bluuebunny/crossref_metadata_2025 huggingface dataset:
A tutorial on calibration measurements and calibration models for clinical prediction models
Authors: Huang Yingxiang , Li Wentao , Macheret Fima , Gabriel Rodney A , Ohno-Machado Lucila
Published: January 2020

Our primary objective is to provide the clinical informatics community with an introductory tutorial on calibration measurements and calibration models for predictive models using existing R packages and custom implemented code in R on real and simulated data. Clinical predictive model performance is commonly published based on discrimination measures, but use of models for individualized predictions requires adequate model calibration. This tutorial is intended for clinical researchers who want to evaluate predictive models in terms of their applicability to a particular population. It is also for informaticians and for software engineers who want to understand the role that calibration plays in the evaluation of a clinical predictive model, and to provide them with a solid starting point to consider incorporating calibration evaluation and calibration models in their work.

Covered topics include (1) an introduction to the importance of calibration in the clinical setting, (2) an illustration of the distinct roles that discrimination and calibration play in the assessment of clinical predictive models, (3) a tutorial and demonstration of selected calibration measurements, (4) a tutorial and demonstration of selected calibration models, and (5) a brief discussion of limitations of these methods and practical suggestions on how to use them in practice.
Effects of inulin supplementation on intestinal barrier function and immunity in specific pathogen-free chickens with Salmonella infection
Authors: Song Jiao , Li Qinghe , Everaert Nadia , Liu Ranran , Zheng Maiqing , Zhao Guiping , Wen Jie
Published: January 2020

We investigated the effects of inulin on intestinal barrier function and mucosal immunity in Salmonella enterica serovar Enteritidis (SE)–infected specific pathogen-free (SPF) chickens. SPF chickens (n = 240, 1-d-old) were divided into 4 groups (6 replicates per group, 10 chickens per replicate): a control group (CON) fed a basal diet without inulin supplementation and 3 SE-infected groups fed a basal diet supplemented with inulin 0% (SE group), 0.5% (0.5% InSE group), and 1% (1% InSE group), respectively. At 28 d of age, the chickens in SE-infected groups were orally infected with SE and in CON group were administrated with phosphated-buffered saline (PBS). Intestinal morphology, mucosal immunity, and intestinal barrier function-related gene expression were analyzed at 1- and 3-d post-infection (dpi). SE challenge significantly increased the mucosal gene expression, such as interleukin-1β (IL-1β), lipopolysaccharide-induced tumor necrosis factor factor (LITAF), interferon-γ (IFN-γ), and interleukin-6 (IL-6), and increased serum IFN-γ, secretory IgA (sIgA), and IgG concentration, and significantly decreased the gene expression levels of mucin 2 (MUC2) and claudin-1 at 3 dpi compared with the CON group (P < 0.05). Inulin supplementation improved the expression levels of these immunity- and intestinal barrier function-related genes, increased villus height (VH), and decreased crypt depth (CD) in the duodenum, jejunum, and ileum at 1 and 3 dpi within the SE-challenged groups (P < 0.05). SE challenge significantly increased ileal Toll-like receptor 4 (TLR4) mRNA at 1 and 3 dpi, suppressor of cytokine signaling 3 (SOCS3) mRNA at 1 dpi, and phospho-signal transducer and activator of transcription 3 (p-STAT3) and Janus kinase1 (JAK1) protein expression at 3 dpi compared with the CON group (P < 0.05). Inulin supplementation suppressed p-STAT3 and JAK1 protein expression and promoted ileal TLR4 and SOCS3 mRNA expression at 3 dpi compared with SE group (P < 0.05). In conclusion, inulin alleviated SE-induced gut injury by decreasing the proinflammatory response and enhancing mucosal immunity in chickens.
The Clinically Relevant Breast Imaging Audit
Authors: D’Orsi Carl Joseph
Published: January 2020

An audit of a breast imaging practice must be based on data with accepted definitions and rules so that the comparisons between breast imaging facilities and interpretive staff are comparable. The four basic data points for calculating these metrics are true positive (TP), true negative (TN), false positive (FP), and false negative (FN). For mammography, the definition of “true” is the presence of a proven malignancy within a year of the exam. The presence or absence of breast cancer within a year of the exam and an increase in patient mobility between different facilities may render the calculation of sensitivity and specificity difficult for most facilities unless a regional cancer registry is available.Thus, the metrics that can be easily calculated within a facility are recall rate (all the positive interpretations divided by all the exams read), positive predictive value (PPV) 1 = percentage of abnormal screening exams that result in a diagnosis of cancer within a year, PPV2 = percentage of all diagnostic exams recommended for biopsy and cancer discovered within a year, PPV3 = benign tissue diagnosis and no cancer within a year, and the cancer detection rate (the true positive exams per one thousand exams). Intuitively, one may assume that accuracy (TP + TN/TP + FP + TN + FN) is the best metric for an interpreter. However, this can produce spurious results. The most accurate method to determine a reader’s skills is the use of the receiver operating characteristic (ROC) curve, which clearly presents, in graphic form, the relationship between the four basic data points.
Byzantium on display
Authors: Lovino Francesco
Published: January 2020

In the early twentieth century, art dealers tailored their activities to the demands of a new generation of collectors who had turned to Byzantine art. The attention paid to Byzantium reached its peak with the Exposition Internationale d’Art Byzantin, at which more than 800 artefacts were displayed in the Pavillon de Marsan at the Musée du Louvre in 1931. This paper aims to investigate the role of private lenders to the exhibition, and particularly that of art dealers, who were instrumental in the founding of many collections of medieval and Byzantine pieces, selecting and importing from the Mediterranean basin fine objects for American and European collectors. The Exposition thus represented for them a prime occasion for the display of goods in a formal and officially recognized environment, and an opportunity to expand their network of clients.
Direct Determination of the Body Content of Radionuclides: Abstract
Authors: Griffith R. , Bergmann H. , Fry F. A. , Hickman D. , Genicot J.-L. , Malatova I. , Neton J. , Rahola T. , Wahl W.
Published: January 2020

Previous ICRU reports have dealt with the formulation and properties of tissue substitutes and phantoms that are used to calibrate in vivo measurement systems. This report provides guidance on the overall process of the direct measurement of radionuclides in the human body for radiation protection and medical applications. It addresses the detectors and electronics used for the measurement; methods of background reduction and control; measurement geometries for whole body, partial body or organ counting; physical and mathematical calibration methods; data analysis; and quality assurance. It is directed to readers who need practical advice on the establishment and operation of direct measurement facilities.
Image Quality in Chest Radiography: Abstract
Authors: Vyborny C. , Bunch P. , Chotas H. , Dobbins J. , Niklason L. , Schaefer-Prokop C.
Published: January 2020

Image quality in chest radiography is an important, but complex, subject. The complicated anatomy of the chest, as well as the various ways that chest disease may manifest itself, require careful consideration of radiographic technique. The manner in which human observers deal with the complexity of chest images adds further dimensions to image analysis that are not found in other radiography examinations. This report describes many issues that are related to the quality of chest radiographic images. In so doing, it relies upon the very extensive literature on this topic, a topic that has been one of the most thoroughly studied in all of radiography. Strategies that are generally agreed to improve the quality of chest radiographs are described, as are approaches to the assessment of image quality.
Migrant workers’ wage offers: the paradox of the involvement of recruitment intermediaries
Authors: Weeraratne Bilesha
Published: January 2020

Recruitment of labor migrants is often mediated by informal intermediaries (subagents) liaising between formal recruitment agents and potential migrants. Many countries of origin of migrant workers are struggling to reign in subagents in the recruitment process for labor migration. This article shows that focusing on migrants can compensate for this difficulty. Using primary data collected from current and potential migrant households in fixed effect models, this article shows that subagents’ unauthorized conduct of collecting passports is correlated with 27–80 per cent lower promised recruitment incentives, while subagents’ conduct of requesting fees for their services is linked to a 22–38 per cent increase in promised wages and 45–82 per cent increase in promised recruitment incentives. Migrants’ misperception that the subagent is compulsory in the recruitment process is associated with lowering wages by 7–15 per cent, while the misperception that subagent showed the identification card is associated with 10–14 per cent lower promised wages, and 32–72 per cent lower promised incentives. These findings show that better informing potential migrants about the role, formal status, and the implications of the involvement of subagents would lead to better wage and incentive negotiations. This approach would contribute toward facilitating orderly, safe, regular, and responsible recruitment for labor migration envisioned by Sustainable Development Goals and the Global Compact for Safe, Orderly, and Regular Migration.
LSQ13ddu: a rapidly evolving stripped-envelope supernova with early circumstellar interaction signatures
Authors: Clark Peter , Maguire Kate , Inserra Cosimo , Prentice Simon , Smartt Stephen J , Contreras Carlos , Hossenizadeh Griffin , Hsiao Eric Y , Kankare Erkki , Kasliwal Mansi , Nugent Peter , Shahbandeh Melissa , Baltay Charles , Rabinowitz David , Arcavi Iair , Ashall Chris , Burns Christopher R , Callis Emma , Chen Ting-Wan , Diamond Tiara , Fraser Morgan , Howell D Andrew , Karamehmetoglu Emir , Kotak Rubina , Lyman Joseph , Morrell Nidia , Phillips Mark , Pignata Giuliano , Pursiainen Miika , Sollerman Jesper , Stritzinger Maximilian , Sullivan Mark , Young David
Published: January 2020

This paper describes the rapidly evolving and unusual supernova LSQ13ddu, discovered by the La Silla-QUEST survey. LSQ13ddu displayed a rapid rise of just 4.8 ± 0.9 d to reach a peak brightness of −19.70 ± 0.02 mag in the LSQgr band. Early spectra of LSQ13ddu showed the presence of weak and narrow $\mathrm{ He}\, {\small I}$ features arising from interaction with circumstellar material (CSM). These interaction signatures weakened quickly, with broad features consistent with those seen in stripped-envelope SNe becoming dominant around two weeks after maximum. The narrow $\mathrm{ He}\, {\small I}$ velocities are consistent with the wind velocities of luminous blue variables but its spectra lack the typically seen hydrogen features. The fast and bright early light curve is inconsistent with radioactive 56Ni powering but can be explained through a combination of CSM interaction and an underlying 56Ni decay component that dominates the later time behaviour of LSQ13ddu. Based on the strength of the underlying broad features, LSQ13ddu appears deficient in He compared to standard SNe Ib.
Drone-based entanglement distribution towards mobile quantum networks
Authors: Liu Hua-Ying , Tian Xiao-Hui , Gu Changsheng , Fan Pengfei , Ni Xin , Yang Ran , Zhang Ji-Ning , Hu Mingzhe , Guo Jian , Cao Xun , Hu Xiaopeng , Zhao Gang , Lu Yan-Qing , Gong Yan-Xiao , Xie Zhenda , Zhu Shi-Ning
Published: January 2020

Satellites have shown free-space quantum-communication ability; however, they are orbit-limited from full-time all-location coverage. Meanwhile, practical quantum networks require satellite constellations, which are complicated and expensive, whereas the airborne mobile quantum communication may be a practical alternative to offering full-time all-location multi-weather coverage in a cost-effective way. Here, we demonstrate the first mobile entanglement distribution based on drones, realizing multi-weather operation including daytime and rainy nights, with a Clauser-Horne-Shimony-Holt S-parameter measured to be 2.41 ± 0.14 and 2.49 ± 0.06, respectively. Such a system shows unparalleled mobility, flexibility and reconfigurability compared to the existing satellite and fiber-based quantum communication, and reveals its potential to establish a multinode quantum network, with a scalable design using symmetrical lens diameter and single-mode-fiber coupling. All key technologies have been developed to pack quantum nodes into lightweight mobile platforms for local-area coverage, and arouse further technical improvements to establish wide-area quantum networks with high-altitude mobile communication.
Status and trends in consumption of grains and dietary fiber among Chinese adults (1982–2015)
Authors: Yu Dongmei , Zhao Liyun , Zhao Wenhua
Published: January 2020

The objectives of this review were to investigate the status and characteristics of national grain consumption and dietary fiber intake among Chinese adults (aged ≥20 years) and to examine trends in consumption from 1982 to 2015. Data from 5 national surveys that collected dietary information using a household food weighing method and 24-hour dietary recall over 3 consecutive days were analyzed. In 2015, mean grain consumption was 281.1 g/per capita/d (rice 145.6 g, wheat flour 120.7 g, other grains 14.8 g). Total dietary fiber intake was 9.7 g/per capita/d, of which 3.8 g/per capita/d came from grains and accounted for nearly 40% of total dietary fiber intake for adults. The other major sources of dietary fiber were vegetables and fruits. The data indicates consumption of grains and dietary fiber in the Chinese population has been continuously declining since 1982 and the consumption of refined grains has increased. In order for the Chinese population to meet dietary recommendations for whole grain and dietary fiber intake, increasing the availability of more appealing whole grain products and public education are recommended.
Low-Dose Naltrexone for the Treatment of Fibromyalgia: Investigation of Dose–Response Relationships
Authors: Bruun-Plesner Karin , Blichfeldt-Eckhardt Morten Rune , Vaegter Henrik Bjarke , Lauridsen Joergen T , Amris Kirstine , Toft Palle
Published: January 2020

Objective

This study explores dose–response relationships when treating fibromyalgia with low-dose naltrexone.

Design

A single-blinded clinical trial was carried out using the “up-and-down” method.

Subjects

Subjects included women with a diagnosis of fibromyalgia aged 18–60 years who had been referred to treatment at a public pain clinic at a Danish university hospital.

Methods

The test doses were in the range 0.75–6 mg, and the dosing interval was 0.75 mg. The method was sequential and allowed predicting the dose effective in 50% (ED50) and 95% (ED95) of the subjects when the dose had shifted direction 10 times, and six pairs of “up-and-down” data were available.

Results

A total of 27 subjects were included in the study; two subjects were withdrawn. After inclusion of 25 evaluable subjects, the dose estimates were calculated as 3.88 mg for ED50 and 5.40 mg for ED95. As a secondary outcome, the effects on 10 common fibromyalgia symptoms were evaluated. A high interindividual variation was observed both in the symptom presentation at baseline and in which symptoms were reduced by low-dose naltrexone.

Conclusions

This study is the first to explore dose–response relationships in the treatment of fibromyalgia with low-dose naltrexone. Future placebo-controlled randomized clinical trials are needed, and according to our findings, 4.5 mg, which has previously been used, seems to be a relevant test dose. We recommend that future studies include additional nonpain fibromyalgia symptoms as outcome measures.
Main Symptomatic Treatment Targets in Suspected and Early Psychosis: New Insights From Network Analysis
Authors: Jimeno Natalia , Gomez-Pilar Javier , Poza Jesus , Hornero Roberto , Vogeley Kai , Meisenzahl Eva , Haidl Theresa , Rosen Marlene , Klosterkötter Joachim , Schultze-Lutter Frauke
Published: January 2020

The early detection and intervention in psychoses prior to their first episode are presently based on the symptomatic ultra-high-risk and the basic symptom criteria. Current models of symptom development assume that basic symptoms develop first, followed by attenuated and, finally, frank psychotic symptoms, though interrelations of these symptoms are yet unknown. Therefore, we studied for the first time their interrelations using a network approach in 460 patients of an early detection service (mean age = 26.3 y, SD = 6.4; 65% male; n = 203 clinical high-risk [CHR], n = 153 first-episode psychosis, and n = 104 depression). Basic, attenuated, and frank psychotic symptoms were assessed using the Schizophrenia Proneness Instrument, Adult version (SPI-A), the Structured Interview for Psychosis-Risk Syndromes (SIPS), and the Positive And Negative Syndrome Scale (PANSS). Using the R package qgraph, network analysis of the altogether 86 symptoms revealed a single dense network of highly interrelated symptoms with 5 discernible symptom subgroups. Disorganized communication was the most central symptom, followed by delusions and hallucinations. In line with current models of symptom development, the network was distinguished by symptom severity running from SPI-A via SIPS to PANSS assessments. This suggests that positive symptoms developed from cognitive and perceptual disturbances included basic symptom criteria. Possibly conveying important insight for clinical practice, central symptoms, and symptoms “bridging” the association between symptom subgroups may be regarded as the main treatment targets, in order to prevent symptomatology from spreading or increasing across the whole network.
Canadian Science Meets Parliament: Building relationships between scientists and policymakers
Authors: Zhao Jiaying , Azad Meghan B , Bertrand Erin M , Burton Cole , Crooks Valorie A , Dawson Jackie , Ford Adam T , Kaida Angela , Krishnaswamy Arjun , Kuok Chikin , Mah Catherine L , McTaggart Matt , Moehring Amanda J , Robert Dominique , Schulte-Hostedde Albrecht , Sparling Heather , De Vera Mary A , Waterman Stephanie , Patel Trushar R
Published: January 2020

The first Science Meets Parliament event in Canada was held in November 2018 in Ottawa, where twenty-eight Tier II Canada Research Chairs (a specific class of Canadian university professor acknowledged by their peers as having the potential to lead in their field) from diverse disciplines met with forty-three Members of Canadian Parliament and Senators. The main goal of this event was to facilitate communication between these two key pillars of the society, to promote mutual understanding of the nature of their respective work, roles, and responsibilities, and to build long-term relationships. Here, we, representatives of the first cohort of scientists to participate in the program, summarize our experiences and lessons learned from this event, as well as our assessment of the benefits of attending this event for scientists, policy decision-makers, and institutions. Furthermore, we provide suggestions for similar future events in Canada and elsewhere.
Competing for Jurisdiction: Practical Legitimation and the Persistence of Informal Recycling in Urban India
Authors: Kornberg Dana
Published: January 2020

How did informal garbage collectors, who had long provided the only door-to-door and recycling services in Delhi, manage to survive the introduction of formal garbage collection trucks? This question raises the larger problem of why informal institutions—well-organized and socially recognized, but legally unauthorized and unregulated platforms for political and economic organization—have proven so persistent. I draw on evidence collected during 20 months of ethnographic research in Delhi, focusing on participant observation with informal collectors during their neighborhood routes and interviews with 50 informal collectors. Bringing together political and urban sociology, postcolonial urban studies, and institutional theory, the paper frames competition over city garbage and recycling as a relational matter. I argue that informal workers preserved their jurisdiction through practical legitimation, depending on everyday actions and social expectations rather than explicit laws or beliefs to secure legitimacy. I demonstrate how status-based relations, here based on caste and labor migration, can confer legitimacy and provide a source of regulation, as actors set out and meet implicit expectations for appropriate actions, relationships, and social boundaries.
Congregational Cohesion, Retention, and the Consequences of Size Reduction: A Longitudinal Network Analysis of an Old Order Amish Church
Authors: Stein Rachel E , Corcoran Katie E , Kowalski Brittany M , Colyer Corey J
Published: January 2020

Congregations depend on their members for their success and survival. Yet there is a lack of research examining congregational retention or exit. Social networks are key to understanding religious group dynamics including retention; however, research on religious communities using network analysis is limited. We use Amish directories to compile longitudinal census data on intracongregational familial ties in our case study. We theorize and find that cohesion is inversely related to congregational size and positively related to retention. We find that splitting congregations reduces cohesion when members central to the network are removed even when congregational size is reduced. The findings may be particularly relevant for understanding retention and group dynamics in small congregations and ethnic congregations in which extended family ties more commonly form the membership base. The results demonstrate the utility of using social network analysis methods to test theoretical predictions drawn from the sociology of religion literature.
At Least Five Major Genes Are Involved in the Avirulence of an Eleusine Isolate of Pyricularia oryzae on Common Wheat
Authors: Asuke Soichiro , Nishimi Shuko , Tosa Yukio
Published: January 2020

Pyricularia oryzae is composed of pathotypes that show host specificity at the plant genus level. To elucidate the genetic mechanisms of the incompatibility between the Eleusine pathotype (pathogenic on finger millet) and common wheat, an Eleusine isolate (MZ5-1-6) was crossed with a Triticum isolate (Br48) pathogenic on wheat, and resulting F1 cultures were sprayed onto common wheat cultivars Hope, Norin 4 (N4), and Chinese Spring (CS). On Hope, avirulent and virulent cultures segregated in a 3:1 ratio, suggesting that two avirulence genes are involved. They were tentatively designated as eA1 and eA2. On N4 and CS, the segregation ratio was not significantly deviated from the 7:1, 15:1, or 31:1 ratios, suggesting that three or more genes are involved. A comparative analysis of the segregation patterns suggested that two of these genes were eA1 and eA2. A complementation test indicated that the third gene (tentatively designated as eA3) was the Ao9 type of the PWT3 gene controlling the avirulence of Avena and Lolium isolates on wheat. The fourth gene (tentatively designated as eA4) was detected by backcrossing 200R72, an F1 culture lacking eA1, eA2, and eA3, with Br48. Comparative analyses of phenotypes and the presence and/or absence of molecular markers in the F1 population revealed that some cultures were avirulent on N4/CS in spite of lacking eA1, eA2, eA3, and eA4, indicating the presence of the fifth gene (tentatively designated as eA5). Taken together, we conclude that at least five avirulence genes are involved in the incompatibility between MZ5-1-6 and N4/CS.
The disruption of hematopoiesis in tumor progression
Authors: Wang Xiaofang , Li Yangqiu
Published: January 2020

Human adult hematopoiesis maintains homeostasis by replacing depleted progeny pools and inducing a primary immune response to infectious diseases and tumors. Recent studies have shown that tumor progression is associated with profound perturbations in hematopoiesis. Scientists have sought to clarify the complex mechanisms underlying the developmental fate of hematopoiesis by assessing hematopoietic stem and progenitor cells in various tumors. Results have shown that tumors disrupt normal hematopoiesis, resulting in extramedullary hematopoiesis and myeloid skewing. The key regulatory roles played by myeloid-derived suppressor cells induce immune suppression. Here, we summarize recent findings and discuss mechanisms underlying the disruption of hematopoiesis in solid tumors.
Macrophages in leukemia microenvironment
Authors: Wang Lina , Zheng Guoguang
Published: January 2020

Macrophages, the important component of tissue microenvironment, play important roles in both physiological and pathological processes, including tumor and leukemia. Tumor-associated macrophages are involved in tumor proliferation, angiogenesis, invasion, metastasis, and chemotherapy resistance. In leukemia, macrophages are educated by leukemia microenvironment to obtain specific activated phenotype and participate in leukemia progression. Recent studies have shown that accumulation of macrophages in leukemia patients or mouse model is correlated with poor prognosis. Hence, increasing attentions have been paid to study the characteristics of them and to develop novel therapeutic strategies targeting macrophages against leukemia. In this article, we summarize recent development of macrophages in leukemia microenvironment.
Tumor heterogeneity of acute myeloid leukemia: insights from single-cell sequencing
Authors: Chen AiLi , Hu ShaoYan , Wang Qian-Fei
Published: January 2020

Individual tumors comprise genetically and epigenetically heterogeneous subclones, each of which is presumably associated with a distinct function, such as self-renewal or drug sensitivity. The dissection of such intratumoral heterogeneity is crucial to understand how tumors evolve during disease progression and under the selection of therapeutic intervention. As a paradigm of cancer intratumoral heterogeneity and clonal evolution, acute myeloid leukemia (AML) has been shown to possess complex clonal architecture based on karyotype studies, as well as deep sequencing of mixed cellular populations using next-generation sequencing (NGS) technologies. The recent development of single-cell sequencing (SCS) methods provides a powerful tool to allow analysis of genomes, transcriptomes, proteomes, and epigenomes at an individual cell level. The technologies applied in AML have broadened our understanding of AML heterogeneity and provided new insights for the development of novel therapeutic strategies. In this review, we summarize the progress in the research of AML heterogeneity using SCS technology and discuss the limitations and future direction regarding how SCS can contribute to AML prognosis and treatment.
The role of cholesterol metabolism in leukemia
Authors: Zhao Liang , Zhan Huien , Jiang Xinya , Li Yangqiu , Zeng Hui
Published: January 2020

Leukemia is a common hematological malignancy with overall poor prognosis. Novel therapies are needed to improve the outcome of leukemia patients. Cholesterol metabolism reprogramming is a featured alteration in leukemia. Many metabolic-related genes and metabolites are essential to the progress and drug resistance of leukemia. Exploring potential therapeutical targets related to cholesterol homeostasis is a promising area. This review summarized the functions of cholesterol and its derived intermediate metabolites, and also discussed potential agents targeting this metabolic vulnerability in leukemia.
Erythroblast island macrophages: recent discovery and future perspectives
Authors: Li Wei , Wang Yaomei , Chen Lixiang , An Xiuli
Published: January 2020

Erythroblastic island (EBI), composed of a central macrophage surrounded by developing erythroid cells, is a structure found in hematopoietic tissues such as fetal liver and bone marrow. It is the first described hematopoietic niche that predominantly supports erythropoiesis. Although it is well accepted that EBIs and EBI macrophage play important roles during erythropoiesis, the mechanisms by which they support erythropoiesis remain largely unclear due to our inability to identify and isolate EBI macrophages. Earlier efforts to identify surface markers for EBI macrophages have focused on the adhesion molecules which are involved in macrophage's interaction with erythroblasts. These include EMP, Vcam1, CD169, CD163, and αV integrin. Findings from these earlier studies suggested that combination of Vcam1, CD169, and mouse macrophage surface marker F4/80 can be used to define mouse EBI macrophage. We found that not all F4/80+Vcam1+CD169+ macrophages are EBI macrophages. Instead, we discovered that EBI macrophages are characterized by the expression of Epor in both mouse and man. RNA-seq analyses of the newly identified EBI macrophages revealed that EBI macrophages have involved specialized function in supporting erythropoiesis. Our findings provide foundation for future studies. Here we will review current knowledge of EBI macrophages and discuss future perspectives.
Therapeutic Vaccine Against Primate Papillomavirus Infections of the Cervix
Authors: Ragonnaud Emeline , Andersson Anne-Marie C. , Mariya Silmi , Pedersen Anders G. , Burk Robert D. , Folgori Antonella , Colloca Stefano , Cortese Riccardo , Nicosia Alfredo , Pamungkas Joko , Iskandriati Diah , Holst Peter J.
Published: January 2020

Currently available prophylactic vaccines have no therapeutic efficacy for preexisting human papillomavirus (HPVs) infections, do not target all oncogenic HPVs and are insufficient to eliminate the burden of HPV induced cancer. We aim to develop an alternative HPV vaccine which is broadly effective and capable of clearing preexisting infection. In an initial attempt to develop a broadly reactive therapeutic vaccine, we designed a putative papillomavirus (PV) ancestor antigen (circulating sequence derived antigenic sequences E1E2—CDSE1E2) based on the conserved E1 and E2 protein sequences from existing oncogenic HPV strains. This antigen was found to be as related to circulating oncogenic Macaca fascicularis papillomaviruses (MfPVs) as to oncogenic HPVs. The CDSE1E2 antigen was fused to a T-cell adjuvant and encoded in chimpanzee 3 and 63 adenoviral vectors. We first showed that the combination of these 2 vaccines induced long-lasting potent CDSE1E2 specific T cell responses in outbred mice. This prime-boost regimen was then tested in female macaques naturally infected with MfPVs. All immunized animals (16/16) responded to the vaccine antigen but with reduced cross-reactivity against existing PVs. Preexisting MfPV infections did not prime vaccine inducible immune responses. Importantly, immunized oncogenic MfPV type 3 (MfPV3) infected animals that responded toward MfPV3 were able to diminish cervical MfPV3 DNA content. Although insufficient breadth was achieved, our results suggest that a relevant level of E1E2 specific T cell immunity is achievable and might be sufficient for the elimination of PV infection. Importantly, naturally infected macaques, offer a relevant model for testing vaccines aimed at eliminating mucosal PV infections.
DNA Vaccine Encoding HPV16 Oncogenes E6 and E7 Induces Potent Cell-mediated and Humoral Immunity Which Protects in Tumor Challenge and Drives E7-expressing Skin Graft Rejection
Authors: Chandra Janin , Dutton Julie L. , Li Bo , Woo Wai-Ping , Xu Yan , Tolley Lynn K. , Yong Michelle , Wells James W. , R. Leggatt Graham , Finlayson Neil , Frazer Ian H.
Published: January 2020

We have previously shown that a novel DNA vaccine technology of codon optimization and the addition of ubiquitin sequences enhanced immunogenicity of a herpes simplex virus 2 polynucleotide vaccine in mice, and induced cell-mediated immunity when administered in humans at relatively low doses of naked DNA. We here show that a new polynucleotide vaccine using the same technology and encoding a fusion protein of the E6 and E7 oncogenes of high-risk human papillomavirus type 16 (HPV16) is immunogenic in mice. This vaccine induces long-lasting humoral and cell-mediated immunity and protects mice from establishment of HPV16-E7-expressing tumors. In addition, it suppresses growth of readily established tumors and shows enhanced efficacy when combined with immune checkpoint blockade targeted at PD-L1. This vaccine also facilitates rejection of HPV16-E7-expressing skin grafts that demonstrate epidermal hyperplasia with characteristics of cervical and vulvar intraepithelial neoplasia. Clinical studies evaluating the efficacy of this vaccine in patients with HPV16+ premalignancies are planned.
Antibiotic Classification and Indication Review for the Infusion Nurse
Authors: Percival Kelly M.
Published: January 2020

Outpatient parenteral antimicrobial therapy (OPAT) has become an increasingly common practice for the treatment of infections. The infusion nurse plays a vital role in administering, monitoring, and educating patients about parenteral antibiotics, while bridging communication between the patient and OPAT team. It is important for the infusion nurse to know common indications, adverse effects, monitoring parameters, and the mechanism of action for antibiotics used in OPAT to provide optimal patient care. This review includes those antibiotics, which are frequently administered or recently approved with a high likelihood of being used in OPAT.
Education Provided to Undergraduate Nursing Students About End-of-Life Care
Authors: Alt-Gehrman Penny
Published: January 2020

Many nurses do not feel prepared to care for patients and families at the end of life (EOL). Because nurses are the health care professionals who spend the most time with patients and their families at the EOL, this is concerning. Nurses will experience death as a part of their practice and must care for the patients' significant others during times of sorrow and stress. The purpose of this literature review was to determine what is provided to undergraduate nursing students regarding EOL. The literature shows that a nurse with a positive attitude can improve the EOL experience for the patient and family. Three main themes emerged from the literature: a positive attitude, knowledge, and confidence/competence/comfort. One glaring omission is the care of the family of the dying patient. More research must be performed.
The Impact of Trauma Type or Number of Traumatic Events on PTSD Diagnosis and Symptom Severity in Treatment Seeking Veterans
Authors: Jakob Jeanne M.D. , Lamp Kristen , Rauch Sheila A.M. , Smith Erin R. , Buchholz Katherine R.
Published: January 2020

Trauma history and increased exposure to combat and sexual trauma may account for heightened rates of PTSD among military populations. This study assessed trauma type and exposure history, diagnostic impressions, and PTSD severity in a large clinical dataset (n = 2463) of veterans presenting for PTSD evaluation at a Midwestern VA Medical Center between the years 2006 and 2013. The degree of lifetime trauma exposure was pronounced, with approximately 76% of the sample reporting exposure to at least four traumatic events. Higher numbers of lifetime trauma and higher levels of combat exposure were associated with more severe PTSD symptoms. Sexual trauma and combat trauma were more predictive of PTSD than other trauma types. Sexual trauma was associated with more severe PTSD than combat and other trauma.
Heterogeneity and heterotypic continuity of emotional and behavioural profiles across development
Authors: Picoito João , Santos Constança , Nunes Carla
Published: January 2020

Purpose

To identify emotional and behavioural symptoms profiles from early childhood to adolescence, their stability across development and associated factors.

Methods

Our sample included 17,216 children assessed at ages 3, 5, 7, 11 and 14 years from the UK Millennium Cohort Study. We used latent profile and latent transition analysis to study their emotional and behavioural profiles from early childhood to adolescence. We included sociodemographic, family and parenting variables to study the effect on latent profile membership and transitions.

Results

The number and specific profiles of emotional and behavioural symptoms changed with the developmental stage. We found a higher number of profiles for ages 3, 5, and 14, suggesting greater heterogeneity in the presentation of emotional and behavioural symptoms in early childhood and adolescence compared to late childhood. There was greater heterotypic continuity between ages 3 and 5, particularly in transitions from higher to lower severity profiles. Children exposed to socioeconomic disadvantages were more likely to belong or transition to any moderate or high emotional and behavioural symptoms profiles. Maternal psychological distress and harsh parenting were associated with internalizing and externalizing profiles, respectively. Higher levels of internalizing and externalizing symptoms across development were associated with lower mental wellbeing and higher rates of self-harm and substance use in adolescence.

Conclusion

Emotional and behavioural symptoms develop early in life, with levels of heterogeneity and heterotypic stability that change throughout development. These results call for interventions to prevent and treat paediatric mental illness that consider the heterogeneity and stability of symptoms across development.
Early screening of autism spectrum disorder using cry features
Authors: Khozaei Aida , Moradi Hadi , Hosseini Reshad , Pouretemad Hamidreza , Eskandari Bahareh
Published: January 2020

Due to the importance of automatic and early autism screening, in this paper, a cry-based screening approach for children with Autism Spectrum Disorder (ASD) is introduced. During the study, we realized that the ASD specific features are not necessarily observable among all children with ASD and among all instances of each child. Therefore, we proposed a new classification approach to be able to find such features and their corresponding instances. We tested the proposed approach and found two features that can be used to distinguish groups of children with ASD from Typically Developing (TD) children. In other words, these features are present in subsets of children with ASD not all of them. The approach has been tested on a dataset including 14 boys and 7 girls with ASD and 14 TD boys and 7 TD girls, between 18 to 53 months old. The sensitivity, specificity, and precision of the proposed approach for boys were 85.71%, 100%, and 92.85%, respectively. These measures were 71.42%, 100%, and 85.71% for girls, respectively.
Collaborative Behavior of Urea and KI in Denaturing Protein Native Structure
Authors: Shao Qiang , Wang Jinan , Zhu Weiliang
Published: January 2020

In this work, the combined influence of urea and KI on protein native structure is quantitatively investigated through the comparative molecular dynamics simulations on the structural dynamics of a polypeptide of TRPZIP4 in a series of urea/KI mixed solutions (urea concentration: 4M, KI salt concentration: 0M-6M). The observed enhanced denaturing ability of urea/KI mixture can be explained by direct interactions of urea/K+/water towards protein (electrostatic and vdW interactions from urea and electrostatic interactions from K+and water) and indirect influence of KI on the strengthened interaction of urea towards protein backbone and side-chain. The latter indirect influence is fulfilled through the weakening of hydrogen bonding network among urea and water by the appearance of K+–water and I—urea interactions. As a result, the denaturing ability enhancement of urea and KI mixed solution is induced by the collaborative behavior of urea and KI salt.
Galantamine alleviates oxidative stress alongside anti-inflammatory and cardio-metabolic effects in subjects with the metabolic syndrome in a randomized trial
Authors: Sangaleti Carine Teles , Katayama Keyla Yukari , De Angelis Kátia , de Moraes Tércio Lemos , Araújo Amanda Aparecida , Lopes Heno F. , Camacho Cleber , Bortolotto Luiz Aparecido , Michelini Lisete Compagno , Irigoyen Maria Cláudia , Barnaby Douglas P. , Tracey Kevin J. , Pavlov Valentin A. , Consolim Colombo Fernanda Marciano
Published: January 2020

Background

The metabolic syndrome (MetS) is an obesity-driven disorder with pandemic proportions and limited treatment options. Oxidative stress, low-grade inflammation and altered autonomic regulation, are important components of MetS pathophysiology. We recently reported that galantamine, an acetylcholinesterase inhibitor and an FDA-approved drug (for Alzheimer’s disease) alleviates the inflammatory state in MetS subjects. Here we examined the effects of galantamine on oxidative stress in parallel with inflammatory and cardio-metabolic parameters in subjects with MetS.

Methods

The effects of galantamine treatment, 8 mg daily for 4 weeks, followed by 16 mg daily for 8 weeks or placebo were studied in randomly assigned subjects with MetS (n=22 per group) of both genders. Oxidative stress, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities, lipid and protein peroxidation, and nitrite levels were analyzed before and at the end of the treatment. In addition, plasma cytokine and adipokine levels, insulin resistance (HOMA-IR) and other relevant cardio-metabolic indices were analyzed. Autonomic regulation was also examined by heart rate variability (HRV) before treatment, and at every 4 weeks of treatment.

Results

Galantamine treatment significantly increased antioxidant enzyme activities, including SOD (+1.65 USOD/mg protein, [95% CI 0.39 to 2.92], P=0.004) and CAT (+0.93 nmol/mg, [95% CI 0.34 to 1.51], P=0.011), decreased lipid peroxidation (thiobarbituric acid reactive substances, -5.45 pmol/mg, [95% CI -10.97 to 0.067], P=0.053) and systemic nitrite levels (-0.05 nit/mg protein, [95% CI -0.21 to 0.10], P=0.038) compared with placebo. In addition, galantamine significantly alleviated the inflammatory state and insulin resistance, and decreased the low frequency/high frequency ratio of HRV, following 8 and 12 weeks of drug treatment.

Conclusion

Low-dose galantamine alleviates oxidative stress, alongside beneficial anti-inflammatory, and metabolic effects, and modulates autonomic regulation in subjects with MetS. These findings are of considerable interest for further studies with galantamine to ameliorate MetS pathophysiology.
Evaluating the performance of the WHO international reference standard for osteoporosis diagnosis in postmenopausal women of varied polygenic score and race
Authors: Wu Qing , Xiao Xiangxue , Xu Yingke
Published: January 2020

Background

Whether the bone mineral density (BMD) T-score performs differently in osteoporosis classification in women of different genetic profiling and race background remains unclear.

Methods

The genomic data in the Women’s Health Initiative study was analyzed (n=2,417). The polygenic score (PGS) was calculated from 63 BMD-associated single nucleotide polymorphisms (SNPs) for each participant. The World Health Organization’s (WHO) definition of osteoporosis (BMD T-score≤-2.5) was used to estimate the cumulative incidence of fracture.

Results

T-score classification significantly underestimated the risk of major osteoporotic fracture (MOF) in the WHI study. An enormous underestimation was observed in African American women (POR: 0.52, 95% CI: 0.30-0.83) and in women with low PGS (predicted/observed ratio [POR]: 0.43, 95% CI: 0.28-0.64). Compared to Caucasian women, African American, African Indian, and Hispanic women respectively had a 59%, 41%, and 55% lower hazard of MOF after the T-score was adjusted for. The results were similar when used for any fractures.

Conclusions

Our study suggested the BMD T-score performance varies significantly by race in postmenopausal women.
Classification of glomerular pathological findings using deep learning and nephrologist–AI collective intelligence approach
Authors: Uchino Eiichiro , Suzuki Kanata , Sato Noriaki , Kojima Ryosuke , Tamada Yoshinori , Hiragi Shusuke , Yokoi Hideki , Yugami Nobuhiro , Minamiguchi Sachiko , Haga Hironori , Yanagita Motoko , Okuno Yasushi
Published: January 2020

Background

Automated classification of glomerular pathological findings is potentially beneficial in establishing an efficient and objective diagnosis in renal pathology. While previous studies have verified the artificial intelligence (AI) models for the classification of global sclerosis and glomerular cell proliferation, there are several other glomerular pathological findings required for diagnosis, and the comprehensive models for the classification of these major findings have not yet been reported. Whether the cooperation between these AI models and clinicians improves diagnostic performance also remains unknown. Here, we developed AI models to classify glomerular images for major findings required for pathological diagnosis and investigated whether those models could improve the diagnostic performance of nephrologists.

Methods

We used a dataset of 283 kidney biopsy cases comprising 15888 glomerular images that were annotated by a total of 25 nephrologists. AI models to classify seven pathological findings: global sclerosis, segmental sclerosis, endocapillary proliferation, mesangial matrix accumulation, mesangial cell proliferation, crescent, and basement membrane structural changes, were constructed using deep learning by fine-tuning of InceptionV3 convolutional neural network. Subsequently, we compared the agreement to truth labels between majority decision among nephrologists with or without the AI model as a voter.

Results

Our model for global sclerosis showed high performance (area under the curve: periodic acid-Schiff, 0.986; periodic acid methenamine silver, 0.983); the models for the other findings also showed performance close to those of nephrologists. By adding the AI model output to majority decision among nephrologists, the sensitivity and specificity were significantly improved in 9 of 14 constructed models compared to those of nephrologists alone.

Conclusion

Our study showed a proof-of-concept for the classification of multiple glomerular findings in a comprehensive method of deep learning and suggested its potential effectiveness in improving diagnostic accuracy of clinicians.