bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aspergillus fumigatus Preexposure Worsens Pathology and Improves Control of Mycobacterium abscessus Pulmonary Infection in Mice
Authors: Monin Leticia , Mehta Shail , Elsegeiny Waleed , Gopal Radha , McAleer Jeremy P. , Oury Tim D. , Kolls Jay , Khader Shabaana A. 
Published: December 2017

ABSTRACT

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Mutations in this chloride channel lead to mucus accumulation, subsequent recurrent pulmonary infections, and inflammation, which, in turn, cause chronic lung disease and respiratory failure. Recently, rates of nontuberculous mycobacterial (NTM) infections in CF patients have been increasing. Of particular relevance is infection with
Mycobacterium abscessus
, which causes a serious, life-threatening disease and constitutes one of the most antibiotic-resistant NTM species. Interestingly, an increased prevalence of NTM infections is associated with worsening lung function in CF patients who are also coinfected with
Aspergillus fumigatus
. We established a new mouse model to investigate the relationship between
A. fumigatus
and
M. abscessus
pulmonary infections. In this model, animals exposed to
A. fumigatus
and coinfected with
M. abscessus
exhibited increased lung inflammation and decreased mycobacterial burden compared with those of mice infected with
M. abscessus
alone. This increased control of
M. abscessus
infection in coinfected mice was mucus independent but dependent on both transcription factors T-box 21 (Tbx21) and retinoic acid receptor (RAR)-related orphan receptor gamma t (RORγ-t), master regulators of type 1 and type 17 immune responses, respectively. These results implicate a role for both type 1 and type 17 responses in
M. abscessus
control in
A. fumigatus
-coinfected lungs. Our results demonstrate that
A. fumigatus
, an organism found commonly in CF patients with NTM infection, can worsen pulmonary inflammation and impact
M. abscessus
control in a mouse model.
Genome-Based Analysis of Enterococcus faecium Bacteremia Associated with Recurrent and Mixed-Strain Infection
Authors: Raven Kathy E. , Gouliouris Theodore , Parkhill Julian , Peacock Sharon J. 
Published: December 2017

ABSTRACT

Vancomycin-resistant
Enterococcus faecium
(VREfm) bloodstream infections are associated with high recurrence rates. This study used genome sequencing to accurately distinguish the frequency of relapse and reinfection in patients with recurrent
E. faecium
bacteremia and to investigate strain relatedness in patients with apparent VREfm and vancomycin-susceptible
E. faecium
(VSEfm) mixed infection. A retrospective study was performed at the Cambridge University Hospitals NHS Foundation Trust (CUH) between November 2006 and December 2012. We analyzed the genomes of 44
E. faecium
isolates from 21 patients (26 VREfm isolates from 12 patients with recurrent bacteremia and 18 isolates from 9 patients with putative VREfm/VSEfm mixed infection). Phenotypic antibiotic susceptibility was determined using a Vitek2 instrument. Genomes were compared with those of a further 263
E. faecium
isolates associated with bacteremia in patients at CUH over the same time period. Pairwise comparison of core genomes indicated that 10 (71%) episodes of recurrent VREfm bacteremia were due to reinfection with a new strain, with reinfection being more likely with increasing time between the two positive cultures. The majority (78%) of patients with a mixed VREfm and VSEfm infection had unrelated strains. More than half (59%) of study isolates were closely related to another isolate associated with bacteremia from CUH. This included 60% of isolates associated with reinfection, indicating acquisition in the hospital. This study provides the first high-resolution insights into recurrence and mixed infection by
E. faecium
and demonstrates that reinfection with a new strain, often acquired from the hospital, is a driver of recurrence.
Parallel Validation of Three Molecular Devices for Simultaneous Detection and Identification of Influenza A and B and Respiratory Syncytial Viruses
Authors: Ling Lifen , Kaplan Samuel E. , Lopez Juan C. , Stiles Jeffrey , Lu Xuedong , Tang Yi-Wei 
Published: December 2017

ABSTRACT

Rapid identification of respiratory pathogens, such as influenza virus A (FluA), influenza virus B (FluB), and respiratory syncytial virus (RSV), reduces unnecessary antimicrobial use and enhances infection control practice. We performed a comparative evaluation of three molecular methods: (i) the Aries Flu A/B & RSV, (ii) the Xpert Xpress Flu/RSV, and (iii) the Cobas Flu A/B & RSV assays. The clinical performances of the three methods were evaluated using 200 remnant nasopharyngeal swab (NPS) specimens against a combined reference standard. The limits of detection (LODs) were determined using FluA, FluB, and RSV control strains with known titers. The 95% LODs were between 1.702 and 0.0003 50% tissue culture infective dose (TCID
50
), with no significant differences revealed among the three assays. Perfect qualitative detection agreement was obtained in the reproducibility study. The Cobas assay failed at the first run on 13 clinical specimens, resulting in an invalid rate of 6.5%. The sensitivities and specificities for all assays were 96.0 to 100.0% and 99.3 to 100% for all three viruses. For on-demand single-specimen and batched 12-specimen workflows, the test turnaround times were 115.5 and 128.8 min for the Aries assay (12 sample capacity), 34.2 and 44.2 min for the Xpress assay (16 sample capacity), and 21.0 and 254.4 min for the Cobas assay (one instrument), respectively. In summary, the Aries, Xpress, and Cobas Liat assays demonstrated excellent sensitivities and specificities for simultaneous detection and identification of FluA, FluB, and RSV from NPS specimens in cancer patients. Test turnaround time was significantly shorter on the Xpress when instrument scalability is unlimited.
Enhancing the Thermostability and Immunogenicity of a Respiratory Syncytial Virus (RSV) Live-Attenuated Vaccine by Incorporating Unique RSV Line19F Protein Residues
Authors: Rostad Christina A. , Stobart Christopher C. , Todd Sean O. , Molina Samuel A. , Lee Sujin , Blanco Jorge C. G. , Moore Martin L. 
Published: December 2017

ABSTRACTRespiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants, and an effective vaccine is not yet available. We previously generated an RSV live-attenuated vaccine (LAV) candidate, DB1, which was attenuated by a low-fusion subgroup B F protein (BAF) and codon-deoptimized nonstructural protein genes. DB1 was immunogenic and protective in cotton rats but lacked thermostability and stability of the prefusion conformation of F compared to strains with the line19F gene. We hypothesized that substitution of unique residues from the thermostable A2-line19F strain could thermostabilize DB1 and boost its immunogenicity. We therefore substituted 4 unique line19F residues into the BAF protein of DB1 by site-directed mutagenesis and rescued the recombinant virus, DB1-QUAD. Compared to DB1, DB1-QUAD had improved thermostability at 4°C and higher levels of prefusion F as measured by enzyme-linked immunosorbent assays (ELISAs). DB1-QUAD was attenuated in normal human bronchial epithelial cells, in BALB/c mice, and in cotton rats but grew to wild-type titers in Vero cells. In mice, DB1-QUAD was highly immunogenic and generated significantly higher neutralizing antibody titers to a panel of RSV A and B strains than did DB1. DB1-QUAD was also efficacious against wild-type RSV challenge in mice and cotton rats. Thus, substitution of unique line19F residues into RSV LAV DB1 enhanced vaccine thermostability, incorporation of prefusion F, and immunogenicity and generated a promising vaccine candidate that merits further investigation.IMPORTANCEWe boosted the thermostability and immunogenicity of an RSV live-attenuated vaccine candidate by substituting 4 unique residues from the RSV line19F protein into the F protein of the heterologous vaccine strain DB1. The resultant vaccine candidate, DB1-QUAD, was thermostable, attenuatedin vivo, highly immunogenic, and protective against RSV challenge in mice and cotton rats.
Death, injury and disability from kinetic impact projectiles in crowd-control settings: a systematic review
Authors: Haar Rohini J , Iacopino Vincent , Ranadive Nikhil , Dandu Madhavi , Weiser Sheri D 
Published: December 2017

ObjectiveWe conducted a systematic review of the available literature on deaths, injuries and permanent disability from rubber and plastic bullets, as well as from bean bag rounds, shot pellets and other projectiles used in arrests, protests and other contexts from 1 January 1990 until 1 June 2017.Data sourcesPubMed, Scopus, JSTOR and grey literature.Data synthesisWe report on descriptive statistics as well as data on injury severity, permanent disability and death. We analysed potential risk factors for injury severity, including the site of impact, firing distance and access to medical care.ResultsOf 3228 identified articles, 26 articles met inclusion criteria. These articles included injury data on 1984 people, 53 of whom died as a result of their injuries. 300 people suffered permanent disability. Deaths and permanent disability often resulted from strikes to the head and neck (49.1% of deaths and 82.6% of permanent disabilities). Of the 2135 injuries in those who survived their injuries, 71% were severe, injuries to the skin and to the extremities were most frequent. Anatomical site of impact, firing distance and timely access to medical care were correlated with injury severity and risk of disability.ConclusionsKinetic impact projectiles (KIPs), often called rubber or plastic bullets, are used commonly in crowd-control settings. We find that these projectiles have caused significant morbidity and mortality during the past 27 years, much of it from penetrative injuries and head, neck and torso trauma. Given their inherent inaccuracy, potential for misuse and associated health consequences of severe injury, disability and death, KIPs do not appear to be appropriate weapons for use in crowd-control settings. There is an urgent need to establish international guidelines on the use of crowd-control weapons to prevent unnecessary injuries and deaths.
Bleeding risk in patients using oral anticoagulants submitted to surgical procedures in dentistry: a systematic review protocol
Authors: Motta Rogério Heládio Lopes , Bergamaschi Cristiane de Cássia , de Andrade Natalia Karol , Guimaraes Caio Chaves , Ramacciato Juliana Cama , Araújo Jimmy de Oliveira , Lopes Luciane Cruz 
Published: December 2017

IntroductionThe management of patients undergoing oral surgical procedures using anticoagulants raises concerns regarding the risk of bleeding. Bleeding rates in those patients during or after oral surgical procedures are uncertain. The aim of this study will be to determine the bleeding rate during and after oral surgeries in patients using anticoagulants.Methods and analysisA systematic review will be conducted and if appropriate, a meta-analysis of randomised clinical trials evaluating the bleeding risk during and after oral surgical procedures in patients using anticoagulants were selected. The literature search will be conducted using electronic databases, such as the Cochrane Central Register of Controlled Trials, MEDLINE (via Ovid), Embase (via Ovid), Cumulative Index to Nursing and Allied Health Literature (via Ovid), LILACS (SciELO) and CAPES database, without restriction of languages or date of publication. The primary outcome will be the occurrence of local bleeding rate during and after oral surgical procedures, and as secondary outcome, the following complications will be considered: implant failure, healing problems and infections. Groups of two independent reviewers will select the titles and abstracts for full-text eligibility. For eligible studies, the same reviewers will perform data extraction, bias risk assessment and determination of the overall quality of evidence for each of the outcomes using the Grading of Recommendations Assessment, Development and Evaluation classification system. Meta-analysis and subgroup analyses will be conducted, to all outcomes, if appropriate.Ethics and disseminationThe systematic review will be published in a peer-reviewed journal, and brief reports of the review’s findings will be released directly to the intended audience. The results will help dentists in the decision-making process to minimise the risk of bleeding in patients using anticoagulants in their clinical practice.PROSPERO registration numberCRD42017056986.
Migration pattern and mortality of ethnic German migrants from the former Soviet Union: a cohort study in Germany
Authors: Kaucher Simone , Deckert Andreas , Becher Heiko , Winkler Volker 
Published: December 2017

ObjectiveWe aimed to investigate all-cause and cause-specific mortality among ethnic German migrants from the former Soviet Union by different immigration periods to describe associations with migration pattern and mortality.DesignWe used pooled data from three retrospective cohort studies in Germany.ParticipantsEthnic German migrants from the former Soviet Union (called resettlers), who immigrated to Germany since 1990 to the federal states North Rhine-Westphalia and Saarland and to the region of Augsburg (n=59 390).OutcomeAll-cause and cause-specific mortality among resettlers in comparison to the general German population, separated by immigration period.MethodsImmigration periods were defined following legislative changes in German immigration policy (1990–1992, 1993–1995, 1996+). Resettlers’ characteristics were described accordingly. To investigate mortality differences by immigration period, we calculated age-standardised mortality rates (ASRs) and standardised mortality ratios (SMRs) of resettlers in comparison to the general German population. Additionally, we modelled sex-specific ASRs with Poisson regression, using age, year and immigration period as independent variables.ResultsThe composition of resettlers differed by immigration period. Since 1993, the percentage of resettlers from the Russian Federation and non-German spouses increased. Higher all-cause mortality was found among resettlers who immigrated in 1996 and after (ASR 628.1, 95% CI 595.3 to 660.8), compared with resettlers who immigrated before 1993 (ASR 561.8, 95% CI 537.2 to 586.4). SMR analysis showed higher all-cause mortality among resettler men from the last immigration period compared with German men (SMR 1.11, 95% CI 1.04 to 1.19), whereas resettlers who immigrated earlier showed lower all-cause mortality. Results from Poisson regression, adjusted for age and year, corroborated those findings.ConclusionsMortality differences by immigration period suggest different risk-factor patterns and possibly deteriorated integration opportunities. Health policy should guard the consequences of immigration law alterations with respect to changing compositions of migrant groups and their health status.
International perception of lung sounds: a comparison of classification across some European borders
Authors: Aviles-Solis Juan Carlos , Vanbelle Sophie , Halvorsen Peder A , Francis Nick , Cals Jochen W L , Andreeva Elena A , Marques Alda , Piirilä Päivi , Pasterkamp Hans , Melbye Hasse 
Published: December 2017

IntroductionLung auscultation is helpful in the diagnosis of lung and heart diseases; however, the diagnostic value of lung sounds may be questioned due to interobserver variation. This situation may also impair clinical research in this area to generate evidence-based knowledge about the role that chest auscultation has in a modern clinical setting. The recording and visual display of lung sounds is a method that is both repeatable and feasible to use in large samples, and the aim of this study was to evaluate interobserver agreement using this method.MethodsWith a microphone in a stethoscope tube, we collected digital recordings of lung sounds from six sites on the chest surface in 20 subjects aged 40 years or older with and without lung and heart diseases. A total of 120 recordings and their spectrograms were independently classified by 28 observers from seven different countries. We employed absolute agreement and kappa coefficients to explore interobserver agreement in classifying crackles and wheezes within and between subgroups of four observers.ResultsWhen evaluating agreement on crackles (inspiratory or expiratory) in each subgroup, observers agreed on between 65% and 87% of the cases. Conger’s kappa ranged from 0.20 to 0.58 and four out of seven groups reached a kappa of ≥0.49. In the classification of wheezes, we observed a probability of agreement between 69% and 99.6% and kappa values from 0.09 to 0.97. Four out of seven groups reached a kappa ≥0.62.ConclusionsThe kappa values we observed in our study ranged widely but, when addressing its limitations, we find the method of recording and presenting lung sounds with spectrograms sufficient for both clinic and research. Standardisation of terminology across countries would improve international communication on lung auscultation findings.
Prevalence and prognostic value of echocardiographic screening for rheumatic heart disease
Authors: Kotit Susy , Said Karim , ElFaramawy Amr , Mahmoud Hani , Phillips David I W , Yacoub Magdi H 
Published: December 2017

ObjectiveRheumatic heart disease (RHD) remains a major health problem in many low-income and middle-income countries. The use of echocardiographic imaging suggests that subclinical disease is far more widespread than previously appreciated, but little is known as to how these mild forms of RHD progress. We have determined the prevalence of subclinical RHD in a large group of schoolchildren in Aswan, Egypt and have evaluated its subsequent progression.MethodsEchocardiographic screening was performed on 3062 randomly selected schoolchildren, aged 5–15 years, in Aswan, Egypt. Follow-up of children with a definite or borderline diagnosis of RHD was carried out 48–60 months later to determine how the valvular abnormalities altered and to evaluate the factors influencing progression.ResultsSixty children were initially diagnosed with definite RHD (19.6 per 1000 children) and 35 with borderline disease (11.4 per 1000); most had mitral valve disease. Of the 72 children followed up progression was documented in 14 children (19.4%) and regression in 30 (41.7%) children. Boys had lower rates of progression while older children had lower rates of regression. Functional defects of the valve even in the presence of structural features were associated with lower rates of progression and higher rates of regression than structural changes.ConclusionsRHD has a high prevalence in Egypt. Although a high proportion of the abnormalities originally detected persisted at follow-up, both progression and regression of valve lesions were demonstrated.
Amplification of Oncolytic Vaccinia Virus Widespread Tumor Cell Killing by Sunitinib through Multiple Mechanisms
Authors: Kim Minah , Nitschké Maximilian , Sennino Barbara , Murer Patrizia , Schriver Brian J. , Bell Alexander , Subramanian Aishwarya , McDonald Corry E. , Wang Jiahu , Cha Howard , Bourgeois-Daigneault Marie-Claude , Kirn David H. , Bell John C. , De Silva Naomi , Breitbach Caroline J. , McDonald Donald M. 
Published: December 2017

Abstract
Oncolytic viruses pose many questions in their use in cancer therapy. In this study, we assessed the potential of mpJX-594 (mouse-prototype JX-594), a replication-competent vaccinia virus administered by intravenous injection, to target the tumor vasculature, produce immune activation and tumor cell killing more widespread than the infection, and suppress invasion and metastasis. These actions were examined in RIP-Tag2 transgenic mice with pancreatic neuroendocrine tumors that developed spontaneously and progressed as in humans. mpJX-594 initially infected tumor vascular endothelial cells, leading to vascular pruning and prolonged leakage in tumors but not in normal organs; parallel effects were observed in U87 gliomas. Viral infection spread to tumor cells, where tumor cell killing was much more widespread than the infection. Widespread tumor cell killing at 5 days was prevented by depletion of CD8+ T lymphocytes and did not require GM-CSF, as mpJX-594 variants that expressed human, mouse, or no GM-CSF produced equivalent amounts of killing. The antivascular, antitumor, and antimetastatic effects of mpJX-594 were amplified by concurrent or sequential administration of sunitinib, a multitargeted receptor tyrosine kinase inhibitor. These effects were not mimicked by selective inhibition of VEGFR2 despite equivalent vascular pruning, but were accompanied by suppression of regulatory T cells and greater influx of activated CD8+ T cells. Together, our results showed that mpJX-594 targets tumor blood vessels, spreads secondarily to tumor cells, and produces widespread CD8+ T-cell–dependent tumor cell killing in primary tumors and metastases, and that these effects can be amplified by coadministration of sunitinib.
Significance: These findings reveal multiple unrecognized features of the antitumor properties of oncolytic vaccinia viruses, all of which can be amplified by the multitargeted kinase inhibitor sunitinib. Cancer Res; 78(4); 922–37. ©2017 AACR.
Inhibition of Translesion DNA Synthesis as a Novel Therapeutic Strategy to Treat Brain Cancer
Authors: Choi Jung-Suk , Kim Casey Seol , Berdis Anthony 
Published: December 2017

Abstract
Temozolomide is a DNA-alkylating agent used to treat brain tumors, but resistance to this drug is common. In this study, we provide evidence that efficacious responses to this drug can be heightened significantly by coadministration of an artificial nucleoside (5-nitroindolyl-2′-deoxyriboside, 5-NIdR) that efficiently and selectively inhibits the replication of DNA lesions generated by temozolomide. Conversion of this compound to the corresponding nucleoside triphosphate, 5-nitroindolyl-2′-deoxyriboside triphosphate, in vivo creates a potent inhibitor of several human DNA polymerases that can replicate damaged DNA. Accordingly, 5-NIdR synergized with temozolomide to increase apoptosis of tumor cells. In a murine xenograft model of glioblastoma, whereas temozolomide only delayed tumor growth, its coadministration with 5-NIdR caused complete tumor regression. Exploratory toxicology investigations showed that high doses of 5-NIdR did not produce the side effects commonly seen with conventional nucleoside analogs. Collectively, our results offer a preclinical pharmacologic proof of concept for the coordinate inhibition of translesion DNA synthesis as a strategy to improve chemotherapeutic responses in aggressive brain tumors.
Significance: Combinatorial treatment of glioblastoma with temozolomide and a novel artificial nucleoside that inhibits replication of damaged DNA can safely enhance therapeutic responses. Cancer Res; 78(4); 1083–96. ©2017 AACR.