bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic biomarkers related to breast cancer recurrence identified based on Logit model analysis
Authors: Zhou Xiaoying , Xiao Chuanguang , Han Tong , Qiu Shusheng , Wang Meng , Chu Jun , Sun Weike , Li Liang , Lin Lili 
Published: September 2020

AbstractBackgroundThis study intended to determine important genes related to the prognosis and recurrence of breast cancer.MethodsGene expression data of breast cancer patients were downloaded from TCGA database. Breast cancer samples with recurrence and death were defined as poor disease-free survival (DFS) group, while samples without recurrence and survival beyond 5 years were defined as better DFS group. Another gene expression profile dataset (GSE45725) of breast cancer was downloaded as the validation data. Differentially expressed genes (DEGs) were screened between better and poor DFS groups, which were then performed function enrichment analysis. The DEGs that were enriched in the GO function and KEGG signaling pathway were selected for cox regression analysis and Logit regression (LR) model analysis. Finally, correlation analysis between LR model classification and survival prognosis was analyzed.ResultsBased on the breast cancer gene expression profile data in TCGA, 540 DEGs were screened between better DFS and poor DFS groups, including 177 downregulated and 363 upregulated DEGs. A total of 283 DEGs were involved in all GO functions and KEGG signaling pathways. Through LR model screening, 10 important feature DEGs were identified and validated, among which,ABCA3,CCL22,FOXJ1,IL1RN,KCNIP3,MAP2K6, andMRPL13, were significantly expressed in both groups in the two data sets.ABCA3,CCL22,FOXJ1,IL1RN, andMAP2K6were good prognostic factors, whileKCNIP3andMRPL13were poor prognostic factors.ConclusionABCA3,CCL22,FOXJ1,IL1RN, andMAP2K6may serve as good prognostic factors, whileKCNIP3andMRPL13may be poor prognostic factors for the prognosis of breast cancer.
Image quality of 4D in-treatment CBCT acquired during lung SBRT using FFF beam: a phantom study
Authors: Kim Jihun , Keum Ki Chang , Lee Ho , Hong Chae-Seon , Park Kwangwoo , Kim Jin Sung 
Published: September 2020

Abstract
Background
Rotational beam delivery enables concurrent acquisition of cone-beam CT (CBCT), thereby facilitating further geometric verification of patient setup during radiation treatment. However, it is challenging to acquire CBCT during stereotactic body radiation therapy (SBRT) using flattening-filter free X-ray beams, in which a high radiation dose is delivered. This study presents quantitative evaluation results of the image quality in four-dimensional (4D) in-treatment CBCT acquired during SBRT delivery.

Methods
The impact of megavoltage (MV) scatter and acquisition parameters on the image quality was evaluated using Catphan 503 and XSight lung tracking phantoms. The in-treatment CBCT images of the phantoms were acquired while delivering 16 SBRT plans. The uniformity, contrast, and contrast-to-noise ratio (CNR) of the in-treatment CBCT images were calculated and compared to those of CBCT images acquired without SBRT delivery. Furthermore, the localizing accuracy of the moving target in the XSight lung phantom was evaluated for 10 respiratory phases.

Results
The CNR of the 3D-reconstucted Catphan CBCT images was reduced from 6.3 to 2.6 due to the effect of MV treatment scatter. Both for the Catphan and XSight phantoms, the CBCT image quality was affected by the tube current and monitor units (MUs) of the treatment plan. The lung target in the XSight tracking phantom was most visible for extreme phases; the mean CNRs of the lung target in the in-treatment CBCT images (with 40 mA tube current) across the SBRT plans were 3.2 for the end-of-exhalation phase and 3.0 for the end-of-inhalation phase. The lung target was localized with sub-millimeter accuracy for the extreme respiratory phases.

Conclusions
Full-arc acquisition with an increased tube current (e.g. 40 mA) is recommended to compensate for degradation in the CBCT image quality due to unflattened MV beam scatter. Acquiring in-treatment CBCT with a high-MU treatment beam is also suggested to improve the resulting CBCT image quality.
The forgotten people with thalassemia in the time of COVID-19: South Asian perspective
Authors: Hossain Mohammad Sorowar , Raheem Enayetur , Siddiqee Mahbubul H. 
Published: September 2020

AbstractSouth Asia is the hotspot of beta-thalassemia, with an estimated 200,000 patients whose lives depend on regular blood transfusion. Due to COVID-19 pandemic, many countries have adopted unprecedented lockdown to minimize the spread of transmission. Restriction of nationwide human mobility and fear of COVID-19 infection has put thalassemia patients in a life-threatening situation because of an acute shortage of blood supply. As a public health preparedness strategy during a crisis like COVID-19 pandemic, the plights of thalassemia patients should be considered. Government-sponsored community blood-banks needs to be established or coverage expanded as a safety net for the thalassemia patients in lower- and middle-income countries.
The VEGF inhibitor vatalanib regulates AD pathology in 5xFAD mice
Authors: Jeon Seong Gak , Lee Hyun-ju , Park HyunHee , Han Kyung-Min , Hoe Hyang-Sook 
Published: September 2020

AbstractAlzheimer’s disease (AD) is a highly prevalent neurodegenerative disease characterized by Aβ accumulation and tau hyperphosphorylation. Epidemiological evidence for a negative correlation between cancer and AD has led to the proposed use of tyrosine kinase inhibitors (TKIs) such as dasatinib and masitinib for AD, with reported beneficial effects in the AD brain. The TKI vatalanib inhibits angiogenesis by inhibiting vascular endothelial growth factor receptor (VEGFR). Although changes in VEGF and VEGFR have been documented in AD, the effect of vatalanib on AD pathology has not been investigated. In this study, the effects of vatalanib on tau phosphorylation and Aβ accumulation in 5xFAD mice, a model of AD, were evaluated by immunohistochemistry. Vatalanib administration significantly reduced tau phosphorylation at AT8 and AT100 by increasing p-GSK-3β (Ser9) in 5xFAD mice. In addition, vatalanib reduced the number and area of Aβ plaques in the cortex in 5xFAD mice. Our results suggest that vatalanib has potential as a regulator of AD pathology.
Integrative analysis of the common genetic characteristics in ovarian cancer stem cells sorted by multiple approaches
Authors: Zhang Xiaoxiao , Su Yue , Wu Xue , Xiao Rourou , Wu Yifan , Yang Bin , Wang Zhen , Guo Lili , Kang Xiaoyan , Wang Changyu 
Published: September 2020

AbstractBackgroundOvarian cancer is the second fatal malignancy of the female reproductive system. Based on the cancer stem cell (CSC) theory, its poor prognosis of ovarian cancer attributed to tumor recurrence caused by CSCs. A variety of cell surface-specific markers have been employed to identify ovarian cancer stem cells (OCSCs). In this study, we attempted to explore the common feature in ovarian cancer stem cells sorted by multiple approaches.MethodsWe collected the gene expression profiles of OCSCs were from 5 public cohorts and employed R software and Bioconductor packages to establish differently expressed genes (DEGs) between OCSCs and parental cells. We extracted the integrated DEGs by protein-protein interaction (PPI) network construction and explored potential treatment by the Cellminer database.ResultsWe identified and integrated the DEGs of OCSCs sorted by multiple isolation approaches. Besides, we identified OCSCs share characteristics in the lipid metabolism and extracellular matrix changes. Moreover, we obtained 16 co-expressed core genes, such asFOXQ1, MMP7, AQP5, RBM47, ETV4, NPW, SUSD2, SFRP2, IDO1, ANPEP, CXCR4, SCNN1A, SPP1andIFI27(upregulated) andSERPINE1, DUSP1, CD40,andIL6(downregulated). Through correlation analysis, we screened out ten potential drugs to target the core genes.ConclusionBased on the comprehensive analysis of the genomic datasets with different sorting methods of OCSCs, we figured out the common driving genes to regulating OCSC and obtained ten new potential therapies for eliminating ovarian cancer stem cells. Hence, the findings of our study might have potential clinical significance.
The evolution of TNF signaling in platyhelminths suggests the cooptation of TNF receptor in the host-parasite interplay
Authors: Bertevello Claudio R. , Russo Bruno R. A. , Tahira Ana C. , Lopes-Junior Ednilson Hilário , DeMarco Ricardo , Oliveira Katia C. 
Published: September 2020

Abstract
Background
The TNF signaling pathway is involved in the regulation of many cellular processes (such as apoptosis and cell proliferation). Previous reports indicated the effect of human TNF-α on metabolism, physiology, gene expression and protein phosphorylation of the human parasite Schistosoma mansoni and suggested that its TNF receptor was responsible for this response. The lack of an endogenous TNF ligand reinforced the idea of the use of an exogenous ligand, but also opens the possibility that the receptor actually binds a non-canonical ligand, as observed for NGFRs.

Methods
To obtain a more comprehensive view, we analyzed platyhelminth genomes deposited in the Wormbase ParaSite database to investigate the presence of TNF receptors and their respective ligands. Using different bioinformatics approaches, such as HMMer and BLAST search tools we identified and characterized the sequence of TNF receptors and ligand homologs. We also used bioinformatics resources for the identification of conserved protein domains and Bayesian inference for phylogenetic analysis.

Results
Our analyses indicate the presence of 31 TNF receptors in 30 platyhelminth species. All platyhelminths display a single TNF receptor, and all are structurally remarkably similar to NGFR. It suggests no events of duplication and diversification occurred in this phylum, with the exception of a single species-specific duplication. Interestingly, we also identified TNF ligand homologs in five species of free-living platyhelminths.

Conclusions
These results suggest that the TNF receptor from platyhelminths may be able to bind canonical TNF ligands, thus strengthening the idea that these receptors are able to bind human TNF-α. This also raises the hypothesis that an endogenous ligand was substituted by the host ligand in parasitic platyhelminths. Moreover, our analysis indicates that death domains (DD) may be present in the intracellular region of most platyhelminth TNF receptors, thus pointing to a previously unreported apoptotic action of such receptors in platyhelminths. Our data highlight the idea that host-parasite crosstalk using the TNF pathway may be widespread in parasitic platyhelminths to mediate apoptotic responses. This opens up a new hypothesis to uncover what might be an important component to understand platyhelminth infections.
UTX/KDM6A suppresses AP-1 and a gliogenesis program during neural differentiation of human pluripotent stem cells
Authors: Xu Beisi , Mulvey Brett , Salie Muneeb , Yang Xiaoyang , Matsui Yurika , Nityanandam Anjana , Fan Yiping , Peng Jamy C. 
Published: September 2020

Abstract
Background
UTX/KDM6A is known to interact and influence multiple different chromatin modifiers to promote an open chromatin environment to facilitate gene activation, but its molecular activities in developmental gene regulation remain unclear.

Results
We report that in human neural stem cells, UTX binding correlates with both promotion and suppression of gene expression. These activities enable UTX to modulate neural stem cell self-renewal, promote neurogenesis, and suppress gliogenesis. In neural stem cells, UTX has a less influence over histone H3 lysine 27 and lysine 4 methylation but more predominantly affects histone H3 lysine 27 acetylation and chromatin accessibility. Furthermore, UTX suppresses components of AP-1 and, in turn, a gliogenesis program.

Conclusions
Our findings revealed that UTX coordinates dualistic gene regulation to govern neural stem cell properties and neurogenesis–gliogenesis switch.
Epigenomics and transcriptomics of systemic sclerosis CD4+ T cells reveal long-range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci
Authors: Li Tianlu , Ortiz-Fernández Lourdes , Andrés-León Eduardo , Ciudad Laura , Javierre Biola M. , López-Isac Elena , Guillén-Del-Castillo Alfredo , Simeón-Aznar Carmen Pilar , Ballestar Esteban , Martin Javier 
Published: September 2020

Abstract
Background
Systemic sclerosis (SSc) is a genetically complex autoimmune disease mediated by the interplay between genetic and epigenetic factors in a multitude of immune cells, with CD4+ T lymphocytes as one of the principle drivers of pathogenesis.

Methods
DNA samples exacted from CD4+ T cells of 48 SSc patients and 16 healthy controls were hybridized on MethylationEPIC BeadChip array. In parallel, gene expression was interrogated by hybridizing total RNA on Clariom™ S array. Downstream bioinformatics analyses were performed to identify correlating differentially methylated CpG positions (DMPs) and differentially expressed genes (DEGs), which were then confirmed utilizing previously published promoter capture Hi-C (PCHi-C) data.

Results
We identified 9112 and 3929 DMPs and DEGs, respectively. These DMPs and DEGs are enriched in functional categories related to inflammation and T cell biology. Furthermore, correlation analysis identified 17,500 possible DMP-DEG interaction pairs within a window of 5 Mb, and utilizing PCHi-C data, we observed that 212 CD4+ T cell-specific pairs of DMP-DEG also formed part of three-dimensional promoter-enhancer networks, potentially involving CTCF. Finally, combining PCHi-C data with SSc GWAS data, we identified four important SSc-associated susceptibility loci, TNIP1 (rs3792783), GSDMB (rs9303277), IL12RB1 (rs2305743), and CSK (rs1378942), that could potentially interact with DMP-DEG pairs cg17239269-ANXA6, cg19458020-CCR7, cg10808810-JUND, and cg11062629-ULK3, respectively.

Conclusion
Our study unveils a potential link between genetic, epigenetic, and transcriptional deregulation in CD4+ T cells of SSc patients, providing a novel integrated view of molecular components driving SSc pathogenesis.
The association of asthma and its subgroups with osteoporosis: a cross-sectional study using KoGES HEXA data
Authors: Wee Jee Hye , Min Chanyang , Park Min Woo , Byun Soo Hwan , Lee Hyo-Jeong , Park Bumjung , Choi Hyo Geun 
Published: September 2020

AbstractBackgroundA few studies have reported the association between asthma and osteoporosis. We aimed to analyze the association of asthma and its subgroups with osteoporosis in the Korean adult population.MethodsWe used the health examinee (HEXA) data from the Korean Genome and Epidemiology Study (KoGES) obtained between 2004 and 2016. We included 162,579 participants (n = 3,160 with asthma; n = 159,419 controls) who reported their previous histories of asthma and osteoporosis. The participants were categorized into 3 groups based on asthma management: participants who did not need further treatment due to controlled symptoms (well controlled); participants with ongoing treatment (being treated); participants who were not treated even though they had symptoms (not being treated). Multiple logistic regression analyses were used to calculate the adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for osteoporosis. Subgroup analyses for age and sex were conducted.ResultsThe prevalence of osteoporosis was higher in patients with asthma (13.6%) than in controls (6.8%). In the full-adjusted model, the aORs for osteoporosis were 1.74 (95% CI 1.55–1.94, P < 0.001) in patients with asthma compared to controls. There were consistent findings across the age and sex subgroups. The aORs for osteoporosis were 1.43 (95% CI 1.10–1.86, P = 0.008) in the well-controlled asthma group; 1.55 (95% CI 1.28–1.89, P < 0.001) in the being treated asthma group; and 1.96 (95% CI 1.66–2.31, P < 0.001) in the not being treated asthma group compared to the control group.ConclusionAsthma was associated with osteoporosis in the Korean adult population. Patients with asthma not being treated showed the highest ORs for osteoporosis.
Immunosuppressive effects of mesenchymal stem cells on lung B cell gene expression in LPS-induced acute lung injury
Authors: Feng Bing , Zhu Jiaqi , Xu Yanping , Chen Wenyi , Sheng Xinyu , Feng Xudong , Shi Xiaowei , Liu Jingqi , Pan Qiaoling , Yang Jinfeng , Yu Jiong , Li Lanjuan , Cao Hongcui 
Published: September 2020

AbstractBackgroundImmune system disorders play important roles in acute lung injury (ALI), and mesenchymal stem cell (MSC) treatment can reduce inflammation during ALI. In this study, we compared the changes in lung B cells during MSC treatment.MethodsWe investigated the effects of MSCs on lung B cells in a mouse model of lipopolysaccharide (LPS)-induced ALI. MSCs were administered intratracheally 4 h after LPS. As vehicle-treated controls, mice were treated with phosphate-buffered saline (PBS) containing 2% C57BL/6 (PBS group). Histopathological changes, survival rate, inflammatory factor levels, and the number of neutrophils in bronchoalveolar lavage fluid (BALF) were determined. Single-cell RNA sequencing (scRNA-Seq) analysis was performed to evaluate the transcriptional changes in lung B cells between the PBS, LPS, and LPS/MSC groups on days 3 and 7.ResultsMSC treatment ameliorated LPS-induced ALI, as indicated by the reductions in mortality, the levels of chemokines and cytokines in BALF, and the severity of lung tissue histopathology in ALI mice. Lung B cells in the PBS group remained undifferentiated and had an inhibitory phenotype. Based on our scRNA-Seq results, the differentially expressed genes (DEGs) in lung B cells in both the PBS group and LPS group were involved in chemotaxis processes and some proinflammatory pathways. MSC treatment inhibited the expression of chemokine genes that were upregulated by LPS and were related to the recruitment of neutrophils into lung tissues. Immunoglobulin-related gene expression was decreased in lung B cells of mice treated with LPS/MSC for 7 days. The DEGs regulated by MSCs were enriched in biological processes, including humoral immune response and apoptotic signaling.ConclusionsLung B cells played an important role in the effects of treatment of ALI with MSCs. These observations provide new insights into the mechanisms underlying the effects of MSC treatment for ALI.
Autoantibodies directed against α1-adrenergic receptor and endothelin receptor A in patients with prostate cancer
Authors: Wallukat Gerd , Jandrig Burkhard , Becker Niels-Peter , Wendler Johann J. , Göttel Peter , Müller Johannes , Schostak Martin , Schimke Ingolf 
Published: September 2020

Abstract
Background
For prostate cancer, signaling pathways induced by over-boarding stimulation of G-protein coupled receptors (GPCR) such as the endothelin, α1- and β-adrenergic, muscarinic and angiotensin 1 receptors were accused to support the carcinogenesis. However, excessive receptor stimulation by physiological receptor ligands is minimized by a control system that induces receptor sensitization and down-regulation. This system is missing when so-called “functional autoantibodies” bind to the GPCR (GPCR-AAB). If GPCR-AAB were found in patients with prostate cancer, uncontrolled GPCR stimulation could make these autoantibodies an additional supporter in prostate cancer.

Methods
Using the bioassay of spontaneously beating cultured rat neonatal cardiomyocytes, GPCR-AAB were identified, quantified and characterized in the serum of 25 patients (aged 56–78 years, median 70 years) with prostate cancer compared to 10 male patients (aged 48–82 years, median 64) with urinary stone disorders (controls).

Results
Of the cancer patients, 24 (96%) and 17 (68%), respectively, carried autoantibodies directed against the α1-adrenergic receptor (α1-AAB) and endothelin receptor A (ETA-AAB). No patient was negative for both GPCR-AAB. In contrast, ETA-AAB and α1-AAB were absent in all (100%) and 9 (90%) of the 10 control patients, respectively. While α1-AAB targeted a specific epitope of the first extracellular loop of the α1-adrenergic receptor subtype A, an epitope of the second extracellular loop of the ETA receptor was identified as a target of ETA-AAB. As demonstrated in vitro, the functional activity of both autoantibodies found in prostate cancer can be neutralized by the aptamer BC007.

Conclusions
We hypothesized that α1-AAB and ETA-AAB, which are highly present in prostate cancer patients, could by their functional activity support carcinogenesis by excessive receptor stimulation. The in vitro demonstrated neutralization of α1- and ETA-AAB by the aptamer BC007 could open the door to complement the treatments already available for prostate cancer.
Implications of human activities for (re)emerging infectious diseases, including COVID-19
Authors: Sabin Nundu Sabiti , Calliope Akintije Simba , Simpson Shirley Victoria , Arima Hiroaki , Ito Hiromu , Nishimura Takayuki , Yamamoto Taro 
Published: September 2020

AbstractSince 1980, the world has been threatened by different waves of emerging disease epidemics. In the twenty-first century, these diseases have become an increasing global concern because of their health and economic impacts in both developed and resource-constrained countries. It is difficult to stop the occurrence of new pathogens in the future due to the interconnection among humans, animals, and the environment. However, it is possible to face a new disease or to reduce the risk of its spread by implementing better early warning systems and effective disease control and prevention, e.g., effective global surveillance, development of technology for better diagnostics, effective treatments, and vaccines, the global political will to respond to any threats and multidisciplinary collaboration involving all sectors in charge of good health maintenance. In this review, we generally describe some factors related to human activities and show how they can play a role in the transmission and spread of infectious diseases by using some diseases as examples. Additionally, we describe and discuss major factors that are facilitating the spread of the new pandemic known as COVID-19 worldwide.