| 1. |
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| 2. |
- Fierrez, Julian, et al.
(author)
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BiosecurID : A Multimodal Biometric Database
- 2010
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In: Pattern Analysis and Applications. - New York, USA : Springer-Verlag New York. - 1433-7541 .- 1433-755X. ; 13:2, s. 235-246
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Journal article (peer-reviewed)abstract
- A new multimodal biometric database, acquired in the framework of the BiosecurID project, is presented together with the description of the acquisition setup and protocol. The database includes eight unimodal biometric traits, namely: speech, iris, face (still images, videos of talking faces), handwritten signature and handwritten text (on-line dynamic signals, off-line scanned images), fingerprints (acquired with two different sensors), hand (palmprint, contour-geometry) and keystroking. The database comprises 400 subjects and presents features such as: realistic acquisition scenario, balanced gender and population distributions, availability of information about particular demographic groups (age, gender, handedness), acquisition of replay attacks for speech and keystroking, skilled forgeries for signatures, and compatibility with other existing databases. All these characteristics make it very useful in research and development of unimodal and multimodal biometric systems. © Springer-Verlag London Limited 2009.
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| 3. |
- Murari, A., et al.
(author)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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In: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Journal article (peer-reviewed)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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| 4. |
- Arnelo, Urban, et al.
(author)
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Intraoperative pancreatoscopy can improve the detection of skip lesions during surgery for intraductal papillary mucinous neoplasia : a pilot study
- 2023
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In: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 23:6, s. 704-711
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Journal article (peer-reviewed)abstract
- Objectives: Intraoperative pancreatoscopy is a promising procedure that might guide surgical resection for suspected main duct (MD) and mixed type (MT) intraductal papillary mucinous neoplasms (IPMNs). The aim of the present study was to assess the diagnostic yield and clinical impact of intraoperative pancreatoscopy in patients operated on for MD and MT-IPMNs.Methods: This is a retrospective cohort study. Patients undergoing surgery for suspected MD or MT-IPMN underwent intraoperative pancreatoscopy and frozen section analysis. In all patients who required extended resection due to pancreatoscopic findings, we compared the final histology with the results of the intraoperative frozen section analysis.Results: In total, 46 patients, 48% females, mean age (range) 67 years (45–82 years) underwent intraoperative pancreatoscopy. No mortality or procedure related complications were observed. Pancreatoscopy changed the operative course in 30 patients (65%), leading to extended resections in 20 patients (43%) and to parenchyma sparing procedures in 10 patients (22%). Analyzing the group of patients who underwent extended resections, 7 (35%) displayed lesions that needed further surgical treatment (six high grade dysplasia and one with G1 pancreatic neuroendocrine tumor) and among those 7, just 1 (14%) would have been detected exclusively with histological frozen section analysis of the transection margin. The combination of both pancreatoscopy and frozen section analysis lead to 86% sensitivity and 92% specificity for the detection of pathological tissue in the remnant pancreas.Conclusion: Intraoperative pancreatoscopy is a safe and feasible procedure and might allow the detection of skip lesions during surgery for suspect MD-involving IPMNs.
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| 5. |
- Baldaque-Silva, Francisco, et al.
(author)
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A Nerve-Wracking Cyst
- 2021
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In: Gastroenterology. - : Elsevier. - 0016-5085 .- 1528-0012. ; 161:5, s. e12-e13
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Journal article (peer-reviewed)
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| 6. |
- Bozoky, Benedek, et al.
(author)
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Stabilization of the classical phenotype upon integration of pancreatic cancer cells into the duodenal epithelium
- 2021
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In: Neoplasia. - : Elsevier. - 1522-8002 .- 1476-5586. ; 23:12, s. 1300-1306
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Journal article (peer-reviewed)abstract
- Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid tumors. Based on transcriptomic classifiers, basal-like and classical PDAC subtypes have been defined that differ in prognosis. Cells of both subtypes can coexist in individual tumors; however, the contribution of either clonal heterogeneity or microenvironmental cues to subtype heterogeneity is unclear. Here, we report the spatial tumor phenotype dynamics in a cohort of patients in whom PDAC infiltrated the duodenal wall, and identify the duodenal epithelium as a distinct PDAC microniche. Materials and methods: We used serial multiplex quantitative immunohistochemistry (smq-IHC) for 24 proteins to phenotypically chart PDAC tumor cells in patients whose tumors infiltrated the duodenal epithelium. Additionally, we used a genetically engineered mouse model to study the PDAC cell phenotype in the small intestinal epithelium in a controlled genetic background. Result: We show that pancreatic cancer cells revert to non-destructive growth upon integration into the duodenal epithelium, where they adopt traits of intestinal cell differentiation, associated with phenotypical stabilization of the classical subtype. The integrated tumor cells replace epithelial cells in an adenoma-like manner, as opposed to invasive growth in the submucosa. Finally, we show that this phenomenon is shared between species, by confirming duodenal integration and phenotypic switching in a genetic PDAC mouse model. Discussion: Our results identify the duodenal epithelium as a distinct PDAC microniche and tightly link microenvironmental cue to cancer transcriptional subtypes. The phenomenon of "intestinal mimicry" provides a unique opportunity for the systematic investigation of microenvironmental influences on pancreatic cancer plasticity.
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| 7. |
- Fernández Moro, Carlos
(author)
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Pancreatic cancer : investigation of the prognostic significance of tumor immunophenotype and establishment of a novel ex-vivo tissue slice culture system for drug sensitivity testing
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Pancreatic ductal adenocarcinoma (PDAC), commonly referred to as pancreatic cancer, is associated with a dismal 5-year overall survival of 9 to 6 %. A major reason for the high mortality is the pronounced resistance to treatment. There is urgent need for the development of novel, effective therapies and for a better understanding as to why some tumors respond better to treatment than others. The process for conventional drug testing relies significantly on cell lines and genetically engineered mouse models. Even if these models recapitulate some of the features of human pancreatic cancer, there are significant limitations, mainly the lack of the native tumor microenvironment and the use of a host that belongs to another species and may be immunocompromised. In Paper I, a large cohort (n = 409) of adenocarcinomas from the main anatomical locations in the pancreatobiliary system is analyzed by immunohistochemistry with a panel of up to 27 antibodies. Hierarchical clustering and differential expression analysis reveal three immunohistochemical tumor types (extrahepatic pancreatobiliary, intestinal and intrahepatic cholangiocarcinoma) and their distinguishing markers. Among patients who underwent surgical resection of the primary tumor, the intestinal type showed an adjusted hazard ratio of 0.19 for overall survival (p value = 0.014) as compared to the extrahepatic pancreatobiliary type. Furthermore, the characteristic immunohistochemical profile supports the positive diagnosis of intrahepatic cholangiocarcinoma, which is commonly regarded as a diagnosis of exclusion. The presented integrative immunohistochemical classification may contribute to improve diagnosis and prognostic stratification for patients with adenocarcinomas of the pancreatobiliary system. Paper II introduces a novel ex-vivo model of precision-cut tissue slices that allows culturing of human PDAC including the native tumor microenvironment. Fresh tumor tissue samples (n = 12) were obtained from surgical resection specimens, cut into 350 μm thick tissue slices, and cultured for at least 96 h. Every 24 h, tissue slices were harvested and processed for analysis, including histomorphology, transmission electron microscopy and immunohistochemistry. These revealed good morphological preservation and ultrastructural integrity of the tissue slices, including cancerous, stromal, and immune cell populations. Each tumor retained its characteristic histological and cytological features and grade of differentiation throughout the entire culture period. A cancerous and, to a lesser extent, nonneoplastic cell outgrowth covered gradually the surface of the tissue slices, while tumor cells retained their proliferative (Ki67) and metabolic (pS6 mTOR pathway) activity. This culture system is a close surrogate of the parent tumor and harbors promising potential for drug sensitivity testing and personalized treatment of PDAC. Paper III is a continuation study in which five tissue slice cultures of human PDAC (from Paper II) are analyzed at the whole transcriptome level (RNASeq). Findings at 24 h intervals (24-72 h of culture) are compared to baseline (0 h, non-cultured tissue). On differential expression analysis, only a limited number of genes (median range 10-25) were up- or downregulated during culture. One culture with morphologically visible regions of necrosis/apoptosis (0-18 % total slice area) showed upregulation of VEGFA and PTGS2. Pathway analysis suggested for this culture a highly significant probability of activation of apoptosis via HIF-1/quercetin/NF-ĸB/AP-1 interaction pathways. These results support that the transcriptome of the parent tumor is largely preserved in ex-vivo cultured tissue slices of PDAC, and that transcriptomic analysis is a valuable complement to morphology for evaluation of the tissue slices. Finally, in Paper IV, the previously established (in Papers II and III) ex-vivo model of precision-cut tissue slices is used for drug sensitivity testing in nine samples of surgically resected human PDAC. PDAC tissue slices were exposed to selenium compounds (selenite and methylselenocysteine) at various concentrations and gemcitabine 1 μM during 48 h of culture. Selenium compounds administered at concentrations below the maximum tolerated dose in humans significantly reduced PDAC cell viability (p < 0.02) and decreased outgrowth of viable tumor cells onto the tissue surface (p < 0.05), while non-neoplastic tissues remained preserved. Transcriptomic analysis revealed downregulation of CEMIP, PLOD2, DDR2 and P4HA1, genes that are involved in extracellular matrix modulation, cancer growth and metastatic potential, while the cell death-inducing genes ATF3 and ACHE were significantly upregulated (p < 0.0001). In conclusion, the results of this thesis support the value of immunohistochemical profiling for the diagnosis of prognostically significant subtypes of periampullary adenocarcinomas. The findings confirm the relevance of the precision-cut tissue slice culture model for anticancer drug sensitivity testing and the potential of selenium compounds as candidate drugs for the treatment of PDAC.
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| 8. |
- Halimi, Asif, et al.
(author)
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Isolation of pancreatic microbiota from cystic precursors of pancreatic cancer with intracellular growth and DNA damaging properties
- 2021
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In: Gut microbes. - : Taylor & Francis Group. - 1949-0976 .- 1949-0984. ; 13:1
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Journal article (peer-reviewed)abstract
- Emerging research suggests gut microbiome may play a role in pancreatic cancer initiation and progression, but cultivation of the cancer microbiome remains challenging. This pilot study aims to investigate the possibility to cultivate pancreatic microbiome from pancreatic cystic lesions associated with invasive cancer. Intra-operatively acquired pancreatic cyst fluid samples showed culture-positivity mainly in the intraductal papillary mucinous neoplasm (IPMN) group of lesions. MALDI-TOF MS profiling analysis shows Gammaproteobacteria and Bacilli dominate among individual bacteria isolates. Among cultivated bacteria, Gammaproteobacteria, particularly Klebsiella pneumoniae, but also Granulicatella adiacens and Enterococcus faecalis, demonstrate consistent pathogenic properties in pancreatic cell lines tested in ex vivo co-culture models. Pathogenic properties include intracellular survival capability, cell death induction, or causing DNA double-strand breaks in the surviving cells resembling genotoxic effects. This study provides new insights into the role of the pancreatic microbiota in the intriguing link between pancreatic cystic lesions and cancer.
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| 9. |
- He, Fei, et al.
(author)
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FPR2 Shapes an Immune-Excluded Pancreatic Tumor Microenvironment and Drives T-cell Exhaustion in a Sex-Dependent Manner
- 2023
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In: Cancer Research. - : American Association for Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 83:10, s. 1628-1645
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Journal article (peer-reviewed)abstract
- Sex-driven immune differences can affect tumor progression and the landscape of the tumor microenvironment. Deeper understanding of these differences in males and females can inform patient selection to improve sex-optimized immunotherapy treatments. In this study, single-cell RNA sequencing and protein analyses uncovered a subpopulation of myeloid cells in pancreatic lesions associated with an immune-excluded tumor phenotype and effector T-cell exhaustion exclusively in females. This myeloid subpopulation was positively correlated with poor survival and genetic signatures of M2-like macrophages and T-cell exhaustion in females. The G-protein coupled receptor formyl peptide receptor 2 (FPR2) mediated these immunosuppressive effects. In vitro, treatment of myeloid cells with a specific FPR2 antagonist prevented exhaustion and enhanced cytotoxicity of effector cells. Proteomic analysis revealed high expression of immunosuppressive secretory proteins PGE2 and galectin-9, enriched integrin pathway, and reduced proinflammatory signals like TNFα and IFNγ in female M2-like macrophages upon FPR2 agonist treatment. In addition, myeloid cells treated with FPR2 agonists induced TIM3 and PD-1 expression only in female T cells. Treatment with anti-TIM3 antibodies reversed T-cell exhaustion and stimulated their ability to infiltrate and kill pancreatic spheroids. In vivo, progression of syngeneic pancreatic tumors was significantly suppressed in FPR2 knockout (KO) female mice compared with wild-type (WT) female mice and to WT and FPR2 KO male mice. In female mice, inoculation of tumors with FPR2 KO macrophages significantly reduced tumor growth compared with WT macrophages. Overall, this study identified an immunosuppressive function of FPR2 in females, highlighting a potential sex-specific precision immunotherapy strategy.
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| 10. |
- Latacz, Emily, et al.
(author)
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Histopathological growth patterns of liver metastasis : updated consensus guidelines for pattern scoring, perspectives and recent mechanistic insights
- 2022
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In: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 127:6, s. 988-1013
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Research review (peer-reviewed)abstract
- The first consensus guidelines for scoring the histopathological growth patterns (HGPs) of liver metastases were established in 2017. Since then, numerous studies have applied these guidelines, have further substantiated the potential clinical value of the HGPs in patients with liver metastases from various tumour types and are starting to shed light on the biology of the distinct HGPs. In the present guidelines, we give an overview of these studies, discuss novel strategies for predicting the HGPs of liver metastases, such as deep-learning algorithms for whole-slide histopathology images and medical imaging, and highlight liver metastasis animal models that exhibit features of the different HGPs. Based on a pooled analysis of large cohorts of patients with liver-metastatic colorectal cancer, we propose a new cut-off to categorise patients according to the HGPs. An up-to-date standard method for HGP assessment within liver metastases is also presented with the aim of incorporating HGPs into the decision-making processes surrounding the treatment of patients with liver-metastatic cancer. Finally, we propose hypotheses on the cellular and molecular mechanisms that drive the biology of the different HGPs, opening some exciting preclinical and clinical research perspectives.
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