bluuebunny/crossref_metadata_2025_split huggingface dataset:
Follow-up of pulmonary right-to-left shunt in hereditary haemorrhagic telangiectasia
Authors: Vorselaars Veronique M.M. , Velthuis Sebastiaan , Snijder Repke J. , Westermann Cornelis J.J. , Vos Jan A. , Mager Johannes J. , Post Martijn C. 
Published: March 2016

Pulmonary arteriovenous malformations (PAVMs) are associated with severe neurological complications in hereditary haemorrhagic telangiectasia (HHT). Transthoracic contrast echocardiography (TTCE) is recommended for screening of pulmonary right-to-left shunts (RLS). Although growth of PAVMs is shown in two small studies, no studies on follow-up with TTCE exist.All HHT patients underwent a second TTCE 5 years after initial screening. Patients with a history of PAVM embolisation were excluded. Pulmonary RLS grade on TTCE after 5 years was compared to the grade at screening.200 patients (53.5% female, mean±sdage at screening 44.7±14.1 years) were included. Increase in RLS grade occurred in 36 (18%) patients, of whom six (17%) underwent embolisation. The change in grade between screening and follow-up was not more than one grade. Of patients with nontreatable pulmonary RLS at screening (n=113), 14 (12.4%) underwent embolisation. In patients without pulmonary RLS at initial screening (n=87), no treatable PAVMs developed during follow-up.Within 5 years, no treatable PAVMs developed in HHT patients without pulmonary RLS at initial screening. Increase in pulmonary RLS grade occurred in 18% of patients, and never increased by more than one grade. Of patients with nontreatable pulmonary RLS at initial screening, 12% underwent embolisation.
Enhanced monocyte migration to CXCR3 and CCR5 chemokines in COPD
Authors: Costa Claudia , Traves Suzanne L. , Tudhope Susan J. , Fenwick Peter S. , Belchamber Kylie B.R. , Russell Richard E.K. , Barnes Peter J. , Donnelly Louise E. 
Published: March 2016

Chronic obstructive pulmonary disease (COPD) patients exhibit chronic inflammation, both in the lung parenchyma and the airways, which is characterised by an increased infiltration of macrophages and T-lymphocytes, particularly CD8+cells. Both cell types can express chemokine (C-X-C motif) receptor (CXCR)3 and C-C chemokine receptor 5 and the relevant chemokines for these receptors are elevated in COPD. The aim of this study was to compare chemotactic responses of lymphocytes and monocytes of nonsmokers, smokers and COPD patients towards CXCR3 ligands and chemokine (C-C motif) ligand (CCL)5.Migration of peripheral blood mononuclear cells, monocytes and lymphocytes from nonsmokers, smokers and COPD patients toward CXCR3 chemokines and CCL5 was analysed using chemotaxis assays.There was increased migration of peripheral blood mononuclear cells from COPD patients towards all chemokines studied when compared with nonsmokers and smokers. Both lymphocytes and monocytes contributed to this enhanced response, which was not explained by increased receptor expression. However, isolated lymphocytes failed to migrate and isolated monocytes from COPD patients lost their enhanced migratory capacity.Both monocytes and lymphocytes cooperate to enhance migration towards CXCR3 chemokines and CCL5. This may contribute to increased numbers of macrophages and T-cells in the lungs of COPD patients, and inhibition of recruitment using selective antagonists might be a treatment to reduce the inflammatory response in COPD.
Illumina error profiles: resolving fine-scale variation in metagenomic sequencing data
Authors: Schirmer Melanie , D’Amore Rosalinda , Ijaz Umer Z. , Hall Neil , Quince Christopher 
Published: March 2016

Abstract
Background
Illumina’s sequencing platforms are currently the most utilised sequencing systems worldwide. The technology has rapidly evolved over recent years and provides high throughput at low costs with increasing read-lengths and true paired-end reads. However, data from any sequencing technology contains noise and our understanding of the peculiarities and sequencing errors encountered in Illumina data has lagged behind this rapid development.

Results
We conducted a systematic investigation of errors and biases in Illumina data based on the largest collection of in vitro metagenomic data sets to date. We evaluated the Genome Analyzer II, HiSeq and MiSeq and tested state-of-the-art low input library preparation methods. Analysing in vitro metagenomic sequencing data allowed us to determine biases directly associated with the actual sequencing process. The position- and nucleotide-specific analysis revealed a substantial bias related to motifs (3mers preceding errors) ending in “GG”. On average the top three motifs were linked to 16 % of all substitution errors. Furthermore, a preferential incorporation of ddGTPs was recorded. We hypothesise that all of these biases are related to the engineered polymerase and ddNTPs which are intrinsic to any sequencing-by-synthesis method. We show that quality-score-based error removal strategies can on average remove 69 % of the substitution errors - however, the motif-bias remains.

Conclusion
Single-nucleotide polymorphism changes in bacterial genomes can cause significant changes in phenotype, including antibiotic resistance and virulence, detecting them within metagenomes is therefore vital. Current error removal techniques are not designed to target the peculiarities encountered in Illumina sequencing data and other sequencing-by-synthesis methods, causing biases to persist and potentially affect any conclusions drawn from the data. In order to develop effective diagnostic and therapeutic approaches we need to be able to identify systematic sequencing errors and distinguish these errors from true genetic variation.
Moderate hyperoxic versus near-physiological oxygen targets during and after coronary artery bypass surgery: a randomised controlled trial
Authors: Smit Bob , Smulders Yvo M. , de Waard Monique C. , Boer Christa , Vonk Alexander B. A. , Veerhoek Dennis , Kamminga Suzanne , de Grooth Harm-Jan S. , García-Vallejo Juan J. , Musters Rene J. P. , Girbes Armand R. J. , Oudemans - van Straaten Heleen M. , Spoelstra - de Man Angelique M. E. 
Published: March 2016

AbstractBackgroundThe safety of perioperative hyperoxia is currently unclear. Previous studies in patients undergoing coronary artery bypass surgery suggest reduced myocardial damage when avoiding extreme perioperative hyperoxia (>400 mmHg). In this study we investigated whether an oxygenation strategy from moderate hyperoxia to a near-physiological oxygen tension reduces myocardial damage and improves haemodynamics, organ dysfunction and oxidative stress.MethodsThis was a single-blind, single-centre, open-label, randomised controlled trial in patients undergoing elective coronary artery bypass surgery. Fifty patients were randomised to a partial pressure of oxygen in arterial blood (PaO2) target of 200–220 mmHg during cardiopulmonary bypass and 130–150 mmHg during intensive care unit (ICU) admission (control group) versus lower targets of 130–150 mmHg during cardiopulmonary bypass and 80–100 mmHg at the ICU (conservative group). Primary outcome was myocardial injury (CK-MB and Troponin-T) at ICU admission and 2, 6 and 12 hours thereafter.ResultsWeighted PaO2during cardiopulmonary bypass was 220 mmHg (interquartile range (IQR) 211–233) vs. 157 (151–162) in the control and conservative group, respectively (P < 0.0001). During ICU admission, weighted PaO2was 107 mmHg (86–141) vs. 90 (84–98) (P = 0.03), respectively. Area under the curve of CK-MB was median 23.5 μg/L/h (IQR 18.4–28.1) vs. 21.5 (15.8–26.6) (P = 0.35) and 0.30 μg/L/h (0.25–0.44) vs. 0.39 (0.24–0.43) (P = 0.81) for Troponin-T. Cardiac index, systemic vascular resistance index, creatinine, lactate and F2-isoprostane levels were not different between groups.ConclusionsCompared to moderate hyperoxia, a near-physiological oxygen strategy does not reduce myocardial damage in patients undergoing coronary artery bypass surgery. Conservative oxygen administration was not associated with increased lactate levels or hypoxic events.Trial registrationNetherlands Trial RegistryNTR4375, registered on 30 January 2014
Liver function predicts survival in patients undergoing extracorporeal membrane oxygenation following cardiovascular surgery
Authors: Roth Christian , Schrutka Lore , Binder Christina , Kriechbaumer Lukas , Heinz Gottfried , Lang Irene M. , Maurer Gerald , Koinig Herbert , Steinlechner Barbara , Niessner Alexander , Distelmaier Klaus , Goliasch Georg 
Published: March 2016

Abstract
Background
Extracorporeal membrane oxygenation (ECMO) represents a valuable and rapidly evolving therapeutic option in patients with severe heart or lung failure following cardiovascular surgery. However, despite significant advances in ECMO techniques and management, prognosis remains poor and accurate risk stratification challenging. We therefore evaluated the predictive value of liver function variables on all-cause mortality in patients undergoing venoarterial ECMO support after cardiovascular surgery.

Methods
We included into our single-center registry a total of 240 patients undergoing venoarterial ECMO therapy following cardiovascular surgery at a university-affiliated tertiary care center.

Results
The median follow-up was 37 months (interquartile range 19–67 months), and a total of 156 patients (65 %) died. Alkaline phosphatase and total bilirubin were the strongest predictors for 30-day mortality, with adjusted hazard ratios (HRs) per 1–standard deviation increase of 1.36 (95 % confidence interval [CI] 1.10–1.68; P = 0.004) and 1.22 (95 % CI 1.07–1.40; P = 0.004), respectively. The observed associations persisted for long-term mortality, with adjusted HRs of 1.27 (95 % CI 1.03–1.56; P = 0.023) for alkaline phosphatase and 1.22 (95 % CI 1.07–1.39; P = 0.003) for total bilirubin.

Conclusions
The present study demonstrates that elevated values of alkaline phosphatase and total bilirubin are sensitive parameters for predicting the short-term and long-term outcomes of ECMO patients.
The association between lactate, mean arterial pressure, central venous oxygen saturation and peripheral temperature and mortality in severe sepsis: a retrospective cohort analysis
Authors: Houwink Aletta P. I. , Rijkenberg Saskia , Bosman Rob J. , van der Voort Peter H. J. 
Published: March 2016

Abstract
Background
During resuscitation in severe sepsis and septic shock, several goals are set. However, usually not all goals are equally met. The aim of this study is to determine the relative importance of the different goals, such as mean arterial pressure (MAP), lactate, central venous oxygen saturation (ScvO2) and central to forefoot temperature (delta-T), and how they relate to intensive care unit (ICU) and hospital mortality.

Methods
In a retrospective cohort study in a 20-bed mixed medical and surgical ICU of a teaching hospital we studied consecutive critically ill patients who were admitted for confirmed infection and severe sepsis or septic shock between 2008 and 2014. All validated MAP, lactate levels, ScvO2 and delta-T for the first 24 hours of ICU treatment were extracted from a clinical database. Logistic regression analyses were performed on validated measurements in the first hour after admission and on mean values over 24 hours. Patients were categorized by MAP (24-hour mean below or above 65 mmHg) and lactate (24-hour mean below or above 2 mmol/l) for Cox regression analysis.

Results
From 837 patients, 821 were eligible for analysis. All had MAP and lactate measurements. The delta-T was available in 812 (99 %) and ScvO2 was available for 193 out of these patients (23.5 %). Admission lactate (p < 0.001) and admission MAP (p < 0.001) were independent predictors of ICU and hospital mortality. The 24-hour mean values for lactate, MAP and delta-T were all independent predictors of ICU mortality. Hospital mortality was independently predicted by the 24-hour mean lactate (odds ratio (OR) 1.34, 95 % confidence interval (CI) 1.30–1.40, p = 0.001) mean MAP (OR 0.96, 95 % CI 0.95–0.97, p = 0.001) and mean delta-T (OR 1.09, 95 % CI 1.06–1.12, p = 0.001). Patients with a 24-hour mean lactate below 2 mmol/l and a 24-hour mean MAP above 65 mmHg had the best survival, followed by patients with a low lactate and a low MAP.

Conclusions
Admission MAP and lactate independently predicted ICU and hospital mortality. The 24-hour mean lactate, mean MAP and mean delta-T independently predicted hospital mortality. A Cox regression analysis showed that 24-hour mean lactate above 2 mmol/l is the strongest predictor for ICU mortality.
Hypoxic conditioned medium from mesenchymal stem cells promotes lymphangiogenesis by regulation of mitochondrial-related proteins
Authors: Lee Chang Youn , Kang Jin Young , Lim Soyeon , Ham Onju , Chang Woochul , Jang Dae-Hyun 
Published: March 2016

Abstract
Background
Recently, cell-based therapeutic lymphangiogenesis has emerged and provided hope for lymphatic regeneration. Previous studies have demonstrated that secretomes of mesenchymal stem cells (MSCs) facilitate the regeneration of various damaged tissues. This study was conducted to evaluate the lymphangiogenic potential of hypoxic conditioned media (HCM) from MSCs.

Methods
To investigate the effects of MSC-secreted factors in starved human lymphatic endothelial cells (hLEC), hLECs were treated with endothelial basal medium (EBM)-2 (control), normoxic conditioned media (NCM), or HCM in vitro and in vivo.

Results
MSCs expressed lymphangiogenic factors including EGF, FGF2, HGF, IGF-1, and VEGF-A and -C. hLECs were treated with each medium. hLEC proliferation, migration, and tube formation were improved under HCM compared with NCM. Moreover, expression of mitochondrial-related factors, MFN1and 2, were improved in HCM-treated hLECs. Lymphedema mice injected with HCM showed markedly decreased lymphedema via increased lymphatic vessel formation when compared with EBM-2- or NCM-treated mice.

Conclusions
This study suggested that HCM from MSCs contain high levels of secreted lymphangiogenic factors and promote lymphangiogenesis by regulating mitochondrial-related factors. Thus, treatment with HCM may be a therapeutic strategy for lymphedema.
Polymer mesh scaffold combined with cell-derived ECM for osteogenesis of human mesenchymal stem cells
Authors: Noh Yong Kwan , Du Ping , Kim In Gul , Ko Jaehoon , Kim Seong Who , Park Kwideok 
Published: March 2016

Abstract

Background
Tissue-engineered scaffold should mimic the structure and biological function of the extracellular matrix and have mechanically supportive properties for tissue regeneration. In this study, we utilized a PLGA/PLA mesh scaffold, coated with cell-derived extracellular matrix (CDM) and assessed its potential as an osteogenic microenvironment for human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs). CDM was obtained by decellularization of in vitro-cultured type I collagen overexpressing (Col I -293 T-DK) cells. Test groups are mesh itself (control), fibronectin-coated (FN-mesh), and CDM-coated mesh scaffold (CDM-mesh). CDM was then solubilized and used for scaffold coating.

Results
CDM was successfully collected and applied to mesh scaffolds. The presence of CDM was confirmed via SEM and FN immunofluorescence. After then, UCB-MSCs were seeded into the scaffolds and subjected to the induction of osteogenic differentiation for 21 days in vitro. We found that the seeded cells were viable and have better proliferation activity on CDM-mesh scaffold. In addition, when osteogenic differentiation of UCB-MSCs was examined for up to 21 days, alkaline phosphatase (ALP) activity and osteogenic marker (COL I, ALP, osteocalcin, bone sialoprotein) expression were significantly improved with UCB-MSCs when cultured in the CDM-mesh scaffold compared to the control and FN-mesh.

Conclusion
Polymer mesh scaffold incorporated with CDM can provide UCB-MSCs with a better microenvironment for osteogenesis in vitro.
Long noncoding RNAs as regulators of Toll-like receptor signaling and innate immunity
Authors: Murphy Michael B , Medvedev Andrei E 
Published: March 2016

Abstract
Sensing of microbial pathogens and endogenous “alarmins” by macrophages and dendritic cells is reliant on pattern recognition receptors, including membrane-associated TLRs, cytosolic nucleotide-binding and oligomerization domain leucine-rich repeat-containing receptors, retinoic acid-inducible gene I-like receptors, and absent in melanoma 2-like receptors. Engagement of TLRs elicits signaling pathways that activate inflammatory genes whose expression is regulated by chromatin-modifying complexes and transcription factors. Long noncoding RNAs have emerged as new regulators of inflammatory mediators in the immune system. They are expressed in macrophages, dendritic cells, neutrophils, NK cells, and T- and B-lymphocytes and are involved in immune cell differentiation and activation. Long noncoding RNAs act via repression or activation of transcription factors, modulation of stability of mRNA and microRNA, regulation of ribosome entry and translation of mRNAs, and controlling components of the epigenetic machinery. In this review, we focus on recent advances in deciphering the mechanisms by which long noncoding RNAs regulate TLR-driven responses in macrophages and dendritic cells and discuss the involvement of long noncoding RNAs in endotoxin tolerance, autoimmune, and inflammatory diseases. The dissection of the role of long noncoding RNAs will improve our understanding of the mechanisms of regulation of inflammation and may provide new targets for therapeutic intervention.
CD63 is tightly associated with intracellular, secretory events chaperoning piecemeal degranulation and compound exocytosis in human eosinophils
Authors: Carmo Lívia A S , Bonjour Kennedy , Ueki Shigeharu , Neves Josiane S , Liu Linying , Spencer Lisa A , Dvorak Ann M , Weller Peter F , Melo Rossana C N 
Published: March 2016

Abstract
Eosinophil activation leads to secretion of presynthesized, granule-stored mediators that determine the course of allergic, inflammatory, and immunoregulatory responses. CD63, a member of the transmembrane-4 glycoprotein superfamily (tetraspanins) and present on the limiting membranes of eosinophil-specific (secretory) granules, is considered a potential surface marker for eosinophil degranulation. However, the intracellular secretory trafficking of CD63 in eosinophils and other leukocytes is not understood. Here, we provide a comprehensive investigation of CD63 trafficking at high resolution within human eosinophils stimulated with inflammatory stimuli, CCL11 and tumor necrosis factor α, which induce distinctly differing secretory processes in eosinophils: piecemeal degranulation and compound exocytosis, respectively. By using different transmission electron microscopy approaches, including an immunonanogold technique, for enhanced detection of CD63 at subcellular compartments, we identified a major intracellular pool of CD63 that is directly linked to eosinophil degranulation events. Transmission electron microscopy quantitative analyses demonstrated that, in response to stimulation, CD63 is concentrated within granules undergoing secretion by piecemeal degranulation or compound exocytosis and that CD63 tracks with the movements of vesicles and granules in the cytoplasm. Although CD63 was observed at the cell surface after stimulation, immunonanogold electron microscopy revealed that a strong CD63 pool remains in the cytoplasm. It is remarkable that CCL11 and tumor necrosis factor α triggered increased formation of CD63+ large vesiculotubular carriers (eosinophil sombrero vesicles), which fused with granules in the process of secretion, likely acting in the intracellular translocation of CD63. Altogether, we identified active, intracellular CD63 trafficking connected to eosinophil granule-derived secretory pathways. This is important for understanding the complex secretory activities of eosinophils underlying immune responses.
PKC-δ activation in neutrophils promotes fungal clearance
Authors: Li Xun , Cullere Xavier , Nishi Hiroshi , Saggu Gurpanna , Durand Enrique , Mansour Michael K , Tam Jenny M , Song Xiu-yu , Lin Xin , Vyas Jatin M , Mayadas Tanya 
Published: March 2016

Abstract
The C-type lectin receptor dectin-1 and the integrin Mac-1 have key roles in controlling fungal infection. Here, we demonstrate that dectin-1- and Mac-1-induced activation of protein kinase Cδ in neutrophils, independent of the Card9 adaptor, is required for reactive oxygen species production and for intracellular killing upon Candida albicans uptake. Protein kinase Cδ was also required for zymosan-induced cytokine generation in neutrophils. In macrophages, protein kinase Cδ deficiency prevented fungi-induced reactive oxygen species generation but had no effect on activation of TGF-β-activated kinase-1, an effector of Card9, or nuclear factor κB activation, nor did it affect phagolysosomal maturation, autophagy, or intracellular C. albicans killing. In vivo, protein kinase Cδ–deficient mice were highly susceptible to C. albicans and Aspergillus fumigatus infection, which was partially rescued with adoptively transferred wild-type neutrophils. Thus, protein kinase Cδ activation downstream of dectin-1 and Mac-1 has an important role in neutrophil, but not macrophage, functions required for host defense against fungal pathogens.
Smoking and Tuberculosis Risk: High Attributable Risk in a Low- Incidence Environment
Authors: Denholm Justin T , Trauer James M , McBryde Emma S 
Published: March 2016

Objectives: To evaluate the potential impact of smoking cessation strategies on TB incidence in Victoria, Australia.
Methods: A previously validated model of TB in migrants was adapted to concentrate on the attributable TB risk arising from smoking. This model included realistic estimates of population smoking rates, and incorporation of risk factors for TB disease such as smoking, HIV and diabetes. A baseline scenario was compared with an alternative scenario in which a hypothetical public health strategy eliminating smoking was introduced.
Outcome measures: The primary outcome was the number of TB cases in the Australian state of Victoria in the year 2050. Secondary outcomes considered were total case burden during the period considered and the population attributable fraction of TB cases related to smoking.
Results: Under the baseline scenario, a median of 318 cases of TB occurred in the target year of 2050, corresponding to an estimated incidence of 3.5 cases/100,000 population. The alternative scenario, where no smoking occurred, found 272 cases (2.95 cases/100,000 population) occurring in 2050; a 14.5% reduction in TB cases. Over the entire period considered, 1650 fewer cases of TB occurred in the alternative scenario, suggesting a population attributable fraction of 11.2% of TB cases from smoking in the Australian context.
Conclusions: Smoking cessation strategies may have disproportionate benefits in TB incidence reduction. Such benefits should be considered in additional to other well-recognised population health effects from smoking reduction.