bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promoting engagement by patients and families to reduce adverse events in acute care settings: a systematic review
Authors: Berger Zackary , Flickinger Tabor E , Pfoh Elizabeth , Martinez Kathryn A , Dy Sydney M 
Published: December 2013

IntroductionPatient-centeredness is central to healthcare. Hospitals should address patients’ unique needs to improve safety and quality. Patient engagement in healthcare, which may help prevent adverse events, can be approached as an independent patient safety practice (PSP) or as part of a multifactorial PSP.ObjectivesThis review examines how interventions encouraging this engagement have been implemented in controlled trials.MethodsWe searched Medline, CINAHL, Embase and Cochrane from 2000 to 2012 for English language studies in hospital settings with prospective controlled designs, addressing the effectiveness or implementation of patient/family engagement in PSPs. We separately reviewed interventions implemented as part of selected broader PSPs by way of example: hand hygiene, ventilator-associated pneumonia, rapid response systems and care transitions.ResultsSix articles met the inclusion criteria for effectiveness with a primary focus on patient engagement. We identified 12 studies implementing patient engagement as an aspect of selected broader PSPs. A number of studies relied on patients’ possible function as a reporter of error to healthcare workers and patients as a source of reminders regarding safety behaviours, while others relied on direct activation of patients or families. Definitions of patient and family engagement were lacking, as well as evidence regarding the types of patients who might feel comfortable engaging with providers, and in what contexts.ConclusionsWhile patient engagement in safety is appealing, there is insufficient high-quality evidence informing real-world implementation. Further work should evaluate the effectiveness of interventions on patient and family engagement and clarify the added benefit of incorporating engagement in multifaceted approaches to improve patient safety endpoints. In addition, strategies to assess and overcome barriers to patients’ willingness to actively engage in their care should be investigated.
Patient Satisfaction: Receiving a copy of the GP letter following fracture or elective orthopaedic clinic
Authors: Pinder Elizabeth , Jefferys S , Loeffler Mark 
Published: December 2013

AbstractFollowing orthopaedic/fracture clinics at our hospital, patients now receive a copy of the letter summarizing an outpatient consultation that is sent to their General Practitioner. We undertook a patient satisfaction questionnaire to determine if patients found this change in practice beneficial.Of the 83 patients who had received this letter, most patients had read the letter (96%) and understood the content (90%). 13% were worried after having read the content and 86% found it helpful. Of the 40 patients who did not receive a copy, 32 (80%) specified that they would wish to in the future. The results support the new practice although it could be improved by identifying those who do not wish to be included thereby reducing costs.
Effect of period, water temperature and agitation on loss of water‐soluble carbohydrates and protein from grass hay: implications for equine feeding management
Authors: Longland A. C. , Barfoot C. , Harris P. A. 
Published: December 2013

The effects of different water‐soaking treatments on removal of water‐soluble carbohydrates (WSC), WSC constituents and protein from four UK hays were determined. Hays were soaked in water for up to 16 hours at mean temperatures of 8°C, 16°C, in hot tap water (initially 49°C) or agitated and rinsed in clean water at 16°C. Initial hay WSC contents ranged from 154 to 216 g/kg dry matter. Losses of WSC from hays after 16 hours soaking at 8°C, 16°C, 16°C plus agitation and 49°C averaged 28, 46, 49 and 44 per cent, respectively. Corresponding percentage losses of fructan were 16, 37, 39 and 33. Percentage losses of sucrose averaged 55 (8°C), 86 (16°C), 91 (16°C+agitation) and 82 (initial temperature 49°C), those of glucose were 60, 85, 75 and 75, and of fructose were 41, 52, 54 and 46. Hay crude protein contents were not significantly changed by any of the soaking treatments. Soaking at 8°C generally resulted in reduced losses of WSC compared to when soaked at the higher temperatures. Thus, in cold weather using warmer water to soak hays may effect greater WSC loss, although very prolonged soaking at warm temperatures might encourage the proliferation of unwanted micro‐organisms in the soak liquor.
Suspected adverse events, 2012
Authors: Davis G. , Rooney A. , Cooles S. , Evans G. 
Published: December 2013

Increase in serious adverse events
Increase in reports involving products marketed under the Small Animal Exemption Scheme
Decrease in injection site reactions

These are some of the results from the surveillance work carried out by the pharmacovigilance unit at the Veterinary Medicines Directorate (VMD), as discussed by Giles Davis and colleagues
A Mechanism of Hypoxia-Mediated Escape from Adaptive Immunity in Cancer Cells
Authors: Barsoum Ivraym B. , Smallwood Chelsea A. , Siemens D. Robert , Graham Charles H. 
Published: December 2013

Abstract
Immune escape is a fundamental trait of cancer in which mechanistic knowledge is incomplete. Here, we describe a novel mechanism by which hypoxia contributes to tumoral immune escape from cytotoxic T lymphocytes (CTL). Exposure of human or murine cancer cells to hypoxia for 24 hours led to upregulation of the immune inhibitory molecule programmed cell death ligand-1 (PD-L1; also known as B7-H1), in a manner dependent on the transcription factor hypoxia-inducible factor-1α (HIF-1α). In vivo studies also demonstrated cellular colocalization of HIF-1α and PD-L1 in tumors. Hypoxia-induced expression of PD-L1 in cancer cells increased their resistance to CTL-mediated lysis. Using glyceryl trinitrate (GTN), an agonist of nitric oxide (NO) signaling known to block HIF-1α accumulation in hypoxic cells, we prevented hypoxia-induced PD-L1 expression and diminished resistance to CTL-mediated lysis. Moreover, transdermal administration of GTN attenuated tumor growth in mice. We found that higher expression of PD-L1 induced in tumor cells by exposure to hypoxia led to increased apoptosis of cocultured CTLs and Jurkat leukemia T cells. This increase in apoptosis was prevented by blocking the interaction of PD-L1 with PD-1, the PD-L1 receptor on T cells, or by addition of GTN. Our findings point to a role for hypoxia/HIF-1 in driving immune escape from CTL, and they suggest a novel cancer immunotherapy to block PD-L1 expression in hypoxic-tumor cells by administering NO mimetics. Cancer Res; 74(3); 665–74. ©2013 AACR.
miRNA-491-5p and GIT1 Serve as Modulators and Biomarkers for Oral Squamous Cell Carcinoma Invasion and Metastasis
Authors: Huang Wei-Chieh , Chan Shih-Hsuan , Jang Te-Hsuan , Chang Jer-Wei , Ko Ying-Chin , Yen Tzu-Chen , Chiang Shang-Lun , Chiang Wei-Fan , Shieh Tien-Yu , Liao Chun-Ta , Juang Jyh-Lyh , Wang Hsueh-Chun , Cheng Ann-Joy , Lu Ya-Ching , Wang Lu-Hai 
Published: December 2013

AbstractMicroRNAs offer tools to identify and treat invasive cancers. Using highly invasive isogenic oral squamous cell carcinoma (OSCC) cells, established using in vitro and in vivo selection protocols from poorly invasive parental cell populations, we used microarray expression analysis to identify a relative and specific decrease in miR-491-5p in invasive cells. Lower expression of miR-491-5p correlated with poor overall survival of patients with OSCCs. miR-491-5p overexpression in invasive OSCC cells suppressed their migratory behavior in vitro and lung metastatic behavior in vivo. We defined the G-protein—coupled receptor kinase-interacting protein 1 (GIT1)—as a direct target gene for miR-491-5p control. GIT1 overexpression was sufficient to rescue miR-491-5p–mediated inhibition of migration/invasion and lung metastasis. Conversely, GIT1 silencing phenocopied the ability of miR-491-5p to inhibit migration/invasion and metastasis of OSCC cells. Mechanistic investigations indicated that miR-491-5p overexpression or GIT1 attenuation reduced focal adhesions, with a concurrent decrease in steady-state levels of paxillin, phospho-paxillin, phospho-FAK, EGF/EGFR-mediated extracellular signal–regulated kinase (ERK1/2) activation, and MMP2/9 levels and activities. In clinical specimens of OSCCs, GIT1 levels were elevated relative to paired normal tissues and were correlated with lymph node metastasis, with expression levels of miR-491-5p and GIT1 correlated inversely in OSCCs, where they informed tumor grade. Together, our findings identify a functional axis for OSCC invasion that suggests miR-491-5p and GIT1 as biomarkers for prognosis in this cancer. Cancer Res; 74(3); 751–64. ©2013 AACR.
Gambogic Acid Induces Apoptosis in Imatinib-Resistant Chronic Myeloid Leukemia Cells via Inducing Proteasome Inhibition and Caspase-Dependent Bcr-Abl Downregulation
Authors: Shi Xianping , Chen Xin , Li Xiaofen , Lan Xiaoying , Zhao Chong , Liu Shouting , Huang Hongbiao , Liu Ningning , Liao Siyan , Song Wenbin , Zhou Ping , Wang Shunqing , Xu Li , Wang Xuejun , Dou Q. Ping , Liu Jinbao 
Published: December 2013

AbstractPurpose: Chronic myelogenous leukemia (CML) is characterized by the constitutive activation of Bcr-Abl tyrosine kinase. Bcr-Abl-T315I is the predominant mutation that causes resistance to imatinib, cytotoxic drugs, and the second-generation tyrosine kinase inhibitors. The emergence of imatinib resistance in patients with CML leads to searching for novel approaches to the treatment of CML. Gambogic acid, a small molecule derived from Chinese herb gamboges, has been approved for phase II clinical trial for cancer therapy by the Chinese Food and Drug Administration (FDA). In this study, we investigated the effect of gambogic acid on cell survival or apoptosis in CML cells bearing Bcr-Abl-T315I or wild-type Bcr-Abl.Experimental Design: CML cell lines (KBM5, KBM5-T315I, and K562), primary cells from patients with CML with clinical resistance to imatinib, and normal monocytes from healthy volunteers were treated with gambogic acid, imatinib, or their combination, followed by measuring the effects on cell growth, apoptosis, and signal pathways. The in vivo antitumor activity of gambogic acid and its combination with imatinib was also assessed with nude xenografts.Results: Gambogic acid induced apoptosis and cell proliferation inhibition in CML cells and inhibited the growth of imatinib-resistant Bcr-Abl-T315I xenografts in nude mice. Our data suggest that GA-induced proteasome inhibition is required for caspase activation in both imatinib-resistant and -sensitive CML cells, and caspase activation is required for gambogic acid–induced Bcr-Abl downregulation and apoptotic cell death.Conclusions: These findings suggest an alternative strategy to overcome imatinib resistance by enhancing Bcr-Abl downregulation with the medicinal compound gambogic acid, which may have great clinical significance in imatinib-resistant cancer therapy. Clin Cancer Res; 20(1); 151–63. ©2013 AACR.
T Lymphocytes Redirected against the Chondroitin Sulfate Proteoglycan-4 Control the Growth of Multiple Solid Tumors both In Vitro and In Vivo
Authors: Geldres Claudia , Savoldo Barbara , Hoyos Valentina , Caruana Ignazio , Zhang Ming , Yvon Eric , Del Vecchio Michele , Creighton Chad J. , Ittmann Michael , Ferrone Soldano , Dotti Gianpietro 
Published: December 2013

Abstract
Purpose: Because of its high expression on various types of tumors and its restricted distribution in normal tissues, chondroitin sulfate proteoglycan-4 (CSPG4) represents an attractive target for the antibody-based therapy of several solid tumors. We tested whether T cells transduced with a CSPG4-specific chimeric antigen receptor (CAR) inhibited the growth of CSPG4-expressing tumor cells both in vitro and in vivo.
Experimental Design: We first independently validated by immunohistochemistry (IHC) the expression of CSPG4 in an extensive panel of tumor arrays and normal tissues as well as queried public gene expression profiling datasets of human tumors. We constructed a second-generation CSPG4-specific CAR also encoding the CD28 costimulatory endodomain (CAR.CSPG4). We then evaluated human T lymphocytes expressing this CAR for their ex vivo and in vivo antitumor activity against a broad panel of solid tumors.
Results: IHC showed that CSPG4 is highly expressed in melanoma, breast cancer, head and neck squamous cell carcinoma (HNSCC), and mesothelioma. In addition, in silico analysis of microarray expression data identified other important potential tumors expressing this target, including glioblastoma, clear cell renal carcinoma, and sarcomas. T lymphocytes genetically modified with a CSPG4-CAR controlled tumor growth in vitro and in vivo in NSG mice engrafted with human melanoma, HNSCC, and breast carcinoma cell lines.
Conclusions: CAR.CSPG4-redirected T cells should provide an effective treatment modality for a variety of solid tumors. Clin Cancer Res; 20(4); 962–71. ©2013 AACR.
Comparative microRNA Profiling of Prostate Carcinomas with Increasing Tumor Stage by Deep Sequencing
Authors: Hart Martin , Nolte Elke , Wach Sven , Szczyrba Jaroslaw , Taubert Helge , Rau Tilman T. , Hartmann Arndt , Grässer Friedrich A. , Wullich Bernd 
Published: December 2013

AbstractMicroRNAs (miRNA) posttranscriptionally regulate gene expression and are important in tumorigenesis. Previous deep sequencing identified the miRNA profile of prostate carcinoma versus nonmalignant prostate tissue. Here, we generated miRNA expression profiles of prostate carcinoma by deep sequencing, with increasing tumor stage relative to corresponding nonmalignant and healthy prostate tissue, and detected clearly changed miRNA expression patterns. The miRNA profiles of the healthy and nonmalignant tissues were consistent with our previous findings, indicating a high fidelity of the method employed. In the tumors, quantitative real-time PCR (qRT-PCR) analysis of 40 paired samples of prostate carcinoma versus normal tissue revealed significant upregulation of miR-20a, miR-148a, miR-200b, and miR-375 and downregulation of miR-143 and miR-145. Hereby, miR-375 increased from normal to organ-confined tumors (pT2 pN0), slightly decreased in tumors with extracapsular growth (pT3 pN0), but was then expressed again at higher levels in lymph node metastasizing (pN1) tumors. The sequencing data for miR-375 were confirmed by Northern blotting and qRT-PCR. The regulation for other selected miRNAs could, however, not be confirmed by qRT-PCR in individual tumor stages. MiR-200b, in addition to miR-200c and miR-375 reduced the expression of SEC23A. Interestingly, miR-375, found by sequencing in pT2 upregulated by us and others in tumor versus normal tissue, and miR-15a, found by sequencing in pT2 and pT3 and in the metastasizing tumors, target the phosphatases PHLPP1 and PHLPP2, respectively. PHLPP1 and PHLPP2 dephosphorylate members of the AKT family of signal transducers, thereby inhibiting cell growth. Coexpression of miR-15a and miR-375 resulted in downregulation of PHLPP1/2 and strongly increased prostate carcinoma cell growth.Implications: These genomic data reveal relevant miRNAs in prostate cancer that may have biomarker and therapeutic potential. Mol Cancer Res; 12(2); 250–63. ©2013 AACR.
RETRACTED: miRNA-302b Suppresses Human Hepatocellular Carcinoma by Targeting AKT2
Authors: Wang Lumin , Yao Jiayi , Zhang Xiaogang , Guo Bo , Le Xiaofeng , Cubberly Mark , Li Zongfang , Nan Kejun , Song Tusheng , Huang Chen 
Published: December 2013

Abstract
miRNAs (miR) play a critical role in human cancers, including hepatocellular carcinoma. Although miR-302b has been suggested to function as a tumor repressor in other cancers, its role in hepatocellular carcinoma is unknown. This study investigated the expression and functional role of miR-302b in human hepatocellular carcinoma. The expression level of miR-302b is dramatically decreased in clinical hepatocellular carcinoma specimens, as compared with their respective nonneoplastic counterparts, and in hepatocellular carcinoma cell lines. Overexpression of miR-302b suppressed hepatocellular carcinoma cell proliferation and G1–S transition in vitro, whereas inhibition of miR-302b promoted hepatocellular carcinoma cell proliferation and G1–S transition. Using a luciferase reporter assay, AKT2 was determined to be a direct target of miR-302b. Subsequent investigation revealed that miR-302b expression was inversely correlated with AKT2 expression in hepatocellular carcinoma tissue samples. Importantly, silencing AKT2 recapitulated the cellular and molecular effects seen upon miR-302b overexpression, which included inhibiting hepatocellular carcinoma cell proliferation, suppressing G1 regulators (Cyclin A, Cyclin D1, CDK2) and increasing p27Kip1 phosphorylation at Ser10. Restoration of AKT2 counteracted the effects of miR-302b expression. Moreover, miR-302b was able to repress tumor growth of hepatocellular carcinoma cells in vivo.
Implications: Taken together, miR-302b inhibits HCC cell proliferation and growth in vitro and in vivo by targeting AKT2. Mol Cancer Res; 12(2); 190–202. ©2013 AACR.
Actin-Binding Protein, Espin: A Novel Metastatic Regulator for Melanoma
Authors: Yanagishita Takeshi , Yajima Ichiro , Kumasaka Mayuko , Kawamoto Yoshiyuki , Tsuzuki Toyonori , Matsumoto Yoshinari , Watanabe Daisuke , Kato Masashi 
Published: December 2013

Abstract
Espin is a multifunctional actin-bundling protein with multiple isoforms, and has special connections to hair cell stereocilia and microvillar specializations of sensory cells in the inner ear. However, there have been no reports showing the expression and function of Espin in cancers, including melanoma. Here, it is demonstrated that Espin expression is significantly increased in melanomas that spontaneously developed in RET-transgenic mice (RET-mice). Importantly, the invasion capacity of Espin-depleted Mel-ret melanoma cells derived from a tumor of the RET-mouse was dramatically less than that of control melanoma cells with reductions of lamellipodia, focal adhesion kinase (FAK), and GTP-Rac1 activities. Correspondingly, the ratio of metastatic foci in Espin-depleted Mel-ret melanoma cells was significantly less than that of control melanoma cells in an in vivo melanoma metastasis model. Moreover, Espin could be a novel biomarker of melanoma in humans, because our immunohistochemical analysis data reveal that percentages of Espin-positive cells in human primary and metastatic melanomas were significantly higher than that of cells in melanocytic nevi. Together, these results indicate that Espin is not only a metastatic regulator for melanoma but also a potential biomarker of disease progression.
Implications: Actin-binding protein Espin is expressed in melanoma, affects metastasis, and is a potential target for melanoma therapy. Mol Cancer Res; 12(3); 440–6. ©2013 AACR.
A Regulator of Secretory Vesicle Size, Kelch-Like Protein 12, Facilitates the Secretion of Apolipoprotein B100 and Very-Low-Density Lipoproteins—Brief Report
Authors: Butkinaree Chutikarn , Guo Liang , Ramkhelawon Bhama , Wanschel Amarylis , Brodsky Jeffrey L. , Moore Kathryn J. , Fisher Edward A. 
Published: December 2013

Objective—
One of the major risk factors for atherosclerosis is the plasma level of low-density lipoprotein (LDL), which is a product of very-low-density lipoprotein (VLDL). Hepatic apolipoprotein B100 (apoB100) is the essential component that provides structural stability to VLDL particles. Newly translated apoB100 is partially lipidated in the endoplasmic reticulum (ER), forming nascent apoB100-VLDL particles. These particles are further modified to form fully mature VLDLs in the Golgi apparatus. Therefore, the transport of nascent VLDL from the ER to the Golgi represents a critical step during VLDL maturation and secretion and in regulating serum LDL cholesterol levels. Our previous studies showed that apoB100 exits the ER in coat complex II vesicles (COPII), but the cohort of related factors that control trafficking is poorly defined.

Approach and Results—
Expression levels of Kelch-like protein 12 (KLHL12), an adaptor protein known to assist COPII–dependent transport of procollagen, were manipulated by using a KLHL12-specific small interfering RNA and a KLHL12 expression plasmid in the rat hepatoma cell line, McArdle RH7777. KLHL12 knockdown decreased the secreted and intracellular pools of apoB100, an effect that was attenuated in the presence of an autophagy inhibitor. KLHL12 knockdown also significantly reduced secretion of the most lipidated apoB100-VLDL species and led to the accumulation of apoB100 in the ER. Consistent with these data, KLHL12 overexpression increased apoB100 recovery and apoB100-VLDL secretion. Images obtained from confocal microscopy revealed colocalization of apoB100 and KLHL12, further supporting a direct link between KLHL12 function and VLDL trafficking from the ER.

Conclusions—
KLHL12 plays a critical role in facilitating the ER exit and secretion of apoB100-VLDL particles, suggesting that KLHL12 modulation would influence plasma lipid levels.
Visible Age-Related Signs and Risk of Ischemic Heart Disease in the General Population
Authors: Christoffersen Mette , Frikke-Schmidt Ruth , Schnohr Peter , Jensen Gorm B. , Nordestgaard Børge G. , Tybjærg-Hansen Anne 
Published: December 2013

Background—
Cardiovascular disease is 1 of the most common age-related diseases, and also 1 of the most common causes of death in the general population. We tested the hypothesis that visible age-related signs associate with risk of ischemic heart disease (IHD), myocardial infarction (MI), and death in the general population, independent of chronological age.

Methods and Results—

10,885 individuals aged 20 to 93 years free of IHD were followed from 1976 through 1978 until June 2011 with 100% complete follow-up. During these 35 years of follow-up, 3401 participants developed IHD and 1708 developed MI. Presence of frontoparietal baldness, crown top baldness, earlobe crease, and xanthelasmata was associated with increased risk of IHD or MI after multifactorial adjustment for chronological age and well-known cardiovascular risk factors. The risk of IHD and MI increased stepwise with increasing number of age-related signs with multifactorially adjusted hazard ratios up to 1.40 (95% confidence interval, 1.20–1.62) for IHD and 1.57 (1.28–1.93) for MI, in individuals with 3 to 4 versus no age-related signs at baseline (
P
for trend <0.001). In all age groups in both women and men, absolute 10-year risk of IHD and MI increased with increasing number of visible age-related signs.

Conclusions—
Male pattern baldness, earlobe crease, and xanthelasmata—alone or in combination—associate with increased risk of ischemic heart disease and myocardial infarction independent of chronological age and other well-known cardiovascular risk factors. This is the first prospective study to show that looking old for your age is a marker of poor cardiovascular health.