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Article ; Online: Feasibility of the pitch efficiency rating: A novel tool for systematic assessment of pitching mechanics in developing throwing athletes.

Kenyon, Charles / Beebe, Alex / Easley, Kirk / Jayanthi, Neeru / Bowers, Robert

PM & R : the journal of injury, function, and rehabilitation

2024 Volume 16, Issue 4, Page(s) 339–346

Abstract: Background: Injuries in younger baseball athletes continue to increase despite work characterizing risk factors. Three-dimensional (3D) motion capture may identify suboptimal pitching mechanics that predispose an athlete to injury, but 3D-motion ... ...

Abstract	Background: Injuries in younger baseball athletes continue to increase despite work characterizing risk factors. Three-dimensional (3D) motion capture may identify suboptimal pitching mechanics that predispose an athlete to injury, but 3D-motion analysis is often inaccessible. Thus, there is a gap between the current biomechanics literature and its practical application in young athletes. The current study aims to assess the reliability of the pitch efficiency rating (PER) as a systematic tool to evaluate throwing mechanics in developing baseball pitchers. Objective: To determine the feasibility of application and reliability of a novel, scientifically informed tool (PER) for the assessment of pitching mechanics. Design: Reliability study using Bland-Altman methods for assessing agreement between two raters. Setting: Academic medical center through community outreach. Participants: Pitching mechanics were assessed and rated with the PER for 40 athletes (26 high school, 14 Division III), average age 19.0 years old (range 15.3-23.7 years old). Interventions: N/A. Main outcome measures: Interrater and intrarater reliability as calculated by intraclass correlation coefficient (ICC). Results: For initial readings comparing interrater reliability between Rater 1 and Rater 2, the ICC was calculated at 0.80 (95% confidence interval [CI] 0.66-0.89) and 0.76 (95% CI 0.60-0.86) for the second set of ratings. Regarding intrarater reliability across reads, ICC was found to be 0.63 (95% CI 0.43-0.79) for Rater 1, and 0.91 for Rater 2 (95% CI 0.85-0.95). Conclusions: The present study introduces the PER as a potential tool for evaluating pitching mechanics. However, the intrarater reliability of the PER did not meet preestablished criteria in one of the two pilot raters. Further study is needed to continue to assess the reliability of the tool across diverse demographics.
MeSH term(s)	Humans ; Adolescent ; Young Adult ; Adult ; Reproducibility of Results ; Feasibility Studies ; Risk Factors ; Baseball ; Biomechanical Phenomena
Language	English
Publishing date	2024-03-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2608988-9
ISSN	1934-1563 ; 1934-1482
ISSN (online)	1934-1563
ISSN	1934-1482
DOI	10.1002/pmrj.13178
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Article: Comparing the Driving Skills of Adolescents with Obstructive Sleep Apnea to Healthy Controls: The Results of a Case-Controlled Observational Study.

Fidler, Andrea L / Zhang, Nanhua / Simakajornboon, Narong / Epstein, Jeffery N / Kirk, Shelley / Beebe, Dean W

Children (Basel, Switzerland)

2023 Volume 10, Issue 10

Abstract: Auto crashes are a leading cause of death and injury among adolescents. Untreated obstructive sleep apnea (OSA) can cause sleepiness and inattention, which could negatively impact novice drivers, but OSA-related studies have focused on older drivers. ... ...

Abstract	Auto crashes are a leading cause of death and injury among adolescents. Untreated obstructive sleep apnea (OSA) can cause sleepiness and inattention, which could negatively impact novice drivers, but OSA-related studies have focused on older drivers. This study used a driving simulator to examine whether licensed 16-19-year-old adolescents with OSA have diminished driving skills. Twenty-one adolescents with OSA and twenty-eight without OSA (both confirmed using polysomnography) completed two randomly ordered driving trials in a simulator (with induced distractions versus without). A mixed ANOVA examined the between-subjects effect of the OSA group, the within-subjects effect of the distraction condition, and the group-by-condition interaction effect on the ability to maintain lane position and the frequency of extended eye glances away from the roadway. T-tests were also used to examine group differences in reported sleepiness and inattention during daily life. The distraction task increased extended off-road glances and difficulties maintaining lane position (
Language	English
Publishing date	2023-09-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2732685-8
ISSN	2227-9067
ISSN	2227-9067
DOI	10.3390/children10101624
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Sharpening Precision Medicine by a Thorough Interrogation of Metabolic Individuality.

Beebe, Kirk / Kennedy, Adam D

Computational and structural biotechnology journal

2016 Volume 14, Page(s) 97–105

Abstract: Precision medicine is an active component of medical practice today, but aspirations are to both broaden its reach to a greater diversity of individuals and improve its "precision" by enhancing the ability to define even more disease states in ... ...

Abstract	Precision medicine is an active component of medical practice today, but aspirations are to both broaden its reach to a greater diversity of individuals and improve its "precision" by enhancing the ability to define even more disease states in combination with associated treatments. Given complexity of human phenotypes, much work is required. In this review, we deconstruct this challenge at a high level to define what is needed to move closer toward these aspirations. In the context of the variables that influence the diverse array of phenotypes across human health and disease - genetics, epigenetics, environmental influences, and the microbiome - we detail the factors behind why an individual's biochemical (metabolite) composition is increasingly regarded as a key element to precisely defining phenotypes. Although an individual's biochemical (metabolite) composition is generally regarded, and frequently shown, to be a surrogate to the phenotypic state, we review how metabolites (and therefore an individual's metabolic profile) are also functionally related to the myriad of phenotypic influencers like genetics and the microbiota. We describe how using the technology to comprehensively measure an individual's biochemical profile - metabolomics - is integrative to defining individual phenotypes and how it is currently being deployed in efforts to continue to elaborate on human health and disease in large population studies. Finally, we summarize instances where metabolomics is being used to assess individual health in instances where signatures (i.e. biomarkers) have been defined.
Language	English
Publishing date	2016-01-21
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2016.01.001
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Quantitative Analysis of The High-Yield Hydrolysis of Kelp by Laminarinase and Alginate Lyase.

Takasuka, Taichi E / Kim, Hoon / Deng, Kai / Bianchetti, Christopher M / Yamashita, Kaho / Beebe, Emily T / Bergeman, Lai F / Vander Meulen, Kirk A / Deutsch, Samuel / Ralph, John / Adams, Paul D / Northen, Trent R / Fox, Brian G

Chembiochem : a European journal of chemical biology

2023 Volume 24, Issue 20, Page(s) e202300357

Abstract: Kelp is an abundant, farmable biomass-containing laminarin and alginate as major polysaccharides, providing an excellent model substrate to study their deconstruction by simple enzyme mixtures. Our previous study showed strong reactivity of the glycoside ...

Abstract	Kelp is an abundant, farmable biomass-containing laminarin and alginate as major polysaccharides, providing an excellent model substrate to study their deconstruction by simple enzyme mixtures. Our previous study showed strong reactivity of the glycoside hydrolase family 55 during hydrolysis of purified laminarin, raising the question of its reactivity with intact kelp. In this study, we determined that a combination of a single glycoside hydrolase family 55 β-1,3-exoglucanase with a broad-specificity alginate lyase from the polysaccharide lyase family 18 gives efficient hydrolysis of untreated kelp to a mixture of simple sugars, that is, glucose, gentiobiose, mannitol-end glucose, and mannuronic and guluronic acids and their soluble oligomers. Quantitative assignments from nanostructure initiator mass spectrometry (NIMS) and 2D HSQC NMR spectroscopy and analysis of the reaction time-course are provided. The data suggest that binary combinations of enzymes targeted to the unique polysaccharide composition of marine biomass are sufficient to deconstruct kelp into soluble sugars for microbial fermentation.
MeSH term(s)	Kelp/metabolism ; Cellulases ; Hydrolysis ; Polysaccharide-Lyases/metabolism ; Polysaccharides ; Glucose ; Glycoside Hydrolases/metabolism ; Substrate Specificity
Chemical Substances	poly(beta-D-mannuronate) lyase (EC 4.2.2.3) ; Cellulases (EC 3.2.1.-) ; Polysaccharide-Lyases (EC 4.2.2.-) ; Polysaccharides ; Glucose (IY9XDZ35W2) ; Glycoside Hydrolases (EC 3.2.1.-)
Language	English
Publishing date	2023-08-28
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2020469-3
ISSN	1439-7633 ; 1439-4227
ISSN (online)	1439-7633
ISSN	1439-4227
DOI	10.1002/cbic.202300357
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Article: Sharpening Precision Medicine by a Thorough Interrogation of Metabolic Individuality

Beebe, Kirk / Adam D. Kennedy

Computational and Structural Biotechnology Journal. 2016, v. 14

2016

Abstract: Precision medicine is an active component of medical practice today, but aspirations are to both broaden its reach to a greater diversity of individuals and improve its “precision” by enhancing the ability to define even more disease states in ... ...

Abstract	Precision medicine is an active component of medical practice today, but aspirations are to both broaden its reach to a greater diversity of individuals and improve its “precision” by enhancing the ability to define even more disease states in combination with associated treatments. Given complexity of human phenotypes, much work is required. In this review, we deconstruct this challenge at a high level to define what is needed to move closer toward these aspirations. In the context of the variables that influence the diverse array of phenotypes across human health and disease – genetics, epigenetics, environmental influences, and the microbiome – we detail the factors behind why an individual's biochemical (metabolite) composition is increasingly regarded as a key element to precisely defining phenotypes. Although an individual's biochemical (metabolite) composition is generally regarded, and frequently shown, to be a surrogate to the phenotypic state, we review how metabolites (and therefore an individual's metabolic profile) are also functionally related to the myriad of phenotypic influencers like genetics and the microbiota. We describe how using the technology to comprehensively measure an individual's biochemical profile – metabolomics – is integrative to defining individual phenotypes and how it is currently being deployed in efforts to continue to elaborate on human health and disease in large population studies. Finally, we summarize instances where metabolomics is being used to assess individual health in instances where signatures (i.e. biomarkers) have been defined.
Keywords	biomarkers ; biotechnology ; epigenetics ; human health ; humans ; medicine ; metabolites ; metabolomics ; microbiome ; microorganisms ; phenotype
Language	English
Size	p. 97-105.
Publishing place	Elsevier B.V.
Document type	Article
ISSN	2001-0370
DOI	10.1016/j.csbj.2016.01.001
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Sharpening Precision Medicine by a Thorough Interrogation of Metabolic Individuality

Kirk Beebe / Adam D. Kennedy

Computational and Structural Biotechnology Journal, Vol 14, Iss C, Pp 97-

2016 Volume 105

Abstract: Precision medicine is an active component of medical practice today, but aspirations are to both broaden its reach to a greater diversity of individuals and improve its “precision” by enhancing the ability to define even more disease states in ... ...

Abstract	Precision medicine is an active component of medical practice today, but aspirations are to both broaden its reach to a greater diversity of individuals and improve its “precision” by enhancing the ability to define even more disease states in combination with associated treatments. Given complexity of human phenotypes, much work is required. In this review, we deconstruct this challenge at a high level to define what is needed to move closer toward these aspirations. In the context of the variables that influence the diverse array of phenotypes across human health and disease – genetics, epigenetics, environmental influences, and the microbiome – we detail the factors behind why an individual's biochemical (metabolite) composition is increasingly regarded as a key element to precisely defining phenotypes. Although an individual's biochemical (metabolite) composition is generally regarded, and frequently shown, to be a surrogate to the phenotypic state, we review how metabolites (and therefore an individual's metabolic profile) are also functionally related to the myriad of phenotypic influencers like genetics and the microbiota. We describe how using the technology to comprehensively measure an individual's biochemical profile – metabolomics – is integrative to defining individual phenotypes and how it is currently being deployed in efforts to continue to elaborate on human health and disease in large population studies. Finally, we summarize instances where metabolomics is being used to assess individual health in instances where signatures (i.e. biomarkers) have been defined.
Keywords	Precision Medicine ; Metabolomics ; Inborn Errors of Metabolism ; Mass Spectrometry ; Genome Wide Association Study ; Untargeted Analysis ; Diagnostics ; Technology ; T ; Chemical technology ; TP1-1185 ; Biotechnology ; TP248.13-248.65
Subject code	006
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Association of Antifolate Response Signature Status and Clinical Activity of Pemetrexed-Platinum Chemotherapy in Non-Small Cell Lung Cancer: The Piedmont Study.

Eisner, Joel R / Mayhew, Gregory M / Davison, James M / Beebe, Kirk D / Shibata, Yoichiro / Guo, Yuelong / Farhangfar, Carol / Farhangfar, Farhang / Uronis, Joshua M / Conroy, Jeffrey M / Milburn, Michael V / Hayes, David Neil / Mileham, Kathryn F

Clinical cancer research : an official journal of the American Association for Cancer Research

2023 Volume 29, Issue 16, Page(s) 3203–3213

Abstract: Purpose: The Piedmont study is a prospectively designed retrospective evaluation of a new 48-gene antifolate response signature (AF-PRS) in patients with locally advanced/metastatic nonsquamous (NS) non-small cell lung cancer (NSCLC) treated with ... ...

Abstract	Purpose: The Piedmont study is a prospectively designed retrospective evaluation of a new 48-gene antifolate response signature (AF-PRS) in patients with locally advanced/metastatic nonsquamous (NS) non-small cell lung cancer (NSCLC) treated with pemetrexed-containing platinum doublet chemotherapy (PMX-PDC). The study tested the hypothesis that AF-PRS identifies patients with NS-NSCLC who have a higher likelihood of responding positively to PMX-PDC. The goal was to gather clinical evidence supporting AF-PRS as a potential diagnostic test. Experimental design: Residual pretreatment FFPE tumor samples and clinical data were analyzed from 105 patients treated with first-line (1L) PMX-PDC. Ninety-five patients had sufficient RNA sequencing (RNA-seq) data quality and clinical annotation for inclusion in the analysis. Associations between AF-PRS status and associate genes and outcome measures including progression-free survival (PFS) and clinical response were evaluated. Results: Overall, 53% of patients were AF-PRS(+), which was associated with extended PFS, but not overall survival, versus AF-PRS(-) (16.6 months vs. 6.6 months; P = 0.025). In patients who were stage I to III patients at the time of treatment, PFS was further extended in AF-PRS(+) versus AF-PRS(-) (36.2 months vs. 9.3 months; P = 0.03). Complete response (CR) to therapy was noted in 14 of 95 patients. AF-PRS(+) preferentially selected a majority (79%) of CRs, which were evenly split between patients stage I to III (six of seven) and stage IV (five of seven) at the time of treatment. Conclusions: AF-PRS identified a significant population of patients with extended PFS and/or clinical response following PMX-PDC treatment. AF-PRS may be a useful diagnostic test for patients indicated for systemic chemotherapy, especially when determining the optimal PDC regimen for locally advanced disease.
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/pathology ; Pemetrexed ; Platinum/therapeutic use ; Folic Acid Antagonists/therapeutic use ; Lung Neoplasms/diagnosis ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/adverse effects
Chemical Substances	Pemetrexed (04Q9AIZ7NO) ; Platinum (49DFR088MY) ; Folic Acid Antagonists
Language	English
Publishing date	2023-05-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-22-2558
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Article ; Online: Distinct Predictive Immunogenomic Profiles of Response to Immune Checkpoint Inhibitors and IL2: A Real-world Evidence Study of Patients with Advanced Renal Cancer.

Eisner, Joel R / Beebe, Kirk D / Mayhew, Gregory M / Shibata, Yoichiro / Guo, Yuelong / Farhangfar, Carol / Farhangfar, Farhang / Uronis, Joshua M / Mooney, Jill / Milburn, Michael V / Foureau, David / White, Richard L / Amin, Asim / Milla, Marcos E

Cancer research communications

2022 Volume 2, Issue 8, Page(s) 894–903

Abstract: Recombinant human high-dose IL2 (HD-IL2; aldesleukin) was one of the first approved immune-oncology agents based upon clinical activity in renal cell carcinoma (RCC) and metastatic melanoma but use was limited due to severe toxicity. Next-generation IL2 ... ...

Abstract	Recombinant human high-dose IL2 (HD-IL2; aldesleukin) was one of the first approved immune-oncology agents based upon clinical activity in renal cell carcinoma (RCC) and metastatic melanoma but use was limited due to severe toxicity. Next-generation IL2 agents designed to improve tolerability are in development, increasing the need for future identification of genomic markers of clinical benefit and/or clinical response. In this retrospective study, we report clinical and tumor molecular profiling from patients with metastatic RCC (mRCC) treated with HD-IL2 and compare findings with patients with RCC treated with anti-PD-1 therapy. Genomic characteristics common and unique to IL2 and/or anti-PD-1 therapy response are presented, with insight into rational combination strategies for these agents. Residual pretreatment formalin-fixed paraffin embedded tumor samples from Significance: Next-generation IL2 agents, designed for improved tolerability over traditional HD-IL2 (aldesleukin), are in clinical development. Retrospective molecular tumor profiling of patients treated with HD-IL2 or anti-PD-1 therapy provides insights into genomic characteristics of therapy response. This study revealed common and distinct immune-related predictive response markers for IL2 and anti-PD-1 therapy which may play a role in therapy guidance, and rational combination strategies for these agents.
MeSH term(s)	Humans ; Carcinoma, Renal Cell/drug therapy ; Immune Checkpoint Inhibitors/pharmacology ; Immune Checkpoint Inhibitors/therapeutic use ; Interleukin-2/genetics ; Kidney Neoplasms/drug therapy ; Retrospective Studies
Chemical Substances	Immune Checkpoint Inhibitors ; Interleukin-2
Language	English
Publishing date	2022-08-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2767-9764
ISSN (online)	2767-9764
DOI	10.1158/2767-9764.CRC-21-0153
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Article ; Online: Identification and characterization of a set of monocot BAHD monolignol transferases.

Smith, Rebecca A / Beebe, Emily T / Bingman, Craig A / Vander Meulen, Kirk / Eugene, Alexis / Steiner, Alexander J / Karlen, Steven D / Ralph, John / Fox, Brian G

Plant physiology

2022 Volume 189, Issue 1, Page(s) 37–48

Abstract: Plant BAHD acyltransferases perform a wide range of enzymatic tasks in primary and secondary metabolism. Acyl-CoA monolignol transferases, which couple a CoA substrate to a monolignol creating an ester linkage, represent a more recent class of such ... ...

Abstract	Plant BAHD acyltransferases perform a wide range of enzymatic tasks in primary and secondary metabolism. Acyl-CoA monolignol transferases, which couple a CoA substrate to a monolignol creating an ester linkage, represent a more recent class of such acyltransferases. The resulting conjugates may be used for plant defense but are also deployed as important "monomers" for lignification, in which they are incorporated into the growing lignin polymer chain. p-Coumaroyl-CoA monolignol transferases (PMTs) increase the production of monolignol p-coumarates, and feruloyl-CoA monolignol transferases (FMTs) catalyze the production of monolignol ferulate conjugates. We identified putative FMT and PMT enzymes in sorghum (Sorghum bicolor) and switchgrass (Panicum virgatum) and have compared their activities to those of known monolignol transferases. The putative FMT enzymes produced both monolignol ferulate and monolignol p-coumarate conjugates, whereas the putative PMT enzymes produced monolignol p-coumarate conjugates. Enzyme activity measurements revealed that the putative FMT enzymes are not as efficient as the rice (Oryza sativa) control OsFMT enzyme under the conditions tested, but the SbPMT enzyme is as active as the control OsPMT enzyme. These putative FMTs and PMTs were transformed into Arabidopsis (Arabidopsis thaliana) to test their activities and abilities to biosynthesize monolignol conjugates for lignification in planta. The presence of ferulates and p-coumarates on the lignin of these transformants indicated that the putative FMTs and PMTs act as functional feruloyl-CoA and p-coumaroyl-CoA monolignol transferases within plants.
MeSH term(s)	Acyltransferases/genetics ; Acyltransferases/metabolism ; Arabidopsis/genetics ; Arabidopsis/metabolism ; Lignin/metabolism ; Oryza/metabolism ; Panicum/metabolism ; Sorghum/genetics ; Sorghum/metabolism ; Transferases
Chemical Substances	Lignin (9005-53-2) ; Transferases (EC 2.-) ; Acyltransferases (EC 2.3.-)
Language	English
Publishing date	2022-02-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	208914-2
ISSN	1532-2548 ; 0032-0889
ISSN (online)	1532-2548
ISSN	0032-0889
DOI	10.1093/plphys/kiac035
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Article ; Online: pHBMT1, a BAHD-family monolignol acyltransferase, mediates lignin acylation in poplar.

de Vries, Lisanne / MacKay, Heather A / Smith, Rebecca A / Mottiar, Yaseen / Karlen, Steven D / Unda, Faride / Muirragui, Emilia / Bingman, Craig / Vander Meulen, Kirk / Beebe, Emily T / Fox, Brian G / Ralph, John / Mansfield, Shawn D

Plant physiology

2021 Volume 188, Issue 2, Page(s) 1014–1027

Abstract: Poplar (Populus) lignin is naturally acylated with p-hydroxybenzoate ester moieties. However, the enzyme(s) involved in the biosynthesis of the monolignol-p-hydroxybenzoates have remained largely unknown. Here, we performed an in vitro screen of the ... ...

Abstract	Poplar (Populus) lignin is naturally acylated with p-hydroxybenzoate ester moieties. However, the enzyme(s) involved in the biosynthesis of the monolignol-p-hydroxybenzoates have remained largely unknown. Here, we performed an in vitro screen of the Populus trichocarpa BAHD acyltransferase superfamily (116 genes) using a wheatgerm cell-free translation system and found five enzymes capable of producing monolignol-p-hydroxybenzoates. We then compared the transcript abundance of the five corresponding genes with p-hydroxybenzoate concentrations using naturally occurring unrelated genotypes of P. trichocarpa and revealed a positive correlation between the expression of p-hydroxybenzoyl-CoA monolig-nol transferase (pHBMT1, Potri.001G448000) and p-hydroxybenzoate levels. To test whether pHBMT1 is responsible for the biosynthesis of monolignol-p-hydroxybenzoates, we overexpressed pHBMT1 in hybrid poplar (Populus alba × P. grandidentata) (35S::pHBMT1 and C4H::pHBMT1). Using three complementary analytical methods, we showed that there was an increase in soluble monolignol-p-hydroxybenzoates and cell-wall-bound monolignol-p-hydroxybenzoates in the poplar transgenics. As these pendent groups are ester-linked, saponification releases p-hydroxybenzoate, a precursor to parabens that are used in pharmaceuticals and cosmetics. This identified gene could therefore be used to engineer lignocellulosic biomass with increased value for emerging biorefinery strategies.
MeSH term(s)	Acylation/genetics ; Acyltransferases/genetics ; Acyltransferases/metabolism ; Gene Expression Regulation, Plant ; Genes, Plant ; Lignin/biosynthesis ; Lignin/genetics ; Plants, Genetically Modified ; Populus/genetics ; Populus/metabolism
Chemical Substances	Lignin (9005-53-2) ; Acyltransferases (EC 2.3.-)
Language	English
Publishing date	2021-12-22
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	208914-2
ISSN	1532-2548 ; 0032-0889
ISSN (online)	1532-2548
ISSN	0032-0889
DOI	10.1093/plphys/kiab546
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