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  • 1
    Language: English
    In: The Journal of clinical investigation, 2009-08, Vol.119 (8), p.2366-2378
    Description: Many microRNAs (miRNAs), posttranscriptional regulators of numerous cellular processes and developmental events, are downregulated in tumors. However, their role in tumorigenesis remains largely unknown. In this work, we examined the role of the muscle-specific miRNAs miR-1 and miR-206 in human rhabdomyosarcoma (RMS), a soft tissue sarcoma thought to arise from skeletal muscle progenitors. We have shown that miR-1 was barely detectable in primary RMS of both the embryonal and alveolar subtypes and that both miR-1 and miR-206 failed to be induced in RMS cell lines upon serum deprivation. Moreover, reexpression of miR-206 in RMS cells promoted myogenic differentiation and blocked tumor growth in xenografted mice by switching the global mRNA expression profile to one that resembled mature muscle. Finally, we showed that the product of the MET proto-oncogene, the Met tyrosine-kinase receptor, which is overexpressed in RMS and has been implicated in RMS pathogenesis, was downregulated in murine satellite cells by miR-206 at the onset of normal myogenesis. Thus, failure of posttranscriptional modulation may underlie Met overexpression in RMS and other types of cancer. We propose that tissue-specific miRNAs such as miR-1 and miR-206, given their ability to modulate hundreds of transcripts and to act as nontoxic differentiating agents, may override the genomic heterogeneity of solid tumors and ultimately hold greater therapeutic potential than single gene-directed drugs.
    Subject(s): Proto-Oncogene Proteins - antagonists & inhibitors ; Rhabdomyosarcoma - prevention & control ; Humans ; Muscle Development - physiology ; Proto-Oncogene Proteins c-met ; Receptors, Growth Factor - antagonists & inhibitors ; Rhabdomyosarcoma - pathology ; Xenograft Model Antitumor Assays ; Receptors, Growth Factor - physiology ; Animals ; Cell Cycle ; Proto-Oncogene Proteins - physiology ; Cell Line, Tumor ; Cell Differentiation ; Mice ; MicroRNAs - genetics ; Rhabdomyosarcoma - genetics ; MicroRNAs - physiology ; Animal experimentation ; Usage ; Growth ; Rhabdomyosarcoma ; Physiological aspects ; Genetic aspects ; Research ; Cell differentiation ; Gene expression ; Methods ; Index Medicus ; Abridged Index Medicus
    ISSN: 0021-9738
    E-ISSN: 1558-8238
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: PubMed Central
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: Journal of clinical oncology, 2012-06-10, Vol.30 (17), p.2112-2118
    Description: We compared two chemotherapy regimens that included methotrexate (MTX), cisplatin (CDP), and doxorubicin (ADM) with or without ifosfamide (IFO) in patients with nonmetastatic osteosarcoma of the extremity. Patients age ≤ 40 years randomly received regimens with the same cumulative doses of drugs (ADM 420 mg/m(2), MTX 120 g/m(2), CDP 600 mg/m(2), and IFO 30 g/m(2)) but with different durations (arm A, 44 weeks; arm B, 34 weeks). IFO was given postoperatively when pathologic response to MTX-CDP-ADM was poor (arm A) or given in the primary phase of chemotherapy with MTX-CDP-ADM (arm B). End points of the study included pathologic response to preoperative chemotherapy, toxicity, and survival. Given the feasibility of accrual, the statistical plan only permitted detection of a 15% difference in 5-year overall survival (OS). From April 2001 to December 2006, 246 patients were enrolled. Two hundred thirty patients (94%) underwent limb salvage surgery (arm A, 92%; arm B, 96%; P = .5). Chemotherapy-induced necrosis was good in 45% of patients (48% in arm A, 42% in arm B; P = .3). Four patients died of treatment-related toxicity (arm A, n = 1; arm B, n = 3). A significantly higher incidence of hematologic toxicity was reported in arm B. With a median follow-up of 66 months (range, 1 to 104 months), 5-year OS and event-free survival (EFS) rates were not significantly different between arm A and arm B, with OS being 73% (95% CI, 65% to 81%) in arm A and 74% (95% CI, 66% to 82%) in arm B and EFS being 64% (95% CI, 56% to 73%) in arm A and 55% (95% CI, 46% to 64%) in arm B. IFO added to MTX, CDP, and ADM from the preoperative phase does not improve the good responder rate and increases hematologic toxicity. IFO should only be considered in patients who have a poor histologic response to MTX, CDP, and ADM.
    Subject(s): Biological and medical sciences ; Medical sciences ; Diseases of the osteoarticular system ; Tumors of striated muscle and skeleton ; Tumors ; Osteosarcoma - drug therapy ; Femur - pathology ; Humans ; Child, Preschool ; Male ; Tibia - pathology ; Cisplatin - administration & dosage ; Humerus - pathology ; Disease-Free Survival ; Ifosfamide - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Chemotherapy, Adjuvant - methods ; Adolescent ; Adult ; Female ; Methotrexate - administration & dosage ; Bone Neoplasms - drug therapy ; Child ; Doxorubicin - administration & dosage
    ISSN: 0732-183X
    E-ISSN: 1527-7755
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 3
    Language: English
    In: Cancer immunology, immunotherapy, 2020-09, Vol.69 (9), p.1905-1916
    Description: Giant cell tumor of bone (GCTB) is a locally aggressive and rarely metastatic tumor, with a relatively unpredictable clinical course. A retrospective series of 46 GCTB and a control group of 24 aneurysmal bone cysts (ABC) were selected with the aim of investigating the PD-L1 expression levels and immune-related gene expression profile, in correlation with clinicopathological features. PD-L1 and Ki67 were immunohistochemically tested in each case. Furthermore, comprehensive molecular analyses were carried out using NanoString technology and nCounter PanCancer Immune Profiling Panel, and the gene expression results were correlated with clinicopathological characteristics. PD-L1 expression was observed in 13/46 (28.3%) GCTB (and in 1/24, 4.2%, control ABC, only) and associated with a shorter disease free interval according to univariate analysis. Moreover, in PD-L1-positive lesions, three genes (CD27, CD6 and IL10) were significantly upregulated (p 〈 0.01), while two were downregulated (LCK and TLR8, showing borderline significance, p = 0.06). Interestingly, these genes can be related to maturation and immune tolerance of bone tissue microenvironment, suggesting a more immature/anergic phenotype of giant cell tumors. Our findings suggest that PD-L1 immunoreactivity may help to select GCTB patients with a higher risk of recurrence who could potentially benefit from immune checkpoint blockade.
    Subject(s): Bone and Bones - pathology ; Prognosis ; Giant Cell Tumors - immunology ; Humans ; Middle Aged ; Giant Cell Tumors - pathology ; Male ; Up-Regulation - genetics ; Bone Neoplasms - immunology ; Transcriptome - immunology ; B7-H1 Antigen - genetics ; Bone Neoplasms - pathology ; Down-Regulation - genetics ; Neoplasm Recurrence, Local - pathology ; Young Adult ; Adolescent ; Giant Cell Tumors - genetics ; Immune Tolerance - genetics ; Adult ; Female ; Neoplasm Recurrence, Local - genetics ; Aged ; Biomarkers, Tumor - genetics ; Bone Neoplasms - genetics ; Index Medicus
    ISSN: 0340-7004
    E-ISSN: 1432-0851
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 4
    Language: English
    In: Journal of surgical oncology, 2020-03-15, Vol.121 (4), p.630-637
    Description: Background and Objectives Limb salvage surgery remains the standard treatment in bone and soft tissue tumors. Toronto Extremity Salvage Score (TESS) is the most used quality of life measure. Our objective was to perform cross‐cultural adaptation and validation in Italian, testing test‐retest reliability, construct validity, and responsiveness. Methods We interviewed patients already treated for content validity. A total of 124 patients completed TESS and other questionnaires presurgery, at 3 months, 3 months + 2 weeks, and 6 months follow‐up. We calculated intraclass correlation coefficients (ICCs) for reliability, associations with Pearson's r, and change over time with paired T tests. Results A new item regarding touch‐screen devices was added to the upper extremity (UE) questionnaire. ICC resulted of 0.99 for lower extremity (LE) and 0.98 for UE patients, Pearson's r between TESS and Musculoskeletal Tumor Society was .66 and .64, EuroQol‐5D‐5L r was .62 and .61, and r between TESS and short form‐36 physical function subscale was .76 and .71 for LE and UE groups, respectively. Paired T test results were statistically significant to detect change over time (0.03, 0.04, and 0.04 for LE groups and 0.03, 0.01, and 0.04 for UE groups). Conclusion The Italian version of TESS can be used for the bone and soft tissue sarcoma population in clinical trials in Italy and with Italian speaking patients abroad to ensure patients’ perspectives for efficacy and efficiency of treatments.
    Subject(s): limb salvage ; Italian ; questionnaire ; sarcoma ; quality of life ; TESS ; Extremities - surgery ; Humans ; Middle Aged ; Male ; Sarcoma - psychology ; Bone Neoplasms - pathology ; Young Adult ; Language ; Aged, 80 and over ; Translating ; Adult ; Female ; Surveys and Questionnaires ; Severity of Illness Index ; Bone Neoplasms - psychology ; Limb Salvage - methods ; Reproducibility of Results ; Osteosarcoma - psychology ; Limb Salvage - psychology ; Extremities - pathology ; Bone Neoplasms - surgery ; Sarcoma - pathology ; Cross-Cultural Comparison ; Osteosarcoma - surgery ; Sarcoma - surgery ; Adolescent ; Quality of Life ; Italy ; Aged ; Osteosarcoma - pathology ; Quality of life ; Tumors ; Index Medicus
    ISSN: 0022-4790
    E-ISSN: 1096-9098
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 5
    Language: English
    In: International journal of environmental research and public health, 2020-11-28, Vol.17 (23), p.8868
    Description: Subcutaneous masses smaller than 5 cm can be malignant, in contrast with the international guidelines. Ultrasound (US) and magnetic resonance imaging (MRI) are useful to distinguish a potentially malignant mass from the numerous benign soft tissue (ST) lesions. Contrast-enhanced ultrasound (CEUS) was applied in ST tumors, without distinguishing the subcutaneous from the deep lesions. We evaluated CEUS and MRI accuracy in comparison to histology in differentiating malignant from nonmalignant superficial ST masses, 50% smaller than 5 cm. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) with their 95% confidence intervals (CI) were calculated. Of malignant cases, 44.4% measured ≤5 cm. At univariate analysis, no statistically significant differences emerged between benign and malignant tumors in relation with clinical characteristics, except for relationship with the deep fascia ( = 0.048). MRI accuracy: sensitivity 52.8% (CI 37.0, 68.0), specificity 74.1% (CI 55.3, 86.8), PPV 73.1% (CI 53.9, 86.3), and NPV 54.1% (CI 38.4, 69.0). CEUS accuracy: sensitivity 75% (CI 58.9, 86.3), specificity 37% (CI 21.5, 55.8), PPV 61.4% (CI 46.6, 74.3), and NPV 52.6% (CI 31.7, 72.7). CEUS showed a sensitivity higher than MRI, whereas PPV and NPV were comparable. Also, masses measuring less than 5 cm can be malignant and referral criteria for centralization could be revised.
    Subject(s): Diagnosis, Differential ; Humans ; Middle Aged ; Male ; Magnetic Resonance Imaging ; Contrast Media ; Sensitivity and Specificity ; Soft Tissue Neoplasms - diagnostic imaging ; Ultrasonography ; Adult ; Female ; Sarcoma - diagnostic imaging ; Aged ; Index Medicus ; standards ; magnetic resonance imaging ; ultrasonography ; soft tissue neoplasms ; contrast media
    ISSN: 1661-7827
    E-ISSN: 1660-4601
    Source: PubMed Central
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 6
    Language: English
    In: European radiology, 2016-07, Vol.26 (7), p.2400-2408
    Description: Soft tissue tumours (STT) require accurate diagnosis in order to identify potential malignancies. Preoperative planning is fundamental to avoid inadequate treatments. The role of contrast-enhanced computed tomography (CT) for local staging remains incompletely assessed. Aims of the study were to evaluate CT accuracy in discriminating active from aggressive tumours compared to histology and evaluate the role of CT angiography (CTA) in surgical planning.This retrospective cohort series of 88 cases from 1200 patients (7 %) was locally studied by contrast-enhanced CT and CTA in a referral centre: 74 malignant tumours, 14 benign lesions. Contrast-enhancement patterns and relationship of the mass with major vessels and bone were compared with histology on surgically excised samples. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were evaluated in discriminating active from aggressive tumours.Sensitivity in differentiating aggressive tumours from active lesions was 89 %, specificity 84 %, PPV 90 %, NPV 82 %. The relationship between mass and major vessels/bone was fundamental for surgical strategy respectively in 40 % and in 58 % of malignant tumours.Contrast-enhanced CT and CTA are effective in differentiating aggressive masses from active lesions in soft tissue and in depicting the relationship between tumour and adjacent bones and major vessels.• Accurate delineation of vascular and bony involvement preoperatively is fundamental for a correct resection.• CT plays a critical role in differential diagnosis of soft tissue masses.• Contrast-enhanced CT and CT angiography are helpful in depicting tumoral vascular involvement.• CT is optimal for characterization of bone involvement in soft tissue malignancies.
    Subject(s): Medicine & Public Health ; Diagnostic Radiology ; Contrast-enhanced CT ; CT angiography ; Soft tissue sarcoma ; Internal Medicine ; Interventional Radiology ; Tumour vascularization ; Imaging / Radiology ; Surgical planning ; Ultrasound ; Neuroradiology ; Extremities - surgery ; Diagnosis, Differential ; Reproducibility of Results ; Humans ; Middle Aged ; Radiographic Image Enhancement - methods ; Tomography, X-Ray Computed - methods ; Male ; Young Adult ; Computed Tomography Angiography - methods ; Contrast Media ; Soft Tissue Neoplasms - surgery ; Extremities - diagnostic imaging ; Sensitivity and Specificity ; Soft Tissue Neoplasms - diagnostic imaging ; Adolescent ; Aged, 80 and over ; Adult ; Female ; Aged ; Retrospective Studies ; Child ; Cohort Studies ; Preoperative Care - methods ; CT imaging ; Diagnosis ; Sarcoma ; Angiography ; Index Medicus
    ISSN: 0938-7994
    E-ISSN: 1432-1084
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 7
    Language: English
    In: Radiologia medica, 2017-11, Vol.122 (11), p.871-879
    Description: To evaluate whether apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) is able to investigate the histological features of soft tissue tumours.We reviewed MRIs of soft tissue tumours performed from 2012 to 2015 to calculate the average ADCs. We included 46 patients (27 male; mean age: 57 years, range 12–85 years) with histologically proven soft tissue tumours (10 benign, 2 intermediate 34 malignant) grouped into eight tumour type classes. An experienced pathologist assigned a semi-quantitative cellularity score (very high, high, medium and low) and tumour grading. The t test, ANOVA and linear regression were used to correlate ADC with clinicopathological data. Approximate receiver operating characteristic curves were created to predict possible uses of ADC to differentiate benign from malignant tumours.There was a significant difference (p 〈 0.01) in ADCs between these three groups excluding myxoid sarcomas. A significant difference was also evident between the tumour type classes (p 〈 0.001), grade II and III myxoid lesions (p 〈 0.05), tumour grading classes (p 〈 0.001) and cellularity scores classes (p 〈 0.001), with the lowest ADCs in the very high cellularity. While the linear regression analysis showed a significant relationship between ADC and tumour cellularity (r = 0.590, p ≤ 0.05) and grading (r = 0.437, p ≤ 0.05), no significant relationship was found with age, gender, tumour size and histological subtype. An optimal cut-off ADC value of 1.45 × 10−3 mm2/s with 76.8% accuracy was found to differentiate benign from malignant tumours.DWI may offer adjunctive information about soft tissue tumours, but its clinical role is still to be defined.
    Subject(s): MR imaging ; Medicine & Public Health ; Diagnostic Radiology ; Soft tissue ; Interventional Radiology ; Tumour ; Imaging / Radiology ; Diffusion ; Ultrasound ; Neuroradiology ; Diagnosis, Differential ; Humans ; Middle Aged ; Male ; Neoplasm Grading ; Biopsy ; Soft Tissue Neoplasms - diagnostic imaging ; Adolescent ; Soft Tissue Neoplasms - pathology ; Aged, 80 and over ; Adult ; Female ; Aged ; Diffusion Magnetic Resonance Imaging - methods ; Child ; Sarcoma ; Diagnostic imaging ; Evaluation ; Quality ; Regression analysis ; Grading ; Lesions ; Diffusion coefficient ; Tumors ; Index Medicus
    ISSN: 0033-8362
    E-ISSN: 1826-6983
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 8
    Language: English
    In: European radiology, 2010-11, Vol.20 (11), p.2740-2748
    Description: Percutaneous biopsies are gaining acceptance in the diagnosis of soft-tissue tumours. Sampling in the most representative area is not easy in sarcomas of huge dimension. We hypothesised that ultrasound (US) contrast medium could identify the representative area for focus core-needle biopsy (CNB) METHODS: This is a retrospective cohort series of 115 soft-tissue masses treated from January 2007 to November 2008. Accuracy of US-guided CNB after contrast-enhanced US (CEUS) was determined by comparing the histology of the biopsy with the definitive diagnosis in 105 surgically excised samples (42 benign, 63 malignant) and with the expected outcome in the remaining ten malignant cases not surgically treated. A myxoid component was present in 21 sarcomas (34.4%). Of samples, 94.8% were adequate for diagnosis with 97.1% sensitivity and 92.5% specificity. Sensitivity and specificity in specific histopathological subgroupings were 100%, and in grading definition they were 100% and 96.8%. US-guided CNB is safe and effective. US contrast medium depicts tumour vascular supply and identifies the representative area(s) for sampling. Sensitivity and specificity are also high in subgrouping and grading, including myxoid types. Discussion about biopsy is part of the essential multidisciplinary strategy for these tumours.
    Subject(s): Predictive Value of Tests ; Humans ; Middle Aged ; Ultrasonography, Interventional ; Male ; Phospholipids ; Sarcoma - pathology ; Young Adult ; Contrast Media ; Sensitivity and Specificity ; Soft Tissue Neoplasms - diagnostic imaging ; Soft Tissue Neoplasms - pathology ; Aged, 80 and over ; Adult ; Female ; Sarcoma - diagnostic imaging ; Aged ; Biopsy, Needle ; Sulfur Hexafluoride ; Sarcoma ; Surgery, Plastic ; Index Medicus
    ISSN: 0938-7994
    E-ISSN: 1432-1084
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 9
    Language: English
    In: Clinical cancer research, 2008-08-01, Vol.14 (15), p.4775-4779
    Description: Purpose: pRb2/p130, a member of the Retinoblastoma gene family, has been shown to be a powerful prognostic factor in several malignancies. We sought to evaluate pRb2/p130 protein expression and its clinical effect in patients affected with soft tissue sarcomas (STS). Experimental Design: Expression of pRb2/p130 was evaluated by immunohistochemistry on formalin-fixed, paraffin-embedded sections in 41 STSs. Results obtained were correlated with clinicopathologic variables and disease-free and overall survival (OS) in univariate and multivariate analysis. Results: Expression of pRb2/p130 was diminished in 25 (61%) tumors, whereas the remaining ones (39%) were classified as high expressors. No correlation between pRb2/p130 expression and clinicopathologic variables was observed. However, a direct relationship between pRb2/p130 expression and clinical outcome of the patients was found in the subgroup of nonmetastatic tumors ( n = 31). In univariate analysis, reduced pRb2/p130 expression was a negative prognostic factor and correlated with shorter disease-free survival ( P = 0.021) and OS ( P = 0.017) survival. In multivariate analysis, reduced pRb2/p130 expression was confirmed to be an independent predictor of shorter OS when considered together with tumor stage and grading (risk ratio, 7.893; confidence interval, 1.618-38.509; P = 0.011). Conclusions: This study shows for the first time the potential prognostic value of pRb2/130 expression evaluated on formalin-fixed, paraffin-embedded sections in STSs patients. pRb2/p130 immunoreactivity can be used to predict OS in patients with nonmetastatic STSs and, therefore, may represent a new prognostic marker.
    Subject(s): pRb2/p130 ; sarcomas ; prognosis ; Tumors of the skin and soft tissue. Premalignant lesions ; Dermatology ; Retinopathies ; Pharmacology. Drug treatments ; Tumors and pseudotumors of the eye, orbit, eyelid, lacrimal apparatus ; Biological and medical sciences ; Medical sciences ; Ophthalmology ; Antineoplastic agents ; Immunohistochemistry ; Multivariate Analysis ; Prognosis ; Retinoblastoma-Like Protein p130 - physiology ; Soft Tissue Neoplasms - mortality ; Humans ; Middle Aged ; Gene Expression Regulation, Neoplastic ; Soft Tissue Neoplasms - metabolism ; Treatment Outcome ; Sarcoma - metabolism ; Disease-Free Survival ; Models, Biological ; Sarcoma - mortality ; Aged, 80 and over ; Adult ; Aged ; Sarcoma - genetics ; Retinoblastoma-Like Protein p130 - biosynthesis ; Soft Tissue Neoplasms - genetics ; Index Medicus
    ISSN: 1078-0432
    E-ISSN: 1557-3265
    Source: HighWire Press (Free Journals)
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 10
    Language: English
    In: Journal of clinical oncology, 2015-05-20, Vol.33 (15_suppl), p.10570-10570
    ISSN: 0732-183X
    E-ISSN: 1527-7755
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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