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Understanding age-related middle ear properties and basilar membrane damage in hearing loss: A finite element analysis and retrospective cohort study

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Computers in Biology and Medicine 2025年 184卷 109376-109376页

作者： Shih, Tzu-Ching Yu, You-Cheng Wang, Tang-Chuan Department of Biomedical Imaging and Radiological Science College of Medicine China Medical University Taichung404328 Taiwan The PhD Program for Medical Engineering and Rehabilitation Science College of Biomedical Engineering China Medical University Taichung404328 Taiwan Master Program for Biomedical Engineering College of Biomedical Engineering China Medical University Taichung404328 Taiwan Department of Otolaryngology-Head and Neck Surgery China Medical University Hsinchu Hospital Zhubei City Hsinchu302056 Taiwan

Age-related hearing loss (ARHL) is primarily attributed to inner-ear factors, yet the role of age-related middle ear characteristics remains elusive. Employing a finite element (FE) model, we conducted a comparative analysis with clinical data extracted from a retrospective cohort study involving 90 younger adults (mean age = 38.1 ± 7.7) and 111 older adults (mean age = 63.8 ± 8.4). The clinical dataset encompassed air-bone gap (ABG) measurements obtained through pure-tone audiometry (PTA) at frequencies of 0.5, 1.0, 2.0, and 4.0 kHz. FE results quantified the normalized stapes displacement value of the simulated form of air-bone gap (ABGSim) between the two age groups. The Mann-Whitney U test, with a significance threshold set at P © 2024

关键词： Bone

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Short-Chain Dense Brush Pegylation on Rigid Nanocarriers Overcomes Anti-Peg Antibody Recognition for Immune-Stealth Drug Delivery

SSRN

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SSRN 2025年

作者： Chen, Ting-Yu Chang, Chi-Yuan Wen, Ting-Chun Xu, Li Lin, Yu-Han Peng, Cheng-Liang Yeh, Yi-Qi Chen, Chueh-Hsuan Chuang, Kuo-Hsiang Wu, Si-Han Graduate Institute of Pharmacognosy Taipei Medical University Taipei11031 Taiwan Graduate Institute of Nanomedicine and Medical Engineering Taipei Medical University Taipei11031 Taiwan Department of Isotope Application National Atomic Research Institute Taoyuan Taiwan National Synchrotron Radiation Research Center Hsinchu Science Park Hsinchu30076 Taiwan Research Center for Applied Science Academia Sinica Taiwan PhD Program in Clinical Drug Development of Chinese Herbal Medicine Taipei Medical University Taipei Taiwan International Ph.D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan

The immunogenicity of polyethylene glycol (PEG) remains a critical challenge in nanomedicine, as pre-existing anti-PEG antibodies can compromise therapeutic efficacy through accelerated blood clearance (ABC) and life-threatening hypersensitivity. Here, we address this challenge by engineering the PEG architecture, creating short-chain dense brush PEGylation (PEG500) on rigid mesoporous silica nanoparticles (MSNs). Unlike conventional PEG2000-liposomes, MSN-PEG500 evades antibodies via three synergistic mechanisms: (1) short-chain PEG500 reduces epitope accessibility, (2) high grafting density (4.43 chains/nm2, according to TGA) forms an dense steric shield, and (3) the rigid silica surface prevents PEG burial. ELISA studies demonstrated that, at equivalent nanoparticle concentrations, MSN-PEG500 exhibits a 26-fold reduction in anti-PEG IgG (6.3) binding and a 1000-fold reduction in anti-PEG IgM (AGP3) binding compared to Lipodox (PEG2000), both of which target the PEG backbone. Furthermore, radiolabeled MSN-PEG500 achieved prolonged circulation and 25% tumor accumulation (ID/g) at 24 hours. In strongly immunized mice, doxorubicin-loaded MSN-PEG500 preserved therapeutic efficacy and 100% survival, whereas Lipodox induced fatal hypersensitivity. Mechanistic investigations revealed that complement activation drives PEG2000 immunotoxicity, and pretreatment with the C3 inhibitor compstatin effectively mitigated temperature drops from 10°C to 2°C in immunized hosts. By demonstrating that nanoscale control of polymer conformation dictates immunological fate, this work provides a clinically translatable blueprint for developing immune-evasive nanomedicines. © 2025, The Authors. All rights reserved.

关键词： Silica nanoparticles

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Probabilistic genotype-phenotype maps reveal mutational robustness of RNA folding, spin glasses, and quantum circuits

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Physical Review Research 2025年第1期7卷 013118-013118页

作者： Anna Sappington Vaibhav Mohanty Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology Cambridge Massachusetts 02139 USA Harvard-MIT Program in Health Sciences and Technology Harvard Medical School Boston Massachusetts 02115 USA and Massachusetts Institute of Technology Cambridge Massachusetts 02139 USA Harvard/MIT MD-PhD Program Harvard Medical School Boston Massachusetts 02115 USA and Massachusetts Institute of Technology Cambridge Massachusetts 02139 USA Department of Chemistry and Chemical Biology Harvard University Cambridge Massachusetts 02138 USA

Recent studies of genotype-phenotype maps have reported universally enhanced phenotypic robustness to genotype mutations, a feature essential to evolution. Virtually all of these studies make a simplifying assumption that each genotype—represented as a sequence—maps deterministically to a single phenotype, such as a discrete structure. Here we introduce probabilistic genotype-phenotype (PrGP) maps, where each genotype maps to a vector of phenotype probabilities, as a more realistic and universal language for investigating robustness in a variety of physical, biological, and computational systems. We study three model systems to show that PrGP maps offer a generalized framework which can handle uncertainty emerging from various physical sources: (1) thermal fluctuation in RNA folding, (2) external field disorder in the spin-glass ground state search problem, and (3) superposition and entanglement in quantum circuits, which are realized experimentally on IBM quantum computers. In all three cases, we observe a biphasic robustness scaling which is enhanced relative to random expectation for more frequent phenotypes and approaches random expectation for less frequent phenotypes. We derive an analytical theory for the behavior of PrGP robustness, and we demonstrate that the theory is highly predictive of empirical robustness.

关键词： Quantum computers

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Labeling phrenic afferents with intrapleural AAV-PHP.S

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Journal of Neuroscience Methods 2025年 419卷 110466页

作者： Morales, Amanda C. Holmes, Taylor C. Sanchez, Felix T. Huang, Haozhi Williams, Jordan J. Streeter, Kristi A. Deparment of Physical Therapy Marquette University Milwaukee WI United States Exercise and Rehabilitation Science Program Department of Physical Therapy Marquette University Milwaukee WI United States Department of Biomedical Engineering Medical College of Wisconsin and Marquette University Milwaukee WI United States

Background: Understanding the role of musculoskeletal afferents in health and disease relies on the ability to selectively label afferents. Traditional approaches involve using adeno-associated viral (AAV) tools to transduce afferents with intrathecal, intramuscular, or direct dorsal root ganglion (DRG) injections. However, these approaches are surgically invasive, have non-specific labeling, or do not target functional groups of afferents. For example, labeling phrenic afferents arising from the diaphragm muscle is challenging due to the presence of musculoskeletal and cutaneous afferents from the forelimb, neck, and shoulder in the C3-C5 DRGs. New method: Using a new capsid variant of AAV9 with enhanced tropism toward afferents (AAV-PHP.S), we investigated if intrapleural injection of AAV-PHP.S transduces phrenic afferents in the cervical DRGs and spinal cord. Results: In animals receiving AAV-PHP.S, we observed robust tdTomato labeling in the DRGs, dorsal roots, dorsal columns, and spinal projections throughout the spinal gray matter. We did not see the same pattern of afferent labeling when we transected the phrenic nerve prior to intrapleural injection, nor did we find any evidence for motor neuron labeling. Classification of labeled afferents suggests preferential labeling of large diameter proprioceptive neurons. Time-course experiments show tdTomato expression in DRG neurons plateaued by 2 weeks. Comparison with existing methods: To our knowledge this is the first AAV-based method that preferentially targets phrenic afferents without also labeling phrenic motor neurons. Conclusions: This approach labels phrenic afferents and may be used in combination with optogenetic or chemogenetic tools to advance our understanding of the functional role of phrenic afferents. © 2025 The Authors

关键词： AAV-PHP.S Breathing Intrapleural injection Phrenic afferents Respiratory Retrograde labeling

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Electron spin dynamics guide cell motility

arXiv

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arXiv 2025年

作者： Wang, Kai Gilmer, Gabrielle Araña, Matheus Cândia Iijima, Hirotaka Bergmann, Juliana Woollard, Antonio Mesits, Boris McGraw, Meghan Zoltowski, Brian Cappellaro, Paola Ungar, Alex Pekker, David Waldeck, David H. Saxena, Sunil Lloyd, Seth Ambrosio, Fabrisia Discovery Center for Musculoskeletal Recovery Schoen Adams Research Institute at Spaulding BostonMA United States Department of Physical Medicine & Rehabilitation Spaulding Rehabilitation Hospital BostonMA United States Department of Physical Medicine & Rehabilitation Harvard Medical School BostonMA United States Cellular and Molecular Pathology Graduate Program University of Pittsburgh PittsburghPA United States Medical Scientist Training Program School of Medicine University of Pittsburgh PittsburghPA United States École Polytechnique Institut Polytechnique de Paris Palaiseau France Department of Physics & Astronomy University of Pittsburgh PittsburghPA United States Department of Chemistry Southern Methodist University DallasTX United States Department of Nuclear Science and Engineering Massachusetts Institute of Technology CambridgeMA02139 United States Department of Physics Massachusetts Institute of Technology CambridgeMA02139 United States Department of Chemistry University of Pittsburgh PittsburghPA United States Department of Mechanical Engineering Massachusetts Institute of Technology BostonMA United States

Diverse organisms exploit the geomagnetic field (GMF) for migration. Migrating birds employ an intrinsically quantum mechanical mechanism for detecting the geomagnetic field: absorption of a blue photon generates a radical pair whose two electrons precess at different rates in the magnetic field, thereby sensitizing cells to the direction of the GMF. In this work, using an in vitro injury model, we discovered a quantum-based mechanism of cellular migration. Specifically, we show that migrating cells detect the GMF via an optically activated, electron spin-based mechanism. Cell injury provokes acute emission of blue photons, and these photons sensitize muscle progenitor cells to the magnetic field. We show that the magnetosensitivity of muscle progenitor cells is (a) activated by blue light, but not by green or red light, and (b) disrupted by the application of an oscillatory field at the frequency corresponding to the energy of the electron-spin/magnetic field interaction. A comprehensive analysis of protein expression reveals that the ability of blue photons to promote cell motility is mediated by activation of calmodulin calcium sensors. Collectively, these data suggest that cells possess a light-dependent magnetic compass driven by electron spin dynamics. © 2025, CC BY.

关键词： Spin dynamics

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Fate and state transitions during human blood vessel organoid development

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Cell 2025年

作者： Nikolova, Marina T. He, Zhisong Seimiya, Makiko Jonsson, Gustav Cao, Wuji Okuda, Ryo Wimmer, Reiner A. Okamoto, Ryoko Penninger, Josef M. Camp, J. Gray Treutlein, Barbara Department of Biosystems Science and Engineering ETH Zurich Basel Switzerland Institute of Molecular Biotechnology of the Austrian Academy of Sciences Vienna Austria Vienna BioCenter PhD Program Doctoral School of the University of Vienna and Medical University of Vienna Vienna 1030 Austria Roche Pharma Research and Early Development Roche Innovation Center Basel Switzerland Department of Medical Genetics Life Science Institute University of British Columbia Vancouver V6T 1Z3 BC Canada Department of Laboratory Medicine Medical University of Vienna Vienna Austria Helmholtz Centre for Infection Research Braunschweig Germany Institute of Human Biology Roche Pharma Research and Early Development Roche Innovation Center Basel Basel Switzerland Biozentrum University of Basel Basel Switzerland

Human blood vessel organoids (hBVOs) have emerged as a system to model human vascular development and disease. Here, we use single-cell multi-omics together with genetic and signaling pathway perturbations to reconstruct hBVO development. Mesodermal progenitors bifurcate into endothelial and mural fates in vitro, and xenografted BVOs acquire definitive arteriovenous endothelial cell specification. We infer a gene regulatory network and use single-cell genetic perturbations to identify transcription factors (TFs) and receptors involved in cell fate specification, including a role for MECOM in endothelial and mural specification. We assess the potential of BVOs to generate organotypic states, identify TFs lacking expression in hBVOs, and find that induced LEF1 overexpression increases brain vasculature specificity. Finally, we map vascular disease-associated genes to hBVO cell states and analyze an hBVO model of diabetes. Altogether, we provide a comprehensive cell state atlas of hBVO development and illuminate the power and limitation of hBVOs for translational research. © 2025 The Authors

关键词： arteriovenous specification human blood vessel organoid human development organoid cell atlas single-cell genomics single-cell perturbation screen

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Universal nanocomposite coating with antifouling and redox capabilities for electrochemical affinity biosensing in complex biological fluids

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Nanoscale Horizons 2024年第5期9卷 843-852页

作者： Bharti, Aditya Manu Rakesh Kumar, R.K. Chuang, Cheng-Hsin Shaikh, Muhammad Omar International PhD Program for Science National Sun Yat-sen University Kaohsiung80424 Taiwan Institute of Medical Science and Technology National Sun Yat-sen University Kaohsiung80424 Taiwan Department of Chemical Engineering National Taiwan University Taipei City10617 Taiwan Institute of Biomedical Engineering and Nanomedicine National Healthcare Research Institutes Miaoli County350 Taiwan National Sun Yat-sen University Kaohsiung80424 Taiwan Sustainability Science and Management Program Tunghai University Taichung407224 Taiwan

Electrochemical affinity biosensors have the potential to facilitate the development of multiplexed point-of-care diagnostics in complex biological fluids. However, their commercial viability has been hindered by challenges such as electrode biofouling and the lack of inherent redox properties. To address this unmet need, we have developed a universal nanocomposite coating which is unique in its ability to not only allow oriented conjugation of the biorecognition element but also specific detection directly in complex biological fluids like serum and urine owing to its built-in antifouling and redox capabilities, thus improving suitability for point of care testing. This multifunctional coating comprises a 3D porous crosslinked bovine serum albumin matrix for oriented conjugation and antifouling properties with embedded graphene nanosheets modified with amino-ferrocene for enhanced conductivity and mediator-free biosensing. The coating showed minimal signal degradation despite prolonged exposure to 1% bovine serum albumin, artificial urine and untreated human serum for up to 30 days. To demonstrate its utility, we fabricated and tested proof-of-concept electrochemical immunosensors for bladder cancer protein biomarkers, specifically interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF). The practical feasibility was highlighted by the excellent sensitivity and specificity observed for IL-8 and VEGF with a limit of detection of 41 pg mL−1 and 67 pg mL−1, respectively. Consequently, this universal nanocomposite-based electrochemical biosensing platform can be extended to the point of care testing of a broad spectrum of biomarkers present in complex biological fluids, thus enabling reliable and early diagnostics. © 2024 The Royal Society of Chemistry

关键词： Biomarkers

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Dynamic analysis of lower limb during swing phase in chronic SCI patients for functional electrical stimulation

Dynamic analysis of lower limb during swing phase in chronic...

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2005 Summer Bioengineering Conference

作者： Kim, Yongchul Schmit, Brian D. Youm, Youngil Department of the Mechanical Engineering Pohang University of Science and Technology Pohang Korea Republic of Department of Biomedical Engineering Marquette University Milwaukee WI Sensory Motor Performance Program Rehabilitation Institute of Chicago Chicago IL Department of Physical Medicine and Rehabilitation Northwestern University Medical School Chicago IL

ISBN: (纸本)0974249211

The aim of this study was to develop the dynamic model of lower limb using static and dynamic reflex properties of flexion reflex. Identification of torque response associated with hip angle and angular velocity was tested in 6 subjects with chronic SCI. Each subject placed in a supine position and lower leg was fixed with the knee at 155°±12 and the ankle at 126°±14. The hip was aligned with the axis of the Biodex motor in order to impose hip movements to the leg. A train of 10 stimulus pulses (50mA, 1ms) as reference pulse were applied at 200Hz to the skin of the medial arch to trigger flexion reflex reflexes. From this experiment, we identified the torque response as linear function of hip angle and angular velocity. In order to simulate the lower limb of spinal cord injured patients for functional electrical stimulation, we developed two dimensional dynamic model with three segments, thigh, shank and foot. Influences of stimulation parameters such as amplitude, frequency and duration time of pulse train were investigated with Taguchi method to obtain best results.

关键词： Physiological models

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The anatomic determinants of conductive hearing loss secondary to tympanic membrane perforation

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Journal of Otology 2017年第3期12卷 125-131页

作者： David J.Carpenter Debara L.Tucci David M.Kaylie Dennis O.Frank-Ito Division of Head and Neck Surgery & Communication Sciences Department of Surgery Duke University Medical Center Durham NC USA Computational Biology & Bioinformatics PhD Program Duke University Durham NC USA Department of Mechanical Engineering and Materials Science Duke University Durham NC USA

Objectives: Recent studies have introduced middle ear volume(MEV) as a novel determinant of perforation-induced conductive hearing loss(CHL) in a mechanism driven by trans-tympanic membrane pressure differences. The primary aims of this preliminary report are to: 1) correlate CHL with perforation size; 2) describe the relationship between CHL and MEV; and 3) compare CHL across a range of cholesteatoma ***: A retrospective pilot study was performed in 31 subjects with audiometry indicative of conductive hearing loss, temporal bone CT scans,and no prior middle ear surgery. Perforation size and MEV were analyzed with respect to CHL in a cohort of 10 perforated ears with no cholesteatoma. CHLs were compared in 3 groups defined by extent of cholesteatoma ***: Ears with large and small perforations showed mean ABG values of 32.0 ± 15.7 dB and 16.0 ± 16.4 dB, respectively. A direct relationship was observed between MEV and CHL for ears with large perforations across all frequencies, whereas this relationship for small perforations was frequency-dependent. Finally, a statistically significant increase in CHL was found across ears with increasing cholesteatoma involvement at 1000 Hz(X^2(2) = 9.786, p = 0.008),2000 Hz(x^2(2) = 8.455, p = 0.015),and 4000 Hz(x^2(2)= 8.253, p = 0.016).Conclusions: These pilot data suggest that greater perforation-induced conductive hearing losses may be associated with larger perforation sizes and cholesteatoma. The correlation between MEV and CHL may require additional study.

关键词： Perforation-induced hearing loss Conductive hearing loss Middle ear volume Three-dimensional volume reconstruction

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Disagreement in middle ear volume estimation between tympanometry and three-dimensional volume reconstruction in the context of tympanic membrane perforation

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Journal of Otology 2017年第2期12卷 74-79页

作者： David J.Carpenter Debara L.Tucci David M.Kaylie Dennis O.Frank-Ito Division of Head and Neck Surgery&Communication Sciences Department of SurgeryDuke University Medical CenterDurhamNCUSA Computational Biology&Bioinformatics PhD Program Duke UniversityDurhamNCUSA Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNCUSA

Introduction: Middle ear volume(MEV) is a clinically relevant parameter across middle ear diseases. MEV values between these techniques have never before been tested for agreement in ears with perforated tympanic membranes(TMs).Methods: Middle ears were identified from 36 patients ranging 18-89 years of age with TM perforations who underwent tympanometry and temporal bone computed tomography(CT) between 2005 and 2015. MEVs calculated by both tympanometry and three-dimensional volume reconstruction(3DVR) were analyzed for agreement using Bland Altman plots. The differences between tympanometric and 3DVR MEV values for each given middle ear were characterized across MEV quartiles(1= smallest; 4= largest) and across increasing states of middle ear disease using Kruskale Wallis and Wilcoxon testing with Bonferroni ***: Bland Altman plots demonstrated significant disagreement between MEV measurement techniques. Differences between tympanometric(T) and 3DVR MEV values were significantly greater with increasing average(i.e.(Tt3DVR)/2)) MEV per linear regression(p < 0.0001). Significance was demonstrated between fourth and first average MEV quartiles(p= 0.0024), fourth and second quartiles(p= 0.0024), third and first quartiles(p= 0.0048), and third and second quartiles(p= 0.048). Absolute MEV difference was not significantly different across varying states of middle ear disease(p= 0.44).Conclusion: Statistically and clinically significant disagreement was demonstrated between tympanometric and 3DVR MEV values. Studies that vary in MEV estimation techniques may be expected to demonstrate significantly different results. These preliminary results suggest that clinicians should endeavor to seek further confirmation when interpreting high tympanometric MEV values.

关键词： Middle ear volume Tympanometry Three-dimensional volume reconstruction Tympanic membrane perforation

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