bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revealing the potential mechanism of Astragalus membranaceus improving prognosis of hepatocellular carcinoma by combining transcriptomics and network pharmacology
Authors: Liu Zhili , Ma Huihan , Lai Zelin 
Published: October 2021

Abstract
Background
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death. Traditional Chinese medicine (TCM) has special advantages in relieving HCC, while Astragalus membranaceus is commonly used in TCM treatment. However, its underlying mechanisms for treatment of HCC are unclear.

Methods
Differentially expressed genes (DEGs) of Astragalus membranaceus treatment in HepG2 cells were identified, and Astragalus membranaceus-gene network was constructed. The hub genes were then obtained via protein-protein interaction (PPI) analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Gene Set Enrichment Analysis (GSEA) were subsequently performed. Furthermore, prognosis genes related to HCC from The Cancer Genome Atlas Program (TCGA) was identified to explore the correlation between Astragalus membranaceus treatment and prognosis of HCC. Finally, Astragalus membranaceus-component-target network was established through SymMap.

Results
Twenty five DEGs (15 up-regulated and 10 down-regulated) of Astragalus membranaceus treatment in HepG2 cells were identified. Among the 25 genes, MT1F, MT1G, MT1X and HMOX1 may play essential roles. Astragalus membranaceus mainly affects the Mineral absorption pathway in HCC. A total of 256 genes (p < 0.01) related to prognosis of HCC were identified, and MT1G is a common gene between prognosis genes and DEGs. Furthermore, Astragalus membranaceus may directly down-regulate MT1G through daidzein to promote ferroptosis of HCC cells and improve prognosis for HCC.

Conclusion
Our study provided new understandings of the pharmacological mechanisms by which Astragalus membranaceus improves the prognosis of HCC, and showed that the combination of transcriptomics and network pharmacology is helpful to explore mechanisms of TCM and traditional medicines from other nations.
PACmn for improved optogenetic control of intracellular cAMP
Authors: Yang Shang , Constantin Oana M. , Sachidanandan Divya , Hofmann Hannes , Kunz Tobias C. , Kozjak-Pavlovic Vera , Oertner Thomas G. , Nagel Georg , Kittel Robert J. , Gee Christine E. , Gao Shiqiang 
Published: October 2021

Abstract
Background
Cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger that transduces extracellular signals in virtually all eukaryotic cells. The soluble Beggiatoa photoactivatable adenylyl cyclase (bPAC) rapidly raises cAMP in blue light and has been used to study cAMP signaling pathways cell-autonomously. But low activity in the dark might raise resting cAMP in cells expressing bPAC, and most eukaryotic cyclases are membrane-targeted rather than soluble. Our aim was to engineer a plasma membrane-anchored PAC with no dark activity (i.e., no cAMP accumulation in the dark) that rapidly increases cAMP when illuminated.

Results
Using a streamlined method based on expression in Xenopus oocytes, we compared natural PACs and confirmed bPAC as the best starting point for protein engineering efforts. We identified several modifications that reduce bPAC dark activity. Mutating a phenylalanine to tyrosine at residue 198 substantially decreased dark cyclase activity, which increased 7000-fold when illuminated. Whereas Drosophila larvae expressing bPAC in mechanosensory neurons show nocifensive-like behavior even in the dark, larvae expressing improved soluble (e.g., bPAC(R278A)) and membrane-anchored PACs exhibited nocifensive responses only when illuminated. The plasma membrane-anchored PAC (PACmn) had an undetectable dark activity which increased >4000-fold in the light. PACmn does not raise resting cAMP nor, when expressed in hippocampal neurons, affect cAMP-dependent kinase (PKA) activity in the dark, but rapidly and reversibly increases cAMP and PKA activity in the soma and dendrites upon illumination. The peak responses to brief (2 s) light flashes exceed the responses to forskolin-induced activation of endogenous cyclases and return to baseline within seconds (cAMP) or ~10 min (PKA).

Conclusions
PACmn is a valuable optogenetic tool for precise cell-autonomous and transient stimulation of cAMP signaling pathways in diverse cell types.
OsnR is an autoregulatory negative transcription factor controlling redox-dependent stress responses in Corynebacterium glutamicum
Authors: Jeong Haeri , Kim Younhee , Lee Heung-Shick 
Published: October 2021

Abstract
Background
Corynebacterium glutamicum is used in the industrial production of amino acids and nucleotides. During the course of fermentation, C. glutamicum cells face various stresses and employ multiple regulatory genes to cope with the oxidative stress. The osnR gene plays a negative regulatory role in redox-dependent oxidative-stress responses, but the underlying mechanism is not known yet.

Results
Overexpression of the osnR gene in C. glutamicum affected the expression of genes involved in the mycothiol metabolism. ChIP-seq analysis revealed that OsnR binds to the promoter region of multiple genes, including osnR and cg0026, which seems to function in the membrane-associated redox metabolism. Studies on the role of the osnR gene involving in vitro assays employing purified OsnR proteins and in vivo physiological analyses have identified that OsnR inhibits the transcription of its own gene. Further, oxidant diamide stimulates OsnR-binding to the promoter region of the osnR gene. The genes affected by the overexpression of osnR have been found to be under the control of σH. In the osnR-overexpressing strain, the transcription of sigH is significantly decreased and the stimulation of sigH transcription by external stress is lost, suggesting that osnR and sigH form an intimate regulatory network.

Conclusions
Our study suggests that OsnR not only functions as a transcriptional repressor of its own gene and of those involved in redox-dependent stress responses but also participates in the global transcriptional regulation by controlling the transcription of other master regulators, such as sigH.
Preliminary study of 3 T-MRI native T1-mapping radiomics in differential diagnosis of non-calcified solid pulmonary nodules/masses
Authors: Yan Qinqin , Yi Yinqiao , Shen Jie , Shan Fei , Zhang Zhiyong , Yang Guang , Shi Yuxin 
Published: October 2021

Abstract
Background
Cumulative CT radiation damage was positively correlated with increased tumor risks. Although it has recently been known that non-radiation MRI is alternative for pulmonary imaging. There is little known about the value of MRI T1-mapping in the diagnosis of pulmonary nodules. This article aimed to investigate the value of native T1-mapping-based radiomics features in differential diagnosis of pulmonary lesions.

Methods
73 patients underwent 3 T-MRI examination in this prospective study. The 99 pulmonary lesions on native T1-mapping images were segmented twice by one radiologist at indicated time points utilizing the in-house semi-automated software, followed by extraction of radiomics features. The inter-class correlation coefficient (ICC) was used for analyzing intra-observer’s agreement. Dimensionality reduction and feature selection were performed via univariate analysis, and least absolute shrinkage and selection operator (LASSO) analysis. Then, the binary logical regression (LR), support vector machine (SVM) and decision tree classifiers with the input of optimal features were selected for differentiating malignant from benign lesions. The receiver operative characteristics (ROC) curve, area under the curve (AUC), sensitivity, specificity and accuracy were calculated. Z-test was used to compare differences among AUCs.

Results
107 features were obtained, of them, 19.5% (n = 21) had relatively good reliability (ICC ≥ 0.6). The remained 5 features (3 GLCM, 1 GLSZM and 1 shape features) by dimensionality reduction were useful. The AUC of LR was 0.82(95%CI: 0.67–0.98), with sensitivity, specificity and accuracy of 70%, 85% and 80%. The AUC of SVM was 0.82(95%CI: 0.67–0.98), with sensitivity, specificity and accuracy of 70, 85 and 80%. The AUC of decision tree was 0.69(95%CI: 0.49–0.87), with sensitivity, specificity and accuracy of 50, 85 and 73.3%.

Conclusions
The LR and SVM models using native T1-mapping-based radiomics features can differentiate pulmonary malignant from benign lesions, especially for uncertain nodules requiring long-term follow-ups.
TBX15/miR-152/KIF2C pathway regulates breast cancer doxorubicin resistance via promoting PKM2 ubiquitination
Authors: Jiang Cheng-Fei , Xie Yun-Xia , Qian Ying-Chen , Wang Min , Liu Ling-Zhi , Shu Yong-Qian , Bai Xiao-Ming , Jiang Bing-Hua 
Published: October 2021

Abstract
Background
Chemoresistance is a critical risk problem for breast cancer treatment. However, mechanisms by which chemoresistance arises remains to be elucidated. The expression of T-box transcription factor 15 (TBX-15) was found downregulated in some cancer tissues. However, role and mechanism of TBX15 in breast cancer chemoresistance is unknown. Here we aimed to identify the effects and mechanisms of TBX15 in doxorubicin resistance in breast cancer.

Methods
As measures of Drug sensitivity analysis, MTT and IC50 assays were used in DOX-resistant breast cancer cells. ECAR and OCR assays were used to analyze the glycolysis level, while Immunoblotting and Immunofluorescence assays were used to analyze the autophagy levels in vitro. By using online prediction software, luciferase reporter assays, co-Immunoprecipitation, Western blotting analysis and experimental animals models, we further elucidated the mechanisms.

Results
We found TBX15 expression levels were decreased in Doxorubicin (DOX)-resistant breast cancer cells. Overexpression of TBX15 reversed the DOX resistance by inducing microRNA-152 (miR-152) expression. We found that KIF2C levels were highly expressed in DOX-resistant breast cancer tissues and cells, and KIF2C was a potential target of miR-152. TBX15 and miR-152 overexpression suppressed autophagy and glycolysis in breast cancer cells, while KIF2C overexpression reversed the process. Overexpression of KIF2C increased DOX resistance in cancer cells. Furthermore, KIF2C directly binds with PKM2 for inducing the DOX resistance. KIF2C can prevent the ubiquitination of PKM2 and increase its protein stability. In addition, we further identified that Domain-2 of KIF2C played a major role in the binding with PKM2 and preventing PKM2 ubiquitination, which enhanced DOX resistance by promoting autophagy and glycolysis.

Conclusions
Our data identify a new mechanism by which TBX15 abolishes DOX chemoresistance in breast cancer, and suggest that TBX15/miR-152/KIF2C axis is a novel signaling pathway for mediating DOX resistance in breast cancer through regulating PKM2 ubiquitination and decreasing PKM2 stability. This finding suggests new therapeutic target and/or novel strategy development for cancer treatment to overcome drug resistance in the future.
Identification of key genes for HNSCC from public databases using bioinformatics analysis
Authors: Ye Yuchu , Wang Jingyi , Liang Faya , Song Pan , Yan Xiaoqing , Wu Sangqing , Huang Xiaoming , Han Ping 
Published: October 2021

Abstract
Background
The cause and underlying molecular mechanisms of head and neck squamous cell carcinoma (HNSCC) are unclear. Our study aims to identify the key genes associated with HNSCC and reveal potential biomarkers.

Methods
In this study, the expression profile dataset GSE83519 of the Gene Expression Omnibus database and the RNA sequencing dataset of HNSCC of The Cancer Genome Atlas were included for analysis. Sixteen differentially expressed genes were screened from these two datasets using R software. Gene Expression Profiling Interactive Analysis 2 (GEPIA2) was then adopted for survival analysis, and finally, three key genes related to the overall survival of HNSCC patients were identified. Furthermore, we verified these three genes using the Oncomine database and from real-time PCR and immunohistochemistry results from HNSCC tissues.

Results
The expression data of 44 samples from GSE83519 and 545 samples from TCGA-HNSC were collected. Using bioinformatics, the two databases were integrated, and 16 DEGs were screened out. Gene Ontology (GO) enrichment analysis showed that the biological functions of DEGs focused primarily on the apical plasma membrane and regulation of anoikis. Kyoto Encyclopedia of Genes and Genomes (KEGG) signalling pathway analysis showed that these DEGs were mainly involved in drug metabolism-cytochrome P450 and serotonergic synapses. Survival analysis identified three key genes, CEACAM5, CEACAM6 and CLCA4, that were closely related to HNSCC prognosis. The Oncomine database, qRT–PCR and IHC verified that all 3 key genes were downregulated in most HNSCC tissues compared to adjacent normal tissues.

Conclusions
This study indicates that integrated bioinformatics analyses play an important role in screening for differentially expressed genes and pathways in HNSCC, helping us better understand the biomarkers and molecular mechanism of HNSCC.
Diverse community leaders’ perspectives about quality primary healthcare and healthcare measurement: qualitative community-based participatory research
Authors: Culhane-Pera Kathleen A. , Pergament Shannon L. , Kasouaher Maiyia Y. , Pattock Andrew M. , Dhore Naima , Kaigama Cindy N. , Alison Marcela , Scandrett Michael , Thao Mai See , Satin David J. 
Published: October 2021

AbstractBackgroundHealthcare quality measurements in the United States illustrate disparities by racial/ethnic group, socio-economic class, and geographic location. Redressing healthcare inequities, including measurement of and reimbursement for healthcare quality, requires partnering with communities historically excluded from decision-making. Quality healthcare is measured according to insurers, professional organizations and government agencies, with little input from diverse communities. This community-based participatory research study aimed to amplify the voices of community leaders from seven diverse urban communities in Minneapolis-Saint Paul Minnesota, view quality healthcare and financial reimbursement based on quality metric scores.MethodsA Community Engagement Team consisting of one community member from each of seven urban communities —Black/African American, Lesbian-Gay-Bisexual-Transgender-Queer-Two Spirit, Hmong, Latino/a/x, Native American, Somali, and White—and two community-based researchers conducted listening sessions with 20 community leaders about quality primary healthcare. Transcripts were inductively analyzed and major themes were identified.ResultsListening sessions produced three major themes, with recommended actions for primary care clinics.#1: Quality Clinics Utilize Structures and Processes that Support Healthcare Equity.#2: Quality Clinics Offer Effective Relationships, Education, and Health Promotion.#3: Funding Based on Current Quality Measures Perpetuates Health Inequities.ConclusionCommunity leaders identified ideal characteristics of quality primary healthcare, most of which are not currently measured. They expressed concern that linking clinic payment with quality metrics without considering social and structural determinants of health perpetuates social injustice in healthcare.
Quercetin attenuates neurotoxicity induced by iron oxide nanoparticles
Authors: Bardestani Akram , Ebrahimpour Shiva , Esmaeili Ali , Esmaeili Abolghasem 
Published: October 2021

AbstractIron oxide nanoparticles (IONPs) have been proposed as targeted carriers to deliver therapeutic molecules in the central nervous system (CNS). However, IONPs may damage neural tissue via free iron accumulation, protein aggregation, and oxidative stress. Neuroprotective effects of quercetin (QC) have been proven due to its antioxidant and anti-inflammatory properties. However, poor solubility and low bioavailability of QC have also led researchers to make various QC-involved nanoparticles to overcome these limitations. We wondered how high doses or prolonged treatment with quercetin conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) could improve cognitive dysfunction and promote neurogenesis without any toxicity. It can be explained that the QC inhibits protein aggregation and acts against iron overload via iron-chelating activity, iron homeostasis genes regulation, radical scavenging, and attenuation of Fenton/Haber–Weiss reaction. In this review, first, we present brain iron homeostasis, molecular mechanisms of iron overload that induced neurotoxicity, and the role of iron in dementia-associated diseases. Then by providing evidence of IONPs neurotoxicity, we discuss how QC neutralizes IONPs neurotoxicity, and finally, we make a brief comparison between QC and conventional iron chelators. In this review, we highlight that QC as supplementation and especially in conjugated form reduces iron oxide nanoparticles neurotoxicity in clinical application.
Multifunctional silica nanocomposites prime tumoricidal immunity for efficient cancer immunotherapy
Authors: Yang Linnan , Li Feng , Cao Yongsheng , Liu Qiang , Jing Guoxin , Niu Jintong , Sun Feiyue , Qian Yechang , Wang Shilong , Li Ang 
Published: October 2021

AbstractThe tumor immune microenvironment (TIME) has been demonstrated to be the main cause of cancer immunotherapy failure in various malignant tumors, due to poor immunogenicity and existence of immunosuppressive factors. Thus, establishing effective treatments for hostile TIME remodeling has considerable potential to enhance immune response rates for durable tumor growth retardation. This study aims to develop a novel nanocomposite, polyethyleneimine-modified dendritic mesoporous silica nanoparticles loaded with microRNA-125a (DMSN-PEI@125a) to synergistically enhance immune response and immunosuppression reversion, ultimately generating a tumoricidal environment. Our results showed that DMSN-PEI@125a exhibited excellent ability in cellular uptake by murine macrophages and the cervical cancer cell line TC-1, repolarization of tumor associated macrophages (TAMs) to M1 type in a synergistic manner, and promotion of TC-1 immunogenic death. Intratumor injection of DMSN-PEI@125a facilitated the release of more damage-related molecular patterns and enhanced the infiltration of natural killer and CD8+ T cells. Meanwhile, repolarized TAMs could function as a helper to promote antitumor immunity, thus inhibiting tumor growth in TC-1 mouse models in a collaborative manner. Collectively, this work highlights the multifunctional roles of DMSN-PEI@125a in generating an inflammatory TIME and provoking antitumor immunity, which may serve as a potential agent for cancer immunotherapy.
Evaluating health related quality of life in outpatients receiving anti-cancer treatment: results from an observational, cross-sectional study
Authors: Oh Hae-Jin Suh , Menéndez Ángeles Flórez , Santos Víctor Sacristán , Martínez Ángeles Rodríguez , Ribeiro Francisca Fernández , Vilanova-Trillo Lucía , Figueiras Manuel Constenla , Ferreiros Manuel Pereiro 
Published: October 2021

Abstract
Background
The aim of the study was to assess health-related quality of life (HRQOL) in outpatients receiving anti-cancer treatment.

Methods
Observational, cross-sectional, single-center study that assessed HRQOL in cancer patients receiving antineoplastic treatment.

Results
A total of 184 patients were included in the study; the median total FACT-G score was 66 ± 12.9; the scores for the physical well-being, social/family well-being, emotional well-being and functional well-being domains were 17.8 + 4.8, 19.1 ± 4.4, 14.8 ± 3.8 and 14.3 ± 4.7 respectively. Patients with adverse events had poorer HRQOL compared to those without them (FACT-G score 62.2 vs. 67.3; p < 0.05). In the multivariate analysis the variables associated with poorer HRQOL in the form of a gradient were tumor stage and performance status (ECOG); female sex was also associated with poorer HRQOL.

Conclusion
In our study, the neoplastic disease and anti-cancer treatment toxicities had an impact on HRQOL. Patients had poorer scores in the functional well-being domain and higher ones in the social/family well-being domain. Variables associated with worse HRQOL were tumor stage, performance status (ECOG) and female sex.
Measuring self-reported ability to perform activities of daily living: a Rasch analysis
Authors: Wæhrens Eva Ejlersen , Kottorp Anders , Nielsen Kristina Tomra 
Published: October 2021

Abstract
Background
Since the number of persons diagnosed with multi-morbidity is increasing, there is a need for generic instruments to be able to assess, measure and compare ADL ability across diagnoses. Accordingly, the ADL-Interview (ADL-I) was developed to be used in rehabilitation research and clinical practice. The aim of this study was to investigate if the ADL-I can be used to provide valid and reliable ADL ability measures across gender and diagnostic groups.

Methods
ADL-I data were extracted from an existing research database on persons with chronic conditions including medical, rheumatological, oncological, neurological, geriatric and psychiatric diagnoses. Data were analysed based on Rasch Measurement methods to examine: the psychometric properties of the rating scale; ADL item and person fit to the Rasch model; if the difficulty of the ADL tasks differs across gender and diagnostic groups, and if the ADL-I provides precise and reliable measures of ADL ability.

Results
Data on n = 2098 persons were included in the final analysis. Initial evaluation of the 0–3 rating scale revealed threshold disordering between categories 1 and 2. After removal of 16 underfitting items, the variance explained by the Rasch dimension increased from 54.3 to 58.0%, thresholds were ordered, but the proportion of persons with misfitting ADL-I measures increased slightly from 8.7 to 9.1%. The person separation index improved slightly from 2.75 to 2.99 (reliability = 0.90). Differential test function analysis, however, supported that the 16 underfitting items did not represent a threat to the measurement system. Similarly, ADL items displaying differential item functioning across gender and diagnoses did not represent a threat to the measurement system. The ADL items and participants were well distributed along the scale, with item and person measures well targeted to each other, indicating a small ceiling effect and no floor effect.

Conclusions
The study results overall suggest that the ADL-I is producing valid and reliable measures across gender and diagnostic groups among persons within a broad range of ADL ability, providing evidence to support generic use of the ADL-I.

Trial registration
N/A.