bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dislodgement of a right atrial thrombus and subsequent pulmonary thromboembolism following tracheal stent deployment in a dog
Authors: Preston Ayla R. , Sullivan Lauren A. 
Published: April 2016

AbstractObjectiveTo report the management of a dog that required 2 treatments with mechanical ventilation; firstly for severe tracheal collapse and secondly following deployment of a nitinol tracheal stent that immediately preceded a nonoxygen responsive pulmonary thromboembolism (PTE), suspected to have originated from the right atrium.Case SummaryA 9‐year‐old female spayed Shetland Sheepdog was presented for management of a gallbladder mucocoele. Pertinent history included iatrogenic hyperadrenocorticism and tracheal collapse. The dog became clinical for tracheal collapse following laparoscopic cholecystectomy. Thoracic radiographs revealed moderate to severe tracheal collapse at the level of the thoracic inlet. Arterial blood gas was consistent with hypoventilation and mechanical ventilation was instituted. Given the severity of tracheal collapse, self‐expanding nitinol tracheal stent placement was elected. Immediately following tracheal stent placement, the dog developed nonoxygen responsive hypoxemia requiring mechanical ventilation. Additional diagnostic tests revealed changes consistent with a PTE and a large thrombus in the right atrium. The dog was humanely euthanized.New or Unique Information ProvidedDislodgement of a preexisting atrial thrombus has not been described as a complication following tracheal stent deployment. Additionally, although PTE is frequently considered to be oxygen responsive, it may not be if the embolism is severe enough.
The Association Between Self‐Management Barriers and Self‐Efficacy in Chinese Patients with Type 2 Diabetes: The Mediating Role of Appraisal
Authors: Cheng Li , Sit Janet W.H. , Leung Doris Y.P. , Li Xiaomei 
Published: April 2016

ABSTRACTBackgroundPatients with higher levels of self‐management barriers are more likely to exhibit a lower level of self‐efficacy. However, the theoretically meaningful mechanisms underlying the association between the two variables have not yet been established.AimsInformed by the Transactional Model of Stress and Coping, this study aimed to examine the potential role of diabetes appraisal on the association of self‐management barriers and self‐efficacy in patients with type 2 diabetes mellitus.MethodsThis article presents the secondary data analyses of a multicenter, cross‐sectional study. A sample of 346 adults with type 2 diabetes was interviewed, using the Personal Diabetes Questionnaire, the Appraisal of Diabetes scale, the Diabetes Empowerment Scale‐Short Form, and the Summary of Diabetes Self‐Care Activities. Structure equation modeling was performed with 10,000 bootstrap samples using Mplus 7.ResultsThe hypothesized model provided a good fit to the data (χ2 = 22.975, df = 33; p = .1144; CFI = 0.989; SRMR = 0.036; RMSEA = 0.042). The mediating effect of diabetes appraisal on the association of self‐management barriers and self‐efficacy was significant (β = ‐0.521; 95% CI: ‐0.865, ‐0.283), explaining 44.82% of the total effect of barriers on self‐efficacy. Significant associations were also detected between diet knowledge and diabetes appraisal (β = 0.148, p = .047).Linking Evidence to ActionDiabetes appraisal plays a mediating role in the association between self‐management barriers and self‐efficacy in patients with type 2 diabetes. Reflecting on patients’ appraisal of diabetes can help to develop evidence‐based and patient‐centered interventions. Interventions that enhance individuals’ positive appraisal of diabetes have the potential to buffer the negative effects of self‐management barriers on self‐efficacy.
Pre-transmetalation intermediates in the Suzuki-Miyaura reaction revealed: The missing link
Authors: Thomas Andy A. , Denmark Scott E. 
Published: April 2016

Where Pd and B meet in Suzuki coupling
The Suzuki-Miyaura reaction is widely used to form carbon-carbon bonds. It operates by transferring a carbon center from boron to palladium, although the handoff itself happens too quickly to see. Thomas and Denmark have caught sight of the previously elusive intermediate complexes linking palladium to boron through an intervening oxygen. Using low-temperature nuclear magnetic resonance spectroscopy, they characterized the intermediate structures just before the carbon transfer event.

Science
, this issue p.
329
Characterization of Influenza Vaccine Hemagglutinin Complexes by Cryo-Electron Microscopy and Image Analyses Reveals Structural Polymorphisms
Authors: McCraw Dustin M. , Gallagher John R. , Harris Audray K. 
Published: April 2016

ABSTRACTInfluenza virus afflicts millions of people worldwide on an annual basis. There is an ever-present risk that animal viruses will cross the species barrier to cause epidemics and pandemics resulting in great morbidity and mortality. Zoonosis outbreaks, such as the H7N9 outbreak, underscore the need to better understand the molecular organization of viral immunogens, such as recombinant influenza virus hemagglutinin (HA) proteins, used in influenza virus subunit vaccines in order to optimize vaccine efficacy. Here, using cryo-electron microscopy and image analysis, we show that recombinant H7 HA in vaccines formed macromolecular complexes consisting of variable numbers of HA subunits (range, 6 to 8). In addition, HA complexes were distributed across at least four distinct structural classes (polymorphisms). Three-dimensional (3D) reconstruction and molecular modeling indicated that HA was in the prefusion state and suggested that the oligomerization and the structural polymorphisms observed were due to hydrophobic interactions involving the transmembrane regions. These experiments suggest that characterization of the molecular structures of influenza virus HA complexes used in subunit vaccines will lead to better understanding of the differences in vaccine efficacy and to the optimization of subunit vaccines to prevent influenza virus infection.
Deep Sequencing of HIV-1 RNA and DNA in Newly Diagnosed Patients with Baseline Drug Resistance Showed No Indications for Hidden Resistance and Is Biased by Strong Interference of Hypermutation
Authors: Dauwe Kenny , Staelens Delfien , Vancoillie Leen , Mortier Virginie , Verhofstede Chris 
Published: April 2016

ABSTRACTDeep sequencing of plasma RNA or proviral DNA may be an interesting alternative to population sequencing for the detection of baseline transmitted HIV-1 drug resistance. Using a Roche 454 GS Junior HIV-1 prototype kit, we performed deep sequencing of the HIV-1 protease and reverse transcriptase genes on paired plasma and buffy coat samples from newly diagnosed HIV-1-positive individuals. Selection was based on the outcome of population sequencing and included 12 patients with either a revertant amino acid at codon 215 of the reverse transcriptase or a singleton resistance mutation, 4 patients with multiple resistance mutations, and 4 patients with wild-type virus. Deep sequencing of RNA and DNA detected 6 and 43 mutations, respectively, that were not identified by population sequencing. A subsequently performed hypermutation analysis, however, revealed hypermutation in 61.19% of 3,188 DNA reads with a resistance mutation. The removal of hypermutated reads dropped the number of additional mutations in DNA from 43 to 17. No hypermutation evidence was found in the RNA reads. Five of the 6 additional RNA mutations and all additional DNA mutations, after full exclusion of hypermutation bias, were observed in the 3 individuals with multiple resistance mutations detected by population sequencing. Despite focused selection of patients with T215 revertants or singleton mutations, deep sequencing failed to identify the resistant T215Y/F or M184V or any other resistance mutation, indicating that in most of these cases there is no hidden resistance and that the virus detected at diagnosis by population sequencing is the original infecting variant.
Does Choice Matter? Reference-Based Alignment for Molecular Epidemiology of Tuberculosis
Authors: Lee Robyn S. , Behr Marcel A. 
Published: April 2016

ABSTRACT

When using genome sequencing for molecular epidemiology, short sequence reads are aligned to an arbitrary reference strain to detect single nucleotide polymorphisms. We investigated whether reference genome selection influences epidemiological inferences of
Mycobacterium tuberculosis
transmission by aligning sequence reads from 162 closely related lineage 4 (Euro-American) isolates to 7 different genomes. Phylogenetic trees were consistent with use of all but the most divergent genomes, suggesting that reference choice can be based on considerations other than
M. tuberculosis
lineage.
Etiological Role and Repeated Infections of Sapovirus among Children Aged Less than 2 Years in a Cohort Study in a Peri-urban Community of Peru
Authors: Liu Xiaofang , Jahuira Helena , Gilman Robert H. , Alva Alicia , Cabrera Lilia , Okamoto Michiko , Xu Hang , Windle Henry J. , Kelleher Dermot , Varela Marco , Verastegui Manuela , Calderon Maritza , Sanchez Gerardo , Sarabia Vanessa , Ballard Sarah B. , Bern Caryn , Mayta Holger , Crabtree Jean E. , Cama Vitaliano , Saito Mayuko , Oshitani Hitoshi 
Published: April 2016

ABSTRACT

Human sapovirus has been shown to be one of the most important etiologies in pediatric patients with acute diarrhea. However, very limited data are available about the causative roles and epidemiology of sapovirus in community settings. A nested matched case-control study within a birth cohort study of acute diarrhea in a peri-urban community in Peru from 2007 to 2010 was conducted to investigate the attributable fraction (AF) and genetic diversity of sapovirus. By quantitative reverse transcription–real-time PCR (qPCR) sapovirus was detected in 12.4% (37/299) of diarrheal and 5.7% (17/300) of nondiarrheal stools (
P
= 0.004). The sapovirus AF (7.1%) was higher in the second year (13.2%) than in the first year (1.4%) of life of children. Ten known genotypes and one novel cluster (
n
= 5) within four genogroups (GI, GII, GIV, and GV) were identified by phylogenetic analysis of a partial VP1 gene. Further sequence analysis of the full VP1 gene revealed a possible novel genotype, tentatively named GII.8. Notably, symptomatic reinfections with different genotypes within the same (
n
= 3) or different (
n
= 5) genogroups were observed in eight children. Sapovirus exhibited a high attributable burden for acute gastroenteritis, especially in the second year of life, of children in a Peruvian community. Further large-scale studies are needed to understand better the global burden, genetic diversity, and repeated infections of sapovirus.
Multiple Natural Substitutions in Avian Influenza A Virus PB2 Facilitate Efficient Replication in Human Cells
Authors: Mänz Benjamin , de Graaf Miranda , Mögling Ramona , Richard Mathilde , Bestebroer Theo M. , Rimmelzwaan Guus F. , Fouchier Ron A. M. 
Published: April 2016

ABSTRACT

A strong restriction of the avian influenza A virus polymerase in mammalian cells generally limits viral host-range switching. Although substitutions like E627K in the PB2 polymerase subunit can facilitate polymerase activity to allow replication in mammals, many human H5N1 and H7N9 viruses lack this adaptive substitution. Here, several previously unknown, naturally occurring, adaptive substitutions in PB2 were identified by bioinformatics, and their enhancing activity was verified using
in vitro
assays. Adaptive substitutions enhanced polymerase activity and virus replication in mammalian cells for avian H5N1 and H7N9 viruses but not for a partially human-adapted H5N1 virus. Adaptive substitutions toward basic amino acids were frequent and were mostly clustered in a putative RNA exit channel in a polymerase crystal structure. Phylogenetic analysis demonstrated divergent dependency of influenza viruses on adaptive substitutions. The novel adaptive substitutions found in this study increase basic understanding of influenza virus host adaptation and will help in surveillance efforts.

IMPORTANCE
Influenza viruses from birds jump the species barrier into humans relatively frequently. Such influenza virus zoonoses may pose public health risks if the virus adapts to humans and becomes a pandemic threat. Relatively few amino acid substitutions—most notably in the receptor binding site of hemagglutinin and at positions 591 and 627 in the polymerase protein PB2—have been identified in pandemic influenza virus strains as determinants of host adaptation, to facilitate efficient virus replication and transmission in humans. Here, we show that substantial numbers of amino acid substitutions are functionally compensating for the lack of the above-mentioned mutations in PB2 and could facilitate influenza virus emergence in humans.
Herpes Simplex Virus 1 Serine Protease VP24 Blocks the DNA-Sensing Signal Pathway by Abrogating Activation of Interferon Regulatory Factor 3
Authors: Zhang Dandan , Su Chenhe , Zheng Chunfu 
Published: April 2016

ABSTRACT
The interferon (IFN)-mediated antiviral response is a central aspect of host defense; however, viruses have evolved multiple strategies to counteract IFN-mediated responses in order to successfully infect the host. Herpes simplex virus 1 (HSV-1), a typical human-restricted DNA virus, is capable of counteracting host immune responses via several distinct viral proteins, thus establishing a lifelong latent infection. In this study, we demonstrate that the VP24 protein, a serine protease of HSV-1 essential for the formation and maturation of capsids, is a novel antagonist of the beta interferon (IFN-β) pathway. Here, VP24 was shown for the first time to dampen interferon stimulatory DNA (ISD)-triggered IFN-β production and inhibit IFN-β promoter activation induced by cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) and by STING, respectively. Further study demonstrated that ectopic expression of VP24 selectively blocked IFN regulatory factor 3 (IRF3) but not NF-κB promoter activation. In addition, VP24 was demonstrated to downregulate ISD-induced phosphorylation and dimerization of IRF3 during HSV-1 infection with a VP24 stable knockdown human foreskin fibroblast cell line. The underlying molecular mechanism is that VP24 abrogates the interaction between TANK-binding kinase 1 (TBK1) and IRF3, hence impairing IRF3 activation. These results illustrate that VP24 is able to block the production of IFN-β by inhibiting IRF3 activation, which may represent a critical adaptation to enable viral effective replication within the host.

IMPORTANCE
This study demonstrated that HSV-1 protein VP24 could inhibit IFN-β production and promoter activation triggered by ISD, cGAS and STING and by STING, respectively. VP24 selectively blocked IRF3 promoter activation and ISD-induced phosphorylation and dimerization of IRF3 without affecting the NF-κB promoter activation during viral infection. VP24 also inhibited IRF3 activation by impeding the interaction between TBK1 and IRF3 during viral infection. This study provides new insights into the immune evasion mediated by HSV-1 and identifies VP24 as a crucial effector for HSV-1 to evade the host DNA-sensing signal pathway.
A Single Amino Acid Substitution in Poliovirus Nonstructural Protein 2C
ATPase
Causes Conditional Defects in Encapsidation and Uncoating
Authors: Asare Emmanuel , Mugavero JoAnn , Jiang Ping , Wimmer Eckard , Paul Aniko V. 
Published: April 2016

ABSTRACT

The specificity of encapsidation of C-cluster enteroviruses depends on an interaction between capsid proteins and nonstructural protein 2C
ATPase
. In particular, residue N
252
of poliovirus 2C
ATPase
interacts with VP3 of coxsackievirus A20, in the context of a chimeric virus. Poliovirus 2C
ATPase
has important roles both in RNA replication and encapsidation. In this study, we searched for additional sites in 2C
ATPase
, near N
252
, that are required for encapsidation. Accordingly, segments adjacent to N
252
were analyzed by combining triple and single alanine mutations to identify residues required for function. Two triple alanine mutants exhibited defects in RNA replication. The remaining two mutations, located in secondary structures in a predicted three-dimensional model of 2C
ATPase
, caused lethal growth phenotypes. Most single alanine mutants, derived from the lethal variants, were either quasi-infectious and yielded variants with wild-type (wt) or temperature-sensitive (
ts
) growth phenotypes or had a lethal growth phenotype due to defective RNA replication. The K
259
A mutation, mapping to an α helix in the predicted structure of 2C
ATPase
, resulted in a cold-sensitive virus.
In vivo
protein synthesis and virus production were strikingly delayed at 33°C relative to the wt, suggesting a defect in uncoating. Studies with a reporter virus indicated that this mutant is also defective in encapsidation at 33°C. Cell imaging confirmed a much-reduced production of K
259
A mature virus at 33°C relative to the wt. In conclusion, we have for the first time linked a cold-sensitive encapsidation defect in 2C
ATPase
(K
259
A) to a subsequent delay in uncoating of the virus particle at 33°C during the next cycle of infection.

IMPORTANCE
Enterovirus morphogenesis, which involves the encapsidation of newly made virion RNA, is a process still poorly understood. Elucidation of this process is important for future drug development for a large variety of diseases caused by these agents. We have previously shown that the specificity of encapsidation of poliovirus and of C-cluster coxsackieviruses, which are prototypes of enteroviruses, is dependent on an interaction of capsid proteins with the multifunctional nonstructural protein 2C
ATPase
. In this study, we have searched for residues in poliovirus 2C
ATPase
, near a presumed capsid-interacting site, important for encapsidation. An unusual cold-sensitive mutant of 2C
ATPase
possessed a defect in encapsidation at 37°C and subsequently in uncoating during the next cycle of infection at 33°C. These studies not only reveal a new site in 2C
ATPase
that is involved in encapsidation but also identify a link between encapsidation and uncoating.
Enhancing exercise tolerance and physical activity in COPD with combined pharmacological and non-pharmacological interventions: PHYSACTO randomised, placebo-controlled study design
Authors: Troosters Thierry , Bourbeau Jean , Maltais François , Leidy Nancy , Erzen Damijan , De Sousa Dorothy , Korducki Lawrence , Hamilton Alan 
Published: April 2016

IntroductionChronic obstructive pulmonary disease (COPD) is associated with exercise limitation and physical inactivity, which are believed to have significant long-term negative health consequences for patients. While a number of COPD treatments and exercise training programmes increase exercise capacity, there is limited evidence for their effects on physical activity levels, with no clear association between exercise capacity and physical activity in clinical trials. Physical activity depends on a number of behaviour, environmental and physiological factors. We describe the design of the PHYSACTO trial, which is investigating the effects of bronchodilators, either alone or with exercise training, in combination with a standardised behaviour-change self-management programme, on exercise capacity and physical activity in patients with COPD. It is hypothesised that bronchodilators in conjunction with a behaviour-change self-management programme will improve physical activity and that this effect will be amplified by the addition of exercise training.Methods and analysisPatients are being recruited from 34 sites in Australia, New Zealand, the USA, Canada and Europe. Patients receiving a multicomponent intervention designed to support behaviour change related to physical activity are randomised to four treatment arms: placebo, tiotropium, tiotropium+olodaterol, and tiotropium+olodaterol+exercise training. The primary outcome is improvement in exercise capacity after 8 weeks, measured by endurance time during a shuttle walk test. The secondary outcome is improvement in physical activity, including objective accelerometer assessment and patient-reported functioning using the Functional Performance Inventory—Short Form and the novel hybrid PROactive instrument. Additionally, the influence of moderating variables (ie, factors influencing a patient's choice to be physically active) on increases in physical activity is also explored.Ethics and disseminationThe study has been approved by the relevant Institutional Review Boards, Independent Ethics Committee and Competent Authority according to national and international regulations. The findings of the trial will be disseminated through relevant peer-reviewed journals and international conference presentations.Trial registration numberNCT02085161.
Diagnostic accuracy of the Depression subscale of the Hospital Anxiety and Depression Scale (HADS-D) for detecting major depression: protocol for a systematic review and individual patient data meta-analyses
Authors: Thombs Brett D , Benedetti Andrea , Kloda Lorie A , Levis Brooke , Azar Marleine , Riehm Kira E , Saadat Nazanin , Cuijpers Pim , Gilbody Simon , Ioannidis John P A , McMillan Dean , Patten Scott B , Shrier Ian , Steele Russell J , Ziegelstein Roy C , Loiselle Carmen G , Henry Melissa , Ismail Zahinoor , Mitchell Nicholas , Tonelli Marcello 
Published: April 2016

IntroductionThe Depression subscale of the Hospital Anxiety and Depression Scale (HADS-D) has been recommended for depression screening in medically ill patients. Many existing HADS-D studies have used exploratory methods to select optimal cut-offs. Often, these studies report results from a small range of cut-off thresholds; cut-offs with more favourable accuracy results are more likely to be reported than others with worse accuracy estimates. When published data are combined in meta-analyses, selective reporting may generate biased summary estimates. Individual patient data (IPD) meta-analyses can address this problem by estimating accuracy with data from all studies for all relevant cut-off scores. In addition, a predictive algorithm can be generated to estimate the probability that a patient has depression based on a HADS-D score and clinical characteristics rather than dichotomous screening classification alone. The primary objectives of our IPD meta-analyses are to determine the diagnostic accuracy of the HADS-D to detect major depression among adults across all potentially relevant cut-off scores and to generate a predictive algorithm for individual patients. We are already aware of over 100 eligible studies, and more may be identified with our comprehensive search.Methods and analysisData sources will include MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, PsycINFO and Web of Science. Eligible studies will have datasets where patients are assessed for major depression based on a validated structured or semistructured clinical interview and complete the HADS-D within 2 weeks (before or after). Risk of bias will be assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Bivariate random-effects meta-analysis will be conducted for the full range of plausible cut-off values, and a predictive algorithm for individual patients will be generated.Ethics and disseminationThe findings of this study will be of interest to stakeholders involved in research, clinical practice and policy.