bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Capsular Polysaccharide of Acinetobacter baumannii Is an Obstacle for Therapeutic Passive Immunization Strategies
Authors: Wang-Lin Shun Xin , Olson Ruth , Beanan Janet M. , MacDonald Ulrike , Balthasar Joseph P. , Russo Thomas A. 
Published: September 2017

ABSTRACT

Acinetobacter baumannii
has become an important concern for human health due to rapid development and wide spread of antimicrobial-resistant strains and high mortality associated with the infection. Passive immunizations with antisera targeting outer membrane proteins (OMPs) have shown encouraging results in protecting mice from
A. baumannii
infection, but monoclonal anti-OMP antibodies have not been developed, and their potential therapeutic properties have not been explored. The goal of this report is to evaluate the antibacterial activity of monoclonal antibodies (MAbs) targeting outer membrane protein A (OmpA) of
A. baumannii
. Five anti-OmpA MAbs were developed using hybridoma technology and showed strong binding to strain ATCC 19606. However, low antibody binding was observed when they were tested against six clinical isolates, which included extensively drug-resistant strains. In contrast, high binding to an isogenic K1 capsule-negative mutant (AB307.30) was shown, suggesting that capsular polysaccharide mediated the inhibition of MAb binding to OmpA. Anti-OmpA MAbs increased the macrophage-mediated bactericidal activity of AB307.30 but failed to increase phagocytic killing of capsule-positive strains. Capsular polysaccharide was also protective against complement-mediated bactericidal activity in human ascites in the presence and absence of opsonization. Lastly, passive immunization with anti-OmpA MAbs did not confer protection against challenge with AB307-0294, the encapsulated parent strain of AB307.30, in a mouse sepsis infection model. These results reveal the important role of capsule polysaccharide in shielding OmpA and thereby inhibiting anti-OmpA MAb binding to clinical isolates. This property of capsule hindered the therapeutic utility of anti-OmpA MAbs, and it may apply to other conserved epitopes in
A. baumannii
.
Interleukin 1α Is Critical for Resistance against Highly Virulent Aspergillus fumigatus Isolates
Authors: Caffrey-Carr Alayna K. , Kowalski Caitlin H. , Beattie Sarah R. , Blaseg Nathan A. , Upshaw Chanell R. , Thammahong Arsa , Lust Hannah E. , Tang Yi-Wei , Hohl Tobias M. , Cramer Robert A. , Obar Joshua J. 
Published: September 2017

ABSTRACT

Heterogeneity among
Aspergillus fumigatus
isolates results in unique virulence potential and inflammatory responses. How these isolates drive specific immune responses and how this affects fungally induced lung damage and disease outcome are unresolved. We demonstrate that the highly virulent CEA10 strain is able to rapidly germinate within the immunocompetent lung environment, inducing greater lung damage, vascular leakage, and interleukin 1α (IL-1α) release than the low-virulence Af293 strain, which germinates with a lower frequency in this environment. Importantly, the clearance of CEA10 was consequently dependent on IL-1α, in contrast to Af293. The release of IL-1α occurred by a caspase 1/11- and P2XR7-independent mechanism but was dependent on calpain activity. Our finding that early fungal conidium germination drives greater lung damage and IL-1α-dependent inflammation is supported by three independent experimental lines. First, pregermination of Af293 prior to
in vivo
challenge drives greater lung damage and an IL-1α-dependent neutrophil response. Second, the more virulent EVOL20 strain, derived from Af293, is able to germinate in the airways, leading to enhanced lung damage and IL-1α-dependent inflammation and fungal clearance. Third, primary environmental
A. fumigatus
isolates that rapidly germinate under airway conditions follow the same trend toward IL-1α dependency. Our data support the hypothesis that
A. fumigatus
phenotypic variation significantly contributes to disease outcomes.
Medical school predictors of later perceived mastery of clinical work among Norwegian doctors: a cohort study with 10-year and 20-year follow-up
Authors: Belfrage Anna , Grotmol Kjersti Støen , Lien Lars , Moum Torbjørn , Wiese Ragna Veslemøy , Tyssen Reidar 
Published: September 2017

ObjectiveDoctors’ self-perceived mastery of clinical work might have an impact on their career and patient care, in addition to their own health and well-being. The aim of this study is to identify predictors at medical school of perceived mastery later in doctors’ careers.DesignA cohort of medical students (n=631) was surveyed in the final year of medical school in 1993/1994 (T1), and 10 (T2) and 20 (T3) years later.SettingNationwide healthcare institutions.ParticipantsMedical students from all universities in Norway.Main outcome measuresPerceived mastery of clinical work was measured at T2 and T3. The studied predictors measured at T1 included personality traits, medical school stress, perceived medical recording skills, identification with the role of doctor, hazardous drinking and drinking to cope, in addition to age and gender. Effects were studied using multiple linear regression models.ResultsResponse rates: T1, 522/631 (83%); T2, 390/522 (75%); and T3, 303/522 (58%). Mean scores at T2 and T3 were 22.3 (SD=4.2) and 24.5 (3.0) (t=8.2, p<0.001), with no gender difference. Adjusted associations at T2 were: role identification (β=0.16; p=0.006; 95% CI 0.05 to 0.28), perceived medical recording skills (β=0.13; p=0.02; 95% CI 0.02 to 0.24) and drinking to cope (β=–2.45; p=0.001; 95% CI –3.88 to –1.03). Adjusted association at T3 was perceived medical recording skills (β=0.11; p=0.015; 95% CI 0.02 to 0.21).ConclusionsPerceived medical recording skills and role identification were associated with higher perceived mastery. Medical schools should provide experiences, teaching and assessment to enhance students’ physician role identification and confidence in their own skills. Drinking to cope was associated with lower perceived mastery, which indicates the importance of acquiring healthier coping strategies in medical school.
A study protocol for a multicentre randomised clinical trial evaluating the safety and feasibility of a bioengineered human allogeneic nanostructured anterior cornea in patients with advanced corneal trophic ulcers refractory to conventional treatment
Authors: González-Andrades Miguel , Mata Rosario , González-Gallardo María del Carmen , Medialdea Santiago , Arias-Santiago Salvador , Martínez-Atienza Juliana , Ruiz-García Antonio , Pérez-Fajardo Lorena , Lizana-Moreno Antonio , Garzón Ingrid , Campos Antonio , Alaminos Miguel , Carmona Gloria , Cuende Natividad 
Published: September 2017

IntroductionThere is a need to find alternatives to the use of human donor corneas in transplants because of the limited availability of donor organs, the incidence of graft complications, as well as the inability to successfully perform corneal transplant in patients presenting limbal deficiency, neo-vascularized or thin corneas, etc. We have designed a clinical trial to test a nanostructured fibrin-agarose corneal substitute combining allogeneic cells that mimics the anterior human native cornea in terms of optical, mechanical and biological behaviour.Methods and analysisThis is a phase I-II, randomised, controlled, open-label clinical trial, currently ongoing in ten Spanish hospitals, to evaluate the safety and feasibility, as well as clinical efficacy evidence, of this bioengineered human corneal substitute in adults with severe trophic corneal ulcers refractory to conventional treatment, or with sequelae of previous ulcers. In the initial phase of the trial (n=5), patients were sequentially recruited, with a safety period of 45 days, receiving the bioengineered corneal graft. In the second phase of the trial (currently ongoing), subjects are block randomised (2:1) to receive either the corneal graft (n=10), or amniotic membrane (n=5), as the control treatment. Adverse events, implant status, infection signs and induced neovascularization are evaluated as determinants of safety and feasibility of the bioengineered graft (main outcomes). Study endpoints are measured along a follow-up period of 24 months, including 27 post-implant assessment visits according to a decreasing frequency. Intention to treat, and per protocol, and safety analysis will be performed.Ethics and disseminationThe trial protocol received written approval by the corresponding Ethics Committee and the Spanish Regulatory Authority and is currently recruiting subjects. On completion of the trial, manuscripts with the results of phases I and II of the study will be published in a peer-reviewed journal.Trial registrationCT.gov identifier:NCT01765244(Jan2013). EudraCT number: 2010-024290-40 (Dec2012).
Association between socio-economic status and dental caries in elderly people in Sichuan Province, China: a cross-sectional study
Authors: Wang Linyan , Cheng Li , Yuan Bo , Hong Xiao , Hu Tao 
Published: September 2017

ObjectivesAs a vulnerable group, the elders’ oral health gained less attention, particularly the relationship between socioeconomic status (SES) and dental caries. This study aimed to assess the associations and to explore the effects of confounders on the associations in elderly people.DesignCross-sectional study.Settings3 neighbourhood committees and 3 village committees in Sichuan Province, China.Participants744 people (362 men and 382 women) aged 65–74 years were included.Outcome measuresOral health outcomes included the decayed, missing and filled teeth (DMFT) index and its components. SES was assigned by educational level, household income and type of household. The bivariate association between the participants’ characteristics and DMFT was analysed using non-parametric tests. Four logistic regression models were used to analyse the associations between SES and dental caries by regulating confounders.ResultsPoor oral health was observed in these participants. Bivariate analysis showed a significant association between SES and DMFT (p﹤0.05). Only adjusting gender, high educational level (adjusted (AOR)=0.34, 95% CI 0.17 to 0.66), high household income (AOR=0.47, 95% CI 0.41 to 0.77) were protective factors against dental caries, and living in agricultural families (AOR=1.86, 95% CI 1.32 to 2.63) was risk factor (p﹤0.05). After adjusting other confounders, SES was partly related to the dental caries. Moreover, an interaction existed among SES indicators.ConclusionsSES is associated with dental caries, and older people with low SES have poor oral health. The associations were explained partly by diet, behaviour and awareness. Our results provide effective evidence in targeted policy-making and intervention measures and implicate that pertinence measures, economic assistance and medical insurance funds should be provided to older people of low SES. Furthermore, a follow-up design should attempt to confirm the causal relationship between SES and dental caries and evaluate the effect of intervention.
Rolling-refresher simulation improves performance and retention of paediatric intensive care unit nurse code cart management
Authors: Singleton Marcy N , Allen Kimberly F , Li Zhongze , McNerney Kevin , Naber Urs H , Braga Matthew S 
Published: September 2017

IntroductionPaediatric Intensive Care Unit Nurses (PICU RNs) manage the code cart during paediatric emergencies at the Children’s Hospital at Dartmouth-Hitchcock. These are low -frequency, high-stakes events.MethodsAn uncontrolled intervention study with 6-month follow-up. A collaboration of physician and nursing experts developed a rolling-refresher training programme consisting of five simulated scenarios, including 22 code cart skills, to establish nursing code cart competency. The cohort of PICU RNs underwent a competency assessment in training 1. To achieve competence, the participating RN received immediate feedback and instruction and repeated each task until mastery during training 1. The competencies were repeated 6 months later, designated training 2.ResultsThirty-two RNs participated in training 1. Sixteen RNs (50%) completed the second training. Our rolling-refresher training programme resulted in a 43% reduction in the odds of first attempt failures between training 1 and training 2 (p=0.01). Multivariate linear regression evaluating the difference in first attempt failure between training 1 and training 2 revealed that the following covariates were not significantly associated with this improvement: interval Paediatric Advanced Life Support training, interval use of the code cart or defibrillator (either real or simulated) and time between training sessions. Univariate analysis between the two trainings revealed a statistically significant reduction in first attempt failures for: preparing an epinephrine infusion (72% vs 41%, p=0.04) and providing bag-mask ventilation (28% vs 0%, p=0.02).ConclusionsOur rolling-refresher training programme demonstrated significant improvement in performance for low-frequency, high-risk skills required to manage a paediatric code cart with retention after initial training.
Operationalisation and validation of the Stopping Elderly Accidents, Deaths, and Injuries (STEADI) fall risk algorithm in a nationally representative sample
Authors: Lohman Matthew C , Crow Rebecca S , DiMilia Peter R , Nicklett Emily J , Bruce Martha L , Batsis John A 
Published: September 2017

BackgroundPreventing falls and fall-related injuries among older adults is a public health priority. The Stopping Elderly Accidents, Deaths, and Injuries (STEADI) tool was developed to promote fall risk screening and encourage coordination between clinical and community-based fall prevention resources; however, little is known about the tool’s predictive validity or adaptability to survey data.MethodsData from five annual rounds (2011–2015) of the National Health and Aging Trends Study (NHATS), a representative cohort of adults age 65 years and older in the USA. Analytic sample respondents (n=7392) were categorised at baseline as having low, moderate or high fall risk according to the STEADI algorithm adapted for use with NHATS data. Logistic mixed-effects regression was used to estimate the association between baseline fall risk and subsequent falls and mortality. Analyses incorporated complex sampling and weighting elements to permit inferences at a national level.ResultsParticipants classified as having moderate and high fall risk had 2.62 (95% CI 2.29 to 2.99) and 4.76 (95% CI 3.51 to 6.47) times greater odds of falling during follow-up compared with those with low risk, respectively, controlling for sociodemographic and health-related risk factors for falls. High fall risk was also associated with greater likelihood of falling multiple times annually but not with greater risk of mortality.ConclusionThe adapted STEADI clinical fall risk screening tool is a valid measure for predicting future fall risk using survey cohort data. Further efforts to standardise screening for fall risk and to coordinate between clinical and community-based fall prevention initiatives are warranted.
The INTEROCC case-control study: risk of meningioma and occupational exposure to selected combustion products, dusts and other chemical agents
Authors: McElvenny Damien M , van Tongeren Martie , Turner Michelle C , Benke Geza , Figuerola Jordi , Fleming Sarah , Hours Martine , Kincl Laurel , Krewski Daniel , McLean Dave , Parent Marie-Élise , Richardson Lesley , Schlehofer Brigitte , Schlaefer Klaus , Sadetzki Siegal , Schüz Joachim , Siemiatycki Jack , Cardis Elisabeth 
Published: September 2017

BackgroundLittle is known about occupational risk factors for meningioma.ObjectivesTo study whether risk of meningioma is associated with several occupational exposures, including selected combustion products, dusts and other chemical agents.MethodsThe INTEROCC study was an international case-control study of brain cancer conducted in seven countries. Data collection by interview included lifetime occupational histories. A job exposure matrix was used to derive estimates of exposure for the 12 agents. ORs for ever versus never exposed and for exposure-response using duration of exposure and cumulative exposure were derived using conditional logistic regression stratified by sex, age group, country/region, adjusted for education.ResultsThese analyses included 1906 cases and 5565 controls. For 11 of the 12 agents, no excess risk was found for ever exposed. For ever exposure to oil mists, an elevated OR of 1.57 (95% CI 1.10 to 2.22, 51 exposed cases) was found. Statistically significant exposure-response relationships were observed with cumulative exposure (p=0.01) and duration of exposure (p=0.04). Among women, there were also significant trends for cumulative and duration of exposure to asbestos and excesses in the highest exposure categories for formaldehyde.ConclusionsMost agents examined did not provoke excess risks of meningioma. The main finding from this study is that it is the first study to identify a statistical association between exposure to oil mists and meningioma. This may be a chance finding or could be due to confounding with iron exposure and further research is required to understand whether the relationship is causal.
Impaired lung repair during neutropenia can be reverted by matrix metalloproteinase-9
Authors: Blázquez-Prieto Jorge , López-Alonso Inés , Amado-Rodríguez Laura , Huidobro Covadonga , González-López Adrián , Kuebler Wolfgang M , Albaiceta Guillermo M 
Published: September 2017

BackgroundNeutrophils may cause tissue disruption during migration and by releasing cytotoxic molecules. However, the benefits of neutrophil depletion observed in experimental models of lung injury do not correspond with the poor outcome of neutropenic patients.MethodsTo clarify the role of neutrophils during repair, mice with ventilator induced lung injury (VILI) were rendered neutropenic after damage, and followed for 48 hours of spontaneous breathing. Lungs were harvested and inflammatory mediators and matrix metalloproteinases measured. Bronchoalveolar lavage fluid (BALF) from ventilated patients with acute respiratory distress syndrome, with or without neutropenia, was collected, the same mediators measured and their effects in an ex vivo model of alveolar repair studied. Finally, neutropenic mice were treated after VILI with exogenous matrix metalloproteinase-9 (MMP-9).ResultsLungs from neutropenic animals showed delayed repair and displayed higher levels of tumour necrosis factor α, interferon γ and macrophage inflammatory protein 2, and absence of MMP-9. BALF from ventilated neutropenic patients with acute respiratory distress syndrome showed similar results. BALFs from neutropenic patients yielded a delayed closure rate of epithelial wounds ex vivo, which was improved by removal of collagen or addition of exogenous MMP-9. Lastly, treatment of neutropenic mice with exogenous MMP-9 after VILI reduced tissue damage without modifying cytokine concentrations.ConclusionRelease of MMP-9 from neutrophils is required for adequate matrix processing and lung repair.
Exploration of subsurface Antarctica: uncovering past changes and modern processes
Authors: Siegert Martin J. , Jamieson Stewart S. R. , White Duanne 
Published: September 2017

Abstract
The Antarctic continent, which contains enough ice to raise sea level globally by around 60 m, is the last major scientific frontier on our planet. We know far more about the surfaces of the Moon, Mars and around half of Pluto than we do about the underside of the Antarctic ice sheet. Geophysical exploration is the key route to measuring the ice sheet's internal structure and the land on which the ice rests. From such measurements, we are able to reveal how the ice sheet flows, and how it responds to atmospheric and ocean warming. By examining landscapes that have been moulded by former ice flow, we are able to identify how the ice sheet behaved in the past. Geophysics is therefore critical to understanding change in Antarctica.
Source potential and depositional environment of Oligocene and Miocene rocks offshore Bulgaria
Authors: Mayer J. , Rupprecht B. J. , Sachsenhofer R. F. , Tari G. , Bechtel A. , Coric S. , Siedl W. , Kosi W. , Floodpage J. 
Published: September 2017

Abstract
Oligo-Miocene (‘Maikopian’) deposits are considered the main source rocks in the Black Sea area, although only a few source-rock data are available. Geochemical logs from nine wells are used together with age constraints provided by calcareous nannoplankton, well and seismic data to determine vertical and lateral changes of the source potential. Oligocene rocks overlie Eocene deposits with a major unconformity on the western Black Sea shelf in Bulgaria. A west–east-trending erosional structure (the Kaliakra canyon) developed during Lower Oligocene time and was filled with Oligo-Miocene deposits. Potential source rocks are present in different stratigraphic units, but the most prolific intervals accumulated during time intervals when the isolation of the Paratethys resulted in oxygen-depleted, brackish environments with high bioproductivity. These include Lower Solenovian rocks related to blooms of calcareous nannoplankton, which form an extensive layer outside the Kaliakra canyon. This unit hosts a good potential to generate oil and gas. Diatom-rich, very good oil-prone source rocks accumulated during a second isolation event in the Kozakhurian. Thick sections of these diatom-rich rocks occur within the canyon and are present in thin layers outside of it. High productivity of siliceous organisms is attributed to upwelling within the canyon. All studied units are thermally immature on the shelf.
Integrated Analysis of Whole-Genome ChIP-Seq and RNA-Seq Data of Primary Head and Neck Tumor Samples Associates HPV Integration Sites with Open Chromatin Marks
Authors: Kelley Dylan Z. , Flam Emily L. , Izumchenko Evgeny , Danilova Ludmila V. , Wulf Hildegard A. , Guo Theresa , Singman Dzov A. , Afsari Bahman , Skaist Alyza M. , Considine Michael , Welch Jane A. , Stavrovskaya Elena , Bishop Justin A. , Westra William H. , Khan Zubair , Koch Wayne M. , Sidransky David , Wheelan Sarah J. , Califano Joseph A. , Favorov Alexander V. , Fertig Elana J. , Gaykalova Daria A. 
Published: September 2017

Abstract
Chromatin alterations mediate mutations and gene expression changes in cancer. Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) has been utilized to study genome-wide chromatin structure in human cancer cell lines, yet numerous technical challenges limit comparable analyses in primary tumors. Here we have developed a new whole-genome analytic pipeline to optimize ChIP-Seq protocols on patient-derived xenografts from human papillomavirus–related (HPV+) head and neck squamous cell carcinoma (HNSCC) samples. We further associated chromatin aberrations with gene expression changes from a larger cohort of the tumor and normal samples with RNA-Seq data. We detect differential histone enrichment associated with tumor-specific gene expression variation, sites of HPV integration in the human genome, and HPV-associated histone enrichment sites upstream of cancer driver genes, which play central roles in cancer-associated pathways. These comprehensive analyses enable unprecedented characterization of the complex network of molecular changes resulting from chromatin alterations that drive HPV-related tumorigenesis. Cancer Res; 77(23); 6538–50. ©2017 AACR.