bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of Whole-Genome Sequencing for Identification and Characterization of Shiga Toxin-Producing Escherichia coli To Produce Standardized Data To Enable Data Sharing
Authors: Holmes Anne , Dallman Timothy J. , Shabaan Sharif , Hanson Mary , Allison Lesley 
Published: December 2017

ABSTRACT

Whole-genome sequencing (WGS) is rapidly becoming the method of choice for outbreak investigations and public health surveillance of microbial pathogens. The combination of improved cluster resolution and prediction of resistance and virulence phenotypes provided by a single tool is extremely advantageous. However, the data produced are complex, and standard bioinformatics pipelines are required to translate the output into easily interpreted epidemiologically relevant information for public health action. The main aim of this study was to validate the implementation of WGS at the Scottish
Escherichia coli
O157/STEC Reference Laboratory (SERL) using the Public Health England (PHE) bioinformatics pipeline to produce standardized data to enable interlaboratory comparison of results generated at two national reference laboratories. In addition, we evaluated the BioNumerics whole-genome multilocus sequence typing (wgMLST) and
E. coli
genotyping plug-in tools using the same data set. A panel of 150 well-characterized isolates of Shiga toxin-producing
E. coli
(STEC) that had been sequenced and analyzed at PHE using the PHE pipeline and database (SnapperDB) was assembled to provide identification and typing data, including serotype (O:H type), sequence type (ST), virulence genes (
eae
and Shiga toxin [
stx
] subtype), and a single-nucleotide polymorphism (SNP) address. To validate the implementation of sequencing at the SERL, DNA was reextracted from the isolates and sequenced and analyzed using the PHE pipeline, which had been installed at the SERL; the output was then compared with the PHE data. The results showed a very high correlation between the data, ranging from 93% to 100%, suggesting that the standardization of WGS between our reference laboratories is possible. We also found excellent correlation between the results obtained using the PHE pipeline and BioNumerics, except for the detection of
stx
2a
and
stx
2c
when these subtypes are both carried by strains.
Major Histocompatibility Complex Class I (FLA-E*01801) Molecular Structure in Domestic Cats Demonstrates Species-Specific Characteristics in Presenting Viral Antigen Peptides
Authors: Liang Ruiying , Sun Yaping , Liu Yanjie , Wang Junya , Wu Yanan , Li Zibin , Ma Lizhen , Zhang Nan , Zhang Lijie , Wei Xiaohui , Qu Zehui , Zhang Nianzhi , Xia Chun 
Published: December 2017

ABSTRACT

Feline immunodeficiency virus (FIV) infection in domestic cats is the smallest usable natural model for lentiviral infection studies. FLA-E*01801 was applied to FIV AIDS vaccine research. We determined the crystal structure of FLA-E*01801 complexed with a peptide derived from FIV (gag positions 40 to 48; RMANVSTGR [RMA9]). The A pocket of the FLA-E*01801 complex plays a valuable restrictive role in peptide binding. Mutation experiments and circular-dichroism (CD) spectroscopy revealed that peptides with Asp at the first position (P1) could not bind to FLA-E*01801. The crystal structure and
in vitro
refolding of the mutant FLA-E*01801 complex demonstrated that Glu
63
and Trp
167
in the A pocket play important roles in restricting P1D. The B pocket of the FLA-E*01801 complex accommodates M/T/A/V/I/L/S residues, whereas the negatively charged F pocket prefers R/K residues. Based on the peptide binding motif, 125 FLA-E*01801-restricted FIV nonapeptides (San Diego isolate) were identified. Our results provide the structural basis for peptide presentation by the FLA-E*01801 molecule, especially A pocket restriction on peptide binding, and identify the potential cytotoxic T lymphocyte (CTL) epitope peptides of FIV presented by FLA-E*01801. These results will benefit both the reasonable design of FLA-E*01801-restricted CTL epitopes and the further development of the AIDS vaccine.

IMPORTANCE
Feline immunodeficiency virus (FIV) is a viral pathogen in cats, and this infection is the smallest usable natural model for lentivirus infection studies. To examine how FLA I presents FIV epitope peptides, we crystallized and solved the first classic feline major histocompatibility complex class I (MHC-I) molecular structure. Surprisingly, pocket A restricts peptide binding. Trp
167
blocks the left side of pocket A, causing P1D to conflict with Glu
63
. We also identified the FLA-E*01801 binding motif X (except D)-(M/T/A/V/I/L/S)-X-X-X-X-X-X-(R/K) based on structural and biochemical experiments. We identified 125 FLA-E*01801-restricted nonapeptides from FIV. These results are valuable for developing peptide-based FIV and human immunodeficiency virus (HIV) vaccines and for studying how MHC-I molecules present peptides.
Cryo-Electron Microscopy Structure of Seneca Valley Virus Procapsid
Authors: Strauss Mike , Jayawardena Nadishka , Sun Eileen , Easingwood Richard A. , Burga Laura N. , Bostina Mihnea 
Published: December 2017

ABSTRACT

Seneca Valley virus (SVV), like some other members of the
Picornaviridae
, forms naturally occurring empty capsids, known as procapsids. Procapsids have the same antigenicity as full virions, so they present an interesting possibility for the formation of stable virus-like particles. Interestingly, although SVV is a livestock pathogen, it has also been found to preferentially infect tumor cells and is being explored for use as a therapeutic agent in the treatment of small-cell lung cancers. Here we used cryo-electron microscopy to investigate the procapsid structure and describe the transition of capsid protein VP0 to the cleaved forms of VP4 and VP2. We show that the SVV receptor binds the procapsid, as evidence of its native antigenicity. In comparing the procapsid structure to that of the full virion, we also show that a cage of RNA serves to stabilize the inside surface of the virus, thereby making it more acid stable.

IMPORTANCE
Viruses are extensively studied to help us understand infection and disease. One of the by-products of some virus infections are the naturally occurring empty virus capsids (containing no genome), termed procapsids, whose function remains unclear. Here we investigate the structure and formation of the procapsids of Seneca Valley virus, to better understand how they form, what causes them to form, how they behave, and how we can make use of them. One potential benefit of this work is the modification of the procapsid to develop it for targeted
in vivo
delivery of therapeutics or to make a stable vaccine against SVV, which could be of great interest to the agricultural industry.
Dissection of Epitope-Specific Mechanisms of Neutralization of Influenza Virus by Intact IgG and Fab Fragments
Authors: Williams James A. , Gui Long , Hom Nancy , Mileant Alexander , Lee Kelly K. 
Published: December 2017

ABSTRACT
The neutralizing antibody (nAb) response against the influenza virus hemagglutinin (HA) fusion glycoprotein is important for preventing viral infection, but we lack a comprehensive understanding of the mechanisms by which these antibodies act. Here we investigated the effect of nAb binding and the role of IgG bivalency in the inhibition of HA function for nAbs targeting distinct HA epitopes. HC19 targets the receptor binding pocket at the distal end of HA, while FI6v3 binds primarily to the HA2 fusion subunit toward the base of the stalk. Surprisingly, HC19 inhibited the ability of HA to induce lipid mixing by preventing the structural rearrangement of HA under fusion-activating conditions. These results suggest that nAbs such as HC19 not only act by blocking receptor binding but also inhibit key late-stage HA conformational changes required for fusion. Intact HC19 IgG was also shown to cross-link separate virus particles, burying large proportions of HA within aggregates where they are blocked from interacting with target membranes; Fabs yielded no such aggregation and displayed weaker neutralization than IgG, emphasizing the impact of bivalency on the ability to neutralize virus. In contrast, the stem-targeting nAb FI6v3 did not aggregate particles. The Fab fragment was significantly less effective than IgG in preventing both membrane disruption and fusion. We infer that interspike cross-linking within a given particle by FI6v3 IgG may be critical to its potent neutralization, as no significant neutralization occurred with Fabs. These results demonstrate that IgG bivalency enhances HA inhibition through functionally important modes not evident in pared-down Fab-soluble HA structures.

IMPORTANCE
The influenza virus hemagglutinin (HA) fusion glycoprotein mediates entry into target cells and is the primary antigenic target of neutralizing antibodies (nAbs). Our current structural understanding of mechanisms of antibody (Ab)-mediated neutralization largely relies on the high-resolution characterization of antigen binding (Fab) fragments in complex with soluble, isolated antigen constructs by cryo-electron microscopy (EM) single-particle reconstruction or X-ray crystallography. Interactions between full-length IgG and whole virions have not been well characterized, and a gap remains in our understanding of how intact Abs neutralize virus and prevent infection. Using structural and biophysical approaches, we observed that Ab-mediated inhibition of HA function and neutralization of virus infectivity occur by multiple coexisting mechanisms, are largely dependent on the specific epitope that is targeted, and are highly dependent on the bivalent nature of IgG molecules.
Healthcare resource availability and cardiovascular health in the USA
Authors: Pilkerton Courtney S , Singh Sarah S , Bias Thomas K , Frisbee Stephanie J 
Published: December 2017

ObjectivesCardiovascular disease (CVD) remains the leading cause of death in the USA. Reducing the population-level burden of CVD disease will require a better understanding and support of cardiovascular health (CVH) in individuals and entire communities. The objectives for this study were to examine associations between community-level healthcare resources (HCrRes) and CVH in individuals and entire communities.SettingThis study consisted of a retrospective, cross-sectional study design, using multivariable epidemiological analyses.ParticipantsAll participants in the 2011 Behavioral Risk Factor Surveillance System (BRFSS) survey were examined for eligibility. CVH, defined using the American Heart Association CVH Index (CVHI), was determined using self-reported responses to 2011 BRFSS questions. Data for determining HCrRes were obtained from the Area Health Resource File. Regression analysis was performed to examine associations between healthcare resources and CVHI in communities (linear regression) and individuals (Poisson regression).ResultsMean CVHI was 3.3±0.005 and was poorer in the Southeast and Appalachian regions of the USA. Supply of primary care physicians and physician assistants were positively associated with individual and community-level CVHI, while CVD specialist supply was negatively associated with CVHI. Individuals benefiting most from increased supply of primary care providers were: middle aged; female; had non-Hispanic other race/ethnicity; those with household income <$25 000/year; and those in non-urban communities with insurance coverage.ConclusionsOur results support the importance of primary care provider supply for both individual and community CVHI, though not all sociodemographic groups benefited equally from additional primary care providers. Further research should investigate policies and factors that can effectively increase primary care provider supply and influence where they practice.
Study protocol forSmartphoneMonitoring forAtrial fibrillation inReal-Time in India (SMART-India): a community-based screening and referral programme
Authors: Soni Apurv , Karna Sunil , Patel Harshil , Fahey Nisha , Raithatha Shyamsundar , Handorf Anna , Bostrom John , Bashar Syed , Talati Kandarp , Shah Ravi , Goldberg Robert J , Thanvi Sunil , Phatak Ajay Gajanan , Allison Jeroan J , Chon Ki , Nimbalkar Somashekhar Marutirao , McManus David D 
Published: December 2017

IntroductionAtrial fibrillation (AF), the world’s most common arrhythmia, often goes undetected and untreated in low-resource communities, including India, where AF epidemiology is undefined. AF is an important risk factor for stroke, which plagues an estimated 1.6 million Indians annually. As such, early detection of AF and management of high-risk patients is critically important to decrease stroke burden in individuals with AF. This study aims to describe the epidemiology of AF in Anand District, Gujarat, India, characterise the clinical profile of individuals who are diagnosed with AF and determine the performance of two mobile technologies for community-based AF screening.MethodsThis observational study builds on findings from a previous feasibility study and leverages two novel technologies as well as an existing community health programme to perform door-to-door AF screening for 2000 people from 60 villages of Anand District, Gujarat, India using local health workers. A single-lead ECG and a pulse-based application is used to screen each individual for AF three times over a period of 5 days. Participants with suspected arrhythmias are followed up by study cardiologist who makes final diagnoses. Participants diagnosed with AF are initiated on treatment based on current anticoagulation guidelines and clinical reasoning.Analytical planAge-stratified and sex-stratified prevalence of AF in the Anand District will be calculated for sample and estimated for Anand distribution using survey design weights. Sociodemographic and clinical factors associated with AF will be evaluated using multivariable regression methods. Performance of each mobile technology in detecting AF will be evaluated using a 12-lead ECG interpretation as the gold standard.Ethics and disseminationThis protocol was approved separately by the Institutional Review Board of University of Massachusetts Medical School and the Human Research Ethics Committee at Charutar Arogya Mandal. The findings of this study will be disseminated through peer-reviewed journals and scientific conferences.
Oral medicine modification for older adults: a qualitative study of nurses
Authors: Mc Gillicuddy Aoife , Crean Abina M , Kelly Maria , Sahm Laura 
Published: December 2017

ObjectiveOral medicines are frequently modified (eg, tablets crushed) for older adults. However, these modifications can have clinical, legal and/or ethical implications. Nurses bear responsibility for medicine administration and hence, perform these modifications. The aim of this study was to investigate the knowledge, attitudes and beliefs of nurses about oral medicine modification for older adults.DesignA qualitative study was conducted using semi-structured, face-to-face interviews with nurses providing care to older adults in acute and long-term care settings. Interviews were audio-recorded, transcribed verbatim and analysed thematically.SettingsSixteen purposively selected care settings; 4 acute-care and 12 long-term care settings were included. Nurses were recruited by convenience sampling at these sites.ParticipantsEighteen nurses participated (83% female, 67% long-term care, 33% acute-care, median age (IQR) 38 years (32.5–52.0)).ResultsThree major themes: modifying—a necessary evil, nurses’ role as patient advocate and modifying—we are working very much as a teamand two minor themes: fractional dosing, and covert administration emerged from the data. Nurses viewed oral medicine modifications as being a routine and necessary occurrence in geriatric patient care due to limitations of available formulations and the presence of age-related challenges in drug administration. Nurses’ knowledge of residents’ requirements ensured that they advocate for those with individualised formulation needs, however, nurses rely on pharmacists for information about modifications. Nurses expressed a desire for supports including increased education and ward-specific, pharmacist-developed recommendations on common modifications.ConclusionsThis study has provided useful insights into the views of nurses regarding oral medicine modification for older adults. The unique and varied formulation requirements of older adults must be acknowledged. Increased engagement by healthcare professionals, the pharmaceutical industry, regulatory agencies and policy-makers is required to facilitate the development of age-appropriate formulations. In the interim, practical interventions, informed by the findings of this study, are required.
Dialogues between nurses, patients with heart failure and their partners during a dyadic psychoeducational intervention: a qualitative study
Authors: Liljeroos Maria , Ågren Susanna , Jaarsma Tiny , Stromberg Anna 
Published: December 2017

ObjectivesTo describe nurses’ documentation of the content in a psychoeducational intervention inspired by Stuifbergen’s model addressing cognitive, supportive and behavioural needs of patient–partner dyads affected by heart failure.DesignA descriptive qualitative design was used analysing nurses’ documentation in a dialogue guide based on a health promotion model.SettingsThe dialogue guide was used during three nurse-led sessions at two heart failure clinics in Sweden with patients affected with heart failure and their partners during the years 2005–2008.ParticipantsThe dialogue guides from 71 patient–partner dyads were analysed using direct deductive content analyses. Patients’ mean age was 69 years and 31% were female, partners’ mean age was 67 years and 69% were female.ResultsThe findings supported the conceptual health promotion model and identified barriers, recourses and self-efficacy described by the dyads within each category.ConclusionThe dyads described that during the sessions, they had gained enhanced knowledge and greater confidence to handle their life situation and expressed that they needed psychoeducational support during the whole illness trajectory. The results may guide and help to improve content and quality when caring for patients affected with heart failure and their partners and also when designing new interventions.Trial registration numberNCT02398799; Post-results.
Mapping Evidence of Patients’ Experiences in Integrated Care Settings: A Protocol for a Scoping Review
Authors: Youssef Alaa T , Constantino Rosa , Chaudhary Zarah K , Lee Andrew , Wiljer David , Mylopoulos Maria , Sockalingam Sanjeev 
Published: December 2017

IntroductionIntegrated care (IC) models have emerged to address gaps in care for individuals with complex healthcare needs. Although the clinical and cost-effectiveness of IC models are well-established, our understanding of whether IC models facilitate a patient-centred care experience from the patients’ perspective is not well understood. This scoping review aims to comprehensively map the literature to provide a broad overview of patients’ experiences in IC settings with a focus on the experiences of complex patients with comorbid mental and physical illnesses. It also aims to describe current gaps identified in the literature in our understanding of aspects of care that are often unrecognised.Methods and analysisUsing established scoping review frameworks and guidelines, we will perform a comprehensive search in the following databases: MEDLINE, EMBASE, PsycINFO, CINAHL, AMED and the Cochrane Library to identify relevant studies on patients’ experiences in IC models. Grey literature sources and studies bibliographies will also be searched to identify relevant studies and documents. Data will be extracted and summarised using descriptive statistical and qualitative analyses. We will also consult with stakeholders from various backgrounds to enhance the comprehensiveness of this review.Ethics and disseminationThis review requires no ethical approval. Findings from this study will be disseminated through publication in a peer-reviewed journal, clinical conferences and in knowledge translation settings, aiming to improve clinical practice and care delivery.
Therapist-guided internet-delivered cognitive–behavioural therapy supplemented with group exposure sessions for adolescents with social anxiety disorder: a feasibility trial
Authors: Nordh Martina , Vigerland Sarah , Öst Lars-Göran , Ljótsson Brjánn , Mataix-Cols David , Serlachius Eva , Högström Jens 
Published: December 2017

ObjectivesSocial anxiety disorder (SAD) is one of the most common psychiatric disorders in youth, with a prevalence of about 3%–4% and increased risk of adverse long-term outcomes, such as depression. Cognitive–behavioural therapy (CBT) is considered the first-line treatment for youth with SAD, but many adolescents remain untreated due to limited accessibility to CBT. The aim of this study was to develop and evaluate the feasibility and preliminary efficacy of a therapist-guided internet-delivered CBT treatment, supplemented with clinic-based group exposure sessions (BIP SOFT).DesignA proof-of-concept, open clinical trial with 6-month follow-up.ParticipantsThe trial was conducted at a child and adolescent psychiatric research clinic, and participants (n=30) were 13–17 years old (83% girls) with a principal diagnosis of SAD.Intervention12 weeks of intervention, consisting of nine remote therapist-guided internet-delivered CBT sessions and three group exposure sessions at the clinic for the adolescents and five internet-delivered sessions for the parents.ResultsAdolescents were generally satisfied with the treatment, and the completion rate of internet modules, as well as attendance at group sessions, was high. Post-treatment assessment showed a significant decrease in clinician-rated, adolescent-rated and parent-rated social anxiety (d=1.17, 0.85 and 0.79, respectively), as well as in general self-rated and parent-rated anxiety and depression (d=0.76 and 0.51), compared with pretreatment levels. Furthermore, 47% of participants no longer met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for SAD at post-treatment. At a 6-month follow-up, symptom reductions were maintained, or further improved, and 57% of participants no longer met criteria for SAD.ConclusionTherapist-guided and parent-guided internet-delivered CBT, supplemented with a limited number of group exposure sessions, is a feasible and promising intervention for adolescents with SAD.Trial registration numberNCT02576171; Results.