Publications by authors named "Hazha Jamal Hidayat"

15 Publications

  • Page 1 of 1

The Role of Circular RNAs in the Carcinogenesis of Bladder Cancer.

Front Oncol 2022 28;12:801842. Epub 2022 Feb 28.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Circular RNAs (circRNAs) are a group of transcripts with enclosed configurations which can regulate gene expression. These transcripts have important roles in normal development and in the pathogenesis of disorders. Recent evidence has supported involvement of circRNAs in the development of bladder cancer. Several circRNAs such as circ_0058063, hsa-circRNA-403658, circPDSS1, circCASC15, circRNA-MYLK, and circRNA_103809 have been upregulated in bladder cancer samples. On the other hand, hsa_circ_0137606, BCRC-3, circFUT8, hsa_circ_001598, circSLC8A1, hsa_circ_0077837, hsa_circ_0004826, and circACVR2A are among downregulated circRNAs in bladder cancer. Numerous circRNAs have diagnostic or prognostic value in bladder cancer. In this review, we aim to outline the latest findings about the role of circRNAs in bladder cancer and introduce circRNAs for further investigations as therapeutic targets.
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http://dx.doi.org/10.3389/fonc.2022.801842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918517PMC
February 2022

Genome sequence analysis of SARS-COV-2 isolated from a COVID-19 patient in Erbil, Iraq.

Appl Nanosci 2022 Feb 7:1-7. Epub 2022 Feb 7.

Department of Biology, College of Education, Salahaddin University, Kurdistan Region, Iraq.

In the city of Wuhan, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first recognized among humans at the end of December 2019, and has since spread to every country around the world. The emergence of this new coronavirus has attracted global attention to work towards finding a treatment and developing an effective vaccine against the virus. In this study, we sequence a full genome of SARS-COV-2 isolated from a male patient in the city of Erbil, Iraq. The virus was sequenced using Sanger sequencer and 21 distinct mutations were found in our isolate compared to the full genome sequence of the SARS-COV-2 isolated from the city of Wuhan/China (Accession number: NC_045512.2). Sequence analysis showed that four of the mutations were located at the spike glycoprotein (S), and ten of them were in nonstructural proteins (nsp1, nsp3, nsp12, and orf3a), which had been shown to be related to structural changes at various sites. Moreover, phylogenetic analysis and transmission supported the conclusion that the cases in Iraq were of independent origins of infections and had a close relation to the isolates from Iran. This is the first report on the DNA sequence of the SARS-CoV-2 genome isolated from the Kurdistan region of Iraq.
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http://dx.doi.org/10.1007/s13204-021-02300-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818371PMC
February 2022

The emerging roles of NGS in clinical oncology and personalized medicine.

Pathol Res Pract 2022 Feb 10;230:153760. Epub 2022 Jan 10.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Next-generation sequencing (NGS) has been increasingly popular in genomics studies over the last decade, as new sequencing technology has been created and improved. Recently, NGS started to be used in clinical oncology to improve cancer therapy through diverse modalities ranging from finding novel and rare cancer mutations, discovering cancer mutation carriers to reaching specific therapeutic approaches known as personalized medicine (PM). PM has the potential to minimize medical expenses by shifting the current traditional medical approach of treating cancer and other diseases to an individualized preventive and predictive approach. Currently, NGS can speed up in the early diagnosis of diseases and discover pharmacogenetic markers that help in personalizing therapies. Despite the tremendous growth in our understanding of genetics, NGS holds the added advantage of providing more comprehensive picture of cancer landscape and uncovering cancer development pathways. In this review, we provided a complete overview of potential NGS applications in scientific and clinical oncology, with a particular emphasis on pharmacogenomics in the direction of precision medicine treatment options.
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http://dx.doi.org/10.1016/j.prp.2022.153760DOI Listing
February 2022

Signaling pathways modulated by miRNAs in breast cancer angiogenesis and new therapeutics.

Pathol Res Pract 2022 Feb 10;230:153764. Epub 2022 Jan 10.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

MicroRNAs (miRNAs) act as oncogenes or tumor suppressors by suppressing the expression of target genes, some of which are engaged in angiogenic signaling pathways directly or indirectly. Tumor development and metastasis are dependent on angiogenesis, and it is the main reason for the poor prognosis of cancer patients. New blood vessels are formed from pre-existing vessels when angiogenesis occurs. Thus, it is essential to develop primary tumors and the spread of cancer to surrounding tissues. MicroRNAs (miRNAs) are small noncoding RNAs involved in various biological processes. They can bind to the 3'-UTR of their target genes and prevent them from expressing. MiRNAs control the activity of endothelial cells (ECs) through altering many biological pathways, which plays a key role in cancer progression and angiogenesis. Recent findings revealed that tumor-derived extracellular vesicles participated directly in the control of tumor angiogenesis by delivering miRNAs to ECs. miRNAs recently show great promise in cancer therapies to inhibit angiogenesis. In this study, we showed the miRNA-regulated signaling pathways in tumor angiogenesis with highlighting the anti-angiogenic therapy response and miRNA delivery methods that have been used to inhibit angiogenesis in both in vivo and in vitro studies.
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http://dx.doi.org/10.1016/j.prp.2022.153764DOI Listing
February 2022

Exploring the interaction of quercetin-3-O-sophoroside with SARS-CoV-2 main proteins by theoretical studies: A probable prelude to control some variants of coronavirus including Delta.

Arab J Chem 2021 Oct 28;14(10):103353. Epub 2021 Jul 28.

Department of Medical Nanotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

The aim of this study was to investigate the mechanism of interaction between quercetin-3-O-sophoroside and different SARS-CoV-2's proteins which can bring some useful details about the control of different variants of coronavirus including the recent case, Delta. The chemical structure of the quercetin-3-O-sophoroside was first optimized. Docking studies were performed by CoV disease-2019 (COVID-19) Docking Server. Afterwards, the molecular dynamic study was done using High Throughput Molecular Dynamics (HTMD) tool. The results showed a remarkable stability of the quercetin-3-O-sophoroside based on the calculated parameters. Docking outcomes revealed that the highest affinity of quercetin-3-O-sophoroside was related to the RdRp with RNA. Molecular dynamic studies showed that the target E protein tends to be destabilized in the presence of quercetin-3-O-sophoroside. Based on these results, quercetin-3-O-sophoroside can show promising inhibitory effects on the binding site of the different receptors and may be considered as effective inhibitor of the entry and proliferation of the SARS-CoV-2 and its different variants. Finally, it should be noted, although this paper does not directly deal with the exploring the interaction of main proteins of SARS-CoV-2 Delta variant with quercetin-3-O-sophoroside, at the time of writing, no direct theoretical investigation was reported on the interaction of ligands with the main proteins of Delta variant. Therefore, the present data may provide useful information for designing some theoretical studies in the future for studying the control of SARS-CoV-2 variants due to possible structural similarity between proteins of different variants.
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http://dx.doi.org/10.1016/j.arabjc.2021.103353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317451PMC
October 2021

MicroRNAs: Important Players in Breast Cancer Angiogenesis and Therapeutic Targets.

Front Mol Biosci 2021 26;8:764025. Epub 2021 Oct 26.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The high incidence of breast cancer (BC) is linked to metastasis, facilitated by tumor angiogenesis. MicroRNAs (miRNAs or miRs) are small non-coding RNA molecules that have an essential role in gene expression and are significantly linked to the tumor development and angiogenesis process in different types of cancer, including BC. There's increasing evidence showed that various miRNAs play a significant role in disease processes; specifically, they are observed and over-expressed in a wide range of diseases linked to the angiogenesis process. However, more studies are required to reach the best findings and identify the link among miRNA expression, angiogenic pathways, and immune response-related genes to find new therapeutic targets. Here, we summarized the recent updates on miRNA signatures and their cellular targets in the development of breast tumor angiogenetic and discussed the strategies associated with miRNA-based therapeutic targets as anti-angiogenic response.
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http://dx.doi.org/10.3389/fmolb.2021.764025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582349PMC
October 2021

Role of lncRNA BANCR in Human Cancers: An Updated Review.

Front Cell Dev Biol 2021 2;9:689992. Epub 2021 Aug 2.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Being located in a gene desert region on 9q21.11-q21.12, BRAF-activated non-protein coding RNA (BANCR) is an lncRNA with 693 bp length. It has been discovered in 2012 in a research aimed at assessment of gene expression in the melanocytes in association with mutation. Increasing numbers of studies have determined its importance in the tumorigenesis through affecting cell proliferation, migration, invasion, apoptosis, and epithelial to mesenchymal transition. BANCR exerts its effects via modulating some tumor-related signaling pathways particularly MAPK and other regulatory mechanisms such as sponging miRNAs. BANCR has been up-regulated in endometrial, gastric, breast, melanoma, and retinoblastoma. Conversely, it has been down-regulated in some other cancers such as those originated from lung, bladder, and renal tissues. In some cancer types such as colorectal cancer, hepatocellular carcinoma and papillary thyroid carcinoma, there is no agreement about BANCR expression, necessitating the importance of additional functional studies in these tissues. In the present manuscript, we review the investigations related to BANCR expression changes in cancerous cell lines, clinical samples, and animal models of cancer. We also discuss the outcome of its deregulation in cancer progression, prognosis, and the underlying mechanisms of these observations.
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http://dx.doi.org/10.3389/fcell.2021.689992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367322PMC
August 2021

The role of circular RNAs in the development of hepatocellular carcinoma.

Pathol Res Pract 2021 Jul 24;223:153495. Epub 2021 May 24.

Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Circular RNAs (circRNAs) are a group of regulatory non-coding transcripts, which partake in the pathobiology of hepatocellular carcinoma (HCC). Numerous micro-array based investigations have discovered aberrant expression of circRNAs in HCC samples in comparison with para-cancerous sections. Furthermore, a number of in vitro and in vivo experimentations have aimed at understanding the molecular pathways of circRNAs contribution in the evolution of HCC. CircRNAs have interplay with a number of transcription factors such as ZEB1 that possibly mediates the effects of these transcripts in the epithelial-mesenchymal transition. Moreover, circRNAs functionally interact with miRNAs. CircRNA_0000502/ miR-124, circ_0001955/ miR-145-5p, circ_0001955/ miR-516a-5p and hsa_circ_0001955/miR-145-5p are examples of such interactions in the context of HCC. CircRNAs not only predict the course of HCC, but also, they can differentiate HCC samples from non-malignant liver tissues. In this review article, we have provided an inclusive summary of researches that quantified circRNAs profile in HCC. We also provide evidence for application of circRNAs as HCC biomarkers.
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http://dx.doi.org/10.1016/j.prp.2021.153495DOI Listing
July 2021

Long Non-coding RNA RMRP in the Pathogenesis of Human Disorders.

Front Cell Dev Biol 2021 30;9:676588. Epub 2021 Apr 30.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

RNA component of mitochondrial RNA processing endoribonuclease (RMRP) is a non-coding transcript firstly acknowledged for its association with the cartilage-hair hypoplasia (CHH) syndrome, a rare autosomal recessive condition. This transcript has been spotted in both nucleus and mitochondria. In addition to its role in the pathogenesis of CHH, RMRP participates in the pathogenesis of cancers. Independent studies in bladder cancer, colon cancer, hepatocellular carcinoma, lung cancer, breast carcinoma and multiple myeloma have confirmed the oncogenic effects of RMRP. Mechanistically, RMRP serves as a sponge for some miRNAs such as miR-206, miR-613, and miR-217. In addition to these miRNAs, expressions of tens of miRNAs have been altered following RMRP silencing, implying the vast extent of RMRP/miRNA network. In the present narrative review, we explain the role of RMRP in the development of cancers and some other non-malignant disorders.
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http://dx.doi.org/10.3389/fcell.2021.676588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120005PMC
April 2021

NF-KappaB interacting LncRNA: Review of its roles in neoplastic and non-neoplastic conditions.

Biomed Pharmacother 2021 Jul 23;139:111604. Epub 2021 Apr 23.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

NF-κB Interacting LncRNA (NKILA) is a long non-coding RNA (lncRNA) which has inhibitory roles on NF-κB. NF-κB regulates expression of several molecules participating in various crucial physiological reaction including immune responses, cell proliferation and differentiation, as well as cell death. Therefore, NKILA can be involved in the pathogenesis of a wide spectrum of human disorders. Numerous studies in hepatocellular carcinoma, breast cancer, melanoma, glioma and other types of neoplasms have indicated the role of NKILA in blockage of tumor growth and inhibition of metastasis. Further in vitro and in vivo assays including apoptosis assays, knock-down and knock-in experiments have verified such roles. In addition to its roles in neoplastic conditions, NKILA is involved in the pathogenesis of immune-related disorders. Dysregulation of expression of NKILA has been reported in patients with diverse conditions such as epilepsy, osteoarthritis, periodontitis and coronary artery disease. In this paper, we recapitulate the contribution of NKILA in neoplastic and non-neoplastic conditions.
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http://dx.doi.org/10.1016/j.biopha.2021.111604DOI Listing
July 2021

The Impact of Non-coding RNAs in the Epithelial to Mesenchymal Transition.

Front Mol Biosci 2021 26;8:665199. Epub 2021 Mar 26.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Epithelial to mesenchymal transition (EMT) is a course of action that enables a polarized epithelial cell to undertake numerous biochemical alterations that allow it to adopt features of mesenchymal cells such as high migratory ability, invasive properties, resistance to apoptosis, and importantly higher-order formation of extracellular matrix elements. EMT has important roles in implantation and gastrulation of the embryo, inflammatory reactions and fibrosis, and transformation of cancer cells, their invasiveness and metastatic ability. Regarding the importance of EMT in the invasive progression of cancer, this process has been well studies in in this context. Non-coding RNAs (ncRNAs) have been shown to exert critical function in the regulation of cellular processes that are involved in the EMT. These processes include regulation of some transcription factors namely SNAI1 and SNAI2, ZEB1 and ZEB2, Twist, and E12/E47, modulation of chromatin configuration, alternative splicing, and protein stability and subcellular location of proteins. In the present paper, we describe the influence of ncRNAs including microRNAs and long non-coding RNAs in the EMT process and their application as biomarkers for this process and cancer progression and their potential as therapeutic targets.
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http://dx.doi.org/10.3389/fmolb.2021.665199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033041PMC
March 2021

MicroRNA: A signature for cancer progression.

Biomed Pharmacother 2021 Jun 23;138:111528. Epub 2021 Mar 23.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

MicroRNAs (miRNAs) are a group of small non-coding RNAs that post-transcriptionally control expression of genes by targeting mRNAs. miRNA alterations partake in the establishment and progression of different types of human cancer. Consequently, expression profiling of miRNA in human cancers has correlations with cancer detection, staging, progression, and response to therapies. Particularly, amplification, deletion, abnormal pattern of epigenetic factors and the transcriptional factors that mediate regulation of primary miRNA frequently change the landscape of miRNA expression in cancer. Indeed, changes in the quantity and quality of miRNAs are associated with the initiation of cancer, its progression and metastasis. Additionally, miRNA profiling has been used to categorize genes that can affect oncogenic pathways in cancer. Here, we discuss several circulating miRNA signatures, their expression profiles in different types of cancer and their impacts on cellular processes.
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http://dx.doi.org/10.1016/j.biopha.2021.111528DOI Listing
June 2021

A Diagnostic Panel for Acquired Immune-Mediated Polyneuropathies Based on the Expression of lncRNAs.

Front Immunol 2021 23;12:643615. Epub 2021 Feb 23.

Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Long non-coding RNAs (lncRNAs) have been shown to alter immune responses, thus contributing to the pathobiology of autoimmune conditions. We investigated the expression levels of ANRIL, PICART1, MALAT1, CCAT1, CCAT2, and CCHE1 lncRNAs in acute and chronic inflammatory demyelinating polyneuropathy (AIDP and CIDP). ANRIL, PICART1, MALAT1, CCAT1, CCAT2, and CCHE1 lncRNAs were significantly downregulated in individuals with both AIDP and CIDP compared with unaffected individuals. Gender-based comparisons also verified such downregulations in both male and female subjects compared with sex-matched unaffected controls for all lncRNAs. There was no significant difference in the expression of any of the lncRNAs between cases with AIDP and cases with CIDP. While the expression levels of ANRIL and PICART1 were significantly correlated in healthy subjects (r = 0.86, = 8.5E-16), similar analysis in cases with AIDP and CIDP revealed no significant correlation. The most robust correlation among patients was detected between ANRIL and MALAT1 lncRNAs (r = 0.59, = 3.52E-6). ANRIL, MALAT1, and PICART1 had the diagnostic power of 0.96, 0.94, and 0.92 in distinguishing between cases with CIDP and controls, respectively. A combination of all lncRNAs resulted in 0.95 diagnostic power with a sensitivity of 0.85 and specificity of 0.96 for this purpose. Diagnostic power values of these lncRNAs in differentiation between cases with AIDP and controls were 0.98, 0.95, and 0.93, respectively. The combinatorial diagnostic power reached 0.98 for differentiation between cases with AIDP and controls. The six-lncRNA panel could differentiate combined cases with AIDP and CIDP from controls with area under the curve (AUC), sensitivity, and specificity values of 0.97, 0.90, and 0.96, respectively. Collectively, the lncRNA panel is suggested as a sensitive and specific diagnostic panel for acquired immune-mediated polyneuropathies.
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http://dx.doi.org/10.3389/fimmu.2021.643615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940672PMC
September 2021

The role of HPV gene expression and selected cellular MiRNAs in lung cancer development.

Microb Pathog 2021 Jan 7;150:104692. Epub 2020 Dec 7.

Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Background: The high mortality rate of lung cancer can be justified that strong need to explore new aspect of tumor biology. Human papillomavirus (HPV) has been detected as risk factor for the development of lung cancer. The aim of this study was to determine the role of HPV and cellular/miRNAs genes expression in the epithelial-mesenchymal transition (EMT) and development of lung cancer.

Methods: In this case-control study, 109 lung cancer tissue and 52 controls were included. We analyzed the presence of HPV infection, its genotypes (in positive samples) and the expression of viral genes (E2, E6 and E7). Also, We examined the expression of celluar factors including (a) p53 and retinoblastoma (Rb) (as anti-carcinogenic genes), (b) EMT related genes, (c) selected miRNAs.

Results: Our results reported 51.4% and 23.1% of HPV genome in tumor tissues and control tissues samples, respectively. There was a significant association between the HPV positive status and lung cancer (OR = 3.26, 95% C.I = 1.47-7.02, P = 0.001). HPV type 16 was the most prevalent genotype in tissues. The expression of p53, RB, TIMP1, CCNG-1, E-cad and PTPN13 were decreased while MMP-2 and N-cad were increased in HPV-positive tumor/control tissues compared to HPV-negative tissues. Also, among miRNAs, let-7, miR-23, miR-34, miR-125, miR-146 were downregulated and miR-20, miR-424 were upregulated in HPV-positve tissues compared to HPV-negative tissues.

Conclusion: This study demonstrated that HPV infection and interaction with cellular genes and miRNAs promote EMT which involved in the lung cancer development.
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http://dx.doi.org/10.1016/j.micpath.2020.104692DOI Listing
January 2021

Down-regulation of Survivin and Bcl-2 concomitant with the activation of caspase-3 as a mechanism of apoptotic death in KG1a and K562 cells upon exposure to a derivative from ciprofloxacin family.

Toxicol Appl Pharmacol 2020 12 7;409:115331. Epub 2020 Nov 7.

Department of Biology, College of Education, Salahaddin University-Erbil, Erbil, Kurdistan Region, Iraq.

Ciprofloxacin derivatives belong to a family of antibiotics called fluoroquinolones. Recently, these compounds have been recommended for the treatment of cancer. In the present study, we assessed the cytotoxicity of several new synthetic ciprofloxacin derivatives and the apoptosis-inducing activity of the most efficient derivative in two human myeloid leukemia K562 and KG1-a cell lines. Among the prepared ciprofloxacin derivatives, 1-cyclopropyl-7-(4-(2-((3,7-dimethyloct-6-en-1-yl)oxy)-2-oxoethyl)piperazin-1-yl)-6-fluoro-4-oxo-1,4dihydroquinoline-3-carboxylic acid (4-DMOCP) was more active compound with IC50 of 19.56 and 22.13 μM for K562 and KG1-a, respectively. Apoptotic activity of the 4-DMOCP was examined morphologically through Hoechst 33258 staining, Annexin V/PI double staining, and caspase-3 activity assays. Changes in the expression level of some apoptosis-related genes and protein, including Bcl-2, Bax, Survivin, p53, Caspase-8 and Caspase-9 were evaluated by the real-time quantitative PCR (qRT PCR) and western blotting. The qRT PCR analysis showed that 4-DMOCP induces apoptosis in both cell lines via the down-regulation of Survivin and Bcl2, up-regulation of caspase-8 and -9, as well as a time-dependent increase in the Bax/Bcl2 transcripts. The mRNA level of p53 was also increased in both cell lines. In addition, western blot analysis revealed that treatment with the compound, down-regulated the protein expression levels of Bcl2 and Survivin and up-regulated the protein level of Bax in both cell lines. These findings suggest that these new compounds can be good candidates for the treatment of acute and chronic myeloid leukemia.
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http://dx.doi.org/10.1016/j.taap.2020.115331DOI Listing
December 2020
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