bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholesterol Flux Is Required for Endosomal Progression of African Swine Fever Virions during the Initial Establishment of Infection
Authors: Cuesta-Geijo Miguel Ángel , Chiappi Michele , Galindo Inmaculada , Barrado-Gil Lucía , Muñoz-Moreno Raquel , Carrascosa José L. , Alonso Covadonga 
Published: November 2015

ABSTRACT
African swine fever virus (ASFV) is a major threat for porcine production that has been slowly spreading in Eastern Europe since its first appearance in the Caucasus in 2007. ASFV enters the cell by endocytosis and gains access to the cytosol to start replication from late endosomes and multivesicular bodies. Cholesterol associated with low-density lipoproteins entering the cell by endocytosis also follows a trafficking pathway similar to that of ASFV. Here we show that cholesterol plays an essential role in the establishment of infection as the virus traffics through the endocytic pathway. In contrast to the case for other DNA viruses, such as vaccinia virus or adenovirus 5, cholesterol efflux from endosomes is required for ASFV release/entry to the cytosol. Accumulation of cholesterol in endosomes impairs fusion, resulting in retention of virions inside endosomes. ASFV also remodels intracellular cholesterol by increasing its cellular uptake and redistributes free cholesterol to viral replication sites. Our analysis reveals that ASFV manipulates cholesterol dynamics to ensure an appropriate lipid flux to establish productive infection.

IMPORTANCE
Since its appearance in the Caucasus in 2007, African swine fever (ASF) has been spreading westwards to neighboring European countries, threatening porcine production. Due to the lack of an effective vaccine, ASF control relies on early diagnosis and widespread culling of infected animals. We investigated early stages of ASFV infection to identify potential cellular targets for therapeutic intervention against ASF. The virus enters the cell by endocytosis, and soon thereafter, viral decapsidation occurs in the acid pH of late endosomes. We found that ASFV infection requires and reorganizes the cellular lipid cholesterol. ASFV requires cholesterol to exit the endosome to gain access to the cytoplasm to establish productive replication. Our results indicate that there is a differential requirement for cholesterol efflux for vaccinia virus or adenovirus 5 compared to ASFV.
In SilicoConstraint-Based Strain Optimization Methods: the Quest for Optimal Cell Factories
Authors: Maia Paulo , Rocha Miguel , Rocha Isabel 
Published: November 2015

SUMMARYShifting from chemical to biotechnological processes is one of the cornerstones of 21st century industry. The production of a great range of chemicals via biotechnological means is a key challenge on the way toward a bio-based economy. However, this shift is occurring at a pace slower than initially expected. The development of efficient cell factories that allow for competitive production yields is of paramount importance for this leap to happen. Constraint-based models of metabolism, together within silicostrain design algorithms, promise to reveal insights into the best genetic design strategies, a step further toward achieving that goal. In this work, a thorough analysis of the mainin silicoconstraint-based strain design strategies and algorithms is presented, their application in real-world case studies is analyzed, and a path for the future is discussed.
The disciplined healthcare professional: a qualitative interview study on the impact of the disciplinary process and imposed measures in the Netherlands
Authors: Verhoef Lise M , Weenink Jan-Willem , Winters Sjenny , Robben Paul B M , Westert Gert P , Kool Rudolf B 
Published: November 2015

ObjectiveIt is known that doctors who receive complaints may have feelings of anger, guilt, shame and depression, both in the short and in the long term. This might lead to functional impairment. Less is known about the impact of the disciplinary process and imposed measures. Previous studies of disciplinary proceedings have mainly focused on identifying characteristics of disciplined doctors and on sentencing policies. Therefore, the aim of this study is to explore what impact the disciplinary process and imposed measures have on healthcare professionals.DesignSemistructured interview study, with purposive sampling and inductive qualitative content analysis.Participants16 healthcare professionals (9 medical specialists, 3 general practitioners, 2 physiotherapists and 2 psychologists) that were sanctioned by the disciplinary tribunal.SettingThe Netherlands.ResultsProfessionals described feelings of misery and insecurity both during the process as in its aftermath. Furthermore, they reported to fear receiving new complaints and provide care more cautiously after the imposed measure. Factors that may enhance psychological and professional impact are the publication of measures online and in newspapers, media coverage, the feeling of treated as guilty before any verdict has been reached, and the long duration of the process.ConclusionsThis study shows that the disciplinary process and imposed measures can have a profound psychological and professional impact on healthcare professionals. Although a disciplinary measure is meant to have a corrective effect, our results suggest that the impact that is experienced by professionals might hamper optimal rehabilitation afterwards. Therefore, organising emotional support should be considered during the disciplinary process and in the period after the verdict.
Neighbourhood urban form and individual-level correlates of leisure-based screen time in Canadian adults
Authors: McCormack Gavin R , Mardinger Cynthia 
Published: November 2015

ObjectivesDespite evidence for an association between the built environment and physical activity, less evidence exists regarding relations between the built environment and sedentary behaviour. This study investigated the extent to which objectively assessed and self-reported neighbourhood walkability, in addition to individual-level characteristics, were associated with leisure-based screen time in adults. We hypothesised that leisure-based screen time would be lower among adults residing in objectively assessed and self-reported ‘high walkable’ versus ‘low walkable’ neighbourhoods.SettingThe study was undertaken in Calgary, Alberta, Canada in 2007/2008.ParticipantsA random cross-section of adults who provided complete telephone interview and postal survey data (n=1906) was included. Captured information included leisure-based screen time, moderate-intensity and vigorous-intensity physical activity, perceived neighbourhood walkability, sociodemographic characteristics, self-reported health status, and self-reported height and weight. Based on objectively assessed built characteristics, participant's neighbourhoods were identified as being low, medium or high walkable.Primary and secondary outcome measuresUsing multiple linear regression, hours of leisure-based screen time per day was regressed on self-reported and objectively assessed walkability adjusting for sociodemographic and health-related covariates.ResultsCompared to others, residing in an objectively assessed high walkable neighbourhood, women, having a college education, at least one child at home, a household income ≥$120 000/year, and a registered motor vehicle at home, reporting very good-to-excellent health and healthy weight, and achieving 60 min/week of vigorous-intensity physical activity were associated (p<0.05) with less leisure-based screen time. Marital status, dog ownership, season, self-reported walkability and achieving 210 min of moderate-intensity physical activity were not significantly associated with leisure-based screen time.ConclusionsImproving neighbourhood walkability could decrease leisure-based television and computer screen time. Programmes aimed at reducing sedentary behaviour may want to consider an individual's sociodemographic characteristics, physical activity level, health status and weight status, in addition to the walkability of their neighbourhood as these factors were found to be important independent correlates of leisure-based screen time.
Rapid cycle development of a multifactorial intervention achieved sustained reductions in central line-associated bloodstream infections in haematology oncology units at a children’s hospital: a time series analysis
Authors: Dandoy Christopher E , Hausfeld Jackie , Flesch Laura , Hawkins Deanna , Demmel Kathy , Best Deanna , Osterkamp Erin , Bracke Tracey , Nagarajan Rajaram , Jodele Sonata , Holt Julie , Giaccone Mary Jo , Davies Stella M , Kotagal Uma , Simmons Jeffrey 
Published: November 2015

BackgroundImmunocompromised children are at high risk for central line-associated bloodstream infections (CLABSIs) and its associated morbidity and mortality. Prevention of CLABSIs depends on highly reliable care.PurposeSince the summer of 2013, we saw an increase in patient volume and acuity in our centre. Additionally, CLABSIs rates more than tripled during this period. The purpose of this initiative was to rapidly identify and mitigate potential underlying drivers to the increased CLABSI rate.MethodsThrough small tests of change, we implemented a standard process for daily hygiene; increased awareness of high-risk patients with CLABSI; improved education/assistance for nurses performing high-risk central venous catheter procedures; and developed a system to improve allocation of resources to de-escalate system stress.ResultsThe CLABSI rate from June 2013 to May 2014 was 2.03 CLABSIs/1000 line days. After implementation of our interventions, we saw a significant decrease in the CLABSI rate to 0.39 CLABSIs/1000 line days (p=0.008). Key processes have become more reliable: 100% of dressing changes are completed with the new two-person standard; daily hygiene adherence has increased from 25% to 70%; 100% of nurses are approached daily by senior nursing for assistance with high-risk procedures; and patients at risk for a CLABSI are identified daily.ConclusionsStress to a complex system caring for high-risk patients can challenge CLABSI rates. Identifying key processes and executing them reliably can stabilise outcomes during times of system stress.
Influence of muscle fibre composition on muscle oxygenation during maximal running
Authors: Kitada Tomoharu , Machida Shuichi , Naito Hisashi 
Published: November 2015

AimsTo investigate the relationship between muscle oxygenation (specifically, the levels of oxygenated haemoglobin and myoglobin [oxyHb/Mb]) during maximal running and muscle fibre composition, and to determine whether muscle fibre composition can be non-invasively estimated from oxyHb/Mb levels during maximal running.MethodsEight male runners (, 60.9± 4.6 mL·kg−1·min−1) performed an incremental running test on a treadmill. OxyHb/Mb levels of the vastus lateralis during maximal running were measured by near-infrared spectroscopy (NIRS). Muscle fibre composition of the vastus lateralis was determined from muscle biopsy samples from the same region measured by NIRS, and the fibre types were classified as type I, type IIa, or type IIb fibres using traditional pH-sensitive ATPase staining. Type I and type IIa fibres together were defined as oxidative fibres.ResultsOxyHb/Mb levels during running were lowest at exhaustion in all participants. OxyHb/Mb levels at exhaustion were positively correlated with the percentages of type I fibres (r=0.755, p<0.05) and oxidative fibres (r=0.944, p<0.01).ConclusionsWe conclude that higher oxyHb/Mb levels at exhaustion during maximal running are correlated with a higher percentage of oxidative fibres, indicating the potential importance of oxidative fibres in the maintenance of oxyHb/Mb levels during maximal running. Additionally, muscle fibre composition could be non-invasively estimated from oxyHb/Mb levels during maximal running tests in runners.
Prevalence factors associated with equine herpesvirus type 1 infection in equids with upper respiratory tract infection and/or acute onset of neurological signs from 2008 to 2014
Authors: Pusterla N. , Mapes S. , Akana N. , Barnett C. , MacKenzie C. , Gaughan E. , Craig B. , Chappell D. , Vaala W. 
Published: November 2015

The objective of the present case‐control study was to determine prevalence factors associated with the detection of equine herpesvirus type 1 (EHV‐1) by quantitative PCR (qPCR) in horses presented to veterinarians with clinical signs related to an upper respiratory tract infection and/or acute onset of neurological disease from March 2008 to December 2014. Nasal secretions and whole blood from 4228 equids with acute onset of fever, respiratory signs and/or neurological deficits were tested by qPCR for EHV‐1. Categorical analyses were performed to determine the association between observations and EHV‐1. A total of 117/4228 (2.7 per cent) equids tested qPCR‐positive for EHV‐1, with most of the isolates belonging to the non‐neuropathogenic genotype (N752). EHV‐1 PCR‐positive equids were over‐represented in racing horses. Depression, anorexia, nasal discharge and coughing were significantly less frequently reported in the EHV‐1 qPCR‐positive equids compared with the EHV‐1 qPCR‐negative cases. Neurological deficits were more frequently reported in the EHV‐1 qPCR‐positive cases. This study provides contemporary information on the frequency of EHV‐1 detection by qPCR in blood and nasal secretions from horses with fever, respiratory signs and neurological deficits.
Compressed baryonic matter at FAIR: JINR participation
Authors: Kurilkin P. , Ladygin V. , Malakhov A. , Senger P. 
Published: November 2015

The scientific mission of the Compressed Baryonic Matter(CBM) experiment is the study of the nuclear matter properties at the high baryon densities in heavy ion collisions at the Facility of Antiproton and Ion Research (FAIR) in Darmstadt. We present the results on JINR participation in the CBM experiment. JINR teams are responsible on the design, the coordination of superconducting(SC) magnet manufacture, its testing and installation in CBM cave. Together with Silicon Tracker System it will provide the momentum resolution better 1[Formula: see text] for different configuration of CBM setup. The characteristics and technical aspects of the magnet are discussed. JINR plays also a significant role in the manufacture of two straw tracker station for the muon detection system. JINR team takes part in the development of new method for simulation, processing and analysis experimental data for different basic detectors of CBM.
Internal structure modification and decay of hadrons in strong magnetic field
Authors: Filip Peter 
Published: November 2015

We discuss the influence of external magnetic field on strong decays of [Formula: see text], [Formula: see text] and [Formula: see text] mesons. Due to increasing energy of [Formula: see text] Landau level of charged decay products, particular decay channels may become suppressed and isospin rules for strong decays can be violated. In the case of [Formula: see text] meson, enhanced production of photons and dileptons (with modified invariant mass) may occur. Similar considerations are applied to decays of [Formula: see text] baryon. We also suggest that static electromagnetic field of sufficient strength can modify the internal structure (wavefunction) of [Formula: see text] J/[Formula: see text] and [Formula: see text] mesons, and specific decay channels (e.g. CP — violating [Formula: see text]) can become enhanced.
Agonists of the TRAIL Death Receptor DR5 Sensitize Intestinal Stem Cells to Chemotherapy-Induced Cell Death and Trigger Gastrointestinal Toxicity
Authors: Finnberg Niklas K. , Gokare Prashanth , Navaraj Arunasalam , Lang Kuhs Krystle A. , Cerniglia George , Yagita Hideo , Takeda Kazuyoshi , Motoyama Noboru , El-Deiry Wafik S. 
Published: November 2015

Abstract
The combination of TRAIL death receptor agonists and radiochemotherapy to treat advanced cancers continues to be investigated in clinical trials. We previously showed that normal cells with a functional DNA damage response (DDR) upregulate the expression of death-inducing receptor DR5/TRAILR2/TNFRSF10B in a p53-dependent manner that sensitizes them to treatment with DR5 agonists. However, it is unclear if targeting DR5 selectively sensitizes cancer cells to agonist treatment following exposure to DNA-damaging chemotherapy, and to what extent normal tissues are targeted. Here, we show that the combined administration of the DR5 agonistic monoclonal antibody (mAb) and chemotherapy to wild-type mice triggered synergistic gastrointestinal toxicities (GIT) that were associated with the death of Lgr5+ crypt base columnar stem cells in a p53- and DR5-dependent manner. Furthermore, we confirmed that normal human epithelial cells treated with the human DR5-agonistic mAb and chemotherapeutic agents were also greatly sensitized to cell death. Interestingly, our data also indicated that genetic or pharmacologic targeting of Chk2 may counteract GIT without negatively affecting the antitumor responses of combined DR5 agonist/chemotherapy treatment, further linking the DDR to TRAIL death receptor signaling in normal cells. In conclusion, the combination of DR5-targeting agonistic mAbs with DNA damaging chemotherapy may pose a risk of developing toxicity-induced conditions, and the effects of mAb-based strategies on the dose-limiting toxicity of chemotherapy must be considered when establishing new combination therapies. Cancer Res; 76(3); 700–12. ©2015 AACR.
Identification of CD25 as STAT5-Dependent Growth Regulator of Leukemic Stem Cells in Ph+ CML
Authors: Sadovnik Irina , Hoelbl-Kovacic Andrea , Herrmann Harald , Eisenwort Gregor , Cerny-Reiterer Sabine , Warsch Wolfgang , Hoermann Gregor , Greiner Georg , Blatt Katharina , Peter Barbara , Stefanzl Gabriele , Berger Daniela , Bilban Martin , Herndlhofer Susanne , Sill Heinz , Sperr Wolfgang R. , Streubel Berthold , Mannhalter Christine , Holyoake Tessa L. , Sexl Veronika , Valent Peter 
Published: November 2015

Abstract
Purpose: In chronic myelogenous leukemia (CML), leukemic stem cells (LSC) represent a critical target of therapy. However, little is known about markers and targets expressed by LSCs. The aim of this project was to identify novel relevant markers of CML LSCs.
Experimental Design: CML LSCs were examined by flow cytometry, qPCR, and various bioassays. In addition, we examined the multipotent CD25+ CML cell line KU812.
Results: In contrast to normal hematopoietic stem cells, CD34+/CD38− CML LSCs expressed the IL-2 receptor alpha chain, IL-2RA (CD25). STAT5 was found to induce expression of CD25 in Lin−/Sca-1+/Kit+ stem cells in C57Bl/6 mice. Correspondingly, shRNA-induced STAT5 depletion resulted in decreased CD25 expression in KU812 cells. Moreover, the BCR/ABL1 inhibitors nilotinib and ponatinib were found to decrease STAT5 activity and CD25 expression in KU812 cells and primary CML LSCs. A CD25-targeting shRNA was found to augment proliferation of KU812 cells in vitro and their engraftment in vivo in NOD/SCID-IL-2Rγ−/− mice. In drug-screening experiments, the PI3K/mTOR blocker BEZ235 promoted the expression of STAT5 and CD25 in CML cells. Finally, we found that BEZ235 produces synergistic antineoplastic effects on CML cells when applied in combination with nilotinib or ponatinib.
Conclusions: CD25 is a novel STAT5-dependent marker of CML LSCs and may be useful for LSC detection and LSC isolation in clinical practice and basic science. Moreover, CD25 serves as a growth regulator of CML LSCs, which may have biologic and clinical implications and may pave the way for the development of new more effective LSC-eradicating treatment strategies in CML. Clin Cancer Res; 22(8); 2051–61. ©2015 AACR.
Hypermutation of DPYD Deregulates Pyrimidine Metabolism and Promotes Malignant Progression
Authors: Edwards Lauren , Gupta Rohit , Filipp Fabian Volker 
Published: November 2015

Abstract
New strategies are needed to diagnose and target human melanoma. To this end, genomic analyses was performed to assess somatic mutations and gene expression signatures using a large cohort of human skin cutaneous melanoma (SKCM) patients from The Cancer Genome Atlas (TCGA) project to identify critical differences between primary and metastatic tumors. Interestingly, pyrimidine metabolism is one of the major pathways to be significantly enriched and deregulated at the transcriptional level in melanoma progression. In addition, dihydropyrimidine dehydrogenase (DPYD) and other important pyrimidine-related genes: DPYS, AK9, CAD, CANT1, ENTPD1, NME6, NT5C1A, POLE, POLQ, POLR3B, PRIM2, REV3L, and UPP2 are significantly enriched in somatic mutations relative to the background mutation rate. Structural analysis of the DPYD protein dimer reveals a potential hotspot of recurring somatic mutations in the ligand-binding sites as well as the interfaces of protein domains that mediated electron transfer. Somatic mutations of DPYD are associated with upregulation of pyrimidine degradation, nucleotide synthesis, and nucleic acid processing while salvage and nucleotide conversion is downregulated in TCGA SKCM.
Implications: At a systems biology level, somatic mutations of DPYD cause a switch in pyrimidine metabolism and promote gene expression of pyrimidine enzymes toward malignant progression. Mol Cancer Res; 14(2); 196–206. ©2015 AACR.
Prevalence of left atrial thrombus in patients with non-valvular atrial fibrillation
Authors: Ambrosino Pasquale , Russo Antonio Dello , Casella Michela , Tremoli Elena , Tondo Claudio , Minno Matteo Nicola Dario Di 
Published: November 2015

SummaryWe performed a meta-analysis about the prevalence of left atrial thrombus (LAT) in patients with atrial fibrillation (AF) undergoing trans-esophageal echocardiography (TEE). Studies reporting on LAT presence in AF patients were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases and the pooled LAT prevalence was evaluated as weighted mean prevalence (WMP). Seventy-two studies (20,516 AF patients) showed a LAT WMP of 9.8 % (95 %CI: 7.6 %-12.5 %). LAT presence was associated with a higher age (mean difference: 2.56, 95 %CI: 1.49–3.62), and higher prevalence of female gender (OR: 1.35, 95 %CI: 1.04–1.75), hypertension (OR: 1.78, 95 %CI: 1.38–2.30), diabetes mellitus (OR: 1.86, 95 %CI: 1.33–2.59) and chronic heart failure (OR: 3.67, 95 %CI: 2.40–5.60). Overall, LAT patients exhibited a higher CHADS2-score (mean difference 0.88, 95 %CI: 0.68–1.07) and a higher risk of stroke/systemic embolism (OR: 3.53, 95 %CI: 2.24–5.56) compared with those without LAT. A meta-regression showed an inverse association between LAT prevalence and the presence of anticoagulation (Z-value: −7.3, p< 0.001). Indeed, studies in which 100 % of patients received oral anticoagulation reported a 3.4 % WMP of LAT (95 %CI: 1.3 %–8.7 %), whereas studies in which 0 % of patients received anticoagulation showed a LAT WMP of 7.4 % (95 %CI: 2.3 %–21.5%). Our data suggest that LAT is present in ≈10 % of AF patients, and is associated with a 3.5-fold increased risk of stroke/systemic embolism. Interestingly, LAT is also reported in some of patients receiving anticoagulation. The implementation of the screening of LAT in AF patients before cardioversion/ablation could be useful for the prevention of vascular events.