bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of Use of Flexible Sigmidoscopy, Colonoscopy and Gastroscopy: A Population‐Based Study in a Canadian Province
Authors: Hilsden Robert J 
Published: March 2016

BACKGROUND & AIMS: Flexible sigmoidoscopy, colonoscopy and gastroscopy are important in the diagnosis and treatment of gastrointestinal (GI) diseases. Pressure on endoscopy resources is expected due to increased screening for GI cancers. The present study examined patterns of use of GI endoscopy in a Canadian province, Alberta, with universal health care insurance.METHODS: Data on physician payments from January 1, 1994 to March 31, 2002 were used to calculate age‐sex adjusted rates and patterns of use.RESULTS: The gastroscopy rate increased by 17%, from 9.7 (95% CI 9.6 to 9.9) to 10.3 (95% CI 10.1 to 10.5). The colonoscopy rate increased by 105%, from 4.8 (95% CI 4.6 to 5.0) to 9.8 (95% CI 9.6 to 10.1). Flexible sigmoidoscopy rates declined by 10%, from 4.68 (95% CI 4.56 to 4.80) to 4.21 (95% CI 4.11 to 4.32). The increase in colonoscopy rates occurred in all age groups, whereas gastroscopy rates increased only in the older age groups. Regional variation in procedure rates was evident, but rural health regions did not have consistently lower rates than the large urban regions. A polypectomy was performed on 23.7% of male patients and 15.4% of female patients at time of colonoscopy. Rates of polypectomy for individual endoscopists ranged from 0% to 60%.CONCLUSIONS: There has been a marked increase in gastroscopy and colonoscopy rates, likely due to a broadening of indications rather than just increased use for cancer screening. Modest regional variation in rates exists, but there is no direct evidence of limited rural access to endoscopy. Reasonable polypectomy rates were seen but important variations between endoscopists exist.
Polysome Profiling Links Translational Control to the Radioresponse of Glioblastoma Stem-like Cells
Authors: Wahba Amy , Rath Barbara H. , Bisht Kheem , Camphausen Kevin , Tofilon Philip J. 
Published: March 2016

Abstract
Changes in polysome-bound mRNA (translatome) are correlated closely with changes in the proteome in cells. Therefore, to better understand the processes mediating the response of glioblastoma to ionizing radiation (IR), we used polysome profiling to define the IR-induced translatomes of a set of human glioblastoma stem-like cell (GSC) lines. Although cell line specificity accounted for the largest proportion of genes within each translatome, there were also genes that were common to the GSC lines. In particular, analyses of the IR-induced common translatome identified components of the DNA damage response, consistent with a role for the translational control of gene expression in cellular radioresponse. Moreover, translatome analyses suggested that IR enhanced cap-dependent translation processes, an effect corroborated by the finding of increased eIF4F–cap complex formation detected after irradiation in all GSC lines. Translatome analyses also predicted that Golgi function was affected by IR. Accordingly, Golgi dispersal was detected after irradiation of each of the GSC lines. In addition to the common responses seen, translatome analyses predicted cell line–specific changes in mitochondria, as substantiated by changes in mitochondrial mass and DNA content. Together, these results suggest that analysis of radiation-induced translatomes can provide new molecular insights concerning the radiation response of cancer cells. More specifically, they suggest that the translational control of gene expression may provide a source of molecular targets for glioblastoma radiosensitization. Cancer Res; 76(10); 3078–87. ©2016 AACR.
Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen
Authors: Andersen Rikke , Donia Marco , Ellebaek Eva , Borch Troels Holz , Kongsted Per , Iversen Trine Zeeberg , Hölmich Lisbet Rosenkrantz , Hendel Helle Westergren , Met Özcan , Andersen Mads Hald , thor Straten Per , Svane Inge Marie 
Published: March 2016

AbstractPurpose: Adoptive cell transfer therapy (ACT) based on autologous tumor-infiltrating lymphocytes (TIL) has achieved impressive clinical results in several phase I and II trials performed outside of Europe. Although transient, the toxicities associated with high-dose (HD) bolus IL2 classically administered together with TILs are severe. To further scrutinize whether similar results can be achieved with lower doses of IL2, we have carried out a phase I/II trial of TIL transfer after classical lymphodepleting chemotherapy followed by an attenuated IL2 regimen.Experimental Design: Twenty-five patients with progressive treatment-refractory metastatic melanoma, good clinical performance, age &lt; 70 years, and at least one resectable metastasis were eligible. TIL infusion was preceded by standard lymphodepleting chemotherapy and followed by attenuated doses of IL2 administered in an intravenous, continuous decrescendo regimen (ClinicalTrials.gov Identifier: NCT00937625).Results: Classical IL2-related toxicities were observed but patients were manageable in a general oncology ward without the need for intervention from the intensive care unit. RECIST 1.0 evaluation displayed three complete responses and seven partial responses (ORR 42%). Median overall survival was 21.8 months. Tumor regression was associated with a higher absolute number of infused tumor-reactive T cells. Moreover, induction and persistence of antimelanoma T-cell responses in the peripheral blood was strongly correlated to clinical response to treatment.Conclusions: TIL-ACT with a reduced IL2 decrescendo regimen results in long-lasting complete responses in patients with treatment-refractory melanoma. Larger randomized trials are needed to elucidate whether clinical efficacy is comparable with TIL-ACT followed by HD bolus IL2. Clin Cancer Res; 22(15); 3734–45. ©2016 AACR.
Myeloma Cell Dynamics in Response to Treatment Supports a Model of Hierarchical Differentiation and Clonal Evolution
Authors: Tang Min , Zhao Rui , van de Velde Helgi , Tross Jennifer G. , Mitsiades Constantine , Viselli Suzanne , Neuwirth Rachel , Esseltine Dixie-Lee , Anderson Kenneth , Ghobrial Irene M. , San Miguel Jesús F. , Richardson Paul G. , Tomasson Michael H. , Michor Franziska 
Published: March 2016

AbstractPurpose: Since the pioneering work of Salmon and Durie, quantitative measures of tumor burden in multiple myeloma have been used to make clinical predictions and model tumor growth. However, such quantitative analyses have not yet been performed on large datasets from trials using modern chemotherapy regimens.Experimental Design: We analyzed a large set of tumor response data from three randomized controlled trials of bortezomib-based chemotherapy regimens (total sample size n = 1,469 patients) to establish and validate a novel mathematical model of multiple myeloma cell dynamics.Results: Treatment dynamics in newly diagnosed patients were most consistent with a model postulating two tumor cell subpopulations, "progenitor cells" and "differentiated cells." Differential treatment responses were observed with significant tumoricidal effects on differentiated cells and less clear effects on progenitor cells. We validated this model using a second trial of newly diagnosed patients and a third trial of refractory patients. When applying our model to data of relapsed patients, we found that a hybrid model incorporating both a differentiation hierarchy and clonal evolution best explains the response patterns.Conclusions: The clinical data, together with mathematical modeling, suggest that bortezomib-based therapy exerts a selection pressure on myeloma cells that can shape the disease phenotype, thereby generating further inter-patient variability. This model may be a useful tool for improving our understanding of disease biology and the response to chemotherapy regimens. Clin Cancer Res; 22(16); 4206–14. ©2016 AACR.
Neoantigen: A Long March toward Cancer Immunotherapy
Authors: Liu Yang 
Published: March 2016

AbstractSomatic mutations in cancer give rise to neoantigens. Technology revolutions in cancer genomics and immunology have made it possible to rapidly identify neoantigens for cancer vaccines. Leisegang and colleagues report that it is practical to rapidly identify neoantigens for adoptive T-cell therapy in a mouse tumor model. Clin Cancer Res; 22(11); 2602–4. ©2016 AACR.See related article by Leisegang et al., p. 2734
Neutralisation of factor VIII inhibitors by anti-idiotypes isolated from phage-displayed libraries
Authors: Schmidt Anja , Brettschneider Kerstin , Kahle Jörg , Orlowski Aleksander , Becker-Peters Karin , Stichel Diana , Schulze Jörg , Braner Markus , Tampé Robert , Schwabe Dirk , Königs Christoph 
Published: March 2016

SummaryFollowing replacement therapy with coagulation factor VIII (FVIII), up to 30 % of haemophilia A patients develop FVIII-specific inhibitory antibodies (FVIII inhibitors). Immune tolerance induction (ITI) is not always successful, resulting in a need for alternative treatments for FVIII inhibitor-positive patients. As tolerance induction in the course of ITI appears to involve the formation of anti-idiotypes specific for anti-FVIII antibodies, such anti-idiotypes might be used to restore haemostasis in haemophilia A patients with FVIII inhibitors. We isolated antiidiotypic antibody fragments (scFvs) binding to murine FVIII inhibitors 2-76 and 2-77 from phage-displayed libraries. FVIII inhibitor/anti-idiotype interactions were very specific as no cross-reactivity with other FVIII inhibitors or isotype controls was observed. ScFvs blocked binding of FVIII inhibitors to FVIII and neutralised their cognate inhibitors in vitro and a monoclonal mouse model. In addition, scFv JkH5 specific for FVIII inhibitor 2-76 stained 2-76-producing hybridoma cells. JkH5 residues R52 and Y226, located in complementary determining regions, were identified as crucial for the JkH5/2-76 interaction using JkH5 alanine mutants. SPR spectroscopy revealed that JkH5 interacts with FVIII inhibitor 2-76 with nanomolar affinity. Thus, FVIII inhibitorspecific, high-affinity anti-idiotypes can be isolated from phagedisplayed libraries and neutralise their respective inhibitors. Furthermore, we show that anti-idiotypic scFvs might be utilised to specifically target inhibitor-specific B cells. Hence, a pool of anti-idiotypes could enable the reestablishment of haemostasis in the presence of FVIII inhibitors in patients or even allow the depletion of inhibitors by targeting inhibitor-specific B cell populations.
Arterial Tortuosity: An Imaging Biomarker of Childhood Stroke Pathogenesis?
Authors: Wei Felix , Diedrich Karl T. , Fullerton Heather J. , deVeber Gabrielle , Wintermark Max , Hodge Jacquie , Kirton Adam , Dowling MM , Benedict SL , Bernard TJ , Fox CK , Friedman NR , Lo WD , Ichord RN , Tan MA , Mackay MT , Hernandez Chavez MI , Humphreys P , Jordan LC , Sultan SM , Rivkin MJ , Rafay MF , Titomanlio L , Kovacevic GS , Yager JY , Amlie-Lefond C , Dlamini N , Condie J , Yeh EA , Kneen R , Bjornson BH , Pergami P , Zou LP , Elbers J , Abdalla A , Chan AK , Farooq O , Lim MJ , Carpenter JL , Pavlakis S , Wong VCN , Forsyth R 
Published: March 2016

Background and Purpose—
Arteriopathy is the leading cause of childhood arterial ischemic stroke. Mechanisms are poorly understood but may include inherent abnormalities of arterial structure. Extracranial dissection is associated with connective tissue disorders in adult stroke. Focal cerebral arteriopathy is a common syndrome where pathophysiology is unknown but may include intracranial dissection or transient cerebral arteriopathy. We aimed to quantify cerebral arterial tortuosity in childhood arterial ischemic stroke, hypothesizing increased tortuosity in dissection.

Methods—

Children (1 month to 18 years) with arterial ischemic stroke were recruited within the Vascular Effects of Infection in Pediatric Stroke (VIPS) study with controls from the Calgary Pediatric Stroke Program. Objective, multi-investigator review defined diagnostic categories. A validated imaging software method calculated the mean arterial tortuosity of the major cerebral arteries using 3-dimensional time-of-flight magnetic resonance angiographic source images. Tortuosity of unaffected vessels was compared between children with dissection, transient cerebral arteriopathy, meningitis, moyamoya, cardioembolic strokes, and controls (ANOVA and post hoc Tukey). Trauma-related versus spontaneous dissection was compared (Student
t
test).

Results—

One hundred fifteen children were studied (median, 6.8 years; 43% women). Age and sex were similar across groups. Tortuosity means and variances were consistent with validation studies. Tortuosity in controls (1.346±0.074; n=15) was comparable with moyamoya (1.324±0.038; n=15;
P
=0.998), meningitis (1.348±0.052; n=11;
P
=0.989), and cardioembolic (1.379±0.056; n=27;
P
=0.190) cases. Tortuosity was higher in both extracranial dissection (1.404±0.084; n=22;
P
=0.021) and transient cerebral arteriopathy (1.390±0.040; n=27;
P
=0.001) children. Tortuosity was not different between traumatic versus spontaneous dissections (
P
=0.70).

Conclusions—
In children with dissection and transient cerebral arteriopathy, cerebral arteries demonstrate increased tortuosity. Quantified arterial tortuosity may represent a clinically relevant imaging biomarker of vascular biology in pediatric stroke.
Recombinant Osteopontin Stabilizes Smooth Muscle Cell Phenotype via Integrin Receptor/Integrin-Linked Kinase/Rac-1 Pathway After Subarachnoid Hemorrhage in Rats
Authors: Wu Jiang , Zhang Yang , Yang Peng , Enkhjargal Budbazar , Manaenko Anatol , Tang Jiping , Pearce William J. , Hartman Richard , Obenaus Andre , Chen Gang , Zhang John H. 
Published: March 2016

Background and Purpose—
Recombinant osteopontin (rOPN) has been reported to be neuroprotective in stroke animal models. The purpose of this study is to investigate a potential role and mechanism of nasal administration of rOPN on preserving the vascular smooth muscle phenotype in early brain injury after subarachnoid hemorrhage (SAH).

Methods—
One hundred and ninety-two male adult Sprague-Dawley rats were used. The SAH model was induced by endovascular perforation. Integrin-linked kinase small interfering RNA was intracerebroventricularly injected 48 hours before SAH. The integrin receptor antagonist fibronectin-derived peptide Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP), focal adhesion kinase inhibitor Fib-14, and Rac-1 inhibitor NSC23766 were administered 1 hour before SAH induction. rOPN was administered via the intracerebroventricular and nasal route after SAH. SAH grade, neurological scores, brain water content, brain swelling, hematoxylin and eosin staining, India ink angiography, Western blots, and immunofluorescence were used to study the mechanisms of rOPN on the vascular smooth muscle phenotypic transformation.

Results—
The marker proteins of vascular smooth muscle phenotypic transformation α-smooth muscle actin decreased and embryonic smooth muscle myosin heavy chain (SMemb) increased significantly at 24 and 72 hours in the cerebral arteries after SAH. rOPN prevented the changes of α-smooth muscle actin and SMemb and significantly alleviated neurobehavioral dysfunction, increased the cross-sectional area and the lumen diameter of the cerebral arteries, reduced the brain water content and brain swelling, and improved the wall thickness of cerebral arteries. These effects of rOPN were abolished by GRGDSP, integrin-linked kinase small interfering RNA, and NSC23766. Intranasal application of rOPN at 3 hours after SAH also reduced neurological deficits.

Conclusions—
rOPN prevented the vascular smooth muscle phenotypic transformation and improved the neurological outcome, which was possibly mediated by the integrin receptor/integrin-linked kinase/Rac-1 pathway.
How many children in Australia are at risk of adult mental illness?
Authors: Guy Sophie , Furber Gareth , Leach Matthew , Segal Leonie 
Published: March 2016

Objective: To estimate the prevalence of children in the Australian population with risk factors for adult mental illness. Method: Key risk factors and risk domains were identified from a 2013 review of longitudinal studies on child and adolescent determinants of adult mental illness. Data items were identified from the Longitudinal Study of Australian Children that map onto the risk domains and were used to estimate the prevalence of these key individual risk factors and the magnitude of multiple risk in children aged 3 months to 13 years. Results: Even by infancy, risk factors for adult mental illness are highly prevalent, with 51.7% of infants having multiple risks. In 10 infants, 1 was born to mothers who consumed daily alcohol and 1 in 8 to mothers who smoked cigarettes daily during pregnancy. Also, 10.5% of infants were in families where the parents had separated, which increased to 18% in 10–11 year-olds. Psychological problems in the clinical range (based on the Strengths and Difficulties Questionnaire total problems score) ranged from 7.8% to 9.7% across the 4–13 years age range. Risks from negative parenting behaviours were highly prevalent across age groups. Two-thirds of children aged 12–13 years had parents who displayed low warmth or exhibited high hostility/anger. Across childhood, one in seven children are in families exposed to 3+ major life stressors. By age 8–9 years, more than 18% of children are exposed to ⩾5 risk factors. Conclusions: We find that modifiable risk factors for adult mental illness occur at the earliest stage in the life course and at greater prevalence than is commonly recognised. Considerable capacity will be required in child and adolescent mental health services and complementary family support programmes if risk factors for adult mental illness that are already apparent in infancy and childhood are to be addressed.
Surgical and Audiologic Outcomes in Endoscopic Stapes Surgery across 4 Institutions
Authors: Hunter Jacob B. , Zuniga M. Geraldine , Leite Janaina , Killeen Daniel , Wick Cameron , Ramirez Julian , Rivas Jose A. , Nogueira Joao F. , Isaacson Brandon , Rivas Alejandro 
Published: March 2016

ObjectivesTo investigate intra‐ and postoperative outcomes of endoscopic stapes surgery.Study DesignCase series with chart review.SettingFour tertiary care otologic centers.Subjects and MethodsSixty‐five subjects 18 years and older who underwent endoscopic stapes surgeries were analyzed. Variables analyzed included surgical techniques and intraoperative findings. Outcomes measured included postoperative hearing and complications to date.ResultsFifty‐one patients met inclusion and exclusion criteria. The average patient age was 48.1 years (range, 26‐87 years), with 60.0% female patients. Patients had a median follow‐up of 5.13 months (range, 0.8‐57.4 months). Of the subjects, 71.7% required scutum removal. The chorda tympani nerve was manipulated in 94.0% of subjects and transected in 12.0%. At last follow‐up visit, the median air‐bone gap decreased from 34.5 dB hearing level (HL) preoperatively to 9.0 dB HL postoperatively (P <. 0001). Ninety percent of subjects had closure of their air‐bone gap ≤20 dB HL. Intraoperative complications included tympanic membrane tears in 8.0% of subjects, all of which resolved at first follow‐up. Postoperatively, 10.0% of subjects complained of altered taste.ConclusionsThe present multicentered study of endoscopic stapes surgery demonstrates similar audiometric and postoperative outcomes previously published in the literature, with a median postoperative air‐bone gap of 9.0 dB HL. Future prospective endoscopic stapes surgery studies, addressing the need for scutum removal, postoperative taste changes, and pain scores, are merited.
A Changing Landscape for Vitamin A Programs
Authors: Klemm Rolf D. W. , Palmer Amanda C. , Greig Alison , Engle-Stone Reina , Dalmiya Nita 
Published: March 2016

Background: Vitamin A deficiency (VAD) remains a widespread public health problem in the developing world, despite changes in under-5 mortality rates, morbidity patterns, and intervention options. Objective: This article considers the implications of a changing epidemiologic and programmatic landscape for vitamin A (VA) programs. Methods: We review progress to prevent VAD and its health consequences, assess gaps in VA status and intervention coverage data, and assess data needed to guide decisions regarding the optimal mix, targeting, and dose of VA interventions to maximize benefit and minimize risk. Results: Vitamin A supplementation programs have contributed to the reduction in under-5 mortality rates, but alone, do not address the underlying problem of inadequate dietary VA intakes and VAD among preschool-aged children in the developing world. A combination of VA interventions (eg, supplementation, fortified foods, multiple micronutrient powders, and lipid-based nutrient supplements) will be required to achieve VA adequacy in most settings. Current efforts to measure the coverage of multiple VA interventions, as well as whether and how much VA children are receiving, are few and fragmented. Conclusions: Where intervention overlap exists, further effort is needed to monitor VA intakes, ensuring that targeted groups are consuming adequate amounts but not exceeding the tolerable upper intake level. Vitamin A status data will also be critical for navigating the changing landscape of VA programs. Data from these monitoring efforts will help to guide decisions on the optimal mix, targeting, and exposure to VA interventions to maximize public health benefit while minimizing any potential risk.
Breastfeeding and Growth of Children in the Peri/postnatal Epigenetic Twins Study (PETS)
Authors: Temples Heide S. , Willoughby Deborah , Holaday Bonnie , Rogers Curtis R. , Wueste Daniel , Bridges William , Saffery Richard , Craig Jeffrey M. 
Published: March 2016

Background: The prevalence of overweight infants and toddlers has increased by 60% in the past 30 years and is a significant contributor to diabetes, cardiovascular disease, and early morbidity and mortality. The World Health Organization’s updated meta-analysis in 2013 observed an association between breastfeeding and a lower prevalence of obesity later in life. The purpose of this study was to assess the growth of children in a cohort of Australian twins to examine associations between duration of breastfeeding and growth at 18 months of age. Our hypothesis is that the anthropometric measurements of the participants will be greater with shorter duration of breastfeeding. Methods: Methods include using cross-sectional data from a cohort at the 18-month visit (n = 179) in the Peri/postnatal Epigenetics Twins Study (PETS) to assess the relationship between duration of breastfeeding and infant size at 18 months of age. Inclusion criteria were birth weight of more than 2000 grams and breastfed for less than 1 month, 1 to 3 months, or 4 to 6 months. Results: The analysis suggested that infants breastfed for 1 to 3 months were significantly larger than infants breastfed for 4 to 6 months in terms of mean body mass index (BMI) (0.61 kg/m2; P = .02; 95% confidence interval [CI], 0.17-1.05), arm circumference (0.66 cm; P = .006; 95% CI, 0.26-1.06), and abdominal circumference (1.16 cm; P = .03; 95% CI, 0.26-2.06). The analysis also suggested that infants breastfed for less than 1 month were significantly larger than infants breastfed for 4 to 6 months in terms of mean arm circumference (0.72 cm; P = .009; 95% CI, 0.26-1.17). Conclusion: Results suggest that supplementing with non–breast milk before 4 months of age was associated with an increased BMI, arm circumference, and abdominal circumference at 18 months of age. The mean BMI decreased from 85% to 65% when infants were breastfeeding for 4 to 6 months as compared to breastfeeding for 1 to 3 months. Breastfeeding for 4 to 6 months appeared to protect against the risk of obesity for the children in the PETS.