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Article ; Online: Clinical validation of the PrecivityAD2 blood test: A mass spectrometry-based test with algorithm combining %p-tau217 and Aβ42/40 ratio to identify presence of brain amyloid.

Meyer, Matthew R / Kirmess, Kristopher M / Eastwood, Stephanie / Wente-Roth, Traci L / Irvin, Faith / Holubasch, Mary S / Venkatesh, Venky / Fogelman, Ilana / Monane, Mark / Hanna, Lucy / Rabinovici, Gil D / Siegel, Barry A / Whitmer, Rachel A / Apgar, Charles / Bateman, Randall J / Holtzman, David M / Irizarry, Michael / Verbel, David / Sachdev, Pallavi /

Ito, Satoshi / Contois, John / Yarasheski, Kevin E / Braunstein, Joel B / Verghese, Philip B / West, Tim

Alzheimer's & dementia : the journal of the Alzheimer's Association

2024

Abstract: ... based assays were used to measure %p-tau217 and amyloid beta (Aβ)42/40 ratio in blood samples from 583 ... by PET.: Results: The area under the receiver operating characteristic curve (AUC-ROC) for %p-tau217 ... 0.94) was statistically significantly higher than that for p-tau217 concentration (0.91). The AUC ...

Abstract	Background: With the availability of disease-modifying therapies for Alzheimer's disease (AD), it is important for clinicians to have tests to aid in AD diagnosis, especially when the presence of amyloid pathology is a criterion for receiving treatment. Methods: High-throughput, mass spectrometry-based assays were used to measure %p-tau217 and amyloid beta (Aβ)42/40 ratio in blood samples from 583 individuals with suspected AD (53% positron emission tomography [PET] positive by Centiloid > 25). An algorithm (PrecivityAD2 test) was developed using these plasma biomarkers to identify brain amyloidosis by PET. Results: The area under the receiver operating characteristic curve (AUC-ROC) for %p-tau217 (0.94) was statistically significantly higher than that for p-tau217 concentration (0.91). The AUC-ROC for the PrecivityAD2 test output, the Amyloid Probability Score 2, was 0.94, yielding 88% agreement with amyloid PET. Diagnostic performance of the APS2 was similar by ethnicity, sex, age, and apoE4 status. Discussion: The PrecivityAD2 blood test showed strong clinical validity, with excellent agreement with brain amyloidosis by PET.
Language	English
Publishing date	2024-03-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.13764
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Article ; Online: Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer's trial selection and disease monitoring.

Ashton, Nicholas J / Janelidze, Shorena / Mattsson-Carlgren, Niklas / Binette, Alexa Pichet / Strandberg, Olof / Brum, Wagner S / Karikari, Thomas K / González-Ortiz, Fernándo / Di Molfetta, Guglielmo / Meda, Francisco J / Jonaitis, Erin M / Koscik, Rebecca Langhough / Cody, Karly / Betthauser, Tobey J / Li, Yan / Vanmechelen, Eugeen / Palmqvist, Sebastian / Stomrud, Erik / Bateman, Randall J /

Zetterberg, Henrik / Johnson, Sterling C / Blennow, Kaj / Hansson, Oskar

Nature medicine

2022 Volume 28, Issue 12, Page(s) 2555–2562

Abstract: ... phosphorylated (p)-tau231 and amyloid-β42/40 ratio were more changed at lower thresholds of amyloid pathology ... Longitudinally, however, only p-tau217 demonstrated marked amyloid-dependent changes over 4-6 years ... in both preclinical and symptomatic stages of the disease, with no such changes observed in p-tau231, p-tau181 ...

Abstract	Blood biomarkers indicative of Alzheimer's disease (AD) pathology are altered in both preclinical and symptomatic stages of the disease. Distinctive biomarkers may be optimal for the identification of AD pathology or monitoring of disease progression. Blood biomarkers that correlate with changes in cognition and atrophy during the course of the disease could be used in clinical trials to identify successful interventions and thereby accelerate the development of efficient therapies. When disease-modifying treatments become approved for use, efficient blood-based biomarkers might also inform on treatment implementation and management in clinical practice. In the BioFINDER-1 cohort, plasma phosphorylated (p)-tau231 and amyloid-β42/40 ratio were more changed at lower thresholds of amyloid pathology. Longitudinally, however, only p-tau217 demonstrated marked amyloid-dependent changes over 4-6 years in both preclinical and symptomatic stages of the disease, with no such changes observed in p-tau231, p-tau181, amyloid-β42/40, glial acidic fibrillary protein or neurofilament light. Only longitudinal increases of p-tau217 were also associated with clinical deterioration and brain atrophy in preclinical AD. The selective longitudinal increase of p-tau217 and its associations with cognitive decline and atrophy was confirmed in an independent cohort (Wisconsin Registry for Alzheimer's Prevention). These findings support the differential association of plasma biomarkers with disease development and strongly highlight p-tau217 as a surrogate marker of disease progression in preclinical and prodromal AD, with impact for the development of new disease-modifying treatments.
MeSH term(s)	Humans ; Alzheimer Disease/pathology ; tau Proteins ; Amyloid beta-Peptides ; Cognitive Dysfunction ; Disease Progression ; Biomarkers ; Atrophy
Chemical Substances	amyloid beta-protein (1-42) ; tau Proteins ; Amyloid beta-Peptides ; Biomarkers
Language	English
Publishing date	2022-12-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-022-02074-w
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Zs.A 4212: 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)
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Article ; Online: The Proposed Specifiers for Conduct Disorder - Parent (PSCD-P): Convergent Validity, Incremental Validity, and Reactions to Unfamiliar Peer Confederates.

Bellamy, Nicholas A / Salekin, Randall T / Makol, Bridget A / Augenstein, Tara M / De Los Reyes, Andres

Research on child and adolescent psychopathology

2023 Volume 51, Issue 8, Page(s) 1097–1113

Abstract: ... P) in a mixed clinical/community sample of 134 adolescents (M ...

Abstract	Youth who experience psychopathy display multiple impairments across interpersonal (grandiose-manipulative [GM]), affective (callous-unemotional [CU]), lifestyle (daring-impulsive [DI]), and potentially antisocial and behavioral features. Recently, it has been acknowledged that the inclusion of psychopathic features can offer valuable information in relation to the etiology of Conduct Disorder (CD). Yet, prior work largely focuses on the affective component of psychopathy, namely CU. This focus creates uncertainty in the literature on the incremental value of a multicomponent approach to understanding CD-linked domains. Consequently, researchers developed the Proposed Specifiers for Conduct Disorder (PSCD; Salekin & Hare, 2016) as a multicomponent approach to assess GM, CU, and DI features in combination with CD symptoms. The notion of considering the wider set of psychopathic features for CD specification requires testing whether multiple personality dimensions predict domain-relevant criterion outcomes above-and-beyond a CU-based approach. Thus, we tested the psychometric properties of parents' reports on the PSCD (PSCD-P) in a mixed clinical/community sample of 134 adolescents (M
MeSH term(s)	Adolescent ; Humans ; Female ; Male ; Conduct Disorder/psychology ; Reproducibility of Results ; Antisocial Personality Disorder/psychology ; Surveys and Questionnaires ; Parents ; Callosities
Language	English
Publishing date	2023-04-25
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3041907-4
ISSN	2730-7174 ; 2730-7166
ISSN (online)	2730-7174
ISSN	2730-7166
DOI	10.1007/s10802-023-01056-x
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Article ; Online: Gut microbiota regulation of P-glycoprotein in the intestinal epithelium in maintenance of homeostasis.

Foley, Sage E / Tuohy, Christine / Dunford, Merran / Grey, Michael J / De Luca, Heidi / Cawley, Caitlin / Szabady, Rose L / Maldonado-Contreras, Ana / Houghton, Jean Marie / Ward, Doyle V / Mrsny, Randall J / McCormick, Beth A

Microbiome

2021 Volume 9, Issue 1, Page(s) 183

Abstract: Background: P-glycoprotein (P-gp) plays a critical role in protection of the intestinal epithelia ... to light that P-gp also confers a critical link in communication between intestinal mucosal barrier ... function and the innate immune system. Yet, despite knowledge for over 10 years that P-gp plays a central ...

Abstract	Background: P-glycoprotein (P-gp) plays a critical role in protection of the intestinal epithelia by mediating efflux of drugs/xenobiotics from the intestinal mucosa into the gut lumen. Recent studies bring to light that P-gp also confers a critical link in communication between intestinal mucosal barrier function and the innate immune system. Yet, despite knowledge for over 10 years that P-gp plays a central role in gastrointestinal homeostasis, the precise molecular mechanism that controls its functional expression and regulation remains unclear. Here, we assessed how the intestinal microbiome drives P-gp expression and function. Results: We have identified a "functional core" microbiome of the intestinal gut community, specifically genera within the Clostridia and Bacilli classes, that is necessary and sufficient for P-gp induction in the intestinal epithelium in mouse models. Metagenomic analysis of this core microbial community revealed that short-chain fatty acid and secondary bile acid production positively associate with P-gp expression. We have further shown these two classes of microbiota-derived metabolites synergistically upregulate P-gp expression and function in vitro and in vivo. Moreover, in patients suffering from ulcerative colitis (UC), we find diminished P-gp expression coupled to the reduction of epithelial-derived anti-inflammatory endocannabinoids and luminal content (e.g., microbes or their metabolites) with a reduced capability to induce P-gp expression. Conclusion: Overall, by means of both in vitro and in vivo studies as well as human subject sample analysis, we identify a mechanistic link between cooperative functional outputs of the complex microbial community and modulation of P-gp, an epithelial component, that functions to suppress overactive inflammation to maintain intestinal homeostasis. Hence, our data support a new cross-talk paradigm in microbiome regulation of mucosal inflammation. Video abstract.
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B ; ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Animals ; Gastrointestinal Microbiome/genetics ; Homeostasis ; Humans ; Intestinal Mucosa ; Mice
Chemical Substances	ATP Binding Cassette Transporter, Subfamily B ; ATP Binding Cassette Transporter, Subfamily B, Member 1
Language	English
Publishing date	2021-09-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Video-Audio Media
ZDB-ID	2697425-3
ISSN	2049-2618 ; 2049-2618
ISSN (online)	2049-2618
ISSN	2049-2618
DOI	10.1186/s40168-021-01137-3
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Article ; Online: Parent Perspectives after the PRISM-P Randomized Trial: A Mixed-Methods Analysis.

Rosenberg, Abby R / Zhou, Chuan / Bradford, Miranda C / Barton, Krysta / Junkins, Courtney C / Taylor, Mallory / Kross, Erin K / Curtis, J Randall / Dionne-Odom, J Nicholas / Yi-Frazier, Joyce P

Journal of palliative medicine

2021 Volume 24, Issue 10, Page(s) 1505–1515

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Adolescent ; Adult ; Child ; Child, Preschool ; Counseling ; Humans ; Neoplasms ; Parents ; Psychotherapy ; Stress, Psychological ; Young Adult
Language	English
Publishing date	2021-03-15
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	1427361-5
ISSN	1557-7740 ; 1096-6218
ISSN (online)	1557-7740
ISSN	1096-6218
DOI	10.1089/jpm.2020.0720
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Article ; Online: Greater specificity for cerebrospinal fluid P-tau231 over P-tau181 in the differentiation of healthy controls from Alzheimer's disease.

Spiegel, Jonathan / Pirraglia, Elizabeth / Osorio, Ricardo S / Glodzik, Lidia / Li, Yi / Tsui, Wai / Saint Louis, Leslie A / Randall, Catherine / Butler, Tracy / Xu, Jinfeng / Zinkowski, Raymond P / Zetterberg, Henrik / Fortea, Juan / Fossati, Silvia / Wisniewski, Thomas / Davies, Peter / Blennow, Kaj / de Leon, Mony J

Journal of Alzheimer's disease : JAD

2015 Volume 49, Issue 1, Page(s) 93–100

Abstract: Cerebrospinal fluid (CSF) measures of phosphorylated-tau (P-tau) 231 and P-tau181 are two ... diagnostic study of 87 normal (NL) subjects and 28 AD subjects compared CSF P-tau231 with CSF P-tau181 ... Logistic regression modeling demonstrated that the P-tau231 was superior to the P-tau181 in the diagnostic ...

Abstract	Cerebrospinal fluid (CSF) measures of phosphorylated-tau (P-tau) 231 and P-tau181 are two biomarkers for the identification of tau pathology as related to Alzheimer's disease (AD). While both are pathologically validated, their relative diagnostic performances are not well known. This cross-sectional diagnostic study of 87 normal (NL) subjects and 28 AD subjects compared CSF P-tau231 with CSF P-tau181. Logistic regression modeling demonstrated that the P-tau231 was superior to the P-tau181 in the diagnostic classifications. At a fixed 85% sensitivity cutoff, the ROC analysis shows that P-tau231 has greater overall specificity than P-tau181. While both P-tau analytes demonstrated equivalent negative predictive accuracies, P-tau231 yielded significantly fewer false positives. Moreover, P-tau231, but not P-tau181, demonstrated sensitivity to the E4 genotype. A postmortem validation with 9 AD subjects confirmed the superiority of the CSF P-tau231 specificity. This study suggests that P-tau231 has the potential to improve the CSF tau biomarker diagnosis of AD.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/cerebrospinal fluid ; Alzheimer Disease/diagnosis ; Amyloid beta-Peptides/cerebrospinal fluid ; Biomarkers/cerebrospinal fluid ; Case-Control Studies ; Cross-Sectional Studies ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Phosphorylation ; ROC Curve ; Sensitivity and Specificity ; tau Proteins/cerebrospinal fluid
Chemical Substances	Amyloid beta-Peptides ; Biomarkers ; tau Proteins
Language	English
Publishing date	2015-03-22
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-150167
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Article ; Online: Gold(III)-P-chirogenic complex induces mitochondrial dysfunction in triple-negative breast cancer.

Olelewe, Chibuzor / Kim, Jong Hyun / Ofori, Samuel / Mertens, Randall T / Gukathasan, Sailajah / Awuah, Samuel G

iScience

2022 Volume 25, Issue 5, Page(s) 104340

Abstract: Chemical agents that specifically exploit metabolic vulnerabilities of cancer cells will be beneficial but are rare. The role of oxidative phosphorylation (OXPHOS) in promoting and maintaining triple-negative breast cancer (TNBC) growth provides new ... ...

Abstract	Chemical agents that specifically exploit metabolic vulnerabilities of cancer cells will be beneficial but are rare. The role of oxidative phosphorylation (OXPHOS) in promoting and maintaining triple-negative breast cancer (TNBC) growth provides new treatment opportunity. In this work, we describe AuPhos-19, a small-molecule gold(III)-based agent bearing a chiral phosphine ligand that selectively disrupts mitochondrial metabolism in murine and human TNBC cells but not normal epithelial cells. AuPhos-19 induces potent cytotoxic effect with half maximal inhibitory concentration (IC
Language	English
Publishing date	2022-04-30
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.104340
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Article ; Online: NAD(P)H fluorescence lifetime imaging of live intestinal nematodes reveals metabolic crosstalk between parasite and host.

Liublin, Wjatscheslaw / Rausch, Sebastian / Leben, Ruth / Lindquist, Randall L / Fiedler, Alexander / Liebeskind, Juliane / Beckers, Ingeborg E / Hauser, Anja E / Hartmann, Susanne / Niesner, Raluca A

Scientific reports

2022 Volume 12, Issue 1, Page(s) 7264

Abstract: ... that, the here presented application of NAD(P)H-FLIM in live tissues constitutes a unique tool to study possible ...

Abstract	Infections with intestinal nematodes have an equivocal impact: they represent a burden for human health and animal husbandry, but, at the same time, may ameliorate auto-immune diseases due to the immunomodulatory effect of the parasites. Thus, it is key to understand how intestinal nematodes arrive and persist in their luminal niche and interact with the host over long periods of time. One basic mechanism governing parasite and host cellular and tissue functions, metabolism, has largely been neglected in the study of intestinal nematode infections. Here we use NADH (nicotinamide adenine dinucleotide) and NADPH (nicotinamide adenine dinucleotide phosphate) fluorescence lifetime imaging of explanted murine duodenum infected with the natural nematode Heligmosomoides polygyrus and define the link between general metabolic activity and possible metabolic pathways in parasite and host tissue, during acute infection. In both healthy and infected host intestine, energy is effectively produced, mainly via metabolic pathways resembling oxidative phosphorylation/aerobic glycolysis features. In contrast, the nematodes shift their energy production from balanced fast anaerobic glycolysis-like and effective oxidative phosphorylation-like metabolic pathways, towards mainly anaerobic glycolysis-like pathways, back to oxidative phosphorylation/aerobic glycolysis-like pathways during their different life cycle phases in the submucosa versus the intestinal lumen. Additionally, we found an increased NADPH oxidase (NOX) enzymes-dependent oxidative burst in infected intestinal host tissue as compared to healthy tissue, which was mirrored by a similar defense reaction in the parasites. We expect that, the here presented application of NAD(P)H-FLIM in live tissues constitutes a unique tool to study possible shifts between metabolic pathways in host-parasite crosstalk, in various parasitic intestinal infections.
MeSH term(s)	Animals ; Mice ; NAD/metabolism ; NADP/metabolism ; Nematospiroides dubius ; Optical Imaging ; Parasites/metabolism
Chemical Substances	NAD (0U46U6E8UK) ; NADP (53-59-8)
Language	English
Publishing date	2022-05-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-10705-y
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Article ; Online: Collisional Loss of One-Dimensional Fermions Near a p-Wave Feshbach Resonance.

Chang, Ya-Ting / Senaratne, Ruwan / Cavazos-Cavazos, Danyel / Hulet, Randall G

Physical review letters

2020 Volume 125, Issue 26, Page(s) 263402

Abstract: We study collisional loss of a quasi-one-dimensional spin-polarized Fermi gas near a p-wave ... Feshbach resonance in ultracold ^{6}Li atoms. We measure the location of the p-wave resonance in quasi-1D ... We discuss the implications of these measurements for observing p-wave pairing in quasi-1D. ...

Abstract	We study collisional loss of a quasi-one-dimensional spin-polarized Fermi gas near a p-wave Feshbach resonance in ultracold ^{6}Li atoms. We measure the location of the p-wave resonance in quasi-1D and observe a confinement-induced shift and broadening. We find that the three-body loss coefficient L_{3} as a function of the quasi-1D confinement has little dependence on confinement strength. We also analyze the atom loss with a two-step cascade three-body loss model in which weakly bound dimers are formed prior to their loss arising from atom-dimer collisions. Our data are consistent with this model. We also find a possible suppression in the rate of dimer relaxation with strong quasi-1D confinement. We discuss the implications of these measurements for observing p-wave pairing in quasi-1D.
Language	English
Publishing date	2020-10-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	208853-8
ISSN	1079-7114 ; 0031-9007
ISSN (online)	1079-7114
ISSN	0031-9007
DOI	10.1103/PhysRevLett.125.263402
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Article ; Online: Corrigendum to "Guideline summary review: an evidence-based clinical guideline for the diagnosis and treatment of low back pain" [The Spine Journal 20/7 (2020) p 998-1024].

Kreiner, D Scott / Matz, Paul / Bono, Christopher M / Cho, Charles H / Easa, John E / Ghiselli, Gary / Ghogawala, Zoher / Reitman, Charles A / Resnick, Daniel K / Watters, William C / Annaswamy, Thiru M / Baisden, Jamie / Bartynski, Walter S / Bess, Shay / Brewer, Randall P / Cassidy, R Carter / Cheng, David S / Christie, Sean D / Chutkan, Norman B /

Cohen, Bernard Allan / Dagenais, Simon / Enix, Dennis E / Dougherty, Paul / Golish, S Raymond / Gulur, Padma / Hwang, Steven W / Kilincer, Cumhur / King, Jeffrey A / Lipson, Adam C / Lisi, Anthony J / Meagher, Richard J / O'Toole, John E / Park, Paul / Pekmezci, Murat / Perry, Daniel R / Prasad, Ravi / Provenzano, David A / Radcliff, Kris E / Rahmathulla, Gazanfar / Reinsel, Tom E / Rich, Robert L / Robbins, Daniel S / Rosolowski, Karie A / Sembrano, Jonathan N / Sharma, Anil K / Stout, Alison A / Taleghani, Christopher K / Tauzell, Ryan A / Trammell, Terry / Vorobeychik, Yakov / Yahiro, Amy M

The spine journal : official journal of the North American Spine Society

2021 Volume 21, Issue 4, Page(s) 726–727

Language	English
Publishing date	2021-02-24
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2037072-6
ISSN	1878-1632 ; 1529-9430
ISSN (online)	1878-1632
ISSN	1529-9430
DOI	10.1016/j.spinee.2021.02.006
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