bluuebunny/crossref_metadata_2025_split huggingface dataset:
Research campaigns in the UK National Health Service: patient recruitment and questions of valuation
Authors: Wienroth Matthias , Pearce Caroline , McKevitt Christopher 
Published: May 2019

AbstractThe National Institute for Health Research (NIHR) aims to improve national ‘health and wealth' by providing infrastructural support to enable clinical research in National Health Service settings in England and Wales. Cognisant of the consequences of studies' failure to achieve required numbers of participants, it also actively campaigns to promote patient awareness of research, and willingness to participate in trials. In this paper, we analyse recent NIHR campaigns and policies designed to encourage patients to participate in clinical research to interrogate how they are implicated in the national bioeconomy. In doing so we expand the notion of ‘clinical labour' to include the work of patient recruitment and highlight an emergent obligation on patients to contribute to research processes. Whereas once patient knowledge and experience may have been devalued, here we draw on the concept of ‘assetisation' (Birch 2012) to explore the emergent relationship between healthcare system and patient as research participant. We consider how patients' contribution goes beyond the provision of standardised objects of valuation so that patients themselves may be perceived as assets to, not only recipients of, the national healthcare system.
Fatality of 33‐Year‐Old Man Involving Kratom Toxicity
Authors: Matson Marcus , Schenk Noel 
Published: May 2019

AbstractKratom is an herbal product commonly used for its effects which are similar to opioids and stimulants. Few studies demonstrate the dangers and lethality of Kratom, and most fatalities from Kratom involve other abused substances. In the current case report, a 33‐year‐old white man with a known history of opioid abuse and mental illnesses was found unresponsive in his basement with no obvious signs of trauma. After resuscitative efforts, he was pronounced dead and taken for autopsy evaluation. Blood from the inferior vena cava was analyzed for common abused substances. The laboratory toxicology work‐up revealed positive findings of caffeine, cotinine, and naloxone with low levels of Δ‐9 tetrahydrocannabinol. However, a marked level of mitragynine at 1.9 mg/L was observed, the highest reported to date. Given the facts and evidence, the medical examiner certified the cause of death as “mitragynine toxicity” and the manner of death was classified as an “accident.”
A Mixture of Functional Complex Extracts from Lycium barbarum and Grape Seed Enhances Immunity Synergistically In Vitro and In Vivo
Authors: You Jiaqi , Chang Yaning , Zhao Di , Zhuang Jiafeng , Zhuang Wei 
Published: May 2019

AbstractA mixture of multiple ingredients is often more effective than the individual ingredients. The functions of Lycium barbarum polysaccharide (LBP) glycoconjugate and grape seed procyanidins (GSP) are widely known. Here, we investigated the synergistic immune‐enhancing activity of LBP and GSP. Atomic force microscopy results suggested that the mixture of LBP and GSP exhibited circular structure unlike LBP alone, and the addition of polyphenols may change the spatial conformation of the sugar chain. The changes in the structure were related to the synergistic effect of the two functional agents on immune recovery. In vitro, the proliferation rate of splenocytes was higher in LBP + GSP group (64.16%), rather than the sum of LBP group (13.01%) and GSP group (43.61%) individually used. This synergistical proliferation of splenocytes may be correlated to the increasing intracellular free calcium levels. Furthermore, the mixture significantly enhanced the immunity in vivo, as evident from the recovery of peripheral white blood cell counts in LBP + GSP group (18.535 × 109/L) to normal group levels (18.115 × 109/L) and higher B cell proliferation than normal group (P < 0.05). These results highlight the immune‐enhancing activity of the combination of LBP and GSP associated with the structural changes, which may facilitate the development of functional foods with fewer resources but enhanced activities.Practical ApplicationThe synergistic effects of LBP and GSP on immunomodulatory were better than the sum of the effects of the individual agents both in vitro and in vivo. Our results may provide a research‐based support for the development of related functional products and an insight into the production of food resources with a fewer but more effective functional agents for better results.
Assessment of volume status and volume responsiveness in the ICU: Protocol for an observational, multicentre cohort study
Authors: Schulz Luis F. , Geri Guillaume , Vieillard‐Baron Antoine , Vignon Philippe , Parkin Geoffrey , Aneman Anders 
Published: May 2019

BackgroundExpansion of the intravascular compartment is common to treat haemodynamic instability in ICU patients. The most useful and accurate variables to guide and evaluate a fluid challenge remain debated and incompletely investigated resulting in significant variability in practice. The analogue mean systemic pressure has been reported as a measure of the intravascular volume state.MethodsThis is a protocol and statistical analysis plan for a review of the application of an analogue of the mean systemic pressure and the use of derived variables to assess the volume state and volume responsiveness. A pulmonary artery catheter was used in 286 postoperative cardiac surgical patients to monitor cardiac output before and after a fluid bolus in addition to arterial and central venous pressures. With otherwise similar monitoring, echocardiography was used in 540 general ICU patients to determine cardiac outputs and indices related to intravascular filling. The responses to a fluid bolus or the passive leg raising manoeuvre will be investigated using continuous and dichotomous definitions of volume responsiveness. The results will be stratified according to the method of monitoring cardiac output.ConclusionsThis study investigating 2 cohorts that encompass a wide variety of reasons for haemodynamic instability will illustrate the applicability of the analogue mean systemic pressure and derived variables to assess the volume state and responsiveness. The results may guide the rationale and design of interventional studies.
Cav1.2 regulates osteogenesis of bone marrow‐derived mesenchymal stem cells via canonical Wnt pathway in age‐related osteoporosis
Authors: Fei Dongdong , Zhang Yang , Wu Junjie , Zhang Hui , Liu Anqi , He Xiaoning , Wang Jinjin , Li Bei , Wang Qintao , Jin Yan 
Published: May 2019

AbstractAimsAge‐related bone mass loss is one of the most prevalent diseases that afflict the elderly population. The decline in the osteogenic differentiation capacity of bone marrow‐derived mesenchymal stem cells (BMMSCs) is regarded as one of the central mediators. Voltage‐gated Ca2+ channels (VGCCs) play an important role in the regulation of various cell biological functions, and disruption of VGCCs is associated with several age‐related cellular characteristics and systemic symptoms. However, whether and how VGCCs cause the decreased osteogenic differentiation abilities of BMMSCs have not been fully elucidated.MethodsVoltage‐gated Ca2+ channels related genes were screened, and the candidate gene was determined in several aging models. Functional role of determined channel on osteogenic differentiation of BMMSCs was investigated through gain and loss of function experiments. Molecular mechanism was explored, and intervention experiments in vivo and in vitro were performed.ResultsWe found that Cav1.2 was downregulated in these aging models, and downregulation of Cav1.2 in Zmpste24−/− BMMSCs contributed to compromised osteogenic capacity. Mechanistically, Cav1.2 regulated the osteogenesis of BMMSCs through canonical Wnt/β‐catenin pathway. Moreover, upregulating the activity of Cav1.2 mitigated osteoporosis symptom in Zmpste24−/− mice.ConclusionImpaired osteogenic differentiation of Zmpste24−/− BMMSCs can be partly attributed to the decreased Cav1.2 expression, which leads to the inhibition of canonical Wnt pathway. Bay K8644 treatment could be an applicable approach for treating age‐related bone loss by ameliorating compromised osteogenic differentiation capacity through targeting Cav1.2 channel.
Off‐farm work and technical efficiency on U.S. dairies
Authors: Sabasi Darlington , Shumway C. Richard , Astill Gregory M. 
Published: May 2019

AbstractIn this study, we investigate the impact of an increase in farm households’ off‐farm work on technical efficiency (TE) of U.S. dairies. We present a theoretical framework that implies that an increase in farm household off‐farm work decreases TE. We use two nationally‐representative samples of U.S. dairies (2010 and 2005 Agricultural Resource Management Surveys) and a parametric approach (stochastic frontier analysis) to empirically test the hypothesis. Results are generally consistent with the hypothesis and show that an increase in off‐farm work by the farm household is associated with a significant decrease in TE. In addition, results show that there is a statistically significant difference in TE between small, medium, and large farms. Small farms are associated with significantly higher off‐farm work and have lower TE than large farms, which implies that less off‐farm work by households with larger farms is at least partially responsible for the evidence of economies of scale in the U.S. dairy industry.
Young children’s perceptions of ubiquitous computing and the Internet of Things
Authors: Mertala Pekka 
Published: May 2019

AbstractUbiquitous computing (ubicomp) and the Internet of things (IoT) are turning into everyday household technology at an ever‐increasing pace, for example, in the form of connected toys. However, while ubicomp and IoT are changing and shaping children’s digital and technological landscape, not much is known about how children perceive these omnipresent and concealed forms of digital technology. This qualitatively oriented paper explores 3‐ to 6‐year‐old Finnish children’s perceptions of ubicomp and IoT via interviews and a design task. Initially, the children were skeptical toward the idea that tangible objects, such as toys, could be computer and/or Internet enabled. However, these perceptions were subject to change when children were introduced to a scientific conception of what computers and the Internet are and asked to apply their knowledge to a technological design task. Implications for early years digital literacy education are discussed in the paper.
Fatigue and cognitive impairment in immune thrombocytopenic purpura remain stable over time: short report from a longitudinal study
Authors: Mitchell Eleanor , Frith James , Newton Julia 
Published: May 2019

SummaryImmune thrombocytopenic purpura (ITP) is an autoimmune disorder characterised by low platelet counts and increased bleeding risk. In 2009, two cross‐sectional studies determined that fatigue and cognitive impairment (CI) were common in ITP. Here, we report the results from a longitudinal study of 34 people with ITP. Fatigue severity remained unchanged over 7 years, and CI significantly improved. Future fatigue and CI severity could be predicted using baseline severity scores. These findings may be reassuring for ITP patients, as symptoms remain stable over time. Furthermore, using baseline scores to predict future severity could aid the clinical management of ITP.
Cell volume regulation in cancer cell migration driven by osmotic water flow
Authors: Morishita Kazuhiro , Watanabe Kengo , Ichijo Hidenori 
Published: May 2019

AbstractCancer metastasis is the most frequent cause of death for patients with cancer. The main current treatment for cancer metastasis is chemotherapy targeting cancer cells’ ability to proliferate. However, some types of cancer cells show resistance to chemotherapy. Recently, cancer cell migration has become the subject of interest as a novel target of cancer therapy. Cell migration requires many factors, such as the cytoskeleton, cell‐matrix adhesion and cell volume regulation. Here, we focus on cell volume regulation and the role of ion/water transport systems in cell migration. Transport proteins, such as ion channels, ion carriers, and aquaporins, are indispensable for cell volume regulation under steady‐state conditions and during exposure to osmotic stress. Studies from the last ~25 years have revealed that cell volume regulation also plays an important role in the process of cell migration. Water flow in accordance with localized osmotic gradients generated by ion transport contributes to the driving force for cell migration. Moreover, it has been reported that metastatic cancer cells have higher expression of these transport proteins than nonmetastatic cancer cells. Thus, ion/water transport proteins involved in cell volume regulation and cell migration could be novel therapeutic targets for cancer metastasis. In this review, after presenting the importance of ion/water transport systems in cell volume regulation, we discuss the roles of transport proteins in a pathophysiological context, especially in the context of cancer cell migration.
Influence of maternal microbiota during pregnancy on infant immunity
Authors: Nyangahu D D , Jaspan H B 
Published: May 2019

SummaryMicrobiota from various maternal sites, including the gut, vagina and breast milk, are known to influence colonization in infants. However, emerging evidence suggests that these sites may exert their influence prior to delivery, in turn influencing fetal immune development. The dogma of a sterile womb continues to be challenged. Regardless, there is convincing evidence that the composition of the maternal gut prior to delivery influences neonatal immunity. Therefore, while the presence and function of placental microbiome is not clear, there is consensus that the gut microbiota during pregnancy is a critical determinant of offspring health. Data supporting the notion of bacterial translocation from the maternal gut to extra-intestinal sites during pregnancy are emerging, and potentially explain the presence of bacteria in breast milk. Much evidence suggests that the maternal gut microbiota during pregnancy potentially determines the development of atopy and autoimmune phenotypes in offspring. Here, we highlight the role of the maternal microbiota prior to delivery on infant immunity and predisposition to diseases. Moreover, we discuss potential mechanisms that underlie this phenomenon.
Expression of brain‐derived neurotrophic factor and structural plasticity in the dentate gyrus and CA2 region correlate with epileptiform activity
Authors: Tulke Susanne , Haas Carola A. , Häussler Ute 
Published: May 2019

AbstractObjectiveHippocampal sclerosis is a hallmark of mesial temporal lobe epilepsy (MTLE), comprising gliosis and neuronal loss in the hippocampus. However, dentate granule cells and CA2 pyramidal cells (PCs) survive, as they share physiological characteristics that may render them less sensitive to hyperexcitation in MTLE. Here, we asked whether both engage similar molecular plasticity mechanisms to support their resilience in MTLE. We chose brain‐derived neurotrophic factor (BDNF), correlated the expression with activity, and used neuropeptide Y (NPY) and principal cell dispersion as plasticity readout.MethodsAdult male mice received a unilateral intrahippocampal kainate injection to induce status epilepticus (SE) and bilateral electrodes into the dentate gyrus and CA2 for in vivo recordings and quantification of epileptiform activity. To assess the time course of Bdnf mRNA expression in these regions, we performed fluorescence in situ hybridization, complemented by immunohistochemistry for NPY and quantification of principal cell dispersion.ResultsWe show that Bdnf expression was transiently up‐regulated during SE in the granule cell layer (GCL) and CA2 and, after a slight reduction at 2 days, increased persistently in both regions ipsilaterally. Intrahippocampal recordings revealed a threshold for the duration of SE to induce these changes. Recurrent epileptiform activity developed in the ipsilateral dentate gyrus and CA2 over time and was correlated with Bdnf mRNA levels, although more pronounced in the dentate gyrus. The dispersion of the GCL and CA2 correlated with Bdnf mRNA expression. NPY protein expression was only increased in granule cells and mossy fibers, remaining unchanged in CA2.SignificanceOur study reveals differential molecular plasticity changes in granule cells and CA2 PCs despite many similarities (epileptiform activity, somatic mossy fiber input, dispersion). These findings contribute to the understanding of common as well as individual characteristics of the cell populations underlying the epileptic hippocampal network.
miR‐216a promotes breast cancer cell apoptosis by targeting PKCα
Authors: Cui Ying , Wang Jinghao , Liu Shanshan , Qu Di , Jin Hong , Zhu Lin , Yang Jiani , Zhang Jingchun , Li Qingwei , Zhang Yanqiao , Yao Yuanfei 
Published: May 2019

AbstractBreast cancer (BC) is the most common cause of death in women throughout the world. MicroRNAs (miRNAs, miR) have been identified as key regulators in carcinogenesis of several cancers, including BC. MicroRNA‐216a (miR‐216a) is downregulated in several cancers. Here, we evaluated the effects of miRNA‐216a on breast cancer cells and the underlying mechanisms. miR‐216a level was quantified by real‐time RT‐PCR. Cell viability was analyzed by MTT assay. Wound‐healing assay was performed for detection of cell migration. Apoptosis was detected by TUNEL and caspase‐3 activity assay. Moreover, the level of protein expression was determined by Western blot. We found that miR‐216a expression was remarkably decreased in both human BC tissues and MCF‐7 cells. miR‐216a overexpression dramatically suppressed the migration and promoted the apoptosis in cultured MCF‐7 cells. We validated PKCα (protein kinase C alpha, PRKCA) as a direct target of miR‐216a. Knockdown of PKCα induced apoptosis and inhibited migration in cultured MCF‐7 cells which were reversed by miR‐216a inhibitor. Moreover, the level of miR‐216a is negatively correlated with PKCα in cell lines. Our results collectively suggest that miR‐216a suppressed migration and promoted apoptosis in breast cancer cells by targeting PKCα. These findings indicate that manipulation of miR‐216a expression may represent a novel therapeutic strategy in the treatment of breast cancer.
Phase‐field‐crystal study on deformation behavior of nanoscale monocrack system in the ductile‐to‐brittle transition region
Authors: Hu Shi 
Published: May 2019

AbstractPhase‐field‐crystal method is applied to study deformation behavior in the ductile‐to‐brittle transition region of the nanoscale monocrack system in this work. The influence of temperature, crystal orientation angle, and crack shape on the deformation behavior is investigated. Temperature can induce fracture mode change, while crystal orientation angle and crack shape can only affect the specific evolutionary behavior. In the ductile region, if the orientation of a vertex is approximately aligned with a certain close‐packed direction, crack extends shortly in cleavage mode at this vertex, which means cleavage crack propagation can be promoted in a particular range of crystal orientation angle. Additionally, the influence of crack shape is achieved by varying the orientation relationship between crack and lattice structure. In the brittle region, crystal orientation angle impacts on the specific cleavage evolution process, and crack shape can promote or hinder plastic deformation by affecting stress concentration.
Ratcheting‐fatigue behaviour of bainite 2.25Cr1MoV steel with tensile and compressed hold loading at 455°C
Authors: Zhao Z. , Yu D. , Chen G. , Chen X. 
Published: May 2019

AbstractThe ratcheting behaviour of a bainite 2.25Cr1MoV steel was studied with various hold periods at 455°C. Particular attention was paid to the effect of stress hold on whole‐life ratcheting deformation, fatigue life, and failure mechanism. Results indicate that longer peak hold periods stimulate a faster accumulation of ratcheting strain by contribution of creep strain, while double hold at peak and valley stress has an even stronger influence. Creep strains produced in peak and valley hold periods are noticeable and result in higher cyclic strain amplitudes. Dimples and acquired defects are found in failed specimen by microstructure observation, and their number and size increase under creep‐fatigue loading. Enlarged cyclic strain amplitude and material deterioration caused by creep lead to fatigue life reduction under creep‐fatigue loading. A life prediction model suitable for asymmetric cycling is proposed based on the linear damage summation rule.
Novel biomarkers to assess in utero effects of maternal opioid use: First steps toward understanding short‐ and long‐term neurodevelopmental sequelae
Authors: Goetzl Laura , Thompson‐Felix Tara , Darbinian Nune , Merabova Nana , Merali Salim , Merali Carmen , Sanserino Kathryne , Tatevosian Tamara , Fant Bruno , Wimmer Mathieu E 
Published: May 2019

AbstractMaternal opioid use disorder is common, resulting in significant neonatal morbidity and cost. Currently, it is not possible to predict which opioid‐exposed newborns will require pharmacotherapy for neonatal abstinence syndrome. Further, little is known regarding the effects of maternal opioid use disorder on the developing human brain. We hypothesized that novel methodologies utilizing fetal central nervous system‐derived extracellular vesicles isolated from maternal blood can address these gaps in knowledge. Plasma from opioid users and controls between 9 and 21 weeks was precipitated and extracellular vesicles were isolated. Mu opioid and cannabinoid receptor levels were quantified. Label‐free proteomics studies and unbiased small RNA next generation sequencing was performed in paired fetal brain tissue. Maternal opioid use disorder increased mu opioid receptor protein levels in extracellular vesicles independent of opioid equivalent dose. Moreover, cannabinoid receptor levels in extracellular vesicles were upregulated with opioid exposure indicating cross talk with endocannabinoids. Maternal opioid use disorder was associated with significant changes in extracellular vesicle protein cargo and fetal brain micro RNA expression, especially in male fetuses. Many of the altered cargo molecules and micro RNAs identified are associated with adverse clinical neurodevelopmental outcomes. Our data suggest that assays relying on extracellular vesicles isolated from maternal blood extracellular vesicles may provide information regarding fetal response to opioids in the setting of maternal opioid use disorder. Prospective clinical studies are needed to evaluate the association between extracellular vesicle biomarkers, risk of neonatal abstinence syndrome and neurodevelopmental outcomes.