Stefan G. Stanciu, Karsten König, Young Min Song, Lior Wolf, Costas A. Charitidis, Paolo Bianchini, Martin Goetz
{"title":"Toward next-generation endoscopes integrating biomimetic video systems, nonlinear optical microscopy, and deep learning","authors":"Stefan G. Stanciu, Karsten König, Young Min Song, Lior Wolf, Costas A. Charitidis, Paolo Bianchini, Martin Goetz","doi":"10.1063/5.0133027","DOIUrl":"https://doi.org/10.1063/5.0133027","url":null,"abstract":"According to the World Health Organization, the proportion of the world's population over 60 years will approximately double by 2050. This progressive increase in the elderly population will lead to a dramatic growth of age-related diseases, resulting in tremendous pressure on the sustainability of healthcare systems globally. In this context, finding more efficient ways to address cancers, a set of diseases whose incidence is correlated with age, is of utmost importance. Prevention of cancers to decrease morbidity relies on the identification of precursor lesions before the onset of the disease, or at least diagnosis at an early stage. In this article, after briefly discussing some of the most prominent endoscopic approaches for gastric cancer diagnostics, we review relevant progress in three emerging technologies that have significant potential to play pivotal roles in next-generation endoscopy systems: biomimetic vision (with special focus on compound eye cameras), non-linear optical microscopies, and Deep Learning. Such systems are urgently needed to enhance the three major steps required for the successful diagnostics of gastrointestinal cancers: detection, characterization, and confirmation of suspicious lesions. In the final part, we discuss challenges that lie en route to translating these technologies to next-generation endoscopes that could enhance gastrointestinal imaging, and depict a possible configuration of a system capable of (i) biomimetic endoscopic vision enabling easier detection of lesions, (ii) label-free in vivo tissue characterization, and (iii) intelligently automated gastrointestinal cancer diagnostic.","PeriodicalId":72405,"journal":{"name":"Biophysics reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136177392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biophysics reviewsPub Date : 2023-03-01Epub Date: 2023-02-21DOI: 10.1063/5.0131452
Made Harumi Padmaswari, Shilpi Agrawal, Mary S Jia, Allie Ivy, Daniel A Maxenberger, Landon A Burcham, Christopher E Nelson
{"title":"Delivery challenges for CRISPR-Cas9 genome editing for Duchenne muscular dystrophy.","authors":"Made Harumi Padmaswari, Shilpi Agrawal, Mary S Jia, Allie Ivy, Daniel A Maxenberger, Landon A Burcham, Christopher E Nelson","doi":"10.1063/5.0131452","DOIUrl":"10.1063/5.0131452","url":null,"abstract":"<p><p>Duchene muscular dystrophy (DMD) is an X-linked neuromuscular disorder that affects about one in every 5000 live male births. DMD is caused by mutations in the gene that codes for dystrophin, which is required for muscle membrane stabilization. The loss of functional dystrophin causes muscle degradation that leads to weakness, loss of ambulation, cardiac and respiratory complications, and eventually, premature death. Therapies to treat DMD have advanced in the past decade, with treatments in clinical trials and four exon-skipping drugs receiving conditional Food and Drug Administration approval. However, to date, no treatment has provided long-term correction. Gene editing has emerged as a promising approach to treating DMD. There is a wide range of tools, including meganucleases, zinc finger nucleases, transcription activator-like effector nucleases, and, most notably, RNA-guided enzymes from the bacterial adaptive immune system clustered regularly interspaced short palindromic repeats (CRISPR). Although challenges in using CRISPR for gene therapy in humans still abound, including safety and efficiency of delivery, the future for CRISPR gene editing for DMD is promising. This review will summarize the progress in CRISPR gene editing for DMD including key summaries of current approaches, delivery methodologies, and the challenges that gene editing still faces as well as prospective solutions.</p>","PeriodicalId":72405,"journal":{"name":"Biophysics reviews","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9969352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10106795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biophysics reviewsPub Date : 2023-03-01Epub Date: 2023-01-13DOI: 10.1063/5.0109400
Erica L Schwarz, Luca Pegolotti, Martin R Pfaller, Alison L Marsden
{"title":"Beyond CFD: Emerging methodologies for predictive simulation in cardiovascular health and disease.","authors":"Erica L Schwarz, Luca Pegolotti, Martin R Pfaller, Alison L Marsden","doi":"10.1063/5.0109400","DOIUrl":"10.1063/5.0109400","url":null,"abstract":"<p><p>Physics-based computational models of the cardiovascular system are increasingly used to simulate hemodynamics, tissue mechanics, and physiology in evolving healthy and diseased states. While predictive models using computational fluid dynamics (CFD) originated primarily for use in surgical planning, their application now extends well beyond this purpose. In this review, we describe an increasingly wide range of modeling applications aimed at uncovering fundamental mechanisms of disease progression and development, performing model-guided design, and generating testable hypotheses to drive targeted experiments. Increasingly, models are incorporating multiple physical processes spanning a wide range of time and length scales in the heart and vasculature. With these expanded capabilities, clinical adoption of patient-specific modeling in congenital and acquired cardiovascular disease is also increasing, impacting clinical care and treatment decisions in complex congenital heart disease, coronary artery disease, vascular surgery, pulmonary artery disease, and medical device design. In support of these efforts, we discuss recent advances in modeling methodology, which are most impactful when driven by clinical needs. We describe pivotal recent developments in image processing, fluid-structure interaction, modeling under uncertainty, and reduced order modeling to enable simulations in clinically relevant timeframes. In all these areas, we argue that traditional CFD alone is insufficient to tackle increasingly complex clinical and biological problems across scales and systems. Rather, CFD should be coupled with appropriate multiscale biological, physical, and physiological models needed to produce comprehensive, impactful models of mechanobiological systems and complex clinical scenarios. With this perspective, we finally outline open problems and future challenges in the field.</p>","PeriodicalId":72405,"journal":{"name":"Biophysics reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10641949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biophysics reviewsPub Date : 2023-03-01Epub Date: 2023-03-29DOI: 10.1063/5.0141269
Chenyan Wang, Ghiska Ramahdita, Guy Genin, Nathaniel Huebsch, Zhen Ma
{"title":"Dynamic mechanobiology of cardiac cells and tissues: Current status and future perspective.","authors":"Chenyan Wang, Ghiska Ramahdita, Guy Genin, Nathaniel Huebsch, Zhen Ma","doi":"10.1063/5.0141269","DOIUrl":"10.1063/5.0141269","url":null,"abstract":"<p><p>Mechanical forces impact cardiac cells and tissues over their entire lifespan, from development to growth and eventually to pathophysiology. However, the mechanobiological pathways that drive cell and tissue responses to mechanical forces are only now beginning to be understood, due in part to the challenges in replicating the evolving dynamic microenvironments of cardiac cells and tissues in a laboratory setting. Although many <i>in vitro</i> cardiac models have been established to provide specific stiffness, topography, or viscoelasticity to cardiac cells and tissues via biomaterial scaffolds or external stimuli, technologies for presenting time-evolving mechanical microenvironments have only recently been developed. In this review, we summarize the range of <i>in vitro</i> platforms that have been used for cardiac mechanobiological studies. We provide a comprehensive review on phenotypic and molecular changes of cardiomyocytes in response to these environments, with a focus on how dynamic mechanical cues are transduced and deciphered. We conclude with our vision of how these findings will help to define the baseline of heart pathology and of how these <i>in vitro</i> systems will potentially serve to improve the development of therapies for heart diseases.</p>","PeriodicalId":72405,"journal":{"name":"Biophysics reviews","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10062054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9296630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biophysics reviewsPub Date : 2023-03-01Epub Date: 2023-03-30DOI: 10.1063/5.0127713
Jonathan D Moreno, Jonathan R Silva
{"title":"Emerging methods to model cardiac ion channel and myocyte electrophysiology.","authors":"Jonathan D Moreno, Jonathan R Silva","doi":"10.1063/5.0127713","DOIUrl":"10.1063/5.0127713","url":null,"abstract":"<p><p>In the field of cardiac electrophysiology, modeling has played a central role for many decades. However, even though the effort is well-established, it has recently seen a rapid and sustained evolution in the complexity and predictive power of the models being created. In particular, new approaches to modeling have allowed the tracking of parallel and interconnected processes that span from the nanometers and femtoseconds that determine ion channel gating to the centimeters and minutes needed to describe an arrhythmia. The connection between scales has brought unprecedented insight into cardiac arrhythmia mechanisms and drug therapies. This review focuses on the generation of these models from first principles, generation of detailed models to describe ion channel kinetics, algorithms to create and numerically solve kinetic models, and new approaches toward data gathering that parameterize these models. While we focus on application of these models for cardiac arrhythmia, these concepts are widely applicable to model the physiology and pathophysiology of any excitable cell.</p>","PeriodicalId":72405,"journal":{"name":"Biophysics reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10071990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9870237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biophysics reviewsPub Date : 2023-03-01Epub Date: 2023-03-28DOI: 10.1063/5.0123664
Kemao Xiu, Jifeng Zhang, Jie Xu, Y Eugene Chen, Peter X Ma
{"title":"Recent progress in polymeric gene vectors: Delivery mechanisms, molecular designs, and applications.","authors":"Kemao Xiu, Jifeng Zhang, Jie Xu, Y Eugene Chen, Peter X Ma","doi":"10.1063/5.0123664","DOIUrl":"10.1063/5.0123664","url":null,"abstract":"<p><p>Gene therapy and gene delivery have drawn extensive attention in recent years especially when the COVID-19 mRNA vaccines were developed to prevent severe symptoms caused by the corona virus. Delivering genes, such as DNA and RNA into cells, is the crucial step for successful gene therapy and remains a bottleneck. To address this issue, vehicles (vectors) that can load and deliver genes into cells are developed, including viral and non-viral vectors. Although viral gene vectors have considerable transfection efficiency and lipid-based gene vectors become popular since the application of COVID-19 vaccines, their potential issues including immunologic and biological safety concerns limited their applications. Alternatively, polymeric gene vectors are safer, cheaper, and more versatile compared to viral and lipid-based vectors. In recent years, various polymeric gene vectors with well-designed molecules were developed, achieving either high transfection efficiency or showing advantages in certain applications. In this review, we summarize the recent progress in polymeric gene vectors including the transfection mechanisms, molecular designs, and biomedical applications. Commercially available polymeric gene vectors/reagents are also introduced. Researchers in this field have never stopped seeking safe and efficient polymeric gene vectors via rational molecular designs and biomedical evaluations. The achievements in recent years have significantly accelerated the progress of polymeric gene vectors toward clinical applications.</p>","PeriodicalId":72405,"journal":{"name":"Biophysics reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10062053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9296631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biophysics reviewsPub Date : 2023-03-01Epub Date: 2023-03-13DOI: 10.1063/5.0131972
Bing Ren, Zhihua Jiang, Walter Lee Murfee, Adam J Katz, Dietmar Siemann, Yong Huang
{"title":"Realizations of vascularized tissues: From <i>in vitro</i> platforms to <i>in vivo</i> grafts.","authors":"Bing Ren, Zhihua Jiang, Walter Lee Murfee, Adam J Katz, Dietmar Siemann, Yong Huang","doi":"10.1063/5.0131972","DOIUrl":"10.1063/5.0131972","url":null,"abstract":"<p><p>Vascularization is essential for realizing thick and functional tissue constructs that can be utilized for <i>in vitro</i> study platforms and <i>in vivo</i> grafts. The vasculature enables the transport of nutrients, oxygen, and wastes and is also indispensable to organ functional units such as the nephron filtration unit, the blood-air barrier, and the blood-brain barrier. This review aims to discuss the latest progress of organ-like vascularized constructs with specific functionalities and realizations even though they are not yet ready to be used as organ substitutes. First, the human vascular system is briefly introduced and related design considerations for engineering vascularized tissues are discussed. Second, up-to-date creation technologies for vascularized tissues are summarized and classified into the engineering and cellular self-assembly approaches. Third, recent applications ranging from <i>in vitro</i> tissue models, including generic vessel models, tumor models, and different human organ models such as heart, kidneys, liver, lungs, and brain, to prevascularized <i>in vivo</i> grafts for implantation and anastomosis are discussed in detail. The specific design considerations for the aforementioned applications are summarized and future perspectives regarding future clinical applications and commercialization are provided.</p>","PeriodicalId":72405,"journal":{"name":"Biophysics reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10015415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9621060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Deep learning in spatial transcriptomics: Learning from the next next-generation sequencing","authors":"A. Ali Heydari, Suzanne S. Sindi","doi":"10.1063/5.0091135","DOIUrl":"https://doi.org/10.1063/5.0091135","url":null,"abstract":"Spatial transcriptomics (ST) technologies are rapidly becoming the extension of single-cell RNA sequencing (scRNAseq), holding the potential of profiling gene expression at a single-cell resolution while maintaining cellular compositions within a tissue. Having both expression profiles and tissue organization enables researchers to better understand cellular interactions and heterogeneity, providing insight into complex biological processes that would not be possible with traditional sequencing technologies. Data generated by ST technologies are inherently noisy, high-dimensional, sparse, and multi-modal (including histological images, count matrices, etc.), thus requiring specialized computational tools for accurate and robust analysis. However, many ST studies currently utilize traditional scRNAseq tools, which are inadequate for analyzing complex ST datasets. On the other hand, many of the existing ST-specific methods are built upon traditional statistical or machine learning frameworks, which have shown to be sub-optimal in many applications due to the scale, multi-modality, and limitations of spatially resolved data (such as spatial resolution, sensitivity, and gene coverage). Given these intricacies, researchers have developed deep learning (DL)-based models to alleviate ST-specific challenges. These methods include new state-of-the-art models in alignment, spatial reconstruction, and spatial clustering, among others. However, DL models for ST analysis are nascent and remain largely underexplored. In this review, we provide an overview of existing state-of-the-art tools for analyzing spatially resolved transcriptomics while delving deeper into the DL-based approaches. We discuss the new frontiers and the open questions in this field and highlight domains in which we anticipate transformational DL applications.","PeriodicalId":72405,"journal":{"name":"Biophysics reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136181299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biophysics reviewsPub Date : 2022-12-01Epub Date: 2022-11-04DOI: 10.1063/5.0057434
Tessa Altair Morris, Sarah Eldeen, Richard Duc Hien Tran, Anna Grosberg
{"title":"A comprehensive review of computational and image analysis techniques for quantitative evaluation of striated muscle tissue architecture.","authors":"Tessa Altair Morris, Sarah Eldeen, Richard Duc Hien Tran, Anna Grosberg","doi":"10.1063/5.0057434","DOIUrl":"10.1063/5.0057434","url":null,"abstract":"<p><p>Unbiased evaluation of morphology is crucial to understanding development, mechanics, and pathology of striated muscle tissues. Indeed, the ability of striated muscles to contract and the strength of their contraction is dependent on their tissue-, cellular-, and cytoskeletal-level organization. Accordingly, the study of striated muscles often requires imaging and assessing aspects of their architecture at multiple different spatial scales. While an expert may be able to qualitatively appraise tissues, it is imperative to have robust, repeatable tools to quantify striated myocyte morphology and behavior that can be used to compare across different labs and experiments. There has been a recent effort to define the criteria used by experts to evaluate striated myocyte architecture. In this review, we will describe metrics that have been developed to summarize distinct aspects of striated muscle architecture in multiple different tissues, imaged with various modalities. Additionally, we will provide an overview of metrics and image processing software that needs to be developed. Importantly to any lab working on striated muscle platforms, characterization of striated myocyte morphology using the image processing pipelines discussed in this review can be used to quantitatively evaluate striated muscle tissues and contribute to a robust understanding of the development and mechanics of striated muscles.</p>","PeriodicalId":72405,"journal":{"name":"Biophysics reviews","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9667907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40699167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biophysics reviewsPub Date : 2022-09-01Epub Date: 2022-09-13DOI: 10.1063/5.0096420
Christina Y Sheng, Young Hoon Son, Jeongin Jang, Sung-Jin Park
{"title":"<i>In vitro</i> skeletal muscle models for type 2 diabetes.","authors":"Christina Y Sheng, Young Hoon Son, Jeongin Jang, Sung-Jin Park","doi":"10.1063/5.0096420","DOIUrl":"10.1063/5.0096420","url":null,"abstract":"<p><p>Type 2 diabetes mellitus, a metabolic disorder characterized by abnormally elevated blood sugar, poses a growing social, economic, and medical burden worldwide. The skeletal muscle is the largest metabolic organ responsible for glucose homeostasis in the body, and its inability to properly uptake sugar often precedes type 2 diabetes. Although exercise is known to have preventative and therapeutic effects on type 2 diabetes, the underlying mechanism of these beneficial effects is largely unknown. Animal studies have been conducted to better understand the pathophysiology of type 2 diabetes and the positive effects of exercise on type 2 diabetes. However, the complexity of <i>in vivo</i> systems and the inability of animal models to fully capture human type 2 diabetes genetics and pathophysiology are two major limitations in these animal studies. Fortunately, <i>in vitro</i> models capable of recapitulating human genetics and physiology provide promising avenues to overcome these obstacles. This review summarizes current <i>in vitro</i> type 2 diabetes models with focuses on the skeletal muscle, interorgan crosstalk, and exercise. We discuss diabetes, its pathophysiology, common <i>in vitro</i> type 2 diabetes skeletal muscle models, interorgan crosstalk type 2 diabetes models, exercise benefits on type 2 diabetes, and <i>in vitro</i> type 2 diabetes models with exercise.</p>","PeriodicalId":72405,"journal":{"name":"Biophysics reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9478902/pdf/BRIEIM-000003-031306_1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10632609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}