bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination vaccine based on citrullinated vimentin and enolase peptides induces potent CD4-mediated anti-tumor responses
Authors: Brentville Victoria A , Metheringham Rachael L , Daniels Ian , Atabani Suha , Symonds Peter , Cook Katherine W , Vankemmelbeke Mireille , Choudhury Ruhul , Vaghela Poonam , Gijon Mohamed , Meiners Ghislaine , Krebber Willem-Jan , Melief Cornelis J M , Durrant Lindy G 
Published: June 2020

BackgroundStress-induced post-translational modifications occur during autophagy and can result in generation of new epitopes and immune recognition. One such modification is the conversion of arginine to citrulline by peptidylarginine deiminase enzymes.MethodsWe used Human leukocyte antigen (HLA) transgenic mouse models to assess the immunogenicity of citrullinated peptide vaccine by cytokine Enzyme linked immunosorbant spot (ELISpot) assay. Vaccine efficacy was assessed in tumor therapy studies using HLA-matched B16 melanoma and ID8 ovarian models expressing either constitutive or interferon-gamma (IFNγ) inducible Major Histocompatibility Complex (MHC) class II (MHC-II) as represented by most human tumors. To determine the importance of CD4 T cells in tumor therapy, we analyzed the immune cell infiltrate into murine tumors using flow cytometry and performed therapy studies in the presence of CD4 and CD8 T cell depletion. We assessed the T cell repertoire to citrullinated peptides in ovarian cancer patients and healthy donors using flow cytometry.ResultsThe combination of citrullinated vimentin and enolase peptides (Modi-1) stimulated strong CD4 T cell responses in mice. Responses resulted in a potent anti-tumor therapy against established tumors and generated immunological memory which protected against tumor rechallenge. Depletion of CD4, but not CD8 T cells, abrogated the primary anti-tumor response as well as the memory response to tumor rechallenge. This was further reinforced by successful tumor regression being associated with an increase in tumor-infiltrating CD4 T cells and a reduction in tumor-associated myeloid suppressor cells. The anti-tumor response also relied on direct CD4 T cell recognition as only tumors expressing MHC-II were rejected. A comparison of different Toll-like receptor (TLR)-stimulating adjuvants showed that Modi-1 induced strong Th1 responses when combined with granulocyte-macrophage colony-stimulating factor (GMCSF), TLR9/TLR4, TLR9, TLR3, TLR1/2 and TLR7 agonists. Direct linkage of the TLR1/2 agonist to the peptides allowed the vaccine dose to be reduced by 10-fold to 100-fold without loss of anti-tumor activity. Furthermore, a CD4 Th1 response to the citrullinated peptides was seen in ovarian cancer patients.ConclusionsModi-1 citrullinated peptide vaccine induces potent CD4-mediated anti-tumor responses in mouse models and a CD4 T cell repertoire is present in ovarian cancer patients to the citrullinated peptides suggesting that Modi-1 could be an effective vaccine for ovarian cancer patients.
Genetic screening for monogenic hypertension in hypertensive individuals in a clinical setting
Authors: Bao Minghui , Li Ping , Li Qifu , Chen Hui , Zhong Ying , Li Shuangyue , Jin Ling , Wang Wenjie , Chen Zhenzhen , Zhong Jiuchang , Geng Bin , Fan Yuxin , Yang Xinchun , Cai Jun 
Published: June 2020

BackgroundMonogenic hypertension describe a series of hypertensive syndromes that are inherited by Mendelian laws. Sometimes genetic testing is required to provide evidence for their diagnoses, precise classification and targeted treatment. This study is the first to investigate the clinical utility of a causative gene screening and the combined yield of gene product expression analyses in cases with suspected monogenic hypertension.MethodsWe performed a large-scale multi-centre clinical genetic research of 1179 expertly selected hypertensive individuals from the Chinese Han population. Targeted sequencing were performed to evaluate 37 causative genes of potential cases of monogenic hypertension. Pathogenic and likely pathogenic variants were classified using the American College of Medical Genetics guidelines. Additionally, 49 variants of unknown significance (VUS) that had relatively high pathogenicity were selected and analysed using immunoblot protein expression assays.Results21 pathogenic or likely pathogenic variants were identified in 33 of 1179 cases (2.80%). Gene product expression analyses showed 27 VUSs harboured by 49 individuals (4.16%) could lead to abnormally expressed protein levels. Consequently, combining genetic screening with gene product expression analyses increased the diagnostic yield from 2.80% to 6.79%. The main aetiologies established were primary aldosteronism (PA; 27, 2.29%) and pheochromocytoma and paraganglioma (PPGL; 10, 0.85%).ConclusionMolecular diagnoses obtained using causative gene screening combined with gene product expression analyses initially achieved a modest diagnostic yield. Our data highlight the predominant roles of PA and PPGL. Furthermore, we provide evidence indicating the enhanced diagnostic ability of combined genetic and functional evaluation.
Influence of rare earth on the microstructure and mechanical properties of Al–Zn alloy
Authors: Mai Bui Thi Ngoc , Dong Nguyen Xuan , Khanh Pham Mai , Huy Tran Duc 
Published: June 2020

This paper discusses the influence of Vietnam rare earth (RE) with the composition of 69.4% Ce and 30.5% La (modification content of 4% and 6%) on the microstructure and mechanical properties of Al–5Zn–3.5Mg–1.2Cu alloy when the temperature modification is changed at [Formula: see text] in 150, 200, 250 s. By optical microscopy, the results showed that the microstructure of the modified sample is finer than the nonmodified sample. By the SEM and EDS analysis, at the grain boundaries of this alloy, [Formula: see text] and/or [Formula: see text] intermetallic phases appeared. The modified elements (La, Ce) in RE and aluminum were formed in the intermetallic [Formula: see text] and [Formula: see text] phases, which prevents the development of the dendritic [Formula: see text] phase. The result showed Al–5Zn–3.5Mg–1.2Cu alloy modified with 4% RE in 150 s which is the most optimal result, the grain size is [Formula: see text] and the hardness is 107 HB.
SRC-3 Functions as a Coactivator of T-bet by Regulating the Maturation and Antitumor Activity of Natural Killer Cells
Authors: Hu Mengjia , Lu Yukai , Qi Yan , Zhang Zihao , Wang Song , Xu Yang , Chen Fang , Tang Yong , Chen Shilei , Chen Mo , Du Changhong , Shen Mingqiang , Wang Fengchao , Su Yongping , Deng Youcai , Wang Junping 
Published: June 2020

Abstract
Natural killer (NK)–cell development and maturation is a well-organized process. The steroid receptor coactivator 3 (SRC-3) is a regulator of the hematopoietic and immune systems; however, its role in NK cells is poorly understood. Here, SRC-3 displayed increased nuclear translocation in NK cells during terminal differentiation and upon inflammatory cytokine stimulation. Targeted deletion of SRC-3 altered normal NK-cell distribution and compromised NK-cell maturation. SRC-3 deficiency led to significantly impaired NK-cell functions, especially their antitumor activity. The expression of several critical T-bet target genes, including Zeb2, Prdm1, and S1pr5, but not T-bet itself, was markedly decreased in NK cells in the absence of SRC-3. There was a physiologic interaction between SRC-3 and T-bet proteins, where SRC-3 was recruited by T-bet to regulate the transcription of the aforementioned genes. Collectively, our findings unmask a previously unrecognized role of SRC-3 as a coactivator of T-bet in NK-cell biology and indicate that targeting SRC-3 may be a promising strategy to increase the tumor surveillance function of NK cells.
Deciphering the Clonal Origin of Relapsed Acute Lymphoblastic Leukemia in Children
Authors: Ogawa Seishi 
Published: June 2020

Abstract

Summary:
In this issue of Blood Cancer Discovery, Waanders and colleagues characterize somatic alterations in a large cohort of relapsed pediatric acute lymphoblastic leukemia (ALL). This comprehensive genomic analysis reveals mutations distinctly associated with primary disease versus response to therapy. In the reconstructed clonal evolution scenarios, relapsed leukemic cells propagate from clones already expanded at diagnosis and rarely from unexpanded dormant ancestral clones. The information gleaned through subclonal mutation analysis at diagnosis may help to estimate relapse risk and select therapeutic options with minimal relapse potential. High prevalence of hypermutation patterns among repeatedly relapsing ALL cases suggests that activating antitumor immunity has a potential to benefit this group of patients.
See related article by Waanders et al., p. 96.
The Genomic Landscape of HIV-Associated Plasmablastic Lymphoma
Authors: Küppers Ralf 
Published: June 2020

Abstract

Summary:
A combined whole-exome and targeted sequencing study of 110 cases of human immunodeficiency virus–associated plasmablastic lymphomas revealed a distinct landscape of genetic lesions for this lymphoma entity, including a particular role of mutations in STAT3 and other members of the JAK–STAT signaling pathway, and of the RAS family in its pathogenesis.
See related article by Liu et al., p. 112.
Aberrant claw forms in the Annulipes Group of mosquitoes (Diptera: Culicidae: Aedes) in Germany
Authors: KUHLISCH CORNELIUS , KAMPEN HELGE , WERNER DOREEN 
Published: June 2020

Specimens of five species of the culicid Annulipes Group (Aedes annulipes, Ae. cantans, Ae. excrucians, Ae. flavescens, Ae. riparius), collected in the framework of the German mosquito monitoring programme, were examined for aberrant tarsal claws. Twenty types of aberrations regarding position, size, multiplication and structural modification of the tarsal claw and its basal tooth that were detected are described and illustrated. Different basal tooth positions found on claws reveal a basic blueprint of possible positions on mosquito tarsal claws. Morphological peculiarities and asymmetric occurrence of the aberrant claw types, as well as possible causes, are discussed with respect to species and gender.
The Multi-Scale Infrastructure for Chemistry and Aerosols (MUSICA)
Authors: Pfister Gabriele G. , Eastham Sebastian D. , Arellano Avelino F. , Aumont Bernard , Barsanti Kelley C. , Barth Mary C. , Conley Andrew , Davis Nicholas A. , Emmons Louisa K. , Fast Jerome D. , Fiore Arlene M. , Gaubert Benjamin , Goldhaber Steve , Granier Claire , Grell Georg A. , Guevara Marc , Henze Daven K. , Hodzic Alma , Liu Xiaohong , Marsh Daniel R. , Orlando John J. , Plane John M. C. , Polvani Lorenzo M. , Rosenlof Karen H. , Steiner Allison L. , Jacob Daniel J. , Brasseur Guy P. 
Published: June 2020

ABSTRACTTo explore the various couplings across space and time and between ecosystems in a consistent manner, atmospheric modeling is moving away from the fractured limited-scale modeling strategy of the past toward a unification of the range of scales inherent in the Earth system. This paper describes the forward-looking Multi-Scale Infrastructure for Chemistry and Aerosols (MUSICA), which is intended to become the next-generation community infrastructure for research involving atmospheric chemistry and aerosols. MUSICA will be developed collaboratively by the National Center for Atmospheric Research (NCAR) and university and government researchers, with the goal of serving the international research and applications communities. The capability of unifying various spatiotemporal scales, coupling to other Earth system components, and process-level modularization will allow advances in both fundamental and applied research in atmospheric composition, air quality, and climate and is also envisioned to become a platform that addresses the needs of policy makers and stakeholders.
A cross-cultural study of attitudes toward suicide among young people in India, Italy and Australia
Authors: Colucci Erminia , Lester David 
Published: June 2020

Background: An understanding of the cultural aspects of suicidal behavior is essential for the development of culturally appropriate suicide prevention and intervention strategies. Aims: This study explored the attitudes toward youth suicide in 686 Italian, Indian and Australian undergraduate students (18–24 years old). Method: A 21-item suicide attitude inventory titled Attitude towards Youth Suicide (AtYS) scale, included in this paper, was used in the three samples. Results: Four factors were extracted, labeled negative attitudes toward suicide, belief that suicide was not preventable, suicide as acceptable and normal, and the existence of risk signs for suicide. Country differences were found for all four subscales, with Indian students having the most negative attitudes toward suicide. Sex differences were found in all three countries with women, on the whole, having less negative attitudes toward suicide, more belief in the preventability of suicide in India and more belief in risk signs for suicide in Italy. Conclusion: Attitudes are linked to suicide in a complex manner. More quantitative and qualitative studies, including in lower-income and non-English speaking Western societies, are needed.
Geovisualization and Spatial Analysis of Infant Mortality and Preterm Birth in Ohio, 2008-2015: Opportunities to Enhance Spatial Thinking
Authors: Root Elisabeth Dowling , Bailey Emelie D. , Gorham Tyler , Browning Christopher , Song Chi , Salsberry Pamela 
Published: June 2020

Objectives Geovisualization and spatial analysis are valuable tools for exploring and evaluating the complex social, economic, and environmental interactions that lead to spatial inequalities in health. The objective of this study was to describe spatial patterns of infant mortality and preterm birth in Ohio by using interactive mapping and spatial analysis. Methods We conducted a retrospective cohort study using Ohio vital statistics records from 2008-2015. We geocoded live births and infant deaths by using residential address at birth. We used multivariable logistic regression to adjust spatial and space–time cluster analyses that examined the geographic clustering of infant mortality and preterm birth and changes in spatial distribution over time. Results The overall infant mortality rate in Ohio during the study period was 6.55 per 1000 births; of 1 097 507 births, 10.3% (n = 112 552) were preterm. We found significant geographic clustering of both infant mortality and preterm birth centered on large urban areas. However, when known demographic risk factors were taken into account, urban clusters disappeared and, for preterm birth, new rural clusters appeared. Conclusions Although many public health agencies have the capacity to create maps of health outcomes, complex spatial analysis and geovisualization techniques are still challenging for public health practitioners to use and understand. We found that actively engaging policymakers in reviewing results of the cluster analysis improved understanding of the processes driving spatial patterns of birth outcomes in the state.
After Graduation
Authors: Hoyt Adelia M. 
Published: June 2020

The story opens on a June afternoon as Mabel Forrester, a young blind girl, is traveling homeward from the State School for the Blind. She graduated with honors, and while she regrets leaving school and being separated from her friends, she is looking forward to a bright and hopeful future. When she is met at the station by her father and they drive to the farm which is their home, and where, since her mother's death, her aunt has been mistress; she is disappointed at the slight interest which her father manifests in her graduation and the discouraging way in which he speaks of her home life. It is no less disheartening when she talks with her aunt and sister, and she realizes that they have no confidence in her ability. She endeavors to help with the household duties, always against their wishes, but the climax is reached when she accidentally upsets a dishpan of water. After this she is not permitted to assist in any way. She wanders around aimlessly, becoming almost distracted at times because of her great disappointment. Finally, realizing that something must be done, she decides to write to Miss Lane, her former teacher, knowing that from her she will receive sympathy and assistance. Miss Lane, to whom Mabel appeals for advice, responds instantly with a very helpful letter. She herself is blind, and so can enter fully into Mabel's difficulties and point the best way out of them. She advises Mabel, instead of despairing over being shut out of the household tasks, to set about finding little unobtrusive ways of helping without asking leave. Mabel acts upon this advice, and though there are many discouraging days, she perseveres, and in time she has the comfort of feeling that little sister Lizzie is finding in the blind sister the nearest approach to a mother's love that she has ever known. Out of this companionship comes one of Mabel's sweetest rewards, for little Lizzie falls into a delightful habit of reading aloud to Mabel, who is hungry for books. Next Mabel finds herself assisting her fifteen-year-old brother Rob with his lessons. Mary, the older sister, too, begins to find in Mabel a very sympathetic companion, and in her turn tries to share her little social pleasures with Mabel. Even the aunt begins to see that this niece is a help to her in many ways. Most of all, Mabel rejoices when her father shows an appreciation of her thoughtfulness toward him, and she feels that she has at last won the confidence and respect of all her family. Almost from the first of her home-coming it has been apparent to Mabel that it was only by strictest economy the father has been able to maintain his large family. Now comes Mabel's hardest trial. She sees Mary ready to help by teaching; Rob, at the close of school, is to work for a neighboring farmer. What can Mabel do to help ? She works and waits and hopes, and of course her opportunity arrives. She has but to act — and act she does.
mRNA expression of ageing-associated genes in calorie reduction is subject to donor variability and can be induced by calorie restriction mimetics
Authors: Matt Katja , Hochecker Barbara , Schöller-Mann Alica , Bergemann Jörg 
Published: June 2020

Background: Finding ways to a healthier ageing are increasingly becoming the focus of geriatric research. One way to accomplish this could be calorie restriction, as this is known to positively influence the ageing of model organisms. Aim: The aim of this study was to investigate the influence of calorie reduction (F. X. Mayr therapy) and of the calorie restriction mimetics resveratrol and spermidine on the expression of ageing-associated genes. Methods: mRNA expression in peripheral blood mononuclear cells (PBMCs) of 18 participants taking part in an F. X. Mayr therapy was analysed. The PBMCs of one additional participant were treated ex vivo with spermidine or resveratrol. mRNA expression of SIRT1, SIRT3, FOXO3 and SOD2 was determined for these two calorie restriction mimetics. For the F. X. Mayr therapy samples, mRNA of XPA was analysed additionally. Results: mRNA expression of the ageing-associated genes showed a distinct donor variation during F. X. Mayr therapy, with a significant increase in mRNA expression of SIRT1. Expression of XPA was similar to SIRT1, with a significant correlation at the last time point tested. Spermidine treatment of PBMCs resulted in a significantly increased expression of all genes tested, whereas resveratrol treatment caused a significant increase of SIRT3, FOXO3 and SOD2 mRNA expression. Conclusions: By increasing SIRT1 and XPA mRNA expression, calorie reduction in the form of F. X. Mayr therapy could contribute to a healthier ageing; however, the donor variability observed showed that not everyone benefited from this. Calorie restriction mimetics may be an option for promote healthier ageing for those who do not benefit from calorie reduction.
FDG PET correlates weakly with HIF-1α expression in solid tumors: a meta-analysis
Authors: Surov Alexey , Schmidt Stefan A , Prasad Vikas , Beer Ambros J , Wienke Andreas 
Published: June 2020

Background Hypoxia-inducible factor (HIF)-1α plays a key role in hypoxic adaptation of tumor cells. Overexpression of HIF-1α is associated with tumor aggressiveness and worse prognosis in several malignancies. Presumably, expression of HIF-1a may be reflected by positron emission tomography with 2-deoxy-2 [fluorine-18] fluoro-D-glucose (18F-FDG PET). There are inconsistent data about relationships between FDG PET and HIF-1α. Purpose To provide evident data about associations between maximum standardized uptake value (SUVmax) and HIF-1α expression in solid tumors. Material and Methods MEDLINE, SCOPUS, and EMBASE databases were screened for relationships between SUV and HIF-1α up to August 2019. Overall, 21 studies with 1154 patients were identified. The following data were extracted from the literature: authors; year of publication; number of patients; and correlation coefficients. Results Correlation coefficients between SUVmax and HIF-1α were in the range of −0.51–0.71. The pooled correlation coefficient was 0.27 (95% confidence interval [CI] = 0.14–0.41). Furthermore, correlation coefficients for some tumor entities were calculated. For this sub-analysis, data for primary tumors with >2 reports were included. The calculated correlation coefficients in the analyzed subgroups were as follows: head and neck squamous cell carcinoma: ρ = 0.25 (95% CI = 0.07–0.42); non-small lung cell cancer: ρ = 0.27 (95% CI = −0.14–0.67); uterine cervical cancer: ρ = −0.09 (95% CI = −0.89–0.71); thymic tumors: ρ = 0.39 (95% CI = 0.04–0.58). Conclusion SUVmax of FDG PET correlated weakly with expression of HIF-1α both in overall sample and tumor subgroups. Therefore, FDG PET cannot be used for prediction of hypoxia in clinical practice.
Sexual Identity and Racial/Ethnic Differences in Awareness of Heart Attack and Stroke Symptoms: Findings From the National Health Interview Survey
Authors: Caceres Billy A. , Turchioe Meghan Reading , Pho Anthony , Koleck Theresa A. , Creber Ruth Masterson , Bakken Suzanne B. 
Published: June 2020

Purpose: Investigate sexual identity and racial/ethnic differences in awareness of heart attack and stroke symptoms. Design: Cross-sectional. Setting: 2014 and 2017 National Health Interview Survey. Sample: 54 326 participants. Measures: Exposure measures were sexual identity (heterosexual, gay/lesbian, bisexual, “something else”) and race/ethnicity. Awareness of heart attack and stroke symptoms was assessed. Analysis: Sex-stratified logistic regression analyses to examine sexual identity and racial/ethnic differences in awareness of heart attack and stroke symptoms. Results: Gay men were more likely than heterosexual men to identify calling 911 as the correct action if someone is having a heart attack (adjusted odds ratio [AOR] = 2.16, 95% CI: 1.18-3.96). The majority of racial/ethnic minority heterosexuals reported lower rates of awareness of heart attack and stroke symptoms than White heterosexuals. Hispanic sexual minority women had lower awareness of heart attack symptoms than White heterosexual women (AOR = 0.43, 95% CI: 0.25-0.74), whereas Asian sexual minority women reported lower awareness of stroke symptoms (AOR = 0.25, 95% CI: 0.08-0.80). Hispanic (AOR = 0.52, 95% CI: 0.33-0.84) and Asian (AOR = 0.35, 95% CI: 0.14-0.84) sexual minority men reported lower awareness of stroke symptoms than White heterosexual men. Conclusion: Hispanic and Asian sexual minorities had lower rates of awareness of heart attack and stroke symptoms. Health information technology may be a platform for delivering health education and targeted health promotion for sexual minorities of color.