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Article ; Online: N,N-Dimethylglycine in patients with progressive multiple sclerosis: result of a pilot double-blind, placebo, controlled randomized clinical trial.

Wolfsegger, Thomas / Böck, Klaus / Schimetta, Wolfgang / von Oertzen, Tim J / Assar, Hamid

Neurological research and practice

2021 Volume 3, Issue 1, Page(s) 29

Abstract: Oral administration of N,N-Dimethylglycine (DMG), a tertiary amino acid, presumably enhances oxygen ...

Abstract	Oral administration of N,N-Dimethylglycine (DMG), a tertiary amino acid, presumably enhances oxygen utilization by tissue and complex with free radicals. Beneficial effects are improved endurance performance and reduction fatigue in humans and animals. This pilot study reports the results over a one-year double-blind, placebo-controlled trial of DMG in 30 randomized patients with progressive multiple sclerosis. No treatment effects were found between the placebo group and the DMG group for disability, fatigue, cognitive, or gait parameters.
Language	English
Publishing date	2021-05-24
Publishing country	England
Document type	Letter
ISSN	2524-3489
ISSN (online)	2524-3489
DOI	10.1186/s42466-021-00126-z
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Article ; Online: Metabolism of vertebrate amino sugars with N-glycolyl groups: resistance of α2-8-linked N-glycolylneuraminic acid to enzymatic cleavage.

Davies, Leela R L / Pearce, Oliver M T / Tessier, Matthew B / Assar, Siavash / Smutova, Victoria / Pajunen, Maria / Sumida, Mizuki / Sato, Chihiro / Kitajima, Ken / Finne, Jukka / Gagneux, Pascal / Pshezhetsky, Alexey / Woods, Robert / Varki, Ajit

The Journal of biological chemistry

2012 Volume 287, Issue 34, Page(s) 28917–28931

Abstract: The sialic acid (Sia) N-acetylneuraminic acid (Neu5Ac) and its hydroxylated derivative N ... may partly explain reduced enzymatic activity. In keeping with this, polymers of N-propionylneuraminic ...

Abstract	The sialic acid (Sia) N-acetylneuraminic acid (Neu5Ac) and its hydroxylated derivative N-glycolylneuraminic acid (Neu5Gc) differ by one oxygen atom. CMP-Neu5Gc is synthesized from CMP-Neu5Ac, with Neu5Gc representing a highly variable fraction of total Sias in various tissues and among different species. The exception may be the brain, where Neu5Ac is abundant and Neu5Gc is reported to be rare. Here, we confirm this unusual pattern and its evolutionary conservation in additional samples from various species, concluding that brain Neu5Gc expression has been maintained at extremely low levels over hundreds of millions of years of vertebrate evolution. Most explanations for this pattern do not require maintaining neural Neu5Gc at such low levels. We hypothesized that resistance of α2-8-linked Neu5Gc to vertebrate sialidases is the detrimental effect requiring the relative absence of Neu5Gc from brain. This linkage is prominent in polysialic acid (polySia), a molecule with critical roles in vertebrate neural development. We show that Neu5Gc is incorporated into neural polySia and does not cause in vitro toxicity. Synthetic polymers of Neu5Ac and Neu5Gc showed that mammalian and bacterial sialidases are much less able to hydrolyze α2-8-linked Neu5Gc at the nonreducing terminus. Notably, this difference was not seen with acid-catalyzed hydrolysis of polySias. Molecular dynamics modeling indicates that differences in the three-dimensional conformation of terminal saccharides may partly explain reduced enzymatic activity. In keeping with this, polymers of N-propionylneuraminic acid are sensitive to sialidases. Resistance of Neu5Gc-containing polySia to sialidases provides a potential explanation for the rarity of Neu5Gc in the vertebrate brain.
MeSH term(s)	Amino Sugars/chemistry ; Amino Sugars/metabolism ; Animals ; Bacteria/chemistry ; Bacteria/metabolism ; Brain/metabolism ; Brain Chemistry/physiology ; Carbohydrate Conformation ; Cattle ; Dolphins ; Elephants ; Evolution, Molecular ; Hydrolysis ; Mice ; N-Acetylneuraminic Acid ; Nerve Tissue Proteins/chemistry ; Nerve Tissue Proteins/metabolism ; Neuraminic Acids/chemistry ; Neuraminic Acids/metabolism ; Neuraminidase/chemistry ; Neuraminidase/metabolism ; Pan troglodytes ; Rats ; Species Specificity ; Swine
Chemical Substances	Amino Sugars ; Nerve Tissue Proteins ; Neuraminic Acids ; N-glycolylneuraminic acid (1113-83-3) ; Neuraminidase (EC 3.2.1.18) ; N-Acetylneuraminic Acid (GZP2782OP0)
Language	English
Publishing date	2012-06-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M112.365056
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Article: Salivary Gland Tumors in Iran: A Systematic Review of 2870 Cases Based on the New WHO Classification.

Assar, Sahar / Assar, Sepideh / Mardanifard, Heidar-Ali / Jaafari-Ashkavandi, Zohreh

Iranian journal of pathology

2023 Volume 18, Issue 1, Page(s) 1–11

Abstract: ... calculated as prevalence (%) * (N/the sum of all N). We used the unpaired Two-sample T-test to compare ...

Abstract	Background & objective: There is no consensus on the prevalence of salivary gland tumors (SGTs) in Iran. Thus, we systematically reviewed the literature about the prevalence of SGTs in Iran and applied the last world health organization (WHO) classification. Methods: The systematic literature search was performed in EMBASE, Scopus, PubMed MEDLINE, Google Scholar, Scientific Information Database (SID), and Magiran; we searched for "salivary gland," "tumor," "prevalence," and "Iran" until 1 March 2021. The studies included were written in the English and Farsi languages. The weighted mean prevalence of SGTs was calculated as prevalence (%) * (N/the sum of all N). We used the unpaired Two-sample T-test to compare the weighted means. Results: A total of 17 studies, including 2870 patients, were selected for the data synthesis. The weighted mean prevalence of benign and malignant tumors was 66% (95% CI: 59-73) and 34% (95% CI: 27-41), respectively. The patients' mean age was reported in 10 out of the 17 studies. The weighted mean age of the patients was 40 (95% CI: 37-42) and 49 (95% CI: 43-55) years for benign and malignant tumors, respectively ( Conclusion: More than one-third of SGTs in Iran were malignant, which is higher than the reports from Middle Eastern countries. Information about risk factors and the burden of SGTs in Iran is insufficient. Thus, further well-designed longitudinal studies are warranted.
Language	English
Publishing date	2023-03-23
Publishing country	Iran
Document type	Journal Article ; Review
ZDB-ID	2478278-6
ISSN	1735-5303 ; 2345-3656
ISSN	1735-5303 ; 2345-3656
DOI	10.30699/IJP.2023.559121.2942
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Article ; Online: Formation of N(epsilon)-(carboxymethyl)lysine and loss of lysine in casein glucose-fatty acid model systems.

Lima, Maria / Assar, Shima H / Ames, Jennifer M

Journal of agricultural and food chemistry

2010 Volume 58, Issue 3, Page(s) 1954–1958

Abstract: ... when proteins are heated with reducing sugar or lipid. N(epsilon)-(Carboxymethyl)lysine (CML) is the most ...

Abstract	Advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs) form when proteins are heated with reducing sugar or lipid. N(epsilon)-(Carboxymethyl)lysine (CML) is the most commonly studied AGE/ALE in foods, but the relative importance of dietary sugar and lipid as its precursors is uncertain. The aim of this study was to determine the relative amounts of CML formed from fatty acid and glucose in a model food system. Model systems were prepared by heating casein (3.2%) with glucose or fatty acid (oleic, linoleic, linolenic, or arachidonic acid) (200 mM) or a mixture of glucose and linolenic acid (200 mM of each precursor) at 95 degrees C for up to 8 h. CML was determined by ultrapressure liquid chromatography-tandem mass spectrometry. The amount of CML formed from casein and glucose incubated at 95 degrees C for 8 h was 15-fold higher than that obtained when casein was heated with arachidonic acid under the same conditions. However, the loss of lysine in the casein-arachidonic acid incubations was 83% compared to 54% loss in the casein-glucose incubations. The loss of lysine in casein-fatty acid model systems increased with degree of unsaturation of the fatty acid. The formation of lipid peroxidation products during oxidation of fatty acids might be a potent factor for loss of lysine in the casein-fatty acid systems.
MeSH term(s)	Animals ; Caseins/chemistry ; Cattle ; Fatty Acids/chemistry ; Glucose/chemistry ; Lysine/analogs & derivatives ; Lysine/chemistry ; Models, Chemical
Chemical Substances	Caseins ; Fatty Acids ; N(6)-carboxymethyllysine (70YDX3Z2O7) ; Glucose (IY9XDZ35W2) ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2010-02-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	241619-0
ISSN	1520-5118 ; 0021-8561
ISSN (online)	1520-5118
ISSN	0021-8561
DOI	10.1021/jf903562c
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Article: Hemophagocytic lymphohistiocytosis accompanying Still's disease: A case report.

Ahmadzadeh, Arman / Babadi, Neda / Farsad, Faraneh / Babadi, Saba / Assar, Shirin

Clinical case reports

2023 Volume 11, Issue 10, Page(s) e7955

Abstract: Hemophagocytic lymphohistiocytosis (HLH) is a rare hematologic disease that occurs due to immune system dysfunction. Clinical manifestations of this disease are fever, increased ferritin level, cytopenia, and hemophagocytosis in the biopsy report of the ... ...

Abstract	Hemophagocytic lymphohistiocytosis (HLH) is a rare hematologic disease that occurs due to immune system dysfunction. Clinical manifestations of this disease are fever, increased ferritin level, cytopenia, and hemophagocytosis in the biopsy report of the bone marrow. We report a 36-year-old woman referred to our hospital with persistent fever, arthralgia in interphalangeal joints, and cutaneous rash on the trunk, was subsequently diagnosed as an adult-onset Still's disease (AOSD), and after bone marrow aspiration, HLH was diagnosed with her.
Language	English
Publishing date	2023-10-10
Publishing country	England
Document type	Case Reports
ZDB-ID	2740234-4
ISSN	2050-0904
ISSN	2050-0904
DOI	10.1002/ccr3.7955
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Article ; Audio / Video: Formation of N(epsilon)-(Carboxymethyl)lysine and Loss of Lysine in Casein Glucose−Fatty Acid Model Systems

Lima, Maria / Assar, Shima H / Ames, Jennifer M

Journal of agricultural and food chemistry. 2010 Feb. 10, v. 58, no. 3

2010

Abstract: Advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs) form when proteins are heated with reducing sugar or lipid. Nε-(Carboxymethyl)lysine (CML) is the most commonly studied AGE/ALE in foods, but the relative importance of ... ...

Abstract	Advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs) form when proteins are heated with reducing sugar or lipid. Nε-(Carboxymethyl)lysine (CML) is the most commonly studied AGE/ALE in foods, but the relative importance of dietary sugar and lipid as its precursors is uncertain. The aim of this study was to determine the relative amounts of CML formed from fatty acid and glucose in a model food system. Model systems were prepared by heating casein (3.2%) with glucose or fatty acid (oleic, linoleic, linolenic, or arachidonic acid) (200 mM) or a mixture of glucose and linolenic acid (200 mM of each precursor) at 95 °C for up to 8 h. CML was determined by ultrapressure liquid chromatography−tandem mass spectrometry. The amount of CML formed from casein and glucose incubated at 95 °C for 8 h was 15-fold higher than that obtained when casein was heated with arachidonic acid under the same conditions. However, the loss of lysine in the casein−arachidonic acid incubations was 83% compared to 54% loss in the casein−glucose incubations. The loss of lysine in casein−fatty acid model systems increased with degree of unsaturation of the fatty acid. The formation of lipid peroxidation products during oxidation of fatty acids might be a potent factor for loss of lysine in the casein−fatty acid systems.
Keywords	glycation ; lysine ; casein ; fatty acids ; model food systems ; Maillard reaction ; heat treatment ; food analysis ; food composition
Language	English
Dates of publication	2010-0210
Size	p. 1954–1958.
Document type	Article ; Audio / Video
ZDB-ID	241619-0
ISSN	1520-5118 ; 0021-8561
ISSN (online)	1520-5118
ISSN	0021-8561
DOI	10.1021/jf903562c
Database	NAL-Catalogue (AGRICOLA)

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Article: Determination of N ε-(carboxymethyl)lysine in food systems by ultra performance liquid chromatography-mass spectrometry

Assar, Shima H / Moloney, Catherine / Lima, Maria / Magee, Ronald / Ames, Jennifer M

Amino acids. 2009 Feb., v. 36, no. 2

2009

Abstract: ... spectrometer operated in multiple reaction monitoring mode to determine the advanced glycation endproduct, N ε ...

Abstract	We report the use of ultra pressure liquid chromatography (UPLC), coupled to a tandem mass spectrometer operated in multiple reaction monitoring mode to determine the advanced glycation endproduct, N ε-(carboxymethyl)lysine (CML). The procedure was applied to acid hydrolyzates of protein isolated from a range of foods (milks processed at different temperatures, butter, cheese, infant formulae, bread, raw and cooked minced beef and olive oil). Highest levels of CML were determined in white bread crust (15.2 ± 0.63 mmol/mol Lys), wholemeal bread crust (13.1 ± 0.61 mmol/mol Lys) and evaporated full-fat milk (4.86 ± 0.77 mmol/mol Lys). Lowest levels of CML were measured in raw minced beef beef (0.03 ± 002 mmol/mol Lys), raw full-fat cow's milk (0.08 ± 0.03 mmol/mol Lys) and pasteurized skimmed cow's milk (0.09 ± 0.002 mmol/mol Lys). CML could not be detected in olive oil.
Language	English
Dates of publication	2009-02
Size	p. 317-326.
Publisher	Springer Vienna
Publishing place	Vienna
Document type	Article
ZDB-ID	1121341-3
ISSN	1438-2199 ; 0939-4451
ISSN (online)	1438-2199
ISSN	0939-4451
DOI	10.1007/s00726-008-0071-4
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Zs.A 3490: Show issues

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Article ; Online: Medical treatment of small abdominal aortic aneurysm.

Assar, A N

The Journal of cardiovascular surgery

2012 Volume 53, Issue 4, Page(s) 517–525

Abstract: Conventional open repair or endovascular aneurysm repair is indicated for infrarenal abdominal aortic aneurysm (AAA) when the diameter of the latter is ≥ 5.5 cm. This therapeutic strategy is based on results of randomized trials of open repair versus ... ...

Abstract	Conventional open repair or endovascular aneurysm repair is indicated for infrarenal abdominal aortic aneurysm (AAA) when the diameter of the latter is ≥ 5.5 cm. This therapeutic strategy is based on results of randomized trials of open repair versus ultrasound surveillance of small AAA (<5.5 cm). Studies of screening for AAA have shown that >90% of aneurysms detected are small aneurysms (<5.5 cm). Despite the low annual risk of rupture of these aneurysms, patients with small AAA are left with a potentially life-threatening disease for which no immediate treatment is available. Hence, medical treatment directed at limiting the expansion of small AAA has emerged as an alternative therapeutic strategy. Randomized trials of doxycycline, roxithromycin, and propranolol in patients with small AAA have been published. The results of the doxycycline and roxithromycin trials suggest that both medications can limit AAA expansion, especially during the first year of treatment. Propranolol did not limit AAA expansion, and the trials were stopped because of its serious side effects. In other studies, statins and indomethacin have also been shown to limit AAA expansion. However, these studies were observational with relatively small numbers of patients. Thus, large randomized controlled trials with long follow-up are needed to objectively assess the efficacy of medications that have shown potential in limiting AAA expansion. In addition, recent evidence of regression of AAA in experimental animal models is likely to change our concepts of the molecular pathogenesis of AAA, and could make medical treatment of small AAA a possibility.
MeSH term(s)	Aortic Aneurysm, Abdominal/diagnosis ; Aortic Aneurysm, Abdominal/drug therapy ; Aortic Aneurysm, Abdominal/etiology ; Cardiovascular Agents/adverse effects ; Cardiovascular Agents/therapeutic use ; Disease Progression ; Doxycycline/therapeutic use ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Indomethacin/therapeutic use ; Propranolol/adverse effects ; Risk Factors ; Risk Reduction Behavior ; Roxithromycin/therapeutic use ; Time Factors ; Treatment Outcome
Chemical Substances	Cardiovascular Agents ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Roxithromycin (21KOF230FA) ; Propranolol (9Y8NXQ24VQ) ; Doxycycline (N12000U13O) ; Indomethacin (XXE1CET956)
Language	English
Publishing date	2012-08
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	80143-4
ISSN	1827-191X ; 0021-9509
ISSN (online)	1827-191X
ISSN	0021-9509
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Article ; Online: Clonal mesenchymal stem cell-derived extracellular vesicles improve mouse model of weight drop-induced traumatic brain injury through reducing cistauosis and apoptosis.

Amini, Azadeh / Shekari, Faezeh / Assar Kashani, Sara / Eslami, Nasim / Nazari, Abdoreza / Tofigh, Nahid / Shahpasand, Koorosh / Akbari Javar, Hamid / Baharvand, Hossein

Experimental neurology

2023 Volume 367, Page(s) 114467

Abstract: Objective: Traumatic brain injury (TBI) is a major risk factor for disabilities globally with no effective treatment thus far. Recently, homogenous population of clonal mesenchymal stem cells (cMSC) and their derived extracellular vesicles (cMSC-EVs) ... ...

Abstract	Objective: Traumatic brain injury (TBI) is a major risk factor for disabilities globally with no effective treatment thus far. Recently, homogenous population of clonal mesenchymal stem cells (cMSC) and their derived extracellular vesicles (cMSC-EVs) have been proposed as a promising TBI treatment strategy. We herein investigated possible therapeutic effect of cMSC-EVs in TBI treatment and the underlying mechanisms considering cis p-tau as an early hallmark of TBI. Methods: We examined the EVs morphology, size distribution, marker expression, and uptake. Moreover, the EVs neuroprotective effects were studied in both in-vitro and in-vivo model. We also examined the anti-cis p-tau antibody-loading characteristics of the EVs. We treated TBI mouse model with EVs; prepared from cMSC-conditioned media. TBI mice were given cMSC-EVs intravenously and their cognitive functions were analyzed two months of the treatment. We employed immunoblot analysis to study the underlying molecular mechanisms. Results: We observed a profound cMSC-EVs uptake by primary cultured neurons. We found a remarkable neuroprotective effect of cMSC-EVs upon nutritional deprivation stress. Furthermore, cMSC-EVs were effectively loaded with an anti-cis p-tau antibody. There was a significant improvement in cognitive function in TBI animal models treated with cMSC-EVs compared to the saline-treated group. There was a decreased cis p-tau and cleaved caspase3 as well as increased p-PI3K in all treated animals. Conclusions: The results revealed that cMSC-EVs efficiently improved animal behaviors after TBI by reducing cistauosis and apoptosis. Moreover, the EVs can be employed as an effective strategy for antibody delivery during passive immunotherapy.
MeSH term(s)	Mice ; Animals ; Brain Injuries, Traumatic/complications ; Brain Injuries, Traumatic/metabolism ; Mesenchymal Stem Cells/metabolism ; Disease Models, Animal ; Extracellular Vesicles ; Apoptosis
Language	English
Publishing date	2023-06-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207148-4
ISSN	1090-2430 ; 0014-4886
ISSN (online)	1090-2430
ISSN	0014-4886
DOI	10.1016/j.expneurol.2023.114467
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Article ; Online: Overexpression of Synoviolin and miR-125a-5p, miR-19b-3p in peripheral blood of rheumatoid arthritis patients after treatment with conventional DMARDs and methylprednisolone.

Karamali, Negin / Mahmoudi, Zahra / Roghani, Seyed Askar / Assar, Shirin / Pournazari, Mehran / Soufivand, Parviz / Karaji, Ali Gorgin / Rezaiemanesh, Alireza

Clinical rheumatology

2023 Volume 43, Issue 1, Page(s) 147–157

Abstract: Purpose: SYVN1 is an endoplasmic reticulum (ER)-resident E3 ubiquitin ligase that has an essential function along with SEL1L in rheumatoid arthritis (RA) pathogenesis. This study aimed to investigate the changes in the expression of peripheral blood ... ...

Abstract	Purpose: SYVN1 is an endoplasmic reticulum (ER)-resident E3 ubiquitin ligase that has an essential function along with SEL1L in rheumatoid arthritis (RA) pathogenesis. This study aimed to investigate the changes in the expression of peripheral blood ncRNAs and SYVN1-SEL1L affected by DMARDs treatment. Methods: Twenty-five newly diagnosed RA patients were randomly assigned to receive conventional DMARDs (csDMARDs) and methylprednisolone for six months. The peripheral blood gene expression of SYVN1 and SEL1L and possible regulatory axes, NEAT1, miR-125a-5p, and miR-19b-3p, were evaluated before and after qRT-PCR. We also compared differences between the patients and healthy controls (HCs), and statistical analyses were performed to determine the correlation between ncRNAs with SYVN1-SEL1L and the clinical parameters of RA. Results: Expression of NEAT1 (P = 0.0001), miR-19b-3p (P = 0.007), miR-125a-5p (P = 0.005), and SYVN1 (P = 0.036) was significantly increased in newly diagnosed patients compared to HCs; also, miR-125a-5p, miR-19b-3p, and SYVN1 were significantly overexpressed after treatment (P = 0.001, P = 0.001, and P = 0.005, respectively). NEAT1 was positively correlated with SYVN1, and miR-125a-5p had a negative correlation with anti-cyclic citrullinated peptides. The ROC curve analysis showed the potential role of selected ncRNAs in RA pathogenesis. Conclusion: The results indicate the ineffectiveness of the csDMARDs in reducing SYVN1 expression. The difference in expression of ncRNAs might be useful markers for monitoring disease activity and determining therapeutic responses in RA patients. Key Points • The expression of NEAT1 is significantly upregulated in RA patients compared to HC subjects. • miR-19b-3p, miR-125a-5p, and SYVN1 are significantly upregulated in RA patients compared to HC subjects. • The expression of miR-19b-3p and miR-125a-5p is significantly increased in RA patients after treatment with DMARDs and methylprednisolone. • NEAT1 is positively correlated with SYVN1.
MeSH term(s)	Humans ; Methylprednisolone/therapeutic use ; MicroRNAs/metabolism ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/genetics ; Polymerase Chain Reaction ; Antirheumatic Agents/therapeutic use ; Proteins/genetics ; Proteins/therapeutic use
Chemical Substances	Methylprednisolone (X4W7ZR7023) ; MicroRNAs ; Antirheumatic Agents ; SEL1L protein, human ; Proteins
Language	English
Publishing date	2023-12-04
Publishing country	Germany
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	604755-5
ISSN	1434-9949 ; 0770-3198
ISSN (online)	1434-9949
ISSN	0770-3198
DOI	10.1007/s10067-023-06808-0
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