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Article ; Online: Clinical Characteristics of Covid-19 in China.

Chen, Andre T C / Coura-Filho, George B / Rehder, Marília H H

2020 Volume 382, Issue 19, Page(s) 1860

MeSH term(s)	Betacoronavirus ; COVID-19 ; China ; Coronavirus ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-03-27
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc2005203
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Article ; Online: Enhancing chimeric antigen receptor T cell therapy by modulating the p53 signaling network with Δ133p53α.

Roselle, Christopher / Horikawa, Izumi / Chen, Linhui / Kelly, Andre R / Gonzales, Donna / Da, Tong / Wellhausen, Nils / Rommel, Philipp C / Baker, Daniel / Suhoski, Megan / Scholler, John / O'Connor, Roddy S / Young, Regina M / Harris, Curtis C / June, Carl H

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

2024 Volume 121, Issue 10, Page(s) e2317735121

Abstract: Chimeric antigen receptor (CAR) T cell dysfunction is a major barrier to achieving lasting ... that Δ133p53α, an endogenous isoform of the human TP53 gene, decreases in expression with age in human T ... cells, and that reconstitution of Δ133p53α in poorly functional T cells can rescue proliferation [A. M ...

Abstract	Chimeric antigen receptor (CAR) T cell dysfunction is a major barrier to achieving lasting remission in hematologic cancers, especially in chronic lymphocytic leukemia (CLL). We have shown previously that Δ133p53α, an endogenous isoform of the human TP53 gene, decreases in expression with age in human T cells, and that reconstitution of Δ133p53α in poorly functional T cells can rescue proliferation [A. M. Mondal
MeSH term(s)	Humans ; Immunotherapy, Adoptive/methods ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/therapy ; Receptors, Chimeric Antigen/genetics ; Receptors, Chimeric Antigen/metabolism ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism ; Antigens, CD19 ; Cell- and Tissue-Based Therapy ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/metabolism
Chemical Substances	Receptors, Chimeric Antigen ; Tumor Suppressor Protein p53 ; Antigens, CD19 ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2024-02-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2317735121
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Article ; Online: Brazilian Landscape of Hepatocellular Carcinoma.

Fonseca, Leonardo G / Chen, Andre T C / de Oliveira, Irai S / Chagas, Aline L / Kruger, Jaime A P / Carrilho, Flair J

JCO global oncology

2023 Volume 9, Page(s) e2200416

Abstract: The incidence of hepatocellular carcinoma (HCC) is expected to increase in the coming years, and strategies to mitigate the burden of this disease are needed in different regions. Geographic variations in epidemiology and risk factors, such as viral ... ...

Abstract	The incidence of hepatocellular carcinoma (HCC) is expected to increase in the coming years, and strategies to mitigate the burden of this disease are needed in different regions. Geographic variations in epidemiology and risk factors, such as viral hepatitis and metabolic disease, pose challenges in adopting programs for early detection programs and management of patients with HCC. Brazil, like other countries, has high economic and social inequality, with heterogeneous access to health care. Viral hepatitis is the main risk factor but there is growing awareness of fatty liver disease. Risk factor monitoring and screening programs are unmet priorities because patients are often diagnosed at later stages. Advances in the management of patients with HCC have been made in recent years, including new tools for selecting patients for liver transplantation, sophisticated surgical techniques, and new systemic agents. High-volume academic centers often achieve favorable results through the adoption and application of established treatments, but this is not a reality in most regions of Brazil, because of disparities in wealth and resources. As HCC management requires a coordinated and multidisciplinary team, the role of local referral centers in decentralizing access to treatments and promoting health education in different regions should be encouraged and supported.
MeSH term(s)	Humans ; Carcinoma, Hepatocellular/diagnosis ; Carcinoma, Hepatocellular/epidemiology ; Carcinoma, Hepatocellular/therapy ; Liver Neoplasms/diagnosis ; Liver Neoplasms/epidemiology ; Liver Neoplasms/therapy ; Brazil/epidemiology ; Risk Factors ; Incidence
Language	English
Publishing date	2023-06-20
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2687-8941
ISSN (online)	2687-8941
DOI	10.1200/GO.22.00416
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Article ; Online: Trends in Outcomes of Heart Transplants Using Extended Criteria Donors: A United Network for Organ Sharing Database Analysis.

Critsinelis, Andre C / Patel, Sagar / Nordan, Taylor / Chen, Frederick Y / Couper, Gregory S / Kawabori, Masashi

The Annals of thoracic surgery

2022 Volume 115, Issue 6, Page(s) 1503–1509

Abstract: ... to 2014, and (4) 2014 to 2018. The 2-sample t test, Kaplan-Meier survival analysis, log-rank test ...

Abstract	Background: Although the use of extended criteria donors (ECDs) is traditionally avoided because of poorer outcomes, management of heart transplant (HTx) recipients has evolved over the past decades. We sought to examine the temporal trends in outcomes of ECDs in HTx. Methods: We queried the United Network for Organ Sharing database for adult HTx recipients who fit the EXPAND Trial criteria for ECDs: ischemic time ≥ 4 hours, ejection fraction < 50%, age > 55 years, and history of coronary artery disease. Transplant years were stratified into the following 4 periods: (1) 2000 to 2004, (2) 2005 to 2009, (3) 2010 to 2014, and (4) 2014 to 2018. The 2-sample t test, Kaplan-Meier survival analysis, log-rank test, analysis of variance, multivariable Cox proportional hazards, and multinomial logistic regression were used to compare data between periods. Results: Through periods 1 to 4, 39,028 patients were stratified as follows: 9217 (2942 ECDs, 31.9%), 9224 (2730 ECDs, 29.6%), 10,309 (2762 ECDs, 26.8%), and 10,278 (2190 ECDs, 21.3%). Transplants using ECDs in periods 1 and 2 had increased 1-year mortality compared with periods 3 and 4 (16.9% and 15.6% vs 11.9% and 10.9% respectively, P < .001). Later periods also demonstrated improved Karnofsky scores (P < .001). Conclusions: Although use of ECDs decreased across the periods, we noted significant improvement in 1-year survival rates and postoperative functional status.
MeSH term(s)	Adult ; Humans ; Middle Aged ; Kidney Transplantation ; Retrospective Studies ; Tissue Donors ; Heart Transplantation ; Kaplan-Meier Estimate ; Treatment Outcome ; Graft Survival
Language	English
Publishing date	2022-09-28
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	211007-6
ISSN	1552-6259 ; 0003-4975
ISSN (online)	1552-6259
ISSN	0003-4975
DOI	10.1016/j.athoracsur.2022.09.027
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Article ; Online: Dietary advanced glycation end-products (dAGEs) intake and its relation to sarcopenia and frailty - The Rotterdam Study.

Waqas, Komal / Chen, Jinluan / Lu, T / van der Eerden, B C J / Rivadeneira, Fernando / Uitterlinden, André G / Voortman, Trudy / Zillikens, M Carola

Bone

2022 Volume 165, Page(s) 116564

Abstract: Studies on mice have shown a relationship between dietary intake of advanced glycation end-products (dAGEs) and deterioration of musculoskeletal health, but human studies are absent. We investigated the relationship between dietary intake of ... ...

Abstract	Studies on mice have shown a relationship between dietary intake of advanced glycation end-products (dAGEs) and deterioration of musculoskeletal health, but human studies are absent. We investigated the relationship between dietary intake of carboxymethyllysine (dCML) - an AGE prototype - and risk of sarcopenia at baseline and after 5 years of follow-up and a single evaluation of physical frailty in participants from the population-based Rotterdam Study. Appendicular lean mass (ALM) was obtained using insight dual-energy X-ray absorptiometry and hand grip strength (HGS) using a hydraulic hand dynamometer. Subjects with both low ALM and weak HGS were classified as having sarcopenia. Frailty (yes/no) was defined by presence of ≥3 and pre-frailty by presence of 1 or 2 components namely, exhaustion, weakness, slowness, weight loss or low physical activity. dCML was calculated using a food frequency questionnaire and dAGE databases. Logistic regression analysis was used to evaluate the odds of physical frailty and prevalent sarcopenia at baseline and follow-up and incident sarcopenia. 2782 participants with an age 66.4 ± 9.9 years and dCML intake 3.3 ± 1.3 mg/day, had data on sarcopenia at both time points. Of whom 84 had sarcopenia at baseline and 73 developed sarcopenia at follow-up. We observed an association of one SD increase in dCML intake with prevalent sarcopenia at baseline [odds ratio, OR = 1.27 (1.01-1.59)] and no association of dCML with incident sarcopenia at 5-year follow-up [OR = 1.12 (0.86-1.44)]. For frailty we analyzed 3577 participants, of whom 1972 were pre-frail and 158 were frail. We observed no association of dCML with either pre-frailty [OR = 0.99 (0.91-1.07)] or frailty [OR = 1.01 (0.83-1.22)] when non-frail subjects were used as reference. Our results show an association of dAGEs with sarcopenia cross-sectionally but not longitudinally where inconclusive findings are observed possibly due to a very low incidence of sarcopenia. There was no association with frailty cross-sectionally.
MeSH term(s)	Humans ; Mice ; Animals ; Child, Preschool ; Middle Aged ; Aged ; Frailty/epidemiology ; Sarcopenia/epidemiology ; Hand Strength ; Glycation End Products, Advanced ; Eating
Chemical Substances	Glycation End Products, Advanced
Language	English
Publishing date	2022-09-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632515-4
ISSN	1873-2763 ; 8756-3282
ISSN (online)	1873-2763
ISSN	8756-3282
DOI	10.1016/j.bone.2022.116564
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Zs.A 1571: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Cyclophilin A supports translation of intrinsically disordered proteins and affects haematopoietic stem cell ageing.

Nature cell biology

2024 Volume 26, Issue 4, Page(s) 593–603

Abstract: Loss of protein function is a driving force of ageing. We have identified peptidyl-prolyl isomerase A (PPIA or cyclophilin A) as a dominant chaperone in haematopoietic stem and progenitor cells. Depletion of PPIA accelerates stem cell ageing. We found ... ...

Abstract	Loss of protein function is a driving force of ageing. We have identified peptidyl-prolyl isomerase A (PPIA or cyclophilin A) as a dominant chaperone in haematopoietic stem and progenitor cells. Depletion of PPIA accelerates stem cell ageing. We found that proteins with intrinsically disordered regions (IDRs) are frequent PPIA substrates. IDRs facilitate interactions with other proteins or nucleic acids and can trigger liquid-liquid phase separation. Over 20% of PPIA substrates are involved in the formation of supramolecular membrane-less organelles. PPIA affects regulators of stress granules (PABPC1), P-bodies (DDX6) and nucleoli (NPM1) to promote phase separation and increase cellular stress resistance. Haematopoietic stem cell ageing is associated with a post-transcriptional decrease in PPIA expression and reduced translation of IDR-rich proteins. Here we link the chaperone PPIA to the synthesis of intrinsically disordered proteins, which indicates that impaired protein interaction networks and macromolecular condensation may be potential determinants of haematopoietic stem cell ageing.
MeSH term(s)	Intrinsically Disordered Proteins/chemistry ; Cyclophilin A/genetics ; Cyclophilin A/metabolism ; RNA-Binding Proteins ; Hematopoietic Stem Cells/metabolism
Chemical Substances	Intrinsically Disordered Proteins ; Cyclophilin A (EC 5.2.1.-) ; RNA-Binding Proteins
Language	English
Publishing date	2024-03-29
Publishing country	England
Document type	Journal Article
ZDB-ID	1474722-4
ISSN	1476-4679 ; 1465-7392
ISSN (online)	1476-4679
ISSN	1465-7392
DOI	10.1038/s41556-024-01387-x
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Zs.A 5169: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 12: Show issues

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Article: Engineering self-propelled tumor-infiltrating CAR T cells using synthetic velocity receptors.

bioRxiv : the preprint server for biology

2024

Abstract: Chimeric antigen receptor (CAR) T cells express antigen-specific synthetic receptors ... which upon binding to cancer cells, elicit T cell anti-tumor responses. CAR T cell therapy has enjoyed success ... However, CAR T therapy for patients with solid tumors has not seen similar success. Solid tumors constitute 90 ...

Abstract	Chimeric antigen receptor (CAR) T cells express antigen-specific synthetic receptors, which upon binding to cancer cells, elicit T cell anti-tumor responses. CAR T cell therapy has enjoyed success in the clinic for hematological cancer indications, giving rise to decade-long remissions in some cases. However, CAR T therapy for patients with solid tumors has not seen similar success. Solid tumors constitute 90% of adult human cancers, representing an enormous unmet clinical need. Current approaches do not solve the central problem of limited ability of therapeutic cells to migrate through the stromal matrix. We discover that T cells at low and high density display low- and high-migration phenotypes, respectively. The highly migratory phenotype is mediated by a paracrine pathway from a group of self-produced cytokines that include IL5, TNFα, IFNγ, and IL8. We exploit this finding to "lock-in" a highly migratory phenotype by developing and expressing receptors, which we call velocity receptors (VRs). VRs target these cytokines and signal through these cytokines' cognate receptors to increase T cell motility and infiltrate lung, ovarian, and pancreatic tumors in large numbers and at doses for which control CAR T cells remain confined to the tumor periphery. In contrast to CAR therapy alone, VR-CAR T cells significantly attenuate tumor growth and extend overall survival. This work suggests that approaches to the design of immune cell receptors that focus on migration signaling will help current and future CAR cellular therapies to infiltrate deep into solid tumors.
Language	English
Publishing date	2024-03-26
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.12.13.571595
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Article: Azepine-Indole Alkaloids From

Kirchweger, Benjamin / Klein-Junior, Luiz C / Pretsch, Dagmar / Chen, Ya / Cretton, Sylvian / Gasper, André L / Heyden, Yvan Vander / Christen, Philippe / Kirchmair, Johannes / Henriques, Amélia T / Rollinger, Judith M

Frontiers in neuroscience

2022 Volume 16, Page(s) 826289

Abstract: Nemorosine A ( ...

Abstract	Nemorosine A (
Language	English
Publishing date	2022-03-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2022.826289
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Article ; Online: Photocleavable Polymer Cubosomes: Synthesis, Self-Assembly, and Photorelease.

Chen, Hui / Schumacher, Marcel / Ianiro, Alessandro / Stank, Tim Julian / Janoszka, Nicole / Chen, Chen / Azhdari, Suna / Hellweg, Thomas / Gröschel, André H

Journal of the American Chemical Society

2024

Abstract: Polymer cubosomes (PCs) are a recent class of self-assembled block copolymer (BCP) microparticles with an accessible periodic channel system. Most reported PCs consist of a polystyrene scaffold, which provides mechanical stability for templating but has ... ...

Abstract	Polymer cubosomes (PCs) are a recent class of self-assembled block copolymer (BCP) microparticles with an accessible periodic channel system. Most reported PCs consist of a polystyrene scaffold, which provides mechanical stability for templating but has a limited intrinsic functionality. Here, we report the synthesis of photocleavable BCPs with compositions suitable for PC formation. We analyze the self-assembly mechanism and study the model release of dyes during irradiation, where the transition of the BCPs from amphiphilic to bishydrophilic causes the rapid disassembly of the PCs. A combination of modeling and experiment shows that the evolution of PCs proceeds first
Language	English
Publishing date	2024-04-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/jacs.4c02651
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Article ; Online: Dietary advanced glycation end-products (dAGEs) intake and its relation to sarcopenia and frailty – The Rotterdam Study

Waqas, Komal / Chen, Jinluan / Lu, T. / van der Eerden, B.C.J. / Rivadeneira, Fernando / Uitterlinden, André G. / Voortman, Trudy / Zillikens, Carola

Bone

2022 Volume 165

Abstract	Studies on mice have shown a relationship between dietary intake of advanced glycation end-products (dAGEs) and deterioration of musculoskeletal health, but human studies are absent. We investigated the relationship between dietary intake of carboxymethyllysine (dCML) – an AGE prototype – and risk of sarcopenia at baseline and after 5 years of follow-up and a single evaluation of physical frailty in participants from the population-based Rotterdam Study. Appendicular lean mass (ALM) was obtained using insight dual-energy X-ray absorptiometry and hand grip strength (HGS) using a hydraulic hand dynamometer. Subjects with both low ALM and weak HGS were classified as having sarcopenia. Frailty (yes/no) was defined by presence of ≥3 and pre-frailty by presence of 1 or 2 components namely, exhaustion, weakness, slowness, weight loss or low physical activity. dCML was calculated using a food frequency questionnaire and dAGE databases. Logistic regression analysis was used to evaluate the odds of physical frailty and prevalent sarcopenia at baseline and follow-up and incident sarcopenia. 2782 participants with an age 66.4 ± 9.9 years and dCML intake 3.3 ± 1.3 mg/day, had data on sarcopenia at both time points. Of whom 84 had sarcopenia at baseline and 73 developed sarcopenia at follow-up. We observed an association of one SD increase in dCML intake with prevalent sarcopenia at baseline [odds ratio, OR = 1.27 (1.01–1.59)] and no association of dCML with incident sarcopenia at 5-year follow-up [OR = 1.12 (0.86–1.44)]. For frailty we analyzed 3577 participants, of whom 1972 were pre-frail and 158 were frail. We observed no association of dCML with either pre-frailty [OR = 0.99 (0.91–1.07)] or frailty [OR = 1.01 (0.83–1.22)] when non-frail subjects were used as reference. Our results show an association of dAGEs with sarcopenia cross-sectionally but not longitudinally where inconclusive findings are observed possibly due to a very low incidence of sarcopenia. There was no association with frailty cross-sectionally.
Keywords	Advanced glycation end products ; Carboxymethyllysine ; Diet ; Frailty ; Sarcopenia
Subject code	796
Language	English
Publishing country	nl
Document type	Article ; Online
ZDB-ID	632515-4
ISSN	1873-2763 ; 8756-3282
ISSN (online)	1873-2763
ISSN	8756-3282
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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