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Article ; Online: Low serum CCL17 as a marker for severe/critical COVID-19: A pathogenic link.

Sharma, Abhay

2021 Volume 778, Page(s) 145486

MeSH term(s)	Biomarkers/blood ; COVID-19/blood ; COVID-19/pathology ; Chemokine CCL17/blood ; Critical Illness ; Female ; Humans ; Male ; SARS-CoV-2/metabolism
Chemical Substances	Biomarkers ; CCL17 protein, human ; Chemokine CCL17
Language	English
Publishing date	2021-02-11
Publishing country	Netherlands
Document type	Letter
ZDB-ID	391792-7
ISSN	1879-0038 ; 0378-1119
ISSN (online)	1879-0038
ISSN	0378-1119
DOI	10.1016/j.gene.2021.145486
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Article ; Online: Randomized trial drug controlled compendious transcriptome analysis supporting broad and phase specific therapeutic potential of multiple candidates in COVID-19.

Sharma, Abhay

Cytokine

2021 Volume 148, Page(s) 155719

Abstract: Effective therapies for coronavirus disease 2019 (COVID-19) are urgently needed. Maladaptive hyperinflammation and excessive cytokine release underlie the disease severity, with antiinflammatory and cytokine inhibiting agents expected to exert ... ...

Abstract	Effective therapies for coronavirus disease 2019 (COVID-19) are urgently needed. Maladaptive hyperinflammation and excessive cytokine release underlie the disease severity, with antiinflammatory and cytokine inhibiting agents expected to exert therapeutic effects. A major present challenge is identification of appropriate phase of the illness for a given intervention to yield optimum outcomes. Considering its established disease biomarker and drug discovery potential, a compendious analysis of existing transcriptomic data is presented here toward addressing this gap. The analysis is based on COVID-19 data related to intensive care unit (ICU) and non-ICU admissions, discharged and deceased patients, ventilation and non-ventilation phases, and high oxygen supplementation. It integrates transcriptomic data related to the effects of, in various cellular treatment models, the COVID-19 randomized clinical trial (RCT) successful drug dexamethasone, and the failed drug, with a potential to harm, hydroxychloroquine/chloroquine. Similarly, effects of various COVID-19 candidate drugs/anticytokines as well as proinflammatory cytokines implicated in the illness are also examined. The underlying assumption was that compared to COVID-19, an effective drug/anticytokine and a disease aggravating agent would affect gene regulation in opposite and same direction, in that order. Remarkably, the assumption was supported with respect to both the RCT drugs. With this control validation, etanercept, followed by tofacitinib and adalimumab, showed transcriptomic effects predictive of benefits in both ventilation and non-ventilation ICU stages as well as in non-ICU phase. On the other hand, canakinumab showed potential for effectiveness in high oxygen supplementation phase. These findings may inform experimental and clinical studies toward drug repurposing in COVID-19.
MeSH term(s)	COVID-19/drug therapy ; COVID-19/genetics ; COVID-19/physiopathology ; Gene Expression Profiling ; Humans ; Intensive Care Units ; Oxygen/therapeutic use ; Patient Discharge ; Proof of Concept Study ; Respiration, Artificial
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2021-09-25
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	1018055-2
ISSN	1096-0023 ; 1043-4666
ISSN (online)	1096-0023
ISSN	1043-4666
DOI	10.1016/j.cyto.2021.155719
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Article ; Online: Inferring molecular mechanisms of dexamethasone therapy in severe COVID-19 from existing transcriptomic data.

Sharma, Abhay

Gene

2021 Volume 788, Page(s) 145665

Abstract: Dexamethasone, a synthetic glucocorticoid, has previously shown mortality benefit in severe coronavirus disease 2019 (COVID-19) in a randomized controlled trial. As the illness is considered to reflect a hyperinflammatory state, this therapeutic ... ...

Abstract	Dexamethasone, a synthetic glucocorticoid, has previously shown mortality benefit in severe coronavirus disease 2019 (COVID-19) in a randomized controlled trial. As the illness is considered to reflect a hyperinflammatory state, this therapeutic effectiveness is presumably ascribed to broad anti-inflammatory activities of glucocorticoids. Here, an unbiased analysis of available transcriptomic data on lung and blood immune cells from severe COVID-19 patients and matching cellular models of dexamethasone treatment is presented that supports this presumption. Comparison of differentially expressed genes in severe COVID-19 with that in dexamethasone treated cells reveals a small set of genes that are regulated in opposite direction between the disease and the drug, and are enriched for genes and processes related to glucocorticoid pathway and receptor binding. This expression signature differentiates as a whole various cytokines from a set of anti-cytokine/anti-inflammatory agents, with the former resembling COVID-19 and the latter dexamethasone in gene regulation. The signature apparently relates to TNF- α, IL-1α, IL-1β, IFN-α, IFN-β, and IFN-γ signaling, but not IL-6 signaling, suggesting that therapeutic effect of dexamethasone in COVID-19 does not involve IL-6 pathway. However, as all these observations are purely based on bioinformatic analysis, experimental evidence will be required to validate the inferences drawn. In conclusion, the present analysis seems to provide a proof of concept for therapeutic mechanisms of dexamethasone in COVID-19.
MeSH term(s)	Anti-Inflammatory Agents/therapeutic use ; Antiviral Agents/therapeutic use ; Cell Line, Tumor ; Cytokines/immunology ; Dexamethasone ; Gene Expression Regulation/drug effects ; Glucocorticoids/therapeutic use ; Humans ; Transcriptome/drug effects ; COVID-19 Drug Treatment
Chemical Substances	Anti-Inflammatory Agents ; Antiviral Agents ; Cytokines ; Glucocorticoids ; Dexamethasone (7S5I7G3JQL)
Language	English
Publishing date	2021-04-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	391792-7
ISSN	1879-0038 ; 0378-1119
ISSN (online)	1879-0038
ISSN	0378-1119
DOI	10.1016/j.gene.2021.145665
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Article ; Online: Epidemiological transcriptomic data supports BCG protection in viral diseases including COVID-19.

Sharma, Abhay

Gene

2021 Volume 783, Page(s) 145574

Abstract: Epidemiological and clinical evidence suggests that Bacille Calmette-Guérin (BCG) vaccine induced trained immunity protects against non-specific infections. Multiple clinical trials are currently underway to assess effectiveness of the vaccine in the ... ...

Abstract	Epidemiological and clinical evidence suggests that Bacille Calmette-Guérin (BCG) vaccine induced trained immunity protects against non-specific infections. Multiple clinical trials are currently underway to assess effectiveness of the vaccine in the coronavirus disease 2019 (COVID-19). However, the durability and mechanism of BCG trained immunity remain unclear. Here, an integrative analysis of available epidemiological transcriptomic data related to BCG vaccination and respiratory tract viral infections as well as of reported transcriptomic alterations in COVID-19 is presented toward addressing this gap. Results suggest that the vaccine induces very long-lasting transcriptomic changes that mimic viral infections by, consistent with the present concept of trained immunity, upregulation of antiviral defense response, and oppose viral infections by, inconsistent with the concept, downregulation of myeloid cell activation. These durability and mechanistic insights argue against possible indiscriminate use of the vaccine and activated innate immune response associated safety concerns in COVID-19, in that order.
MeSH term(s)	Adult ; Antiviral Agents/therapeutic use ; BCG Vaccine/immunology ; BCG Vaccine/therapeutic use ; COVID-19/epidemiology ; COVID-19/immunology ; Child ; Datasets as Topic ; Gene Expression Profiling ; Humans ; Immunity, Innate/drug effects ; Infant ; Respiratory Tract Infections/drug therapy ; Respiratory Tract Infections/immunology ; Transcriptome ; Virus Diseases/drug therapy ; Virus Diseases/immunology ; COVID-19 Drug Treatment
Chemical Substances	Antiviral Agents ; BCG Vaccine
Language	English
Publishing date	2021-03-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	391792-7
ISSN	1879-0038 ; 0378-1119
ISSN (online)	1879-0038
ISSN	0378-1119
DOI	10.1016/j.gene.2021.145574
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Article ; Online: Housing shortage in a mega city: a spatio-temporal analysis of NCT-Delhi, 2001–2011

Abhay, Rajesh Kumar / Sharma, Madhuri

GeoJournal. 2023 Feb., v. 88, no. 1 p.261-278

2023

Abstract: Access to safe housing is considered an essential service as per the United Nation’s sustainable development goals. India is currently home to 2.4 billion houses of which 1.6 billion is rural. During 2001–2011, more than half a billion homes were added, ... ...

Abstract	Access to safe housing is considered an essential service as per the United Nation’s sustainable development goals. India is currently home to 2.4 billion houses of which 1.6 billion is rural. During 2001–2011, more than half a billion homes were added, and yet there exists acute shortage of quality housing with good public amenities. A report on urban housing shortage prepared by the Technical Group (TG-12) appointed by the Government of India estimated that the total number of households without “decent” housing condition in Indian cities counts to 18.78 million. Lack of sufficient number of houses adds to congestion and shortage. Misappropriation of funds further aggravates housing dilapidation, making the existing homes non-serviceable. Using the framework of TG-12, this study conducts an inter-district analysis of the obsolescence factor, congestion factor and homeless households across the megacity of Delhi for the years 2001 and 2011. Using district as the scale of analysis, housing shortage is measured by the Composite Index, computed for all nine districts for 2001 and 2011. We find that the composite index values are unequally distributed across the megacity’s districts. During 2001–2011, the overall shortage of housing had increased in NCT-Delhi, with the highest housing shortage felt in North, Central and New Delhi districts. Out of all nine districts, six showed increase in housing shortage. Also, the percentage of homeless households increased across all nine districts whereas the percentage of rental accommodations increased in seven out of nine districts.
Keywords	cities ; sustainable development ; India
Language	English
Dates of publication	2023-02
Size	p. 261-278.
Publishing place	Springer Netherlands
Document type	Article ; Online
ZDB-ID	715360-0
ISSN	1572-9893 ; 0343-2521
ISSN (online)	1572-9893
ISSN	0343-2521
DOI	10.1007/s10708-022-10597-5
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Article ; Online: Urban growth and quality of life: inter-district and intra-district analysis of housing in NCT-Delhi, 2001-2011-2020.

Sharma, Madhuri / Abhay, Rajesh Kumar

GeoJournal

2022 Volume 87, Issue Suppl 4, Page(s) 797–819

Abstract: One out of three people in India is urban. In 2011, there were about 53 urban agglomerations larger than 1 million population as against only 35 in 2001. Much of this urban expansion has been occurring in the country's largest metropolises including the ... ...

Abstract	One out of three people in India is urban. In 2011, there were about 53 urban agglomerations larger than 1 million population as against only 35 in 2001. Much of this urban expansion has been occurring in the country's largest metropolises including the National Capital Territory of Delhi which has expanded horizontally and vertically both. This has also added to overall decline in its already dilapidated housing stock and quality of life. Delhi, a historical hub for regional, national, and international commerce, and a place for the socio-political elites, has failed to provide basic life amenities to its average citizens. This research critiques the (un)sustainable elements of Delhi's urbanization and concomitant decline in basic amenities pertaining to quality-of-life by examining the growth and expansion of its urban-built-up areas during 2001-2011-2020 and provides nuanced insights into its 'livability' by examining select quality-of-life attributes. The LANDSAT imageries for 2010 and 2020 are used to measure NDB-Index that assesses its built-up area and change, which are later corroborated with Census household data to examine change in its 'livable' and 'dilapidated' housing structures. Significant sub-regional disparity exists in the availability of good and livable homes, with almost 20-30% of several districts still without drinking water source inside premises. However, significant progress is also noted for basic amenities like lighting, latrine and bathing facilities, and majority of Delhi's built-up area has expanded along newer developments and transportation corridors. This calls for goal-oriented strategic interventions by policymakers to help achieve the SDG-11 on Sustainable Cities.
Language	English
Publishing date	2022-01-07
Publishing country	Germany
Document type	Journal Article
ZDB-ID	715360-0
ISSN	1572-9893 ; 0343-2521
ISSN (online)	1572-9893
ISSN	0343-2521
DOI	10.1007/s10708-021-10570-8
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Article ; Online: Multi-omics data analysis implicating epigenetic inheritance in evolution and disease.

Sharma, Abhay

Biochimica et biophysica acta. General subjects

2019 Volume 1864, Issue 3, Page(s) 129477

MeSH term(s)	Biological Evolution ; DNA Methylation/genetics ; Data Analysis ; Epigenesis, Genetic/genetics ; Epigenome/genetics ; Epigenomics/methods ; Evolution, Molecular ; Humans ; Male ; Spermatozoa/metabolism
Language	English
Publishing date	2019-11-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	60-7
ISSN	1872-8006 ; 1879-2596 ; 1879-260X ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1872-8006 ; 1879-2596 ; 1879-260X ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbagen.2019.129477
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Article ; Online: Phenotypic cross-species conservation and cross-generation directionality switching in epigenetic inheritance.

Bhalla, Ameek / Sharma, Abhay

Molecular ecology

2023 Volume 32, Issue 14, Page(s) 3908–3921

Abstract: Evidence supporting non-DNA sequence-based inheritance in animals has increasingly been described in recent years, often under intergenerational inheritance or transgenerational epigenetic inheritance (TEI). Existence of the latter, a stronger indicator ... ...

Abstract	Evidence supporting non-DNA sequence-based inheritance in animals has increasingly been described in recent years, often under intergenerational inheritance or transgenerational epigenetic inheritance (TEI). Existence of the latter, a stronger indicator of germline transmission, has been demonstrated in invertebrates and mammals alike. The mechanisms and physiological implications of TEI, however, remain unclear. Here, in an unbiased approach, we compared existing transcriptomic data associated with so far available Drosophila models of inter- and trans-, and rodent models of inter-generational inheritance; observed phenotypic cross-species conservation and cross-generation directionality shift therein; and confirmed these observations experimentally in flies. Specifically, previous models of cold and diet-induced inheritance in both flies and mice were commonly associated with altered regulation of proteolysis genes. Besides, fly TEI models were in general characterized by opposite phenotypic regulation in transgenerational offsprings, compared to the ancestors. As insulin-producing cell (IPC) ablation was also associated with proteolysis gene dysregulation in one of the mouse models, we opted to use genetic ablation of IPCs in flies for the experimental validation. Remarkably, the ablation led to transcriptomic alterations across multiple generations, with dysregulated genes showing proteolysis enrichment. Similarly, phenotypic directionality changed in the opposite direction in transgenerational offsprings, in comparison of the ancestors. These results support evolutionary conservation, and both physiologically adaptive and maladaptive consequences of germline mediated epigenetic inheritance.
MeSH term(s)	Animals ; Mice ; Epigenesis, Genetic ; Inheritance Patterns/genetics ; Germ Cells ; Mammals/genetics ; Transcriptome/genetics ; Drosophila/genetics ; DNA Methylation
Language	English
Publishing date	2023-05-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1126687-9
ISSN	1365-294X ; 0962-1083
ISSN (online)	1365-294X
ISSN	0962-1083
DOI	10.1111/mec.16969
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Article: Epidemiological transcriptomic data supports BCG protection in viral diseases including COVID-19

Sharma, Abhay

Gene. 2021 May 30, v. 783

2021

Abstract	Epidemiological and clinical evidence suggests that Bacille Calmette-Guérin (BCG) vaccine induced trained immunity protects against non-specific infections. Multiple clinical trials are currently underway to assess effectiveness of the vaccine in the coronavirus disease 2019 (COVID-19). However, the durability and mechanism of BCG trained immunity remain unclear. Here, an integrative analysis of available epidemiological transcriptomic data related to BCG vaccination and respiratory tract viral infections as well as of reported transcriptomic alterations in COVID-19 is presented toward addressing this gap. Results suggest that the vaccine induces very long-lasting transcriptomic changes that mimic viral infections by, consistent with the present concept of trained immunity, upregulation of antiviral defense response, and oppose viral infections by, inconsistent with the concept, downregulation of myeloid cell activation. These durability and mechanistic insights argue against possible indiscriminate use of the vaccine and activated innate immune response associated safety concerns in COVID-19, in that order.
Keywords	COVID-19 infection ; durability ; genes ; innate immunity ; respiratory system ; transcriptomics ; vaccination ; vaccines
Language	English
Dates of publication	2021-0530
Publishing place	Elsevier B.V.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	391792-7
ISSN	1879-0038 ; 0378-1119
ISSN (online)	1879-0038
ISSN	0378-1119
DOI	10.1016/j.gene.2021.145574
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Article: Inferring molecular mechanisms of dexamethasone therapy in severe COVID-19 from existing transcriptomic data

Sharma, Abhay

Gene. 2021 July 01, v. 788

2021

Abstract	Dexamethasone, a synthetic glucocorticoid, has previously shown mortality benefit in severe coronavirus disease 2019 (COVID-19) in a randomized controlled trial. As the illness is considered to reflect a hyperinflammatory state, this therapeutic effectiveness is presumably ascribed to broad anti-inflammatory activities of glucocorticoids. Here, an unbiased analysis of available transcriptomic data on lung and blood immune cells from severe COVID-19 patients and matching cellular models of dexamethasone treatment is presented that supports this presumption. Comparison of differentially expressed genes in severe COVID-19 with that in dexamethasone treated cells reveals a small set of genes that are regulated in opposite direction between the disease and the drug, and are enriched for genes and processes related to glucocorticoid pathway and receptor binding. This expression signature differentiates as a whole various cytokines from a set of anti-cytokine/anti-inflammatory agents, with the former resembling COVID-19 and the latter dexamethasone in gene regulation. The signature apparently relates to TNF- α, IL-1α, IL-1β, IFN-α, IFN-β, and IFN-γ signaling, but not IL-6 signaling, suggesting that therapeutic effect of dexamethasone in COVID-19 does not involve IL-6 pathway. However, as all these observations are purely based on bioinformatic analysis, experimental evidence will be required to validate the inferences drawn. In conclusion, the present analysis seems to provide a proof of concept for therapeutic mechanisms of dexamethasone in COVID-19.
Keywords	COVID-19 infection ; bioinformatics ; dexamethasone ; gene expression regulation ; genes ; glucocorticoids ; interleukin-6 ; mortality ; randomized clinical trials ; therapeutics ; transcriptomics
Language	English
Dates of publication	2021-0701
Publishing place	Elsevier B.V.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	391792-7
ISSN	1879-0038 ; 0378-1119
ISSN (online)	1879-0038
ISSN	0378-1119
DOI	10.1016/j.gene.2021.145665
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