bluuebunny/crossref_metadata_2025_split huggingface dataset:
How to become a killer, or is it all accidental? Virulence strategies in oral streptococci
Authors: Sitkiewicz I. 
Published: July 2017

SummaryStreptococci are a diverse group of Gram‐positive microorganisms sharing common virulence traits and similar strategies to escape the oral niche and establish an infection in other parts of the host organism. Invasive infection with oral streptococci is “a perfect storm” that requires the concerted action of multiple biotic and abiotic factors. Our understanding of streptococcal pathogenicity and infectivity should probably be less mechanistic and driven not only by the identification of novel virulence factors. The observed diversity of the genus, including the range of virulence and pathogenicity mechanisms, is most likely the result of interspecies interactions, a massive horizontal gene transfer between streptococci within a shared oral niche, recombination events, selection of specialized clones, and modification of regulatory circuits. Selective pressure by the host and bacterial communities is a driving force for the selection of virulence traits and shaping the streptococcal genome. Global regulatory events driving niche adaptation and interactions with bacterial communities and the host steer research interests towards attempts to define the oral interactome on the transcriptional level and define signal cross‐feeding and co‐expression and co‐regulation of virulence genes.
Recommendations for analysis of repeated‐measures designs: testing and correcting for sphericity and use of manova and mixed model analysis
Authors: Armstrong Richard A. 
Published: July 2017

AbstractPurposeA common experimental design in ophthalmic research is the repeated‐measures design in which at least one variable is a within‐subject factor. This design is vulnerable to lack of ‘sphericity’ which assumes that the variances of the differences among all possible pairs of within‐subject means are equal. Traditionally, this design has been analysed using a repeated‐measures analysis of variance (RM‐anova) but increasingly more complex methods such as multivariate anova (manova) and mixed model analysis (MMA) are being used. This article surveys current practice in the analysis of designs incorporating different factors in research articles published in three optometric journals, namely Ophthalmic and Physiological Optics (OPO), Optometry and Vision Science (OVS), and Clinical and Experimental Optometry (CXO), and provides advice to authors regarding the analysis of repeated‐measures designs.Recent findingsOf the total sample of articles, 66% used a repeated‐measures design. Of those articles using a repeated‐measures design, 59% and 8% analysed the data using RM‐anova or manova respectively and 33% used MMA. The use of MMA relative to RM‐anova has increased significantly since 2009/10. A further search using terms to select those papers testing and correcting for sphericity (‘Mauchly's test’, ‘Greenhouse‐Geisser’, ‘Huynh and Feld’) identified 66 articles, 62% of which were published from 2012 to the present.SummaryIf the design is balanced without missing data then manova should be used rather than RM‐anova as it gives better protection against lack of sphericity. If the design is unbalanced or with missing data then MMA is the method of choice. However, MMA is a more complex analysis and can be difficult to set up and run, and care should be taken first, to define appropriate models to be tested and second, to ensure that sample sizes are adequate.
The auditory oddball paradigm revised to improve bedside detection of consciousness in behaviorally unresponsive patients
Authors: Morlet Dominique , Ruby Perrine , André‐Obadia Nathalie , Fischer Catherine 
Published: July 2017

AbstractActive paradigms requiring subjects to engage in a mental task on request have been developed to detect consciousness in behaviorally unresponsive patients. Using auditory ERPs, the active condition consists in orienting patient's attention toward oddball stimuli. In comparison with passive listening, larger P300 in the active condition identifies voluntary processes. However, contrast between these two conditions is usually too weak to be detected at the individual level. To improve test sensitivity, we propose as a control condition to actively divert the subject's attention from the auditory stimuli with a mental imagery task that has been demonstrated to be within the grasp of the targeted patients: navigate in one's home. Twenty healthy subjects were presented with a two‐tone oddball paradigm in the three following condition: (a) passive listening, (b) mental imagery, (c) silent counting of deviant stimuli. Mental imagery proved to be more efficient than passive listening to lessen P300 response to deviant tones as compared with the active counting condition. An effect of attention manipulation (oriented vs. diverted) was observed in 19/20 subjects, of whom 18 showed the expected P300 effect and 1 showed an effect restricted to the N2 component. The only subject showing no effect also proved insufficient engagement in the tasks. Our study demonstrated the efficiency of diverting attention using mental imagery to improve the sensitivity of the active oddball paradigm. Using recorded instructions and requiring a small number of electrodes, the test was designed to be conveniently and economically used at the patient's bedside.
The effect of young children's faeces disposal practices on child growth: evidence from 34 countries
Authors: Bauza Valerie , Guest Jeremy S. 
Published: July 2017

AbstractObjectiveTo characterize the relationship between child faeces disposal and child growth in low‐ and middle‐income countries.MethodsWe analysed caregiver responses and anthropometric data from Demographic and Health Surveys (2005–2014) for 202 614 children under five and 82 949 children under two to examine the association between child faeces disposal and child growth.ResultsChild faeces disposal in an improved toilet was associated with reduced stunting for children under five [adjusted prevalence ratio (aPR) = 0.90, 95% confidence interval (CI) 0.89–0.92] and a 0.12 increase in height‐for‐age z‐score (HAZ; 95% CI: 0.10–0.15) among all households. Among households with improved sanitation access, practicing improved child faeces disposal was still associated with a decrease in stunting (aPR = 0.94, 95% CI: 0.91–0.96) and a 0.09 increase in HAZ (95% CI: 0.06–0.13). Improved child faeces disposal was also associated with reductions in underweight and wasting, and an increase in weight‐for‐age z‐score (WAZ), but not an increase in weight‐for‐height z‐score (WHZ). Community coverage level of improved child faeces disposal was also associated with stunting, with 75–100% coverage associated with the greatest reduction in stunting. Child faeces disposal in an unimproved toilet was associated with reductions in underweight and wasting, but not stunting.ConclusionsImproved child faeces disposal practices could achieve greater reductions in child undernutrition than improving toilet access alone. Additionally, the common classification of child faeces disposal as ‘safe’ regardless of the type of toilet used for disposal may underestimate the benefits of disposal in an improved toilet and overestimate the benefits of disposal in an unimproved toilet.
Molecular Diagnostics Update for the Emerging (If Not Already Widespread) Sexually Transmitted Infection Agent Mycoplasma genitalium: Just About Ready for Prime Time
Authors: Munson Erik 
Published: July 2017

ABSTRACT

Mycoplasma genitalium
is an important and emerging agent of sexually transmitted infection in females and males, carrying the potential for postinfection genital tract sequelae. Past efforts to identify this organism on a routine basis, which were problematic due to the fastidious nature of the bacterium and its antigenic intricacies, have recently become supplemented by molecular diagnostics. A number of these assays are available commercially. This minireview describes the format and performance indices of a number of
M. genitalium
DNA- and RNA-based amplification assays; many of these assays have contributed to an improved clinical and epidemiologic understanding of this organism.
Susceptibility Testing for the Polymyxins: Two Steps Back, Three Steps Forward?
Authors: Vasoo Shawn 
Published: July 2017

ABSTRACT

Optimizing and standardizing susceptibility testing for the polymyxins have become pressing issues, given the rise in multidrug-resistant Gram-negative bacilli. Recently, both the CLSI and EUCAST have recommended broth microdilution (BMD) (without polysorbate) as the reference method for polymyxin susceptibility testing. In this issue, K. L. Chew et al. (J Clin Microbiol 55:2609–2616, 2017,
https://doi.org/10.1128/JCM.00268-17
) compare the performances of three commercial BMD panels and the Etest to the reference, BMD, for polymyxin B and colistin, using 76
Enterobacteriaceae
isolates (21 of which were
mcr-1
positive). Although none of the commercial BMD panels strictly met FDA performance standards in this evaluation, possibly because of the small number isolates tested, the Sensititre panel achieved >90% categorical agreement for both polymyxin compounds. These results also reaffirm CLSI and EUCAST guidance that gradient diffusion testing, which had unacceptable error rates, should be abandoned. In a simulated analysis with lowered breakpoints (susceptible, ≤1 mg/liter; intermediate, 2 mg/liter; resistant, ≥4 mg/liter), error rates and agreement were improved across the various methods and the rate of detection of
mcr-1
-positive isolates improved. These observations, taken together with recent pharmacokinetic data on optimizing target attainment for the polymyxins, suggest that more-stringent (lower) breakpoints may be reasonable, although such an approach may be limited by the inherent reliability of current testing methodologies and a lack of robust clinical correlative data, which are sorely needed.
Synthetic Toll-Like Receptor 4 (TLR4) and TLR7 Ligands Work Additively via MyD88 To Induce Protective Antiviral Immunity in Mice
Authors: Goff Peter H. , Hayashi Tomoko , He Wenqian , Yao Shiyin , Cottam Howard B. , Tan Gene S. , Crain Brian , Krammer Florian , Messer Karen , Pu Minya , Carson Dennis A. , Palese Peter , Corr Maripat 
Published: July 2017

ABSTRACT

We previously demonstrated that the combination of synthetic small-molecule Toll-like receptor 4 (TLR4) and TLR7 ligands is a potent adjuvant for recombinant influenza virus hemagglutinin, inducing rapid and sustained immunity that is protective against influenza viruses in homologous, heterologous, and heterosubtypic murine challenge models. Combining the TLR4 and TLR7 ligands balances Th1 and Th2-type immune responses for long-lived cellular and neutralizing humoral immunity against the viral hemagglutinin. Here, we demonstrate that the protective response induced in mice by this combined adjuvant is dependent upon TLR4 and TLR7 signaling via myeloid differentiation primary response gene 88 (MyD88), indicating that the adjuvants function
in vivo
via their known receptors, with negligible off-target effects, to induce protective immunity. The combined adjuvant acts via MyD88 in both bone marrow-derived and non-bone marrow-derived radioresistant cells to induce hemagglutinin-specific antibodies and protect mice against influenza virus challenge. The protective efficacy generated by immunization with this adjuvant and recombinant hemagglutinin antigen is transferable with serum from immunized mice to recipient mice in a homologous, but not a heterologous, H1N1 viral challenge model. Depletion of CD4
+
cells after an established humoral response in immunized mice does not impair protection from a homologous challenge; however, it does significantly impair recovery from a heterologous challenge virus, highlighting an important role for vaccine-induced CD4
+
cells in cross-protective vaccine efficacy. The combination of the two TLR agonists allows for significant dose reductions of each component to achieve a level of protection equivalent to that afforded by either single agent at its full dose.

IMPORTANCE
Development of novel adjuvants is needed to enhance immunogenicity to provide better protection from seasonal influenza virus infection and improve pandemic preparedness. We show here that several dose combinations of synthetic TLR4 and TLR7 ligands are potent adjuvants for recombinant influenza virus hemagglutinin antigen induction of humoral and cellular immunity against viral challenges. The components of the combined adjuvant work additively to enable both antigen and adjuvant dose sparing while retaining efficacy. Understanding an adjuvant's mechanism of action is a critical component for preclinical safety evaluation, and we demonstrate here that a combined TLR4 and TLR7 adjuvant signals via the appropriate receptors and the MyD88 adaptor protein. This novel adjuvant combination contributes to a more broadly protective vaccine while demonstrating an attractive safety profile.
Cervical cancer screening in rural Bhutan with thecareHPV test on self-collected samples: an ongoing cross-sectional, population-based study (REACH-Bhutan)
Authors: Baussano Iacopo , Tshering Sangay , Choden Tashi , Lazzarato Fulvio , Tenet Vanessa , Plummer Martyn , Franceschi Silvia , Clifford Gary M , Tshomo Ugyen 
Published: July 2017

ObjectivesThe Bhutanese Screening Programme recommends a Pap smear every 3 years for women aged 25–65 years, and coverage ranges from 20% to 60%, being especially challenging in rural settings. The ‘REACH-Bhutan’ study was conducted to assess the feasibility and outcomes of a novel approach to cervical cancer screening in rural Bhutan.DesignCross-sectional, population-based study of cervical cancer screening based on thecareHPV test on self-collected samples.SettingWomen were recruited in rural primary healthcare centres, that is, Basic Health Units (BHU), across Bhutan.ParticipantsOverall, 3648 women aged 30–60 were invited from 15 BHUs differing in accessibility, size and ethnic composition of the population.InterventionsParticipants provided a self-collected cervicovaginal sample and were interviewed. Samples were tested usingcareHPV in Thimphu (the Bhutanese capital) referral laboratory.Main outcome measuresScreening participation by geographic area, centre, age and travelling time. Previous screening history andcareHPV positivity by selected characteristics of the participants.ResultsIn April/May 2016, 2590 women (median age: 41) were enrolled. Study participation was 71% and significantly heterogeneous by BHU (range: 31%–96%). Participation decreased with increase in age (81% in women aged 30–39 years; 59% in ≥50 years) and travelling time (90% in women living <30 min from the BHU vs 62% among those >6 hours away). 50% of participants reported no previous screening, with the proportion of never-screened women varying significantly by BHU (range: 2%–72%). 265 women (10%; 95% CI 9% to 11%) werecareHPV positive, with a significant variation by BHU (range: 5%–19%) and number of sexual partners (prevalence ratio for ≥3 vs 0–1, 1.55; 95% CI 1.05 to 2.27).ConclusionsCommunity-based cervical cancer screening by testing self-collected samples for human papillomavirus (HPV) can achieve high coverage in rural Bhutan. However, solutions to bring self-collection, HPV testing and precancer treatment closer to the remotest villages are needed.
Severe energy deficit upregulates leptin receptors, leptin signaling, and PTP1B in human skeletal muscle
Authors: Perez-Suarez Ismael , Ponce-González Jesús Gustavo , de La Calle-Herrero Jaime , Losa-Reyna Jose , Martin-Rincon Marcos , Morales-Alamo David , Santana Alfredo , Holmberg Hans-Christer , Calbet Jose A. L. 
Published: July 2017

In obesity, leptin receptors (OBR) and leptin signaling in skeletal muscle are downregulated. To determine whether OBR and leptin signaling are upregulated with a severe energy deficit, 15 overweight men were assessed before the intervention (PRE), after 4 days of caloric restriction (3.2 kcal·kg body wt−1·day−1) in combination with prolonged exercise (CRE; 8 h walking + 45 min single-arm cranking/day) to induce an energy deficit of ~5,500 kcal/day, and following 3 days of control diet (isoenergetic) and reduced exercise (CD). During CRE, the diet consisted solely of whey protein ( n = 8) or sucrose ( n = 7; 0.8 g·kg body wt−1·day−1). Muscle biopsies were obtained from the exercised and the nonexercised deltoid muscles and from the vastus lateralis. From PRE to CRE, serum glucose, insulin, and leptin were reduced. OBR expression was augmented in all examined muscles associated with increased maximal fat oxidation. Compared with PRE, after CD, phospho-Tyr1141OBR, phospho-Tyr985OBR, JAK2, and phospho-Tyr1007/1008JAK2 protein expression were increased in all muscles, whereas STAT3 and phospho-Tyr705STAT3 were increased only in the arms. The expression of protein tyrosine phosphatase 1B (PTP1B) in skeletal muscle was increased by 18 and 45% after CRE and CD, respectively ( P < 0.05). Suppressor of cytokine signaling 3 (SOCS3) tended to increase in the legs and decrease in the arm muscles (ANOVA interaction: P < 0.05). Myosin heavy chain I isoform was associated with OBR protein expression ( r = −0.75), phospho-Tyr985OBR ( r = 0.88), and phospho-Tyr705STAT3/STAT3 ( r = 0.74). In summary, despite increased PTP1B expression, skeletal muscle OBR and signaling are upregulated by a severe energy deficit with greater response in the arm than in the legs likely due to SOCS3 upregulation in the leg muscles. NEW & NOTEWORTHY This study shows that the skeletal muscle leptin receptors and their corresponding signaling cascade are upregulated in response to a severe energy deficit, contributing to increase maximal fat oxidation. The responses are more prominent in the arm muscles than in the legs but partly blunted by whey protein ingestion and high volume of exercise. This occurs despite an increase of protein tyrosine phosphatase 1B protein expression, a known inhibitor of insulin and leptin signaling.
Time-course effects of aerobic physical training in the prevention of cigarette smoke-induced COPD
Authors: Toledo-Arruda Alessandra C. , Vieira Rodolfo P. , Guarnier Flávia A. , Suehiro Camila L. , Caleman-Neto Agostinho , Olivo Clarice R. , Arantes Petra M. M. , Almeida Francine M. , Lopes Fernanda D. T. Q. S. , Ramos Ercy M. C. , Cecchini Rubens , Lin Chin Jia , Martins Milton Arruda 
Published: July 2017

A previous study by our group showed that regular exercise training (ET) attenuated pulmonary injury in an experimental model of chronic exposure to cigarette smoke (CS) in mice, but the time-course effects of the mechanisms involved in this protection remain poorly understood. We evaluated the temporal effects of regular ET in an experimental model of chronic CS exposure. Male C57BL/6 mice were divided into four groups: Control (sedentary + air), Exercise (aerobic training + air), Smoke (sedentary + smoke), and Smoke + Exercise (aerobic training + smoke). Mice were exposed to CS and ET for 4, 8, or 12 wk. Exercise protected mice exposed to CS from emphysema and reductions in tissue damping and tissue elastance after 12 wk ( P < 0.01). The total number of inflammatory cells in the bronchoalveolar lavage increased in the Smoke group, mainly due to the recruitment of macrophages after 4 wk, neutrophils and lymphocytes after 8 wk, and lymphocytes and macrophages after 12 wk ( P < 0.01). Exercise attenuated this increase in mice exposed to CS. The protection conferred by exercise was mainly observed after exercise adaptation. Exercise increased IL-6 and IL-10 in the quadriceps and lungs ( P < 0.05) after 12 wk. Total antioxidant capacity and SOD was increased and TNF-α and oxidants decreased in lungs of mice exposed to CS after 12 wk ( P < 0.05). The protective effects of exercise against lung injury induced by cigarette smoke exposure suggests that anti-inflammatory mediators and antioxidant enzymes play important roles in chronic obstructive pulmonary disease development mainly after the exercise adaptation. NEW & NOTEWORTHY These experiments investigated for the first time the temporal effects of regular moderate exercise training in cigarette smoke-induced chronic obstructive pulmonary disease. We demonstrate that aerobic conditioning had a protective effect in emphysema development induced by cigarette smoke exposure. This effect was most likely secondary to an effect of exercise on oxidant-antioxidant balance and anti-inflammatory mediators.
Analysis of the substrate specificity of Factor VII activating protease (FSAP) and design of specific and sensitive peptide substrates
Authors: Kara Emrah , Manna Dipankar , Løset Åge , Schneider Eric L. , Craik Charles S. , Kanse Sandip M. 
Published: July 2017

SummaryFactor VII (FVII) activating protease (FSAP) is a circulating serine protease that is likely to be involved in a number of disease conditions such as stroke, atherosclerosis, liver fibrosis, thrombosis and cancer. To date, no systematic information is available about the substrate specificity of FSAP. Applying phage display and positional scanning substrate combinatorial library (PS-SCL) approaches we have characterised the specificity of FSAP towards small peptides. Results were evaluated in the context of known protein substrates as well as molecular modelling of the peptides in the active site of FSAP. The representative FSAP-cleaved sequence obtained from the phage display method was Val-Leu-Lys-Arg-Ser (P4-P1’). The sequence X-Lys/Arg-Nle-Lys/Arg (P4-P1) was derived from the PS-SCL method. These results show a predilection for cleavage at a cluster of basic amino acids on the nonprime side. Quenched fluorescent substrate (Ala-Lys-Nle-Arg-AMC) (amino methyl coumarin) and (Ala-Leu-Lys-Arg-AMC) had a higher selectivity for FSAP compared to other proteases from the hemostasis system. These substrates could be used to measure FSAP activity in a complex biological system such as plasma. In histonetreated plasma there was a specific activation of pro-FSAP as validated by the use of an FSAP inhibitory antibody, corn trypsin inhibitor to inhibit Factor XIIa and hirudin to inhibit thrombin, which may account for some of the haemostasis-related effects of histones. These results will aid the development of further selective FSAP activity probes as well as specific inhibitors that will help to increase the understanding of the functions of FSAP in vivo.Supplementary Material to this article is available online at www.thrombosis-online.com.