bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytotoxic cell involvement in human cutaneous leishmaniasis: assessments in active disease, under therapy and after clinical cure
Authors: Cunha C. F. , Ferraz R. , Pimentel M. I. F. , Lyra M. R. , Schubach A. O. , Da‐Cruz A. M. , Bertho A. L. 
Published: March 2016

SummaryCutaneous leishmaniasis (CL) is an important public health issue worldwide. The control of Leishmania infection depends on cellular immune mechanisms, and the inflammatory response may contribute to pathogenesis. A beneficial role of CD8+ T lymphocytes has been proposed; nevertheless, other studies suggest a cytotoxic role of CD8+ T lymphocytes involved in tissue damage, showing controversial role of these cells. The goal of the current study was to understand the immunopathology of CL and determine the profile of cytotoxic cells – such as CD4+ T, natural killer and natural killer T cells – that might be involved in triggering immunological mechanisms, and may lead to cure or disease progression. The frequencies of cytotoxic cell populations in peripheral blood, obtained from patients with active disease, during treatment and after clinical healing, were assessed by flow cytometry. Cytotoxicity could not be related to a deleterious role in Leishmania braziliensis infection, as patients with active CL showed similar percentages of degranulation to healthy individuals (HI). Cured patients exhibited a lower percentage of degranulating cells, which may be due to a downregulation of the immune response. The understanding of the immunopathological mechanisms involved in CL and the commitment of cytotoxic cells enables improvements in therapeutic strategies.
Counting by Weighing: Know Your Numbers with Confidence
Authors: Liu W. , Han Y. , Bretz F. , Wan F. , Yang P. 
Published: March 2016

SummaryCounting by weighing is often more efficient than counting manually, which is time consuming and prone to human errors, especially when the number of items (e.g. plant seeds, printed labels or coins) is large. Papers in the statistical literature have focused on how to count, by weighing, a random number of items that is close to a prespecified number in some sense. The paper considers the new problem, arising from a consultation with a company, of making inference about the number of 1p coins in a bag with known weight for infinitely many bags, by using the estimated distribution of coin weight from one calibration data set only. Specifically, a lower confidence bound has been constructed on the number of 1p coins for each of infinitely many future bags of 1p coins, as required by the company. As the same calibration data set is used repeatedly in the construction of all these lower confidence bounds, the interpretation of coverage frequency of the lower confidence bounds that is proposed is different from that of a usual confidence set.
Severe cryptococcal‐associated neurological immune reconstitution inflammatory syndrome in a renal transplant recipient treated with adalimumab
Authors: Deshayes S. , Bouvier N. , Chatelet V. , Hurault de Ligny B. , Dargère S. , Bonhomme J. , Béchade C. 
Published: March 2016

AbstractCryptococcosis is a major concern in organ transplant recipients. A decrease in immunosuppressants following the initiation of antifungal therapy is currently recommended, but can occasionally be complicated by the onset of immune reconstitution inflammatory syndrome (IRIS). We report on a case of cryptococcosis in a kidney transplant recipient, compounded by severe neurological IRIS, the outcome of which was unfavorable despite the use of anti‐tumor necrosis factor‐alpha monoclonal antibodies.
Acute kidney injury in pregnancy and the use of non‐steroidal anti‐inflammatory drugs
Authors: Wiles Kate S , Banerjee Anita 
Published: March 2016

Key contentSerum creatinine falls in normal pregnancy and a new serum creatinine level above 90 micromol/l in pregnancy should trigger investigation for acute kidney injury.Causes of acute kidney injury in pregnancy include pre‐eclampsia,HELLP(haemolysis, elevated liver enzymes and low platelet count), microangiopathic haemolytic anaemia, acute fatty liver of pregnancy, lupus nephritis, renal tract obstruction and drug use.Non‐steroidal anti‐inflammatory drugs (NSAIDs) can cause acute kidney injury as well as cardiovascular and gastrointestinal adverse effects.NSAIDs should be avoided in pre‐eclampsia, volume depletion, acute kidney injury and chronic kidney disease.WhenNSAIDs are used, ibuprofen has the best safety profile. It should be used at the lowest effective dose and discontinued as soon as possible.Learning objectivesTo be able to diagnose acute kidney injury in pregnancy and understand the importance of supportive treatment.To gain an overview of the possible causes of acute kidney injury in pregnancy and their management.To appreciate the adverse effect profile ofNSAIDs and be able to modify prescribing for high‐risk patients.Ethical issuesWhen prescribing in pregnancy and the postpartum period the risks and benefits of treatment must be considered for each individual patient.Acute kidney injury in pregnancy is more prevalent in low and middle income countries where there is often a lower provision of supportive renal care.
Origin of and resulting floristic composition from seedbanks in agroforestry systems of Tomé‐Açu, Eastern Amazon
Authors: Lacerda F , Miranda I , Lima T T S , Mafra N A , Leão F M , Do Vale I , Bispo C J C , Kato O R 
Published: March 2016

SummaryThe objective of this study was to verify the origin of and resulting floristic composition from seedbanks in different agroforestry systems in Tomé‐Açu, Brazil. The seedbanks were sampled in three smallholder farmers (Demonstration Units = DU), each with three agroforestry treatments and secondary forest as control. Seedling emergence in a glasshouse was used to quantify and identify the seeds collected in 2008. The floristic composition of the above‐ground community was characterised with annual floristic surveys from 2008 to 2011. The total densities and diversity of the seedbanks were not different among the treatments within a given DU, but differences occurred among DU. The most abundant woody species had higher seed densities in the secondary forests than in DU. Conversely, among the herbaceous species, two groups were differentiated: species with similar densities between the DU and the secondary forest and species with higher density in the DU. In the DU, the similarity between the floristic composition of the seedbank and the flora surveyed in 2008 was high, but decreased in subsequent years. The species present in the seedbank of agroforestry systems are highly influenced by the secondary forest, but provide little information about the floristic composition that will arise in the future.
‘Adipaging’: ageing and obesity share biological hallmarks related to a dysfunctional adipose tissue
Authors: Pérez Laura M. , Pareja‐Galeano Helios , Sanchis‐Gomar Fabián , Emanuele Enzo , Lucia Alejandro , Gálvez Beatriz G. 
Published: March 2016

AbstractThe increasing ageing of our societies is accompanied by a pandemic of obesity and related cardiometabolic disorders. Progressive dysfunction of the white adipose tissue is increasingly recognized as an important hallmark of the ageing process, which in turn contributes to metabolic alterations, multi‐organ damage and a systemic pro‐inflammatory state (‘inflammageing’). On the other hand, obesity, the paradigm of adipose tissue dysfunction, shares numerous biological similarities with the normal ageing process such as chronic inflammation and multi‐system alterations. Accordingly, understanding the interplay between accelerated ageing related to obesity and adipose tissue dysfunction is critical to gain insight into the ageing process in general as well as into the pathophysiology of obesity and other related conditions. Here we postulate the concept of ‘adipaging’ to illustrate the common links between ageing and obesity and the fact that, to a great extent, obese adults are prematurely aged individuals.image
European Project “Supercritical Water Reactor-Fuel Qualification Test”: Summary of General Corrosion Tests
Authors: Novotný Radek , Janík Přemysl , Toivonen Aki , Ruiz Anna , Szaraz Zoltan , Zhang Lefu , Siegl Jan , Haušild Petr , Penttilä Sami , Macák Jan 
Published: March 2016

The main target of the EUROATOM FP7 project “Fuel Qualification Test for SCWR” is to make significant progress toward the design, analysis, and licensing of a fuel assembly cooled with supercritical water in a research reactor. The program of dedicated Work Package (WP4)-Prequalification was focused on evaluation of general corrosion resistance of three preselected austenitic stainless steels, 08Cr18Ni10Ti, AISI 347H, and AISI 316L, which should be prequalified for application as a cladding material for fuel qualification tests in supercritical water. Therefore, the experiments in support of WP4 concentrated on 2000-hr corrosion exposures in 25-MPa supercritical water (SCW) at two different temperatures 550°C and 500°C dosed with both 150 and 2000 ppb of dissolved oxygen content. Moreover, the water chemistry effect was investigated by conducting tests in 550°C SCW with 1.5 ppm of dissolved hydrogen content. At first, corrosion coupons were exposed for 600, 1400, and 2000 hrs in Joint Research Centre-Institute for Energy and Transport (JRC-IET), VTT Technical Research Centre of Finland Ltd. (VTT), and Shanghai Jiao Tong University (SJTU) autoclaves connected to the recirculation loop, allowing continual water chemistry control during the test. The following examination of exposed specimens consisted of weight-change calculations and detailed macro- and microscopic investigation of oxide layers using scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDX). With respect to general corrosion results, all tested steels showed sufficient corrosion resistance in SCW conditions taking into account the conditions foreseen for future fuel qualification test in the research reactor in CVR Rez. When the results of weight-change calculations were compared for all three materials, it was found that the corrosion resistance increased in the following order: 316L<347H<08Cr18Ni10Ti. Results obtained in hydrogen water chemistry (HWC) did not indicate any significant beneficial effect compared to tests in SCW with 150 or 2000 ppb dissolved oxygen content. Additional tests were dedicated to investigation of the surface-finish effect. In these exposures, polished, sand-blasted, and plane-milled surface-finish techniques were investigated. The beneficial effect of surface cold work in particular of sand-blasting was clearly demonstrated.
Visual‐search observers for assessing tomographic x‐ray image quality
Authors: Gifford Howard C. , Liang Zhihua , Das Mini 
Published: March 2016

Purpose:Mathematical model observers commonly used for diagnostic image‐quality assessments in x‐ray imaging research are generally constrained to relatively simple detection tasks due to their need for statistical prior information. Visual‐search (VS) model observers that employ morphological features in sequential search and analysis stages have less need for such information and fewer task constraints. The authors compared four VS observers against human observers and an existing scanning model observer in a pilot study that quantified how mass detection and localization in simulated digital breast tomosynthesis (DBT) can be affected by the number P of acquired projections.Methods:Digital breast phantoms with embedded spherical masses provided single‐target cases for a localization receiver operating characteristic (LROC) study. DBT projection sets based on an acquisition arc of 60° were generated for values of P between 3 and 51. DBT volumes were reconstructed using filtered backprojection with a constant 3D Butterworth postfilter; extracted 2D slices were used as test images. Three imaging physicists participated as observers. A scanning channelized nonprewhitening (CNPW) observer had knowledge of the mean lesion‐absent images. The VS observers computed an initial single‐feature search statistic that identified candidate locations as local maxima of either a template matched‐filter (MF) image or a gradient‐template MF (GMF) image. Search inefficiencies that modified the statistic were also considered. Subsequent VS candidate analyses were carried out with (i) the CNPW statistical discriminant and (ii) the discriminant computed from GMF training images. These location‐invariant discriminants did not utilize covariance information. All observers read 36 training images and 108 study images per P value. Performance was scored in terms of area under the LROC curve.Results:Average human‐observer performance was stable for P between 7 and 35. In the absence of search inefficiencies, the VS models based on the GMF analysis provided the best correlation (Pearson ρ ≥ 0.62) with the human results. The CNPW‐based VS observers deviated from the humans primarily at lower values of P. In this limited study, search inefficiencies allowed for good quantitative agreement with the humans for most of the VS observers.Conclusions:The computationally efficient training requirements for the VS observer are suitable for high‐resolution imaging, indicating that the observer framework has the potential to overcome important task limitations of current model observers for x‐ray applications.
The Effectiveness of Injury Prevention Programs for Youth and Adolescent Athletes
Authors: Weber Michelle L. , Lam Kenneth C. , McLeod Tamara C. Valovich 
Published: March 2016

Clinical Question:In youth and adolescent athletes, are jumping/plyometric exercises more effective than balance exercises in preventing sport-related injuries?Objective:The aim of this article is to examine the meta-analysis by Rössler et al.1 as it relates to the clinical question.Conclusion:Evidence in this meta-analysis suggests that injury prevention programs provide beneficial effects in injury reduction for youth and adolescent athletes. Prevention programs that contained jumping or plyometric exercises and were targeted toward females appeared to be especially beneficial for decreasing injury risk.
Efficacy and Safety of Pyronaridine-Artesunate for Treatment of Uncomplicated Plasmodium falciparum Malaria in Western Cambodia
Authors: Leang Rithea , Canavati Sara E. , Khim Nimol , Vestergaard Lasse S. , Borghini Fuhrer Isabelle , Kim Saorin , Denis Mey Bouth , Heng Pisal , Tol Bunkea , Huy Rekol , Duparc Stephan , Dondorp Arjen M. , Menard Didier , Ringwald Pascal 
Published: March 2016

ABSTRACT

Pyronaridine-artesunate efficacy for the treatment of uncomplicated
Plasmodium falciparum
malaria was assessed in an area of artemisinin resistance in western Cambodia. This nonrandomized, single-arm, observational study was conducted between 2014 and 2015. Eligible patients were adults or children with microscopically confirmed
P. falciparum
infection and fever. Patients received pyronaridine-artesunate once daily for 3 days, dosed according to body weight. The primary outcome was an adequate clinical and parasitological response (ACPR) on day 42, estimated by using Kaplan-Meier analysis, PCR adjusted to exclude reinfection. One hundred twenty-three patients were enrolled. Day 42 PCR-crude ACPRs were 87.2% (95% confidence interval [CI], 79.7 to 92.6%) for the overall study, 89.8% (95% CI, 78.8 to 95.3%) for Pursat, and 82.1% (95% CI, 68.4 to 90.2%) for Pailin. Day 42 PCR-adjusted ACPRs were 87.9% (95% CI, 80.6 to 93.2%) for the overall study, 89.8% (95% CI, 78.8 to 95.3%) for Pursat, and 84.0% (95% CI, 70.6 to 91.7%) for Pailin (
P
= 0.353 by a log rank test). Day 28 PCR-crude and -adjusted ACPRs were 93.2% (95% CI, 82.9 to 97.4%) and 88.1% (95% CI, 75.3 to 94.5%) for Pursat and Pailin, respectively. A significantly lower proportion of patients achieved day 3 parasite clearance in Pailin (56.4% [95% CI, 43.9 to 69.6%]) than in Pursat (86.7% [95% CI, 76.8 to 93.8%];
P
= 0.0019). Fever clearance was also extended at Pailin versus Pursat (
P
< 0.0001). Most patients (95.9% [116/121]) harbored
P. falciparum
kelch13
C580Y mutant parasites. Pyronaridine-artesunate was well tolerated; mild increases in hepatic transaminase levels were consistent with data from previous reports. Pyronaridine-artesunate efficacy was below the World Health Organization-recommended threshold at day 42 for medicines with a long half-life (90%) for first-line treatment of
P. falciparum
malaria in western Cambodia despite high efficacy elsewhere in Asia and Africa. (This study has been registered at ClinicalTrials.gov under registration number NCT02389439.)
Sequential Treatment of Biofilms with Aztreonam and Tobramycin Is a Novel Strategy for Combating Pseudomonas aeruginosa Chronic Respiratory Infections
Authors: Rojo-Molinero Estrella , Macià María D. , Rubio Rosa , Moyà Bartolomé , Cabot Gabriel , López-Causapé Carla , Pérez José L. , Cantón Rafael , Oliver Antonio 
Published: March 2016

ABSTRACT

Traditional therapeutic strategies to control chronic colonization in cystic fibrosis (CF) patients are based on the use of a single nebulized antibiotic. In this study, we evaluated the therapeutic efficacy and dynamics of antibiotic resistance in
Pseudomonas aeruginosa
biofilms under sequential therapy with inhaled aztreonam (ATM) and tobramycin (TOB). Laboratory strains PAO1, PAOMS (hypermutable), PAOMA (mucoid), and PAOMSA (mucoid and hypermutable) and two hypermutable CF strains, 146-HSE (Liverpool epidemic strain [LES-1]) and 1089-HSE (ST1089), were used. Biofilms were developed using the flow cell system. Mature biofilms were challenged with peak and 1/10-peak concentrations of ATM (700 mg/liter and 70 mg/liter), TOB (1,000 mg/liter and 100 mg/liter), and their alternations (ATM/TOB/ATM and TOB/ATM/TOB) for 2 (
t
= 2), 4 (
t
= 4), and 6 days (
t
= 6). The numbers of viable cells (CFU) and resistant mutants were determined. Biofilm structural dynamics were monitored by confocal laser scanning microscopy and processed with COMSTAT and IMARIS software programs. TOB monotherapy produced an intense decrease in CFU that was not always correlated with a reduction in biomass and/or a bactericidal effect on biofilms, particularly for the CF strains. The ATM monotherapy bactericidal effect was lower, but effects on biofilm biomass and/or structure, including intense filamentation, were documented. The alternation of TOB and ATM led to an enhancement of the antibiofilm activity against laboratory and CF strains compared to that with the individual regimens, potentiating the bactericidal effect and/or the reduction in biomass, particularly at peak concentrations. Resistant mutants were not documented in any of the regimens at the peak concentrations and only anecdotally at the 1/10-peak concentrations. These results support the clinical evaluation of sequential regimens with inhaled antibiotics in CF, as opposed to the current maintenance treatments with just one antibiotic in monotherapy.
Optimization of Polymyxin B in Combination with Doripenem To Combat Mutator Pseudomonas aeruginosa
Authors: Ly Neang S. , Bulman Zackery P. , Bulitta Jürgen B. , Baron Christopher , Rao Gauri G. , Holden Patricia N. , Li Jian , Sutton Mark D. , Tsuji Brian T. 
Published: March 2016

ABSTRACT

Development of spontaneous mutations in
Pseudomonas aeruginosa
has been associated with antibiotic failure, leading to high rates of morbidity and mortality. Our objective was to evaluate the pharmacodynamics of polymyxin B combinations against rapidly evolving
P. aeruginosa
mutator strains and to characterize the time course of bacterial killing and resistance via mechanism-based mathematical models. Polymyxin B or doripenem alone and in combination were evaluated against six
P. aeruginosa
strains: wild-type PAO1, mismatch repair (MMR)-deficient (
mutS
and
mutL
) strains, and 7,8-dihydro-8-oxo-deoxyguanosine system (GO) base excision repair (BER)-deficient (
mutM
,
mutT
, and
mutY
) strains over 48 h. Pharmacodynamic modeling was performed using S-ADAPT and facilitated by SADAPT-TRAN. Mutator strains displayed higher mutation frequencies than the wild type (>600-fold). Exposure to monotherapy was followed by regrowth, even at high polymyxin B concentrations of up to 16 mg/liter. Polymyxin B and doripenem combinations displayed enhanced killing activity against all strains where complete eradication was achieved for polymyxin B concentrations of >4 mg/liter and doripenem concentrations of 8 mg/liter. Modeling suggested that the proportion of preexisting polymyxin B-resistant subpopulations influenced the pharmacodynamic profiles for each strain uniquely (fraction of resistance values are −8.81 log
10
for the wild type, −4.71 for the
mutS
mutant, and −7.40 log
10
for the
mutM
mutant). Our findings provide insight into the optimization of polymyxin B and doripenem combinations against
P. aeruginosa
mutator strains.
Fluoroquinolone and Third-Generation-Cephalosporin Resistance among Hospitalized Patients with Urinary Tract Infections Due to Escherichia coli: Do Rates Vary by Hospital Characteristics and Geographic Region?
Authors: Bidell Monique R. , Palchak Melissa , Mohr John , Lodise Thomas P. 
Published: March 2016

ABSTRACT

This analysis of nearly 10,000 hospital-associated urinary tract infection (UTI) episodes due to
Escherichia coli
showed that fluoroquinolone and third-generation-cephalosporin resistance rates were 34.5% and 8.6%, respectively; the rate of concurrent resistance to both agents was 7.3%. Fluoroquinolone resistance rates exceeded 25% regardless of geographic location or hospital characteristics. The findings suggest that fluoroquinolones should be reserved and third-generation cephalosporins be used with caution as empirical agents for hospitalized patients with UTIs due to
E. coli
.
Cytotoxic and Inflammatory Responses Induced by Outer Membrane Vesicle-Associated Biologically Active Proteases from Vibrio cholerae
Authors: Mondal Ayan , Tapader Rima , Chatterjee Nabendu Sekhar , Ghosh Amit , Sinha Ritam , Koley Hemanta , Saha Dhira Rani , Chakrabarti Manoj K. , Wai Sun Nyunt , Pal Amit 
Published: March 2016

ABSTRACT

Proteases in
Vibrio cholerae
have been shown to play a role in its pathogenesis.
V. cholerae
secretes Zn-dependent hemagglutinin protease (HAP) and calcium-dependent trypsin-like serine protease (VesC) by using the type II secretion system (TIISS). Our present studies demonstrated that these proteases are also secreted in association with outer membrane vesicles (OMVs) and transported to human intestinal epithelial cells in an active form. OMV-associated HAP induces dose-dependent apoptosis in Int407 cells and an enterotoxic response in the mouse ileal loop (MIL) assay, whereas OMV-associated VesC showed a hemorrhagic fluid response in the MIL assay, necrosis in Int407 cells, and an increased interleukin-8 (IL-8) response in T84 cells, which were significantly reduced in OMVs from VesC mutant strain. Our results also showed that serine protease VesC plays a role in intestinal colonization of
V. cholerae
strains in adult mice. In conclusion, our study shows that
V. cholerae
OMVs secrete biologically active proteases which may play a role in cytotoxic and inflammatory responses.