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  1. Article: Comparison of digital and traditional skin wound closure assessment methods in mice.

    Huang, Coco X / Siwan, Elisha / Fox, Sarah L / Longfield, Matilda / Twigg, Stephen M / Min, Danqing

    Laboratory animal research

    2023  Volume 39, Issue 1, Page(s) 25

    Abstract: Background: Chronic skin wounds are a common complication of many diseases such as diabetes. Various traditional methods for assessing skin wound closure are used in animal studies, including wound tracing, calliper measurements and histological ... ...

    Abstract Background: Chronic skin wounds are a common complication of many diseases such as diabetes. Various traditional methods for assessing skin wound closure are used in animal studies, including wound tracing, calliper measurements and histological analysis. However, these methods have poorly defined wound closure or practical limitations. Digital image analysis of wounds is an increasingly popular, accessible alternative, but it is unclear whether digital assessment is consistent with traditional methods. This study aimed to optimise and compare digital wound closure assessment with traditional methods, using a diabetic mouse model. Diabetes was induced in male C57BL/6J mice by high-fat diet feeding combined with low dose (65 mg/kg of body weight) streptozotocin injections. Mice fed normal chow were included as controls. After 18 weeks, four circular full-thickness dorsal skin wounds of 4 mm diameter were created per mouse. The wounds were photographed and measured by callipers. Wound closure rate (WCR) was digitally assessed by two reporters using two methods: wound outline (WCR-O) and re-epithelialisation (WCR-E). Wounded skin tissues were collected at 10-days post-wounding and wound width was measured from haematoxylin and eosin-stained skin tissue.
    Results: Between reporters, WCR-O was more consistent than WCR-E, and WCR-O correlated with calliper measurements. Histological analysis supported digital assessments, especially WCR-E, when wounds were histologically closed.
    Conclusions: WCR-O could replace calliper measurements to measure skin wound closure, but WCR-E assessment requires further refinement. Small animal studies of skin wound healing can greatly benefit from standardised definitions of wound closure and more consistent digital assessment protocols.
    Language English
    Publishing date 2023-10-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 2623220-0
    ISSN 2233-7660 ; 1738-6055
    ISSN (online) 2233-7660
    ISSN 1738-6055
    DOI 10.1186/s42826-023-00176-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Imaging-guided bioreactor for de-epithelialization and long-term cultivation of

    Mir, Seyed Mohammad / Chen, Jiawen / Pinezich, Meghan R / O'Neill, John D / Huang, Sarah X L / Vunjak-Novakovic, Gordana / Kim, Jinho

    Lab on a chip

    2022  Volume 22, Issue 5, Page(s) 1018–1031

    Abstract: Recent synergistic advances in organ-on-chip and tissue engineering technologies offer opportunities to ... ...

    Abstract Recent synergistic advances in organ-on-chip and tissue engineering technologies offer opportunities to create
    MeSH term(s) Animals ; Bioreactors ; Cartilage ; Rats ; Re-Epithelialization ; Tissue Engineering/methods ; Tissue Scaffolds ; Trachea
    Language English
    Publishing date 2022-03-01
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2056646-3
    ISSN 1473-0189 ; 1473-0197
    ISSN (online) 1473-0189
    ISSN 1473-0197
    DOI 10.1039/d1lc01105g
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Comparison of digital and traditional skin wound closure assessment methods in mice

    Coco X. Huang / Elisha Siwan / Sarah L. Fox / Matilda Longfield / Stephen M. Twigg / Danqing Min

    Laboratory Animal Research, Vol 39, Iss 1, Pp 1-

    2023  Volume 9

    Abstract: Abstract Background Chronic skin wounds are a common complication of many diseases such as diabetes. Various traditional methods for assessing skin wound closure are used in animal studies, including wound tracing, calliper measurements and histological ... ...

    Abstract Abstract Background Chronic skin wounds are a common complication of many diseases such as diabetes. Various traditional methods for assessing skin wound closure are used in animal studies, including wound tracing, calliper measurements and histological analysis. However, these methods have poorly defined wound closure or practical limitations. Digital image analysis of wounds is an increasingly popular, accessible alternative, but it is unclear whether digital assessment is consistent with traditional methods. This study aimed to optimise and compare digital wound closure assessment with traditional methods, using a diabetic mouse model. Diabetes was induced in male C57BL/6J mice by high-fat diet feeding combined with low dose (65 mg/kg of body weight) streptozotocin injections. Mice fed normal chow were included as controls. After 18 weeks, four circular full-thickness dorsal skin wounds of 4 mm diameter were created per mouse. The wounds were photographed and measured by callipers. Wound closure rate (WCR) was digitally assessed by two reporters using two methods: wound outline (WCR-O) and re-epithelialisation (WCR-E). Wounded skin tissues were collected at 10-days post-wounding and wound width was measured from haematoxylin and eosin-stained skin tissue. Results Between reporters, WCR-O was more consistent than WCR-E, and WCR-O correlated with calliper measurements. Histological analysis supported digital assessments, especially WCR-E, when wounds were histologically closed. Conclusions WCR-O could replace calliper measurements to measure skin wound closure, but WCR-E assessment requires further refinement. Small animal studies of skin wound healing can greatly benefit from standardised definitions of wound closure and more consistent digital assessment protocols.
    Keywords Digital imaging ; Wound closure rate ; Skin wound ; Wound healing ; Mouse model ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
    Subject code 571 ; 616
    Language English
    Publishing date 2023-10-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Homogeneous Distribution of Exogenous Cells onto De-epithelialized Rat Trachea via Instillation of Cell-Loaded Hydrogel.

    Chen, Jiawen / Mir, Seyed Mohammad / Pinezich, Meghan R / O'Neill, John D / Guenthart, Brandon A / Bacchetta, Matthew / Vunjak-Novakovic, Gordana / Huang, Sarah X L / Kim, Jinho

    ACS biomaterials science & engineering

    2021  Volume 8, Issue 1, Page(s) 82–88

    Abstract: Injured or diseased airway epithelium due to repeated environmental insults or genetic mutations can lead to a functional decline of the lung and incurable lung diseases. Bioengineered airway tissue constructs can ... ...

    Abstract Injured or diseased airway epithelium due to repeated environmental insults or genetic mutations can lead to a functional decline of the lung and incurable lung diseases. Bioengineered airway tissue constructs can facilitate
    MeSH term(s) Animals ; Epithelial Cells ; Hydrogels ; Lung ; Rats ; Tissue Engineering ; Trachea
    Chemical Substances Hydrogels
    Language English
    Publishing date 2021-12-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2373-9878
    ISSN (online) 2373-9878
    DOI 10.1021/acsbiomaterials.1c01031
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Non-destructive vacuum-assisted measurement of lung elastic modulus.

    Chen, Jiawen / Mir, Mohammad / Pinezich, Meghan R / O'Neill, John D / Guenthart, Brandon A / Bacchetta, Matthew / Vunjak-Novakovic, Gordana / Huang, Sarah X L / Kim, Jinho

    Acta biomaterialia

    2021  Volume 131, Page(s) 370–380

    Abstract: In living tissues, mechanical stiffness and biological function are intrinsically linked. Alterations in the stiffness of tissues can induce pathological interactions that affect cellular activity and tissue function. Underlying connections between ... ...

    Abstract In living tissues, mechanical stiffness and biological function are intrinsically linked. Alterations in the stiffness of tissues can induce pathological interactions that affect cellular activity and tissue function. Underlying connections between tissue stiffness and disease highlights the importance of accurate quantitative characterizations of soft tissue mechanics, which can improve our understanding of disease and inform therapeutic development. In particular, accurate measurement of lung mechanical properties has been especially challenging due to the anatomical and mechanobiological complexities of the lung. Discrepancies between measured mechanical properties of dissected lung tissue samples and intact lung tissues in vivo has limited the ability to accurately characterize integral lung mechanics. Here, we report a non-destructive vacuum-assisted method to evaluate mechanical properties of soft biomaterials, including intact tissues and hydrogels. Using this approach, we measured elastic moduli of rat lung tissue that varied depending on stress-strain distribution throughout the lung. We also observed that the elastic moduli of enzymatically disrupted lung parenchyma increased by at least 64%. The reported methodology enables assessment of the nonlinear viscoelastic characteristics of intact lungs under normal and abnormal (i.e., injured, diseased) conditions and allows measurement of mechanical properties of tissue-mimetic biomaterials for use in therapeutics or in vitro models. STATEMENT OF SIGNIFICANCE: Accurate quantification of tissue stiffness is critical for understanding mechanisms of disease and developing effective therapeutics. Current modalities to measure tissue stiffness are destructive and preclude accurate assessment of lung mechanical properties, as lung mechanics are determined by complex features of the intact lung. To address the need for alternative methods to assess lung mechanics, we report a non-destructive vacuum-based approach to quantify tissue stiffness. We applied this method to correlate lung tissue mechanics with tissue disruption, and to assess the stiffness of biomaterials. This method can be used to inform the development of tissue-mimetic materials for use in therapeutics and disease models, and could potentially be applied for in-situ evaluation of tissue stiffness as a diagnostic or prognostic tool.
    MeSH term(s) Animals ; Elastic Modulus ; Hydrogels ; Lung ; Rats
    Chemical Substances Hydrogels
    Language English
    Publishing date 2021-06-27
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2173841-5
    ISSN 1878-7568 ; 1742-7061
    ISSN (online) 1878-7568
    ISSN 1742-7061
    DOI 10.1016/j.actbio.2021.06.037
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Stem cells of the respiratory system: from identification to differentiation into functional epithelium.

    Green, Michael D / Huang, Sarah X L / Snoeck, Hans-Willem

    BioEssays : news and reviews in molecular, cellular and developmental biology

    2013  Volume 35, Issue 3, Page(s) 261–270

    Abstract: We review recent progress in the stem cell biology of the respiratory system, and discuss its scientific and translational ramifications. Several studies have defined novel stem cells in postnatal lung and airways and implicated their roles in tissue ... ...

    Abstract We review recent progress in the stem cell biology of the respiratory system, and discuss its scientific and translational ramifications. Several studies have defined novel stem cells in postnatal lung and airways and implicated their roles in tissue homeostasis and repair. In addition, significant advances in the generation of respiratory epithelium from pluripotent stem cells (PSCs) now provide a novel and powerful platform for understanding lung development, modeling pulmonary diseases, and implementing drug screening. Finally, breakthroughs have been made in the generation of decellularized lung matrices that can serve as a scaffold for repopulation with respiratory cells derived from either postnatal or PSCs. These studies are a critical step forward towards the still distant goal of stem cell-based regenerative medicine for diseases of lung and airways.
    MeSH term(s) Animals ; Cell Differentiation ; Epithelial Cells/cytology ; Epithelium/growth & development ; Humans ; Respiratory System/cytology ; Stem Cells/cytology
    Language English
    Publishing date 2013-03
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 50140-2
    ISSN 1521-1878 ; 0265-9247
    ISSN (online) 1521-1878
    ISSN 0265-9247
    DOI 10.1002/bies.201200090
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  7. Article ; Online: HIV vaccines induce CD8

    Migueles, Stephen A / Nettere, Danielle M / Gavil, Noah V / Wang, Lawrence T / Toulmin, Sushila A / Kelly, Elizabeth P / Ward, Addison J / Lin, Siying / Thompson, Sarah A / Peterson, Bennett A / Abdeen, Cassidy S / Sclafani, Carina R / Pryal, Patrick F / Leach, Benjamin G / Ludwig, Amanda K / Rogan, Daniel C / Przygonska, Paulina A / Cattani, Angela / Imamichi, Hiromi /
    Sachs, Abraham / Cafri, Gal / Huang, Ning-Na / Patamawenu, Andy / Liang, C Jason / Hallahan, Claire W / Kambach, Diane M / Han, Edward X / Coupet, Tiffany / Chen, Jonathan / Moir, Susan L / Chun, Tae-Wook / Coates, Emily E / Ledgerwood, Julie / Schmidt, Julien / Taillandier-Coindard, Marie / Michaux, Justine / Pak, HuiSong / Bassani-Sternberg, Michal / Frahm, Nicole / McElrath, M Juliana / Connors, Mark

    Science (New York, N.Y.)

    2023  Volume 382, Issue 6676, Page(s) 1270–1276

    Abstract: Current HIV vaccines designed to stimulate ... ...

    Abstract Current HIV vaccines designed to stimulate CD8
    MeSH term(s) Humans ; AIDS Vaccines/immunology ; Clone Cells ; HIV Infections/prevention & control ; Receptors, Antigen, T-Cell/metabolism ; Cytotoxicity, Immunologic ; T-Lymphocytes, Cytotoxic/immunology ; Cell Degranulation/immunology
    Chemical Substances AIDS Vaccines ; Receptors, Antigen, T-Cell
    Language English
    Publishing date 2023-12-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.adg0514
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  8. Article ; Online: Hereditary retinoblastoma iPSC model reveals aberrant spliceosome function driving bone malignancies.

    Tu, Jian / Huo, Zijun / Yu, Yao / Zhu, Dandan / Xu, An / Huang, Mo-Fan / Hu, Ruifeng / Wang, Ruoyu / Gingold, Julian A / Chen, Yi-Hung / Tsai, Kuang-Lei / Forcioli-Conti, Nicolas R / Huang, Sarah X L / Webb, Thomas R / Su, Jie / Bazer, Danielle A / Jia, Peilin / Yustein, Jason T / Wang, Lisa L /
    Hung, Mien-Chie / Zhao, Zhongming / Huff, Chad D / Shen, Jingnan / Zhao, Ruiying / Lee, Dung-Fang

    Proceedings of the National Academy of Sciences of the United States of America

    2022  Volume 119, Issue 16, Page(s) e2117857119

    Abstract: The RB1 gene is frequently mutated in human cancers but its role in tumorigenesis remains incompletely defined. Using an induced pluripotent stem cell (iPSC) model of hereditary retinoblastoma (RB), we report that the spliceosome is an up-regulated ... ...

    Abstract The RB1 gene is frequently mutated in human cancers but its role in tumorigenesis remains incompletely defined. Using an induced pluripotent stem cell (iPSC) model of hereditary retinoblastoma (RB), we report that the spliceosome is an up-regulated target responding to oncogenic stress in RB1-mutant cells. By investigating transcriptomes and genome occupancies in RB iPSC–derived osteoblasts (OBs), we discover that both E2F3a, which mediates spliceosomal gene expression, and pRB, which antagonizes E2F3a, coregulate more than one-third of spliceosomal genes by cobinding to their promoters or enhancers. Pharmacological inhibition of the spliceosome in RB1-mutant cells leads to global intron retention, decreased cell proliferation, and impaired tumorigenesis. Tumor specimen studies and genome-wide TCGA (The Cancer Genome Atlas) expression profile analyses support the clinical relevance of pRB and E2F3a in modulating spliceosomal gene expression in multiple cancer types including osteosarcoma (OS). High levels of pRB/E2F3a–regulated spliceosomal genes are associated with poor OS patient survival. Collectively, these findings reveal an undiscovered connection between pRB, E2F3a, the spliceosome, and tumorigenesis, pointing to the spliceosomal machinery as a potentially widespread therapeutic vulnerability of pRB-deficient cancers.
    MeSH term(s) Bone Neoplasms/genetics ; Bone Neoplasms/pathology ; Carcinogenesis/genetics ; E2F3 Transcription Factor/genetics ; E2F3 Transcription Factor/metabolism ; Gene Expression Regulation, Neoplastic ; Genes, Retinoblastoma ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Mutation ; Osteosarcoma/genetics ; Osteosarcoma/pathology ; Retinal Neoplasms/genetics ; Retinoblastoma/genetics ; Retinoblastoma Binding Proteins/genetics ; Retinoblastoma Binding Proteins/metabolism ; Spliceosomes/genetics ; Spliceosomes/metabolism ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism
    Chemical Substances E2F3 Transcription Factor ; RB1 protein, human ; Retinoblastoma Binding Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
    Language English
    Publishing date 2022-04-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2117857119
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Multimodal Covariance Network Reflects Individual Cognitive Flexibility.

    Jiang, Lin / Eickhoff, Simon B / Genon, Sarah / Wang, Guangying / Yi, Chanlin / He, Runyang / Huang, Xunan / Yao, Dezhong / Dong, Debo / Li, Fali / Xu, Peng

    International journal of neural systems

    2024  Volume 34, Issue 4, Page(s) 2450018

    Abstract: Cognitive flexibility refers to the capacity to shift between patterns of mental function and relies on functional activity supported by anatomical structures. However, how the brain's structural-functional covarying is preconfigured in the resting state ...

    Abstract Cognitive flexibility refers to the capacity to shift between patterns of mental function and relies on functional activity supported by anatomical structures. However, how the brain's structural-functional covarying is preconfigured in the resting state to facilitate cognitive flexibility under tasks remains unrevealed. Herein, we investigated the potential relationship between individual cognitive flexibility performance during the trail-making test (TMT) and structural-functional covariation of the large-scale multimodal covariance network (MCN) using magnetic resonance imaging (MRI) and electroencephalograph (EEG) datasets of 182 healthy participants. Results show that cognitive flexibility correlated significantly with the intra-subnetwork covariation of the visual network (VN) and somatomotor network (SMN) of MCN. Meanwhile, inter-subnetwork interactions across SMN and VN/default mode network/frontoparietal network (FPN), as well as across VN and ventral attention network (VAN)/dorsal attention network (DAN) were also found to be closely related to individual cognitive flexibility. After using resting-state MCN connectivity as representative features to train a multi-layer perceptron prediction model, we achieved a reliable prediction of individual cognitive flexibility performance. Collectively, this work offers new perspectives on the structural-functional coordination of cognitive flexibility and also provides neurobiological markers to predict individual cognitive flexibility.
    MeSH term(s) Humans ; Executive Function ; Magnetic Resonance Imaging ; Electroencephalography ; Neural Pathways/diagnostic imaging ; Cognition ; Brain/diagnostic imaging ; Brain Mapping
    Language English
    Publishing date 2024-02-17
    Publishing country Singapore
    Document type Journal Article
    ISSN 1793-6462
    ISSN (online) 1793-6462
    DOI 10.1142/S0129065724500187
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  10. Article ; Online: Comparison of PD-L1 (22C3) Expression in Paired Primary and Metastatic Breast Carcinoma.

    Huang, Xiao / Anderson, Sarah A / Siegal, Gene P / Wei, Shi / Liu, Shanrun / Yang, Jingyun / Roisin, Puentes / Pickens, J Taylor / Huo, Lei / Sahin, Aysegul A / Granada, Carlos Prieto / Chen, Shuojun

    Clinical breast cancer

    2024  

    Abstract: Introduction: PD-L1 immunohistochemistry (IHC) is being used as a predictive marker of the benefit derived from immunotherapy in several cancer types, including breast cancer. However, the insight gleaned of the prognostic and predictive value of PD-L1 ... ...

    Abstract Introduction: PD-L1 immunohistochemistry (IHC) is being used as a predictive marker of the benefit derived from immunotherapy in several cancer types, including breast cancer. However, the insight gleaned of the prognostic and predictive value of PD-L1 status and its correlation with molecular characteristics during breast cancer progression remains limited.
    Methods: We performed an PD-L1 (22C3) assay in pre-treatment primary and metastatic tumor sections from 33 patients with breast carcinoma, matched for post neoadjuvant chemotherapy (p-NACT). PD-L1 expression was evaluated using 3 scoring methods: immune cell (IC) and tumor cell (TC) with a 1% as the cutoff value, and combined positive scores (CPS) with a 1 as the cutoff value. Twenty-two samples from 11 patients had successful fluorescence in situ hybridization (FISH)-based molecular data available for analysis.
    Results: In the 33 pre-treatment primary tumors, PD-L1 IC, TC, and CPS showed positive correlation with stromal tumor infiltrate lymphocytes (sTIL), histological grade 3, and triple negative breast carcinoma (TNBC). In the matched metastatic tumors, only PD-L1 IC showed a positive correlation with sTIL. The primary tumors showed a higher PD-L1 expression than the matched metastatic tumors by IC and CPS. Negative to positive conversion by CPS was identified in the metastatic tumors from lung, pleura and liver. p-NACT tumors also showed a trend of lower PD-L1 expression compared to the pre-treatment tumors. Six patients had matched samples for molecular and PD-L1 comparison, and none of them showed consistent gene alterations or PD-L1 expression among the primary, p-NACT and metastatic tumors.
    Conclusion: Our study showed a decrease in PD-L1 expression and disconnected molecular features during breast cancer progression. Repeating PD-L1 IHC testing could be considered in some specific metastatic sites if primary tumors were negative. Further studies are needed to identify other predictive factors for immune checkpoint inhibitor (ICI) therapy in patients with breast carcinoma.
    Language English
    Publishing date 2024-02-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2106734-X
    ISSN 1938-0666 ; 1526-8209
    ISSN (online) 1938-0666
    ISSN 1526-8209
    DOI 10.1016/j.clbc.2024.02.010
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