bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myeloid-Derived Suppressor Cells Mediate Immunosuppression After Cardiopulmonary Bypass
Authors: Hübner Max , Tomasi Roland , Effinger David , Wu Tingting , Klein Gregor , Bender Martin , Kilger Erich , Juchem Gerd , Schwedhelm Edzard , Kreth Simone 
Published: May 2019

Objectives:
Cardiopulmonary bypass is associated with severe immune dysfunctions. Particularly, a cardiopulmonary bypass–related long-lasting immunosuppressive state predisposes patients to a higher risk of postoperative complications, such as persistent bacterial infections. This study was conducted to elucidate mechanisms of post-cardiopulmonary bypass immunosuppression.

Design:
In vitro studies with human peripheral blood mononuclear cells.

Setting:
Cardiosurgical ICU, University Research Laboratory.

Patients:
Seventy-one patients undergoing cardiac surgery with cardiopulmonary bypass (enrolled May 2017 to August 2018).

Interventions:
Peripheral blood mononuclear cells before and after cardiopulmonary bypass were analyzed for the expression of immunomodulatory cell markers by real-time quantitative reverse transcription polymerase chain reaction. T cell effector functions were determined by enzyme-linked immunosorbent assay, carboxyfluorescein succinimidyl ester staining, and cytotoxicity assays. Expression of cell surface markers was assessed by flow cytometry. CD15+ cells were depleted by microbead separation. Serum arginine was measured by mass spectrometry. Patient peripheral blood mononuclear cells were incubated in different arginine concentrations, and T cell functions were tested.

Measurements and Main Results:
After cardiopulmonary bypass, peripheral blood mononuclear cells exhibited significantly reduced levels of costimulatory receptors (inducible T-cell costimulator, interleukin 7 receptor), whereas inhibitory receptors (programmed cell death protein 1 and programmed cell death 1 ligand 1) were induced. T cell effector functions (interferon γ secretion, proliferation, and CD8+-specific cell lysis) were markedly repressed. In 66 of 71 patients, a not yet described cell population was found, which could be characterized as myeloid-derived suppressor cells. Myeloid-derived suppressor cells are known to impair immune cell functions by expression of the arginine-degrading enzyme arginase-1. Accordingly, we found dramatically increased arginase-1 levels in post-cardiopulmonary bypass peripheral blood mononuclear cells, whereas serum arginine levels were significantly reduced. Depletion of myeloid-derived suppressor cells from post-cardiopulmonary bypass peripheral blood mononuclear cells remarkably improved T cell effector function in vitro. Additionally, in vitro supplementation of arginine enhanced T cell immunocompetence.

Conclusions:
Cardiopulmonary bypass strongly impairs the adaptive immune system by triggering the accumulation of myeloid-derived suppressor cells. These myeloid-derived suppressor cells induce an immunosuppressive T cell phenotype by increasing serum arginine breakdown. Supplementation with L-arginine may be an effective measure to counteract the onset of immunoparalysis in the setting of cardiopulmonary bypass.
Experiencing God in Nursing
Authors: Simon Elizabeth B. , Hodges Ryan , Schoonover-Shoffner Kathy 
Published: May 2019

ABSTRACT
Christian faith supports the idea that God is always at work in the world. God invites people into relationship with him and then to join in his work. Three nurses relay supernatural events where God worked in and through their nursing practice, reinforcing the understanding of what author Henry Blackaby calls experiencing God. Christian nurses are called to enter deeply into relationship with God.
Psychological Comorbidities in Childhood Celiac Disease
Authors: Coburn Shayna Skelley , Puppa Elaine Leonard , Blanchard Samra 
Published: May 2019

ABSTRACTObjectives:Mental health disorders comorbid to chronic illness are associated with higher medical care utilization and costs for adults and children. Celiac disease (CD) has a substantial perceived treatment burden and is associated with higher rates of psychopathology in adults. However, establishing the risk for psychological comorbidities in children with CD is still needed. This study aimed to review existing research on mental health concerns in pediatric CD and propose an initial psychosocial research and clinical agenda.Methods:Databases, including Scopus and PubMed. Additional publications were accessed and reviewed from the references provided by initially identified publications. Two investigators screened studies using predetermined criteria (peer‐reviewed, published in English, electronically available, inclusive of child participants, and examining CD). One investigator initially extracted data, with subsequent review by the second investigator.Results:Twenty‐six publications met criteria for the current review (16 case‐control, 9 observational, and 1 clinical trial). Publications were heterogeneous in symptoms examined, methodology, and population characteristics. Several studies found elevated risk for psychological comorbidities and poorer quality of life in children with CD. However, many studies were limited by small sample sizes and inconsistent or nonvalidated approaches to measuring psychological symptoms.Conclusions:Many existing studies have found increased prevalence of comorbid CD and psychological symptoms or diagnoses. Therefore, screening for psychological symptoms in CD and also screening for CD in psychological clinic populations is needed. We have identified the importance for further study of mechanisms and risk, and identify preliminary priorities for psychosocial research and clinical care in pediatric CD.
Anatomical selectivity in overlap of chronic facial and bodily pain
Authors: Slade Gary D. , Rosen Jonathan D. , Ohrbach Richard , Greenspan Joel D. , Fillingim Roger B. , Parisien Marc , Khoury Samar , Diatchenko Luda , Maixner William , Bair Eric 
Published: May 2019

Abstract

Background:
Chronic facial pain often overlaps with pain experienced elsewhere in the body, although previous studies have focused on a few, selected pain conditions when assessing the degree of overlap.

Aim:
To quantify the degree of overlap between facial pain and pain reported at multiple locations throughout the body.

Methods:
Data were from a case–control study of US adults participating in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) project. They were interviewed to determine the presence of chronic facial pain (n = 424 cases) or its absence (n = 912 controls). A mailed questionnaire with a body drawing asked about pain at other locations. Odds ratios (ORs) and 95% confidence limits (95% CLs) quantified the degree of overlap between facial pain and pain at other locations. For replication, cross-sectional data were analyzed from the UK Biobank study (n = 459,604 participants) and the US National Health Interview Survey (n = 27,731 participants).

Results:
In univariate analysis, facial pain had greatest overlap with headache (OR = 14.2, 95% CL = 9.7–20.8) followed by neck pain (OR = 8.5, 95% CL = 6.5–11.0), whereas overlap decreased substantially (ORs of 4.4 or less) for pain at successively remote locations below the neck. The same anatomically based ranking of ORs persisted in multivariable analysis that adjusted for demographics and risk factors for facial pain. Findings were replicated in the UK Biobank study and the US National Health Interview Survey. The observed anatomical selectivity in the degree of overlap could be a consequence of neurosensory and/or affective processes that differentially amplify pain according to its location.
Stillbirth in Women Living With HIV Delivering in the United Kingdom and Ireland: 2007–2015
Authors: Favarato Graziella , Townsend Claire L. , Peters Helen , Sconza Rebecca , Bailey Heather , Cortina-Borja Mario , Tookey Pat , Thorne Claire 
Published: May 2019

Background:
Women living with HIV have a higher risk of adverse birth outcomes, but questions remain regarding their specific risk factors for stillbirth and the extent to which maternal HIV is associated with stillbirth.

Methods:
Using data on pregnant women with HIV reported within population-based surveillance in the United Kingdom/Ireland, we described stillbirth rates in 2007–2015 stratified by type of antiretroviral therapy (ART) and evaluated risk factors using Poisson regression. General population stillbirth rates by maternal world region of origin were derived from national annual birth statistics, and compared with rates in women with HIV, using standardized stillbirth ratios with the general population as the reference.

Results:
Between 2007 and 2015, there were 10,434 singleton deliveries in 8090 women with HIV; 75% of pregnancies were in women of African origin; and 49% were conceived on ART. The stillbirth rate was 8.5 (95% confidence interval: 6.9 to 10.5) per 1000 births. Risk factors for stillbirth included pre-eclampsia, diabetes, Asian maternal origin (versus United Kingdom/Ireland), CD4 count <350 cells/mm3, older maternal age, and primiparity. Conceiving on ART did not increase the risk. The stillbirth rates (per 1000 births) by type of ART were 14.3, 11.7, 8.3, and 6.0, respectively for NVP + XTC/TDF–, LPV/r + 3TC/ZDV–, NVP + XTC/ABC–, and NVP + XTC/ZDV–exposed pregnancies (P value = 0.40). The standardized stillbirth ratio was 129 (95% confidence interval: 101 to 165) in women with HIV compared with the general population.

Conclusion:
After adjusting for maternal origin, the stillbirth rate remained higher in women with HIV than the general population. We recommend further studies to understand and prevent this excess.
Plasmodium PIMMS43 is required for ookinete evasion of the mosquito complement-like response and sporogonic development in the oocyst
Authors: Ukegbu Chiamaka V. , Giorgalli Maria , Tapanelli Sofia , Rona Luisa D.P. , Jaye Amie , Wyer Claudia , Angrisano Fiona , Blagborough Andrew M. , Christophides George K. , Vlachou Dina 
Published: May 2019

AbstractMalaria transmission requires Plasmodium parasites to successfully infect a female Anopheles mosquito, surviving a series of robust innate immune responses. Understanding how parasites evade these responses can highlight new ways to block malaria transmission. We show that ookinete and sporozoite surface protein PIMMS43 is required for Plasmodium ookinete evasion of the Anopheles coluzzii complement-like system and for sporogonic development in the oocyst. Disruption of P. berghei PIMMS43 triggers robust complement activation and ookinete elimination upon mosquito midgut traversal. Silencing the complement-like system restores ookinete-to-oocyst transition. Antibodies that bind PIMMS43 interfere with parasite immune evasion when ingested with the infectious blood meal and significantly reduce the prevalence and intensity of infection. PIMMS43 genetic structure across African P. falciparum populations indicates allelic adaptation to sympatric vector populations. These data significantly add to our understanding of mosquito-parasite interactions and identify PIMMS43 as a target of interventions aiming at malaria transmission blocking.Author summaryMalaria is a devastating disease transmitted among humans through mosquito bites. Mosquito control has significantly reduced clinical malaria cases and deaths in the last decades. However, as mosquito resistance to insecticides is becoming widespread impacting on current control tools, such as insecticide impregnated bed nets and indoor spraying, new interventions are urgently needed, especially those that target disease transmission. Here, we characterize a protein found on the surface of malaria parasites, which serves to evade the mosquito immune system ensuring disease transmission. Neutralization of PIMMS43, either by eliminating it from the parasite genome or by pre-incubating parasites with antibodies that bind to the protein, is shown to inhibit mosquito infection by malaria parasites. Differences in PIMMS43 detected between malaria parasite populations sampled across Africa suggest that these populations have adapted for transmission by different mosquito vectors that are also differentially distributed across the continent. We conclude that interventions targeting PIMMS43 could block malaria parasites inside mosquitoes before they can infect humans.
A compositional letter code in high-level visual cortex explains how we read jumbled words
Authors: Agrawal Aakash , Hari K.V.S. , Arun S. P. 
Published: May 2019

ABSTRACTWe read words and even jubmled wrods effortlessly, but the neural representations underlying this remarkable ability remain unknown. We hypothesized that word processing is driven by a visual representation that is compositional i.e. with string responses systematically related to letters. To test this hypothesis, we devised a model in which neurons tuned to letter shape respond to longer strings by linearly summing letter responses. This letter model explained human performance in both visual search as well as word reading tasks. Brain imaging revealed that viewing a string activates this compositional letter code in the lateral occipital (LO) region, and that subsequent comparisons to known words are computed by the visual word form area (VWFA). Thus, seeing a word activates a compositional letter code that enables efficient reading.
Markov chains applied to molecular evolution simulation
Authors: Ortega Joel Valdivia 
Published: May 2019

AbstractToday we are able to describe genome evolution but, there are still several open questions on this area such as: Which is the probability that a mutation occurs at a nucleotide level? Is it possible to predict the evolution of a particular genome?, or talking about preservation, is there a way to simulate the genetic diversity for endangered species? In this paper it is shown that it is possible to make a mathematical model not only of mutations on the genome of species, but of evolution itself, including factors such as artificial and natural selection. It is also presented the algorithm to obtain the probabilities of mutation for each specific part of the genome and for each specie. The potential of having this tool is giantic going from genetic engineering applied to medicine to filling up blank spaces in phylogenetic studies or preservation of endangered species due to genetic diversity.
Distinct effects of amyloid and tau deposition on eigenvector centrality during hippocampal down-regulation: a real-time fMRI virtual reality closed-loop neurofeedback study with CSF biomarkers
Authors: Skouras Stavros , Torner Jordi , Andersson Patrik , Koush Yury , Falcon Carles , Minguillon Carolina , Fauria Karine , Alpiste Francesc , Blenow Kaj , Zetterberg Henrik , Gispert Juan D. , Molinuevo José L. ,   for the ALFA Study
Published: May 2019

AbstractHippocampal down-regulation is associated with genetic predisposition to Alzheimer’s disease (AD), neurodevelopmental processes and disease symptoms. Resting state eigenvector centrality (EC) patterns resemble those of FDG-PET in AD, they can predict self-regulation performance and they are related to functional compensation across the pathophysiological continuum of AD. We acquired cerebrospinal fluid (CSF) biomarkers from a cognitively unimpaired sample at risk for AD (N=48), to investigate the effect of β- amyloid peptide 42 (Aβ42) and phosphorylated tau (p-Tau) levels on EC during the down-regulation of hippocampal subfield cornu ammonis 1, with real-time fMRI closed-loop neurofeedback. Controlling the effects of confounding variables (age, sex, number of APOE ε4 alleles, cognitive reserve, brain reserve and hippocampal down-regulation performance), CSF Aβ42 levels correlated positively with EC in the anterior cingulate cortex (BA24, BA32) and primary motor cortex (BA4). CSF p-Tau levels correlated with EC positively in the ACC (BA32, BA10) ventral striatum (caudate, nucleus accumbens, putamen) and left primary somatosensory cortex (BA2), as well as negatively in the posterior cingulate cortex, precuneus, cuneus and left frontal pole (BA9). Controlling for CSF biomarkers and other prognosis variables, age correlated negatively with EC in the midcingulate cortex, insula, primary somatosensory cortex (BA2) and inferior parietal lobule (BA40), as well as positively with EC in the inferior temporal gyri. Taken together, we identified patterns of functional connectomics in individuals at risk of AD during hippocampal down-regulation, which resemble those found during resting state at advanced AD stages. Moreover, we provide a standard paradigm to replicate and extend this work on a global level. This opens new avenues for further research applications, which quantify and monitor disease progression, by identifying early alterations in the self-regulation of brain function, with potential for non-invasive prognostic screening.HighlightsACC centrality decreases with early Aβ42ACC centrality increases with p-TauPCC centrality decreases with p-TauMCC centrality decreases in healthy aging
A Protein Kinase A-Regulated Network Encodes Short- and Long-Lived Cellular Memory
Authors: Jiang Yanfei , AkhavanAghdam Zohreh , Li Yutian , Zid Brian M. , Hao Nan 
Published: May 2019

AbstractCells can store memories of prior experiences to modulate their responses to subsequent stresses, as seen for the protein kinase A (PKA)-mediated general stress response in yeast, which is required for resistance against future stressful conditions. Using microfluidics and time-lapse microscopy, we quantitatively analyzed how cellular memory of stress adaptation is encoded in single yeast cells. We found that cellular memory is biphasic. Short-lived memory was mediated by trehalose synthase and trehalose metabolism. Long-lived memory was mediated by PKA-regulated stress-responsive transcription factors and cytoplasmic messenger ribonucleoprotein (mRNP) granules. Strikingly, short- and long-lived memory could be selectively induced by different priming input dynamics. Computational modeling revealed how the PKA-mediated regulatory network could encode previous stimuli into memories with distinct dynamics. This biphasic memory-encoding scheme, analogous to innate and adaptive immune responses in mammals, might represent a general strategy to prepare for future challenges in rapidly changing environments.
Serum Alpha-2-Macroglobulin as an intrinsic radioprotective factor in patients undergoing thoracic radiation therapy
Authors: von Reibnitz Donata , Yorke Ellen D. , Oh Jung Hun , Apte Aditya P. , Yang Jie , Pham Hai , Thor Maria , Wu Abraham J. , Fleisher Martin , Gelb Emily , Deasy Joseph O. , Rimner Andreas 
Published: May 2019

AbstractObjectiveTo investigate the impact of alpha-2-macroglobulin (A2M), a suspected intrinsic radioprotectant, on radiation pneumonitis and esophagitis. Additionally, we establish multifactorial predictive models for pneumonitis and esophagitis.Materials/MethodsBaseline A2M levels were obtained for 258 patients prior to thoracic radiotherapy (RT). Dose-volume characteristics were extracted from treatment plans. Spearman’s correlation (Rs) test was used to correlate A2M levels, smoking status and dosimetric variables with toxicities. Esophagitis and pneumonitis prediction models were built using least absolute shrinkage and selection operator (LASSO) logistic regression on 1000 bootstrapped datasets. Models were built using 2/3 of the data for training and 1/3 for validation.ResultsThere were 36 (14.0%) patients with grade ≥2 pneumonitis and 61 (23.6%) with grade ≥2 esophagitis. The median A2M level was 191 mg/dL (range: 94-511). Never/former/current smoker status was 47 (18.2%)/179 (69.4%)/32 (12.4%). We found a significant correlation between baseline A2M levels and esophagitis (Rs=-0.18/p=0.003) and between A2M and smoking status (former or current) (Rs=0.13/p=0.04) but not between A2M and pneumonitis. On univariate analysis, significant parameters for grade ≥2 esophagitis included number of fractions (Rs=0.47/p<0.0001), treatment days (Rs=0.44/p<0.0001), chemotherapy use (Rs=0.40/p<0.0001), dose per fraction (Rs=-0.34/p<0.0001), total dose (Rs=0.29/p<0.0001), age (Rs=-0.22/p=0.0003), and several dosimetric variables in esophagus with Rs>0.5 (p<0.0001). For pneumonitis, significant clinical parameters were treatment days (Rs=0.24/p=0.0001), chemotherapy use (Rs=0.22/p=0.0004), number of fractions (Rs=0.21/p=0.0007), dose per fraction (Rs=-0.18/p=0.0035), and total dose (Rs=0.15/p=0.013). The most significant dosimetric variable in lung and heart was D70 (Rs=0.28/p<0.0001) and max dose (Rs=0.27/p<0.0001), respectively. LASSO bootstrap logistic regression models on the validation data resulted in the area under the receiver operating characteristic curve of 0.84 and 0.75 for esophagitis and pneumonitis, respectively.ConclusionOur findings show an association of higher A2M values with lower risk of radiation esophagitis and smoking status. Multivariate predictive models also confirmed a role of heart dose in the risk of pneumonitis.
A systematic investigation on the involvement of complement pathway in diabetic retinopathy
Authors: Shahulhameed Shahna , Vishwakarma Sushma , Chhablani Jay , Tyagi Mudit , Pappuru Rajeev R , Chakrabarti Subhabrata , Kaur Inderjeet 
Published: May 2019

AbstractBackgroundComplement system play a crucial role in retinal homeostasis. Several proteomic studies have shown deposition of complement protein in ocular tissues from diabetic retinopathy, however, their exact involvement in pathogenesis of DR remains unclear.MethodsWe evaluated major complement pathway proteins in the classical and alternative pathway including C1q, C4b, C3, CFB and CFH in vitreous humor and serum samples from PDR patients and controls by western blotting. Quantitative real time (QRT) PCR was done for PDR, NPDR and no-DM controls for correlating the expression of several key pro and anti -angiogenic genes with their correspondingprotein levels. Inflammation in the vitreous humor samples was assessed by ELISA and metalloproteinase activity measured by gelatin zymography. Glial activation and its association with complement activation in diabetic eyes was assessed by immunohistochemistry.ResultsA significant increase in C3 proteins, its activated fragment C3bα’ (110kDa) along with a concurrent up regulation of CFH was observed for PDR vitreous. QRT identified a significant upregulation of angiogenic genes and downregulation of antiangiogenic genes in PDR and NPDR cases. PDR vitreous had increased MMP9 activity and upregulation of inflammatory markers IL8, sPECAM and down regulation of anti-inflammatory marker IL-10. Increased C3 deposition and CFH upregulation were observed in DM retina. CFH was found co-localizing with CD11b+ve activated microglial cells in inner nuclear layer of DM retina.ConclusionsThe present study confirms increased activation of alternative complement pathway in PDR. The co-localization of CFH in CD11b +ve cells further suggests microglia as a source of CFH in diabetic retina. Increased CFH levels could be a feedback mechanism for arresting excessive complement activation DR eyes.