bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perception of disease burden and treatment satisfaction in patients with ulcerative colitis from outpatient clinics in Spain: UC-LIFE survey
Authors: Carpio Daniel , López-Sanromán Antonio , Calvet Xavier , Romero Cristina , Cea-Calvo Luis , Juliá Berta , Argüelles-Arias Federico 
Published: June 2016

Objectives
Ulcerative colitis (UC) conditions patients’ everyday life. With this survey, we aimed to assess the perceived disease burden, preferred treatment attributes, and treatment satisfaction reported by Spanish UC patients.

Methods
Consecutive unselected UC patients aged at least 18 years were recruited from outpatient hospital clinics. Patients completed the survey at home, returning it by postmail. With test-like questions, they described UC behavior, preferences, and satisfaction with treatment.

Results
Of 585 patients invited, 436 (75%) returned the survey (mean age 46 years, 53% men). Of these, 47.1% described their disease during the past year as ‘controlled or nearly controlled’, 28.0% as ‘symptoms not impairing everyday life,’ and 24.9% ‘disruptive symptoms’. Only 8.7% reported the complete absence of symptoms during the previous year, and 18.8, 30.7, and 47.4%, respectively, described at least one hospital admission, emergency room visit, or nonscheduled visit because of UC activity. Urgency of defecation was the most disruptive symptom. The most important therapy attribute was continuous control of symptoms (44.6%). Most patients (78.8%) were ‘very satisfied’ or ‘satisfied’ with current treatment, even those reporting a high burden of symptoms.

Conclusion
Half of the patients considered their UC as ‘controlled or nearly controlled’ and the degree of satisfaction with their therapies was high. However, they reported a high burden of symptoms and resource consumption during the previous year. These findings indicate that patients may get used to living with symptoms, underestimating the potential of therapy for achieving a complete remission. Urgency of defecation was mentioned as highly disrupting and should probably be included in scores and patient-reported outcomes.
Dos and don’ts for hospital cleaning
Authors: Dancer Stephanie J. 
Published: June 2016

Purpose of review
More evidence is emerging on the role of cleaning and decontamination for reducing hospital-acquired infection. Timely and adequate removal of environmental pathogens leads to measurable clinical benefits for patients. This article considers studies published from 2013 examining hospital decontamination technologies and evidence for cost-effectiveness.

Recent findings
Novel biocides and cleaning products, antimicrobial coatings, monitoring practices and automated equipment are widely accessible. They do not necessarily remove all environmental pathogens, however, and most have yet to be comprehensively assessed against patient outcome. Some studies are confounded by concurrent infection control and/or antimicrobial stewardship initiatives. Few contain data on costs.

Summary
As automated dirt removal is assumed to be superior to human effort, there is a danger that traditional cleaning methods are devalued or ignored. Fear of infection encourages use of powerful disinfectants for eliminating real or imagined pathogens in hospitals without appreciating toxicity or cost benefit. Furthermore, efficacy of these agents is compromised without prior removal of organic soil. Microbiocidal activity should be compared and contrasted against physical removal of soil in standardized and controlled studies to understand how best to manage contaminated healthcare environments.
First case report of pulmonary nocardiosis caused by Nocardia mexicana
Authors: kuchibiro Tomokazu , Ikeda Takeshi , Nakanishi Hirotaka , Morishita Yukiko , Houdai Katsuyuki , Ito Junko , Gonoi Tohru 
Published: June 2016

Introduction:

Nocardia species usually cause opportunistic infections, and the frequency of these infections is increasing owing to the growing population of immunocompromised hosts. However, Nocardia species may sometimes cause an infection disease in immunocompetent hosts. Nocardia mexicana infections are the least common and are very rare.

Case presentation:
Herein, we report the first case of a pulmonary infection with N. mexicana in a 61-year-old Japanese woman with a history of hyperlipidaemia and bronchiectasis and a 6-month history of non-productive hacking cough. A sample of bronchial lavage fluid obtained by bronchofiberscopy showed filamentous branching gram-positive rods and acid-fast filamentous branching rods, and a colony of suspected Nocardia was cultured. Based on 16S rRNA, gyrB,
rpoB, secA1 and hsp65 gene sequence analyses and biochemical and physiological properties, the strain was identified as N. mexicana. The strain was resistant to the antimicrobial agents amoxicillin-clavulanic acid, clarithromycin, minocycline, gentamycin, tobramycin, ciprofloxacin and trimethoprim-sulfamethoxazole. The patient was treated with biapenem followed by intravenous amikacin and oral linezolid.

Conclusion:
Despite its rarity, the species require attention owing to the existence of multidrug-resistant strains.
The impact of structural variation on human gene expression
Authors: Chiang Colby , Scott Alexandra J. , Davis Joe R. , Tsang Emily K. , Li Xin , Kim Yungil , Damani Farhan N. , Ganel Liron ,   GTEx Consortium, Montgomery Stephen B. , Battle Alexis , Conrad Donald F. , Hall Ira M. 
Published: June 2016

AbstractStructural variants (SVs) are an important source of human genetic diversity but their contribution to traits, disease, and gene regulation remains unclear. The Genotype-Tissue Expression (GTEx) project presents an unprecedented opportunity to address this question due to the availability of deep whole genome sequencing (WGS) and multi-tissue RNA-seq data from 147 individuals. We used comprehensive methods to identify 24,157 high confidence SVs, and mapped cis expression quantitative trait loci (eQTLs) in 13 tissues via joint analysis of SVs, single nucleotide (SNV) and short insertion/deletion (indel) variants. We identified 24,801 eQTLs affecting the expression of 10,101 distinct genes. Based on haplotype structure and heritability partitioning, we estimate that SVs are the causal variant at 3.3-7.0% of eQTLs, which is nearly an order of magnitude higher than prior estimates from low coverage WGS and represents a 26- to 54-fold enrichment relative to their scarcity in the genome. Expression-altering SVs also have significantly larger effect sizes than SNVs and indels. We identified 787 putatively causal SVs predicted to directly alter gene expression, most of which (88.3%) are noncoding variants that show significant enrichment at enhancers and other regulatory elements. By evaluating linkage disequilibrium between SVs, SNVs and indels, we nominate 49 SVs as plausible causal variants at published genome-wide association study (GWAS) loci. Remarkably, 29.9% of the common SV-eQTLs are not well tagged by flanking SNVs, and we observe a notable abundance (relative to SNVs and indels) of rare, high impact SVs associated with aberrant expression of nearby genes. These results suggest that comprehensive WGS-based SV analyses will increase the power of both common and rare variant association studies.
HIV-1gag-polmRNA localization regulates the site of virion assembly
Authors: Becker Jordan T. , Sherer Nathan M. 
Published: June 2016

ABSTRACTHIV-1 full-length, unspliced genomic RNAs (gRNAs) serve both as mRNAs encoding the Gag and Gag-Pol capsid proteins as well as the genetic material packaged by Gag into virions that assemble at the plasma membrane (PM). Whether localized Gag synthesis contributes to assembly at the PM is unknown. Here we show that artificially tethering gRNAs or surrogategag-pol mRNAs to non-PM membranes or the actin cytoskeleton can markedly affect Gag’s distribution in the cytoplasm, causing aberrant subcellular sites of assembly and severe reductions to virus particle output. Onlygag-polmRNAs competent for translation were capable of altering Gag’s distribution within the cell, and the activity mapped to twocis-acting RNA regulatory elements; the 5’ packaging signal (Psi) bound by Gag and, unexpectedly, the Rev response element (RRE) that regulates the nuclear export of gRNAs and other intron-retaining viral RNAs. Taken together, our results suggest a model wherein localized translation of gRNAs at the PM helps to compartmentalize Gag-gRNA interactions, thereby promoting efficient genome encapsidation.AUTHOR SUMMARYThe spatial distribution of messenger RNAs (mRNAs) within the cytoplasm can be a crucial determinant of gene expression. Here we provide evidence that a devastating viral pathogen, human immunodeficiency virus type 1 (HIV-1), exploits localized translation to favor the formation of infectious, transmissible virions at the surface of infected cells. Artificially tethering viral mRNAs encoding the Gag and Gag-Pol capsid proteins (gag-polmRNAs) to alternative regions of the cell such as cytoplasmic vesicles or the actin cytoskeletion markedly alters Gag subcellular distribution, perturbs sites of assembly, and reduces virus particle production. These and additional findings suggest a model for HIV-1 assembly wherein localized Gag/Gag-Pol translation coupled to confined interactions between Gag and viral genomes ensures infectious virion production at the right place and the right time. Perturbing HIV-1 mRNA subcellular localization could represent a novel antiviral strategy.
Effect of X-ray irradiation on ancient DNA in sub-fossil bones – Guidelines for safe X-ray imaging
Authors: Immel Alexander , Le Cabec Adeline , Bonazzi Marion , Herbig Alexander , Temming Heiko , Schuenemann Verena J. , Bos Kirsten I. , Langbein Frauke , Harvati Katerina , Bridault Anne , Pion Gilbert , Julien Marie-Anne , Krotova Oleksandra , Conard Nicholas J. , Muenzel Susanne C. , Drucker Dorothée G. , Viola Bence , Hublin Jean-Jacques , Tafforeau Paul , Tafforeau Paul 
Published: June 2016

AbstractSub-fossilised remains may still contain highly degraded ancient DNA (aDNA) useful for palaeogenetic investigations. Whether X-ray computed [micro-] tomography ([μ]CT) imaging of these fossils may further damage aDNA remains debated. Although the effect of X-ray on DNA in living organisms is well documented, its impact on aDNA molecules is unexplored.Here we investigate the effects of synchrotron X-ray irradiation on aDNA from Pleistocene bones. A clear correlation appears between decreasing aDNA quantities and accumulating X-ray dose-levels above 2000 Gray (Gy). We further find that strong X-ray irradiation reduces the amount of nucleotide misincorporations at the aDNA molecule ends. No representative effect can be detected for doses below 200 Gy. Dosimetry shows that conventional μCT usually does not reach the risky dose level, while classical synchrotron imaging can degrade aDNA significantly. Optimised synchrotron protocols and simple rules introduced here are sufficient to ensure that fossils can be scanned without impairing future aDNA studies.
DNA sequence properties that predict susceptibility to epiallelic switching
Authors: Catoni Marco , Griffiths Jayne , Becker Claude , Zabet Nicolae Radu , Bayon Carlos , Dapp Mélanie , Lieberman-Lazarovich Michal , Weigel Detlef , Paszkowski Jerzy 
Published: June 2016

AbstractTransgenerationally heritable epialleles are defined by the stable propagation of alternative transcriptional states through mitotic and meiotic cell cycles. Given that the propagation of DNA methylation at CpG sites, mediated in Arabidopsis by MET1, plays a central role in epigenetic inheritance, we examined genome-wide DNA methylation in partial and complete loss-of-functionmet1mutants. We interpreted the data in relation to transgenerational epiallelic stability and provide evidence that DNA sequence features such as density of CpGs and genomic repetitiveness can be used to predict susceptibility to epiallelic switching. The importance of these rules was confirmed by analyses of common epialleles in natural Arabidopsis accessions and verified in rice.
Diversity of Sericostomatidae (Trichoptera) Caddisflies in the Montseny Mountain Range
Authors: Macher Jan Niklas , Weiss Martina , Beermann Arne J. , Leese Florian 
Published: June 2016

AbstractBiodiversity is under threat by the ongoing global change and especially freshwater ecosystems are under threat by intensified land use, water abstraction and other anthropogenic stressors. In order to monitor the impacts that stressors have on freshwater biodiversity, it is important to know the current state of ecosystems and species living in them. This is often hampered by lacking knowledge on species and genetic diversity due to the fact that many taxa are complexes of several morphologically cryptic species. Lacking knowledge on species identity and ecology can lead to wrong biodiversity and stream quality assessments and molecular tools can greatly help resolving this problem. Here, we studied larvae of the caddisfly family Sericostomatidae in the Montseny mountains on the Iberian Peninsula. We expected to find cryptic species and that species would not occur in syntopy due to different ecological niches. We sampled 44 stream sites and sequenced 247 larval specimens for the barcoding region of the mitochondrial cytochrome c oxidase gene. A modeling approach was used to assess the bioclimatic preferences of the found species. Two molecular groups were identified. One could be assigned toSchizopelex furciferaand one toSericostomaspp. We did find both taxa in syntopy in >50% of sampling sites and could show that the taxa prefer similar bioclimatic conditions. A reexamination of larval specimens showed thatSericostomaandSchizopelexlarvae could not be unambiguously identified to the genus level. Overall, our results show the importance of including molecular tools into biodiversity assessments in order to correctly identify the species diversity of a region and to prevent wrong assessment results.
Initiation of Retina Regeneration By a Conserved Mechanism of Adult Neurogenesis
Authors: Rao Mahesh , Didiano Dominic , Patton James G. 
Published: June 2016

AbstractRetina damage or disease in humans often leads to reactive gliosis, preventing the formation of new cells and resulting in visual impairment or blindness. Current efforts to repair damaged retinas are inefficient and not capable of fully restoring vision. Conversely, the zebrafish retina is capable of spontaneous regeneration upon damage, using Müller glia (MG) derived progenitors. Understanding how zebrafish MG initiate regeneration may help develop new treatments that prompt mammalian retinas to regenerate. Here we show that inhibition of GABA signaling facilitates initiation of MG proliferation. GABA levels decrease following damage, and MG are positioned to detect the decrease. Using pharmacological and genetic approaches we demonstrate that GABAA receptor inhibition stimulates regeneration in undamaged retinas while activation inhibits regeneration in damaged retinas. GABA induced proliferation causes upregulation of regeneration associated genes. This is the first evidence that neurotransmitters control retina regeneration in zebrafish through an evolutionarily conserved mechanism of neurogenesis.
Predicting Targeted Cancer Therapeutics
Authors: Wise Aaron , Cobanoglu Murat Can 
Published: June 2016

AbstractMotivation:Cancer is a complex and evolving disease, making it difficult to discover effective treatments. Traditional drug discovery relies on high-throughput screening on reductionist models in order to enable the testing of 105or 106compounds. These assays lack the complexity of the human disease. Functional assays overcome this limitation by testing drugs on human tumors, however they can only test few drugs, and remain restricted to diagnostic use. An algorithm that identifies hits with fewer experiments could enable the use of functional assays forde novodrug discovery.Results:We developed a novel approach that we termed ‘algorithmic ideation’ (AI) to select experiments, and demonstrated that this approach discovers hits 104times more effectively than brute-force screening. The algorithm trains on known drug-target-disease associations assembled as a tensor, built from the (public) TCGA and STITCH databases and predicts novel associations. We evaluated our tensor completion approach using a temporal cutoff with data prior to 2012 used as training data, and data from 2012 to 2015 used as testing data. Our approach achieved 104-fold more efficient hit discovery than the traditional brute-force high-throughput screening. We further tested the method in a sparse, low data regime by removing up to 90% of the training data, and demonstrated the robustness of the approach. Finally we test predictive performance on drugs with no previously known interactions, and the algorithm demonstrates 103-fold improvement in this challenging problem. Thus algorithmic ideation can potentially enable targeted antineoplastic discovery on functional assays.Availability:Freely accessible athttps://bitbucket.org/aiinc/drugx.Contact:quejebo@gmail.com,mcancobanoglug@gmail.com
Oligogenic Adaptation, Soft Sweeps, and Parallel Melanic Evolution inDrosophila melanogaster
Authors: Bastide Héloïse , Lange Jeremy D. , Lack Justin B. , Amir Yassin , Pool John E. 
Published: June 2016

AbstractUnraveling the genetic architecture of adaptive phenotypic divergence is a fundamental quest in evolutionary biology. InDrosophila melanogaster,high-altitude melanism has evolved in separate mountain ranges in sub-Saharan Africa, potentially as an adaptation to UV intensity. We investigated the genetic basis of this melanism in three populations using a new bulk segregant analysis mapping method. Although hundreds of genes are known to affect cuticular pigmentation inD. melanogaster,we identified only 19 distinct QTLs from 9 mapping crosses, with several QTL peaks being shared among two or all populations. Surprisingly, we did not find wide signals of genetic differentiation (Fst) between lightly and darkly pigmented populations at these QTLs, in spite of the pronounced phenotypic difference in pigmentation. Instead, we found small numbers of highly differentiated SNPs at the probable causative genes. A simulation analysis showed that these patterns of polymorphism are consistent with selection on standing genetic variation (leading to “soft sweeps“). Our results thus support a role for oligogenic selection on standing genetic variation in driving parallel ecological adaptation.
Drosophilasensory cilia lacking MKS-proteins exhibit striking defects during development but only subtle defects in adults
Authors: Pratt Metta B. , Titlow Joshua S. , Davis Ilan , Barker Amy R. , Dawe Helen R. , Raff Jordan W. , Roque Helio 
Published: June 2016

AbstractCilia are conserved organelles that have important motility, sensory and signalling roles. The transition zone (TZ) at the base of the cilium is critical for cilia function, and defects in several TZ proteins are associated with human congenital ciliopathies such as Nephronophthisis (NPHP) and Meckel Gruber syndrome (MKS). In several species, MKS and NPHP proteins form separate complexes that cooperate with Cep290 to assemble the TZ, but flies lack an obvious NPHP complex. We show that MKS proteins in flies are spatially separated from Cep290 at the TZ, and that flies mutant for individualMKSgenes fail to recruit other MKS proteins to the TZ, while Cep290 appears to be recruited normally. Although there are abnormalities in microtubule and membrane organisation in developingMKSmutant cilia, these defects are less apparent in adults, where sensory cilia and sperm flagella function quite normally. Thus, surprisingly, MKS proteins are not essential for cilia or flagella function in flies.
The urban domino effect: a conceptualization of cities’ interconnectedness of risk
Authors: Wamsler Christine , Brink Ebba 
Published: June 2016

Purpose
Cities are both at risk and the cause of risk. The interconnectedness of urban features and systems increases the likelihood of complex disasters and a cascade or “domino” effect from related impacts. However, the lack of research means that our knowledge of urban risk is both scarce and fragmented. Against this background, the purpose of this paper is to examine the unique dynamics of risk in urban settings.

Design/methodology/approach
Based on literal reading, grounded theory and systems analysis, this conceptual paper presents a framework for understanding and addressing urban risk. It conceptualizes how interdependent, interconnected risk is shaped by urban characteristics and exemplifies its particularities with data and analysis of specific cases. From this, it identifies improvements both in the content and the indicators of the successor to the Hyogo Framework for Action (HFA2) that will be adopted in 2015.

Findings
While it is common to see disasters as “causes”, and the destruction of the built environment as “effects”, this paper highlights that the intricate links between cities and disasters cannot be described by a unidirectional cause-and-effect relationship. The city–disasters nexus is a bidirectional relationship, which constantly shapes, and is shaped by, other processes (such as climate change).

Practical implications
This paper argues that in-depth knowledge of the links between cities’ characteristic features, related systems and disasters is indispensable for addressing root causes and mainstreaming risk reduction into urban sector work. It enables city authorities and other urban actors to improve and adapt their work without negatively influencing the interconnectedness of urban risk.

Originality/value
This paper presents a framework for understanding and addressing urban risk and further demonstrates how the characteristics of the urban fabric (physical/spatial, environmental, social, economic and political/institutional) and related systems increase risk by: intensifying hazards or creating new ones, exacerbating vulnerabilities and negatively affecting existing response and recovery mechanisms.
Measuring disaster resilience in communities and households
Authors: Arbon Paul , Steenkamp Malinda , Cornell Victoria , Cusack Lynette , Gebbie Kristine 
Published: June 2016

Purpose
This paper aims to discuss the development of two toolkits that were designed to help communities and households measure their level of disaster resilience and provide practical tools to help them increase and maintain these levels.

Design/methodology/approach
The toolkits were developed across two studies, with the community toolkit development being undertaken first. A literature review was conducted to develop a definition and model of community disaster resilience; and a Scorecard was designed to assess levels of existing community disaster resilience. The definition and Scorecard were reviewed and refined with the help of two communities before a final version was trialled in four communities across Australia. The household toolkit project followed a similar approach, with trialling being undertaken in conjunction with two non-government organisations that carry out outreach work in the community.

Findings
The development and trial of the Scorecards was extremely valuable. The conclusion voiced by communities and reached by the study project teams was that the user-friendly Scorecard is a workable tool for people to assess their household and community disaster resilience and to come together to plan what might further strengthen resilience. Critical to the Scorecards’ success was an understanding of the purpose of the assessment tool and the meaning of resilience.

Originality/value
The toolkits take an all-hazards approach and help community members, individuals and local policymakers to set priorities, allocate funds and develop emergency and disaster management programmes that build local community resilience.