bluuebunny/crossref_metadata_2025_split huggingface dataset:
A hot‐water extract of Sanguisorba officinalis ameliorates endotoxin‐induced septic shock by inhibiting inflammasome activation
Authors: Seo Dong‐Won , Cho Yong‐Il , Gu Suna , Kim Da‐Hee , Yi Young‐Joo , Lee Sang‐Myeong 
Published: November 2017

ABSTRACTThe inflammasome is a multiprotein signaling complex that mediates inflammatory innate immune responses through caspase 1 activation and subsequent IL‐1β secretion. However, because its aberrant activation often leads to inflammatory diseases, targeting the inflammasome holds promise for the treatment of inflammation‐related diseases. In this study, it was found that a hot‐water extract of Sanguisorba officinalis (HSO) suppresses inflammasome activation triggered by adenosine 5′‐triphosphate, nigericin, microbial pathogens, and double stranded DNA in bone marrow‐derived macrophages. HSO was found to significantly suppress IL‐1β production in a dose‐dependent manner; this effect correlated well with small amounts of caspase 1 and little ASC pyroptosome formation in HSO‐treated cells. The anti‐inflammatory activity of HSO was further confirmed in a mouse model of endotoxin‐induced septic shock. Oral administration of HSO reduced IL‐1β titers in the serum and peritoneal cavity, increasing the survival rate. Taken together, our results suggest that HSO is an inhibits inflammasome activation through nucleotide‐binding domain and leucine‐rich repeat pyrin domain 3, nucleotide‐binding domain and leucine‐rich repeat caspase recruitment domain 4 and absent in melanoma 2 pathways, and may be useful for treatment of inflammasome‐mediated diseases.
Obstacles and challenges for tissue engineering and regenerative medicine: Australian nuances
Authors: Grounds Miranda D 
Published: November 2017

SummaryThe clinical need and historical approaches to tissue engineering as applied to regenerative medicine are introduced, along with comments on activities in this field around Australia, and then the huge advances for tissue culture studies are discussed (Part A). Combinations of human stem cells and new approaches for generating bioscaffolds present great opportunities for in vitro studies of basic biology and physiology, drug testing and high throughput screening for the pharmaceutical industry, and the advanced tissue engineering of organs and devices. The future here is bright. The major obstacles arise with in vivo application of these bioengineering advances using animal models and humans (Part B), and the complexity of living tissues and the challenges of increased scale required for clinical translation to the large human situation are first discussed. While clinical success seen with implantation of acellular bioscaffolds (with population by host cells) is likely to expand for human use, the major challenge relates to (generally) low survival in vivo of (donor or autologous) cells that are expanded and grown in tissue culture before implantation into the living body. Another major challenge is revascularisation of implanted tissues/organs at the human scale. The innovative approaches and rapid advances in tissue bioengineering hold great promise for overcoming these major obstacles and extending the clinical applications of these technologies.
Synergism of amlodipine and candesartan on blood pressure reduction and organ protection in hypertensive rats
Authors: Cheng Yan‐Qiong , Tan Bing‐Yi , Yu Xu‐Hong , Dong Wen‐Zhe , Su Ding‐Feng , Zhu De‐Qiu , Liu Ai‐Jun 
Published: November 2017

SummaryThis study was designed to investigate the possible synergism of amlodipine and candesartan on the reduction of blood pressure (BP) in hypertensive rats. The end organ protection was also observed. In acute experiment, spontaneously hypertensive rats (SHRs) were treated with intragastric administration of amlodipine (0.5, 1, 2, 3 mg/kg), candesartan (1, 2, 3, 4, 6, 8 mg/kg), and 14 different combinations to find the possible ratio of synergistic interaction. In two kidneys, one clip (2K1C) rats, the effects of amlodipine (1 mg/kg), canderastan (2 mg/kg) and their combination on BP reduction were also observed. In chronic study, SHRs were treated with amlodipine (1 mg/kg), candesartan (2 mg/kg), and their combination for 5 months. Organ damage evaluation was performed after BP recording. The probability sum test (q test) was used to evaluate the synergistic action. There is a synergistic interaction between amlodipine and candesartan on BP reduction. The optimal dose ratio is 1:2. The synergistic effect was also confirmed by 2K1C hypertensive rats. In chronic study, this combination (1:2) possessed an obvious synergism on the reduction of BP and BP variability (BPV) and protection on end organs. Multiple regression analysis showed that heart and aortic hypertrophy indexes and glomerular damage parameters were positively related to BP and BPV. In conclusion, combination of amlodipine and candesartan exhibited a potent antihypertensive effect and possessed an obvious synergism on BP reduction and organ protection in hypertension. The optimal proportion was 1:2. BP and BPV reduction may both importantly contribute to end organ protection.
Board effectiveness in Chinese fund management companies
Authors: Tam On K. , Zhou Jing , Yu Ping 
Published: November 2017

AbstractWith a generally weak investor protection environment and no governance voice in the fund management companies (FMC) to which their investment is entrusted, fund investors in China are left with the internal governance mechanisms to safeguard their interest. Using a panel data of 288 firm‐year observations covering more than 98% of FMC in China from the period between 2006 and 2010, the present paper examines the corporate governance challenges confronting the fledging Chinese fund management industry by analysing how key governance settings affect the performance of the board of directors in protecting the interest of fund investors. The results show that board effectiveness can be enhanced if a listed company is the controlling shareholder. In addition, having a female CEO or board chairperson and a small‐sized board may help to reduce investors’ fees. Other internal corporate governance mechanisms, such as shareholder concentration, having state‐owned financial companies as controlling shareholders and board independence, are found to exhibit no significant impact on the effectiveness of FMC boards.
Preterm birth with placental evidence of malperfusion is associated with cardiovascular risk factors after pregnancy: a prospective cohort study
Authors: Catov JM , Muldoon MF , Reis SE , Ness RB , Nguyen LN , Yamal J‐M , Hwang H , Parks WT 
Published: November 2017

ObjectivePreterm birth (PTB) is associated with excess maternal cardiovascular disease risk. We considered that women with PTB and placental evidence of maternal malperfusion would be particularly affected.DesignPregnancy cohort study.SettingPittsburgh, PA, USA.PopulationWomen with PTB (n = 115) and term births (n = 210) evaluated 4–12 years after pregnancy.MethodsCardiometabolic risk markers were compared in women with prior PTB versus term births; pre‐eclampsia and growth restriction cases were excluded. Placental evidence of maternal vascular malperfusion (vasculopathy, infarct, advanced villous maturation, perivillous fibrin, intervillous fibrin deposition), acute infection/inflammation (chorioamnionitis, funisitis, deciduitus) and villitis of unknown aetiology (chronic inflammation) was used to classify PTBs.Main outcome measuresCarotid artery intima‐media thickness (IMT), fasting lipids, blood pressure (BP) and inflammatory markers measured after delivery.ResultsWomen with PTB and malperfusion lesions had higher total cholesterol (+13.5 mg/dl) and systolic BP (+4.0 mmHg) at follow up compared with women with term births, accounting for age, race, pre‐pregnancy BMI, and smoking (P < 0.05). Women with PTB and malperfusion accompanied by inflammatory lesions had the most atherogenic profile after pregnancy (cholesterol +18.7, apolipoprotein B + 12.7 mg/dl; all P < 0.05), adjusted for pre‐pregnancy features. Carotid IMT was higher in this group (+0.037 cm, P = 0.031) accounting for pre‐pregnancy factors; differences were attenuated after adjusting for BP and atherogenic lipids at follow up (+0.027, P = 0.095).ConclusionPTBs with placental malperfusion were associated with an excess maternal cardiometabolic risk burden in the decade after pregnancy. The placenta may offer insight into subtypes of PTB related to maternal cardiovascular disease.Tweetable abstractPreterm births with placental malperfusion may mark women at higher cardiovascular disease risk.
Quality of Life and Depression Among Mexican Americans on Hemodialysis: A Preliminary Report
Authors: Debnath Subrata , O'Connor Jason , Hura Claudia , Kasinath Balakuntalam , Lorenzo Carlos 
Published: November 2017

AbstractHealth‐related quality of life (QOL) and depression burden of Mexican Americans with end‐stage renal disease (ESRD) are not known. This observational cross‐sectional study assessed QOL and depression and examined their inter‐relatedness in Mexican Americans with type 2 diabetes and ESRD on maintenance hemodialysis (HD) treatment. Prevalent Mexican Americans on HD (N = 40) completed the Kidney Disease Quality of Life‐Short Form (KDQOL‐SF) and the Beck Depression Inventory II. The overall median scores for the mental component summary and the physical component summary scales in the KDQOL‐SF were 40.9 and 34.0, respectively. The prevalence of severe depression was 40%. The most significant differences between depressed and non‐depressed groups were symptom/problem list, cognitive function, and emotional well‐ being (P < 0.0001 for all). Mexican Americans with depression endure a more dismal QOL compared to non‐depressed peers. Significant negative correlations between depression and several QOL scales underscore plausible interactions between the two conditions which warrants further evaluation.
Neuropeptide CART prevents memory loss attributed to withdrawal of nicotine following chronic treatment in mice
Authors: Borkar Chandrashekhar D. , Sagarkar Sneha , Sakharkar Amul J. , Subhedar Nishikant K. , Kokare Dadasaheb M. 
Published: November 2017

AbstractAlthough chronic nicotine administration does not affect memory, its withdrawal causes massive cognitive deficits. The underlying mechanisms, however, have not been understood. We test the role of cocaine‐ and amphetamine‐regulated transcript peptide (CART), a neuropeptide known for its procognitive properties, in this process. The mice on chronic nicotine treatment/withdrawal were subjected to novel object recognition task. The capability of the animal to discriminate between the novel and familiar objects was tested and represented as discrimination index (DI); reduction in the index suggested amnesia. Nicotine for 49 days had no effect on DI, but 8‐hour withdrawal caused a significant reduction, followed by full recovery at 24‐hour withdrawal timepoint. Bilateral CART infusion in dorsal hippocampus rescued deficits in DI at 8‐hours, whereas CART‐antibody infusion into the dorsal hippocampus attenuated the recovery at 24‐hours. Commensurate changes were observed in the CART as well as CART mRNA profiles in the hippocampus. CART mRNA expression and the peptide immunoreactivity did not change significantly following chronic nicotine treatment. However, there was a significant reduction at 8‐hour withdrawal, followed by a drastic increase in CART immunoreactivity as well as CART mRNA at 24‐hour withdrawal, compared with 8‐hour withdrawal. Distinct α7‐nicotinic receptor immunoreactivity was detected on the hippocampal CART neurons, suggesting cholinergic inputs. An increase in the synaptophysin immunoreactive elements around CART cells in the dentate gyrus, cornu ammonis 3 and subiculum at 24‐hour post‐withdrawal timepoint suggested neuronal plasticity. CART circuit dynamics in the hippocampus seems to modulate short‐term memory associated with nicotine withdrawal.
Nicotinamide and skin cancer chemoprevention: The jury is still out
Authors: Gilmore Stephen J 
Published: November 2017

AbstractFollowing the publication of the results of a Phase III trial, the administration of oral nicotinamide has been widely advocated as effective in non‐melanoma skin cancer chemoprevention in high‐risk individuals. However, I performed a Bayesian analysis of the reported findings and show there is insufficient evidence to demonstrate its efficacy, highlighting the significant probability that the positive conclusions drawn will not be reproducible. Given the potential widespread use of oral nicotinamide, future position statements regarding its efficacy are likely to require higher standards of evidence.
Amniotic fluid pentraxins: Potential early markers for identifying intra‐amniotic inflammatory complications in preterm pre‐labor rupture of membranes
Authors: Musilova Ivana , Andrys Ctirad , Krejsek Jan , Drahosova Marcela , Zednikova Barbora , Pliskova Lenka , Zemlickova Helena , Jacobsson Bo , Kacerovsky Marian 
Published: November 2017

In this study, pentraxin 3 (PTX3), C‐reactive protein (CRP), and serum amyloid P component (SAP) concentrations in the amniotic fluid of women with preterm pre‐labor rupture of membranes (PPROM) were evaluated based on evidence of microbial invasion of the amniotic cavity (MIAC), intra‐amniotic inflammation (IAI), and microbial‐associated IAI. A total of 149 women with PPROM were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis. Amniotic fluid PTX3, SAP, and CRP concentrations were assessed using enzyme‐linked immunosorbent assay. PTX3 and CRP concentrations were higher in women with MIAC, IAI, and microbial‐associated IAI than in women without these conditions. SAP concentrations were only higher in the presence of IAI and microbial‐associated IAI. Amniotic fluid PTX3 concentrations of 11 ng/mL were found to be the best value for identifying the presence of microbial‐associated IAI and IAI in women with PPROM. To conclude, amniotic fluid pentraxins are involved in intra‐amniotic inflammatory responses in pregnancies complicated by PPROM.
The incidence and outcome of clinically significant antibodies detected in Rhesus‐D positive pregnant women of the Northern Territory
Authors: Andersson Lauren , Szabo Ferenc 
Published: November 2017

BackgroundHaemolytic disease of the fetus/newborn secondary to clinically significant non‐Rhesus‐D antibodies has risen in importance since the advent of immunoprophylactic anti‐D administration to Rhesus‐D negative women. Of interest is the incidence of these antibodies in Rhesus‐D positive women, who receive less frequent antenatal alloantibody screening. This is of particular concern if the antibodies arise late in pregnancy and may go undetected.AimsTo assess the proportion of Rhesus‐D positive pregnant women with late developing clinically significant antibodies for haemolytic disease of the fetus/newborn, and whether these resulted in adverse fetal outcomes.Materials and MethodsA retrospective analysis over a 12‐month period at a tertiary hospital in the Northern Territory. Group and antibody screen results in addition to clinical data regarding pregnancy/newborn were collected.ResultsSixty‐four of 2612 women (2.5%) had red blood cell antibodies detected during their pregnancy. Of these, 21 clinically significant antibodies were detected in 19 women (0.7% of initial cohort). The most common antibody detected was anti‐c (28.5%). In six of these women (0.23% of initial cohort), the antibodies were late developing. Mild jaundice was noted in three newborns with phototherapy required in one.ConclusionsAlthough clinically significant antibodies were detected during pregnancy, and in a small proportion of cases as a late developing antibody undetected in the first trimester screening, clinical outcomes for the newborn were mild. As such, the cost of retesting all Rhesus‐D positive pregnant women in the third trimester would be considerable and unlikely to result in any meaningful clinical benefit.
A Regression Framework for Assessing Covariate Effects on the Reproducibility of High-Throughput Experiments
Authors: Li Qunhua , Zhang Feipeng 
Published: November 2017

SummaryThe outcome of high-throughput biological experiments is affected by many operational factors in the experimental and data-analytical procedures. Understanding how these factors affect the reproducibility of the outcome is critical for establishing workflows that produce replicable discoveries. In this article, we propose a regression framework, based on a novel cumulative link model, to assess the covariate effects of operational factors on the reproducibility of findings from high-throughput experiments. In contrast to existing graphical approaches, our method allows one to succinctly characterize the simultaneous and independent effects of covariates on reproducibility and to compare reproducibility while controlling for potential confounding variables. We also establish a connection between our model and certain Archimedean copula models. This connection not only offers our regression framework an interpretation in copula models, but also provides guidance on choosing the functional forms of the regression. Furthermore, it also opens a new way to interpret and utilize these copulas in the context of reproducibility. Using simulations, we show that our method produces calibrated type I error and is more powerful in detecting difference in reproducibility than existing measures of agreement. We illustrate the usefulness of our method using a ChIP-seq study and a microarray study.
A single‐institution retrospective cohort study of first‐line R‐EPOCH chemoimmunotherapy for Richter syndrome demonstrating complex chronic lymphocytic leukaemia karyotype as an adverse prognostic factor
Authors: Rogers Kerry A. , Huang Ying , Ruppert Amy S. , Salem Galena , Stephens Deborah M. , Heerema Nyla A. , Andritsos Leslie A. , Awan Farrukh T. , Byrd John C. , Flynn Joseph M. , Maddocks Kami J. , Jones Jeffrey A. 
Published: November 2017

SummaryRichter Syndrome, an aggressive lymphoma occurring in patients with chronic lymphocytic leukaemia (CLL), has a generally poor prognosis and anthracycline‐based chemoimmunotherapy regimens designed to treat de novo diffuse large B‐cell lymphoma achieve modest clinical benefit. R‐EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) has demonstrated greater activity against aggressive B‐cell histologies but has not been studied in Richter Syndrome. We conducted a retrospective cohort study of 46 Richter Syndrome patients treated with first‐line R‐EPOCH at our institution between 1 January 2006 and 31 May 2014. The median progression‐free survival (PFS) was 3·5 months [95% confidence interval (CI): 2·0–7·6] and median overall survival (OS) was 5·9 months (95% CI: 3·2–10·3). Toxicity was high and 30% of patients died without progression or response. Patients with a complex CLL karyotype had significantly shorter PFS and OS (P = 0·005 and P = 0·002, respectively). Multivariable analysis identified complex CLL karyotype as the most significant predictor of decreased survival [Hazard ratio (HR) 2·72, 95% CI: 1·14–6·52, P = 0·025], adjusting for number of prior CLL treatments (P = 0·036). Richter Syndrome patients with complex CLL karyotype experience poor survival with R‐EPOCH treatment and novel approaches are needed for these patients. In contrast, survival of patients without a complex CLL karyotype was similar to patients with de novo diffuse large B‐cell lymphoma.
The exomic landscape of t(14;18)‐negative diffuse follicular lymphoma with 1p36 deletion
Authors: Zamò Alberto , Pischimarov Jordan , Horn Heike , Ott German , Rosenwald Andreas , Leich Ellen 
Published: November 2017

SummaryPredominantly diffuse t(14;18) negative follicular lymphoma (FL) with 1p36 deletion shows distinctive clinical, morphological and molecular features that distinguish it from classical FL. In order to investigate whether it possesses a unique mutation profile, we performed whole exome sequencing of six well‐characterised cases. Our analysis showed that the mutational landscape of this subtype is largely distinct from classical FL. It appears to harbour several recurrent mutations, affecting STAT6, CREBBP and basal membrane protein genes with high frequency. Our data support the view that this FL subtype should be considered a separate entity from classical FL.
Donor‐specific anti‐HLA antibodies are not associated with nonanastomotic biliary strictures but both are independent risk factors for graft loss after liver transplantation
Authors: den Dulk Anne Claire , Shi Xiaolei , Verhoeven Cornelia. J. , Dubbeld Jeroen , Claas Frans H. J. , Wolterbeek Ron , Brand‐Schaaf Simone H. , Verspaget Hein W. , Sarasqueta Arantza Fariña , van der Laan Luc J. W. , Metselaar Herold J. , van Hoek Bart , Kwekkeboom Jaap , Roelen Dave L. 
Published: November 2017

AbstractDonor‐specific alloantibodies (DSA) have been associated with rejection and shorter graft survival after orthotopic liver transplantation (OLT). We examined the role of DSA in nonanastomotic biliary strictures (NAS) after OLT. Patients receiving first OLT who developed NAS (n = 68) and a control group without NAS (n = 83), with pre‐OLT and 12 months post‐OLT serum samples, were included. DSA were specified using the Luminex single antigen test. Risk factors for NAS and graft survival were analyzed. The presence of preformed DSA was not significantly different between patients with NAS and controls (P = .89). After 12 months, 26.5% of NAS patients and 16.9% of controls had generated de novo DSA (P = .15). Neither de novo class I DSA nor de novo class II DSA were associated with NAS. De novo DSA generally developed after the diagnosis of NAS. Time‐dependent regression analysis identified both NAS (aHR 8.05, CI 3.28 – 19.77, P < .01) and de novo class II DSA (aHR 2.84, CI 1.38 – 5.82, P < .01) as independent risk factors for graft loss. Preformed or de novo DSA were not associated with the development of NAS. However, NAS as well as de novo class II DSA were independent risk factors for graft loss after OLT.
Inflammatory and Physiological Consequences of Debridement of Fibrous Tissue after Volumetric Muscle Loss Injury
Authors: Corona Benjamin T. , Rivera Jessica C. , Greising Sarah M. 
Published: November 2017

AbstractVolumetric muscle loss (VML) injuries present chronic loss of muscle fibers followed by expansive fibrotic tissue deposition. Regenerative medicine therapies are under development to promote regeneration. However, mitigation of the expansive fibrous tissue is required for integration with the remaining muscle. Using a porcine VML model, delayed debridement of injury fibrosis was performed 3 months post‐VML and observed for an additional 4 weeks. A second group underwent the initial VML and was observed for 4 weeks, allowing comparison of initial fibrosis formation and debrided groups. The following salient observations were made: (i) debridement neither exacerbated nor ameliorated strength deficits; (ii) debridement results in recurrent fibrotic tissue deposition of a similar magnitude and composition as acute VML injury; and (iii) similarly upregulated transcriptional fibrotic and transcriptional pathways persist 4 weeks after initial VML or delayed debridement. This highlights the need for future studies to investigate adjunctive antifibrotic treatments for the fibrosed musculature.