bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of viable conidia of Monilinia fructicola in flower and stone fruit combining propidium monoazide (PMA) and qPCR
Authors: Vilanova L. , Usall J. , Teixidó N. , Torres R. 
Published: January 2017

Brown rot is the most economically important fungal disease of stone fruits and is primarily caused by Monilinia laxa and M. fructicola. Conventional methods used to identify M. fructicola are mainly based on phenotypic characteristics and pathogen quantification is not always accurate. In contrast, methodologies based on molecular tools improve pathogen characterization and identification but are not able to differentiate between live and dead conidia. In this study the PMA‐qPCR methodology was optimized, validated and applied to quantify viable cells of M. fructicola in artificially and naturally infected samples. qPCR methodology showed good primer efficiency and sensitivity with quantification limits lower than obtained using a plate count method. The conditions of propidium monoazide (PMA) pretreatment were 60 μm PMA for 20 min incubation and 30 min of light‐emitting diode (LED) exposure that, combined with qPCR, measured live cells accurately without overestimation of dead cells. Using this methodology in naturally infected samples, M. fructicola live cells were quantified specifically, in contrast to other traditional methodologies that cannot distinguish among Monilinia spp. The developed methodology based on combined PMA‐qPCR will be a new tool to quantify viable M. fructicola in further epidemiological and ecological studies of this fungus.
Effect of systemic insulin treatment on diabetic wound healing
Authors: Vatankhah Nasibeh , Jahangiri Younes , Landry Gregory J. , Moneta Gregory L. , Azarbal Amir F. 
Published: January 2017

AbstractThis study investigates if different diabetic treatment regimens affect diabetic foot ulcer healing. From January 2013 to December 2014, 107 diabetic foot ulcers in 85 patients were followed until wound healing, amputation or development of a nonhealing ulcer at the last follow‐up visit. Demographic data, diabetic treatment regimens, presence of peripheral vascular disease, wound characteristics, and outcome were collected. Nonhealing wound was defined as major or minor amputation or those who did not have complete healing until the last observation. Median age was 60.0 years (range: 31.1–90.1 years) and 58 cases (68.2%) were males. Twenty‐four cases reached a complete healing (healing rate: 22.4%). The median follow‐up period in subjects with classified as having chronic wounds was 6.0 months (range: 0.7–21.8 months). Insulin treatment was a part of diabetes management in 52 (61.2%) cases. Insulin therapy significantly increased the wound healing rate (30.3% [20/66 ulcers] vs. 9.8% [4/41 ulcers]) (p = 0.013). In multivariate random‐effect logistic regression model, adjusting for age, gender, smoking status, type of diabetes, hypertension, chronic kidney disease, peripheral arterial disease, oral hypoglycemic use, wound infection, involved side, presence of Charcot's deformity, gangrene, osteomyelitis on x‐ray, and serum hemoglobin A1C levels, insulin treatment was associated with a higher chance of complete healing (beta ± SE: 15.2 ± 6.1, p = 0.013). Systemic insulin treatment can improve wound healing in diabetic ulcers after adjusting for multiple confounding covariates.
Effect of sex on the acute skeletal muscle response to sprint interval exercise
Authors: Skelly Lauren E. , Gillen Jenna B. , MacInnis Martin J. , Martin Brian J. , Safdar Adeel , Akhtar Mahmood , MacDonald Maureen J. , Tarnopolsky Mark A. , Gibala Martin J. 
Published: January 2017

New Findings
What is the central question of this study?
Are there sex‐based differences in the acute skeletal muscle response to sprint interval training (SIT)?

What is the main finding and its importance?
In response to a SIT protocol that involved three 20 s bouts of ‘all‐out’ cycling, the expression of multiple genes associated with mitochondrial biogenesis, metabolic control and structural remodelling was largely similar between men and women matched for fitness. Our findings cannot explain previous reports of sex‐based differences in the adaptive response to SIT and suggest that the mechanistic basis for these differences remains to be elucidated.

A few studies have reported sex‐based differences in response to several weeks of sprint interval training (SIT). These findings may relate to sex‐specific responses to an acute session of SIT. We tested the hypothesis that the acute skeletal muscle response to SIT differs between sexes. Sedentary but healthy men (n = 10) and women (n = 9) were matched for age (22 ± 3 versus 22 ± 3 years old) and cardiorespiratory fitness [45 ± 7 versus 43 ± 10 ml O2 (kg fat‐free mass)−1 min−1], with women tested in the mid‐follicular phase of their menstrual cycles. Subjects performed three 20 s ‘all‐out’ cycling efforts against a resistance of 5% of body mass, interspersed with 2 min of recovery. Relative mean power outputs [7.6 ± 0.5 versus 7.5 ± 0.9 W (kg fat‐free mass)−1] were similar between men and women (P > 0.05). Furthermore, there were no differences in the exercise‐induced changes in mRNA expression of PGC‐1α, PRC, PPARD, SIRT1, RIP140, HSL, HKII, PDK4, PDP1, FOXO3, MURF‐1, Myf5, MyoD and VEGFA at 3 h of recovery versus rest (P < 0.05, main effect of time). The only sex‐specific responses to exercise were an increase in the mRNA expression of GLUT4 and LPL in women only and Atrogin‐1 in men only (P < 0.05). Women also had higher expression of HKII and lower expression of FOXO3 compared with men (P < 0.05, main effect of sex). We conclude that the acute skeletal muscle response to SIT is largely similar in young men and women. The mechanistic basis for sex‐based differences in response to several weeks of SIT that has been previously reported remains to be elucidated.
“Eso no es lo mío”: un análisis de conflictos en la apropiación de prácticas de literacidad académica
Authors: Sito Luanda , Kleiman Angela B. 
Published: January 2017

<p>En este artículo, examinamos conflictos que emergieron en la apropiación de prácticas de literacidad académica, con base en trayectorias de universitarios afros e indígenas que ingresaron en universidades públicas por acciones afirmativas – en Brasil y Colombia. Para eso, analizamos parte de un corpus generado para una investigación doctoral, cuyo objeto fue la literacidad académica. En ese estudio, de carácter cualitativo, utilizamos entrevistas a estudiantes y documentos oficiales de la política afirmativa. Desde el marco de la Lingüística Aplicada, nuestra investigación se fundamenta en los <em>Nuevos Estudios de Literacidad</em> y en la teoría del Círculo de Bajtín. Los conflictos en las trayectorias de literacidad académica de esos estudiantes, además de denotar (des)encuentros con la universidad, interpelan las políticas interculturales desde sus experiencias, revelando aspectos de la vida universitaria que no suelen ser contemplados en las discusiones de permanencia de los programas de acción afirmativa, como la interculturalidad y el lenguaje.</p>
Pseudomonas aeruginosa
Pore-Forming Exolysin and Type IV Pili Cooperate To Induce Host Cell Lysis
Authors: Basso Pauline , Ragno Michel , Elsen Sylvie , Reboud Emeline , Golovkine Guillaume , Bouillot Stephanie , Huber Philippe , Lory Stephen , Faudry Eric , Attrée Ina 
Published: January 2017

ABSTRACT

Clinical strains of
Pseudomonas aeruginosa
lacking the type III secretion system genes employ a toxin, exolysin (ExlA), for host cell membrane disruption. Here, we demonstrated that ExlA export requires a predicted outer membrane protein, ExlB, showing that ExlA and ExlB define a new active two-partner secretion (TPS) system of
P. aeruginosa
. In addition to the TPS signals, ExlA harbors several distinct domains, which include one hemagglutinin domain, five arginine-glycine-aspartic acid (RGD) motifs, and a C-terminal region lacking any identifiable sequence motifs. However, this C-terminal region is important for the toxic activity, since its deletion abolishes host cell lysis. Using lipid vesicles and eukaryotic cells, including red blood cells, we demonstrated that ExlA has a pore-forming activity which precedes cell membrane disruption of nucleated cells. Finally, we developed a high-throughput cell-based live-dead assay and used it to screen a transposon mutant library of an ExlA-producing
P. aeruginosa
clinical strain for bacterial factors required for ExlA-mediated toxicity. The screen resulted in the identification of proteins involved in the formation of type IV pili as being required for ExlA to exert its cytotoxic activity by promoting close contact between bacteria and the host cell. These findings represent the first example of cooperation between a pore-forming toxin of the TPS family and surface appendages in host cell intoxication.

IMPORTANCE
The course and outcome of acute, toxigenic infections by
Pseudomonas aeruginosa
clinical isolates rely on the deployment of one of two virulence strategies: delivery of effectors by the well-known type III secretion system or the cytolytic activity of the recently identified two-partner secreted toxin, exolysin. Here, we characterize several features of the mammalian cell intoxication process mediated by exolysin. We found that exolysin requires the outer membrane protein ExlB for export into extracellular medium. Using
in vitro
recombinant protein and
ex vivo
assays, we demonstrated a pore-forming activity of exolysin. A cellular cytotoxicity screen of a transposon mutant library, made in an exolysin-producing clinical strain, identified type IV pili as bacterial appendages required for exolysin toxic function. This work deciphers molecular mechanisms underlying the activity of novel virulence factors used by
P. aeruginosa
clinical strains lacking the type III secretion system, including a requirement for the toxin-producing bacteria to be attached to the targeted cell to induce cytolysis, and defines new targets for developing antivirulence strategies.
Incidence, risk factors and risk prediction of hospital-acquired suspected adverse drug reactions: a prospective cohort of Ugandan inpatients
Authors: Kiguba Ronald , Karamagi Charles , Bird Sheila M 
Published: January 2017

ObjectivesTo determine the incidence and risk factors of hospital-acquired suspected adverse drug reactions (ADRs) among Ugandan inpatients. We also constructed risk scores to predict and qualitatively assess for peculiarities betweenlow-riskandhigh-riskADR patients.MethodsProspective cohort of consented adults admitted on medical and gynaecological wards of the 1790-bed Mulago National Referral Hospital. Hospital-acquired suspected ADRs were dichotomised aspossible(possible/probable/definite) ornotandprobable(probable/definite) ornot, using the Naranjo scale. Risk scores were generated from coefficients of ADR risk-factor logistic regression models.ResultsThe incidence ofpossiblehospital-acquired suspected ADRs was 25% (194/762, 95% CI: 22% to 29%): 44% (85/194) experienced seriouspossibleADRs. The risk ofprobableADRs was 11% (87/762, 95% CI 9% to 14%): 46% (40/87) had seriousprobableADRs. Antibacterials-only (51/194), uterotonics-only (21/194), cardiovascular drugs-only (16/194), antimalarials-only (12/194) and analgesics-only (10/194) were the most frequently implicated. Treatment with six or more conventional medicines during hospitalisation (OR=2.31, 95% CI 1.29 to 4.15) and self-reported herbal medicine use during the 4 weeks preadmission (OR=1.96, 95% CI 1.22 to 3.13) were the risk factors forprobablehospital-acquired ADRs. Risk factors forpossiblehospital-acquired ADRs were: treatment with six or more conventional medicines (OR=2.72, 95% CI 1.79 to 4.13), herbal medicine use during the 4 weeks preadmission (OR=1.68, 95% CI 1.16 to 2.43), prior 3 months hospitalisation (OR=1.57, 95% CI 1.09 to 2.26) and being on gynaecological ward (OR=2.16, 95% CI 1.36 to 3.44). More drug classes were implicated amonghigh-riskADR-patients, with cardiovascular drugs being the most frequently linked topossibleADRs.ConclusionsThe risk of hospital-acquired suspected ADRs was higher with preadmission herbal medicine use and treatment with six or more conventional medicines during hospitalisation. Our risk scores should be validated in large-scale studies and tested in routine clinical care.
Assessing potential population impact of statin treatment for primary prevention of atherosclerotic cardiovascular diseases in the USA: population-based modelling study
Authors: Yang Quanhe , Zhong Yuna , Gillespie Cathleen , Merritt Robert , Bowman Barbara , George Mary G , Flanders W Dana 
Published: January 2017

ObjectiveNew cholesterol treatment guidelines from American College of Cardiology/American Heart Association recommend statin treatment for more of US population to prevent atherosclerotic cardiovascular disease (ASCVD). It is important to assess how new guidelines may affect population-level health. This study assessed the impact of statin use for primary prevention of ASCVD under the new guidelines.MethodsWe used data from 2010 US Multiple Cause Mortality, Third National Health and Nutrition Examination Survey (NHANES III) Linked Mortality File (1988–2006, n=8941) and NHANES 2005–2010 (n=3178) participants 40–75 years of age for the present study.ResultsAmong 33.0 million adults meeting new guidelines for primary prevention of ASCVD, 8.8 million were taking statins; 24.2 million, including 7.7 million with diabetes, are eligible for statin treatment. If all those with diabetes used a statin, 2514 (95% CI 592 to 4142) predicted ASCVD deaths would be prevented annually with 482 (0 to 2239) predicted annual additional cases of myopathy based on randomised clinical trials (RCTs), and 11 801 (9251 to 14 916) using population-based study. Among 16.5 million without diabetes, 5425 (1276 to 8935) ASCVD deaths would be prevented annually with 16 406 (4922 to 26 250) predicted annual additional cases of diabetes and between 1030 (0 to 4791) and 24 302 (19 363 to 30 292) additional cases of myopathy based on RCTs and population-based study. Assuming 80% eligible population take statins with 80% medication adherence, among those without diabetes, the corresponding numbers were 3472 (817 to 5718) deaths, 10 500 (3150 to 16 800) diabetes, 660 (0 to 3066) myopathy (RCTs), and 15 554 (12 392 to 19 387) myopathy (population-based). The estimated total annual cost of statins use ranged from US$1.65 to US$6.5 billion if 100% of eligible population take statins.ConclusionsThis population-based modelling study focused on impact of statin use on ASCVD mortality. Under the new guidelines, if all those eligible for primary prevention of ASCVD take statins, up to 12.6% of annual ASCVD deaths might be prevented, though additional cases of diabetes and myopathy likely occur.Disclaimer:The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Estimated generic prices of cancer medicines deemed cost-ineffective in England: a cost estimation analysis
Authors: Hill Andrew , Redd Christopher , Gotham Dzintars , Erbacher Isabelle , Meldrum Jonathan , Harada Ryo 
Published: January 2017

ObjectivesThe aim of this study was to estimate lowest possible treatment costs for four novel cancer drugs, hypothesising that generic manufacturing could significantly reduce treatment costs.SettingThis research was carried out in a non-clinical research setting using secondary data.ParticipantsThere were no human participants in the study. Four drugs were selected for the study: bortezomib, dasatinib, everolimus and gefitinib. These medications were selected according to their clinical importance, novel pharmaceutical actions and the availability of generic price data.Primary and secondary outcome measuresTarget costs for treatment were to be generated for each indication for each treatment. The primary outcome measure was the target cost according to a production cost calculation algorithm. The secondary outcome measure was the target cost as the lowest available generic price; this was necessary where export data were not available to generate an estimate from our cost calculation algorithm. Other outcomes included patent expiry dates and total eligible treatment populations.ResultsTarget prices were £411 per cycle for bortezomib, £9 per month for dasatinib, £852 per month for everolimus and £10 per month for gefitinib. Compared with current list prices in England, these target prices would represent reductions of 74–99.6%. Patent expiry dates were bortezomib 2014–22, dasatinib 2020–26, everolimus 2019–25 and gefitinib 2017. The total global eligible treatment population in 1 year is 769 736.ConclusionsOur findings demonstrate that affordable drug treatment costs are possible for novel cancer drugs, suggesting that new therapeutic options can be made available to patients and doctors worldwide. Assessing treatment cost estimations alongside cost-effectiveness evaluations is an important area of future research.
AspiriN To Inhibit SEPSIS (ANTISEPSIS) randomised controlled trial protocol
Authors: Eisen Damon P , Moore Elizabeth M , Leder Karin , Lockery Jessica , McBryde Emma S , McNeil John J , Pilcher David , Wolfe Rory , Woods Robyn L 
Published: January 2017

IntroductionSepsis is a leading global cause of morbidity and mortality, and is more common at the extremes of age. Moreover, the cost of in-hospital care for elderly patients with sepsis is significant. There are indications from experimental and observational studies that aspirin may reduce inflammation associated with infection. This paper describes the rationale and design of the AspiriN To Inhibit SEPSIS (ANTISEPSIS) trial, a substudy of ASPirin in Reducing Events in the Elderly (ASPREE). ANTISEPSIS primarily aims to determine whether low-dose aspirin reduces sepsis-related deaths in older people. Additionally, it will assess whether low-dose aspirin reduces sepsis-related hospitalisations and sepsis-related Intensive Care Unit (ICU) admissions.Methods and analysisASPREE is a double-blinded, randomised, placebo-controlled primary prevention trial that will determine whether daily low-dose aspirin extends disability-free longevity in 19 000 healthy older people recruited in Australia and the USA. The ANTISEPSIS substudy involves additional ASPREE trial data collection to assess the impact of daily low-dose aspirin on sepsis-related events in the 16 703 ASPREE participants aged 70 years and over, recruited in Australia. The intervention is a daily 100 mg dose of enteric-coated aspirin versus matching placebo, with 1:1 randomisation. The primary outcome for the ANTISEPSIS substudy is the incidence of sepsis-related death in eligible patients. The incidence of sepsis-related hospital and ICU admissions are secondary outcomes. ANTISEPSIS is to be conducted between 2012 and 2018.DiscussionThis substudy will determine whether aspirin, an inexpensive and accessible therapy, safely reduces sepsis-related deaths and hospitalisations in older Australians. If shown to be the case, this would have profound effects on the health of older Australians.Trial registration numberPre-results,ACTRN12613000349741.
Associations of apolipoprotein B/apolipoprotein A-I ratio with pre-diabetes and diabetes risks: a cross-sectional study in Chinese adults
Authors: Zheng Shuang , Han Tingting , Xu Hua , Zhou Huan , Ren Xingxing , Wu Peihong , Zheng Jun , Wang Lihua , Zhang Ming , Jiang Yihong , Chen Yawen , Qiu Huiying , Liu Wei , Hu Yaomin 
Published: January 2017

BackgroundApolipoprotein B/apolipoprotein A-I (ApoB/ApoA-I) ratio is a useful predictor of cardiovascular risk. However, the association between the ApoB/ApoA-I ratio and the risk of type 2 diabetes mellitus (T2DM) is still obscure.AimsTo investigate the associations between the ApoB/ApoA-I ratio and the risk of T2DM and pre-diabetes in a Chinese population, and to assess the role of gender in these associations.MethodsA stratified random sampling design was used in this cross-sectional study which included 264 men and 465 women with normal glucose tolerance (NGT), pre-diabetes or T2DM. Serum ApoB, ApoA-I and other lipid and glycaemic traits were measured. Pearson's partial correlation and multivariable logistic analysis were used to evaluate the associations between ApoB/ApoA-I ratio and the risk of T2DM and pre-diabetes.ResultsThe ApoB/ApoA-I ratios were significantly increased across the spectrum of NGT, pre-diabetes and T2DM. Women showed higher levels of ApoB/ApoA-I ratio and ApoB than men in the pre-diabetic and T2DM groups, but not in the NGT group. The ApoB/ApoA-I ratio was closely related with triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and other glycaemic traits. Moreover, in women, the risk of diabetes and pre-diabetes in the top and middle tertiles of the ApoB/ApoA-I ratio were 3.65-fold (95% CI 1.69 to 6.10) and 2.19-fold (95% CI 1.38 to 2.84) higher than in the bottom tertile, respectively, after adjusting for potential confounding factors. However, the associations disappeared in men after adjusting for other factors.ConclusionsThe ApoB/ApoA-I ratio showed positive associations with the risk of diabetes and pre-diabetes in Chinese women.
EZH2 or HDAC1 Inhibition Reverses Multiple Myeloma–Induced Epigenetic Suppression of Osteoblast Differentiation
Authors: Adamik Juraj , Jin Shunqian , Sun Quanhong , Zhang Peng , Weiss Kurt R. , Anderson Judith L. , Silbermann Rebecca , Roodman G. David , Galson Deborah L. 
Published: January 2017

AbstractIn multiple myeloma, osteolytic lesions rarely heal because of persistent suppressed osteoblast differentiation resulting in a high fracture risk. Herein, chromatin immunoprecipitation analyses reveal that multiple myeloma cells induce repressive epigenetic histone changes at the Runx2 locus that prevent osteoblast differentiation. The most pronounced multiple myeloma–induced changes were at the Runx2-P1 promoter, converting it from a poised bivalent state to a repressed state. Previously, it was observed that multiple myeloma induces the transcription repressor GFI1 in osteoblast precursors, which correlates with decreased Runx2 expression, thus prompting detailed characterization of the multiple myeloma and TNFα-dependent GFI1 response element within the Runx2-P1 promoter. Further analyses reveal that multiple myeloma–induced GFI1 binding to Runx2 in osteoblast precursors and recruitment of the histone modifiers HDAC1, LSD1, and EZH2 is required to establish and maintain Runx2 repression in osteogenic conditions. These GFI1-mediated repressive chromatin changes persist even after removal of multiple myeloma. Ectopic GFI1 is sufficient to bind to Runx2, recruit HDAC1 and EZH2, increase H3K27me3 on the gene, and prevent osteogenic induction of endogenous Runx2 expression. Gfi1 knockdown in MC4 cells blocked multiple myeloma–induced recruitment of HDAC1 and EZH2 to Runx2, acquisition of repressive chromatin architecture, and suppression of osteoblast differentiation. Importantly, inhibition of EZH2 or HDAC1 activity in pre-osteoblasts after multiple myeloma exposure in vitro or in osteoblast precursors from patients with multiple myeloma reversed the repressive chromatin architecture at Runx2 and rescued osteoblast differentiation.Implications: This study suggests that therapeutically targeting EZH2 or HDAC1 activity may reverse the profound multiple myeloma–induced osteoblast suppression and allow repair of the lytic lesions. Mol Cancer Res; 15(4); 405–17. ©2017 AACR.