bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypic and functional alterations of regulatory B cell subsets in adult allergic asthma patients
Authors: Wiest Mathew , Upchurch Katherine , Hasan Md Mahmudul , Cardenas Jacob , Lanier Bobby , Millard Mark , Turner Jacob , Oh SangKon , Joo HyeMee 
Published: May 2019

AbstractBackgroundIL‐10‐producing regulatory B cells (Bregs) are widely ascribed immune regulatory functions. However, Breg subsets in human asthma have not been fully investigated.ObjectiveWe studied Breg subsets in adult allergic asthma patients by assessing two major parameters, frequency and IL‐10 expression. We then investigated factors that affect these two parameters in patients.MethodsPeripheral blood mononuclear cells (PBMCs) of adult allergic asthma patients (N = 26) and non‐asthmatic controls (N = 28) were used to assess the frequency of five subsets of transitional B cells (TBs), three subsets of CD24highCD27+ B cells and B1 cells. In addition to clinical data, IL‐10 expression by individual Breg subsets was assessed by flow cytometry.ResultsAsthma patients had decreases of CD5+ and CD1d+CD5+, but an increase of CD27+ TBs which was significant in patients with moderate asthma (60 < FEV1 < 80). Regardless of asthma severity, there was no significant alteration in the frequencies of 6 other Breg subsets tested. However, we found that oral corticosteroid (OCS) significantly affected the frequency of Bregs in Breg subset‐specific manners. OCS decreased CD5+ and CD1d+CD5+ TBs, but increased CD27+ TBs and CD10+CD24highCD27+ cells. Furthermore, OCS decreased IL‐10 expression by CD27+ TBs, all 3 CD24highCD27+ B cell subsets (CD5+, CD10+ and CD1d+) and B1 cells. OCS‐mediated inhibition of IL‐10 expression was not observed in the other Breg subsets tested.Conclusion & Clinical RelevanceAlterations in the frequency of Bregs and their ability to express IL‐10 are Breg subset‐specific. OCS treatment significantly affects the frequency as well as their ability to express IL‐10 in Breg subset‐specific manners.
Detection of myocarditis using T1 and ECV mapping is not improved by early compared to late post‐contrast imaging
Authors: Lundin Magnus , Sörensson Peder , Vishnevskaya Liya , Maret Eva , Kellman Peter , Sigfridsson Andreas , Ugander Martin 
Published: May 2019

SummaryBackgroundCardiovascular magnetic resonance (CMR) of myocarditis may include early gadolinium enhancement (EGE) and global relative enhancement (GRE) by T1‐weighted images acquired before and early after contrast administration. However, the importance of timing for post‐contrast imaging has not been evaluated using T1 mapping. We aimed to improve the understanding of the contrast mechanisms by evaluating whether early or late post‐contrast T1 mapping was better at detecting myocarditis.MethodsControls and patients referred to evaluate myocarditis underwent 1·5T CMR. T1 mapping was performed before, and 3 min (early) and 21 min (late) after intravenous contrast (0·2 mmol kg−1). Extracellular volume fraction (ECV) and the GRE and EGE equivalents by T1 mapping were calculated. Focally affected myocardium in myocarditis was defined as increased native T1 compared to remote myocardium.ResultsThe GRE equivalent by T1 mapping was higher in myocarditis (n = 19) compared to controls (n = 19) both early (P<0·001) and late (P<0·001). While remote myocardium in myocarditis had higher enhancement relative to skeletal muscle compared to controls early (P = 0·002) and late (P<0·001), ECV of skeletal muscle was lower compared to controls both early (P = 0·03) and late (P = 0·004), and remote myocardial ECV did not differ from controls early (P = 0·37) or late (P = 0·52). The difference in ECV between affected and remote myocardium was higher late compared to early by 5·3 ± 0·7 versus 4·0 ± 0·6%‐points (P = 0·002).ConclusionQuantitative evaluation by T1 mapping shows that early post‐contrast imaging does not improve the detection of myocarditis compared to late post‐contrast imaging. Focal myocardial abnormalities were more conspicuous late post‐contrast.
Ganglioside GM1 promotes contact inhibition of growth by regulating the localization of epidermal growth factor receptor from glycosphingolipid‐enriched microdomain to caveolae
Authors: Zhuo Dinghao , Guan Feng 
Published: May 2019

AbstractObjectivesAccumulating data show that gangliosides are involved in regulation of cell proliferation. Specific changes in gangliosides expression associated with growth density of cells have been documented in several cell lines. However, the function and the potential mechanism of ganglioside GM1 in contact inhibition of growth are not clear.Materials and MethodsEdU incorporation assay and western blot were applied to detect the contact inhibition of growth in human mammary epithelial cells. GM1 manipulation of cell proliferation and epidermal growth factor receptor (EGFR) activation was investigated by immunoprecipitation, OptiPrep density gradient centrifugation and immunofluorescence. The function of GM1 on contact inhibition of growth was further studied by using GM1 stably knockdown and overexpression cells.ResultsMCF‐10A, MCF‐7 and MDA‐MB‐231 cells showed contact inhibition of growth in high‐density condition. Exogenous addition of GM1 to high‐density cells clearly inhibited cell growth and deactivated EGFR signalling. Compared to normal‐density cells, distribution of EGFR in high‐density cells was decreased in glycosphingolipid‐enriched microdomain (GEM), but more concentrated in caveolae, and incubation with GM1 obviously promoted this translocation. Furthermore, the cell growth and EGFR activation were increased in GM1 stably knockdown cells and decreased in GM1 stably overexpression cells when cultured in high density.ConclusionsOur results demonstrated that GM1 suppressed EGFR signalling and promoted contact inhibition of growth by changing the localization of EGFR from GEM to caveolae.
Addressing the conflict between partner notification and patient confidentiality in serodiscordant relationships: How can Ubuntu help?
Authors: Ewuoso Cornelius 
Published: May 2019

AbstractThis study evaluates the conflict between patient confidentiality and partner notification in sero‐discordant relationships, and argues the thesis that based on a theoretical formulation of Ubuntu, a health provider is obliged to facilitate friendly relationships in which individuals are true subjects and/or objects of communal friendship. In serodiscordant relationships, the health professional can fulfil this obligation by notifying “others” (particularly a partner with whom an HIV positive patient has a “present” and “actual relationship”) of their spouse's HIV seroconversion, since without such relevant information a partner (subject) of an HIV positive patient cannot “appropriately” care for the patient's condition (object). There is a need to move away from the medical traditional emphasis that has for so long put primacy on doctor‐patient confidentiality as is the case with the Health Professions Council of South Africa Guidelines (Booklet 12) which favours patient confidentiality over partner notification. Given empirical evidence to support effectiveness of partner notification amongst sero‐discordant couples, there is thus, a need to focus emphasis on latter. This shift is necessary for achieving the United Nations’ Sustainable Development of Goal of ending HIV/AIDS epidemic by 2030. I proposed in this study that African ethics, specifically Ubuntu, will do a better job than current ethical frameworks at ensuring that partner notification receives more emphasis in the care of serodiscordant couples. If this framework is integrated into ethical guidelines and codes, it would significantly enhance the care of serodiscordant couples, as well as further boost global effort at ending HIV/AIDS epidemic by 2030.
Does group feeding by toxic prey confer a defensive benefit? Aristolochic acid content, group size and survival of first‐instar pipevine swallowtail (Battus philenor L.) larvae
Authors: Wilmoth Lauren W. , Fordyce James A. 
Published: May 2019

1. Aggregative feeding of larvae is widespread in the Lepidoptera, and many hypotheses have been proposed to explain the adaptive significance of this trait. Group feeding occurs disproportionately more in species with aposematic, chemically defended larvae compared with species with cryptic, non‐chemically defended larvae, consistent with the hypothesis that group feeding provides an enhanced aposematic signal to natural enemies. Most species characterised as having chemically defended larvae are cryptic during the first instar, when they are most highly aggregated and most vulnerable to predation.2. The benefits of group feeding in terms of decreased predation were explored for first‐instar larvae of the pipevine swallowtail, Battus philenor, a species that sequesters aristolochic acids from its Aristolochia host plant and exhibits aposematism in later instars and as adults. We found that groups of larvae with experimentally enhanced aristolochic acid content had significantly lower survivorship due to predation both in the field and in laboratory experiments compared with groups of larvae without enhanced chemical defence.3. A laboratory experiment found that aristolochic acid does not deter the generalist predator Hippodamia convergens.4. No evidence was found that was consistent with the hypothesis that group feeding and increased sequestered chemical defence interact to decrease rates of larval mortality in non‐aposematic, first‐instar larvae. Future research on chemical defence, aposematism, and aggregative feeding should continue to appreciate that particular chemical defences and feeding behaviours are not universally effective against all natural enemies.
A non‐pollinating moth inflicts higher seed predation than two co‐pollinators in an obligate pollination mutualism
Authors: Finch Jonathan T. D. , Power Sally A. , Welbergen Justin A. , Cook James M. 
Published: May 2019

1. Mutualisms are relationships of mutual exploitation, in which interacting species receive a net benefit from their association. In obligate pollination mutualisms (OPMs), female pollinators move pollen between the flowers of a single plant species and oviposit eggs within the female flowers that they visit.2. Competition between co‐occurring pollinator species is predicted to increase pollinator virulence, i.e. laying more eggs or consuming more seeds per fruit. Plants involved in OPMs frequently host various non‐pollinating seed parasites and parasitoids that may influence the outcome of the mutualism. Quantifying the prevalence of parasites and parasitoids and competition between pollinators is important for understanding the factors that influence OPM evolutionary stability.3. This study investigated the pollination mutualism occurring between the leaf flower plant, Breynia oblongifolia, and its co‐pollinating Epicephala moths. A third moth, Herpystis, also occurs in B. oblongifolia fruits as a non‐pollinating seed parasite.4. Breynia oblongifolia fruits were collected to quantify seed predation and compare seed predation costs between the three moth species. Results showed that the larvae of the two pollinator species consume similar numbers of seeds, and that adults deposit similar numbers of eggs per flower. As such, no evidence of increases in virulent behaviours was detected as a result of competition between co‐pollinators.5. By contrast, the seed parasite Herpystis consumed more seeds than either pollinator species, and fruit crops with a high proportion of Herpystis had significantly lower net seed production.6. This work adds to the growing understanding of the ecology and dynamics of plant–pollinator mutualisms.
Genetic basis of unexplained erythrocytosis in Indian patients
Authors: Mallik Nabhajit , Sharma Prashant , Kaur Hira Jasbir , Chhabra Sanjeev , Sreedharanunni Sreejesh , Kumar Narender , Naseem Shano , Sachdeva Man Updesh Singh , Ahluwalia Jasmina , Malhotra Pankaj , Varma Neelam , Varma Subhash , Das Reena 
Published: May 2019

AbstractObjectiveTo evaluate the spectrum of genetic defects in Indian patients with unexplained erythrocytosis.MethodsFifteen families (18 patients) with unexplained erythrocytosis were enrolled after excluding polycythemia vera and secondary erythrocytosis. Focused Sanger sequencing from genomic DNA was performed for EPOR (exon 8), VHL (exons 2‐3), EGLN1 (exons 2‐5), EPAS1 (exon 12), and all exons of HBB, HBA1, and HBA2 genes.ResultsEleven of the 18 patients (including two pairs of brothers) had Chuvash polycythemia, that is, homozygosity for VHL:c.598C > T (p.Arg200Trp). Three patients (two of whom were brothers) had HBB mutations associated with increased oxygen‐affinity hemoglobin—one had a heterozygous Hb McKees Rocks HBB:c.438T > A (p.Tyr146*), and two brothers showed heterozygous Hb Rainier HBB:c.437A > G (p.Tyr146Cys). No pathogenic variants were found in the remaining four cases.ConclusionA gene‐by‐gene Sanger sequencing approach could determine a genetic basis for erythrocytosis in 11 of the 15 (73%) Indian families, with homozygous VHL:c.598C > T (p.Arg200Trp) being the commonest pathogenic variant. This first study from the Indian subcontinent provides a rationale for analyzing this variant in patients with suspected congenital erythrocytosis from this region.Rare first occurrences of Hb McKees Rocks and Hb Rainier in Indians are also being reported.
Multi‐trait genomic selection for weevil resistance, growth, and wood quality in Norway spruce
Authors: Lenz Patrick R. N. , Nadeau Simon , Mottet Marie‐Josée , Perron Martin , Isabel Nathalie , Beaulieu Jean , Bousquet Jean 
Published: May 2019

AbstractPlantation‐grown trees have to cope with an increasing pressure of pest and disease in the context of climate change, and breeding approaches using genomics may offer efficient and flexible tools to face this pressure. In the present study, we targeted genetic improvement of resistance of an introduced conifer species in Canada, Norway spruce (Picea abies (L.) Karst.), to the native white pine weevil (Pissodes strobi Peck). We developed single‐ and multi‐trait genomic selection (GS) models and selection indices considering the relationships between weevil resistance, intrinsic wood quality, and growth traits. Weevil resistance, acoustic velocity as a proxy for mechanical wood stiffness, and average wood density showed moderate‐to‐high heritability and low genotype‐by‐environment interactions. Weevil resistance was genetically positively correlated with tree height, height‐to‐diameter at breast height (DBH) ratio, and acoustic velocity. The accuracy of the different GS models tested (GBLUP, threshold GBLUP, Bayesian ridge regression, BayesCπ) was high and did not differ among each other. Multi‐trait models performed similarly as single‐trait models when all trees were phenotyped. However, when weevil attack data were not available for all trees, weevil resistance was more accurately predicted by integrating genetically correlated growth traits into multi‐trait GS models. A GS index that corresponded to the breeders’ priorities achieved near maximum gains for weevil resistance, acoustic velocity, and height growth, but a small decrease for DBH. The results of this study indicate that it is possible to breed for high‐quality, weevil‐resistant Norway spruce reforestation stock with high accuracy achieved from single‐trait or multi‐trait GS.
The effects of six‐week resistance, aerobic and combined exercises on the pro‐inflammatory and anti‐inflammatory markers in overweight patients with moderate haemophilia A: A randomized controlled trial
Authors: Parhampour Behrouz , Dadgoo Mehdi , Vasaghi‐Gharamaleki Behnoosh , Torkaman Giti , Ravanbod Roya , Mirzaii-Dizgah Iraj , Reza Baghaipour Mohammad , Saneii Seyed Hassan 
Published: May 2019

AbstractIntroductionOverweight increases the secretion of pro‐inflammatory cytokines and serves as a major risk factor for arthropathy and cardiovascular diseases (CVD). This condition is becoming increasingly prevalent among patients with haemophilia (PWH). Different forms of exercise training could favourably modify weight‐related complications, cardiovascular risk factors and the inflammation.AimTo investigate the effects of resistance, aerobic and combined exercises on the pro‐inflammatory and anti‐inflammatory markers in overweight patients with moderate haemophilia A.MethodsForty‐eight patients with moderate haemophilia A, aged 35‐55 years, and body mass index (BMI) of 25‐30 kg/m2 were randomly assigned to resistance training (RT, n = 12), aerobic (AT, n = 12), combined training (CT, n = 12) and control (n = 12) groups. The patients participated in 45‐minutes exercise sessions three times a week for 6 weeks. Waist circumference (WC), waist‐to‐hip ratio (WHR), fat mass, fat‐free mass, interleukin‐10 (IL‐10), adiponectin, tumour necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6) and high sensitive C‐reactive protein (hs‐CRP) were measured before and after the 6 weeks of training.ResultsThere was significant decrease in WC, WHR, BMI and weight in the AT, RT and CT groups as compared to the control group. Total HJHS scores decreased in the AT, RT, CT groups compared to the control groups (P ≤ 0.001). The decrease in hs‐CRP, IL‐6 and TNF‐α in the CT group was significant compared to the control group (P ≤ 0.02). The increase in IL‐10 and adiponectin was not significant in the RT, AT and CT groups compared to the control group.ConclusionCT was the most effective training mode for decreasing the pro‐inflammatory cytokines and increasing anti‐inflammatory markers in overweight patients with haemophilia A.
Clinical Pharmacology Review of Plasma‐derived and Recombinant Protein Products: CBER Experience and Perspectives on Model‐Informed Drug Development
Authors: Tegenge Million A. , Mahmood Iftekhar , Forshee Richard 
Published: May 2019

AbstractIntroductionClinical pharmacology studies are one of the major types of regulatory data submitted for review of therapeutic proteins regulated by the Center for Biologics Evaluation and Research (CBER).AimThe primary objective of the current study is to provide an overview of the role of clinical pharmacology including pharmacokinetics (PK), pharmacodynamics (PD) and exposure‐response analysis at CBER. Furthermore, we aim to provide a baseline estimate for the use of quantitative clinical pharmacology studies prior to implementation of FDA's model‐informed drug development (MIDD) pilot programme.MethodsWe survey original Biologics License Applications (BLAs) for plasma‐derived and related recombinant therapeutic protein products approved by CBER/FDA (2008‐2017).ResultsThere were 37 original BLAs that met our inclusion criteria, and 34 of these products (92%) contained human PK data as part of the biological licensing. The products were broadly classified as coagulation factors (54%), IgG and related proteins (24%), and other therapeutic proteins (22%). Coagulation factor VIII and IX products constitute 32% of the BLAs and indicated for treatment of haemophilia A and B, respectively. Twelve products (35%) used model‐based approaches (population PK/PD and exposure‐response). Over the past 5 years (2013 to 2017), there is a trend for increased application of MIDD approaches as compared to the previous cohort years (2008 to 2012).ConclusionIn conclusion, clinical pharmacology has played a major role in regulatory review of plasma‐derived products, and we expect that the application of quantitative methods will further evolve for these products under the FDA MIDD programme.
Increased monocyte activation with age among HIV‐infected long term non‐progressor children: implications for early treatment initiation
Authors: D'Souza RR , Gopalan BP , Rajnala N , Phetsouphanh C , Shet A 
Published: May 2019

ObjectivesThe key to newer therapeutic and eradication approaches often lies in understanding slow disease progression in HIV infection. The paediatric population has been poorly studied in this regard. We aimed to describe a cohort of perinatally infected long‐term nonprogressor (LTNP) children living with HIV in India and to evaluate the immune biomarkers of disease progression.MethodsLTNPs (ART‐naïve, with a CD4 count ≥ 500 cells/μL at age ≥ 7 years) among the cohort of HIV‐infected children were identified and monitored longitudinally, and their CD4 T‐cell counts and plasma viral loads were measured every 6 months. The plasma monocyte/macrophage activation markers, namely soluble CD14 (sCD14), soluble CD163 (sCD163) and interferon‐inducible protein‐10 (IP‐10) were measured by enzyme‐linked immunosorbent assay (ELISA) in LTNPs and progressors. The Mann–Whitney U‐test was used to compare the two groups and P values < 0.05 were considered statistically significant. Spearman's rank or Pearson's correlation coefficient (r) was calculated to determine the associations between variables.ResultsAmong 378 children living with HIV‐1 surveyed in our cohort, 40 (10.6%) were LTNPs. Longitudinal analysis of the LTNP data showed that both CD4 count and viral load declined significantly with age (P < 0.0001 for both). Plasma sCD14 levels were significantly (P < 0.005) higher in progressors and sCD163 levels were significantly (P < 0.0001) higher in LTNPs.ConclusionsThe prevalence of LTNPs in our cohort of perinatally infected children living with HIV was 10.6%. We observed a trend for associations between the increasing sCD163 monocyte/macrophage activation marker levels, declining CD4 counts and the gradual loss of nonprogressor status with age in the LTNPs. These findings underscore the need for early antiretroviral therapy in those children with proven slow disease progression.
The microbiome and immune memory formation
Authors: McCoy Kathy D , Burkhard Regula , Geuking Markus B 
Published: May 2019

AbstractThe microbiota plays an important role in regulating both the innate and adaptive immune systems. Many studies have focused on the ability of microbes to shape the immune system by stimulating B‐cell and antibody responses and the differentiation of T helper cell function. However, an important feature of the immune system is its ability to generate memory responses, which provide increased survival for the host. This review will highlight the role of the microbiota in the induction of immune memory with a focus on both adaptive and innate memory as well as vaccine efficacy.
Prevalence of burnout in mental health nurses and related factors: a systematic review and meta‐analysis
Authors: López‐López Isabel María , Gómez‐Urquiza José Luis , Cañadas Gustavo Raúl , De la Fuente Emilia Inmaculada , Albendín‐García Luis , Cañadas‐De la Fuente Guillermo Arturo 
Published: May 2019

AbstractThe aim of this study was to determine the prevalence of burnout in mental health nurses and to identify its predictors. A systematic review was conducted of studies published in the following databases: CINAHL, Dialnet, LILACS, ProQuest, PsycINFO, PubMed, SciELO, and Scopus. The search equation used was “Nurs * AND Burnout AND mental health”. Subsequently, three fixed‐effects meta‐analyses were performed, one for each dimension of burnout, to calculate its prevalence and the corresponding confidence intervals. The data were analysed using StatsDirect meta‐analysis software. Eleven studies were finally included (n = 11). In most cases, the literature informs about moderate levels of emotional exhaustion, depersonalization, and personal accomplishment. The studies inform that variables such as work overload, work‐related stress, professional seniority, male gender, being single, and aggression at work, among other factors, contribute to burnout development. The meta‐analytic prevalence estimations of burnout with a sample of n = 868 mental health nurses are 25% for high emotional exhaustion, 15% for depersonalization, and 22% for low personal accomplishment. From a workforce development and safety perspective, it is important for managers to address the emotional exhaustion and low personal accomplishment aspects of burnout reported in the workplace by mental health nurses.