المؤلفون: Annarita Fanizzi, Maria Colomba Comes, Samantha Bove, Elisa Cavalera, Paola de Franco, Alessia Di Rito, Angelo Errico, Marco Lioce, Francesca Pati, Maurizio Portaluri, Concetta Saponaro, Giovanni Scognamillo, Ippolito Troiano, Michele Troiano, Francesco Alfredo Zito, Raffaella Massafra

المصدر: Scientific Reports, Vol 14, Iss 1, Pp 1-8 (2024)

مصطلحات موضوعية: Human papillomavirus, Oropharyngeal squamous cell carcinoma, Convolutional neural network, Explainable artificial intelligence, Grad-CAM, Medicine, Science

الوصف: Abstract Several studies have emphasised how positive and negative human papillomavirus (HPV+ and HPV−, respectively) oropharyngeal squamous cell carcinoma (OPSCC) has distinct molecular profiles, tumor characteristics, and disease outcomes. Different radiomics-based prediction models have been proposed, by also using innovative techniques such as Convolutional Neural Networks (CNNs). Although some of these models reached encouraging predictive performances, there evidence explaining the role of radiomic features in achieving a specific outcome is scarce. In this paper, we propose some preliminary results related to an explainable CNN-based model to predict HPV status in OPSCC patients. We extracted the Gross Tumor Volume (GTV) of pre-treatment CT images related to 499 patients (356 HPV+ and 143 HPV−) included into the OPC-Radiomics public dataset to train an end-to-end Inception-V3 CNN architecture. We also collected a multicentric dataset consisting of 92 patients (43 HPV+ , 49 HPV−), which was employed as an independent test set. Finally, we applied Gradient-weighted Class Activation Mapping (Grad-CAM) technique to highlight the most informative areas with respect to the predicted outcome. The proposed model reached an AUC value of 73.50% on the independent test. As a result of the Grad-CAM algorithm, the most informative areas related to the correctly classified HPV+ patients were located into the intratumoral area. Conversely, the most important areas referred to the tumor edges. Finally, since the proposed model provided additional information with respect to the accuracy of the classification given by the visualization of the areas of greatest interest for predictive purposes for each case examined, it could contribute to increase confidence in using computer-based predictive models in the actual clinical practice.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/3a58af39bb7947f98b520802b8a424b4Test

المؤلفون: Luigi Russo, Paolo Andreozzi, Francesco P Zito, Letizia Vozzella, Ivana G Savino, Giovanni Sarnelli, Rosario Cuomo

المصدر: The Saudi Journal of Gastroenterology, Vol 21, Iss 2, Pp 104-110 (2015)

مصطلحات موضوعية: Constipation, guar gum, irritable bowel syndrome, Diseases of the digestive system. Gastroenterology, RC799-869

الوصف: Background/Aims: Partially hydrolyzed guar gum (PHGG) relieves symptoms in constipation-predominant irritable bowel syndrome (IBS) and may have prebiotic properties. However, the correlation between the effectiveness of PHGG and patient characteristics has not been examined. We aimed to investigate the effect of PHGG in symptom relief on constipation-predominant IBS according to gender, age, and body mass index (BMI). Patients and Methods: Sixty-eight patients with IBS entered a 2-week run-in period, followed by a 4-week study period with PHGG. Patients completed a daily questionnaire to assess the presence of abdominal pain/discomfort, swelling, and the sensation of incomplete evacuation. The number of evacuations/day, the daily need for laxatives/enemas and stool consistency-form were also evaluated. All patients also underwent a colonic transit time (CTT) evaluation. Results: PHGG administration was associated with a significant improvement in symptom scores, use of laxatives/enemas, stool form/consistency and CTT. At the end of the study period and compared with baseline, the number of evacuations improved in women, patients aged ≥ 45 years and those with BMI ≥ 25 (P < 0.05 for all comparisons); abdominal bloating improved in males (P < 0.05), patients < 45 years (P < 0.01) and those with BMI < 25 (P < 0.05). A decrease in the number of perceived incomplete evacuations/day was reported in patients with a BMI ≥ 25 (P < 0.05). Reductions in laxative/enema use were recorded in females (P < 0.05), patients < 45 years (P < 0.01), and patients with BMI < 25 (P < 0.05). Conclusions: Gender, age, and BMI seem to influence the effect of PHGG supplementation in constipated IBS patients. Further studies are needed to clarify the interaction of such parameters with a fiber-enriched diet.

وصف الملف: electronic resource

العلاقة: http://www.saudijgastro.com/article.asp?issn=1319-3767;year=2015;volume=21;issue=2;spage=104;epage=110;aulast=RussoTest; https://doaj.org/toc/1319-3767Test; https://doaj.org/toc/1998-4049Test

الوصول الحر: https://doaj.org/article/6a6cf802e23741c4bc75de2210b040b9Test

المؤلفون: Luisa Galati, Purnima Gupta, Antonio Tufaro, Mariarosaria Marinaro, Concetta Saponaro, David Israel Escobar Marcillo, Donato Loisi, Rajdip Sen, Alexis Robitaille, Rosario N. Brancaccio, Cyrille Cuenin, Sandrine McKay-Chopin, Angelo Virgilio Paradiso, Václav Liška, Pavel Souček, Francesco Alfredo Zito, David J. Hughes, Massimo Tommasino, Tarik Gheit

المصدر: Infectious Agents and Cancer, Vol 18, Iss 1, Pp 1-7 (2023)

مصطلحات موضوعية: Human papillomavirus, HPV16, Colorectal cancer, Next generation sequencing, Luminex, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Infectious and parasitic diseases, RC109-216

الوصف: Abstract Background Although the role of viral agents, such as human papillomavirus (e.g. HPV16, HPV18) in colorectal cancer (CRC) has been previously investigated, results remain inconclusive. Methods To further evaluate the involvement of oncogenic HPV types in CRC, 40 frozen neoplastic and 40 adjacent colonic tissues collected from Italian patients were analyzed by Luminex-based assays that detect a broad spectrum of HPV types, i.e. Alpha (n = 21), Beta (n = 46) and Gamma HPVs (n = 52). In addition, 125 frozen CRC samples and 70 surrounding mucosal tissues were collected from Czech patients and analyzed by broad spectrum PCR protocols: (i) FAP59/64, (ii) FAPM1 and (iii) CUT combined with Next Generation Sequencing (NGS). Results Using Luminex-basedassays, DNA from HPV16 was detected in 5% (2/40) CRC tissues from Italian patients. One HPV16 DNA-positive CRC case was subsequently confirmed positive for E6*I mRNA. Cutaneous beta HPV types were detected in 10% (4/40) adjacent tissues only, namely HPV111 (n = 3) and HPV120 (n = 1), while gamma HPV168 (n = 1) and HPV199 (n = 1) types were detected in adjacent and in tumor tissues, respectively. The NGS analysis of the CRC Czech samples identified HPV sequences from mucosal alpha-3 (HPV89), alpha-7 (HPV18, 39, 68 and 70) and alpha-10 species (HPV11), as well as cutaneous beta-1 (HPV20, 24, 93, 98, 105,124) beta-2 (HPV23), beta-3 (HPV49) and gamma-1 species (HPV205). Conclusions Our findings indicate that HPV types belonging to the mucosal alpha, and the ‘cutaneous’ beta and gamma genera can be detected in the colonic mucosal samples with a low prevalence rate and a low number of HPV reads by Luminex and NGS, respectively. However, additional studies are required to corroborate these findings.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1750-9378Test

الوصول الحر: https://doaj.org/article/6b68842a603b48a9ac7b98a65fce0ab6Test

المؤلفون: Rosanna Dammacco, Jyotirmay Biswas, Amanda Mohanan-Earatt, Walter Lisch, Francesco Alfredo Zito, Giuseppe Rubini, Carlo Manno, Sebastiano Cicco, Giovanni Alessio, Franco Dammacco

المصدر: BMC Ophthalmology, Vol 23, Iss 1, Pp 1-14 (2023)

مصطلحات موضوعية: Granulomatosis with polyangiitis, Episcleritis, Scleritis, Orbital inflammatory disease, ANCA-associated vasculitis, Rituximab, Ophthalmology, RE1-994

الوصف: Abstract Background Ocular manifestations of granulomatosis with polyangiitis (GPA) have been reported in a limited number of studies and with largely variable frequency. Here we report on the clinical, diagnostic, and therapeutic features of a cohort of 63 GPA patients, with particular regard to 22 of them with ophthalmic involvement (35%). Methods Clinical manifestations, results of immunological findings, histopathological pictures, imaging data, Birmingham Vasculitis Activity Score, therapeutic regimens, and outcomes were retrospectively analyzed. At diagnosis, in addition to a structured clinical assessment, all patients underwent a comprehensive ophthalmologic examination. Results The most frequently involved organs were kidneys, lungs, ear/nose/throat, and eyes. Ocular manifestations were bilateral in 32%. The three most commonly diagnosed ophthalmologic manifestations were scleritis (36%), retro-orbital pseudotumor or orbital mass (23%), and episcleritis (13%). Ocular and systemic involvement were simultaneously present at onset in 41% of the patients; systemic involvement was followed by ocular lesions in 36%; ocular inflammation was followed by systemic manifestations in 18%; and an orbital mass in the absence of systemic disease characterized 5%. Glucocorticoids plus cyclophosphamide and glucocorticoids plus rituximab were the combined therapies most frequently employed during remission induction and remission maintenance, respectively. Persistent ophthalmologic and extra-ocular remissions were achieved in 77 and 64% of the patients, respectively. One to three systemic relapses were diagnosed in 7 patients (31.8%). At the last follow-up, a visual outcome 20/40 or better in 31 (70%) of 44 eyes was determined. Conclusions The eye was involved in over one third of our patients with GPA. Increased awareness, early diagnosis, and multi-specialty collaboration are critical in achieving a favorable outcome of GPA.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2415Test

الوصول الحر: https://doaj.org/article/6d385f7bc4b24ba499ed636b484c7394Test

المؤلفون: Nicola Altini, Emilia Puro, Maria Giovanna Taccogna, Francescomaria Marino, Simona De Summa, Concetta Saponaro, Eliseo Mattioli, Francesco Alfredo Zito, Vitoantonio Bevilacqua

المصدر: Bioengineering, Vol 10, Iss 4, p 396 (2023)

مصطلحات موضوعية: nuclei detection, tumor cellularity, instance segmentation, explainable artificial intelligence, Technology, Biology (General), QH301-705.5

الوصف: The segmentation and classification of cell nuclei are pivotal steps in the pipelines for the analysis of bioimages. Deep learning (DL) approaches are leading the digital pathology field in the context of nuclei detection and classification. Nevertheless, the features that are exploited by DL models to make their predictions are difficult to interpret, hindering the deployment of such methods in clinical practice. On the other hand, pathomic features can be linked to an easier description of the characteristics exploited by the classifiers for making the final predictions. Thus, in this work, we developed an explainable computer-aided diagnosis (CAD) system that can be used to support pathologists in the evaluation of tumor cellularity in breast histopathological slides. In particular, we compared an end-to-end DL approach that exploits the Mask R-CNN instance segmentation architecture with a two steps pipeline, where the features are extracted while considering the morphological and textural characteristics of the cell nuclei. Classifiers that are based on support vector machines and artificial neural networks are trained on top of these features in order to discriminate between tumor and non-tumor nuclei. Afterwards, the SHAP (Shapley additive explanations) explainable artificial intelligence technique was employed to perform a feature importance analysis, which led to an understanding of the features processed by the machine learning models for making their decisions. An expert pathologist validated the employed feature set, corroborating the clinical usability of the model. Even though the models resulting from the two-stage pipeline are slightly less accurate than those of the end-to-end approach, the interpretability of their features is clearer and may help build trust for pathologists to adopt artificial intelligence-based CAD systems in their clinical workflow. To further show the validity of the proposed approach, it has been tested on an external validation dataset, which was collected from IRCCS Istituto Tumori “Giovanni Paolo II” and made publicly available to ease research concerning the quantification of tumor cellularity.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2306-5354/10/4/396Test; https://doaj.org/toc/2306-5354Test

الوصول الحر: https://doaj.org/article/ad99363331c948249ed69c3ae29f1b5dTest

المؤلفون: Margherita Sonnessa, Sara Sergio, Concetta Saponaro, Michele Maffia, Daniele Vergara, Francesco Alfredo Zito, Andrea Tinelli

المصدر: Frontiers in Oncology, Vol 12 (2022)

مصطلحات موضوعية: NHERF1, gynecological cancers, cervical cancer, ovarian cancer, Wnt/beta-catenin pathway, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Gynecological cancer management remains challenging and a better understanding of molecular mechanisms that lead to carcinogenesis and development of these diseases is needed to improve the therapeutic approaches. The Na+/H+ exchanger regulatory factor 1 (NHERF1) is a scaffold protein that contains modular protein-interaction domains able to interact with molecules with an impact on carcinogenesis and cancer progression. During recent years, its involvement in gynecological cancers has been explored, suggesting that NHERF1 could be a potential biomarker for the development of new targeted therapies suitable to the management of these tumors. This comprehensive review provides an update on the recent study on NHERF1 activity and its pathological role in cervical and ovarian cancer, as well as on its probable involvement in the therapeutic landscape of these cancer types.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fonc.2022.836630/fullTest; https://doaj.org/toc/2234-943XTest

الوصول الحر: https://doaj.org/article/e991a8d8bf2641999dfed4207cd6b666Test

المؤلفون: Concetta Saponaro, Emanuela Scarpi, Margherita Sonnessa, Antonella Cioffi, Francesca Buccino, Francesco Giotta, Maria Irene Pastena, Francesco Alfredo Zito, Anita Mangia

المصدر: Frontiers in Oncology, Vol 11 (2021)

مصطلحات موضوعية: NLRP3 inflammasome, breast cancer, prognostic biomarker, PYCARD, TLR4, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Inflammasome complexes play a pivotal role in different cancer types. NOD-like receptor protein 3 (NLRP3) inflammasome is one of the most well-studied inflammasomes. Activation of the NLRP3 inflammasome induces abnormal secretion of soluble cytokines, generating advantageous inflammatory surroundings that support tumor growth. The expression levels of the NLRP3, PYCARD and TLR4 were determined by immunohistochemistry in a cohort of primary invasive breast carcinomas (BCs). We observed different NLRP3 and PYCARD expressions in non-tumor vs tumor areas (p

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fonc.2021.705331/fullTest; https://doaj.org/toc/2234-943XTest

الوصول الحر: https://doaj.org/article/be8e5b059b7a4fb2ac3de55b5ca89664Test

المؤلفون: Nicola Altini, Antonio Brunetti, Emilia Puro, Maria Giovanna Taccogna, Concetta Saponaro, Francesco Alfredo Zito, Simona De Summa, Vitoantonio Bevilacqua

المصدر: Bioengineering, Vol 9, Iss 9, p 475 (2022)

مصطلحات موضوعية: nuclei segmentation, histopathology, deep learning, Grad-CAM, semantic segmentation, instance segmentation, Technology, Biology (General), QH301-705.5

الوصف: Nuclei identification is a fundamental task in many areas of biomedical image analysis related to computational pathology applications. Nowadays, deep learning is the primary approach by which to segment the nuclei, but accuracy is closely linked to the amount of histological ground truth data for training. In addition, it is known that most of the hematoxylin and eosin (H&E)-stained microscopy nuclei images contain complex and irregular visual characteristics. Moreover, conventional semantic segmentation architectures grounded on convolutional neural networks (CNNs) are unable to recognize distinct overlapping and clustered nuclei. To overcome these problems, we present an innovative method based on gradient-weighted class activation mapping (Grad-CAM) saliency maps for image segmentation. The proposed solution is comprised of two steps. The first is the semantic segmentation obtained by the use of a CNN; then, the detection step is based on the calculation of local maxima of the Grad-CAM analysis evaluated on the nucleus class, allowing us to determine the positions of the nuclei centroids. This approach, which we denote as NDG-CAM, has performance in line with state-of-the-art methods, especially in isolating the different nuclei instances, and can be generalized for different organs and tissues. Experimental results demonstrated a precision of 0.833, recall of 0.815 and a Dice coefficient of 0.824 on the publicly available validation set. When used in combined mode with instance segmentation architectures such as Mask R-CNN, the method manages to surpass state-of-the-art approaches, with precision of 0.838, recall of 0.934 and a Dice coefficient of 0.884. Furthermore, performance on the external, locally collected validation set, with a Dice coefficient of 0.914 for the combined model, shows the generalization capability of the implemented pipeline, which has the ability to detect nuclei not only related to tumor or normal epithelium but also to other cytotypes.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2306-5354/9/9/475Test; https://doaj.org/toc/2306-5354Test

الوصول الحر: https://doaj.org/article/a98f1b273da14ef0845b7839f300f72fTest

المؤلفون: Angela Lombardi, Nicola Amoroso, Loredana Bellantuono, Samantha Bove, Maria Colomba Comes, Annarita Fanizzi, Daniele La Forgia, Vito Lorusso, Alfonso Monaco, Sabina Tangaro, Francesco Alfredo Zito, Roberto Bellotti, Raffaella Massafra

المصدر: Applied Sciences, Vol 12, Iss 14, p 7227 (2022)

مصطلحات موضوعية: sentinel lymph node, imbalanced dataset, data augmentation, breast cancer, machine learning, interpretability, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999

الوصف: The current guidelines recommend the sentinel lymph node biopsy to evaluate the lymph node involvement for breast cancer patients with clinically negative lymph nodes on clinical or radiological examination. Machine learning (ML) models have significantly improved the prediction of lymph nodes status based on clinical features, thus avoiding expensive, time-consuming and invasive procedures. However, the classification of sentinel lymph node status represents a typical example of an unbalanced classification problem. In this work, we developed a ML framework to explore the effects of unbalanced populations on the performance and stability of feature ranking for sentinel lymph node status classification in breast cancer. Our results indicate state-of-the-art AUC (Area under the Receiver Operating Characteristic curve) values on a hold-out set (67%) while providing particularly stable features related to tumor size, histological subtype and estrogen receptor expression, which should therefore be considered as potential biomarkers.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2076-3417/12/14/7227Test; https://doaj.org/toc/2076-3417Test

الوصول الحر: https://doaj.org/article/aaf36b281ca24345804fe579e8cb3e10Test

المؤلفون: Concetta Saponaro, Annarita Fanizzi, Margherita Sonnessa, Paolo Mondelli, Daniele Vergara, Donato Loisi, Raffaella Massafra, Agnese Latorre, Francesco A. Zito, Laura Schirosi

المصدر: Pharmaceuticals, Vol 15, Iss 6, p 651 (2022)

مصطلحات موضوعية: inflammasome NLRP3, PYCARD, CyclinD1, MYC, CCND1, Medicine, Pharmacy and materia medica, RS1-441

الوصف: Inflammasomes are protein complexes involved in the regulation of different biological conditions. Over the past few years, the role of NLRP3 in different tumor types has gained interest. In breast cancer (BC), NLRP3 has been associated with multiple processes including epithelia mesenchymal transition, invasion and metastization. Little is known about molecular modifications of NLRP3 up-regulation. In this study, in a cohort of BCs, the expression levels of NLRP3 and PYCARD were analyzed in combination with CyclinD1 and MYC ones and their gene alterations. We described a correlation between the NLRP3/PYCARD axis and CyclinD1 (p < 0.0001). NLRP3, PYCARD and CyclinD1’s positive expression was observed in estrogen receptor (ER) and progesterone receptor (PgR) positive cases (p < 0.0001). Furthermore, a reduction of NLRP3 and PYCARD expression has been observed in triple negative breast cancers (TNBCs) with respect to the Luminal phenotypes (p = 0.017 and p = 0.0015, respectively). The association NLRP3+/CCND1+ or PYCARD+/CCND1+ was related to more aggressive clinicopathological characteristics and a worse clinical outcome, both for progression free survival (PFS) and overall survival (OS) with respect to NLRP3+/CCND1− or PYCARD+/CCND1− patients, both in the whole cohort and also in the subset of Luminal tumors. In conclusion, our study shows that the NLRP3 inflammasome complex is down-regulated in TNBC compared to the Luminal subgroup. Moreover, the expression levels of NLRP3 and PYCARD together with the alterations of CCND1 results in Luminal subtype BC’ss poor prognosis.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1424-8247/15/6/651Test; https://doaj.org/toc/1424-8247Test

الوصول الحر: https://doaj.org/article/30f836eaad17433698bbc277a5b2fc64Test