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Article ; Online: 165 Rates of SGLT2 Inhibitor Use in Patients With Diabetes and Heart Failure in the Southeastern United States

Apoorva Gangavelli / Zihao Liu / Jeffrey Wang / Alexis Okoh / Shivani Patel / Alanna A. Morris

Journal of Clinical and Translational Science, Vol 6, Pp 19-

2022 Volume 19

Abstract: OBJECTIVES/GOALS: Clinical trials of SGLT2 inhibitors in patients with heart failure (HF) have confirmed a reduction in hospitalization and death. Adoption of novel therapeutics has been slower in Black and female patients. We investigated utilization of ...

Abstract	OBJECTIVES/GOALS: Clinical trials of SGLT2 inhibitors in patients with heart failure (HF) have confirmed a reduction in hospitalization and death. Adoption of novel therapeutics has been slower in Black and female patients. We investigated utilization of SGLT2 inhibitor in patients with HF and type 2 diabetes and if there were utilization differences by race or gender. METHODS/STUDY POPULATION: We created a retrospective cohort of outpatients with HF at Emory Healthcare from 2015 to 2020. Additional inclusion criteria included presence of heart failure and a diagnosis of T2D. SGLT2 inhibitor use was identified by a presence of SGLT2 inhibitor prescription at the time of the clinic visit. We estimated differences in prescription of SGLT2 inhibitors by race and gender using Chi-square analysis. RESULTS/ANTICIPATED RESULTS: The cohort included 5829 patients, age 69.47 years Â± 13.44, 47.67 % female, 54.62% Black. Overall prescription of SGLT2 inhibitors was low but increased over time (1.4% in 2015 to 5.6% in 2020; p<0.0001). On average, SGLT2 inhibitor use increased annually by 44.77%. From 2015 to 2020, fewer female than male patients were on an SGLT2 inhibitor (1.94% vs. 2.73%, p=0.0033). A similar percentage of Black and non-Black patients were on an SGLT2 inhibitor (2.13% vs. 2.64%, p=0.0591). DISCUSSION/SIGNIFICANCE: Prescription rates of SGLT2 inhibitors remain low in patients with T2D and HF, especially for female patients, despite evidence of their benefit on hospitalizations and mortality. Implementing use of SGLT2 inhibitors in this population represent an opportunity to improve cardiovascular outcomes.
Keywords	Medicine ; R
Subject code	610 ; 616
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Cambridge University Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Aliskiren Hemifumarate Proliposomes for Improved Oral Drug Delivery

Priyanka Kunamaneni / Surya Kovvasu / Steven Yeung / Jeffrey Wang / Salim Shah / Guru Betageri

Molecules, Vol 27, Iss 4828, p

Formulation Development, In Vitro and In Vivo Permeability Testing

2022 Volume 4828

Abstract: The objective of this study was to develop proliposomal formulations for a poorly bioavailable drug, aliskiren hemifumarate (AKH). A solvent evaporation method was used to prepare proliposomes using different lipids. The lipids of selection were soy ... ...

Abstract	The objective of this study was to develop proliposomal formulations for a poorly bioavailable drug, aliskiren hemifumarate (AKH). A solvent evaporation method was used to prepare proliposomes using different lipids. The lipids of selection were soy phosphatidylcholine (SPC), dimyristoylphosphatidylcholine (DMPC), and dimyristoylphosphatidylglycerol sodium (DMPG Na), stearylamine, and cholesterol in various ratios. Proliposomes were evaluated for particle size, zeta potential, in vitro drug release, in vitro permeability, and in vivo pharmacokinetics upon hydration with aqueous phase. In vitro drug release studies were conducted in 0.01 N hydrochloric acid using USP type II dissolution apparatus. Parallel artificial membrane permeation assay (PAMPA) and Caco-2 cell line models were used to study the in vitro drug permeation. Male Sprague-Dawley (SD) rats were used to conduct in vivo pharmacokinetic studies. Among different formulations, proliposomes with drug/DMPC/cholesterol/stearylamine in the ratio of 1:5:0.025:0.050 ( w/w / w / w ) demonstrated the desired particle size, higher zeta potential, and higher encapsulation efficiency. The PAMPA and Caco-2 cell line experiments showed a significantly higher permeability of AKH with proliposomes as compared to pure AKH. In animal studies, the optimized formulation of proliposomes showed significant improvement in the rate and extent of absorption of AKH. Specifically, following a single oral administration, the relative bioavailability of AKH proliposome formulation was 230% when compared to pure AKH suspension.
Keywords	aliskiren hemifumarate ; proliposomes ; PAMPA ; Caco-2 ; pharmacokinetic studies ; Organic chemistry ; QD241-441
Subject code	500
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Promotion of a synthetic degradation of activated STAT6 by PARP-1 inhibition

Jeffrey Wang / Mohamed A. Ghonim / Salome V. Ibba / Hanh H. Luu / Yucel Aydin / Peter A. Greer / A. Hamid Boulares

Journal of Translational Medicine, Vol 20, Iss 1, Pp 1-

roles of poly(ADP-ribosyl)ation, calpains and autophagy

2022 Volume 14

Abstract: Abstract Background We reported that PARP-1 regulates genes whose products are crucial for asthma, in part, by controlling STAT6 integrity speculatively through a calpain-dependent mechanism. We wished to decipher the PARP-1/STAT6 relationship in the ... ...

Abstract	Abstract Background We reported that PARP-1 regulates genes whose products are crucial for asthma, in part, by controlling STAT6 integrity speculatively through a calpain-dependent mechanism. We wished to decipher the PARP-1/STAT6 relationship in the context of intracellular trafficking and promoter occupancy of the transcription factor on target genes, its integrity in the presence of calpains, and its connection to autophagy. Methods This study was conducted using primary splenocytes or fibroblasts derived from wild-type or PARP-1−/− mice and Jurkat T cells to mimic Th2 inflammation. Results We show that the role for PARP-1 in expression of IL-4-induced genes (e.g. gata-3) in splenocytes did not involve effects on STAT6 phosphorylation or its subcellular trafficking, rather, it influenced its occupancy of gata-3 proximal and distal promoters in the early stages of IL-4 stimulation. At later stages, PARP-1 was crucial for STAT6 integrity as its inhibition, pharmacologically or by gene knockout, compromised the fate of the transcription factor. Calpain-1 appeared to preferentially degrade JAK-phosphorylated-STAT6, which was blocked by calpastatin-mediated inhibition or by genetic knockout in mouse fibroblasts. The STAT6/PARP-1 relationship entailed physical interaction and modification by poly(ADP-ribosyl)ation independently of double-strand-DNA breaks. Poly(ADP-ribosyl)ation protected phosphorylated-STAT6 against calpain-1-mediated degradation. Additionally, our results show that STAT6 is a bonafide substrate for chaperone-mediated autophagy in a selective and calpain-dependent manner in the human Jurkat cell-line. The effects were partially blocked by IL-4 treatment and PARP-1 inhibition. Conclusions The results demonstrate that poly(ADP-ribosyl)ation plays a critical role in protecting activated STAT6 during Th2 inflammation, which may be synthetically targeted for degradation by inhibiting PARP-1.
Keywords	Autophagy ; Calpains ; Poly(ADP-ribosyl)ation ; Th2 inflammation ; Olaparib ; PARP-1 ; Medicine ; R
Subject code	616
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Oral Bioavailability Evaluation of Celastrol-Encapsulated Silk Fibroin Nanoparticles Using an Optimized LC-MS/MS Method

Shuyu Zhan / Amy Paik / Felicia Onyeabor / Baoyue Ding / Sunil Prabhu / Jeffrey Wang

Molecules, Vol 25, Iss 3422, p

2020 Volume 3422

Abstract: Celastrol (CL), a compound isolated from Tripterygium wilfordii , possesses various bioactivities such as antitumor, anti-inflammatory and anti-obesity effects. In previous studies, we developed CL-encapsulated silk fibroin nanoparticles (CL-SFNP) with ... ...

Abstract	Celastrol (CL), a compound isolated from Tripterygium wilfordii , possesses various bioactivities such as antitumor, anti-inflammatory and anti-obesity effects. In previous studies, we developed CL-encapsulated silk fibroin nanoparticles (CL-SFNP) with satisfactory formulation properties and in vitro cancer cytotoxicity effect. For further in vivo oral bioavailability evaluation, in this study, a simple and reliable LC-MS/MS method was optimized and validated to determine CL concentration in rat plasma. The separation of CL was performed on a C18 column (150 by 2 mm, 5 µm) following sample preparation using liquid–liquid extraction with the optimized extraction solvent of tert -butyl methylether. The assay exhibited a good linearity in the concentration range of 0.5–500 ng/mL with the lower limit of quantification (LLOQ) of 0.5 ng/mL. The method was validated to meet the requirements for bioassay with accuracy of 91.1–110.0%, precision (RSD%) less than 9.1%, extraction recovery of 63.5–74.7% and matrix effect of 87.3–101.2%. The developed method was successfully applied to the oral bioavailability evaluation of CL-SFNP. The pharmacokinetic results indicated the AUC 0-∞ values of CL were both significantly ( p < 0.05) higher than those for pure CL after intravenous (IV) or oral (PO) administration of equivalent CL in rats. The oral absolute bioavailability ( F , %) of CL significantly ( p < 0.05) increased from 3.14% for pure CL to 7.56% for CL-SFNP after dosage normalization. This study provides valuable information for future CL product development.
Keywords	LC-MS/MS ; celastrol ; silk fibroin nanoparticles ; pharmacokinetics ; bioavailability ; Organic chemistry ; QD241-441
Subject code	500
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Transfersome Encapsulated with the R-carvedilol Enantiomer for Skin Cancer Chemoprevention

Md Abdullah Shamim / Ayaz Shahid / Pabitra K. Sardar / Steven Yeung / Jeremiah Reyes / Jenny Kim / Cyrus Parsa / Robert Orlando / Jeffrey Wang / Kristen M. Kelly / Frank L. Meyskens / Bradley T. Andresen / Ying Huang

Nanomaterials, Vol 13, Iss 929, p

2023 Volume 929

Abstract: The R-carvedilol enantiomer, present in the racemic mixture of the chiral drug carvedilol, does not bind to the β-adrenergic receptors, but exhibits skin cancer preventive activity. For skin delivery, R-carvedilol-loaded transfersomes were prepared using ...

Abstract	The R-carvedilol enantiomer, present in the racemic mixture of the chiral drug carvedilol, does not bind to the β-adrenergic receptors, but exhibits skin cancer preventive activity. For skin delivery, R-carvedilol-loaded transfersomes were prepared using various ratios of drug, lipids, and surfactants, and characterized for particle size, zeta potential, encapsulation efficiency, stability, and morphology. Transfersomes were compared for in vitro drug release and ex vivo skin penetration and retention. Skin irritation was evaluated by viability assay on murine epidermal cells and reconstructed human skin culture. Single-dose and repeated-dose dermal toxicity was determined in SKH-1 hairless mice. Efficacy was evaluated in SKH-1 mice exposed to single or multiple ultraviolet (UV) radiations. Transfersomes released the drug at a slower rate, but significantly increased skin drug permeation and retention compared with the free drug. The transfersome with a drug–lipid–surfactant ratio of 1:3:0.5 (T-RCAR-3) demonstrated the highest skin drug retention and was selected for further studies. T-RCAR-3 at 100 µM did not induce skin irritation in vitro and in vivo. Topical treatment with T-RCAR-3 at 10 µM effectively attenuated acute UV-induced skin inflammation and chronic UV-induced skin carcinogenesis. This study demonstrates feasibility of using R-carvedilol transfersome for preventing UV-induced skin inflammation and cancer.
Keywords	β-blocker ; carvedilol ; R-carvedilol ; ultraviolet ; skin cancer ; chemoprevention ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: RBC Storage Lesion Studies in Humans and Experimental Models of Shock

Willard N. Applefeld / Jeffrey Wang / Steven B. Solomon / Junfeng Sun / Harvey G. Klein / Charles Natanson

Applied Sciences, Vol 10, Iss 5, p

2020 Volume 1838

Abstract: The finding of toxicity in a meta-analysis of observational clinical studies of transfused longer stored red blood cells (RBC) and ethical issues surrounding aging blood for human studies prompted us to develop an experimental model of RBC transfusion. ... ...

Abstract	The finding of toxicity in a meta-analysis of observational clinical studies of transfused longer stored red blood cells (RBC) and ethical issues surrounding aging blood for human studies prompted us to develop an experimental model of RBC transfusion. Transfusing older RBCs during canine pneumonia increased mortality rates. Toxicity was associated with in vivo hemolysis with release of cell-free hemoglobin (CFH) and iron. CFH can scavenge nitric oxide, causing vasoconstriction and endothelial injury. Iron, an essential bacterial nutrient, can worsen infections. This toxicity was seen at commonly transfused blood volumes (2 units) and was altered by the severity of pneumonia. Washing longer-stored RBCs mitigated these detrimental effects, but washing fresh RBCs actually increased them. In contrast to septic shock, transfused longer stored RBCs proved beneficial in hemorrhagic shock by decreasing reperfusion injury. Intravenous iron was equivalent in toxicity to transfusion of longer stored RBCs and both should be avoided during infection. Storage of longer-stored RBCs at 2 °C instead of higher standard temperatures (4−6 °C) minimized the release of CFH and iron. Haptoglobin, a plasma protein that binds CFH and increases its clearance, minimizes the toxic effects of longer-stored RBCs during infection and is a biologically plausible novel approach to treat septic shock.
Keywords	blood transfusion ; sepsis ; cell free hemoglobin ; iron ; haptoglobin ; shock ; pneumonia ; Technology ; T ; Engineering (General). Civil engineering (General) ; TA1-2040 ; Biology (General) ; QH301-705.5 ; Physics ; QC1-999 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Optimization of Preparation and Preclinical Pharmacokinetics of Celastrol-Encapsulated Silk Fibroin Nanoparticles in the Rat

Felicia Onyeabor / Amy Paik / Surya Kovvasu / Baoyue Ding / Jelissa Lin / Md Arif Wahid / Sunil Prabhu / Guru Betageri / Jeffrey Wang

Molecules, Vol 24, Iss 18, p

2019 Volume 3271

Abstract: Celastrol (CL), a bioactive compound isolated from Tripterygium wilfordii , has demonstrated bioactivities against a variety of diseases including cancer and obesity. However, its poor water solubility and rapid in vivo clearance limit its clinical ... ...

Abstract	Celastrol (CL), a bioactive compound isolated from Tripterygium wilfordii , has demonstrated bioactivities against a variety of diseases including cancer and obesity. However, its poor water solubility and rapid in vivo clearance limit its clinical applications. To overcome these limitations, nanotechnology has been employed to improve its pharmacokinetic properties. Nanoparticles made of biological materials offer minimal adverse effects while maintaining the efficacy of encapsulated therapeutics. Silk fibroin (SF) solution was prepared successfully by extraction from the cocoons of silkworms, and a final concentration of 2 mg/mL SF solution was used for the preparation of CL-loaded SF nanoparticles (CL-SFNP) by the desolvation method. A stirring speed of 750 rpm and storage time of 20 h at −20 °C resulted in optimized product yield. A high-performance liquid chromatography (HPLC) method was developed and validated for the analysis of CL in rat plasma in terms of selectivity, linearity, intra-/inter-day precision and accuracy, and recovery. No interference was observed in rat plasma. Linearity in the concentration range of 0.05−5 µg/mL was observed with R 2 of 0.999. Precision and accuracy values were below the limit of acceptance criteria, i.e., 15% for quality control (QC) samples and 20% for lower limit of quantification (LLOQ) samples. Rats were given intravenous (IV) administration of 1 mg/kg of pure CL in PEG 300 solution or CL-SFNP. The pharmacokinetic profile was improved with CL-SFNP compared to pure CL. Pure CL resulted in a maximum concentration (C max ) value of 0.17 µg mL −1 at 5 min following administration, whereas that for CL-SFNP was 0.87 µg mL −1 and the extrapolated initial concentrations (C 0 ) were 0.25 and 1.09 µg mL −1 , respectively, for pure CL and CL-SFNP. A 2.4-fold increase in total area under the curve (AUC 0-inf ) (µg h mL −1 ) was observed with CL-SFNP when compared with pure CL. CL-SFNP demonstrated longer mean residence time (MRT; 0.67 h) than pure CL (0.26 h). In conclusion, ...
Keywords	silk fibroin nanoparticles ; celastrol ; optimized formulation ; bioanalysis ; pharmacokinetics ; Organic chemistry ; QD241-441
Subject code	333
Language	English
Publishing date	2019-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Treating Type 2 Diabetes Mellitus with Traditional Chinese and Indian Medicinal Herbs

Zhijun Wang / Jeffrey Wang / Patrick Chan

Evidence-Based Complementary and Alternative Medicine, Vol

2013 Volume 2013

Abstract: Type II diabetes mellitus (T2DM) is a fast-growing epidemic affecting people globally. Furthermore, multiple complications and comorbidities are associated with T2DM. Lifestyle modifications along with pharmacotherapy and patient education are the ... ...

Abstract	Type II diabetes mellitus (T2DM) is a fast-growing epidemic affecting people globally. Furthermore, multiple complications and comorbidities are associated with T2DM. Lifestyle modifications along with pharmacotherapy and patient education are the mainstay of therapy for patients afflicted with T2DM. Western medications are frequently associated with severe adverse drug reactions and high costs of treatment. Herbal medications have long been used in the treatment and prevention of T2DM in both traditional Chinese medicine (TCM) and traditional Indian medicine (TIM). This review examines in vivo, in vitro, and clinical evidence supporting the use of various herbs used in TCM and TIM. The problems, challenges, and opportunities for the incorporation of herbal frequently used in TCM and TIM into Western therapy are presented and discussed.
Keywords	Other systems of medicine ; RZ201-999
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Development and validation of an HPLC method for the simultaneous quantification of indole-3-carbinol acetate, indole-3-carbinol, and 3,3â²-diindolylmethane in mouse plasma, liver, and kidney tissues

Moussata, Justin / Jeffrey Wang / Zhijun Wang

Journal of Chromatography B. 2014 May 01, v. 958

2014

Abstract: A novel Indole-3-carbinol derivative (I3C) prodrug, indole-3-carbinol acetate (I3CA), was synthesized and a rapid high-performance liquid chromatography (HPLC) method for the quantification of I3CA, I3C, and the major metabolite of I3C, diindolylmethane ( ...

Abstract	A novel Indole-3-carbinol derivative (I3C) prodrug, indole-3-carbinol acetate (I3CA), was synthesized and a rapid high-performance liquid chromatography (HPLC) method for the quantification of I3CA, I3C, and the major metabolite of I3C, diindolylmethane (DIM), in mouse plasma, liver and kidney tissues was developed and validated. 4-Methoxy-1-methylindole was used as the internal standard. Chromatographic separation was achieved on a SymmetryÂ® C18 column (75mmÃ4.6mm, 3.5Î¼m) and the detection was made at 280nm. A gradient elution was programmed with the mobile phases of water (A) and acetonitrile (B) and a flow rate of 1ml/min. The total run time was 15min. The calibration curves were linear over the range of 0.06â1.6Î¼g/ml for both I3C and DIM with a correlation coefficient (r2) higher than 0.997 and the lower limit of quantitation (LLOQ) of 0.06Î¼g/ml. The calibration curve of I3CA was linear over the range of 0.15â4.0Î¼g/ml, with a r2>0.995 and LLOQ of 0.15Î¼g/ml. I3CA, I3C, and DIM intra-day accuracy values of plasma, liver and kidney samples ranged from 90.0 to 101.3%, while the inter-day ones were between 93.3 and 101.9%. Precision evaluated by the relative standard deviation was ranged from 2.0 to 14.8% for intra-day and 1.9 to 14.4% for inter-day variability. I3CA, I3C, and DIM were stable in mouse plasma, liver and kidney samples containing an esterase inhibitor dichlorvos. This method was successfully applied to a pharmacokinetic study in mice following oral and intravenous administration of I3C and I3CA.
Keywords	acetates ; acetonitrile ; dichlorvos ; esterases ; high performance liquid chromatography ; intravenous injection ; kidneys ; liver ; metabolites ; mice ; pharmacokinetics
Language	English
Dates of publication	2014-0501
Size	p. 1-9.
Publishing place	Elsevier B.V.
Document type	Article
ISSN	1570-0232
DOI	10.1016/j.jchromb.2014.02.026
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Sulfated non-anticoagulant heparin blocks Th2-induced asthma by modulating the IL-4/signal transducer and activator of transcription 6/Janus kinase 1 pathway

Mohamed A. Ghonim / Jeffrey Wang / Salome V. Ibba / Hanh H. Luu / Kusma Pyakurel / Ilyes Benslimane / Shaker Mousa / A. Hamid Boulares

Journal of Translational Medicine, Vol 16, Iss 1, Pp 1-

2018 Volume 12

Abstract: Abstract Background The efficacy of heparins and low-MW-heparins (LMWH) against human asthma has been known for decades. However, the clinical utility of these compounds has been hampered by their anticoagulant properties. Much effort has been put into ... ...

Abstract	Abstract Background The efficacy of heparins and low-MW-heparins (LMWH) against human asthma has been known for decades. However, the clinical utility of these compounds has been hampered by their anticoagulant properties. Much effort has been put into harnessing the anti-inflammatory properties of LMWH but none have been used as therapy for asthma. Sulfated-non-anticoagulant heparin (S-NACH) is an ultra-LMWH with no systemic anticoagulant effects. Objective The present study explored the potential of S-NACH in blocking allergic asthma and examined the potential mechanism by which it exerts its effects. Methods Acute and chronic ovalbumin-based mouse models of asthma, splenocytes, and a lung epithelial cell line were used. Mice were challenged with aerosolized ovalbumin and administered S-NACH or saline 30 min after each ovalbumin challenge. Results Sulfated-non-anticoagulant heparin administration in mice promoted a robust reduction in airway eosinophilia, mucus production, and airway hyperresponsiveness even after chronic repeated challenges with ovalbumin. Such effects were linked to suppression of Th2 cytokines IL-4/IL-5/IL-13/GM-CSF and ovalbumin-specific IgE without any effect on IFN-γ. S-NACH also reduced lung fibrosis in mice that were chronically-exposed to ovalbumin. These protective effects of S-NACH may be attributed to modulation of the IL-4/JAK1 signal transduction pathway through an inhibition of STAT6 phosphorylation and a subsequent inhibition of GATA-3 and inducible NO synthase expression. The effect of the drug on STAT6 phosphorylation coincided with a reduction in JAK1 phosphorylation upon IL-4 treatment. The protective effects of S-NACH treatment was associated with reduction of the basal expression of the two isoforms of arginase ARG1 and ARG2 in lung epithelial cells. Conclusions Our study demonstrates that S-NACH constitutes an opportunity to benefit from the well-known anti-asthma properties of heparins/LMWH while bypassing the risk of bleeding. Our results show, for the first time, that ...
Keywords	Low-MW-heparins (LMWH) ; S-NACH ; Th2 inflammation ; Ovalbumin ; Allergy ; Therapeutic potential ; Medicine ; R
Subject code	610
Language	English
Publishing date	2018-09-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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