bluuebunny/crossref_metadata_2025_split huggingface dataset:
LDK378 inhibits the recruitment of myeloid‐derived suppressor cells to spleen via the p38–GRK2–CCR2 pathway in mice with sepsis
Authors: Hu Jie , Zhang Wenqin , Liu Yanjuan , Yang Yang , Tan Chuyi , Wei Xue , Wang Yufang , Tan Sipin , Liu Meidong , Liu Ke , Liu Ying , Zhang Huali , Xiao Xianzhong 
Published: August 2019

AbstractMyeloid‐derived suppressor cells (MDSCs) are functionally immunosuppressive cells that are persistently increased in abundance and associated with adverse clinical outcomes in sepsis. Here, we investigated the therapeutic potential of an anaplastic lymphoma kinase inhibitor, LDK378, in cecal ligation and puncture (CLP)‐induced polymicrobial sepsis and examined its effects on the recruitment of MDSCs. LDK378 significantly improved the survival of CLP‐induced polymicrobial septic mice, which was paralleled by reduced organ injury, decreased release of inflammatory cytokines and decreased recruitment of MDSCs to the spleen. Importantly, LDK378 inhibited the migration of MDSCs to the spleen by blocking the CLP‐mediated upregulation of CC chemokine receptor 2 (CCR2), a chemokine receptor critical for the recruitment of MDSCs. Mechanistically, LDK378 treatment blocked the CLP‐induced CCR2 upregulation of MDSCs via partially inhibiting the phosphorylation of p38 and G‐protein‐coupled receptor kinase‐2 (GRK2) in bone marrow MDSCs of septic mice. Furthermore, in vitro experiments also showed that lipopolysaccharide (LPS)‐induced migration of MDSCs was similarly owing to the activation of GRK2 and upregulation of CCR2 by LPS, whereas the treatment with LDK378 partially blocked the LPS‐induced phosphorylation of p38 and GRK2 and decreased the expression of CCR2 on the cell surface, therefore leading to the suppression of MDSC migration. Together, these findings unravel a novel function of LDK378 in the host response to infection and suggest that LDK378 could be a potential therapeutic agent for sepsis.See also: News and Commentary by Patil
Epidemiologic evaluation of calcium oxalate urolithiasis in dogs in the United States: 2010‐2015
Authors: Hunprasit Vachira , Schreiner Pamela J. , Bender Jeffrey B. , Lulich Jody P. 
Published: August 2019

AbstractBackgroundPositive health implications of early recognition of calcium oxalate (CaOx) urolithiasis include increased opportunity for nonsurgical removal, early dietary modification to minimize urolith growth, early removal to avoid urinary obstruction, and early recognition of genetic and metabolic diseases before they contribute to additional morbidity.ObjectivesTo identify high‐ and low‐risk dog breeds for CaOx uroliths and to determine the relationship of age and sex to the development of CaOx uroliths.AnimalsCalcium oxalate urolith submissions between 2010 and 2015.MethodsA comparative cross‐sectional study was conducted to identify high‐ and low‐risk breeds for CaOx uroliths by comparing cases to multiple comparison groups. At‐risk breeds were identified if odds ratios were significant (Pvalue <.05) across all comparison groups.ResultsOf 258 898 urolith submissions, 124 285 were CaOx. Calcium oxalate was identified in 212 breeds. Twelve breeds were identified as high‐risk breeds, and 14 breeds were identified as low‐risk breeds. All high‐risk breeds were small dog breeds, and all low‐risk breeds were medium to large dog breeds. Overall, the mean age ± standard deviation of the first CaOx urolith was 8.4 ± 2.8 years.Conclusions and Clinical ImportanceTo achieve the health benefits of preclinical evaluation, breeds at high risk for CaOx urolithiasis should be screened at 5 to 6 years of age, which is 2 to 3 years before likely development of clinical urolithiasis.
Disentangling the effects of plea discount and potential trial sentence on decisions to plead guilty
Authors: Schneider Ryan A. , Zottoli Tina M. 
Published: August 2019

BackgroundMost criminal convictions are a result of guilty pleas. Concerns have been raised that large differentials between plea and potential trial sentences can be coercive to some defendants, especially when the threat of potential trial sentence is very large. The limited research, to date, suggests that the likelihood of pleading guilty goes up with increasing size of potential trial sentence. However, existing studies have failed to separate the effects of trial sentence and plea discount; as a result, in almost all studies, large potential trial sentences are paired with large discounts and small trial sentences with small discounts, making it difficult to know how the threat of trial sentence actually affects defendant decisions.MethodIn this study, we examined the effects of guilt, magnitude of potential trial sentence (5 years and 25 years), and size of plea discount (20%, 50%, and 75%) in a fully crossed, between‐subjects design, with acceptance of plea offer as the dependent variable.ResultsWe found that potential trial sentence and plea discount had independent and opposite effects on plea decisions, with discount carrying the most weight. Specifically, participants accepted more plea offers in higher relative to lower discount conditions and when potential trial sentence was 5 years rather than 25 years. The pattern of effects was similar for participants in guilty and innocent conditions.ImplicationsOur results run somewhat counter to conventional wisdom on how discount and potential trial sentence affect plea decisions and suggest that, given similar discounts, the likelihood for pleading guilty may be higher for defendants facing less serious charges that carry less severe sentences. We discuss the policy and research implications of these data.
Independent genetic control of drought resistance, recovery, and growth of Eucalyptus globulus seedlings
Authors: Ammitzboll Hans , Vaillancourt René E. , Potts Brad M. , Harrison Peter A. , Brodribb Tim , Sussmilch Frances C. , Freeman Jules S. 
Published: August 2019

AbstractDrought is a major stress impacting forest ecosystems worldwide. We utilized quantitative trait loci (QTL) analysis to study the genetic basis of variation in (a) drought resistance and recovery and (b) candidate traits that may be associated with this variation in the forest tree Eucalyptus globulus. QTL analysis was performed using a large outcrossed F2 mapping population from which 300 trees were phenotyped based on the mean performance of their open‐pollinated F3 progeny. Progenies were grown in a glasshouse in a randomized complete block design. A subset of seedlings was subjected to a drought treatment after which they were rewatered and scored for damage and growth postdrought. Nondroughted seedlings were assessed for growth traits as well as lignotuber size and resprouting following severe damage to the main stem. QTL were detected for most traits. Importantly, independent QTL were detected for (a) drought damage and plant size, (b) drought damage and growth recovery, and (c) lignotuber size and resprouting capacity. Such independence argues that trade‐offs are unlikely to be a major limitation to the response to selection and at the early life history stage studied; there are opportunities to improve resilience to drought without adverse effects on productivity.
Age‐dependent loss of seed viability is associated with increased lipid oxidation and hydrolysis
Authors: Wiebach Janine , Nagel Manuela , Börner Andreas , Altmann Thomas , Riewe David 
Published: August 2019

AbstractThe accumulation of reactive oxygen species has been associated with a loss of seed viability. Therefore, we have investigated the germination ability of a range of seed stocks, including two wheat collections and one barley collection that had been dry‐aged for 5–40 years. Metabolite profiling analysis revealed that the accumulation of glycerol was negatively correlated with the ability to germinate in all seed sets. Furthermore, lipid degradation products such as glycerol phosphates and galactose were accumulated in some seed sets. A quantitative analysis of nonoxidized and oxidized lipids was performed in the wheat seed set that showed the greatest variation in germination. This analysis revealed that the levels of fully acylated and nonoxidized storage lipids like triacylglycerols and structural lipids like phospho‐ and galactolipids were decreasing. Moreover, the abundance of oxidized variants and hydrolysed products such as mono‐/diacylglycerols, lysophospholipids, and fatty acids accumulated as viability decreased. The proportional formation of oxidized and nonoxidized fatty acids provides evidence for an enzymatic hydrolysis of specifically oxidized lipids in dry seeds. The results link reactive oxygen species with lipid oxidation, structural damage, and death in long‐term aged seeds.
Severe hypernatremia and transient azotemia in a cat following inadvertent intravenous administration of a commercial polyethylene glycol solution
Authors: Hoehne Sabrina N. , Kohen Casey J. , Puschner Birgit , Gennity Ingrid , Hagley Simon P. , Farrell Kate S. , Unger Karin , Cagle Laura A. , Jandrey Karl E. 
Published: August 2019

AbstractObjectiveTo describe the clinical signs, clinicopathologic abnormalities, treatment, and outcome after IV administration of polyethylene glycol 3350 (PEG3350) in a cat.Case SummaryA cat was inadvertently administered 6 g/kg of PEG3350 in electrolyte solution, IV, resulting in severe hypernatremia (203 mmol/L), diffuse encephalopathy, hemolysis, and moderate azotemia. The hemolysis and acute kidney injury observed immediately following PEG3350 administration resolved with supportive care. Administration of IV and oral electrolyte‐free water slowly corrected the hypernatremia and the neurologic signs subsequently improved. Complete resolution of clinical signs was documented one month following hospital discharge. The PEG3350 concentrations in serum, plasma, and urine samples confirmed toxic exposure to PEG3350. Efficacy of treatment was evident by decreasing concentrations of PEG3350 in serum after the first 24 hours of treatment. Renal elimination of PEG3350 was significant and PEG3350 was still detected in the urine 17 days after exposure.New Information ProvidedThis is the first report to describe the clinical signs and clinicopathologic abnormalities in a cat intoxicated with IV PEG3350. Potential pathophysiologic mechanisms are discussed, and the successful supportive medical treatment is outlined.
Factors secreted from high glucose treated endothelial cells impair expansion and differentiation of human skeletal muscle satellite cells
Authors: Kargl Christopher K. , Nie Yaohui , Evans Sheelagh , Stout Julianne , Shannahan Jonathan H. , Kuang Shihuan , Gavin Timothy P. 
Published: August 2019

Key points
Cellular communication occurs between endothelial cells and skeletal muscle satellite cells and is mitogenic for both cell types under normal conditions.
Skeletal muscle atrophy and endothelial cell dysfunction occur in tandem in cardiovascular disease, type II diabetes and ageing.
The present study investigated how induction of endothelial cell dysfunction via high glucose treatment impacts growth and differentiation of human skeletal muscle satellite cells in vitro.
Secreted factors from high glucose treated endothelial cells impaired satellite cell expansion and differentiation via decreased proliferation and dysregulation of p38 mitogen‐activated protein kinase in satellite cells committed to myogenesis.
These findings highlight a novel potential role for endothelial cells in the development and pathology of skeletal muscle atrophy, which is common in patients with endothelial dysfunction related pathologies.
AbstractCross‐talk between endothelial cells (ECs) and skeletal muscle satellite cells (MuSC) has been identified as an important regulator of cellular functions in both cell types. In healthy conditions, EC secreted factors promote MuSC growth and differentiation. Endothelial and satellite cell dysfunction occur in tandem in many disease states; however, no data exist examining the impact of dysfunctional EC signalling on satellite cells. Therefore, the present study aimed to evaluate the effect that factors secreted from high glucose (HG) treated ECs have on the growth and differentiation of human satellite cells (HMuSC) using a conditioned medium (CM) cell culture model. Satellite cells were isolated from human skeletal muscle and grown in CM from normal or HG treated human umbilical vein ECs (HUVECs). Satellite cells grown in CM from HG treated HUVECs reduced growth (25%), differentiation (25%) and myonuclear fusion (35%). These responses were associated with increased superoxide (50%) and inflammatory cytokines (25–50%) in HG treated HUVECs and HG‐CM. Decreased expansion of HG‐CM treated HMuSCs was driven by a decrease in proliferation. Impaired gene expression and protein content of myogenic differentiation factors were preceded by decreased phosphorylation of p38 mitogen‐activated protein kinase in HMuSC treated with CM from HG treated HUVECs. The results obtained in the present study are the first to show that factors secreted from HG treated ECs cause impairments in human muscle satellite cell growth and differentiation in vitro, highlighting endothelial cell health and secretion as a potential target for treating vascular disease‐associated skeletal muscle dysfunction.
von Willebrand factor as a biomarker of clinically significant portal hypertension and severe portal hypertension: a systematic review and meta-analysis
Authors: Zou Ziyuan , Yan Xinwen , Li Cheng , Li Xiaofeng , Ma Xiaofen , Zhang Chunqing , Ju Shenghong , Tian Junzhang , Qi Xiaolong 
Published: August 2019

ObjectiveThis meta-analysis was performed to investigate the correlation between von Willebrand factor (vWF) antigen and hepatic venous pressure gradient (HVPG) and to evaluate the diagnostic performance of vWF to detect clinically significant portal hypertension (CSPH) and severe portal hypertension (SPH).DesignSystematic review and meta-analysis.MethodsMEDLINE, EMBASE, Web of Science and the Cochrane Library were screened up to 5 April 2018. Studies related to the diagnostic performance of vWF to detect CSPH and/or SPH with HVPG as the reference standard were included. Study quality was assessed by using the Quality Assessment of Diagnostic Accuracy Studies scale. Two authors independently used a standardised form to extract data.OutcomesThe primary outcome was the correlation coefficient between vWF and HVPG. The secondary outcome was the diagnostic performance of vWF to detect CSPH or SPH.ResultsA total of six articles involving 994 patients were included in this study. Five of the included articles were used to stratify the results for the correlation coefficient, three for the diagnostic performance of CSPH and two for SPH. The pooled correlation coefficient based on the random effects model was 0.54 (95% CI 0.35 to 0.69), thus suggesting a moderate correlation between vWF and HVPG. The pooled sensitivity, specificity and area under the curve of vWF for CSPH detection were 82% (95% CI 78 to 86), 76% (95% CI 68 to 83) and 0.87 (95% CI 0.80 to 0.94), respectively. Regarding the ability of vWF to detect SPH, the pooled sensitivity and specificity were 86% (95% CI 80 to 90) and 75% (95% CI 66 to 83), respectively. These results supported the satisfactory diagnostic performance of vWF for CSPH and SPH detection.ConclusionsvWF, as a novel biomarker, has a moderate correlation with HVPG and shows a satisfactory performance for the diagnosis of CSPH and SPH in patients with cirrhosis.
The James Lind Alliance process approach: scoping review
Authors: Nygaard Agnete , Halvorsrud Liv , Linnerud Siv , Grov Ellen Karine , Bergland Astrid 
Published: August 2019

ObjectiveTo summarise study descriptions of the James Lind Alliance (JLA) approach to the priority setting partnership (PSP) process and how this process is used to identify uncertainties and to develop lists of top 10 priorities.DesignScoping review.Data sourcesThe Embase, Medline (Ovid), PubMed, CINAHL and the Cochrane Library as of October 2018.Study selectionAll studies reporting the use of JLA process steps and the development of a list of top 10 priorities, with adult participants aged 18 years.Data extractionA data extraction sheet was created to collect demographic details, study aims, sample and patient group details, PSP details (eg, stakeholders), lists of top 10 priorities, descriptions of JLA facilitator roles and the PSP stages followed. Individual and comparative appraisals were discussed among the scoping review authors until agreement was reached.ResultsDatabase searches yielded 431 potentially relevant studies published in 2010–2018, of which 37 met the inclusion criteria. JLA process participants were patients, carers and clinicians, aged 18 years, who had experience with the study-relevant diagnoses. All studies reported having a steering group, although partners and stakeholders were described differently across studies. The number of JLA PSP process steps varied from four to eight. Uncertainties were typically collected via an online survey hosted on, or linked to, the PSP website. The number of submitted uncertainties varied across studies, from 323 submitted by 58 participants to 8227 submitted by 2587 participants.ConclusionsJLA-based PSP makes a useful contribution to identifying research questions. Through this process, patients, carers and clinicians work together to identify and prioritise unanswered uncertainties. However, representation of those with different health conditions depends on their having the capacity and resources to participate. No studies reported difficulties in developing their top 10 priorities.
Cardiovascular fitness and risk of migraine: a large, prospective population-based study of Swedish young adult men
Authors: Nyberg Jenny , Gustavsson Sara , Linde Mattias , Åberg N David , Rohmann Jessica L , Åberg Maria , Kurth Tobias , Waern Margda , Kuhn Georg Hans 
Published: August 2019

ObjectivesTo examine the longitudinal relationship between cardiovascular fitness in young adult men and future risk of migraine and to estimate eventual differential effects among categories of body mass index (BMI) and blood pressure.DesignNational, prospective, population-based cohort study.SettingSweden 1968–2014.Participants18-year-old Swedish men (n=1 819 828) who underwent mandatory military conscription examinations during the years 1968–2005.Primary and secondary outcomesThe primary outcome was the first dispensation of prescribed migraine-specific medication, identified using the Swedish Prescribed Drug Register. The secondary outcome was documented migraine diagnosis from the Swedish National Hospital Register.ResultsDuring follow-up, 22 533 men filled a prescription for migraine-specific medication. After confounding adjustment, compared with high cardiovascular fitness, low and medium fitness increased the risk of migraine-specific medication (risk ratio (RR)low: 1.29, 95% CI 1.24 to 1.35; population attributable fraction: 3.6%, 95% CI 1.7% to 5.3% and RRmedium: 1.15, 95% CI 1.12 to 1.19; population attributable fraction: 8.0%, 95% CI 4.0% to 11.7%). To assess potential effect measure modification, stratified analyses of these association by levels of BMI and blood pressure showed that lower fitness levels increased risk of migraine across all groups except among underweight men or men with high diastolic blood pressure.ConclusionsYoung men with a lower cardiovascular fitness had a higher long-term risk of developing pharmacological prescription-requiring migraine. This study contributes with information regarding risk factors for migraine in men, an understudied population in migraine research.
C reactive protein level as a marker for dyslipidaemia, diabetes and metabolic syndrome: results from the Korea National Health and Nutrition Examination Survey
Authors: Jeong Hyemin , Baek Sun-Young , Kim Seon Woo , Park Eun-Jung , Lee Jaejoon , Kim Hyungjin , Jeon Chan Hong 
Published: August 2019

ObjectivePlasma C reactive protein (CRP) is a marker of inflammation, and increased plasma CRP is reported in many diseases, including cardiovascular disease, diabetes, metabolic syndrome, arthritis and malignancies. The aim of the study was to evaluate the association between plasma CRP levels and cardiovascular disease, metabolic syndrome, malignancies and other comorbidities.DesignA retrospective, cross-sectional survey study.SettingLarge population survey in Korea.MethodsA total of 5887 (weighted n=40 251 868) participants aged 19 years or older from the 2016 Korea National Health and Nutrition Examination Survey were included for analysis. Weighted prevalence and OR of comorbidities were analysed according to the continuous variable of log plasma high-sensitivity CRP levels.ResultsThe mean age was 46.7±0.37 years and the median plasma CRP was 0.58 mg/L (IQR 0.36–1.09). The mean plasma CRP levels were higher in participants with cardiovascular diseases and cardiovascular risk factors, osteoarthritis, rheumatoid arthritis, pulmonary tuberculosis, and several cancers, including gastric, colon, breast and cervix, than in the general population. In the multivariable analysis, plasma CRP concentration was associated with increased prevalence of hypertriglyceridaemia (OR 1.157, 95% CI 1.040 to 1.287, p=0.007), diabetes (OR 1.204, 95% CI 1.058 to 1.371, p=0.005) and metabolic syndrome (OR 1.228, 95% CI 1.112 to 1.357, p<0.001) after adjustment for socioeconomic and lifestyle characteristics. There was no significant association between plasma CRP level and cancers.ConclusionPlasma CRP was associated with an increased risk of dyslipidaemia, diabetes and metabolic syndrome in the general population.
Diagnostic performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at estimating glomerular filtration rate in adults with diabetes mellitus: a systematic review and meta-analysis protocol
Authors: Zafari Neda , Churilov Leonid , MacIsaac Richard J , Torkamani Niloufar , Baxter Helen , Kiburg Katerina V , Ekinci Elif 
Published: August 2019

IntroductionTimely detection leading to the implementation of reno-protective measures reduces the progression of diabetic kidney disease. Estimated glomerular filtration rate (eGFR) is a major surrogate of kidney function. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Equation is a tool to estimate GFR. This protocol outlines a systematic-review, assessing the diagnostic accuracy of the CKD-EPI equation in adults with diabetes.Methods and analysisMEDLINE, Embase, Cochrane Central Register of Controlled Trials and grey literature will be searched for publications in English, Farsi, Dutch and Chinese from 2009 (when CKD-EPI was first introduced) to January 2019. Bridging searches will be conducted to capture literature published from January 2019 until final review publication. The inclusion criteria will be (1) study participants with diabetes; (2) age ≥18 years; (3) creatinine-based CKD-EPI eGFR as index test; (4) measured GFR using the clearance/plasma disappearance of inulin, iohexol, iothalamate, diethylenetriamine-pentaacetic acid (DTPA) or chromium labelled ethylenediaminetetraacetic acid (Cr-EDTA) as reference test; (5) report of the diagnostic accuracy of the index test. Exclusion criteria will be participants with renal transplant, chronic use of corticosteroids, chronic inflammatory diseases, pregnancy, non-diabetes related kidney disease, thalassaemia, heart failure, pregnancy and potential kidney donors as well as critically ill patients. Screening, eligibility check, risk of bias assessment and data extraction will be carried out by two independent reviewers. Any discrepancies will be discussed, and third-party opinion will be sought. The risk of bias will be assessed using the Quality Assessment of Diagnostic Accuracy Studies−2 tool. A quantitative synthesis of the aggregated-data will be used if the included studies are homogenous.Ethics and disseminationNo ethics approval is required. The outcome will be published in a peer-reviewed journal. The results will help researchers and clinicians evaluate the diagnostic accuracy of the creatinine-based CKD-EPI eGFR in adults with diabetes.PROSPERO registration numberCRD42018108776