bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstructing memories, deconstructing the self
Authors: Chadha Monima
Published: July 2018

The paper evaluates a well‐known argument for a self from episodic memories—that remembering that I did something or thought something involves experiencing the identity of my present self with the past doer or thinker. Shaun Nichols argues that although it phenomenologically appears to be the case that we are identical with the past self, no metaphysical conclusion can be drawn from the phenomenology. I draw on literature from contemporary psychology and Buddhist resources to arrive at a more radical conclusion: that there is no phenomenological sense of identity with a past self; the sense of self in episodic memory depends on narrative construction of the self.
RaxM regulates the AvrXa21 (RaxX)‐mediated immune response
Authors: Xu Chunli , Wang Yaxin , Liu Shiyao , Xie Qingbiao , He Na , Shi Chenyi , Niu Xiaolei , He Chaozu , Li Chunxia , Tao Jun
Published: July 2018

Xanthomonas oryzae pv. oryzae (Xoo) is the causal agent of rice bacterial blight disease, which causes a reduction in rice production. The interaction between Xoo and rice is a model for the study of the gene‐for‐gene hypothesis, in which a resistance (R) gene encoding a product interacts with an effector molecule encoded by a corresponding bacterial avirulence (avr) gene. Rice XA21 functions as a plant innate immune receptor (R protein) and recognizes the avirulence protein (RaxX) of Xoo to induce the immune response and cope with pathogen attack. The sulphuration of RaxX by the tyrosine sulphotransferase RaxST is essential to its activity. The expression of raxST is regulated by the RaxH/RaxR and phoP/phoQ two‐component systems. However, the regulation of raxX expression remains unclear. Here, we showed that a gene (raxM) encodes a small protein, which functions as a regulator of raxX expression. raxX and raxM are located upstream of raxST. Transcriptional analysis indicates that raxX and raxM are separately transcribed and the promoter of raxX is located at the raxM coding region. The RaxM protein regulates its own and raxX expression, and is required for the XA21‐mediated immunity response. Therefore, we identified a regulator of raxX expression and of the Xoo–rice interaction. Our findings suggest that RaxX is not only regulated at the post‐translational level, but also at the transcriptional level.
The Meloidogyne graminicola effector Mg16820 is secreted in the apoplast and cytoplasm to suppress plant host defense responses
Authors: Naalden Diana , Haegeman Annelies , de Almeida‐Engler Janice , Birhane Eshetu Firehiwot , Bauters Lander , Gheysen Godelieve
Published: July 2018

On invasion of roots, plant‐parasitic nematodes secrete effectors to manipulate the cellular regulation of the host to promote parasitism. The root‐knot nematode Meloidogyne graminicola is one of the most damaging nematodes of rice. Here, we identified a novel effector of this nematode, named Mg16820, expressed in the nematode subventral glands. We localized the Mg16820 effector in the apoplast during the migration phase of the second‐stage juvenile in rice roots. In addition, during early development of the feeding site, Mg16820 was localized in giant cells, where it accumulated in the cytoplasm and the nucleus. Using transient expression in Nicotiana benthamiana leaves, we demonstrated that Mg16820 directed to the apoplast was able to suppress flg22‐induced reactive oxygen species production. In addition, expression of Mg16820 in the cytoplasm resulted in the suppression of the R2/Avr2‐ and Mi‐1.2‐induced hypersensitive response. A potential target protein of Mg16820 identified with the yeast two‐hybrid system was the dehydration stress‐inducible protein 1 (DIP1). Bimolecular fluorescence complementation resulted in a strong signal in the nucleus. DIP1 has been described as an abscisic acid (ABA)‐responsive gene and ABA is involved in the biotic and abiotic stress response. Our results demonstrate that Mg16820 is able to act in two cellular compartments as an immune suppressor and targets a protein involved in the stress response, therefore indicating an important role for this effector in parasitism.
Viroid‐derived small RNA induces early flowering in tomato plants by RNA silencing
Authors: Adkar‐Purushothama Charith Raj , Sano Teruo , Perreault Jean‐Pierre
Published: July 2018

Viroid infection often leads to early flowering in the host plant. This report describes the targeting of the FRIGIDA‐like protein 3 (FRL3) mRNA in tomato plants by a small RNA derived from the conserved left terminal region of the potato spindle tuber viroid (PSTVd). This targeting leads to the silencing of the FRL3 mRNA. Viroid infection assays using a severe variant of PSTVd induced early flowering in tomato plants by the down‐regulation of greater amounts of the target than did a mild PSTVd variant. The targeting of the FRL3 mRNA by RNA silencing was validated by both an artificial microRNA experiment transiently expressing viroid‐derived small RNAs in tomato plants, and by 5′ RNA ligase‐mediated rapid amplification of cDNA ends (RACE). These data unambiguously demonstrated the role of small RNAs in the early flowering seen in viroid‐infected plants.
Molecular properties of gp100‐reactive T‐cell receptors drive the cytokine profile and antitumor efficacy of transgenic host T cells
Authors: Eby Jonathan M. , Smith Angela R. , Riley Timothy P. , Cosgrove Cormac , Ankney Christian M. , Henning Steven W. , Paulos Chrystal M. , Garrett‐Mayer Elizabeth , Luiten Rosalie M. , Nishimura Michael I. , Baker Brian M. , Le Poole I. Caroline
Published: July 2018

To study the contribution of T‐cell receptors (TCR) to resulting T‐cell responses, we studied three different human αβ TCRs, reactive to the same gp100‐derived peptide presented in the context of HLA‐A*0201. When expressed in primary CD8 T cells, all receptors elicited classic antigen‐induced IFN‐γ responses, which correlated with TCR affinity for peptide–MHC in the order T4H2 > R6C12 > SILv44. However, SILv44 elicited superior IL‐17A release. Importantly, in vivo, SILv44‐transgenic T cells mediated superior antitumor responses to 888‐A2 + human melanoma tumor cells upon adoptive transfer into tumor‐challenged mice while maintaining IL‐17 expression. Modeling of the TCR ternary complexes suggested architectural differences between SILv44 and the other complexes, providing a potential structural basis for the observed differences. Overall, the data reveal a more prominent role for the T‐cell receptor in defining host T‐cell physiology than traditionally assumed, while parameters beyond IFN‐γ secretion and TCR affinity ultimately determine the reactivity of tumor‐reactive T cells.
Older adults’ dependence in activities of daily living: Implications for oral health
Authors: Saintrain Maria Vieira de Lima , Saintrain Suzanne Vieira , Sampaio Edgar Gomes Marques , Ferreira Bruno Souza P. , Nepomuceno Taffarel Canuto , Frota Mirna Albuquerque , Vieira‐Meyer Anya PGF
Published: July 2018

Objective

To assess the relationship between ADL and oral health status in older adults.

Design and Sample

Quantitative, analytical, cross‐sectional research with 280 people aged ≥60 in public primary health care centers in the city of Fortaleza, Northeastern Brazil.

Measures

Collection of sociodemographic data, oral discomfort data, and general health data and application of the Community Oral Health Indicator—COHI and the activities of daily living scale.

Results

Significant differences in functional dependence were found between age groups (p < .001), incomes (p = .034), and levels of education (p = .003). Tooth loss (OR = 2.13; p = 0.025), having no teeth (OR = 2.97), difficulties in chewing and swallowing food (OR = 2.56; p = 0.003), problems with taste of food (OR = 2.06; p = .044), poor self‐rated general health (OR = 3.7; p = .001), hearing problems (OR = 2.23; p = .009) and speech problems (OR = 3.15; p = .002) increased chances for functional dependence. Dependent individuals were less likely to use toothpaste, thereby increasing the potential for caries (p = .013). Age 80 or older (p < .001), ages 70–79 (p < .001), three or more visible dental cavities (p = .030) and difficulty chewing and swallowing food (p = .027) remained associated with dependence in ADL in the logistic regression model.

Conclusion

Functional dependence in activities of daily living has implications for the oral health status of older people.
Alpha‐band functional connectivity during cued versus implicit modality‐specific anticipatory attention: EEG‐source coherence analysis
Authors: Talalay I. V. , Kurgansky A. V. , Machinskaya R. I.
Published: July 2018

The anticipation of future events based on a background experience is one of the main components of any goal‐directed behavior. Anticipatory attention can be either voluntary (explicit) or involuntary (implicit). We presumed that these two types of anticipatory attention differed in terms of cortical functional organization. We examined this assumption with an experimental model consisting of three experimental sessions (cued attention, implicit learning, and baseline) that were equal in terms of stimuli, motor responses, and cognitive task. Participants were asked to discriminate the temporal order of stimuli within a pair presented in either the visual or auditory sensory modality. Prestimulus functional connectivity was assessed via alpha‐band coherence computed in the source space for preselected regions of interests. Functional links between the cortices of the frontoparietal control system increased during the cued attention condition and did not increase during the implicit anticipation condition. The buildup of implicit anticipation was accompanied by the strengthening of functional links between the intraparietal, ventral premotor, and presupplementary motor areas. It was discovered that both cued and implicit types of anticipation were underlain by functional modality‐specific cortical links.
Pulmonary infarction: A disease of the (mostly) young
Authors: Tapson Victor F.
Published: July 2018

See related Article
Validity and reliability of the Danish version of the Ice Expressive Family Functioning and Ice Family Perceived Support questionnaires
Authors: Konradsen Hanne , Dieperink Karin Brochstedt , Lauridsen Jørgen , Sorknaes Anne Dichmann , Ostergaard Birte
Published: July 2018

Aim

International research has only rarely examined the functioning of families experiencing chronic illness and the perception of nurses towards involving families in patient care. This has also been the case in Denmark. To undertake this kind of research, carefully translated questionnaires are needed. The purpose of this study was therefore to translate the Ice Expressive Family Functioning (ICE‐EFFQ) and the Ice Family Perceived Support (ICE‐FPSQ) into Danish, and to test the validity and reliability of the Danish versions.

Methods

The study had a cross‐sectional design. The questionnaires were translated into Danish using forward–backward translation. Then, they were tested empirically among adult patients with chronic diseases and their family members in three different settings. A total of 81 patients were included in the testing of ICE‐EFFQ and 70 patients were included in the testing of ICE‐FPSQ. Internal consistency reliability was assessed followed by confirmatory factor analysis.

Results

Both questionnaires showed acceptable construct validity, reliability (Cronbach's alpha 0.93 and 0.94), internal consistency were confirmed, and there was good reproducibility (Cronbach's alpha 0.76 and 0.77). Furthermore, confirmatory factor analysis showed acceptable to good fit for both questionnaires.

Conclusions

The ICE‐EFFQ and the ICE‐FPSQ were both found to be valid and reliable instruments to measure family functioning and perceived support among families experiencing chronic illness in a Danish context.
Extended HLA‐G haplotypes in patients with age‐related macular degeneration
Authors: Svendsen S. G. , Nilsson L. L. , Djurisic S. , Funck T. , Wu C.‐L. , Faber C. , Falk M. K. , Singh A. , Sørensen T. L. , Carosella E. D. , LeMaoult J. , Hviid T. V. F. , Nissen M. H.
Published: July 2018

This study aims to determine if genetic polymorphisms in the HLA‐G gene are associated with age‐related macular degeneration (AMD). HLA‐G is important for immunological tolerance, and it is also known to have angiogenic effects. Polymorphisms in the 5′‐upstream regulatory region and 3′‐untranslated region (UTR) of HLA‐G have been associated with a number of diseases, especially with respect to a 14 bp insertion/deletion (ins/del) polymorphism in the 3′UTR. Full gene sequencing was performed on a cohort of 146 AMD patients and 63 healthy controls aged ≥60 and HLA‐G haplotypes were determined. Analyses were performed on a publicly available gene expression dataset from the NCBI GEO database (accession number GSE29801) from which expression data for HLA‐G, ‐C, and ‐A were extracted. Analysis of the GEO dataset showed that both HLA‐G and ‐C were expressed in the back of the eye and that expression was upregulated in the macular area of AMD. No differences were observed between patients and controls when analyzing the distribution of haplotypes in the HLA‐G promoter, coding region, 3′UTR, or the 14 bp ins/del polymorphism of the 3′UTR. The increased expression of HLA‐G in the macula of AMD patients indicates a role of HLA‐G in the micro environment as part of the AMD pathogenesis. This is supported by the expression of HLA‐C, which has previously been shown to play a role in AMD. The HLA‐G haplotype distribution did not display any differences between AMD patients and controls.
Investigation of the utility of lymph node fine‐needle aspiration cytology for the staging of malignant solid tumors in dogs
Authors: Fournier Quentin , Cazzini Paola , Bavcar Spela , Pecceu Evi , Ballber Clara , Elders Richard
Published: July 2018

Background

Fine‐needle aspiration cytology (FNAC) of lymph nodes (LNs) is routinely used for staging canine malignant solid tumors, but studies evaluating its efficacy are limited.

Objectives

The primary objectives of this study were to evaluate the sensitivity/specificity of FNAC and the significance of nondiagnostic FNAC when staging canine malignant tumors. A secondary objective was to determine the prevalence of multiple nodal metastases.

Methods

Lymph nodes draining malignant solid tumors assessed with FNAC and histopathology were included. The sensitivity/specificity of FNAC was determined for LNs with diagnostic FNAC, using histopathology as the gold standard. The proportion of nondiagnostic FNAC and associated histopathologic prevalence of metastasis were determined. Among the tumors with multiple LNs assessed, the prevalence of multiple nodal metastases was determined.

Results

The sensitivity of FNAC (194 LNs) was 67% for sarcomas, 100% for carcinomas, 63% for melanomas, 75% for mast cell tumors, and 100% for other round cell tumors. The specificity varied between 83% and 96%. Nondiagnostic FNAC was reported in 25% of LNs sampled (65/259), most of which were nonenlarged and/or difficult to access, and 20% of which were metastatic on histopathology. When several LNs were assessed (88/189 tumors), the prevalence of multiple nodal metastases was 24%.

Conclusions

Histopathologic LN evaluation cannot be robustly substituted with FNAC when staging selected canine solid tumors. When a diagnostic FNAC is elusive, the histopathologic assessment remains ideal. Finally, staging should not always be limited to the assessment of a single LN.
Tectonic vicariance versus Messinian dispersal in western Mediterranean ground beetles
Authors: Faille Arnaud , Casale Achille , Hernando Carles , Aït Mouloud Salah , Ribera Ignacio
Published: July 2018

The complex geological history of the western Mediterranean region conceals the interpretation of the evolutionary history of its current fauna, as similar distribution patterns may have very different temporal and geographic origins. Particularly intriguing are some subterranean species in islands, which origin is usually difficult to interpret as their strongly modified morphologies obscure their relationships. We studied subterranean taxa and their likely relatives of two groups of ground beetles in the western Mediterranean: theDuvaliuslineage (“isotopic” Trechini) and Molopina (Pterostichini). We included specimens from the islands of Mallorca, Sardinia and Sicily, plus mainland Europe and North Africa. Phylogenetic relationships were reconstructed with a combination of mitochondrial and nuclear data, and divergence dates were estimated with Bayesian methods using the same a priori molecular evolutionary rates for the same gene fragments in the two groups. In theDuvaliuslineage, the subgenusTrechopsis, including all the highly modified cave or nivicolous species, was found to be polyphyletic: the species from Mallorca was found to be of Pleistocene origin and sister to the less modified species of subgenusDuvaliusfrom the same island, whereas the Algerian species ofTrechopsiswere, on the contrary, related to the SicilianDuvalius, indicating a northern colonisation route during the late Pliocene. Molopina was divided into three main lineages: the generaAbax,Percus, and theMolopsgroups of genera. The basal diversification of the latter was dated within a temporal window (35–25 Ma) fully congruent with the tectonic opening of the western Mediterranean basin and included six main lineages with uncertain relationships among them: the epigean genera (a)Molopsand (b)Tanythrix; and the subterranean (c)Typhlochoromus(Eastern Alps), (d)Speomolops(Sardinia), (e)Henrotius(Mallorca) and (f) a strongly supported clade including the Pyrenean generaZariquieya,OscadytesandMolopidius. Despite the similar distribution of some of their subterranean taxa, the two studied groups show a strongly contrasting origin and mode of diversification. While theDuvaliuslineage had a recent origin, with complex colonisation patterns and widespread morphological convergence among the subterranean species, the subterranean Molopina had an ancient vicariant origin resulting from the tectonic opening of the western Mediterranean basin.
Del Cafetero, de Maruja Hinestrosa, al Hombre macho, de Adán Guevara: género y transnacionalidad entre Colombia y Costa Rica
Authors: Mesa Martínez Luis Gabriel
Published: July 2018

La música latinoamericana recoge un amplio espectro de tradiciones compartidas que desafían la noción convencional de fronteras nacionales y abren discusiones sobre factores de identidad personal, regional, nacional y continental. Este artículo toma como ejemplo un pasillo colombiano compuesto por una mujer de origen nariñense, el cual fue reinterpretado por un cantautor costarricense y territorializado como una pieza representativa del folclor de Guanacaste. La obra original se conoce en Colombia como el Cafetero, de la pianista pastusa Maruja Hinestrosa Eraso. La versión costarricense tiene el título de El hombre macho, y por muchos años ha sido atribuida al guanacasteco Adán Guevara Centeno. El objetivo del articulo apunta a profundizar y analizar los alcances de estas correspondencias, señalando ejes de relación que conecten las historias de la música en ambos países y cuestionando las posturas regionalistas en torno a estas composiciones. La metodología integra el análisis de fuentes escritas y sonoras, en articulación con un trabajo de campo que inició en Pasto (Colombia) y se complementó con una estancia de investigación en San José y Guanacaste (Costa Rica). Los resultados dan cuenta de los estrechos vínculos que se presentan en distintas músicas latinoamericanas, proponiendo una discusión fundamentada en dos conceptos relevantes para las obras musicales en cuestión: género y transnacionalidad.
Inmersión y estereoscopia por la Barranquilla de comienzos del siglo xx
Authors: Piedrahita Angélica
Published: July 2018

Los tours estereoscópicos fueron dispositivos precinematográficos que desde la inmersión y la fotografía diseñaron la posibilidad de viajar a distancia a partir de simulaciones ópticas. Antecediendo a los actuales recorridos virtuales, estos tours intentaron categorizar el mundo desde una mirada marcadamente colonial simplificando y generalizando la visita a otros países. El artículo presenta una reflexión a la mirada y el acto de observar tomando como objeto de análisis un tour estereoscópico realizado por la compañía norteamericana Underwood & Underwood en Barranquilla a comienzos del siglo XX. En primer lugar, el trabajo busca desplegar las especificidades de la experiencia del ojo en estos espacios estereoscópicos y la manera en la que desde el movimiento ocular se produce la sensación de profundidad, con el fin de señalar el aporte de este dispositivo a las experiencias visuales. En segundo lugar, se narra la experiencia de explorar los espacios fotografiados e interactuar con los actuales habitantes a quienes se les presentan las imágenes de archivo. Al presentar el dispositivo a los barranquilleros de la zona, se propician memorias sobre el desarrollo urbano de la ciudad y la preocupación sobre su patrimonio. Además, se detectan anhelos de desarrollo económico a partir del turismo, visibilizando la correspondencia del producto con prácticas contemporáneas de memoria visual desde la explotación turística. A lo largo del artículo, se revisa el concepto de inmersión vinculado a la técnica y el turismo, en busca de conceptos que contesten a corrientes mercantiles y tecnócratas del resurgimiento de la estereoscopia en la realidad virtual y aumentada
La evaluación holística de la investigación en las artes en España: la necesidad y complejidad de confluir las dinámicas de los campos académico y artístico.
Authors: Rubio Arostegui Juan Arturo , Caerols Mateo Raquel
Published: July 2018

La naturaleza epistemológica y del arte y sus modos de hacer determinan las formas de evaluar la calidad de la investigación en esta disciplina. La coexistencia de diferentes modos de definir la investigación en las artes y sus enfoques complejiza las formas institucionales de evaluar la investigación, pues se constatan nuevas formas de investigar como consecuencia del giro performativo en las ciencias sociales. En esta situación, los profesores de artes en las universidades españolas encuentran dificultades para articular sus prácticas creativas y solventar sus resultados de investigación con las agencias de evaluación del sistema universitario, lo cual tiene como consecuencia una debilidad en su capital académico-investigador y una evidencia en los indicadores de la cienciometría. La teoría de los campos de Bourdieu nos permite tanto analizar las dinámicas de los campos académico y artístico como plantear posibles soluciones teóricas y prácticas para una mejor evaluación institucional de la investigación. Para abordar la problemática descrita, nos planteamos un análisis cualitativo de la dimensión epistemológica y académica de la cuestión, y otro cualitativo centrado en los indicadores de calidad de las principales bases de datos. Detectadas las deficiencias y las incongruencias del modelo académico y el perfil del profesorado de las artes, apuntamos la necesidad de plantear un modelo desarrollado por los decanos de las facultades de bellas artes pero que no ha sido aplicado a dichas facultades.
Transmutaciones del cuerpo como sonido proyectado
Authors: Ariza Pomareta Javier
Published: July 2018

La investigación que aquí se presenta reflexiona sobre el carácter del cuerpo y su identidad a partir de los contextos tecnológicos iniciales que permitieron interpretarlo como una naturaleza incorpórea y principalmente sonora. El objetivo pretende destacar el impacto social que supuso desde una perspectiva creativa la transmutación del cuerpo como sonido proyectado técnicamente, así como revelar prácticas artísticas fundamentales realizadas en entornos mediáticos en los que habita la voz sin cuerpo.
Para ello, se recurre a una metodología cualitativa indagando las principales claves de carácter teórico-práctico acontecidas en contextos esenciales como la fonografía, el teléfono y la radio. Se han analizado numerosos textos, documentos y obras resaltando aquellas fuentes que remitían a la percepción del cuerpo como un acontecimiento sonoro desplazado en el tiempo y el espacio. El resultado ofrece una lectura particular del devenir tecnológico en su vertiente sonora que subraya el valor de la voz proyectada como alegoría de un cuerpo virtual e inmaterial que se expresa y comunica. Esta se realiza desde el ámbito de las bellas artes haciendo hincapié en el interés de prácticas creativas concretas que fomentan la reflexión e interpretación como paradigmas. A modo de conclusión, se determinó que las tecnologías del sonido y sus contextos mediáticos contribuyeron desde sus inicios a transformar de forma irreversible el concepto de sujeto e identidad en una nueva sustancia de naturaleza tecnológica, inmaterial, alegórica y virtual. El aporte fundamental de la investigación ha sido la de revelar a través de la reflexión particular algunas de estas claves acontecidas en las prácticas artísticas.
By the Numbers: Will Trucking Go Electric?
Authors: Winters Jeffrey
Published: July 2018

This article presents details of a report on new and future trends in trucking. According to the report, fleet owners may quickly adopt electronic vehicles (EV) for medium-haul routes. In November 2017, Tesla CEO Elon Musk unveiled the design for a battery-powered semi that could travel 500 miles on a single charge. According to Musk, the company would begin producing the trucks in 2019. The report highlighted the regional light-duty delivery market in Europe, where fuel costs are higher than in the United States. Designing vehicles and business models around the capabilities of electric powertrains—capabilities that differ from those of diesel trucks—are expected to enable battery-electric trucks to penetrate the market more quickly.
Minimal Solutions
Authors: Siegel R.P.
Published: July 2018

This article discusses aspects of different manufacturing developments where manufacturers are working with researchers to develop ways to make products using less material and energy. Manufacturers looking to make American factories more competitive with foreign-based facilities are finding opportunities through re-engineering long-held wasteful practices. As a part of a multi-pronged approach, Pradeep Rohatgi, professor of materials science and engineering at the University of Wisconsin, Milwaukee, is leading an effort at reducing embodied-energy and decreasing emissions (REMADE) to examine manufacturing processes. REMADE aims to develop technology enablers to accomplish such goals as reducing primary feedstock consumption in manufacturing by 30 percent, reducing energy demand of secondary material processing by 30 percent, and achieving a 25 percent improvement in embodied energy efficiency of materials such as metals, polymers, fibers, and electronic waste. According to an expert, with embedded energy as the measuring stick, it is also possible to find manufacturing processes that produce very low life-cycle energy costs using carbon fiber composites or high-strength steels.
Age effects on perceptual organization of speech: Contributions of glimpsing, phonemic restoration, and speech segregation
Authors: Bologna William J. , Vaden Kenneth I. , Ahlstrom Jayne B. , Dubno Judy R.
Published: July 2018

In realistic listening environments, speech perception requires grouping together audible fragments of speech, filling in missing information, and segregating the glimpsed target from the background. The purpose of this study was to determine the extent to which age-related difficulties with these tasks can be explained by declines in glimpsing, phonemic restoration, and/or speech segregation. Younger and older adults with normal hearing listened to sentences interrupted with silence or envelope-modulated noise, presented either in quiet or with a competing talker. Older adults were poorer than younger adults at recognizing keywords based on short glimpses but benefited more when envelope-modulated noise filled silent intervals. Recognition declined with a competing talker but this effect did not interact with age. Results of cognitive tasks indicated that faster processing speed and better visual-linguistic closure were predictive of better speech understanding. Taken together, these results suggest that age-related declines in speech recognition may be partially explained by difficulty grouping short glimpses of speech into a coherent message.
Novel Potent Capsid Assembly Modulators Regulate Multiple Steps of the Hepatitis B Virus Life Cycle
Authors: Lahlali Thomas , Berke Jan Martin , Vergauwen Karen , Foca Adrien , Vandyck Koen , Pauwels Frederik , Zoulim Fabien , Durantel David
Published: July 2018

The assembly of hepatitis B virus (HBV) core protein (HBc) into capsids represents a critical step of viral replication. HBc has multiple functions during the HBV life cycle, which makes it an attractive target for antiviral therapies.
Impaired Autophagy in Intestinal Epithelial Cells Alters Gut Microbiota and Host Immune Responses
Authors: Yang Lingyu , Liu Chao , Zhao Wenjing , He Chuan , Ding Jinmei , Dai Ronghua , Xu Ke , Xiao Lu , Luo Lingxiao , Liu Shuyun , Li Wei , Meng He
Published: July 2018

The homeostasis of host-microbiota interactions is of great importance to host health. Previous studies demonstrated that disruption of autophagy was linked to inflammatory bowel disease. However, the interaction mechanism of gut microbiota regulated by autophagy was obscure. In an intestinal epithelium-specific autophagy-related 5 (Atg5) knockout mouse model, we observed a significant alteration and decreased diversity in the gut microbiota ofAtg5-deficient mice compared with that of wild-type mice. Although the numbers of some organisms (e.g.,Akkermansia muciniphilaand members of theLachnospiraceaefamily) associated with the control of inflammation decreased, those of proinflammationory bacteria (e.g., “CandidatusArthromitus”) and potential pathogens (thePasteurellaceaefamily) increased inAtg5−/−mice. Differential gene expression analysis revealed that two key genes,RORCandTBX21, involved in inflammatory bowel disease were upregulated inAtg5−/−mice. Our study suggests thatAtg5deficiency results in an imbalance of the host-microbe interaction and deterioration of the gut microenvironment.
Evaluation of Adenylate Cyclase Toxoid Antigen in Acellular Pertussis Vaccines by Using a Bordetella pertussis Challenge Model in Mice
Authors: Boehm Dylan T. , Hall Jesse M. , Wong Ting Y. , DiVenere Andrea M. , Sen-Kilic Emel , Bevere Justin R. , Bradford Shelby D. , Blackwood Catherine B. , Elkins Cody M. , DeRoos Katherine A. , Gray Mary C. , Cooper C. Garret , Varney Melinda E. , Maynard Jennifer A. , Hewlett Erik L. , Barbier Mariette , Damron F. Heath
Published: July 2018

Bordetella pertussis
is the primary causative agent of pertussis (whooping cough), which is a respiratory infection that leads to a violent cough and can be fatal in infants. There is a need to develop more effective vaccines because of the resurgence of cases of pertussis in the United States since the switch from the whole-cell pertussis vaccines (wP) to the acellular pertussis vaccines (aP; diphtheria-tetanus-acellular-pertussis vaccine/tetanus-diphtheria-pertussis vaccine).
Enhancer Control of MicroRNA miR-155 Expression in Epstein-Barr Virus-Infected B Cells
Authors: Wood C. David , Carvell Thomas , Gunnell Andrea , Ojeniyi Opeoluwa O. , Osborne Cameron , West Michelle J.
Published: July 2018

MicroRNA miR-155 is expressed at high levels in many human cancers, particularly lymphomas. Epstein-Barr virus (EBV) infects human B cells and drives the development of numerous lymphomas. Two genes carried by EBV (LMP1 and EBNA2) upregulate miR-155 expression, and miR-155 expression is required for the growth of EBV-infected B cells. We show that the EBV transcription factor EBNA2 upregulates miR-155 expression by activating an enhancer upstream from the miR-155 host gene (
miR-155HG
) from which miR-155 is derived. We show that EBNA2 also indirectly activates
miR-155
expression through enhancer-mediated activation of
IRF4
. IRF4 then activates both the
miR-155HG
promoter and the upstream enhancer, independently of EBNA2. Gene editing to remove the
miR-155HG
enhancer leads to a reduction in
miR-155HG
expression. We therefore identify enhancer-mediated activation of
miR-155HG
as a critical step in promoting B cell growth and a likely contributor to lymphoma development.
Kaposi's Sarcoma-Associated Herpesvirus Latency Locus Renders B Cells Hyperresponsive to Secondary Infections
Authors: Sin Sang-Hoon , Eason Anthony B. , Bigi Rachele , Kim Yongbaek , Kang SunAh , Tan Kelly , Seltzer Tischan A. , Venkataramanan Raman , An Hyowon , Dittmer Dirk P.
Published: July 2018

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes latency in B cells and is stringently linked to primary effusion lymphoma (PEL) and the premalignant B cell hyperplasia multicentric Castleman's disease (MCD). To investigate potential genetic background effects, we expressed the KSHV miRNAs in BALB/c transgenic mice. BALB/c mice are the preferred strain for B cell hybridoma development because of their propensity to develop predictable B cell responses to antigen. The BALB/c latency mice exhibited a higher incidence of B cell hyperplasia as well as sustained hyperglobulinemia. The development of neutralizing antibodies against ZIKV was augmented in BALB/c latency mice. Hyperglobulinemia was dampened by everolimus, a derivative of rapamycin, suggesting a role for mTOR inhibitors in managing immune activation, which is hallmark of KSHV infection as well as HIV infection.
Structure-Function Analysis of the Curli Accessory Protein CsgE Defines Surfaces Essential for Coordinating Amyloid Fiber Formation
Authors: Klein Roger D. , Shu Qin , Cusumano Zachary T. , Nagamatsu Kanna , Gualberto Nathaniel C. , Lynch Aaron J. L. , Wu Chao , Wang Wenjie , Jain Neha , Pinkner Jerome S. , Amarasinghe Gaya K. , Hultgren Scott J. , Frieden Carl , Chapman Matthew R.
Published: July 2018

Curli amyloid fibers are produced as part of the extracellular biofilm matrix and are composed primarily of the major structural subunit CsgA. The CsgE chaperone facilitates the secretion of CsgA through CsgG by forming a cap at the base of the nonameric CsgG outer membrane pore. We elucidated a series of finely tuned nonpolar and charge-charge interactions that facilitate the oligomerization of CsgE and its ability to transport unfolded CsgA to CsgG for translocation. CsgE oligomerization
in vitro
is temperature dependent and is disrupted by mutations in the W48 and F79 residues. Using nuclear magnetic resonance (NMR), we identified two regions of CsgE involved in the CsgE-CsgA interaction: a head comprising a positively charged patch centered around R47 and a stem comprising a negatively charged patch containing E31 and E85. Negatively charged residues in the intrinsically disordered N- and C-terminal “tails” were not implicated in this interaction. Head and stem residues were mutated and interrogated using
in vivo
measurements of curli production and
in vitro
amyloid polymerization assays. The R47 head residue of CsgE is required for stabilization of CsgA- and CsgE-mediated curli fiber formation. Mutation of the E31 and E85 stem residues to positively charged side chains decreased CsgE-mediated curli fiber formation but increased CsgE-mediated stabilization of CsgA. No single-amino-acid substitutions in the head, stem, or tail regions affected the ability of CsgE to cap the CsgG pore as determined by a bile salt sensitivity assay. These mechanistic insights into the directed assembly of functional amyloids in extracellular biofilms elucidate possible targets for biofilm-associated bacterial infections.

IMPORTANCE
Curli represent a class of functional amyloid fibers produced by
Escherichia coli
and other Gram-negative bacteria that serve as protein scaffolds in the extracellular biofilm matrix. Despite the lack of sequence conservation among different amyloidogenic proteins, the structural and biophysical properties of functional amyloids such as curli closely resemble those of amyloids associated with several common neurodegenerative diseases. These parallels are underscored by the observation that certain proteins and chemicals can prevent amyloid formation by the major curli subunit CsgA and by alpha-synuclein, the amyloid-forming protein found in Lewy bodies during Parkinson’s disease. CsgA subunits are targeted to the CsgG outer membrane pore by CsgE prior to secretion and assembly into fibers. Here, we use biophysical, biochemical, and genetic approaches to elucidate a mechanistic understanding of CsgE function in curli biogenesis.
Does glucagon-like peptide-1 (GLP-1) receptor agonist stimulation reduce alcohol intake in patients with alcohol dependence: study protocol of a randomised, double-blinded, placebo-controlled clinical trial
Authors: Antonsen Kerstin K , Klausen Mette K , Brunchmann Amanda S , le Dous Nina , Jensen Mathias E , Miskowiak Kamilla Woznica , Fisher Patrick M , Thomsen Gerda K , Rindom Henrik , Fahmy Thomas P , Vollstaedt-Klein Sabine , Benveniste Helene , Volkow Nora D , Becker Ulrik , Ekstrøm Claus , Knudsen Gitte Moos , Vilsbøll Tina , Fink-Jensen Anders
Published: July 2018

Introduction

Alcohol dependence is a major public health problem. It is underdiagnosed and undertreated. Even when treated, more than 2/3 of patients in abstinence-oriented treatment will relapse within the first year. Thus, there is an urgent need for efficacious medical treatment of alcohol dependence. Glucagon-like peptide-1 (GLP-1) receptor stimulation has proven to reduce alcohol consumption in preclinical experiments. However, the effect of GLP-1 receptor agonists in humans has to our knowledge, not yet been investigated.

Methods and analysis

Design, participants and intervention: The effect of the once-weekly GLP-1-receptor-agonist exenatide will be investigated in a double-blinded, placebo-controlled, randomised clinical trial. 114 outpatients will be recruited and randomised to treatment with either placebo or exenatide once weekly for 26 weeks as a supplement to cognitive–behavioural therapy.The primary endpointis reduction in number of ‘heavy drinking days’.The secondary endpointsinclude changes in total alcohol consumption, days without consumption, changes in brain activity and function, smoking status, cognition, measures of quality of life and changes in phosphatidylethanol as a biomarker of alcohol consumption from baseline to follow-up at week 26.

Status: Currently recruiting patients.

Ethics and dissemination

Ethical approval has been obtained. Before screening, all patients will be provided oral and written information about the trial. The study results will be disseminated by peer-review publications and conference presentations and has the potential to reveal a completely new medical treatment of alcohol dependence.
Who teaches medical billing? A national cross-sectional survey of Australian medical education stakeholders
Authors: Faux Margaret , Wardle Jonathan , Thompson-Butel Angelica G , Adams Jon
Published: July 2018

Importance

Billing errors and healthcare fraud have been described by the WHO as ‘the last great unreduced health-care cost’. Estimates suggest that 7% of global health expenditure (US$487 billion) is wasted from this phenomenon. Irrespective of different payment models, challenges exist at the interface of medical billing and medical practice across the globe. Medical billing education has been cited as an effective preventative strategy, with targeted education saving $A250 million in Australia in 1 year from an estimated $A1–3 billion of waste.

Objective

This study attempts to systematically map all avenues of medical practitioner education on medical billing in Australia and explores the perceptions of medical education stakeholders on this topic.

Design

National cross-sectional survey between April 2014 and June 2015. No patient or public involvement. Data analysis—descriptive statistics via frequency distributions.

Participants

All stakeholders who educate medical practitioners regarding clinical practice (n=66). 86% responded.

Results

There is little medical billing education occurring in Australia. The majority of stakeholders (70%, n=40) did not offer/have never offered a medical billing course. 89% thought medical billing should be taught, including 30% (n=17) who were already teaching it. There was no consensus on when medical billing education should occur.

Conclusions

To our knowledge, this is the first attempt of any country to map the ways doctors learn the complex legal and administrative infrastructure in which they work. Consistent with US findings, Australian doctors may not have expected legal and administrative literacy. Rather than reliance on ad hoc training, development of an Australian medical billing curriculum should be encouraged to improve compliance, expedite judicial processes and reduce waste. In the absence of adequate education, disciplinary bodies in all countries must consider pleas of ignorance by doctors under investigation, where appropriate, for incorrect medical billing.
Prevalence and risk factors of MRSA colonisations: a cross-sectional study among personnel in outpatient care settings in Hamburg, Germany
Authors: Peters Claudia , Kleinmüller Olaf , Nienhaus Albert , Schablon Anja
Published: July 2018

Objectives

Healthcare workers frequently come into contact with infected individuals and are at a greater risk of infection than the general population due to their occupation. Multidrug-resistant organisms (MDROs) also pose a significant challenge for personnel and medical facilities. Currently, little is known about the occupational risk of methicillin-resistantStaphylococcus aureus(MRSA) in outpatient care settings. Therefore, a cross-sectional study was conducted in Hamburg to investigate MRSA colonisation among outpatient nursing staff.

Methods

MRSA screening with nasal swabs was carried out, the known risk factors for colonisation were determined and information on infection control was inquired. Where tests were positive, a control swab was taken; if this confirmed a positive result, decolonisation was offered. A molecular biological examination of the MRSA samples was performed. The occupational MRSA exposure and risk factors were compared with the situation for personnel in inpatient geriatric care.

Results

A total of 39 outpatient services participated in the study and 579 employees were tested. The MRSA prevalence was 1.2% in all and 1.7% in nursing staff. Most of the employees that tested positive had close or known contact with MRSA patients. Health personnel frequently reported personal protective measures and their application. Compared with inpatient care staff, outpatient staff were older and had worked in their profession for a longer time.

Conclusion

This study marks the first time that data has been made available on the occupational MRSA risk of outpatient care personnel in Hamburg. The MRSA prevalence is low and provides a good basis for describing the MRSA risk of occupational exposure by health personnel in outpatient care.
Effectiveness of early assessment and intervention by interdisciplinary teams including health and social care professionals in the emergency department: protocol for a systematic review
Authors: Cassarino Marica , Robinson Katie , Quinn Rosie , Naddy Breda , O’Regan Andrew , Ryan Damien , Boland Fiona , Ward Marie E , McNamara Rosa , McCarthy Gerard , Galvin Rose
Published: July 2018

Introduction

Finding cost-effective strategies to improve patient care in the emergency department (ED) is an increasing imperative given growing numbers of ED attendees. Encouraging evidence indicates that interdisciplinary teams including health and social care professionals (HSCPs) enhance patient care across a variety of healthcare settings. However, to date no systematic reviews of the effectiveness of early assessment and/or interventions carried by such teams in the ED exist. This systematic review aims to explore the impact of early assessment and/or intervention carried out by interdisciplinary teams including HSCPs in the ED on the quality, safety and cost-effectiveness of care, and to define the content of the assessment and/or intervention offered by HSCPs.

Methods and analysis

Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standardised guidelines, we will conduct a systematic review of randomised controlled trials (RCTs), non-RCTs, controlled before–after studies, interrupted time series and repeated measures studies that report the impact of early assessment and/or intervention provided to adults aged 18+ by interdisciplinary teams including HSCPs in the ED. Searches will be carried in Cumulative Index of Nursing and Allied Health Literature, Embase, Cochrane Library and MEDLINE from inception to March 2018. We will also hand-search the reference lists of relevant studies. Following a two-step screening process, two independent reviewers will extract data on the type of population, intervention, comparison, outcomes and study design. The quality of the studies will be appraised using the Cochrane Risk of Bias Tool. The findings will be synthesised in a narrative summary, and a meta-analysis will be conducted where appropriate.

Ethics and dissemination

Ethical approval will not be sought since it is not required for systematic reviews. The results of this review will be disseminated through publication in a peer-review journal and presented at relevant conferences.

Trial registration number

CRD42018091794.
Case of severe acute hepatitis A virus infection in United Nations peacekeepers in South Sudan
Authors: Li Chen , Su H , Hu J , Duan H , Ji J
Published: July 2018

Hepatitis A virus (HAV) is a major cause of acute viral hepatitis, which can lead to severe cases and acute liver failure. A 41-year-old Chinese military officer of the United Nations peacekeeping forces in South Sudan manifested fever, jaundice and coagulation dysfunction. The patient initially had a negative anti-HAV IgM antibody test result but a positive anti-HAV-IgM antibody test result five days after his alanine aminotransferase (ALT) levels peaked. He was given telemedicine consultation and was transferred to a Chinese military hospital specialising in infectious diseases for treatment of severe acute HAV infection. The peak ALT, aspartate aminotransferase, total bilirubin and international standard ratio were 5410 U/L, 3475 U/L, 225.1 µmol/L and 2.12 during hospitalisation, respectively. Military personnel undergoing missions in areas with high prevalence of HAV should be tested for previous HAV infection before departure if they have not been previously vaccinated. If negative results are obtained, they should be vaccinated. Anti-HAV-IgM examination should be repeated after the first negative test result is obtained to eliminate the effects of a window period if a clinical suspicion exists. If a life-threatening case of HAV infection is present, the patient should be transported to a base military hospital specialising in infectious diseases for treatment.