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Article ; Online: [The Nobel Prize in Physiology or Medicine 2023].

Jonsdottir, Ingileif

2023 Volume 109, Issue 12, Page(s) 547

MeSH term(s)	Humans ; Nobel Prize ; Medicine
Language	Icelandic
Publishing date	2023-11-30
Publishing country	Iceland
Document type	Editorial
ZDB-ID	806661-9
ISSN	1670-4959 ; 0023-7213
ISSN (online)	1670-4959
ISSN	0023-7213
DOI	10.17992/lbl.2023.12.769
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Article ; Online: [Revolutionary vaccine development].

Jonsdottir, Ingileif

Laeknabladid

2021 Volume 107, Issue 3, Page(s) 119

MeSH term(s)	Biomedical Research ; Humans ; Vaccines/adverse effects
Chemical Substances	Vaccines
Language	Icelandic
Publishing date	2021-02-24
Publishing country	Iceland
Document type	Editorial
ZDB-ID	806661-9
ISSN	1670-4959 ; 0023-7213
ISSN (online)	1670-4959
ISSN	0023-7213
DOI	10.17992/lbl.2021.03.623
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Article ; Online: The adjuvants dmLT and mmCT enhance humoral immune responses to a pneumococcal conjugate vaccine after both parenteral or mucosal immunization of neonatal mice.

Molina Estupiñan, Jenny Lorena / Aradottir Pind, Audur Anna / Foroutan Pajoohian, Poorya / Jonsdottir, Ingileif / Bjarnarson, Stefania P

Frontiers in immunology

2023 Volume 13, Page(s) 1078904

Abstract: Immaturity of the neonatal immune system contributes to increased susceptibility to infectious diseases and poor vaccine responses. Therefore, better strategies for early life vaccination are needed. Adjuvants can enhance the magnitude and duration of ... ...

Abstract	Immaturity of the neonatal immune system contributes to increased susceptibility to infectious diseases and poor vaccine responses. Therefore, better strategies for early life vaccination are needed. Adjuvants can enhance the magnitude and duration of immune responses. In this study we assessed the effects of the adjuvants dmLT and mmCT and different immunization routes, subcutaneous (s.c.) and intranasal (i.n.), on neonatal immune response to a pneumococcal conjugate vaccine Pn1-CRM
MeSH term(s)	Animals ; Mice ; Adjuvants, Immunologic/pharmacology ; Animals, Newborn ; Immunity, Humoral ; Immunization ; Immunoglobulin A ; Immunoglobulin G ; Vaccination ; Vaccines, Conjugate
Chemical Substances	Adjuvants, Immunologic ; Immunoglobulin A ; Immunoglobulin G ; Vaccines, Conjugate
Language	English
Publishing date	2023-01-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1078904
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Article ; Online: A comparative study of adjuvants effects on neonatal plasma cell survival niche in bone marrow and persistence of humoral immune responses.

Aradottir Pind, Audur Anna / Thorsdottir, Sigrun / Magnusdottir, Gudbjorg Julia / Meinke, Andreas / Del Giudice, Giuseppe / Jonsdottir, Ingileif / Bjarnarson, Stefania P

Frontiers in immunology

2022 Volume 13, Page(s) 904415

Abstract: The neonatal immune system is distinct from the immune system of older individuals rendering neonates vulnerable to infections and poor responders to vaccination. Adjuvants can be used as tools to enhance immune responses to co-administered antigens. ... ...

Abstract	The neonatal immune system is distinct from the immune system of older individuals rendering neonates vulnerable to infections and poor responders to vaccination. Adjuvants can be used as tools to enhance immune responses to co-administered antigens. Antibody (Ab) persistence is mediated by long-lived plasma cells that reside in specialized survival niches in the bone marrow, and transient Ab responses in early life have been associated with decreased survival of plasma cells, possibly due to lack of survival factors. Various cells can secrete these factors and which cells are the main producers is still up for debate, especially in early life where this has not been fully addressed. The receptor BCMA and its ligand APRIL have been shown to be important in the maintenance of plasma cells and Abs. Herein, we assessed age-dependent maturation of a broad range of bone marrow accessory cells and their expression of the survival factors APRIL and IL-6. Furthermore, we performed a comparative analysis of the potential of 5 different adjuvants; LT-K63, mmCT, MF59, IC31 and alum, to enhance expression of survival factors and BCMA following immunization of neonatal mice with tetanus toxoid (TT) vaccine. We found that APRIL expression was reduced in the bone marrow of young mice whereas IL-6 expression was higher. Eosinophils, macrophages, megakaryocytes, monocytes and lymphocytes were important secretors of survival factors in early life but undefined cells also constituted a large fraction of secretors. Immunization and adjuvants enhanced APRIL expression but decreased IL-6 expression in bone marrow cells early after immunization. Furthermore, neonatal immunization with adjuvants enhanced the proportion of plasmablasts and plasma cells that expressed BCMA both in spleen and bone marrow. Enhanced BCMA expression correlated with enhanced vaccine-specific humoral responses, even though the effect of alum on BCMA was less pronounced than those of the other adjuvants at later time points. We propose that low APRIL expression in bone marrow as well as low BCMA expression of plasmablasts/plasma cells in early life together cause transient Ab responses and could represent targets to be triggered by vaccine adjuvants to induce persistent humoral immune responses in this age group.
MeSH term(s)	Adjuvants, Immunologic ; Adjuvants, Pharmaceutic/metabolism ; Animals ; B-Cell Maturation Antigen/metabolism ; Bone Marrow ; Cell Survival ; Immunity, Humoral ; Interleukin-6/metabolism ; Mice ; Oligodeoxyribonucleotides/metabolism ; Plasma Cells ; Tetanus Toxoid ; Tuberculosis/metabolism ; Tuberculosis Vaccines
Chemical Substances	Adjuvants, Immunologic ; Adjuvants, Pharmaceutic ; B-Cell Maturation Antigen ; Interleukin-6 ; Oligodeoxyribonucleotides ; Tetanus Toxoid ; Tuberculosis Vaccines
Language	English
Publishing date	2022-08-03
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.904415
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Article ; Online: Genome-wide investigation of persistence with methotrexate treatment in early rheumatoid arthritis.

Sysojev, Anton Öberg / Saevarsdottir, Saedis / Diaz-Gallo, Lina-Marcela / Silberberg, Gilad N / Alfredsson, Lars / Klareskog, Lars / Baecklund, Eva / Björkman, Lena / Kastbom, Alf / Rantapää-Dahlqvist, Solbritt / Turesson, Carl / Jonsdottir, Ingileif / Stefansson, Kari / Frisell, Thomas / Padyukov, Leonid / Askling, Johan / Westerlind, Helga

Rheumatology (Oxford, England)

2023 Volume 63, Issue 5, Page(s) 1221–1229

Abstract: Objectives: To investigate the influence of genetic factors on persistence with treatment of early RA with MTX monotherapy.: Methods: We conducted a genome-wide association study (GWAS) in a sample of 3902 Swedish early-RA patients initiating MTX in ... ...

Abstract	Objectives: To investigate the influence of genetic factors on persistence with treatment of early RA with MTX monotherapy. Methods: We conducted a genome-wide association study (GWAS) in a sample of 3902 Swedish early-RA patients initiating MTX in DMARD monotherapy as their first-ever DMARD. The outcome, short- and long-term MTX treatment persistence, was defined as remaining on MTX at 1 and at 3 years, respectively, with no additional DMARDs added. As genetic predictors, we investigated individual SNPs, and then calculated a polygenic risk score (PRS) based on SNPs associated with RA risk. The SNP-based heritability of persistence was estimated overall and by RA serostatus. Results: No individual SNP reached genome-wide significance (P < 5 × 10-8), either for persistence at 1 year or at 3 years. The RA PRS was not significantly associated with MTX treatment persistence at 1 year [relative risk (RR) = 0.98 (0.96-1.01)] or at 3 years [RR = 0.96 (0.93-1.00)]. The heritability of MTX treatment persistence was estimated to be 0.45 (0.15-0.75) at 1 year and 0.14 (0-0.40) at 3 years. The results in seropositive RA were comparable with those in the analysis of RA overall, while heritability estimates and PRS RRs were attenuated towards the null in seronegative RA. Conclusion: Despite being the largest GWAS on an MTX treatment outcome to date, no genome-wide significant associations were detected. The modest heritability observed, coupled with the broad spread of suggestively associated loci, indicate that genetic influence is of polygenic nature. Nevertheless, MTX monotherapy persistence was lower in patients with a greater genetic disposition, per the PRS, towards RA.
MeSH term(s)	Humans ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/genetics ; Methotrexate/therapeutic use ; Genome-Wide Association Study ; Antirheumatic Agents/therapeutic use ; Female ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Adult ; Sweden ; Medication Adherence/statistics & numerical data
Chemical Substances	Methotrexate (YL5FZ2Y5U1) ; Antirheumatic Agents
Language	English
Publishing date	2023-06-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/kead301
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Article ; Online: Effect of booster vaccination against Delta and Omicron SARS-CoV-2 variants in Iceland.

Norddahl, Gudmundur L / Melsted, Pall / Gunnarsdottir, Kristbjorg / Halldorsson, Gisli H / Olafsdottir, Thorunn A / Gylfason, Arnaldur / Kristjansson, Mar / Magnusson, Olafur T / Sulem, Patrick / Gudbjartsson, Daniel F / Thorsteinsdottir, Unnur / Jonsdottir, Ingileif / Stefansson, Kari

Nature communications

2022 Volume 13, Issue 1, Page(s) 5701

Abstract: By the end of July 2021, the majority of the Icelandic population had received vaccination against COVID-19. In mid-July a wave of SARS-CoV-2 infections, dominated by the Delta variant, spread through the population, followed by an Omicron wave in ... ...

Abstract	By the end of July 2021, the majority of the Icelandic population had received vaccination against COVID-19. In mid-July a wave of SARS-CoV-2 infections, dominated by the Delta variant, spread through the population, followed by an Omicron wave in December. A booster vaccination campaign was initiated to curb the spread of the virus. We estimate the risk of infection for different vaccine combinations using vaccination data from 276,028 persons and 963,557 qPCR tests for 277,687 persons. We measure anti-Spike-RBD antibody levels and ACE2-Spike binding inhibitory activity in 371 persons who received one of four recommended vaccination schedules with or without an mRNA vaccine booster. Overall, we find different antibody levels and inhibitory activity in recommended vaccination schedules, reflected in the observed risk of SARS-CoV-2 infections. We observe an increased protection following mRNA boosters, against both Omicron and Delta variant infections, although BNT162b2 boosters provide greater protection against Omicron than mRNA-1273 boosters.
MeSH term(s)	Angiotensin-Converting Enzyme 2 ; Antibodies, Viral/metabolism ; BNT162 Vaccine ; COVID-19/epidemiology ; COVID-19/prevention & control ; Humans ; Iceland/epidemiology ; RNA, Messenger ; SARS-CoV-2/genetics ; Vaccination ; Vaccines, Synthetic ; Viral Vaccines ; mRNA Vaccines
Chemical Substances	Antibodies, Viral ; RNA, Messenger ; Vaccines, Synthetic ; Viral Vaccines ; mRNA Vaccines ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2022-09-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-33076-4
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Article ; Online: Challenges in early clinical development of adjuvanted vaccines.

Della Cioppa, Giovanni / Jonsdottir, Ingileif / Lewis, David

Vaccine

2015 Volume 33 Suppl 2, Page(s) B47–51

Abstract: A three-step approach to the early development of adjuvanted vaccine candidates is proposed, the goal of which is to allow ample space for exploratory and hypothesis-generating human experiments and to select dose(s) and dosing schedule(s) to bring into ... ...

Abstract	A three-step approach to the early development of adjuvanted vaccine candidates is proposed, the goal of which is to allow ample space for exploratory and hypothesis-generating human experiments and to select dose(s) and dosing schedule(s) to bring into full development. Although the proposed approach is more extensive than the traditional early development program, the authors suggest that by addressing key questions upfront the overall time, size and cost of development will be reduced and the probability of public health advancement enhanced. The immunogenicity end-points chosen for early development should be critically selected: an established immunological parameter with a well characterized assay should be selected as primary end-point for dose and schedule finding; exploratory information-rich end-points should be limited in number and based on pre-defined hypothesis generating plans, including system biology and pathway analyses. Building a pharmacodynamic profile is an important aspect of early development: to this end, multiple early (within 24h) and late (up to one year) sampling is necessary, which can be accomplished by sampling subgroups of subjects at different time points. In most cases the final target population, even if vulnerable, should be considered for inclusion in early development. In order to obtain the multiple formulations necessary for the dose and schedule finding, "bed-side mixing" of various components of the vaccine is often necessary: this is a complex and underestimated area that deserves serious research and logistical support.
MeSH term(s)	Adjuvants, Immunologic/administration & dosage ; Adjuvants, Immunologic/pharmacokinetics ; Adjuvants, Immunologic/pharmacology ; Clinical Studies as Topic ; Humans ; Immunization Schedule ; Vaccination/methods ; Vaccines/administration & dosage ; Vaccines/immunology ; Vaccines/pharmacokinetics
Chemical Substances	Adjuvants, Immunologic ; Vaccines
Language	English
Publishing date	2015-06-08
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2015.02.031
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Article ; Online: LT-K63 Enhances B Cell Activation and Survival Factors in Neonatal Mice That Translates Into Long-Lived Humoral Immunity.

Aradottir Pind, Audur Anna / Molina Estupiñan, Jenny Lorena / Magnusdottir, Gudbjorg Julia / Del Giudice, Giuseppe / Jonsdottir, Ingileif / Bjarnarson, Stefania P

Frontiers in immunology

2020 Volume 11, Page(s) 527310

Abstract: Adjuvants enhance magnitude and duration of immune responses induced by vaccines. In this study we assessed in neonatal mice if and how the adjuvant LT-K63 given with a pneumococcal conjugate vaccine, Pnc1-TT, could affect the expression of tumor ... ...

Abstract	Adjuvants enhance magnitude and duration of immune responses induced by vaccines. In this study we assessed in neonatal mice if and how the adjuvant LT-K63 given with a pneumococcal conjugate vaccine, Pnc1-TT, could affect the expression of tumor necrosis factor receptor (TNF-R) superfamily members, known to be involved in the initiation and maintenance of antibody responses; B cell activating factor receptor (BAFF-R) and B cell maturation antigen (BCMA) and their ligands, BAFF, and a proliferation inducing ligand (APRIL). Initially we assessed the maturation status of different B cell populations and their expression of BAFF-R and BCMA. Neonatal mice had dramatically fewer B cells than adult mice and the composition of different subsets within the B cell pool differed greatly. Proportionally newly formed B cells were most abundant, but they had diminished BAFF-R expression which could explain low proportions of marginal zone and follicular B cells observed. Limited BCMA expression was also detected in neonatal pre-plasmablasts/plasmablasts. LT-K63 enhanced vaccine-induced BAFF-R expression in splenic marginal zone, follicular and newly formed B cells, leading to increased plasmablast/plasma cells, and their enhanced expression of BCMA in spleen and bone marrow. Additionally, the induction of BAFF and APRIL expression occurred early in neonatal mice immunized with Pnc1-TT either with or without LT-K63. However, BAFF
MeSH term(s)	Animals ; Animals, Newborn ; B-Lymphocytes/cytology ; B-Lymphocytes/immunology ; Bacterial Toxins/pharmacology ; Enterotoxins/pharmacology ; Escherichia coli Proteins/pharmacology ; Immunity, Humoral/drug effects ; Lymphocyte Activation/drug effects ; Mice
Chemical Substances	Bacterial Toxins ; Enterotoxins ; Escherichia coli Proteins ; heat-labile enterotoxin, E coli (D9K3SN2LNY)
Language	English
Publishing date	2020-10-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.527310
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Article: Transitional B Cells and TLR9 Responses Are Defective in Selective IgA Deficiency.

Lemarquis, Andri L / Einarsdottir, Helga K / Kristjansdottir, Rakel N / Jonsdottir, Ingileif / Ludviksson, Bjorn R

Frontiers in immunology

2018 Volume 9, Page(s) 909

Abstract: Selective IgA deficiency (IgAD) is the most common primary antibody deficiency in the western world with affected individuals suffering from an increased burden of autoimmunity, atopic diseases and infections. It has been shown that IgAD B cells can be ... ...

Abstract	Selective IgA deficiency (IgAD) is the most common primary antibody deficiency in the western world with affected individuals suffering from an increased burden of autoimmunity, atopic diseases and infections. It has been shown that IgAD B cells can be induced with germinal center mimicking reactions to produce IgA. However, IgA is the most prevalent antibody in mucosal sites, where antigen-independent responses are important. Much interest has recently focused on the role of TLR9 in both naïve and mature B cell differentiation into IgA secreting plasma cells. Here, we analyze the phenotype and function of T and B cells in individuals with IgAD following IgA-inducing CpG-TLR9 stimulations. The IgAD individuals had significantly lower numbers of transitional B cells (CD19
MeSH term(s)	Adult ; Aged ; B-Lymphocytes/pathology ; Cell Differentiation ; Female ; Humans ; IgA Deficiency/immunology ; Immunoglobulin A/biosynthesis ; Immunoglobulin Class Switching ; Interleukin-10/genetics ; Lymphocyte Activation ; Male ; Middle Aged ; Oligodeoxyribonucleotides ; Precursor Cells, B-Lymphoid/drug effects ; T-Lymphocytes, Regulatory/drug effects ; Toll-Like Receptor 9/immunology
Chemical Substances	IL10 protein, human ; Immunoglobulin A ; Oligodeoxyribonucleotides ; TLR9 protein, human ; Toll-Like Receptor 9 ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2018-04-27
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2018.00909
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Article ; Online: Variant in the synaptonemal complex protein SYCE2 associates with pregnancy loss through effect on recombination.

Steinthorsdottir, Valgerdur / Halldorsson, Bjarni V / Jonsson, Hakon / Palsson, Gunnar / Oddsson, Asmundur / Westergaard, David / Arnadottir, Gudny A / Stefansdottir, Lilja / Banasik, Karina / Esplin, M Sean / Hansen, Thomas Folkmann / Brunak, Søren / Nyegaard, Mette / Ostrowski, Sisse Rye / Pedersen, Ole Birger Vesterager / Erikstrup, Christian / Thorleifsson, Gudmar / Nadauld, Lincoln D / Haraldsson, Asgeir /

Steingrimsdottir, Thora / Tryggvadottir, Laufey / Jonsdottir, Ingileif / Gudbjartsson, Daniel F / Hoffmann, Eva R / Sulem, Patrick / Holm, Hilma / Nielsen, Henriette Svarre / Stefansson, Kari

Nature structural & molecular biology

2024 Volume 31, Issue 4, Page(s) 710–716

Abstract: Two-thirds of all human conceptions are lost, in most cases before clinical detection. The lack of detailed understanding of the causes of pregnancy losses constrains focused counseling for future pregnancies. We have previously shown that a missense ... ...

Abstract	Two-thirds of all human conceptions are lost, in most cases before clinical detection. The lack of detailed understanding of the causes of pregnancy losses constrains focused counseling for future pregnancies. We have previously shown that a missense variant in synaptonemal complex central element protein 2 (SYCE2), in a key residue for the assembly of the synaptonemal complex backbone, associates with recombination traits. Here we show that it also increases risk of pregnancy loss in a genome-wide association analysis on 114,761 women with reported pregnancy loss. We further show that the variant associates with more random placement of crossovers and lower recombination rate in longer chromosomes but higher in the shorter ones. These results support the hypothesis that some pregnancy losses are due to failures in recombination. They further demonstrate that variants with a substantial effect on the quality of recombination can be maintained in the population.
MeSH term(s)	Humans ; Female ; Pregnancy ; Synaptonemal Complex/metabolism ; Nuclear Proteins/metabolism ; Genome-Wide Association Study ; Chromosomal Proteins, Non-Histone/metabolism ; Recombination, Genetic ; Meiosis
Chemical Substances	Nuclear Proteins ; Chromosomal Proteins, Non-Histone
Language	English
Publishing date	2024-01-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2126708-X
ISSN	1545-9985 ; 1545-9993
ISSN (online)	1545-9985
ISSN	1545-9993
DOI	10.1038/s41594-023-01209-y
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