bluuebunny/crossref_metadata_2025_split huggingface dataset:
High‐dose prednisolone after intravenous methylprednisolone improves prognosis of acute exacerbation in idiopathic interstitial pneumonias
Authors: Arai Toru , Tachibana Kazunobu , Sugimoto Chikatoshi , Inoue Yasushi , Tokura Sayoko , Okuma Tomohisa , Akira Masanori , Kitaichi Masanori , Hayashi Seiji , Inoue Yoshikazu 
Published: May 2017

ABSTRACT
Background and objectiveAcute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) (AE‐IPF) is a poor prognostic disorder. AE is also reported to occur in other idiopathic interstitial pneumonias (IIPs). There are limited data available regarding the effectiveness of treatment for AE‐IIPs. The objective of this study was to clarify the prognostic impact of the initial dose of prednisolone (PSL) for treating AE‐IIPs.MethodsEighty‐five patients with AE‐IIPs, diagnosed according to the criteria of the Japanese Respiratory Society, were enrolled in this study (IPF/non‐IPF: 63/22 patients) from 2004 to 2013. We performed multivariate Cox proportional hazard regression analysis to identify poor prognostic factors. HRCT patterns at the onset of AE‐IIPs were classified as diffuse or non‐diffuse. We evaluated the prognostic significance of the initial dose of PSL by adjusting for other prognostic factors.ResultsMedian survival time (MST) after AE‐IIPs diagnosis was 49 days. MST of AE‐IPF and AE‐non‐IPF was 39 and 49 days, respectively. A diffuse HRCT pattern, lower serum IgG and higher serum surfactant protein‐D at AE diagnosis, long‐term oxygen therapy (LTOT) before AE and positive pressure ventilation (PPV) use for AE were significant poor prognostic factors for all patients, as were LTOT before AE and lower serum IgG for no‐PPV patients. High‐dose PSL ≥ 0.6 mg/kg was a significant prognostic factor for no‐PPV patients after adjusting for other prognostic factors.ConclusionWe concluded that a dose of PSL ≥ 0.6 mg/kg after i.v. high‐dose methylprednisolone therapy should be recommended for the treatment of AE‐IIPs.
Book Review: The Foundations of Immunology and their Pertinence to Medicine
Authors: Corthay A. 
Published: May 2017

AbstractWe are in the era cursed with overspecialization. Charles Darwin's foundational Origin of Species, published in 1859, was accessible to the broadly educated individual. Starting with this statement, Peter Bretscher in his new book aimed at explaining foundational concepts of immunology to a broad public. His standpoint is that foundational ideas usually can be simply expressed. This book describes first how foundational concepts of immunology have evolved over the last two and a half centuries. The importance of self–non‐self‐discrimination by the immune system is acknowledged, and models for immunological tolerance are compared. A main focus concerns the understanding of immune class regulation. According to Bretscher's Threshold Hypothesis, a low antigen dose or low degree of foreignness results in Th1 immunity whereas a high antigen dose or high degree of foreignness induces Th2 responses. A novel vaccination strategy is proposed with an ultra‐low number of live, attenuated organisms. It is described in details how this approach may potentially be used to prevent or treat HIV infection, tuberculosis and cancer. The book is very well written in a clear, simple and stimulating style which makes it accessible not only to immunologists but also non‐specialists, teachers, medical students and clinicians. It will convince many that the immune system is not too complex to be understood. By Peter Bretscher. FriesenPress, 2016. 200 pp. ISBN: 978‐1‐4602‐9656‐1.
High‐frequency ultrasound quantification of acute radiation dermatitis: pilot study of patients undergoing radiotherapy for breast cancer
Authors: Garnier M. , Champeaux E. , Laurent E. , Boehm A. , Briard O. , Wachter T. , Vaillant L. , Patat F. , Bens G. , Machet L. 
Published: May 2017

BackgroundAcute radiation dermatitis (ARD) is a frequent complication after breast cancer radiotherapy and is usually assessed by semi‐quantitative clinical scores, which may be subject to inter‐observer variability. High‐frequency ultrasound imaging of the skin can reliably quantify thickness and edema in diseased skin. We aimed to compare the relative increase in dermal thickness of the irradiated zone in breast‐cancer patients undergoing radiotherapy, with clinical severity.MethodsA consecutive series of patients undergoing treatment for breast cancer by lumpectomy and radiotherapy in a 6‐month period also underwent clinical and ultrasound evaluation of ARD.ResultsWe included 34 female patients 17 had grade 1 (group 1), 17 had grade 2 or grade 3 ARD (group 2). The mean relative increase in dermal thickness in irradiated skin (RIDTIS) was greater for group 2 than 1: 0.53 vs 0.29 mm (P=.023). On univariate analysis, ARD was associated with skin phototype, breast volume and RIDTIS, and on multivariable analysis, breast volume and age remained predictive of the disease.ConclusionPatients with more severe dermatitis showed significantly increased dermal thickness. Dermal thickness is a quantitative variable that could help quantify the efficacy of drugs and improve the treatment of this disease in patients undergoing radiotherapy.
Active Travel to and From School Among School-Age Children During 1997–2011 and Associated Factors in China
Authors: Yang Yong , Hong Xue , Gurney James G. , Wang Youfa 
Published: May 2017

Background:Active travel to school (ATS) is positively associated with various health indicators. The rapid social, economic, and environmental changes in China provide a unique setting to study changes and predictors of ATS over time.Methods:Using logistic regression modeling, we analyzed data from the China Health and Nutrition Survey during 1997 to 2011 (N = 9487, ages 6 to 17 years) to estimate the change over time in ATS and to identify associated factors.Results:The prevalence of reported ATS among children dropped from 95.8% in 1997 to 69.3% in 2011. ATS was common in children living closer to school, in middle school, from low-income households, with low parental education status, and those without a private vehicle. Children who were living in a metropolitan area and who had more than 40 minutes of total PA per day were less likely to report ATS.Conclusions:The decrease of ATS had been concurrent with the increase of the children living at a longer distance from school and the increase of household owning private vehicles which were associated with the rapid urbanization and economic growth in China. Factors associated with the decreased ATS in China are similar to other countries but the underlying reasons may be different.
Development of Physical Activity–Related Parenting Practices Scales for Urban Chinese Parents of Preschoolers: Confirmatory Factor Analysis and Reliability
Authors: Suen Yi-nam , Cerin Ester , Barnett Anthony , Huang Wendy Y.J. , Mellecker Robin R. 
Published: May 2017

Background:Valid instruments of parenting practices related to children’s physical activity (PA) are essential to understand how parents affect preschoolers’ PA. This study developed and validated a questionnaire of PA-related parenting practices for Chinese-speaking parents of preschoolers in Hong Kong.Methods:Parents (n = 394) completed a questionnaire developed using findings from formative qualitative research and literature searches. Test-retest reliability was determined on a subsample (n = 61). Factorial validity was assessed using confirmatory factor analysis. Subscale internal consistency was determined.Results:The scale of parenting practices encouraging PA comprised 2 latent factors: Modeling, structure and participatory engagement in PA (23 items), and Provision of appropriate places for child’s PA (4 items). The scale of parenting practices discouraging PA scale encompassed 4 latent factors: Safety concern/overprotection (6 items), Psychological/behavioral control (5 items), Promoting inactivity (4 items), and Promoting screen time (2 items). Test-retest reliabilities were moderate to excellent (0.58 to 0.82), and internal subscale reliabilities were acceptable (0.63 to 0.89).Conclusion:We developed a theory-based questionnaire for assessing PA-related parenting practices among Chinese-speaking parents of Hong Kong preschoolers. While some items were context and culture specific, many were similar to those previously found in other populations, indicating a degree of construct generalizability across cultures.
Do Sitting, Standing, or Treadmill Desks Impact Psychobiological Indicators of Work Productivity?
Authors: Gilson Nicholas D. , Hall Caitlin , Renton Angela , Ng Norman , von Hippel William 
Published: May 2017

Background:This pilot study investigated the links between psychobiological indicators of work productivity, prolonged desk sitting, and conditions whereby office workers were able to interrupt sitting using a sit–stand or treadmill desk.Methods:Twenty participants visited our laboratory and completed their own desk work in counterbalanced sit-only, sit–stand (Varidesk Pro Plus 48™), and sit–walk conditions (Infiniti TR1200-DTS™). Steady-state visually evoked potentials calculated from electroencephalography recordings during a set task at the end of the workday assessed attentional resource. Salivary cortisol samples were taken during the morning and afternoon to measure stress response. Within-subject analyses were used to compare work productivity indicators relative to condition.Results:No significant differences in mean steady-state visually evoked potential amplitude were observed, although attentional resource allocation was found to be the most effective following the sit–stand [1.01 (0.46) μV] compared with the sit–walk [0.9 (0.28) μV] and sit-only [0.91 (0.32) μV] conditions. The mean magnitude of decrease in cortisol was most apparent when workers used treadmill (1.5 nmol/L; P = .007) and sit–stand (1.6 nmol/L; P = .001) desks, and least evident in the sit-only condition (1.0 nmol/L; P = .146).Conclusions:The findings highlight the potential benefits of standing or active deskwork to the allocation of attentional resources and the regulation of stress.
Application of Acoustic Radiation Force Impulse Elastography in Imaging of Delayed Onset Muscle Soreness: A Comparative Analysis With 3T MRI
Authors: Hotfiel Thilo , Kellermann Marion , Swoboda Bernd , Wildner Dane , Golditz Tobias , Grim Casper , Raithel Martin , Uder Michael , Heiss Rafael 
Published: May 2017

Context: Delayed onset muscle soreness is one of the most common reasons for impaired muscle performance in sports and is associated with reduced muscle strength and frequently observed both in professional and recreational athletes. Objective: To emphasize the diagnostic value of acoustic radiation force impulse (ARFI) in imaging of delayed onset muscle soreness by comparing findings with high-resolution 3T magnetic resonance imaging T2-weighted sequences. Design: Case series. Setting: Laboratory environment. Participants: Fifteen healthy students (7 females and 8 males; mean [SD]: age 24 [4] y, height 178 [10] cm, body weight 67 [12] kg). Main Outcome Measures: ARFI values, represented as shear wave velocities of the gastrocnemius muscle and soleus muscle, as well as conventional ultrasound, high-resolution 3T magnetic resonance imaging, creatine kinase activity, extension range of the ankle joint, calf circumference, and muscle soreness were assessed before (baseline) and 60 hours after (postintervention) a standardized eccentric exercise. Results: ARFI shear wave velocity values of the gastrocnemius muscle revealed a statistically significant decrease of 19.1% between baseline (2.2 [0.26] m/s) and postintervention (1.78 [0.24] m/s); P = .01. At follow-up, the magnetic resonance imaging investigations showed intramuscular edema for the gastrocnemius muscle in all participants corresponding to a significant raise in T2 signal intensity (P = .001) and in T2-time values (P = .004). Conclusions: ARFI elastography seems to be an additional sensitive diagnostic modality in the diagnostic workup of delayed onset muscle soreness. Intramuscular shear wave velocities could represent an additional imaging marker for the assessment and monitoring of ultrastructural muscle injuries and therefore be helpful for individual training composition in elite sports.
Limited Colonization Undermined by Inadequate Early Immune Responses Defines the Dynamics of Decidual Listeriosis
Authors: Rizzuto Gabrielle , Tagliani Elisa , Manandhar Priyanka , Erlebacher Adrian , Bakardjiev Anna I. 
Published: May 2017

ABSTRACTThe bacterial pathogenListeria monocytogenescauses foodborne systemic disease in pregnant women, which can lead to preterm labor, stillbirth, or severe neonatal disease. Colonization of the maternal decidua appears to be an initial step in the maternal component of the disease as well as bacterial transmission to the placenta and fetus. Host-pathogen interactions in the decidua during this early stage of infection remain poorly understood. Here, we assessed the dynamics ofL. monocytogenesinfection in primary human decidual organ cultures and in the murine deciduain vivo. A high inoculum was necessary to infect both human and mouse deciduas, and the data support the existence of a barrier to initial colonization of the murine decidua. If successful, however, colonization in both species was followed by significant bacterial expansion associated with an inability of the decidua to mount appropriate innate cellular immune responses. The innate immune deficits included the failure of bacterial foci to attract macrophages and NK cells, cell types known to be important for early defenses againstL. monocytogenesin the spleen, as well as a decrease in the tissue density of inflammatory Ly6Chimonocytesin vivo. These results suggest that the infectivity of the decidua is not the result of an enhanced recruitment ofL. monocytogenesto the gestational uterus but rather is due to compromised local innate cellular immune responses.
Conformational Flexibility in the Immunoglobulin-Like Domain of the Hepatitis C Virus Glycoprotein E2
Authors: Vasiliauskaite Ieva , Owsianka Ania , England Patrick , Khan Abdul Ghafoor , Cole Sarah , Bankwitz Dorothea , Foung Steven K. H. , Pietschmann Thomas , Marcotrigiano Joseph , Rey Felix A. , Patel Arvind H. , Krey Thomas 
Published: May 2017

ABSTRACT
The hepatitis C virus (HCV) glycoprotein E2 is the major target of neutralizing antibodies and is therefore highly relevant for vaccine design. Its structure features a central immunoglobulin (Ig)-like β-sandwich that contributes to the binding site for the cellular receptor CD81. We show that a synthetic peptide corresponding to a β-strand of this Ig-like domain forms an α-helix in complex with the anti-E2 antibody DAO5, demonstrating an inside-out flip of hydrophobic residues and a secondary structure change in the composite CD81 binding site. A detailed interaction analysis of DAO5 and cross-competing neutralizing antibodies with soluble E2 revealed that the Ig-like domain is trapped by different antibodies in at least two distinct conformations. DAO5 specifically captures retrovirus particles bearing HCV glycoproteins (HCVpp) and infectious cell culture-derived HCV particles (HCVcc). Infection of cells by DAO5-captured HCVpp can be blocked by a cross-competing neutralizing antibody, indicating that a single virus particle simultaneously displays E2 molecules in more than one conformation on its surface. Such conformational plasticity of the HCV E2 receptor binding site has important implications for immunogen design.

IMPORTANCE
Recent advances in the treatment of hepatitis C virus (HCV) infection with direct-acting antiviral drugs have enabled the control of this major human pathogen. However, due to their high costs and limited accessibility in combination with the lack of awareness of the mostly asymptomatic infection, there is an unchanged urgent need for an effective vaccine. The viral glycoprotein E2 contains regions that are crucial for virus entry into the host cell, and antibodies that bind to these regions can neutralize infection. One of the major targets of neutralizing antibodies is the central immunoglobulin (Ig)-like domain within E2. We show here that this Ig-like domain is conformationally flexible at the surface of infectious HCV particles and pseudoparticles. Our study provides novel insights into the interactions of HCV E2 with the humoral immune system that should aid future vaccine development.
Glutathionylation of
Yersinia pestis
LcrV and Its Effects on Plague Pathogenesis
Authors: Mitchell Anthony , Tam Christina , Elli Derek , Charlton Thomas , Osei-Owusu Patrick , Fazlollahi Farbod , Faull Kym F. , Schneewind Olaf 
Published: May 2017

ABSTRACT

Glutathionylation, the formation of reversible mixed disulfides between glutathione and protein cysteine residues, is a posttranslational modification previously observed for intracellular proteins of bacteria. Here we show that
Yersinia pestis
LcrV, a secreted protein capping the type III secretion machine, is glutathionylated at Cys
273
and that this modification promotes association with host ribosomal protein S3 (RPS3), moderates
Y. pestis
type III effector transport and killing of macrophages, and enhances bubonic plague pathogenesis in mice and rats. Secreted LcrV was purified and analyzed by mass spectrometry to reveal glutathionylation, a modification that is abolished by the codon substitution Cys
273
Ala in
lcrV
. Moreover, the
lcrV

C273A

mutation enhanced the survival of animals in models of bubonic plague. Investigating the molecular mechanism responsible for these virulence attributes, we identified macrophage RPS3 as a ligand of LcrV, an association that is perturbed by the Cys
273
Ala substitution. Furthermore, macrophages infected by the
lcrV

C273A

variant displayed accelerated apoptotic death and diminished proinflammatory cytokine release. Deletion of
gshB
, which encodes glutathione synthetase of
Y. pestis
, resulted in undetectable levels of intracellular glutathione, and we used a
Y. pestis
Δ
gshB
mutant to characterize the biochemical pathway of LcrV glutathionylation, establishing that LcrV is modified after its transport to the type III needle via disulfide bond formation with extracellular oxidized glutathione.

IMPORTANCE
Yersinia pestis
, the causative agent of plague, has killed large segments of the human population; however, the molecular bases for the extraordinary virulence attributes of this pathogen are not well understood. We show here that LcrV, the cap protein of bacterial type III secretion needles, is modified by host glutathione and that this modification contributes to the high virulence of
Y. pestis
in mouse and rat models for bubonic plague. These data suggest that
Y. pestis
exploits glutathione in host tissues to activate a virulence strategy, thereby accelerating plague pathogenesis.
The Fungal Cell Wall: Structure, Biosynthesis, and Function
Authors: Gow Neil A. R. , Latge Jean-Paul , Munro Carol A. 
Published: May 2017

ABSTRACTThe molecular composition of the cell wall is critical for the biology and ecology of each fungal species. Fungal walls are composed of matrix components that are embedded and linked to scaffolds of fibrous load-bearing polysaccharides. Most of the major cell wall components of fungal pathogens are not represented in humans, other mammals, or plants, and therefore the immune systems of animals and plants have evolved to recognize many of the conserved elements of fungal walls. For similar reasons the enzymes that assemble fungal cell wall components are excellent targets for antifungal chemotherapies and fungicides. However, for fungal pathogens, the cell wall is often disguised since key signature molecules for immune recognition are sometimes masked by immunologically inert molecules. Cell wall damage leads to the activation of sophisticated fail-safe mechanisms that shore up and repair walls to avoid catastrophic breaching of the integrity of the surface. The frontiers of research on fungal cell walls are moving from a descriptive phase defining the underlying genes and component parts of fungal walls to more dynamic analyses of how the various components are assembled, cross-linked, and modified in response to environmental signals. This review therefore discusses recent advances in research investigating the composition, synthesis, and regulation of cell walls and how the cell wall is targeted by immune recognition systems and the design of antifungal diagnostics and therapeutics.
The Role of ESX-1 in
Mycobacterium tuberculosis
Pathogenesis
Authors: Wong Ka-Wing 
Published: May 2017

ABSTRACT

In this article, we have described several cellular pathological effects caused by the
Mycobacterium tuberculosis
ESX-1. The effects include induction of necrosis, NOD2 signaling, type I interferon production, and autophagy. We then attempted to suggest that these pathological effects are mediated by the cytosolic access of
M. tuberculosis
-derived materials as a result of the phagosome-disrupting activity of the major ESX-1 substrate ESAT-6. Such activity of ESAT-6 is most likely due to its pore-forming activity at the membrane. The amyloidogenic characteristic of ESAT-6 is reviewed here as a potential mechanism of membrane pore formation. In addition to ESAT-6, the ESX-1 substrate EspB interferes with membrane-mediated innate immune mechanisms such as efferocytosis and autophagy, most likely through its ability to bind phospholipids. Overall, the
M. tuberculosis
ESX-1 secretion system appears to be a specialized system for the deployment of host membrane-targeting proteins, whose primary function is to interrupt key steps in innate immune mechanisms against pathogens. Inhibitors that block the ESX-1 system or block host factors critical for ESX-1 toxicity have been identified and should represent attractive potential new antituberculosis drugs.
Duodenal biopsies for the diagnosis of coeliac disease: are we adhering to current guidance?
Authors: Husnoo Nilofer , Ahmed Wafaa , Shiwani Muhammad Hanif 
Published: May 2017

BackgroundThe British Society of Gastroenterology guidelines recommend taking at least four duodenal biopsy specimens at the time of upper gastrointestinal (UGI) endoscopy if coeliac disease (CD) is suspected and it has been shown to increase the diagnostic yield of CD. We assessed the compliance to these guidelines within our institution. We then applied measures to improve our compliance rate and assessed the resulting impact on our diagnostic rate of CD.MethodsWe performed a retrospective audit of electronic records for all patients, with no prior diagnosis of CD, who underwent UGI endoscopy with duodenal biopsies between August 2014 and May 2015. We implemented measures to raise awareness among endoscopy users at our institution and carried out a reaudit between February and May 2016.Results924 patients were found to be eligible in the first part of the study and 278 in the second part. The proportion of patients who had ≥4 biopsy specimens submitted increased from 21.9% to 60.8% (p<0.001). The diagnostic rate of CD increased from 3.5% in the audit group to 7.6% in the reaudit group (p=0.004). A positive serology result and suspected CD as an indication for biopsy were found to be independent predictors of the likelihood of complying with guidelines.ConclusionsOur study suggests that taking <4 duodenal biopsy specimens to assess for the presence of CD may lead to the diagnosis of CD being missed. Simple measures can improve the local compliance rate to current guidelines.