bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of hospital-acquired pneumonia on long-term recovery and hospital resource utilization following moderate to severe traumatic brain injury
Authors: Kumar Raj G. , Kesinger Matthew R. , Juengst Shannon B. , Brooks Maria M. , Fabio Anthony , Dams-O'Connor Kristen , Pugh Mary Jo , Sperry Jason L. , Wagner Amy K. 
Published: December 2019

BACKGROUND
Individuals with traumatic brain injury (TBI) have extended inpatient hospital stays that include prolonged mechanical ventilation, increasing risk for infections, including pneumonia. Studies show the negative short-term effects of hospital-acquired pneumonia (HAP) on hospital-based outcomes; however, little is known of its long-term effects.

METHODS
A prospective cohort study was conducted. National Trauma Databank and Traumatic Brain Injury Model Systems were merged to derive a cohort of 3,717 adults with moderate-to-severe TBI. Exposure data were gathered from the National Trauma Databank, and outcomes were gathered from the Traumatic Brain Injury Model Systems. The primary outcome was the Glasgow Outcome Scale—Extended (GOS-E), which was collected at 1, 2, and 5 years postinjury. The GOS-E was categorized as favorable (>5) or unfavorable (≤5) outcomes. A generalized estimating equation model was fitted estimating the effects of HAP on GOS-E over the first 5 years post-TBI, adjusting for age, race, ventilation status, brain injury severity, injury severity score, thoracic Abbreviated Injury Scale score of 3 or greater, mechanism of injury, intraventricular hemorrhage, and subarachnoid hemorrhage.

RESULTS
Individuals with HAP had a 34% (odds ratio, 1.34; 95% confidence interval, 1.15–1.56) increased odds for unfavorable GOS-E over the first 5 years post-TBI compared with individuals without HAP, after adjustment for covariates. There was a significant interaction between HAP and follow-up, such that the effect of HAP on GOS-E declined over time. Sensitivity analyses that weighted for nonresponse bias and adjusted for differences across trauma facilities did not appreciably change the results. Individuals with HAP spent 10.1 days longer in acute care and 4.8 days longer in inpatient rehabilitation and had less efficient functional improvement during inpatient rehabilitation.

CONCLUSION
Individuals with HAP during acute hospitalization have worse long-term prognosis and greater hospital resource utilization. Preventing HAP may be cost-effective and improve long-term recovery for individuals with TBI. Future studies should compare the effectiveness of different prophylaxis methods to prevent HAP.

LEVEL OF EVIDENCE
Prospective cohort study, level III.
rs641738C>T nearMBOAT7is positively associated with liver fat, ALT, and histological severity of NAFLD: a meta-analysis
Authors: Teo Kevin , Abeysekera Kushala W. M. , Adams Leon , Aigner Elmar , Banales Jesus M. , Banerjee Rajarshi , Basu Priyadarshi , Berg Thomas , Bhatnagar Pallav , Buch Stephan , Canbay Ali , Caprio Sonia , Chatterjee Ankita , Chen Yii-Der Ida , Chowdhury Abhijit , Datz Christian , de Gracia Hahn Dana , DiStefano Johanna K. , Dong Jiawen , Duret Amedine ,   EU-PNAFLD Investigators, Emdin Connor , Fairey Madison , Gerhard Glenn S ,   GOLD Consortium, Guo Xiuqing , Hampe Jochen , Hickman Matthew , Heintz Lena , Hudert Christian , Hunter Harriet , Kelly Matt , Kozlitina Julia , Krawczyk Marcin , Lammert Frank , Langenberg Claudia , Lavine Joel , Li Lin , Lim Hong Kai , Loomba Rohit , Luukkonen Panu K. , Melton Phillip E. , Mori Trevor A. , Palmer Nicholette D. , Parisinos Constantinos A. , Pillai Sreekumar G , Qayyum Faiza , Reichert Matthias C. , Romeo Stefano , Rotter Jerome I. , Im Yu Ri , Santoro Nicola , Schafmayer Clemens , Speliotes Elizabeth K. , Stender Stefan , Stickel Felix , Still Christopher D. , Strnad Pavel , Taylor Kent D. , Tybjærg-Hansen Anne , Umano Giuseppina Rosaria , Utukuri Mrudula , Valenti Luca , Wagenknecht Lynne E. , Wareham Nicholas J. , Watanabe Richard M. , Wattacheril Julia , Yaghootkar Hanieh , Yki-Järvinen Hannele , Young Kendra A. , Mann Jake P. 
Published: December 2019

ABSTRACTBackground & AimsA common genetic variant nearMBOAT7(rs641738C>T) has been previously associated with hepatic fat and advanced histology in non-alcoholic fatty liver disease (NAFLD), however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and characterize its role in the regulation of related metabolic phenotypes through meta-analysis.MethodsWe performed meta-analysis of studies with data on the association between rs641738C>T genotype and: liver fat, NAFLD histology, and serum ALT, lipids, or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed random effects meta-analysis using recessive, additive, and dominant genetic models.ResultsData from 1,047,265 participants (8,303 with liver biopsies) across 42 studies was included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI: 0.02 - 0.05]) and diagnosis of NAFLD (OR 1.22 [95% CI 1.08 - 1.39]) in Caucasian adults. The variant was also positively associated with presence of severe steatosis, NASH, and advanced fibrosis (OR: 1.32 [95% CI: 1.06 - 1.63]) in Caucasian adults using a recessive model of inheritance (CC+CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (Pz=0.002) and lower serum triglycerides (Pz=1.5×10−4). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD.ConclusionOur study validates rs641738C>T nearMBOAT7as a risk factor for the presence and severity of NAFLD in individuals of European descent.
Dynamic competition for hexon binding between core protein VII and lytic protein VI promotes adenovirus maturation and entry
Authors: Hernando-Pérez Mercedes , Martín-González Natalia , Pérez-Illana Marta , Suomalainen Maarit , Ostapchuk Philomena , Condezo Gabriela. N. , Menéndez M. , Greber Urs F. , Hearing Patrick , Pablo Pedro J. de , Martín Carmen San 
Published: December 2019

AbstractAdenovirus minor coat protein VI contains a membrane-disrupting peptide which is inactive when VI is bound to hexon trimers. Protein VI must be released during entry to ensure endosome escape. Hexon:VI stoichiometry has been uncertain, and only fragments of VI have been identified in the virion structure. Recent findings suggest an unexpected relationship between VI and the major core protein, VII. According to the high resolution structure of the mature virion, VI and VII may compete for the same binding site in hexon; and non-infectious human adenovirus type 5 particles assembled in the absence of VII (Ad5-VII-) are deficient in proteolytic maturation of protein VI and endosome escape. Here we show that Ad5-VII- particles are trapped in the endosome because they fail to increase VI exposure during entry. This failure was not due to increased particle stability, because capsid disruption happened at lower thermal or mechanical stress in Ad5-VII- compared to wildtype (Ad5-wt) particles. Cryo-EM difference maps indicated that VII can occupy the same binding pocket as VI in all hexon monomers, strongly arguing for binding competition. In the Ad5-VII- map, density corresponding to the immature amino-terminal region of VI indicates that in the absence of VII the lytic peptide is trapped inside the hexon cavity, and clarifies the hexon:VI stoichiometry conundrum. We propose a model where dynamic competition between proteins VI and VII for hexon binding facilitates the complete maturation of VI, and is responsible for releasing the lytic protein from the hexon cavity during entry and stepwise uncoating.Significance StatementCorrect assembly of an adenovirus infectious particle involves the highly regulated interaction of more than ten different proteins as well as the viral genome. Here we examine the interplay between two of these proteins: the major core protein VII, involved in genome condensation, and the multifunctional minor coat protein VI. Protein VI binds to the inner surface of adenovirus hexons (trimers of the major coat protein) and contains a lytic peptide which must be released during entry to ensure endosome rupture. We present data supporting a dynamic competition model between proteins VI and VII for hexon binding during assembly. This competition facilitates the release of the lytic peptide from the hexon cavity and ensures virus escape from the early endosome.
Highly clustered de novo frameshift variants in the neuronal splicing factor NOVA2 result in a specific abnormal C terminal part and cause a severe form of intellectual disability with autistic features
Authors: Mattioli Francesca , Hayot Gaelle , Drouot Nathalie , Isidor Bertrand , Courraud Jérémie , Mau-Them Frederic Tran , Sellier Chantal , Hinckelmann Maria-Victoria , Goldman Alica , Telegrafi Aida , Boughton Alicia , Gamble Candace , Moutton Sebastien , Quartier Angélique , Jean Nolwenn , Ness Paul Van , Grotto Sarah , Nambot Sophie , Douglas Ganka , Si Yue Cindy , Chelly Jamel , Shad Zohra , Kaplan Elisabeth , Dineen Richard , Golzio Christelle , Charlet Nicolas , Jean-Louis Mandel , Amélie Piton 
Published: December 2019

ABSTRACTThe Neuro-Oncological Ventral Antigen 2 NOVA2 protein is a major factor regulating neuron specific alternative splicing, previously associated with an acquired neurologic condition, the paraneoplastic opsoclonus-myoclonus ataxia (POMA). We report here six individuals with de novo frameshift variants in the NOVA2 gene affected with a severe neurodevelopmental disorder characterized by intellectual disability (ID), motor and speech delay, autistic features, hypotonia, feeding difficulties, spasticity or ataxic gait and abnormal brain MRI. The six variants lead to the same reading frame, adding a common 133 aa long proline rich C-terminus part instead of the last KH RNA binding domain. We detected forty-one genes differentially spliced after NOVA2 inactivation in human neural cells. The mutant NOVA2 protein shows decreased ability to bind a target RNA, to regulate specific splicing events and to rescue the phenotype of altered retinotectal axonal pathfinding induced by loss of NOVA2 ortholog in zebrafish. Our results suggest a partial loss-of-function mechanism rather than a full heterozygous loss of function, although a specific contribution of the novel C terminal extension cannot be excluded on the basis of the genetic findings.
Non-clonal emergence of colistin resistance associated with mutations in the BasRS two-component system in Escherichia coli bloodstream isolates
Authors: Janssen Axel B. , Bartholomew Toby L. , Marciszewska Natalia P. , Bonten Marc J.M. , Willems Rob J.L. , Bengoechea Jose A. , van Schaik Willem 
Published: December 2019

AbstractInfections by multidrug-resistant Gram-negative bacteria are increasingly common, prompting the renewed interest in the use of colistin. Colistin specifically targets Gram-negative bacteria by interacting with the anionic lipid A moieties of lipopolysaccharides, leading to membrane destabilization and cell death. Here, we aimed to uncover the mechanisms of colistin resistance in nine colistin-resistant Escherichia coli strains and one E. albertii strain. These were the only colistin-resistant strains out of 1140 bloodstream Escherichia isolates collected in a tertiary hospital over a ten-year period (2006 - 2015). Core genome phylogenetic analysis showed that each patient was colonised by a unique strain, suggesting that colistin resistance was acquired independently in each strain. All colistin-resistant strains had lipid A that was modified with phosphoethanolamine. In addition, two E. coli strains had hepta-acylated lipid A species, containing an additional palmitate compared to the canonical hexa-acylated E. coli lipid A. One E. coli strain carried the mobile colistin resistance (mcr) gene mcr-1.1 on an IncX4-type plasmid. Through construction of chromosomal transgene integration mutants, we experimentally determined that mutations in basRS, encoding a two-component signal transduction system, contributed to colistin resistance in four strains. We confirmed these observations by reversing the mutations in basRS to the sequences found in reference strains, resulting in loss of colistin resistance. While the mcr-genes have become a widely studied mechanism of colistin resistance in E. coli, sequence variation in basRS is another, potentially more prevalent but relatively underexplored, cause of colistin resistance in this important nosocomial pathogen.ImportanceMultidrug resistance among Gram-negative bacteria has led to the use of colistin as a last-resort drug. The cationic colistin kills Gram-negative bacteria through electrostatic interaction with the anionic lipid A moiety of lipopolysaccharides. Due to increased use in clinical and agricultural settings, colistin resistance has recently started to emerge. In this study, we used a combination of whole genome sequence analysis and experimental validation to characterise the mechanisms through which E. coli strains from bloodstream infections can develop colistin resistance. We found no evidence of direct transfer of colistin-resistant isolates between patients. The lipid A of all isolates was modified by the addition of phosphoethanolamine. In four isolates, colistin resistance was experimentally verified to be caused by mutations in the basRS genes, encoding a two-component regulatory system. Our data show that chromosomal mutations are an important cause of colistin resistance among clinical E. coli isolates.
Evolution of populations with strategy-dependent time delays
Authors: Miȩkisz Jacek , Bodnar Marek 
Published: December 2019

AbstractWe address the issue of stability of coexistence of two strategies with respect to time delays in evolving populations. It is well known that time delays may cause oscillations. Here we report a novel behavior. We show that a microscopic model of evolutionary games with a unique mixed evolutionarily stable strategy (a globally asymptotically stable interior stationary state in the standard replicator dynamics) and with strategy-dependent time delays leads to a new type of replicator dynamics. It describes the time evolution of fractions of the population playing given strategies and the size of the population. Unlike in all previous models, an interior stationary state of such dynamics depends continuously on time delays and at some point it might disappear, no cycles are present. In particular, this means that an arbitrarily small time delay changes an interior stationary state. Moreover, at certain time delays, there may appear another interior stationary state.Author summarySocial and biological processes are usually described by ordinary or partial differential equations, or by Markov processes if we take into account stochastic perturbations. However, interactions between individuals, players or molecules, naturally take time. Results of biological interactions between individuals may appear in the future, and in social models, individuals or players may act, that is choose appropriate strategies, on the basis of the information concerning events in the past. It is natural therefore to introduce time delays into evolutionary game models. It was usually observed, and expected, that small time delays do not change the behavior of the system and large time delays may cause oscillations. Here we report a novel behavior. We show that microscopic models of evolutionary games with strategy-dependent time delays, in which payoffs appear some time after interactions of individuals, lead to a new type of replicator dynamics. Unlike in all previous models, interior stationary states of such dynamics depend continuously on time delays. This shows that effects of time delays are much more complex than it was previously thought.
Surfactin production is not essential for pellicle and root-associated biofilm development ofBacillus subtilis
Authors: Thérien Maude , Kiesewalter Heiko T. , Auria Emile , Charron-Lamoureux Vincent , Wibowo Mario , Maróti Gergely , Kovács Ákos T. , Beauregard Pascale B. 
Published: December 2019

AbstractSecondary metabolites have an important impact on the biocontrol potential of soil-derived microbes. In addition, various microbe-produced chemicals have been suggested to impact the development and phenotypic differentiation of bacteria, including biofilms. The non-ribosomal synthesized lipopeptide ofBacillus subtilis, surfactin, has been described to impact the plant promoting capacity of the bacterium. Here, we investigated the impact of surfactin production on biofilm formation ofB. subtilisusing the laboratory model systems; pellicle formation at the air-medium interface and architecturally complex colony development, in addition to plant root-associated biofilms. We found that the production of surfactin byB. subtilisis not essential for pellicle biofilm formation neither in the well-studied strain, NCIB 3610, nor in the newly isolated environmental strains, but lack of surfactin reduces colony expansion. Further, plant root colonization was comparable both in the presence or absence of surfactin synthesis. Our results suggest that surfactin-related biocontrol and plant promotion inB. subtilisstrains are independent of biofilm formation.
Evolution of multifunctionality through a pleiotropic substitution in the innate immune protein S100A9
Authors: Harman Joseph L. , Loes Andrea N. , Warren Gus D. , Heaphy Maureen C. , Lampi Kirsten J. , Harms Michael J. 
Published: December 2019

ABSTRACTMultifunctional proteins are evolutionary puzzles: how do proteins evolve to satisfy multiple functional constraints? S100A9 is one such multifunctional protein. It potently amplifies inflammation via Toll-like receptor 4 and is antimicrobial as part of a heterocomplex with S100A8. These two functions are seemingly regulated by proteolysis: S100A9 is readily degraded, while S100A8/S100A9 is resistant. We take an evolutionary biochemical approach to show that S100A9 evolved both functions and lost proteolytic resistance from a weakly proinflammatory, proteolytically resistant amniote ancestor. We identify a historical substitution that has pleiotropic effects on S100A9 proinflammatory activity and proteolytic resistance but has little effect on S100A8/S100A9 antimicrobial activity. We thus propose that mammals evolved S100A8/S100A9 antimicrobial and S100A9 proinflammatory activities concomitantly with a proteolytic “timer” to selectively regulate S100A9. This highlights how the same mutation can have pleiotropic effects on one functional state of a protein but not another, thus facilitating the evolution of multifunctionality.
Gender in service quality expectations in hospitals
Authors: Abu-Salim Taghreed , Mustafa Nermeen , Onyia Okey Peter , Watson Alastair William 
Published: December 2019

Purpose
Despite evidence largely confirming gender-based differences in service quality perceptions in healthcare, little research has considered patients’ expectations. This study aims to examine the gender-based differences in both the affective and cognitive components of customers’ service quality expectations.

Design/methodology/approach
Data were collected through random sampling from three outpatient hospitals in the UAE. Hypothesized relationships between the cognitive and affective components (moderated by gender) were tested by means of CFA and ANOVA.

Findings
The results indicate that the differences between male and female expectations of overall service quality as a singular construct were not statistically significant, except for the empathy dimension. However, when measured as affective and cognitive, the results confirm that significant differences do exist between male and female patients.

Research limitations/implications
The research was limited to the UAE. However, identifying gender differences in patients’ expectations would enable healthcare providers to engage and manage patients’ expectations.

Originality/value
This paper provides theoretical and practical implications on how the male and female are different in the cognitive and affective components of service quality expectations.
International students in professional placements: supervision strategies for positive learning experiences
Authors: Attrill Stacie , Lincoln Michelle , McAllister Sue 
Published: December 2019

AbstractBackgroundProfessional placements are critical elements of speech–language pathology qualifying programmes that can be complex learning environments for international students. Students are supported by placement educators who facilitate their developing skills and competencies for professional practice in these placements. However, strategies that facilitate international students’ learning in placements have not been identified.AimsTo identify strategies that are reported by speech–language pathology international students and placement educators to facilitate positive learning experiences and competency development in practice placements.Methods & ProceduresThis study used an exploratory research design to gather data from four focus groups with international students and five focus groups with placement educators. Thematic analysis was used to identify strategies, and these were interpreted using two theories of learning.Outcomes & ResultsFour themes were identified that described international students’ placement experiences and learning. For each theme, strategies were identified that placement educators can practically and responsively implement with international students to enable positive placement learning experiences.Conclusions & ImplicationsThese strategies support international students to manage acculturative adjustments for the cultural and learning requirements of placements that may facilitate their successful participation, and provide structure to reduce their cognitive load. However, strategies to develop communication skills for practice were less feasible. Through fostering positive placement experiences, these strategies may also facilitate opportunities for educators and international students to share intercultural skills and knowledge that may be transferable to practice.
Is Moderate Drinking Protective Against Heart Disease? The Science, Politics and History of a Public Health Conundrum
Authors: OPPENHEIMER GERALD M. , BAYER RONALD 
Published: December 2019

Policy Points
For more than 40 years, most research by epidemiologists, social scientists, and alcohol policy experts found that moderate alcohol consumption was cardioprotective.
In the early 2000s, that consensus was shaken by new critics who subjected the previous research to vigorous methodological and empirical analysis, precipitating a bitter controversy, seemingly unresolvable despite numerous observational epidemiological studies.
The effort to finally put that debate to rest through a large, multiyear randomized controlled trial under the aegis of the National Institute on Alcohol Abuse and Alcoholism, generated external criticism and adverse newspaper coverage, particularly because the trial was largely funded by the alcohol industry, forcing National Institutes of Health leadership to abruptly terminate the study shortly after it started.
In the absence of definitive evidence and given the contentious debate over the risks and benefits of moderate alcohol consumption, those who formulate health policy have a responsibility to clearly acknowledge to the public the existence of evidentiary uncertainty when making recommendations.