bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prevalence of Dermatophilus congolensis in horses with pastern dermatitis using PCR to diagnose infection in a population of horses in southern USA
Authors: Aufox Erin E. , Frank Linda A. , May Elizabeth R. , Kania Stephen A. 
Published: June 2018

BackgroundDermatophilus congolensis is a facultative anaerobic actinomycete that causes papular to exudative dermatitis with crusting in horses. This organism is frequently implicated as a cause of pastern dermatitis, but few data are available validating the organism's association with this disease.Hypothesis/ObjectivesThe aim of this study was to evaluate if D. congolensis is associated with pastern dermatitis in horses utilizing RT‐qPCR.AnimalsFifteen client‐owned horses diagnosed with pastern dermatitis and eight client‐owned unaffected control horses were utilized for this study.MethodsA cross‐sectional study was performed. History and physical examination findings were recorded, and samples were collected and tested for D. congolensis utilizing cytological evaluation and RT‐qPCR. Dermatophyte culture and superficial skin scrapings were also performed.ResultsTen of 15 horses with pastern dermatitis had feathered pasterns. Dermatophilus congolensis was identified by RT‐qPCR from one nonfeathered horse but none with feathered pasterns. Cytological evaluation identified bacteria in all horses but failed to identify organisms resembling D. congolensis in any horse. Four of 15 horses, all feathered, were positive for Chorioptes mites. Fungal culture was negative for dermatophytes in all horses. All test results were negative for the eight control horses.Conclusions and clinical importanceDermatophilus congolensis was uncommonly associated with pastern dermatitis in horses in this population. However, chorioptic mange was commonly associated with pastern dermatitis in feathered horses and represented an important differential diagnosis for this clinical presentation.
Targeted ablation of cardiac sympathetic neurons attenuates adverse postinfarction remodelling and left ventricular dysfunction
Authors: Xiong Liang , Liu Yu , Zhou Mingmin , Wang Guangji , Quan Dajun , Shuai Wei , Shen Caijie , Kong Bin , Huang Congxin , Huang He 
Published: June 2018

New Findings
What is the central question of this study?
Can targeted ablation of cardiac sympathetic neurons suppress myocardial infarction‐induced adverse cardiac remodelling and left ventricular dysfunction?

What is the main finding and its importance?
Targeted ablation of cardiac sympathetic neurons significantly alleviated sympathetic remodelling and neuroendocrine activation, attenuated cardiac hypertrophy and fibrosis and improved left ventricular function. Thus, targeted ablation of cardiac sympathetic neurons might have a beneficial effect on adverse postinfarction remodelling and left ventricular dysfunction.

AbstractSympathetic overactivation is crucial in the development and progression of adverse cardiac remodelling and dysfunction. Targeted ablation of cardiac sympathetic neurons (TACSN) is an effective approach to inhibit overactivation of the sympathetic nervous system. The aim of this study was to investigate whether TACSN could suppress myocardial infarction (MI)‐induced adverse cardiac remodelling and dysfunction, thereby producing protective effects. Thirty‐eight dogs were randomly assigned into the sham‐operated, MI or MI‐TACSN group. The TACSN was induced by injecting cholera toxin B subunit–saporin compound into the stellate ganglia 1 week after MI. Five weeks after MI surgery, echocardiographic and haemodynamic parameters of cardiac function were significantly improved in the TACSN group compared with the MI group. In addition, TACSN attenuated the extent of cardiac hypertrophy and fibrosis and suppressed the increase in the plasma concentrations of noradrenaline, nerve growth factor, atrial natriuretic peptide, brain natriuretic peptide, angiotensin II and aldosterone. Furthermore, TACSN alleviated the growth associated protein‐43‐positive and tyrosine hydroxylase‐positive nerve densities in the infarcted border zone and restored protein expression of the β1‐adrenergic receptor in the left ventricular myocardium. These findings indicate that TACSN might have a beneficial effect on adverse postinfarction remodelling and left ventricular dysfunction, which might be attributable, at least in part, to the attenuation of both sympathetic remodelling and the cardiac neuroendocrine system.
Motor cortical and corticospinal function differ during an isometric squat compared with isometric knee extension
Authors: Brownstein Callum G. , Ansdell Paul , Škarabot Jakob , Frazer Ash , Kidgell Dawson , Howatson Glyn , Goodall Stuart , Thomas Kevin 
Published: June 2018

New Findings
What is the central question of this study?
In order to discern information about testing modalities when assessing neuroplastic responses to squat resistance training, the present study investigated whether corticospinal and intracortical function was different between a joint‐angle‐matched isometric squat and isometric knee extension.

What is the main finding and its importance?
The present data show poor agreement of corticospinal and intracortical function between the isometric squat and isometric knee extension. The data reinforce the notion that task specificity is of the utmost importance for assessing neuroplasticity.

AbstractIt has been suggested that task‐specific changes in neurophysiological function (neuroplasticity) should be assessed using testing modalities that replicate the characteristics of the intervention. The squat is a commonly prescribed resistance exercise that has been shown to elicit changes in CNS function. However, previous studies have assessed squat‐induced neuroplasticity using isometric knee extension, potentially confounding the results. The aim of the present study was to assess the agreement between corticospinal and intracortical activity relating to the knee extensors during isometric knee extension compared with an isometric squat task. Eleven males completed a neurophysiological assessment in an isometric squat (IS) and knee‐extension (KE) task matched for joint angles (hip, knee and ankle). Single‐ and paired‐pulse transcranial magnetic stimulation was delivered during isometric contractions at a range of intensities to assess short‐interval cortical inhibition (SICI) and corticospinal excitability. Group mean values for SICI (70 ± 14 versus 63 ± 12% of unconditioned motor evoked potential during IS and KE, respectively) and corticospinal excitability (mean differences 2–5% of the maximal compound muscle action potential at 25, 50, 75 and 100% maximal voluntary contraction between the IS and KE) were not different between the two tasks (P > 0.05) in the vastus lateralis. However, limits of agreement were wide, with poor‐to‐moderate average intraclass correlation coefficients (ICCs) (SICI, ICC3,1 = 0.15; corticospinal excitability, average ICC3,1 range = 0.0–0.63), indicating disparate corticospinal and intracortical activity between the IS and KE. These data highlight the importance of task specificity when assessing the modulation of corticospinal excitability and SICI in response to interventions resulting in neuroplastic changes.
Microvascular abnormalities secondary to radiation therapy in neovascular age-related macular degeneration: findings from the INTREPID clinical trial
Authors: Freiberg Florentina Joyce , Michels Stephan , Muldrew Alyson , Slakter Jason , O’Shaughnessy Denis , Czeszynski Alan , Danielson Linda , Jackson Timothy L , Chakravarthy Usha 
Published: June 2018

PurposeTo report the incidence and features of retinal microvascular abnormalities (MVAs) occurring secondary to stereotactic radiotherapy (SRT) in a randomised double-masked sham-controlled clinical trial at 21 European sites.MethodsTwo hundred and thirty participants with neovascular age-related macular degeneration (AMD) treated with at least three intravitreal antivascular endothelial growth factor (anti-VEGF) injections prior to enrolment, and demonstrating a continuing need for re-treatment. Interventions: 16 Gy, 24 Gy or sham SRT. All three groups received pro re nata anti-VEGF injections if the lesion was judged to be active at review visits. Colour fundus images from baseline and 6 months and fluorescein angiograms from baseline and annual visits were graded for measures of morphological outcome and safety using a prespecified protocol with accompanying definitions to distinguish RT-related MVA from non-specific retinal vessel abnormalities that are known to occur in neovascular AMD. The main outcome measure was MVA detected by months 12, 24 and 36 after enrolment.ResultsThe frequency of MVAs in the combined SRT arms was 0% in year 1, 13.1% in year 2 and 30.3% in year 3. The area of MVA was small and the mean change in visual acuity in year 2 was similar in a subset of SRT eyes with MVAs, versus those without MVAs. MVA was considered to have possibly contributed to vision loss in 2 of 18 cases with MVA in year 2, and 5 of 37 cases in year 3.ConclusionTreatment with SRT is associated with development of subtle MVAs that have little or no impact on visual outcome. These findings can help clinicians recognise the retinal MVAs that occur in response to SRT.
Online Matching in Regular Bipartite Graphs
Authors: Barrière Lali , Muñoz Xavier , Fuchs Janosch , Unger Walter 
Published: June 2018

In an online problem, the input is revealed one piece at a time. In every time step, the online algorithm has to produce a part of the output, based on the partial knowledge of the input. Such decisions are irrevocable, and thus online algorithms usually lead to nonoptimal solutions. The impact of the partial knowledge depends strongly on the problem. If the algorithm is allowed to read binary information about the future, the amount of bits read that allow the algorithm to solve the problem optimally is the so-called advice complexity. The quality of an online algorithm is measured by its competitive ratio, which compares its performance to that of an optimal offline algorithm. In this paper we study online bipartite matchings focusing on the particular case of bipartite matchings in regular graphs. We give tight upper and lower bounds on the competitive ratio of the online deterministic bipartite matching problem. The competitive ratio turns out to be asymptotically equal to the known randomized competitive ratio. Afterwards, we present an upper and lower bound for the advice complexity of the online deterministic bipartite matching problem.
Role of the placenta in serum autotaxin elevation during maternal cholestasis
Authors: Macias Rocio I. R. , Matilla Sonia , Lozano Elisa , Estiú Maria C. , Oude Elferink Ronald P. , Marin Jose J. G. 
Published: June 2018

Intrahepatic cholestasis of pregnancy (ICP) is frequently accompanied by pruritus, whose etiology has been associated with an enhanced production of lysophosphatidic acid (LPA) by the combined action of phospholipase A1/A2 (PLA1/PLA2) and autotaxin (ATX). Here, we have investigated whether the placenta is involved in LPA release to maternal circulation during ICP. Serum levels of ATX and LPA (determined by ELISA) were elevated in women with ICP, and a correlation between both parameters was found. No relationship between serum levels of ATX or LPA and bile acids was found. Expression levels of ATX and PLA2 were determined by RT-qPCR and Western blot. Placenta ATX but not PLA2 was significantly upregulated in ICP, and a tendency to increase was found at the protein level. A correlation between serum ATX and placental ATX mRNA levels was found. In human placenta at term, ATX was clearly detected (by immunofluorescence) in Hofbauer cells, but only faintly in trophoblast cells. In pregnant rats, the expression of Atx and Pla2 in placenta was lower than in liver. When obstructive cholestasis was imposed by bile duct ligation from day 14 of gestation until term, placenta Atx and Pla2 expression was markedly enhanced, and overexpression was confirmed at the protein level for Pla2, whereas Atx protein was not detected. In conclusion, the placenta substantially participates in LPA production during gestation. This contribution is markedly higher during maternal cholestasis and hence, may be involved in ICP-associated pruritus. NEW & NOTEWORTHY Fetal placental macrophages and, to a lesser extent, trophoblast cells express high levels of autotaxin at term. An increased expression of mRNA and protein autotaxin, the key secretory enzyme responsible for the production of lysophosphatidic acid in serum, has been observed in placentas of women with cholestasis of pregnancy, which supports that the placenta can contribute to an increased production of this pruritogenic compound in women suffering from this liver disease.
Dietary fat stimulates pancreatic cancer growth and promotes fibrosis of the tumor microenvironment through the cholecystokinin receptor
Authors: Nadella Sandeep , Burks Julian , Al-Sabban Abdulhameed , Inyang Gloria , Wang Juan , Tucker Robin D. , Zamanis Marie E. , Bukowski William , Shivapurkar Narayan , Smith Jill P. 
Published: June 2018

The gastrointestinal peptide cholecystokinin (CCK) is released from the duodenum in response to dietary fat to aid in digestion, and plasma CCK levels are elevated with the consumption of high-fat diets. CCK is also a trophic peptide for the pancreas and has also been shown to stimulate growth of pancreatic cancer. In the current investigation, we studied the influence of a diet high in saturated fat on the growth of pancreatic cancer in syngeneic murine models before the mice became obese to exclude the confounding factors associated with obesity. The high-fat diet significantly increased growth and metastasis of pancreatic cancer compared with the control diet, and the stimulatory effect was blocked by the CCK-receptor antagonist proglumide. We then selectively knocked out the CCK receptor on the pancreatic cancer cells using clustered regularly interspaced short palindromic repeats technology and showed that without CCK-receptors, dietary fat was unable to stimulate cancer growth. We next demonstrated that dietary fat failed to influence pancreatic cancer xenograft growth in genetically engineered CCK peptide knockout mice. The tumor-associated fibrosis that is so prevalent in the pancreatic cancer microenvironment was significantly decreased with CCK-receptor antagonist therapy because fibroblasts also have CCK receptors. The CCK-receptor antagonist proglumide also altered tumor metalloprotease expression and increased tumor suppressor genes by a PCR array. Our studies confirm that a diet high in saturated fat promotes growth of pancreatic cancer and the action is mediated by the CCK-receptor pathway. NEW & NOTEWORTHY Diets high in long-chain saturated fats promote growth of pancreatic cancer independent of obesity. The mechanism through which dietary fat promotes cancer is mediated through the cholecystokinin (CCK) receptor pathway. Therapy with a CCK-receptor antagonist altered the tumor microenvironment by reducing fibrosis, increasing cluster of differentiation 8+ lymphocytes, increasing tumor suppressor genes, and thus decreasing metastases. Use of CCK-receptor antagonist therapy with standard chemotherapy for pancreatic cancer may improve response by altering the tumor microenvironment.
Rho kinase inhibition maintains intestinal and vascular barrier function by upregulation of occludin in experimental necrotizing enterocolitis
Authors: Grothaus Justyna S. , Ares Guillermo , Yuan Carrie , Wood Douglas R. , Hunter Catherine J. 
Published: June 2018

Necrotizing enterocolitis (NEC) is a deadly disease that occurs in 5–10% of neonates. Although NEC has been extensively studied, no single therapeutic target has been identified. Rho kinase (ROCK) is a serine/threonine kinase that affects multiple cellular processes, including tight junction (TJ) function, cellular permeability, and apoptosis. We hypothesized that ROCK inhibition would decrease cellular permeability, stabilize TJ proteins (occludin), and decrease the severity of NEC. To test this hypothesis, human colon epithelial cells (Caco-2) and human endothelial cells were studied. Cells were treated with lipopolysaccharide to simulate an in vitro model of NEC. The effect of ROCK inhibition was measured by transepithelial membrane resistance (TEER) and cellular permeability to FITC-dextran. The effects of ROCK inhibition in vivo were analyzed in the rat pup model of NEC. NEC was induced by feeding formula supplemented with Cronobacter sakazakii with or without gavaged ROCK inhibitor. Rat intestines were scored based on histological degree of injury. RNA and protein assays for occludin protein were performed for all models of NEC. Treatment with ROCK inhibitor significantly decreased cellular permeability in Caco-2 cells and increased TEER. Intestinal injury scoring revealed decreased scores in ROCK inhibitor-treated pups compared with NEC only. Both cell and rat pup models demonstrated an upregulation of occludin expression in the ROCK inhibitor-treated groups. Therefore, we conclude that ROCK inhibition protects against experimental NEC by strengthening barrier function via upregulation of occludin. These data suggest that ROCK may be a potential therapeutic target for patients with NEC. NEW & NOTEWORTHY These studies are the first to demonstrate an upregulation of occludin tight junction protein in response to Rho kinase (ROCK) inhibition. Furthermore, we have demonstrated that ROCK inhibition in experimental models of necrotizing enterocolitis (NEC) is protective against NEC in both in vitro and in vivo models of disease.
ACEI/D gene variant predicts ACE enzyme content in blood but not the ACE, UCP2, and UCP3 protein content in human skeletal muscle in the Gene SMART study
Authors: Yan Xu , Dvir Noam , Jacques Macsue , Cavalcante Luiz , Papadimitriou Ioannis D. , Munson Fiona , Kuang Jujiao , Garnham Andrew , Landen Shanie , Li Jia , O’Keefe Lannie , Tirosh Oren , Bishop David J. , Voisin Sarah , Eynon Nir 
Published: June 2018

Angiotensin-converting enzyme (ACE) is expressed in human skeletal muscle. The ACE I/D polymorphism has been associated with athletic performance in some studies. Studies have suggested that the ACE I/D gene variant is associated with ACE enzyme content in serum, and there is an interaction between ACE and uncoupling proteins 2 and 3 (UCP2 and UCP3). However, no studies have explored the effect of ACE I/D on ACE, UCP2, and UCP3 protein content in human skeletal muscle. Utilizing the Gene SMART cohort ( n = 81), we investigated whether the ACE I/D gene variant is associated with ACE enzyme content in blood and ACE, UCP2, and UCP3 protein content in skeletal muscle at baseline and following a session of high-intensity interval exercise (HIIE). Using a stringent and robust statistical analyses, we found that the ACE I/D gene variant was associated with ACE enzyme content in blood ( P < 0.005) at baseline but not the ACE, UCP2, and UCP3 protein content in muscle at baseline. A single session of HIIE tended (0.005 < P < 0.05) to increase blood ACE content immediately postexercise, whereas muscle ACE protein content was lower 3 h after a single session of HIIE ( P < 0.005). Muscle UCP3 protein content decreased immediately after a single session of HIIE ( P < 0.005) and remained low 3 h postexercise. However, those changes in the muscle were not genotype dependent. In conclusion, The ACE I/D gene variant predicts ACE enzyme content in blood but not the ACE, UCP2, and UCP3 protein content of human skeletal muscle.NEW & NOTEWORTHY This paper describes the association between ACE I/D gene variant and ACE protein content in blood and ACE, UCP2, and UCP3 protein content in skeletal muscle at baseline and after exercise in a large cohort of healthy males. Our data suggest that ACE I/D is a strong predictor of blood ACE content but not muscle ACE content.
CD271+ Cells Are Diagnostic and Prognostic and Exhibit Elevated MAPK Activity in SHH Medulloblastoma
Authors: Liang Lisa , Coudière-Morrison Ludivine , Tatari Nazanin , Stromecki Margaret , Fresnoza Agnes , Porter Christopher J. , Del Bigio Marc R. , Hawkins Cynthia , Chan Jennifer A. , Ryken Timothy C. , Taylor Michael D. , Ramaswamy Vijay , Werbowetski-Ogilvie Tamra E. 
Published: June 2018

Abstract
The extensive heterogeneity both between and within the medulloblastoma subgroups underscores a critical need for variant-specific biomarkers and therapeutic strategies. We previously identified a role for the CD271/p75 neurotrophin receptor (p75NTR) in regulating stem/progenitor cells in the SHH medulloblastoma subgroup. Here, we demonstrate the utility of CD271 as a novel diagnostic and prognostic marker for SHH medulloblastoma using IHC analysis and transcriptome data across 763 primary tumors. RNA sequencing of CD271+ and CD271− cells revealed molecularly distinct, coexisting cellular subsets, both in vitro and in vivo. MAPK/ERK signaling was upregulated in the CD271+ population, and inhibiting this pathway reduced endogenous CD271 levels, stem/progenitor cell proliferation, and cell survival as well as cell migration in vitro. Treatment with the MEK inhibitor selumetinib extended survival and reduced CD271 levels in vivo, whereas, treatment with vismodegib, a well-known smoothened (SMO) inhibitor currently in clinical trials for the treatment of recurrent SHH medulloblastoma, had no significant effect in our models. Our study demonstrates the clinical utility of CD271 as both a diagnostic and prognostic tool for SHH medulloblastoma tumors and reveals a novel role for MEK inhibitors in targeting CD271+ SHH medulloblastoma cells.
Significance: This study identifies CD271 as a specific and novel biomarker of SHH-type medulloblastoma and that targeting CD271+ cells through MEK inhibition represents a novel therapeutic strategy for the treatment of SHH medulloblastoma. Cancer Res; 78(16); 4745–59. ©2018 AACR.
Shear Stress and VE-Cadherin
Authors: Caolo Vincenza , Peacock Hanna M. , Kasaai Bahar , Swennen Geertje , Gordon Emma , Claesson-Welsh Lena , Post Mark J. , Verhamme Peter , Jones Elizabeth A.V. 
Published: June 2018

Objective—
Vascular fusion represents an important mechanism of vessel enlargement during development; however, its significance in postnatal vessel enlargement is still unknown. During fusion, 2 adjoining vessels merge to share 1 larger lumen. The aim of this research was to identify the molecular mechanism responsible for vascular fusion.

Approach and Results—

We previously showed that both low shear stress and DAPT (
N
-[
N
-(3,5-difluorophenacetyl)-L-alanyl]-
S
-phenylglycine t-butyl ester) treatment in the embryo result in a hyperfused vascular plexus and that increasing shear stress levels could prevent DAPT-induced fusion. We, therefore, investigated vascular endothelial-cadherin (VEC) phosphorylation because this is a common downstream target of low shear stress and DAPT treatment. VEC phosphorylation increases after DAPT treatment and decreased shear stress. The increased phosphorylation occurred independent of the cleavage of the Notch intracellular domain. Increasing shear stress rescues hyperfusion by DAPT treatment by causing the association of the phosphatase vascular endothelial-protein tyrosine phosphatase with VEC, counteracting VEC phosphorylation. Finally, Src (proto-oncogene tyrosine-protein kinase Src) inhibition prevents VEC phosphorylation in endothelial cells and can rescue hyperfusion induced by low shear stress and DAPT treatment. Moesin, a VEC target that was previously reported to mediate endothelial cell rearrangement during lumenization, relocalizes to cell membranes in vascular beds undergoing hyperfusion.

Conclusions—
This study provides the first evidence that VEC phosphorylation, induced by DAPT treatment and low shear stress, is involved in the process of fusion during vascular remodeling.