bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prosecuting Crimes against Peace
Authors: Schabas William A. 
Published: November 2018

Abstract
Within the Allied countries, there is near unanimous support for the view that Germany, led by the Kaiser, started the war. International law is at a turning point, with a growing willingness to consider that provoking a war of aggression is not only contrary to international law, but also a crime for which individuals can be punished. Sessions of the Commission on Responsibilities are the first forum for debates about this question. The British and the French insist upon progressive development of the law, evoking a ‘new justice’, while the Americans insist that new rules cannot be applied retroactively. Compromise is reached on this point with a recommendation by the Commission against prosecution of the Kaiser for starting the war, but at the same time a declaration condemning his conduct.
The Kaiser in Limbo
Authors: Schabas William A. 
Published: November 2018

Abstract
The Kaiser did not seem overly concerned about trial and there is no evidence he made any preparations for his defence. With Dutch Government approval, he bought a permanent residence in Doorn, near Utrecht, and proceeded to renovate the place.r The Pope took the initiative to campaign against trial of the Kaiser, and European royalty joined in a variety of initiatives to protect their ‘cousin’. Dutch public opinion appeared to harden in favour of refusing any surrender of the Kaiser. Then, at the end of the year, incriminating documents known as the Kautsky papers were published in Germany showing the Kaiser’s belligerence during the fateful weeks of July 1914.
Developmental Trajectories for the Early Clinical Assessment of Balance by Gross Motor Function Classification System Level for Children With Cerebral Palsy
Authors: LaForme Fiss Alyssa , McCoy Sarah Westcott , Bartlett Doreen , Avery Lisa , Hanna Steven E ,   On Track Study Team
Published: November 2018

Abstract

Background
Children with cerebral palsy (CP) characteristically present with impairments in balance. Currently, the pattern and timing of the development of balance ability have not been described for children with CP of varying Gross Motor Function Classification System (GMFCS) levels.

Objective
The purpose of this study was to document longitudinal developmental trajectories in a measure of balance, the Early Clinical Assessment of Balance (ECAB) scores, along with age-specific reference percentiles and the amount of change typical over a 1-year period for children within different GMFCS levels.

Design
The design was a longitudinal cohort study.

Methods
Participants included 708 children with CP, aged 18 months through their 12th birthday, and their families. Children participated in 2 to 5 assessments using the GMFCS and ECAB.

Results
Longitudinal trajectories describing the average change in the ECAB score with respect to age were created by fitting separate nonlinear mixed-effect models for children in each GMFCS level. Reference percentiles were constructed using quantile regression of ECAB data from the first visit (baseline) and 12-month and 24-month visits. Using these reference points, the amount of change in percentiles was calculated for all children by subtracting the baseline percentile score from the 12-month percentile score. Children whose percentile changes are within the 80% limits can usually be described as “developing as expected” for their age and GMFCS levels.

Limitations
Limitations of this study included use of a convenience sample, a ceiling effect of the ECAB for some children in GMFCS levels I and II, and the use of both a 12-month and 24-month study protocol that impacted the number of children available for each assessment session.

Conclusions
When used appropriately to monitor development and change over time for children with CP, the ECAB longitudinal trajectories, reference percentiles, and the associated change scores presented here should assist therapists and families in collaborative interaction to proactively plan services and interventions relative to balance ability.
Circulating CD24hiCD38hi regulatory B cells correlate inversely with the ThEM17 cell frequency in granulomatosis with polyangiitis patients
Authors: von Borstel Anouk , Lintermans Lucas L , Heeringa Peter , Rutgers Abraham , Stegeman Coen A , Sanders Jan Stephan , Abdulahad Wayel H 
Published: November 2018

Abstract

Objectives
To investigate whether there is a direct relation between expanded proportions of Th17 effector memory (ThEM17) cells and regulatory B cells (Bregs) in peripheral blood of granulomatosis with polyangiitis (GPA) patients.

Methods
Frequencies of Bregs and ThEM17 cells, as well as ThEM1 cells, were determined by flow cytometry in blood samples from 42 GPA patients in remission and 18 matched healthy controls (HCs). The Breg frequency was defined as CD24hiCD38hiCD19+ cells. ThEM17 cells were defined as CCR6+CXCR3-CCR4+ cells and ThEM1 cells as CCR6-CXCR3+CCR4- cells within the CD3+CD4+CD45RO+CCR7- population. In addition, CD3+CD4+ Th cells from 9 GPA patients were co-cultured in vitro with either total B cells or a Breg-depleted B cell fraction. Cultured cells were stimulated with Staphylococcus Enterotoxin B (SEB) and CpG-oligodeoxynucleotides (CpG-ODN). Th17- (IL-17+) and Th1 cell (IFNγ+) frequencies were determined at baseline and day 5 upon restimulation with phorbol myristate acetate (PMA) and Ca-I.

Results
A decreased Breg frequency was found in treated GPA patients, whereas an increased ThEM17 cell frequency was observed in treated and untreated GPA patients compared with HCs. Additionally, a decreased ThEM1 cell frequency was seen in untreated GPA patients compared with HCs. In untreated GPA patients circulating Breg frequencies correlated negatively with ThEM17 cells (r = −0.533; P = 0.007) and positively with ThEM1 cells (r = −0.473; P = 0.015). The co-culture experiments revealed a significant increase in the frequency of IL-17+ Th cells in Breg-depleted samples (median: 3%; range: 1–7.5%) compared with Breg-undepleted samples (P = 0.002; undepleted samples median: 2.1%; range: 0.9–6.4%), whereas no difference in the frequency of IFNγ+ Th cells in Breg-depleted cultures was observed (undepleted median: 11.8%; range: 2.8–21% vs Breg-depleted median: 12.2%; range: 2.6–17.6%).

Conclusion
Bregs modulate ThEM17 responses in GPA patients. Future studies should elaborate on clinical and therapeutical implications of the Breg-Th17 interaction in GPA patients.
Effects of rumen-protected carbohydrate supplementation on performance and blood metabolites in feedlot finishing steers during heat stress
Authors: Russi Juan P , DiLorenzo Nicolas , Relling Alejandro E 
Published: November 2018

Abstract
The objective of this experiment was to evaluate the inclusion of a rumen-protected carbohydrate (RPC) on growth performance and blood metabolites of finishing steers during the summer. A 62-d feedlot study was conducted using 135 Angus crossbred steers (body weight = 287 ± 13 kg). All animals were fed a basal diet (BD), then treatments were top-dressed. The treatments were the same composition and only varied in ruminal degradability. Treatments were 1) a BD with 1 kg/d of a control supplement (0RPC), 2) the BD plus 0.5 kg/d of the control supplement and 0.5 kg/d of RPC (0.5RCP), and 3) the BD with 1 kg/d of RPC supplement (1RPC). Temperature humidity index and cattle panting scores (CPS) were measured daily during the experiment. Growth performance, back-fat over the 12th rib (BF), LM area, blood glucose and plasma insulin, urea, and nonesterified fatty acid concentrations were measured. Data were statistically analyzed (PROC Mixed, SAS) using treatment, time, and their interaction as a fixed variable and pen as a random variable. There were no differences (P &gt; 0.10) between the three treatments on CPS, BF, and LM area on day 62. There was a trend (P = 0.06) for treatment effect for a greater body weight on the 0.5RPC, and a treatment effect for dry matter intake (P = 0.05). Treatment × day interactions were observed for average daily gain (ADG, P =0.04), suggesting a different response to treatments during the different sampling periods. There was a treatment effect for blood glucose concentration (P = 0.03), having the 0RPC the greatest concentration. Treatment × day interactions were found for plasma insulin concentration (P = 0.01). The results suggest that the response to RPC supplementation depends in part on environment. The use of 0.5 kg/d of RPC tends to improve overall body weight; however, the response to RPC on ADG and plasma insulin concentration depend on the time of sampling.
Effects of exercise on HDL functionality
Authors: Ruiz-Ramie Jonathan J. , Barber Jacob L. , Sarzynski Mark A. 
Published: November 2018

Purpose of review
Low HDL-cholesterol (HDL-C) levels are a strong predictor of cardiovascular disease risk and can be improved with regular exercise. However, raising HDL-C levels pharmacologically has not shown convincing clinical benefits. Thus, research has recently focused on identifying therapies that improve HDL function, with exercise representing such a potential therapy. The purpose of this review is to summarize the effects of exercise interventions on HDL function.

Recent findings
The effects of exercise and lifestyle interventions on the primary atheroprotective functions of HDL are reviewed, namely, cholesterol efflux, antioxidative, and anti-inflammatory properties. Differences in study design, study population, and assays are discussed to aid in the interpretation of the reviewed studies.

Summary
There is mixed evidence that regular aerobic exercise improves cholesterol efflux capacity, with recent research suggesting an exercise dose threshold needs to be exceeded to produce beneficial effects. There is preliminary evidence that exercise improves the antioxidative and anti-inflammatory properties of HDL. Although exercise represents a potential therapeutic approach to improve HDL function, the heterogeneity and/or lack of findings warrants more and larger studies to determine what HDL function(s) are most responsive to regular exercise and what dose of exercise elicits the greatest improvements in HDL functionality.
Blended Facilitation as an Effective Implementation Strategy for Quality Improvement and Research in Nursing Homes
Authors: Pimentel Camilla B. , Mills Whitney L. , Palmer Jennifer A. , Dillon Kristen , Sullivan Jennifer L. , Wewiorski Nancy J. , Snow Andrea Lynn , Allen Rebecca S. , Hopkins Susan D. , Hartmann Christine W. 
Published: November 2018

Background:
Blended facilitation, which leverages the complementary skills and expertise of external and internal facilitators, is a powerful strategy that nursing stakeholders and researchers may use to improve implementation of quality improvement (QI) innovations and research performed in nursing homes.

Problem:
Nursing homes present myriad challenges (eg, time constraints, top-down flow of communication, high staff turnover) to QI implementation and research.

Approach:
This methods article describes the theory and practical application of blended facilitation and its components (external facilitation, internal facilitation, relationship building, and skill building), using examples from a mixed QI and research intervention in Veterans Health Administration nursing homes.

Conclusions:
Blended facilitation invites nursing home stakeholders to be equal partners in QI and research processes. Its intentional use may overcome many existing barriers to QI and research performed in nursing homes and, by strengthening relationships between researchers and stakeholders, may accelerate implementation of innovative care practices.
NDRG2 Regulates Adherens Junction Integrity to Restrict Colitis and Tumorigenesis
Authors: Wei Mengying , Ma Yongzheng , Shen Liangliang , Xu Yuqiao , Liu Lijun , Bu Xin , Guo Zhihao , Qin Hongyan , Li Zengshan , Wang Zhe , Wu Kaichun , Yao Libo , Li Jipeng , Zhang Jian 
Published: November 2018

ABSTRACTParacellular barriers play an important role in the pathogenesis of IBDs and maintain gut homeostasis. N-myc downstream-regulated gene 2 (NDRG2) has been reported to be a tumor suppressor gene and inhibits colorectal cancer metastasis. However, whether NDRG2 affects colitis initiation and colitis-associated colorectal cancer is unclear. Here, We found that intestine-specificNdrg2deficiency caused mild spontaneous colitis with ageing, aggravated DSS and TNBS induced colitis, increased AOM-DSS induced colitis-associated tumor.Ndrg2loss led to adherens junction (AJ) structure destructionviaE-cadherin expression attenuation, resulting in diminished epithelial barrier function and increased intestinal epithelial permeability. Mechanistically, NDRG2 enhancing the interaction of E3 ligase FBXO11 with Snail, the repressor of E-cadherin, to promote Snail degradation by ubiquitination, and maintained E-cadherin expression. In human ulcerative colitis patients, reduced NDRG2 expression is positively correlated with severe inflammation. These findings demonstrate that NDRG2 is an essential colonic epithelial barrier regulator and plays important role in gut homeostasis maintenance and colitis-associated tumor development.SUMMARYAdherens junctoin (AJ) as the key part of intestinal epithelial barrier plays important role in the pathogenesis of IBDs. Intestinal specificNdrg2loss attenuates E-cadherin expression and disrupts the integrity of AJ structure which is feasible for colitis and tumor development.
Epigenetic regulation of PAR4-related platelet activation: mechanistic links between environmental exposure and cardiovascular disease
Authors: Corbin Laura J. , Taylor Amy E. , White Stephen J. , Williams Christopher M. , Taylor Kurt , den Bosch Marion T. van , Teasdale Jack E. , Jones Matthew , Bond Mark , Harper Matthew T. , Falk Louise , Groom Alix , Hazell Georgina G J , Paternoster Lavinia , Munafò Marcus R. , Nordestgaard Børge G. , Tybjaerg-Hansen Anne , Bojesen Stig E. , Relton Caroline , Min Josine L. ,   for the GoDMC Consortium, Smith George Davey , Mumford Andrew D. , Poole Alastair W. , Timpson Nicholas J. 
Published: November 2018

AbstractProtease-activated receptor 4 (PAR4) is a potent thrombin receptor. Epigenetic control of theF2RL3locus (which encodes for PAR4) via DNA methylation is associated with both smoking and cardiovascular disease. We examined the association between DNA hypomethylation atF2RL3and risk of cardiovascular disease, focusing on acute myocardial infarction (AMI) (n=853 cases / 2,352 controls). We usedin vitrocell models to dissect the role of DNA methylation in regulating expression ofF2RL3.We investigated the interplay betweenF2RL3DNA methylation and platelet function in human (n=41). Lastly, we used Mendelian randomization to unify observational and functional work by assessing evidence for causal relationships using data from UK Biobank (n=407,141) and CARDIoGRAMplusC4D (n=184,305). Observationally, one standard deviation (SD) decrease in DNA methylation atF2RL3was associated with a 25% increase in the odds of AMI.In vitro, short-term exposure of cells to cigarette smoke reducedF2RL3DNA methylation and increased gene expression. Transcriptional assays flagged a role for a CEBP recognition sequence in modulating the enhancer activity ofF2RL3exon 2. Lower DNA methylation atF2RL3was associated with increased platelet reactivity in human. The estimated casual odds ratio of ischaemic heart disease was 1.03 (95% CI: 1.00, 1.07) per 1 SD decrease inF2RL3DNA. In conclusion, we show that DNA methylation-dependent platelet activation is part of a complex system of features contributing to cardiovascular health. Tailoring therapeutic intervention to new knowledge ofF2RL3/PAR4 function should be explored to ameliorate the detrimental effects of this risk factor on cardiovascular health.One sentence summaryDNA methylation-dependent platelet activation is a likely causal contributor to cardiovascular health.
Shared striatal activity in decisions to satisfy curiosity and hunger at the risk of electric shocks
Authors: Lau Johnny King L , Ozono Hiroki , Kuratomi Kei , Komiya Asuka , Murayama Kou 
Published: November 2018

AbstractCuriosity is often portrayed as a desirable feature of human faculty. However, curiosity may come at a cost that sometimes puts people in a harmful situation. Here, with a set of behavioural and neuroimaging experiments using stimuli that strongly trigger curiosity (e.g., magic tricks), we examined the psychological and neural mechanisms underlying the motivational effect of curiosity. We consistently demonstrated that across different samples, people were indeed willing to gamble, subjecting themselves to physical risks (i.e. electric shocks) in order to satisfy their curiosity for trivial knowledge that carries no apparent instrumental value. Also, this influence of curiosity shares common neural mechanisms with that of extrinsic incentives (i.e. hunger for food). In particular, we showed that acceptance (compared to rejection) of curiosity/incentive-driven gambles was accompanied by enhanced activity in the ventral striatum (when curiosity was elicited), which extended into the dorsal striatum (when participants made a decision).
Reconfigurable MRI coil technology can substantially reduce RF heating at the tips of bilateral deep brain stimulation implants
Authors: Golestanirad Laleh , Keil Boris , Downs Sean , Kirsch John , Elahi Behzad , Pilitsis Julie , Wald Lawrence L 
Published: November 2018

AbstractPatients with deep brain stimulation (DBS) implants can significantly benefit from magnetic resonance imaging (MRI) examination, however, access to MRI is restricted in this patients because of safety concerns due to RF heating of the leads. Recently we introduced a patient-adjustable reconfigurable MRI coil system to reduce the SAR at the tip of deep brain stimulation implants during MRI at 1.5T. A simulation study with realistic models of single (unilateral) DBS leads demonstrated a substantial reduction in the local SAR up to 500-fold could be achieved using the coil system compared to quadrature birdcage coils. Many patients however, have bilateral DBS implants and the question arises whether the rotating coil system can be used in for them. This work reports the results of phantom experiments measuring the temperature rise at the tips of bilateral DBS implants with realistic trajectories extracted from postoperative CT images of 10 patients (20 leads in total). A total of 200 measurements were performed to record temperature rise at the tips of the leads during 2 minutes of scanning with the coil rotated to cover all accessible rotation angles. In all patients, we were able to find an optimum coil rotation angle and reduced the heating of both left and right leads to a level below the heating produced by the body coil. An average heat reduction of 65% was achieved for bilateral leads. Reconfigurable coil technology introduces a promising approach for imaging of patients with DBS implants.
Modelling invasive pathogen load from non-destructive sampling data
Authors: Martínková Nátalia , Škrabánek Pavel , Pikula Jiri 
Published: November 2018

AbstractWhere microbes colonizing skin surface may help maintain organism homeostasis, those that invade living skin layers cause disease. In bats, white-nose syndrome is a fungal skin infection that affects animals during hibernation and may lead to mortality in severe cases. Here, we inferred the amount of fungus that had invaded skin tissue of diseased animals. We used simulations to estimate the unobserved disease severity in a non-lethal wing punch biopsy and to relate the simulated pathology to the measured fungal load in paired biopsies. We found that a single white-nose syndrome skin lesion packed with spores and hyphae of the causative agent, Pseudogymnoascus destructans, contains 48.93 pg of the pathogen DNA, which amounts to about 1560 P. destructans genomes in one skin lesion. Relating the information to the known UV fluorescence in Nearctic and Palearctic bats shows that Nearctic bats carry about 1.7 μg of fungal DNA per cm2, whereas Palearctic bats have 0.04 μg cm−2 of P. destructans DNA. With the information on the fungal load that had invaded the host skin, the researchers can now calculate disease severity as a function of invasive fungal growth using non-destructive UV light transillumination of each bat □s wing membranes. Our results will enable and promote thorough disease severity assessment in protected bat species without the need for extensive animal and laboratory labor sacrifices.
Single cell transcriptomic analysis of the adult mouse pituitary reveals a novel multi-hormone cell cluster and physiologic demand-induced lineage plasticity
Authors: Ho Yugong , Hu Peng , Peel Michael T. , Chen Sixing , Camara Pablo G. , Epstein Douglas J. , Wu Hao , Liebhaber Stephen A. 
Published: November 2018

AbstractThe anterior pituitary gland drives a set of highly conserved physiologic processes in mammalian species. These hormonally-controlled processes are central to somatic growth, pubertal transformation, fertility, lactation, and metabolism. Current models, largely built upon candidate gene based immuno-histochemical and mRNA analyses, suggest that each of the seven hormones synthesized by the pituitary is produced by a specific and exclusive cell lineage. However, emerging evidence suggests more complex models of hormone specificity and cell plasticity. Here we have applied massively parallel single-cell RNA sequencing (scRNA-seq), in conjunction with a set of orthogonal mRNA and protein imaging studies, to systematically map the cellular composition of adult male and female mouse pituitaries at single-cell resolution and in the setting of major physiologic demands. These analyses reveal sex-specific cellular diversity associated with normal pituitary homeostasis, and identify an array of cells with complex complements of hormone-enrichment as well as a series of non-hormone producing interstitial and supporting cell lineages. These scRNA-seq studies identify a major cell population that is characterized by a unique multi-hormone gene expression profile. The detection of dynamic shifts in cellular representations and transcriptome profiles in response to two well-defined physiologic stresses suggests corresponding roles of a number of these clusters in cellular plasticity within the adult pituitary. These studies point to an unanticipated complexity and plasticity in pituitary cellular composition that expands upon current models and concepts of pituitary gene expression and hormone production.
The long noncoding RNAHand2asorchestrates heart development through regulation of precise expression ofHAND2
Authors: Han Xue , Zhang Jiejie , Liu Yaxi , Fan Xiaoying , Ai Shanshan , Luo Yingjie , Li Xin , Luo Sai , Zheng Hui , Yue Yanzhu , Chang Zai , Yang Zhongzhou , Tang Fuchou , He Aibin , Shen Xiaohua 
Published: November 2018

AbstractRigorous exploration and dissection of potential actions and effects of long noncoding RNA (lncRNA) in animals remain challenging. Here using multiple knockout mouse models and single- cell RNA sequencing, we demonstrate that the divergent lncRNAHand2ashas a key, complex modulatory effect on the expression of its neighboring geneHAND2and subsequently on heart development and function, largely independent ofHand2astranscription and transcripts. Full-length deletion ofHand2asin mouse causes moderate yet prevalent upregulation ofHAND2in hundreds of cardiac cells, resulting in profound biological consequences, including dysregulated cardiac gene programs, congenital heart defects and perinatal lethality. We propose acis-functional role for theHand2aslocus in dampeningHAND2expression to restrain cardiomyocyte proliferation, thereby orchestrating a balanced development of cardiac cell lineages. This study highlights the need for complementary genetic and single-cell approaches to delineate the function and primary molecular effects of an lncRNA in animals.Impact statementThe long noncoding RNAHand2ascritically controls the precise expression of its neighboring geneHAND2, thereby balancing cardiac lineages and expression programs that are essential for heart development and function.