{"title":"An optimized convolutional neural network architecture for lung cancer detection.","authors":"Sameena Pathan, Tanweer Ali, Sudheesh P G, Vasanth Kumar P, Divya Rao","doi":"10.1063/5.0208520","DOIUrl":"10.1063/5.0208520","url":null,"abstract":"<p><p>Lung cancer, the treacherous malignancy affecting the respiratory system of a human body, has a devastating impact on the health and well-being of an individual. Due to the lack of automated and noninvasive diagnostic tools, healthcare professionals look forward toward biopsy as a gold standard for diagnosis. However, biopsy could be traumatizing and expensive process. Additionally, the limited availability of dataset and inaccuracy in diagnosis is a major drawback experienced by researchers. The objective of the proposed research is to develop an automated diagnostic tool for screening of lung cancer using optimized hyperparameters such that convolutional neural network (CNN) model generalizes well for universally obtained computerized tomography (CT) slices of lung pathologies. The aforementioned objective is achieved in the following ways: (i) Initially, a preprocessing methodology specific to lung CT scans is formulated to avoid the loss of information due to random image smoothing, and (ii) a sine cosine algorithm optimization algorithm (SCA) is integrated in the CNN model, to optimally select the tuning parameters of CNN. The error rate is used as an objective function, and the SCA algorithm tries to minimize. The proposed method successfully achieved an average classification accuracy of 99% in classification of lung scans in normal, benign, and malignant classes. Further, the generalization ability of the proposed model is tested on unseen dataset, thereby achieving promising results. The quantitative results prove the efficacy of the system to be used by radiologists in a clinical scenario.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 2","pages":"026121"},"PeriodicalIF":6.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11168751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-06-10eCollection Date: 2024-06-01DOI: 10.1063/5.0195249
Wenjun Wang, Matthew R Zanotelli, Lindsey N Sabo, Emily D Fabiano, Natalie M Goldfield, Chloe Le, Elle P Techasiriwan, Santiago Lopez, Emily D Berestesky, Cynthia A Reinhart-King
{"title":"Collagen density regulates tip-stalk cell rearrangement during angiogenesis via cellular bioenergetics.","authors":"Wenjun Wang, Matthew R Zanotelli, Lindsey N Sabo, Emily D Fabiano, Natalie M Goldfield, Chloe Le, Elle P Techasiriwan, Santiago Lopez, Emily D Berestesky, Cynthia A Reinhart-King","doi":"10.1063/5.0195249","DOIUrl":"10.1063/5.0195249","url":null,"abstract":"<p><p>Tumor vasculature plays a crucial role in tumor progression, affecting nutrition and oxygen transportation as well as the efficiency of drug delivery. While targeting pro-angiogenic growth factors has been a significant focus for treating tumor angiogenesis, recent studies indicate that metabolism also plays a role in regulating endothelial cell behavior. Like cancer cells, tumor endothelial cells undergo metabolic changes that regulate rearrangement for tip cell position during angiogenesis. Our previous studies have shown that altered mechanical properties of the collagen matrix regulate angiogenesis and can promote a tumor vasculature phenotype. Here, we examine the effect of collagen density on endothelial cell tip-stalk cell rearrangement and cellular energetics during angiogenic sprouting. We find that increased collagen density leads to an elevated energy state and an increased rate of tip-stalk cell switching, which is correlated with the energy state of the cells. Tip cells exhibit higher glucose uptake than stalk cells, and inhibition of glucose uptake revealed that invading sprouts rely on glucose to meet elevated energy requirements for invasion in dense matrices. This work helps to elucidate the complex interplay between the mechanical microenvironment and the endothelial cell metabolic status during angiogenesis, which could have important implications for developing new anti-cancer therapies.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 2","pages":"026120"},"PeriodicalIF":6.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11170328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-06-06eCollection Date: 2024-06-01DOI: 10.1063/5.0199024
Somayadineshraj Devarasou, Minwoo Kang, Jennifer H Shin
{"title":"Biophysical perspectives to understanding cancer-associated fibroblasts.","authors":"Somayadineshraj Devarasou, Minwoo Kang, Jennifer H Shin","doi":"10.1063/5.0199024","DOIUrl":"10.1063/5.0199024","url":null,"abstract":"<p><p>The understanding of cancer has evolved significantly, with the tumor microenvironment (TME) now recognized as a critical factor influencing the onset and progression of the disease. This broader perspective challenges the traditional view that cancer is primarily caused by mutations, instead emphasizing the dynamic interaction between different cell types and physicochemical factors within the TME. Among these factors, cancer-associated fibroblasts (CAFs) command attention for their profound influence on tumor behavior and patient prognoses. Despite their recognized importance, the biophysical and mechanical interactions of CAFs within the TME remain elusive. This review examines the distinctive physical characteristics of CAFs, their morphological attributes, and mechanical interactions within the TME. We discuss the impact of mechanotransduction on CAF function and highlight how these cells communicate mechanically with neighboring cancer cells, thereby shaping the path of tumor development and progression. By concentrating on the biomechanical regulation of CAFs, this review aims to deepen our understanding of their role in the TME and to illuminate new biomechanical-based therapeutic strategies.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 2","pages":"021507"},"PeriodicalIF":6.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11161195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141297005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-06-05eCollection Date: 2024-06-01DOI: 10.1063/5.0204393
Andrew M Howes, Nova C Dea, Deepraj Ghosh, Krishangi Krishna, Yihong Wang, Yanxi Li, Braxton Morrison, Kimani C Toussaint, Michelle R Dawson
{"title":"Fibroblast senescence-associated extracellular matrix promotes heterogeneous lung niche.","authors":"Andrew M Howes, Nova C Dea, Deepraj Ghosh, Krishangi Krishna, Yihong Wang, Yanxi Li, Braxton Morrison, Kimani C Toussaint, Michelle R Dawson","doi":"10.1063/5.0204393","DOIUrl":"10.1063/5.0204393","url":null,"abstract":"<p><p>Senescent cell accumulation in the pulmonary niche is associated with heightened susceptibility to age-related disease, tissue alterations, and ultimately a decline in lung function. Our current knowledge of senescent cell-extracellular matrix (ECM) dynamics is limited, and our understanding of how senescent cells influence spatial ECM architecture changes over time is incomplete. Herein is the design of an <i>in vitro</i> model of senescence-associated extracellular matrix (SA-ECM) remodeling using a senescent lung fibroblast-derived matrix that captures the spatiotemporal dynamics of an evolving senescent ECM architecture. Multiphoton second-harmonic generation microscopy was utilized to examine the spatial and temporal dynamics of fibroblast SA-ECM remodeling, which revealed a biphasic process that established a disordered and heterogeneous architecture. Additionally, we observed that inhibition of transforming growth factor-β signaling during SA-ECM remodeling led to improved local collagen fiber organization. Finally, we examined patient samples diagnosed with pulmonary fibrosis to further tie our results of the <i>in vitro</i> model to clinical outcomes. Moreover, we observed that the senescence marker p16 is correlated with local collagen fiber disorder. By elucidating the temporal dynamics of SA-ECM remodeling, we provide further insight on the role of senescent cells and their contributions to pathological ECM remodeling.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 2","pages":"026119"},"PeriodicalIF":6.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11161856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141297006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-06-03eCollection Date: 2024-06-01DOI: 10.1063/5.0189221
Finn Snow, Cathal O'Connell, Peiqi Yang, Magdalena Kita, Elena Pirogova, Richard J Williams, Rob M I Kapsa, Anita Quigley
{"title":"Engineering interfacial tissues: The myotendinous junction.","authors":"Finn Snow, Cathal O'Connell, Peiqi Yang, Magdalena Kita, Elena Pirogova, Richard J Williams, Rob M I Kapsa, Anita Quigley","doi":"10.1063/5.0189221","DOIUrl":"10.1063/5.0189221","url":null,"abstract":"<p><p>The myotendinous junction (MTJ) is the interface connecting skeletal muscle and tendon tissues. This specialized region represents the bridge that facilitates the transmission of contractile forces from muscle to tendon, and ultimately the skeletal system for the creation of movement. MTJs are, therefore, subject to high stress concentrations, rendering them susceptible to severe, life-altering injuries. Despite the scarcity of knowledge obtained from MTJ formation during embryogenesis, several attempts have been made to engineer this complex interfacial tissue. These attempts, however, fail to achieve the level of maturity and mechanical complexity required for <i>in vivo</i> transplantation. This review summarizes the strategies taken to engineer the MTJ, with an emphasis on how transitioning from static to mechanically inducive dynamic cultures may assist in achieving myotendinous maturity.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 2","pages":"021505"},"PeriodicalIF":6.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Insights into the mechanobiology of cancer metastasis via microfluidic technologies.","authors":"Lanfeng Liang, Xiao Song, Hao Zhao, Chwee Teck Lim","doi":"10.1063/5.0195389","DOIUrl":"10.1063/5.0195389","url":null,"abstract":"<p><p>During cancer metastasis, cancer cells will encounter various microenvironments with diverse physical characteristics. Changes in these physical characteristics such as tension, stiffness, viscosity, compression, and fluid shear can generate biomechanical cues that affect cancer cells, dynamically influencing numerous pathophysiological mechanisms. For example, a dense extracellular matrix drives cancer cells to reorganize their cytoskeleton structures, facilitating confined migration, while this dense and restricted space also acts as a physical barrier that potentially results in nuclear rupture. Identifying these pathophysiological processes and understanding their underlying mechanobiological mechanisms can aid in the development of more effective therapeutics targeted to cancer metastasis. In this review, we outline the advances of engineering microfluidic devices <i>in vitro</i> and their role in replicating tumor microenvironment to mimic <i>in vivo</i> settings. We highlight the potential cellular mechanisms that mediate their ability to adapt to different microenvironments. Meanwhile, we also discuss some important mechanical cues that still remain challenging to replicate in current microfluidic devices in future direction. While much remains to be explored about cancer mechanobiology, we believe the developments of microfluidic devices will reveal how these physical cues impact the behaviors of cancer cells. It will be crucial in the understanding of cancer metastasis, and potentially contributing to better drug development and cancer therapy.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 2","pages":"021506"},"PeriodicalIF":6.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Electrodynamic interaction between tumor treating fields and microtubule electrophysiological activities.","authors":"Xing Li, Kaida Liu, Haohan Fang, Zirong Liu, Yuchen Tang, Ping Dai","doi":"10.1063/5.0197900","DOIUrl":"10.1063/5.0197900","url":null,"abstract":"<p><p>Tumor treating fields (TTFields) are a type of sinusoidal alternating current electric field that has proven effective in inhibiting the reproduction of dividing tumor cells. Despite their recognized impact, the precise biophysical mechanisms underlying the unique effects of TTFields remain unknown. Many of the previous studies predominantly attribute the inhibitory effects of TTFields to mitotic disruption, with intracellular microtubules identified as crucial targets. However, this conceptual framework lacks substantiation at the mesoscopic level. This study addresses the existing gap by constructing force models for tubulin and other key subcellular structures involved in microtubule electrophysiological activities under TTFields exposure. The primary objective is to explore whether the electric force or torque exerted by TTFields significantly influences the normal structure and activities of microtubules. Initially, we examine the potential effect on the dynamic stability of microtubule structures by calculating the electric field torque on the tubulin dimer orientation. Furthermore, given the importance of electrostatics in microtubule-associated activities, such as chromosome segregation and substance transport of kinesin during mitosis, we investigate the interaction between TTFields and these electrostatic processes. Our data show that the electrodynamic effects of TTFields are most likely too weak to disrupt normal microtubule electrophysiological activities significantly. Consequently, we posit that the observed cytoskeleton destruction in mitosis is more likely attributable to non-mechanical mechanisms.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 2","pages":"026118"},"PeriodicalIF":6.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-05-30eCollection Date: 2024-06-01DOI: 10.1063/5.0198382
Sabrina N Campelo, Zaid S Salameh, Julio P Arroyo, James L May, Sara O Altreuter, Jonathan Hinckley, Rafael V Davalos, John H Rossmeisl
{"title":"Burst sine wave electroporation (B-SWE) for expansive blood-brain barrier disruption and controlled non-thermal tissue ablation for neurological disease.","authors":"Sabrina N Campelo, Zaid S Salameh, Julio P Arroyo, James L May, Sara O Altreuter, Jonathan Hinckley, Rafael V Davalos, John H Rossmeisl","doi":"10.1063/5.0198382","DOIUrl":"10.1063/5.0198382","url":null,"abstract":"<p><p>The blood-brain barrier (BBB) limits the efficacy of treatments for malignant brain tumors, necessitating innovative approaches to breach the barrier. This study introduces burst sine wave electroporation (B-SWE) as a strategic modality for controlled BBB disruption without extensive tissue ablation and compares it against conventional pulsed square wave electroporation-based technologies such as high-frequency irreversible electroporation (H-FIRE). Using an <i>in vivo</i> rodent model, B-SWE and H-FIRE effects on BBB disruption, tissue ablation, and neuromuscular contractions are compared. Equivalent waveforms were designed for direct comparison between the two pulsing schemes, revealing that B-SWE induces larger BBB disruption volumes while minimizing tissue ablation. While B-SWE exhibited heightened neuromuscular contractions when compared to equivalent H-FIRE waveforms, an additional low-dose B-SWE group demonstrated that a reduced potential can achieve similar levels of BBB disruption while minimizing neuromuscular contractions. Repair kinetics indicated faster closure post B-SWE-induced BBB disruption when compared to equivalent H-FIRE protocols, emphasizing B-SWE's transient and controllable nature. Additionally, finite element modeling illustrated the potential for extensive BBB disruption while reducing ablation using B-SWE. B-SWE presents a promising avenue for tailored BBB disruption with minimal tissue ablation, offering a nuanced approach for glioblastoma treatment and beyond.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 2","pages":"026117"},"PeriodicalIF":6.0,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Silk fibroin promotes H3K9me3 expression and chromatin reorganization to regulate endothelial cell proliferation.","authors":"Kaixiang Gao, Yafan Xie, Fangning Xu, Qin Peng, Li Fu, Guixue Wang, Juhui Qiu","doi":"10.1063/5.0203858","DOIUrl":"10.1063/5.0203858","url":null,"abstract":"<p><p>Silk fibroin (SF), which is extensively utilized in tissue engineering and vascular grafts for enhancing vascular regeneration, has not been thoroughly investigated for its epigenetic effects on endothelial cells (EC). This study employed RNA sequencing analysis to evaluate the activation of histone modification regulatory genes in EC treated with SF. Subsequent investigations revealed elevated H3K9me3 levels in SF-treated EC, as evidenced by immunofluorescence and western blot analysis. The study utilized H2B-eGFP endothelial cells to demonstrate that SF treatment results in the accumulation of H2B-marked chromatin in the nuclear inner cavities of EC. Inhibition of H3K9me3 levels by a histone deacetylase inhibitor TSA decreased cell proliferation. Furthermore, the activation of the MAPK signaling pathway using chromium picolinate decreased the proliferative activity and H3K9me3 level in SF-treated EC. SF also appeared to enhance cell growth and proliferation by modulating the H3K9me3 level and reorganizing chromatin, particularly after oxidative stress induced by H<sub>2</sub>O<sub>2</sub> treatment. In summary, these findings indicate that SF promotes EC proliferation by increasing the H3K9me3 level even under stress conditions.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 2","pages":"026115"},"PeriodicalIF":6.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
APL BioengineeringPub Date : 2024-05-29eCollection Date: 2024-06-01DOI: 10.1063/5.0204201
Alessandro Gulotta, Saskia Bucciarelli, Felix Roosen-Runge, Olaf Holderer, Peter Schurtenberger, Anna Stradner
{"title":"Testing mixing rules for structural and dynamical quantities in multi-component crowded protein solutions.","authors":"Alessandro Gulotta, Saskia Bucciarelli, Felix Roosen-Runge, Olaf Holderer, Peter Schurtenberger, Anna Stradner","doi":"10.1063/5.0204201","DOIUrl":"10.1063/5.0204201","url":null,"abstract":"<p><p>Crowding effects significantly influence the phase behavior and the structural and dynamic properties of the concentrated protein mixtures present in the cytoplasm of cells or in the blood serum. This poses enormous difficulties for our theoretical understanding and our ability to predict the behavior of these systems. While the use of course grained colloid-inspired models allows us to reproduce the key physical solution properties of concentrated monodisperse solutions of individual proteins, we lack corresponding theories for complex polydisperse mixtures. Here, we test the applicability of simple mixing rules in order to predict solution properties of protein mixtures. We use binary mixtures of the well-characterized bovine eye lens proteins <i>α</i> and <i>γ<sub>B</sub></i> crystallin as model systems. Combining microrheology with static and dynamic scattering techniques and observations of the phase diagram for liquid-liquid phase separation, we show that reasonably accurate descriptions are possible for macroscopic and mesoscopic signatures, while information on the length scale of the individual protein size requires more information on cross-component interaction.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":"8 2","pages":"026116"},"PeriodicalIF":6.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}