bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment Regimens with Bypassing Agents in Patients with Hemophilia A and Inhibitors: A Survey from the Italian Association of Hemophilia Centers (AICE)
Authors: Coppola Antonio , Franchini Massimo , Castaman Giancarlo , Santagostino Elena , Santoro Cristina , Santoro Rita , Morfini Massimo , Di Minno Giovanni , Rocino Angiola ,   on behalf of the AICE ad hoc Working Group
Published: May 2018

AbstractThe development of neutralizing antibodies (inhibitors) against infused factor VIII currently represents the main complication of replacement therapy in patients with severe hemophilia A. Inhibitors, indeed, particularly high-titer inhibitors (>5 BU/mL), greatly complicate the management of bleeding, exposing patients to an increased morbidity and mortality risk, thus representing a significant burden for physicians of Hemophilia Treatment Centers (HTCs). Although bypassing agents (i.e., activated prothrombin complex concentrate [APCC] and recombinant activated factor VII [rFVIIa]) are available for the treatment and prevention of bleeding in inhibitor patients, their efficacy, safety, and cost–benefit outcomes are poorly known in the long term and should be further improved. In the frame of the update of recommendations for the management of inhibitor patients by the Italian Association of Hemophilia Centers (AICE), to collect more information on real-life therapeutic approaches with bypassing agents in this setting, a survey was conducted among the Directors of the Italian HTCs. From questionnaires returned by 55% of them, data on the use of rFVIIa and APCC in children, adolescent, and adult patients with hemophilia A and inhibitors were obtained and are summarized in this article, including information about the implementation of prophylaxis with both bypassing agents, the adopted regimens, and reasons for starting, adjusting, and interrupting such a therapeutic approach.
FAQ: MVZ – Gründung, Aufkauf, Nachbesetzung und Übernahme von Praxissitzen
Authors: Jaeger Berit , Werle Christiane 
Published: May 2018

ZusammenfassungBei einem Medizinischen Versorgungszentrum, kurz MVZ, muss zwischen einem „Angestellten-MVZ“ und einem „Freiberufler-MVZ“ unterschieden werden. Ob die Gründung eines MVZ im Einzelfall sinnvoll ist und, falls dem so ist, in welcher Form eine solche Gründung erfolgen sollte, hängt von den Umständen des Einzelfalls ab sowie davon, ob überhaupt die jeweiligen Gründereigenschaften vorliegen. Anhand der bestehenden Unterschiede zwischen einer Berufsausübungsgemeinschaft (BAG) und einem MVZ sollte überdacht werden, ob die MVZ-Gründung für das beabsichtigte Ziel sinnvoll und erforderlich ist. Dabei ist zu berücksichtigen, dass sich ein MVZ insbesondere hinsichtlich der Gründung, der möglichen Gesellschaftsform, der Möglichkeit der Anzahl der angestellten Ärzte, der Nachbesetzung von Arztsitzen bzw. Arztstellen, der Anzahl der möglichen Standorte und der Gewinnverteilungsmöglichkeiten von einer BAG unterscheidet.
Psychosoziale Evaluation von Transplantationspatienten – Empfehlungen für die Richtlinien zur Organtransplantation
Authors: Kröncke Sylvia , Greif-Higer Gertrud , Albert Wolfgang , de Zwaan Martina , Erim Yesim , Eser-Valeri Daniela , Papachristou Christina , Petersen Irene , Schulz Karl-Heinz , Tigges-Limmer Katharina , Vitinius Frank , Ziegler Kristin , Künsebeck Hans-Werner 
Published: May 2018

ZusammenfassungSeit einigen Jahren befinden sich die Richtlinien zur Transplantationsmedizin der Bundesärztekammer in einem umfassenden Revisionsprozess. Der vorliegende Beitrag präsentiert Empfehlungen zur psychosozialen Evaluation von Patienten vor Organtransplantation, die von Experten der Kommission Psychologie/Psychosomatik der Deutschen Transplantationsgesellschaft erarbeitet wurden mit dem Ziel, diese Empfehlungen in die Richtlinien einzubringen. Wichtigstes Anliegen ist dabei die Etablierung einer obligatorischen psychosozialen Evaluation für alle Patienten vor Aufnahme in die Transplantationswarteliste. Beschrieben werden Inhalte, potenzielle Kontraindikationen und das Prozedere der Evaluation. Außerdem wird ausführlich die für die Untersucher für notwendig erachtete Qualifikation thematisiert. Abschließend wird der zukünftige Handlungsbedarf festgestellt.
Key clusters as indicators of translator style
Authors: Mastropierro Lorenzo 
Published: April 2018

AbstractThis paper discusses the issue of translator style through the comparison of two Italian translations of H. P. Lovecraft’sAt the Mountains of Madness. Using a corpus linguistic approach, this paper proposes a method for the identification of potential indicators of translator style based on key cluster analysis. Comparing the two translations with this method identifies which clusters – i.e., repeated sequences of words – are used more frequently by one translator compared to the other. The analysis shows that the two translators differ in their usage of some linguistic features, specifically Italian euphonic-d, locative clitics, and distal demonstratives, which are then analysed as stylistic divergences.
Adaptation and mitigation for combating climate change – from single to joint
Authors: Zhao Chunli , Yan Yan , Wang Chenxing , Tang Mingfang , Wu Gang , Ding Ding , Song Yang 
Published: May 2018

ABSTRACT

Introduction:
Adaptation and mitigation are two main approaches to combating climate change. Mitigation is considered as the most important tasks in dealing with climate change in scientific research, financial support and technical practices as global warming intensifies; while currently the warming trend still cannot be reversed, and adaptation task seemed to gain urgency although it is late-starting. The synergies and tradeoffs of these two strategies revealed increasingly importance on reducing adverse climate effects. Research on synergistic relationships has developed from definition and feasible analysis, to the development of quantitative tools and exploration in practice and application, though the latter aspect is still in its initial stage.

Outcomes/other:
Our review shows that the traits of mitigation and adaptation, the differences and similarities between them, then illustrate the significance and mechanism of their synergies and tradeoffs. And it is explained that methods and applications of single and integrated models, and cost-effectiveness analysis.

Discussion/ Conclusion:
We hold the opinion that the future research and applications should be enhanced in terms of four aspects: reinforcement of interrelations and common mechanisms between mitigation and adaptation actions study; building and improving the monitoring and evaluating systems; promoting departmental and regional scale investigations and applications; and establishing policy and security systems.
Haemodynamics, dyspnoea, and pulmonary reserve in heart failure with preserved ejection fraction
Authors: Obokata Masaru , Olson Thomas P , Reddy Yogesh N V , Melenovsky Vojtech , Kane Garvan C , Borlaug Barry A 
Published: April 2018

Abstract

Aims
Increases in left ventricular filling pressure are a fundamental haemodynamic abnormality in heart failure with preserved ejection fraction (HFpEF). However, very little is known regarding how elevated filling pressures cause pulmonary abnormalities or symptoms of dyspnoea. We sought to determine the relationships between simultaneously measured central haemodynamics, symptoms, and lung ventilatory and gas exchange abnormalities during exercise in HFpEF.

Methods and results
Subjects with invasively-proven HFpEF (n = 50) and non-cardiac causes of dyspnoea (controls, n = 24) underwent cardiac catheterization at rest and during exercise with simultaneous expired gas analysis. During submaximal (20 W) exercise, subjects with HFpEF displayed higher pulmonary capillary wedge pressures (PCWP) and pulmonary artery pressures, higher Borg perceived dyspnoea scores, and increased ventilatory drive and respiratory rate. At peak exercise, ventilation reserve was reduced in HFpEF compared with controls, with greater dead space ventilation (higher VD/VT). Increasing exercise PCWP was directly correlated with higher perceived dyspnoea scores, lower peak exercise capacity, greater ventilatory drive, worse New York Heart Association (NYHA) functional class, and impaired pulmonary ventilation reserve.

Conclusion
This study provides the first evidence linking altered exercise haemodynamics to pulmonary abnormalities and symptoms of dyspnoea in patients with HFpEF. Further study is required to identify the mechanisms by which haemodynamic derangements affect lung function and symptoms and to test novel therapies targeting exercise haemodynamics in HFpEF.
Isomorphisms Between Big Mapping Class Groups
Authors: Bavard Juliette , Dowdall Spencer , Rafi Kasra 
Published: April 2018

Abstract
We show that any isomorphism between mapping class groups of orientable infinite-type surfaces is induced by a homeomorphism between the surfaces. Our argument additionally applies to automorphisms between finite-index subgroups of these “big” mapping class groups and shows that each finite-index subgroup has finite outer automorphism group. As a key ingredient, we prove that all simplicial automorphisms between curve complexes of infinite-type orientable surfaces are induced by homeomorphisms.
Validation of previously reported predictors for radiation-induced hypothyroidism in nasopharyngeal cancer patients treated with intensity-modulated radiation therapy, a post hoc analysis from a Phase III randomized trial
Authors: Lertbutsayanukul Chawalit , Kitpanit Sarin , Prayongrat Anussara , Kannarunimit Danita , Netsawang Buntipa , Chakkabat Chakkapong 
Published: April 2018

Abstract
This study aimed to validate previously reported dosimetric parameters, including thyroid volume, mean dose, and percentage thyroid volume, receiving at least 40, 45 and 50 Gy (V40, V45 and V50), absolute thyroid volume spared (VS) from 45, 50 and 60 Gy (VS45, VS50 and VS60), and clinical factors affecting the development of radiation-induced hypothyroidism (RHT). A post hoc analysis was performed in 178 euthyroid nasopharyngeal cancer (NPC) patients from a Phase III study comparing sequential versus simultaneous-integrated boost intensity-modulated radiation therapy. RHT was determined by increased thyroid-stimulating hormone (TSH) with or without reduced free thyroxin, regardless of symptoms. The median follow-up time was 42.5 months. The 1-, 2- and 3-year freedom from RHT rates were 78.4%, 56.4% and 43.4%, respectively. The median latency period was 21 months. The thyroid gland received a median mean dose of 53.5 Gy. Female gender, smaller thyroid volume, higher pretreatment TSH level (≥1.55 μU/ml) and VS60 < 10 cm3 were significantly associated with RHT in univariate analyses. Only pretreatment TSH ≥ 1.55 μU/ml and VS60 < 10 cm3 were significant predictors in multivariate analysis. Our results suggested that patients with pretreatment TSH ≥ 1.55 μU/ml should be cautious about the risk of RHT. The VS60 ≥ 10 cm3 is recommended for treatment planning.
eNetXplorer: an R package for the quantitative exploration of elastic net families for generalized linear models
Authors: Candia Julián , Tsang John S. 
Published: April 2018

AbstractBackgroundRegularized generalized linear models (GLMs) are popular regression methods in bioinformatics, particularly useful in scenarios with fewer observations than parameters/features or when many of the features are correlated. In both ridge and lasso regularization, feature shrinkage is controlled by a penalty parameter λ. The elastic net introduces a mixing parameter α to tune the shrinkage continuously from ridge to lasso. Selecting α objectively and determining which features contributed significantly to prediction after model fitting remain a practical challenge given the paucity of available software to evaluate performance and statistical significance.ResultseNetXplorer builds on top of glmnet to address the above issues for linear (Gaussian), binomial (logistic), and multinomial GLMs. It provides new functionalities to empower practical applications by using a cross validation framework that assesses the predictive performance and statistical significance of a family of elastic net models (as α is varied) and of the corresponding features that contribute to prediction. The user can select which quality metrics to use to quantify the concordance between predicted and observed values, with defaults provided for each GLM. Statistical significance for each model (as defined by α) is determined based on comparison to a set of null models generated by random permutations of the response; the same permutation-based approach is used to evaluate the significance of individual features. In the analysis of large and complex biological datasets, such as transcriptomic and proteomic data, eNetXplorer provides summary statistics, output tables, and visualizations to help assess which subset(s) of features have predictive value for a set of response measurements, and to what extent those subset(s) of features can be expanded or reduced via regularization.ConclusionsThis package presents a framework and software for exploratory data analysis and visualization. By making regularized GLMs more accessible and interpretable, eNetXplorer guides the process to generate hypotheses based on features significantly associated with biological phenotypes of interest, e.g. to identify biomarkers for therapeutic responsiveness. eNetXplorer is also generally applicable to any research area that may benefit from predictive modeling and feature identification using regularized GLMs.Availability and implementationThe package is available under GPL-3 license at the CRAN repository, https://CRAN.R-project.org/package=eNetXplorer
Parallel Evolution of Key Genomic Features and Cellular Bioenergetics Across the Marine Radiation of a Bacterial Phylum
Authors: Getz Eric W. , Tithi Saima Sultana , Zhang Liqing , Aylward Frank O. 
Published: April 2018

AbstractDiverse bacterial and archaeal lineages drive biogeochemical cycles in the global ocean, but the evolutionary processes that have shaped their genomic properties and physiological capabilities remain obscure. Here we track the genome evolution of the globally-abundant marine bacterial phylum Marinimicrobia across its diversification into modern marine environments and demonstrate that extant lineages have repeatedly switched between epipelagic and mesopelagic habitats. Moreover, we show that these habitat transitions have been accompanied by repeated and fundamental shifts in genomic organization, cellular bioenergetics, and metabolic modalities. Lineages present in epipelagic niches independently acquired genes necessary for phototrophy and environmental stress mitigation, and their genomes convergently evolved key features associated with genome streamlining. Conversely, lineages residing in mesopelagic waters independently acquired nitrate respiratory machinery and a variety of cytochromes, consistent with the use of alternative terminal electron acceptors in oxygen minimum zones (OMZs). Further, while surface water clades have retained an ancestral Na+-pumping respiratory complex, deep water lineages have largely replaced this complex with a canonical H+-pumping respiratory complex I, potentially due to the increased efficiency of the latter together with more energy-limiting environments deep in the ocean’s interior. These parallel evolutionary trends across disparate clades suggest that the evolution of key features of genomic organization and cellular bioenergetics in abundant marine lineages may in some ways be predictable and driven largely by environmental conditions and nutrient dynamics.
Genome-wide CRISPR-Cas9 screen in E. coli identifies design rules for efficient targeting
Authors: Gutierrez Belen , Ng Jérôme Wong , Cui Lun , Becavin Christophe , Bikard David 
Published: April 2018

AbstractThe main outcome of efficient CRISPR-Cas9 cleavage in the chromosome of bacteria is cell death. This can be conveniently used to eliminate specific genotypes from a mixed population of bacteria, which can be achieved both in vitro, e.g. to select mutants, or in vivo as an antimicrobial strategy. The efficiency with which Cas9 kills bacteria has been observed to be quite variable depending on the specific target sequence, but little is known about the sequence determinants and mechanisms involved. Here we performed a genome-wide screen of Cas9 cleavage in the chromosome of E. coli to determine the efficiency with which each guide RNA kills the cell. Surprisingly we observed a large-scale pattern where guides targeting some regions of the chromosome are more rapidly depleted than others. Unexpectedly, this pattern arises from the influence of degrading specific chromosomal regions on the copy number of the plasmid carrying the guide RNA library. After taking this effect into account, it is possible to train a neural network to predict Cas9 efficiency based on the target sequence. We show that our model learns different features than previous models trained on Eukaryotic CRISPR-Cas9 knockout libraries. Our results highlight the need for specific models to design efficient CRISPR-Cas9 tools in bacteria.
Genetic Determinants of Telomere Length in African American Youth
Authors: Zeiger Andrew M. , White Marquitta J. , Oh Sam S. , Witonsky Jonathan , Contreras Maria G. , Goddard Pagé C. , Lee Eunice Y. , Keys Kevin L. , Samedy Lesly-Anne , Liberto Jennifer R. , Mak Angel C.Y. , Magaña Joaquín , Risse-Adams Oona , Eng Celeste , Hu Donglei , Huntsman Scott , Salazar Sandra , Davis Adam , Meade Kelley , Brigino-Buenaventura Emerita , LeNoir Michael A. , Farber Harold J. , Bibbins-Domingo Kirsten , Borrell Luisa N. , Burchard Esteban G. 
Published: April 2018

ABSTRACTTelomere length (TL) is associated with numerous disease states and is affected by genetic and environmental factors. However, TL has been mostly studied in adult populations of European or Asian ancestry. These studies have identified 34 TL-associated genetic variants recently used as genetic proxies for TL. The generalizability of these associations to pediatric populations and racially diverse populations, specifically of African ancestry, remains unclear. Furthermore, six novel variants associated with TL in a population of European children have been identified but not validated. We measured TL from whole blood samples of 492 healthy African American youth (children and adolescents between 8 and 20 years old) and performed the first genome-wide association study of TL in this population. We were unable to replicate neither the 34 reported genetic associations found in adults nor the six genetic associations found in European children. However, we discovered a novel genome-wide significant association between TL and rs1483898 on chromosome 14. Our results underscore the importance of examining these genetic associations with TL in diverse pediatric populations such as African Americans.
Identifying Gene Expression Programs of Cell-type Identity and Cellular Activity with Single-Cell RNA-Seq
Authors: Kotliar Dylan , Veres Adrian , Nagy M. Aurel , Tabrizi Shervin , Hodis Eran , Melton Douglas A. , Sabeti Pardis C. 
Published: April 2018

AbstractIdentifying gene expression programs underlying both cell-type identity and cellular activities (e.g. life-cycle processes, responses to environmental cues) is crucial for understanding the organization of cells and tissues. Although single-cell RNA-Seq (scRNA-Seq) can quantify transcripts in individual cells, each cell’s expression profile may be a mixture of both types of programs, making them difficult to disentangle. Here we illustrate and enhance the use of matrix factorization as a solution to this problem. We show with simulations that a method that we call consensus non-negative matrix factorization (cNMF) accurately infers identity and activity programs, including the relative contribution of programs in each cell. Applied to published brain organoid and visual cortex scRNA-Seq datasets, cNMF refines the hierarchy of cell types and identifies both expected (e.g. cell cycle and hypoxia) and intriguing novel activity programs. We propose that one of the novel programs may reflect a neurosecretory phenotype and a second may underlie the formation of neuronal synapses. We make cNMF available to the community and illustrate how this approach can provide key insights into gene expression variation within and between cell types.
Inter-annual variation in seasonal dengue epidemics driven by multiple interacting factors in Guangzhou, China
Authors: Oidtman Rachel J. , Lai Shengjie , Huang Zhoujie , Yang Juan , Siraj Amir S. , Reiner Robert C. , Tatem Andrew J. , Alex Perkins T. , Yu Hongjie 
Published: April 2018

ABSTRACTVector-borne diseases display wide inter-annual variation in seasonal epidemic size due to their complex dependence on temporally variable environmental conditions and other factors. In 2014, Guangzhou, China experienced its worst dengue epidemic on record, with incidence exceeding the historical average by two orders of magnitude. To disentangle contributions from multiple factors to inter-annual variation in epidemic size, we fitted a semi-mechanistic model to time series data from 2005-2015 and performed a series of factorial simulation experiments in which seasonal epidemics were simulated under all combinations of year-specific patterns of four time-varying factors: imported cases, mosquito density, temperature, and residual variation in local conditions not explicitly represented in the model. Our results indicate that while epidemics in most years were limited by unfavorable conditions with respect to one or more factors, the epidemic in 2014 was made possible by the combination of favorable conditions for all factors considered in our analysis.