rate of kinetic energy outside the core of the surface vortex while severely hindering intensification of υm within the core for at least several days. The processes controlling the evolution of the misalignment associated with inefficient development are examined in detail for a selected simulation. It is found that adiabatic mechanisms are capable of driving the transient amplification of tilt, whereas diabatic processes are essential to ultimate alignment of the tropical cyclone.
Topographic Forcing from East Asia and North America in the Northern Winter Stratosphere and Their Mutual Interference
Authors: Ren Rongcai , Xia Xin , Rao Jian 
Published: September 2019

AbstractThis study uses the stratosphere-resolved Whole Atmosphere Community Climate Model to demonstrate the “independent” and “dependent” topographic forcing from the topography of East Asia (EA) and North America (NA), and their “joint” forcing in the northern winter stratosphere. The mutual interference between the EA and NA forcing is also demonstrated. Specifically, without EA, an independent NA can also, like EA, induce a severe polar warming and weakening of the stratospheric polar vortex. While EA favors a displacement of the polar vortex toward Eurasia, NA favors a displacement toward the North America–Atlantic region. However, the independent-EA-forced weakening effect on the polar vortex can be largely decreased and changes to a location displacement when NA exists, and the interference the other way around is even more critical, being able to completely offset the independent-NA-forced effect, because EA can substantively obstruct NA’s effect on the tropospheric wave pattern over the Eurasia–Pacific region. The much stronger (weaker) interference of EA (NA) is associated with its stronger (weaker) downstream weakening effect on the zonal flow that impinges on NA (EA). The mutual interference always tends to further destruct the upward wave fluxes over the eastern North Pacific and enhance the downward wave fluxes over North America. The overall changes in upward wave fluxes, as well as that in the Rossby stationary wavenumber responsible for the stratospheric changes, are related to changes in the zonal-mean flow pattern. The joint effects of EA and NA, rather than being a linear superimposition of their independent effects, are largely dominated by the effects of EA.
The Connection between the Southern Annular Mode and a Feature-Based Perspective on Southern Hemisphere Midlatitude Winter Variability
Authors: Spensberger Clemens , Reeder Michael J. , Spengler Thomas , Patterson Matthew 
Published: September 2019

AbstractThis article provides a reconciling perspective on the two main, but contradictory, interpretations of the southern annular mode (SAM). SAM was originally thought to characterize meridional shifts in the storm track across the entire hemisphere. This perspective was later questioned, and SAM was interpreted as a statistical artifact depending on the choice of base region for the principal component analysis. Neither perspective, however, fully describes SAM. We show that SAM cannot be interpreted in terms of midlatitude variability, as SAM merely modulates the most poleward part of the cyclone tracks and only marginally influences the distribution of other weather-related features of the storm track (e.g., position of jet axes and Rossby wave breaking). Instead, SAM emerges as the leading pattern of geopotential variability due to strong correlations of sea level pressure around the Antarctic continent. As SAM correlates strongly both with the pan-Antarctic mean temperature and the meridional heat flux through 65°S, we hypothesize that SAM can be interpreted as a measure of the degree of the (de)coupling between Antarctica and the southern midlatitudes. As an alternative way of characterizing southern midlatitude variability, we seek domains in which the leading EOF patterns of both the geopotential and storm-track features yield a dynamically consistent picture. This approach is successful for the South Pacific. Here the leading variability patterns are closely related to the Pacific–South America pattern and point toward an NAO-like variability.
Toward a Consistent Definition between Satellite and Model Clear-Sky Radiative Fluxes
Authors: Loeb Norman G. , Rose Fred G. , Kato Seiji , Rutan David A. , Su Wenying , Wang Hailan , Doelling David R. , Smith William L. , Gettelman Andrew 
Published: September 2019

AbstractA new method of determining clear-sky radiative fluxes from satellite observations for climate model evaluation is presented. The method consists of applying adjustment factors to existing satellite clear-sky broadband radiative fluxes that make the observed and simulated clear-sky flux definitions more consistent. The adjustment factors are determined from the difference between observation-based radiative transfer model calculations of monthly mean clear-sky fluxes obtained by ignoring clouds in the atmospheric column and by weighting hourly mean clear-sky fluxes with imager-based clear-area fractions. The global mean longwave (LW) adjustment factor is −2.2 W m−2at the top of the atmosphere and 2.7 W m−2at the surface. The LW adjustment factors are pronounced at high latitudes during winter and in regions with high upper-tropospheric humidity and cirrus cloud cover, such as over the west tropical Pacific, and the South Pacific and intertropical convergence zones. In the shortwave (SW), global mean adjustment is 0.5 W m−2at TOA and −1.9 W m−2at the surface. It is most pronounced over sea ice off of Antarctica and over heavy aerosol regions, such as eastern China. However, interannual variations in the regional SW and LW adjustment factors are small compared to those in cloud radiative effect. After applying the LW adjustment factors, differences in zonal mean cloud radiative effect between observations and climate models decrease markedly between 60°S and 60°N and poleward of 65°N. The largest regional improvements occur over the west tropical Pacific and Indian Oceans. In contrast, the impact of the SW adjustment factors is much smaller.