bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solitary serum methotrexate level 36 hours post high‐dose methotrexate: A safe, efficacious, and cost‐effective strategy to monitor methotrexate toxicities in childhood leukemia in resource‐limited centers
Authors: Khera Sanjeev , Kapoor Rajan , Pramanik Suman Kumar 
Published: May 2020

AbstractBackgroundThe standard practice during high‐dose methotrexate (HD‐MTX) in acute lymphoblastic leukemia (ALL) to mitigate toxicity is to serially monitor levels till serum MTX < 0.01 μmol/L. Most resource‐limited centers lack in‐house access to MTX levels, and therefore repeated monitoring is costly and cumbersome. We studied the efficacy and safety of “solitary 36 hours post HD‐MTX levels (MTX36).”ProcedureThis prospective observational study consecutively enrolled children with ALL receiving HD‐MTX. Cycles with unavailable MTX36 and MTX36 > 10 μmol/L were excluded. HD‐MTX was administered over 24 hours (BFM‐2009 protocol) with 12 hours of prehydration. MTX36 were performed at other centers. Leucovorin was given in six hourly doses 36 hours post HD‐MTX. Hydration was continued until the last dose of leucovorin. MTX toxicities, including change of creatinine from baseline at 36 hours (∆Cr36), were noted. Two groups depending on MTX36(≤1 μmol/L vs > 1 μmol/L) received six versus eight doses of leucovorin, and toxicities were compared.ResultsTwenty‐nine children with median age five years (1‐11) who received 100 HD‐MTX cycles with a median MTX dose of 3 g/m2 (2‐5) were analyzed. The median MTX36 level was 1.165 μmol/L (0.1‐7.32). Toxicities of HD‐MTX (CTCAE‐4.0): transaminitis‐22%; creatinine elevation ≥ 1.25 times baseline‐24%; cytopenias‐16%; mucositis‐17%; acute kidney injury (AKI)‐6%. All toxicities were ≤CTCAE grade 3. Creatinine elevation, AKI, and mucositis were significantly higher in the group with higher MTX36. There was no correlation (r = 0.3) between ∆Cr36 and MTX36. MTX36 was thrice more economical than the standard protocol.ConclusionMTX36 is a potential cost‐effective, efficacious, and safe limited sample strategy to monitor HD‐MTX, particularly in centers where in‐house MTX levels are unavailable.
Larvicidal and histopathological efficacy of inhabitant pathogenic bacterial strains to reduce the dengue vector competence
Authors: Rajagopal Gopalan , Jeyavani Jeyaraj , Ilango Sakkanan 
Published: May 2020

AbstractBACKGROUNDAedes aegyptiis a primary vector of dengue virus, and the causative agent of dengue is emerging globally as one of the most important arboviral diseases currently threatening human populations. Therefore, vector control is presently the primary intervention method of population reduction, in which naturalA. aegyptipopulations would be reduced with inhabitant bacterial strains that are unable to transmit dengue virus.RESULTBased on the pathogenicity of strains, only four isolates effectively show larvicidal activity. The 16S rRNA gene sequences and the phylogeny depicted that the potential isolates wereBacillus firmus(MK791255),Bacillus paramycoides(MK788268),Bacillus siamensis(MK788212), andBacillus licheniformis(MK791256). After 24 and 48 hours exposure, theB. licheniformisstrain (cell mass of 2.2 × 107CFU mL–1) showed potent larvicidal activity with LC50of 16.22 μg mL–1and 9.57 μg mL–1and theB. paramycoides(cell mass of 3.1 × 107CFU mL–1) strain inhibits the larval and pupal development with LC50of 42.62 μg mL–1and 26.97 μg mL–1. Intermittent stages and causes of abscess in the gut and siphon regions were observed through histopathological studies. These two bacterial strains extend larval duration up to 15–16 days as well as reduce development.CONCLUSIONThese studies demonstrate the challenge for dengue vector in reducing developmental and reproduction competence. © 2020 Society of Chemical Industry
Observer normal forms for a class of nonlinear systems by means of coupled auxiliary dynamics
Authors: Wang Li‐Fei , Boutat Driss , Liu Da‐Yan 
Published: May 2020

SummaryThis work aims at developing a class of nonlinear dynamical systems that can be converted into nonlinear observer normal forms, which support the well‐known high gain observer. This will be performed by means of the so‐called dynamics extension method, which explicitly supplies a set of auxiliary dynamics and changes of coordinates. In this work, the target nonlinear observer normal forms depend on both the output of the studied dynamical systems and the auxiliary variables involved in the definition of the extended dynamics. The method is proposed in a comprehensible way because it does not use differential geometry techniques, such as the Lie brackets calculations of some vector fields. The proposed class of dynamical systems has many practical applications such as epidemic systems, social networks, and so on. To highlight the effectiveness of this algorithm, it supplies an example based on the Maternal Immune Susceptible Exposed Infected and Recovered model.
Understanding Nanomaterial Biotransformation: An Unmet Challenge to Achieving Predictive Nanotoxicology
Authors: Milosevic Ana , Romeo Daina , Wick Peter 
Published: May 2020

AbstractMore than a decade has passed since the first concepts of predictive nanotoxicology were formulated. During this time, many advancements have been achieved in multiple disciplines, including the success stories of the fiber paradigm and the oxidative stress paradigm. However, important knowledge gaps are slowing down the development of predictive nanotoxicology and require a mutidisciplinary effort to be overcome. Among these gaps, understanding, reproducing, and modeling of nanomaterial biotransformation in biological environments is a central challenge, both in vitro and in silico. This dynamic and complex process is still a challenge for today's bioanalytics. This work explores and discusses selected approaches of the multidisciplinary efforts taken in the last decade and the challenges that remain unmet, in particular concerning nanomaterial biotransformation. It highlights some future advancements that, together, can help to understand such complex processes and accelerate the development of predictive nanotoxicology.
Cerebral blood flow and cognitive functioning in patients with disorders along the heart–brain axis
Authors: Leeuwis Anna E. , Hooghiemstra Astrid M. , Bron Esther E. , Kuipers Sanne , Oudeman Eline A. , Kalay Tugba , Brunner‐La Rocca Hans‐Peter , Kappelle L. Jaap , van Oostenbrugge Robert J. , Greving Jacoba P. , Niessen Wiro J. , van Buchem Mark A. , van Osch Matthias J.P. , van Rossum Albert C. , Prins Niels D. , Biessels Geert‐Jan , Barkhof Frederik ,   Heart–Brain Connection consortium, van der Flier Wiesje M. 
Published: May 2020

AbstractIntroductionWe examined the role of hemodynamic dysfunction in cognition by relating cerebral blood flow (CBF), measured with arterial spin labeling (ASL), to cognitive functioning, in patients with heart failure (HF), carotid occlusive disease (COD), and patients with cognitive complaints and vascular brain injury on magnetic resonance imaging (MRI; ie, possible vascular cognitive impairment [VCI]).MethodsWe included 439 participants (124 HF; 75 COD; 127 possible VCI; 113 reference participants) from the Dutch multi‐center Heart–Brain Study. We used pseudo‐continuous ASL to estimate whole‐brain and regional partial volume‐corrected CBF. Neuropsychological tests covered global cognition and four cognitive domains.ResultsCBF values were lowest in COD, followed by VCI and HF, compared to reference participants. This did not explain cognitive impairment, as we did not find an association between CBF and cognitive functioning.DiscussionWe found that reduced CBF is not the major explanatory factor underlying cognitive impairment in patients with hemodynamic dysfunction along the heart–brain axis.
Expression of yeast homolog of the mammal BCRP gene coding for riboflavin efflux protein activates vitamin B2 production in the flavinogenic yeast Candida famata
Authors: Tsyrulnyk Andriy O. , Andreieva Yuliia A. , Ruchala Justyna , Fayura Lyubov R. , Dmytruk Kostyantyn V. , Fedorovych Daria V. , Sibirny Andriy A. 
Published: May 2020

AbstractCandida famata is a representative of a group of so‐called flavinogenic yeast species that overproduce riboflavin (vitamin B2) in response to iron limitation. Overproduced riboflavin accumulates in the cultural medium rather than in the cells suggesting existence of the special mechanisms involved in riboflavin excretion. The corresponding protein and gene have not been identified in yeasts. At the same time, the corresponding gene BCRP has been identified in mammal mammary glands. Several homologs of the mammal BCRP gene encoding putative riboflavin efflux protein (excretase) were identified in Debaryomyces hansenii. The closest homolog was expressed under the control of D. hansenii TEF1 promoter in the riboflavin overproducing strain of C. famata. Resulted transformants overexpressed the corresponding gene and produced 1.4‐ to 1.8‐fold more riboflavin as compared with the parental strain. They also were characterized by overexpression of RIB1 and RIB6 genes of riboflavin synthesis and exhibited elevated specific activity of GTP‐cyclohydrolase II. Membrane localization of the riboflavin excretase was confirmed by fluorescent microscopy.
Simulation and Design of Quantum Circuits
Authors: Zulehner Alwin , Wille Robert 
Published: May 2020

Abstract
Currently, there is an ongoing “race” to build the first practically useful quantum computer that provides substantial speed-ups for certain problems compared to conventional computers. In addition to the development of such devices, this also requires the development of automated tools and methods that provide assistance in the simulation and design of corresponding applications. Otherwise, a situation might be reached where we have powerful quantum computers but hardly any proper means to actually use them. This work provides an overview of corresponding solutions for the task of quantum circuit simulation, the task of quantum circuit design, as well as corresponding mapping tasks. The covered solutions utilise expertise on efficient data structures and algorithms gained in the design of conventional circuits and systems over the last decades. While the respective descriptions are kept brief and mainly convey the general ideas, references to further readings are provided for a more detailed treatment.
Reversible Languages and Incremental State Saving in Optimistic Parallel Discrete Event Simulation
Authors: Schordan Markus , Oppelstrup Tomas , Thomsen Michael Kirkedal , Glück Robert 
Published: May 2020

Abstract
Optimistic parallel discrete event simulation (PDES) requires to do a distributed rollback if conflicts are detected during a simulation due to the massively parallel optimistic execution approach. When a rollback of a simulation is performed each node that is determined to be in a wrong state must be restored to one of its previous states. This can be achieved through reverse computation or by restoring a previous checkpoint. In this paper we investigate and compare both approaches, reverse computation and a variant of checkpointing, incremental state saving (also called incremental checkpointing), to restore a previous program state as part of an optimistic parallel discrete event simulation. We present a benchmark model that is specifically designed for evaluating the performance of approaches to reversibility in PDES. Our benchmarking model has mathematical properties that allow to tune the amount of arithmetic operations relative to the amount of memory operations. These tuning opportunities are the basis for our systematic performance evaluation.
Mind your step: learning to walk in complex environments
Authors: Mowbray Rachel , Cowie Dorothy 
Published: May 2020

AbstractIn everyday contexts, children must respond to both self-related constraints (their own skills and abilities) and environmental constraints (external obstacles and goals). How do young children simultaneously accommodate these to support skilled and flexible behaviour? We used walking in a complex environment as a testbed for two hypotheses. Hypothesis 1: children will accommodate the self-related constraint of high foot placement variability via dynamic scaling. Hypothesis 2: children will plan ahead, even in complex environments. In our task, 3- to 5-year-olds and adults walked over obstacle sequences of varying complexity. We measured foot placement around the first obstacle in the sequence. Hypothesis 1 was partially supported. In simple, single obstacle environments, children engaged in dynamic scaling like adults. Those with more variable foot placement left greater margins of error between the feet and the obstacle. However, in complex, multiple obstacle settings, children employed large, un-tailored margins of error. This parallels other multisensory tasks in which children do not rely on the relative variability of sensory inputs. Hypothesis 2 was supported. Like adults, children planned ahead for environmental constraints. Children adjusted foot placement around the first obstacle depending on the upcoming obstacle sequence. In doing so, they demonstrate surprisingly sophisticated planning. We, therefore, show that in the motor domain, even very young children simultaneously control both self-related and environmental constraints. This allows flexible, safe and efficient behaviour.
Using Blue Intensity from drought-sensitive Pinus sylvestris in Fennoscandia to improve reconstruction of past hydroclimate variability
Authors: Seftigen Kristina , Fuentes Mauricio , Ljungqvist Fredrik Charpentier , Björklund Jesper 
Published: May 2020

AbstractHigh-resolution hydroclimate proxy records are essential for distinguishing natural hydroclimate variability from possible anthropogenically-forced changes, since instrumental precipitation observations are too short to represent the whole spectrum of natural variability. In Northern Europe, progress in this field has been hampered by a relative lack of long and truly moisture-sensitive proxy records. In this study, we provide the first assessment of the dendroclimatic potential of Blue Intensity (BI) and partial ring-width measurements (latewood and earlywood width series) from a network of cold and drought-prone Pinus sylvestris L. sites in Sweden. Our results show that all tree-ring parameters and sites share a clear and strong sensitivity to warm-season precipitation. The ΔBI parameter, in particular, shows considerable potential for hydroclimate reconstructions, here permitting a cross-validated precipitation reconstruction capable of explaining 56% (1901–2010 period) of regional-scale warm-season high-frequency precipitation variance. Using ΔBI as an alternative to ring-width improves the predictive skill with nearly a 20 percentage points increase in explained variance, reduces signal instability over time as well as allows a broader seasonal window (May–July) to be reconstructed. Additionally, we found that earlywood BI also reflect a positive late winter through early summer temperature signal. These findings emphasize that tree-rings, and in particular wood density parameters such as from BI, are capable of providing fundamental information to advance our understanding of hydroclimate variability in regions with a cool and rather humid climate regime that traditionally has been overlooked in studies of past droughts. Increasing the spatio-temporal coverage of hydroclimate records in northern Europe, and taking full advantage of the opportunities offered by the wood densitometric properties should be considered a research priority.
Patient interactive digital support for women with adjuvant endocrine therapy in order to increase compliance and quality of life
Authors: Bergqvist Jenny , Lundström Staffan , Wengström Yvonne 
Published: May 2020

Abstract
Purpose
The primary aim of the study was to develop and investigate a patient interactive digital support (an app) for patients on adjuvant endocrine breast cancer treatment. Patient’s interactive digital applications are a fast-growing area for research and development. In general, patients want more information and support with regard to their diagnosis, treatment and self-care. At the same time, the health care system has limited resources for follow-up. Our primary endpoints were usability of the app and if it added any value to the patients.

Methods
We designed and constructed a prototype, in dialogue with patients, containing four main modules for registration of drug compliance, performed physical exercise, self-care activities, and questions on health and quality of life. The app was then tested by patients and improved further before we completed a pilot study in which 15 patients used the app for 3 months.

Results
Patients perceived the app easy to use with a very high median system usability score of 88.8, range 30–100. The 15 women registered in total 4251 times, range 118 to 372. The majority of registrations concerned compliance (adherence to treatment) and physical exercise.

Conclusion
The app was perceived easy to use and of support in every-day life of breast cancer survivors. How to best integrate electronically collected patient reported outcome measures in clinical routine needs to be further studied, and future research will show if it will be cost-effective in terms of better health outcome and less resource use.
„Pain is inevitable, suffering is optional“: Fallkonzeption in der Kognitiven Verhaltenstherapie
Authors: Mitmansgruber Horst , Fahlböck Andrea , Fink Alexander , Mäni Kogler Liselotte , Müller Ilse , Painold Annamaria , Streicher-Pehböck Christa , Gatterer Gerald 
Published: May 2020

ZusammenfassungAnhand eines praktischen Beispiels werden der diagnostische Prozess und die Fallkonzeption in der Kognitiven Verhaltenstherapie präsentiert. Die Diagnose stellt einen wichtigen Ausgangspunkt für die theoretische Konzeptualisierung und praktische Behandlung mit evidenz-basierten therapeutischen Methoden dar. Die Unterschiede zwischen Patient*innen und ihre idiosynkratische Beziehungsgestaltung in der Therapie erfordern allerdings eine individuelle Fallkonzeption. In einem Diathese-Stress-Modell werden als „Arbeitshypothese“ (1) lebensgeschichtliche Ereignisse und Bedingungen (Stressoren, Traumata etc.) identifiziert und beschrieben, die (2) langjährige (auch interaktionelle) Denk- und Verhaltensmuster als Vulnerabilität nach sich gezogen haben. Zusammen mit (3) Auslösern (aktuellen schema-aktivierenden Situationen) bringen sie (4) die Symptomatik als Muster von Gedanken, Gefühlen und Verhalten hervor. Diese wird (5) durch dysfunktionale Bewältigungsversuche aufrechterhalten und in „Teufelskreisen“ stabilisiert. Kernstück der Diagnostik sind sog. horizontale und vertikale Verhaltensanalysen, die in ein „hypothetisches Bedingungsmodell“ münden. Dieses Modell stellt ein Gesamtbild der Problematik und der interaktionellen Muster auch unter Berücksichtigung der Stärken und Ressourcen einer Person dar. Klinisch nützlich ist ein Fallkonzept, wenn es kollaborativ (in aktiver Mitarbeit von Patient*innen) erstellt und diskutiert wurde und die unmittelbare Ableitung von gemeinsamen therapeutischen Ansatzpunkten und Zielen erlaubt. Gleichzeitig weist es auf mögliche Schwierigkeiten von Patient*innen im therapeutischen Prozess hin (d. h. eventuelle motivationale Barrieren und „Widerstände“). Zentrale Elemente unseres Vorgehens im Entwickeln einer kognitiv-verhaltenstherapeutischen Fallkonzeption illustrieren wir mit dem Fall einer 34-jährigen depressiven Patientin.
Bullying victimization and stress sensitivity in help-seeking youth: findings from an experience sampling study
Authors: Rauschenberg Christian , van Os Jim , Goedhart Matthieu , Schieveld Jan N. M. , Reininghaus Ulrich 
Published: May 2020

AbstractBullying victimization confers the risk for developing various mental disorders, but studies investigating candidate mechanisms remain scarce, especially in the realm of youth mental health. Elevated stress sensitivity may constitute a mechanism linking bullying victimization and mental health problems. In the current study, we aimed to investigate whether exposure to bullying victimization amplifies stress sensitivity in youth’s daily life. The Experience Sampling Method (ESM) was used to measure stress sensitivity [i.e. the association of momentary stress with (i) negative affect and (ii) psychotic experiences] in 42 help-seeking youths (service users), 17 siblings, and 40 comparison subjects (mean age 15 years). Before ESM assessments, bullying victimization at school as well as various psychopathological domains (i.e. depression, anxiety, psychosis) were assessed. Service users exposed to high levels of overall (primary hypotheses) as well as specific types (secondary hypotheses; physical and indirect, but not verbal) of bullying victimization experienced more intense negative affect and psychotic experiences in response to stress compared to those with low exposure levels (all p < 0.05), whereas, in contrast, controls showed either less intense negative affect or no marked differences in stress sensitivity by exposure levels. In siblings, a less consistent pattern of findings was observed. Findings suggest that stress sensitivity may constitute a potential risk and resilience mechanism linking bullying victimization and youth mental health. Interventions that directly target individuals’ reactivity to stress by providing treatment components in real-life using mHealth tools may be a promising novel therapeutic approach.
The importance of non-forest tree stand features for protection of the Syrian Woodpecker Dendrocopos syriacus in agricultural landscape: a case study from South-Eastern Poland
Authors: Michalczuk Jerzy 
Published: May 2020

AbstractNon-forest tree stands are important habitats for many species of birds in the agricultural landscape. They are also the main habitat of the Syrian Woodpecker Dendrocopos syriacus, whose numbers have been decreasing in recent years in some parts of Europe. Recognition of the habitat requirements of this species may help better planning of its protection in the context of the treed agricultural landscapes. During this study, the habitat preferences of the Syrian Woodpecker were determined in the agricultural landscape of South-Eastern Poland. A set of 12 habitat parameters of tree stands located in the breeding territories of the Syrian Woodpecker (n = 122) and in randomly chosen control areas (n = 122) located outside the range of the breeding territories of this species were characterized. The number and species diversity of trees was significantly higher in stands located in Syrian Woodpecker territories than in the random control areas. Stands occupied by breeding pairs also had trees of worse health condition and a larger proportion of fruit trees. The model best explaining the probability of the occurrence of the species indicates that the Syrian Woodpecker requires mainly the presence of tree stands with a greater species diversity of trees, as well as tree stands in worse health condition. When planning the protection of this species’ habitats in the agricultural landscape, the characteristics of non-forest tree stands noted above should be taken into account.