bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis C Genotype Determination by Melting Curve Analysis with a Single Set of Fluorescence Resonance Energy Transfer Probes
Authors: Bullock Grant C , Bruns David E , Haverstick Doris M 
Published: January 2020

Abstract
Background: The genotype of hepatitis C virus (HCV) is a predictor of antiviral therapeutic response. We describe an approach for HCV genotype determination by real-time PCR and melting curve analysis.
Methods: After automated nucleic acid extraction, we used reverse transcription-PCR in a block cycler to amplify nucleotides 6–329 of the 5′-untranslated region of HCV. The product was further amplified by single-tube real-time seminested PCR in a LightCyclerTM instrument (Roche). The final product was analyzed by melting curves with the use of fluorescence resonance energy transfer (FRET) probes. The FRET sensor probe was directed at nucleotides 151–170 of type 1 HCV and was designed to distinguish types 1a/b, 2a/c, 2b, 3a, and 4, with melting temperatures (Tms) predicted to differ by 1 °C. Genotypes were compared in a blinded fashion with those of the INNO-LiPATM test (Bayer Diagnostics) on 111 serum samples.
Results: In preliminary experiments, the Mg2+ concentration was found to be critical in allowing clear separation of melting points, with the best separation at a Mg2+ concentration of 2 mmol/L. The results for 111 samples clustered at expected Tms for genotypes 1a/b (n = 78), 2a/c (n = 2), 2b (n = 11), 3a (n = 14), and 4 (n = 2). Of the 111 samples, results for 110 were concordant with the comparison method at the level of type 1, 2, 3, or 4. Subtyping results were discordant for two samples, both of type 2. For 108 samples concordant with INNO-LiPA at the genotype and subtype levels, the mean Tms were 64.1, 59.5, 54.2, 52.6, and 50.1 °C for types 1a/b, 2a/c, 4, 2b, and 3a, respectively, with SDs of 0.2, 0.3, 0.3, 0.2, and 0.3 °C. All 78 samples identified as type 1 were concordant with results of the comparison method.
Conclusions: Melting analysis with a single pair of FRET probes can rapidly provide information about HCV genotypes and identifies type 1 samples with high specificity.
Multiplex Minisequencing of the 21-Hydroxylase Gene as a Rapid Strategy to Confirm Congenital Adrenal Hyperplasia
Authors: Krone Nils , Braun Andreas , Weinert Stefanie , Peter Michael , Roscher Adelbert A , Partsch Carl-Joachim , Sippell Wolfgang G 
Published: January 2020

Abstract
Background: Congenital adrenal hyperplasia (CAH) is a frequent autosomal recessive disease, with a wide range of clinical manifestations, most commonly attributable to mutations in the 21-hydroxylase gene (CYP21). Large gene deletions, large gene conversions, a small 8-basepair deletion, and eight point mutations in CYP21 account for ∼95% of all enzyme deficiencies. We developed a new strategy for a rapid CYP21 analysis.
Methods: DNA samples from 40 CAH patients previously genotyped by direct DNA sequencing were reanalyzed by allele-specific amplification of the functional CYP21 gene followed by a multiplex minisequencing reaction using 13 primers. In addition, a second PCR that amplified a part of exon 3 was used to demonstrate the presence or absence of at least one functional gene.
Results: The assay detected the P453S mutation and nine of the most common mutations (P30L, intron 2 splice, Δ8bp, I172N, exon 6 cluster, V281L, F306+t, Q318X, and R356W) caused by microconversions from the CYP21P pseudogene. The concordance was 100% for detecting these mutations, including gene deletions and large gene conversions. The 40 patient DNA samples were analyzed in 1.5 working days by one technician (actual hands-on time, 3.5 h). The material cost for analyzing one sample was approximately €10.00 (US $9.00).
Conclusions: This novel mutation screening strategy rapidly detects 90–95% of all mutations associated with CAH and appears applicable as a tool for confirmation of increased 17-hydroxyprogesterone found in neonatal CAH screening.
Evaluation of a No-Pretreatment Cyclosporin A Assay on the Dade Behring Dimension RxL Clinical Chemistry Analyzer
Authors: Terrell Andrea R , Daly Thomas M , Hock Karl G , Kilgore Daniel C , Wei Tie Q , Hernandez Sharon , Weibe Don , Fields Leona , Shaw Leslie M , Scott Mitchell G 
Published: January 2020

Abstract
Background: Monitoring whole-blood concentrations of cyclosporin A (CsA) is common practice in the management of solid organ and bone marrow transplant recipients. In a multicenter study we evaluated a new, direct (no pretreatment) CsA assay on the Dade Behring Dimension RxLTM system and compared results with those from the Abbott TDx CsA immunoassay and a HPLC method.
Methods: Whole-blood samples from heart (n = 111; 35 patients), liver (n = 201; 44 patients), kidney (n = 279; 65 patients), and miscellaneous organ (n = 77; 12 lung, 12 bone marrow, 5 kidney/pancreas, and 1 pancreas patient) recipients were obtained from patient populations of the participating institutions. Routine clinical monitoring of CsA was performed using either the TDx method or HPLC.
Results: The minimum detectable concentration of CsA averaged 9.4 μg/L, and the lower limit of quantification was 30 μg/L. The method was linear from 30 to 500 μg/L. Cross-reactivity with seven different CsA metabolites ranged from 0.0% to 5.7% for the Dimension RxL assay compared with 0.4–15.9% for the TDx assay. Total imprecision (CV) averaged 6.2%, and within-run imprecision averaged 4.9%. Passing–Bablok linear regression analyses of all samples from two sites yielded the following: RxL = 0.81 × TDx − 16.8; and RxL = 1.12 × HPLC − 1.7.
Conclusions: The Dade Behring CsA assay for the random-access Dimension platform offers adequate performance characteristics for routine clinical use, does not require a manual pretreatment step, and demonstrates less cross-reactivity with CsA metabolites than another commonly used immunoassay.
Relationship of Serum HER-2/neu and Serum CA 15-3 in Patients with Metastatic Breast Cancer
Authors: Ali Suhail M , Leitzel Kim , Chinchilli Vernon M , Engle Linda , Demers Laurence , Harvey Harold A , Carney Walter , Allard Jeffrey W , Lipton Allan 
Published: January 2020

Abstract
Background: Serum HER-2/neu antigen concentrations have been reported to correlate with increased tumor volume in patients with breast cancer. We measured serum CA 15-3, a surrogate marker of disease burden, and correlated serum CA 15-3 with serum HER-2/neu and analyzed the association of both markers with clinical outcomes.
Methods: Pretreatment serum samples from 566 patients were retrospectively analyzed from 2 phase III clinical trials of estrogen receptor-positive (ER+), ER−/progesterone receptor-positive, or ER status unknown metastatic breast cancer patients randomized in two similar studies to receive second-line hormone therapy with either megestrol acetate or an aromatase inhibitor (fadrozole). The extracellular domain of the HER-2/neu (c-erbB-2) oncogene and serum CA 15-3 were measured by ELISA on the Bayer Immuno 1.
Results: Serum HER-2/neu protein was increased in 168 patients (30%), and CA 15-3 was increased in 337 (60%) patients. Serum CA 15-3 and HER-2/neu were weakly correlated (r = 0.39; P &lt;0.0001). The clinical benefit (complete responses plus partial responses plus stable disease) of endocrine therapy was significantly lower in patients with increased serum HER-2/neu. When adjusted for serum HER-2/neu, serum CA 15-3 was not predictive of response rates. The median time to progression was shorter in patients with increased serum HER-2/neu (89 days) compared with patients with normal serum HER-2/neu (176 days). Survival was significantly shorter in patients with increased serum HER-2/neu (513 vs 869 days; P &lt;0.0001) or increased serum CA 15-3 (689 vs 939 days; P &lt;0.0001). This observation was confirmed by multivariate analysis.
Conclusions: Serum HER-2/neu is a significant independent predictive and prognostic factor in hormone receptor-positive metastatic breast cancer, even when adjusted for tumor burden as measured by CA 15-3. The combination of increased serum HER-2/neu and increased serum CA 15-3 predicts a worse prognosis than does increased CA 15-3 alone.
Stromal Cells in the Pathogenesis of Inflammatory Bowel Disease
Authors: Barnhoorn M C , Hakuno S K , Bruckner R S , Rogler G , Hawinkels L J A C , Scharl M 
Published: January 2020

Abstract
Up till now, research on inflammatory bowel disease [IBD] has mainly been focused on the immune cells present in the gastrointestinal tract. However, recent insights indicate that stromal cells also play an important and significant role in IBD pathogenesis. Stromal cells in the intestines regulate both intestinal epithelial and immune cell homeostasis. Different subsets of stromal cells have been found to play a role in other inflammatory diseases [e.g. rheumatoid arthritis], and these various stromal subsets now appear to carry out also specific functions in the inflamed gut in IBD. Novel potential therapies for IBD utilize, as well as target, these pathogenic stromal cells. Injection of mesenchymal stromal cells [MSCs] into fistula tracts of Crohn’s disease patients is already approved and used in clinical settings. In this review we discuss the current knowledge of the role of stromal cells in IBD pathogenesis. We further outline recent attempts to modify the stromal compartment in IBD with agents that target or replace the pathogenic stroma.
Comparison of newer generation self-expandable vs. balloon-expandable valves in transcatheter aortic valve implantation: the randomized SOLVE-TAVI trial
Authors: Thiele Holger , Kurz Thomas , Feistritzer Hans-Josef , Stachel Georg , Hartung Philipp , Eitel Ingo , Marquetand Christoph , Nef Holger , Doerr Oliver , Lauten Alexander , Landmesser Ulf , Abdel-Wahab Mohamed , Sandri Marcus , Holzhey David , Borger Michael , Ince Hüseyin , Öner Alper , Meyer-Saraei Roza , Wienbergen Harm , Fach Andreas , Frey Norbert , König Inke R , Vonthein Reinhard , Rückert Yvonne , Funkat Anne-Kathrin , de Waha-Thiele Suzanne , Desch Steffen 
Published: January 2020

Abstract

Aims
Transcatheter aortic valve implantation (TAVI) has emerged as established treatment option in patients with symptomatic aortic stenosis. Technical developments in valve design have addressed previous limitations such as suboptimal deployment, conduction disturbances, and paravalvular leakage. However, there are only limited data available for the comparison of newer generation self-expandable valve (SEV) and balloon-expandable valve (BEV).

Methods and results
SOLVE-TAVI is a multicentre, open-label, 2 × 2 factorial, randomized trial of 447 patients with aortic stenosis undergoing transfemoral TAVI comparing SEV (Evolut R, Medtronic Inc., Minneapolis, MN, USA) with BEV (Sapien 3, Edwards Lifesciences, Irvine, CA, USA). The primary efficacy composite endpoint of all-cause mortality, stroke, moderate/severe prosthetic valve regurgitation, and permanent pacemaker implantation at 30 days was powered for equivalence (equivalence margin 10% with significance level 0.05). The primary composite endpoint occurred in 28.4% of SEV patients and 26.1% of BEV patients meeting the prespecified criteria of equivalence [rate difference −2.39 (90% confidence interval, CI −9.45 to 4.66); P equivalence = 0.04]. Event rates for the individual components were as follows: all-cause mortality 3.2% vs. 2.3% [rate difference −0.93 (90% CI −4.78 to 2.92); P equivalence &lt; 0.001], stroke 0.5% vs. 4.7% [rate difference 4.20 (90% CI 0.12 to 8.27); P equivalence = 0.003], moderate/severe paravalvular leak 3.4% vs. 1.5% [rate difference −1.89 (90% CI −5.86 to 2.08); P equivalence = 0.0001], and permanent pacemaker implantation 23.0% vs. 19.2% [rate difference −3.85 (90% CI −10.41 to 2.72) in SEV vs. BEV patients; P equivalence = 0.06].

Conclusion
In patients with aortic stenosis undergoing transfemoral TAVI, newer generation SEV and BEV are equivalent for the primary valve-related efficacy endpoint. These findings support the safe application of these newer generation percutaneous valves in the majority of patients with some specific preferences based on individual valve anatomy.
COMPARE: prospective, randomized, non-inferiority trial of high- vs. low-dose paclitaxel drug-coated balloons for femoropopliteal interventions
Authors: Steiner Sabine , Schmidt Andrej , Zeller Thomas , Tepe Gunnar , Thieme Marcus , Maiwald Lars , Schröder Henrik , Euringer Wulf , Ulrich Matthias , Brechtel Klaus , Brucks Steffen , Blessing Erwin , Schuster Johannes , Langhoff Ralf , Schellong Sebastian , Weiss Norbert , Scheinert Dierk 
Published: January 2020

Abstract

Aims
Drug-coated balloons (DCBs) for femoropopliteal interventions have not been tested against each other. We aimed to directly compare efficacy and safety of a high-dose (In.Pact™) vs. low-dose (Ranger™) DCB with nominal paclitaxel densities of 3.5 vs. 2.0 μg/mm2.

Methods and results
Within a prospective, multicentre, non-inferiority, clinical trial 414 patients with symptomatic femoropopliteal lesions (Rutherford classification 2–4) were randomly assigned in a 1:1 ratio to endovascular treatment with either high- or low-dose DCB after stratification for lesion length. Primary efficacy and safety endpoints comprised primary patency and freedom from major adverse events (i.e. device and procedure-related deaths through 1 month, major amputations, and clinically driven target lesion revascularization through 12 months). We set a non-inferiority margin of −10% at 12 months. Total occlusions were observed frequently (&gt;40%) and provisional stenting was performed in every fourth intervention. Non-inferiority was determined for both primary efficacy and safety endpoints at 12 months. Primary patency was 81.5% in the high-dose and 83.0% in low-dose DCB group {difference: 1.5% [lower bound of the 90% two-sided confidence interval (CI) −5.2%]; P non-inferiority &lt; 0.01}. Freedom from major adverse events was determined in 92.6% in high-dose and in 91.0% in low-dose DCB group [difference −1.6% (lower bound of the 90% two-sided CI −6.5%); P non-inferiority &lt; 0.01]. Overall death rate was low (2.0%) and no major amputation occurred.

Conclusion
Two DCBs with different coating characteristics exhibited comparable results with excellent effectiveness and safety through 12 months for femoropopliteal interventions including a wide range of lesion lengths.

Clinical trial registration
The trial is registered with ClinicalTrials.gov (NCT02701543).
Integrated management of atrial fibrillation in primary care: results of the ALL-IN cluster randomized trial
Authors: van den Dries Carline J , van Doorn Sander , Rutten Frans H , Oudega Ruud , van de Leur Sjef J C M , Elvan Arif , Oude Grave Lisa , Bilo Henk J G , Moons Karel G M , Hoes Arno W , Geersing Geert-Jan 
Published: January 2020

Abstract

Aims
To evaluate whether integrated care for atrial fibrillation (AF) can be safely orchestrated in primary care.

Methods and results
The ALL-IN trial was a cluster randomized, open-label, pragmatic non-inferiority trial performed in primary care practices in the Netherlands. We randomized 26 practices: 15 to the integrated care intervention and 11 to usual care. The integrated care intervention consisted of (i) quarterly AF check-ups by trained nurses in primary care, also focusing on possibly interfering comorbidities, (ii) monitoring of anticoagulation therapy in primary care, and finally (iii) easy-access availability of consultations from cardiologists and anticoagulation clinics. The primary endpoint was all-cause mortality during 2 years of follow-up. In the intervention arm, 527 out of 941 eligible AF patients aged ≥65 years provided informed consent to undergo the intervention. These 527 patients were compared with 713 AF patients in the control arm receiving usual care. Median age was 77 (interquartile range 72–83) years. The all-cause mortality rate was 3.5 per 100 patient-years in the intervention arm vs. 6.7 per 100 patient-years in the control arm [adjusted hazard ratio (HR) 0.55; 95% confidence interval (CI) 0.37–0.82]. For non-cardiovascular mortality, the adjusted HR was 0.47 (95% CI 0.27–0.82). For other adverse events, no statistically significant differences were observed.

Conclusion
In this cluster randomized trial, integrated care for elderly AF patients in primary care showed a 45% reduction in all-cause mortality when compared with usual care.
Peri-procedural management, implantation feasibility, and short-term outcomes in patients undergoing implantation of leadless pacemakers: European Snapshot Survey
Authors: Lenarczyk Radosław , Boveda Serge , Mansourati Jacques , Russo Vincenzo , Marijon Eloi , Lane Deirdre A , Dagres Nikolaos , Potpara Tatjana S 
Published: January 2020

Abstract
The aim of this European Heart Rhythm Association (EHRA) prospective snapshot survey is to assess procedural settings, safety measures, and short-term outcomes associated with implantation of leadless pacemakers (LLPM), across a broad range of tertiary European electrophysiology centres. An internet-based electronic questionnaire (30 questions) concerning implantation settings, peri-procedural routines, complications, and in-hospital patient outcomes was circulated to centres routinely implanting both LLPMs and transvenous pacemakers (TV-PM). The centres were requested to prospectively include consecutive patients implanted with either LLPMs or TV-PMs during the 10-week enrolment period. Overall, 21 centres from four countries enrolled 825 consecutive patients between November 2018 and January 2019, including 69 (9%) implanted with LLPMs. Leadless pacemakers were implanted mainly under local anaesthesia (69%), by an electrophysiologist (60%), in the electrophysiology laboratory (71%); 95% of patients received prophylactic antibiotics prior to implantation. Most patients on chronic oral anticoagulation were operated on-drug (35%), or during short-term (to 48 h) drug withdrawal (54%). Implantation was successful in 98% of patients and the only in-hospital procedure-related complication was groyne haematoma in one patient. This EHRA snapshot survey provides important insights into LLPM implantation routines and patient outcomes. These findings suggest that despite the unfavourable clinical profile of pacemaker recipients, LLPM implantation is associated with relatively low risk of complications and good short-term outcomes.
Incidence, mechanisms, and clinical impact of inappropriate shocks in patients with a subcutaneous defibrillator
Authors: Rudic Boris , Tülümen Erol , Fastenrath Fabian , Röger Susanne , Goranova Diana , Akin Ibrahim , Borggrefe Martin , Kuschyk Jürgen 
Published: January 2020

Abstract

Aims
Inappropriate shocks (IAS) remain a challenge for patients and physicians after implantation of the subcutaneous implantable cardioverter-defibrillator (S-ICD). The aims were to assess and characterize different patterns of IAS.

Methods and results
Two hundred and thirty-nine patients were implanted with an S-ICD between 2010 and 2018 for primary and secondary prevention. Follow-up data of at least 6 months were analysed. During a mean follow-up of 34.9 ± 16.0 months, a total of 73 shocks occurred in 38 patients (6%). Forty-three (59%) shocks were considered appropriate due to ventricular tachycardia/ventricular fibrillation, while 30 (41%) were inappropriate and occurred in 19 patients (8%). Myopotentials/noise was the most frequent cause of inappropriate shocks (n = 8), followed by T-wave oversensing (n = 6) and undersensing of the QRS, resulting in adaptation of the automatic gain control and inappropriate shock (n = 5). Seventy-four percent of all IAS occurred on the primary vector, while no IAS occurred on the alternate vector. In seven of eight patients (88%), IAS related to myopotentials have occurred on the primary sensing vector. Multivariate analysis identified taller patients, primary sensing vector and first-generation S-ICD device as predictors for IAS. SMART pass effectively reduced the occurrence of IAS in the second-generation S-ICD system.

Conclusion
Inappropriate therapies are less frequently observed on the alternate vector. The primary vector seems to be unfavourable with regard to oversensing caused by myopotentials. Inappropriate shocks were associated with an increased rate of rehospitalization but not mortality. These observations have implications for the prevention of inappropriate S-ICD shocks.
Motion, Contact and Profanity in Rutebeuf’s Tales of ‘Charlot Le Juif’: (Not) Going There, (Not) Touching That
Authors: Simpson James R 
Published: January 2020

Abstract
This article explores what we can learn about the context of thirteenth-century Paris from the relation between what is explicit and implicit in Rutebeuf’s tales of Charlot the Jew. Dated to the 1260s, these two texts – ‘La Disputaison de Charlot et du Barbier de Melun’ and ‘Charlot le juif qui chia dans la peau du lièvre’ – survive in Paris, BnF, MS fr. 1635. In themselves, in relation to one another and in their manuscript context, these tales reveal much about the function of hints and hidden jokes as soundings of intercommunal tensions and polemic in the period between the Paris Disputation of 1240 and the outbursts of violence later in the century. The discussion of the text focuses on the representation of cultural and religious provocation, and especially Rutebeuf ’s possible adumbrating of sensitive issues not always addressed in explicit fashion. Charlot’s seeming resistance to provocation in various regards may thus reflect a context in which Louis IX encouraged the lay population to take direct action in response to any perceived insults against Christianity from the Jewish population.
Developing a European Toolbox to manage potential invasion by emerald ash borer (Agrilus planipennis) and bronze birch borer (Agrilus anxius), important pests of ash and birch
Authors: Evans H F , Williams D , Hoch G , Loomans A , Marzano M 
Published: January 2020

AbstractThe threats posed by the buprestid beetles emerald ash borer (Agrilus planipennis Fairmaire) and bronze birch borer (Agrilus anxius Gory) have been the subject of considerable research, primarily to develop methods for detection and management of the pests. PREPSYS, a Euphresco project, has worked with collaborators globally to assess the ‘state of the art’ for the two insect pests and to identify those measures that would best prepare Europe for potential invasion by the pests, especially emerald ash borer which is now in the western part of Russia and in eastern Ukraine. Building on an excellent exchange of knowledge and discussion at the OECD-sponsored international conference held in Vienna in October 2018, the concept of a European Toolbox to increase preparedness for dealing with the pests has been developed. This includes key components including surveillance, direct intervention, use of natural enemies and increased awareness of the problems associated with the pests. Collaboration is essential in delivering and refining the European Toolbox.