bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclin-Dependent Kinase 5 Decreases in Gastric Cancer and Its Nuclear Accumulation Suppresses Gastric Tumorigenesis
Authors: Cao Longlong , Zhou Jiechao , Zhang Junrong , Wu Sijin , Yang Xintao , Zhao Xin , Li Huifang , Luo Ming , Yu Qian , Lin Guangtan , Lin Huizhong , Xie Jianwei , Li Ping , Hu Xiaoqing , Zheng Chaohui , Bu Guojun , Zhang Yun-wu , Xu Huaxi , Yang Yongliang , Huang Changming , Zhang Jie 
Published: January 2015

Abstract
Purpose: As a cyclin-independent atypical CDK, the role of CDK5 in regulating cell proliferation in gastric cancer remains unknown.
Experimental Design: Expression of CDK5 in gastric tumor and paired adjacent noncancerous tissues from 437 patients was measured by Western blotting, immunohistochemistry, and real-time PCR. The subcellular translocation of CDK5 was monitored during gastric cancer cell proliferation. The role of nuclear CDK5 in gastric cancer tumorigenic proliferation and ex vivo xenografts was explored. Furthermore, by screening for compounds in the PubChem database that disrupt CDK5 association with its nuclear export facilitator, we identified a small molecular (NS-0011) that inhibits gastric cancer cell growth.
Results: CDK5 level was significantly decreased in the majority of gastric tumor tissues, and the reduction of CDK5 correlated with the severity of gastric cancer based on tumor and lymph node metastasis and patient 5-year fatality rate. Nuclear localization of CDK5 was found to be significantly decreased in tumor tissues and gastric cancer cell lines, whereas exogenously expression of nucleus-targeted CDK5 inhibited the proliferation and xenograft implantation of gastric cancer cells. Treatment with the small molecule NS-0011, which increases CDK5 accumulation in the nucleus, suppressed both cancer cell proliferation and xenograft tumorigenesis.
Conclusions: Our results suggest that low CDK5 expression is associated with poor overall survival in patients with gastric cancer, and nuclear accumulation of CDK5 inhibits the proliferation and tumorigenicity of human gastric cancer cells. Clin Cancer Res; 21(6); 1419–28. ©2015 AACR.
Acquisition of Relative Interstrand Crosslinker Resistance and PARP Inhibitor Sensitivity in Fanconi Anemia Head and Neck Cancers
Authors: Lombardi Anne J. , Hoskins Elizabeth E. , Foglesong Grant D. , Wikenheiser-Brokamp Kathryn A. , Wiesmüller Lisa , Hanenberg Helmut , Andreassen Paul R. , Jacobs Allison J. , Olson Susan B. , Keeble Winifred W. , Hays Laura E. , Wells Susanne I. 
Published: January 2015

Abstract
Purpose: Fanconi anemia is an inherited disorder associated with a constitutional defect in the Fanconi anemia DNA repair machinery that is essential for resolution of DNA interstrand crosslinks. Individuals with Fanconi anemia are predisposed to formation of head and neck squamous cell carcinomas (HNSCC) at a young age. Prognosis is poor, partly due to patient intolerance of chemotherapy and radiation requiring dose reduction, which may lead to early recurrence of disease.
Experimental Design: Using HNSCC cell lines derived from the tumors of patients with Fanconi anemia, and murine HNSCC cell lines derived from the tumors of wild-type and Fancc−/− mice, we sought to define Fanconi anemia–dependent chemosensitivity and DNA repair characteristics. We utilized DNA repair reporter assays to explore the preference of Fanconi anemia HNSCC cells for non-homologous end joining (NHEJ).
Results: Surprisingly, interstrand crosslinker (ICL) sensitivity was not necessarily Fanconi anemia–dependent in human or murine cell systems. Our results suggest that the increased Ku-dependent NHEJ that is expected in Fanconi anemia cells did not mediate relative ICL resistance. ICL exposure resulted in increased DNA damage sensing and repair by PARP in Fanconi anemia–deficient cells. Moreover, human and murine Fanconi anemia HNSCC cells were sensitive to PARP inhibition, and sensitivity of human cells was attenuated by Fanconi anemia gene complementation.
Conclusions: The observed reliance upon PARP-mediated mechanisms reveals a means by which Fanconi anemia HNSCCs can acquire relative resistance to the ICL-based chemotherapy that is a foundation of HNSCC treatment, as well as a potential target for overcoming chemoresistance in the chemosensitive individual. Clin Cancer Res; 21(8); 1962–72. ©2015 AACR.
“To B(MP-2) or Not To B(MP-2)” or “Much Ado About Nothing”: Are Orthobiologics in Tumor Surgery Worth the Risks?
Authors: Weiss Kurt R. 
Published: January 2015

Abstract
Geller and colleagues report that adjuvant chemotherapy affected the adequacy of osteosarcoma local surgical control. Exogenous bone morphogenetic protein-2 (BMP-2) did not increase local recurrence, but the limited theoretical benefits of BMP-2 for a subset of patients with osteosarcoma may not justify the systemic and long-term risks. Clin Cancer Res; 21(13); 2889–91. ©2015 AACR.
See related article by Geller et al., p. 3003
Bone-marrow-derived very small embryonic-like stem cells in patients with critical leg ischaemia: evidence of vasculogenic potential
Authors: Guerin Coralie L. , Loyer Xavier , Vilar José , Cras Audrey , Mirault Tristan , Gaussem Pascale , Silvestre Jean-Sébastien , Smadja David M. 
Published: January 2015

SummaryVery small embryonic-like stem cells (VSELs) are multipotent stem cells localised in adult bone marrow (BM) that may be mobilised into peripheral blood (PB) in response to tissue injury. We aimed to quantify VSELs in BM and PB of patients with critical limb ischaemia (CLI) and to test their angiogenic potential in vitro as well as their therapeutic capacity in mouse model of CLI. We isolated BM VSELs from patients with CLI and studied their potential to differentiate into vascular lineages. Flow and imaging cytometry showed that VSEL counts were lower in BM (p< 0.001) and higher (p< 0.001) in PB from CLI patients compared to healthy controls, suggesting that ischaemia may trigger VSELs mobilisation in this patient population. Sorted BM-VSELs cultured in angiogenic media acquired a mesenchymal phenotype (CD90+, Thy-1 gene positive expression). VSEL-derived cells had a pattern of secretion similar to that of endothelial progenitor cells, as they released low levels of VEGF-A and inflammatory cytokines. Noteworthy, VSELs triggered post-ischaemic revascularisation in immunodeficient mice (p< 0.05 vs PBS treatment), and acquired an endothelial phenotype either in vitro when cultured in the presence of VEGF-B (Cdh-5 gene positive expression), or in vivo in Matrigel implants (human CD31+ staining in neo-vessels from plug sections). In conclusion, VSELs are a potential new source of therapeutic cells that may give rise to cells of the endothelial lineage in humans.
Impact of Left Ventricular Hypertrophy on Troponin Release During Acute Myocardial Infarction: New Insights From a Comprehensive Translational Study
Authors: Fernández‐Jiménez Rodrigo , Silva Jacobo , Martínez‐Martínez Sara , López‐Maderuelo Mª Dolores , Nuno‐Ayala Mario , García‐Ruiz José Manuel , García‐Álvarez Ana , Fernández‐Friera Leticia , Pizarro Tech Gonzalo , García‐Prieto Jaime , Sanz‐Rosa David , López‐Martin Gonzalo , Fernández‐Ortiz Antonio , Macaya Carlos , Fuster Valentin , Redondo Juan Miguel , Ibanez Borja 
Published: January 2015

Background

Biomarkers are frequently used to estimate infarct size (
IS
) as an endpoint in experimental and clinical studies. Here, we prospectively studied the impact of left ventricular (LV) hypertrophy (
LVH
) on biomarker release in clinical and experimental myocardial infarction (MI).

Methods and Results

ST
‐segment elevation myocardial infarction (
STEMI
) patients (n=140) were monitored for total creatine kinase (
CK
) and cardiac troponin I (
cTnI
) over 72 hours postinfarction and were examined by cardiac magnetic resonance (
CMR
) at 1 week and 6 months postinfarction. MI was generated in pigs with induced
LVH
(n=10) and in sham‐operated pigs (n=8), and serial total
CK
and
cTnI
measurements were performed and
CMR
scans conducted at 7 days postinfarction. Regression analysis was used to study the influence of
LVH
on total
CK
and
cTnI
release and
IS
estimated by
CMR
(gold standard). Receiver operating characteristic (
ROC
) curve analysis was performed to study the discriminatory capacity of the area under the curve (
AUC)
of
cTnI
and total
CK
in predicting
LV
dysfunction. Cardiomyocyte
cTnI
expression was quantified in myocardial sections from
LVH
and sham‐operated pigs. In both the clinical and experimental studies,
LVH
was associated with significantly higher peak and
AUC
of
cTnI
, but not with differences in total
CK
.
ROC
curves showed that the discriminatory capacity of
AUC
of
cTnI
to predict
LV
dysfunction was significantly worse for patients with
LVH
.
LVH
did not affect the capacity of total
CK
to estimate
IS
or
LV
dysfunction. Immunofluorescence analysis revealed significantly higher
cTnI
content in hypertrophic cardiomyocytes.

Conclusions

Peak and
AUC
of
cTnI
both significantly overestimate
IS
in the presence of
LVH
, owing to the higher troponin content per cardiomyocyte. In the setting of
LVH
,
cTnI
release during
STEMI
poorly predicts postinfarction
LV
dysfunction. LV mass should be taken into consideration when
IS
or
LV
function are estimated by troponin release.
<p align="left">Oreocharis tsaii, a new species of Gesneriaceae from southern Yunnan, China
Authors: YunHong TAN , JIANWU LI , JIANTAO YIN 
Published: January 2015

Oreocharis tsaii, a new species of Gesneriaceae from southern Yunnan, China, is here described and illustrated. It is morphologically similar to O. hirsuta and O. aurea, but can be easily distinguished from the latter by its smaller cordate to ovate leaves; cymes with 1–5 flowers, corolla tube narrowing gradually from base to throat, constricted at the throat, corolla lobes mostly more than half as long as the tube; filaments sparsely glandular-pubescent and pilose, style sparsely glandular-pubescent.
Seasonal Forecasting of Global Hydrologic Extremes: System Development and Evaluation over GEWEX Basins
Authors: Yuan Xing , Roundy Joshua K. , Wood Eric F. , Sheffield Justin 
Published: January 2015

Abstract
Seasonal hydrologic extremes in the form of droughts and wet spells have devastating impacts on human and natural systems. Improving understanding and predictive capability of hydrologic extremes, and facilitating adaptations through establishing climate service systems at regional to global scales are among the grand challenges proposed by the World Climate Research Programme (WCRP) and are the core themes of the Regional Hydroclimate Projects (RHP) under the Global Energy and Water Cycle Experiment (GEWEX). An experimental global seasonal hydrologic forecasting system has been developed that is based on coupled climate forecast models participating in the North American Multimodel Ensemble (NMME) project and an advanced land surface hydrologic model. The system is evaluated over major GEWEX RHP river basins by comparing with ensemble streamflow prediction (ESP). The multimodel seasonal forecast system provides higher detectability for soil moisture droughts, more reliable low and high f low ensemble forecasts, and better “real time” prediction for the 2012 North American extreme drought. The association of the onset of extreme hydrologic events with oceanic and land precursors is also investigated based on the joint distribution of forecasts and observations. Climate models have a higher probability of missing the onset of hydrologic extremes when there is no oceanic precursor. But oceanic precursor alone is insufficient to guarantee a correct forecast—a land precursor is also critical in avoiding a false alarm for forecasting extremes. This study is targeted at providing the scientific underpinning for the predictability of hydrologic extremes over GEWEX RHP basins and serves as a prototype for seasonal hydrologic forecasts within the Global Framework for Climate Services (GFCS).
Precursor Environmental Conditions Associated with the Termination of Madden–Julian Oscillation Events
Authors: Stachnik Justin P. , Waliser Duane E. , Majda Andrew J. 
Published: January 2015

Abstract
This study presents an analysis of the precursor environmental conditions related to the termination of Madden–Julian oscillation (MJO) events. A simple climatology is created using a real-time MJO monitoring index, documenting the locations and frequencies of MJO decay. Lead–lag composites of several atmospheric variables including temperature, moisture, and intraseasonal wind anomalies are generated from three reanalyses. There is remarkable agreement among the datasets with long-term, lower-tropospheric moisture deficits over the local domain best identifying termination events over the Indian Ocean. MJO termination in the Indian Ocean is also linked to a northward shift of the intertropical convergence zone (ITCZ) with possible lead times as much as 20 days prior to MJO decay.
Statistically significant differences in the low-level vertical velocity and specific humidity are also identified more than 10 days in advance of MJO termination events in the western Pacific, though the differences here are more symmetric about the equator. Unlike the Indian Ocean and western Pacific, MJOs that terminate over the Maritime Continent appear to be related to their own intensity rather than the downstream conditions. As such, only the strongest MJOs tend to propagate into the warm pool region.
Finally, a budget analysis is performed on the three-dimensional moisture advection equation in order to better elucidate what time scales and physical mechanisms are most important for MJO termination. The combination of intraseasonal vertical circulation anomalies coupled with the mean-state specific humidity best explain the anomalous moisture patterns associated with MJO termination, suggesting that the downstream influence of the MJO circulation can eventually lead to its future demise.
Evaluation of WRF Mesoscale Climate Simulations over the Tibetan Plateau during 1979–2011
Authors: Gao Yanhong , Xu Jianwei , Chen Deliang 
Published: January 2015

Abstract
To develop a finescale dataset for the purpose of analyzing historical climatic change over the Tibet Plateau (TP), a high-resolution regional climate simulation for 1979–2011 was conducted using the Weather Research and Forecasting (WRF) Model driven by the ERA-Interim (ERA-Int). This work evaluates the high-resolution (30 km) WRF simulation in terms of annual variation, spatial structure, and 33-yr temporal trends of surface air temperature (Tair) and precipitation (Prec) over the TP, with reference to station observations. Another focus is on the examination of the height–temperature relationship. Inheriting from its forcing, the WRF simulation presents an apparent cold bias in the TP. The cold bias is largely reduced by a lapse rate correction of the simulated surface air temperature with help of the station and model elevations. ERA-Int presents the same sign of Tair and Prec trends as the observations, but with smaller magnitude, especially in the dry season. Compared to its forcing, the WRF simulation improves the simulation of the annual cycles and temporal trends of Tair and Prec in the wet season. In the dry season, however, there is hardly any improvement. The observed Tair presents a downward linear trend in the lapse rate. This feature is examined in the WRF simulation in comparison to ERA-Int. The WRF simulation captures the observed lapse rate and its temporal trend better than ERA-Int. The decreasing lapse rate over time confirms that Tair change in the TP is elevation dependent.
Designing Detection and Attribution Simulations for CMIP6 to Optimize the Estimation of Greenhouse Gas–Induced Warming
Authors: Ribes Aurélien , Gillett Nathan P. , Zwiers Francis W. 
Published: January 2015

AbstractClimate change detection and attribution studies rely on historical simulations using specified combinations of forcings to quantify the contributions from greenhouse gases and other forcings to observed climate change. In the last CMIP5 exercise, in addition to the so-called all-forcings simulations, which are driven with a combination of anthropogenic and natural forcings, natural forcings–only and greenhouse gas–only simulations were prioritized among other possible experiments. This study addresses the question of optimally designing this set of experiments to estimate the recent greenhouse gas–induced warming, which is highly relevant to the problem of constraining estimates of the transient climate response. Based on Monte Carlo simulations and considering experimental designs with a fixed budget for the number of simulations that modeling centers can perform, the most accurate estimate of historical greenhouse gas–induced warming is obtained with a design using a combination of all-forcings, natural forcings–only, and aerosol forcing–only simulations. An investigation of optimal ensemble sizes, given the constraint on the total number of simulations, indicates that allocating larger ensemble sizes to weaker forcings, such as natural-only, is optimal.
Effects of peripheral FAAH blockade on NTG-induced hyperalgesia—evaluation of URB937 in an animal model of migraine
Authors: Greco R , Bandiera T , Mangione AS , Demartini C , Siani F , Nappi G , Sandrini G , Guijarro A , Armirotti A , Piomelli D , Tassorelli C 
Published: January 2015

Background Systemic nitroglycerin (NTG) activates brain nuclei involved in nociceptive transmission as well as in neuroendocrine and autonomic functions in rats. These changes are considered relevant for migraine because NTG consistently provokes spontaneous-like migraine attacks in migraineurs. Several studies have suggested a relationship between the endocannabinoid levels and pain mediation in migraine. URB937, a peripheral inhibitor of fatty acid amide hydrolase (FAAH)—the enzyme that degrades anandamide, produces analgesia in animal models of pain, but there is no information on its effects in migraine. Aim We evaluated whether URB937 alters nociceptive responses in the animal model of migraine based on NTG administration in male rats, using the tail flick test and the plantar and orofacial formalin tests, under baseline conditions and after NTG administration. Furthermore, we investigated whether URB937 affects NTG-induced c-Fos expression in the brain. Results During the tail flick test, URB937 showed an antinociceptive effect in baseline conditions and it blocked NTG-induced hyperalgesia. URB937 also proved effective in counteracting NTG-induced hyperalgesia during both the plantar and orofacial formalin tests. Mapping of brain nuclei activated by NTG indicates that URB937 significantly reduces c-Fos expression in the nucleus trigeminalis caudalis and the locus coeruleus. Conclusions The data suggest that URB937 is capable of changing, probably via indirect mechanisms, the functional status of central structures that are important for pain transmission in an animal model of migraine.
Perceptions, Barriers, and Knowledge of Inpatient Glycemic Control
Authors: Beliard Regine , Muzykovsky Karina , Vincent William , Shah Bupendra , Davanos Evangelia 
Published: January 2015

Objectives: To assess knowledge and perceptions of health care workers regarding optimal care for patients with hyperglycemia and identify commonly perceived barriers for the development of a hospital-wide education program. Research Design and Methods: A cross-sectional design was utilized to survey health care workers involved in managing hyperglycemia in an urban, community teaching hospital. Each health care worker received a survey specific to their health care role. Results: Approximately 50% of questions about best clinical practices were answered correctly. Correct responses varied across disciplines (n, mean ± standard deviation [SD]), that is, physicians (n = 112, 53% ± 26%), nurses (n = 43, 52% ± 35%), pharmacists (n = 20, 64% ± 23%), dietitians (n = 5, 48% ± 30%), and patient care assistants (n = 12, 38% ± 34%). Most health care workers perceived hyperglycemia treatment to be very important and that sliding scale insulin was commonly used because of convenience but not efficacy. Conclusion: Knowledge regarding hyperglycemia management was suboptimal across a sample of health care workers when compared to clinical best practices. Hyperglycemia management was perceived to be important but convenience seemed to influence the management approach more than efficacy. Knowledge, perceptions, and barriers seem to play an important role in patient care and should be considered when developing education programs prior to implementation of optimized glycemic protocols.
Health Beliefs Describing Patients Enrolling in Community Pharmacy Disease Management Programs
Authors: Luder Heidi , Frede Stacey , Kirby James , King Keith , Heaton Pamela 
Published: January 2015

Objectives: The purpose of this study was to survey new enrollees in a community pharmacy, employer-based diabetes and hypertension coaching program to describe the characteristics, health beliefs, and cues to action of newly enrolled participants. Methods: A 70-question, 5-point Likert-type survey was developed using constructs from the Health Belief Model (HBM), Theory of Planned Behavior (TPB), and Theory of Reasoned Action (TRA). New enrollees in the coaching programs completed the survey. Survey responses between controlled and uncontrolled patients and patient demographics were compared. Results: Between November 2011 and November 2012, 154 patients completed the survey. Patients were fairly well controlled with a mean hemoglobin A1C of 7.3% and a mean blood pressure of 134/82 mm Hg. The strongest cue to action for enrollment was the financial incentives offered by the employer (mean: 3.33, median: 4). White patients were significantly more motivated by financial incentives. More patients indicated they had not enrolled previously in the program because they were unaware it was available (mean: 2.89, median 3.0) and these patients were more likely to have an uncontrolled condition ( P ≤ 0.050). Conclusion: A top factor motivating patients to enroll in a disease management coaching program was the receipt of financial incentives. Significant differences in HBM, TPB, and TRA responses were seen for patients with different demographics.
An Evaluation of Adverse Drug Reactions Associated With Antipsychotic Use for the Treatment of Delirium in the Intensive Care Unit
Authors: Hale Genevieve M. , Kane-Gill Sandra L. , Groetzinger Lara , Smithburger Pamela L. 
Published: January 2015

Purpose: This investigation evaluated the incidence, severity, and harm of adverse drug reactions (ADRs) associated with antipsychotic use for intensive care unit (ICU) delirium. Methods: In this prospective, observational study patients were screened for development of delirium with the Intensive Care Delirium Screening Checklist (ICDSC). An ICDSC score of ≥4 was considered delirious. Patients with delirium were screened daily for ADRs. Suspected ADRs were evaluated for drug causality using 3 published, objective assessment tools. Suspected ADRs were considered positive when 2 of 3 instruments had an agreement rating of “possible” or greater. ADR severity was defined as “mild/moderate” or “severe” using the National Cancer Institute’s Common Terminology Criteria for Adverse Events scale. A modified National Coordinating Council Medication Error Reporting Index for Categorizing Errors categorized ADRs into “no harm” or “harmful.” Results: Of 90 patients with delirium, 56 received antipsychotics. Ten suspected ADRs occurred attributed to antipsychotic use. QTc prolongation was the most observed ADR (50%). Patients with ADRs had higher mean Acute Physiology and Chronic Health Evaluation II (APACHE II) scores ( P = .038). Patients who received haloperidol experienced more severe ( P = .048) ADRs. Conclusions: ADRs were observed in 18% of patients having delirium treated with antipsychotics with about half considered severe or harmful. A risk versus benefit assessment is needed before initiating antipsychotic therapy in ICU patients.