bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving time to antibiotics and implementing the "Sepsis 6"
Authors: McGregor Calum 
Published: January 2014

AbstractIt has been shown that completion of the "Sepsis 6" within 1 hour reduces mortality (1). This project aims to assess compliance with this standard and evaluate the effectiveness of a sepsis improvement plan in a district general hospital in the UK.A baseline audit was performed, examining case notes of “septic patients” retrospectively (those on intravenous antibiotics). Compliance with each element of the sepsis six plus time to first antibiotic (TTFA) was assessed. A sepsis improvement plan was introduced consisting of staff education, reinforcing vigilance, regular multidisciplinary meetings and incorporating a standardised approach through the use of a sepsis proforma. Following the introduction of this, and after some refinement, the average time to antibiotic fell from 6 hours to 1.4 hours.In conclusion, an educational drive along with a systematic change in processes has seen reduced TTFA along with enhanced compliance with most elements of the sepsis 6. Through continued assessment and further improving upon systematic processes with continued education we would anticipate consistent improvement in the management of septic patients.
A system for the management, display and integration of pre-hospital healthcare activity in the deployed environment
Authors: Grant Simon , Wheatley R J 
Published: January 2014

AimTo create and implement a system through which pre-hospital healthcare activity across an entire operational theatre could be made available in real-time to support healthcare delivery, governance and assurance activity.MethodsAn IT-based system was created that could display, manage and integrate the pre-hospital healthcare activity on Op HERRICK 18. The system was based on the Defence Medical Services Common Assurance Framework and run through Microsoft Office SharePoint.ResultsPre-hospital healthcare activity was made available and visible across an operational theatre. This supported delivery, assurance and governance at any time. Activity from each medical facility could be integrated and display automatically improving theatre wide situational awareness. The availability of information resulted in a shift towards a more continuous process of assurance and governance rather than reliance on inherently threatening and increasingly intermittent inspection regimes.DiscussionThe ability to review healthcare activity remotely at anytime significantly improves the validity of assurance possible for a deployed force. Governance activity can be more responsive and less reliant on the fixed timescale and datasets of reports from outlying medical facilities. However, assurance and governance authorities must not allow such a wealth of information to impact local leadership and innovation through a perception of, or actual, micro-management.
Alarmin IL-33 Acts as an Immunoadjuvant to Enhance Antigen-Specific Tumor Immunity
Authors: Villarreal Daniel O. , Wise Megan C. , Walters Jewell N. , Reuschel Emma L. , Choi Min Joung , Obeng-Adjei Nyamekye , Yan Jian , Morrow Matthew P. , Weiner David B. 
Published: January 2014

Abstract
Studies of interleukin (IL)-33 reveal a number of pleiotropic properties. Here, we report that IL-33 has immunoadjuvant effects in a human papilloma virus (HPV)–associated model for cancer immunotherapy where cell-mediated immunity is critical for protection. Two biologically active isoforms of IL-33 exist that are full-length or mature, but the ability of either isoform to function as a vaccine adjuvant that influences CD4 T helper 1 or CD8 T-cell immune responses is not defined. We showed that both IL-33 isoforms are capable of enhancing potent antigen-specific effector and memory T-cell immunity in vivo in a DNA vaccine setting. In addition, although both IL-33 isoforms drove robust IFN-γ responses, neither elevated secretion of IL-4 or immunoglobulin E levels. Further, both isoforms augmented vaccine-induced antigen-specific polyfunctional CD4+ and CD8+ T-cell responses, with a large proportion of CD8+ T cells undergoing plurifunctional cytolytic degranulation. Therapeutic studies indicated that vaccination with either IL-33 isoform in conjunction with an HPV DNA vaccine caused rapid and complete regressions in vivo. Moreover, IL-33 could expand the magnitude of antigen-specific CD8+ T-cell responses and elicit effector–memory CD8+ T cells. Taken together, our results support the development of these IL-33 isoforms as immunoadjuvants in vaccinations against pathogens, including in the context of antitumor immunotherapy. Cancer Res; 74(6); 1789–800. ©2014 AACR.
Fragmented Sleep Accelerates Tumor Growth and Progression through Recruitment of Tumor-Associated Macrophages and TLR4 Signaling
Authors: Hakim Fahed , Wang Yang , Zhang Shelley X.L. , Zheng Jiamao , Yolcu Esma S. , Carreras Alba , Khalyfa Abdelnaby , Shirwan Haval , Almendros Isaac , Gozal David 
Published: January 2014

Abstract
Sleep fragmentation (SF) is a highly prevalent condition and a hallmark of sleep apnea, a condition that has been associated with increased cancer incidence and mortality. In this study, we examined the hypothesis that sleep fragmentation promotes tumor growth and progression through proinflammatory TLR4 signaling. In the design, we compared mice that were exposed to sleep fragmentation one week before engraftment of syngeneic TC1 or LL3 tumor cells and tumor analysis four weeks later. We also compared host contributions through the use of mice genetically deficient in TLR4 or its effector molecules MYD88 or TRIF. We found that sleep fragmentation enhanced tumor size and weight compared with control mice. Increased invasiveness was apparent in sleep fragmentation tumors, which penetrated the tumor capsule into surrounding tissues, including adjacent muscle. Tumor-associated macrophages (TAM) were more numerous in sleep fragmentation tumors, where they were distributed in a relatively closer proximity to the tumor capsule compared with control mice. Although tumors were generally smaller in both MYD88−/− and TRIF−/− hosts, the more aggressive features produced by sleep fragmentation persisted. In contrast, these more aggressive features produced by sleep fragmentation were abolished completely in TLR4−/− mice. Our findings offer mechanistic insights into how sleep perturbations can accelerate tumor growth and invasiveness through TAM recruitment and TLR4 signaling pathways. Cancer Res; 74(5); 1329–37. ©2014 AACR.
Calcium/Calmodulin-Dependent Protein Kinase II and Its Endogenous Inhibitor α in Medullary Thyroid Cancer
Authors: Russo Eleonora , Salzano Marcella , De Falco Valentina , Mian Caterina , Barollo Susi , Secondo Agnese , Bifulco Maurizio , Vitale Mario 
Published: January 2014

Abstract
Purpose: Calcium/calmodulin-dependent kinase II (CaMKII) is involved in the regulation of cell proliferation. Its endogenous inhibitor (hCaKIINα) is expressed in some cell types. We determined the role of CaMKII in RET-stimulated proliferation and hCaMKIINα in medullary thyroid carcinoma (MTC).
Experimental Design: We analyzed the role of RET mutants on CaMKII activation in NIH3T3 and in MTC cell lines, and determined the effect of CaMKII inhibition on RET/ERK pathway and cell proliferation. Then the expression of hCaKIINα mRNA was determined by real-time PCR in primary MTC and it was correlated with some clinicopathologic parameters.
Results: RET C634Y and RETM918T mutants expressed in NIH3T3 cells induced CaMKII activation. CaMKII was activated in unstimulated MTC cells carrying the same RET mutants and it was inhibited by RET inhibition. Inhibition of CaMKII in these cells induced a reduction of Raf-1, MEK, and ERK phosphorylation, cyclin D expression, and cell proliferation. hCaKIINα mRNA expression in primary MTC was very variable and did not correlate with gender and age at diagnosis. Serum calcitonin, (R2 = 0.032; P = 0.017), tumor volume (P = 0.0079), lymph node metastasis (P = 0.033), and staging (P = 0.0652) were negatively correlated with the hCaKIINα mRNA expression.
Conclusions: CaMKII is activated by RET mutants and is activated at baseline in MTC cells where it mediates the oncogenic pathway leading to cell proliferation. The mRNA expression of its endogenous inhibitor hCaKIINα inversely correlates with the severity of MTC. CaMKII might represent a new target for MTC therapy and hCaKIINα is a marker of disease extension. Clin Cancer Res; 20(6); 1513–20. ©2014 AACR.
hERG1 Channels Regulate VEGF-A Secretion in Human Gastric Cancer: Clinicopathological Correlations and Therapeutical Implications
Authors: Crociani Olivia , Lastraioli Elena , Boni Luca , Pillozzi Serena , Romoli Maria Raffaella , D'Amico Massimo , Stefanini Matteo , Crescioli Silvia , Taddei Antonio , Bencini Lapo , Bernini Marco , Farsi Marco , Beghelli Stefania , Scarpa Aldo , Messerini Luca , Tomezzoli Anna , Vindigni Carla , Morgagni Paolo , Saragoni Luca , Giommoni Elisa , Gasperoni Silvia , Di Costanzo Francesco , Roviello Franco , De Manzoni Giovanni , Bechi Paolo , Arcangeli Annarosa 
Published: January 2014

AbstractPurpose: hERG1 channels are aberrantly expressed in several types of human cancers, where they affect different aspects of cancer cell behavior. A thorough analysis of the functional role and clinical significance of hERG1 channels in gastric cancer is still lacking.Experimental Design: hERG1 expression was tested in a wide (508 samples) Italian cohort of surgically resected patients with gastric cancer, by immunohistochemistry and real-time quantitative PCR. The functional link between hERG1 and the VEGF-A was studied in different gastric cancer cell lines. The effects of hERG1 and VEGF-A inhibition were evaluated in vivo in xenograft mouse models.Results: hERG1 was positive in 69% of the patients and positivity correlated with Lauren's intestinal type, fundus localization of the tumor, G1–G2 grading, I and II tumor—node—metastasis stage, and VEGF-A expression. hERG1 activity modulated VEGF-A secretion, through an AKT-dependent regulation of the transcriptional activity of the hypoxia inducible factor. Treatment of immunodeficient mice xenografted with human gastric cancer cells, with a combination of hERG1 blockers and anti-VEGF-A antibodies, impaired tumor growth more than single-drug treatments.Conclusion: Our results show that hERG1 (i) is aberrantly expressed in human gastric cancer since its early stages; (ii) drives an intracellular pathway leading to VEGF-A secretion; (iii) can be exploited to identify a gastric cancer patients' group where a combined treatment with antiangiogenic drugs and noncardiotoxic hERG1 inhibitors could be proposed. Clin Cancer Res; 20(6); 1502–12. ©2014 AACR.
P-Cadherin Promotes Ovarian Cancer Dissemination Through Tumor Cell Aggregation and Tumor–Peritoneum Interactions
Authors: Usui Akihiro , Ko Song Yi , Barengo Nicolas , Naora Honami 
Published: January 2014

Abstract
More than 60% of patients who are diagnosed with epithelial ovarian cancer (EOC) present with extensive peritoneal carcinomatosis. EOC cells typically disseminate by shedding into the peritoneal fluid in which they survive as multicellular aggregates and then implant onto peritoneal surfaces. However, the mechanism that facilitates aggregation and implantation of EOC cells is poorly understood. The cell adhesion molecule P-cadherin has been reported to be induced during early progression of EOC and to promote tumor cell migration. In this study, P-cadherin not only promoted migration of EOC cells, but also facilitated the assembly of floating EOC cells into multicellular aggregates and inhibited anoikis in vitro. Furthermore, inhibiting P-cadherin by short hairpin RNAs (shRNA) or a neutralizing antibody prevented EOC cells from attaching to peritoneal mesothelial cells in vitro. In mouse intraperitoneal xenograft models of EOC, inhibition of P-cadherin decreased the aggregation and survival of floating tumor cells in ascites and reduced the number of tumor implants on peritoneal surfaces. These findings indicate that P-cadherin promotes intraperitoneal dissemination of EOC by facilitating tumor cell aggregation and tumor–peritoneum interactions in addition to promoting tumor cell migration.
Implications: Inhibiting P-cadherin blocks multiple key steps of EOC progression and has therapeutic potential. Mol Cancer Res; 12(4); 504–13. ©2014 AACR.
Effects of Physical Activity and Sedentary Time on the Risk of Heart Failure
Authors: Young Deborah Rohm , Reynolds Kristi , Sidell Margo , Brar Somjot , Ghai Nirupa R. , Sternfeld Barbara , Jacobsen Steven J. , Slezak Jeffrey M. , Caan Bette , Quinn Virginia P. 
Published: January 2014

Background—
Although the benefits of physical activity for risk of coronary heart disease are well established, less is known about its effects on heart failure (HF). The risk of prolonged sedentary behavior on HF is unknown.

Methods and Results—

The study cohort included 82 695 men aged ≥45 years from the California Men’s Health Study without prevalent HF who were followed up for 10 years. Physical activity, sedentary time, and behavioral covariates were obtained from questionnaires, and clinical covariates were determined from electronic medical records. Incident HF was identified through
International Classification of Diseases, Ninth Revision
codes recorded in electronic records. During a mean follow-up of 7.8 years (646 989 person-years), 3473 men were diagnosed with HF. Controlling for sedentary time, sociodemographics, hypertension, diabetes mellitus, unfavorable lipid levels, body mass index, smoking, and diet, the hazard ratio (95% confidence interval [CI]) of HF in the lowest physical activity category compared with those in the highest category was 1.52 (95% CI, 1.39–1.68). Those in the medium physical activity category were also at increased risk (hazard ratio, 1.17 [95% CI, 1.06–1.29]). Controlling for the same covariates and physical activity, the hazard ratio (95% CI) of HF in the highest sedentary category compared with the lowest was 1.34 (95% CI, 1.21–1.48). Medium sedentary time also conveyed risk (hazard ratio, 1.13 [95% CI, 1.04–1.24]). Results showed similar trends across white and Hispanic subgroups, body mass index categories, baseline hypertension status, and prevalent coronary heart disease.

Conclusions—
Both physical activity and sedentary time may be appropriate intervention targets for preventing HF.
Administration of a Loading Dose Has No Additive Effect on Platelet Aggregation During the Switch From Ongoing Clopidogrel Treatment to Ticagrelor in Patients With Acute Coronary Syndrome
Authors: Caiazzo Gianluca , De Rosa Salvatore , Torella Daniele , Spaccarotella Carmen , Mongiardo Annalisa , Giampà Salvatore , Micieli Mariella , Palella Eleonora , Gulletta Elio , Indolfi Ciro 
Published: January 2014

Background—
Ticagrelor outperforms clopidogrel in preventing cardiovascular events in acute coronary syndrome. Despite the inclusion of a loading dose in the Platelet Inhibition and Patient Outcomes (PLATO) trial for all patients randomized to ticagrelor, it may not be necessary in patients receiving ongoing clopidogrel therapy. The aim of the present study was to assess whether a ticagrelor loading dose is associated with a further platelet inhibition during the switch from clopidogrel to ticagrelor in patients with acute coronary syndrome receiving ongoing antiplatelet treatment.

Methods and Results—

Fifty patients with acute coronary syndrome receiving aspirin and clopidogrel treatment were randomly assigned to a starting dose of ticagrelor (group 1, 90 mg; group 2, 180 mg). Platelet aggregation was measured using multiple electrode aggregometry and standard light transmission aggregometry just before the switch and at 2, 6, 24, and 72 hours. No relevant difference in platelet aggregation was observed between the 2 study arms at baseline (
P
=0.256). Residual platelet aggregation was significantly reduced in both arms 2 hours after the first administration of ticagrelor (
P
<0.001 for both), with no difference in aggregation between groups (multiple electrode aggregometry, 17.6±7.2 versus 18.1±6 U;
P
=0.281). Similar results were observed with LTA.

Conclusions—
Switching from clopidogrel to ticagrelor without a reloading dose is feasible, and it does not hinder platelet aggregation inhibition in patients with acute coronary syndrome. Further prospective studies are needed to assess the clinical relevance of our findings.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01795820.
Analysis of Low-Frequency Precipitation Variability in CMIP5 Historical Simulations for Southwestern North America
Authors: Langford Sally , Stevenson Samantha , Noone David 
Published: January 2014

AbstractDrier future conditions are projected for the arid southwest of North America, increasing the chances of the region experiencing severe and prolonged drought. To examine the mechanisms of decadal variability, 47 global climate model historical simulations performed for phase 5 of the Coupled Model Intercomparison Project (CMIP5) were assessed. On average, the CMIP5 models have higher climatological precipitation over the past century in southwestern North America than current instrumental or reanalysis products. The timing of the winter peak in climatological precipitation over California and Nevada is accurately represented. Models with resolutions coarser than 2° show a larger spread in the location and strength of the North American monsoon ridge and subsequent summer precipitation, in comparison with the higher-resolution models. Less than 20% of decadal variability in wintertime precipitation over California is associated with North Pacific sea surface temperature anomalies, a larger proportion than is associated with the tropical forcing but not sufficient for making decadal drought predictions. North American monsoon precipitation is strongly associated with local land temperatures on interannual-to-decadal time scales attributable to evaporative cooling and radiation changes driven by varying cloud cover. Soil moisture in Texas and Oklahoma in April is shown to be positively correlated with monsoon precipitation for the following summer, indicating a potential source of nonoceanic interseasonal persistence in southwestern North American hydroclimate. To make meaningful decadal predictions in the future, it is likely that forecasting will move away from sea surface temperature–driven anomaly patterns, and focus on land surface processes, which can allow persistence of precipitation anomalies via feedbacks.
Estimation and Comparison of Horizontal Winds Using Various Spectral Estimation Methods on Profiler Radars
Authors: Anandan V. K. , Sureshbabu V. N. , Tsuda Toshitaka , Furumoto Jun-ichi , Rao S. Vijayabhaskara 
Published: January 2014

Abstract
The lower atmospheric wind profiles are obtained by the postset beam steering (PBS) technique on middle and upper (MU) atmosphere radar data. The Capon beamformer is used to improve the beam synthesizing in the desired directions within the radar transmit beamwidth. From a synthesized beam, the power spectrum is obtained by various spectral estimators, such as Fourier, multiple signal classification (MUSIC), and eigenvector (EV). The wind vector components are derived from radial velocities estimated from the power spectra of synthesized beams. As the reliability of the PBS wind estimate depends on the choice of spectral estimators, a detailed analysis is carried out to compare the performance of estimators in deriving wind profiles on the radar data. The results suggest that EV shows a better performance in deriving possible spectrum parameters and is useful for reliable wind profiling up to the lower stratosphere. The wind profiles derived by PBS with EV are more consistent with near-time observations using GPS sonde and Doppler beam swinging (DBS) methods. The study also suggests that MUSIC cannot be used to reliably estimate atmospheric spectrum parameters.
Submandibular Gland Preservation during Concurrent Neck Dissection and Transoral Surgery for Oropharyngeal Squamous Cell Carcinoma
Authors: Howard Brittany E. , Hinni Michael L. , Nagel Thomas H. , Chang Yu‐Hui , Cheng Meng‐Ru , Hayden Richard E. 
Published: January 2014

ObjectivesAnalyze the effect of ipsilateral submandibular gland preservation on patients undergoing concurrent neck dissection and transoral surgery for oropharyngeal squamous cell carcinoma. Evaluate for (1) intraoperative and postoperative communications between the oropharynx and neck and (2) oncologic outcomes.Study DesignRetrospective chart review of prospectively collected data.SettingTertiary academic referral center.Methods and SubjectsRetrospective chart review of patients undergoing transoral laser resection of oropharyngeal squamous cell carcinoma with simultaneous neck dissection(s) for primary, persistent, recurrent, and second primary disease between January 1999 and February 2013. Data analyzed for operative technique, pathologic diagnosis, postoperative course, complications, and oncologic outcomes.ResultsOverall 253 patients were identified. Of these, 96 patients underwent ipsilateral submandibular gland preservation and 157 underwent ipsilateral submandibular gland removal at the time of neck dissection. The prevalence of intraoperative communication between the neck and oropharynx was significantly lower in cases with submandibular gland preservation (2/96, 2.08%) compared to those with submandibular gland removal (22/157, 14.13%). No postoperative leaks occurred in the gland preservation group (0/96, 0%) compared to a leak prevalence of 8.92% (14/157) when the gland was removed (P =. 0041). There was no difference in local, regional, or distant disease recurrence between submandibular gland preservation and gland removal. Similarly, Kaplan‐Meier analysis showed no difference in disease free survival, disease specific survival, or overall survival.ConclusionsSubmandibular gland preservation during neck dissection in patients undergoing transoral surgery for oropharyngeal squamous cell carcinoma significantly reduces the risk of intraoperative and postoperative salivary leaks without compromising oncologic outcomes.
Fibrous Incudostapedial Joint in Congenital Aural Atresia
Authors: Balaker Ashley E. , Roberson Joseph B. , Goldsztein Hernan 
Published: January 2014

Objectives(1) Determine the prevalence of a non‐bony or fibrous incudostapedial (IS) joint in the setting of congenital aural atresia. (2) Assess this anomaly's impact on surgical management and associated hearing outcomes.Study DesignRetrospective chart review.SettingSubspecialty private practice.Subjects and MethodsOperative reports and audiometric data of patients who underwent congenital aural atresia repair by a single surgeon from 2007 to 2011 were reviewed for operative anatomic findings and audiometric outcomes.ResultsTwo hundred twenty‐eight operations on 206 ears were performed. Median age was 5 years old. Fifty‐five (26.7%) of these ears had a fibrous IS joint. The severity of this anomaly was graded as mild in 23 ears, moderate in 20 ears, and severe in 12 ears. Mean postoperative pure tone air conduction (PTA2) in the severely fibrous group was 51 compared to 46 in the moderate group (P =. 03) and 41 in the mild group (P =. 006). Patients with a fibrous IS joint who underwent successful ossicular chain reconstruction (OCR) had a mean postoperative PTA2 of 30, which was a significantly better outcome than in patients with moderately or severely fibrous IS joints who did not have OCR (P <. 05).ConclusionA fibrous IS joint was seen in 27% of patients undergoing repair of congenital aural atresia. The severity of this anomaly has important implications for postoperative hearing results. These findings suggest that ossicular chain reconstruction should be performed in moderately or severely fibrous cases.