bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post-transplant Malignancies Show Reduced T-cell Abundance and Tertiary Lymphoid Structures as Correlates of Impaired Cancer Immunosurveillance
Authors: Datta Rabi R. , Schran Simon , Persa Oana-Diana , Aguilar Claire , Thelen Martin , Lehmann Jonas , Garcia-Marquez Maria A. , Wennhold Kerstin , Preugszat Ella , Zentis Peter , von Bergwelt-Baildon Michael S. , Quaas Alexander , Bruns Christiane J. , Kurschat Christine , Mauch Cornelia , Löser Heike , Stippel Dirk L. , Schlößer Hans A. 
Published: February 2022

AbstractPurpose:An increased risk to develop cancer is one of the most challenging negative side effects of long-term immunosuppression in organ transplant recipients and impaired cancer immunosurveillance is assumed as underlying mechanism. This study aims to elucidate transplant-related changes in the tumor immune microenvironment (TME) of cancer.Experimental Design:Data from 123 organ transplant recipients (kidney, heart, lung, and liver) were compared with historic data from non-immunosuppressed patients. Digital image analysis of whole-section slides was used to assess abundance and spatial distribution of T cells and tertiary lymphoid structures (TLS) in the TME of 117 tumor samples. Expression of programmed cell death 1 ligand 1 (PD-L1) and human-leucocyte-antigen class I (HLA-I) was assessed on tissue microarrays.Results:We found a remarkably reduced immune infiltrate in the center tumor (CT) regions as well as the invasive margins (IM) of post-transplant cancers. These differences were more pronounced in the IM than in the CT and larger for CD8+ T cells than for CD3+ T cells. The Immune-score integrating results from CT and IM was also lower in transplant recipients. Density of TLS was lower in cancer samples of transplant recipients. The fraction of samples with PD-L1 expression was higher in controls whereas decreased expression of HLA-I was more common in transplant recipients.Conclusions:Our study demonstrates the impact of immunosuppression on the TME and supports impaired cancer immunosurveillance as important cause of post-transplant cancer. Modern immunosuppressive protocols and cancer therapies should consider the distinct immune microenvironment of post-transplant malignancies.
Shedding Light on ecDNA Behavior Using CRISPR-Based Live-Cell Imaging
Authors: Henssen Anton G. 
Published: February 2022

Abstract

Summary:
Extrachromosomal oncogene amplification on extrachromosomal DNA (ecDNA) has emerged as a hallmark of many cancers. In this issue, Yi and colleagues developed a CRISPR-based method for imaging ecDNA in live cells, termed ecTag. Using ecTag, the authors reveal important features of ecDNA in cancer cells such as their random mitotic segregation and clustering into transcriptionally active hubs after mitosis.
See related article by Yi et al., p. 468.
Invenção democrática brasileira e os fantasmas totalitários: o caso do judiciário aplicado à obra de Claude Lefort
Authors: Bezerra André Augusto Salvador 
Published: February 2022

As ideias de Claude Lefort são aplicáveis à realidade brasileira posterior à década de 1980. Trata-se do período coincidente a um amplo processo de invenção democrática, produto de mobilização social cujas bandeiras políticas transformaram-se em direitos previstos na Constituição de 1988. Por outro lado, a sociedade não logrou eliminar antigas estruturas ditatoriais do Estado e nem evitar o crescimento de um Poder Administrativo politicamente excludente, oriundo de ideias neoliberais. É o que ocorre no Judiciário brasileiro, chamado pela população para efetivar os direitos, mas ainda estruturado ditatorialmente e submetido a reformas que ampliam o Poder Administrativo a pretexto de garantir segurança jurídica. O presente trabalho pretende relacionar as ideias de Lefort ao atual contexto de fortalecimento de estruturas autoritárias no Judiciário em plena vigência de Constituição democrática.
O erro e o método proustiano
Authors: Almeida Alexandre Bebiano de 
Published: February 2022

Este artigo tem como objetivo discutir o erro no romance de Marcel Proust. O que configura um erro em um romance como Em busca do tempo perdido? Talvez se possa dizer que o acerto é o que respeita ali o jogo retórico da ficcção, ao passo que o erro é o que revela aspectos falhos desse jogo. Veremos, contudo, que os virtuais erros encontrados no romance não desmerecem sua construção, mas antes salientam seu caráter composto e, mais do que isso, inacabado.
Um radical democrático
Authors: Aguiar Joaquim Alves de 
Published: February 2022

Excerto de “Ensaios de Antonio Candido: um roteiro de leitura”, primeira parte da tese de livre-docência, O crítico luminoso e o narrador acabrunhado O crítico luminoso e o narrador acabrunhado em dois estudos, defendida pelo professor do Departamento de Teoria Literária e Literatura Comparada da FFLCH USP, no ano de 2012. O texto foi adaptado para esta publicação.
Lower Socioeconomic Position Is Associated with Greater Activity in and Integration within an Allostatic-Interoceptive Brain Network in Response to Affective Stimuli
Authors: Alvarez Gabriella M. , Rudolph Marc D. , Cohen Jessica R. , Muscatell Keely A. 
Published: February 2022

Abstract
Socioeconomic inequities shape physical health and emotional well-being. As such, recent work has examined the neural mechanisms through which socioeconomic position (SEP) may influence health. However, there remain critical gaps in knowledge regarding the relationships between SEP and brain function. These gaps include a lack of research on: (1) the association between SEP and brain functioning in later life, (2) relationships between SEP and functioning of the whole brain beyond specific regions of interest, and (3) how neural responses to positive affective stimuli differ by SEP. The current study addressed these gaps by examining the association between SEP (i.e., education, income) and neural responses to affective stimuli among 122 mid- to late-life adults. During MRI scanning, participants viewed 30 positive, 30 negative, and 30 neutral images; activation and network connectivity analyses explored associations between SEP and neural responses to these affective stimuli. Analyses revealed that those with lower SEP showed greater neural activity to both positive and negative images in regions within the allostatic-interoceptive network, a system of regions implicated in representing and regulating physiological states of the body and the external environment. There were no positive associations between SEP and neural responses to negative or positive images. In addition, graph–theory network analyses showed that individuals with lower SEP demonstrated greater global efficiency within the allostatic-interoceptive network and executive control network, across all task conditions. The findings suggest that lower SEP is associated with enhanced neural sensitivity to affective cues that may be metabolically costly to maintain over time and suggest a mechanism by which SEP might get “under the skull” to influence mental and physical well-being.
Dietrich of Freiberg’s Theory of Perfectional Forms
Authors: Roudaut Sylvain 
Published: February 2022

Abstract
This article investigates the philosophical elaboration of the concept of “perfectional form” (forma perfectionalis) in Dietrich of Freiberg’s works. Although Dietrich draws on the traditional notion of perfection to a certain extent, it appears that in his view, what he calls perfectional forms represent a special type of form distinct from the classical division between substantial and accidental forms. The main part of the article analyzes the different uses of this concept made by Dietrich, from his theory of light to his views on the essence of the intellect. The final part of this study aims to evaluate the influence of Dietrich’s theory on the so-called German Dominican school. It is argued that, while Dietrich’s influence on Nicholas of Strasbourg is possible but cannot be firmly established, his theory was explicitly taken up and extended to a more metaphysical dimension by Berthold of Moosburg.
A Review of Drama Education (UK) and Integral Drama Based Pedagogy (China), Western and Eastern Perspectives and Influences
Authors: Holmwood Clive 
Published: February 2022

Abstract
This article will consider similarities to and connections with western progressive based drama education and recent developments in China, namely Integral Drama Based Pedagogy (idbp). It will also consider links between dramatherapy and idbp which considers drama from a more emotional and integral education perspective. It will begin by giving a brief history of drama and progressive education in the UK followed by the development of integral education in general and then make connections between the training of dramatherapists in the west to that of student of idbp.
Networks and Reform in American Education
Authors: Lieberman Ann , Grolnick Maureen 
Published: February 2022

Educational reform networks are becoming increasingly important as alternative forms of teacher and school development in this time of unprecedented reform of schools. These networks appear to be a way of engaging school-based educators in better directing their own learning; allowing them to sidestep the limitations of institutional roles, hierarchies, and geographic locations; and encouraging them to work with many different kinds of people. In a study of sixteen educational reform networks, we found that they shared organizational themes relating to: (1) purposes and direction; (2) building collaboration, consensus, and commitment; (3) activities and relationships as important building blocks; (4) leadership as cross-cultural brokering and facilitating; and (5) dealing with the funding problem. Regardless of their differences, the sixteen networks we studied appear to have in common agendas more often challenging than prescriptive; learning that is more indirect than direct; formats more collaborative than individualistic; work that is intentionally more integrated than fragmented; leadership more facilitative than directive; thinking that encourages more multiple perspectives; values that are both context-specific and generalized; and structures more movement-like than organization- like.
Unexpected severe hepatic and skin toxicities during high dose methotrexate course for osteosarcoma
Authors: Salaün Hélène , Le Nail Louis Romée , Simon Corinne , Narciso Berengere , De Pinieux Gonzague , Vegas Hélène , Vinceneux Armelle 
Published: February 2022

Introduction high dose methotrexate (HD-MTX) regimen is used in osteosarcoma, leukemia and lymphoma treatment. Osteosarcoma is mostly diagnosed in children and adolescents. Most frequent methotrexate toxicities are mucositis, myelosuppression, renal failure, hepatitis and necrotizing encephalopathy. Toxicities increase with renal impairment, denutrition, in older patients, with some pharmacogenetics factors or with drug interactions. Case report We report a 16th years old woman diagnosed with osteosarcoma and experienced an unexpected severe hepatic and skin toxicities as toxic epidermal necrolys, Steven Johnson syndrome. Management and outcome This toxicity occurred despite acid folinic rescue performed as good practice recommendation. Fourteen hours after methotrexate administration, renal failure was observed and after 72 h an erythematous rash and epidermal detachment with toxic epidermal necrolys. Seven days after methotrexate administration, hepatic failure began until grade IV cytolysis. High dose of folinic acid were administered during all severe toxicities. Methotrexate were not longer administered to this young patient and chemotherapy with ifosfamide (IFO), doxorubicine and cisplatin were performed in this patient and complete histologic response were observed in the surgical bone resection. Discussion No classical toxicities risk factors were identified in this patient but a homozygote mutation of MTHFR gene and homozygote SLCO1B1 gene mutation were found. MTHFR and SLCO1B1 are both implicated in methotrexate metabolism.
Effect of Nicotinamide in Skin Cancer and Actinic Keratoses Chemoprophylaxis, and Adverse Effects Related to Nicotinamide: A Systematic Review and Meta-Analysis
Authors: Mainville Laurence , Smilga Anne-Sophie , Fortin Paul R. 
Published: February 2022

Background Oral nicotinamide is recommended in individuals with a field of cancerization or with ≥1 previous cutaneous squamous cell carcinoma (cSCC). Objective To evaluate the effect of nicotinamide in prevention of skin cancers. Methods We conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the effect of nicotinamide. We used Medline, EMBASE, CENTRAL, and Web of Science databases from their inception to October 2020 to search the following concepts: “nicotinamide”; “randomized controlled trial” (validated filters). Two independent reviewers screened titles and abstracts for intervention and study design before searching full texts for eligibility criteria. To be eligible, ≥1 outcome had to be covered. We used a standardized collection grid to complete data extraction in duplicate. The primary outcome was skin cancers (all types). Secondary outcomes were basal cell carcinomas (BCCs); cSCCs; actinic keratoses; melanomas; digestive, cutaneous, and biochemical adverse effects (AEs). Subgroup analyses were planned a priori. Results We screened 4730 citations and found 29 trials (3039 patients) meeting inclusion criteria. Nicotinamide was associated with a significant reduction in skin cancers compared to control (rate ratio 0.50 (95% CI, 0.29-0.85; I 2 = 64%; 552 patients; 5 trials); moderate strength of the evidence). Heterogeneity was explained by risk of bias. Nicotinamide was associated with a significant reduction in BCCs and cSCCs, and increased risk of digestive AEs. Conclusion Oral nicotinamide should be considered in healthy patients or organ transplant recipients with history of skin cancer (GRADE: weak recommendation; moderate-quality evidence), in particular of BCC and cSCC.
Determinants of COVID-19 vaccine uptake and barriers to being vaccinated among first-round eligibles for COVID-19 vaccination in Eastern Ethiopia: A community based cross-sectional study
Authors: Alemayehu Astawus , Yusuf Mohammed , Demissie Abebaw , Abdullahi Yasin 
Published: February 2022

Objective: Coronavirus disease is a deadly virus that continues to afflict many countries worldwide. Ethiopia has planned to give vaccines to 20% of the population by March 2022. This study aimed to assess determinants of vaccine uptake and barriers to being vaccinated among first-round eligibles for coronavirus disease vaccination in Harar, eastern Ethiopia. Methods: A community-based cross-sectional study design was conducted among 820 randomly selected coronavirus disease first-round eligible groups in Harar from August 20 to September 15, 2021. Descriptive summary statistics were done. Logistic regression analyses were computed to identify associations between dependent and independent variables. Variables with a p value of <0.05 were declared statistically significant. Result: Out of 820, only 39.4% of participants took the coronavirus disease vaccine. The main barriers to being vaccinated were, belief vaccine has no use (24%), and belief vaccine causes blood clots (17.9%). Being a merchant (adjusted odds ratio: 7.9, 95% confidence interval: 2.6, 24), people who had no schooling (adjusted odds ratio: 2.5, 95% confidence interval: 1.3, 4.9), having attitude below the mean score (adjusted odds ratio: 2.1, 95% confidence interval: 1.4, 2.8), having coronavirus disease prevention practice above the mean score (adjusted odds ratio: 2.1, 95% confidence interval: 1.4, 2.8), and family size < 5 members (adjusted odds ratio: 0.64, 95% confidence interval: 0.4, 0.9) were found to be significantly associated with coronavirus disease vaccination. Conclusion: Overall, coronavirus disease-19’s first-round vaccination status was low. The number of people vaccinated was higher among 50–60 age groups than those who are >60 years. Being female, being a person with no schooling, being a merchant, being a farmer, and having low coronavirus disease prevention practice was found to be significantly associated with coronavirus disease vaccination. We recommend that the Federal Ministry of Health, Harari Regional Health Bureau, and other concerned stakeholders should work more diligently to provide continued campaigning on coronavirus disease vaccination and better vaccine awareness creation, as this is the only way out of this epidemic.
Genome sequencing-based coverage analyses facilitate high-resolution detection of deletions linked to phenotypes of gamma-irradiated wheat mutants
Authors: Komura Shoya , Jinno Hironobu , Sonoda Tatsuya , Oono Youko , Handa Hirokazu , Takumi Shigeo , Yoshida Kentaro , Kobayashi Fuminori 
Published: February 2022

AbstractBackgroundGamma-irradiated mutants ofTriticum aestivumL., hexaploid wheat, provide novel and agriculturally important traits and are used as breeding materials. However, the identification of causative genomic regions of mutant phenotypes is challenging because of the large and complicated genome of hexaploid wheat. Recently, the combined use of high-quality reference genome sequences of common wheat and cost-effective resequencing technologies has made it possible to evaluate genome-wide polymorphisms, even in complex genomes.ResultsTo investigate whether the genome sequencing approach can effectively detect structural variations, such as deletions, frequently caused by gamma irradiation, we selected a grain-hardness mutant from the gamma-irradiated population of Japanese elite wheat cultivar “Kitahonami.” TheHardness(Ha) locus, including the puroindoline protein-encoding genesPina-D1andPinb-D1on the short arm of chromosome 5D, primarily regulates the grain hardness variation in common wheat. We performed short-read genome sequencing of wild-type and grain-hardness mutant plants, and subsequently aligned their short reads to the reference genome of the wheat cultivar “Chinese Spring.” Genome-wide comparisons of depth-of-coverage between wild-type and mutant strains detected ~ 130 Mbp deletion on the short arm of chromosome 5D in the mutant genome. Molecular markers for this deletion were applied to the progeny populations generated by a cross between the wild-type and the mutant. A large deletion in the region including theHalocus was associated with the mutant phenotype, indicating that the genome sequencing is a powerful and efficient approach for detecting a deletion marker of a gamma-irradiated mutant phenotype. In addition, we investigated a pre-harvest sprouting tolerance mutant and identified a 67.8 Mbp deletion on chromosome 3B whereViviparous-B1and GRAS family transcription factors are located. Co-dominant markers designed to detect the deletion-polymorphism confirmed the association with low germination rate, leading to pre-harvest sprouting tolerance.ConclusionsShort read-based genome sequencing of gamma-irradiated mutants facilitates the identification of large deletions linked to mutant phenotypes when combined with segregation analyses in progeny populations. This method allows effective application of mutants with agriculturally important traits in breeding using marker-assisted selection.
Defining the mutation sites in chickpea nodulation mutants PM233 and PM405
Authors: Frailey Daniel C. , Zhang Qian , Wood David J. , Davis Thomas M. 
Published: February 2022

Abstract
Background
Like most legumes, chickpeas form specialized organs called root nodules. These nodules allow for a symbiotic relationship with rhizobium bacteria. The rhizobia provide fixed atmospheric nitrogen to the plant in a usable form. It is of both basic and practical interest to understand the host plant genetics of legume root nodulation. Chickpea lines PM233 and PM405, which harbor the mutationally identified nodulation genes rn1 and rn4, respectively, both display nodulation-deficient phenotypes. Previous investigators identified the rn1 mutation with the chickpea homolog of Medicago truncatula nodulation gene NSP2, but were unable to define the mutant rn1 allele. We used Illumina and Nanopore sequencing reads to attempt to identify and characterize candidate mutation sites responsible for the PM233 and PM405 phenotypes.

Results
We aligned Illumina reads to the available desi chickpea reference genome, and did a de novo contig assembly of Nanopore reads. In mutant PM233, the Nanopore contigs allowed us to identify the breakpoints of a ~ 35 kb deleted region containing the CaNSP2 gene, the Medicago truncatula homolog of which is involved in nodulation. In mutant PM405, we performed variant calling in read alignments and identified 10 candidate mutations. Genotyping of a segregating progeny population narrowed that pool down to a single candidate gene which displayed homology to M. truncatula nodulation gene NIN.

Conclusions
We have characterized the nodulation mutation sites in chickpea mutants PM233 and PM405. In mutant PM233, the rn1 mutation was shown to be due to deletion of the entire CaNSP2 nodulation gene, while in mutant PM405 the rn4 mutation was due to a single base deletion resulting in a frameshift mutation between the predicted RWP-RK and PB1 domains of the NIN nodulation gene. Critical to characterization of the rn1 allele was the generation of Nanopore contigs for mutant PM233 and its wild type parent ICC 640, without which the deletional boundaries could not be defined. Our results suggest that efforts of prior investigators were hampered by genomic misassemblies in the CaNSP2 region of both the desi and kabuli reference genomes.
Comparative analysis of background EEG activity in juvenile myoclonic epilepsy during valproic acid treatment: a standardized, low-resolution, brain electromagnetic tomography (sLORETA) study
Authors: Moon Ja-Un , Lee Joo-Young , Kim Kwang-Yeon , Eom Tae-Hoon , Kim Young-Hoon , Lee In-Goo 
Published: February 2022

Abstract
Background
By definition, the background EEG is normal in juvenile myoclonic epilepsy (JME) patients and not accompanied by other developmental and cognitive problems. However, some recent studies using quantitative EEG (qEEG) reported abnormal changes in the background activity. QEEG investigation in patients undergoing anticonvulsant treatment might be a useful approach to explore the electrophysiology and anticonvulsant effects in JME.

Methods
We investigated background EEG activity changes in patients undergoing valproic acid (VPA) treatment using qEEG analysis in a distributed source model. In 17 children with JME, non-parametric statistical analysis using standardized low-resolution brain electromagnetic tomography was performed to compare the current density distribution of four frequency bands (delta, theta, alpha, and beta) between untreated and treated conditions.

Results
VPA reduced background EEG activity in the low-frequency (delta-theta) bands across the frontal, parieto-occipital, and limbic lobes (threshold log-F-ratio = ±1.414, p < 0.05; threshold log-F-ratio= ±1.465, p < 0.01). In the delta band, comparative analysis revealed significant current density differences in the occipital, parietal, and limbic lobes. In the theta band, the analysis revealed significant differences in the frontal, occipital, and limbic lobes. The maximal difference was found in the delta band in the cuneus of the left occipital lobe (log-F-ratio = −1.840) and the theta band in the medial frontal gyrus of the left frontal lobe (log-F-ratio = −1.610).

Conclusions
This study demonstrated the anticonvulsant effects on the neural networks involved in JME. In addition, these findings suggested the focal features and the possibility of functional deficits in patients with JME.