Article
Cell Biology
Wen-Jing Liu, Ying-Xue Huang, Wei Wang, Ye Zhang, Bing-Jie Liu, Jian-Ge Qiu, Bing-Hua Jiang, Ling-Zhi Liu
Summary: High NOX4 levels are detected in human ovarian cancer samples, induced by HIF-1 alpha and IGF-1, playing a crucial role in chemotherapy and radiotherapy resistance. Knockdown of NOX4 increases sensitivity to targeted therapy and radiotherapy by reducing expression of HER3 and NF-kappa B p65, revealing a new pathway for overcoming therapeutic resistance in ovarian cancer.
Article
Oncology
Luana S. Lenz, Juliano L. Faccioni, Paula A. Bracco, Jephesson A. F. Santos, Luiza C. Pereira, Julieti H. Buss, Mauricio T. Tamborindeguy, Daphne Torgo, Thayana Monteiro, Giovana B. Mantovani, Carolina N. Santo, Julia C. Marcolin, Eloisa Dalsin, Alvaro Vigo, Sidia M. Callegari-Jacques, Andrew O. Silva, Giovana R. Onzi, Karine R. Begnini, Guido Lenz
Summary: The fitness of cancer cells in colony formation is dynamic, influenced by factors such as ERK activity, cell-cycle duration, and DNA repair capacity. Colonies exhibit dynamic resistance to drugs, indicating an adaptability to drug presence.
Article
Oncology
Yi-Ping Wang, I-Ju Liu, Kai-Chi Chen, Han-Chung Wu
Summary: In squamous cell carcinoma of head and neck (SCCHN), high expression of HER3 and its ligand NRG1 is associated with increased regional lymphatic metastasis. HER3 is positively regulated by NOTCH1 through AKT pathway and USP8 deubiquitinating enzyme to inhibit protein degradation. Exclusion of patients with NOTCH1-inactivated SCCHN may benefit future clinical trials targeting HER3.
Article
Cell Biology
A. Tate Lasher, Liou Y. Sun
Summary: Our previous research has shown that mice lacking functional GHRH exhibit unique physiological characteristics and an extended lifespan. In this study, we investigated the response to glucagon in these mice and found that they exhibit reduced glucose production and increased energy expenditure. Alterations in pancreatic islet architecture and hepatic glucagon signaling were also observed. These findings suggest that changes in glucagon signaling may contribute to the metabolic phenotype observed in these long-lived mice.
Article
Materials Science, Multidisciplinary
Amadeo Sena-Torralba, Helena Torne-Morato, Claudio Parolo, Saba Ranjbar, Mohammad Amin Farahmand Nejad, Ruslan Alvarez-Diduk, Andrea Idili, Mohammad Reza Hormozi-Nezhad, Arben Merkoci
Summary: The majority of lateral flow assays use single-color labels, but this method has two limitations: it is prone to misinterpretation and does not allow precise modulation of sensitivity and dynamic range. To overcome these limitations, a ratiometric approach is developed that allows for adjustment of the assay's analytical properties.
ADVANCED MATERIALS TECHNOLOGIES
(2022)
Article
Obstetrics & Gynecology
Chendi Zhu, Wei Luo, Zhuqing Li, Xiruo Zhang, Jingmei Hu, Shidou Zhao, Xue Jiao, Yingying Qin
Summary: The study revealed a continuous decline in serum INSL3 levels with progression of ovarian insufficiency, showing strong associations with FSH and other markers, serving as a good predictor for bPOI and POI. There was no significant difference in INSL3 levels in follicular fluid between bPOI patients and control women.
FERTILITY AND STERILITY
(2021)
Article
Multidisciplinary Sciences
Charlotte Vogt, Florian Meirer, Matteo Monai, Esther Groeneveld, Davide Ferri, Rutger A. van Santen, Maarten Nachtegaal, Raymond R. Unocic, Anatoly I. Frenkel, Bert M. Weckhuysen
Summary: In this study, structure insensitivity in catalysis was found to be linked to reaction-dependent particle size dependent restructuring. We observed particle size-dependent effects such as restructuring during ethene hydrogenation, which increased with increasing particle size, while no such effects were observed during CO2 hydrogenation. Additionally, we demonstrated that the rate of carbon diffusion on and into nanoparticles increases with particle size.
NATURE COMMUNICATIONS
(2021)
Article
Genetics & Heredity
Fan Yang, Wei Wei, Ganghua Li, Qiongyu Lan, Xiwei Liu, Lin Gao, Chao Zhang, Jiangtao Fan, Jundong Li
Summary: Platinum-based chemotherapy is the first-line treatment for ovarian cancer, but the response to this therapy varies among patients. In this study, genetic features associated with platinum sensitivity and prognosis were identified, and an integrated scoring model was developed to better predict patients' response to therapy and outcomes compared to HRDetect.
FRONTIERS IN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Nihal Kaplan, Min Liu, Junyi Wang, Wending Yang, Elaina Fiolek, Han Peng, Robert M. Lavker
Summary: This study demonstrates a link between miR-210 and EphA2/Ephrin-A1 signaling that potentially regulates corneal epithelial migration.
Article
Computer Science, Information Systems
Zafor Ahmed, Evren Eryilmaz, Ahmed Ibrahim Alzahrani
Summary: Our research explores the enterprise IS diffusion phenomenon using a perspective of control balancing and stakeholder orientation. Through analyzing large-scale IS implementation projects in a Canadian government organization, we find that integrating a dynamic control configuration perspective with stakeholder engagement, sensitivity, and shifting orientations can offer a synergistic approach to IS diffusion. We also develop the construct of stakeholder orientation and identify four distinct orientations that impact IS diffusion stages.
INFORMATION & MANAGEMENT
(2022)
Article
Cell Biology
Boya Zhang, Putao Yuan, Guang Xu, Zhijun Chen, Zhifei Li, Huali Ye, Jiying Wang, Peihua Shi, Xuewu Sun
Summary: This study identified the role of miR-181a/DUSP6 in the progression of osteoporosis through the ERK2 and SMAD2 signaling pathways, suggesting that DUSP6 may represent a novel target for the treatment of osteoclast-related diseases in the future.
CELL DEATH & DISEASE
(2021)
Article
Developmental Biology
Okiko Habara, Catriona Y. Logan, Masami Kanai-Azuma, Roeland Nusse, Hinako M. Takase
Summary: Canonical WNT signaling is crucial for the activation of pre-granulosa cells during primordial follicle activation, supporting oocyte growth in mammalian ovaries.
Article
Oncology
Lei Duan, Sarah J. Calhoun, Ricardo E. Perez, Virgilia Macias, Fatima Mir, Paolo Gattuso, Carl G. Maki
Summary: Researchers have found that high expression of PRCP in ER+ breast tumors is associated with poor prognosis and earlier recurrence. PRCP also enhances IGF1R/HER3 signaling and AKT activation in ER+ breast cancer cells. PRCPi can enhance the response of breast cancer tumors to endoxifen.
CANCER BIOLOGY & THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Lipeng Pei, Feng Zhao, Yi Zhang
Summary: This study reveals that USP43 is highly expressed in epithelial ovarian cancer (EOC) and its overexpression promotes cancer cell proliferation, migration, invasion, and chemoresistance. USP43 achieves these effects by inhibiting HDAC2 degradation and activating the Wnt/beta-catenin signaling pathway. These findings suggest that USP43 may be a potential target for controlling ovarian cancer progression.
Article
Immunology
Arun Cumpelik, David Heja, Yuan Hu, Gabriele Varano, Farideh Ordikhani, Mark P. Roberto, Zhengxiang He, Dirk Homann, Sergio A. Lira, David Dominguez-Sola, Peter S. Heeger
Summary: Activated B cells dynamically regulate the expression of complement regulatory proteins through the transcription factor BCL6, affecting B cell activation, germinal center formation, and increased antigen receptor affinity. Repression of decay-accelerating factor and other regulators, while increasing the expression of CD59, allows for C3 cleavage without membrane attack complex formation on GC B cells, crucial for positive selection. Disruption of this pathway limits mechanistic target of rapamycin activation, causing premature GC collapse and impaired affinity maturation.
Article
Public, Environmental & Occupational Health
Min Gao, Paul Aveyard, Nicola Lindson, Jamie Hartmann-Boyce, Peter Watkinson, Duncan Young, Carol Coupland, Ashley K. Clift, David Harrison, Doug Gould, Ian D. Pavord, Margaret Smith, Julia Hippisley-Cox
Summary: Current smoking is associated with a lower risk of severe COVID-19 compared to never smokers, while former smokers have a higher risk. The association between e-cigarette use and severe COVID-19 is unclear.
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
(2022)
Article
Critical Care Medicine
David A. Harrison, Ben C. Creagh-Brown, Kathryn M. Rowan
Summary: Persistent critical illness is a common clinical syndrome in the ICU, which is associated with increased healthcare utilization and adverse outcomes. This study aimed to assess the predictive factors for survival in patients with persistent critical illness and compare the characteristics and outcomes of these patients with others. The findings suggest the need for improved understanding of long-term outcomes and the development of tools for prognostication.
JOURNAL OF THE INTENSIVE CARE SOCIETY
(2023)
Article
Critical Care Medicine
Robert Darnell, Christopher Newell, Julia Edwards, Emma Gendall, David Harrison, Stefan Sprinckmoller, Paul Mouncey, Doug Gould, Matt Thomas
JOURNAL OF THE INTENSIVE CARE SOCIETY
(2023)
Article
Oncology
Jennifer Bre, Alison L. Dickson, Oliver J. Read, Ying Zhang, Fiona G. McKissock, Peter Mullen, Peijun Tang, Greice M. Zickuhr, Clarissa M. Czekster, David J. Harrison
Summary: NUC-3373 is a modified version of 5-fluorodeoxyuridine that shows higher anti-cancer activity and better safety profile compared to 5-FU, overcoming its limitations and pharmacologic challenges in clinical use.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Christina Fell, Mahnaz Mohammadi, David Morrison, Ognjen Arandjelovic, Sheeba Syed, Prakash Konanahalli, Sarah Bell, Gareth Bryson, David J. Harrison, David Harris-Birtill
Summary: In this study, AI was used to categorise endometrial biopsy whole slide images into malignant, other, benign, or insufficient categories. The digitalisation of pathology has led to the automation of image analysis, and a model that can classify slides in this way would help prioritise pathologists' workload and reduce diagnosis time for cancer patients. The final model achieved an accuracy of 90% in classifying slides correctly and 97% in the malignant class, demonstrating its effectiveness in assisting pathologists.
Article
Oncology
Georges Bedran, Hans-Christof Gasser, Kenneth Weke, Tongjie Wang, Dominika Bedran, Alexander Laird, Christophe Battail, Fabio Massimo Zanzotto, Catia Pesquita, Hakan Axelson, Ajitha Rajan, David J. Harrison, Aleksander Palkowski, Maciej Pawlik, Maciej Parys, Robert O'Neill, Paul M. Brennan, Stefan N. Symeonides, David R. Goodlett, Kevin Litchfield, Robin Fahraeus, Ted R. Hupp, Sachin Kote, Javier A. Alfaro
Summary: Using deep learning mass spectrometry, we developed a proteogenomic pipeline to discover noncanonical MHC class I-associated peptides (ncMAP) from noncoding regions. Analyzing data from 26 MHC class I immunopeptidomic studies across 11 different cancer types, we identified an atlas of 8,601 ncMAPs and suggested 17 cancer-selective ncMAPs as attractive therapeutic targets.
CANCER IMMUNOLOGY RESEARCH
(2023)
Article
Computer Science, Information Systems
Georg Wolflein, In Hwa Um, David J. Harrison, Ognjen Arandjelovic
Summary: In recent years, efforts have been made to digitize whole-slide images of cancer tissue, providing new opportunities for deep learning in oncology. One promising application is virtual staining, where a deep learning model reproduces the appearance of stained tissue sections based on different input stains. However, there is a scarcity of supervised training data with aligned input and output stains on the same tissue sections. In this work, a dataset of ten whole-slide images of clear cell renal cell carcinoma tissue sections, along with over 600,000 patches and cell segmentation masks, is introduced to facilitate the development of deep learning methods for digital pathology and benchmark virtual staining models.
Article
Biochemistry & Molecular Biology
Suneeta Devi, Anna E. Carberry, Greice M. Zickuhr, Alison L. Dickson, David J. Harrison, Rafael G. da Silva
Summary: DNPH1 catalyzes the N-ribosidic bond cleavage of 5-hydroxymethyl-2'-deoxyuridine 5'-monophosphate to generate 2-deoxyribose 5-phosphate and 5-hydroxymethyluracil. The crystal structures of unliganded DNPH1 and DNPH1 bound with 2'-deoxyuridine 5'-monophosphate were solved, revealing the interaction between the catalytic Glu residue and a conserved Tyr residue. Functional data supported the proposed mechanism, with hydrolysis of dUMP confirmed by liquid chromatography-mass spectrometry analysis. The pH-rate profile and solvent isotope effects provided insights into the catalytic mechanism.
Article
Cell Biology
Mustafa Elshani, In Hwa Um, Steve Leung, Paul A. Reynolds, Alex Chapman, Mary Kudsy, David J. Harrison
Summary: This study investigates the expression of NFE2L1 in podocytes and its correlation with kidney disease. The results show that NFE2L1 expression is decreased in renal diseases, and its nuclear expression is reduced under PAN treatment.
Article
Computer Science, Artificial Intelligence
Clarisse F. de Vries, Samantha J. Colosimo, Roger T. Staff, Jaroslaw A. Dymiter, Joseph Yearsley, Deirdre Dinneen, Moragh Boyle, David J. Harrison, Lesley A. Anderson, Gerald Lip
Summary: Artificial intelligence (AI) tools may be helpful in breast screening mammography programs, but their generalizability to new settings should be validated. This study assessed the performance of a commercially available breast screening AI algorithm in a specific clinical site using a 3-year dataset. The algorithm's recall rates were high initially but reduced after threshold calibration and were influenced by software upgrades. Validating AI performance and thresholds in new clinical settings is important, and quality assurance systems should ensure consistency.
RADIOLOGY-ARTIFICIAL INTELLIGENCE
(2023)
Proceedings Paper
Computer Science, Artificial Intelligence
Georg Wolflein, In Hwa Um, David J. Harrison, Ognjen Arandjelovic
Summary: Understanding the presence and density of specific immune cell types is crucial for evaluating a patient's immune response to cancer. However, traditional immunofluorescence staining methods for identifying T cell subtypes are costly, time-consuming, and not commonly used in clinical settings. In this study, we propose a framework that utilizes generative adversarial networks to virtually stain Hoechst images with CD3 and CD8 markers, enabling the identification of T cell subtypes in clear cell renal cell carcinoma. By jointly learning both staining tasks, our method incorporates mutually beneficial information to improve accuracy. We also introduce a novel metric to evaluate the quality of virtual staining.
2023 IEEE/CVF WINTER CONFERENCE ON APPLICATIONS OF COMPUTER VISION (WACV)
(2023)