bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Epstein–Barr virus and human papillomavirus infection on macrophage migration inhibitory factor and macrophage polarization in nasopharyngeal carcinoma
Authors: Feng Guofei , Xu Yifei , Ma Ning , Midorikawa Kaoru , Oikawa Shinji , Kobayashi Hatasu , Nakamura Satoshi , Ishinaga Hajime , Zhang Zhe , Huang Guangwu , Takeuchi Kazuhiko , Murata Mariko 
Published: August 2021

Abstract
Background
To assess the effects of Epstein–Barr virus (EBV) and human papillomavirus (HPV) infection on the tumor microenvironment, we examined the relationship between viral infection status, macrophage migration inhibitory factor (MIF), and tumor-associated macrophages in nasopharyngeal carcinoma (NPC).

Methods
A tissue microarray containing 150 cores from 90 patients with NPC and six with chronic inflammation was used. EBV and HPV status were detected using in situ hybridization with commercial EBER1 and HPV16/18 probes. Immunofluorescence double staining of MIF, pan-macrophage marker CD68, M1 macrophage marker CD11c, and M2 macrophage marker CD163 were analyzed using the same tissue microarray. The levels of these markers between NPC and inflammation cases and between tumor nests and stroma were compared. Correlations among these markers were analyzed.

Results
We found EBER1(+) cases in 90% of NPC patients, including 10% EBV/HPV co-infection. M1 macrophages mainly infiltrated the tumor nest, while M2 macrophages infiltrated the tumor stroma. We found a significant positive correlation between EBER1 levels and MIF levels in tumor nests and a significant positive correlation between HPV16/18 and CD11c(+) cell levels in NPC tissues.

Conclusions
It is suggested that MIF is associated with EBV, and M1 macrophage infiltration is affected by HPV status in NPC.
Scrutinize of healthy school canteen policy in Iran’s primary schools: a mixed method study
Authors: Babashahi Mina , Omidvar Nasrin , Joulaei Hassan , Zargaraan Azizollaah , Zayeri Farid , Veisi Elnaz , Doustmohammadian Azam , Kelishadi Roya 
Published: August 2021

Abstract
Background
Schools provide an opportunity for developing strategies to create healthy food environments for children. The present study aimed to analyze the Healthy School Canteen (HSC) policy and identify challenges of its implementation to improve the school food environment in Iran.

Methods
This mixed method study included two qualitative and quantitative phases. In the qualitative phase, triangulation approach was applied by using semi-structured interviews with key informants, documents review and direct observation. Data content analysis was conducted through policy analysis triangle framework. In the quantitative phase, food items available in 64 canteens of primary schools of Tehran province were gathered. The food’s nutrient data were evaluated using their nutrition facts label. The number and proportion of foods that met the criteria based on Iran’s HSC guideline and the World Health Organization nutrient profile model for the Eastern Mediterranean Region (WHO-EMR) were determined.

Results
The main contextual factors that affected adoption of HSC policy included health (nutritional transition, high prevalence of non-communicable diseases and unhealthy food environment in and around the schools), political (upstream supportive policies and joint memorandums about health children between the Ministry of Health and Medical Education and Ministry of Education), structural (the lack of unified stewardship, inadequate human resource capacity, poor inter-sectional cooperation), economic (school financial problems, poor fiscal supportive of food policies), and socio-cultural (mothers working outside the home, the role of children’s peer group, low nutrition knowledge of school principals) factors. Assessment of the school canteens showed that a large proportion of available foods did not comply with the national guidelines (54.7 ± 2.54%) and WHO-EMR model (85.6 ± 2.34%). The main reasons identified for incomplete implementation of the policy were inadequate physical and economic infrastructure to set up standard school canteens, lack of scientific criteria for food categorization, poor monitoring, high price of healthy foods, and conflict of interest among the actors.

Conclusion
The majority of foods and beverages available in the school canteens did not comply with national and regional standards. Iran HSC policy needs to be improved by using an evidence-based approach and active interaction between all key actors.
Similar outcomes in computer-assisted and conventional total knee arthroplasty: ten-year results of a prospective randomized study
Authors: Beyer Franziska , Pape Alexander , Lützner Cornelia , Kirschner Stephan , Lützner Jörg 
Published: August 2021

AbstractBackgroundComputer-assisted navigation (CAS) was developed to improve the surgical accuracy and precision. Many studies demonstrated better alignment in the coronal plane in CAS TKA compared to conventional technique. The influence on the functional outcome is still unclear. Only few studies report long-term results of CAS TKA. This study was initiated to investigate 10-year patient-reported outcome of CAS and conventional TKA.MethodsFrom initially 80 patients of a randomized study of CAS and conventional TKA a total of 50 patients could be evaluated at the 10-year follow-up. The Knee Society Score and EuroQuol Questionnaire were assessed. For all patients a competing risk analysis for revision was performed.ResultsThe patient-reported outcome measures demonstrated similar values for both groups. The 10-year risk for revision was 2.5% for conventional TKA and 7.5% for CAS TKA (p=0.237).ConclusionsThere was no difference between CAS and conventional TKA with regard to patient-reported outcome and revision risk ten years after surgery.Trial registrationThis study was registered at clinicaltrials.gov on 11/30/2009, ID:NCT01022099.
Long-term results of type B aortic dissection patients with tumor after endovascular repair or optimal medical therapy: a single—center and retrospective cohort study
Authors: Liang Taiping , Zhu Hongqiao , Zhang Lei , Li Shuangshuang , He Xiaomin , Zhao Kaiwen , Jing Zaiping , Zhou Jian 
Published: August 2021

Abstract
Background
The effect of thoracic endovascular aortic repair (TEVAR) for acute Type B aortic has been confirmed, However, when patients with malignant disease suffer from acute type B aortic dissection (ATBAD), the effect of TEVAR intervention is still unclear.

Methods
ATBAD patients were identified from electronic medical records between 2009 and 2019. The 5 year overall and aortic-disease free survival rates were analyzed and compared between the two groups.

Results
Of the 40 enrolled patients, 27 (67.5%) received TEVAR and 13 (32.5%) received OMT. The baseline characteristics of the two groups were not significantly different. Kaplan‒Meier survival curve showed that the 5 year overall survival and 5 year aortic-disease free survival of the TEVAR group were better than those of the OMT group. The Cox proportional hazard model with unadjusted risk showed an 83.0% decrease in 5 year overall mortality (HR, 0.17; 95% CI, 0.05–0.56) and a lower aortic-disease related risk (HR, 0.08; 95% CI, 0.02–0.39) in TEVAR group compared to OMT group. After adjusted for age, gender, smoking, drinking and comorbidities (diabetes mellitus, hypertension and coronary artery diseases), the hazard ratio of 5 year overall mortality was 78.0% lower (HR, 0.22; 95% CI, 0.06.0.81) and the risk of aortic-disease related mortality was 93.0% lower (HR, 0.07; 95% CI, 0.01–0.61) in TEVAR group compared to OMT group. In the cohort stratified by age, sex, the risk of the 5 year overall or aortic-disease related mortality in TEVAR group was relatively reduced compared to OMT group.

Conclusions
Compared to OMT, TEVAR improves the 5 year overall and aortic-disease free survival rates in the cohort of ATBAD patients with a single type of malignant tumors.
Acute myocardial infarction and arterial embolism in a patient with newly diagnosed renal mass: management dilemmas! A case report
Authors: Martin Benedikt , Greinacher Andreas , Bülow Robin , Hammer Fabian , Hoene Andreas , Burchardt Martin , Zimmermann Uwe 
Published: August 2021

Abstract
Background
Cancer is often associated with a hypercoagulable state and new thrombosis is often the first clinical manifestation of cancer. Surgical treatment of the primary tumor is crucial since it provides the only curative approach in most cases, but management of patients is highly complex, especially in the presence of new antiplatelet drugs and/or anticoagulants. Paraneoplastic syndromes (PNS) represent a frequent complication of renal cell carcinomas (RCC) and include different hematological symptoms in patients, whilst occlusion of arterial blood vessels displays a rare form of PNS accompanying renal tumors.

Case presentation
We report the case of a 62-year old man who was initially hospitalized due to acute coronary syndrome. He subsequently underwent coronary angioplasty treatment including multiple stenting and treatment with ticagrelor and aspirin. Post-interventional, acute arterial thrombotic emboli of several limb arteries required thrombectomy. By computer tomography we identified a renal lesion suspicious for an RCC and suspected a PNS as underlying cause of the thrombotic complications. Triple anticoagulant therapy was maintained with therapeutic dose low molecular weight heparin (LMWH), aspirin, and clopidogrel, by which we replaced ticagrelor. Surgery was postponed for 4 weeks. We paused LMWH, aspirin and clopidogrel only at the day of surgery and perioperatively restored hemostasis by transfusion of two platelet concentrates. Laparoscopic nephrectomy was uneventful. Pathology confirmed a clear cell RCC. The patient fully recovered whilst slowly reducing anticoagulation dose.

Conclusions
A multidisciplinary team approach of experts in urology, cardiology and hemostasis was key in managing this patient since a personalized thrombosis consult was needed to minimize the risk of reinfarction due to in-stent thrombosis. We report a therapeutic protocol that may be helpful for the management of similar cases. Furthermore, the finding of thrombotic arterial occlusions in larger blood vessels represents a novel complication of PNS in RCC and adds to the varied possible manifestations of this clinical chameleon.
Effects of iRoot SP on osteogenic differentiation of human stem cells from apical papilla
Authors: Wu Laidi , Xue Kaiyang , Hu Guang , Du Hanman , Gan Kang , Zhu Juanfang , Du Tianfeng 
Published: August 2021

Abstract
Background
Research shows that nano-bioceramics can modulate the differentiation of dental stem cells. The novel ready-to-use calcium-silicate-based root-canal sealer iRoot SP is widely used in root filling. Accordingly, the aim of this study was to evaluate the effects of iRoot SP on proliferation and osteogenic differentiation in human stem cells from the apical papilla (hSCAPs).

Methods
hSCAPs were isolated and characterized in vitro, then cultured with various concentrations of iRoot SP extract. Cell proliferation was assessed by CCK-8 assay, and scratch-wound-healing assays were performed to evaluate cell-migration capacity. hSCAPs were then cultured in osteogenic medium supplemented with iRoot SP extracts. Alkaline phosphatase (ALP) activity assay was used to evaluate ALP enzyme levels. Alizarin red staining and cetylpyridinium chloride (CPC) assays were performed to assess calcified-nodule formation and matrix-calcium accumulation of hSCAPs. The mRNA and protein expression levels of the osteogenic markers OCN, OSX, Runx2, and DSPP were determined by qRT-PCR and Western blotting. The data were analyzed using one-way ANOVA and LSD-t tests.

Results
iRoot SP at low concentrations (2, 0.2, and 0.02 mg/mL) is nontoxic to hSCAPs. iRoot SP at concentrations of 0.02 and 0.2 mg/mL significantly increases cell-migration capacity. In terms of osteogenic differentiation, 0.2 mg/mL iRoot SP promotes intracellular ALP activity and the formation of mineralized nodules. Moreover, the expression of osteogenic markers at the mRNA and protein levels are upregulated by iRoot SP.

Conclusion
iRoot SP is an effective filling material for periapical bone regeneration.
Classifying patient and professional voice in social media health posts
Authors: Alex Beatrice , Whyte Donald , Duma Daniel , Owen Roma English , Fairley Elizabeth A. L. 
Published: August 2021

Abstract
Background
Patient-based analysis of social media is a growing research field with the aim of delivering precision medicine but it requires accurate classification of posts relating to patients’ experiences. We motivate the need for this type of classification as a pre-processing step for further analysis of social media data in the context of related work in this area. In this paper we present experiments for a three-way document classification by patient voice, professional voice or other. We present results for a convolutional neural network classifier trained on English data from two different data sources (Reddit and Twitter) and two domains (cardiovascular and skin diseases).

Results
We found that document classification by patient voice, professional voice or other can be done consistently manually (0.92 accuracy). Annotators agreed roughly equally for each domain (cardiovascular and skin) but they agreed more when annotating Reddit posts compared to Twitter posts. Best classification performance was obtained when training two separate classifiers for each data source, one for Reddit and one for Twitter posts, when evaluating on in-source test data for both test sets combined with an overall accuracy of 0.95 (and macro-average F1 of 0.92) and an F1-score of 0.95 for patient voice only.

Conclusion
The main conclusion resulting from this work is that combining social media data from platforms with different characteristics for training a patient and professional voice classifier does not result in best possible performance. We showed that it is best to train separate models per data source (Reddit and Twitter) instead of a model using the combined training data from both sources. We also found that it is preferable to train separate models per domain (cardiovascular and skin) while showing that the difference to the combined model is only minor (0.01 accuracy). Our highest overall F1-score (0.95) obtained for classifying posts as patient voice is a very good starting point for further analysis of social media data reflecting the experience of patients.
Long-term persistence of crAss-like phage crAss001 is associated with phase variation in Bacteroides intestinalis
Authors: Shkoporov Andrey N. , Khokhlova Ekaterina V. , Stephens Niamh , Hueston Cara , Seymour Samuel , Hryckowian Andrew J. , Scholz Dimitri , Ross R. Paul , Hill Colin 
Published: August 2021

Abstract
Background
The crAss-like phages are ubiquitous and highly abundant members of the human gut virome that infect commensal bacteria of the order Bacteroidales. Although incapable of lysogeny, these viruses demonstrate long-term persistence in the human gut microbiome, dominating the virome in some individuals.

Results
Here we show that rapid phase variation of alternate capsular polysaccharides in Bacteroides intestinalis cultures plays an important role in a dynamic equilibrium between phage sensitivity and resistance, allowing phage and bacteria to multiply in parallel. The data also suggests the role of a concomitant phage persistence mechanism associated with delayed lysis of infected cells, similar to carrier state infection. From an ecological and evolutionary standpoint, this type of phage-host interaction is consistent with the Piggyback-the-Winner model, which suggests a preference towards lysogenic or other “benign” forms of phage infection when the host is stably present at high abundance.

Conclusion
Long-term persistence of bacteriophage and host could result from mutually beneficial mechanisms driving bacterial strain-level diversity and phage survival in complex environments.
Genes underlying the evolution of tetrapod testes size
Authors: Baker Joanna , Meade Andrew , Venditti Chris 
Published: August 2021

Abstract
Background
Testes vary widely in mass relative to body mass across species, but we know very little about which genes underlie and contribute to such variation. This is partly because evidence for which genes are implicated in testis size variation tends to come from investigations involving just one or a few species. Contemporary comparative phylogenetic methods provide an opportunity to test candidate genes for their role in phenotypic change at a macro-evolutionary scale—across species and over millions of years. Previous attempts to detect genotype-phenotype associations across species have been limited in that they can only detect where genes have driven directional selection (e.g. brain size increase).

Results
Here, we introduce an approach that uses rates of evolutionary change to overcome this limitation to test whether any of twelve candidate genes have driven testis size evolution across tetrapod vertebrates—regardless of directionality. We do this by seeking a relationship between the rates of genetic and phenotypic evolution. Our results reveal five genes (Alkbh5, Dmrtb1, Pld6, Nlrp3, Sp4) that each have played unique and complex roles in tetrapod testis size diversity. In all five genes, we find strong significant associations between the rate of protein-coding substitutions and the rate of testis size evolution. Such an association has never, to our knowledge, been tested before for any gene or phenotype.

Conclusions
We describe a new approach to tackle one of the most fundamental questions in biology: how do individual genes give rise to biological diversity? The ability to detect genotype-phenotype associations that have acted across species has the potential to build a picture of how natural selection has sculpted phenotypic change over millions of years.
Production of neoagarooligosaccharides by probiotic yeast Saccharomyces cerevisiae var. boulardii engineered as a microbial cell factory
Authors: Jin Yerin , Yu Sora , Liu Jing-Jing , Yun Eun Ju , Lee Jae Won , Jin Yong-Su , Kim Kyoung Heon 
Published: August 2021

Abstract
Background
Saccharomyces cerevisiae var. boulardii is a representative probiotic yeast that has been widely used in the food and pharmaceutical industries. However, S. boulardii has not been studied as a microbial cell factory for producing useful substances. Agarose, a major component of red macroalgae, can be depolymerized into neoagarooligosaccharides (NAOSs) by an endo-type β-agarase. NAOSs, including neoagarotetraose (NeoDP4), are known to be health-benefiting substances owing to their prebiotic effect. Thus, NAOS production in the gut is required. In this study, the probiotic yeast S. boulardii was engineered to produce NAOSs by expressing an endo-type β-agarase, BpGH16A, derived from a human gut bacterium Bacteroides plebeius.

Results
In total, four different signal peptides were compared in S. boulardii for protein (BpGH16A) secretion for the first time. The SED1 signal peptide derived from Saccharomyces cerevisiae was selected as optimal for extracellular production of NeoDP4 from agarose. Expression of BpGH16A was performed in two ways using the plasmid vector system and the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 system. The production of NeoDP4 by engineered S. boulardii was verified and quantified. NeoDP4 was produced by S. boulardii engineered using the plasmid vector system and CRISPR-Cas9 at 1.86 and 0.80 g/L in a 72-h fermentation, respectively.

Conclusions
This is the first report on NAOS production using the probiotic yeast S. boulardii. Our results suggest that S. boulardii can be considered a microbial cell factory to produce health-beneficial substances in the human gut.

Graphical abstract
Fundamental challenges in assessing the impact of research infrastructure
Authors: Zakaria Sana , Grant Jonathan , Luff Jane 
Published: August 2021

AbstractClinical research infrastructure is one of the unsung heroes of the scientific response to the current COVID-19 pandemic. The extensive, long-term funding into research support structures, skilled people, and technology allowed the United Kingdom research response to move off the starting blocks at pace by utilizing pre-existing platforms. The increasing focus from funders on evaluating the outcomes and impact of research infrastructure investment requires both a reframing and progression of the current models in order to address the contribution of the underlying support infrastructure. The majority of current evaluation/outcome models focus on a “pipeline” approach using a methodology which follows the traditional research funding route with the addition of quantitative metrics. These models fail to embrace the complexity caused by the interplay of previous investment, the coalescing of project outputs from different funders, the underlying infrastructure investment, and the parallel development across different parts of the system. Research infrastructure is the underpinning foundation of a project-driven research system and requires long-term, sustained funding and capital investment to maintain scientific and technological expertise. Therefore, the short-term focus on quantitative metrics that are easy to collect and interpret and that can be assessed in a roughly 5-year funding cycle needs to be addressed. The significant level of investment in research infrastructure necessitates investment to develop bespoke methodologies that develop fit-for-purpose, longer-term/continual approach(es) to evaluation. Real-world research should reflect real-world evaluation and allow for the accrual of a narrative of value indicators that build a picture of the contribution of infrastructure to research outcomes. The linear approach is not fit for purpose, the research endeavour is a complex, twisted road, and the evaluation approach needs to embrace this complexity through the development of realist approaches and the rapidly evolving data ecosystem. This paper sets out methodological challenges and considers the need to develop bespoke methodological approaches to allow a richer assessment of impact, contribution, attribution, and evaluation of research infrastructure. This paper is the beginning of a conversation that invites the community to “take up the mantle” and tackle the complexity of real-world research translation and evaluation.