Evidence map›Paper›PMID 41731256›Full record

ArticleJournal of the Association for Research in Otolaryngology : JARO2026

Integrated Histology and Molecular Profiling of Postmortem Human Auditory and Vestibular Organs via a Poly (Methyl Methacrylate)-Based Workflow.

David Bächinger, Brock Peyton, Jacqueline Neubauer, Anbuselvan Dharmarajan, MengYu Zhu, Jennifer T O'Malley, Venus Kallupurackal, Steven Senese, Alison Brown, Sabina Wunderlin and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the Association for Research in Otolaryngology : JARO, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

David BächingerDepartment of Otorhinolaryngology, Head and Neck Surgery, University Hospital Zurich, Zurich, Switzerland.
Brock PeytonOtopathology Laboratory, Mass Eye and Ear, Boston, MA, USA.
Jacqueline NeubauerZurich Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland.
Anbuselvan DharmarajanOtopathology Laboratory, Mass Eye and Ear, Boston, MA, USA.
MengYu ZhuOtopathology Laboratory, Mass Eye and Ear, Boston, MA, USA.
Jennifer T O'MalleyOtopathology Laboratory, Mass Eye and Ear, Boston, MA, USA.
Venus KallupurackalZurich Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland.
Steven SeneseDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Alison BrownLaboratory for Molecular Medicine, Personalized Medicine, Mass General Brigham, Cambridge, MA, USA.
Sabina WunderlinLaboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Susanne KreutzerFunctional Genomics Center Zurich, ETH Zurich and University of Zurich, Zurich, Switzerland.
Nora M WeissDepartment of Otorhinolaryngology, Head and Neck Surgery "Otto Körner", University Medical Center, Rostock, Germany.
Heiko RichterLLS Rowiak LaserLabSolutions GmbH, Hannover, Germany.
Adrian DalbertDepartment of Otorhinolaryngology, Head and Neck Surgery, University Hospital Zurich, Zurich, Switzerland.
Christof RöösliDepartment of Otorhinolaryngology, Head and Neck Surgery, University Hospital Zurich, Zurich, Switzerland.
Anja KiparLaboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Zsuzsanna VargaDepartment of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
Brigitte von RechenbergMusculoskeletal Research Unit, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Sami S AmrLaboratory for Molecular Medicine, Personalized Medicine, Mass General Brigham, Cambridge, MA, USA.
Andreas H EckhardOtopathology Laboratory, Mass Eye and Ear, Boston, MA, USA. aeckhard@meei.harvard.edu.ORCID http://orcid.org/0000-0002-4921-6043

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeHearing and balance disorders are among the most prevalent sensory impairments globally, yet their cellular and molecular basis remains poorly understood. This gap stems from the inaccessibility of the inner ear, which is encased in the temporal bone (TB)-the hardest bone in the body-and cannot be biopsied in living patients. Conventional histopathology workflows, particularly the century-old celloidin method, are time-consuming, labor-intensive, and incompatible with modern molecular analyses. We aimed to develop a faster, more versatile histology workflow for human TBs that preserves both morphology and molecular integrity.

methodsWe developed a reversible polymethyl methacrylate (rPMMA) embedding protocol for formalin-fixed, calcified TBs using low-temperature resin infiltration (-40 to +4 °C). Precision near-serial sections (10-50 µm) were generated via femtosecond laser microtomy or precision diamond wire sawing. Deacrylation was performed to restore tissue accessibility for histological staining, multiplex immunofluorescence, whole-genome sequencing, and in situ RNA detection (RNAscope™).

resultsCompared to the celloidin workflow, our method reduced processing time and costs by over 90% while preserving histomorphology of comparable quality (n = 7 human TBs). It maintained antigenicity for multiplexed immunofluorescence, preserved native tissue-implant interfaces in implant-containing specimens, yielded high-quality DNA suitable for whole-genome sequencing (mean coverage 7.4 × in specimens with postmortem intervals < 24 h), and enabled mRNA detection at single-cell resolution. Celloidin-embedded controls consistently failed to support these molecular assays.

conclusionThis rPMMA-based workflow combines gold-standard histomorphology with full compatibility for advanced molecular analyses. With dramatically reduced time and cost, it offers a new benchmark for integrated, spatially resolved studies of human hearing and balance pathologies.

Indexed as

Ear, InnerPolymethyl MethacrylateVestibule, LabyrinthHumansWorkflowPolymethyl MethacrylateCelloidinDNAImmunohistochemistryInner earLaser microtomyTechnovit® 9100

Identifiers

PMID41731256
PMCPMC13090407

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.