bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caenorhabditis elegans
RIG-I Homolog Mediates Antiviral RNA Interference Downstream of Dicer-Dependent Biogenesis of Viral Small Interfering RNAs
Authors: Coffman Stephanie R. , Lu Jinfeng , Guo Xunyang , Zhong Jing , Jiang Hongshan , Broitman-Maduro Gina , Li Wan-Xiang , Lu Rui , Maduro Morris , Ding Shou-wei 
Published: March 2017

ABSTRACT

Dicer enzymes process virus-specific double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs) to initiate specific antiviral defense by related RNA interference (RNAi) pathways in plants, insects, nematodes, and mammals. Antiviral RNAi in
Caenorhabditis elegans
requires Dicer-related helicase 1 (DRH-1), not found in plants and insects but highly homologous to mammalian retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), intracellular viral RNA sensors that trigger innate immunity against RNA virus infection. However, it remains unclear if DRH-1 acts analogously to initiate antiviral RNAi in
C. elegans
. Here, we performed a forward genetic screen to characterize antiviral RNAi in
C. elegans
. Using a mapping-by-sequencing strategy, we uncovered four loss-of-function alleles of
drh-1
, three of which caused mutations in the helicase and C-terminal domains conserved in RLRs. Deep sequencing of small RNAs revealed an abundant population of Dicer-dependent virus-derived small interfering RNAs (vsiRNAs) in
drh-1
single and double mutant animals after infection with Orsay virus, a positive-strand RNA virus. These findings provide further genetic evidence for the antiviral function of DRH-1 and illustrate that DRH-1 is not essential for the sensing and Dicer-mediated processing of the viral dsRNA replicative intermediates. Interestingly, vsiRNAs produced by
drh-1
mutants were mapped overwhelmingly to the terminal regions of the viral genomic RNAs, in contrast to random distribution of vsiRNA hot spots when DRH-1 is functional. As RIG-I translocates on long dsRNA and DRH-1 exists in a complex with Dicer, we propose that DRH-1 facilitates the biogenesis of vsiRNAs in nematodes by catalyzing translocation of the Dicer complex on the viral long dsRNA precursors.

IMPORTANCE
The helicase and C-terminal domains of mammalian RLRs sense intracellular viral RNAs to initiate the interferon-regulated innate immunity against RNA virus infection. Both of the domains from human RIG-I can substitute for the corresponding domains of DRH-1 to mediate antiviral RNAi in
C. elegans
, suggesting an analogous role for DRH-1 as an intracellular dsRNA sensor to initiate antiviral RNAi. Here, we developed a forward genetic screen for the identification of host factors required for antiviral RNAi in
C. elegans
. Characterization of four distinct
drh-1
mutants obtained from the screen revealed that DRH-1 did not function to initiate antiviral RNAi. We show that DRH-1 acted in a downstream step to enhance Dicer-dependent biogenesis of viral siRNAs in
C. elegans
. As mammals produce Dicer-dependent viral siRNAs to target RNA viruses, our findings suggest a possible role for mammalian RLRs and interferon signaling in the biogenesis of viral siRNAs.
Staphylococcal β-Toxin Modulates Human Aortic Endothelial Cell and Platelet Function through Sphingomyelinase and Biofilm Ligase Activities
Authors: Herrera Alfa , Kulhankova Katarina , Sonkar Vijay K. , Dayal Sanjana , Klingelhutz Aloysius J. , Salgado-Pabón Wilmara , Schlievert Patrick M. 
Published: March 2017

ABSTRACT

Staphylococcus aureus
causes many infections, such as skin and soft tissue, pneumonia, osteomyelitis, and infective endocarditis (IE). IE is an endovascular infection of native and prosthetic valves and the lining of the heart; it is characterized by the formation of cauliflower-like “vegetations” composed of fibrin, platelets, other host factors, bacteria, and bacterial products. β-Toxin is an
S. aureus
virulence factor that contributes to the microorganism’s ability to cause IE. This cytolysin has two enzymatic activities: sphingomyelinase (SMase) and biofilm ligase. Although both activities have functions in a rabbit model of IE, the mechanism(s) by which β-toxin directly affects human cells and is involved in the infectious process has not been elucidated. Here, we compared the
in vitro
effects of purified recombinant wild-type β-toxin, SMase-deficient β-toxin (H289N), and biofilm ligase-deficient β-toxin (H162A and/or D163A) on human aortic endothelial cells (HAECs) and platelets. β-Toxin was cytotoxic to HAECs and inhibited the production of interleukin 8 (IL-8) from these cells by both SMase and biofilm ligase activities. β-Toxin altered HAEC surface expression of CD40 and vascular cell adhesion molecule 1 (VCAM-1). HAECs treated with β-toxin displayed granular membrane morphology not seen in treatment with the SMase-deficient mutant. The altered morphology resulted in two possibly separable activities, cell rounding and redistribution of cell membranes into granules, which were not the result of endosome production from the Golgi apparatus or lysosomes. β-Toxin directly aggregated rabbit platelets via SMase activity.

IMPORTANCE
Each year there are up to 100,000 cases of infective endocarditis (IE) in the United States.
S. aureus
is the most common pathogen in patients with health care-associated IE and the leading cause of community-associated IE in the developed world. Multiple clonal group strains as defined by the Centers for Disease Control and Prevention, particularly USA200 and other clones encoding β-toxin, are highly associated with IE. Considering the strong association and established contribution of β-toxin in animal models of IE, determining how β-toxin directly affects human cell types, including endothelial cells and platelets, is important. In this study, we demonstrate that β-toxin functions to modulate endothelial cells and platelets by both toxin sphingomyelinase and biofilm ligase activities. Our data suggest that these activities modulate inflammation and increase infection severity.
Analysis of Anti-Influenza Virus Neuraminidase Antibodies in Children, Adults, and the Elderly by ELISA and Enzyme Inhibition: Evidence for Original Antigenic Sin
Authors: Rajendran Madhusudan , Nachbagauer Raffael , Ermler Megan E. , Bunduc Paul , Amanat Fatima , Izikson Ruvim , Cox Manon , Palese Peter , Eichelberger Maryna , Krammer Florian 
Published: March 2017

ABSTRACTAntibody responses to influenza virus hemagglutinin provide protection against infection and are well studied. Less is known about the human antibody responses to the second surface glycoprotein, neuraminidase. Here, we assessed human antibody reactivity to a panel of N1, N2, and influenza B virus neuraminidases in different age groups, including children, adults, and the elderly. Using enzyme-linked immunosorbent assays (ELISA), we determined the breadth, magnitude, and isotype distribution of neuraminidase antibody responses to historic, current, and avian strains, as well as to recent isolates to which these individuals have not been exposed. It appears that antibody levels against N1 neuraminidases were lower than those against N2 or B neuraminidases. The anti-neuraminidase antibody levels increased with age and were, in general, highest against strains that circulated during the childhood of the tested individuals, providing evidence for “original antigenic sin.” Titers measured by ELISA correlated well with titers measured by the neuraminidase inhibition assays. However, in the case of the 2009 pandemic H1N1 virus, we found evidence of interference from antibodies binding to the conserved stalk domain of the hemagglutinin. In conclusion, we found that antibodies against the neuraminidase differ in magnitude and breadth between subtypes and age groups in the human population. (This study has been registered at ClinicalTrials.gov under registration no. NCT00336453, NCT00539981, and NCT00395174.)IMPORTANCEAnti-neuraminidase antibodies can afford broad protection from influenza virus infection in animal models and humans. However, little is known about the breadth and magnitude of the anti-neuraminidase response in the human population. Here we assessed antibody levels of children, adults, and the elderly against a panel of N1, N2, and type B influenza virus neuraminidases. We demonstrated that antibody levels measured by ELISA correlate well with functional neuraminidase inhibition titers. This is an important finding since ELISA is a simpler method than functional assays and can be implemented in high-throughput settings to analyze large numbers of samples. Furthermore, we showed that low titers of broadly cross-reactive antibodies against neuraminidase are prevalent in humans. By the use of an appropriate vaccination strategy, these titers could potentially be boosted to levels that might provide broad protection from influenza virus infection.
Financing for universal health coverage in small island states: evidence from the Fiji Islands
Authors: Asante Augustine D , Irava Wayne , Limwattananon Supon , Hayen Andrew , Martins Joao , Guinness Lorna , Ataguba John E , Price Jennifer , Jan Stephen , Mills Anne , Wiseman Virginia 
Published: March 2017

BackgroundUniversal health coverage (UHC) is critical to global poverty alleviation and equity of health systems. Many low-income and middle-income countries, including small island states in the Pacific, have committed to UHC and reforming their health financing systems to better align with UHC goals. This study provides the first comprehensive evidence on equity of the health financing system in Fiji, a small Pacific island state. The health systems of such states are poorly covered in the international literature.MethodsThe study employs benefit and financing incidence analyses to evaluate the distribution of health financing benefits and burden across the public and private sectors. Primary data from a cross-sectional survey of 2000 households were used to assess healthcare benefits and secondary data from the 2008–2009 Fiji Household Income and Expenditure Survey to assess health financing contributions. These were analysed by socioeconomic groups to determine the relative benefit and financing incidence across these groups.FindingsThe distribution of healthcare benefits in Fiji slightly favours the poor—around 61% of public spending for nursing stations and 26% of spending for government hospital inpatient care were directed to services provided to the poorest 20% of the population. The financing system is significantly progressive with wealthier groups bearing a higher share of the health financing burden.ConclusionsThe healthcare system in Fiji achieves a degree of vertical equity in financing, with the poor receiving a higher share of benefits from government health spending and bearing a lower share of the financing burden than wealthier groups.
Scoping review of potential quality indicators for hip fracture patient care
Authors: Pitzul Kristen B , Munce Sarah E P , Perrier Laure , Beaupre Lauren , Morin Suzanne N , McGlasson Rhona , Jaglal Susan B 
Published: March 2017

ObjectiveThe purpose of this study is to identify existing or potential quality of care indicators (ie, current indicators as well as process and outcome measures) in the acute or postacute period, or across the continuum of care for older adults with hip fracture.DesignScoping review.SettingAll care settings.Search strategyEnglish peer-reviewed studies published from January 2000 to January 2016 were included. Literature search strategies were developed, and the search was peer-reviewed. Two reviewers independently piloted all forms, and all articles were screened in duplicate.ResultsThe search yielded 2729 unique articles, of which 302 articles were included (11.1%). When indicators (eg, in-hospital mortality, acute care length of stay) and potential indicators (eg, comorbidities developed in hospital, walking ability) were grouped by the outcome or process construct they were trying to measure, the most common constructs were measures of mortality (outcome), length of stay (process) and time-sensitive measures (process). There was heterogeneity in definitions within constructs between studies. There was also a paucity of indicators and potential indicators in the postacute period.ConclusionsTo improve quality of care for patients with hip fracture and create a more efficient healthcare system, mechanisms for the measurement of quality of care across the entire continuum, not just during the acute period, are required. Future research should focus on decreasing the heterogeneity in definitions of quality indicators and the development and implementation of quality indicators for the postacute period.
A multifaceted approach to improving the quality of ENT Emergency Clinic referrals
Authors: Swords Chloe , Leach Laura , Kasbekar Anand , Jani Piyush 
Published: March 2017

It is imperative that primary care referrals are directed to the appropriate secondary care service. Patients presenting to a primary care physician with ENT conditions may require review in an Emergency Clinic. The latter clinics provide patients with rapid access to secondary care, for urgent, yet non-life-threatening conditions. In our department, we noticed that patients with conditions inappropriate to the capabilities of the Clinic were being booked in or reviewed too late; thus causing wasted journeys for the patient. We conducted a Quality Improvement Project to improve the efficiency of the referral process. A prospective evaluation of referrals was collected continuously over a two-month period. Overall, 5 domains were deemed crucial to enable timely and accurate booking of patients to clinic: booking date, urgency, legibility, patient identification and appropriateness. Our proposed standard set for this project was 100% compliance over the 5 domains. Three separate interventions were instigated following the first cycle. The main components of the intervention were the phased development of an electronic referral system and an educational initiative for junior doctors.20 referral forms were analysed during the initial 3-week period. No referrals met the recommended overall compliance standard of 100% (mean number of domains achieved: 3.38; standard deviation (SD): 0.637). Legibility and patient information were included in 21% and 30% of referrals, respectively. There was a trend of improvement following initiation of interventions. The mean number of domains achieved was 4.27 (SD 0.647; n=13) in the second data collection period, 4.53 (SD 0.514; n=16) in the third, and 4.75 (SD 0.452; n=24) in the fourth. Using linear regression, this change demonstrates a statistically significant improvement (p<0.001).An e-Proforma referral system represents a safe and efficient communication technology. When implementing policy change, it is crucial to acquire managerial and consultant support.
Patient-reported outcomes from a phase III study of baricitinib in patients with conventional synthetic DMARD-refractory rheumatoid arthritis
Authors: Emery Paul , Blanco Ricardo , Maldonado Cocco Jose , Chen Ying-Chou , Gaich Carol L , DeLozier Amy M , de Bono Stephanie , Liu Jiajun , Rooney Terence , Chang Cecile Hsiao-Chun , Dougados Maxime 
Published: March 2017

ObjectivesTo evaluate the effect of baricitinib on patient-reported outcomes (PROs) in patients with active rheumatoid arthritis (RA) and an inadequate response or intolerance to conventional synthetic disease-modifying antirheumatic drugs.MethodsIn this phase III study, patients were randomised 1:1:1 to placebo (N=228), baricitinib 2 mg once daily (QD, N=229) or baricitinib 4 mg QD (N=227). PROs included the Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient's Global Assessment of Disease Activity (PtGA), patient's assessment of pain, measures from patient electronic daily diaries (duration and severity of morning joint stiffness (MJS), Worst Tiredness, Worst Joint Pain), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), SF-36, EuroQol 5-D index scores and visual analogue scales (VAS) and the Work Productivity and Activity Impairment Questionnaire-RA. The primary time point for the study was week 12. Treatment comparisons were assessed with logistic regression for categorical measures and analysis of covariance for continuous variables.ResultsStatistically significant improvements were observed for both baricitinib groups versus placebo in HAQ-DI, PtGA, pain, daily diary measures, EuroQoL index scores and SF-36 physical component score at week 12 and for those measures when assessed at week 24. Baricitinib 2 mg and baricitinib 4 mg were statistically significantly improved versus placebo for the EuroQoL VAS and FACIT-F, respectively, at week 24.ConclusionsBaricitinib 2 or 4 mg provided significant improvement versus placebo in PROs across different domains of RA, including physical function, MJS, fatigue, pain and quality of life.Trial registration numberNCT01721057; Results.
Prediction on structural, mechanical and thermal properties of Al4SiC4, Al4C3 and 4H-SiC under high pressure by first-principles calculation
Authors: Sun Liang , Gao Yimin , Yoshida Katsumi , Yano Toyohiko , Wang Wen 
Published: March 2017

A theoretical study is conducted by first-principles theory to study the structural, electronic, elastic and thermal properties of Al4SiC4, Al4C3 and 4H-SiC phases under pressure. The calculated results indicated that the volumetric shrinkage of Al4SiC4 declines to 16% compared with 4H-SiC for 12% and its length of lattice parameter along c-axis decreases faster than that of along other axes in cell structures. The mechanical properties of Al4SiC4 like elastic constants and elastic moduli increase continuously under pressure. The thermal expansion coefficient of three compounds under pressure are studied first. When temperature is lower than 500 K, the coefficient increases rapidly first then gradually tends to a linear accession at higher temperature and the propensity of increment becomes moderate. The [Formula: see text] data decreases slightly with pressure but increases dramatically with temperature for all compounds.
Measures Matter: The Local Exposure/Isolation (LEx/Is) Metrics and Relationships between Local-Level Segregation and Breast Cancer Survival
Authors: Bemanian Amin , Beyer Kirsten M.M. 
Published: March 2017

Abstract
Background: The Black-to-White disparity in breast cancer survival is increasing, and racial residential segregation is a potential driver for this trend. However, study findings have been mixed, and no study has comprehensively compared the effectiveness of different local-level segregation metrics in explaining cancer survival.
Methods: We proposed a set of new local segregation metrics named local exposure and isolation (LEx/Is) and compared our new local isolation metric with two related metrics, the location quotient (LQ) and the index of concentration at extremes (ICE), across the 102 largest U.S. metropolitan areas. Then, using case data from the Milwaukee, WI, metropolitan area, we used proportional hazards models to explore associations between segregation and breast cancer survival.
Results: Across the 102 metropolitan areas, the new local isolation metric was less skewed than the LQ or ICE. Across all races, Hispanic isolation was associated with poorer all-cause survival, and Hispanic LQ and Hispanic-White ICE were found to be associated with poorer survival for both breast cancer–specific and all-cause mortality. For Black patients, Black LQ was associated with lower all-cause mortality and Black local isolation was associated with reduced all-cause and breast cancer–specific mortality. ICE was found to suffer from high multicollinearity.
Conclusions: Local segregation is associated with breast cancer survival, but associations varied based on patient race and metric employed.
Impact: We highlight how selection of a segregation measure can alter study findings. These relationships need to be validated in other geographic areas. Cancer Epidemiol Biomarkers Prev; 26(4); 516–24. ©2017 AACR.
See all the articles in this CEBP Focus section, “Geospatial Approaches to Cancer Control and Population Sciences.”
The planktonic copepods of the Marchile I expedition and of the "Eltanin" cruises 3-6 taken in the SE Pacific
Authors: Bjornberg Tagea K. S. 
Published: March 2017

Foram obtidos 261 espécies de copépodos planctônicos de coletas oblíquas quantitativas da camada superior de 140m de espessura nas 98 estações visitadas pela expedição Marchile I assim como de 77 amostras do USARP (horizontais e verticais) obtidas ao largo da América do Sul Ocidental. As distribuições horizontal e vertical destas espécies foram determinadas de 22º34'N até 64º54' lat. S no Pacífico SE.
Electron microscope studies of insect muscle. III. Variations in ultra structure
Authors: Edwards George A. , Santos Persio De Souza , Santos Helena De Souza , Sawaya Paulo 
Published: March 2017

Com a finalidade de aumentar resultados anteriores e de apresentar novo material para comparar os diversos músculos de vários insetos foi feito um estudo por meio de microscópio eletrônico. Usamos 8 músculos diferentes de cada um dos 14 insetos, representativos de 8 ordens.As fibras dos músculos foram preparadas por meio de maceração em glicerina ou fixação em formol a 5%, seguida de trituração num microblendor, secagem na telinha e assombreadas com cromo a um ângulo de 12 graus. Acreditamos que um dos resultados mais importantes neste trabalho é a demonstração das variações que podem ocorrer nos músculos especializados dum dado animal. Assim, a porta acha-se aberta para outras pesquisas sôbre os vários músculos especializados de vários animais no reino animal. Parece que não existe "o músculo estriado", mas que a estrutura do músculo varia com a sua função e com a posição filogenética do animal.
Sobre o genero Siphonops Wagler (1828) - Amphibia-Apoda-, com descripção de duas variedades novas: S. annulatus (Mikan) var. marmoratus e S. paulensis Boettg. var. maculatus
Authors: Sawaya Paulo 
Published: March 2017

Revisão do genero Siphonops com descrição de S. annulatus var. marmoratus e S. paulensis var. maculatus. Nova tabella para classificação. Resumo zoogeographico e notas sobre a histologia do tegumento e sobre a biologia do genero.
Ocorrência de Ephydatia crateriformis (Potts) na América do Sul
Authors: Carvalho João De Paiva 
Published: March 2017

Trata o presente trabalho de um espongiário encontrado no rio Ribeira de Iguape, tanto na lagôa denominada de "Pastinho" como de outra, sem nome certo, situada a montante, próximo à embocadura do rio Jacupiranga. Na localidade mais exposta à corrente e rica em substâncias alimentícias (Mapa I-b) houve colónias massiças, assaz volumosas; nas águas menos ricas em matéria orgânica (Mapa I-a) e, ao mesmo tempo, mais calmas, as colónias cresceram, em geral, digitiformemente. Ambas as regiões sofrem diariamente a influência das marés, que se faz sentir até pouco acima da barra do citado rio. A espécie deve, pois, ser considerada como de água doce e salôbra. Doas achados mensalmente realizados de janeiro (1941) a outubro, as gêmulas apareceram somente no período de junho a agosto. E. crateriformis não foi até agora verificada na América do sul, sendo as duas localidades mais próximas, a península de Yucatan e a zona fronteiriça entre o México e a Calofórnia. Confrontando as espículas das gêmulas do material atual com as da forma típica de Ephydatia crateriformis (Potts), verifiquei entroncamento ou robutez não presente na forma típica. A conselho do Prof. Dr. Walter Arndt (Berlin), considerei o dito carater como sinal distintivo duma nova forma, E. crateriformis forma arndti, denominada em homenagem àquele pesquizador.