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Article: Serum Vitamin E Levels of Adults with Nonalcoholic Fatty Liver Disease: An Inverse Relationship with All-Cause Mortality in Non-Diabetic but Not in Pre-Diabetic or Diabetic Subjects.

Tsou, Peiling / Wu, Chang-Jiun

2019 Volume 8, Issue 7

Abstract: Nonalcoholic fatty liver disease (NAFLD) is a growing health threat worldwide. Vitamin E supplementation is recommended for nonalcoholic steatohepatitis (NASH) patients, but only for non-diabetic subjects. We aimed to investigate whether serum vitamin E ... ...

Abstract	Nonalcoholic fatty liver disease (NAFLD) is a growing health threat worldwide. Vitamin E supplementation is recommended for nonalcoholic steatohepatitis (NASH) patients, but only for non-diabetic subjects. We aimed to investigate whether serum vitamin E levels differently impact long-term prognosis in diabetic versus non-diabetic NAFLD individuals. A total of 2404 ultrasonographically defined NAFLD individuals from National Health and Nutrition Examination Survey (NHANES) III were stratified by their glycemic statuses into diabetic (
Language	English
Publishing date	2019-07-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm8071057
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Mapping Driver Mutations to Histopathological Subtypes in Papillary Thyroid Carcinoma: Applying a Deep Convolutional Neural Network.

Tsou, Peiling / Wu, Chang-Jiun

Journal of clinical medicine

2019 Volume 8, Issue 10

Abstract: Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancers and informative biomarkers are critical for risk stratification and treatment guidance. About half of PTCs ... ...

Abstract	Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancers and informative biomarkers are critical for risk stratification and treatment guidance. About half of PTCs harbor
Language	English
Publishing date	2019-10-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm8101675
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Article ; Online: Sex-Dimorphic Association of Plasma Fatty Acids with Cardiovascular Fitness in Young and Middle-Aged General Adults: Subsamples from NHANES 2003⁻2004.

Tsou, Pei-Ling / Wu, Chang-Jiun

Nutrients

2018 Volume 10, Issue 10

Abstract: To explore the potential association of plasma fatty acids (FAs) and cardiovascular fitness level (CVFL), data of 449 subjects from 2003⁻2004 National Health and Nutrition Examination Survey (NHANES) were analyzed. Among these 249 men and 200 women, aged ...

Abstract	To explore the potential association of plasma fatty acids (FAs) and cardiovascular fitness level (CVFL), data of 449 subjects from 2003⁻2004 National Health and Nutrition Examination Survey (NHANES) were analyzed. Among these 249 men and 200 women, aged 20⁻50 years (33.4 ± 8.4 year, mean ± Standard Deviation), 79 low, 166 moderate and 204 high CVFL were categorized by age- and gender- specific percentile, respectively. Twenty-four fatty acids were quantified from fasting plasma. Higher levels of 2 very long-chain saturated FAs (VLSFAs): Arachidic acid (AR1, C20:0) and Docosanoic acid (DA1, C22:0) as well as 2
MeSH term(s)	Adult ; Fatty Acids/blood ; Female ; Humans ; Male ; Middle Aged ; Nutrition Surveys ; Physical Fitness ; Sex Factors ; Young Adult
Chemical Substances	Fatty Acids
Language	English
Publishing date	2018-10-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu10101558
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Article: Diagnostic rate of germline pathogenic variants in pancreatic ductal adenocarcinoma patients using whole genome sequencing.

Chung, An-Ko / Lin, Ro-Ting / Yeh, Chun-Chieh / Yang, Chi-Ying / Wu, Chang-Jiun / Chen, Pei-Lung / Lin, Jaw-Town

Frontiers in genetics

2023 Volume 14, Page(s) 1172365

Abstract: Identification of germline pathogenic variants in cancer patients is critical for treatment planning, genetic counseling, and health policymaking. However, previous estimates of the prevalence of germline etiology of pancreatic ductal adenocarcinoma ( ... ...

Abstract	Identification of germline pathogenic variants in cancer patients is critical for treatment planning, genetic counseling, and health policymaking. However, previous estimates of the prevalence of germline etiology of pancreatic ductal adenocarcinoma (PDAC) were biased because they were based only on sequencing data of protein-coding regions of known PDAC candidate genes. To determine the percentage of patients with PDAC carrying germline pathogenic variants, we enrolled the inpatients from the digestive health clinics, hematology and oncology clinics, and surgical clinics of a single tertiary medical center in Taiwan for whole genome sequencing (WGS) analysis of genomic DNA. The virtual gene panel of 750 genes comprised PDAC candidate genes and those listed in the COSMIC Cancer Gene Census. The genetic variant types under investigation included single nucleotide substitutions, small indels, structural variants, and mobile element insertions (MEIs). In 8 of 24 (33.3%) patients with PDAC, we identified pathogenic/likely pathogenic variants, including single nucleotide substitutions and small indels in
Language	English
Publishing date	2023-05-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2023.1172365
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Article ; Online: On the peptide binding affinity changes in population-specific HLA repertoires to the SARS-CoV-2 variants Delta and Omicron.

Chen, Lu-Chun / Nersisyan, Stepan / Wu, Chang-Jiun / Chang, Che-Mai / Tonevitsky, Alexander / Guo, Chin-Lin / Chang, Wei-Chiao

Journal of autoimmunity

2022 Volume 133, Page(s) 102952

Abstract: Objective: To investigate the changes of Spike protein-HLA binding affinity profiles between the Wuhan strain and two dominant variants, the Delta and the Omicron strains, among the Taiwanese, the British and the Russian populations.: Methods: The ... ...

Abstract	Objective: To investigate the changes of Spike protein-HLA binding affinity profiles between the Wuhan strain and two dominant variants, the Delta and the Omicron strains, among the Taiwanese, the British and the Russian populations. Methods: The HLA frequencies and the HLA-peptide binding affinity profiles in the T-CoV database were combined to conduct the study. We focused on the public alleles in the three populations (HLA-A, HLA-B, HLA-C, HLA-DRB1, and/or HLA-DPA1/DPB1 alleles) and the altered peptides of the spike protein (compared to the Wuhan strain) in the Delta G/478K·V1 (B.1.617.2 + AY.1 + AY.2) and the Omicron (BA.1) strains. Results: For the Delta strain, tight bindings of the altered peptides to the HLA alleles decrease in all three populations and almost vanish in the Taiwanese population. For the Omicron strain, tight bindings are mostly preserved for both HLA classes and in the Taiwanese and the British populations, with a slight reduction in HLA class II in the Taiwanese (1.4%), while the Russian population preserves a relatively high fraction of tight bindings for both HLA classes. Conclusion: We comprehensively reported the changes in the HLA-associated SARS-CoV-2 Spike protein peptide binding profiles among the Taiwanese, the British, and the Russian populations. Further studies are needed to understand the immunological mechanisms and the clinical value of our findings.
MeSH term(s)	Humans ; Spike Glycoprotein, Coronavirus/genetics ; SARS-CoV-2/genetics ; COVID-19/epidemiology ; COVID-19/genetics
Chemical Substances	spike protein, SARS-CoV-2 ; Spike Glycoprotein, Coronavirus
Language	English
Publishing date	2022-11-11
Publishing country	England
Document type	Journal Article
ZDB-ID	639452-8
ISSN	1095-9157 ; 0896-8411
ISSN (online)	1095-9157
ISSN	0896-8411
DOI	10.1016/j.jaut.2022.102952
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Article: Sex-Dimorphic Association of Plasma Fatty Acids with Cardiovascular Fitness in Young and Middle-Aged General Adults: Subsamples from NHANES 2003–2004

Tsou, Pei-Ling / Wu, Chang-Jiun

Nutrients. 2018 Oct. 20, v. 10, no. 10

2018

Abstract: To explore the potential association of plasma fatty acids (FAs) and cardiovascular fitness level (CVFL), data of 449 subjects from 2003–2004 National Health and Nutrition Examination Survey (NHANES) were analyzed. Among these 249 men and 200 women, aged ...

Abstract	To explore the potential association of plasma fatty acids (FAs) and cardiovascular fitness level (CVFL), data of 449 subjects from 2003–2004 National Health and Nutrition Examination Survey (NHANES) were analyzed. Among these 249 men and 200 women, aged 20–50 years (33.4 ± 8.4 year, mean ± Standard Deviation), 79 low, 166 moderate and 204 high CVFL were categorized by age- and gender- specific percentile, respectively. Twenty-four fatty acids were quantified from fasting plasma. Higher levels of 2 very long-chain saturated FAs (VLSFAs): Arachidic acid (AR1, C20:0) and Docosanoic acid (DA1, C22:0) as well as 2 n-6 polyunsaturated FAs (PUFAs): Arachidonic acid (AA, C20:4n-6) and Docosatetraenoic acid (DTA, C22:4n-6) were observed in the subjects with low CVFL. Notably this association exists only in men. Estimated maximal oxygen consumption (VO<inf>2max</inf>), the marker for cardiorespiratory fitness, was used for further regression analysis. After the adjustment of potential confounding factors (age, smoking, hypertension status, body mass index (BMI), insulin resistance status, and C-reactive protein (CRP), AA was the only FA correlated with low VO<inf>2max</inf> in women; while in men AR1, DA1, AA, and DTA remain negatively associated with VO<inf>2max</inf>. This preliminary analysis suggests a sex-dimorphic relationship between these plasma VLSFAs and n-6 PUFAs with CVFL and merits further investigation.
Keywords	C-reactive protein ; National Health and Nutrition Examination Survey ; adults ; arachidonic acid ; body mass index ; cardiorespiratory fitness ; fasting ; gender ; hypertension ; insulin resistance ; men ; peak oxygen uptake ; regression analysis ; standard deviation ; women
Language	English
Dates of publication	2018-1020
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2518386-2
ISSN	2072-6643
ISSN	2072-6643
DOI	10.3390/nu10101558
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: LncRNA Malat1 suppresses pyroptosis and T cell-mediated killing of incipient metastatic cells.

Kumar, Dhiraj / Gurrapu, Sreeharsha / Wang, Yan / Bae, Seong-Yeon / Pandey, Poonam R / Chen, Hong / Mondal, Jayanta / Han, Hyunho / Wu, Chang-Jiun / Karaiskos, Spyros / Yang, Fei / Sahin, Aysegul / Wistuba, Ignacio I / Gao, Jianjun / Tripathy, Debasish / Gao, Hua / Izar, Benjamin / Giancotti, Filippo G

Nature cancer

2024 Volume 5, Issue 2, Page(s) 262–282

Abstract: The contribution of antitumor immunity to metastatic dormancy is poorly understood. Here we show that the long noncoding RNA Malat1 is required for tumor initiation and metastatic reactivation in mouse models of breast cancer and other tumor types. ... ...

Abstract	The contribution of antitumor immunity to metastatic dormancy is poorly understood. Here we show that the long noncoding RNA Malat1 is required for tumor initiation and metastatic reactivation in mouse models of breast cancer and other tumor types. Malat1 localizes to nuclear speckles to couple transcription, splicing and mRNA maturation. In metastatic cells, Malat1 induces WNT ligands, autocrine loops to promote self-renewal and the expression of Serpin protease inhibitors. Through inhibition of caspase-1 and cathepsin G, SERPINB6B prevents gasdermin D-mediated induction of pyroptosis. In this way, SERPINB6B suppresses immunogenic cell death and confers evasion of T cell-mediated tumor lysis of incipient metastatic cells. On-target inhibition of Malat1 using therapeutic antisense nucleotides suppresses metastasis in a SERPINB6B-dependent manner. These results suggest that Malat1-induced expression of SERPINB6B can titrate pyroptosis and immune recognition at metastatic sites. Thus, Malat1 is at the nexus of tumor initiation, reactivation and immune evasion and represents a tractable and clinically relevant drug target.
MeSH term(s)	Animals ; Mice ; Cell Line, Tumor ; Pyroptosis ; RNA Splicing ; RNA, Long Noncoding/genetics ; T-Lymphocytes/metabolism
Chemical Substances	RNA, Long Noncoding ; Malat1 long non-coding RNA, mouse
Language	English
Publishing date	2024-01-09
Publishing country	England
Document type	Journal Article
ISSN	2662-1347
ISSN (online)	2662-1347
DOI	10.1038/s43018-023-00695-9
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Article ; Online: Type I collagen deletion in αSMA

Chen, Yang / Kim, Jiha / Yang, Sujuan / Wang, Huamin / Wu, Chang-Jiun / Sugimoto, Hikaru / LeBleu, Valerie S / Kalluri, Raghu

Cancer cell

2021 Volume 39, Issue 4, Page(s) 548–565.e6

Abstract: Stromal desmoplastic reaction in pancreatic ductal adenocarcinoma (PDAC) involves significant accumulation of type I collagen (Col1). However, the precise molecular and mechanistic contribution of Col1 in PDAC progression remains unknown. Activated ... ...

Abstract	Stromal desmoplastic reaction in pancreatic ductal adenocarcinoma (PDAC) involves significant accumulation of type I collagen (Col1). However, the precise molecular and mechanistic contribution of Col1 in PDAC progression remains unknown. Activated pancreatic stellate cells/αSMA
MeSH term(s)	Animals ; CD8-Positive T-Lymphocytes/pathology ; Carcinoma, Pancreatic Ductal/pathology ; Cell Line, Tumor ; Collagen Type I/metabolism ; Disease Models, Animal ; Mice ; Myofibroblasts/pathology ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/immunology ; Pancreatic Neoplasms/metabolism ; Pancreatic Neoplasms/pathology ; Pancreatic Stellate Cells/pathology ; Tumor Microenvironment/immunology
Chemical Substances	Collagen Type I
Language	English
Publishing date	2021-03-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2078448-X
ISSN	1878-3686 ; 1535-6108
ISSN (online)	1878-3686
ISSN	1535-6108
DOI	10.1016/j.ccell.2021.02.007
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Article ; Online: Oncogenic collagen I homotrimers from cancer cells bind to α3β1 integrin and impact tumor microbiome and immunity to promote pancreatic cancer.

Chen, Yang / Yang, Sujuan / Tavormina, Jena / Tampe, Desiree / Zeisberg, Michael / Wang, Huamin / Mahadevan, Krishnan K / Wu, Chang-Jiun / Sugimoto, Hikaru / Chang, Chia-Chi / Jenq, Robert R / McAndrews, Kathleen M / Kalluri, Raghu

Cancer cell

2022 Volume 40, Issue 8, Page(s) 818–834.e9

Abstract: In contrast to normal type I collagen (Col1) heterotrimer (α1/α2/α1) produced by fibroblasts, pancreatic cancer cells specifically produce unique Col1 homotrimer (α1/α1/α1). Col1 homotrimer results from epigenetic suppression of the Col1a2 gene and ... ...

Abstract	In contrast to normal type I collagen (Col1) heterotrimer (α1/α2/α1) produced by fibroblasts, pancreatic cancer cells specifically produce unique Col1 homotrimer (α1/α1/α1). Col1 homotrimer results from epigenetic suppression of the Col1a2 gene and promotes oncogenic signaling, cancer cell proliferation, tumor organoid formation, and growth via α3β1 integrin on cancer cells, associated with tumor microbiome enriched in anaerobic Bacteroidales in hypoxic and immunosuppressive tumors. Deletion of Col1 homotrimers increases overall survival of mice with pancreatic ductal adenocarcinoma (PDAC), associated with reprograming of the tumor microbiome with increased microaerophilic Campylobacterales, which can be reversed with broad-spectrum antibiotics. Deletion of Col1 homotrimers enhances T cell infiltration and enables efficacy of anti-PD-1 immunotherapy. This study identifies the functional impact of Col1 homotrimers on tumor microbiome and tumor immunity, implicating Col1 homotrimer-α3β1 integrin signaling axis as a cancer-specific therapeutic target.
MeSH term(s)	Animals ; Carcinogenesis ; Carcinoma, Pancreatic Ductal/genetics ; Collagen ; Collagen Type I ; Integrin alpha3beta1 ; Mice ; Microbiota ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms
Chemical Substances	Collagen Type I ; Integrin alpha3beta1 ; Collagen (9007-34-5)
Language	English
Publishing date	2022-07-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2078448-X
ISSN	1878-3686 ; 1535-6108
ISSN (online)	1878-3686
ISSN	1535-6108
DOI	10.1016/j.ccell.2022.06.011
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Article ; Online: AR-negative prostate cancer is vulnerable to loss of JMJD1C demethylase.

Yoshihama, Yohei / LaBella, Kyle A / Kim, Eiru / Bertolet, Lori / Colic, Medina / Li, Jiexi / Shang, Xiaoying / Wu, Chang-Jiun / Spring, Denise J / Wang, Y Alan / Hart, Traver / DePinho, Ronald A

Proceedings of the National Academy of Sciences of the United States of America

2021 Volume 118, Issue 36

Abstract: Prostate cancer is a leading cause of cancer-related mortality in men. The widespread use of androgen receptor (AR) inhibitors has generated an increased incidence of AR-negative prostate cancer, triggering the need for effective therapies for such ... ...

Abstract	Prostate cancer is a leading cause of cancer-related mortality in men. The widespread use of androgen receptor (AR) inhibitors has generated an increased incidence of AR-negative prostate cancer, triggering the need for effective therapies for such patients. Here, analysis of public genome-wide CRISPR screens in human prostate cancer cell lines identified histone demethylase JMJD1C (KDM3C) as an AR-negative context-specific vulnerability. Secondary validation studies in multiple cell lines and organoids, including isogenic models, confirmed that small hairpin RNA (shRNA)-mediated depletion of JMJD1C potently inhibited growth specifically in AR-negative prostate cancer cells. To explore the cooperative interactions of AR and JMJD1C, we performed comparative transcriptomics of 1) isogenic AR-positive versus AR-negative prostate cancer cells, 2) AR-positive versus AR-negative prostate cancer tumors, and 3) isogenic JMJD1C-expressing versus JMJD1C-depleted AR-negative prostate cancer cells. Loss of AR or JMJD1C generates a modest tumor necrosis factor alpha (TNFα) signature, whereas combined loss of AR and JMJD1C strongly up-regulates the TNFα signature in human prostate cancer, suggesting TNFα signaling as a point of convergence for the combined actions of AR and JMJD1C. Correspondingly, AR-negative prostate cancer cells showed exquisite sensitivity to TNFα treatment and, conversely, TNFα pathway inhibition via inhibition of its downstream effector MAP4K4 partially reversed the growth defect of JMJD1C-depleted AR-negative prostate cancer cells. Given the deleterious systemic side effects of TNFα therapy in humans and the viability of JMJD1C-knockout mice, the identification of JMJD1C inhibition as a specific vulnerability in AR-negative prostate cancer may provide an alternative drug target for prostate cancer patients progressing on AR inhibitor therapy.
MeSH term(s)	Apoptosis/drug effects ; Cell Line, Tumor ; Databases, Genetic ; Histone Demethylases/metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Jumonji Domain-Containing Histone Demethylases/genetics ; Jumonji Domain-Containing Histone Demethylases/metabolism ; Male ; Oxidoreductases, N-Demethylating/genetics ; Oxidoreductases, N-Demethylating/metabolism ; Promoter Regions, Genetic/drug effects ; Prostate/pathology ; Prostatic Neoplasms/genetics ; Protein Serine-Threonine Kinases/genetics ; Receptors, Androgen/genetics ; Receptors, Androgen/metabolism ; Signal Transduction/drug effects ; Transcriptional Activation/drug effects ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	Intracellular Signaling Peptides and Proteins ; Receptors, Androgen ; Tumor Necrosis Factor-alpha ; Histone Demethylases (EC 1.14.11.-) ; JMJD1C protein, human (EC 1.14.11.-) ; Jumonji Domain-Containing Histone Demethylases (EC 1.14.11.-) ; Oxidoreductases, N-Demethylating (EC 1.5.-) ; MAP4K4 protein, human (EC 2.7.1.11) ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2021-09-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2026324118
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