bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant methylated key genes of methyl group metabolism within the molecular etiology of urothelial carcinogenesis
Authors: Erichsen Lars , Ghanjati Foued , Beermann Agnes , Poyet Cedric , Hermanns Thomas , Schulz Wolfgang A. , Seifert Hans-Helge , Wild Peter J. , Buser Lorenz , Kröning Alexander , Braunstein Stefan , Anlauf Martin , Jankowiak Silvia , Hassan Mohamed , Bendhack Marcelo L. , Araúzo-Bravo Marcos J. , Santourlidis Simeon 
Published: February 2018

AbstractUrothelial carcinoma (UC), the most common cancer of the urinary bladder causes severe morbidity and mortality, e.g. about 40.000 deaths in the EU annually, and incurs considerable costs for the health system due to the need for prolonged treatments and long-term monitoring. Extensive aberrant DNA methylation is described to prevail in urothelial carcinoma and is thought to contribute to genetic instability, altered gene expression and tumor progression. However, it is unknown how this epigenetic alteration arises during carcinogenesis. Intact methyl group metabolism is required to ensure maintenance of cell-type specific methylomes and thereby genetic integrity and proper cellular function. Here, using two independent techniques for detecting DNA methylation, we observed DNA hypermethylation of the 5′-regulatory regions of the key methyl group metabolism genes ODC1, AHCY and MTHFR in early urothelial carcinoma. These hypermethylation events are associated with genome-wide DNA hypomethylation which is commonly associated with genetic instability. We therefore infer that hypermethylation of methyl group metabolism genes acts in a feed-forward cycle to promote additional DNA methylation changes and suggest a new hypothesis on the molecular etiology of urothelial carcinoma.
BigR is a sulfide sensor that regulates a sulfur transferase/dioxygenase required for aerobic respiration of plant bacteria under sulfide stress
Authors: de Lira Nayara Patricia Vieira , Pauletti Bianca Alves , Marques Ana Carolina , Perez Carlos Alberto , Caserta Raquel , de Souza Alessandra Alves , Vercesi Aníbal Eugênio , Paes Leme Adriana Franco , Benedetti Celso Eduardo 
Published: February 2018

AbstractTo cope with toxic levels of H2S, the plant pathogens Xylella fastidiosa and Agrobacterium tumefaciens employ the bigR operon to oxidize H2S into sulfite. The bigR operon is regulated by the transcriptional repressor BigR and it encodes a bifunctional sulfur transferase (ST) and sulfur dioxygenase (SDO) enzyme, Blh, required for H2S oxidation and bacterial growth under hypoxia. However, how Blh operates to enhance bacterial survival under hypoxia and how BigR is deactivated to derepress operon transcription is unknown. Here, we show that the ST and SDO activities of Blh are in vitro coupled and necessary to oxidize sulfide into sulfite, and that Blh is critical to maintain the oxygen flux during A. tumefaciens respiration when oxygen becomes limited to cells. We also show that H2S and polysulfides inactivate BigR leading to operon transcription. Moreover, we show that sulfite, which is produced by Blh in the ST and SDO reactions, is toxic to Citrus sinensis and that X. fastidiosa-infected plants accumulate sulfite and higher transcript levels of sulfite detoxification enzymes, suggesting that they are under sulfite stress. These results indicate that BigR acts as a sulfide sensor in the H2S oxidation mechanism that allows pathogens to colonize plant tissues where oxygen is a limiting factor.
Space climate and space weather over the past 400 years: 2. Proxy indicators of geomagnetic storm and substorm occurrence
Authors: Lockwood Mike , Owens Mathew J. , Barnard Luke A. , Scott Chris J. , Watt Clare E. , Bentley Sarah 
Published: February 2018

Using the reconstruction of power input to the magnetosphere presented in Paper 1 Lockwood et al. [J Space Weather Space Clim 7 (2017a)], we reconstruct annual means of the geomagnetic Ap and AE indices over the past 400 years to within a 1-sigma error of ±20%. In addition, we study the behaviour of the lognormal distribution of daily and hourly values about these annual means and show that we can also reconstruct the fraction of geomagnetically-active (storm-like) days and (substorm-like) hours in each year to accuracies of to accuracies of ~50%, including the large percentage uncertainties in near-zero values. The results are the first physics-based quantification of the space weather conditions in both the Dalton and Maunder minima. Looking to the future, the weakening of Earth's magnetic moment means that the terrestrial disturbance levels during a future repeats of the solar Dalton and Maunder minima will be weaker and we here quantify this effect for the first time.
The effect of turbulence strength on meandering field lines and Solar Energetic Particle event extents
Authors: Laitinen Timo , Effenberger Frederic , Kopp Andreas , Dalla Silvia 
Published: February 2018

Insights into the processes of Solar Energetic Particle (SEP) propagation are essential for understanding how solar eruptions affect the radiation environment of near-Earth space. SEP propagation is influenced by turbulent magnetic fields in the solar wind, resulting in stochastic transport of the particles from their acceleration site to Earth. While the conventional approach for SEP modelling focuses mainly on the transport of particles along the mean Parker spiral magnetic field, multi-spacecraft observations suggest that the cross-field propagation shapes the SEP fluxes at Earth strongly. However, adding cross-field transport of SEPs as spatial diffusion has been shown to be insufficient in modelling the SEP events without use of unrealistically large cross-field diffusion coefficients. Recently, Laitinen et al. [ApJL 773 (2013b); A&A 591 (2016)] demonstrated that the early-time propagation of energetic particles across the mean field direction in turbulent fields is not diffusive, with the particles propagating along meandering field lines. This early-time transport mode results in fast access of the particles across the mean field direction, in agreement with the SEP observations. In this work, we study the propagation of SEPs within the new transport paradigm, and demonstrate the significance of turbulence strength on the evolution of the SEP radiation environment near Earth. We calculate the transport parameters consistently using a turbulence transport model, parametrised by the SEP parallel scattering mean free path at 1 AU, λ∥*, and show that the parallel and cross-field transport are connected, with conditions resulting in slow parallel transport corresponding to wider events. We find a scaling σφ,max∝(1/λ∥*)1/4 for the Gaussian fitting of the longitudinal distribution of maximum intensities. The longitudes with highest intensities are shifted towards the west for strong scattering conditions. Our results emphasise the importance of understanding both the SEP transport and the interplanetary turbulence conditions for modelling and predicting the SEP radiation environment at Earth.
Periosteal Graft Myringoplasty: Our Experience
Authors: ElTaher Mostafa , Othman Yosry , Mohammed Ibrahim , Ali Khaled 
Published: February 2018

Introduction Different types of autologous graft materials are used for myringoplasty, with the temporalis fascia and cartilage being the most frequently used tissues. Periosteal tissue has been used for a long time in our department, and many advantages support its use in myringoplasty. To the best of our knowledge, this issue is scarcely discussed in the previously published literature.
Objective To present our experience with periosteal graft myringoplasty, describing the technique and the anatomical and functional outcomes.
Methods A prospective clinical study involving 88 patients (72 females and 16 males) with a mean age 26.9 years. The patients underwent myringoplasty using the mastoid cortex periosteum; they were all operated using the postauricular approach, and the graft was applied using the underlay technique. The patients performed pre- and postoperative pure tone audiometry for tested frequencies (0.5 kHz, 1 kHz, 2 kHz, and 4 kHz). All patients were followed-up for at least 12 months after the operation.
Results The anatomical success rate among all patients was of 93%, which is comparable to the rate of success in procedures using other usual grafting materials. In addition, there was a highly significant postoperative improvement in pure tone audiometry results as compared with the preoperative ones (the main hearing gain was of ∼ 11 dB; p < 0.001).
Conclusion The periosteal graft is easily harvested, easy to apply, with excellent anatomical and functional success.
Simplifying Arterial Coupling in Microsurgery—A Preclinical Assessment of an Everter Device to Aid with Arterial Anastomosis
Authors: Sando Ian , Plott Jeffrey , McCracken Brendan , Tiba Mohamad , Ward Kevin , Kozlow Jeffrey , Cederna Paul , Momoh Adeyiza 
Published: February 2018

Background A novel arterial everter device was engineered to simplify microvascular coupling of arteries by reliably securing the stiff, muscular wall of arteries over coupler pins. We compare microvascular coupling with the everter device to manual suturing for arterial anastomoses in a live large animal model.
Materials and Methods In this preliminary study, bilateral external femoral arteries of five male swine were exposed and sharply divided. Arteries were anastomosed using either interrupted sutures (n = 5) or the everter device and Synovis Coupler (n = 5). The efficiency in engaging coupler pins, the time taken to perform the anastomosis, and vessel patency immediately post-op and at 1-week postanastomosis were evaluated. Vessel wall injury and luminal stenosis were compared between groups using histomorphometric analyses.
Results On an average, 80% of coupler pins engaged the vessel walls after a single pass of the everter. The average time to perform the anastomosis was significantly less when using the everter/coupler compared with manual suturing (6:35 minutes versus 25:09 minutes, p < 0.001). Immediately post-op, 100% patency was observed in both groups. At 1 week post-op, four of five (80%) of coupled arteries and all five (100%) of hand-sewn arteries were patent. The degree of arterial wall injury, neointimal formation, and luminal stenosis for patent arteries were similar between groups.
Conclusions Successful arterial anastomoses using the everter device with the Synovis Coupler was easier and significantly more efficient when compared with a standard hand-sewn technique. Both techniques had acceptable patency rates and similar effects on the vessel wall and intima.
Operative Time and Flap Failure in Unilateral and Bilateral Free Flap Breast Reconstruction
Authors: Edwards Kyle , Donato Daniel , Tatro Eric , Xu Yizhe , Presson Angela , Agarwal Jayant , Kwok Alvin 
Published: February 2018

Background There is an increasing trend toward bilateral breast reconstruction. Using the National Surgical Quality Improvement Program (NSQIP) database, we sought to understand the association between unilateral and bilateral free flap breast reconstruction and operative time and flap failure.
Methods We selected a cohort of patients undergoing free flap breast reconstruction using the 2005 to 2010 NSQIP database. Cases were divided into unilateral and bilateral reconstruction. Subgroup analyses were performed dividing cases into delayed and immediate reconstruction. The effect of patient characteristics including age, body mass index (BMI), history of diabetes, and the American Society of Anesthesiologists' classification on operative time and flap failure was examined using univariable and multivariable regression models. Rates and odds ratios (OR) were reported using the multivariable gamma and logistic regression models, respectively.
Results There were 691 free flap breast reconstructions performed in the cohort and 29.1% were bilateral cases. There was a 78-minute increase in the median operative time when comparing unilateral and bilateral reconstruction (p = 0.005). Patients undergoing bilateral reconstructions were generally younger and had fewer comorbidities compared with unilateral reconstructions. There was no significant association between bilateral reconstruction and flap failure. Immediate bilateral reconstructions had a significant increase in median operative time compared with immediate unilateral reconstructions (563 versus 480 minutes, p = 0.002) but no significant increase in operative time was noted when comparing delayed unilateral and delayed bilateral reconstructions. Prolonged operative time was associated with flap failure after adjusting for age and BMI (OR 1.17, p < 0.001).
Conclusions Bilateral free flap breast reconstruction can be performed safely despite an increase in operative time when compared with unilateral reconstruction.
Variants Associated with Infantile Cholestatic Syndromes Detected in Extrahepatic Biliary Atresia by Whole Exome Studies: A 20-Case Series from Thailand
Authors: Laochareonsuk Wison , Maneechay Wanwisa , Kayasut Kanita , Chiengkriwate Piyawan , Sangkhathat Surasak 
Published: February 2018

AbstractBiliary atresia (BA) is the most severe form of obstructive cholangiopathy occurring in infants. Definitive diagnosis of BA usually relies on operative findings together with supporting pathological patterns found in the extrahepatic bile duct. In infancy, overlapping clinical patterns of cholestasis can be found in other diseases including biliary hypoplasia and progressive familial intrahepatic cholestasis. In addition, BA has been reported as a phenotype in some rare genetic syndromes. Unlike BA, other cholangiopathic phenotypes have their own established genetic markers. In this study, we used these markers to look for other cholestasis entities in cases diagnosed with BA. DNA from 20 cases of BA, diagnosed by operative findings and histopathology, were subjected to a study of 19 genes associated with infantile cholestasis syndromes, using whole exome sequencing. Variant selection focused on those with allele frequencies in dbSNP150 of less than 0.01. All selected variants were verified by polymerase chain reaction–direct sequencing. Of the 20 cases studied, 13 rare variants were detected in 9 genes: 4 in JAG1 (Alagille syndrome), 2 in MYO5B (progressive familial intrahepatic cholestasis [PFIC] type 6), and one each in ABCC2 (Dubin–Johnson syndrome), ABCB11 (PFIC type 2), UG1A1 (Crigler–Najjar syndrome), MLL2 (Kabuki syndrome), RFX6 (Mitchell–Riley syndrome), ERCC4 (Fanconi anemia), and KCNH1 (Zimmermann–Laband syndrome). Genetic lesions associated with various cholestatic syndromes detected in cases diagnosed with BA raised the hypothesis that severe inflammatory cholangiopathy in BA may not be a distinct disease entity, but a shared pathology among several infantile cholestatic syndromes.
Die Spinalkanalstenose – ein Überblick
Authors: Beyerlein Jörg 
Published: February 2018

ZusammenfassungDie hohe Lebenserwartung in Deutschland wird dazu führen, dass Ärzte und Therapeuten häufiger Patienten mit
degenerativen Erkrankungen untersuchen und behandeln werden. Die degenerative Spinalkanalstenose gehört zu
diesen Pathologien. Dr. Jörg Beyerlein fasst klinisches Bild, Diagnostik und Therapiemöglichkeiten
zusammen.
Editing out five
Serpina1
paralogs to create a mouse model of genetic emphysema
Authors: Borel Florie , Sun Huaming , Zieger Marina , Cox Andrew , Cardozo Brynn , Li Weiying , Oliveira Gabriella , Davis Airiel , Gruntman Alisha , Flotte Terence R. , Brodsky Michael H. , Hoffman Andrew M. , Elmallah Mai K. , Mueller Christian 
Published: February 2018

Significance
Chronic obstructive pulmonary disease affects 10% of the worldwide population, and the leading genetic cause is a genetic disease, α-1 antitrypsin (AAT) deficiency. Humans have only one gene that codes for the AAT protein, but mice have up to six, which made it impossible for decades to create a mouse model of the disease. Here we succeeded in creating this mouse model using CRISPR technology to target all of the mouse genes at once. Importantly, this mouse model spontaneously develops lung disease and recapitulates many aspects of the human disease. We anticipate that this model will be highly relevant not only to the preclinical development of therapeutics for AAT deficiency, but also to emphysema and smoking research.
Perspectival representation and fallacies in metaethics
Authors: Kölbel Max 
Published: February 2018

AbstractThe prevailing theoretical framework for theorising about representation construes all representation as involving objective representational contents. This classic framework has tended to drive philosophers either to claim that evaluative judgements are representations and therefore objective, or else to claim that evaluative judgements are not really representations, because they are not objective. However, a more general, already well-explored framework is available, which will allow theorists to treat evaluative judgements as full-fledged representations (thus doing justice to their representational aspects) while leaving open whether they are objective. Such a more general conception of representational content is exemplified, e.g. by Lewis's ‘centred contents’ and Gibbard's framework of ‘contents of judgement’, thus it is not new. I shall start in §1 by introducing the more general framework of perspectival contents and then illustrate in §2 how awareness of it can help expose the fallaciousness of certain widely used forms of argumentation in metaethics.
Reasons for emotion and moral motivation
Authors: Blackman Reid 
Published: February 2018

AbstractInternalism about normative reasons is the view that an agent’s normative reasons depend on her motivational constitution. On the assumption that there are reasons for emotion I argue that (a) externalism about reasons for emotion entails that all rational agents have reasons to be morally motivated and (b) internalism about reasons for emotion is implausible. If the arguments are sound we can conclude that all rational agents have reasons to be morally motivated. Resisting this conclusion requires either justifying internalism about reasons for emotion in a way hitherto unarticulated or giving up on reasons for emotion altogether.
Immunoaffinity‐based isolation of melanoma cell‐derived exosomes from plasma of patients with melanoma
Authors: Sharma Priyanka , Ludwig Sonja , Muller Laurent , Hong Chang Sook , Kirkwood John M , Ferrone Soldano , Whiteside Theresa L. 
Published: February 2018

ABSTRACTTumour‐derived exosomes (TEX) are a subset of extracellular vesicles (EVs) present in body fluids of patients with cancer. The role of this exosome subset in melanoma progression has been of interest ever since ex vivo studies of exosomes produced by melanoma cell lines were shown to suppress anti‐melanoma immune responses. To study the impact of melanoma‐derived exosomes (MTEX) present in patients’ plasma on melanoma progression, isolation of MTEX from total plasma exosomes is necessary. We have developed an immunoaffinity‐based method for MTEX capture from plasma of melanoma patients. Using mAb 763.74 specific for the CSPG4 epitope uniquely expressed on melanoma cells, we separated MTEX from non‐tumour cell‐derived exosomes and evaluated the protein cargo of both fractions by quantitative flow cytometry. Melanoma‐associated antigens were carried by MTEX but were not detectable in exosomes produced by normal cells. Separation of plasma‐derived MTEX from non‐MTEX provides an opportunity for future evaluation of MTEX as potential biomarkers of melanoma progression and as surrogates of melanoma in tumour liquid biopsy studies.
A model for AGN variability on multiple time-scales
Authors: Sartori Lia F , Schawinski Kevin , Trakhtenbrot Benny , Caplar Neven , Treister Ezequiel , Koss Michael J , Megan Urry C , Zhang Ce 
Published: February 2018

Abstract
We present a framework to link and describe active galactic nuclei (AGN) variability on a wide range of time-scales, from days to billions of years. In particular, we concentrate on the AGN variability features related to changes in black hole fuelling and accretion rate. In our framework, the variability features observed in different AGN at different time-scales may be explained as realisations of the same underlying statistical properties. In this context, we propose a model to simulate the evolution of AGN light curves with time based on the probability density function (PDF) and power spectral density (PSD) of the Eddington ratio (L/LEdd) distribution. Motivated by general galaxy population properties, we propose that the PDF may be inspired by the L/LEdd distribution function (ERDF), and that a single (or limited number of) ERDF+PSD set may explain all observed variability features. After outlining the framework and the model, we compile a set of variability measurements in terms of structure function (SF) and magnitude difference. We then combine the variability measurements on a SF plot ranging from days to Gyr. The proposed framework enables constraints on the underlying PSD and the ability to link AGN variability on different time-scales, therefore providing new insights into AGN variability and black hole growth phenomena.
Influence of Residual Disease Following Surgical Resection in Newly Diagnosed Glioblastoma on Clinical, Neurocognitive, and Patient Reported Outcomes
Authors: Hall William A , Pugh Stephanie L , Wefel Jeffrey S , Armstrong Terri S , Gilbert Mark R , Brachman David G , Werner-Wasik Maria , Wendland Merideth M , Brown Paul D , Chao Samuel T , Roof Kevin S , Robins H Ian , Mehta Minesh P , Curran Walter J , Movsas Benjamin 
Published: February 2018

Abstract

BACKGROUND
The influence of subtotal resection (STR) on neurocognitive function (NCF), quality of life, and symptom burden in glioblastoma is unknown. If bevacizumab preferentially benefits patients with STR is unknown.

OBJECTIVE
To examine these uncertainties.

METHODS
NCF and patient reported outcomes (PRO) were prospectively collected in NRG Oncology RTOG 0525 and 0825. Changes in NCF and PRO measures from baseline to prespecified times were examined by Wilcoxon test, and mixed effects longitudinal modeling, to assess differences between patients who received STR vs gross-total resection. Changes were also compared among STR patients on 0825 receiving placebo vs bevacizumab to assess for a preferential therapeutic effect. Overall survival between STR and gross-total resection patients was compared using the Kaplan–Meier method.

RESULTS
A total of 427 patients were eligible with STR present in 37%. At baseline, patients with STR had worse NCF, worse MD Anderson Symptom Inventory Brain Tumor Neurological Factor ratings (P = .004), and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (P = .002). Longitudinal multivariate analysis associated STR with worse NCF (Hopkins Verbal Learning Test–Revised Delayed Recognition [P = .048], Trail Making Test Part A [P = .035], and Controlled Oral Word Association [P = .049]). One hundred eighty-three STR patients from 0825 were analyzed (89 bevacizumab, 94 placebo); bevacizumab failed to demonstrate improvement in select NCF or PRO measures.

CONCLUSION
STR patients had worse NCF and PROs before therapy. During adjuvant therapy, STR patients had worse objective NCF, despite accounting for tumor location. STR did not result in a detriment to OS. The addition of bevacizumab did not preferentially improve PRO or NCF outcomes in STR patients.