bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomised controlled trial of long-term maintenance corticosteroid therapy in patients with autoimmune pancreatitis
Authors: Masamune Atsushi , Nishimori Isao , Kikuta Kazuhiro , Tsuji Ichiro , Mizuno Nobumasa , Iiyama Tatsuo , Kanno Atsushi , Tachibana Yuichi , Ito Tetsuhide , Kamisawa Terumi , Uchida Kazushige , Hamano Hideaki , Yasuda Hiroaki , Sakagami Junichi , Mitoro Akira , Taguchi Masashi , Kihara Yasuyuki , Sugimoto Hiroyuki , Hirooka Yoshiki , Yamamoto Satoshi , Inui Kazuo , Inatomi Osamu , Andoh Akira , Nakahara Kazuyuki , Miyakawa Hiroyuki , Hamada Shin , Kawa Shigeyuki , Okazaki Kazuichi , Shimosegawa Tooru 
Published: August 2016

ObjectiveCorticosteroid has been established as the standard therapy for autoimmune pancreatitis (AIP), but the requirement for maintenance corticosteroid therapy is controversial. We conducted a randomised controlled trial to clarify the efficacy of maintenance corticosteroid therapy in patients with AIP.DesignWe conducted a multicentre, tertiary setting, randomised controlled trial. After the induction of remission with the initial oral prednisolone (PSL) treatment, maintenance therapy with PSL at 5–7.5 mg/day was continued for 3 years or withdrawn at 26 weeks. The primary endpoint was relapse-free survival over 3 years and the secondary endpoint was serious corticosteroid-related complications. All analyses were performed on an intention-to-treat basis.ResultsBetween April 2009 and March 2012, 49 patients with AIP were randomly assigned to the maintenance therapy group (n=30) or the cessation group (n=19). Baseline characteristics were not different between the two groups. Relapses occurred within 3 years in 11 out of 19 (57.9%) patients assigned to the cessation group, and in 7 of 30 (23.3%) patients in the maintenance therapy group. The relapse rate over 3 years was significantly lower in the maintenance therapy group than that in the cessation group (p=0.011). The relapse-free survival was significantly longer in the maintenance therapy group than that in the cessation group (p=0.007). No serious corticosteroid-related complications requiring discontinuation of PSL were observed.ConclusionsMaintenance corticosteroid therapy for 3 years may decrease relapses in patients with AIP compared with those who discontinued the therapy at 26 weeks.Trial registration numberUMIN000001818; Results.
The usefulness of a novel fully automated PCR-based Idylla test for detection of the BRAF V600E mutation in thyroid tissue: comparison with PNA-clamping PCR, real-time PCR and pyrosequencing
Authors: Yeo Min-Kyung , Jung Min-Kyu , Lee Su-Yel , Lee Yong-Moon , Hur Gang Min , Kim Jin-Man 
Published: August 2016

IntroductionThe BRAF V600E mutation is the most common genetic event in papillary thyroid carcinoma (PTC). The BRAF V600E mutational status has a significant diagnostic and prognostic role in PTC since it can be detected in 32%–87% of PTC by various molecular methods.Aim(s)A novel, fully automated real-time PCR-based Idylla test is assessed to detect the BRAF mutation in formalin-fixed paraffin-embedded (FFPE) thyroid samples.Methods99 PTC and 11 nodular hyperplasia FFPE thyroid tissues are evaluated for the BRAF V600E mutation by the Idylla tests and compared with peptide nucleic acid-clamping PCR, real-time PCR and pyrosequencing.ResultsThe sensitivity and specificity of the Idylla test to detect BRAF V600E are 98.8% and 100%, which is superior to real-time PCR and pyrosequencing. The concordance between Idylla and true positive is highest at 0.974.ConclusionsThis study validates that the Idylla test is a sensitive and specific method to detect BRAF V600E in FFPE thyroid tissues. A simple, quick and easy to handle Idylla test is a useful and reliable molecular technique to evaluate BRAF mutations.
Interaction between the stent strut and thrombus characterized by contrast-enhanced high-resolution cone beam CT during deployment of the Solitaire stent retriever
Authors: Tsumoto Tomoyuki , Tsurusaki Yuichiro , Tokunaga So 
Published: August 2016

BackgroundThe mechanism by which a stent retriever removes intraluminal thrombus from an occluded vessel in humans has not previously been studied. This study performed contrast-enhanced high-resolution cone beam CT (CE-HRCBCT) during deployment of the stent retriever to observe the interaction between the strut and intraluminal thrombus intraoperatively. We also discuss the mechanism by which the thrombus is retrieved.MethodsIn 11 patients, mechanical thrombectomy was performed with a Solitaire stent retriever. The presence or absence of flow restoration (FR) was evaluated immediately and at least 5 min after deployment. Stent retriever findings on CE-HRCBCT were divided into two groups: (1) complete expansion; and (2) incomplete expansion.ResultsFR was observed in all 11 cases (100%) immediately after deployment of the Solitaire stent retriever. Complete expansion was observed in only one case and incomplete expansion was observed in 10 cases. The thrombus was observed mainly near to or outside the strut of the stent retriever by CE-HRCBCT. Loss of FR was seen in only one of the 11 cases. Regardless of this, successful recanalization was achieved with only the stent retriever in nine cases.ConclusionsCE-HRCBCT showed that the Solitaire stent retriever rarely expanded fully and the thrombus was mainly near to or outside the strut. It may not be necessary to wait a long time to allow the stent to expand fully into the thrombus because the main capture mechanism seems to be engagement of the clot between the crossings of the struts of the Solitaire.
The modified ‘no touch’ technique in the antegrade endovascular approach for left common carotid artery ostial stenosis stenting
Authors: Tang Xiaobin , Long Whitney Annie , Hu Chang , Tang Feng , Wang Qian , Li Lei 
Published: August 2016

BackgroundOpen surgery and the retrograde endovascular approach via the distal left common carotid artery (LCCA) have some limitations in LCCA ostial stenosis treatment. The ‘no touch’ technique used in the renal artery was modified for this situation.MethodsFifteen selective LCCA stenosis patients were treated by the modified ‘no touch’ technique in the antegrade endovascular approach from March 2013 to March 2016. Thirteen underwent the transfemoral approach and the other two had the transbrachial approach due to a ‘bovine aortic arch’. Distal embolic protection devices were used in all cases. Follow-up included a neurological examination, carotid duplex scan, and office interview. Mean follow-up time was 18.2±11.5 months.ResultsThe initial technical success rate was 100%. The average procedure time was 84.0±16.3 min. There were no procedure-related deaths. No clinical neurological complications occurred during the in-hospital stay. No incidence of death or major stroke occurred during the follow-up period; 6.7% (1/15) of patients had a contralateral minor stroke, 66.7% (4/6) of symptomatic patients were relieved of initial symptoms, and the rest showed improvement. No patient developed new ipsilateral neurological symptoms and no in-stent restenosis occurred during the follow-up period. These results were confirmed by ultrasound.ConclusionsThe modified ‘no touch’ antegrade endovascular technique is a feasible method for treating LCCA ostial lesions with a satisfactory initial success rate, acceptable procedure time, and comparable mid- and long-term results. This technique could be considered as a complementary option for LCCA ostial stenosis in addition to open surgery and the retrograde endovascular approach.
Prognostic indicators and generation of novel risk equations for estimation of 10-year and 20-year mortality following acute coronary syndrome
Authors: Magri Caroline J , Debono Roberto , Calleja Neville , Galea Joseph , Fava Stephen 
Published: August 2016

ABSTRACTObjectivesAlthough risk assessment is an integral part of management, there are currently no risk calculators of long-term mortality after acute coronary syndrome (ACS). The aim was to provide risk equations for 10-year and 20-year mortality following ACS.MethodsPatients hospitalised with ACS from December 1990 to June 1994 were recruited and followed up through 31 December 2012.ResultsThe study followed 881 patients for 10 years and 712 patients for 20 years. Using Cox regression analysis, 20-year all-cause mortality was associated with myocardial infarction (MI) in the index admission, age and diabetes mellitus (DM). Twenty-year cardiovascular disease (CVD) and cardiac mortality were both associated with MI in the index admission, age, DM and female gender. 10-year all-cause mortality was associated with age and total cholesterol levels; age, DM and total cholesterol levels were found to be independent predictors of 10-year CVD and cardiac mortality. Risk equations were consequently generated for 10-year and 20-year cardiac, cardiovascular and all-cause mortality, with age and DM emerging as the strongest and most consistent predictors of all outcomes studied.ConclusionsNovel risk equations for all-cause, cardiovascular and cardiac mortality at 10 and 20 years were generated using follow-up data in a large patient population.
Characterisation of antimicrobial usage in cats and dogs attending UK primary care companion animal veterinary practices
Authors: Buckland E. L. , O'Neill D. , Summers J. , Mateus A. , Church D. , Redmond L. , Brodbelt D. 
Published: August 2016

There is scant evidence describing antimicrobial (AM) usage in companion animal primary care veterinary practices in the UK. The use of AMs in dogs and cats was quantified using data extracted from 374 veterinary practices participating in VetCompass. The frequency and quantity of systemic antibiotic usage was described.Overall, 25 per cent of 963,463 dogs and 21 per cent of 594,812 cats seen at veterinary practices received at least one AM over a two‐year period (2012–2014) and 42 per cent of these animals were given repeated AMs. The main agents used were aminopenicillin types and cephalosporins. Of the AM events, 60 per cent in dogs and 81 per cent in cats were AMs classified as critically important (CIAs) to human health by the World Health Organisation. CIAs of highest importance (fluoroquinolones, macrolides, third‐generation cephalosporins) accounted for just over 6 per cent and 34 per cent of AMs in dogs and cats, respectively. The total quantity of AMs used within the study population was estimated to be 1473 kg for dogs and 58 kg for cats.This study has identified a high frequency of AM usage in companion animal practice and for certain agents classified as of critical importance in human medicine. The study highlights the usefulness of veterinary practice electronic health records for studying AM usage.
Impaired Planar Germ Cell Division in the Testis, Caused by Dissociation of RHAMM from the Spindle, Results in Hypofertility and Seminoma
Authors: Li Huaibiao , Frappart Lucien , Moll Jürgen , Winkler Anne , Kroll Torsten , Hamann Jana , Kufferath Iris , Groth Marco , Taudien Stefan , Schütte Moritz , Yaspo Marie-Laure , Heuer Heike , Lange Bodo M.H. , Platzer Matthias , Zatloukal Kurt , Herrlich Peter , Ploubidou Aspasia 
Published: August 2016

Abstract
Hypofertility is a risk factor for the development of testicular germ cell tumors (TGCT), but the initiating event linking these pathologies is unknown. We hypothesized that excessive planar division of undifferentiated germ cells promotes their self-renewal and TGCT development. However, our results obtained from mouse models and seminoma patients demonstrated the opposite. Defective planar divisions of undifferentiated germ cells caused their premature exit from the seminiferous tubule niche, resulting in germ cell depletion, hypofertility, intratubular germ cell neoplasias, and seminoma development. Oriented divisions of germ cells, which determine their fate, were regulated by spindle-associated RHAMM—a function we found to be abolished in 96% of human seminomas. Mechanistically, RHAMM expression is regulated by the testis-specific polyadenylation protein CFIm25, which is downregulated in the human seminomas. These results suggested that spindle misorientation is oncogenic, not by promoting self-renewing germ cell divisions within the niche, but by prematurely displacing proliferating cells from their normal epithelial milieu. Furthermore, they suggested RHAMM loss-of-function and spindle misorientation as an initiating event underlying both hypofertility and TGCT initiation. These findings identify spindle-associated RHAMM as an intrinsic regulator of male germ cell fate and as a gatekeeper preventing initiation of TGCTs. Cancer Res; 76(21); 6382–95. ©2016 AACR.
Parents' Support for School-Entry Requirements for Human Papillomavirus Vaccination: A National Study
Authors: Calo William A. , Gilkey Melissa B. , Shah Parth D. , Moss Jennifer L. , Brewer Noel T. 
Published: August 2016

AbstractBackground: The number of states proposing school-entry requirements for human papillomavirus (HPV) vaccination has increased over the last decade. However, data are currently limited regarding parents' support of such laws. We sought to obtain the first national estimates of parents' support of HPV vaccination school-entry requirements.Methods: A national sample of 1,501 parents of 11- to 17-year-old children completed a web-based survey between November 2014 and January 2015. Analyses used multivariable logistic regression to assess correlates of support for school-entry requirements for HPV vaccination.Results: Overall, 21% of parents agreed that laws requiring HPV vaccination for school attendance “are a good idea,” and 54% disagreed. If school-entry requirements included opt-out provisions, agreement increased to 57%, and only 21% disagreed. Parents more often agreed with requirements without opt-out provisions if they were Hispanic [OR = 1.53; 95% confidence interval (CI), 1.05–2.22], believed HPV vaccine was as or more important than other adolescent vaccines (OR = 2.76; 95% CI, 1.98–3.83), or believed HPV vaccine was effective for preventing cervical cancer (OR = 2.55; 95% CI, 1.93–3.37). Parents less often agreed if they resided in Midwest states or believed that HPV vaccine was being pushed to make money for drug companies (both P &lt; 0.05).Conclusion: Opt-out provisions almost tripled parents' support for HPV vaccine school-entry requirements. Our findings suggest that race/ethnicity, attitudes about HPV vaccine, and region of residence may influence support for requirements without opt-out provisions.Impact: Opt-out provisions greatly increase parent support of school-entry requirements for HPV vaccination but may make them ineffective. Cancer Epidemiol Biomarkers Prev; 25(9); 1317–25. ©2016 AACR.
Comparison of Collection Methods for Fecal Samples for Discovery Metabolomics in Epidemiologic Studies
Authors: Loftfield Erikka , Vogtmann Emily , Sampson Joshua N. , Moore Steven C. , Nelson Heidi , Knight Rob , Chia Nicholas , Sinha Rashmi 
Published: August 2016

Abstract
Background: The gut metabolome may be associated with the incidence and progression of numerous diseases. The composition of the gut metabolome can be captured by measuring metabolite levels in the feces. However, there are little data describing the effect of fecal sample collection methods on metabolomic measures.
Methods: We collected fecal samples from 18 volunteers using four methods: no solution, 95% ethanol, fecal occult blood test (FOBT) cards, and fecal immunochemical test (FIT). One set of samples was frozen after collection (day 0), and for 95% ethanol, FOBT, and FIT, a second set was frozen after 96 hours at room temperature. We evaluated (i) technical reproducibility within sample replicates, (ii) stability after 96 hours at room temperature for 95% ethanol, FOBT, and FIT, and (iii) concordance of metabolite measures with the putative “gold standard,” day 0 samples without solution.
Results: Intraclass correlation coefficients (ICC) estimating technical reproducibility were high for replicate samples for each collection method. ICCs estimating stability at room temperature were high for 95% ethanol and FOBT (median ICC &gt; 0.87) but not FIT (median ICC = 0.52). Similarly, Spearman correlation coefficients (rs) estimating metabolite concordance with the “gold standard” were higher for 95% ethanol (median rs = 0.82) and FOBT (median rs = 0.70) than for FIT (median rs = 0.40).
Conclusions: Metabolomic measurements appear reproducible and stable in fecal samples collected with 95% ethanol or FOBT. Concordance with the “gold standard” is highest with 95% ethanol and acceptable with FOBT.
Impact: Future epidemiologic studies should collect feces using 95% ethanol or FOBT if interested in studying fecal metabolomics. Cancer Epidemiol Biomarkers Prev; 25(11); 1483–90. ©2016 AACR.
Survival and Proliferation of Neural Progenitor–Derived Glioblastomas Under Hypoxic Stress is Controlled by a CXCL12/CXCR4 Autocrine-Positive Feedback Mechanism
Authors: Calinescu Anda-Alexandra , Yadav Viveka Nand , Carballo Erica , Kadiyala Padma , Tran Dustin , Zamler Daniel B. , Doherty Robert , Srikanth Maithreyi , Lowenstein Pedro Ricardo , Castro Maria Graciela 
Published: August 2016

Abstract
Purpose: One likely cause of treatment failure in glioblastoma is the persistence of glioma stem-like cells (GSLCs) which are highly resistant to therapies currently employed. We found that CXCL12 has highest expression in glioma cells derived from neural progenitor cells (NPC). The development and molecular signature of NPC-derived glioblastomas were analyzed and the therapeutic effect of blocking CXCL12 was tested.
Experimental Design: Tumors were induced by injecting DNA into the lateral ventricle of neonatal mice, using the Sleeping Beauty transposase method. Histology and expression of GSLC markers were analyzed during disease progression. Survival upon treatment with pharmacologic (plerixafor) or genetic inhibition of CXCR4 was analyzed. Primary neurospheres were generated and analyzed for proliferation, apoptosis, and expression of proteins regulating survival and cell-cycle progression.
Results: Tumors induced from NPCs display histologic features of human glioblastoma and express markers of GSLC. In vivo, inhibiting the CXCL12/CXCR4 signaling axis results in increased survival of tumor-bearing animals. In vitro, CXCR4 blockade induces apoptosis and inhibits cell-cycle progression, downregulates molecules regulating survival and proliferation, and also blocks the hypoxic induction of HIF-1α and CXCL12. Exogenous administration of CXCL12 rescues the drug-induced decrease in proliferation.
Conclusions: This study demonstrates that the CXCL12/CXCR4 axis operates in glioblastoma cells under hypoxic stress via an autocrine-positive feedback mechanism, which promotes survival and cell-cycle progression. Our study brings new mechanistic insight and encourages further exploration of the use of drugs blocking CXCL12 as adjuvant agents to target hypoxia-induced glioblastoma progression, prevent resistance to treatment, and recurrence of the disease. Clin Cancer Res; 23(5); 1250–62. ©2016 AACR.
Safety and Pharmacodynamics of the PDE4 Inhibitor Roflumilast in Advanced B-cell Malignancies
Authors: Kelly Kevin , Mejia Alex , Suhasini Avvaru N. , Lin An-Ping , Kuhn John , Karnad Anand B. , Weitman Steven , Aguiar Ricardo C.T. 
Published: August 2016

Abstract
Purpose: In this study, we aimed to validate our extensive preclinical data on phosphodiesterase 4 (PDE4) as actionable target in B-cell malignancies. Our specific objectives were to determine the safety, pharmacokinetics, and pharmacodynamics (PI3K/AKT activity), as well as to capture any potential antitumor activity of the PDE4 inhibitor roflumilast in combination with prednisone in patients with advanced B-cell malignancies.
Experimental Design: Single-center, exploratory phase Ib open-label, nonrandomized study. Roflumilast (500 mcg PO) was given daily for 21 days with prednisone on days 8 to 14. Additional 21-day cycles were started if patients tolerated cycle 1 and had at least stable disease.
Results: Ten patients, median age 65 years with an average of three prior therapies, were enrolled. The median number of cycles administered was 4 (range, 1–13). Treatment was well tolerated; the most common ≥grade 2 treatment-related adverse events were fatigue, anorexia (≥25%), and transient ≥ grade 2 neutropenia (30%). Treatment with roflumilast as a single agent significantly suppressed PI3K activity in the 77% of patients evaluated; on average, patients with PI3K/AKT suppression stayed in trial for 156 days (49–315) versus 91 days (28–139 days) for those without this biomarker response. Six of the nine evaluable patients (66%) had partial response or stable disease. The median number of days in trial was 105 days (range, 28–315).
Conclusions: Repurposing the PDE4 inhibitor roflumilast for treatment of B-cell malignancies is safe, suppresses the oncogenic PI3K/AKT kinases, and may be clinically active. Clin Cancer Res; 23(5); 1186–92. ©2016 AACR.
A Phase I Study of the Cyclin-Dependent Kinase 4/6 Inhibitor Ribociclib (LEE011) in Patients with Advanced Solid Tumors and Lymphomas
Authors: Infante Jeffrey R. , Cassier Philippe A. , Gerecitano John F. , Witteveen Petronella O. , Chugh Rashmi , Ribrag Vincent , Chakraborty Abhijit , Matano Alessandro , Dobson Jason R. , Crystal Adam S. , Parasuraman Sudha , Shapiro Geoffrey I. 
Published: August 2016

Abstract
Purpose: Ribociclib (an oral, highly specific cyclin-dependent kinase 4/6 inhibitor) inhibits tumor growth in preclinical models with intact retinoblastoma protein (Rb+). This first-in-human study investigated the MTD, recommended dose for expansion (RDE), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of ribociclib in patients with Rb+ advanced solid tumors or lymphomas.
Experimental Design: Patients received escalating doses of ribociclib (3-weeks-on/1-week-off or continuous). Dose escalation was guided by a Bayesian Logistic Regression Model with overdose control principle.
Results: Among 132 patients, 125 received ribociclib 3-weeks-on/1-week-off and 7 were dosed continuously. Nine dose-limiting toxicities were observed among 70 MTD/RDE evaluable patients during cycle 1, most commonly neutropenia (n = 3) and thrombocytopenia (n = 2). The MTD and RDE were established as 900 and 600 mg/day 3-weeks-on/1-week-off, respectively. Common treatment-related adverse events were (all-grade; grade 3/4) neutropenia (46%; 27%), leukopenia (43%; 17%), fatigue (45%; 2%), and nausea (42%; 2%). Asymptomatic Fridericia's corrected QT prolongation was specific to doses ≥600 mg/day (9% of patients at 600 mg/day; 33% at doses &gt;600 mg/day). Plasma exposure increases were slightly higher than dose proportional; mean half-life at the RDE was 32.6 hours. Reduced Ki67 was observed in paired skin and tumor biopsies, consistent with ribociclib-mediated antiproliferative activity. There were 3 partial responses and 43 patients achieved a best response of stable disease; 8 patients were progression-free for &gt;6 months.
Conclusions: Ribociclib demonstrated an acceptable safety profile, dose-dependent plasma exposure, and preliminary signs of clinical activity. Phase I–III studies of ribociclib are under way in various indications. Clin Cancer Res; 22(23); 5696–705. ©2016 AACR.