Publications by authors named "Santanu Dasgupta"

119 Publications

Clinicopathologic significance and race-specific prognostic association of MYB overexpression in ovarian cancer.

Sci Rep 2021 Jun 18;11(1):12901. Epub 2021 Jun 18.

Department of Pathology, College of Medicine, University of South Alabama, Mobile, AL, 36617, USA.

Late diagnosis, unreliable prognostic assessment, and poorly-guided therapeutic planning result in dismal survival of ovarian cancer (OC) patients. Therefore, identifying novel functional biomarker(s) is highly desired for improved clinical management. MYB is an oncogenic transcription factor with emerging functional significance in OC. Here we examined its clinicopathologic significance by immunohistochemistry and TCGA/GTex data analyses. Aberrant MYB expression was detected in 94% of OC cases (n = 373), but not in the normal ovarian tissues (n = 23). MYB was overexpressed in all major epithelial OC histological subtypes exhibiting the highest incidence (~ 97%) and overall expression in serous and mucinous carcinomas. MYB expression correlated positively with tumor grades and stages. Moreover, MYB exhibited race-specific prognostic association. Moderate-to-high MYB levels were significantly associated with both poor overall- (p = 0.02) and progression-free (p = 0.02) survival in African American (AA), but not in the Caucasian American (CA) patients. Consistent with immunohistochemistry data, we observed significantly higher MYB transcripts in OC cases (n = 426) than normal ovary (n = 88). MYB transcripts were significantly higher in all epithelial OC subtypes, compared to normal, and its greater levels predicted poor survival in AA OC, but not CA OC, patients. Thus, MYB appears to be a useful clinical biomarker for prognostication, especially in AA patients.
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http://dx.doi.org/10.1038/s41598-021-92352-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213794PMC
June 2021

Microalgae as feed ingredients: recent developments on their role in immunomodulation and gut microbiota of aquaculture species.

FEMS Microbiol Lett 2021 06;368(11)

Reliance Technology Group, Reliance Industries Limited, Reliance Corporate Park, Ghansoli, Thane-Belapur Road, Navi Mumbai 400701, India.

Microalgae are rapidly evolving alternative ingredients in food and feed. Desirable nutritional and functional qualities make them high potential sources of feed ingredients. Certain microalgae species are known to accumulate large amounts of protein, containing all essential amino acids while some species contain essential fatty acids and bioactive compounds hence offering several possible health benefits. However, successful inclusion of microalgae-based products in feed requires a clear understanding of physiological responses and microbiota of animals receiving microalgae diets. In this review, key microalgae-based feed ingredients and their effect on gut microbiome and immunomodulatory responses of microalgae fed animals, with a focus on aquatic species will be discussed.
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http://dx.doi.org/10.1093/femsle/fnab071DOI Listing
June 2021

Mitochondrial fusion and fission: The fine-tune balance for cellular homeostasis.

FASEB J 2021 06;35(6):e21620

Mitchell Cancer Institute, University of South Alabama, Mobile, AL, USA.

Mitochondria are highly dynamic, maternally inherited cytoplasmic organelles, which fulfill cellular energy demand through the oxidative phosphorylation system. Besides, they play an active role in calcium and damage-associated molecular patterns signaling, amino acid, and lipid metabolism, and apoptosis. Thus, the maintenance of mitochondrial integrity and homeostasis is extremely critical, which is achieved through continual fusion and fission. Mitochondrial fusion allows the transfer of gene products between mitochondria for optimal functioning, especially under metabolic and environmental stress. On the other hand, fission is crucial for mitochondrial division and quality control. The imbalance between these two processes is associated with various ailments such as cancer, neurodegenerative and cardiovascular diseases. This review discusses the molecular mechanisms that control mitochondrial fusion and fission and how the disruption of mitochondrial dynamics manifests into various disease conditions.
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http://dx.doi.org/10.1096/fj.202100067RDOI Listing
June 2021

Characterization of nanocellulose production by strains of Komagataeibacter sp. isolated from organic waste and Kombucha.

Carbohydr Polym 2021 Aug 7;266:118176. Epub 2021 May 7.

Synthetic Biology Group, Research and Development Centre, Reliance Industries Limited, India.

Bacterial nanocellulose production is gaining popularity owing to its applications in food, cosmetics and medical industry. Three Acetobacter strains isolated from organic waste and fermented tea were identified using 16S rDNA sequencing and their ability to produce nanocellulose was studied. Strain isolated from Kombucha has 99% homology with Komagataeibacter rhaeticus DSM 16663 T. This is the first report where nanocellulose productivity of this strain with different carbon sources such as glucose, glycerol, fructose and sucrose has been studied. 1% glycerol was found to be optimal concentration, with up to 69% of the utilized carbon converted to nanocellulose. Maximum productivity of 4.5 g/L of bacterial nanocellulose was obtained. Average nitrogen and phosphorus consumption rate was 45 mg/L/day each. Physical properties such as crystallinity, fibril dimensions, and glass transition temperature were studied. Bacterial cellulose was 80% crystalline when glycerol and glucose were used as carbon source and 73% for fructose and sucrose. Renewable materials such as bacterial cellulose with their unique properties are the future for applications in the field of cosmetics, composite and wound care.
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http://dx.doi.org/10.1016/j.carbpol.2021.118176DOI Listing
August 2021

Intracellular localization of the mycobacterial stressosome complex.

Sci Rep 2021 May 12;11(1):10060. Epub 2021 May 12.

Department of Cell and Molecular Biology, Biomedical Centre, Uppsala University, Box 596, 751 24, Uppsala, Sweden.

Microorganisms survive stresses by alternating the expression of genes suitable for surviving the immediate and present danger and eventually adapt to new conditions. Many bacteria have evolved a multiprotein "molecular machinery" designated the "Stressosome" that integrates different stress signals and activates alternative sigma factors for appropriate downstream responses. We and others have identified orthologs of some of the Bacillus subtilis stressosome components, RsbR, RsbS, RsbT and RsbUVW in several mycobacteria and we have previously reported mutual interactions among the stressosome components RsbR, RsbS, RsbT and RsbUVW from Mycobacterium marinum. Here we provide evidence that "STAS" domains of both RsbR and RsbS are important for establishing the interaction and thus critical for stressosome assembly. Fluorescence microscopy further suggested co-localization of RsbR and RsbS in multiprotein complexes visible as co-localized fluorescent foci distributed at scattered locations in the M. marinum cytoplasm; the number, intensity and distribution of such foci changed in cells under stressed conditions. Finally, we provide bioinformatics data that 17 (of 244) mycobacteria, which lack the RsbRST genes, carry homologs of Bacillus cereus genes rsbK and rsbM indicating the existence of alternative σ activation pathways among mycobacteria.
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http://dx.doi.org/10.1038/s41598-021-89069-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115616PMC
May 2021

Empowering blue economy: From underrated ecosystem to sustainable industry.

J Environ Manage 2021 Aug 29;291:112697. Epub 2021 Apr 29.

Reliance Technology Group, Reliance Industries Limited, Reliance Corporate Park, Ghansoli, Thane- Belapur Road, Navi Mumbai, 400701, India. Electronic address:

With increasing demand for resources to achieve global food-water-energy nexus and rapid decline in land-based sources, oceans represent both solution and boost to sustainable environment and economy. In addition to fundamental part of earth's ecosystem for uncatalogued diversity of life, oceans are undervalued economy powerhouse with gross marine product value. With sustainable management of existing assets including shipping, transportation, manufacturing, fisheries, tourism and exploration of new business like marine biotechnology and renewable energy, the ocean or blue economy has potential to fulfill sustainable development goals (SDG). In spite of recognition of blue economy as a new economic frontier, investments by existing industries and emergence of new ones are limited and less known, hence require more in depth attention and scientific understanding. In the present study, authors present a systematic comparative assessment of blue economy sectors with distinct challenges and strategies to be further explored and implemented for industrial deployment. The conceptualization of integrated routes of bio(economy) by the current study can act as gateway for key stakeholders, i.e. governance, bluepreneurs (scientists and industries) to prioritize technologies for sustainable applications of marine resources.
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http://dx.doi.org/10.1016/j.jenvman.2021.112697DOI Listing
August 2021

Phycoremediation and photosynthetic toxicity assessment of lead by two freshwater microalgae Scenedesmus acutus and Chlorella pyrenoidosa.

Physiol Plant 2021 Feb 13. Epub 2021 Feb 13.

School of Biotechnology, Presidency University, Kolkata, India.

Heavy metal (HM) pollution is a serious agro-economic concern and algae can be used as one of the bioremediating agents as it can grow in different water bodies. In this study, the Scenedesmus acutus and Chlorella pyrenoidosa were exposed to various concentrations of Pb for 96 h and a multidimensional toxicity assessment has been performed by pulse amplitude modulation technique and Fourier transform infrared spectroscopy (FTIR). High-angle annular dark-field scanning transmission electron microscopy coupled energy dispersive spectroscopy (HAADF-S/TEM-EDS) detected intracellular localization of Pb , thus confirming algal bio-accumulation abilities. Sensitivity assay demonstrated that 500 and 400 ppm of Pb as minimum inhibitory concentrations (MIC50) for S. acutus and C. pyrenoidosa, respectively, which inhibited growth (OD) by >50% in 96 h. During bioremoval studies, S. acutus and C. pyrenoidosa were found to remove ∼52 and ∼32% of total Pb , respectively. The particulate analysis of Pb by ICP-OES showed >99.5% biosorption capacity by both the species. The biomass characterization by FTIR showed the involvement of various cell wall functional groups such as hydroxyl, alkane, and C=C groups in the biosorption of Pb by both the species. The noninvasive chlorophyll fluorescence techniques provide a quick insight on heavy metal stress and can be adapted as a rapid detection tool to study the Pb stress. S. acutus strain showed higher tolerance and higher bioremoval capacity than C. pyrenoidosa. However, both the species can be exploited for biosorption of Pb from aquatic streams as an alternative way for low cost Pb recovery systems.
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http://dx.doi.org/10.1111/ppl.13368DOI Listing
February 2021

An overview on mechanism, cause, prevention and multi-nation policy level interventions of dietary iron deficiency.

Crit Rev Food Sci Nutr 2021 Feb 5:1-15. Epub 2021 Feb 5.

Synthetic Biology Group, Reliance Corporate Park, Reliance Industries Limited, Ghansoli, Navi Mumbai, India.

Iron deficiency anemia (IDA) is probably the most ignored situation in the world of malnutrition-largely due to its slow progression. Multiple reasons can be attributed as the cause of IDA, which is not limited to any specific region or population; therefore, making it a matter of global concern. Despite the human body's ability to absorb and conserve iron stores, the gradual loss due to various physiological conditions leads to net deficiency of iron. Countless commercial iron supplements are available, but at given physiological conditions, almost all of these "Bio-not-available" iron forms quite often become ineffective. World Health Organization and other government bodies have jointly developed health advisories and tried to developed nutrition supplements several times in the last two decades. IDA, when combined with other disease conditions, becomes a life-threatening situation. At the same time, an overdose of iron could also be very harmful to the body. Therefore, it is important to deal with this situation with caution. This article covers iron metabolism, available options for iron supplementation, regulatory aspects and strategies to prevent IDA.
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http://dx.doi.org/10.1080/10408398.2021.1879005DOI Listing
February 2021

Photoautotrophic cultivation of Chlamydomonas reinhardtii in open ponds of greenhouse.

Arch Microbiol 2021 May 3;203(4):1439-1450. Epub 2021 Jan 3.

Reliance Industries Ltd, Mumbai, Maharashtra, 400701, India.

Chlamydomonas reinhardtii is one of the most characterized green algae. The open-pond cultivation can be challenging due to sensitivity of strain to fluctuating environmental conditions and unavailability of low-cost photoautotrophic media. In this study, the photoautotrophic growth of C. reinhardtii was evaluated in 1-m open ponds placed in greenhouse. Sodium bicarbonate (NaHCO) was evaluated as an alternative buffering agent to tris. The effect of buffer and pH was tested. The growth was studied in the presence of various nitrogen [urea and ammonium bicarbonate (NHHCO)] sources. In the study, it was found that 125-ppm NaHCO as an optimum concentration. The buffering agent in the media was found to have major impact on growth. Without buffering agent, culture did not grow, and pH drop was observed. The sodium bicarbonate-buffered media reported to have the lowest bacterial contamination (18.3%), highest AFDW per OD (0.39 ± 0.027 g/L) and higher Fv/Fm (0.714 ± 0.016), whereas these values were found to be 62%, 0.19 ± 0.02 g/L and 0.537 ± 0.053 for tris-grown culture, respectively. The pH 7.0-7.5 was determined as an optimum, whereas pH 6.5-7.0 and 8.0-8.5 were found to affect the growth and induce palmelloidy. The OD and AFDW of culture grown in NHHCO were found equivalent to a standard nitrogen source (NHCl), whereas culture shown poor growth in urea. Based on these data, NHHCO media recipe and the optimized cultivation parameters were selected for photoautotrophic cultivation of Chlamydomonas in greenhouse open ponds.
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http://dx.doi.org/10.1007/s00203-020-02124-2DOI Listing
May 2021

CRISPR-Cas12a (Cpf1): A Versatile Tool in the Plant Genome Editing Tool Box for Agricultural Advancement.

Front Plant Sci 2020 2;11:584151. Epub 2020 Nov 2.

Chinese Academy of Agricultural Sciences, Biotechnology Research Institute, Beijing China.

Global population is predicted to approach 10 billion by 2050, an increase of over 2 billion from today. To meet the demands of growing, geographically and socio-economically diversified nations, we need to diversity and expand agricultural production. This expansion of agricultural productivity will need to occur under increasing biotic, and environmental constraints driven by climate change. Clustered regularly interspaced short palindromic repeats-site directed nucleases (CRISPR-SDN) and similar genome editing technologies will likely be key enablers to meet future agricultural needs. While the application of CRISPR-Cas9 mediated genome editing has led the way, the use of CRISPR-Cas12a is also increasing significantly for genome engineering of plants. The popularity of the CRISPR-Cas12a, the type V (class-II) system, is gaining momentum because of its versatility and simplified features. These include the use of a small guide RNA devoid of trans-activating crispr RNA, targeting of T-rich regions of the genome where Cas9 is not suitable for use, RNA processing capability facilitating simpler multiplexing, and its ability to generate double strand breaks (DSB) with staggered ends. Many monocot and dicot species have been successfully edited using this Cas12a system and further research is ongoing to improve its efficiency in plants, including improving the temperature stability of the Cas12a enzyme, identifying new variants of Cas12a or synthetically producing Cas12a with flexible PAM sequences. In this review we provide a comparative survey of CRISPR-Cas12a and Cas9, and provide a perspective on applications of CRISPR-Cas12 in agriculture.
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http://dx.doi.org/10.3389/fpls.2020.584151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668199PMC
November 2020

Cadmium biosorption and biomass production by two freshwater microalgae Scenedesmus acutus and Chlorella pyrenoidosa: An integrated approach.

Chemosphere 2021 Apr 27;269:128755. Epub 2020 Oct 27.

School of Biotechnology, Presidency University, Kolkata, West Bengal, India. Electronic address:

Cadmium (Cd) contamination in different water bodies is a matter of serious concern, as it can cause biomagnification in our food chain up to several trophic levels. In this study, Cd toxicity was investigated in the micro-algae Chlorella pyrenoidosa and Scenedesmus acutus exposed to various concentrations of Cd for 96 h. The inhibitory and toxic effects of Cd on growth and photosynthetic parameters of algae were demonstrated. The bioremediation potentials of these algae were investigated and bioremoval mechanisms were confirmed using qualitative electron microscopic assay such as scanning/transmission electron microscope (S/TEM). The photochemical quenching (Fv/Fm), quantum yield (YII), relative electron transfer rate (rETR) and non-photochemical quenching (NPQ) were inhibited significantly and reduced by ≥ 50% of the control at MIC 50 values. The C. pyrenoidosa and S. acutus biomass have shown 30% and 20% reduction in carbon content and 10% and 12% reduction in nitrogen content at MIC50 values of Cd treatment, respectively. During bioremoval studies, C. pyrenoidosa and S. acutus have shown 45.45% and 57.14% Cd removal of Cd from initial concentration of 1.5 ppm. Out of total cadmium removal C. pyrenoidosa was reported 3% bioaccumulation and 97% biosorption. Whereas S. acutus showed 1.5% accumulation and 98.5% biosorption. The S/TEM images showed the surface accumulation and bioaccumulation of cadmium inside the cytoplasm, vacuoles, and chloroplast. Thus cultivating C. pyrenoidosa and S. acutus would be beneficial in Cd contaminated water bodies as they serve the dual purpose by Cd remediation and algal biomass production.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128755DOI Listing
April 2021

Potential of natural astaxanthin in alleviating the risk of cytokine storm in COVID-19.

Biomed Pharmacother 2020 Dec 16;132:110886. Epub 2020 Oct 16.

Synthetic Biology Group, Reliance Research & Development Centre, Reliance Industries Limited, Navi Mumbai, Maharashtra, 400701, India.

Host excessive inflammatory immune response to SARS-CoV-2 infection is thought to underpin the pathogenesis of COVID-19 associated severe pneumonitis and acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Once an immunological complication like cytokine storm occurs, anti-viral based monotherapy alone is not enough. Additional anti-inflammatory treatment is recommended. It must be noted that anti-inflammatory drugs such as JAK inhibitors, IL-6 inhibitors, TNF-α inhibitors, colchicine, etc., have been either suggested or are under trials for managing cytokine storm in COVID-19 infections. Natural astaxanthin (ASX) has a clinically proven safety profile and has antioxidant, anti-inflammatory, and immunomodulatory properties. There is evidence from preclinical studies that supports its preventive actions against ALI/ARDS. Moreover, ASX has a potent PPARs activity. Therefore, it is plausible to speculate that ASX could be considered as a potential adjunctive supplement. Here, we summarize the mounting evidence where ASX is shown to exert protective effect by regulating the expression of pro-inflammatory factors IL-1β, IL-6, IL-8 and TNF-α. We present reports where ASX is shown to prevent against oxidative damage and attenuate exacerbation of the inflammatory responses by regulating signaling pathways like NF-ĸB, NLRP3 and JAK/STAT. These evidences provide a rationale for considering natural astaxanthin as a therapeutic agent against inflammatory cytokine storm and associated risks in COVID-19 infection and this suggestion requires further validation with clinical studies.
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http://dx.doi.org/10.1016/j.biopha.2020.110886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566765PMC
December 2020

CRISPR based targeted genome editing of Chlamydomonas reinhardtii using programmed Cas9-gRNA ribonucleoprotein.

Mol Biol Rep 2020 Nov 19;47(11):8747-8755. Epub 2020 Oct 19.

Synthetic Biology Group, Reliance Corporate Park, Reliance Industries Ltd, Ghansoli, Navi Mumbai, 400701, India.

The clustered regularly interspaced short palindromic repeats (CRISPR) - Cas associated protein 9 (Cas9) system is very precise, efficient and relatively simple in creating genetic modifications at a predetermined locus in the genome. Genome editing with Cas9 ribonucleoproteins (RNPs) has reduced cytotoxic effects, off-target cleavage and increased on-target activity and the editing efficiencies. The unicellular alga Chlamydomonas reinhardtii is an emerging model for studying the production of high-value products for industrial applications. Development of C. reinhardtii as an industrial biotechnology host can be achieved more efficiently through genetic modifications using genome editing tools. We made an attempt to target MAA7 gene that encodes the tryptophan synthase β-Subunit using CRISPR-Cas9 RNPs to demonstrate knock-out and knock-in through homology-dependent repair template at the target site. In this study, we have demonstrated targeted gene knock-out in C. reinhardtii using programmed RNPs. Targeted editing of MAA7 gene was confirmed by sequencing the clones that were resistant to 5-Fluoroindole (5-FI). Non-homologous end joining (NHEJ) repair mechanism led to insertion, deletion, and/or base substitution in the Cas9 cleavage vicinity, encoding non-functional MAA7 protein product (knock-out), conferring resistance to 5-FI. Here, we report an efficient protocol for developing knock-out mutants in Chlamydomonas using CRISPR-Cas9 RNPs. The high potential efficiency of editing may also eliminate the need to select mutants by phenotype. These research findings would be more likely applied to other green algae for developing green cell factories to produce high-value molecules.
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http://dx.doi.org/10.1007/s11033-020-05922-5DOI Listing
November 2020

CRISPR-based assays for rapid detection of SARS-CoV-2.

Methods 2020 Oct 9. Epub 2020 Oct 9.

Reliance Industries Ltd, R&D-Synthetic Biology group, Reliance Corporate park, Navi Mumbai, India. Electronic address:

COVID-19 pandemic posed an unprecedented threat to global public health and economies. There is no effective treatment of the disease, hence, scaling up testing for rapid diagnosis of SARS-CoV-2 infected patients and quarantine them from healthy individuals is one the best strategies to curb the pandemic. Establishing globally accepted easy-to-access diagnostic tests is extremely important to understanding the epidemiology of the present pandemic. While nucleic acid based tests are considered to be more sensitive with respect to serological tests but present gold standard qRT-PCR-based assays possess limitations such as low sample throughput, requirement for sophisticated reagents and instrumentation. To overcome these shortcomings, recent efforts of incorporating LAMP-based isothermal detection, and minimizing the number of reagents required are on rise. CRISPR based novel techniques, when merge with isothermal and allied technologies, promises to provide sensitive and rapid detection of SARS-CoV-2 nucleic acids. Here, we discuss and present compilation of state-of-the-art detection techniques for COVID-19 using CRISPR technology which has tremendous potential to transform diagnostics and epidemiology.
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http://dx.doi.org/10.1016/j.ymeth.2020.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546951PMC
October 2020

Cellular and Molecular Progression of Prostate Cancer: Models for Basic and Preclinical Research.

Cancers (Basel) 2020 Sep 17;12(9). Epub 2020 Sep 17.

Cancer Biology Program, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.

We have witnessed noteworthy progress in our understanding of prostate cancer over the past decades. This basic knowledge has been translated into efficient diagnostic and treatment approaches leading to the improvement in patient survival. However, the molecular pathogenesis of prostate cancer appears to be complex, and histological findings often do not provide an accurate assessment of disease aggressiveness and future course. Moreover, we also witness tremendous racial disparity in prostate cancer incidence and clinical outcomes necessitating a deeper understanding of molecular and mechanistic bases of prostate cancer. Biological research heavily relies on model systems that can be easily manipulated and tested under a controlled experimental environment. Over the years, several cancer cell lines have been developed representing diverse molecular subtypes of prostate cancer. In addition, several animal models have been developed to demonstrate the etiological molecular basis of the prostate cancer. In recent years, patient-derived xenograft and 3-D culture models have also been created and utilized in preclinical research. This review is an attempt to succinctly discuss existing information on the cellular and molecular progression of prostate cancer. We also discuss available model systems and their tested and potential utility in basic and preclinical prostate cancer research.
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http://dx.doi.org/10.3390/cancers12092651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563251PMC
September 2020

Comprehensive Analysis of Expression, Clinicopathological Association and Potential Prognostic Significance of RABs in Pancreatic Cancer.

Int J Mol Sci 2020 Aug 4;21(15). Epub 2020 Aug 4.

Department of Pathology, College of Medicine, University of South Alabama, Mobile, AL 36617, USA.

RAB proteins (RABs) represent the largest subfamily of Ras-like small GTPases that regulate a wide variety of endosomal membrane transport pathways. Their aberrant expression has been demonstrated in various malignancies and implicated in pathogenesis. Using The Cancer Genome Atlas (TCGA) database, we analyzed the differential expression and clinicopathological association of genes in pancreatic ductal adenocarcinoma (PDAC). Of the 62 genes analyzed, five and ) exhibited statistically significant upregulation, while five ( and ) were downregulated in PDAC as compared to the normal pancreas. Racially disparate expression was also reported for and . However, no clear trend of altered expression was observed with increasing stage and grade, age, and gender of the patients. PDAC from occasional drinkers had significantly higher expression of compared to daily or weekly drinkers, whereas expression was significantly higher in social drinkers, compared to occasional ones. The expression of was significantly reduced in PDAC from diabetic patients, whereas was significantly lower in pancreatitis patients. More importantly, a significant association of high expression of and , and low expression of and was observed with poorer survival of PC patients. Together, our study suggests potential diagnostic and prognostic significance of RABs in PDAC, warranting further investigations to define their functional and mechanistic significance.
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http://dx.doi.org/10.3390/ijms21155580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432855PMC
August 2020

Author Correction: Extensive genomic diversity among Mycobacterium marinum strains revealed by whole genome sequencing.

Sci Rep 2020 Mar 18;10(1):5246. Epub 2020 Mar 18.

Department of Cell and Molecular Biology, Box 596, Biomedical Centre, SE-751 24, Uppsala, Sweden.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-61218-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078255PMC
March 2020

Author Correction: Cancer Testis Antigen Promotes Triple Negative Breast Cancer Metastasis and is Traceable in the Circulating Extracellular Vesicles.

Sci Rep 2020 Jan 31;10(1):1907. Epub 2020 Jan 31.

Departments of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-58045-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994463PMC
January 2020

Insight into the biology of Mycobacterium mucogenicum and Mycobacterium neoaurum clade members.

Sci Rep 2019 12 17;9(1):19259. Epub 2019 Dec 17.

Department of Cell and Molecular Biology, Box 596, BMC, Uppsala University, SE 751 24, Uppsala, Sweden.

Nontuberculous mycobacteria, NTM, are of growing concern and among these members of the Mycobacterium mucogenicum (Mmuc) and Mycobacterium neoaurum (Mneo) clades can cause infections in humans and they are resistant to first-line anti-tuberculosis drugs. They can be isolated from different ecological niches such as soil, tap water and ground water. Mycobacteria, such as Mmuc and Mneo, are classified as rapid growing mycobacteria, RGM, while the most familiar, Mycobacterium tuberculosis, belongs to the slow growing mycobacteria, SGM. Modern "omics" approaches have provided new insights into our understanding of the biology and evolution of this group of bacteria. Here we present comparative genomics data for seventeen NTM of which sixteen belong to the Mmuc- and Mneo-clades. Focusing on virulence genes, including genes encoding sigma/anti-sigma factors, serine threonine protein kinases (STPK), type VII (ESX genes) secretion systems and mammalian cell entry (Mce) factors we provide insight into their presence as well as phylogenetic relationship in the case of the sigma/anti-sigma factors and STPKs. Our data further suggest that these NTM lack ESX-5 and Mce2 genes, which are known to affect virulence. In this context, Mmuc- and Mneo-clade members lack several of the genes in the glycopeptidolipid (GLP) locus, which have roles in colony morphotype appearance and virulence. For the M. mucogenicum type strain, Mmuc, we provide RNASeq data focusing on mRNA levels for sigma factors, STPK, ESX proteins and Mce proteins. These data are discussed and compared to in particular the SGM and fish pathogen Mycobacterium marinum. Finally, we provide insight into as to why members of the Mmuc- and Mneo-clades show resistance to rifampin and isoniazid, and why Mmuc forms a rough colony morphotype.
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http://dx.doi.org/10.1038/s41598-019-55464-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917791PMC
December 2019

Mitochondrion: I am more than a fuel server.

Authors:
Santanu Dasgupta

Ann Transl Med 2019 Oct;7(20):594

Department of Medicine, The University of Texas Health Science Center at Tyler, Tyler, Texas, USA.

Apart from reliable management of the "powerhouse" of the cell, mitochondria faithfully orchestrate a diverse array of important and critical functions in governing cellular signaling, apoptosis, autophagy, mitophagy and innate and adaptive immune system. Introduction of instability and imbalance in the mitochondrial own genome or the nuclear encoded mitochondrial proteome would result in the manifestation of various diseases through alterations in the oxidative phosphorylation system (OXPHOS) and nuclear-mitochondria retrograde signaling. Understanding mitochondrial biology and dynamism are thus of paramount importance to develop strategies to prevent or treat various diseases caused due to mitochondrial alterations.
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http://dx.doi.org/10.21037/atm.2019.08.22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861786PMC
October 2019

Editorial for focused issue "Cancer Health and Medicine: A new era".

Authors:
Santanu Dasgupta

Ann Transl Med 2019 Oct;7(20):592

Department of Medicine, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.

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http://dx.doi.org/10.21037/atm.2019.09.103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861784PMC
October 2019

Cervical Cancer Prevention in Racially Disparate Rural Populations.

Medicines (Basel) 2019 Sep 4;6(3). Epub 2019 Sep 4.

Department of Medicine, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.

Undergoing a timely Pap smear, high-risk human papilloma virus (HPV)- and colposcopy-based testing can reduce HPV-associated cervical cancer (CC) development in women. However, in rural areas, women and minorities without insurance do not undergo periodic assessment and remain at greater risk of HPV infection and CC. In this study, 173 women from rural East Texas with various ethnic backgrounds were examined thorough HPV/Pap-based testing and colposcopic assessment. Of the 113 informative cases, 77% (87/113) were positive for high-risk HPV infection and 23% of subjects (26/113) were negative. Associations between HPV positivity with young age ( = 0.002), and a low number of pregnancy ( = 0.004) and births ( = 0.005) were evident. Women with long-term use of contraceptives (OR 1.93, 95% CI, 0.80-4.69) were associated with increased risk of HPV infection. African-American women had a higher risk of abnormal Pap outcome compared to Caucasians (OR 5.31, 95% CI, 0.67-42.0). HPV seemed to be a predictor of abnormal Pap outcome (OR 1.77, 95% CI, 0.48-6.44) in these subjects. Unmarried/widowed/divorced women had an increased abnormal Pap test outcome compared to married women or women living with a partner ( = 0.01), with over 278% increased odds (OR 3.78 at 95% CI, 1.29-11.10). Insured women undergoing periodic checkups were detected early with high-risk HPV infection and abnormal Pap test/colposcopic outcome. Comprehensive and timely screening of uninsured women and minorities in rural East Texas are warranted, which could potentially prevent the onset of HPV-associated CC.
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http://dx.doi.org/10.3390/medicines6030093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789706PMC
September 2019

Differential expression of efferocytosis and phagocytosis associated genes in tumor associated macrophages exposed to African American patient derived prostate cancer microenvironment.

J Solid Tumors 2019 Oct 27;9(2):22-27. Epub 2019 Jun 27.

Chemistry Department, Morgan State University, Baltimore, United States.

Macrophages are the first line of defense in the cellular environment in response to any antigenic or foreign invasion. Since cancer cells express antigenic molecules and create a tumor microenvironment quite different from the normal cellular environment, macrophages will attack this cancer cells as foreign Invaders. However, the cancer cells adept their ability to suppress macrophage activity by secreting compounds/proteins through unknown mechanisms and train these macrophages to aid in tumorigenesis. These macrophages are commonly known as tumor associated macrophages (TAM). In this study, our goal was to find out key regulatory molecules involved in this conversion of cancer-fighting macrophages to cancer friendly macrophages. We used African American(AA) patient derived established human prostate cancer cells along with the human derived macrophages followed by Affymetrix cDNA microarray analysis. Microarray analysis of the PCa cell exposed macrophages revealed appreciable decrease in mRNA expression of several genes associated with phagocytosis process. Aberrant expression of several noncoding RNAs that control the expression of such phagocytosis associated molecules were also evident. Increased expression of oncogenic miR such as, miR-148, 615, 515, 130, 139 and markedly decreased expression of tumor suppressive miR's MiR-3130, let7c,101,103, 383 were noted. Further, TARGET SCAN analysis demonstrated these differential expression of non-coding RNA's causing down regulation of phagocytosis promoting genes elf5A, Meg3, Tubb5, Sparcl-1, Uch-1, Bsg(CD147), Ube2v, GULP, Stabilin 1 and Pamr1. There is an increase of RAP1GAP gene that causes concomitant decrease in the expression of tubulin genes that promote cytoskeletal assembly in forming phagosomes. In addition Ingenuity pathway analysis of the gene expression data also showed upregulation of antiphagocytic genes IL-10, CD 16, IL-18 and MMP-9. Some core canonical pathways showing physiology of cellular signaling obtained by data analyzed by the Ingenuity software is confirmed a very complex mechanism still to be deciphered involved in the biology of TAM formation by which the rogue cancer cells tame their enemies, the macrophages and actually make them their helper cells to survive and propagate in the tumor microenvironment and thus prepare for epithelial mesenchymal transition for future metastasis and cancer stem cell formation and progression.
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http://dx.doi.org/10.5430/jst.v9n2p22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707537PMC
October 2019

Cancer Testis Antigen Promotes Triple Negative Breast Cancer Metastasis and is Traceable in the Circulating Extracellular Vesicles.

Sci Rep 2019 08 12;9(1):11632. Epub 2019 Aug 12.

Departments of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas, USA.

Triple negative breast cancer (TNBC) has poor survival, exhibits rapid metastases, lacks targeted therapies and reliable prognostic markers. Here, we examined metastasis promoting role of cancer testis antigen SPANXB1 in TNBC and its utility as a therapeutic target and prognostic biomarker. Expression pattern of SPANXB1 was determined using matched primary cancer, lymph node metastatic tissues and circulating small extracellular vesicles (sEVs). cDNA microarray analysis of TNBC cells stably integrated with a metastasis suppressor SH3GL2 identified SPANXB1 as a potential target gene. TNBC cells overexpressing SH3GL2 exhibited decreased levels of both SPANXB1 mRNA and protein. Silencing of SPANXB1 reduced migration, invasion and reactive oxygen species production of TNBC cells. SPANXB1 depletion augmented SH3GL2 expression and decreased RAC-1, FAK, A-Actinin and Vinculin expression. Phenotypic and molecular changes were reversed upon SPANXB1 re-expression. SPANXB1 overexpressing breast cancer cells with an enhanced SPANXB1:SH3GL2 ratio achieved pulmonary metastasis within 5 weeks, whereas controls cells failed to do so. Altered expression of SPANXB1 was detected in the sEVs of SPANXB1 transduced cells. Exclusive expression of SPANXB1 was traceable in circulating sEVs, which was associated with TNBC progression. SPANXB1 represents a novel and ideal therapeutic target for blocking TNBC metastases due to its unique expression pattern and may function as an EV based prognostic marker to improve TNBC survival. Uniquely restricted expression of SPANXB1 in TNBCs, makes it an ideal candidate for targeted therapeutics and prognostication.
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http://dx.doi.org/10.1038/s41598-019-48064-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690992PMC
August 2019

Human Papilloma Virus-Associated Cervical Cancer and Health Disparities.

Cells 2019 06 21;8(6). Epub 2019 Jun 21.

Medicine, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.

Cervical cancer develops through persistent infection with high-risk human papilloma virus (hrHPV) and is a leading cause of death among women worldwide and in the United States. Periodic surveillance through hrHPV and Pap smear-based testing has remarkably reduced cervical cancer incidence worldwide and in the USA. However, considerable discordance in the occurrence and outcome of cervical cancer in various populations exists. Lack of adequate health insurance appears to act as a major socioeconomic burden for obtaining cervical cancer preventive screening in a timely manner, which results in disparate cervical cancer incidence. On the other hand, cervical cancer is aggressive and often detected in advanced stages, including African American and Hispanic/Latina women. In this context, our knowledge of the underlying molecular mechanism and genetic basis behind the disparate cervical cancer outcome is limited. In this review, we shed light on our current understanding and knowledge of racially disparate outcomes in cervical cancer.
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http://dx.doi.org/10.3390/cells8060622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628030PMC
June 2019

Comparative genomics of Mycobacterium mucogenicum and Mycobacterium neoaurum clade members emphasizing tRNA and non-coding RNA.

BMC Evol Biol 2019 06 18;19(1):124. Epub 2019 Jun 18.

Department of Cell and Molecular Biology, Biomedical Centre, Box 596, SE-751 24, Uppsala, Sweden.

Background: Mycobacteria occupy various ecological niches and can be isolated from soil, tap water and ground water. Several cause diseases in humans and animals. To get deeper insight into our understanding of mycobacterial evolution focusing on tRNA and non-coding (nc)RNA, we conducted a comparative genome analysis of Mycobacterium mucogenicum (Mmuc) and Mycobacterium neoaurum (Mneo) clade members.

Results: Genome sizes for Mmuc- and Mneo-clade members vary between 5.4 and 6.5 Mbps with the complete Mmuc (type strain) genome encompassing 6.1 Mbp. The number of tRNA genes range between 46 and 79 (including one pseudo tRNA gene) with 39 tRNA genes common among the members of these clades, while additional tRNA genes were probably acquired through horizontal gene transfer. Selected tRNAs and ncRNAs (RNase P RNA, tmRNA, 4.5S RNA, Ms1 RNA and 6C RNA) are expressed, and the levels for several of these are higher in stationary phase compared to exponentially growing cells. The rare tRNATAT isoacceptor and two for mycobacteria novel ncRNAs: the Lactobacillales-derived GOLLD RNA and a homolog to the antisense Salmonella typhimurium phage Sar RNA, were shown to be present and expressed in certain Mmuc-clade members.

Conclusions: Phages, IS elements, horizontally transferred tRNA gene clusters, and phage-derived ncRNAs appears to have influenced the evolution of the Mmuc- and Mneo-clades. While the number of predicted coding sequences correlates with genome size, the number of tRNA coding genes does not. The majority of the tRNA genes in mycobacteria are transcribed mainly from single genes and the levels of certain ncRNAs, including RNase P RNA (essential for the processing of tRNAs), are higher at stationary phase compared to exponentially growing cells. We provide supporting evidence that Ms1 RNA represents a mycobacterial 6S RNA variant. The evolutionary routes for the ncRNAs RNase P RNA, tmRNA and Ms1 RNA are different from that of the core genes.
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http://dx.doi.org/10.1186/s12862-019-1447-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582537PMC
June 2019

CRISPR-Cas9 System for Genome Engineering of Photosynthetic Microalgae.

Mol Biotechnol 2019 Aug;61(8):541-561

A2O - Biology, Reliance Technology Group, Reliance Industries Limited, RCP, Navi Mumbai, 400701, India.

Targeted genome editing using RNA-guided endonucleases is an emerging tool in algal biotechnology. Recently, CRISPR-Cas systems have been widely used to manipulate the genome of some freshwater and marine microalgae. Among two different classes, and six distinct types of CRISPR systems, Cas9-driven type II system has been widely used in most of the studies for targeted knock-in, knock-out and knock-down of desired genes in algae. CRISPR technology has been demonstrated in microalgae including diatoms to manifest the function of the particular gene (s) and developing industrial traits, such as improving lipid content and biomass productivity. Instead of these, there are a lot of gears to be defined about improving efficiency and specificity of targeted genome engineering of microalgae using CRISPR-Cas system. Optimization of tools and methods of CRISPR technology can undoubtedly transform the research toward the industrial-scale production of commodity chemicals, food and biofuels using photosynthetic cell factories. This review has been focused on the efforts made so far to targeted genome engineering of microalgae, identified scopes about the hurdles related to construction and delivery of CRISPR-Cas components, algae transformation toolbox, and outlined the future prospect toward developing the CRISPR platform for high-throughput genome-editing of microalgae.
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http://dx.doi.org/10.1007/s12033-019-00185-3DOI Listing
August 2019

Microbiome Diversity in Sputum of Nontuberculous Mycobacteria Infected Women with a History of Breast Cancer.

Cell Physiol Biochem 2019 28;52(2):263-279. Epub 2019 Feb 28.

Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX, USA,

Background/aims: The nontuberculous mycobacterial lung disease (NTM), caused by Mycobacterium avium complex (MAC) is an increasing health problem in the USA and worldwide. The NTM disease is prevalent in Caucasian women with a current diagnosis or history of breast cancer (BCa), posing a significant challenge towards treatment. We hypothesize that NTM affected women with considerable therapeutic resistance may harbor pathogenic microbes other than nontuberculous mycobacterium, aiding in disease progression and therapeutic resistance.

Methods: We assessed microbiome diversity in sputa from healthy women, women with nontuberculous mycobacterial lung disease (NTM) and women with both nontuberculous mycobacterial lung disease and breast cancer (NTM-BCa). First, we collected sputa and isolated DNA from sputa of these healthy women and women with NTM and NTM-BCa. We also isolated DNA from sera derived extracellular vesicles from women with NTM-BCa. To identify diverse pathogenic microbes in various groups of subjects, we then performed 16S rDNA sequencing. Data analysis was performed utilizing the analytical pipelines at the Center for Metagenomic and Microbiome Research (CMMR), Baylor College of Medicine.

Results: A large community of resident microbes, including bacteria, virus, Archeas and Fungi live in the human body are being increasingly recognized as the key components of human health and disease. We identified a diverse microbiome community in the sputa and the extracellular vesicles dominated by Streptococcus, Haemophillus, Veillonella, Neisseria, Prevotella, Fusobacterium, Bacteroides, Allistipes, Faecalibacterium and Staphylococcus in women with nontuberculous mycobacterial lung disease as well as women with both nontuberculous mycobacterial lung disease and breast cancer. Some of these genera, including Fusobacterium, Bacteroides, and Allistipes have estrobolome activity and associated with breast and other neoplasms.

Conclusion: This work confirms the presence of a distinct pathogenic microbiome other than nontuberculous mycobacteria in the sputa and the circulating extracellular vesicles of these patients. This information could be useful for better therapeutic design to treat the NTM patients.
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http://dx.doi.org/10.33594/000000020DOI Listing
March 2019

Extensive genomic diversity among Mycobacterium marinum strains revealed by whole genome sequencing.

Sci Rep 2018 08 13;8(1):12040. Epub 2018 Aug 13.

Department of Cell and Molecular Biology, Box 596, Biomedical Centre, SE-751 24, Uppsala, Sweden.

Mycobacterium marinum is the causative agent for the tuberculosis-like disease mycobacteriosis in fish and skin lesions in humans. Ubiquitous in its geographical distribution, M. marinum is known to occupy diverse fish as hosts. However, information about its genomic diversity is limited. Here, we provide the genome sequences for 15 M. marinum strains isolated from infected humans and fish. Comparative genomic analysis of these and four available genomes of the M. marinum strains M, E11, MB2 and Europe reveal high genomic diversity among the strains, leading to the conclusion that M. marinum should be divided into two different clusters, the "M"- and the "Aronson"-type. We suggest that these two clusters should be considered to represent two M. marinum subspecies. Our data also show that the M. marinum pan-genome for both groups is open and expanding and we provide data showing high number of mutational hotspots in M. marinum relative to other mycobacteria such as Mycobacterium tuberculosis. This high genomic diversity might be related to the ability of M. marinum to occupy different ecological niches.
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http://dx.doi.org/10.1038/s41598-018-30152-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089878PMC
August 2018

Sputum Detection of Predisposing Genetic Mutations in Women with Pulmonary Nontuberculous Mycobacterial Disease.

Sci Rep 2018 07 27;8(1):11336. Epub 2018 Jul 27.

Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas, USA.

Nontuberculous mycobacterial lung disease (NTM), including Mycobacterium avium complex (MAC), is a growing health problem in North America and worldwide. Little is known about the molecular alterations occurring in the tissue microenvironment during NTM pathogenesis. Utilizing next generation sequencing, we sequenced sputum and matched lymphocyte DNA in 15 MAC patients for a panel of 19 genes known to harbor cancer susceptibility associated mutations. Thirteen of 15 NTM subjects had a diagnosis of breast cancer (BCa) before or after NTM infection. Thirty three percent (4/12) of these NTM-BCa cases exhibited at least 3 somatic mutations in sputa compared to matched lymphocytes. Twenty four somatic mutations were detected with at least one mutation in ATM, ERBB2, BARD1, BRCA1, BRCA2, AR, TP53, PALB2, CASP8, BRIP1, NBN and TGFB1 genes. All four NTM-BCa patients harboring somatic mutations also exhibited 15 germ line BRCA1 and BRCA2 mutations. The two NTM subjects without BCa exhibited twenty somatic mutations spanning BRCA1, BRCA1, BARD1, BRIP1, CHEK2, ERBB2, TP53, ATM, PALB2, TGFB1 and 3 germ line mutations in BRCA1 and BRCA2 genes. A single copy loss of STK11 and AR gene was noted in NTM-BCa subjects. Periodic screening of sputa may aid to develop risk assessment biomarkers for neoplastic diseases in NTM patients.
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http://dx.doi.org/10.1038/s41598-018-29471-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063893PMC
July 2018
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