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Article ; Online: Model of retention time and density of gradient peak capacity for improved LC-MS method optimization: Application to metabolomics.

Gritti, Fabrice / David, Mark / Brothy, Patrick / Lewis, Matthew R

2022 Volume 1197, Page(s) 339492

Abstract: A general and deterministic model is derived from the fundamentals of liquid chromatography to calculate retention time, peak width, peak capacity, and density of peak capacity in gradient liquid chromatography. The calculation of these chromatographic ... ...

Abstract	A general and deterministic model is derived from the fundamentals of liquid chromatography to calculate retention time, peak width, peak capacity, and density of peak capacity in gradient liquid chromatography. The calculation of these chromatographic properties accounts for 1) the presence of initial (separation of the earliest eluters) and final (column wash) isocratic steps before and after the linear gradient, respectively, 2) the pre- (flow through needle and preheater tubes) and post-column (outlet and emitter tubes before MS detection) dispersion, 3) the compression of the chromatographic band, and 4) the retention of the organic modifier onto the RPLC column. The multiple and variable method parameters may include the column dimensions, particle size, flow rate, temperature, initial and final isocratic hold times, gradient time, gradient steepness, column conditioning/sample load time, and the pre- and post-column tube dimensions. The model enables the users to perform robust multi-dimensional optimization of UHPLC-MS methods and offers the possibility to predict the expected MS feature density for increased method performance. Method optimization can be further improved by matching the observed MS feature density (number of metabolites detected as function of time) to the predicted density of peak capacity. It is directly applied to the optimization of high-throughput RPLC separation methods specifically designed for large-scale urinary metabolic phenotyping.
MeSH term(s)	Chromatography, Liquid ; Metabolomics ; Particle Size ; Pressure ; Tandem Mass Spectrometry
Language	English
Publishing date	2022-01-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1483436-4
ISSN	1873-4324 ; 0003-2670
ISSN (online)	1873-4324
ISSN	0003-2670
DOI	10.1016/j.aca.2022.339492
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Article ; Online: Mass recalibration for desorption electrospray ionization mass spectrometry imaging using endogenous reference ions.

Inglese, Paolo / Huang, Helen Xuexia / Wu, Vincen / Lewis, Matthew R / Takats, Zoltan

BMC bioinformatics

2022 Volume 23, Issue 1, Page(s) 133

Abstract: Background: Mass spectrometry imaging (MSI) data often consist of tens of thousands of mass spectra collected from a sample surface. During the time necessary to perform a single acquisition, it is likely that uncontrollable factors alter the validity ... ...

Abstract	Background: Mass spectrometry imaging (MSI) data often consist of tens of thousands of mass spectra collected from a sample surface. During the time necessary to perform a single acquisition, it is likely that uncontrollable factors alter the validity of the initial mass calibration of the instrument, resulting in mass errors of magnitude significantly larger than their theoretical values. This phenomenon has a two-fold detrimental effect: (a) it reduces the ability to interpret the results based on the observed signals, (b) it can affect the quality of the observed signal spatial distributions. Results: We present a post-acquisition computational method capable of reducing the observed mass drift by up to 60 ppm in biological samples, exploiting the presence of typical molecules with a known mass-to-charge ratio. The procedure, tested on time-of-flight and Orbitrap mass spectrometry analyzers interfaced to a desorption electrospray ionization (DESI) source, improves the molecular annotation quality and the spatial distributions of the detected ions. Conclusion: The presented method represents a robust and accurate tool for performing post-acquisition mass recalibration of DESI-MSI datasets and can help to increase the reliability of the molecular assignment and the data quality.
MeSH term(s)	Calibration ; Diagnostic Imaging ; Ions ; Reproducibility of Results ; Spectrometry, Mass, Electrospray Ionization/methods
Chemical Substances	Ions
Language	English
Publishing date	2022-04-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2041484-5
ISSN	1471-2105 ; 1471-2105
ISSN (online)	1471-2105
ISSN	1471-2105
DOI	10.1186/s12859-022-04671-5
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Article ; Online: Associations of NAFLD with circulating ceramides and impaired glycemia.

Gadgil, Meghana D / Sarkar, Monika / Sands, Caroline / Lewis, Matthew R / Herrington, David M / Kanaya, Alka M

Diabetes research and clinical practice

2022 Volume 186, Page(s) 109829

Abstract: Aim: Determine the association of circulating ceramides with NAFLD and glycemic impairment.: Methods: Sample: 669 participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort aged 40-84 years without ... ...

Abstract	Aim: Determine the association of circulating ceramides with NAFLD and glycemic impairment. Methods: Sample: 669 participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort aged 40-84 years without cardiovascular disease, cirrhosis, or significant alcohol intake. Clinical measures: Computed tomography scans at baseline for hepatic attenuation. Fasting serum specimens at baseline and after 5 years. Lipidomics: LC-MS-based analysis of 19 known ceramide signals. Statistical analysis: Linear and logistic regression models of log-transformed ceramides, hepatic attenuation and glucose adjusted for age, sex, calories, study site, BMI, exercise, diet quality, alcohol, saturated fat, lipid-lowering medications and fasting glucose. Results: Average age was 55 years, 44% were women, mean BMI was 25.9 kg/m2, and 8% had NAFLD. In adjusted models, Cer(d16:1/20:0) and Cer(d18:1/18:0) were associated with lower mean hepatic attenuation (increased liver fat) (β -4.29; 95% CI [-5.98, -2.59]) and (β -3.40; 95% CI [-5.11, -1.70]), and LacCer(d18:1/16:0) with higher attenuation (β 4.44; 95% CI [2.15, 6.73]). All three ceramides partially mediated the relationship between hepatic attenuation and fasting glucose by 16%, 11% and 5%, respectively, after 5-years. Conclusions: Three circulating ceramides were strongly associated with NAFLD and fasting glucose after 5 years, and partially mediated this association.
MeSH term(s)	Blood Glucose ; Ceramides ; Cohort Studies ; Female ; Humans ; Lipidomics ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease
Chemical Substances	Blood Glucose ; Ceramides
Language	English
Publishing date	2022-03-12
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	632523-3
ISSN	1872-8227 ; 0168-8227
ISSN (online)	1872-8227
ISSN	0168-8227
DOI	10.1016/j.diabres.2022.109829
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Article ; Online: Establishing a framework for best practices for quality assurance and quality control in untargeted metabolomics.

Mosley, Jonathan D / Schock, Tracey B / Beecher, Chris W / Dunn, Warwick B / Kuligowski, Julia / Lewis, Matthew R / Theodoridis, Georgios / Ulmer Holland, Candice Z / Vuckovic, Dajana / Wilson, Ian D / Zanetti, Krista A

Metabolomics : Official journal of the Metabolomic Society

2024 Volume 20, Issue 2, Page(s) 20

Abstract: Background: Quality assurance (QA) and quality control (QC) practices are key tenets that facilitate study and data quality across all applications of untargeted metabolomics. These important practices will strengthen this field and accelerate its ... ...

Abstract	Background: Quality assurance (QA) and quality control (QC) practices are key tenets that facilitate study and data quality across all applications of untargeted metabolomics. These important practices will strengthen this field and accelerate its success. The Best Practices Working Group (WG) within the Metabolomics Quality Assurance and Quality Control Consortium (mQACC) focuses on community use of QA/QC practices and protocols and aims to identify, catalogue, harmonize, and disseminate current best practices in untargeted metabolomics through community-driven activities. Aim of review: A present goal of the Best Practices WG is to develop a working strategy, or roadmap, that guides the actions of practitioners and progress in the field. The framework in which mQACC operates promotes the harmonization and dissemination of current best QA/QC practice guidance and encourages widespread adoption of these essential QA/QC activities for liquid chromatography-mass spectrometry. Key scientific concepts of review: Community engagement and QA/QC information gathering activities have been occurring through conference workshops, virtual and in-person interactive forum discussions, and community surveys. Seven principal QC stages prioritized by internal discussions of the Best Practices WG have received participant input, feedback and discussion. We outline these stages, each involving a multitude of activities, as the framework for identifying QA/QC best practices. The ultimate planned product of these endeavors is a "living guidance" document of current QA/QC best practices for untargeted metabolomics that will grow and change with the evolution of the field.
MeSH term(s)	Humans ; Metabolomics/methods ; Quality Control ; Surveys and Questionnaires ; Data Accuracy
Language	English
Publishing date	2024-02-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2250617-2
ISSN	1573-3890 ; 1573-3882
ISSN (online)	1573-3890
ISSN	1573-3882
DOI	10.1007/s11306-023-02080-0
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Article: Genetic Evidence of Introduced Redeye Bass and Alabama Bass and Hybridization with Native Micropterus spp. in Town Creek, Alabama, USA

Lewis, Matthew R. / Ekema, Phil / Holley, Mike / Peatman, Eric J.

North American journal of fisheries management. 2021 Feb., v. 41, no. 1

2021

Abstract: The black basses Micropterus spp. are among the most important game fishes in the United States. Translocation by both anglers and state agencies for increased angling opportunity has led to widespread hybridization between native and nonnative species. ... ...

Abstract	The black basses Micropterus spp. are among the most important game fishes in the United States. Translocation by both anglers and state agencies for increased angling opportunity has led to widespread hybridization between native and nonnative species. The use of species‐diagnostic single‐nucleotide polymorphism (SNP) markers for black basses has allowed for rapid assessment of species identification and hybridization in rivers and streams. Here, we report genetic evidence for the presence of Redeye Bass M. coosae and Alabama Bass M. henshalli outside of their native range and their hybridization with native species of black bass in Town Creek, a tributary of the Tennessee River. To determine which black bass species were present in the creek, four sites were sampled using both angling and backpack electrofishing. Sampled DNA from fin clips was analyzed using a diagnostic SNP panel. Genetic results confirmed that Redeye Bass and Alabama Bass were present as nonnative congeners in the creek. Interestingly, no pure individual Smallmouth Bass M. dolomieu or Spotted Bass M. punctulatus were found, although both species are native to the stream. Phenotypic identification followed by genotypic classification revealed that 62% of the fish collected for this study were misidentified in the field, with 100% of those being hybrids, indicating the importance of genetic assessment in conjunction with classic morphometrics for the management of black basses. Further studies are needed to determine whether seasonality plays a role in species presence and abundance and whether population profiles identified here are observed more broadly within the Tennessee River system.
Keywords	DNA ; Micropterus coosae ; Micropterus dolomieu ; administrative management ; bass ; hybridization ; indigenous species ; introduced species ; morphometry ; phenotype ; rapid methods ; single nucleotide polymorphism ; species identification ; streams ; Alabama ; Tennessee River
Language	English
Dates of publication	2021-02
Size	p. 78-85.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	779391-1
ISSN	0275-5947
ISSN	0275-5947
DOI	10.1002/nafm.10531
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Article: Failure of Phenotypic Markers to Accurately Identify Black Bass Species and Associated Hybrids in the Mobile River Basin, Alabama

Lewis, Matthew R. / Silliman, Katherine E. / Beck, Benjamin / Sammons, Steven M. / Peatman, Eric J.

North American journal of fisheries management. 2021 Oct., v. 41, no. 5

2021

Abstract: Hybridization among the black basses Micropterus spp. occurs due to weak postzygotic reproductive barriers and anthropogenic factors, such as habitat alteration. Introduction of previously allopatric species can also result in hybrid swarms and, in some ... ...

Abstract	Hybridization among the black basses Micropterus spp. occurs due to weak postzygotic reproductive barriers and anthropogenic factors, such as habitat alteration. Introduction of previously allopatric species can also result in hybrid swarms and, in some cases, extirpation of native species. Introgressive hybridization is a major conservation concern for the more range‐restricted black basses, which underscores the need for accurate identification of hybrids that often have cryptic phenotypes. To that end, we collected 1,723 fish from four river systems in the Mobile River basin, Alabama, to compare phenotypic identification in the field based on morphology with genotype determined from single‐nucleotide polymorphism analysis using diagnostic markers for black basses. Results indicated that phenotypic identification among these cryptic hybrids was only 11% accurate. Only 4% of the fish collected were identified as hybrids in the field, whereas genotype analysis classified 22% of the fish as hybrids. The majority of those misidentified in the field were hybrids between Alabama Bass M. henshalli and Redeye Bass M. coosae or between those species and another black bass species. Hybrid individuals composed 5–38% of the total number of fish collected from the four river systems, but 28–68% were misidentified in each river system. These results underscore the need for genetic tools to augment classic field surveys of the black basses, as cryptic hybridization may lead to errant management decisions based on inaccurate species distribution assessments.
Keywords	Micropterus coosae ; administrative management ; allopatry ; bass ; genotype ; geographical distribution ; habitat destruction ; hybrids ; indigenous species ; introgression ; phenotype ; rivers ; single nucleotide polymorphism ; watersheds ; Alabama
Language	English
Dates of publication	2021-10
Size	p. 1591-1601.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	779391-1
ISSN	0275-5947
ISSN	0275-5947
DOI	10.1002/nafm.10673
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: NMRpQuant: an automated software for large scale urinary total protein quantification by one-dimensional 1H NMR profiles.

Takis, Panteleimon G / Vuckovic, Ivan / Tan, Tricia / Denic, Aleksandar / Lieske, John C / Lewis, Matthew R / Macura, Slobodan

Bioinformatics (Oxford, England)

2022 Volume 38, Issue 18, Page(s) 4437–4439

Abstract: Summary: 1H nuclear magnetic resonance (NMR) spectroscopy is an established bioanalytical technology for metabolic profiling of biofluids in both clinical and large-scale population screening applications. Recently, urinary protein quantification has ... ...

Abstract	Summary: 1H nuclear magnetic resonance (NMR) spectroscopy is an established bioanalytical technology for metabolic profiling of biofluids in both clinical and large-scale population screening applications. Recently, urinary protein quantification has been demonstrated using the same 1D 1H NMR experimental data captured for metabolic profiling. Here, we introduce NMRpQuant, a freely available platform that builds on these findings with both novel and further optimized computational NMR approaches for rigorous, automated protein urine quantification. The results are validated by interlaboratory comparisons, demonstrating agreement with clinical/biochemical methodologies, pointing at a ready-to-use tool for routine protein urinalyses. Availability and implementation: NMRpQuant was developed on MATLAB programming environment. Source code and Windows/macOS compiled applications are available at https://github.com/pantakis/NMRpQuant, and working examples are available at https://doi.org/10.6084/m9.figshare.18737189.v1. Supplementary information: Supplementary data are available at Bioinformatics online.
MeSH term(s)	Proton Magnetic Resonance Spectroscopy ; Software ; Magnetic Resonance Spectroscopy/methods ; Magnetic Resonance Imaging ; Metabolomics/methods
Language	English
Publishing date	2022-08-09
Publishing country	England
Document type	Journal Article
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btac502
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Article ; Online: The impact of bariatric surgery on serum tryptophan-kynurenine pathway metabolites.

Yeung, Kai Tai Derek / Penney, Nicholas / Whiley, Luke / Ashrafian, Hutan / Lewis, Matthew R / Purkayastha, Sanjay / Darzi, Ara / Holmes, Elaine

Scientific reports

2022 Volume 12, Issue 1, Page(s) 294

Abstract: This study aims to explore the immediate effects of bariatric surgery on serum tryptophan-kynurenine pathway metabolites in individuals with type 2 diabetes and BMI > 30. With the goal of providing insight into the link between tryptophan pathway ... ...

Abstract	This study aims to explore the immediate effects of bariatric surgery on serum tryptophan-kynurenine pathway metabolites in individuals with type 2 diabetes and BMI > 30. With the goal of providing insight into the link between tryptophan pathway metabolites, type 2 diabetes, and chronic obesity-induced inflammation. This longitudinal study included 20 participants. Half were diagnosed with type 2 diabetes. 11 and 9 underwent RYGB and SG respectively. Blood samples were obtained at pre-operative and 3 months post-operative timepoints. Tryptophan and downstream metabolites of the kynurenine pathway were quantified with an ultrahigh-performance liquid chromatography tandem mass spectrometry with electrospray ionisation method. At 3 months post-operation, RYGB led to significant reductions in tryptophan, kynurenic acid and xanthurenic acid levels when compared to baseline. Significant reductions of the same metabolites after surgery were also observed in individuals with T2D irrespective of surgical procedure. These metabolites were significantly correlated with serum HbA1c levels and BMI. Bariatric surgery, in particular RYGB reduces serum levels of tryptophan and its downstream kynurenine metabolites. These metabolites are associated with T2D and thought to be potentially mechanistic in the systemic processes of obesity induced inflammation leading to insulin resistance. Its reduction after surgery is associated with an improvement in glycaemic control (HbA1c).
MeSH term(s)	Adult ; Biomarkers/blood ; Body Mass Index ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/diagnosis ; Female ; Gastrectomy ; Gastric Bypass ; Glycated Hemoglobin A/metabolism ; Humans ; Kynurenine/blood ; Longitudinal Studies ; Male ; Middle Aged ; Obesity/blood ; Obesity/diagnosis ; Obesity/surgery ; Prospective Studies ; Time Factors ; Treatment Outcome ; Tryptophan/blood ; Xanthurenates/blood
Chemical Substances	Biomarkers ; Glycated Hemoglobin A ; Xanthurenates ; hemoglobin A1c protein, human ; Kynurenine (343-65-7) ; xanthurenic acid (58LAB1BG8J) ; Tryptophan (8DUH1N11BX)
Language	English
Publishing date	2022-01-07
Publishing country	England
Document type	Comparative Study ; 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/s41598-021-03833-4
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Article ; Online: Metabolomic profiling in small vessel disease identifies multiple associations with disease severity.

Harshfield, Eric L / Sands, Caroline J / Tuladhar, Anil M / de Leeuw, Frank Erik / Lewis, Matthew R / Markus, Hugh S

Brain : a journal of neurology

2022 Volume 145, Issue 7, Page(s) 2461–2471

Abstract: Cerebral small vessel disease is a major cause of vascular cognitive impairment and dementia. There are few treatments, largely reflecting limited understanding of the underlying pathophysiology. Metabolomics can be used to identify novel risk factors to ...

Abstract	Cerebral small vessel disease is a major cause of vascular cognitive impairment and dementia. There are few treatments, largely reflecting limited understanding of the underlying pathophysiology. Metabolomics can be used to identify novel risk factors to better understand pathogenesis and to predict disease progression and severity. We analysed data from 624 patients with symptomatic cerebral small vessel disease from two prospective cohort studies. Serum samples were collected at baseline and patients underwent MRI scans and cognitive testing at regular intervals with up to 14 years of follow-up. Using ultra-performance liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy, we obtained metabolic and lipidomic profiles from 369 annotated metabolites and 54 764 unannotated features and examined their association with respect to disease severity, assessed using MRI small vessel disease markers, cognition and future risk of all-cause dementia. Our analysis identified 28 metabolites that were significantly associated with small vessel disease imaging markers and cognition. Decreased levels of multiple glycerophospholipids and sphingolipids were associated with increased small vessel disease load as evidenced by higher white matter hyperintensity volume, lower mean diffusivity normalized peak height, greater brain atrophy and impaired cognition. Higher levels of creatine, FA(18:2(OH)) and SM(d18:2/24:1) were associated with increased lacune count, higher white matter hyperintensity volume and impaired cognition. Lower baseline levels of carnitines and creatinine were associated with higher annualized change in peak width of skeletonized mean diffusivity, and 25 metabolites, including lipoprotein subclasses, amino acids and xenobiotics, were associated with future dementia incidence. Our results show multiple distinct metabolic signatures that are associated with imaging markers of small vessel disease, cognition and conversion to dementia. Further research should assess causality and the use of metabolomic screening to improve the ability to predict future disease severity and dementia risk in small vessel disease. The metabolomic profiles may also provide novel insights into disease pathogenesis and help identify novel treatment approaches.
MeSH term(s)	Cerebral Small Vessel Diseases/complications ; Dementia/complications ; Humans ; Leukoaraiosis ; Magnetic Resonance Imaging/methods ; Prospective Studies ; Severity of Illness Index
Language	English
Publishing date	2022-03-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awac041
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Article ; Online: Diet Patterns Are Associated with Circulating Metabolites and Lipid Profiles of South Asians in the United States.

Gadgil, Meghana D / Kanaya, Alka M / Sands, Caroline / Chekmeneva, Elena / Lewis, Matthew R / Kandula, Namratha R / Herrington, David M

The Journal of nutrition

2022 Volume 152, Issue 11, Page(s) 2358–2366

Abstract: Background: South Asians are at higher risk for cardiometabolic disease than many other racial/ethnic minority groups. Diet patterns in US South Asians have unique components associated with cardiometabolic disease.: Objectives: We aimed to ... ...

Abstract	Background: South Asians are at higher risk for cardiometabolic disease than many other racial/ethnic minority groups. Diet patterns in US South Asians have unique components associated with cardiometabolic disease. Objectives: We aimed to characterize the metabolites associated with 3 representative diet patterns. Methods: We included 722 participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort study aged 40-84 y without known cardiovascular disease. Fasting serum specimens and diet and demographic questionnaires were collected at baseline and diet patterns previously generated through principal components analysis. LC-MS-based untargeted metabolomic and lipidomic analysis was conducted with targeted integration of known metabolite and lipid signals. Linear regression models of diet pattern factor score and log-transformed metabolites adjusted for age, sex, caloric intake, and BMI and adjusted for multiple comparisons were performed, followed by elastic net linear regression of significant metabolites. Results: There were 443 metabolites of known identity extracted from the profiling data. The "animal protein" diet pattern was associated with 61 metabolites and lipids, including glycerophospholipids phosphatidylethanolamine PE(O-16:1/20:4) and/or PE(P-16:0/20:4) (β: 0.13; 95% CI: 0.11, 0.14) and N-acyl phosphatidylethanolamines (NAPEs) NAPE(O-18:1/20:4/18:0) and/or NAPE(P-18:0/20:4/18:0) (β: 0.13; 95% CI: 0.11, 0.14), lysophosphatidylinositol (LPI) (22:6/0:0) (β: 0.14; 95% CI: 0.12, 0.17), and fatty acid (FA) (22:6) (β: 0.15; 95% CI: 0.13, 0.17). The "fried snacks, sweets, high-fat dairy" pattern was associated with 12 lipids, including PC(16:0/22:6) (β: -0.08; 95% CI: -0.09, -0.06) and FA (22:6) (β: 0.14; 95% CI: -0.17, -0.10). The "fruits, vegetables, nuts, and legumes" pattern was associated with 5 metabolites including proline betaine (β: 0.17; 95% CI: 0.09, 0.25) (P < 0.0002). Conclusions: Three predominant dietary patterns in US South Asians are associated with circulating metabolites differentiated by lipids including glycerophospholipids and PUFAs and the amino acid proline betaine.
MeSH term(s)	Humans ; United States ; Ethnicity ; Cohort Studies ; South Asian People ; Minority Groups ; Diet ; Cardiovascular Diseases ; Vegetables ; Lipids
Chemical Substances	Lipids
Language	English
Publishing date	2022-08-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	218373-0
ISSN	1541-6100 ; 0022-3166
ISSN (online)	1541-6100
ISSN	0022-3166
DOI	10.1093/jn/nxac191
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