bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors predicting prostate cancer upgrading on magnetic resonance imaging–targeted biopsy in an active surveillance population
Authors: Lai Win Shun , Gordetsky Jennifer B. , Thomas John V. , Nix Jeffrey W. , Rais‐Bahrami Soroush 
Published: January 2017

BACKGROUNDThe objective of this study was to create a nomogram model integrating clinical and multiparametric magnetic resonance imaging (MP‐MRI)–based variables to predict prostate cancer upgrading in a population of active surveillance (AS) patients.METHODSProstate cancer patients on AS who underwent MP‐MRI with magnetic resonance imaging (MRI)/ultrasound (US) fusion–guided biopsy were identified. Clinical and imaging variables, including the prostate‐specific antigen density (PSAD), number of lesions, total lesion volume, total lesion density, Prostate Imaging Reporting and Data System magnetic resonance imaging suspicion score (MRI‐SS), and duration between prereferral systematic and MRI/US fusion–guided biopsy sessions, were assessed. Logistic regression modeling was used to assess upgrading on MRI/US fusion–guided biopsy. A predictive model for upgrading was calculated with the significant factors identified.RESULTSSeventy‐six patients were analyzed with a mean age of 62.5 years and a median prostate‐specific antigen (PSA) level of 5.1 ng/mL. The average duration between prereferral and MRI/US biopsies was 21 months. Twenty patients (26.32%) were upgraded. The PSAD, duration between prereferral and MRI/US biopsies, MRI‐SS, and MRI total lesion density were significantly associated with upgrading. A logistic regression model using these factors to predict upgrading on confirmatory MRI/US fusion biopsy had an area under the curve (AUC) of 0.84, whereas the AUC was 0.69 with PSA alone. On the basis of this model, a nomogram was generated, and using a probability cutoff of 22% as an indication of upgrading, it produced sensitivity, specificity, positive predictive, and negative predictive values of 80%, 81.25%, 57.1%, and 92.86%, respectively.CONCLUSIONSThe integration of MRI findings with clinical parameters can add value to a model predicting upgrading from a Gleason score of 3 + 3 = 6 in men on AS. This can potentially be used as a noninvasive approach to confirm AS patients with low‐risk disease for whom biopsy may be deferred. Cancer 2017;123:1941–1948. © 2017 American Cancer Society.
A qualitative investigation in the role of the baby in recovery from postpartum psychosis
Authors: Plunkett Charlene , Peters Sarah , Wieck Angelika , Wittkowski Anja 
Published: January 2017

Psychosis after childbirth is a rare but severe type of mental health difficulty experienced by perinatal women. Research has explored mothers' experiences of onset and recovery from psychosis after childbirth. This study explored the role of the baby in 12 mothers' experiences of recovery. A thematic analysis of the data identified three core themes that described the role of the baby in the mothers' recovery from psychosis after childbirth. Findings revealed that the baby was central to recovery, experienced by mothers as both helpful and unhelpful. The baby interacted with the mother, increasing self‐efficacy, and reducing emotional distress. Findings also showed that the baby could act as a barrier to recovery by increasing the women's emotional distress and hindering access to help and self‐care. The findings of the study add to the existing evidence based on recovery from psychosis after childbirth. The research and clinical implications of these findings are discussed with reference to the existing literature.Key Practitioner Message

The baby has an important role in recovery from psychosis after childbirth.
The baby can be perceived by mothers to both hinder and help their recovery.
Interacting with the baby can be helpful for the mothers' recovery by improving their self‐efficacy and reducing emotional distress.
Specialist interventions offered by a mother and baby unit can provide practical support that facilitates mother–baby interactions, which helps move women forward in the recovery process.
Quantitative tumor heterogeneity assessment on a nuclear population basis
Authors: Wessel Lindberg Anne‐Sofie , Conradsen Knut , Larsen Rasmus , Friis Lippert Michael , Røge Rasmus , Vyberg Mogens 
Published: January 2017

AbstractImmunohistochemistry Ki‐67 stain is widely used for visualizing cell proliferation. The common method for scoring the proliferation is to manually select and score a hot spot. This method is time‐consuming and will often not give reproducible results due to subjective selection of the hotspots and subjective scoring. An automatic hotspot detection and proliferative index scoring would be time‐saving, make the determination of the Ki‐67 score easier and minimize the uncertainty of the score by introducing a more objective and standardized score.Tissue Micro Array cores stained for Ki‐67 and their neighbor slide stained for Pan Cytokeratin were aligned and Ki‐67 positive and negative nuclei were identified inside tumor regions. A heatmap was calculated based on these and illustrates the distribution of the heterogenous response of Ki‐67 positive nuclei in the tumor tissue. An automatic hot spot detection was developed and the Ki‐67 score was calculated. All scores were compared with scores provided by a pathologist using linear regression models.No significant difference was found between the Ki‐67 scores guided by the developed heatmap and the scores provided by a pathologist. For comparison, scores were also calculated at a random place outside the hot spot and these scores were found to be significantly different from the pathologist scores.A heatmap visualizing the heterogeneity in tumor tissue expressed by Ki‐67 was developed and used for an automatic identification of hot spots in which a Ki‐67 score was calculated. The Ki‐67 scores did not differ significantly from scores provided by a pathologist. © 2017 International Society for Advancement of Cytometry
Two‐step adaptive management for choosing between two management actions
Authors: Moore Alana L. , Walker Leila , Runge Michael C. , McDonald‐Madden Eve , McCarthy Michael A. 
Published: January 2017

AbstractAdaptive management is widely advocated to improve environmental management. Derivations of optimal strategies for adaptive management, however, tend to be case specific and time consuming. In contrast, managers might seek relatively simple guidance, such as insight into when a new potential management action should be considered, and how much effort should be expended on trialing such an action. We constructed a two‐time‐step scenario where a manager is choosing between two possible management actions. The manager has a total budget that can be split between a learning phase and an implementation phase. We use this scenario to investigate when and how much a manager should invest in learning about the management actions available. The optimal investment in learning can be understood intuitively by accounting for the expected value of sample information, the benefits that accrue during learning, the direct costs of learning, and the opportunity costs of learning. We find that the optimal proportion of the budget to spend on learning is characterized by several critical thresholds that mark a jump from spending a large proportion of the budget on learning to spending nothing. For example, as sampling variance increases, it is optimal to spend a larger proportion of the budget on learning, up to a point: if the sampling variance passes a critical threshold, it is no longer beneficial to invest in learning. Similar thresholds are observed as a function of the total budget and the difference in the expected performance of the two actions. We illustrate how this model can be applied using a case study of choosing between alternative rearing diets for hihi, an endangered New Zealand passerine. Although the model presented is a simplified scenario, we believe it is relevant to many management situations. Managers often have relatively short time horizons for management, and might be reluctant to consider further investment in learning and monitoring beyond collecting data from a single time period.
Immunosuppressive treatment in fulminant myocarditis and gene expression pattern associated with, but no histological confirmation of giant cell myocarditis
Authors: Fruhwald Friedrich , Lassner Dirk , Fruhwald Sonja , Gross Ulrich M. , Dapunt Otto , Schultheiss Heinz‐Peter 
Published: January 2017

AbstractA healthy woman with acute onset of pulmonary oedema and severely depressed left ventricular function underwent endomyocardial biopsy under the clinical suspicion of fulminant myocarditis. While awaiting the results of biopsy, the situation deteriorated to Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) and extracorporeal membrane oxygenation was implanted. Finally, immunohistochemistry in biopsy specimen corresponded to fulminant lymphocytic myocarditis, although active myocarditis was excluded. Furthermore, gene expression profiling identified giant cell myocarditis although multinuclear cells were absent. This prompted the start of immunosuppression with cortisone and cyclosporine. The patient fully recovered.
The Role of Learning in Health Technology Assessments: An Empirical Assessment of Endovascular Aneurysm Repairs in German Hospitals
Authors: Varabyova Yauheniya , Blankart Carl Rudolf , Schreyögg Jonas 
Published: January 2017

AbstractChanges in performance due to learning may dynamically influence the results of a technology evaluation through the change in effectiveness and costs. In this study, we estimate the effect of learning using the example of two minimally invasive treatments of abdominal aortic aneurysms: endovascular aneurysm repair (EVAR) and fenestrated EVAR (fEVAR). The analysis is based on the administrative data of over 40,000 patients admitted with unruptured abdominal aortic aneurysm to more than 500 different hospitals over the years 2006 to 2013. We examine two patient outcomes, namely, in‐hospital mortality and length of stay using hierarchical regression models with random effects at the hospital level. The estimated models control for patient and hospital characteristics and take learning interdependency between EVAR and fEVAR into account. In case of EVAR, we observe a significant decrease both in the in‐hospital mortality and length of stay with experience accumulated at the hospital level; however, the learning curve for fEVAR in both outcomes is effectively flat. To foster the consideration of learning in health technology assessments of medical devices, a general framework for estimating learning effects is derived from the analysis. © 2017 The Authors. Health Economics published by John Wiley & Sons, Ltd.
Comparison of protocols measuring diffusion and partition coefficients in the stratum corneum
Authors: Rothe H. , Obringer C. , Manwaring J. , Avci C. , Wargniez W. , Eilstein J. , Hewitt N. , Cubberley R. , Duplan H. , Lange D. , Jacques‐Jamin C. , Klaric M. , Schepky A. , Grégoire S. 
Published: January 2017

AbstractPartition (K) and diffusion (D) coefficients are important to measure for the modelling of skin penetration of chemicals through the stratum corneum (SC). We compared the feasibility of three protocols for the testing of 50 chemicals in our main studies, using three cosmetics‐relevant model chemicals with a wide range of logP values. Protocol 1: SC concentration‐depth profile using tape‐stripping (measures KSC/v and DSC/HSC2, where HSC is the SC thickness); Protocol 2A: incubation of isolated SC with chemical (direct measurement of KSC/v only) and Protocol 2B: diffusion through isolated SC mounted on a Franz cell (measures KSC/v and DSC/HSC2, and is based on Fick's laws). KSC/v values for caffeine and resorcinol using Protocol 1 and 2B were within 30% of each other, values using Protocol 2A were ~two‐fold higher, and all values were within 10‐fold of each other. Only indirect determination of KSC/v by Protocol 2B was different from the direct measurement of KSC/v by Protocol 2A and Protocol 1 for 7‐EC. The variability of KSC/v for all three chemicals using Protocol 2B was higher compared to Protocol 1 and 2A. DSC/HSC2 values for the three chemicals were of the same order of magnitude using all three protocols. Additionally, using Protocol 1, there was very little difference between parameters measured in pig and human SC. In conclusion, KSC/v, and DSC values were comparable using different methods. Pig skin might be a good surrogate for human skin for the three chemicals tested. Copyright © 2017 The Authors Journal of Applied Toxicology published by John Wiley & Sons Ltd.
Micropatterning of reagent‐free, high energy crosslinked gelatin hydrogels for bioapplications
Authors: Heyart Benedikt , Weidt Astrid , Wisotzki Emilia I. , Zink Mareike , Mayr Stefan G. 
Published: January 2017

AbstractHydrogels are crosslinked polymeric gels of great interest in the field of tissue engineering, particularly as biocompatible cell or drug carriers. Reagent‐free electron irradiated gelatin is simple to manufacture, inexpensive and biocompatible. Here, the potential to micropattern gelatin hydrogel surfaces during electron irradiation crosslinking was demonstrated as a promising microfabrication technique to produce thermally stable structures on highly relevant length scales for bioapplications. In the present work, grooves of 3.75 to 170 µm width and several hundred nanometers depth were transferred onto gelatin hydrogels during electron irradiation and characterized by 3D confocal microscopy after exposure to ambient and physiological conditions. The survival and influence of these microstructures on cellular growth was further characterized using NIH 3T3 fibroblasts. Topographical modifications produced surface structures on which the cultured fibroblasts attached and responded by adapting their morphologies. This developed technique allows for simple and effective structuring of gelatin and opens up new possibilities for irradiation crosslinked hydrogels in biomedical applications in which cell attachment and contact guidance are favored. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 320–330, 2018.
Temperature‐Induced Phase Transition Characterization of Responsive Polymer Brushes Grafted onto Nanoparticles
Authors: Schweizerhof Sjören , Demco Dan Eugen , Mourran Ahmed , Keul Helmut , Fechete Radu , Möller Martin 
Published: January 2017

Temperature‐induced phase transition parameters of responsive free polymer and brushes onto nanoparticles are measured using high‐resolution magic‐angle sample spinning (HRMAS) NMR spectroscopy. To this purpose, a two‐state statistical model of temperature dependence of thermodynamic observables is developed and applied to obtain parameters which characterize the process of temperature‐induced phase transition of stimuli‐sensitive polymers. In this investigation the thermodynamic observable is the integral intensity of the 1H HRMAS NMR spectrum peaks and the derived thermodynamic parameters are transition temperature and transition entropy. This approach is applied to investigate the dependence of temperature‐induced coil‐to‐globule transition of poly(N‐isopropylacrylamide), (PNIPAm), asymmetric end functionalized with benzyl and thiol groups (Bn–PNIPAm–SH) on molecular weight in the range 3600–30 000 g mol–1 in aqueous solutions. The characteristics of the phase transition represented by transition temperature, and transition entropy are compared to that of Bn–PNIPAm–SH brushes onto gold nanorods in the same range of molecular weight. The method used for measuring the characteristics of phase transition is based on transverse magnetization relaxation (T2) spin‐echo enhance editing of the integral intensities of the 1H HRMAS NMR spectra. This NMR observable reflects changes in transverse relaxation times as an indicative of the polymer chains conformations and dynamics reached in the process of temperature‐induced phase transition.
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PAX3–FOXO1 is essential for tumour initiation and maintenance but not recurrence in a human myoblast model of rhabdomyosarcoma
Authors: Pandey Puspa R , Chatterjee Bishwanath , Olanich Mary E , Khan Javed , Miettinen Markku M , Hewitt Stephen M , Barr Frederic G 
Published: January 2017

AbstractThe PAX3–FOXO1 fusion gene is generated by a 2;13 chromosomal translocation and is a characteristic feature of an aggressive subset of rhabdomyosarcoma (RMS). To dissect the mechanism of oncogene action during RMS tumourigenesis and progression, doxycycline‐inducible PAX3–FOXO1 and constitutive MYCN expression constructs were introduced into immortalized human myoblasts. Although myoblasts expressing PAX3–FOXO1 or MYCN alone were not transformed in focus formation assays, combined PAX3–FOXO1 and MYCN expression resulted in transformation. Following intramuscular injection into immunodeficient mice, myoblasts expressing PAX3–FOXO1 and MYCN formed rapidly growing RMS tumours, whereas myoblasts expressing only PAX3–FOXO1 formed tumours after a longer latency period. Doxycycline withdrawal in myoblasts expressing inducible PAX3–FOXO1 and constitutive MYCN following tumour formation in vivo or focus formation in vitro resulted in tumour regression or smaller foci associated with myogenic differentiation and cell death. Following regression, most tumours recurred in the absence of doxycycline. Analysis of recurrent tumours revealed a subset without PAX3–FOXO1 expression, and cell lines derived from these recurrent tumours showed transformation in the absence of doxycycline. The doxycycline‐independent oncogenicity in these recurrent tumour‐derived lines persisted even after PAX3–FOXO1 was inactivated with a CRISPR/Cas9 editing strategy. Whereas cell lines derived from primary tumours were dependent on PAX3–FOXO1 and differentiated following doxycycline withdrawal, recurrent tumour‐derived cells without PAX3–FOXO1 expression did not differentiate under these conditions. These findings indicate that PAX3–FOXO1 collaborates with MYCN during early RMS tumourigenesis to dysregulate proliferation and inhibit myogenic differentiation and cell death. Although most cells in the primary tumours are dependent on PAX3–FOXO1, recurrent tumours can develop by a PAX3–FOXO1‐independent mechanism, in which rare cells are postulated to acquire secondary transforming events that were activated or selected by initial PAX3–FOXO1 expression. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
On optimal predefined‐time stabilization
Authors: Jiménez‐Rodríguez E. , Sánchez‐Torres J. D. , Loukianov A. G. 
Published: January 2017

SummaryThis paper addresses the problem of optimal predefined‐time stability. Predefined‐time stable systems are a class of fixed‐time stable dynamical systems for which the minimum bound of the settling‐time function can be defined a priori as an explicit parameter of the system. Sufficient conditions for a controller to solve the optimal predefined‐time stabilization problem for a given nonlinear system are provided. These conditions involve a Lyapunov function that satisfies a certain differential inequality for guaranteeing predefined‐time stability. It also satisfies the steady‐state Hamilton–Jacobi–Bellman equation for ensuring optimality. Furthermore, for nonlinear affine systems and a certain class of performance index, a family of optimal predefined‐time stabilizing controllers is derived. This class of controllers is applied to optimize the sliding manifold reaching phase in predefined time, considering both the unperturbed and perturbed cases. For the perturbed case, the idea of integral sliding mode control is jointly used to ensure robustness. Finally, as a study case, the predefined‐time optimization of the sliding manifold reaching phase in a pendulum system is performed using the developed methods, and numerical simulations are carried out to show their behavior. Copyright © 2017 John Wiley & Sons, Ltd.
Mesenchymal Stem Cell-Derived Extracellular Vesicles as Mediators of Anti-Inflammatory Effects: Endorsement of Macrophage Polarization
Authors: Lo Sicco Claudia , Reverberi Daniele , Balbi Carolina , Ulivi Valentina , Principi Elisa , Pascucci Luisa , Becherini Pamela , Bosco Maria Carla , Varesio Luigi , Franzin Chiara , Pozzobon Michela , Cancedda Ranieri , Tasso Roberta 
Published: January 2017

Abstract
Mesenchymal Stem Cells (MSCs) are effective therapeutic agents enhancing the repair of injured tissues mostly through their paracrine activity. Increasing evidences show that besides the secretion of soluble molecules, the release of extracellular vesicles (EVs) represents an alternative mechanism adopted by MSCs. Since macrophages are essential contributors toward the resolution of inflammation, which has emerged as a finely orchestrated process, the aim of the present study was to carry out a detailed characterization of EVs released by human adipose derived-MSCs to investigate their involvement as modulators of MSC anti-inflammatory effects inducing macrophage polarization. The EV-isolation method was based on repeated ultracentrifugations of the medium conditioned by MSC exposed to normoxic or hypoxic conditions (EVNormo and EVHypo). Both types of EVs were efficiently internalized by responding bone marrow-derived macrophages, eliciting their switch from a M1 to a M2 phenotype. In vivo, following cardiotoxin-induced skeletal muscle damage, EVNormo and EVHypo interacted with macrophages recruited during the initial inflammatory response. In injured and EV-treated muscles, a downregulation of IL6 and the early marker of innate and classical activation Nos2 were concurrent to a significant upregulation of Arg1 and Ym1, late markers of alternative activation, as well as an increased percentage of infiltrating CD206pos cells. These effects, accompanied by an accelerated expression of the myogenic markers Pax7, MyoD, and eMyhc, were even greater following EVHypo administration. Collectively, these data indicate that MSC-EVs possess effective anti-inflammatory properties, making them potential therapeutic agents more handy and safe than MSCs.
Making Sense of Learner Performance on Tests of Productive Vocabulary Knowledge
Authors: Fitzpatrick Tess , Clenton Jon 
Published: January 2017

This article offers a solution to a significant problem for teachers and researchers of language learning that confounds their interpretations and expectations of test data: The apparent simplicity of tests of vocabulary knowledge masks the complexity of the constructs they claim to measure. The authors first scrutinise task elements in two widely cited productive vocabulary measures, Lex30 (Meara & Fitzpatrick, 2000) and the Lexical Frequency Profile (LFP; Laufer & Nation, 1995), to gain a more precise understanding of the relationship between test performance and learner knowledge. Next, in three empirical studies (N = 80, 80, 100) they compare second language learners’ performance on Lex30, as the static point of reference, with LFP and with two new tests designed to investigate specific elements of the vocabulary test tasks. Correlation analyses indicate systematic differences in the tests’ capacity to capture information about the quality of learners’ word knowledge and the size of their vocabulary resource. Using the findings from this empirical work, the authors formulate a model of vocabulary capture onto which test tasks can be mapped. They demonstrate how capturing key elements of the relationship between test scores and lexical competence can guide teachers and researchers in applying and interpreting vocabulary tests.