bluuebunny/crossref_metadata_2025_split huggingface dataset:
The hirudin-like factors HLF3 and HLF4—hidden hirudins of European medicinal leeches
Authors: Müller Christian , Lukas Phil , Sponholz Dana , Hildebrandt Jan-Peter 
Published: May 2020

AbstractThe hirudin-like factors 3 (HLF3) and 4 (HLF4) belong to a new class of leech-derived factors and are present in specimens of the three European medicinal leeches, Hirudo medicinalis, Hirudo verbana, and Hirudo orientalis, respectively. Here we describe the functional analysis of natural and synthetic variants of HLF3 and HLF4. Whereas the natural variants display only very low or no detectable anti-coagulatory activities, modifications within the N-termini in combination with an exchange of the central globular domain have the potency to greatly enhance the inhibitory effects of respective HLF3 and HLF4 variants on blood coagulation. Our results support previous observations on the crucial importance of all parts (both the N- and C-termini as well as the central globular domains) of hirudin and HLF molecules for thrombin inhibition.
A dynamical view of nonlinear conjugate gradient methods with applications to FFT-based computational micromechanics
Authors: Schneider Matti 
Published: May 2020

AbstractFor fast Fourier transform (FFT)-based computational micromechanics, solvers need to be fast, memory-efficient, and independent of tedious parameter calibration. In this work, we investigate the benefits of nonlinear conjugate gradient (CG) methods in the context of FFT-based computational micromechanics. Traditionally, nonlinear CG methods require dedicated line-search procedures to be efficient, rendering them not competitive in the FFT-based context. We contribute to nonlinear CG methods devoid of line searches by exploiting similarities between nonlinear CG methods and accelerated gradient methods. More precisely, by letting the step-size go to zero, we exhibit the Fletcher–Reeves nonlinear CG as a dynamical system with state-dependent nonlinear damping. We show how to implement nonlinear CG methods for FFT-based computational micromechanics, and demonstrate by numerical experiments that the Fletcher–Reeves nonlinear CG represents a competitive, memory-efficient and parameter-choice free solution method for linear and nonlinear homogenization problems, which, in addition, decreases the residual monotonically.
Dissecting innovative trend analysis
Authors: Serinaldi Francesco , Chebana Fateh , Kilsby Chris G. 
Published: May 2020

AbstractInvestigating the nature of trends in time series is one of the most common analyses performed in hydro-climate research. However, trend analysis is also widely abused and misused, often overlooking its underlying assumptions, which prevent its application to certain types of data. A mechanistic application of graphical diagnostics and statistical hypothesis tests for deterministic trends available in ready-to-use software can result in misleading conclusions. This problem is exacerbated by the existence of questionable methodologies that lack a sound theoretical basis. As a paradigmatic example, we consider the so-called Şen’s ‘innovative’ trend analysis (ITA) and the corresponding formal trend tests. Reviewing each element of ITA, we show that (1) ITA diagrams are equivalent to well-known two-sample quantile-quantile (q–q) plots; (2) when applied to finite-size samples, ITA diagrams do not enable the type of trend analysis that it is supposed to do; (3) the expression of ITA confidence intervals quantifying the uncertainty of ITA diagrams is mathematically incorrect; and (4) the formulation of the formal tests is also incorrect and their correct version is equivalent to a standard parametric test for the difference between two means. Overall, we show that ITA methodology is affected by sample size, distribution shape, and serial correlation as any parametric technique devised for trend analysis. Therefore, our results call into question the ITA method and the interpretation of the corresponding empirical results reported in the literature.
Review and reflections about pulsatile ventricular assist devices from history to future: concerning safety and low haemolysis—still needed
Authors: Köhne Inge 
Published: May 2020

AbstractSince the first use of a ventricular assist device in 1963 many extracorporeal and implantable pulsatile blood pumps have been developed. After the invention of continuous flow blood pumps the implantable pulsatile pumps are not available anymore. The new rotary pumps spend a better quality of life because many of the patients can go home. Nevertheless, the extracorporeal pulsatile pumps have some advantages. They are low-cost systems, produce less haemolysis and heart-recovery can be tested easily. Pump failure is easy to realize because the pumps can be observed visually. Pump exchange can be done easily without any chirurgic surgery. As volume displacement pumps they can produce high blood pressure, so they are the only ones suitable for pediatric patients. Therefore, they are indispensable for clinical use today and in the future. In this work, nearly all pulsatile blood pumps used in clinical life are described.
Propensity score matching/reweighting analysis comparing intravenous golimumab to infliximab for ankylosing spondylitis using data from the GO-ALIVE and ASSERT trials
Authors: Gensler L. S. , Chakravarty S. D. , Cameron Chris , Peterson S. , Spin P. , Kafka S. , Nair S. , Deodhar A. 
Published: May 2020

Abstract
Objective
To compare the relative efficacy of intravenous golimumab (GOL IV) and infliximab (IFX) for active ankylosing spondylitis (AS).

Methods
Propensity score (PS) methods were used to compare the efficacy of GOL IV 2 mg/kg and IFX 5 mg/kg using individual patient data (IPD) from the active arms of the phase 3 GO-ALIVE and ASSERT studies. Outcomes included the proportion of patients with a ≥ 20% improvement in the Assessment of Spondyloarthritis International Society Criteria (ASAS20), change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) score, and change from baseline in C-reactive protein (CRP) levels from weeks 4–52.

Results
Before matching, 105 patients were treated with GOL IV and 201 patients were treated with IFX. After matching on all covariates, 118 patients were included in the ASAS20 analysis, 96 in the BASFI analysis, and 160 in the CRP analysis. After matching, GOL IV showed significantly greater improvement in ASAS20 response than IFX for weeks 28–44 (e.g., OR = 9.05 [95% CI 1.62–50.4] at week 44) and was comparable in change from baseline in BASFI scores and CRP levels to IFX at all time points. Results were robust for inclusion of different sets of covariates in scenario analyses.

Conclusions
This is the first analysis of its kind to leverage clinical trial data to compare two biologics using PS methods in the treatment of active AS. Overall, GOL IV was associated with greater improvement in ASAS20 response than IFX in patients with AS at 28, 36, and 44 weeks of follow-up.

Key Points• Although intravenous golimumab (GOL IV) and infliximab (IFX) are the only two IV-based tumor necrosis factor (TNF) inhibitors with demonstrated phase 3 clinical efficacy in patients with ankylosing spondylitis (AS), no study has evaluated their comparative efficacy in a head-to-head trial.• Propensity score matching was used to derive indirect treatment comparisons of GOL IV and IFX for ≥ 20% in the Assessment of Spondyloarthritis International Society Criteria (ASAS20), change in Bath Ankylosing Spondylitis Functional Index (BASFI), and change in C-reactive protein (CRP) using individual patient data from the GO-ALIVE and ASSERT phase 3 trials.• Propensity score matched indirect comparisons showed improved relative efficacy of GOL IV compared to IFX; after matching for up to 16 baseline covariates, GOL IV was associated with significantly greater odds of ASAS20 response at weeks 28, 36, and 44 than IFX as well as equivalent changes from baseline in BASFI and CRP.• This novel application of propensity score matching using data from phase 3 trials, the first analysis of its kind in AS, allowed adjustment for important imbalances in prognostic factors between trials to generate estimates of comparative efficacy between GOL IV and IFX in the absence of a head-to-head trial between these treatments.
Analysis of Drug Effects on iPSC Cardiomyocytes with Machine Learning
Authors: Juhola Martti , Penttinen Kirsi , Joutsijoki Henry , Aalto-Setälä Katriina 
Published: May 2020

AbstractPatient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offer an attractive experimental platform to investigate cardiac diseases and therapeutic outcome. In this study, iPSC-CMs were utilized to study their calcium transient signals and drug effects by means of machine learning, a central part of artificial intelligence. Drug effects were assessed in six iPSC-lines carrying different mutations causing catecholaminergic polymorphic ventricular tachycardia (CPVT), a highly malignant inherited arrhythmogenic disorder. The antiarrhythmic effect of dantrolene, an inhibitor of sarcoplasmic calcium release, was studied in iPSC-CMs after adrenaline, an adrenergic agonist, stimulation by machine learning analysis of calcium transient signals. First, beats of transient signals were identified with our peak recognition algorithm previously developed. Then 12 peak variables were computed for every identified peak of a signal and by means of this data signals were classified into different classes corresponding to those affected by adrenaline or, thereafter, affected by a drug, dantrolene. The best classification accuracy was approximately 79% indicating that machine learning methods can be utilized in analysis of iPSC-CM drug effects. In the future, data analysis of iPSC-CM drug effects together with machine learning methods can create a very valuable and efficient platform to individualize medication in addition to drug screening and cardiotoxicity studies.
The role of the understory in litter DOC and nutrient leaching in boreal forests
Authors: Hensgens Geert , Laudon Hjalmar , Peichl Matthias , Gil Itziar Aguinaga , Zhou Quan , Berggren Martin 
Published: May 2020

AbstractDissolved organic carbon (DOC) derived from plant litter plays an important role in the ecosystem carbon balance and soil biogeochemistry. However, in boreal coniferous forests no integrated understanding exists of how understory vegetation contributes to litter leaching of DOC, nitrogen (N) and phosphorus (P) with different bioavailability at the forest stand level. We characterized water extractable leachates from fresh and decayed litter of dominant canopy and understory sources in a boreal coniferous forest, in order to explore the contribution of understory vegetation as a source of both total and bioavailable forms of DOC, N and P. Recently produced litter from deciduous species (including Vaccinium myrtillus) yielded the highest amounts of DOC. However, this leaching potential decreased exponentially with mass loss through litter decay. The DOC lability generally showed little interspecific variation, although wood derived DOC was more recalcitrant. Lability decreased progressively with litter aging. Water extractable nutrients increased proportionally with DOC, and roughly a quarter (N) or half (P) had directly bioavailable inorganic forms. Scaled to annual litterfall at the forest stand, understory vegetation contributed ~ 80% of the water extractable DOC and nutrients from fresh litter, with > 60% coming from Vaccinium myrtillus alone. However, as litter decomposes, the data suggest a lower leaching potential is maintained with a larger contribution from needle, wood and moss litter. Our study shows that understory vegetation, especially V. myrtillus, is a key driver of litter DOC and nutrient leaching in boreal coniferous forests.
Spatiotemporal Dynamics of Single and Paired Pulse TMS-EEG Responses
Authors: de Goede Annika A. , Cumplido-Mayoral Irene , van Putten Michel J. A. M. 
Published: May 2020

AbstractFor physiological brain function a particular balance between excitation and inhibition is essential. Paired pulse transcranial magnetic stimulation (TMS) can estimate cortical excitability and the relative contribution of inhibitory and excitatory networks. Combining TMS with electroencephalography (EEG) enables additional assessment of the spatiotemporal dynamics of neuronal responses in the stimulated brain. This study aims to evaluate the spatiotemporal dynamics and stability of single and paired pulse TMS-EEG responses, and assess long intracortical inhibition (LICI) at the cortical level. Twenty-five healthy subjects were studied twice, approximately one week apart. Manual coil positioning was applied in sixteen subjects and robot-guided positioning in nine. Both motor cortices were stimulated with 50 single pulses and 50 paired pulses at each of the five interstimulus intervals (ISIs): 100, 150, 200, 250 and 300 ms. To assess stability and LICI, the intraclass correlation coefficient and cluster-based permutation analysis were used. We found great resemblance in the topographical distribution of the characteristic TMS-EEG components for single and paired pulse TMS. Stimulation of the dominant and non-dominant hemisphere resulted in a mirrored spatiotemporal dynamics. No significant effect on the TMS-EEG responses was found for either stimulated hemisphere, time or coil positioning method, indicating the stability of both single and paired pulse TMS-EEG responses. For all ISIs, LICI was characterized by significant suppression of the late N100 and P180 components in the central areas, without affecting the early P30, N45 and P60 components. These observations in healthy subjects can serve as reference values for future neuropsychiatric and pharmacological studies.
Angiography-based quantitative coronary contrast-flow ratio measurements correlate with myocardial ischemia assessed by stress MRI
Authors: Lenk Karsten , Schwarzbach Valentin , Antoniadis Marios , Blum Maximilian , Zeynalova Samira , Hagendorff Andreas , Leistner David , Landmesser Ulf , Lavall Daniel , Laufs Ulrich 
Published: May 2020

AbstractContrast-flow quantitative flow ratio (cQFR) is a new technology for quantitative evaluation of coronary stenosis using computational fluid dynamics based on angiograms. The aim of this study was to assess the sensitivity and specificity of cQFR to detect myocardial ischemia using stress magnetic resonance imaging (MRI) as a reference standard. Patients who received stress MRI and coronary angiography were selected from the hospital database. Relevant ischemia on stress MRI was defined as a perfusion deficit in ≥ 2 of 16 segments. cQFR was quantitated based on 3-dimensional quantitative coronary angiography using QAngio XA3D1.1 software by two blinded and independent investigators. A cQFR of ≤ 0.80 was considered abnormal. Among 87 patients 230 vessels met the criteria for full analysis by cQFR (88%). In vascular territories with a significant perfusion deficit, cQFR was significantly lower compared to areas with normal perfusion (0.72 (0.62–0.78) vs. 0.96 (0.89–0.99); p < 0.001). The sensitivity of cQFR in detecting significant epicardial stenoses of coronary vessels with documented ischemia in stress MRI was 81% (68–90%), the specificity was 88% (82–92%). Diameter stenoses (DS) and area stenoses (AS) in vessels with positive stress MRI were significantly higher than in vessels without ischemia (DS 59.1% (49.4–68.4%) vs. 34.8% (27.1–46.1%) p < 0.001; AS 75.6% (63.0–85.2%) vs. 45.0% (30.8–63.6%), p < 0.001). The analysis reveals a high correlation between coronary stenosis measured by cQFR and ischemic areas detected by stress MRI. The data set the stage to plan randomized studies assessing cQFR measurements with regard to clinical outcomes.
Revisiting Gilbert’s known-key distinguisher
Authors: Grassi Lorenzo , Rechberger Christian 
Published: May 2020

AbstractKnown-key distinguishers have been introduced by Knudsen and Rijmen in 2007 to better understand the security of block ciphers in situations where the key can not be considered to be secret, i.e. the “thing between secret-key model and hash function use-cases”. Trying to find a rigorous model to fit this intuition is still ongoing. The most recent advance by Gilbert (Asiacrypt 2014) describes a new model that—even if it is well justified—seemingly does not match this intuition. AES is often considered as a target of such analyses, simply because AES or its building blocks are used in many settings that go beyond classical encryption. Consider AES-128. Results in the secret-key model cover up to 6 rounds, while results in the chosen-key model reach up to 9 rounds. Gilbert however showed a result in the known-key model that goes even further, covering 10 rounds. Does it mean that the use cases corresponding to the cryptanalysis of hash-function use-cases are inherently less efficient, or is it rather an artifact of the new model? In this paper we give strong evidence for the latter. In Gilbert’s work, two types of arguments or rather conjectures are put forward suggesting that the new model is meaningful. Firstly that the number of “extension rounds” due to the new model is limited to two. And secondly that only a distinguisher that exploits the uniform distribution property can be extended in such way. We disprove both conjectures and arrive at the following results: First, we are also able to show that more than two extension rounds are possible. As a result of this, we describe the first known-key distinguishers on 12 rounds of AES that fit into Gilbert’s model. The second conjecture is disproven by showing that the technique proposed by Gilbert can also be used to extend a known-key distinguisher based on another property: truncated differentials. A potential conclusion of this work would be that the counter-intuitive gap between Gilbert’s known-key model and the chosen-key model is wider than initially thought. We however conclude that results in Gilbert’s model are due to an artifact in the model. To remedy this situation, we propose a refinement of the known-key model which restores its original intent to fit the original intuition.
Objectives, design and main findings until 2020 from the Rotterdam Study
Authors: Ikram M. Arfan , Brusselle Guy , Ghanbari Mohsen , Goedegebure André , Ikram M. Kamran , Kavousi Maryam , Kieboom Brenda C. T. , Klaver Caroline C. W. , de Knegt Robert J. , Luik Annemarie I. , Nijsten Tamar E. C. , Peeters Robin P. , van Rooij Frank J. A. , Stricker Bruno H. , Uitterlinden André G. , Vernooij Meike W. , Voortman Trudy 
Published: May 2020

AbstractThe Rotterdam Study is an ongoing prospective cohort study that started in 1990 in the city of Rotterdam, The Netherlands. The study aims to unravel etiology, preclinical course, natural history and potential targets for intervention for chronic diseases in mid-life and late-life. The study focuses on cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, otolaryngological, locomotor, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. Since 2016, the cohort is being expanded by persons aged 40 years and over. The findings of the Rotterdam Study have been presented in over 1700 research articles and reports. This article provides an update on the rationale and design of the study. It also presents a summary of the major findings from the preceding 3 years and outlines developments for the coming period.
The development of multicultural effectiveness in international student mobility
Authors: Zimmermann Julia , Greischel Henriette , Jonkmann Kathrin 
Published: May 2020

AbstractInternational student mobility (ISM) is an important educational means to increase students’ multicultural effectiveness and their (international) job market potential. In the present study, we investigated ISM effects by addressing the following three research questions: First, how do future sojourners differ from control students in terms of their pre-departure multicultural effectiveness? Second, how does ISM affect the development of multicultural effectiveness above and beyond effects of students’ demographic characteristics, their cultural and educational background, and their previous international mobility experiences? And third, do any of these variables moderate ISM development effects and thus help to explain who benefits most from ISM? We used a sample of N = 3070 students at German higher education institutions who were assigned to three groups (i.e., control students with no mobility plans, present sojourners who participated in ISM during the study period, and a waiting group of future sojourners who participated in ISM in the semester sequencing the study period). The analyses with (moderated) latent change models showed substantially higher pre-departure multicultural effectiveness in present and future sojourners compared with control students as well as positive effects of ISM on the development of multicultural effectiveness. The strongest effects were observed amongst students without previous international mobility experiences. Theoretical implications for the understanding of adaptive development in a globalized world as well as practical inferences for ISM outreach and recruitment strategies are discussed.
Drug Abuse Amongst Adolescent Learners in Townships
Authors: Sedibe Mabatho , Hendricks Nellie Gloria Patricia 
Published: May 2020

AbstractThe study explored the experiences of adolescent learners regarding drug abuse in previously disadvantaged townships in South Africa. A phenomenological research paradigm was employed, and an inductive research approach was implemented. The study followed a qualitative research design focusing on interviews and document analysis as data collection methods. Purposive sampling was done and one-on-one interviews with Life Orientation (LO) teachers in two Gauteng secondary schools were conducted as well as three Non-Governmental Organisations (NGO’s) and Non-Profit Organisations (NPO’s) from different organisations. Focus group interviews were conducted with adolescent learners in two Gauteng secondary schools. I further utilised an inductive content analysis using open coding and axial coding to decipher information gathered from interviews conducted with participants.The study leaned on two theoretical frameworks which include Bronfenbrenner’s Nested System and Erikson’s Eight Stages of Psychosocial Development. The findings indicated that adolescent learners get involved in the use of drugs due to their lack of identity formation and the need to belong. It was also discovered that adolescent learners did not master the adolescence stage successfully, hence getting involved in the use of drugs.