bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prodrugs of herpes simplex thymidine kinase inhibitors
Authors: Yanachkova Milka , Xu Wei-Chu , Dvoskin Sofya , Dix Edward J , Yanachkov Ivan B , Focher Federico , Savi Lida , Sanchez M Dulfary , Foster Timothy P , Wright George E 
Published: October 2015

Background Because guanine-based herpes simplex virus thymidine kinase inhibitors are not orally available, we synthesized various 6-deoxy prodrugs of these compounds and evaluated them with regard to solubility in water, oral bioavailability, and efficacy to prevent herpes simplex virus-1 reactivation from latency in a mouse model. Methods Organic synthesis was used to prepare compounds, High Performance Liquid Chromatography (HPLC) to analyze hydrolytic conversion, Mass Spectrometry (MS) to measure oral bioavailability, and mouse latent infection and induced reactivation to evaluate the efficacy of a specific prodrug. Results Aqueous solubilities of prodrugs were improved, oxidation of prodrugs by animal cytosols occurred in vitro, and oral absorption of the optimal prodrug sacrovir™ (6-deoxy- mCF3PG) in the presence of the aqueous adjuvant Soluplus® and conversion to active compound N2-[3-(trifluoromethyl)pheny])guanine ( mCF3PG) were accomplished in mice. Treatment of herpes simplex virus-1 latent mice with sacrovir™ in 1% Soluplus in drinking water significantly suppressed herpes simplex virus-1 reactivation and viral genomic replication. Conclusions Ad libitum oral delivery of sacrovir™ was effective in suppressing herpes simplex virus-1 reactivation in ocularly infected latent mice as measured by the numbers of mice shedding infectious virus at the ocular surface, numbers of trigeminal ganglia positive for infectious virus, number of corneas that had detectable infectious virus, and herpes simplex virus-1 genome copy numbers in trigeminal ganglia following reactivation. These results demonstrate the statistically significant effect of the prodrug on suppressing herpes simplex virus-1 reactivation in vivo.
Unplanned Readmission to the Pediatric Cardiac Intensive Care Unit
Authors: Brunetti Marissa A. , Glatz Andrew C. , McCardle Ken , Mott Antonio R. , Ravishankar Chitra , Gaynor J. William 
Published: October 2015

Background: Factors leading to cardiac intensive care unit (CICU) readmission and the impact on mortality have yet to be well delineated. We sought to define the prevalence and outcome for unscheduled CICU readmission. Secondary objectives were to identify indications and risk factors for unscheduled CICU readmission. Methods: Retrospective analysis of prospectively collected registry data at a tertiary care children’s hospital. Pediatric and adult patients with congenital and acquired heart disease who survived to initial CICU discharge were included. Patients with unexpected return to the CICU for acute change in clinical status were defined as unscheduled readmissions. Results: Of the 645 discharges that met inclusion criteria, 37 resulted in unplanned readmission to the CICU. Patients requiring unscheduled readmission had higher mortality rates (16.2% vs 0.5%, P < .0001). Cardiac symptoms were the most common reason for readmission. On multivariate analysis, genetic anomaly ( P = .001) and longer length of stay (LOS) during the index CICU admission ( P = .01) were independently associated with readmission. For surgical patients, genetic anomaly ( P = .001), single-ventricle anatomy ( P = .05), and longer surgical support time ( P < .001) were independently associated with readmission. Conclusion: Unscheduled readmission to the CICU within the same hospitalization was uncommon but associated with a higher mortality rate. Genetic anomaly and longer initial LOS were important risk factors for the entire cohort. Single-ventricle anatomy and longer intraoperative course were risk factors for surgical readmissions.
Confessions of PCICU Leaders
Authors: da Cruz Eduardo M. , Tabbutt Sarah , Eisenhaur Mary C. , Jacobs Jeffrey P. , Graham Eric M. , Smith Liz C. , Simsic Janet , Laussen Peter C. 
Published: October 2015

Background: The pediatric cardiac intensive care environment is challenging and unpredictable due to the heterogeneous patient population. Leadership within this complex environment is critical for optimal outcomes. Methods: The 10th International Meeting of the Pediatric Cardiac Intensive Care Society provided a forum for leaders to share their own practice and experience that concluded with take-home messages regarding quality, safety, clinical effectiveness, stewardship, and leadership. Results: Presentations defined vital aspects for successful outcomes and highlighted ongoing challenges. Conclusions: Accomplishing exceptional outcomes requires a blend of clinical expertise, leadership, communication skills with briefing and debriefing, meaningful use of data, and transparency among peers and toward patients and their families.
Variability of Pulmonary Regurgitation in Proportion to Pulmonary Vascular Resistance in a Porcine Model of Total Resection of the Pulmonary Valve
Authors: Ko Yoshihiro , Morita Kiyozo , Abe Takayuki , Nakao Mitsutaka , Hashimoto Kazuhiro 
Published: October 2015

Introduction: Pulmonary regurgitation (PR) is a major concern after right ventricular (RV) outflow tract surgery. We assessed the impact of physiological changes in pulmonary vasculature on hemodynamic severity of PR and RV function and their potential clinical implications for postoperative management using a porcine model with severe PR. Materials and Methods: Eight porcine models of acute PR were established by means of resection of pulmonary valve on cardiopulmonary bypass. After separation from bypass and stabilization, blood flow in the main pulmonary artery was measured by a pulsed Doppler flowmeter, and RV systolic function was assessed on the basis of RV segment shortening (RVSS), which was analyzed by sonomicrometry. In the acute PR model, we verified the impact of pulmonary vascular resistance (Rp) on pulmonary regurgitant fraction (PRF) and RV function. Pulmonary vascular resistance was changed by manipulating the level of PaCo2 and by inhalation of nitric oxide (NO). Results: After bypass, the mean PRF was 40% ± 5%, and there was a deterioration of RV function. Under each ventilation condition (high Co2, low Co2, and NO 20 ppm), Rp was 836 ± 207 dyne × s × cm−5, 499 ± 125 dyne × s × cm−5, and 340 ± 102 dyne × s × cm−5, respectively, and PRF was 60% ± 10%, 37% ± 5%, and 24% ± 4%, respectively, under each condition. They also showed a positive correlation in all animals. Cardiac output and RVSS were decreased by hypercapnia, while they were significantly improved after NO inhalation. Conclusions: This study indicates that low Rp after right ventricular outflow tract reconstruction (RVOTR) resulting in acute PR is advantageous in reducing the severity of PR and RV volume load. These findings may have clinical implications for early and long-term postoperative management of patients subjected to RVOTR with resulting pulmonary valve incompetence.
B-cell non-Hodgkin lymphoma linked to Coxiella burnetii
Authors: Melenotte Cléa , Million Matthieu , Audoly Gilles , Gorse Audrey , Dutronc Hervé , Roland Gauthier , Dekel Michal , Moreno Asuncion , Cammilleri Serge , Carrieri Maria Patrizia , Protopopescu Camelia , Ruminy Philippe , Lepidi Hubert , Nadel Bertrand , Mege Jean-Louis , Xerri Luc , Raoult Didier 
Published: October 2015

Key PointsCoxiella burnetii is associated with an increased risk of lymphoma; its presence in the tumor microenvironment may favor lymphomagenesis. Lymphoma has to be considered in patients with Q fever and lymphoid disorders, especially those with persistent focalized infections.
Report of the European Respiratory Society/European Cystic Fibrosis Society task force on the care of adults with cystic fibrosis
Authors: Elborn J. Stuart , Bell Scott C. , Madge Susan L. , Burgel Pierre-Regis , Castellani Carlo , Conway Steven , De Rijcke Karleen , Dembski Birgit , Drevinek Pavel , Heijerman Harry G.M. , Innes J. Alistair , Lindblad Anders , Marshall Bruce , Olesen Hanne V. , Reimann Andreas L. , Solé Ampara , Viviani Laura , Wagner Thomas O.F. , Welte Tobias , Blasi Francesco 
Published: October 2015

The improved survival in people with cystic fibrosis has led to an increasing number of patients reaching adulthood. This trend is likely to be maintained over the next decades, suggesting a need to increase the number of centres with expertise in the management of adult patients with cystic fibrosis. These centres should be capable of delivering multidisciplinary care addressing the complexity of the disease, in addition to addressing the psychological burden on patients and their families. Further issues that require attention are organ transplantation and end of life management.Lung disease in adults with cystic fibrosis drives most of the clinical care requirements, and major life-threatening complications, such as respiratory infection, respiratory failure, pneumothorax and haemoptysis, and the management of lung transplantation require expertise from trained respiratory physicians. The taskforce therefore strongly reccommends that medical leadership in multidisciplinary adult teams should be attributed to a respiratory physician adequately trained in cystic fibrosis management.The task force suggests the implementation of a core curriculum for trainees in adult respiratory medicine and the selection and accreditation of training centres that deliver postgraduate training to the standards of the HERMES programme.
The serotonin-lir nervous system of the Bryozoa (Lophotrochozoa): a general pattern in the Gymnolaemata and implications for lophophore evolution of the phylum
Authors: Schwaha Thomas F. , Wanninger Andreas 
Published: October 2015

AbstractBackgroundSerotonin represents an evolutionary ancient neurotransmitter that is ubiquitously found among animals including the lophotrochozoan phylum Bryozoa, a group of colonial filter-feeders. Comparatively little is known on their nervous system, and data on their serotonin-lir nervous system currently are mostly limited to the basal phylactolaemates. Previous investigations indicated a common ground-pattern of the serotonin-lir nervous system in these animals, but in order to assess this on a larger scale, 21 gymnolaemate species from 21 genera were comparatively analysed herein.MethodsTwenty-one species from 21 gymnolaemate genera were analysed by immunocytochemical stainings and confocal laser scanning microscopy.ResultsIn all species the serotonin-lir signal is concentrated in the cerebral ganglion from where a nerve tract emanates laterally and traverses orally to engulf the foregut. Serotonin-lir perikarya are situated at the base of the tentacles that almost always correspond to the number of tentacles minus two. The oral side in almost all species shows three serotonin-lir perikarya followed by a ‘serotonergic gap’ that to our knowledge is not reflected in the morphology of the nervous system. Some species show additional serotonin-lir signal in tentacle nerves, visceral innervation and pore complexes.Paludicella articulatais exceptional as it shows signal in the latero-visceral nerves with serotonin-lir perikarya in the esophagus, parts of the tentacle sheath nerves as well as the frontal body wall around the parietal muscle bundles.ConclusionsIn general, the serotonin-lir nervous system in the Bryozoa shows a consistent pattern among its different clades with few deviations. Preliminary data on phylactolaemates suggest the presence of a ‘serotonergic gap’ similar to gymnolaemates. Both show a subset of oral tentacles and the remaining tentacles in gymnolaemates which correspond to the lateral tentacles of phylactolaemates. The lophophoral concavity lacks serotonin-lir perikarya indicating that due to their larger sizes and increased tentacle number, the horse-shoe shaped arrangement could represent an apomorphy of phylactolaemates.
Complete genome sequence of Mycobacterium tuberculosis K from a Korean high school outbreak, belonging to the Beijing family
Authors: Han Seung Jung , Song Taeksun , Cho Yong-Joon , Kim Jong-Seok , Choi Soo Young , Bang Hye-Eun , Chun Jongsik , Bai Gill-Han , Cho Sang-Nae , Shin Sung Jae 
Published: October 2015

AbstractMycobacterium tuberculosis K, a member of the Beijing family, was first identified in 1999 as the most prevalent genotype in South Korea among clinical isolates of M. tuberculosis from high school outbreaks. M. tuberculosis K is an aerobic, non-motile, Gram-positive, and non-spore-forming rod-shaped bacillus. A transmission electron microscopy analysis displayed an abundance of lipid bodies in the cytosol. The genome of the M. tuberculosis K strain was sequenced using two independent sequencing methods (Sanger and Illumina). Here, we present the genomic features of the 4,385,518-bp-long complete genome sequence of M. tuberculosis K (one chromosome, no plasmid, and 65.59 % G + C content) and its annotation, which consists of 4194 genes (3447 genes with predicted functions), 48 RNA genes (3 rRNA and 45 tRNA) and 261 genes with peptide signals.
Estrogen Receptor-Selective Agonists Modulate Learning in Female Rats in a Dose- and Task-Specific Manner
Authors: Pisani Samantha L. , Neese Steven L. , Katzenellenbogen John A. , Schantz Susan L. , Korol Donna L. 
Published: October 2015

Abstract
Estrogens are well known for their enhancing effects on hippocampus-sensitive cognition. However, estrogens can also impair learning and memory, particularly the acquisition of striatum-sensitive tasks. These cognitive shifts appear to be mediated through local estrogen receptor (ER) activation in each neural structure, but little information is known regarding which specific ER subtypes drive the opposing effects on learning. Elucidating the mnemonic roles of discrete ER subtypes is essential for predicting how treatments with distinct ER pharmacology such as drugs, hormone therapies, and phytoestrogen supplements affect cognitive abilities in and thus the daily lives of the women who take them. The present study examined the effects of the ERα-selective compound propyl pyrazole triol and the ERβ-selective compounds diarylpropionitrile and Br-ERb-041 on place and response learning in young adult female rats. Long-Evans rats were ovariectomized and maintained on phytoestrogen-free chow for 3 weeks before behavioral training, with treatments administered via subcutaneous injection 48 and 24 hours before testing. A dose-response paradigm was used, with each compound tested at 4 different doses in separate groups of rats. Propyl pyrazole triol, diarylpropionitrile, and Br-ERb-041 all enhanced place learning and impaired response learning, albeit with distinct dose-response patterns for each compound and task. These results are consistent with the detection of ERα and ERβ in the hippocampus and striatum and suggest that learning is modulated via activation of either ER subtype.
Cardiomyocyte and Vascular Smooth Muscle-Independent 11β-Hydroxysteroid Dehydrogenase 1 Amplifies Infarct Expansion, Hypertrophy, and the Development of Heart Failure After Myocardial Infarction in Male Mice
Authors: White Christopher I. , Jansen Maurits A. , McGregor Kieran , Mylonas Katie J. , Richardson Rachel V. , Thomson Adrian , Moran Carmel M. , Seckl Jonathan R. , Walker Brian R. , Chapman Karen E. , Gray Gillian A. 
Published: October 2015

Abstract
Global deficiency of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an enzyme that regenerates glucocorticoids within cells, promotes angiogenesis, and reduces acute infarct expansion after myocardial infarction (MI), suggesting that 11β-HSD1 activity has an adverse influence on wound healing in the heart after MI. The present study investigated whether 11β-HSD1 deficiency could prevent the development of heart failure after MI and examined whether 11β-HSD1 deficiency in cardiomyocytes and vascular smooth muscle cells confers this protection. Male mice with global deficiency in 11β-HSD1, or with Hsd11b1 disruption in cardiac and vascular smooth muscle (via SM22α-Cre recombinase), underwent coronary artery ligation for induction of MI. Acute injury was equivalent in all groups. However, by 8 weeks after induction of MI, relative to C57Bl/6 wild type, globally 11β-HSD1-deficient mice had reduced infarct size (34.7 ± 2.1% left ventricle [LV] vs 44.0 ± 3.3% LV, P = .02), improved function (ejection fraction, 33.5 ± 2.5% vs 24.7 ± 2.5%, P = .03) and reduced ventricular dilation (LV end-diastolic volume, 0.17 ± 0.01 vs 0.21 ± 0.01 mL, P = .01). This was accompanied by a reduction in hypertrophy, pulmonary edema, and in the expression of genes encoding atrial natriuretic peptide and β-myosin heavy chain. None of these outcomes, nor promotion of periinfarct angiogenesis during infarct repair, were recapitulated when 11β-HSD1 deficiency was restricted to cardiac and vascular smooth muscle. 11β-HSD1 expressed in cells other than cardiomyocytes or vascular smooth muscle limits angiogenesis and promotes infarct expansion with adverse ventricular remodeling after MI. Early pharmacological inhibition of 11β-HSD1 may offer a new therapeutic approach to prevent heart failure associated with ischemic heart disease.
Mechanism of the Formation of Hierarchical-structured Bismuth Tungstate Photocatalyst Particles through Counter-flow Supply of Bismuth and Tungsten Sources
Authors: Hori Haruna , Takase Mai , Amano Fumiaki , Ohtani Bunsho 
Published: October 2015

Abstract
The mechanism of formation of hierarchical “flake-ball”-structured bismuth tungstate (BTO) particles was studied on the basis of structural analyses and was revealed to be the growth of plate-like BTO crystallites on the tungsten oxide/BTO-modified surface of bismuth hydroxide particles by supplying tungsten and bismuth from the outside and inside of the core particles, respectively.
Codeposition of Colloidal Platinum Particles and Iron Chloride Precursor on TiO2 for Efficient Catalytic Oxidation of CO to CO2
Authors: Einaga Hisahiro , Shiranita Ryo , Saito Hikaru , Hata Satoshi 
Published: October 2015

Abstract
Codeposition of metal chlorides with Pt colloidal nanoparticles on TiO2 followed by oxidation at 400 °C and reduction at 200 °C improved the activity for Pt-catalyzed CO oxidation with stoichiometric amount of O2. The highest activity was obtained when FeCl3 was used as the additive with the Fe/Pt ratio of 0.2. XAFS, X-EDS, FTIR, and catalytic studies revealed that the deposition of Fe species on the reduced Pt sites gave active sites, which exhibited CO oxidation with high efficiency.
RNA-Seq workflow: gene-level exploratory analysis and differential expression
Authors: Love Michael I. , Anders Simon , Kim Vladislav , Huber Wolfgang 
Published: October 2015

Here we walk through an end-to-end gene-level RNA-Seq differential expression workflow using Bioconductor packages. We will start from the FASTQ files, show how these were aligned to the reference genome, and prepare a count matrix which tallies the number of RNA-seq reads/fragments within each gene for each sample. We will perform exploratory data analysis (EDA) for quality assessment and to explore the relationship between samples, perform differential gene expression analysis, and visually explore the results.
Educating the Common Agent: Kant on the Varieties of Moral Education
Authors: Sticker Martin 
Published: October 2015

Abstract:I discuss the relation between Kant’s trust in the rational capacities of ordinary agents and education. First, I show that Kant is very optimistic regarding our common moral capacities. Then I discuss what room this leaves for moral education. I argue that a discussion of Kant’s conception of moral education should distinguish between different functions of education: (i) education is necessary for agents to make the transition from a purely instrumental to a pure practical use of reason (Basic Education); (ii) education can strengthen the motivational force of the moral law by presenting the moral law in all its dignity and clarity (Motivational Education); (iii) education can instruct agents about the source of morality and offer an abstract formula of the Categorical Imperative (Philosophical Education); and (iv) education can enhance agents’ capacity to apply general moral principles to concrete cases (Education of Judgement).
User interfaces for cyber-physical systems
Authors: Paelke Volker , Röcker Carsten , Koch Nils , Flatt Holger , Büttner Sebastian 
Published: October 2015

Abstract
In this paper, we analyze the specific requirements of interacting with
cyber-physical systems and propose a design approach that is driven by user
needs and makes use of an expanded toolbox that contains state-of-the-art
interaction technologies including Smart Glasses and Wearables. We present
several examples of assistance systems in industrial production that use these
interaction technologies and discuss the corresponding usability and
implementation aspects.
Data-driven anomaly detection in cyber-physical production systems
Authors: Niggemann Oliver , Frey Christian 
Published: October 2015

Abstract
Due to global competition and increasing product complexity, the complexity of production systems has grown significantly in recent
years. This places an increasing burden on automation developers, systems engineers and plant constructors. Intelligent assistance
systems and smart automation systems are a possible solution to face this complexity: The machines, i.e. the software and assistance
systems, take over tasks that were previously carried out manually by experts. At the heart of this concept are intelligent anomaly
detection approaches based on models of the system behaviors. Intelligent assistance systems learn these models automatically: Based on
data, these systems extract most necessary knowledge about the diagnosis task. This paper outlines this data-driven approach to plant
analysis using several use cases from industry.
First data on the biological variation and quality specifications for plasma ammonia concentrations in healthy subjects
Authors: Ucar Fatma , Erden Gonul , Ozdemir Seyda , Ozcan Nurgul , Bulut Erdem , Ozturk Alpaslan 
Published: October 2015

AbstractBackground:Most of the factors causing preanalytical and analytical variation in ammonia measurement have been identified. Biological variation data for ammonia is still lacking. We therefore estimated the components of biological variation (within-subject=CVMethods:Blood samples from 20 healthy subjects were collected in K2EDTA tubes daily over a period of 4 consecutive days from each subject. Each plasma sample was split into two aliquots; one was immediately analyzed as the samples were collected and the other was stored –80 °C until testing at the end of the collection period and analyzed at once in one analytical run. All samples were analyzed in duplicate. Estimations were calculated according to Fraser and Harris methods.Results:CVConclusions:The present study for the first time described the components of biological variation for ammonia in healthy individuals. These data regarding biological variation of ammonia could be useful for a better evaluation of ammonia test results in clinical interpretation and for determining quality specifications based on biological variation.