PeerJ
type: channel
link: https://peerj.com/articles/
description: Articles published in PeerJ
publisher: PeerJ Inc.
publication name: PeerJ
issn: 2167-8359
items: CD14 and CD26 from serum exosomes are associated with type 2 diabetes, exosomal Cystatin C and CD14 are associated with metabolic syndrome and atherogenic index of plasma
items: Prevalence of HPV genotypes and assessment of their clinical relevance in laryngeal squamous cell carcinoma in a northeastern state of Brazil—a retrospective study
items: Comparative full-length transcriptome analysis by Oxford Nanopore Technologies reveals genes involved in anthocyanin accumulation in storage roots of sweet potatoes (Ipomoea batatas L.)
items: Characterization of human tear proteome reveals differentially abundance proteins in thyroid-associated ophthalmopathy
items: Downregulation of the enhancer of zeste homolog 1 transcriptional factor predicts poor prognosis of triple-negative breast cancer patients
items: Cyclocytidine hydrochloride inhibits the synthesis of relaxed circular DNA of hepatitis B virus
items: Estimating bite force in extinct dinosaurs using phylogenetically predicted physiological cross-sectional areas of jaw adductor muscles
items: Automated detection and removal of flat line segments and large amplitude fluctuations in neonatal electroencephalography
items: GABRP promotes CD44s-mediated gemcitabine resistance in pancreatic cancer
items: Tucuxi-BLAST: Enabling fast and accurate record linkage of large-scale health-related administrative databases through a DNA-encoded approach

CD14 and CD26 from serum exosomes are associated with type 2 diabetes, exosomal Cystatin C and CD14 are associated with metabolic syndrome and atherogenic index of plasma
type: item
type: AcademicArticle
description: Background Exosomes are microvesicles that actively participate in signaling mechanisms and depending on their content can contribute to the development of different pathologies, such as diabetes and cardiovascular disease. Objective The aim of this study was to evaluate the association of cystatin C, CD26, and CD14 proteins in serum exosomes from patients with Type 2 Diabetes (T2D), metabolic syndrome (MetS), and atherogenic index of plasma (AIP). Methods Serum exosomes were isolated by ultracentrifugation from 147 individuals with and without diabetes. Both anthropometric and metabolic parameters were registered from everyone. The levels of exosomal proteins cystatin C, CD26, and CD14 were quantified by ELISA. The association between protein levels and T2D or atherogenic risk factors was analyzed by linear regression and generalized regression models. Results We observed a significant correlation of increased glucose with elevated levels of Cystatin C, and an effect of T2D on the levels of CD26 (β = 45.8 pg/µg; p = 0.001) and CD14 (β = 168 pg/µg; p < 0.001) compared to subjects without T2D. CD14 was significantly related to T2D, metabolic syndrome, glucose, and the Atherogenic Index of Plasma (AIP). Additionally, we observed a significant effect of metabolic syndrome MetS on the increase of exosomal Cystatin C and CD14. Conclusions T2D may contribute to the increase of CD14 protein contained in exosomes, as well as to the predisposition of atherogenic events development due to its relationship with the increase in serum triglyceride concentrations and the AIP score. Finally, the increased levels of CD14 and Cystatin C in exosomes are related to MetS. The analysis of exosome contents of diabetic patients remains an incipient field, so extensive characterization is crucial for their use as biomarkers or to analyze their possible contribution to diabetic complications.
format: application/pdf
format: text/html
creator: Claudia Paola Pérez-Macedonio
creator: Eugenia Flores-Alfaro
creator: Luz del C. Alarcón-Romero
creator: Amalia Vences-Velázquez
creator: Natividad Castro-Alarcón
creator: Eduardo Martínez-Martínez
creator: Monica Ramirez
subject: Diabetes and Endocrinology
subject: Metabolic Sciences
description: doi:10.7717/peerj.13656
publisher: PeerJ Inc.
rights: © 2022 Pérez-Macedonio et al.
abstract: Background Exosomes are microvesicles that actively participate in signaling mechanisms and depending on their content can contribute to the development of different pathologies, such as diabetes and cardiovascular disease. Objective The aim of this study was to evaluate the association of cystatin C, CD26, and CD14 proteins in serum exosomes from patients with Type 2 Diabetes (T2D), metabolic syndrome (MetS), and atherogenic index of plasma (AIP). Methods Serum exosomes were isolated by ultracentrifugation from 147 individuals with and without diabetes. Both anthropometric and metabolic parameters were registered from everyone. The levels of exosomal proteins cystatin C, CD26, and CD14 were quantified by ELISA. The association between protein levels and T2D or atherogenic risk factors was analyzed by linear regression and generalized regression models. Results We observed a significant correlation of increased glucose with elevated levels of Cystatin C, and an effect of T2D on the levels of CD26 (β = 45.8 pg/µg; p = 0.001) and CD14 (β = 168 pg/µg; p < 0.001) compared to subjects without T2D. CD14 was significantly related to T2D, metabolic syndrome, glucose, and the Atherogenic Index of Plasma (AIP). Additionally, we observed a significant effect of metabolic syndrome MetS on the increase of exosomal Cystatin C and CD14. Conclusions T2D may contribute to the increase of CD14 protein contained in exosomes, as well as to the predisposition of atherogenic events development due to its relationship with the increase in serum triglyceride concentrations and the AIP score. Finally, the increased levels of CD14 and Cystatin C in exosomes are related to MetS. The analysis of exosome contents of diabetic patients remains an incipient field, so extensive characterization is crucial for their use as biomarkers or to analyze their possible contribution to diabetic complications.
bibliographic citation: Pérez-Macedonio et al. (2022) CD14 and CD26 from serum exosomes are associated with type 2 diabetes, exosomal Cystatin C and CD14 are associated with metabolic syndrome and atherogenic index of plasma. PeerJ 10:e13656 https://doi.org/10.7717/peerj.13656
date submitted: 2021-10-18
date accepted: 2022-06-09
issued: 2022-07-12
is part of: PeerJ
license: https://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Pérez-Macedonio
  given name: Claudia Paola
author list: Agent
  family name: Flores-Alfaro
  given name: Eugenia
author list: Agent
  family name: Alarcón-Romero
  given name: Luz del C.
author list: Agent
  family name: Vences-Velázquez
  given name: Amalia
author list: Agent
  family name: Castro-Alarcón
  given name: Natividad
author list: Agent
  family name: Martínez-Martínez
  given name: Eduardo
author list: Agent
  family name: Ramirez
  given name: Monica
doi: 10.7717/peerj.13656
volume: 10
issn: 2167-8359
publication name: PeerJ
publication date: 2022-07-12
copyright: ©2022 Pérez-Macedonio et al.
attribution name: Pérez-Macedonio et al.

Prevalence of HPV genotypes and assessment of their clinical relevance in laryngeal squamous cell carcinoma in a northeastern state of Brazil—a retrospective study
type: item
type: AcademicArticle
description: Background A high prevalence and incidence of head and neck tumors make Brazil the country with the third-highest number of cases of these malignant neoplasms. The main risk factors are smoking and alcohol consumption; however, cases related to the human papillomavirus (HPV) have tripled in number, demonstrating a changing disease profile. Studies have reported the prevalence of HPV in laryngeal squamous cell carcinoma (LSCC) to vary between 8% and 83%. The role of HPV as an important causative factor in LSCC remains unclear. Methods This retrospective study included 82 patients with LSCC diagnosed between 2014 and 2019 at two oncology hospitals in São Luís, Brazil. Sociodemographic and clinical data, and the histopathologic characteristics of the tumors, were collected directly from medical records. Genetic material was extracted from paraffin-embedded samples using nested polymerase chain reaction (PCR) and automated sequencing for HPV detection and genotyping. The results by social and clinicopathologic variables were then compared using the chi-squared test and multivariate analysis. Results Sociodemographic analysesdemonstrated that most patients were men (87.8%), brown-skinned (75.6%), and resident in the state capital (53.7%). They generally had a poor education status (53.7%), having only an elementary school education (completed/incomplete), and 51.2% were self-employed in occupations such as farming or fishing. Smoking and alcohol consumption habits were observed in approximately half the patients. With respect to clinical characteristics, 39% of patients exhibited T1/T2 staging, 51.2% had no distant metastasis, and 30.5% had lymph node invasion. HPV DNA was detected in half the samples (50%), with the high oncogenic type 16 being the most prevalent. There was no significant relationship observed between the economic, educational, occupational with the HPV LSCC in the presented data, although multivariate analysis demonstrated that HPV DNA was more likely …
format: application/pdf
format: text/html
creator: Charlles Brito
creator: Rachel D. Cossetti
creator: Diego Agra de Souza
creator: Marcos Catanha
creator: Pablo de Matos Monteiro
creator: Flavia Castello Branco Vidal
subject: Molecular Biology
subject: Virology
subject: Infectious Diseases
subject: Oncology
description: doi:10.7717/peerj.13684
publisher: PeerJ Inc.
rights: © 2022 Brito et al.
abstract: Background A high prevalence and incidence of head and neck tumors make Brazil the country with the third-highest number of cases of these malignant neoplasms. The main risk factors are smoking and alcohol consumption; however, cases related to the human papillomavirus (HPV) have tripled in number, demonstrating a changing disease profile. Studies have reported the prevalence of HPV in laryngeal squamous cell carcinoma (LSCC) to vary between 8% and 83%. The role of HPV as an important causative factor in LSCC remains unclear. Methods This retrospective study included 82 patients with LSCC diagnosed between 2014 and 2019 at two oncology hospitals in São Luís, Brazil. Sociodemographic and clinical data, and the histopathologic characteristics of the tumors, were collected directly from medical records. Genetic material was extracted from paraffin-embedded samples using nested polymerase chain reaction (PCR) and automated sequencing for HPV detection and genotyping. The results by social and clinicopathologic variables were then compared using the chi-squared test and multivariate analysis. Results Sociodemographic analysesdemonstrated that most patients were men (87.8%), brown-skinned (75.6%), and resident in the state capital (53.7%). They generally had a poor education status (53.7%), having only an elementary school education (completed/incomplete), and 51.2% were self-employed in occupations such as farming or fishing. Smoking and alcohol consumption habits were observed in approximately half the patients. With respect to clinical characteristics, 39% of patients exhibited T1/T2 staging, 51.2% had no distant metastasis, and 30.5% had lymph node invasion. HPV DNA was detected in half the samples (50%), with the high oncogenic type 16 being the most prevalent. There was no significant relationship observed between the economic, educational, occupational with the HPV LSCC in the presented data, although multivariate analysis demonstrated that HPV DNA was more likely …
bibliographic citation: Brito et al. (2022) Prevalence of HPV genotypes and assessment of their clinical relevance in laryngeal squamous cell carcinoma in a northeastern state of Brazil—a retrospective study. PeerJ 10:e13684 https://doi.org/10.7717/peerj.13684
date submitted: 2022-03-08
date accepted: 2022-06-14
issued: 2022-07-12
is part of: PeerJ
license: https://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Brito
  given name: Charlles
author list: Agent
  family name: Cossetti
  given name: Rachel D.
author list: Agent
  family name: de Souza
  given name: Diego Agra
author list: Agent
  family name: Catanha
  given name: Marcos
author list: Agent
  family name: de Matos Monteiro
  given name: Pablo
author list: Agent
  family name: Vidal
  given name: Flavia Castello Branco
doi: 10.7717/peerj.13684
volume: 10
issn: 2167-8359
publication name: PeerJ
publication date: 2022-07-12
copyright: ©2022 Brito et al.
attribution name: Brito et al.

Comparative full-length transcriptome analysis by Oxford Nanopore Technologies reveals genes involved in anthocyanin accumulation in storage roots of sweet potatoes (Ipomoea batatas L.)
type: item
type: AcademicArticle
description: Background Storage roots of sweet potatoes (Ipomoea batatas L.) with different colors vary in anthocyanin content, indicating different economically agronomic trait. As the newest DNA/RNA sequencing technology, Oxford Nanopore Technologies (ONT) have been applied in rapid transcriptome sequencing for investigation of genes related to nutrient metabolism. At present, few reports concern full-length transcriptome analysis based on ONT for study on the molecular mechanism of anthocyanin accumulation leading to color change of tuberous roots of sweet potato cultivars. Results The storage roots of purple-fleshed sweet potato (PFSP) and white-fleshed sweet potato (WFSP) at different developmental stages were subjected to anthocyanin content comparison by UV-visible spectroscopy as well as transcriptome analysis at ONT MinION platform. UV-visible spectrophotometric measurements demonstrated the anthocyanin content of PFSP was much higher than that of WFSP. ONT RNA-Seq results showed each sample generated average 2.75 GB clean data with Full-Length Percentage (FL%) over 70% and the length of N50 ranged from 1,192 to 1,395 bp, indicating reliable data for transcriptome analysis. Subsequent analysis illustrated intron retention was the most prominent splicing event present in the resulting transcripts. As compared PFSP with WFSP at the relative developmental stages with the highest (PH vs. WH) and the lowest (PL vs. WL) anthocyanin content, 282 and 216 genes were up-regulated and two and 11 genes were down-regulated respectively. The differential expression genes involved in flavonoid biosynthesis pathway include CCoAOMT, PpLDOX, DFR, Cytochrome P450, CHI, and CHS. The genes encoding oxygenase superfamily were significantly up-regulated when compared PFSP with WFSP at the relative developmental stages. Conclusions Comparative full-length transcriptome analysis based on ONT serves as an effective approach to detect the differences in anthocyanin accumulation in the storage roo…
format: application/pdf
format: text/html
creator: Jun Xiong
creator: Xiuhua Tang
creator: Minzheng Wei
creator: Wenjin Yu
subject: Bioinformatics
subject: Molecular Biology
subject: Plant Science
description: doi:10.7717/peerj.13688
publisher: PeerJ Inc.
rights: © 2022 Xiong et al.
abstract: Background Storage roots of sweet potatoes (Ipomoea batatas L.) with different colors vary in anthocyanin content, indicating different economically agronomic trait. As the newest DNA/RNA sequencing technology, Oxford Nanopore Technologies (ONT) have been applied in rapid transcriptome sequencing for investigation of genes related to nutrient metabolism. At present, few reports concern full-length transcriptome analysis based on ONT for study on the molecular mechanism of anthocyanin accumulation leading to color change of tuberous roots of sweet potato cultivars. Results The storage roots of purple-fleshed sweet potato (PFSP) and white-fleshed sweet potato (WFSP) at different developmental stages were subjected to anthocyanin content comparison by UV-visible spectroscopy as well as transcriptome analysis at ONT MinION platform. UV-visible spectrophotometric measurements demonstrated the anthocyanin content of PFSP was much higher than that of WFSP. ONT RNA-Seq results showed each sample generated average 2.75 GB clean data with Full-Length Percentage (FL%) over 70% and the length of N50 ranged from 1,192 to 1,395 bp, indicating reliable data for transcriptome analysis. Subsequent analysis illustrated intron retention was the most prominent splicing event present in the resulting transcripts. As compared PFSP with WFSP at the relative developmental stages with the highest (PH vs. WH) and the lowest (PL vs. WL) anthocyanin content, 282 and 216 genes were up-regulated and two and 11 genes were down-regulated respectively. The differential expression genes involved in flavonoid biosynthesis pathway include CCoAOMT, PpLDOX, DFR, Cytochrome P450, CHI, and CHS. The genes encoding oxygenase superfamily were significantly up-regulated when compared PFSP with WFSP at the relative developmental stages. Conclusions Comparative full-length transcriptome analysis based on ONT serves as an effective approach to detect the differences in anthocyanin accumulation in the storage roo…
bibliographic citation: Xiong et al. (2022) Comparative full-length transcriptome analysis by Oxford Nanopore Technologies reveals genes involved in anthocyanin accumulation in storage roots of sweet potatoes (Ipomoea batatas L.). PeerJ 10:e13688 https://doi.org/10.7717/peerj.13688
date submitted: 2021-10-19
date accepted: 2022-06-16
issued: 2022-07-12
is part of: PeerJ
license: https://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Xiong
  given name: Jun
author list: Agent
  family name: Tang
  given name: Xiuhua
author list: Agent
  family name: Wei
  given name: Minzheng
author list: Agent
  family name: Yu
  given name: Wenjin
doi: 10.7717/peerj.13688
volume: 10
issn: 2167-8359
publication name: PeerJ
publication date: 2022-07-12
copyright: ©2022 Xiong et al.
attribution name: Xiong et al.

Characterization of human tear proteome reveals differentially abundance proteins in thyroid-associated ophthalmopathy
type: item
type: AcademicArticle
description: Background Thyroid-associated ophthalmopathy (TAO) is a common orbital inflammatory disease, but the abnormal expression of proteins in tears of TAO patients has not been systematically studied. The purpose of this study is to compare and analyze the total tear protein profile of TAO patients and to provide protein cues for TAO pathogenesis. Methods Tear samples were isolated from 30 TAO patients with obvious ocular surface damage and 30 healthy control subjects. Tear samples from 30 individuals were mixed and divided into three sample pools. Easy nano-scale LC-MS/MS based on labeling-free quantitative technology was utilized to profile tear proteome. Results Here, electrospray ionization mass spectra and SDS-PAGE results confirmed the good parallelisms among samples. A total of 313 proteins were obtained from six tear pools, among them, 103 differential abundance proteins (DAPs) were identified, including 99 up-regulated DAPs (including APOA1, HV103, IGH, and Transferrin variant) and four down-regulated DAPs (including FABA, VCC1, NUCB2, and E-cadherin) in the TAO group compared with the control group. GO analysis showed that up-regulated DAPs were mainly enriched in lipid metabolism and platelet molecular function, and down-regulated DAPs were involved in binding, cell junction, and cellular process. KEGG results indicated that DAPs were involved in 117 kinds of signal transduction pathways, among which the immune-related pathway of complement and coagulation cascades had the greatest relevance. Conclusion In conclusion, label-free LC-MS/MS is an effective strategy for profiling tear proteins component. Our study provides proteins and pathways altered in TAO and provides protein cues for further study on the precise mechanism of TAO pathogenesis.
format: application/pdf
format: text/html
creator: Xiaoqing Zhou
creator: Ruili Wei
creator: Rui Wang
subject: Biochemistry
subject: Bioinformatics
subject: Molecular Biology
description: doi:10.7717/peerj.13701
publisher: PeerJ Inc.
rights: © 2022 Zhou et al.
abstract: Background Thyroid-associated ophthalmopathy (TAO) is a common orbital inflammatory disease, but the abnormal expression of proteins in tears of TAO patients has not been systematically studied. The purpose of this study is to compare and analyze the total tear protein profile of TAO patients and to provide protein cues for TAO pathogenesis. Methods Tear samples were isolated from 30 TAO patients with obvious ocular surface damage and 30 healthy control subjects. Tear samples from 30 individuals were mixed and divided into three sample pools. Easy nano-scale LC-MS/MS based on labeling-free quantitative technology was utilized to profile tear proteome. Results Here, electrospray ionization mass spectra and SDS-PAGE results confirmed the good parallelisms among samples. A total of 313 proteins were obtained from six tear pools, among them, 103 differential abundance proteins (DAPs) were identified, including 99 up-regulated DAPs (including APOA1, HV103, IGH, and Transferrin variant) and four down-regulated DAPs (including FABA, VCC1, NUCB2, and E-cadherin) in the TAO group compared with the control group. GO analysis showed that up-regulated DAPs were mainly enriched in lipid metabolism and platelet molecular function, and down-regulated DAPs were involved in binding, cell junction, and cellular process. KEGG results indicated that DAPs were involved in 117 kinds of signal transduction pathways, among which the immune-related pathway of complement and coagulation cascades had the greatest relevance. Conclusion In conclusion, label-free LC-MS/MS is an effective strategy for profiling tear proteins component. Our study provides proteins and pathways altered in TAO and provides protein cues for further study on the precise mechanism of TAO pathogenesis.
bibliographic citation: Zhou et al. (2022) Characterization of human tear proteome reveals differentially abundance proteins in thyroid-associated ophthalmopathy. PeerJ 10:e13701 https://doi.org/10.7717/peerj.13701
date submitted: 2022-03-29
date accepted: 2022-06-17
issued: 2022-07-12
is part of: PeerJ
license: https://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Zhou
  given name: Xiaoqing
author list: Agent
  family name: Wei
  given name: Ruili
author list: Agent
  family name: Wang
  given name: Rui
doi: 10.7717/peerj.13701
volume: 10
issn: 2167-8359
publication name: PeerJ
publication date: 2022-07-12
copyright: © 2022 Zhou et al.
attribution name: Zhou et al.

Downregulation of the enhancer of zeste homolog 1 transcriptional factor predicts poor prognosis of triple-negative breast cancer patients
type: item
type: AcademicArticle
description: Background Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer and lacks effective biomarkers. This study seeks to unravel the expression status and the prospective transcriptional mechanisms of EZH1/EZH2 in TNBC tissue samples. Moreover, another objective of this study is to reveal the prognostic molecular signatures for risk stratification in TNBC patients. Methods To determine the expression status of EZH1/EZH2 in TNBC tissue samples, microarray analysis and immunohistochemistry were performed on in house breast cancer tissue samples. External mRNA expression matrices were used to verify its expression patterns. Furthermore, the prospective transcriptional mechanisms of EZH1/EZH2 in TNBC were explored by performing differential expression analysis, co-expression analysis, and chromatin immunoprecipitation sequencing analysis. Kaplan–Meier survival analysis and univariate Cox regression analysis were utilized to detect the prognostic molecular signatures in TNBC patients. Nomogram and time-dependent receiver operating characteristic curves were plotted to predict the risk stratification ability of the prognostic-signatures-based Cox model. Results In-house TMAs (66 TNBC vs. 106 non-TNBC) and external gene microarrays, as well as RNA-seq datasets (1,135 TNBC vs. 6,198 non-TNBC) results, confirmed the downregulation of EZH1 at both the protein and mRNA levels (SMD = −0.59 [−0.80, −0.37]), as is opposite to that of EZH2 (SMD = 0.74 [0.40, 1.08]). The upregulated transcriptional target genes of EZH1 were significantly aggregated in the cell cycle pathway, where CCNA2, CCNB1, MAD2L1, and PKMYT1 were determined as key transcriptional targets. Additionally, the downregulated transcriptional targets of EZH2 were enriched in response to the hormone, where ESR1 was identified as the hub gene. The six-signature-based prognostic model produced an impressive performance in this study, with a training AUC of 0.753, 0.981, and 0.977 at 3-, 5-, and…
format: application/pdf
format: text/html
creator: Wei Peng
creator: Wei Tang
creator: Jian-Di Li
creator: Rong-Quan He
creator: Jia-Yuan Luo
creator: Zu-Xuan Chen
creator: Jiang-Hui Zeng
creator: Xiao-Hua Hu
creator: Jin-Cai Zhong
creator: Yang Li
creator: Fu-Chao Ma
creator: Tian-Yi Xie
creator: Su-Ning Huang
creator: Lian-Ying Ge
subject: Biochemistry
subject: Bioinformatics
subject: Molecular Biology
subject: Pathology
subject: Histology
description: doi:10.7717/peerj.13708
publisher: PeerJ Inc.
rights: © 2022 Peng et al.
abstract: Background Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer and lacks effective biomarkers. This study seeks to unravel the expression status and the prospective transcriptional mechanisms of EZH1/EZH2 in TNBC tissue samples. Moreover, another objective of this study is to reveal the prognostic molecular signatures for risk stratification in TNBC patients. Methods To determine the expression status of EZH1/EZH2 in TNBC tissue samples, microarray analysis and immunohistochemistry were performed on in house breast cancer tissue samples. External mRNA expression matrices were used to verify its expression patterns. Furthermore, the prospective transcriptional mechanisms of EZH1/EZH2 in TNBC were explored by performing differential expression analysis, co-expression analysis, and chromatin immunoprecipitation sequencing analysis. Kaplan–Meier survival analysis and univariate Cox regression analysis were utilized to detect the prognostic molecular signatures in TNBC patients. Nomogram and time-dependent receiver operating characteristic curves were plotted to predict the risk stratification ability of the prognostic-signatures-based Cox model. Results In-house TMAs (66 TNBC vs. 106 non-TNBC) and external gene microarrays, as well as RNA-seq datasets (1,135 TNBC vs. 6,198 non-TNBC) results, confirmed the downregulation of EZH1 at both the protein and mRNA levels (SMD = −0.59 [−0.80, −0.37]), as is opposite to that of EZH2 (SMD = 0.74 [0.40, 1.08]). The upregulated transcriptional target genes of EZH1 were significantly aggregated in the cell cycle pathway, where CCNA2, CCNB1, MAD2L1, and PKMYT1 were determined as key transcriptional targets. Additionally, the downregulated transcriptional targets of EZH2 were enriched in response to the hormone, where ESR1 was identified as the hub gene. The six-signature-based prognostic model produced an impressive performance in this study, with a training AUC of 0.753, 0.981, and 0.977 at 3-, 5-, and…
bibliographic citation: Peng et al. (2022) Downregulation of the enhancer of zeste homolog 1 transcriptional factor predicts poor prognosis of triple-negative breast cancer patients. PeerJ 10:e13708 https://doi.org/10.7717/peerj.13708
date submitted: 2022-03-02
date accepted: 2022-06-19
issued: 2022-07-12
is part of: PeerJ
license: https://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Peng
  given name: Wei
author list: Agent
  family name: Tang
  given name: Wei
author list: Agent
  family name: Li
  given name: Jian-Di
author list: Agent
  family name: He
  given name: Rong-Quan
author list: Agent
  family name: Luo
  given name: Jia-Yuan
author list: Agent
  family name: Chen
  given name: Zu-Xuan
author list: Agent
  family name: Zeng
  given name: Jiang-Hui
author list: Agent
  family name: Hu
  given name: Xiao-Hua
author list: Agent
  family name: Zhong
  given name: Jin-Cai
author list: Agent
  family name: Li
  given name: Yang
author list: Agent
  family name: Ma
  given name: Fu-Chao
author list: Agent
  family name: Xie
  given name: Tian-Yi
author list: Agent
  family name: Huang
  given name: Su-Ning
author list: Agent
  family name: Ge
  given name: Lian-Ying
doi: 10.7717/peerj.13708
volume: 10
issn: 2167-8359
publication name: PeerJ
publication date: 2022-07-12
copyright: © 2022 Peng et al.
attribution name: Peng et al.

Cyclocytidine hydrochloride inhibits the synthesis of relaxed circular DNA of hepatitis B virus
type: item
type: AcademicArticle
description: Background Cyclocytidine hydrochloride (HCl) has been reported to inhibit DNA synthesis by affecting DNA polymerase. Here, we tested the antiviral effect of cyclocytidine on hepatitis B virus (HBV) DNA synthesis, which is reliant on DNA polymerase activity. Materials and Methods Cyclocytidine HCl was treated to HBV-producing HepAD38 cells or added to an endogenous polymerase reaction, and HBV DNA was detected by Southern blot. Results Treatment of 20 µM cyclocytidine HCl significantly decreased the production of relaxed circular (rc) DNA in HepAD38 cells and block rcDNA synthesis in endogenous polymerase reaction (EPR), a cell free assay, possibly by inhibiting the HBV DNA polymerase activity. Conclusion Cyclocytidine HCl could inhibit the synthesis of HBV rcDNA, the precursor of covalently closed circular DNA, and this result provides a case for the usage of “old” drugs for “new” applications.
format: application/pdf
format: text/html
creator: Xue Wang
creator: Yihan Xiao
creator: Zhigang Cui
creator: Zongxin Li
creator: Lihua Li
creator: Lixian Wu
creator: Feifei Yin
creator: Xiuji Cui
subject: Biochemistry
subject: Cell Biology
subject: Microbiology
subject: Virology
description: doi:10.7717/peerj.13719
publisher: PeerJ Inc.
rights: © 2022 Wang et al.
abstract: Background Cyclocytidine hydrochloride (HCl) has been reported to inhibit DNA synthesis by affecting DNA polymerase. Here, we tested the antiviral effect of cyclocytidine on hepatitis B virus (HBV) DNA synthesis, which is reliant on DNA polymerase activity. Materials and Methods Cyclocytidine HCl was treated to HBV-producing HepAD38 cells or added to an endogenous polymerase reaction, and HBV DNA was detected by Southern blot. Results Treatment of 20 µM cyclocytidine HCl significantly decreased the production of relaxed circular (rc) DNA in HepAD38 cells and block rcDNA synthesis in endogenous polymerase reaction (EPR), a cell free assay, possibly by inhibiting the HBV DNA polymerase activity. Conclusion Cyclocytidine HCl could inhibit the synthesis of HBV rcDNA, the precursor of covalently closed circular DNA, and this result provides a case for the usage of “old” drugs for “new” applications.
bibliographic citation: Wang et al. (2022) Cyclocytidine hydrochloride inhibits the synthesis of relaxed circular DNA of hepatitis B virus. PeerJ 10:e13719 https://doi.org/10.7717/peerj.13719
date submitted: 2022-04-11
date accepted: 2022-06-22
issued: 2022-07-12
is part of: PeerJ
license: https://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Wang
  given name: Xue
author list: Agent
  family name: Xiao
  given name: Yihan
author list: Agent
  family name: Cui
  given name: Zhigang
author list: Agent
  family name: Li
  given name: Zongxin
author list: Agent
  family name: Li
  given name: Lihua
author list: Agent
  family name: Wu
  given name: Lixian
author list: Agent
  family name: Yin
  given name: Feifei
author list: Agent
  family name: Cui
  given name: Xiuji
doi: 10.7717/peerj.13719
volume: 10
issn: 2167-8359
publication name: PeerJ
publication date: 2022-07-12
copyright: ©2022 Wang et al.
attribution name: Wang et al.

Estimating bite force in extinct dinosaurs using phylogenetically predicted physiological cross-sectional areas of jaw adductor muscles
type: item
type: AcademicArticle
description: I present a Bayesian phylogenetic predictive modelling (PPM) framework that allows the prediction of muscle parameters (physiological cross-sectional area, APhys) in extinct archosaurs from skull width (WSk) and phylogeny. This approach is robust to phylogenetic uncertainty and highly versatile given its ability to base predictions on simple, readily available predictor variables. The PPM presented here has high prediction accuracy (up to 95%), with downstream biomechanical modelling yielding bite force estimates that are in line with previous estimates based on muscle parameters from reconstructed muscles. This approach does not replace muscle reconstructions but one that provides a powerful means to predict APhys from skull geometry and phylogeny to the same level of accuracy as that measured from reconstructed muscles in species for which soft tissue data are unavailable or difficult to obtain.
format: application/pdf
format: text/html
creator: Manabu Sakamoto
subject: Biophysics
subject: Computational Biology
subject: Evolutionary Studies
subject: Paleontology
subject: Zoology
description: doi:10.7717/peerj.13731
publisher: PeerJ Inc.
rights: © 2022 Sakamoto
abstract: I present a Bayesian phylogenetic predictive modelling (PPM) framework that allows the prediction of muscle parameters (physiological cross-sectional area, APhys) in extinct archosaurs from skull width (WSk) and phylogeny. This approach is robust to phylogenetic uncertainty and highly versatile given its ability to base predictions on simple, readily available predictor variables. The PPM presented here has high prediction accuracy (up to 95%), with downstream biomechanical modelling yielding bite force estimates that are in line with previous estimates based on muscle parameters from reconstructed muscles. This approach does not replace muscle reconstructions but one that provides a powerful means to predict APhys from skull geometry and phylogeny to the same level of accuracy as that measured from reconstructed muscles in species for which soft tissue data are unavailable or difficult to obtain.
bibliographic citation: Sakamoto (2022) Estimating bite force in extinct dinosaurs using phylogenetically predicted physiological cross-sectional areas of jaw adductor muscles. PeerJ 10:e13731 https://doi.org/10.7717/peerj.13731
date submitted: 2022-04-27
date accepted: 2022-06-23
issued: 2022-07-12
is part of: PeerJ
license: https://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Sakamoto
  given name: Manabu
doi: 10.7717/peerj.13731
volume: 10
issn: 2167-8359
publication name: PeerJ
publication date: 2022-07-12
copyright: © 2022 Sakamoto
attribution name: Sakamoto

Automated detection and removal of flat line segments and large amplitude fluctuations in neonatal electroencephalography
type: item
type: AcademicArticle
description: Background Artefact removal in neonatal electroencephalography (EEG) by visual inspection generally depends on the expertise of the operator, is time consuming and is not a consistent pre-processing step to the pipeline for the automated EEG analysis. Therefore, there is the need for the automated detection and removal of artefacts in neonatal EEG, especially of distinct and predominant artefacts such as flat line segments (mainly caused by instrumental error where contact between electrodes and head box is lost) and large amplitude fluctuations (related to neonatal movements). Method A threshold-based algorithm for the automated detection and removal of flat line segments and large amplitude fluctuations in neonatal EEG of infants at term-equivalent age is developed. The algorithm applies thresholds to the absolute second difference, absolute amplitude, absolute first difference and the ratio between the frequency content above 50 Hz and the frequency content across all frequencies. Results The algorithm reaches a median accuracy of 0.91, a median hit rate of 0.91 and a median false discovery rate of 0.37. Also, a significant improvement (≈10%) in the performance of a four-stage sleep classifier is observed after artefact removal with the proposed algorithm as compared to before its application. Significance An automated artefact removal method contributes to the pipeline of automated EEG analysis. The proposed algorithm has shown to have good performance and to be effective in neonatal EEG applications.
format: application/pdf
format: text/html
creator: Gabriella Tamburro
creator: Katrien Jansen
creator: Katrien Lemmens
creator: Anneleen Dereymaeker
creator: Gunnar Naulaers
creator: Maarten De Vos
creator: Silvia Comani
subject: Bioinformatics
subject: Neuroscience
subject: Neurology
subject: Pediatrics
subject: Radiology and Medical Imaging
description: doi:10.7717/peerj.13734
publisher: PeerJ Inc.
rights: © 2022 Tamburro et al.
abstract: Background Artefact removal in neonatal electroencephalography (EEG) by visual inspection generally depends on the expertise of the operator, is time consuming and is not a consistent pre-processing step to the pipeline for the automated EEG analysis. Therefore, there is the need for the automated detection and removal of artefacts in neonatal EEG, especially of distinct and predominant artefacts such as flat line segments (mainly caused by instrumental error where contact between electrodes and head box is lost) and large amplitude fluctuations (related to neonatal movements). Method A threshold-based algorithm for the automated detection and removal of flat line segments and large amplitude fluctuations in neonatal EEG of infants at term-equivalent age is developed. The algorithm applies thresholds to the absolute second difference, absolute amplitude, absolute first difference and the ratio between the frequency content above 50 Hz and the frequency content across all frequencies. Results The algorithm reaches a median accuracy of 0.91, a median hit rate of 0.91 and a median false discovery rate of 0.37. Also, a significant improvement (≈10%) in the performance of a four-stage sleep classifier is observed after artefact removal with the proposed algorithm as compared to before its application. Significance An automated artefact removal method contributes to the pipeline of automated EEG analysis. The proposed algorithm has shown to have good performance and to be effective in neonatal EEG applications.
bibliographic citation: Tamburro et al. (2022) Automated detection and removal of flat line segments and large amplitude fluctuations in neonatal electroencephalography. PeerJ 10:e13734 https://doi.org/10.7717/peerj.13734
date submitted: 2022-02-21
date accepted: 2022-06-24
issued: 2022-07-12
is part of: PeerJ
license: https://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Tamburro
  given name: Gabriella
author list: Agent
  family name: Jansen
  given name: Katrien
author list: Agent
  family name: Lemmens
  given name: Katrien
author list: Agent
  family name: Dereymaeker
  given name: Anneleen
author list: Agent
  family name: Naulaers
  given name: Gunnar
author list: Agent
  family name: De Vos
  given name: Maarten
author list: Agent
  family name: Comani
  given name: Silvia
doi: 10.7717/peerj.13734
volume: 10
issn: 2167-8359
publication name: PeerJ
publication date: 2022-07-12
copyright: © 2022 Tamburro et al.
attribution name: Tamburro et al.

GABRP promotes CD44s-mediated gemcitabine resistance in pancreatic cancer
type: item
type: AcademicArticle
description: Background Pancreatic ductal adenocarcinoma (PDAC) has the worst five-year overall survival rate among all cancer types. Acquired chemoresistance is considered one of the main reasons for this dismal prognosis, and the mechanism of chemoresistance is unknown. Methods We previously identified a subpopulation of chemoresistant CD44high-expressing PDAC cells. Subsequently, we selected the candidate gene, gamma-aminobutyric acid receptor subunit Pi (GABRP), from three Gene Expression Omnibus datasets as the potential CD44 downstream target mediating the gemcitabine resistance. Loss and gain of function such as stable knockdown of CD44 by small hairpin (sh) RNA-mediated silencing technique and overexpression (O/E) of CD44s had been studied for comparing the gemcitabine resistance among CD44high-expressing cells, shCD44 cells, CD44low-expressing cells and O/E CD44s expressing cells. Functional assays including cell viability, colony formation, invasion, quantitative PCR and western blotting techniques were performed to validate the roles of CD44 and GABRP playing in mediating the gemcitabine resistance in pancreatic cancer cells. Results CD44s depletion significantly reduced gemcitabine resistance in shCD44 single clone cells compared to CD44high-expressing cells. Knockdown of CD44 cells formed less colonies, became less invasive and remarkably decreased the mRNA level of GABRP. While overexpression of CD44s had the opposite effect on gemcitabine resistance, colony formation and invasive property. Of note, long term gemcitabine resistant pancreatic cancer cells detected increased expression of CD44 and GABRP. Clinically, GABRP expression was significantly upregulated in the tissues of patients with pancreatic cancer compared to the normal samples, and the overall survival rate of patients with low GABRP expression was longer. CD44 and GABRP co-expression was positively correlated in 178 pancreatic cancer patients. Conclusion Our findings suggest that GABRP may serve as a …
format: application/pdf
format: text/html
creator: Chen Chen
creator: Binfeng Wu
creator: Mingge Wang
creator: Jinghua Chen
creator: Zhaohui Huang
creator: Jin-Song Shi
subject: Bioinformatics
subject: Cell Biology
subject: Molecular Biology
subject: Oncology
description: doi:10.7717/peerj.12728
publisher: PeerJ Inc.
rights: © 2022 Chen et al.
abstract: Background Pancreatic ductal adenocarcinoma (PDAC) has the worst five-year overall survival rate among all cancer types. Acquired chemoresistance is considered one of the main reasons for this dismal prognosis, and the mechanism of chemoresistance is unknown. Methods We previously identified a subpopulation of chemoresistant CD44high-expressing PDAC cells. Subsequently, we selected the candidate gene, gamma-aminobutyric acid receptor subunit Pi (GABRP), from three Gene Expression Omnibus datasets as the potential CD44 downstream target mediating the gemcitabine resistance. Loss and gain of function such as stable knockdown of CD44 by small hairpin (sh) RNA-mediated silencing technique and overexpression (O/E) of CD44s had been studied for comparing the gemcitabine resistance among CD44high-expressing cells, shCD44 cells, CD44low-expressing cells and O/E CD44s expressing cells. Functional assays including cell viability, colony formation, invasion, quantitative PCR and western blotting techniques were performed to validate the roles of CD44 and GABRP playing in mediating the gemcitabine resistance in pancreatic cancer cells. Results CD44s depletion significantly reduced gemcitabine resistance in shCD44 single clone cells compared to CD44high-expressing cells. Knockdown of CD44 cells formed less colonies, became less invasive and remarkably decreased the mRNA level of GABRP. While overexpression of CD44s had the opposite effect on gemcitabine resistance, colony formation and invasive property. Of note, long term gemcitabine resistant pancreatic cancer cells detected increased expression of CD44 and GABRP. Clinically, GABRP expression was significantly upregulated in the tissues of patients with pancreatic cancer compared to the normal samples, and the overall survival rate of patients with low GABRP expression was longer. CD44 and GABRP co-expression was positively correlated in 178 pancreatic cancer patients. Conclusion Our findings suggest that GABRP may serve as a …
bibliographic citation: Chen et al. (2022) GABRP promotes CD44s-mediated gemcitabine resistance in pancreatic cancer. PeerJ 10:e12728 https://doi.org/10.7717/peerj.12728
date submitted: 2021-06-18
date accepted: 2021-12-10
issued: 2022-07-11
is part of: PeerJ
license: https://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Chen
  given name: Chen
author list: Agent
  family name: Wu
  given name: Binfeng
author list: Agent
  family name: Wang
  given name: Mingge
author list: Agent
  family name: Chen
  given name: Jinghua
author list: Agent
  family name: Huang
  given name: Zhaohui
author list: Agent
  family name: Shi
  given name: Jin-Song
doi: 10.7717/peerj.12728
volume: 10
issn: 2167-8359
publication name: PeerJ
publication date: 2022-07-11
copyright: ©2022 Chen et al.
attribution name: Chen et al.

Tucuxi-BLAST: Enabling fast and accurate record linkage of large-scale health-related administrative databases through a DNA-encoded approach
type: item
type: AcademicArticle
description: Background Public health research frequently requires the integration of information from different data sources. However, errors in the records and the high computational costs involved make linking large administrative databases using record linkage (RL) methodologies a major challenge. Methods We present Tucuxi-BLAST, a versatile tool for probabilistic RL that utilizes a DNA-encoded approach to encrypt, analyze and link massive administrative databases. Tucuxi-BLAST encodes the identification records into DNA. BLASTn algorithm is then used to align the sequences between databases. We tested and benchmarked on a simulated database containing records for 300 million individuals and also on four large administrative databases containing real data on Brazilian patients. Results Our method was able to overcome misspellings and typographical errors in administrative databases. In processing the RL of the largest simulated dataset (200k records), the state-of-the-art method took 5 days and 7 h to perform the RL, while Tucuxi-BLAST only took 23 h. When compared with five existing RL tools applied to a gold-standard dataset from real health-related databases, Tucuxi-BLAST had the highest accuracy and speed. By repurposing genomic tools, Tucuxi-BLAST can improve data-driven medical research and provide a fast and accurate way to link individual information across several administrative databases.
format: application/pdf
format: text/html
creator: José Deney Araujo
creator: Juan Carlo Santos-e-Silva
creator: André Guilherme Costa-Martins
creator: Vanderson Sampaio
creator: Daniel Barros de Castro
creator: Robson F. de Souza
creator: Jeevan Giddaluru
creator: Pablo Ivan P. Ramos
creator: Robespierre Pita
creator: Mauricio L. Barreto
creator: Manoel Barral-Netto
creator: Helder I. Nakaya
subject: Bioinformatics
subject: Epidemiology
subject: Public Health
description: doi:10.7717/peerj.13507
publisher: PeerJ Inc.
rights: © 2022 Araujo et al.
abstract: Background Public health research frequently requires the integration of information from different data sources. However, errors in the records and the high computational costs involved make linking large administrative databases using record linkage (RL) methodologies a major challenge. Methods We present Tucuxi-BLAST, a versatile tool for probabilistic RL that utilizes a DNA-encoded approach to encrypt, analyze and link massive administrative databases. Tucuxi-BLAST encodes the identification records into DNA. BLASTn algorithm is then used to align the sequences between databases. We tested and benchmarked on a simulated database containing records for 300 million individuals and also on four large administrative databases containing real data on Brazilian patients. Results Our method was able to overcome misspellings and typographical errors in administrative databases. In processing the RL of the largest simulated dataset (200k records), the state-of-the-art method took 5 days and 7 h to perform the RL, while Tucuxi-BLAST only took 23 h. When compared with five existing RL tools applied to a gold-standard dataset from real health-related databases, Tucuxi-BLAST had the highest accuracy and speed. By repurposing genomic tools, Tucuxi-BLAST can improve data-driven medical research and provide a fast and accurate way to link individual information across several administrative databases.
bibliographic citation: Araujo et al. (2022) Tucuxi-BLAST: Enabling fast and accurate record linkage of large-scale health-related administrative databases through a DNA-encoded approach. PeerJ 10:e13507 https://doi.org/10.7717/peerj.13507
date submitted: 2022-03-09
date accepted: 2022-05-06
issued: 2022-07-11
is part of: PeerJ
license: https://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Araujo
  given name: José Deney
author list: Agent
  family name: Santos-e-Silva
  given name: Juan Carlo
author list: Agent
  family name: Costa-Martins
  given name: André Guilherme
author list: Agent
  family name: Sampaio
  given name: Vanderson
author list: Agent
  family name: de Castro
  given name: Daniel Barros
author list: Agent
  family name: de Souza
  given name: Robson F.
author list: Agent
  family name: Giddaluru
  given name: Jeevan
author list: Agent
  family name: Ramos
  given name: Pablo Ivan P.
author list: Agent
  family name: Pita
  given name: Robespierre
author list: Agent
  family name: Barreto
  given name: Mauricio L.
author list: Agent
  family name: Barral-Netto
  given name: Manoel
author list: Agent
  family name: Nakaya
  given name: Helder I.
doi: 10.7717/peerj.13507
volume: 10
issn: 2167-8359
publication name: PeerJ
publication date: 2022-07-11
copyright: © 2022 Araujo et al.
attribution name: Araujo et al.

PeerJ
type: Periodical
uri: PeerJ
issn: 2167-8359