bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep learning-based amyloid PET positivity classification model in the Alzheimer’s disease continuum by using 2-[18F]FDG PET
Authors: Kim Suhong , Lee Peter , Oh Kyeong Taek , Byun Min Soo , Yi Dahyun , Lee Jun Ho , Kim Yu Kyeong , Ye Byoung Seok , Yun Mi Jin , Lee Dong Young , Jeong Yong ,   the Alzheimer’s Disease Neuroimaging Initiative,   the KBASE Research Group
Published: June 2021

Abstract
Background
Considering the limited accessibility of amyloid position emission tomography (PET) in patients with dementia, we proposed a deep learning (DL)-based amyloid PET positivity classification model from PET images with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (2-[18F]FDG).

Methods
We used 2-[18F]FDG PET datasets from the Alzheimer's Disease Neuroimaging Initiative and Korean Brain Aging Study for the Early diagnosis and prediction of Alzheimer’s disease for model development. Moreover, we used an independent dataset from another hospital. A 2.5-D deep learning architecture was constructed using 291 submodules and three axes images as the input. We conducted the voxel-wise analysis to assess the regions with substantial differences in glucose metabolism between the amyloid PET-positive and PET-negative participants. This facilitated an understanding of the deep model classification. In addition, we compared these regions with the classification probability from the submodules.

Results
There were 686 out of 1433 (47.9%) and 50 out of 100 (50%) amyloid PET-positive participants in the training and internal validation datasets and the external validation datasets, respectively. With 50 times iterations of model training and validation, the model achieved an AUC of 0.811 (95% confidence interval (CI) of 0.803–0.819) and 0.798 (95% CI, 0.789–0.807) on the internal and external validation datasets, respectively. The area under the curve (AUC) was 0.860 when tested with the model with the highest value (0.864) on the external validation dataset. Moreover, it had 75.0% accuracy, 76.0% sensitivity, 74.0% specificity, and 75.0% F1-score. We found an overlap between the regions within the default mode network, thus generating high classification values.

Conclusion
The proposed model based on the 2-[18F]FDG PET imaging data and a DL framework might successfully classify amyloid PET positivity in clinical practice, without performing amyloid PET, which have limited accessibility.
Down-regulation of biofilm-associated genes in mecA-positive methicillin-resistant S. aureus treated with M. communis extract and its antibacterial activity
Authors: Khaleghi Moj , Khorrami Sadegh 
Published: June 2021

AbstractConsidering the prevalence of resistance to antibiotics, the discovery of effective agents against resistant pathogens is of extreme urgency. Herein, 26mecA-positive methicillin-resistantS. aureus(MRSA) isolated from clinical samples were identified, and their resistance to 11 antibiotics was investigated. Next, the antibacterial and anti-biofilm activity of the ethanolic extract ofM. communison these strains was evaluated. Furthermore, the effect of this extract on the expression of biofilm-associated genes,icaA,icaD,bap,sarA, andagr, was studied. According to the results, all isolated strains were multidrug-resistant and showed resistance to oxacillin and tetracycline. Also, 96.15 and 88.46 % of them were resistant to gentamicin and erythromycin. However, the extract could effectively combat the strains. The minimum inhibitory concentration (MIC) against different strains ranged from 1.56 to 25 mg/ml and the minimum bactericidal concentration (MBC) was between 3.125 and 50 mg/ml. Even though most MRSA (67 %) strongly produced biofilm, the sub-MIC concentration of the extract destroyed the pre-formed biofilm and affected the bacterial cells inside the biofilm. It could also inhibit biofilm development by significantly decreasing the expression oficaA,icaD,sarAandbapgenes involved in biofilm formation and development. In conclusion, the extract inhibits biofilm formation, ruins pre-formed biofilm, and kills cells living inside the biofilm. Furthermore, it down-regulates the expression of necessary genes and nips the biofilm formation in the bud.
Blocking siglec-10hi tumor-associated macrophages improves anti-tumor immunity and enhances immunotherapy for hepatocellular carcinoma
Authors: Xiao Nan , Zhu Xiaodong , Li Kangshuai , Chen Yifan , Liu Xuefeng , Xu Bin , Lei Ming , Xu Jiejie , Sun Hui-Chuan 
Published: June 2021

AbstractBackgroundTumor-associated macrophages (TAMs) promote key processes in the modulation of tumor microenvironment (TME). However, the clinical significance of heterogeneous subpopulations of TAMs in hepatocellular carcinoma (HCC) remains unknown.MethodsHCC tissues from Zhongshan Hospital and data from The Cancer Genome Atlas were obtained and analyzed. Immunohistochemistry and flow cytometry were performed to detect the characteristics of sialic acid-binding immunoglobulin-like lectin 10high(Siglec-10hi) TAMs and explore their impact on the TME of HCC. The effect of Siglec-10 blockade was evaluated in vitro based on fresh human tumor tissues.ResultsOur data revealed that Siglec-10 was abundant in a large proportion of HCC specimens and prominently distributed on macrophages. Kaplan–Meier curves and Cox regression analysis showed that intratumoral Siglec-10+cell enrichment was associated with unfavorable prognosis in patients with HCC. Notably, multiple anti-inflammatory cytokines and inhibitory receptors were enriched in Siglec-10hiTAMs. RNA sequencing data also revealed that numerous M2-like signaling pathways were significantly upregulated in Siglec-10hiTAMs. High infiltration of Siglec-10hiTAMs was associated with impaired CD8+T cell function in HCC. Of note, blocking Siglec-10 with the competitive binding antibody Siglec-10 Fc led to decreased expression of immunosuppressive molecules and increased the cytotoxic effects of CD8+T cells against HCC cells. Moreover, blocking Siglec-10 promoted the anti-tumor efficacy of the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab.ConclusionsSiglec-10hiTAMs are associated with immune suppression in the TME, and indicate poor prognosis in patients with HCC. Targeting Siglec-10hiTAMs may serve as a promising immunotherapy approach for HCC.
Access to care and worsening eating disorder symptomatology in youth during the COVID-19 pandemic
Authors: Spigel Rebecca , Lin Jessica A. , Milliren Carly E. , Freizinger Melissa , Vitagliano Julia A. , Woods Elizabeth R. , Forman Sara F. , Richmond Tracy K. 
Published: June 2021

Abstract
Background
Shelter-in-place orders and social distancing guidelines, in response to the COVID-19 pandemic, have limited traditional face-to-face interactions and led to many clinical providers transitioning to the use of videoconferencing platforms. The present study aims to assess how the COVID-19 pandemic has impacted adolescents’/young adults’ (AYA) eating disorder (ED)-related care, and how access to, changes in, perceived disruptions to, and quality of care are associated with ED thoughts and behaviors.

Methods
AYA enrolled in the RECOVERY study, a pre-existing web-based longitudinal study, and completed a COVID-19-specific survey (n = 89). We examined bivariate associations of four markers of care: i) access to care, ii) changes in care, iii) perceived disruption to care, and iv) quality of care. Using multiple logistic regression, we examined the associations of pandemic-related markers of care with changes in ED thoughts and behaviors. We excluded those not engaged in treatment pre-pandemic (n = 16).

Results
In the remaining 73 participants, reported access to care was high, with 92% of respondents continuing care with at least one ED provider during the pandemic; however, 47% stopped some treatment during the pandemic. Nearly one-third (32%) perceived a disruption in treatment. Quality of care remained high with 67% reporting care to be better than or as good as pre-pandemic. Respondents acknowledged heightened symptomatology: 81% reported increased ED thoughts and 81% reported increased ED behaviors due to COVID-19-related factors. However, none of the markers of care described were significantly associated with ED thoughts or behaviors in regression analyses adjusting for demographic variables and baseline characteristics, except our quality of care measure which was approaching significance (p = 0.07).

Conclusions
Our findings show the majority of AYA who had care prior to the pandemic continued receiving some element of their multi-disciplinary ED treatment and perceived their care as high quality. None of the markers of care described were statistically associated with increased ED thoughts and behaviors.
LncRNAs serve as novel biomarkers for diagnosis and prognosis of childhood ALL
Authors: Huang Xuanmei , Huang Libin , Xie Qing , Zhang Ling , Huang Shaohui , Hong Mingye , Li Jiangbin , Huang Zunnan , Zhang Hua 
Published: June 2021

Abstract
Background
Although some studies have demonstrated that lncRNAs are dysregulated in hematopoietic malignancies and may regulate the progression of leukemia, the detailed mechanism underlying tumorigenesis is still unclear. This study aimed to investigate lncRNAs that are differentially expressed in childhood B-cell acute lymphoblastic leukemia (B-ALL) and T-cell acute lymphoblastic leukemia (T-ALL) and their potential roles in the progression of childhood ALL.

Methods
Microarrays were used to detect differentially expressed lncRNAs and mRNAs. Several aberrantly expressed lncRNAs were validated by qRT-PCR. Leukemia-free survival was analyzed using the Kaplan–Meier method with a log-rank test. The co-expression correlations of lncRNAs and mRNAs were determined by Spearman’s correlation coefficient. CCK-8 assays and flow cytometry were performed to measure cell proliferation and apoptosis.

Results
We revealed that many lncRNAs were abnormally expressed in B-ALL and T-ALL. LncRNA/mRNA co-expression and the gene locus network showed that dysregulated lncRNAs are involved in diverse cellular processes. We also assessed the diagnostic value of the differentially expressed lncRNAs and confirmed the optimal combination of TCONS_00026679, uc002ubt.1, ENST00000411904, and ENST00000547644 with an area under the curve of 0.9686 [95 % CI: 0.9369–1.000, P < 0.001], with 90.7 % sensitivity and 92.19 % specificity, at a cut-off point of -0.5700 to distinguish childhood B-ALL patients from T-ALL patients, implying that these specific lncRNAs may have potential to detect subsets of childhood ALL. Notably, we found that the 8-year leukemia-free survival of patients with high TCONS_00026679 (p = 0.0081), ENST00000522339 (p = 0.0484), ENST00000499583 (p = 0.0381), ENST00000457217 (p = 0.0464), and ENST00000451368 (p = 0.0298) expression levels was significantly higher than that of patients with low expression levels of these lncRNAs, while patients with high uc002ubt.1 (p = 0.0499) and ENST00000547644 (p = 0.0451) expression levels exhibited markedly shorter 8-year leukemia-free survival. In addition, some lncRNAs were found to play different roles in cell proliferation and apoptosis in T-ALL and B-ALL.

Conclusions
Dysregulated lncRNAs involved in different regulatory mechanisms underlying the progression of childhood T-ALL and B-ALL might serve as novel biomarkers to distinguish ALL subsets and indicate poor outcomes.
Novel sensitivity method for evaluating the first derivative of the feed-forward neural network outputs
Authors: Kiran Ravi , Naik Dayakar L. 
Published: June 2021

AbstractEvaluating the exact first derivative of a feedforward neural network (FFNN) output with respect to the input feature is pivotal for performing the sensitivity analysis of the trained neural network with respect to the inputs. In this paper, a novel method is presented that computes the analytical quality first derivative of a trained feedforward neural network output with respect to the input features without the need for backpropagation. To this end, the complex step derivative approximation is illustrated, and its implementation in the framework of the feedforward neural network is described. Artificial datasets are generated, and the efficacy of the proposed method for both regression and classification tasks is demonstrated. The results obtained for the regression task indicated that the proposed method is capable of obtaining analytical quality derivatives, and in the case of the classification task, the least relevant features could be identified.
Using miniaturized GPS archival tags to assess home range features of a small plunge-diving bird: the European Kingfisher (Alcedo atthis)
Authors: Musseau Raphaël , Bastianelli Melina , Bely Clementine , Rousselle Céline , Dehorter Olivier 
Published: June 2021

AbstractBackgroundThe European Kingfisher (Alcedo atthis) is a small plunge-diving bird, today considered a species of conservation concern in Europe given its rapid population decline observed across the continent. We implemented a pilot study aimed at providing first data allowing to: (1) assess home range features of the European Kingfisher for populations with unevenly distributed feeding habitats; (2) define conservation implications for habitats exploited by such populations; and (3) evaluate possibilities for developing GPS tracking schemes dedicated to home range studies for this species that could be possibly applied to other small plunge-diving birds.MethodsIn 2018 and 2019, we equipped 16 breeding European Kingfishers sampled within the marshes of the Gironde Estuary (France), with miniaturized and waterproof GPS archival tags deployed with leg-loop harnesses (total equipment mass = 1.4 g; average bird mass = 40.18 ± 1.12 g).ResultsOn average, we collected 35.31 ± 6.66 locations usable for analyses, without a significant effect on bird body condition (n = 13 tags retrieved). Data analyses highlighted rather limited home ranges exploited by birds (average = 2.50 ± 0.55 ha), composed on average by 2.78 ± 0.40 location nuclei. Our results also underscore: (1) a rather important home range fragmentation index (0.36 ± 0.08); and (2) the use by birds of different types of small wetlands (wet ditches, small ponds or small waterholes), often exploited in addition to habitats encompassing nest locations.ConclusionsOur study reveals interesting GPS tracking possibilities for small plunge-diving birds such as the European Kingfisher. For this species, today classified as vulnerable in Europe, our results underline the importance of developing conservation and ecological restoration policies for wetland networks that would integrate small wetlands particularly sensitive to global change.
Racial equity in the fight against COVID-19: a qualitative study examining the importance of collecting race-based data in the Canadian context
Authors: Ahmed Ranie , Jamal Omer , Ishak Waleed , Nabi Kiran , Mustafa Nida 
Published: June 2021

Abstract
Background
A failure to ensure racial equity in response to the COVID-19 pandemic has caused Black communities in Canada to disproportionately be impacted. The aim of the current study was to determine the needs and concerns of Black communities in the Greater Toronto Area (GTA) and to highlight the importance of collecting race-based COVID-19 data early on to address these needs.

Methods
Six qualitative interviews were conducted with local community health centre leaders who serve a high population of racialized communities within the GTA. Content analysis was used to extract the main themes and concerns raised during the interviews.

Results
The findings from this study provide further evidence of the disproportionate impact COVID-19 has had on Black and other racialized communities. Difficulty self-isolating due to overcrowded housing, food insecurity, and less social support for seniors were concerns identified by community health leaders. Also, enhanced financial support for front-line workers, such as Personal Support Workers (PSWs), was an important concern raised. In order to lessen the impact of the pandemic on these communities, leaders noted the need for greater accessibility of testing centres in these areas and a greater investment in tailored health promotion approaches.

Conclusions
Overall, our findings point to the importance of collecting race-based data to ensure an equitable response to the pandemic. The current “one size fits all” response is not effective for all individuals, especially Black communities. Not all populations have access to the same resources, nor do they live in the same conditions (Kantamneni, J Vocal Behav 119:103439, 2020). A deeper consideration of the social determinants of health are needed when implementing COVID-19 policies and responses. Also, a lack of attention to Black communities only continues to perpetuate the under-acknowledged issue of anti-Black racism prevalent in Canada.
Comparative analysis of Rosetta stone events in Klebsiella pneumoniae and Streptococcus pneumoniae for drug target identification
Authors: Ramesh Poornima , Nagendrappa Jayashree Honnebailu , Shivashankara Santosh Kumar Hulikal 
Published: June 2021

Abstract
Background
Drug target identification is a fast-growing field of research in many human diseases. Many strategies have been devised in the post-genomic era to identify new drug targets for infectious diseases. Analysis of protein sequences from different organisms often reveals cases of exon/ORF shuffling in a genome. This results in the fusion of proteins/domains, either in the same genome or that of some other organism, and is termed Rosetta stone sequences. They help link disparate proteins together describing local and global relationships among proteomes. The functional role of proteins is determined mainly by domain-domain interactions and leading to the corresponding signaling mechanism. Putative proteins can be identified as drug targets by re-annotating their functional role through domain-based strategies.

Results
This study has utilized a bioinformatics approach to identify the putative proteins that are ideal drug targets for pneumonia infection by re-annotating the proteins through position-specific iterations. The putative proteome of two pneumonia-causing pathogens was analyzed to identify protein domain abundance and versatility among them. Common domains found in both pathogens were identified, and putative proteins containing these domains were re-annotated. Among many druggable protein targets, the re-annotation of EJJ83173 (which contains the GFO_IDH_MocA domain) showed that its probable function is glucose-fructose oxidoreduction. This protein was found to have sufficient interactor proteins and homolog in both pathogens but no homolog in the host (human), indicating it as an ideal drug target. 3D modeling of the protein showed promising model parameters. The model was utilized for virtual screening which revealed several ligands with inhibitory activity. These ligands included molecules documented in traditional Chinese medicine and currently marketed drugs.

Conclusions
This novel strategy of drug target identification through domain-based putative protein re-annotation presents a prospect to validate the proposed drug target to confer its utility as a typical protein targeting both pneumonia-causing species studied herewith.
FOXR2 Stabilizes MYCN Protein and Identifies Non–MYCN-Amplified Neuroblastoma Patients With Unfavorable Outcome
Authors: Schmitt-Hoffner Felix , van Rijn Sjoerd , Toprak Umut H. , Mauermann Monika , Rosemann Felix , Heit-Mondrzyk Anke , Hübner Jens-Martin , Camgöz Aylin , Hartlieb Sabine , Pfister Stefan M. , Henrich Kai-Oliver , Westermann Frank , Kool Marcel 
Published: June 2021

PURPOSE Clinical outcomes of patients with neuroblastoma range from spontaneous tumor regression to fatality. Hence, understanding the mechanisms that cause tumor progression is crucial for the treatment of patients. In this study, we show that FOXR2 activation identifies a subset of neuroblastoma tumors with unfavorable outcome and we investigate the mechanism how FOXR2 relates to poor outcome in patients. MATERIALS AND METHODS We analyzed three independent transcriptional data sets of in total 1030 primary neuroblastomas with full clinical annotation. We performed immunoprecipitation for FOXR2 and MYCN and silenced FOXR2 expression in two neuroblastoma cell lines to examine the effect on cellular processes, transcriptome, and MYCN protein levels. Tumor samples were analyzed for protein levels of FOXR2 and MYCN. RESULTS In three combined neuroblastoma data sets, 9% of tumors show expression of FOXR2 but have low levels of MYCN mRNA. FOXR2 expression identifies a group of patients with unfavorable outcome, showing 10-year overall survival rates of 53%-59%, and proves to be an independent prognostic factor compared with established risk factors. Transcriptionally, FOXR2-expressing tumors are very similar to MYCN-amplified tumors, suggesting that they might share a common mechanism of tumor initiation. FOXR2 knockdown in FOXR2-expressing neuroblastoma cell lines resulted in cell cycle arrest, reduced cell growth, cell death, and reduced MYCN protein levels, all indicating that FOXR2 is essential for these tumors. Finally, we show that FOXR2 binds and stabilizes MYCN protein and MYCN protein levels are highly increased in FOXR2-expressing tumors, in several cases comparable with MYCN-amplified samples. CONCLUSION The stabilization of MYCN by FOXR2 represents an alternative mechanism to MYCN amplification to increase MYCN protein levels. As such, FOXR2 expression identifies another subset of neuroblastoma patients with unfavorable clinical outcome.
The World in Question
Authors: Garrido Germán 
Published: June 2021

Abstract
This essay focuses on two radical gay/homosexual organizations of the early 1970s: Third World Gay Revolution (TWGR)—a small group of radical Black and Latinx activists that spun off from the Gay Liberation Front in 1970—and the Argentine organization Homosexual Liberation Front (FLH), which was active between 1971 and 1976. By analyzing periodicals, bulletins, and other ephemera produced by them, Garrido demonstrates how both groups not only articulated demands related to queer sexualities in relation to those of other oppressed communities but also inscribed their gay struggles in a movement for the liberation of all peoples on a planetary scale within the framework provided by third world anticolonial and anti-imperialist struggles being waged in African, Asian, and Latin American countries at the time. TWGR and the FLH engaged in “dissident forms of cosmopolitanism” (Chela Sandoval) that drew, in part, from the imaginary of a world in dispute—a world in which colonial and (neo)colonial/imperialist powers were being challenged and third worldism as a global emancipatory project led by “the darker nations” (Vijay Prashad) was gaining ground. At the dawn of neoliberal globalization, both organizations advanced a radical political agenda based on values of social justice with a spirit of transnational solidarity that, Garrido argues, may inspire the multidimensional nature of a queer cosmopolitics to come.