Article
Medical Laboratory Technology
Ramanath Majumdar, Julie A. Vrana, Justin W. Koepplin, Dragana Milosevic, Anja C. Roden, Joaquin J. Garcia, Benjamin R. Kipp, Ann M. Moyer
Summary: This study developed a qualitative test for detecting SARS-CoV-2 in formalin-fixed paraffin-embedded (FFPE) tissues using droplet digital PCR (ddPCR). The results showed reliable detection of SARS-CoV-2, and the assay has broad clinical utility in various applications, including evaluation of pregnancy loss and liver transplant rejection.
CLINICA CHIMICA ACTA
(2022)
Article
Genetics & Heredity
Samar Ijaz Gul, Aqsa Ayoub, Syed Aoun Ali, Sharoon Hanook, Deeba Noreen Baig
Summary: The study revealed significant dysregulation in the transcriptional pattern of Pfn3 in brain tumors, suggesting a potential correlation between molecular variations in Pfn3 and the malignancy of brain tumors, similar to the role of tumor suppressor genes in other types of cancer.
Article
Biochemistry & Molecular Biology
Allison K. Miller, Cara L. Brosnahan, Anjali Pande, Cindy F. Baker, Jemma L. Geoghegan, Jane Kitson, Neil J. Gemmell, Edwina J. Dowle
Summary: Infectious diseases have a significant impact on various organisms, and understanding the interactions between hosts and pathogens is crucial for their conservation and management. The use of genomic approaches has made it easier to obtain this knowledge quickly, however, many species still face challenges in accessing appropriate samples and data. Archival materials, such as formalin-fixed paraffin-embedded tissue samples, may provide a valuable resource for studying pathogen emergence and host responses over long periods of time.
MOLECULAR ECOLOGY RESOURCES
(2023)
Article
Biochemistry & Molecular Biology
Hua Zhang, Vamsi Krishna Polavarapu, Pengwei Xing, Miao Zhao, Lucy Mathot, Linxuan Zhao, Gabriela Rosen, Fredrik J. Swartling, Tobias Sjoblom, Xingqi Chen
Summary: Archived FFPE samples are widely used for cancer research, and we developed a highly sensitive method (FFPE-ATAC) to decode chromatin accessibility in FFPE tissues. This method generates high-quality chromatin accessibility profiles and allows analysis of chromatin profiles in regions of interest from a single FFPE tissue section.
Article
Chemistry, Analytical
Jie Pu, Chao Xue, Shihan Huo, Qingqing Shen, Yang Qu, Xinxin Yang, Bo An, Thomas E. Angel, Zhuo Chen, John T. Mehl, Huaping Tang, Eric Yang, Timothy W. Sikorski, Jun Qu
Summary: This study extensively investigated the challenges of accurate quantification of target proteins in formalin-fixed paraffin-embedded (FFPE) tissues using liquid chromatography-mass spectrometry (LC-MS) and developed a strategy enabling precise quantification. The study demonstrated efficient recovery of target signature peptides from FFPE tissues, indicated that FFPE tissue storage mainly causes decreased immunoreactivity but not chemical degradation of proteins, and proposed a novel calibration approach for accurate quantification. The pipeline was successfully applied to measure the pharmacokinetics of monoclonal antibody (mAb) and its target in FFPE tissues, showing excellent correlation with fresh tissues.
ANALYTICAL CHEMISTRY
(2022)
Review
Pathology
Giuseppa Zannini, Gaetano Facchini, Marco De Sio, Ferdinando De Vita, Andrea Ronchi, Michele Orditura, Maria Teresa Vietri, Fortunato Ciardiello, Renato Franco, Marina Accardo, Federica Zito Marino
Summary: BRCA1 and BRCA2 are genes involved in DNA repair mechanism and their mutations increase the risk of several cancer types. FDA has approved PARP inhibitors for treating BRCA1/2 mutated ovarian, breast, pancreatic, and prostate cancer patients. Guidelines for BRCA testing vary between tumor types, and there is limited data on detecting BRCA1/2 somatic mutations in FFPE samples. This review provides an overview of BRCA mutations, testing guidelines, molecular assays, and approved PARP inhibitors for various cancers, including breast, ovarian, fallopian tube, primary peritoneal, prostate, and pancreatic cancer.
PATHOLOGY RESEARCH AND PRACTICE
(2023)
Article
Oncology
Stefania Damiani, Michelangelo Fiorentino, Alessandra De Palma, Maria Pia Foschini, Tiziana Lazzarotto, Liliana Gabrielli, Pier Luigi Viale, Luciano Attard, Mattia Riefolo, Antonia D'Errico
Summary: Italy was the first European nation to be heavily affected by SARS-CoV-2, with over 33,000 deaths recorded by the end of May 2020. Autopsies on nine patients who died of SARS-CoV-2-associated disease revealed diffuse alveolar damage in lung tissues, with vascular involvement and eosinophilic infiltrate. The presence of SARS-CoV-2 viral RNA in the lung tissues of all nine patients was also confirmed.
JOURNAL OF PATHOLOGY
(2021)
Article
Pathology
Timothy Carll, Christine Fuja, Tatjana Antic, Ricardo Lastra, Peter Pytel
Summary: This study analyzes the contamination of tissue carryovers that may occur during the grossing and embedding process of tissue blocks. The experiment found that liquid transport media may be a possible avenue for contamination during the submission and transportation of tissue cassettes, emphasizing the need to pay attention to the friability of tissue and the physical agitation of cassettes.
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
(2022)
Article
Chemistry, Analytical
Kenneth Weke, Sachin Kote, Jakub Faktor, Sofian Al Shboul, Naomi Uwugiaren, Paul M. Brennan, David R. Goodlett, Ted R. Hupp, Irena Dapic
Summary: Developments in quantitative proteomics and DIA methodology have enabled protein quantification in biological samples, including formalin-fixed paraffin-embedded (FFPE) tissues. In this study, a simple and precise DIA-MS workflow was established to detect and quantify immune- and glioblastoma (GBM)-relevant proteins in FFPE patient materials. The results showed successful detection and quantification of more than 1700 proteins, including GBM-relevant proteins and immune-related proteins. This strategy has great potential for routine protein quantification in FFPE tissue samples.
ANALYTICA CHIMICA ACTA
(2022)
Review
Biochemistry & Molecular Biology
Ekenedirichukwu N. Obi, Daniel A. Tellock, Gabriel J. Thomas, Timothy D. Veenstra
Summary: The recent developments in mass spectrometry (MS) have provided new opportunities in biomarker discovery and diagnostics, particularly in analyzing clinical samples at a deeper level. While most developments have focused on blood, there is potential in utilizing archived formalin-fixed paraffin-embedded (FFPE) tissues, which were previously considered difficult to analyze using proteomics techniques. Researchers have developed methods to extract proteins from FFPE tissues, allowing for their analysis using state-of-the-art technologies like MS and protein arrays. This review discusses the history of these developments and their current applications in identifying biomarkers and diagnosing diseases such as cancer.
Article
Multidisciplinary Sciences
Rochelle Hockney, Caroline H. Orr, Gareth J. Waring, Inge Christiaens, Gillian Taylor, Stephen P. Cummings, Stephen C. Robson, Andrew Nelson
Summary: This study investigated the feasibility of using FFPE fetal membrane samples for microbiota research. The results showed differences in bacterial composition between FFPE and frozen samples, as well as lower DNA quality in FFPE samples. Additionally, the microbiota of FFPE samples was influenced by processing methods and could not differentiate between tissue samples and surrounding wax blocks. Therefore, contamination prevention and detection methods should be considered when using FFPE samples for microbiota research.
Article
Biology
Masachika Ikegami, Shinji Kohsaka, Takeshi Hirose, Toshihide Ueno, Satoshi Inoue, Naoki Kanomata, Hideko Yamauchi, Taisuke Mori, Shigeki Sekine, Yoshihiro Inamoto, Yasushi Yatabe, Hiroshi Kobayashi, Sakae Tanaka, Hiroyuki Mano
Summary: The researchers developed MicroSEC, a filtering pipeline to remove sequencing artifacts from archival formalin-fixed and paraffin-embedded samples. The sensitivity and specificity of MicroSEC were confirmed to be 97% and 96% respectively using amplicon-based sequencing with 97 mutations. This tool may improve the reliability of clinical sequencing and advance cancer research using formalin-fixed, paraffin-embedded samples, which are of great interest for genomic analysis.
COMMUNICATIONS BIOLOGY
(2021)
Article
Chemistry, Analytical
Tae Hee Lee, Young Jun Kim, Woo Sun Rou, Hyuk Soo Eun
Summary: CTCs, rare circulating tumor cells, are promising diagnostic biomarkers but their analysis is often limited due to rarity and short-term presence. This study introduces a new method combining hydrogel core-mediated CTC accumulation and FFPE technology to prepare CTC blocks, showing great potential in cytopathological CTC studies.
Article
Biochemistry & Molecular Biology
Georgia Mitsa, Qianyu Guo, Christophe Goncalves, Samuel E. J. Preston, Vincent Lacasse, Adriana Aguilar-Mahecha, Naciba Benlimame, Mark Basik, Alan Spatz, Gerald Batist, Wilson H. Miller, Sonia del Rincon, Rene P. Zahedi, Christoph H. Borchers
Summary: The article presents a 'green' xylene-free protocol for accelerated sample preparation of FFPE tissues, enabling streamlined and reproducible quantitative proteomic profiling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Analytical
Yunxia Guo, Junjie Ma, Zhengyue Li, Kaitong Dang, Qinyu Ge, Yan Huang, Guang-zhong Wang, Xiangwei Zhao
Summary: This study investigates the effects of fixation and storage time on the nuclear transcriptome signatures of the brain. The fixation time has a greater impact on the transcriptomic profiles than the retention time of FFPE samples. The findings will guide the preparation of FFPE samples for single-nucleus RNA-seq, especially in transcriptomic studies of brain diseases.
ANALYTICA CHIMICA ACTA
(2023)
Article
Pathology
Nassim Bouteldja, David Laurin Hoelscher, Barbara Mara Klinkhammer, Roman David Buelow, Johannes Lotz, Nick Weiss, Christoph Daniel, Kerstin Amann, Peter Boor
Summary: This research proposes a novel concept of stain augmentation to develop stain-independent CNNs for digital pathology. It outperforms state-of-the-art techniques and enables segmentation on immunohistochemical stainings without additional annotations, achieving performance comparable to the annotated stain. Examples of application in inflammation and fibrosis quantification are presented, indicating the effectiveness of stain augmentation in deep-learning segmentation algorithms.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Francesca Ferraro, Anja Steinle, Harini Narasimhan, Andreas Bleilevens, Paula-Marie Stolzenberg, Till Braunschweig, Elmar Stickeler, Jochen Maurer
Summary: Breast cancer stem cells (BCSCs) play a crucial role in tumor recurrence and therapy resistance. Researchers have successfully established primary BCSC cultures from triple-negative breast cancer (TNBC) patients, providing an excellent model for studying breast cancer treatment options. IRAK2 downregulation shows promising results in inhibiting the aggressive growth and pathways involved in TNBC progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Urology & Nephrology
Ting Jia, Tong Xu, Bart Smeets, Eva Miriam Buhl, Marcus Johannes Moeller, Juergen Floege, Barbara Mara Klinkhammer, Peter Boor
Summary: The study suggests that PDGF-B and its receptor PDGFR-beta play a crucial role in the development and progression of FSGS by affecting the activation, proliferation, and fibrotic characteristics of PECs. The molecular crosstalk between podocytes and PECs mediated by PDGF-B and PDGFR-beta drives glomerulosclerosis and the progression of FSGS. Treatment with PDGF-B neutralizing antibody can improve kidney function and reduce the occurrence of FSGS.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Multidisciplinary Sciences
David L. Hoelscher, Nassim Bouteldja, Mehdi Joodaki, Maria L. Russo, Yu-Chia Lan, Alireza Vafaei Sadr, Mingbo Cheng, Vladimir Tesar, Saskia V. Stillfried, Barbara M. Klinkhammer, Jonathan Barratt, Juergen Floege, Ian S. D. Roberts, Rosanna Coppo, Ivan G. Costa, Roman D. Buelow, Peter Boor
Summary: Pathology diagnostics still rely on tissue morphology assessment by trained experts. Here, the authors perform deep-learning-based segmentation followed by large-scale feature extraction of histological images, i.e., next-generation morphometry, to enable outcome-relevant and disease-specific pathomics analysis of non-tumor kidney pathology.
NATURE COMMUNICATIONS
(2023)
Letter
Neurosciences
Juliane Bremer, Johannes Friemann, Saskia von Stillfried, Peter Boor, Joachim Weis
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Moritz Uhlig, Marc Hein, Moriz A. Habigt, Rene H. Tolba, Till Braunschweig, Marius J. Helmedag, Melissa Arici, Alexander Theissen, Axel Klinkenberg, Uwe Klinge, Mare Mechelinck
Summary: Cirrhotic patients often experience cirrhotic cardiomyopathy (CCM), which is studied in detail through animal models of bile duct ligation (BDL) and a second surgery. The study reveals delayed adaptability, impaired contractility at rest, reduced contractile reserve, increased creatine and transaminase levels, myocardial fibrosis, macrophage infiltration, systemic inflammation, altered expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1a), and increased expression of caspase-3. Structural changes in the myocardium are observed after 8 weeks. Transient myocardial insufficiency and secondary organ dysfunction occur after the second surgery.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Marcelo A. S. de Toledo, Xuhuang Fu, Tiago Maie, Eva M. Buhl, Katrin Goetz, Susanne Schmitz, Anne Kaiser, Peter Boor, Till Braunschweig, Nicolas Chatain, Ivan G. Costa, Tim H. Bruemmendorf, Steffen Koschmieder, Martin Zenke
Summary: In this study, human induced pluripotent stem cells were differentiated into mast cells, which exhibited characteristics of systemic mastocytosis disease. These cells can be used for disease modeling and drug screening.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Axel Dievernich, Johannes Stegmaier, Pascal Achenbach, Svetlana Warkentin, Till Braunschweig, Ulf Peter Neumann, Uwe Klinge
Summary: Liver cancer, particularly hepatocellular carcinoma (HCC), is a common and deadly form of cancer worldwide. Numerous studies have examined the impact of immune infiltrates on cancer patient prognosis, but accurately delineating the cancer area has been challenging due to heterogeneity and operator variability. However, advancements in multiplex analyses and machine learning techniques offer potential for objective identification of cancer areas and analysis of prognostic immune parameters.
Review
Cell Biology
Sabine Weiskirchen, Sarah K. K. Schroeder, Eva Miriam Buhl, Ralf Weiskirchen
Summary: The cultivation of cells in a favorable artificial environment has become an essential tool in cellular and molecular biology research. However, cell lines are often affected by misidentification, contamination, and specific biological and chemical hazards. This review offers an introduction to common problems encountered in cell culture laboratories and provides guidelines for preventing and addressing these issues.
Article
Computer Science, Interdisciplinary Applications
Isaac Shiri, Behrooz Razeghi, Alireza Vafaei Sadr, Mehdi Amini, Yazdan Salimi, Sohrab Ferdowsi, Peter Boor, Deniz Guenduez, Slava Voloshynovskiy, Habib Zaidi
Summary: A federated learning (FL) framework was developed for multi-institutional PET/CT image segmentation. The FL algorithms showed comparable performance to centralized learning methods and outperformed the single center-based baseline. The results have promising implications for HN tumor segmentation from PET/CT images.
COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Elisabeth Zechendorf, Christian Beckers, Nadine Frank, Sandra Kraemer, Carolina Neu, Thomas Breuer, Michael Dreher, Edgar Dahl, Gernot Marx, Lukas Martin, Tim-Philipp Simon
Summary: This study investigated the potential association between ribonuclease 1 (RNase 1) and the outcome in COVID-19 patients, as well as the impact of changes in RNase 1 levels during the course of the disease. The results showed a significant increase in RNase 1 serum levels in the increasing group of both patient cohorts. Patients in the increasing group who died had significantly higher RNase 1 levels compared to survivors. The findings suggest that RNase 1 may play a role in renal dysfunction associated with ICU COVID-19 patients and could serve as a potential biomarker to predict outcome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Barbara Mara Klinkhammer, Peter Boor
Summary: An increasing number of patients worldwide suffers from chronic kidney disease (CKD). Currently, there is no specific antifibrotic therapy for kidney patients and invasive renal biopsy remains the only option for specific detection and quantification of kidney fibrosis. This review discusses emerging diagnostic approaches and potential therapeutic options for fibrosis, as well as the importance of translational research in establishing fibrosis-specific endpoints for clinical trials.
MOLECULAR ASPECTS OF MEDICINE
(2023)
Article
Mathematical & Computational Biology
Roman D. Buelow, David L. Hoelscher, Ivan G. Costa, Peter Boor
NPJ SYSTEMS BIOLOGY AND APPLICATIONS
(2023)
Article
Gastroenterology & Hepatology
Mohamed Ramadan Mohamed, Johannes Haybaeck, Hanghang Wu, Huan Su, Matthias Bartneck, Cheng Lin, Mark V. Boekschoten, Peter Boor, Benjamin Goeppert, Christian Rupp, Pavel Strnad, Roger J. Davis, Francisco Javier, Christian Trautwein
Summary: This study investigated the role of JNK1/2 during cholestasis and its hepatocyte-specific function. The results showed that Jnk1 and Jnk2 work together to protect hepatocytes from cholestatic liver disease by controlling Apelin signalling. Blocking Apelin signalling attenuated liver injury and fibrosis induced by cholestasis. Targeting Jnk1/2 in hepatocytes may be a new molecular strategy for treating cholestatic liver disease.
Article
Surgery
Alton B. Farris, Mariam P. Alexander, Ulysses G. J. Balis, Laura Barisoni, Peter Boor, Roman D. Bulow, Lynn D. Cornell, Anthony J. Demetris, Evan Farkash, Meyke Hermsen, Julien Hogan, Renate Kain, Jesper Kers, Jun Kong, Richard M. Levenson, Alexandre Loupy, Maarten Naesens, Pinaki Sarder, John E. Tomaszewski, Jeroen van der Laak, Dominique van Midden, Yukako Yagi, Kim Solez
Summary: The Banff Digital Pathology Working Group aims to establish a digital pathology repository and promote collaborations through the development, validation, and sharing of image analysis models, as well as regular videoconferencing. AI-based support systems for transplantation pathology were presented during the discussions, and potential collaborations in competitions/trials on AI applied to kidney transplant specimens were also discussed.
TRANSPLANT INTERNATIONAL
(2023)
