bluuebunny/crossref_metadata_2025_split huggingface dataset:
Verticillium dahliae manipulates plant immunity by glycoside hydrolase 12 proteins in conjunction with carbohydrate‐binding module 1
Authors: Gui Yue‐Jing , Chen Jie‐Yin , Zhang Dan‐Dan , Li Nan‐Yang , Li Ting‐Gang , Zhang Wen‐Qi , Wang Xin‐Yan , Short Dylan P. G. , Li Lei , Guo Wei , Kong Zhi‐Qiang , Bao Yu‐Ming , Subbarao Krishna V. , Dai Xiao‐Feng 
Published: February 2017

SummaryGlycoside hydrolase 12 (GH12) proteins act as virulence factors and pathogen‐associated molecular patterns (PAMPs) in oomycetes. However, the pathogenic mechanisms of fungal GH12 proteins have not been characterized. In this study, we demonstrated that two of the six GH12 proteins produced by the fungus Verticillium dahliae Vd991, VdEG1 and VdEG3 acted as PAMPs to trigger cell death and PAMP‐triggered immunity (PTI) independent of their enzymatic activity in Nicotiana benthamiana. A 63‐amino‐acid peptide of VdEG3 was sufficient for cell death‐inducing activity, but this was not the case for the corresponding peptide of VdEG1. Further study indicated that VdEG1 and VdEG3 trigger PTI in different ways: BAK1 is required for VdEG1‐ and VdEG3‐triggered immunity, while SOBIR1 is specifically required for VdEG1‐triggered immunity in N. benthamiana. Unlike oomycetes, which employ RXLR effectors to suppress host immunity, a carbohydrate‐binding module family 1 (CBM1) protein domain suppressed GH12 protein‐induced cell death. Furthermore, during infection of N. benthamiana and cotton, VdEG1 and VdEG3 acted as PAMPs and virulence factors, respectively indicative of host‐dependent molecular functions. These results suggest that VdEG1 and VdEG3 associate differently with BAK1 and SOBIR1 receptor‐like kinases to trigger immunity in N. benthamiana, and together with CBM1‐containing proteins manipulate plant immunity.
Association between leukocyte telomere length and angiogenic cytokines in knee osteoarthritis
Authors: Poonpet Thitiya , Saetan Natthaphon , Tanavalee Aree , Wilairatana Vajara , Yuktanandana Pongsak , Honsawek Sittisak 
Published: February 2017

AbstractAimThe aims of this study were to compare leukocyte relative telomere length (RTL) in knee osteoarthritis (OA) patients and healthy controls and to investigate associations between plasma angiogenic cytokine concentrations and leukocyte RTL.MethodEighty knee OA patients and 60 age‐matched controls were enrolled. Leukocyte RTL was assessed using real‐time quantitative polymerase chain reaction (qPCR). Angiogenic cytokines were measured by a multiplex immunoassay.ResultsLeukocyte RTL in knee OA patients was significantly lower than that in healthy controls (1.1 ± 0.4 vs. 1.3 ± 0.6, P = 0.039). Plasma angiopoietin‐2, follistatin, granulocyte‐colony stimulating factor (G‐CSF), hepatocyte growth factor (HGF), interleukin‐8 (IL‐8), platelet endothelial cell adhesion molecule‐1 (PECAM‐1), and vascular endothelial growth factor (VEGF) levels in knee OA patients were higher than those in controls (P < 0.01). Correlation analysis revealed significant negative correlations between leukocyte RTL and plasma levels of HGF (r = −0.377, P = 0.017), VEGF (r = −0.405, P = 0.009) and G‐CSF (r = −0.347, P = 0.026). In contrast, plasma angiopoietin‐2, follistatin, IL‐8, leptin, platelet‐derived growth factor‐BB and PECAM‐1 were not correlated with leukocyte RTL.ConclusionTelomere length was shortened in knee OA patients compared to healthy controls. Plasma HGF, VEGF and G‐CSF were negatively correlated with leukocyte RTL, suggesting involvement of telomere shortening and these cytokines in knee OA.
A multiparametric magnetic resonance imaging‐based risk model to determine the risk of significant prostate cancer prior to biopsy
Authors: van Leeuwen Pim J. , Hayen Andrew , Thompson James E. , Moses Daniel , Shnier Ron , Böhm Maret , Abuodha Magdaline , Haynes Anne‐Maree , Ting Francis , Barentsz Jelle , Roobol Monique , Vass Justin , Rasiah Krishan , Delprado Warick , Stricker Phillip D. 
Published: February 2017

ObjectiveTo develop and externally validate a predictive model for detection of significant prostate cancer.Patients and MethodsDevelopment of the model was based on a prospective cohort including 393 men who underwent multiparametric magnetic resonance imaging (mpMRI) before biopsy. External validity of the model was then examined retrospectively in 198 men from a separate institution whom underwent mpMRI followed by biopsy for abnormal prostate‐specific antigen (PSA) level or digital rectal examination (DRE). A model was developed with age, PSA level, DRE, prostate volume, previous biopsy, and Prostate Imaging Reporting and Data System (PIRADS) score, as predictors for significant prostate cancer (Gleason 7 with >5% grade 4, ≥20% cores positive or ≥7 mm of cancer in any core). Probability was studied via logistic regression. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling.ResultsIn all, 393 men had complete data and 149 (37.9%) had significant prostate cancer. While the variable model had good accuracy in predicting significant prostate cancer, area under the curve (AUC) of 0.80, the advanced model (incorporating mpMRI) had a significantly higher AUC of 0.88 (P < 0.001). The model was well calibrated in internal and external validation. Decision analysis showed that use of the advanced model in practice would improve biopsy outcome predictions. Clinical application of the model would reduce 28% of biopsies, whilst missing 2.6% significant prostate cancer.ConclusionsIndividualised risk assessment of significant prostate cancer using a predictive model that incorporates mpMRI PIRADS score and clinical data allows a considerable reduction in unnecessary biopsies and reduction of the risk of over‐detection of insignificant prostate cancer at the cost of a very small increase in the number of significant cancers missed.
Opposite effects of a glucokinase activator and metformin on glucose‐regulated gene expression in hepatocytes
Authors: Al‐Oanzi Ziad H. , Fountana Sophia , Moonira Tabassum , Tudhope Susan J. , Petrie John L. , Alshawi Ahmed , Patman Gillian , Arden Catherine , Reeves Helen L. , Agius Loranne 
Published: February 2017

AimSmall molecule activators of glucokinase (GKAs) have been explored extensively as potential anti‐hyperglycaemic drugs for type 2 diabetes (T2D). Several GKAs were remarkably effective in lowering blood glucose during early therapy but then lost their glycaemic efficacy chronically during clinical trials.Materials and MethodsWe used rat hepatocytes to test the hypothesis that GKAs raise hepatocyte glucose 6‐phosphate (G6P, the glucokinase product) and down‐stream metabolites with consequent repression of the liver glucokinase gene (
Gck). We compared a GKA with metformin, the most widely prescribed drug for T2D.ResultsTreatment of hepatocytes with 25 mM glucose raised cell G6P, concomitantly with Gck repression and induction of G6pc (glucose 6‐phosphatase) and Pklr (pyruvate kinase). A GKA mimicked high glucose by raising G6P and fructose‐2,6‐bisphosphate, a regulatory metabolite, causing a left‐shift in glucose responsiveness on gene regulation. Fructose, like the GKA, repressed Gck but modestly induced G6pc. 2‐Deoxyglucose, which is phosphorylated by glucokinase but not further metabolized caused Gck repression but not G6pc induction, implicating the glucokinase product in Gck repression. Metformin counteracted the effect of high glucose on the elevated G6P and fructose 2,6‐bisphosphate and on Gck repression, recruitment of Mlx‐ChREBP to the G6pc and Pklr promoters and induction of these genes.ConclusionsElevation in hepatocyte G6P and downstream metabolites, with consequent liver
Gck repression, is a potential contributing mechanism to the loss of GKA efficacy during chronic therapy. Cell metformin loads within the therapeutic range attenuate the effect of high glucose on G6P and on glucose‐regulated gene expression.
From salmon to shad: Shifting sources of marine‐derived nutrients in the Columbia River Basin
Authors: Haskell Craig A. 
Published: February 2017

AbstractLike Pacific salmon (Oncorhynchus spp.), nonnative American shad (Alosa sapidissima) have the potential to convey large quantities of nutrients between the Pacific Ocean and freshwater spawning areas in the Columbia River Basin (CRB). American shad are now the most numerous anadromous fish in the CRB, yet the magnitude of the resulting nutrient flux owing to the shift from salmon to shad is unknown. Nutrient flux models revealed that American shad conveyed over 15,000 kg of nitrogen (N) and 3,000 kg of phosphorus (P) annually to John Day Reservoir, the largest mainstem reservoir in the lower Columbia River. Shad were net importers of N, with juveniles and postspawners exporting just 31% of the N imported by adults. Shad were usually net importers of P, with juveniles and postspawners exporting 46% of the P imported by adults on average. American shad contributed <0.2% of the total annual P load into John Day Reservoir, but during June when most adult shad are migrating into John Day Reservoir, they contributed as much as 2.0% of the P load. Nutrient inputs by American shad were similar to current but far less than historical inputs of Pacific salmon owing to their smaller size. Given the relatively high background P levels and low retention times in lower Columbia River reservoirs, it is unlikely that shad marine‐derived nutrients affect nutrient balances or food web productivity through autotrophic pathways. However, a better understanding of shad spawning aggregations in the CRB is needed.
Natural history and clinical characteristics of inhibitors in previously treated haemophilia A patients: a case series
Authors: Iorio A. , Barbara A. M. , Makris M. , Fischer K. , Castaman G. , Catarino C. , Gilman E. , Kavakli K. , Lambert T. , Lassila R. , Lissitchkov T. , Mauser‐Bunschoten E. , Mingot‐Castellano M. E. , Ozdemir N. , Pabinger I. , Parra R. , Pasi J. , Peerlinck K. , Rauch A. , Roussel‐Robert V. , Serban M. , Tagliaferri A. , Windyga J. , Zanon E. 
Published: February 2017

BackgroundDevelopment of inhibitors is the most serious complication in haemophilia A treatment. The assessment of risk for inhibitor formation in new or modified factor concentrates is traditionally performed in previously treated patients (PTPs). However, evidence on risk factors for and natural history of inhibitors has been generated mostly in previously untreated patients (PUPs). The purpose of this study was to examine cases of de novo inhibitors in PTPs reported in the scientific literature and to the EUropean HAemophilia Safety Surveillance (EUHASS) programme, and explore determinants and course of inhibitor development.MethodsWe used a case series study design and developed a case report form to collect patient level data; including detection, inhibitor course, treatment, factor VIII products used and events that may trigger inhibitor development (surgery, vaccination, immune disorders, malignancy, product switch).ResultsWe identified 19 publications that reported 38 inhibitor cases and 45 cases from 31 EUHASS centres. Individual patient data were collected for 55/83 (66%) inhibitor cases out of 12 330 patients. The median (range) peak inhibitor titre was 4.4 (0.5–135.0), the proportion of transient inhibitors was 33% and only two cases of 12 undergoing immune tolerance induction failed this treatment. In the two months before inhibitor development, surgery was reported in nine (22%) cases, and high intensity treatment periods reported in seven (17%) cases.ConclusionsBy studying the largest cohort of inhibitor development in PTPs assembled to date, we showed that inhibitor development in PTPs, is on average, a milder event than in PUPs.
Can the diagnostic reliability of the thrombin generation test as a global haemostasis assay be improved? The impact of calcium chloride concentration
Authors: Parunov L. A. , Surov S. S. , Liang Y. , Lee T. K. , Ovanesov M. V. 
Published: February 2017

BackgroundThrombin generation test (TGT) is a global haemostasis assay with a potential to predict bleeding tendencies and treatment effects in patients with haemophilia. Despite 15 years of clinical research, the diagnostic value of TGT remains controversial, possibly due to suboptimal sensitivity to coagulation deficiencies, robustness and reproducibility.ObjectiveThe goal of this study was to explore the effect of calcium chloride (CaCl2) concentration on the TGT's response to intrinsic coagulation factors (F) VIII, IX and XIa.MethodsNormal and factor‐deficient plasmas supplemented with lacking coagulation factor and different CaCl2 levels were tested by calibrated thrombinography assay.ResultsThrombin peak height (TPH) was strongly CaCl2 dependent, increasing sharply from no TG at 5 mm to a peak at 13.8 mm of CaCl2 (95% confidence interval [CI]: 13.0, 14.5) in normal and normalized deficient plasmas and at 11.9 mm (CI: 9.7, 14.2) in deficient plasmas, and then decreasing slowly to a complete inhibition at 30–40 mm. In contrast, TG lag time, time to peak and endogenous thrombin potential were nearly insensitive to CaCl2 concentrations between 10 and 20 mm. The maximal difference between the TPH in deficient and supplemented plasmas was observed at 15.5 mm (CI: 12.8, 18.1).ConclusionVariations in CaCl2 concentration in the assay mixture and sodium citrate concentrations in patient plasma samples may affect TGT responses, sensitivity and result in increased inter‐ and intra‐laboratory variance. Implementation of TGT by clinical and quality control laboratories may require optimization of CaCl2 concentration.
Antigenic cross‐reactivity between Schistosoma mansoni and peanut: a role for cross‐reactive carbohydrate determinants (CCDs) and implications for the hygiene hypothesis
Authors: Igetei Joseph E. , El‐Faham Marwa , Liddell Susan , Doenhoff Michael J. 
Published: February 2017

SummaryThe antigenic reactivity of constituents of Schistosoma mansoni and peanut (Arachis hypogaea) was investigated to determine whether identical antigenic epitopes possessed by both organisms provided a possible explanation for the negative correlation between chronic schistosome infection and atopy to allergens. Aqueous extracts of peanuts were probed in Western immunoblots with rabbit IgG antibodies raised against the egg, cercarial and adult worm stages of S. mansoni. Several molecules in the peanut extract were antigenically reactive with antibodies from the various rabbit anti‐schistosome sera. A pair of cross‐reactive peanut molecules at ~30 000–33 000 molecular weight was purified and both proteins were identified by mass spectrometric analysis as the peanut allergen Ara h 1. Anti‐S. mansoni soluble egg antigen antibodies that were eluted off the peanut molecules reacted with two S. mansoni egg antigens identified by mass spectrometry as IPSE/α‐1 and κ‐5. Alignments of the amino acid sequences of Ara h 1 and either IPSE/α‐1 or κ‐5 revealed a low level of peptide sequence identity. Incubation of nitrocellulose paper carrying electrophoresed peanut molecules, six constituents of other allergic plants and S. mansoni egg antigens in a mild solution of sodium metaperiodate before probing with antibodies, inhibited most of the cross‐reactivities. The results are consistent with the antigenic cross‐reactive epitopes of S. mansoni egg antigens, peanut and other allergic plants being cross‐reactive carbohydrate determinants (CCDs). These findings are novel and an explanation based on ‘blocking antibodies’ could provide an insight for the inverse relationship observed between schistosome infection and allergies.
Structural and functional changes to lymph nodes in ageing mice
Authors: Turner Vivian M. , Mabbott Neil A. 
Published: February 2017

SummaryLymph nodes (LN) are secondary lymphoid organs spread throughout the lymphatic system. They function to filter pathogenic material from the lymphatic fluid to maintain the health of the organism. Subcapsular sinus macrophages (SCSM) are among the first‐responders within the LN due to their strategic location within the subcapsular sinus region. These macrophages aid the delivery of immune complexes to B cells and follicular dendritic cells (FDC) within the LN. Here we show an increase in SCSM and other macrophage populations within aged LN. However, immune complex uptake by macrophages within LN was not altered with age, nor was immune complex uptake by B cells. LN stromal cell populations, important in immune responses and the localization and survival of leucocytes, were altered in their representation and distribution in aged LN. In particular, FDC regions were decreased in size and had decreased chemokine CXCL13 expression. Furthermore, the retention of immune complexes by FDC was decreased in aged LN at 24 hr post‐injection. As FDC are important in the maintenance of germinal centre responses, the decreased retention of immune complex in aged LN may contribute to the reduced germinal centre responses observed in aged mice.
Novel multiplex assay platforms to detect influenza A hemagglutinin subtype‐specific antibody responses for high‐throughput and in‐field applications
Authors: Li Zhu‐Nan , Trost Jessica F. , Weber Kimberly M. , LeMasters Elizabeth H. , Nasreen Sharifa , Esfandiari Javan , Gunasekera Angelo H. , McCausland Megan , Sturm‐Ramirez Katharine , Wrammert Jens , Gregory Sean , Veguilla Vic , Stevens James , Miller Joseph D. , Katz Jacqueline M. , Levine Min Z. 
Published: February 2017

BackgroundDetections of influenza A subtype‐specific antibody responses are often complicated by the presence of cross‐reactive antibodies. We developed two novel multiplex platforms for antibody detection. The multiplexed magnetic fluorescence microsphere immunoassay (MAGPIX) is a high‐throughput laboratory‐based assay. Chembio Dual Path Platform (DPP) is a portable and rapid test that could be used in the field.MethodsTwelve recombinant globular head domain hemagglutinin (GH HA1) antigens from A(H1N1)pdm09 (pH1N1), A(H2N2), A(H3N2), A(H5N1), A(H7N9), A(H9N2), A(H13N9), B/Victoria lineage, B/Yamagata lineage viruses, and protein A control were used. Human sera from U.S. residents either vaccinated (with H5N1 or pH1N1) or infected with pH1N1 influenza viruses and sera from live bird market workers in Bangladesh (BDPW) were evaluated. GH HA1 antigens and serum adsorption using full ectodomain recombinant hemagglutinins from A(pH1N1) and A(H3N2) were introduced into the platforms to reduce cross‐reactivity.ResultsSerum adsorption reduced cross‐reactivity to novel subtype HAs. Compared to traditional hemagglutination inhibition or microneutralization assays, when serum adsorption and the highest fold rise in signals were used to determine positivity, the correct subtype‐specific responses were identified in 86%‐100% of U.S. residents exposed to influenza antigens through vaccination or infection (N=49). For detection of H5N1‐specific antibodies in sera collected from BDPW, H5 sensitivity was 100% (six of six) for MAGPIX, 83% (five of six) for DPP, H5 specificity was 100% (15/15), and cross‐reactivity against other subtype was 0% (zero of six) for both platforms.ConclusionMAGPIX and DPP platforms can be utilized for high‐throughput and in‐field detection of novel influenza virus infections.
Supporting existential care with protected mealtimes: patients' experiences of a mealtime intervention in a neurological ward
Authors: Beck Malene , Birkelund Regner , Poulsen Ingrid , Martinsen Bente 
Published: February 2017

AbstractAimThe aim of this study was to explore the experiences of patients who were admitted to the neurological ward during an intervention – inspired by Protected Mealtime – that changed the traditional mealtime practice.BackgroundMealtimes are busy events in hospitals and patients are often interrupted by high‐priority tasks (e.g. taking blood samples) while eating. Protected mealtimes is a British concept that changes the organizational structure of mealtimes and provides a focus on the mealtime by ceasing all non‐acute activities while patients are eating.DesignInfluenced by protected mealtimes and based on the British Medical Research Council (MRC) guidelines, a clinical intervention called Quiet Please was developed, modified and tested in a department of neurology in November 2014.MethodsTo evaluate the Quiet Please intervention, 13 semi‐structured interviews were conducted with patients who were admitted to the neurological ward. The interviews were recorded and transcribed. These data were thoroughly analysed and interpreted with inspiration from the French philosopher, Paul Ricouer.FindingsThree themes were identified from the analysis and interpretation: (1) being powered by the bell; (2) being embraced by calmness and aesthetics and (3) being in a trust‐bearing agreement.ConclusionsPatients experienced mealtimes as meaningful events that nourished them in an existential manner because the calming and aesthetically pleasing environment made them feel embraced and allowed them to reflect on the day for a while. The mealtime change, influenced by protected mealtimes, made the patients feel recognized as humans and established positive mealtime experiences that were considered professional and trust bearing.
Parental psychopathology and expectations for the futures of children with autism spectrum disorder
Authors: Thomas Paul Andrew , King Jake S , Mendelson Jenna L , Nelson‐Gray Rosemery O 
Published: February 2017

BackgroundThe influence of parental psychopathology and parental expectations on child well‐being is well documented among typically developing populations. However, to date little research has examined the relationship among these factors in families of children with autism spectrum disorder (ASD). This study examines an observed relationship between parental psychopathology and expectations in families with children with ASD in the light of research in other populations.MethodTwenty‐four parents of children diagnosed with ASD were assessed for symptoms of psychopathology. Parents completed measures of child ASD severity as well as their expectations for possible outcomes of their child.ResultsTwo main effects were found: higher parental psychopathology and ASD severity were both related to lower expectations. Interaction of ASD severity and parental psychopathology in relation to parent expectations was not observed.ConclusionThese results emphasize the necessity of providing services not only to individuals diagnosed with ASD, but to caregivers as well.
Post‐extraction mesio‐distal gap reduction assessment by confocal laser scanning microscopy – a clinical 3‐month follow‐up study
Authors: García‐Herraiz Ariadna , Silvestre Francisco Javier , Leiva‐García Rafael , Crespo‐Abril Fortunato , García‐Antón José 
Published: February 2017

AbstractAimThe aim of this 3‐month follow‐up study is to quantify the reduction in the mesio‐distal gap dimension (MDGD) that occurs after tooth extraction through image analysis of three‐dimensional images obtained with the confocal laser scanning microscopy (CLSM) technique.Materials and MethodsFollowing tooth extraction, impressions of 79 patients 1 month and 72 patients 3 months after tooth extraction were obtained. Cast models were processed by CLSM, and MDGD changes between time points were measured.ResultsThe mean mesio‐distal gap reduction 1 month after tooth extraction was 343.4 μm and 3 months after tooth extraction was 672.3 μm. The daily mean gap reduction rate during the first term (between baseline and 1 month post‐extraction measurements) was 10.3 μm/day and during the second term (between 1 and 3 months) was 5.4 μm/day.ConclusionsThe mesio‐distal gap reduction is higher during the first month following the extraction and continues in time, but to a lesser extent. When the inter‐dental contacts were absent, the mesio‐distal gap reduction is lower. When a molar tooth is extracted or the distal tooth to the edentulous space does not occlude with an antagonist, the mesio‐distal gap reduction is larger. The consideration of mesio‐distal gap dimension changes can help improve dental treatment planning.