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Article ; Online: High serum concentrations of growth differentiation factor-15 and their association with Crohn’s disease and a low skeletal muscle index

Hiroyuki Yamamoto / Fuminao Takeshima / Masafumi Haraguchi / Yuko Akazawa / Kayoko Matsushima / Moto Kitayama / Kumi Ogihara / Maiko Tabuchi / Keiichi Hashiguchi / Naoyuki Yamaguchi / Hisamitsu Miyaaki / Hisayoshi Kondo / Kazuhiko Nakao

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 8

Abstract: Abstract Sarcopenia comprises a low skeletal muscle index (SMI) and low muscle strength (MS) or low physical function. Many sarcopenia biomarkers have been reported. With Crohn’s disease (CD), a low SMI is predictive of intestinal complications. ... ...

Abstract	Abstract Sarcopenia comprises a low skeletal muscle index (SMI) and low muscle strength (MS) or low physical function. Many sarcopenia biomarkers have been reported. With Crohn’s disease (CD), a low SMI is predictive of intestinal complications. Therefore, many CD studies have reported that sarcopenia is defined by SMI alone. This study investigated the sarcopenia frequency by assessing the SMI and MS of Japanese patients with CD and biomarkers predicting a low SMI. We evaluated the SMI using a bioelectrical impedance analysis, handgrip strength, and C-reactive protein, albumin, interleukin-6, tumor necrosis factor-α, growth differentiation factor (GDF)-8, and GDF-15 levels as biomarker candidates for 78 CD patients at our hospital. Sarcopenia and a low SMI were observed in 7.7% and 42.3% of the patients, respectively. There was a significant difference in the GDF-15 levels of the low SMI group and normal group according to the multivariate analysis (P = 0.028; odds ratio [OR], 1.001; 95% confidence interval [CI] 1.000–1.002). When evaluated by sex, males exhibited a negative correlation between the GDF-15 level and SMI (Pearson’s r = − 0.414; P = 0.0031), and the multivariate analysis indicated a significant difference in the GDF-15 levels (P = 0.011; OR, 1.001; 95% CI 1.000–1.002). GDF-15 levels may indicate a low SMI with CD.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Significance of serum palmitoleic acid levels in inflammatory bowel disease

Yuko Akazawa / Tomohito Morisaki / Hiroko Fukuda / Kiyuu Norimatsu / Junya Shiota / Keiichi Hashiguchi / Maiko Tabuchi / Moto Kitayama / Kayoko Matsushima / Naoyuki Yamaguchi / Hisayoshi Kondo / Fumihiko Fujita / Hiroaki Takeshita / Kazuhiko Nakao / Fuminao Takeshima

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 8

Abstract: Abstract Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic intestinal diseases of unknown etiology that present with variable disease extents and outcomes. The use of biomarkers for the diagnosis ... ...

Abstract	Abstract Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic intestinal diseases of unknown etiology that present with variable disease extents and outcomes. The use of biomarkers for the diagnosis and management of IBDs is considered beneficial. Palmitoleic acid (PO) is an adipose tissue-derived mono-unsaturated free fatty acid that potentially serves as a lipokine in metabolic and inflammatory diseases. The aim of this study was to investigate the significance of PO levels in the serum of patients with UC and CD. The study included patients with UC (n = 22), patients with CD (n = 35), and controls (n = 22). The levels of serum PO were analyzed using gas chromatography. The association of serum PO levels with the clinical features and disease outcomes in IBD was examined. Serum PO levels were significantly higher in patients with CD than in controls, whereas no difference in these levels was observed between patients with UC and controls. Serum PO levels were significantly associated with the CD activity index. Additionally, high serum PO levels were associated with an increased risk of surgical intervention requirement during follow-up. In a pilot study with a few patients, high PO levels were observed in the mesenteric tissue in the active disease site of patients with CD (n = 7) compared with those with colon cancer (n = 6). Elevated serum PO levels might serve as a marker for local inflammation and prognosis in patients with CD.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparative efficacy of antitumor necrosis factor agents and tacrolimus in naïve steroid-refractory ulcerative colitis patients

Moto Kitayama / Yuko Akazawa / Daisuke Yoshikawa / Shuntaro Higashi / Tomohito Morisaki / Hidetoshi Oda / Maho Ikeda / Yujiro Nakashima / Maiko Tabuchi / Keiichi Hashiguchi / Kayoko Matsushima / Naoyuki Yamaguchi / Hisayoshi Kondo / Kazuhiko Nakao / Fuminao Takeshima

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 9

Abstract: Abstract While retrospective studies have compared the efficacy of anti–tumour necrosis factor (TNF) agents and tacrolimus (TAC) in ulcerative colitis (UC), information regarding first-time use of these agents is limited. The aim of our study was to ... ...

Abstract	Abstract While retrospective studies have compared the efficacy of anti–tumour necrosis factor (TNF) agents and tacrolimus (TAC) in ulcerative colitis (UC), information regarding first-time use of these agents is limited. The aim of our study was to investigate the short- and long-term efficacy of anti-TNF agents [adalimumab (ADA) and infliximab (IFX)] and TAC in anti-TNF agent- and TAC-naïve steroid-refractory UC patients. We evaluated 150 steroid-refractory UC patients receiving anti-TNF agents (IFX: n = 30, ADA: n = 41) or TAC (n = 79) at eight institutions in Japan. Clinical response rates at 8 weeks were 73.2% and 75.9% while remission rates were 30.1% and 25.3% in the anti-TNF and TAC groups, respectively. Logistic regression analysis showed the male sex and higher C-reactive protein to be independent factors for response to anti-TNF agents and TAC, respectively. Use of TAC was an independent factor for relapse. No differences in response to the treatment or relapse were observed between IFX and ADA. In conclusion, TAC and anti-TNF agents promoted similar short-term effects, but anti-TNF agents ensured better long-term outcomes at first-time treatment of steroid-refractory UC patients.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Correction

Ikuko Takahara / Yuko Akazawa / Maiko Tabuchi / Katsuya Matsuda / Hisamitsu Miyaaki / Youko Kido / Yasuko Kanda / Naota Taura / Ken Ohnita / Fuminao Takeshima / Yusuke Sakai / Susumu Eguchi / Masahiro Nakashima / Kazuhiko Nakao

PLoS ONE, Vol 15, Iss 7, p e

Toyocamycin attenuates free fatty acid-induced hepatic steatosis and apoptosis in cultured hepatocytes and ameliorates nonalcoholic fatty liver disease in mice.

2020 Volume 0235729

Abstract: This corrects the article DOI:10.1371/journal.pone.0170591.]. ...

Abstract	[This corrects the article DOI:10.1371/journal.pone.0170591.].
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A novel method for rapid detection of a Helicobacter pylori infection using a γ-glutamyltranspeptidase-activatable fluorescent probe

Taro Akashi / Hajime Isomoto / Kayoko Matsushima / Mako Kamiya / Tsutomu Kanda / Masayuki Nakano / Takumi Onoyama / Masashi Fujii / Junko Akada / Yuko Akazawa / Ken Ohnita / Fuminao Takeshima / Kazuhiko Nakao / Yasuteru Urano

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 9

Abstract: Abstract A γ-glutamyl hydroxymethyl rhodamine green probe (gGlu-HMRG) reacts with γ-glutamyltranspeptidase (GGT) and immediately produces fluorescence, is clinically applied for real-time cancers’ visualization. Since Helicobacter pylori produces GGT, ... ...

Abstract	Abstract A γ-glutamyl hydroxymethyl rhodamine green probe (gGlu-HMRG) reacts with γ-glutamyltranspeptidase (GGT) and immediately produces fluorescence, is clinically applied for real-time cancers’ visualization. Since Helicobacter pylori produces GGT, this study aimed to investigate whether gGlu-HMRG can be used to detect H. pylori infections. A wild-type H. pylori strain and the ggt gene-disrupted mutant were cultured and treated with gGlu-HMRG. This fluorescent probe assay was used to quantify GGT activity of H. pylori ex vivo using gastric biopsy specimens. The H. pylori diagnostic capabilities of the assay were determined from altered fluorescence intensity (FI) values at 5 min (FIV-5) and 15 minutes (FIV-15). Distinct fluorescence was identified in wild H. pylori strain, using gGlu-HMRG, whereas no fluorescence was observed in ggt gene-disrupted mutant strain. On ex vivo imaging of gGlu-HMRG, fluorescence intensity increased markedly with time in H. pylori-positive specimens; however, the H. pylori-negative specimens displayed a slight increase in FI. FIV-5 and FIV-15 differed significantly between H. pylori-positive and -negative specimens. FIV-15 differed significantly between H. pylori-positive and -eradicated group. This assay sensitivity and specificity were 75.0% and 83.3% in the antrum and 82.6% and 89.5% in the stomach body. GGT-activatable fluorescence probe is applicable for rapid diagnosis of H. pylori.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2019-07-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Toyocamycin attenuates free fatty acid-induced hepatic steatosis and apoptosis in cultured hepatocytes and ameliorates nonalcoholic fatty liver disease in mice.

PLoS ONE, Vol 12, Iss 3, p e

2017 Volume 0170591

Abstract: BACKGROUND AND AIMS:A high serum level of saturated free fatty acids (FFAs) is associated with the development of nonalcoholic fatty liver disease (NAFLD). X-box binding protein-1 (XBP-1) is activated by FFA treatment upon splicing. XBP-1 is a ... ...

Abstract	BACKGROUND AND AIMS:A high serum level of saturated free fatty acids (FFAs) is associated with the development of nonalcoholic fatty liver disease (NAFLD). X-box binding protein-1 (XBP-1) is activated by FFA treatment upon splicing. XBP-1 is a transcription factor induced by the endoplasmic reticulum (ER) stress sensor endoribonuclease inositol-requiring enzyme 1 alpha (IRE1α). However, the role of XBP-1 in NAFLD remains relatively unexplored. Toyocamycin was recently reported to attenuate the activation of XBP-1, possibly by inducing a conformational change in IRE1α. In this study, we examined the effect of toyocamycin on hepatocyte lipoapoptosis and steatosis. We also explored the effects of toyocamycin in a mouse model of NAFLD. METHODS:Huh-7 cells and isolated rat primary hepatocytes were treated with palmitic acid (PA), which is a saturated FFA, in the presence or absence of toyocamycin. In addition, male C57BL/6J mice were fed a diet rich in saturated fat, fructose, and cholesterol (FFC) for 4 months, after which the effect of toyocamycin was assessed. RESULTS:Toyocamycin attenuated FFA-induced steatosis. It also significantly reduced PA-induced hepatocyte lipoapoptosis. In addition, toyocamycin reduced the expression of cytosine-cytosine-adenosine-adenosine-thymidine enhancer-binding protein homologous protein (CHOP), which is a key player in ER stress-mediated apoptosis, as well as its downstream cell death modulator, death receptor 5. In the in vivo study, toyocamycin ameliorated the liver injury caused by FFC-induced NAFLD. It also reduced hepatic steatosis and the expression of lipogenic genes. CONCLUSIONS:The data we obtained suggest that toyocamycin attenuates hepatocyte lipogenesis and ameliorates NAFLD in vivo and may therefore be beneficial in the treatment of NAFLD in humans.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: New endoscopic indicator of esophageal achalasia

Hitomi Minami / Hajime Isomoto / Satoshi Miuma / Yasutoshi Kobayashi / Naoyuki Yamaguchi / Shigetoshi Urabe / Kayoko Matsushima / Yuko Akazawa / Ken Ohnita / Fuminao Takeshima / Haruhiro Inoue / Kazuhiko Nakao

PLoS ONE, Vol 10, Iss 2, p e

"pinstripe pattern".

2015 Volume 0101833

Abstract: Endoscopic diagnosis of esophageal achalasia lacking typical endoscopic features can be extremely difficult. The aim of this study was to identify simple and reliable early indicator of esophageal achalasia.This single-center retrospective study included ...

Abstract	Endoscopic diagnosis of esophageal achalasia lacking typical endoscopic features can be extremely difficult. The aim of this study was to identify simple and reliable early indicator of esophageal achalasia.This single-center retrospective study included 56 cases of esophageal achalasia without previous treatment. As a control, 60 non-achalasia subjects including reflux esophagitis and superficial esophageal cancer were also included in this study. Endoscopic findings were evaluated according to Descriptive Rules for Achalasia of the Esophagus as follows: (1) esophageal dilatation, (2) abnormal retention of liquid and/or food, (3) whitish change of the mucosal surface, (4) functional stenosis of the esophago-gastric junction, and (5) abnormal contraction. Additionally, the presence of the longitudinal superficial wrinkles of esophageal mucosa, "pinstripe pattern (PSP)" was evaluated endoscopically. Then, inter-observer diagnostic agreement was assessed for each finding.The prevalence rates of the above-mentioned findings (1-5) were 41.1%, 41.1%, 16.1%, 94.6%, and 43.9%, respectively. PSP was observed in 60.7% of achalasia, while none of the control showed positivity for PSP. PSP was observed in 26 (62.5%) of 35 cases with shorter history < 10 years, which usually lacks typical findings such as severe esophageal dilation and tortuosity. Inter-observer agreement level was substantial for food/liquid remnant (k = 0.6861) and PSP (k = 0.6098), and was fair for abnormal contraction and white change. The accuracy, sensitivity, and specificity for achalasia were 83.8%, 64.7%, and 100%, respectively."Pinstripe pattern" could be a reliable indicator for early discrimination of primary esophageal achalasia.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Background coloration of squamous epithelium in esophago-pharyngeal squamous cell carcinoma

Hitomi Minami / Hajime Isomoto / Toshiyuki Nakayama / Tomayoshi Hayashi / Naoyuki Yamaguchi / Kayoko Matsushima / Yuko Akazawa / Ken Ohnita / Fuminao Takeshima / Haruhiro Inoue / Kazuhiko Nakao

PLoS ONE, Vol 9, Iss 1, p e

what causes the color change?

2014 Volume 85553

Abstract: OBJECTIVES: This study aims to clarify the cause of background coloration in the epithelia between each dilated intra papillary capillary loop in esophago-pharyngeal squamous cell carcinoma. DESIGN: This is a single center retrospective study including ... ...

Abstract	OBJECTIVES: This study aims to clarify the cause of background coloration in the epithelia between each dilated intra papillary capillary loop in esophago-pharyngeal squamous cell carcinoma. DESIGN: This is a single center retrospective study including 124 patients with 160 lesions who underwent esophagogastroduodenoscopy in Nagasaki University Hospital from September 2007 to March 2012; a detailed comparison between endoscopic images and pathology was performed. Immunohistological assessment using anti-human hemoglobin antibody (anti-Hb Ab) was performed to verify the presence of hemoglobin (Hb) component in the cancer cells. Real-time polymerase chain reaction (RT-PCR) and in situ hybridization (ISH) on Hb-β mRNA were performed to assess the production of Hb component within the cancer cells. RESULTS: A strong positivity for anti-Hb Ab was observed in the squamous cell carcinoma area, whereas non-cancerous mucosa showed no immunopositivity for Hb. The concordance rate between anti-Hb Ab immunoreactivity and the presence of BC was as high as 80.9%. The amount of Hb-β mRNA expression was three times higher in cancer tissues compared with the surrounding non-cancerous mucosa. ISH images showed that the expression exclusively occurred in cancer cells, indicating that Hb is probably produced within cancer cells. CONCLUSIONS: The background coloration observed is partly due to an extravascular component of Hb. RT-PCR and ISH analyses indicate that Hb is produced within cancer cells.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Novel serine/threonine kinase 11 gene mutations in Peutz-Jeghers syndrome patients and endoscopic management

Kazuhiro Tsukamoto / Kazuhiko Nakao / Masahiro Ito / Saburo Shikuwa / Fuminao Takeshima / Tatsuki Ichikawa / Ken Ohnita / Naoyuki Yamaguchi / Hiroaki Nishioka / Hajime Isomoto / Hiroyuki Yajima / Shigeru Kohno

World Journal of Gastrointestinal Endoscopy, Vol 5, Iss 3, Pp 102-

2013 Volume 110

Abstract: AIM: To explore mutations in serine/threonine kinase 11 (STK11) gene in Peutz-Jeghers syndrome (PJS) with gastrointestinal (GI) hamartomatous polyps. METHODS: Six Japanese PJS patients in 3 families were enrolled in this study. Each of the cases had ... ...

Abstract	AIM: To explore mutations in serine/threonine kinase 11 (STK11) gene in Peutz-Jeghers syndrome (PJS) with gastrointestinal (GI) hamartomatous polyps. METHODS: Six Japanese PJS patients in 3 families were enrolled in this study. Each of the cases had hamartomatous polyposis in the gastrointestinal tract, including the small intestine, along with mucocutaneous hyperpigmentation. Narrow-band imaging (NBI)-magnification endoscopy was employed to detect microvascular and microsurface irregularities in the GI lesions. NBI magnification findings could be classified into three groups (type A, type B, or type C). Endoscopic polypectomy was performed using double-balloon enteroscopy or colonoscopy. Genomic DNA was extracted from a whole blood sample from each subject. All of the coding exons of STK11 gene, its boundary regions, and the promoter region containing the polymorphic regions were amplified by polymerase chain reaction, and direct sequencing was performed to assess the germline mutations. RESULTS: NBI-magnification endoscopic observation could detect the abnormalities in microvessels and microsurface structures of GI polyps. Overall, we found 5 cases of type A and one case without the examination for the gastric polyps, while there were 4 cases of type B and 2 case of type A for the colorectal polyps. Seventy-nine small-bowel and 115 colorectal polyps over 27 sessions for each were resected endoscopically without significant complications. The only delayed complication included the occurrence of bleeding in a case, and this was successfully managed with hemoclips. Resected polyps contained no malignant components. Based on mutation analysis, all 3 cases in Family I exhibited the +658C>T nonsense mutation in exon 5, which resulted in the production of a truncated protein (Q220X). In Family II, a case had -252C>A and -193C>A in the promoter region. In Family III, a case was found to have the +1062C>G (F342L) mutation in exon 8. CONCLUSION: We found two novel mutations of STK11 in association with PJS. Endoscopic polypectomy of GI polyps in PJS patients appears to be useful to prevent emergency laparotomies and reduce the cancer risk.
Keywords	Peutz-Jeghers syndrome ; Serine/threonine kinase 11 ; Gastrointestinal hamartomatous polyps ; Double-balloon enteroscopy ; Narrow-band imaging ; Diseases of the digestive system. Gastroenterology ; RC799-869 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Gastroenterology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences ; Surgery ; RD1-811 ; DOAJ:Surgery
Subject code	571
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Baishideng Publishing Group Co., Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genetic Polymorphisms of IL-17F and TRAF3IP2 Could Be Predictive Factors of the Long-Term Effect of Infliximab against Crohn’s Disease

Shigetoshi Urabe / Hajime Isomoto / Tetsuya Ishida / Kazumi Maeda / Tatsuo Inamine / Shinji Kondo / Norihide Higuchi / Kayoko Sato / Ryohei Uehara / Hiroyuki Yajima / Haruhisa Machida / Chun Chuan Chen / Yasuhiro Fukuda / Fuminao Takeshima / Kazuhiko Nakao / Kazuhiro Tsukamoto

BioMed Research International, Vol

2015 Volume 2015

Abstract: Background. We aimed to identify certain genes related to response to infliximab (IFX) and biomarkers to predict the IFX effect for Japanese Crohn’s disease (CD) patients by performing an association study of single nucleotide polymorphisms (SNPs) in ... ...

Abstract	Background. We aimed to identify certain genes related to response to infliximab (IFX) and biomarkers to predict the IFX effect for Japanese Crohn’s disease (CD) patients by performing an association study of single nucleotide polymorphisms (SNPs) in candidate genes in the interleukin- (IL-) 17 signaling pathway with response to IFX after 1 year of treatment. Methods. A total of 103 patients were divided into two groups, responders and nonresponders. Twenty-eight tag SNPs in 5 genes were genotyped. The frequencies of alleles and genotypes of each SNP were compared between responders and nonresponders in three different inheritance models. A genetic test was performed using a combination of the associated SNPs as biomarkers. Results. Multivariate logistic regression analysis indicated that the four variable factors, concomitant use of immunomodulators, penetrating disease, a G/G genotype of rs766748 in IL-17F, and a C/C or C/A genotype of rs1883136 in TRAF3IP2, independently contributed to response to IFX after 1 year of treatment. Genetic test using the polymorphisms of these genes perfectly predicted the responder and nonresponder CD patients with both concomitant use of immunomodulators and penetrating disease. Conclusion. IL17F and TRAF3IP2 are one of IFX-related genes, useful as biomarkers of IFX response, and may be target molecules for new therapeutic drugs.
Keywords	Medicine ; R
Subject code	610 ; 616
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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