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963 results on '"Papadimitriou, Christos A."'

6. Dose-dense sequential adjuvant chemotherapy in the trastuzumab era: final long-term results of the Hellenic Cooperative Oncology Group Phase III HE10/05 Trial

Author

Zagouri, Flora, Koliou, Georgia-Angeliki, Dimitrakopoulos, Foteinos, Papadimitriou, Christos, Binas, Ioannis, Koutras, Angelos, Papakostas, Pavlos, Markopoulos, Christos, Venizelos, Vasileios, Xepapadakis, Grigorios, Andrikopoulou, Αngeliki, Karanikiotis, Charisios, Psyrri, Amanda, Bafaloukos, Dimitrios, Kosmidis, Paris, Aravantinos, Gerasimos, Res, Eleni, Mauri, Davide, Koumarianou, Anna, Petraki, Kalliopi, Tsipoura, Anna, Pectasides, Dimitrios, Gogas, Helen, and Fountzilas, George

Published
2022
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11. Molecular Alterations in Paired Epithelial Ovarian Tumors in Patients Treated with Neoadjuvant Chemotherapy.

Author

Nikolaidi, Adamantia, Papadopoulou, Eirini, Haidopoulos, Dimitrios, Liontos, Michalis, Fountzilas, Elena, Tsaousis, Georgios, Goula, Kalliroi, Tsolaki, Eleftheria, Christopoulou, Athina, Binas, Ioannis, Stamatopoulou, Sofia, Koumarianou, Anna, Karageorgopoulou, Sofia, Goussia, Anna, Psyrri, Amanda, Papadimitriou, Christos, and Gogas, Helen

Abstract

Simple Summary: The standard of care for most women with advanced ovarian cancer is primary cytoreduction followed by platinum-based chemotherapy and paclitaxel. However, the use of neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) and adjuvant chemotherapy is not inferior, according to prospective randomized trials. Ovarian cancer has a low mutational load but exhibits a high detection rate of molecular alterations in various genes. It remains unclear whether this is an intrinsic feature of ovarian cancer or if it is due to the administration of a platinum combination during NACT. Our study aimed to determine whether NACT affects the tumor's molecular profile. Any modifications in these areas would need to be identified in the initial therapeutic planning, especially in the era of poly (ADP-ribose) polymerase (PARP) inhibitors. Background: Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) and adjuvant chemotherapy is a therapeutic choice for women with advanced ovarian cancer. Whether NACT affects the tumor's molecular profile has not been determined. Methods: This was a retrospective study of patients with advanced-stage epithelial ovarian cancer treated with NACT at oncology departments affiliated with the Hellenic Cooperative Oncology Group (HeCOG). Tumor molecular profiling was performed on formalin-fixed and paraffin-embedded (FFPE) tumor pre- and post-NACT tissues. Homologous recombination deficiency (HRD), tumor-infiltrating lymphocytes (TILs), tumor molecular alterations, and tumor mutational burden (TMB) via next-generation sequencing analysis were assessed. Results: Overall, tumors from 36 patients were assessed, and molecular profiling was evaluated in 20 paired tumor samples. HRD positivity exhibited no significant change between pre- and post-NACT tumors. The BRCA1/2 mutational status remained constant, irrespective of the treatment administration. Pre-NACT tumors tended to exhibit a lower percentage of intratumoral TILs compared to post-NACT tumors (p = 0.004). Differences in the mutation profile between pre- and post-treatment tissue were observed in 33.33% (6/18) of the cases. The mean tumor cell content (TCC) (p-value: 0.0840) and the mean genomic instability score (p-value: 0.0636) decreased slightly numerically after therapy. A moderate inverse relationship was observed between the pre-NACT TMB and the chemotherapy response score (p-value: 0.038), indicating this correlation is statistically significant. Conclusion: This study provides insights into the effect of NACT on the tumor molecular landscape. While BRCA1/2 and HRD status remained stable, an increase in TIL proportion and changes in the mutational profiles were observed post-treatment. [ABSTRACT FROM AUTHOR]

Published
2024
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12. The Clinical and Genetic Landscape of Hereditary Cancer: Experience from a Single Clinical Diagnostic Laboratory.

Author

TSOULOS, NIKOLAOS, AGIANNITOPOULOS, KONSTANTINOS, POTSKA, KEVISA, KATSELI, ANASTASIA, NTOGKA, CHRISTINA, PEPE, GEORGIA, BOUZARELOU, DIMITRA, PAPATHANASIOU, ATHANASIOS, GRIGORIADIS, DIMITRIOS, TSAOUSIS, GEORGIOS N., GOGAS, HELEN, TROUPIS, THEODORE, PAPAZISIS, KONSTANTINOS, NATSIOPOULOS, IOANNIS, VENIZELOS, VASSILEIOS, AMARANTIDIS, KYRIAKOS, GIASSAS, STYLIANOS, PAPADIMITRIOU, CHRISTOS, FOUNTZILAS, ELENA, and STATHOULOPOULOU, MAROULIO

Subjects
NUCLEOTIDE sequencing, GENETIC testing, FAMILY history (Medicine), CANCER patients, PROSTATE cancer, OVARIAN cancer
Abstract

Background/Aim: The application of next generation sequencing (NGS) technology in the genetic investigation of hereditary cancer is important for clinical surveillance, therapeutic approach, and reducing the risk of developing new malignancies. The aim of the study was to explore genetic predisposition in individuals referred for hereditary cancer. Materials and Methods: A total of 8,261 individuals were referred for multigene genetic testing, during the period 2020-2023, in the laboratory, and underwent multigene genetic testing using NGS. Among the examined individuals, 56.17% were diagnosed with breast cancer, 6.77% with ovarian cancer, 2.88% with colorectal cancer, 1.91% with prostate cancer, 6.43% were healthy with a significant family history of cancer, while 3.06% had a different type of cancer and 0.21% had not provided any information. Additionally, in 85 women with breast cancer we performed whole exome sequencing analysis. Results: 20% of the examined individuals carried a pathogenic variant. Specifically, 54.8% of the patients had a pathogenic variant in a clinically significant gene (BRCA1, BRCA2, PALB2, RAD51C, PMS2, CDKN2A, MLH1, MSH2, TP53, MSH6, APC, RAD51D, PTEN, RET, CDH1, MEN1, and VHL). Among the different types of pathogenic variants detected, a significant percentage (6.52%) represented copy number variation (CNV). With WES analysis, the following findings were detected: CTC1: c.880C>T, p.(Gln294*); MLH3: c.405del, p.(Asp136Metfs*2), PPM1D: c.1426_1430del, p.(Glu476Leufs*3), and SDHB: c.395A>G, p.(His132Arg). Conclusion: Comprehensive multigene genetic testing is necessary for appropriate clinical management of pathogenic variants’ carriers. Additionally, the information obtained is important for determining the risk of malignancy development in family members of the examined individuals. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Online Stochastic Max-Weight Bipartite Matching: Beyond Prophet Inequalities.

Author

Papadimitriou, Christos, Pollner, Tristan, Saberi, Amin, and Wajc, David

Subjects
POLYNOMIAL time algorithms, ONLINE algorithms, COMPUTATIONAL complexity, PROPHETS
Abstract

The rich literature on online Bayesian selection problems has long focused on so-called prophet inequalities, which compare the gain of an online algorithm to that of a "prophet" who knows the future. An equally natural, though significantly less well-studied, benchmark is the optimum online algorithm, which may be omnipotent (i.e., computationally unbounded), but not omniscient. What is the computational complexity of the optimum online? How well can a polynomial-time algorithm approximate it? Motivated by applications in ride hailing, we study the above questions for the online stochastic maximum-weight matching problem under vertex arrivals. For this problem, a number of 1/2 -competitive algorithms are known. This is the best possible ratio for this problem, as it generalizes the original single-item prophet inequality problem. We present a polynomial-time algorithm, which approximates the optimal online algorithm within a factor of 0.51—strictly more than the best-possible constant against a prophet. In contrast, we show that it is PSPACE-hard to approximate this problem within some universal constant α<1. Funding: Financial support from the National Science Foundation [Grants CCF1763970, CCF1812919, and CCF191070], the Office of Naval Research [Grant N000141912550], and Cisco Research is gratefully acknowledged. [ABSTRACT FROM AUTHOR]

Published
2024
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16. About Place Cells and Grid Cells : About Place Cells and Grid Cells

Author

Papadimitriou, Christos H., Hutchison, David, Series Editor, Kanade, Takeo, Series Editor, Kittler, Josef, Series Editor, Kleinberg, Jon M., Series Editor, Mattern, Friedemann, Series Editor, Mitchell, John C., Series Editor, Naor, Moni, Series Editor, Pandu Rangan, C., Series Editor, Steffen, Bernhard, Series Editor, Terzopoulos, Demetri, Series Editor, Tygar, Doug, Series Editor, Weikum, Gerhard, Series Editor, Böckenhauer, Hans-Joachim, editor, Komm, Dennis, editor, and Unger, Walter, editor

Published
2018
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17. Prognostic implications of mismatch repair deficiency in patients with nonmetastatic colorectal and endometrial cancer

Author

Fountzilas, Elena, Kotoula, Vassiliki, Pentheroudakis, George, Manousou, Kyriaki, Polychronidou, Genovefa, Vrettou, Eleni, Poulios, Christos, Papadopoulou, Eirini, Raptou, Georgia, Pectasides, Eirini, Karayannopoulou, Georgia, Chrisafi, Sofia, Papakostas, Pavlos, Makatsoris, Thomas, Varthalitis, Ioannis, Psyrri, Amanda, Samantas, Epaminontas, Bobos, Mattheos, Christodoulou, Christos, Papadimitriou, Christos, Nasioulas, George, Pectasides, Dimitrios, and Fountzilas, George

Published
2019
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18. Oxaliplatin-induced Acute Neurotoxicity Recovers Between Repeat Infusion Cycles: An Axonal Excitability Repeated Multiple Measurements Study.

Author

KOKOTIS, PANAGIOTIS, PAPANTONIOU, MICHAIL, CARR, RICHARD W., SCHMELZ, MARTIN, SIAKAVELLA, DIMITRA, SKAFIDA, EFTHYMIA, and PAPADIMITRIOU, CHRISTOS

Subjects
NEUROTOXICOLOGY, COLORECTAL cancer, ALCOHOLISM, OXALIPLATIN, CANCER patients
Abstract

Background/Aim: Oxaliplatin, a platinum-based chemotherapy used in the treatment of colorectal cancer, induces acute neurotoxicity following infusion. The aim of this study was to establish whether alterations in axonal excitability develop progressively with higher cumulative doses and whether there is a recovery in motor axons after each cycle of treatment. Patients and Methods: Twenty consecutive patients with a colorectal cancer diagnosis, referred from the Oncology Department of Aretaieion Hospital of Athens, were enrolled in this study between October 2018 and May 2019. None of the participants had diabetes, alcohol abuse, known neuropathy or were previously treated with another neo-adjuvant therapy. Threshold Tracking techniques and Qtrac software were used for assessing axonal excitability in motor axons. Excitability recordings were undertaken before and immediately after the end of oxaliplatin infusion. Results: Statistically significant changes were found (p<0.01) in axonal excitability (relative refractory period, refractoriness at 2 ms and 2.5 ms, subexcitability and super-excitability) before and after oxaliplatin infusion. No statistically significant changes (p>0.05) were found in threshold electrotonus and strengthduration parameters before and after oxaliplatin infusion. We also did not find statistically significant differences (p>0.05) between means of excitability parameters before infusion at each cycle. Conclusion: Our study confirms oxaliplatin-induced acute neurotoxicity following infusion and suggests that motor axons recover between repeat infusion cycles. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Correlation of MYC Gene and Protein Status With Breast Cancer Subtypes and Outcome of Patients Treated With Anthracycline-Based Adjuvant Chemotherapy. Pooled Analysis of 2 Hellenic Cooperative Group Phase III Trials

Author

Batistatou, Anna, Kotoula, Vassiliki, Bobos, Mattheos, Kouvatseas, George, Zagouri, Flora, Tsolaki, Eleftheria, Gogas, Helen, Koutras, Angelos, Pentheroudakis, George, Timotheadou, Eleni, Pervana, Stavroula, Goussia, Anna, Petraki, Kalliopi, Sotiropoulou, Maria, Koletsa, Triantafyllia, Razis, Evangelia, Kosmidis, Paris, Aravantinos, Gerasimos, Papadimitriou, Christos, Pectasides, Dimitrios, and Fountzilas, George

Published
2018
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23. Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients

Author

Koroveshi, Dhurata, Bouzid, Kamel, Casalnuovo, Monica, Cascallar, Diana, Korbenfeld, Ernesto Pablo, Bastick, Patricia, Beith, Jane, Colosimo, Maree, Friedlander, Michael, Ganju, Vinod, Green, Michael, Patterson, Kevin, Redfern, Andrew, Richardson, Gary, Ceric, Timur, Gordana, Kecman, Beato, Carlos Augusto, Ferrari, Marcela, Hegg, Roberto, Helena, Vanessa, Ismael, Gustavo Fernando, Lessa, Alvaro Edson, Mano, Max, Morelle, Alessandra, Nogueira, Jose Alberto, Timcheva, Konstanta, Tomova, Antoaneta, Tsakova, Maya, Zlatareva-Petrova, Ani, Asselah, Jamil, Assi, Hazem, Brezden-Masley, Christine, Chia, Stephen, Freedman, Ori, Harb, Mohammed, Joy, Anil Abraham, Kulkarni, Swati, Prady, Catherine, Gaete, Alejandro Andres Acevedo, Matamala, Luis, Torres, Roberto, Yanez, Eduardo, Franco, Sandra, Urrego, Marcela, Gugić, Damir, Vrbanec, Damir, Melichar, Bohuslav, Prausová, Jana, Vyzula, Rostislav, Pilarte, Rafael Gutierrez, León, María Isabel, Muñoz, Rene, Ramos, Glenda, Azeem, Hamdy Abdel, Aziz, Amr Abdel, El Zawahry, Heba, Osegueda, Finlander Rosales, Alexandre, Jerome, Artignan, Xavier, Barletta, Hugues, Beguier, Emmanuel, Berdah, Jean-François, Marty, Chantal Bernard, Bollet, Marc, Bourgeois, Hugues, Bressac, Claude, Burki, Franck, Campone, Mario, Coeffic, David, Cojocarasu, Oana Zveltlana, Dagada, Corinne, Dalenc, Florence, Del Piano, Francesco, Desauw, Christophe, Desmoulins, Isabelle, Dohollou, Nadine, Egreteau, Joelle, Ferrero, Jean-Marc, Foa, Cyril, Garidi, Reda, Gasnault, Laurent, Gligorov, Joseph, Guardiola, Emmanuel, Hamizi, Salima, Jarcau, Rosana, Jacquin, Jean-Philippe, Jaubert, Dominique, Jolimoy, Geneviève, Mineur, Hortense Laharie, Largillier, Remy, Leduc, Bernard, Martin, Philippe, Melis, Adrien, Monge, Jeremy, Moullet, Isabelle, Mousseau, Mireille, Nguyen, Suzanne, Orfeuvre, Hubert, Petit, Thierry, Pivot, Xavier, Priou, Frank, Bach, Isabelle Sillet, Simon, Helene, Stefani, Laetitia, Uwer, Lionel, Youssef, Ali, Aktas, Bahriye, von der Assen, Albert, Augustin, Doris, Balser, Christina, Bauer, Lelia-Eveline, Bechtner, Christina, Beyer, Greta, Brucker, Cosima, Bückner, Ute, Busch, Steffi, Christensen, Bernd, Deryal, Mustafa, Farrokh, Andre, Faust, Elke, Friedrichs, Kay, Graf, Heiko, Griesshammer, Martin, Grischke, Eva-Maria, Hänle, Claudia, Heider, Andrea, Henschen, Stephan, Hesse, Tobias, Jackisch, Christian, Kisro, Jens, Köhler, Andreas, Kuemmel, Sherko, Lampe, Dieter, Lantzsch, Tilmann, Latos, Kunibert, Lex, Benno, Liedtke, Cornelia, Luedders, Doerte, Maintz, Christoph, Müller, Volkmar, Overkamp, Friedrich, Park-Simon, Tjoung-won, Paul, Marion, Prechtl, Anita, Ringsdorf, Uta, Runnebaum, Ingo, Ruth, Sylvia, Salat, Christoph, Scheffen, Iris, Schilling, Jörg, Schmatloch, Sabine, Schmidt, Marcus, Schneeweiss, Andreas, Schrader, Iris, Seipelt, Gernot, Simon, Elke, Stefek, Andrea, Stickeler, Elmar, Thill, Marc, Tio, Joke, Tuczek, Anna, Warm, Mathias, Weigel, Michael, Wischnik, Arthur, Wojcinski, Sebastian, Ziegler-Löhr, Katja, Aravantinos, Gerasimos, Ardavanis, Alexandros, Fountzilas, George, Gogas, Helen, Kakolyris, Stylianos, Mavroudis, Dimitris, Papadimitriou, Christos, Papandreou, Christos, Papazisis, Konstantinos, Castro, Hugo, Hernandez-Monroy, Cesar Estuardo, Ngan, Roger, Yeo, Winnie, Bittner, Nora, Boer, Katalin, Csejtei, Andras, Horvath, Zsolt, Kocsis, Judit, Mangel, László Csaba, Mezei, Klara, Nagy, Zsuzsanna, Szanto, Janos, Atmakusuma, Djumhana, Fadjari, Heri, Kurnianda, Djohan, Prayogo, Nugroho, Tanggo, Eddie Herman, Coate, Linda, Hennessy, Bryan, Kelly, Cathy, Martin, Michael, Nasim, Saira, O'Connor, Miriam, Aieta, Michele, Allegrini, Giacomo, Amadori, Dino, Bidoli, Paolo, Biti, Giampaolo, Bordonaro, Roberto, Bottini, Alberto, Carterni, Giacomo, Cavanna, Luigi, Cazzaniga, Marina, Cognetti, Francesco, Contu, Antonio, Cruciani, Giorgio, Donadio, Michela, Falcone, Alfredo, Farci, Daniele, Forcignanò, R. Chiara, Frassoldati, Antonio, Gaion, Fernando, Gamucci, Teresa, Giotta, Francesco, de Laurentiis, Michele, Livi, Lorenzo, Lorusso, Vito, Maiello, Evaristo, Marchetti, Paolo, Mariani, Gabriella, Mion, Marta, Moscetti, Luca, Musolino, Antonino, Pazzola, Antonio, Pedrazzoli, Paolo, Pigi, Andrea, de Placido, Sabino, Caremoli, Elena Rota, Santoro, Armando, Tienghi, Amelia, Ahn, Jin-Seok, Jung, Kyung Hae, Lee, Keun Seok, Lee, Soo Hyeon, Seo, Jae Hong, Sohn, Joo-Hyuk, Cesas, Alvydas, Juozaityte, Elona, Cheah, Nellie Lay Chin, Chong, Flora Li Tze, Devi, Beena C.R., Phua, Vincent, Teoh, Darren, Ching, Lee Wei, Yusof, Mastura, Corona, Jorge, Dominguez, Adriana, Mendoza, René Lazaro González, Hernandez, Carlos Alberto, Ramiro, Alejandro Juarez, Santos, Juan Matos, Espinosa, Paola Morales, Villarreal Garza, Cynthia Mayte, Errihani, Hassan, Bakker, Sandra, van den Berkmortel, Franchette, Blaisse, R.J.B., Huinink, Daan ten Bokkel, van den Bosch, J., Braun, J.J., Dercksen, M.W., Droogendijk, Helga, Erdkamp, Frans, Haringhuizen, Annebeth, de Jongh, F.E., Kok, T.C., Los, Maartje, Madretsma, Stanley, Terwogt, Jetske M. Meerum, van der Padt, Annemieke, van Rossum-Schornagel, Quirine Clementine, Smilde, T.J., de Valk, Bart, van der Velden, Annette, van Warmerdam, Laurence, van de Wouw, A.J., North, Richard, Kersten, Christian, Mjaaland, Ingvild, Wist, Erik, Aziz, Zeba, Masood, Nehal, Rashid, Kamran, Shah, Mazhar, Alcedo, Juan Carlos, Aleman, Diana, Neciosup, Silvia, Reategui, Rocio, Valdiviezo, Natalia, Vera, Luis, Fernando, Gracieux, Roque, Fernando, Strebel, Heinrik Martin, Krzemieniecki, Krzysztof, Litwiniuk, Maria, Mruk, Andrzej, Pienkowski, Tadeusz, Sawrycki, Piotr, Slomian, Grzegorz, Tomczak, Piotr, Afonso, Noemia, Cardoso, Fátima, Damasceno, Margarida, Nave, Monica, Badulescu, Florinel, Ciule, Larisa, Curescu, Stefan, Eniu, Alexandru, Filip, Dumitru, Grecea, Daniela, Jinga, Dan-Corneliu, Lungulescu, Dan, Oprean, Cristina Marinela, Stanculeanu, Dana Lucia, Turdean, Maria, Dvornichenko, Viktoria, Emelyanov, Sergey, Lichinitser, Mikhail, Manikhas, Alexey, Sakaeva, Dina, Shirinkin, Vadim, Stroyakovskiy, Daniil, Abulkhair, Omalkhair, Zekri, Jamal, Filipovic, Sladjana, Kovcin, Vladimir, Nedovic, Jasmina, Pesic, Jasna, Vasovic, Suzana, Ng, Raymond, Bystricky, Branislav, Leskova, Jaroslava, Mardiak, Jozef, Mišurová, Etela, Wagnerova, Maria, Takač, Iztok, Demetriou, Georgia Savva, Dreosti, Lydia, Govender, Poovandren, Jordaan, Johannes Petrus, Veersamy, Petrosian, Romero, Jose Luis Alonso, Lopez, Norberto Batista, Arias, Carmen Cañabate, Chacon, Jose, Aramburo, Antonio Fernandez, Morales, Luis Antonio Fernandez, Garcia, Mirta, Estevez, Laura Garcia, Garcia-Palomo Perez, Andres, Garcia Saenz, Jose Angel, Garcia Sanchis, Laura, Cubells, Laia Garrigos, Cortijo, Lucia Gonzalez, Santiago, Santiago Gonzalez, De Aranguiz, Blanca Hernando Fernandez, Mañas, José Juan Illarramendi, Gallego, Pedro Jimenez, Cussac, Antonio Llombart, Ferrandiz, Cristina Llorca, Garrido, Maria Lomas, Alvarez, Pilar Lopez, Vega, Jose Manuel Lopez, Del Prado, Purificacion Martinez, Jañez, Noelia Martinez, Murillo, Serafin Morales, Rosales, Adolfo Murias, Jaso, Laura Murillo, Fernandez, Ignacio Pelaez, Martorell, Antonia Perello, Carrion, Ramon Perez, Simon, Sonia Pernas, Alcibar, Arrate Plazaola, Lorenzo, Jose Ponce, Garcia, Vanesa Quiroga, Asensio, Teresa Ramon y Cajal, Maicas, Maria Dolores Torregrosa, Villanueva Silva, Maria Jose, Killander, Fredrika, Svensson, Jan Henry, Fehr, Mathias, Hauser, Nik, Müller, Andreas, Pagani, Olivia, Passmann-Kegel, Heike, Popescu, Razvan, Rabaglio, Manuela, Rauch, Daniel, Schlatter, Christina, Zaman, Khalil, Chang, Tsai-Wang, Huang, Chiun-Sheng, Wang, Hwei-Chung, Yu, Jyh-Cherng, Bandidwattanawong, Chanyoot, Maneechavakajorn, Jedzada, Seetalarom, Kasan, Dejthevaporn, Thitiya (Sirisinha), Somwangprasert, Areewan, Vongsaisuwon, Mawin, Akbulut, Hakan, Altundag, Kadri, Arican, Ali, Bozcuk, Hakan, Eralp, Yesim, Idris, Mohamed, Isikdogan, Abdurrahman, Senol, Coskun Hasan, Sevinc, Alper, Uygun, Kazim, Yucel, Eftal, Yucel, Idris, Yumuk, Fulden, Shparyk, Yaroslav, Voitko, Nataliia, Jaloudi, Mohammed, Adams, Jocelyn, Agrawal, Rajiv, Ahmed, Samreen, Alhasso, Abdulla, Allerton, Rozenn, Anwar, Suhail, Archer, Caroline, Ashford, Richard, Barraclough, Lisa, Bertelli, Gianfilippo, Bishop, Jill, Branson, Tony, Butt, Mohammed, Chakrabarti, Amit, Chakraborti, Prabir, Churn, Mark, Crowley, Clare, Davis, Ruth, Dhadda, Amandeep, Eldeeb, Hany, Fraser, Judith, Hall, Julia, Hickish, Tamas, Hogg, Martin, Howe, Theresa, Joffe, Jonathan, Kelleher, Muireann, Kelly, Stephen, Kendall, Anne, Kristeleit, Hartmut, Lumsden, Graeme, Macmillan, Craig, MacPherson, Iain, Malik, Zafar, Mithal, Natasha, Neal, Anthony, Panwar, Udaiveer, Proctor, Andrew, Proctor, Steven John, Raj, Sanjay, Rehman, Shazza, Sandri, Ines, Scatchard, Kate, Sherwin, Elizabeth, Sims, Eliot, Singer, Julian, Smith, Sarah, Tahir, Saad, Taylor, Wendy, Tsalic, Medy, Verrill, Mark, Wardley, Andrew, Waters, Simon, Wheatley, Duncan, Wright, Kathryn, Yuille, Frances, Alonso, Isabel, Artagaveytia, Nora, Rodriguez, Robinson, Arbona, Esther, Garcia, Yuraima, Lion, Lorena, Marcano, Dalila, Van Thuan, Tran, Gligorov, J., Ataseven, B., Verrill, M., De Laurentiis, M., Jung, K.H., Azim, H.A., Al-Sakaff, N., Lauer, S., Shing, M., and Pivot, X.

Published
2017
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25. The Architecture of a Biologically Plausible Language Organ

Author

Mitropolsky, Daniel and Papadimitriou, Christos H.

Subjects
FOS: Computer and information sciences, Computer Science - Computation and Language, FOS: Biological sciences, Quantitative Biology - Neurons and Cognition, Neurons and Cognition (q-bio.NC), Computation and Language (cs.CL)
Abstract

We present a simulated biologically plausible language organ, made up of stylized but realistic neurons, synapses, brain areas, plasticity, and a simplified model of sensory perception. We show through experiments that this model succeeds in an important early step in language acquisition: the learning of nouns, verbs, and their meanings, from the grounded input of only a modest number of sentences. Learning in this system is achieved through Hebbian plasticity, and without backpropagation. Our model goes beyond a parser previously designed in a similar environment, with the critical addition of a biologically plausible account for how language can be acquired in the infant's brain, not just processed by a mature brain., 9 pages, 4 figures

Published
2023

26. Computation with Sequences in the Brain

Author

Dabagia, Max, Papadimitriou, Christos H., and Vempala, Santosh S.

Subjects
FOS: Computer and information sciences, Computer Science - Machine Learning, Artificial Intelligence (cs.AI), Computer Science - Artificial Intelligence, FOS: Biological sciences, Quantitative Biology - Neurons and Cognition, Computer Science - Neural and Evolutionary Computing, Neurons and Cognition (q-bio.NC), Neural and Evolutionary Computing (cs.NE), Machine Learning (cs.LG)
Abstract

Even as machine learning exceeds human-level performance on many applications, the generality, robustness, and rapidity of the brain's learning capabilities remain unmatched. How cognition arises from neural activity is a central open question in neuroscience, inextricable from the study of intelligence itself. A simple formal model of neural activity was proposed in Papadimitriou [2020] and has been subsequently shown, through both mathematical proofs and simulations, to be capable of implementing certain simple cognitive operations via the creation and manipulation of assemblies of neurons. However, many intelligent behaviors rely on the ability to recognize, store, and manipulate temporal sequences of stimuli (planning, language, navigation, to list a few). Here we show that, in the same model, time can be captured naturally as precedence through synaptic weights and plasticity, and, as a result, a range of computations on sequences of assemblies can be carried out. In particular, repeated presentation of a sequence of stimuli leads to the memorization of the sequence through corresponding neural assemblies: upon future presentation of any stimulus in the sequence, the corresponding assembly and its subsequent ones will be activated, one after the other, until the end of the sequence. Finally, we show that any finite state machine can be learned in a similar way, through the presentation of appropriate patterns of sequences. Through an extension of this mechanism, the model can be shown to be capable of universal computation. We support our analysis with a number of experiments to probe the limits of learning in this model in key ways. Taken together, these results provide a concrete hypothesis for the basis of the brain's remarkable abilities to compute and learn, with sequences playing a vital role., 24 pages, 12 figures

Published
2023

29. Safety and Tolerability of Anthracycline-Containing Adjuvant Chemotherapy in Elderly High-Risk Breast Cancer Patients

Author

Karavasilis, Vasilios, Papadimitriou, Christos, Gogas, Helen, Kouvatseas, George, Pentheroudakis, George, Koutras, Angelos, Christodoulou, Christos, Bafaloukos, Dimitrios, Samantas, Epaminontas, Pisanidis, Nikolaos, Papakostas, Pavlos, Aravantinos, Gerasimos, Karanikiotis, Charisios, Kosmidis, Paris, Pectasides, Dimitrios, Dimopoulos, Meletios-Athanassios, and Fountzilas, George

Published
2016
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31. Neuroscience needs Network Science

Author

Barabási, Dániel L, Bianconi, Ginestra, Bullmore, Ed, Burgess, Mark, Chung, SueYeon, Eliassi-Rad, Tina, George, Dileep, Kovács, István A., Makse, Hernán, Papadimitriou, Christos, Nichols, Thomas E., Sporns, Olaf, Stachenfeld, Kim, Toroczkai, Zoltán, Towlson, Emma K., Zador, Anthony M, Zeng, Hongkui, Barabási, Albert-László, Bernard, Amy, and Buzsáki, György

Subjects
FOS: Biological sciences, Quantitative Biology - Neurons and Cognition, Neurons and Cognition (q-bio.NC)
Abstract

The brain is a complex system comprising a myriad of interacting elements, posing significant challenges in understanding its structure, function, and dynamics. Network science has emerged as a powerful tool for studying such intricate systems, offering a framework for integrating multiscale data and complexity. Here, we discuss the application of network science in the study of the brain, addressing topics such as network models and metrics, the connectome, and the role of dynamics in neural networks. We explore the challenges and opportunities in integrating multiple data streams for understanding the neural transitions from development to healthy function to disease, and discuss the potential for collaboration between network science and neuroscience communities. We underscore the importance of fostering interdisciplinary opportunities through funding initiatives, workshops, and conferences, as well as supporting students and postdoctoral fellows with interests in both disciplines. By uniting the network science and neuroscience communities, we can develop novel network-based methods tailored to neural circuits, paving the way towards a deeper understanding of the brain and its functions., 19 pages, 1 figure, 1 box

Published
2023

34. RediScore: Prospective validation of a pipeline for homologous recombination deficiency analysis.

Author

TSANTIKIDI, AIKATERINI, PAPAZISIS, KONSTANTINOS, FLOROS, THEOFANIS, GAZOULI, MARIA, PAPADOPOULOU, EIRINI, TSAOUSIS, GEORGIOS, NASIOULAS, GEORGIOS, MESTER, ANDRA, MILAN, KUBELAC PAUL, GOZMAN, BOGDAN, AFRASANIE, VLAD, STANCULEANU, DANA LUCIA, TRIFANESCU, OANA, PESCARU, FLORENTINA, MILITARU, CLAUDIA, and PAPADIMITRIOU, CHRISTOS

Subjects
OVARIAN cancer, SINGLE nucleotide polymorphisms, NUCLEOTIDE sequencing, GENETIC mutation, CANCER patients
Abstract

Tumors harboring homologous recombination deficiency (HRD) are considered optimal candidates for poly(ADP-ribose) polymerase 1 (PARP) inhibitor treatment. Such deficiency can be detected by analyzing breast cancer type (BRCA)1/2 gene mutations, as well as mutations in other genes of the homologous recombination pathway. The algorithmic measurement of the HRD effect by identifying genomic instability (GI) has been used as biomarker. As compared with the direct measurement of somatic gene alterations, this approach increases the number of patients who could benefit from PARP inhibitor treatment. In the present study, the performance of the Oncoscan CNV assay, accompanied by appropriate bioinformatic algorithms, was evaluated for its performance in GI calculation and was compared with that of a validated next-generation sequencing (NGS) test (myChoice HRD test). In addition, the clinical utility of the GI score (GIS) and BRCA1/2 tumor analysis were investigated in a cohort of 444 patients with ovarian cancer. For that reason, single nucleotide polymorphism (SNP) arrays and appropriate bioinformatics algorithms were used to calculate GIS in 29 patients with ovarian cancer with known GIS status using a validated NGS test. Furthermore, BRCA1/2 analysis results were compared between the aforementioned assay and the amplicon-based Oncomine™ BRCA Research Assay. BRCA1/2 analysis was performed in 444 patients with ovarian cancer, while GIS was calculated in 175 BRCA1/2-negative cases. The bioinformatics algorithm developed for GIS calculation in combination with NGS BRCA1/2 analysis (RediScore), and the OncoscanR pipeline exhibited a high overall agreement with the validated test (93.1%). In addition, the Oncomine NGS assay had a 100% agreement with the validated test. The BRCA1/2 mutation frequency was 26.5% in the examined patients with ovarian cancer. GIS was positive in 40% of the BRCA1/2-negative cases. The RediScore bioinformatics algorithm developed for GIS calculation in combination with NGS BRCA1/2 analysis is a viable and effective approach for HRD calculation in patients with ovarian cancer, offering a positive prediction for PARP inhibitor responsiveness in 55% of the patients. [ABSTRACT FROM AUTHOR]

Published
2023
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35. An impossibility theorem in game dynamics.

Author

Milionis, Jason, Papadimitriou, Christos, Piliouras, Georgios, and Spendlove, Kelly

Subjects
*NASH equilibrium, *GAME theory, *DYNAMICAL systems, *COMPUTATIONAL complexity, *GAMES
Abstract

The Nash equilibrium—a, combination of choices by the players of a game from which no self-interested player would deviate—is the predominant solution concept in game theory. Even though every game has a Nash equilibrium, it is not known whether there are deterministic behaviors of the players who play a game repeatedly that are guaranteed to converge to a Nash equilibrium of the game from all starting points. If one assumes that the players’ behavior is a discrete-time or continuous-time rule whereby the current mixed strategy profile is mapped to the next, this question becomes a problem in the theory of dynamical systems. We apply this theory, and in particular Conley index theory, to prove a general impossibility result: There exist games, for which all game dynamics fail to converge to Nash equilibria from all starting points. The games which help prove this impossibility result are degenerate, but we conjecture that the same result holds, under computational complexity assumptions, for nondegenerate games. We also prove a stronger impossibility result for the solution concept of approximate Nash equilibria: For a set of games of positive measure, no game dynamics can converge to the set of approximate Nash equilibria for a sufficiently small yet substantial approximation bound. Our results establish that, although the notions of Nash equilibrium and its computation-inspired approximations are universally applicable in all games, they are fundamentally incomplete as predictors of long-term player behavior. [ABSTRACT FROM AUTHOR]

Published
2023
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36. The Utility of NGS Analysis in Homologous Recombination Deficiency Tracking.

Author

Tsantikidi, Aikaterini, Papadopoulou, Eirini, Metaxa-Mariatou, Vasiliki, Kapetsis, George, Tsaousis, Georgios, Meintani, Angeliki, Florou-Chatzigiannidou, Chrysiida, Gazouli, Maria, Papadimitriou, Christos, Timotheadou, Eleni, Kotsakis, Athanasios, Boutis, Anastasios, Boukovinas, Ioannis, Kampletsas, Eleftherios, Kontovinis, Loukas, Fountzilas, Elena, Andreadis, Charalampos, Karanikiotis, Charisios, Filippou, Dimitrios, and Theodoropoulos, Georgios

Subjects
BRCA genes, PANCREATIC cancer, POLY(ADP-ribose) polymerase, GENETIC mutation, HETEROZYGOSITY, PANCREATIC tumors, OVARIAN cancer
Abstract

Several tumor types have been efficiently treated with PARP inhibitors (PARPis), which are now approved for the treatment of ovarian, breast, prostate, and pancreatic cancers. The BRCA1/2 genes and mutations in many additional genes involved in the HR pathway may be responsible for the HRD phenomenon. The aim of the present study was to investigate the association between genomic loss of heterozygosity (gLOH) and alterations in 513 genes with targeted and immuno-oncology therapies in 406 samples using an NGS assay. In addition, the %gLOHs of 24 samples were calculated using the Affymetrix technology in order to compare the results obtained via the two methodologies. HR variations occurred in 20.93% of the malignancies, while BRCA1/2 gene alterations occurred in 5.17% of the malignancies. The %LOH was highly correlated with alterations in the BRCA1/2 genes, since 76.19% (16/21) of the BRCA1/2 positive tumors had a high %LOH value (p = 0.007). Moreover, the LOH status was highly correlated with the TP53 and KRAS statuses, but there was no association with the TMB value. Lin's concordance correlation coefficient for the 24 samples simultaneously examined via both assays was 0.87, indicating a nearly perfect agreement. In conclusion, the addition of gLOH analysis could assist in the detection of additional patients eligible for treatment with PARPis. [ABSTRACT FROM AUTHOR]

Published
2023
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41. Extremal combinatorics, iterated pigeonhole arguments, and generalizations of PPP

Author

Pasarkar, Amol, Papadimitriou, Christos, and Yannakakis, Mihalis

Subjects
FOS: Computer and information sciences, Extremal Combinatorics, Computer Science - Computational Complexity, Total Complexity, FOS: Mathematics, Pigeonhole Principle, Mathematics - Combinatorics, Combinatorics (math.CO), Computational Complexity (cs.CC), Theory of computation → Complexity classes
Abstract

We study the complexity of computational problems arising from existence theorems in extremal combinatorics. For some of these problems, a solution is guaranteed to exist based on an iterated application of the Pigeonhole Principle. This results in the definition of a new complexity class within TFNP, which we call PLC (for "polynomial long choice"). PLC includes all of PPP, as well as numerous previously unclassified total problems, including search problems related to Ramsey’s theorem, the Sunflower theorem, the Erdős-Ko-Rado lemma, and König’s lemma. Whether the first two of these four problems are PLC-complete is an important open question which we pursue; in contrast, we show that the latter two are PPP-complete. Finally, we reframe PPP as an optimization problem, and define a hierarchy of such problems related to Turàn’s theorem., LIPIcs, Vol. 251, 14th Innovations in Theoretical Computer Science Conference (ITCS 2023), pages 88:1-88:20

Published
2022

45. Neuroscience Needs Network Science.

Author

Barabási, Dániel L., Bianconi, Ginestra, Bullmore, Ed, Burgess, Mark, SueYeon Chung, Eliassi-Rad, Tina, George, Dileep, Kovács, István A., Makse, Hernán, Nichols, Thomas E., Papadimitriou, Christos, Sporns, Olaf, Stachenfeld, Kim, Toroczkai, Zoltán, Towlson, Emma K., Zador, Anthony M., Hongkui Zeng, Barabási, Albert-László, Bernard, Amy, and Buzsáki, György

Subjects
NEUROSCIENCES, BRAIN physiology, DIAGNOSTIC imaging
Abstract

The brain is a complex system comprising a myriad of interacting neurons, posing significant challenges in understanding its structure, function, and dynamics. Network science has emerged as a powerful tool for studying such interconnected systems, offering a framework for integrating multiscale data and complexity. To date, network methods have significantly advanced functional imaging studies of the human brain and have facilitated the development of control theory-based applications for directing brain activity. Here, we discuss emerging frontiers for network neuroscience in the brain atlas era, addressing the challenges and opportunities in integrating multiple data streams for understanding the neural transitions from development to healthy function to disease. We underscore the importance of fostering interdisciplinary opportunities through workshops, conferences, and funding initiatives, such as supporting students and postdoctoral fellows with interests in both disciplines. By bringing together the network science and neuroscience communities, we can develop novel network-based methods tailored to neural circuits, paving the way toward a deeper understanding of the brain and its functions, as well as offering new challenges for network science. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
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46. The Role of EMT-Related lncRNAs in Ovarian Cancer.

Author

Lampropoulou, Dimitra Ioanna, Papadimitriou, Marios, Papadimitriou, Christos, Filippou, Dimitrios, Kourlaba, Georgia, Aravantinos, Gerasimos, and Gazouli, Maria

Subjects
OVARIAN cancer, LINCRNA, EPITHELIAL-mesenchymal transition, DELAYED diagnosis, INDUCED ovulation, DRUG resistance
Abstract

Ovarian cancer (OC) is one of the deadliest cancers worldwide; late diagnosis and drug resistance are two major factors often responsible for high morbidity and treatment failure. Epithelial-to-mesenchymal transition (EMT) is a dynamic process that has been closely linked with cancer. Long non-coding RNAs (lncRNAs) have been also associated with several cancer-related mechanisms, including EMT. We conducted a literature search in the PubMed database in order to sum up and discuss the role of lncRNAs in regulating OC-related EMT and their underlying mechanisms. Seventy (70) original research articles were identified, as of 23 April 2023. Our review concluded that the dysregulation of lncRNAs is highly associated with EMT-mediated OC progression. A comprehensive understanding of lncRNAs' mechanisms in OC will help in identifying novel and sensitive biomarkers and therapeutic targets for this malignancy. [ABSTRACT FROM AUTHOR]

Published
2023
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47. Anti-Tumor Immunity and Preoperative Radiovaccination: Emerging New Concepts in the Treatment of Breast Cancer.

Author

Koukourakis, Ioannis M., Papadimitriou, Marios, Desse, Dimitra, Zygogianni, Anna, and Papadimitriou, Christos

Subjects
CANCER treatment, IMMUNE checkpoint inhibitors, BREAST cancer, NEOADJUVANT chemotherapy, IMMUNITY
Abstract

Neoadjuvant chemotherapy (NACT) for certain breast cancer (BC) subtypes confers significant tumor regression rates and a survival benefit for patients with a complete pathologic response. Clinical and preclinical studies have demonstrated that immune-related factors are responsible for better treatment outcomes, and thus, neoadjuvant immunotherapy (IO) has emerged as a means to further improve patient survival rates. Innate immunological "coldness", however, of specific BC subtypes, especially of the luminal ones, due to their immunosuppressive tumor microenvironment, hinders the efficacy of immune checkpoint inhibitors. Treatment policies aiming to reverse this immunological inertia are, therefore, needed. Moreover, radiotherapy (RT) has been proven to have a significant interplay with the immune system and promote anti-tumor immunity. This "radiovaccination" effect could be exploited in the neoadjuvant setting of BC and significantly enhance the effects of the already established clinical practice. Modern stereotactic irradiation techniques directed to the primary tumor and involved lymph nodes may prove important for the RT-NACT-IO combination. In this review, we provide an overview and critically discuss the biological rationale, clinical experience, and ongoing research underlying the interplay between neoadjuvant chemotherapy, anti-tumor immune response, and the emerging role of RT as a preoperative adjunct with immunological therapeutic implications in BC. [ABSTRACT FROM AUTHOR]

Published
2023
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48. Center-Embedding and Constituency in the Brain and a New Characterization of Context-Free Languages

Author

Mitropolsky, Daniel, Ejaz, Adiba, Shi, Mirah, Yannakakis, Mihalis, and Papadimitriou, Christos H.

Subjects
FOS: Computer and information sciences, Computer Science - Computation and Language, Computation and Language (cs.CL)
Abstract

A computational system implemented exclusively through the spiking of neurons was recently shown capable of syntax, that is, of carrying out the dependency parsing of simple English sentences. We address two of the most important questions left open by that work: constituency (the identification of key parts of the sentence such as the verb phrase) and the processing of dependent sentences, especially center-embedded ones. We show that these two aspects of language can also be implemented by neurons and synapses in a way that is compatible with what is known, or widely believed, about the structure and function of the language organ. Surprisingly, the way we implement center embedding points to a new characterization of context-free languages., NALOMA 2022

Published
2022

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