bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the
glpQ2
Gene on Virulence in a Streptococcus pneumoniae Serotype 19A Sequence Type 320 Strain
Authors: Chuang Yi-Ping , Peng Zih-Rong , Tseng Shun-Fu , Lin Yu-Chun , Sytwu Huey-Kang , Hsieh Yu-Chia 
Published: November 2014

ABSTRACT

Glycerophosphodiester phosphodiesterase (GlpQ) metabolizes glycerophosphorylcholine from the lung epithelium to produce free choline, which is transformed into phosphorylcholine and presented on the surfaces of many respiratory pathogens. Two orthologs of
glpQ
genes are found in
Streptococcus pneumoniae
:
glpQ
, with a membrane motif, is widespread in pneumococci, whereas
glpQ2
, which shares high similarity with
glpQ
in
Haemophilus influenzae
and
Mycoplasma pneumoniae
, is present only in
S. pneumoniae
serotype 3, 6B, 19A, and 19F strains. Recently, serotype 19A has emerged as an epidemiological etiology associated with invasive pneumococcal diseases. Thus, we investigated the pathophysiological role of
glpQ2
in a serotype 19A sequence type 320 (19AST320) strain, which was the prevalent sequence type in 19A associated with severe pneumonia and invasive pneumococcal disease in pediatric patients. Mutations in
glpQ2
reduced phosphorylcholine expression and the anchorage of choline-binding proteins to the pneumococcal surface during the exponential phase, where the mutants exhibited reduced autolysis and lower natural transformation abilities than the parent strain. The deletion of
glpQ2
also decreased the adherence and cytotoxicity to human lung epithelial cell lines, whereas these functions were indistinguishable from those of the wild type in complementation strains. In a murine respiratory tract infection model,
glpQ2
was important for nasopharynx and lung colonization. Furthermore, infection with a
glpQ2
mutant decreased the severity of pneumonia compared with the parent strain, and
glpQ2
gene complementation restored the inflammation level. Therefore,
glpQ2
enhances surface phosphorylcholine expression in
S. pneumoniae
19AST320 during the exponential phase, which contributes to the severity of pneumonia by promoting adherence and host cell cytotoxicity.
Toll-Like Receptor 2 and NLRP3 Cooperate To Recognize a Functional Bacterial Amyloid, Curli
Authors: Rapsinski Glenn J. , Wynosky-Dolfi Meghan A. , Oppong Gertrude O. , Tursi Sarah A. , Wilson R. Paul , Brodsky Igor E. , Tükel Çagla 
Published: November 2014

ABSTRACT

Amyloids are proteins with cross-β-sheet structure that contribute to pathology and inflammation in complex human diseases, including Alzheimer's disease, Parkinson's disease, type II diabetes, and secondary amyloidosis. Bacteria also produce amyloids as a component of their extracellular matrix during biofilm formation. Recently, several human amyloids were shown to activate the NLRP3 inflammasome, leading to the activation of caspase 1 and production of interleukin 1β (IL-1β). In this study, we investigated the activation of the NLRP3 inflammasome by bacterial amyloids using curli fibers, produced by
Salmonella enterica
serovar Typhimurium and
Escherichia coli
. Here, we show that curli fibers activate the NLRP3 inflammasome, leading to the production of IL-1β via caspase 1 activation. Investigation of the underlying mechanism revealed that activation of Toll-like receptor 2 (TLR2) by curli fibers is critical in the generation of IL-1β. Interestingly, activation of the NLRP3 inflammasome by curli fibers or by amyloid β of Alzheimer's disease does not cause cell death in macrophages. Overall, these data identify a cross talk between TLR2 and NLRP3 in response to the bacterial amyloid curli and generation of IL-1β as a product of this interaction.
Gym exercising patterns, lifestyle and high-risk sexual behaviour in men who have sex with men and in heterosexual men
Authors: Mor Z , Parfionov K , Davidovitch N , Grotto I 
Published: November 2014

ObjectiveLifestyle may be associated with risk behaviours. This study compares gym exercise and sexual risk behaviour between men who have sex with men (MSM) and heterosexual men. The research was based on the assumption that men who become muscular and physically attractive increase their number of sex partners and consequently their risk of HIV or other sexually transmitted infections (STIs).SettingFive gyms in central Tel Aviv, Israel.ParticipantsIn 2012, a sample of 182 (48%) MSM and 197 (52%) heterosexual men who train in gyms completed anonymous questionnaires regarding their training, health and sexual behaviours.OutcomesParticipants in this cross-sectional study who exercised more than the median number of anaerobic training hours were defined as performing intensive anaerobic training (IAT), and those who had performed more than one act of unprotected anal/vaginal intercourse in the preceding 6 months with a partner whose HIV status was unknown were defined as high risk.ResultsMSM showed a stronger desire to become muscular than heterosexual men, were more likely to perform IAT, and used protein powders or anabolic steroids. They reported that improving their body shape and increasing their self-confidence were their main reasons for training, whereas heterosexual men indicated weight loss and health improvement as the main reasons for training. MSM engaged in riskier sexual behaviour than heterosexual men. Of all the high-risk men, 61.9% (N=70) performed IAT, while 38.1% (N=43) performed moderate anaerobic training (p<0.01). The association between IAT and sexual risk was stronger in MSM than in heterosexual men (p<0.01 vs p=0.05, respectively). The interaction between MSM and IAT in high-risk participants was multiplicative.ConclusionsMSM practised more IAT than heterosexual men, and their interaction between IAT and sexual risk was multiplicative. The MSM community could benefit from a holistic approach to sexual health and its association with body image and IAT. The gym MSM culture demonstrates how internal dynamics and social norms are possible factors driving MSM to high-risk behaviour for HIV/STI.Study registrationThe study was approved by the Wolfson Hospital Review Board, Holon, Israel (WOMC-0058-09).
Recognition and reporting of suspected adverse drug reactions by surveyed healthcare professionals in Uganda: key determinants
Authors: Kiguba Ronald , Karamagi Charles , Waako Paul , Ndagije Helen B , Bird Sheila M 
Published: November 2014

ObjectiveTo assess extent and determinants of past-month recognition of suspected adverse drug reactions (ADR) and past-year ADR reporting among healthcare professionals (HCPs) in Uganda.SettingGeographically diverse health facilities (public, private for-profit, private not-for-profit).ParticipantsOf 2000 questionnaires distributed, 1345 were completed: return rate of 67%.Primary and secondary outcome measuresPer cent HCPs who suspected ADR in the past month; reported ADR in the past year.ResultsNurses were the majority (59%, 792/1345). Only half the respondents had heard about pharmacovigilance: 39% of nurses (295/763; 95% CI 35% to 42%), 70% otherwise (383/547; 95% CI 66% to 74%). One fifth (268/1289 or 21%; 95% CI 19% to 23%) had suspected an ADR in the previous 4 weeks, 111 of them were nurses; 15% (190/1296) had reported a suspected ADR in the past year, 103 of them were nurses. Past-month ADR suspicion was more likely by non-nurses (OR=1.7, 95% CI 1.16 to 2.40) and with medical research involvement (OR=1.5, 95% CI 1.05 to 2.15) but past-month receipt of patient ADR-complaint predominated (OR=19, 95% CI 14 to 28). Past-year ADR reporting was higher by hospital staff (OR=1.9, 95% CI 1.18 to 3.10), especially in medicine (OR=2.3, 95% CI 1.08 to 4.73); but lower from private for-profit health facilities (OR=0.5, 95% CI 0.28 to 0.77) and by older staff (OR=0.6, 95% CI 0.43 to 0.91); more likely by HCPs who had ever encountered a fatal ADR (OR=2.9, 95% CI 1.94 to 4.25), knew to whom to report (OR=1.7, 95% CI 1.18 to 2.46), or suggested how to improve ADR reporting (OR=1.6, 95% CI 1.04 to 2.49). Two attitudinal factors were important: diffidence and lethargy.ConclusionsOne in five HCPs suspected an ADR in the past-month and one in seven reported ADR in the previous year. Empowering patients could strengthen ADR detection and reporting in Africa.
Hospitalisation for chronic obstructive pulmonary disease and risk of suicide: a population-based case–control study
Authors: Strid Jennie Maria Christin , Christiansen Christian Fynbo , Olsen Morten , Qin Ping 
Published: November 2014

ObjectivesTo examine risk of suicide among individuals with hospitalised chronic obstructive pulmonary disease (COPD) and to profile differences according to sex, age, psychiatric history, and recency and frequency of COPD hospitalisations.DesignNested case–control study.SettingData were retrieved from Danish national registries.ParticipantsAll suicide cases aged 40–95 years deceased between 1981 and 2006 in Denmark (n=19 869) and up to 20 live population controls per case matched on sex and date of birth (n=321 867 controls).Main outcome measuresThe relative risk of suicide associated with COPD was computed using conditional logistic regression and adjusted for effects of psychiatric history and important sociodemographic factors.ResultsIn our study population, 3% of suicide cases had been hospitalised for COPD compared with 1% of matched population controls. Thus, a hospitalised COPD was associated with a significantly increased risk for suicide (OR 2.6; 95% CI 2.3 to 2.8). The increased risk remained significant after adjustment for psychiatric history and sociodemographic variables (OR 2.0; 95% CI 1.8 to 2.2), and increased progressively with frequency and recency of COPD hospitalisation. At the same time, suicide risk associated with COPD differed significantly by sex, age and psychiatric status. The relative risk was more pronounced in women, in individuals older than 60 years and in persons with no history of psychiatric illness.ConclusionsCOPD confers an important risk factor for suicide completion. Risk assessment and prevention efforts should take patients’ sex, age and psychiatric history into consideration.
Stakeholder attitudes towards the role and application of informed consent for newborn bloodspot screening: a study protocol
Authors: Nicholls S G , Tessier L , Etchegary H , Brehaut J C , Potter B K , Hayeems R Z , Chakraborty P , Marcadier J , Milburn J , Pullman D , Turner L , Wilson B J 
Published: November 2014

Introduction Newborn bloodspot screening (NBS) involves testing a small sample of blood taken from the heel of the newborn for a number of serious and life-limiting conditions. In Canada, newborn screening programmes fall under provincial and territorial jurisdiction with no federal coordination. To date, we know very little about the underlying beliefs around different consent practices or how terminology is interpreted by different individuals. Differences in attitudes may have important healthcare consequences. This study will provide empirical data comparing stakeholder opinions on their understanding of consent-related terminology, the perceived applicability of different consent approaches to newborn screening, and the requirements of these different approaches.Methods and analysisParents, healthcare professionals and policymakers will be recruited in the provinces of Ontario and Newfoundland and Labrador. Parents will be identified through records held by each provincial screening programme. Healthcare professionals will be purposively sampled on the basis of engagement with newborn screening. Within each province we will identify policymakers who have policy analysis or advisory responsibilities relating to NBS. Data collection will be by qualitative interviews. We will conduct 20 interviews with parents of young children, 10 interviews with key healthcare professionals across the range of appropriate specialties and 10 with policymakers at each site (40 per site, total, N=80). The examination of the transcripts will follow a thematic analysis approach. Recruitment started in June 2014 and is expected to be complete by June 2015.Ethics and disseminationThis study received ethics approval from the Ottawa Health Science Network Research Ethics Board, the Children's Hospital of Eastern Ontario Research Ethics Board (both Ontario), and the Health Research Ethics Authority (Newfoundland and Labrador).ResultsThese will be reported in peer-reviewed publications and conference presentations. The results will have specific application to the development of parent education materials for newborn screening.
Treatment Efficacy and Resistance Mechanisms Using the Second-Generation ALK Inhibitor AP26113 in Human NPM-ALK–Positive Anaplastic Large Cell Lymphoma
Authors: Ceccon M. , Mologni L. , Giudici G. , Piazza R. , Pirola A. , Fontana D. , Gambacorti-Passerini C. 
Published: November 2014

Abstract
ALK is a tyrosine kinase receptor involved in a broad range of solid and hematologic tumors. Among 70% to 80% of ALK+ anaplastic large cell lymphomas (ALCL) are caused by the aberrant oncogenic fusion protein NPM-ALK. Crizotinib was the first clinically relevant ALK inhibitor, now approved for the treatment of late-stage and metastatic cases of lung cancer. However, patients frequently develop drug resistance to Crizotinib, mainly due to the appearance of point mutations located in the ALK kinase domain. Fortunately, other inhibitors are available and in clinical trial, suggesting the potential for second-line therapies to overcome Crizotinib resistance. This study focuses on the ongoing phase I/II trial small-molecule tyrosine kinase inhibitor (TKI) AP26113, by Ariad Pharmaceuticals, which targets both ALK and EGFR. Two NPM-ALK+ human cell lines, KARPAS-299 and SUP-M2, were grown in the presence of increasing concentrations of AP26113, and eight lines were selected that demonstrated resistance. All lines show IC50 values higher (130 to 1,000-fold) than the parental line. Mechanistically, KARPAS-299 populations resistant to AP26113 show NPM-ALK overexpression, whereas SUP-M2–resistant cells harbor several point mutations spanning the entire ALK kinase domain. In particular, amino acid substitutions: L1196M, S1206C, the double F1174V+L1198F and L1122V+L1196M mutations were identified. The knowledge of the possible appearance of new clinically relevant mechanisms of drug resistance is a useful tool for the management of new TKI-resistant cases.
Implications: This work defines reliable ALCL model systems of AP26113 resistance and provides a valuable tool in the management of all cases of relapse upon NPM-ALK–targeted therapy. Mol Cancer Res; 13(4); 775–83. ©2014 AACR.
Sexual Dimorphism of Doxorubicin-Mediated Cardiotoxicity
Authors: Moulin Maryline , Piquereau Jérôme , Mateo Philippe , Fortin Dominique , Rucker-Martin Catherine , Gressette Mélanie , Lefebvre Florence , Gresikova Milada , Solgadi Audrey , Veksler Vladimir , Garnier Anne , Ventura-Clapier Renée 
Published: November 2014

Background—
Cardiovascular diseases are the major cause of mortality among both men and women with a lower incidence in women before menopause. The clinical use of doxorubicin, widely used as an antineoplastic agent, is markedly hampered by severe cardiotoxicity. Even if there is a significant sex difference in incidence of cardiovascular disease at the adult stage, it is not known whether a difference in doxorubicin-related cardiotoxicity between men and women also exists. The objective of this work was to explore the cardiac side effects of doxorubicin in adult rats and decipher whether signaling pathways involved in cardiac toxicity differ between sexes.

Methods and Results—
After 7 weeks of doxorubicin (2 mg/kg per week), males developed major signs of cardiomyopathy with cardiac atrophy, reduced left ventricular ejection fraction and 50% mortality. In contrast, no female died and their left ventricular ejection fraction was only moderately affected. Surprisingly, neither global oxidation levels nor the antioxidant response nor the apoptosis signaling pathways were altered by doxorubicin. However, the level of total adenosine monophosphate–activated protein kinase was severely decreased only in males. Moreover, markers of mitochondrial biogenesis and cardiolipin content were strongly reduced only in males. To analyze the onset of the pathology, maximal oxygen consumption rate of left ventricular permeabilized fibers after 4 weeks of treatment was reduced only in doxorubicin-treated males.

Conclusions—
Altogether, these results clearly evidence sex differences in doxorubicin toxicity. Cardiac mitochondrial dysfunction and adenosine monophosphate–activated protein kinase seem as critical sites of sex differences in cardiotoxicity as evidenced by significant statistical interactions between sex and treatment effects.
Derivation and High Engraftment of Patient-Specific Cardiomyocyte Sheet Using Induced Pluripotent Stem Cells Generated From Adult Cardiac Fibroblast
Authors: Zhang Liying , Guo Jing , Zhang Pengyuan , Xiong Qiang , Wu Steven C. , Xia Lily , Roy Samit Sunny , Tolar Jakub , O’Connell Timothy D. , Kyba Michael , Liao Kenneth , Zhang Jianyi 
Published: November 2014

Background—
Induced pluripotent stem cells (iPSCs) can be differentiated into potentially unlimited lineages of cell types for use in autologous cell therapy. However, the efficiency of the differentiation procedure and subsequent function of the iPSC-derived cells may be influenced by epigenetic factors that the iPSCs retain from their tissues of origin; thus, iPSC-derived cells may be more effective for treatment of myocardial injury if the iPSCs were engineered from cardiac-lineage cells, rather than dermal fibroblasts.

Methods and Results—
We show that human cardiac iPSCs (hciPSCs) can be generated from cardiac fibroblasts and subsequently differentiated into exceptionally pure (>92%) sheets of cardiomyocytes (CMs). The hciPSCs passed through all the normal stages of differentiation before assuming a CM identity. When using the fibrin gel–enhanced delivery of hciPSC-CM sheets at the site of injury in infarcted mouse hearts, the engraftment rate was 31.91%±5.75% at Day 28 post transplantation. The hciPSC-CM in the sheet also appeared to develop a more mature, structurally aligned phenotype 28 days after transplantation and was associated with significant improvements in cardiac function, vascularity, and reduction in apoptosis.

Conclusions—
These data strongly support the potential of hciPSC-CM sheet transplantation for the treatment of heart with acute myocardial infarction.
Impacts of the Decadal Urbanization on Thermally Induced Circulations in Eastern China
Authors: Li Mengmeng , Mao Zhichun , Song Yu , Liu Mingxu , Huang Xin 
Published: November 2014

AbstractSignificant urbanization has occurred in the Yangtze River Delta region of eastern China, which exerts important effects on the local thermally induced circulations through regulating the heat flux and thermal structure. Previous studies lack a correct representation of the seasonal vegetation phenology associated with urban expansion, and therefore it is difficult to accurately describe the land–atmosphere coupling. In this study, high-resolution Moderate Resolution Imaging Spectroradiometer (MODIS) observations are used to describe the changes in land surface characteristics, including land-cover type, green vegetation fraction, and leaf area index with the Weather Research and Forecasting Model. The use of MODIS satellite observations provides a clear improvement in model performance when compared with ground-based measurements. A typical urban heat island is generated around Shanghai, Wuxi–Suzhou–Yangzhou, and cities along the Yangtze River and Hangzhou Bay, which subsequently modifies the local thermal circulations. The sea breeze is significantly enhanced over the north bank of Hangzhou Bay because of the increased land–sea temperature contrast. Several surface convergent zones are generated along the Shanghai–Suzhou–Wuxi city belt as a result of the combined effects of the urban heat island, the enhanced sea breeze, and the lake breeze at Lake Tai.
Use of Specific Attenuation for Rainfall Measurement at X-Band Radar Wavelengths. Part I: Radar Calibration and Partial Beam Blockage Estimation
Authors: Diederich Malte , Ryzhkov Alexander , Simmer Clemens , Zhang Pengfei , Trömel Silke 
Published: November 2014

Abstract
In a two-part paper, radar rain-rate retrievals using specific attenuation A suggested by Ryzhkov et al. are thoroughly investigated. Continuous time series of overlapping measurements from two twin polarimetric X-band weather radars in Germany during the summers of 2011–13 are used to analyze various aspects of rain-rate retrieval, including miscalibration correction, mitigation of ground clutter contamination and partial beam blockage (PBB), sensitivity to precipitation characteristics, and the temperature assumptions of the R(A) technique. In this paper, the relations inherent to the R(A) method are used to estimate radar reflectivity Z from A and compare it to the measured Z in order to estimate PBB and calibration offsets for both radars. The fields of Z estimated from A for both radars are consistent, and the differences between Z(A) and measured Z are in good agreement with the ones calculated using either consistency relations between reflectivity at horizontal polarization ZH, differential reflectivity ZDR, and specific differential phase KDP in rain or a digital elevation model in the presence of PBB. In the analysis, the dependence of A on temperature appears to have minimal effects on the overall performance of the method. As expected, the difference between Z(A) and attenuation-corrected measured Z observations varies with rain type and exhibits a weak systematic dependency on rainfall intensity; thus, averaging over several rain events is required to obtain reliable estimates of the Z biases caused by radar miscalibration and PBB.
A randomised test of printed educational materials about melanoma detection: Varying skin self-examination technique and visual image dose
Authors: King Andy J , Carcioppolo Nick , Grossman Douglas , John Kevin K , Jensen Jakob D 
Published: November 2014

Objective: Melanoma incidence and mortality rates continue to rise globally, making it essential for researchers to identify effective approaches to disseminating information to the public that improve key outcomes. This study compared two skin self-examination (SSE) educational strategies: the ABCDE (asymmetry, border irregularity, multiple colours, diameter greater than 6 mm and evolution over time) approach and the ugly duckling sign (UDS). Design: A randomised experiment testing different presentations of SSE techniques and visual image dose. Setting: The experiment took place at a shopping centre in the Midwest USA. Method: Participants ( N = 301) participated in the study in which they viewed brochures featuring one of two SSE training methods, ABCDE or UDS, along with a low, moderate or high dosage (frequency) of visual images. Results: The brochures improved willingness to perform SSE and skin cancer knowledge across all groups, with brochures featuring the UDS increasing willingness to perform SSE as visual image dose increased. Sensitivity and specificity outcomes were similar across all groups, with a slight advantage found for displaying a moderate visual image dose visualising the ABCDE condition (sensitivity = .63, specificity = .79). Conclusions: Overall, both the ABCDE and UDS approaches demonstrated utility in improving early skin cancer detection and education. A balanced presentation of typical and atypical nevi images seems to be an important consideration when presenting visual and written information about melanoma to laypersons.