Evidence map›Paper›PMID 30168727›Full record

ArticleArchives of pathology & laboratory medicine2019

Validation of a Muscle-Specific Tissue Image Analysis Tool for Quantitative Assessment of Dystrophin Staining in Frozen Muscle Biopsies.

Famke Aeffner, Crystal Faelan, Steven A Moore, Alexander Moody, Joshua C Black, Jay S Charleston, Diane E Frank, Johannes Dworzak, J Kris Piper, Manish Ranjitkar and 6 more

Open access · diamondAbstract readValidation Study
In one paragraph

Article in Archives of pathology & laboratory medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.6field-weighted citation impact, top 34% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 14 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 2 institutions in 1 country.

Famke AeffnerFrom Flagship Biosciences Inc, Westminster, Colorado (Drs Aeffner, Faelan, Black, Wilson, Kanaly, Rudmann, Lange, Young, and Milici and Mr Moody); the Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City (Dr Moore); and Sarepta Therapeutics Inc, Cambridge, Massachusetts (Drs Charleston and Frank and Messrs Dworzak, Piper, and Ranjitkar). Dr Moore is now with Oregon Health and Science University, Portland, and Dr Rudmann is now with Charles River Laboratories, Ashland, Ohio.
Crystal FaelanFrom Flagship Biosciences Inc, Westminster, Colorado (Drs Aeffner, Faelan, Black, Wilson, Kanaly, Rudmann, Lange, Young, and Milici and Mr Moody); the Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City (Dr Moore); and Sarepta Therapeutics Inc, Cambridge, Massachusetts (Drs Charleston and Frank and Messrs Dworzak, Piper, and Ranjitkar). Dr Moore is now with Oregon Health and Science University, Portland, and Dr Rudmann is now with Charles River Laboratories, Ashland, Ohio.
Steven A MooreFrom Flagship Biosciences Inc, Westminster, Colorado (Drs Aeffner, Faelan, Black, Wilson, Kanaly, Rudmann, Lange, Young, and Milici and Mr Moody); the Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City (Dr Moore); and Sarepta Therapeutics Inc, Cambridge, Massachusetts (Drs Charleston and Frank and Messrs Dworzak, Piper, and Ranjitkar). Dr Moore is now with Oregon Health and Science University, Portland, and Dr Rudmann is now with Charles River Laboratories, Ashland, Ohio.
Alexander MoodyFrom Flagship Biosciences Inc, Westminster, Colorado (Drs Aeffner, Faelan, Black, Wilson, Kanaly, Rudmann, Lange, Young, and Milici and Mr Moody); the Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City (Dr Moore); and Sarepta Therapeutics Inc, Cambridge, Massachusetts (Drs Charleston and Frank and Messrs Dworzak, Piper, and Ranjitkar). Dr Moore is now with Oregon Health and Science University, Portland, and Dr Rudmann is now with Charles River Laboratories, Ashland, Ohio.
Joshua C BlackFrom Flagship Biosciences Inc, Westminster, Colorado (Drs Aeffner, Faelan, Black, Wilson, Kanaly, Rudmann, Lange, Young, and Milici and Mr Moody); the Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City (Dr Moore); and Sarepta Therapeutics Inc, Cambridge, Massachusetts (Drs Charleston and Frank and Messrs Dworzak, Piper, and Ranjitkar). Dr Moore is now with Oregon Health and Science University, Portland, and Dr Rudmann is now with Charles River Laboratories, Ashland, Ohio.
Jay S CharlestonFrom Flagship Biosciences Inc, Westminster, Colorado (Drs Aeffner, Faelan, Black, Wilson, Kanaly, Rudmann, Lange, Young, and Milici and Mr Moody); the Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City (Dr Moore); and Sarepta Therapeutics Inc, Cambridge, Massachusetts (Drs Charleston and Frank and Messrs Dworzak, Piper, and Ranjitkar). Dr Moore is now with Oregon Health and Science University, Portland, and Dr Rudmann is now with Charles River Laboratories, Ashland, Ohio.
Diane E FrankFrom Flagship Biosciences Inc, Westminster, Colorado (Drs Aeffner, Faelan, Black, Wilson, Kanaly, Rudmann, Lange, Young, and Milici and Mr Moody); the Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City (Dr Moore); and Sarepta Therapeutics Inc, Cambridge, Massachusetts (Drs Charleston and Frank and Messrs Dworzak, Piper, and Ranjitkar). Dr Moore is now with Oregon Health and Science University, Portland, and Dr Rudmann is now with Charles River Laboratories, Ashland, Ohio.
Johannes DworzakFrom Flagship Biosciences Inc, Westminster, Colorado (Drs Aeffner, Faelan, Black, Wilson, Kanaly, Rudmann, Lange, Young, and Milici and Mr Moody); the Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City (Dr Moore); and Sarepta Therapeutics Inc, Cambridge, Massachusetts (Drs Charleston and Frank and Messrs Dworzak, Piper, and Ranjitkar). Dr Moore is now with Oregon Health and Science University, Portland, and Dr Rudmann is now with Charles River Laboratories, Ashland, Ohio.
J Kris PiperFrom Flagship Biosciences Inc, Westminster, Colorado (Drs Aeffner, Faelan, Black, Wilson, Kanaly, Rudmann, Lange, Young, and Milici and Mr Moody); the Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City (Dr Moore); and Sarepta Therapeutics Inc, Cambridge, Massachusetts (Drs Charleston and Frank and Messrs Dworzak, Piper, and Ranjitkar). Dr Moore is now with Oregon Health and Science University, Portland, and Dr Rudmann is now with Charles River Laboratories, Ashland, Ohio.
Manish RanjitkarFrom Flagship Biosciences Inc, Westminster, Colorado (Drs Aeffner, Faelan, Black, Wilson, Kanaly, Rudmann, Lange, Young, and Milici and Mr Moody); the Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City (Dr Moore); and Sarepta Therapeutics Inc, Cambridge, Massachusetts (Drs Charleston and Frank and Messrs Dworzak, Piper, and Ranjitkar). Dr Moore is now with Oregon Health and Science University, Portland, and Dr Rudmann is now with Charles River Laboratories, Ashland, Ohio.
Kristin WilsonFrom Flagship Biosciences Inc, Westminster, Colorado (Drs Aeffner, Faelan, Black, Wilson, Kanaly, Rudmann, Lange, Young, and Milici and Mr Moody); the Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City (Dr Moore); and Sarepta Therapeutics Inc, Cambridge, Massachusetts (Drs Charleston and Frank and Messrs Dworzak, Piper, and Ranjitkar). Dr Moore is now with Oregon Health and Science University, Portland, and Dr Rudmann is now with Charles River Laboratories, Ashland, Ohio.
Suzanne KanalyFrom Flagship Biosciences Inc, Westminster, Colorado (Drs Aeffner, Faelan, Black, Wilson, Kanaly, Rudmann, Lange, Young, and Milici and Mr Moody); the Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City (Dr Moore); and Sarepta Therapeutics Inc, Cambridge, Massachusetts (Drs Charleston and Frank and Messrs Dworzak, Piper, and Ranjitkar). Dr Moore is now with Oregon Health and Science University, Portland, and Dr Rudmann is now with Charles River Laboratories, Ashland, Ohio.
Daniel G RudmannFrom Flagship Biosciences Inc, Westminster, Colorado (Drs Aeffner, Faelan, Black, Wilson, Kanaly, Rudmann, Lange, Young, and Milici and Mr Moody); the Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City (Dr Moore); and Sarepta Therapeutics Inc, Cambridge, Massachusetts (Drs Charleston and Frank and Messrs Dworzak, Piper, and Ranjitkar). Dr Moore is now with Oregon Health and Science University, Portland, and Dr Rudmann is now with Charles River Laboratories, Ashland, Ohio.
Holger LangeFrom Flagship Biosciences Inc, Westminster, Colorado (Drs Aeffner, Faelan, Black, Wilson, Kanaly, Rudmann, Lange, Young, and Milici and Mr Moody); the Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City (Dr Moore); and Sarepta Therapeutics Inc, Cambridge, Massachusetts (Drs Charleston and Frank and Messrs Dworzak, Piper, and Ranjitkar). Dr Moore is now with Oregon Health and Science University, Portland, and Dr Rudmann is now with Charles River Laboratories, Ashland, Ohio.
G David YoungFrom Flagship Biosciences Inc, Westminster, Colorado (Drs Aeffner, Faelan, Black, Wilson, Kanaly, Rudmann, Lange, Young, and Milici and Mr Moody); the Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City (Dr Moore); and Sarepta Therapeutics Inc, Cambridge, Massachusetts (Drs Charleston and Frank and Messrs Dworzak, Piper, and Ranjitkar). Dr Moore is now with Oregon Health and Science University, Portland, and Dr Rudmann is now with Charles River Laboratories, Ashland, Ohio.
Anthony J MiliciFrom Flagship Biosciences Inc, Westminster, Colorado (Drs Aeffner, Faelan, Black, Wilson, Kanaly, Rudmann, Lange, Young, and Milici and Mr Moody); the Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City (Dr Moore); and Sarepta Therapeutics Inc, Cambridge, Massachusetts (Drs Charleston and Frank and Messrs Dworzak, Piper, and Ranjitkar). Dr Moore is now with Oregon Health and Science University, Portland, and Dr Rudmann is now with Charles River Laboratories, Ashland, Ohio.
Sarepta Therapeutics (United States) · USUniversity of Iowa · US

Funding

Therapeutic Potential of ESC-Derived Myogenic PrecursorsU54NS053672 · NINDS · UNIVERSITY OF IOWA · PI CAMPBELL, KEVIN P. · 2005 to 2019
$22.0M
NINDS NIH HHS U54 NS053672
6 · The paper itself

Abstract

CONTEXT.—: Duchenne muscular dystrophy is a rare, progressive, and fatal neuromuscular disease caused by dystrophin protein loss. Common investigational treatment approaches aim at increasing dystrophin expression in diseased muscle. Some clinical trials include assessments of novel dystrophin production as a surrogate biomarker of efficacy, which may predict a clinical benefit from treatment. OBJECTIVES.—: To establish an immunofluorescent scanning and digital image analysis workflow that provides an objective approach for staining intensity assessment of the immunofluorescence dystrophin labeling and determination of the percentage of biomarker-positive fibers in muscle cryosections. DESIGN.—: Optimal and repeatable digital image capture was achieved by a rigorously qualified fluorescent scanning process. After scanning qualification, the MuscleMap (Flagship Biosciences, Westminster, Colorado) algorithm was validated by comparing high-power microscopic field total and dystrophin-positive fiber counts obtained by trained pathologists to data derived by MuscleMap. Next, the algorithm was tested on whole-slide images of immunofluorescent-labeled muscle sections from Duchenne muscular dystrophy, Becker muscular dystrophy, and control patients. RESULTS.—: When used under the guidance of a trained pathologist, the digital image analysis tool met predefined validation criteria and demonstrated functional and statistical equivalence with manual assessment. This work is the first, to our knowledge, to qualify and validate immunofluorescent scanning and digital tissue image-analysis workflow, respectively, with the rigor required to support the clinical trial environments. CONCLUSIONS.—: MuscleMap enables analysis of all fibers within an entire muscle biopsy section and provides data on a fiber-by-fiber basis. This will allow future clinical trials to objectively investigate myofibers' dystrophin expression at a greater level of consistency and detail.

Indexed as

AdolescentBiopsyChildChild, PreschoolDystrophinFemaleFrozen SectionsHumansImage Interpretation, Computer-AssistedMaleMiddle AgedMuscle, SkeletalMuscular Dystrophy, DuchenneDystrophin

Identifiers

PMID30168727
PMCPMC6813837
OpenAlexW2888880127

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.