bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signs of deterioration in infants discharged home following congenital heart surgery in the first year of life: a qualitative study
Authors: Tregay Jenifer , Brown Katherine L , Crowe Sonya , Bull Catherine , Knowles Rachel L , Smith Liz , Wray Jo 
Published: January 2016

AimsTo describe the ways in which parents recognise and make decisions about their child's symptoms following discharge home after congenital heart interventions in the first year of life and their experiences of seeking help.MethodsThis was a qualitative study involving semistructured interviews with parents. Twenty-one parents were recruited to the study. Parents all had a child who had congenital heart surgery in their first year of life between September 2009 and October 2013 at one of three UK cardiac centres; the children had either died or were readmitted as an emergency following initial discharge.ResultsSome parents were unable to identify any early warning signs. Others described symptoms of deterioration including changes in feeding and appearance, respiratory distress and subtle behavioural changes that may not be routinely highlighted to parents at discharge. Several barriers to accessing prompt medical assistance were identified including parents feeling that their concerns were not taken seriously, long wait times and lack of protocols at A&E.ConclusionsOur study highlights behavioural symptoms as being a potentially underemphasised sign of deterioration and identifies a number of barriers to parents accessing support when they are concerned. It is important that parents are encouraged to seek advice at the earliest opportunity and that those health professionals at the front line have access to the information they need in order to respond in an appropriate and timely way. A role for home monitoring was also noted as potentially useful in identifying at risk children who appear clinically well.
Impact of point-of-care diagnostics on maternal outcomes in HIV-infected women: systematic review and meta-analysis protocol
Authors: Mashamba-Thompson T P , Sartorius B , Thabane L , Shi C X , Drain P K 
Published: January 2016

IntroductionStudies indicate substandard diagnostic care, delayed and missed diagnosis as some of the contributing factors to maternal mortality. The clinical impact of point-of-care (POC) diagnostics has been shown in the monitoring and treatment of a variety of infectious diseases, including HIV/AIDS and tuberculosis. The objective of this systematic review is to investigate the impact of POC diagnostics on maternal outcomes for HIV-infected women.MethodsWe will conduct a systematic review to evaluate the impact of POC diagnostics for improving desired healthcare outcomes for HIV-infected women. The search strategy will involve electronic databases including: Cochrane Infectious Disease Group Specialised Register; Cochrane Central Register of Control Trials, published in The Cochrane Library; PubMed; EBSCOhost and LILACS. The studies will be mapped in 2 stages: stage 1 will map studies descriptively by focus and method; stage 2 will involve additional inclusion criteria, quality assessment and data extraction undertaken by 2 reviewers in parallel. Evidence will be synthesised using relevant systematic research tools: meta-analysis and subgroup analysis will be conducted usingRevManand Stata 13 will be used for meta-regressions. We will follow recommendations described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the Cochrane Handbook for Intervention Reviews.Ethics and disseminationWe anticipate finding a large number of studies on POC diagnostic interventions on maternal outcomes in HIV-infected women, which, once summarised, will be useful to guide future diagnostic interventions. The protocol for the systematic review has been registered in PROSPERO. The study will be disseminated electronically and in print. It will also be presented to conferences related to HIV/AIDS, POC diagnostics and maternal health.Trial registration numberPROSPERO CRD42014015439.
Effect of the adjuvanted (AS03) A/H1N1 2009 pandemic influenza vaccine on the risk of rejection in solid organ transplant recipients in England: a self-controlled case series
Authors: Cohet Catherine , Haguinet François , Dos Santos Gaël , Webb Dave , Logie John , LC Ferreira Germano , Rosillon Dominique , Shinde Vivek 
Published: January 2016

ObjectiveTo assess the risk of solid organ transplant (SOT) rejection after vaccination with the adjuvanted (AS03) A/H1N1 2009 pandemic influenza vaccinePandemrix.DesignSelf-controlled case series (SCCS) in the UK Clinical Practice Research Datalink (CPRD) and its linked component of the Hospital Episodes Statistics (HES) inpatient database. Analyses were conducted using the SCCS method for censored, perturbed or curtailed post-event exposure.ParticipantsOf the 184 transplant recipients having experienced at least one SOT rejection (liver, kidney, lung, heart or pancreas) during the study period from 1 October 2009 to 31 October 2010, 91 participants were included in the main analysis, of which 71 had been exposed toPandemrix.Main outcome measuresOccurrence of SOT rejection during risk (30 and 60 days after anyPandemrixdose) and control periods. Covariates in the CPRD included time since transplantation, seasonal influenza vaccination, bacterial and viral infections, previous SOT rejections and malignancies.ResultsThe relative incidence (RI) of rejection of any one of the five transplanted organs, adjusted for time since transplantation, was 1.05 (95% CI 0.52 to 2.14) and 0.80 (95% CI 0.42 to 1.50) within 30 and 60 days after vaccination, respectively. Similar estimates were observed for rejection of a kidney only, the most commonly transplanted organ (RI within 30 days after vaccination: 0.85 (95% CI 0.38 to 1.90)). Across various models and sensitivity analyses, RI estimates remained stable and within a consistent range around 1.0.ConclusionsThese results suggest a reassuring safety profile forPandemrixwith regard to the risk of rejection in SOT recipients in England and contribute to inform the benefit–risk of AS03-adjuvanted pandemic influenza vaccines in transplanted patients in the event of future pandemics.Trial registration numberNCT01715792.
Did the use of the Guideliner V2TMguide catheter extension increase complications? A review of the incidence of complications related to the use of the V2 catheter, the influence of right brachiocephalic arterial anatomy and the redesign of the V3TMGuideliner and clinical outcomes
Authors: Alkhalil Mohammad , Smyth Alison , Walsh Simon J , McQuillan Conor , Spence Mark S , Owens Colum G , Hanratty Colm G 
Published: January 2016

ObjectiveWe sought to investigate the incidence of complications associated with V2 Guideliner, understand the mechanisms and evaluate the impact of alterations made to the V3 Guideliner.MethodsRetrospective analysis of consecutive cases employing V2 Guideliner from two university teaching hospitals. Complications were identified, analysed and classified into major versus minor ones. To understand the potential anatomical mechanism of these complications, analysis of normal great vessel anatomy was undertaken in separate cohort of patients undergoing cardiac catheterisation via right radial approach. Further analysis of consecutive cases employing V3 Gudieliner took place and the incidence of complications were compared between V2 and V3 groups.ResultsTotal of 188 cases of V2 Guideliner use were identified. One major complication was reported (coronary dissection). Proximal collar interaction and stent damage occurred in 19 cases (10%). Anatomical data suggest that extending the V2 Guideliner tubing sited the proximal collar of the device in the brachiocephalic/subclavian artery, a potential site of tortuosity and potential cause of the Guideliner proximal collar-stent interaction. Further analysis of 124 cases of V3 Guideliner use demonstrated no cases with proximal collar-stent interactions, one case of longitudinal stent deformation and two incidents of stent interaction with the distal edge of the V3 Guideliner.ConclusionsWe have demonstrated a higher incidence of V2 Guideliner complications compared to previous series. The change in design of the V2 Guideliner was a likely contributor but the modifications with V3 Guideliner appear to have ameliorated this issue.
Birth Size Characteristics and Risk of Brain Tumors in Early Adulthood: Results from a Swedish Cohort Study
Authors: Tettamanti Giorgio , Ljung Rickard , Mathiesen Tiit , Schwartzbaum Judith , Feychting Maria 
Published: January 2016

AbstractBackground: Despite extensive research on the effect of birth size characteristics on childhood brain tumors, very few studies have evaluated the effect of birth size characteristics on the risk of adult brain tumor, and they have provided inconsistent results.Methods: All individuals born in Sweden between 1973 and 1995 who were still alive and cancer free at their 15th birthday were included in the study (n = 2,032,727). At the end of the study period (December 31, 2010), the study participants were 15 to 37 years old. Incident cases of primary brain tumors were identified through the Swedish Cancer Register.Results: No association was observed between any birth size characteristics and glioma, although an indication of increased glioma risk associated with high birth weight, or being large for gestational age at birth, was found among men [relative risk (RR) = 1.36, 95% confidence interval (CI), 0.97–1.90; RR = 1.44, 95% CI, 0.99–2.09, respectively]. An increased risk of meningioma was observed among individuals born with a large head circumference (RR = 1.76, 95% CI, 1.01–3.05). Large head circumference was also associated with an elevated risk of neuroma (RR = 1.86, 95% CI, 0.94–3.68). Being born small for gestational age was also related to a higher risk of neuroma (RR = 2.50, 95% CI, 1.31–4.78).Conclusion: Selected birth size characteristics were associated with increased risk of some brain tumor subtypes in young adults.Impact: We have presented additional evidence suggesting that birth size characteristics are associated with subsequent primary brain tumor risk in young adults. Cancer Epidemiol Biomarkers Prev; 25(4); 678–85. ©2016 AACR.
Next-Generation Sequencing in Diffuse Large B-Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study
Authors: Dubois Sydney , Viailly Pierre-Julien , Mareschal Sylvain , Bohers Elodie , Bertrand Philippe , Ruminy Philippe , Maingonnat Catherine , Jais Jean-Philippe , Peyrouze Pauline , Figeac Martin , Molina Thierry J. , Desmots Fabienne , Fest Thierry , Haioun Corinne , Lamy Thierry , Copie-Bergman Christiane , Brière Josette , Petrella Tony , Canioni Danielle , Fabiani Bettina , Coiffier Bertrand , Delarue Richard , Peyrade Frédéric , Bosly André , André Marc , Ketterer Nicolas , Salles Gilles , Tilly Hervé , Leroy Karen , Jardin Fabrice 
Published: January 2016

Abstract
Purpose: Next-generation sequencing (NGS) has detailed the genomic characterization of diffuse large B-cell lymphoma (DLBCL) by identifying recurrent somatic mutations. We set out to design a clinically feasible NGS panel focusing on genes whose mutations hold potential therapeutic impact. Furthermore, for the first time, we evaluated the prognostic value of these mutations in prospective clinical trials.
Experimental Design: A Lymphopanel was designed to identify mutations in 34 genes, selected according to literature and a whole exome sequencing study of relapsed/refractory DLBCL patients. The tumor DNA of 215 patients with CD20+de novo DLBCL in the prospective, multicenter, and randomized LNH-03B LYSA clinical trials was sequenced to deep, uniform coverage with the Lymphopanel. Cell-of-origin molecular classification was obtained through gene expression profiling with HGU133+2.0 Affymetrix GeneChip arrays.
Results: The Lymphopanel was informative for 96% of patients. A clear depiction of DLBCL subtype molecular heterogeneity was uncovered with the Lymphopanel, confirming that activated B-cell–like (ABC), germinal center B-cell like (GCB), and primary mediastinal B-cell lymphoma (PMBL) are frequently affected by mutations in NF-κB, epigenetic, and JAK–STAT pathways, respectively. Novel truncating immunity pathway, ITPKB, MFHAS1, and XPO1 mutations were identified as highly enriched in PMBL. Notably, TNFAIP3 and GNA13 mutations in ABC patients treated with R-CHOP were associated with significantly less favorable prognoses.
Conclusions: This study demonstrates the contribution of NGS with a consensus gene panel to personalized therapy in DLBCL, highlighting the molecular heterogeneity of subtypes and identifying somatic mutations with therapeutic and prognostic impact. Clin Cancer Res; 22(12); 2919–28. ©2016 AACR.
See related commentary by Lim and Elenitoba-Johnson, p. 2829
Adjuvant Immunotherapy to Improve Outcome in High-Risk Pediatric Sarcomas
Authors: Merchant Melinda S. , Bernstein Donna , Amoako Martha , Baird Kristin , Fleisher Thomas A. , Morre Michel , Steinberg Seth M. , Sabatino Marianna , Stroncek Dave F. , Venkatasan Aradhana M. , Wood Bradford J. , Wright Matthew , Zhang Hua , Mackall Crystal L. 
Published: January 2016

Abstract
Purpose: Patients with metastatic or relapsed pediatric sarcomas receive cytotoxic regimens that induce high remission rates associated with profound lymphocyte depletion, but ultimately few survive long term. We administered adjuvant immunotherapy to patients with metastatic and recurrent pediatric sarcomas in an effort to improve outcomes.
Experimental Design: Mononuclear cells were collected via apheresis, and tumor lysate was acquired via percutaneous biopsy at enrollment. Participants received standard antineoplastic therapy, followed by autologous lymphocytes, tumor lysate/keyhole limpet hemocyanin–pulsed dendritic cell vaccinations ± recombinant human IL7. Primary outcomes were toxicity and vaccine responses. Secondary outcomes were immune reconstitution, event-free survival, and overall survival (OS).
Results: Forty-three patients enrolled and 29 received immunotherapy. The regimen was well tolerated. Intent-to-treat analysis demonstrated 5-year OS of 51% with significant differences based upon histologic group (63% vs. 0% for Ewing/rhabdomyosarcoma vs. other sarcomas) and response to standard therapy (74% no residual disease vs. 0% residual disease). Five-year intent-to-treat OS of patients with newly diagnosed metastatic Ewing/rhabdomyosarcoma was 77%, higher than previously reported in this population and higher than observed in a similar group treated with an earlier adjuvant immunotherapy regimen (25% 5-year OS). T-cell responses to autologous tumor lysate were identified in 62% of immunotherapy recipients, and survival was higher in those patients (73% 5-year OS with vs. 37% without immune response, P = 0.017). Immune reconstitution, measured by CD4 count recovery, was significantly enhanced in subjects treated with recombinant human IL7.
Conclusions: Adjuvant immunotherapy may improve survival in patients with metastatic pediatric sarcoma. Clin Cancer Res; 22(13); 3182–91. ©2016 AACR.
Modeling Therapy Response and Spatial Tissue Distribution of Erlotinib in Pancreatic Cancer
Authors: Grüner Barbara M. , Winkelmann Isabel , Feuchtinger Annette , Sun Na , Balluff Benjamin , Teichmann Nicole , Herner Alexander , Kalideris Evdokia , Steiger Katja , Braren Rickmer , Aichler Michaela , Esposito Irene , Schmid Roland M. , Walch Axel , Siveke Jens T. 
Published: January 2016

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is likely the most aggressive and therapy-resistant of all cancers. The aim of this study was to investigate the emerging technology of matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) as a powerful tool to study drug delivery and spatial tissue distribution in PDAC. We utilized an established genetically engineered mouse model of spontaneous PDAC to examine the distribution of the small-molecule inhibitor erlotinib in healthy pancreas and PDAC. MALDI IMS was utilized on sections of single-dose or long-term–treated mice to measure drug tissue distribution. Histologic and statistical analyses were performed to correlate morphology, drug distribution, and survival. We found that erlotinib levels were significantly lower in PDAC compared with healthy tissue (P = 0.0078). Survival of long-term–treated mice did not correlate with overall levels of erlotinib or with overall histologic tumor grade but did correlate both with the percentage of atypical glands in the cancer (P = 0.021, rs = 0.59) and the level of erlotinib in those atypical glands (P = 0.019, rs = 0.60). The results of this pilot study present MALDI IMS as a reliable technology to study drug delivery and spatial distribution of compounds in a preclinical setting and support drug imaging–based translational approaches. Mol Cancer Ther; 15(5); 1145–52. ©2016 AACR.
GSK-3β Governs Inflammation-Induced NFATc2 Signaling Hubs to Promote Pancreatic Cancer Progression
Authors: Baumgart Sandra , Chen Nai-Ming , Zhang Jin-San , Billadeau Daniel D. , Gaisina Irina N. , Kozikowski Alan P. , Singh Shiv K. , Fink Daniel , Ströbel Philipp , Klindt Caroline , Zhang Lizhi , Bamlet William R. , Koenig Alexander , Hessmann Elisabeth , Gress Thomas M. , Ellenrieder Volker , Neesse Albrecht 
Published: January 2016

AbstractWe aimed to investigate the mechanistic, functional, and therapeutic role of glycogen synthase kinase 3β (GSK-3β) in the regulation and activation of the proinflammatory oncogenic transcription factor nuclear factor of activated T cells (NFATc2) in pancreatic cancer. IHC, qPCR, immunoblotting, immunofluorescence microscopy, and proliferation assays were used to analyze mouse and human tissues and cell lines. Protein–protein interactions and promoter regulation were analyzed by coimmunoprecipitation, DNA pulldown, reporter, and ChIP assays. Preclinical assays were performed using a variety of pancreatic cancer cells lines, xenografts, and a genetically engineered mouse model (GEMM). GSK-3β–dependent SP2 phosphorylation mediates NFATc2 protein stability in the nucleus of pancreatic cancer cells stimulating pancreatic cancer growth. In addition to protein stabilization, GSK-3β also maintains NFATc2 activation through a distinct mechanism involving stabilization of NFATc2–STAT3 complexes independent of SP2 phosphorylation. For NFATc2–STAT3 complex formation, GSK-3β–mediated phosphorylation of STAT3 at Y705 is required to stimulate euchromatin formation of NFAT target promoters, such as cyclin-dependent kinase-6, which promotes tumor growth. Finally, preclinical experiments suggest that targeting the NFATc2–STAT3–GSK-3β module inhibits proliferation and tumor growth and interferes with inflammation-induced pancreatic cancer progression in KrasG12D mice. In conclusion, we describe a novel mechanism by which GSK-3β fine-tunes NFATc2 and STAT3 transcriptional networks to integrate upstream signaling events that govern pancreatic cancer progression and growth. Furthermore, the therapeutic potential of GSK-3β is demonstrated for the first time in a relevant Kras and inflammation-induced GEMM for pancreatic cancer. Mol Cancer Ther; 15(3); 491–502. ©2016 AACR.
Enhancing the Tumor Selectivity of a Picornavirus Virotherapy Promotes Tumor Regression and the Accumulation of Infiltrating CD8+ T Cells
Authors: Bell Michael P. , Pavelko Kevin D. 
Published: January 2016

Abstract
Picornaviruses have emerged as promising cancer therapies due to their ability to drive cytotoxic cellular immune responses and for promoting oncolysis. These properties include preferential replication in tumor cells, the induction of strong innate and adaptive immune responses, and the ease with which their genomes can be manipulated. We have developed Theiler's murine encephalomyelitis virus (TMEV) as an immunotherapy vector that promotes strong adaptive immune responses to tumor antigens embedded within its genome. To further explore its usefulness as cancer therapy, we investigated whether direct intratumoral delivery of TMEV could promote tumor regression. We generated several picornavirus hybrids using substrains of TMEV that have unique immunopathologic characteristics, despite their extensive sequence homology. These hybrids exhibit a unique propensity to infect and replicate in melanoma. We have identified GD7-KS1, a virus that is particularly effective at replicating and infecting B16 melanoma in vitro and provides benefit as an oncolytic therapy in vivo after intratumoral injection. In addition, this virus promotes the mobilization and accumulation of CD8+ T cells within treated tumors. Altogether, these findings demonstrate that picornavirus substrains can be used to rationally design virus hybrids that promote antitumor responses and add to the known strategies identified by us and others to further enhance the therapeutic potential of vectors used to treat cancer. Mol Cancer Ther; 15(3); 523–30. ©2016 AACR.
Tigecycline Inhibits Glioma Growth by Regulating miRNA-199b-5p–HES1–AKT Pathway
Authors: Yang Rui , Yi Liang , Dong Zhen , Ouyang Qing , Zhou Ji , Pang Yi , Wu Yanan , Xu Lunshan , Cui Hongjuan 
Published: January 2016

Abstract
Tigecycline is a broad-spectrum, first-in-class glycylcycline antibiotic currently used to treat complicated skin infections and community-acquired pneumonia. However, there is accumulating evidence showing that tigecycline has anticancer properties. In this study, we found tigecycline could inhibit cell proliferation by inducing cell-cycle arrest, but not apoptosis in glioma. To find the underlying mechanism of how tigecycline inhibits cell proliferation, the expression of miRNAs, which were related to regulating cell-cycle progression, was detected with miRNA assay. We found that miR-199b-5p expression was significantly increased after tigecycline treatment, and miR-199b-5p target gene HES1 was downregulated. In addition, the PI3K/AKT pathway was inhibited and p21 expression was increased. When treated with tigecycline and miR-199b-5p antagomir simultaneously in glioma cells, we found that miR-199b-5p antagomir could partly block the effects induced by tigecycline. Tigecycline effectively upregulated miR-199b-5p expression and inhibited tumor growth in the xenograft tumor model of U87 glioma cells. These results suggest that tigecycline may induce cell-cycle arrest and inhibit glioma growth by regulating miRNA-199b-5p–HES1–AKT pathway. Thus, tigecycline is a promising agent in the treatment of malignant gliomas. Mol Cancer Ther; 15(3); 421–9. ©2016 AACR.