Biomolecular Concepts最新文献

{"title":"Everolimus-induced effector mechanism in macrophages and survivability of Erdman, CDC1551 and HN878 strains of <i>Mycobacterium tuberculosis</i> infection.","authors":"Ruoqiong Cao, Kimberly To, Nala Kachour, Abrianna Beever, James Owens, Airani Sathananthan, Pooja Singh, Afsal Kolloli, Selvakumar Subbian, Vishwanath Venketaraman","doi":"10.1515/bmc-2021-0006","DOIUrl":"10.1515/bmc-2021-0006","url":null,"abstract":"<p><p>With a disease as widespread and destructive as tuberculosis, more effective drugs and healthcare strategies, in addition to the current antibiotics regimen, are crucial for the enhanced well-being of millions of people suffering from the disease. Host-directed therapy is a new and emerging concept in treating chronic infectious diseases, such as tuberculosis. Repurposing of anti-cancer drugs, such as everolimus, may be an effective way to supplement the standard antibiotic treatment. Individuals with type 2 diabetes are increasingly susceptible to co-morbidities and co-infections including <i>Mycobacterium tuberculosis,</i> the causative agent of tuberculosis. We demonstrated in this study that <i>in vitro</i> everolimus treatment of granulomas from individuals with type 2 diabetes caused significant reduction in the viability of <i>Mycobacterium tuberculosis.</i>Further investigations revealed the effects of everolimus in targeting foamy macrophages, a macrophage phenotype that forms around granulomas, and is characterized by a higher lipid accumulation inside the cells. These foamy macrophages are thought to harbor dormant bacilli, which are potential sources of disease reactivation. Therefore, blocking foamy macrophage formation would help better killing of intracellular bacteria. Here, we report the potential of everolimus treatment to downregulate lipid content within the foamy macrophages of <i>in vitro</i> granulomas, thus leading to a potential decrease in the number of foamy macrophages and a more robust response to <i>Mycobacterium tuberculosis</i>.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"46-54"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/bmc-2021-0006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39039261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myosteatosis in NAFLD patients correlates with plasma Cathepsin D.","authors":"Lingling Ding,&nbsp;Toon J I De Munck,&nbsp;Yvonne Oligschlaeger,&nbsp;Inês Magro Dos Reis,&nbsp;Jef Verbeek,&nbsp;Ger H Koek,&nbsp;Tom Houben,&nbsp;Ronit Shiri-Sverdlov","doi":"10.1515/bmc-2021-0004","DOIUrl":"https://doi.org/10.1515/bmc-2021-0004","url":null,"abstract":"<p><p>Previously, we have shown that hepatic lipid accumulation induces the secretion of cathepsin D (CTSD), and that plasma CTSD levels are associated with increased inflammation and disease severity in nonalcoholic fatty liver disease (NAFLD). Although it is clear that the liver is a major source of plasma CTSD, it is unknown whether other metabolically active organs such as the muscle, also associate with plasma CTSD levels in NAFLD patients. Therefore, the aim of this study was to explore the relation between lipid accumulation in the muscle (myosteatosis) and plasma CTSD levels in forty-five NAFLD patients. We observed that hepatic steatosis positively associated with plasma CTSD levels, confirming the previously established link between plasma CTSD and the liver. Furthermore, a positive association between myosteatosis and plasma CTSD levels was observed, which was independent of sex, age, BMI, waist circumference and hepatic steatosis. By establishing a positive association between myosteatosis and plasma CTSD levels, our findings suggest that, in addition to the liver, the muscle is also linked to plasma CTSD levels in NAFLD patients. The observed link between myosteatosis and plasma CTSD levels supports the concept of a significant role of the skeletal muscle in metabolic disturbances in metabolic syndrome-related disorders.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"27-35"},"PeriodicalIF":0.0,"publicationDate":"2021-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/bmc-2021-0004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38984937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of Oral Liposomal Glutathione and In Vitro Everolimus in Altering the Immune Responses against <i>Mycobacterium bovis</i> BCG Strain in Individuals with Type 2 Diabetes.","authors":"Kimberly To,&nbsp;Ruoqiong Cao,&nbsp;Aram Yegiazaryan,&nbsp;James Owens,&nbsp;Kayvan Sasaninia,&nbsp;Charles Vaughn,&nbsp;Mohkam Singh,&nbsp;Edward Truong,&nbsp;Airani Sathananthan,&nbsp;Vishwanath Venketaraman","doi":"10.1515/bmc-2021-0003","DOIUrl":"https://doi.org/10.1515/bmc-2021-0003","url":null,"abstract":"<p><p>Tuberculosis (TB) caused by <i>Mycobacterium tuberculosis</i> (<i>M. tb</i>) still remains a devastating infectious disease in the world. There has been a daunting increase in the incidence of Type 2 Diabetes Mellitus (T2DM) worldwide. T2DM patients are three times more vulnerable to <i>M. tb</i> infection compared to healthy individuals. TB-T2DM coincidence is a challenge for global health control. Despite some progress in the research, <i>M. tb</i> still has unexplored characteristics in successfully evading host defenses. The lengthy duration of treatment, the emergence of multi-drug-resistant strains and extensive-drug-resistant strains of <i>M. tb</i> have made TB treatment very challenging. Previously, we have tested the antimycobacterial effects of everolimus within <i>in vitro</i> granulomas generated from immune cells derived from peripheral blood of healthy subjects. However, the effectiveness of everolimus treatment against mycobacterial infection in individuals with T2DM is unknown. Furthermore, the effectiveness of the combination of <i>in vivo</i> glutathione (GSH) supplementation in individuals with T2DM along with <i>in vitro</i> treatment of isolated immune cells with everolimus against mycobacterial infection has never been tested. Therefore, we postulated that liposomal glutathione (L-GSH) and everolimus would offer great hope for developing adjunctive therapy for mycobacterial infection. L-GSH or placebo was administered to T2DM individuals orally for three months. Study subjects' blood was drawn pre- and post-L-GSH/or placebo supplementation, where Peripheral Blood Mononuclear Cells (PBMCs) were isolated from whole blood to conduct <i>in vitro</i> studies with everolimus. We found that <i>in vitro</i> treatment with everolimus, an mTOR (membrane target of rapamycin) inhibitor, significantly reduced intracellular <i>M. bovis</i> BCG infection alone and in conjunction with L-GSH supplementation. Furthermore, we found L-GSH supplementation coupled with <i>in vitro</i> everolimus treatment produced a greater effect in inhibiting the growth of intracellular <i>Mycobacterium bovis</i> BCG, than with the everolimus treatment alone. We also demonstrated the functions of L-GSH along with <i>in vitro</i> everolimus treatment in modulating the levels of cytokines such as IFN-γ, TNF-α, and IL-2 and IL-6, in favor of improving control of the mycobacterial infection. In summary, <i>in vitro</i> everolimus-treatment alone and in combination with oral L-GSH supplementation for three months in individuals with T2DM, was able to increase the levels of T-helper type 1 (Th1) cytokines IFN-γ, TNF-α, and IL-2 as well as enhance the abilities of granulomas from individuals with T2DM to improve control of a mycobacterial infection.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"16-26"},"PeriodicalIF":0.0,"publicationDate":"2021-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/bmc-2021-0003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38963936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Doxorubicin loaded magnetism nanoparticles based on cyclodextrin dendritic-graphene oxide inhibited MCF-7 cell proliferation.","authors":"Ainaz Mihanfar,&nbsp;Niloufar Targhazeh,&nbsp;Shirin Sadighparvar,&nbsp;Saber Ghazizadeh Darband,&nbsp;Maryam Majidinia,&nbsp;Bahman Yousefi","doi":"10.1515/bmc-2021-0002","DOIUrl":"https://doi.org/10.1515/bmc-2021-0002","url":null,"abstract":"<p><p>Doxorubicin (DOX) is an effective chemotherapeutic agent used for the treatment of various types of cancer. However, its poor solubility, undesirable side effects, and short half-life have remained a challenge. We used a formulation based on graphene oxide as an anticancer drug delivery system for DOX in MCF-7 breast cancer cells, to address these issues. <i>In vitro</i> release studies confirmed that the synthesized formulation has an improved release profile in acidic conditions (similar to the tumor microenvironment). Further <i>in vitro</i> studies, including MTT, uptake, and apoptosis assays were performed. The toxic effects of the nanocarrier on the kidney, heart and liver of healthy rats were also evaluated. We observed that the DOX-loaded carrier improved the cytotoxic effect of DOX on the breast cell line compared to free DOX. In summary, our results introduce the DOX-loaded carrier as a potential platform for <i>in vitro</i> targeting of cancer cells and suggest further studies are necessary to investigate its <i>in vivo</i> anti-cancer potential.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"8-15"},"PeriodicalIF":0.0,"publicationDate":"2021-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/bmc-2021-0002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38891530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Our Image: The Ethics of CRISPR Genome Editing.","authors":"Joel C Eissenberg","doi":"10.1515/bmc-2021-0001","DOIUrl":"https://doi.org/10.1515/bmc-2021-0001","url":null,"abstract":"<p><p>The advent of genome editing technology promises to transform human health, livestock and agriculture, and to eradicate pest species. This transformative power demands urgent scrutiny and resolution of the ethical conflicts attached to the creation and release of engineered genomes. Here, I discuss the ethics surrounding the transformative CRISPR/Cas9-mediated genome editing technology in the contexts of human genome editing to eradicate genetic disease and of gene drive technology to eradicate animal vectors of human disease.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2021-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/bmc-2021-0001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25335497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulation of epigenetic related genes in Diabetic Trigger finger Patients; preliminary analysis of Patient-Derived Samples.","authors":"Michael Cain,&nbsp;Mohamed E Awad,&nbsp;Ravindra Kolhe,&nbsp;Ashis K Mondal,&nbsp;Umar Ghilzai,&nbsp;Carlos Isales,&nbsp;Mark Fulcher,&nbsp;Sadanand Fulzele","doi":"10.1515/bmc-2020-0020","DOIUrl":"https://doi.org/10.1515/bmc-2020-0020","url":null,"abstract":"<p><strong>Background: </strong>Trigger finger (TF), a painful condition involving a finger flexor tendon, is a common problem with a prevalence of ~2-3% in the general population. However, the TF prevalence is higher among diabetic patients-ranges from 6.7% to 10%. We have analyzed the expression of the extracellular matrix, inflammation, and epigenetic related genes in diabetic and non-diabetes TF. We hypothesized that Diabetes condition induces alter the expression of epigenetic modification genes in diabetic patients and one of the underlying determinants for more prevalence of TF in diabetic patients.</p><p><strong>Method: </strong>Tissues from the fingers of patients with symptomatic trigger fingers were collected. We had three groups: carpal tunnel syndrome (as a control), trigger finger, and diabetic trigger finger. A quantitative real-time polymerase chain reaction was performed. The gene expression of Extracellular matrix (ECM) components [COL-I, COL-II, COL-X, Aggrecan], DNA methyltransferases enzymes (DNMT1, DNMT3), growth factors (TGF-b, IGF), and Histone deacetylase enzymes (HDAC1, HDAC2) were evaluated in all groups.</p><p><strong>Results: </strong>The mRNA expression of COL-I, COL-II, Aggrecan was significantly higher in the pully A1 of diabetic patients (p= 0.0164, p=0.0351, p=0.0399, respectively) as compared to non-diabetic TF patients. Diabetes was associated with a significant increase in the DNMT3 expression compared to non-diabetic TF patients (p=0.0485). HDAC1 and HDAC2 gene expression were up-regulated in diabetic TF than non-diabetic TF.</p><p><strong>Conclusion: </strong>The chronic state of hyperglycemia induces epigenetic modification of gene expressions in trigger fingers. This seems to have a significant impact on the development, recurrence, and progression of trigger finger in diabetic patients.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"221-229"},"PeriodicalIF":0.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/bmc-2020-0020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39161853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Graphene Oxide: A Promising Material for Regenerative Medicine and Tissue Engineering.","authors":"Masomeh Maleki,&nbsp;Reza Zarezadeh,&nbsp;Mohammad Nouri,&nbsp;Aydin Raei Sadigh,&nbsp;Farhad Pouremamali,&nbsp;Zatollah Asemi,&nbsp;Hossein Samadi Kafil,&nbsp;Forough Alemi,&nbsp;Bahman Yousefi","doi":"10.1515/bmc-2020-0017","DOIUrl":"https://doi.org/10.1515/bmc-2020-0017","url":null,"abstract":"<p><p>Regenerative medicine and tissue engineering have been considered pioneer fields in the life sciences, with an ultimate goal of restoring or switching lost or impaired body parts. Graphene oxide (GO) is the product of graphene oxidation and presents a great opportunity to make substantial progress in the field of regenerative medicine; for example, it supports the possibility of creating a cellular niche for stem cells on a nanoparticle surface. GO creates a fascinating structure for regulating stem cell behavior, as it can potentially applied to the noninvasive chase of stem cells <i>in vivo</i>, the liberation of active biological factors from stem cell-containing delivery systems, and the intracellular delivery of factors such as growth factors, DNA, or synthetic proteins in order to modulate stem cell differentiation and proliferation. Due to the interesting physicochemical properties of GO and its possible usage in tissue engineering approaches, the present review aims to elaborate on the ways in which GO can improve current regenerative strategies. In this respect, the applicability of GO to the repair and regeneration of various tissues and organs, including cardiac muscle, skeletal muscle, and nervous, bone, cartilage, adipose, and skin tissues, is discussed.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"182-200"},"PeriodicalIF":0.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/bmc-2020-0017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39161850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcium Dynamics Regulate Protective Responses and Growth of Staphylococcus aureus in Macrophages.","authors":"Chaitenya Verma,&nbsp;Kumar Rana Ankush,&nbsp;Vandana Anang,&nbsp;Brijendra K Tiwari,&nbsp;Aayushi Singh,&nbsp;Shakuntala Surender Kumar Saraswati,&nbsp;Malini Shariff,&nbsp;Krishnamurthy Natarajan","doi":"10.1515/bmc-2020-0021","DOIUrl":"https://doi.org/10.1515/bmc-2020-0021","url":null,"abstract":"<p><p>Staphylococcus aureus (S. aureus) is a gram-positive bacteria, which causes various fatal respiratory infections including pneumonia. The emergence of Methicillin-Resistance Staphylococcus aureus (MRSA) demands a thorough understanding of host-pathogen interactions. Here we report the role of calcium in regulating defence responses of S. aureus in macrophages. Regulating calcium fluxes in cells by different routes differentially governs the expression of T cell costimulatory molecule CD80 and Th1 promoting IL-12 receptor. Inhibiting calcium influx from extracellular medium increased expression of IFN-γ and IL-10 while blocking calcium release from the intracellular stores inhibited TGF-β levels. Blocking voltage-gated calcium channels (VGCC) inhibited the expression of multiple cytokines. While VGCC regulated the expression of apoptosis protein Bax, extracellular calcium-regulated the expression of Cytochrome-C. Similarly, VGCC regulated the expression of autophagy initiator Beclin-1. Blocking VGCC or calcium release from intracellular stores promoted phagosome-lysosome fusion, while activating VGCC inhibited phagosomelysosome fusion. Finally, calcium homeostasis regulated intracellular growth of Staphylococcus, although using different mechanisms. While blocking extracellular calcium influx seems to rely on IFN-γ and IL-12Rβ receptor mediated reduction in bacterial survival, blocking either intracellular calcium release or via VGCC route seem to rely on enhanced autophagy mediated reduction of intracellular bacterial survival. These results point to fine-tuning of defence responses by routes of calcium homeostasis.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"230-239"},"PeriodicalIF":0.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/bmc-2020-0021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25494136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of phase partitioning in coordinating DNA damage response: focus on the Apurinic Apyrimidinic Endonuclease 1 interactome.","authors":"Damiano Tosolini,&nbsp;Giulia Antoniali,&nbsp;Emiliano Dalla,&nbsp;Gianluca Tell","doi":"10.1515/bmc-2020-0019","DOIUrl":"https://doi.org/10.1515/bmc-2020-0019","url":null,"abstract":"<p><p>Liquid-liquid phase separation (LLPS) is a way to concentrate biochemical reactions while excluding noninteracting components. Disordered domains of proteins, as well as interaction with RNA, favor condensation but are not mandatory for modulating this process. Recent insights about phase-separation mechanisms pointed to new fascinating models that could explain how cells could cope with DNA damage responses, conferring both spatial and temporal fine regulation. APE1 is a multifunctional protein belonging to the Base Excision Repair (BER) pathway, bearing additional 'non-canonical' DNA-repair functions associated with processes like RNA metabolism. Recently, it has been highlighted that several DNA repair enzymes, such as 53BP1 and APE1, are endowed with RNA binding abilities. In this work, after reviewing the recent literature supporting a role of LLPS in DDR, we analyze, as a proof of principle, the interactome of APE1 using a bioinformatics approach to look for clues of LLPS in BER. Some of the APE1 interactors are associated with cellular processes in which LLPS has been either proved or proposed and are involved in different pathogenic events. This work might represent a paradigmatical pipeline for evaluating the relevance of LLPS in DDR.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"209-220"},"PeriodicalIF":0.0,"publicationDate":"2020-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/bmc-2020-0019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39161852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alzheimer's disease: exploring nature's 'medicinal chest' for new therapeutic agents.","authors":"Anthony Tsarbopoulos","doi":"10.1515/bmc-2020-0018","DOIUrl":"https://doi.org/10.1515/bmc-2020-0018","url":null,"abstract":"<p><p>Natural products have served humanity as a valuable source for the discovery and development of therapeutic agents. In addition, these phytochemicals can function as lead compounds for the development of synthetic analogs aimed at treating human diseases. In our aging society, Alzheimer's disease (AD) is the most common cause of dementia, which is characterized by a significant and progressive loss of memory and other cognitive functions. As society demographics change, the predominance of AD and other age-related dementias is increasing, with concurrent financial and societal costs.AD represents one of the most remarkable scientific challenges for drug discovery as the search for effective disease-modifying agents has been unsuccessful. Medicinal plants have been used for their \"anti-aging\" properties, and cognitive enhancing properties. In the past decades, natural products have been studied for their anti-AD properties, and their potential for developing therapeutic agents against several molecular targets has been evaluated. This insight evaluates the prospects of medicinal plants for providing disease-modifying, as well as disease-preventing, agents for AD.</p>","PeriodicalId":38392,"journal":{"name":"Biomolecular Concepts","volume":" ","pages":"201-208"},"PeriodicalIF":0.0,"publicationDate":"2020-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/bmc-2020-0018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39161851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}