bluuebunny/crossref_metadata_2025_split huggingface dataset:
Similar long‐term efficacy of dual therapy containing raltegravir and a boosted protease inhibitor versus standard triple therapies in pretreated HIV‐1‐infected patients in a retrospective, real‐life cohort of 14 years
Authors: Krznaric I , Bickel M , Carganico A , De Leuw P , Haberl A , Knecht G , Koegl C , Lauscher P , Schüttfort G , Stephan C , Wolf E , Wolf T 
Published: July 2018

ObjectivesRaltegravir is used in many antiretroviral combinations, but its use in treatment‐experienced patients without knowledge of baseline resistance is discussed controversially as a number of comparative studies have shown a higher rate of virological failure. However, it has been used frequently for the management of treatment failure, as it was the first integrase inhibitor to become available, and thus offered new options for patients with multiple resistance. The strategic use of raltegravir in this setting is examined in this study.MethodsIn order to examine the efficacy of raltegravir in second and later lines of antiretroviral combinations, data for 740 patients from three clinical cohorts were analysed with a focus on the combinations that were used. These were stratified into the combination of two nonnucleoside reverse transcriptase inhibitors and raltegravir (2NRTIs + RAL), the combination of a boosted protease inhibitor and raltegravir (bPI + RAL), and other raltegravir‐containing combinations.ResultsThe overall rate of virological suppression to < 50 HIV‐1 RNA copies/mL was 69.5%. Although the baseline rate of virological suppression was higher for 2NRTIs + RAL than for the other strata, the outcomes were similar for all three groups at weeks 24, 48, 72 and 96.ConclusionsThese data indicate that, in a real‐life setting, raltegravir can be used with a high virological success rate in treatment‐experienced patients, and that the different combinations analysed (2NRTIs + RAL, bPI + RAL and others) show comparable rates of virological suppression.
Geochronology, petrogenesis, and tectonic setting of Late Triassic volcanic rocks of the Hadataolegai Formation, central Great Xing'an Range, Northeast China
Authors: Tang Zong‐Yuan , Sun De‐You , Gou Jun , Yang Dong‐Guang 
Published: July 2018

AbstractIn this study, new geochemical, zircon U–Pb, and Lu–Hf isotopic data are presented for volcanics from the Hadataolegai Formation of the central Great Xing'an Range (GXR) in Northeast China. These new data offer insights into the petrogenesis of the volcanics of the Hadataolegai Formation and the tectonic evolution of the Paleo–Asian Ocean (PAO) and Mongol–Okhotsk Ocean (MOO). These volcanics of the Hadataolegai Formation are divided into andesite‐trachyandesites and dacite‐trachydacites. Zircon U–Pb ages show that the volcanics of the Hadataolegai Formation erupted between 230 Ma and 228 Ma during the Late Triassic, which agrees with recently obtained data. The volcanic rocks in this study have low Y (9.9–21.1 ppm) and Yb (0.78–2.02 ppm) contents, high Sr (444–954 ppm) contents, and slight Eu anomalies (δEu = 0.82 to 0.94), similar to ‘adakite‐like’ rocks. The dacites were formed by fractional crystallization of coeval andesitic magmas. The zircons within the andesite and trachyandesite yield higher positive εHf(t) values (+6.3 to +12.0) and model ages (TDM2) between 860 Ma and 453 Ma, which indicates that the magmas were generated by a newly accreted continental crustal source. Moreover, some of the volcanics are relatively high in MgO contents. These characteristics indicate that the volcanic magmas were derived from the partial melting of delaminated lower crust and mixing with mantle materials. Combining these data with previous studies, we suggest that the magmatism in the central GXR was governed by extension due to the closure of the PAO and the back‐arc extension associated with the southward subduction of the MOO plate (western GXR, near the Erguna Block).
Age composition of winter irruptive Snowy Owls in North America
Authors: Santonja Pablo , Mestre Irene , Weidensaul Scott , Brinker David , Huy Steve , Smith Norman , Mcdonald Tom , Blom Mike , Zazelenchuck Dan , Weber Drew , Gauthier Gilles , Lecomte Nicolas , Therrien Jean‐François 
Published: July 2018

Patterns of winter irruptions in several owl species apparently follow the ‘lack of food’ hypothesis, which predicts that individuals leave their breeding grounds in search of food when prey populations do not allow breeding and are too small to ensure survival. Recent analyses, however, suggest an alternative mechanism dubbed the ‘breeding success’ hypothesis, which predicts that winter irruptions might instead be the result of a very successful breeding season, with a large pool of young birds subsequently migrating south from the breeding grounds. Here we assessed age‐class (juvenile vs. non‐juvenile) composition of winter irruptive Snowy OwlsBubo scandiacusover a 25‐year period (winter 1991–1992 to 2015–2016) between regular (North American Prairies and Great Plains) and irregular wintering areas (northeastern North America) using live‐trapped individuals and high‐resolution images of individual owls. Our results show that the proportion of juveniles (birds less than 1 year of age) varies considerably annually but is positively correlated with irruption intensity in both regions. In irregular wintering areas, it can constitute the majority (up to more than 90%) of winter irruptive Snowy Owls over a large geographical area. These results are consistent with the idea that large winter irruptions at temperate latitudes are not the result of adults massively leaving the Arctic in search of food after a breeding failure but are more likely to be a consequence of good reproductive conditions in the Arctic that create a large pool of winter migrants.
Recent advances in cytogenetic characterization of multiple myeloma
Authors: Saxe Debra , Seo Eul‐Ju , Beaulieu Bergeron Melanie , Han Jin‐Yeong 
Published: July 2018

AbstractThe detection of cytogenetic abnormalities in multiple myeloma (MM) has received more importance over last years for risk stratification and the new risk‐adapted treatment strategies. Conventional G‐banding analysis should be included in a routine procedure for the initial diagnostic workup for patients suspected of MM. However, the detection of chromosomal abnormalities in MM by conventional cytogenetics is limited owing to the low proliferative activity of malignant plasma cells as well as the low number of plasma cells in bone marrow specimens. Fluorescence in situ hybridization (FISH) or microarray‐based technologies can overcome some of those drawbacks and detect specific target arrangements as well as chromosomal copy number changes. In this review, we will discuss different cytogenetic approaches and compare their strength and weakness to provide genetic information for risk stratification and prediction of outcome in MM patients.
Local exchange of metabolites shapes immunity
Authors: Richter Felix Clemens , Obba Sandrine , Simon Anna Katharina 
Published: July 2018

SummaryImmune cell differentiation and function depend on metabolic changes for the provision of energy and metabolites. Consequently, cellular metabolism relies on the availability of micronutrients such as vitamins and energy‐rich sources including amino acids and fatty acids. The bone marrow controls the continuous production of blood cells and is thereby reliant on the sophisticated interplay of progenitor and mature immune cells with its stromal microenvironment. The significance of stromal subsets in immunopoiesis is undisputed; however, our current knowledge is limited to their role in the production and secretion of a variety of soluble proteins such as cytokines. In contrast, the role of the haematopoietic niche in controlling and providing nutrients such as fatty acids, amino acids and vitamins, which are required for immune cell differentiation and function, remains largely elusive. In this review, we summarize the current understanding of local nutritional exchange and control between immune and stromal cells in peripheral tissue and, when it is known, in the bone marrow. The parallels found between peripheral tissues and bone marrow stroma raises the question of how local metabolism is capable of influencing haematopoiesis and immunopoiesis. A better understanding of the local exchange of nutrients in the bone marrow can be used to improve immune cell formation during ageing, after haematopoietic stem cell transplantation and during immune challenge.
Evaluation of the immune response against Trypanosoma cruzi cytosolic tryparedoxin peroxidase in human natural infection
Authors: Girard Magalí C. , Acevedo Gonzalo R. , López Lucía , Ossowski Micaela S. , Piñeyro María D. , Grosso Juan P. , Fernandez Marisa , Hernández Vasquez Yolanda , Robello Carlos , Gómez Karina A. 
Published: July 2018

SummaryTrypanosoma cruzi, the aetiological agent of Chagas disease, has a highly efficient detoxification system to deal with the oxidative burst imposed by its host. One of the antioxidant enzymes involved is the cytosolic tryparedoxin peroxidase (c‐TXNPx), which catalyses the reduction to hydrogen peroxide, small‐chain organic hydroperoxides and peroxynitrite. This enzyme is present in all parasite stages, and its overexpression renders parasites more resistant to the oxidative defences of macrophages, favouring parasite survival. This work addressed the study of the specific humoral and cellular immune response triggered by c‐TXNPx in human natural infection. Thus, sera and peripheral blood mononuclear cells (PBMC) were collected from chronically infected asymptomatic and cardiac patients, and non‐infected individuals. Results showed that levels of IgG antibodies against c‐TXNPx were low in sera from individuals across all groups. B‐cell epitope prediction limited immunogenicity to a few, small regions on the c‐TXNPx sequence. At a cellular level, PBMC from asymptomatic and cardiac patients proliferated and secreted interferon‐γ after c‐TXNPx stimulation, compared with mock control. However, only proliferation was higher in asymptomatic patients compared with cardiac and non‐infected individuals. Furthermore, asymptomatic patients showed an enhanced frequency of CD19+ CD69+ cells upon exposure to c‐TXNPx. Overall, our results show that c‐TXNPx fails to induce a strong immune response in natural infection, being measurable only in those patients without any clinical symptoms. The low impact of c‐TXNPx in the human immune response could be strategic for parasite survival, as it keeps this crucial antioxidant enzyme activity safe from the mechanisms of adaptive immune response.
Interleukin‐6 signalling mediates Galectin‐8 co‐stimulatory activity of antigen‐specific CD4 T‐cell response
Authors: Carabelli Julieta , Prato Cecilia A. , Sanmarco Liliana M. , Aoki Maria P. , Campetella Oscar , Tribulatti María V. 
Published: July 2018

SummaryGalectin‐8 (Gal‐8) is a mammalian lectin endowed with the ability to co‐stimulate antigen‐specific immune responses. We have previously demonstrated that bone‐marrow‐derived dendritic cells produce high levels of interleukin‐6 (IL‐6) in response to Gal‐8 stimulation. As IL‐6 is a pleiotropic cytokine that has a broad effect on cells of the immune system, we aimed to elucidate whether IL‐6 was involved in Gal‐8‐dependent co‐stimulatory signals during antigen recognition by specific CD4 T cells. With this aim, splenocytes from DO11.10 mice were incubated with a low dose of the cognate ovalbumin peptide in combination with Gal‐8. Interleukin‐6 was found significantly increased in cultures stimulated with Gal‐8 alone or Gal‐8 plus cognate peptide. Moreover, IL‐6 signalling was triggered during Gal‐8‐induced co‐stimulation, as determined by phosphorylation of signal transducer and activator of transcription 3. Interleukin‐6 blockade by neutralizing monoclonal antibody precluded Gal‐8 co‐stimulatory activity but did not affect the antigen‐specific T‐cell receptor activation. Different subsets of dendritic cells, as well as macrophages and B cells, were identified as the cellular source of IL‐6 during Gal‐8‐induced co‐stimulation. To confirm that IL‐6 mediated the Gal‐8 co‐stimulatory effect, antigen‐presenting cells from IL‐6‐deficient or wild‐type mice were co‐cultured with purified CD4 T cells from OTII mice in the presence of cognate peptide and Gal‐8. Notably, Gal‐8‐induced co‐stimulation, but not the antigen‐specific response, was significantly impaired in the presence of IL‐6‐deficient antigen‐presenting cells. In addition, exogenous IL‐6 fully restored Gal‐8‐induced co‐stimulation. Taken together, our results demonstrate that IL‐6 signalling mediates the Gal‐8 immune‐stimulatory effect.
Analysing Multivariate Spatial Point Processes with Continuous Marks: A Graphical Modelling Approach
Authors: Eckardt Matthias , Mateu Jorge 
Published: July 2018

SummaryThis paper discusses the application of graphical modelling in the statistical analysis of marked point patterns. We consider a multivariate planar point process with quantitative marks. After a survey of statistical methods for marked point processes, a new graphical model is presented. The sub‐processes of marked points with identical discrete marks are identified with nodes of a graph, which is used to describe aspects of the spatial relationship: If two sub‐patterns are similar, then an arc is made between the corresponding nodes. Similarity is defined based on spectral densities, which makes the computations efficient. The resulting graph presents all these pairwise similarities simultaneously. We demonstrate the application of our method in the analysis of a multi‐species forest, where the points are tree locations, the discrete marks tree species and the quantitative marks are the diameters at breast height.
Yield potential and salt tolerance of quinoa on salt‐degraded soils of Pakistan
Authors: Iqbal Shahid , Basra Shahzad M. A. , Afzal Irfan , Wahid Abdul , Saddiq Muhammad S. , Hafeez Muhammad B. , Jacobsen Sven‐Erik 
Published: July 2018

AbstractQuinoa is recently introduced to Pakistan as a salt‐tolerant crop of high nutritional value. Open field trials were conducted to evaluate its performance on normal and salinity/sodicity‐degraded lands at two locations of different salinity/sodicity levels, S1 (UAF Farm, Normal Soil), S2 (Paroka Farm UAF, saline sodic), S3 (SSRI Farm, normal) and S4 (SSRI Farm, saline sodic) during 2013–2014. Two genotypes (Q‐2 and Q‐7) were grown in lines and were allowed to grow till maturity under RCBD split‐plot arrangement. Maximum seed yield (3,062 kg/ha) was achieved by Q‐7 at normal field (S1) soil which was statistically similar with yield of same genotype obtained from salt‐affected field S2 (2,870 kg/ha). Furthermore, low yield was seen from both genotypes from both S3 and S4 as compared to S1 and S2. Q‐7 was best under all four conditions. Minimum yield was recorded from Q‐2 (1,587 kg/ha) at S4. Q‐7 had higher SOD, proline, phenolic and K+ contents, and lower Na+ content in leaves as compared to Q‐2. High levels of antioxidants and K+/Na+ of Q‐7 helped to withstand salt stress and might be the cause of higher yields under both normal and salt‐affected soils. Seed quality (mineral and protein) did not decrease considerably under salt‐affected soils even improved seed K+, Mg2+ and Mn2+.
Randomized controlled trials of U‐Pace instruction: Outcomes in two gateway courses
Authors: Fleming Raymond , Kienzler Sarah , Stoiber Leah , Fleming Ryan R. , Pedrick Laura E. , Reddy Diane M. 
Published: July 2018

AbstractLess than optimal student success in gateway courses figures prominently in college noncompletion. Past findings suggest that U‐Pace instruction holds promise for increasing student success. However, all published studies of U‐Pace instruction were conducted in the gateway course context of introductory psychology. The objective of this research was to rigorously evaluate the efficacy of U‐Pace instruction in introductory sociology and introductory political science for students at‐risk for college noncompletion and students not at‐risk. The findings from both randomized controlled trials indicate that regardless of risk status, U‐Pace students outperformed their conventionally taught face‐to‐face counterparts earning a greater percentage of final grades of A or B and higher scores on a proctored cumulative assessment of learning, independent of final grades. The results not only confirm previous findings of greater academic success and greater learning associated with U‐Pace instruction but also clearly demonstrate that U‐Pace instruction produces greater learning and greater academic success. Further, the findings of this research reveal that these student outcomes generalize across courses in two disciplines for both students at‐risk for college noncompletion and students not at‐risk, providing strong support for the efficacy of U‐Pace instruction.
Long non‐coding RNA AFAP1‐AS1/miR‐320a/RBPJ axis regulates laryngeal carcinoma cell stemness and chemoresistance
Authors: Yuan Zhennan , Xiu Cheng , Song Kaibin , Pei Rong , Miao Susheng , Mao Xionghui , Sun Ji , Jia Shenshan 
Published: July 2018

AbstractAFAP1‐AS1 is a long non‐coding RNA that is associated with tumorigenesis and poor prognosis in a variety of cancers. We have been suggested that AFAP1‐AS1 increases tumorigenesis in laryngeal carcinoma specifically by enhancing stemness and chemoresistance. We assessed AFAP1‐AS1 expression in human laryngeal specimens, paired adjacent normal tissues and human HEp‐2 cells. Indeed, we found not only that AFAP1‐AS1 was up‐regulated in laryngeal carcinoma specimens and cells, but also that stemness‐associated genes were overexpressed. Silencing of AFAP1‐AS1 promoted HEp‐2 cell chemoresistance under cisplatin treatment. Expression of AFAP1‐AS1 was increased in drug‐resistant Hep‐2 cells. We then probed the mechanism of AFAP1‐AS1 activity and determined that miR‐320a was a potential molecular target of AFAP1‐AS1. Luciferase reporter and qRT‐PCR assays of AFAP1‐AS1 and miR‐320a levels in human specimens and cell cultures indicated that AFAP1‐AS1 negatively regulates miR‐320a. To discover the molecular mechanism of miR‐320a, we again used the DIANA Tools algorithm to predict its genetic target, RBPJ. After cloning the 3′‐untranslated regions (3′‐UTR) of RBPJ into a luciferase reporter, we determined that miR‐320a did in fact reduce RBPJ mRNA and protein levels. Ultimately, we determined that AFAP1‐AS1 increases RBPJ expression by negatively regulating miR‐320a and RBPJ overexpression rescues stemness and chemoresistance inhibited by AFAP1‐AS1 silencing. Taken together, these results suggest that AFAP1‐AS1 can serve as a prognostic biomarker in laryngeal carcinoma and that miR‐320a has the potential to improve standard therapeutic approaches to the disease, especially for cases in which cancer cell stemness and drug resistance present significant barriers to effective treatment.
Captopril mitigates splenomegaly and myelofibrosis in the Gata1low murine model of myelofibrosis
Authors: Corey Seth J. , Jha Jyoti , McCart Elizabeth A. , Rittase William B. , George Jeffy , Mattapallil Joseph J. , Mehta Hrishikesh , Ognoon Mungunsukh , Bylicky Michelle A. , Summers Thomas A. , Day Regina M. 
Published: July 2018

AbstractAllogeneic stem cell transplantation is currently the only curative therapy for primary myelofibrosis (MF), while the JAK2 inhibitor, ruxolitinib. Has been approved only for palliation. Other therapies are desperately needed to reverse life‐threatening MF. However, the cell(s) and cytokine(s) that promote MF remain unclear. Several reports have demonstrated that captopril, an inhibitor of angiotensin‐converting enzyme that blocks the production of angiotensin II (Ang II), mitigates fibrosis in heart, lung, skin and kidney. Here, we show that captopril can mitigate the development of MF in the Gata1low mouse model of primary MF. Gata1low mice were treated with 79 mg/kg/d captopril in the drinking water from 10 to 12 months of age. At 13 months of age, bone marrows were examined for fibrosis, megakaryocytosis and collagen expression; spleens were examined for megakaryocytosis, splenomegaly and collagen expression. Treatment of Gata1low mice with captopril in the drinking water was associated with normalization of the bone marrow cellularity; reduced reticulin fibres, splenomegaly and megakaryocytosis; and decreased collagen expression. Our findings suggest that treating with the ACE inhibitors captopril has a significant benefit in overcoming pathological changes associated with MF.
Astragaloside IV modulates TGF‐β1‐dependent epithelial‐mesenchymal transition in bleomycin‐induced pulmonary fibrosis
Authors: Qian Weibin , Cai Xinrui , Qian Qiuhai , Zhang Wei , Wang Dongli 
Published: July 2018

AbstractEpithelial‐mesenchymal transition (EMT) plays an important role in idiopathic pulmonary fibrosis (IPF). Astragaloside IV (ASV), a natural saponin from astragalus membranaceus, has shown anti‐fibrotic property in bleomycin (BLM)‐induced pulmonary fibrosis. The current study was undertaken to determine whether EMT was involved in the beneficial of ASV against BLM‐induced pulmonary fibrosis and to elucidate its potential mechanism. As expected, in BLM‐induced IPF, ASV exerted protective effects on pulmonary fibrosis and ASV significantly reversed BLM‐induced EMT. Intriguing, transforming growth factor‐β1 (TGF‐β1) was found to be up‐regulated, whereas Forkhead box O3a (FOXO3a) was hyperphosphorylated and less expressed. However, ASV treatment inhibited increased TGF‐β1 and activated FOXO3a in lung tissues. TGF‐β1 was administered to alveolar epithelial cells A549 to induce EMT in vitro. Meanwhile, stimulation with TGF‐β1‐activated phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) pathway and induced FOXO3a hyperphosphorylated and down‐regulated. It was found that overexpression of FOXO3a leading to the suppression of TGF‐β1‐induced EMT. Moreover, ASV treatment, similar with the TGF‐β1 or PI3K/Akt inhibitor, reverted these cellular changes and inhibited EMT in A549 cells. Collectively, the results suggested that ASV significantly inhibited TGF‐β1/PI3K/Akt‐induced FOXO3a hyperphosphorylation and down‐regulation to reverse EMT during the progression of fibrosis.
Saliva and serum biomarkers in periodontitis and coronary artery disease
Authors: Lahdentausta Laura S. J. , Paju Susanna , Mäntylä Päivi , Buhlin Kåre , Tervahartiala Taina , Pietiäinen Milla , Alfthan Henrik , Nieminen Markku S. , Sinisalo Juha , Sorsa Timo , Pussinen Pirkko J. 
Published: July 2018

AbstractAimMatrix metalloproteinase (MMP)‐8, MMP‐9, tissue inhibitor of matrix metalloproteinase (TIMP)‐1 and myeloperoxidase (MPO) participate in extracellular matrix breakdown both in periodontium and atherosclerotic plaques. We investigated the diagnostic value of serum and saliva biomarkers in periodontitis and acute coronary syndrome (ACS).Materials and methodsThe population was PAROGENE (n = 481), a random cohort of patients with an indication for coronary angiography. All patients underwent a clinical and radiographic oral examination. Groups consisting of periodontitis versus non‐periodontitis, and ACS versus non‐ACS patients were compared.ResultsSaliva MMP‐8, MMP‐9 and MPO provided significant area‐under‐curve (AUC) values for periodontitis, 0.69 (<0.001), 0.66 (<0.001) and 0.68 (<0.001), respectively. Serum MMP‐8, MMP‐9 and MPO levels distinguished ACS from non‐ACS patients with AUCs of 0.73 (<0.001), 0.58 (0.03) and 0.68 (<0.001), respectively. Periodontitis confounded the use of serum MMP‐9 in diagnostics of ACS. Cardiac status complicated the use of saliva TIMP‐1 in periodontal diagnostics. Saliva biomarkers could not be used in ACS diagnosis, and serum biomarkers were not useful in diagnosis of periodontitis.ConclusionsMMP‐8, MMP‐9, TIMP‐1and MPO are valuable biomarkers for both ACS and periodontitis, but the selection of sample material is crucial; serum is suitable for ACS and saliva for periodontal diagnostic aid.