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Article ; Online: Natural killer cytotoxicity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a multi-site clinical assessment of ME/CFS (MCAM) sub-study.

Querec, Troy D / Lin, Jin-Mann S / Chen, Yang / Helton, Britany / Kogelnik, Andreas M / Klimas, Nancy G / Peterson, Daniel L / Bateman, Lucinda / Lapp, Charles / Podell, Richard N / Natelson, Benjamin H / Unger, Elizabeth R

Journal of translational medicine

2023 Volume 21, Issue 1, Page(s) 242

Abstract: Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem illness characterized by substantial reduction in function accompanied by profound unexplained fatigue not significantly relieved by rest, post-exertional malaise, ... ...

Abstract	Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem illness characterized by substantial reduction in function accompanied by profound unexplained fatigue not significantly relieved by rest, post-exertional malaise, and other symptoms. Reduced natural killer (NK) cell count and cytotoxicity has been investigated as a biomarker for ME/CFS, but few clinical laboratories offer the test and multi-site verification studies have not been conducted. Methods: We determined NK cell counts and cytotoxicity in 174 (65%) ME/CFS, 86 (32%) healthy control (HC) and 10 (3.7%) participants with other fatigue associated conditions (ill control [IC]) from the Multi-Site Clinical Assessment of ME/CFS (MCAM) study using an assay validated for samples shipped overnight instead of testing on day of venipuncture. Results: We found a large variation in percent cytotoxicity [mean and (IQR) for ME/CFS and HC respectively, 34.1% (IQR 22.4-44.3%) and 33.6% (IQR 22.9-43.7%)] and no statistically significant differences between patients with ME/CFS and HC (p-value = 0.79). Analysis stratified on illness domain measured with standardized questionnaires did not identify an association of NK cytotoxicity with domain scores. Among all participants, NK cytotoxicity was not associated with survey results of physical and mental well-being, or health factors such as history of infection, obesity, smoking, and co-morbid conditions. Conclusion: These results indicate this assay is not ready for clinical implementation and studies are needed to further explore immune parameters that may be involved in the pathophysiology of ME/CFS.
MeSH term(s)	Humans ; Fatigue Syndrome, Chronic ; Killer Cells, Natural ; TRPM Cation Channels ; CD146 Antigen
Chemical Substances	TRPM Cation Channels ; MCAM protein, human ; CD146 Antigen
Language	English
Publishing date	2023-04-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-023-03958-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Origins of direction selectivity in the primate retina.

Kim, Yeon Jin / Peterson, Beth B / Crook, Joanna D / Joo, Hannah R / Wu, Jiajia / Puller, Christian / Robinson, Farrel R / Gamlin, Paul D / Yau, King-Wai / Viana, Felix / Troy, John B / Smith, Robert G / Packer, Orin S / Detwiler, Peter B / Dacey, Dennis M

Nature communications

2022 Volume 13, Issue 1, Page(s) 2862

Abstract: From mouse to primate, there is a striking discontinuity in our current understanding of the neural coding of motion direction. In non-primate mammals, directionally selective cell types and circuits are a signature feature of the retina, situated at the ...

Abstract	From mouse to primate, there is a striking discontinuity in our current understanding of the neural coding of motion direction. In non-primate mammals, directionally selective cell types and circuits are a signature feature of the retina, situated at the earliest stage of the visual process. In primates, by contrast, direction selectivity is a hallmark of motion processing areas in visual cortex, but has not been found in the retina, despite significant effort. Here we combined functional recordings of light-evoked responses and connectomic reconstruction to identify diverse direction-selective cell types in the macaque monkey retina with distinctive physiological properties and synaptic motifs. This circuitry includes an ON-OFF ganglion cell type, a spiking, ON-OFF polyaxonal amacrine cell and the starburst amacrine cell, all of which show direction selectivity. Moreover, we discovered that macaque starburst cells possess a strong, non-GABAergic, antagonistic surround mediated by input from excitatory bipolar cells that is critical for the generation of radial motion sensitivity in these cells. Our findings open a door to investigation of a precortical circuitry that computes motion direction in the primate visual system.
MeSH term(s)	Amacrine Cells/physiology ; Animals ; Connectome ; Evoked Potentials, Visual/physiology ; Macaca/physiology ; Mammals ; Mice ; Primates/physiology ; Retina/physiology ; Retinal Ganglion Cells/physiology ; Synapses/physiology
Language	English
Publishing date	2022-05-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-30405-5
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Article ; Online: Natural killer cytotoxicity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Troy D. Querec / Jin-Mann S. Lin / Yang Chen / Britany Helton / Andreas M. Kogelnik / Nancy G. Klimas / Daniel L. Peterson / Lucinda Bateman / Charles Lapp / Richard N. Podell / Benjamin H. Natelson / Elizabeth R. Unger / the MCAM Study Group

Journal of Translational Medicine, Vol 21, Iss 1, Pp 1-

a multi-site clinical assessment of ME/CFS (MCAM) sub-study

2023 Volume 8

Abstract: Abstract Background Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem illness characterized by substantial reduction in function accompanied by profound unexplained fatigue not significantly relieved by rest, post-exertional ... ...

Abstract	Abstract Background Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem illness characterized by substantial reduction in function accompanied by profound unexplained fatigue not significantly relieved by rest, post-exertional malaise, and other symptoms. Reduced natural killer (NK) cell count and cytotoxicity has been investigated as a biomarker for ME/CFS, but few clinical laboratories offer the test and multi-site verification studies have not been conducted. Methods We determined NK cell counts and cytotoxicity in 174 (65%) ME/CFS, 86 (32%) healthy control (HC) and 10 (3.7%) participants with other fatigue associated conditions (ill control [IC]) from the Multi-Site Clinical Assessment of ME/CFS (MCAM) study using an assay validated for samples shipped overnight instead of testing on day of venipuncture. Results We found a large variation in percent cytotoxicity [mean and (IQR) for ME/CFS and HC respectively, 34.1% (IQR 22.4–44.3%) and 33.6% (IQR 22.9–43.7%)] and no statistically significant differences between patients with ME/CFS and HC (p-value = 0.79). Analysis stratified on illness domain measured with standardized questionnaires did not identify an association of NK cytotoxicity with domain scores. Among all participants, NK cytotoxicity was not associated with survey results of physical and mental well-being, or health factors such as history of infection, obesity, smoking, and co-morbid conditions. Conclusion These results indicate this assay is not ready for clinical implementation and studies are needed to further explore immune parameters that may be involved in the pathophysiology of ME/CFS.
Keywords	Natural killer cell (NK) ; Cytotoxicity ; Comorbidity ; Multimorbidity (multiple medical conditions) ; Multicenter study ; Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) ; Medicine ; R
Subject code	610
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
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Article ; Online: Origins of direction selectivity in the primate retina

Yeon Jin Kim / Beth B. Peterson / Joanna D. Crook / Hannah R. Joo / Jiajia Wu / Christian Puller / Farrel R. Robinson / Paul D. Gamlin / King-Wai Yau / Felix Viana / John B. Troy / Robert G. Smith / Orin S. Packer / Peter B. Detwiler / Dennis M. Dacey

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 20

Abstract: Neural coding for motion direction has been studied intensively in the visual cortex of non-human primates. Here, the authors establish an origin for direction selectivity in the retina of the macaque monkey. ...

Abstract	Neural coding for motion direction has been studied intensively in the visual cortex of non-human primates. Here, the authors establish an origin for direction selectivity in the retina of the macaque monkey.
Keywords	Science ; Q
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article ; Online: User testing of a diagnostic decision support system with machine-assisted chart review to facilitate clinical genomic diagnosis.

Kulchak Rahm, Alanna / Walton, Nephi A / Feldman, Lynn K / Jenkins, Conner / Jenkins, Troy / Person, Thomas N / Peterson, Joeseph / Reynolds, Jonathon C / Robinson, Peter N / Woltz, Makenzie A / Williams, Marc S / Segal, Michael M

BMJ health & care informatics

2021 Volume 28, Issue 1

Abstract: Objectives: There is a need in clinical genomics for systems that assist in clinical diagnosis, analysis of genomic information and periodic reanalysis of results, and can use information from the electronic health record to do so. Such systems should ... ...

Abstract	Objectives: There is a need in clinical genomics for systems that assist in clinical diagnosis, analysis of genomic information and periodic reanalysis of results, and can use information from the electronic health record to do so. Such systems should be built using the concepts of human-centred design, fit within clinical workflows and provide solutions to priority problems. Methods: We adapted a commercially available diagnostic decision support system (DDSS) to use extracted findings from a patient record and combine them with genomic variant information in the DDSS interface. Three representative patient cases were created in a simulated clinical environment for user testing. A semistructured interview guide was created to illuminate factors relevant to human factors in CDS design and organisational implementation. Results: Six individuals completed the user testing process. Tester responses were positive and noted good fit with real-world clinical genetics workflow. Technical issues related to interface, interaction and design were minor and fixable. Testers suggested solving issues related to terminology and usability through training and infobuttons. Time savings was estimated at 30%-50% and additional uses such as in-house clinical variant analysis were suggested for increase fit with workflow and to further address priority problems. Conclusion: This study provides preliminary evidence for usability, workflow fit, acceptability and implementation potential of a modified DDSS that includes machine-assisted chart review. Continued development and testing using principles from human-centred design and implementation science are necessary to improve technical functionality and acceptability for multiple stakeholders and organisational implementation potential to improve the genomic diagnosis process.
MeSH term(s)	Decision Support Systems, Clinical/organization & administration ; Electronic Health Records/organization & administration ; Genomics/organization & administration ; Humans ; Natural Language Processing ; Terminology as Topic ; Time Factors ; User-Centered Design
Language	English
Publishing date	2021-05-04
Publishing country	England
Document type	Journal Article
ISSN	2632-1009
ISSN (online)	2632-1009
DOI	10.1136/bmjhci-2021-100331
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Article ; Online: Response to Dr Khursheed Jeejeebhoy.

Sheean, Patricia M / Peterson, Sarah J / Perez, Sandra Gomez / Troy, Karen L / Patel, Ankur / Sclamberg, Joy S / Ajanaku, Folabomi C / Braunschweig, Carol A

JPEN. Journal of parenteral and enteral nutrition

2015 Volume 39, Issue 3, Page(s) 271–272

MeSH term(s)	Body Composition ; Female ; Humans ; Male ; Muscle, Skeletal ; Nutritional Status ; Respiratory Insufficiency/complications ; Sarcopenia/epidemiology
Language	English
Publishing date	2015-02-21
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	800861-9
ISSN	1941-2444 ; 0148-6071
ISSN (online)	1941-2444
ISSN	0148-6071
DOI	10.1177/0148607114562889
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Article ; Online: User testing of a diagnostic decision support system with machine-assisted chart review to facilitate clinical genomic diagnosis

Conner Jenkins / Troy Jenkins / Thomas N Person / Peter N Robinson / Alanna Kulchak Rahm / Nephi A Walton / Lynn K Feldman / Joeseph Peterson / Jonathon C Reynolds / Makenzie A Woltz / Marc S Williams / Michael M Segal

BMJ Health & Care Informatics, Vol 28, Iss

2021 Volume 1

Abstract: Objectives There is a need in clinical genomics for systems that assist in clinical diagnosis, analysis of genomic information and periodic reanalysis of results, and can use information from the electronic health record to do so. Such systems should be ... ...

Abstract	Objectives There is a need in clinical genomics for systems that assist in clinical diagnosis, analysis of genomic information and periodic reanalysis of results, and can use information from the electronic health record to do so. Such systems should be built using the concepts of human-centred design, fit within clinical workflows and provide solutions to priority problems.Methods We adapted a commercially available diagnostic decision support system (DDSS) to use extracted findings from a patient record and combine them with genomic variant information in the DDSS interface. Three representative patient cases were created in a simulated clinical environment for user testing. A semistructured interview guide was created to illuminate factors relevant to human factors in CDS design and organisational implementation.Results Six individuals completed the user testing process. Tester responses were positive and noted good fit with real-world clinical genetics workflow. Technical issues related to interface, interaction and design were minor and fixable. Testers suggested solving issues related to terminology and usability through training and infobuttons. Time savings was estimated at 30%–50% and additional uses such as in-house clinical variant analysis were suggested for increase fit with workflow and to further address priority problems.Conclusion This study provides preliminary evidence for usability, workflow fit, acceptability and implementation potential of a modified DDSS that includes machine-assisted chart review. Continued development and testing using principles from human-centred design and implementation science are necessary to improve technical functionality and acceptability for multiple stakeholders and organisational implementation potential to improve the genomic diagnosis process.
Keywords	Computer applications to medicine. Medical informatics ; R858-859.7
Subject code	670
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
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Article ; Online: The prevalence of sarcopenia in patients with respiratory failure classified as normally nourished using computed tomography and subjective global assessment.

Sheean, Patricia M / Peterson, Sarah J / Gomez Perez, Sandra / Troy, Karen L / Patel, Ankur / Sclamberg, Joy S / Ajanaku, Folabomi C / Braunschweig, Carol A

JPEN. Journal of parenteral and enteral nutrition

2013 Volume 38, Issue 7, Page(s) 873–879

Abstract: Background: Declines in nutrition status and adverse body composition changes frequently occur in the critically ill. The objective of this cross-sectional study was to examine the prevalence of sarcopenia and its occurrence in patients classified as ... ...

Abstract	Background: Declines in nutrition status and adverse body composition changes frequently occur in the critically ill. The objective of this cross-sectional study was to examine the prevalence of sarcopenia and its occurrence in patients classified as normal nourished using subjective global assessment (SGA). Methods: Exploiting diagnostic CT images, skeletal muscle mass at the L3 region was quantified and used to determine sarcopenia and its association with normal nutrition status in 56 patients with respiratory failure. Sarcopenia was defined as an L3 skeletal muscle index of ≤38.5 cm(2)/m(2) for women and ≤52.4 cm(2)/m(2) for men. CT imaging and SGA classifications completed within 14, 10 and 7 days of each other were analyzed to assess sarcopenia and the influence of time between scans on misclassification (ie, normal nourished and sarcopenic). Descriptive statistics were conducted. Results: The average patient was 59.2 (± 15.6) years old, admitted with sepsis/infection, an APACHE II score of 26 (± 8.0), and BMI of 28.3 (± 5.8). Sarcopenia and sarcopenic obesity were prevalent in a minimum of 56% and 24% of patients, respectively, depending on the number of days between CT imaging and SGA assessment. Misclassified individuals were predominantly male, minority and overweight or obese. Controlling for age, no significant differences were noted for patients classified as normal nourished vs malnourished by SGA for lumbar muscle cross-sectional, whole-body lean mass, or skeletal muscle index. Conclusions: Sarcopenia is highly prevalent among patients with respiratory failure requiring mechanical ventilation (MV) and not readily detected in patients classified as normal nourished using SGA.
MeSH term(s)	Adult ; Aged ; Body Composition ; Body Mass Index ; Critical Illness ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Minority Groups ; Muscle, Skeletal ; Nutrition Assessment ; Nutritional Status ; Obesity/complications ; Overweight ; Prevalence ; Reference Values ; Respiration, Artificial ; Respiratory Insufficiency/complications ; Sarcopenia/complications ; Sarcopenia/epidemiology ; Sepsis ; Sex Factors ; Tomography
Language	English
Publishing date	2013-08-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	800861-9
ISSN	1941-2444 ; 0148-6071
ISSN (online)	1941-2444
ISSN	0148-6071
DOI	10.1177/0148607113500308
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Article ; Online: P2 receptors for extracellular nucleotides in the central nervous system: role of P2X7 and P2Y₂ receptor interactions in neuroinflammation.

Weisman, Gary A / Camden, Jean M / Peterson, Troy S / Ajit, Deepa / Woods, Lucas T / Erb, Laurie

Molecular neurobiology

2012 Volume 46, Issue 1, Page(s) 96–113

Abstract: Extracellular nucleotides induce cellular responses in the central nervous system (CNS) through the activation of ionotropic P2X and metabotropic P2Y nucleotide receptors. Activation of these receptors regulates a wide range of physiological and ... ...

Abstract	Extracellular nucleotides induce cellular responses in the central nervous system (CNS) through the activation of ionotropic P2X and metabotropic P2Y nucleotide receptors. Activation of these receptors regulates a wide range of physiological and pathological processes. In this review, we present an overview of the current literature regarding P2X and P2Y receptors in the CNS with a focus on the contribution of P2X7 and P2Y(2) receptor-mediated responses to neuroinflammatory and neuroprotective mechanisms.
MeSH term(s)	Animals ; Central Nervous System/metabolism ; Central Nervous System/pathology ; Humans ; Inflammation/pathology ; Neuroprotective Agents/metabolism ; Nucleotides/metabolism ; Receptors, Purinergic P2X7/metabolism ; Receptors, Purinergic P2Y2/metabolism
Chemical Substances	Neuroprotective Agents ; Nucleotides ; Receptors, Purinergic P2X7 ; Receptors, Purinergic P2Y2
Language	English
Publishing date	2012-04-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-012-8263-z
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Article ; Online: Molecular predictors of immunophenotypic measurable residual disease clearance in acute myeloid leukemia.

Stahl, Maximilian / Derkach, Andriy / Farnoud, Noushin / Bewersdorf, Jan Philipp / Robinson, Troy / Famulare, Christopher / Cho, Christina / Devlin, Sean / Menghrajani, Kamal / Patel, Minal A / Cai, Sheng F / Miles, Linde A / Bowman, Robert L / Geyer, Mark B / Dunbar, Andrew / Epstein-Peterson, Zachary D / McGovern, Erin / Schulman, Jessica / Glass, Jacob L /

American journal of hematology

2022 Volume 98, Issue 1, Page(s) 79–89

Abstract: Measurable residual disease (MRD) is a powerful prognostic factor in acute myeloid leukemia (AML). However, pre-treatment molecular predictors of immunophenotypic MRD clearance remain unclear. We analyzed a dataset of 211 patients with pre-treatment next- ...

Abstract	Measurable residual disease (MRD) is a powerful prognostic factor in acute myeloid leukemia (AML). However, pre-treatment molecular predictors of immunophenotypic MRD clearance remain unclear. We analyzed a dataset of 211 patients with pre-treatment next-generation sequencing who received induction chemotherapy and had MRD assessed by serial immunophenotypic monitoring after induction, subsequent therapy, and allogeneic stem cell transplant (allo-SCT). Induction chemotherapy led to MRD- remission, MRD+ remission, and persistent disease in 35%, 27%, and 38% of patients, respectively. With subsequent therapy, 34% of patients with MRD+ and 26% of patients with persistent disease converted to MRD-. Mutations in CEBPA, NRAS, KRAS, and NPM1 predicted high rates of MRD- remission, while mutations in TP53, SF3B1, ASXL1, and RUNX1 and karyotypic abnormalities including inv (3), monosomy 5 or 7 predicted low rates of MRD- remission. Patients with fewer individual clones were more likely to achieve MRD- remission. Among 132 patients who underwent allo-SCT, outcomes were favorable whether patients achieved early MRD- after induction or later MRD- after subsequent therapy prior to allo-SCT. As MRD conversion with chemotherapy prior to allo-SCT is rarely achieved in patients with specific baseline mutational patterns and high clone numbers, upfront inclusion of these patients into clinical trials should be considered.
MeSH term(s)	Humans ; Prognosis ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/therapy ; Stem Cell Transplantation ; Remission Induction ; Transplantation, Homologous ; Neoplasm, Residual/genetics ; Hematopoietic Stem Cell Transplantation
Language	English
Publishing date	2022-10-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.26757
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