bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population pharmacokinetic–pharmacodynamic modelling of the relationship between testosterone and prostate specific antigen in patients with prostate cancer during treatment with leuprorelin
Authors: Snelder Nelleke , Drenth Henk‐Jan , Riber Bergmann Kirsten , Wood Nolan David , Hibberd Mark , Scott Graham 
Published: February 2019

AimsThis investigation aimed to quantitatively characterize the relationship between the gonadotropin‐releasing hormone agonist leuprorelin, testosterone (T) and prostate specific antigen (PSA) concentrations over time, to aid identification of a target T concentration that optimises the balance of the benefits of T suppression whilst reducing the risk of side effects related to futile over‐suppression.MethodsData from a single dose study to investigate the effect of leuprorelin in a 6‐month depot formulation on T and PSA in prostate cancer patients were analysed using a population pharmacokinetic–pharmacodynamic modelling approach. The developed model was qualified using external data from 3 studies, in which the effect of different formulations of leuprorelin on T and PSA was evaluated in prostate cancer patients.ResultsThe effect of leuprorelin on the relationship between T and PSA was adequately characterized by the Romero model with minor modifications, combined with a turnover model to describe the delay in response between T and PSA. The data were significantly better described when assuming a minimum PSA level that is independent on the treatment‐related reduction in T, as compared to a model with a proportional reduction in PSA and T.ConclusionsThe model‐based analysis suggests that on a population level, reducing T concentrations below 35 ng/dL does not result in a further decrease in PSA levels (>95% of the minimal PSA level is reached). More data are required to support this relationship in the lower T and PSA range.
Childhood, adolescent and young adult non‐Hodgkin lymphoma: current perspectives
Authors: Cairo Mitchell S. , Beishuizen Auke 
Published: February 2019

SummaryThe 6th International Symposium on Childhood, Adolescent and Young Adult (CAYA) Non‐Hodgkin Lymphoma (NHL) was held in Rotterdam, Netherlands, 26–29 September, 2018. This summary manuscript is a perspective on the presentations from the plenary scientific sessions, including wellness and survivorship, B‐cell NHL, AYA lymphoma, translational NHL biology, lymphoma immunology, bone marrow transplantation and cell therapy, T/Natural Killer cell lymphoma, anaplastic large cell lymphoma, lymphoblastic lymphoma, novel lymphoma therapeutics and Hodgkin lymphoma. The symposium was attended by over 260 registrants from 42 different countries and included young, middle and senior investigators. Finally, the Angelo Rosolen, MD, Memorial Lecture was delivered by Alfred Reiter, MD.
Epidemiology, outcome, targeted agents and immunotherapy in adolescent and young adult non‐Hodgkin and Hodgkin lymphoma
Authors: Metzger Monika L. , Mauz‐Körholz Christine 
Published: February 2019

SummaryThe epidemiology, outcome and targeted immunotherapy in adolescent and young adult non‐Hodgkin and Hodgkin lymphoma were discussed during the 6th International Symposium on Childhood, Adolescent and Young Adult Non‐Hodgkin Lymphoma September 26th–29th 2018 in Rotterdam, the Netherlands. This review summarizes some of those presentations, as well as other current and novel antibody therapy, immune check‐point inhibitors, chimeric antigen receptor T cells, cancer vaccines and cytotoxic T lymphocyte therapy.
Mast cells participate in regulation of lung‐gut axis during Staphylococcus aureus pneumonia
Authors: Liu Chao , Yang Liping , Han Yu , Ouyang Wei , Yin Wei , Xu Feng 
Published: February 2019

AbstractObjectivesThe lung‐gut axis is known to be involved in the pathogenesis of Staphylococcus aureus pneumonia. However, the underlying mechanisms remain unclear. We examined the role of pulmonary mast cells (MCs) in the regulation of the lung‐gut axis during S. aureus pneumonia.Materials and MethodsWe created a mouse model of S. aureus pneumonia using MC‐deficient mice (KitW‐sh/W‐sh) and examined the level of inflammation, bacterial burden, expression of cathelicidin‐related antimicrobial peptide (CRAMP) and composition of the gut microbiota. We further evaluated anti‐bacterial immunity by administering bone marrow MCs (BMMCs) or CRAMP into the lungs of KitW‐sh/W‐sh mice.ResultsAfter S. aureus challenge, the MC‐deficient mice, compared with wild‐type (WT) mice, displayed attenuated lung inflammation, decreased expression of CRAMP, higher bacterial lung load and disturbance of the intestinal microbiota. Adoptive transfer of BMMCs into the lung effectively reconstituted the host defence against S. aureus in KitW‐sh/W‐sh mice, thus resulting in recovery of S. aureus pneumonia‐induced intestinal dysfunction. Similarly, exogenous administration of CRAMP significantly enhanced anti‐bacterial immunity in the lungs of MC‐deficient mice.ConclusionsThis study provides evidence for the involvement of MCs in the regulation of the lung‐gut axis during S. aureus pneumonia.
Predicting range shifts of Asian elephants under global change
Authors: Kanagaraj Rajapandian , Araujo Miguel B. , Barman Rathin , Davidar Priya , De Rahul , Digal Dinesh K. , Gopi G. V. , Johnsingh A. J. T. , Kakati Kashmira , Kramer‐Schadt Stephanie , Lamichhane Babu R. , Lyngdoh Salvador , Madhusudan M. D. , Ul Islam Najar Muneer , Parida Jyotirmayee , Pradhan Narendra M. B. , Puyravaud Jean‐Philippe , Raghunath R. , Rahim P. P. Abdul , Muthamizh Selvan K. , Subedi Naresh , Trabucco Antonio , Udayraj Swati , Wiegand Thorsten , Williams Amirtharaj C. , Goyal Surendra P. 
Published: February 2019

AbstractAimClimate change alters the water cycle, potentially affecting the distribution of species. Using an ensemble of species distribution models (SDMs), we predicted changes in distribution of the Asian elephant in South Asia due to increasing climatic variability under warming climate and human pressures.LocationIndia and Nepal.MethodsWe compiled a comprehensive geodatabase of 115 predictor variables, which included climatic, topographic, human pressures and land use, at a resolution of 1 km2, and an extensive database on current distribution of elephants. For variable selection, we first developed 14 candidate models based on different hypotheses on elephant habitat selection. For each candidate model, a series of 240 individual models were evaluated using several metrics. Using three climatic and one land use change datasets for two greenhouse gas scenarios, ensemble SDMs were used to predict future projections.ResultsNine predictor variables were selected for ensemble SDMs. Elephant distribution is driven predominantly by changes in climatic water balance (>60%), followed by changes in temperature and human‐induced disturbance. The results suggest that around 41.8% of the 256,518 km2 of habitat available at present will be lost by the end of this century due to combined effects of climate change and human pressure. Projected habitat loss will be higher in human‐dominated sites at lower elevations due to intensifying droughts, leading elephants to seek refuge at higher elevations along valleys with greater water availability in the Himalayan Mountains.Main conclusionsChanges in climatic water balance could play a crucial role in driving species distributions in regions with monsoonal climates. In response, species would shift their range upwards along gradients of water availability and seasonal droughts. Conservation and management of elephant populations under global change should include design of movement corridors to enable dispersal of the elephant and other associated species to more conducive environments.
High cycle fatigue life estimation of materials processed by laser powder bed fusion
Authors: Hovig Even W. , Azar Amin S. , Sunding Martin F. , Andreassen Erik , Sørby Knut 
Published: February 2019

AbstractThe fatigue life of metal components is known to depend on the surface topography. For components made by laser powder bed fusion, the roughness of the as‐built surfaces depends on the orientation of the component surface with respect to the build plate. Surface topographies of AlSi10Mg and Inconel 718 specimens built at 0° to 90° inclination, with 15° increments, were characterised by white light interferometry. Two methods for calculating the stress concentration factor using the surface roughness data are proposed, and the results of each approach are presented and compared. Moreover, a finite element model was developed, in order to analyse the stress field when subsurface porosity is present. The fatigue lifetime estimates suggest that the lifetime of components may differ up to two orders of magnitude, depending on the build orientation.
How “The Blob” affected groundfish distributions in the Gulf of Alaska
Authors: Yang Qiong , Cokelet Edward D. , Stabeno Phyllis J. , Li Lingbo , Hollowed Anne B. , Palsson Wayne A. , Bond Nicholas A. , Barbeaux Steven J. 
Published: February 2019

AbstractWe investigated the distributional shifts of groundfish in response to anomalous ocean conditions, particularly the recent anomalously warm period (2014–2016; “The Blob”), based on data from ten Gulf of Alaska bottom trawl surveys conducted by the Alaska Fisheries Science Center during 1996–2015. Six groundfish species were considered: Pacific cod (Gadus macrocephalus), arrowtooth flounder (Atheresthes stomias), walleye pollock (Gadus chalcogrammus), Pacific ocean perch (Sebastes alutus), northern rock sole (Lepidopsetta polyxystra), and southern rock sole (Lepidopsetta bilineata). Ontogenetic differences were examined by dividing data for each fish species into size classes. Our study demonstrated that after accounting for size‐specific depth preferences, the spatial responses of groundfish to anomalous ocean conditions differed by species and foraging guild in the central Gulf of Alaska. Pacific cod and arrowtooth flounder showed similar responses to ocean warming, but different responses to cooling. In general, Pacific cod moved to deeper depths in warmer years and moved to shallower depths in colder years. Arrowtooth flounder also moved deeper in warmer years. However, in colder years, large arrowtooth flounder (>40 cm) shifted toward shallower depths while smaller‐sized fish shifted toward deeper depths. In warmer years, large pollock (>30 cm) moved to deeper waters while smaller pollock (10–20 cm) moved to shallower waters. Pacific ocean perch exhibited an opposite response to thermal changes in habitat compared with Pacific cod and arrowtooth flounder. They moved deeper in colder years, but there was no clear change in depth as a function of size in response to warmer habitat.
Evidence for the development of local anoxia during the Cambrian SPICE event in eastern North America
Authors: LeRoy Matthew A. , Gill Benjamin C. 
Published: February 2019

AbstractThe later Cambrian Steptoean Positive Carbon Isotope Excursion (SPICE) event was an episode marked by pronounced changes to the global biogeochemical cycles of carbon and sulfur and significant extinctions on several paleocontinents including Laurentia (North America). While the exact cause(s) of these events remains debated, various lines of evidence suggest an increase in the areal extent of anoxia at the seafloor was a likely feature. Here, we explore whether changes in local oxygenation accompanied the onset of the SPICE in southern Laurentia using cores of the Nolichucky and Eau Claire Formations from Ohio and Kentucky, USA, that represent a transect into the Rome Trough/Conasauga intrashelf basin. At our study locations, the initial positive δ13C shift of the SPICE occurs in conjunction with increases in the abundance and δ34S of sedimentary pyrite. Further local redox conditions, tracked using iron speciation analysis, indicate anoxic conditions developed at the two proximal locations after the start of the paired isotopic excursions. However, the location near the basin center shows no indication for anoxia before or during the onset of the SPICE. While this signal may reflect the structure of local redox conditions within the basin, with the development of anoxia limited to the basin margins, we argue that authigenic iron enrichments were muted by sedimentary dilution and/or the enhanced authigenesis of iron‐bearing sheet silicates near the basin center, masking the signal for anoxia there. Regardless of the areal extent of anoxia within the basin, in either scenario the timing of the development of anoxic bottom waters was concurrent with local faunal turnover, features broadly consistent with a global expansion of anoxia playing a role in driving the isotopic trends and extinctions observed during the event.
Scholarships versus training for happiness gained from an education in creativity: A dynamic analytical model
Authors: Zagonari Fabio 
Published: February 2019

AbstractThis paper presents a mathematical model of the dynamic interrelationships between education, creativity and happiness based on both theoretical insights and evidence from recent empirical neurological studies. In this context, the results are conditional on an individual’s learning effort and risk‐aversion. Specifically, I focus on two main determinants of creativity (divergent and convergent thinking) and compare two main educational policies (scholarships versus unstructured training) with regard to their impacts on the happiness gained from creativity in the general and healthy population. A test is provided by matching the model’s predictions with the results of recent neuroscience research. Numerical simulations suggested that improving convergent thinking is more important than improving divergent thinking for creativity to generate happiness throughout an individual’s life, provided that both divergent and convergent thinking have been achieved to a sufficiently large degree, and that unstructured training (i.e., extra‐curricular activities) in divergent thinking (e.g., in accounting schools) is necessary to reach wealthier students who have more difficulty learning. In contrast, scholarships or unstructured training in convergent thinking (e.g., in art schools) are necessary to reach students who learn easily but who are less wealthy.
Agricultural intensification drives butterfly decline
Authors: Habel Jan Christian , Ulrich Werner , Biburger Nina , Seibold Sebastian , Schmitt Thomas 
Published: February 2019

Abstract

Severe losses of insects have taken place over major parts of Europe. This negative trend is assumed to be largely the result of agricultural intensification.

To analyse potential factors causing this loss of species, we assessed butterfly communities at 21 grassland patches. Seventeen of these were distributed across an agricultural landscape dominated by crop fields; four were embedded in two adjoining managed semi‐natural grassland areas. We assessed environmental parameters such as patch size and habitat quality for each grassland patch. We further incorporated the surrounding land‐cover considering different degrees of land‐use intensity. We classified butterfly species into generalists and specialists according their ecological and behavioural characteristics.

As in the managed semi‐natural reference grasslands, species richness and abundance were higher in patches surrounded by extensively used grasslands and unsprayed crop fields, and lower in patches surrounded by sprayed crop fields. Furthermore, blossom density positively affected butterfly occurrence.

Our data revealed that specialised butterfly species mainly occur in managed semi‐natural grassland sites, and are largely absent from other grassland plots embedded in the agricultural matrix.

Our study underlines the negative impacts of intense conventional agriculture on butterfly species richness and abundance and reveals the urgent need for more nature‐friendly cultivation methods. In situ experiments may help to understand and disentangle single drivers causing this negative trend.
Chondroprotection of PPARα activation by WY14643 via autophagy involving Akt and ERK in LPS‐treated mouse chondrocytes and osteoarthritis model
Authors: Zhou Yang , Chen Xiaolei , Qu Ning , Zhang Bing , Xia Chun 
Published: February 2019

AbstractAutophagy maintains cellular homoeostasis. The enhancement of autophagy in chondrocytes could prevent osteoarthritis (OA) progression in articular cartilage. Peroxisome proliferator‐activated receptor α (PPARα) activation may also protect articular chondrocytes against cartilage degradation in OA. However, whether the protective effect of activated PPARα is associated with autophagy induction in chondrocytes is not determined. In this study, we investigated the effect of PPARα activation by its agonist, WY14643, on the protein expression level of Aggrecan and ADAMTS5, and the protein expression level of autophagy biomarkers, including LC3B and P62, using Western blotting analysis in isolated mouse chondrocytes pre‐treated with lipopolysaccharides (LPS, mimicking OA chondrocytes) with or without the autophagy inhibitor chloroquine diphosphate salt. Furthermore, Akt and ERK phosphorylation was detected in LPS‐treated chondrocytes in response to WY14643. In addition, the effect of intra‐articularly injected WY14643 on articular cartilage in a mouse OA model established by the destabilization of the medial meniscus was assessed using the Osteoarthritis Research Society International (OARSI) histopathology assessment system, along with the detection of Aggrecan, ADAMTS5, LC3B and P62 protein levels using immunohistochemistry assay. The results indicated that PPARα activation by WY14643 promoted proteoglycan synthesis by autophagy enhancement in OA chondrocytes in vivo and in vitro concomitant with the elevation of Akt and ERK phosphorylation. Therefore, autophagy could contribute to the chondroprotection of PPARα activation by WY14643, with the implication that PPARα activation by WY14643 may be a potential approach for OA therapy.
Serum semaphorin 7A is associated with the risk of acute atherothrombotic stroke
Authors: You Tao , Zhu Zhengbao , Zheng Xiaowei , Zeng Nimei , Hu Shuhong , Liu Yifei , Ren Lijie , Lu Qiongyu , Tang Chaojun , Ruan Changgeng , Zhang Yonghong , Zhu Li 
Published: February 2019

AbstractSemaphorin 7A (Sema7A), a neural guidance cue, was recently identified to regulate atherosclerosis in mice. However, the clinical relevance of Sema7A with atherosclerotic diseases remains unknown. The aim of this study was to investigate the association between serum Sema7A and the risk of acute atherothrombotic stroke (AAS). We measured serum concentrations of Sema7A in 105 newly onset AAS cases and 105 age‐ and sex‐matched controls, showing that median Sema7A level in AAS cases was over three times of that in controls (5.86 vs 1.66 ng/mL). Adjusted for hypertension, body mass index, fasting blood glucose, total cholesterol, triglyceride, high‐density lipoprotein (HDL)‐cholesterol, low‐density lipoprotein (LDL)‐cholesterol, current smoking and alcohol consumption, multivariate logistic regression showed that higher Sema7A was independently associated with the odds of AAS (OR = 6.40, 95% CI: 2.88‐14.25). Each 1‐standard deviation increase in Sema7A was associated with a threefold higher odds of AAS (OR = 3.42, 95% CI: 1.84‐6.35). Importantly, adding Sema7A to a multivariate logistic model containing conventional cardiovascular risk factors improved the area under receiver operating characteristic curves from 0.831 to 0.891 for the association with AAS. In conclusion, elevated serum Sema7A is independently associated with the risk of AAS, suggesting that it may play a potential role in AAS.
MiR‐802 causes nephropathy by suppressing NF‐κB‐repressing factor in obese mice and human
Authors: Sun Da , Chen Jia , Wu Wei , Tang Ju , Luo Li , Zhang Kun , Jin Libo , Lin Sue , Gao Yitian , Yan Xiaoqing , Zhang Chi 
Published: February 2019

AbstractObesity is associated with significant microvascular complications including renal injuries and may induce end‐stage renal disease. Emerging studies have demonstrated microRNAs (miRNAs) are potential mediators in the pathophysiological process of nephropathy. The present study aimed to investigate the role of miR‐802 in obesity‐related nephropathy and potential molecular mechanisms. Through utilizing obese mouse model and human subjects, we explored the therapeutic benefits and clinical application of miR‐802 in protecting against nephropathy. Renal miR‐802 level was positively correlated with functional parameters, including blood urea nitrogen and creatinine in obese mice. Specific silencing of renal miR‐802 improved high fat diet (HFD)‐induced renal dysfunction, structural disorders and fibrosis. The up‐regulated inflammatory response and infiltrated macrophages were also significantly decreased in miR‐802 inhibitor‐treated obese mice. Mechanistically, miR‐802 directly bond to 3ʹ‐UTR of NF‐κB‐repressing factor (NRF) and suppressed its expression. In clinical study, the circulating miR‐802 level was significantly increased in obese subjects, and positively correlated with plasma creatinine level but negatively correlated with creatinine clearance. Taken together, our findings provided evidence that miR‐802/NRF signalling was an important pathway in mediating obesity‐related nephropathy. It is a possible useful clinical approach of treating miR‐802 inhibitor to combat nephropathy.
Maternal and Child Health During Forced Displacement
Authors: Hirani Shela Akbar Ali , Richter Solina 
Published: February 2019

AbstractPurposeTo discuss the effects of forced displacement on maternal and child health, highlight the major pitfalls in delivering humanitarian services to this vulnerable group, and underscore the need for multilayered interventions to improve health, protect rights, and reduce vulnerabilities during forced displacements.MethodsA comprehensive literature search was undertaken from databases including Medline, the Cumulative Index to Nursing and Allied Health Literature (CINAHL),EBSCOhost, Google Scholar, Scopus, and ProQuest. No restrictions were placed on geographical region, type, and year of publication. The key words used were displacement, children, women, health, challenges, disaster response, emergency medicine, terrorism, maladjustment, morbidity, disaster response, cultural sensitivity, and interventions.ConclusionsForced displacement negatively affects maternal and child health. The key challenges during forced displacement include food insecurity, lack of shelter, unavailability of clean water and sanitation, poor infrastructure of healthcare services, unavailability of birth attendants and healthcare professionals to manage medical emergencies, inaccessibility to educational and training facilities, and lack of cultural sensitivity of humanitarian workers. The ultimate outcome of forced displacement is a sudden rise in maternal and child mortality and morbidity, maladjustment, psychological issues, altered familial roles, displaced parenting, and vulnerability to exploitation. In view of Bronfenbrenner's socio‐ecological framework, multilayered interventions are proposed to improve maternal and child health during forced displacements.Clinical RelevanceIn view of the effects of forced displacement on maternal and child health and considering the major pitfalls in the delivery of humanitarian services to this vulnerable group, the proposed multilayered interventions can improve health, protect rights, and reduce vulnerabilities surrounding maternal and child health during forced displacements.