bluuebunny/crossref_metadata_2025_split huggingface dataset:
The future of oncology pharmacy: European Conference of Oncology Pharmacy 2018
Authors: Meier Klaus , Astier Alain , Boşnak Ahmet Sami , Goněc Roman 
Published: September 2019

Abstract
The way we treat cancer is changing. Scientific and technological advances such as tumour profiling, ‘big data,’ and an increasing number of targeted therapies and combination regimens will result in a paradigm shift away from a ‘one-size-fits-all’ concept toward personalized, on-demand, precision medicine, which will result in smaller, more defined patient populations.
In parallel, the global incidence of cancer is rising, which is placing an increasing strain on medical oncology centres, and driving the evolution of oncology pharmacy. Clinical pharmacists can reduce the pressures on other healthcare resources by taking an increased role in patient care and providing a broader range of services. Pharmacists recognize that technological developments will lead to significant changes in pharmacy services, which will require greater integration with other services within the healthcare system.
Members of the European Society of Oncology Pharmacy (ESOP) met at the 4th European Conference of Oncology Pharmacy (ECOP) meeting in October 2018 for a symposium entitled The Future of Oncology Pharmacy 2025. This review summarizes several topics discussed at the meeting, including the future of medicine, oncology and pharmacy healthcare, provides an update on ESOP activities and presents the ECOP 2018 resolution. This position statement outlines the ESOP perspective on how oncology pharmacy will change over the next decade, and how it will respond to these changes to support oncology pharmacists and achieve better outcomes for patients with cancer.
Force distribution and multiscale mechanics in the mussel byssus
Authors: Cohen Noy , Waite J. Herbert , McMeeking Robert M. , Valentine Megan T. 
Published: September 2019

The byssi of sessile mussels have the extraordinary ability to adhere to various surfaces and withstand static and dynamic loadings arising from hostile environmental conditions. Many investigations aimed at understanding the unique properties of byssal thread–plaque structures have been conducted and have inspired the enhancement of fibre coatings and adhesives. However, a systems-level analysis of the mechanical performance of the composite materials is lacking. In this work, we discuss the anatomy of the byssus and the function of each of the three components (the proximal thread portion, the distal thread portion and the adhesive plaque) of its structures. We introduce a basic nonlinear system of springs that describes the contribution of each component to the overall mechanical response and use this model to approximate the elastic modulus of the distal thread portion as well as the plaque, the response of which cannot be isolated through experiment alone. We conclude with a discussion of unresolved questions, highlighting areas of opportunity where additional experimental and theoretical work is needed.
This article is part of the theme issue ‘Transdisciplinary approaches to the study of adhesion and adhesives in biological systems’.
Graph combinatorics based group-level network inference
Authors: Chen Shuo , Wu Qiong , Hong L. Elliot 
Published: September 2019

AbstractWe consider group-level statistical inference for networks, where outcomes are multivariate edge variables constrained in an adjacency matrix. The graph notation is used to represent a network, where nodes are identical biological units (e.g. brain regions) shared across subjects and edge-variables indicate the strengths of interactive relationships between nodes. Edge-variables vary across subjects and may be associated with covariates of interest. The statistical inference for multivariate edge-variables is challenging because both localized inference on individual edges and the joint inference of a combinatorial of edges (network-level) are desired. Different from conventional multivariate variables (e.g. omics data), the inference of a combinatorial of edges is closely linked with network topology and graph combinatorics. We propose a novel objective function with 𝓁0 norm regularization to robustly capture subgraphs/subnetworks from the whole brain connectome and thus reveal the latent network topology of phenotype-related edges. Our statistical inferential procedure and theories are constructed based on graph combinatorics. We apply the proposed approach to a brain connectome study to identify latent brain functional subnetworks that are associated with schizophrenia and verify the findings using an independent replicate data set. The results demonstrate that the proposed method achieves superior performance with remarkably increased replicability.
IL-10 Promotes Endothelial Progenitor Cell Driven Wound Neovascularization and Enhances Healing via STAT3
Authors: Balaji Swathi , Steen Emily , Wang Xinyi , Vangapandu Hima V. , Templeman Natalie , Blum Alexander J. , Moles Chad M. , Li Hui , Narmoneva Daria A. , Crombleholme Timothy M. , Butte Manish J. , Bollyky Paul L. , Keswani Sundeep G. 
Published: September 2019

AbstractEvidence from prior studies of cutaneous trauma, burns, and chronic diabetic wound repair demonstrates that endothelial progenitor cells (EPCs) contribute tode novoangiogenesis, anti-inflammatory reactions, tissue regeneration, and remodeling. We have shown that IL-10, a potent anti-inflammatory cytokine, promotes regenerative tissue repair in an adult model of dermal scar formation via the regulation of fibroblast-specific hyaluronan synthesis in a STAT3 dependent manner. While it is known that IL-10 drives EPC recruitment and neovascularization after myocardial infarction, its specific mode of action, particularly in dermal wound healing and neovascularization in both control and diabetic wounds remains to be defined. Here we show that IL-10 promotes EPC recruitment into the dermal wound microenvironment to facilitate neovascularization and wound healing of control and diabetic (db/db) wounds via vascular endothelial growth factor (VEGF) and stromal-cell derived factor 1 (SDF-1α) signaling. Inducible skin-specific STAT3 knockout (KO) mice were studied to determine whether the impact of IL-10 on the neovascularization and wound healing is STAT3 dependent. We found that IL-10 treatment significantly promotes dermal wound healing with enhanced wound closure, robust granulation tissue formation and neovascularization. This was associated with elevated wound EPC counts as well as increased VEGF and high SDF-1α levels in control mice, an effect that was abrogated in STAT3 KO transgenic mice. These findings were supportedin vitro, wherein IL-10-enhanced VEGF and SDF-1α synthesis in primary murine dermal fibroblasts. IL-10-conditioned fibroblast media was shown to promote sprouting and network formation in aortic ring assays. We conclude that overexpression of IL-10 in the wound-specific milieu recruits EPCs and promote neovascularization, which occurs in a STAT3-dependent manner via regulation of VEGF and SDF-1α levels. Collectively, our studies demonstrate that IL-10 increases EPC recruitment leading to enhanced neovascularization and healing of dermal wounds.
Defining the adult hippocampal neural stem cell secretome: in vivo versus in vitro transcriptomic differences and their correlation to secreted protein levels
Authors: Denninger JK. , Chen X. , Turkoglu AM. , Sarchet P. , Volk AR. , Yan P. , Kirby ED. 
Published: September 2019

AbstractRecent evidence shows that adult hippocampal neural stem and progenitor cells (NSPCs) secrete a variety of proteins that affect tissue function. Though several individual NSPC-derived proteins have been shown to impact cellular processes like neuronal maturation and stem cell maintenance, a broad characterization of NSPC-secreted factors is lacking. Secretome profiling of low abundance stem cell populations is typically achieved via proteomic characterization of in vitro, isolated cells. Here, we analyzed the in vitro NSPC secretome using conditioned media from cultured adult mouse hippocampal NSPCs and detected over 200 different bioactive proteins with an antibody array. We next assessed the NSPC secretome on a transcriptional level with RNA sequencing (RNAseq) of cultured NSPCs. This comparison revealed that quantification of gene expression did not accurately predict relative protein abundance for several factors. Furthermore, comparing our transcriptional data with previously published single cell RNA sequencing datasets of freshly isolated hippocampal NSPCs, we found key differences in gene expression of secreted proteins between cultured and acutely isolated NSPCs. Understanding the components and functions of the NSPC secretome is essential to understanding how these cells may modulate the hippocampal neurogenic niche, as well as how they can be applied therapeutically. Cumulatively, our data emphasize the importance of using proteomic analysis in conjunction with transcriptomic studies and highlights the need for better methods of global unbiased secretome profiling.
Intracranial pressure elevation alters CSF clearance pathways
Authors: Vinje Vegard , Eklund Anders , Mardal Kent-Andre , Rognes Marie E. , Støverud Karen-Helene 
Published: September 2019

AbstractBackgroundInfusion testing is a common procedure to determine whether shunting will be beneficial in patients with normal pressure hydrocephalus. The method has a well-developed theoretical foundation and corresponding mathematical models that describe the CSF circulation from the choroid plexus to the arachnoid granulations. Here, we investigate to what extent the proposed glymphatic or paravascular pathway (or similar pathways) modifies the results of the traditional mathematical models.MethodsWe used a two-compartment model consisting of the subarachnoid space and the paravascular spaces. For the arachnoid granulations, the cribriform plate, capillaries and paravascular spaces, resistances were calculated and used to estimate flow before and during an infusion test. Next, pressure in the subarachnoid space and paravascular spaces were computed. Finally, different variations to the model were tested to evaluate the sensitivity of selected parameters.ResultsAt baseline, we found a very small paravascular flow directed into the subarachnoid space, while 60% of the fluid left through the arachnoid granulations and 40% left through the cribriform plate. However, during the infusion, paravascular flow reversed and 25% of the fluid left through these spaces, while 60% went through the arachnoid granulations and only 15% through the cribriform plate.ConclusionsThe relative distribution of CSF flow to different clearance pathways depends on intracranial pressure (ICP), with the arachnoid granulations as the main contributor to outflow. As such, ICP increase is an important factor that should be addressed when determining the pathways of injected substances in the subarachnoid space.
Variational Autoencoder Modular Bayesian Networks (VAMBN) for Simulation of Heterogeneous Clinical Study Data
Authors: Gootjes-Dreesbach Luise , Sood Meemansa , Sahay Akrishta , Hofmann-Apitius Martin , Fröhlich Holger 
Published: September 2019

AbstractIn the area of Big Data one of the major obstacles for the progress of biomedical research is the existence of data “silos”, because legal and ethical constraints often do not allow for sharing sensitive patient data from clinical studies across institutions. While federated machine learning now allows for building models from scattered data, there is still the need to investigate, mine and understand clinical data that cannot be accessed directly. Simulation of sufficiently realistic virtual patients could be a way to fill this gap.In this work we propose a new machine learning approach (VAMBN) to learn a generative model of longitudinal clinical study data. VAMBN considers typical key aspects of such data, namely limited sample size coupled with comparable many variables of different numerical scales and statistical properties, and many missing values. We show that with VAMBN we can simulate virtual patients in a sufficiently realistic manner while making theoretical guarantees on data privacy. In addition, VAMBN allows for simulating counterfactual scenarios. Hence, VAMBN could facilitate data sharing as well as design of clinical trials.
SLR-superscaffolder: a de novo scaffolding tool for synthetic long reads using a top-to-bottom scheme
Authors: Guo Lidong , Xu Mengyang , Wang Wenchao , Gu Shengqiang , Zhao Xia , Chen Fang , Wang Ou , Xu Xun , Fan Guangyi , Deng Li , Liu Xin 
Published: September 2019

AbstractSynthetic long reads (SLR) with long-range co-barcoding information have been recently developed and widely applied in genomics researches. We proposed a scaffolding model of the co-barcoding information and developed a scaffolding tool with adopting a top-to-bottom scheme to make full use of the complementary information in SLR datasets and a screening algorithm to reduce negative effects from misassembled contigs in an input assembly. In comparison with other available SLR scaffolding tools, our tool obtained the best quality improvement for different input assemblies, especially for those assembled by the next-generation sequencing reads, where the improvement of contiguity is about several hundred-folds.
Simultaneous Quantitative Determination of Amphetamines, Opiates, Ketamine, Cocaine and Metabolites in Human Hair: Application to Forensic Cases of Drug Abuse
Authors: Zhuo Yue , Wang Xin , Wu Jingjie , Zhang Sujing , Deng Hongxiao , Liu Wei , Wu Hejian , Xiang Ping , Shen Min 
Published: September 2019

AbstractA method using liquid chromatography–tandem mass spectrometry (LC–MS/MS) to simultaneously quantify amphetamines, opiates, ketamine, cocaine, and metabolites in human hair is described. Hair samples (50 mg) were extracted with methanol utilizing cryogenic grinding. Calibration curves for all the analytes were established in the concentration range 0.05–10 ng/mg. The recoveries were above 72%, except for AMP at the limit of quantification (LOQ), which was 48%. The accuracies were within ±20% at the LOQ (0.05 ng/mg) and between −11% and 13.3% at 0.3 and 9.5 ng/mg, respectively. The intraday and interday precisions were within 19.6% and 19.8%, respectively. A proficiency test was applied to the validated method with z‐scores within ±2, demonstrating the accuracy of the method for the determination of drugs of abuse in the hair of individuals suspected of abusing drugs. The hair concentration ranges, means, and medians are summarized for abused drugs in 158 authentic cases.
Can Employee Stock Options Contribute to Less Risk‐Taking?
Authors: Billings Bruce K. , Moon James R. , Morton Richard M. , Wallace Dana M. 
Published: September 2019

ABSTRACTThe executive compensation literature presumes that shareholders offer risk‐averse managers stock options to entice them to take on more risk, resulting in riskier investment decisions and thus a greater return on investment. However, recent empirical work challenges this assumption, and theoretical research even argues that high levels of option‐based compensation for generally under‐diversified managers may actually lead to greater risk aversion. We evaluate the incentive structure of employee stock options by examining the level of R&D investment and the return on that investment conditional on the portfolio “vega,” which captures the sensitivity of option value to stock price volatility. Our results suggest that both investment in R&D and the return on R&D, as measured by future earnings and patent awards, varies concavely with vega. That is, low to moderate levels of vega correspond to increasing investment in and returns on R&D, consistent with vega inducing more profitable investments, but marginal returns decline as vega increases. Collectively, these results, bolstered by several supplemental analyses, suggest that this surprising relation between vega and risky investment is driven by greater risk aversion at higher levels of vega. Overall, our results imply that employee stock options may not always align the incentives of managers and shareholders.
Effects of grazing regime on the relative body mass of the endangered pygmy bluetongue lizard (Tiliqua adelaidensis)
Authors: Nielsen Torben Peiter , Bull Christopher Michael 
Published: September 2019

AbstractMany animals rely on fat reserves, to keep them alive through extended periods of food shortage, such as the winter, and to provide additional energy for reproduction. Fat reserves, measured relative to an animal's size, are often referred to as the animal's body condition. The present study investigated how different levels of grazing by domestic stock in native grassland habitat affect the body condition of the pygmy bluetongue lizard (Tiliqua adelaidensis), and if these effects are related to changes in the abundance and size of grasshoppers which are the lizards primary source of food. The initial hypothesis was that lizards would have the highest body condition in moderately grazed paddocks, because those paddocks would have more grasshoppers than heavily grazed paddocks, and better visual conditions for lizards to catch those grasshoppers than in ungrazed paddocks. The results, however, showed that both lizard body condition and the abundance of grasshoppers increased with decreasing grazing intensity. The connection between lizard body condition and abundance of grasshoppers was complex. Within an activity season, lizard body condition generally declined from spring to summer, while the number of grasshoppers grew. The mean size of grasshoppers seemed to be more important, as lizard body condition was higher in spring, the time of year with the largest grasshoppers. These results show that the intensity of grazing by domestic stock influences the body condition of pygmy bluetongue lizards, but that this effect is not entirely due to the reduction in the number of grasshoppers resulting from grazing.
A homozygous mutation in CMAS causes autosomal recessive intellectual disability in a Kazakh family
Authors: Qu Ronggui , Sang Qing , Wang Xueqian , Xu Yao , Chen Biaobang , Mu Jian , Zhang Zhihua , Jin Li , He Lin , Wang Lei 
Published: September 2019

AbstractIntellectual disability (ID) describes a wide range of serious human diseases caused by defects in central nervous system development and function. Some mutant genes have been found to be associated with these diseases, but not all cases can be explained, thus suggesting that other disease‐causing genes have not yet been discovered. Sialic acid is involved in a number of key biological processes, including embryo formation, nerve cell growth, and cancer cell metastasis, and very recently it has been suggested that N‐acetylneuraminic acid synthase‐mediated synthesis of sialic acid is required for brain and skeletal development. CMP‐sialic acid synthetase (CMAS) is one of four enzymes involved in NeuNAc metabolism, as it catalyzes the formation of CMP‐NeuNAc. Before the present study, no links between mutations in CMAS and incidences of human ID had been reported. In the current study, we recruited a recessive nonsyndromic ID pedigree with consanguineous marriage in which all patients have typical clinical manifestations of ID. We identified the NM_018686.3:c.563G > A (p.Arg188His) substitution in CMAS as being responsible for the disease in this family. Conservation analysis, structural prediction, and enzyme activity experiments demonstrated that (p.Arg188His) influences protein dimerization and alters CMAS enzyme activity. Our results offer a new orientation for future research and clinical diagnosis.
Dementia as a source of social disadvantage and exclusion
Authors: Biggs Simon , Carr Ashley , Haapala Irja 
Published: September 2019

ObjectiveTo explore perceptions of the impacts of dementia on people living with the condition and those close to them and examine the relationship between dementia, disadvantage and social exclusion.MethodsSemi‐structured in‐depth interviews were conducted with 111 participants: people with dementia (n = 19), carers (n = 28), health‐care professionals (n = 21), social workers (n = 23) and service professionals (n = 20). NVivo 11 was used to code descriptions and identify impact areas.ResultsParticipants described social, psychological, carer, material, service‐based and disparity impacts associated with the experience of dementia. Some of these impacts correspond to social exclusion associated with age, but some are distinctive to dementia.DiscussionIt is argued that dementia generates its own forms of social disadvantage and exclusion. This is in addition to being subject to structural risk factors. The implications of the active effects of dementia as a social phenomenon should give rise to new policy and practice priorities.
Offsetting Uncertainty: Reassurance with Two‐Sided Incomplete Information
Authors: Haynes Kyle , K. Yoder Brandon 
Published: September 2019

AbstractConventional models of bargaining and reassurance under incomplete information assume that actors' behavioral signals are objectively cooperative or noncooperative. Even if actors are uncertain of each other's preferences, they know what types of actions the other will view as cooperative. Yet on many real‐world issues, cooperation is subjective, and what constitutes a cooperative action is conditional on the receiver's preferences. We present a formal model showing that in these cases, two‐sided incomplete information actually incentivizes honest behavior and facilitates credible signaling. Because uncertain senders do not know whether a particular action will be interpreted as cooperative, they have little incentive to misrepresent, and instead honestly pursue their true goals. Thus, where cooperation is subjective, mutual uncertainty is “offsetting,” such that credible signals allow actors to quickly and accurately update their beliefs. We illustrate this logic through a case study of the Sino–Soviet split, and highlight the model's implications for contemporary U.S.–China relations.
The association between clinically diagnosed insomnia and age‐related macular degeneration: a population‐based cohort study
Authors: Tsai Der‐Chong , Chen Hsi‐Chung , Leu Hsin‐Bang , Chen Shih‐Jen , Hsu Nai‐Wei , Huang Chin‐Chou , Chen Jaw‐Wen , Lin Shing‐Jong , Chou Pesus 
Published: September 2019

AbstractPurposeThe decreased level of melatonin, the substance involved in the control of the sleep–wake cycle, has been reported among the patients with age‐related macular degeneration (AMD). However, knowledge about the relationship between sleep disturbance and AMD is still limited. This longitudinal case–control study aims to investigate the risk of incident AMD among the patients with clinically diagnosed insomnia using the Taiwan National Health Insurance Research Database.MethodsThe insomnia cohort (n = 15 465) consisted of newly diagnosed insomnia cases aged ≥55 years between 2000 and 2009. Subjects without insomnia, matched for age, gender and enrolment time, were randomly sampled as the control cohort (n = 92 790). Cox proportional hazard regressions were performed to calculate the hazard ratios (HR) of incident AMD for the two cohorts after adjusting for potential confounders.ResultsOf the 108 255 sampled subjects, 2094 (1.9%) were diagnosed with AMD, including 214 (0.2%) with neovascular AMD, during a mean follow‐up period of 5.1 ± 2.8 years. Insomnia patients were more likely to have subsequent AMD than those without insomnia (2.5% versus 1.8%, p < 0.001). Further, the incidence of exudative AMD was also higher in the insomnia cohort than the control cohort (0.3% versus 0.2%, p = 0.002). The adjusted HR was 1.33 (95% confidence interval [CI], 1.18–1.48, p < 0.001) for AMD and 1.67 (95% CI, 1.20–2.33, p = 0.002) for exudative AMD.ConclusionsClinically diagnosed insomnia is an independent indicator for the increased risk of subsequent AMD development.