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1. The artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma

Author

Pan, Xiaoxi, AbdulJabbar, Khalid, Coelho-Lima, Jose, Grapa, Anca-Ioana, Zhang, Hanyun, Cheung, Alvin Ho Kwan, Baena, Juvenal, Karasaki, Takahiro, Wilson, Claire Rachel, Sereno, Marco, Veeriah, Selvaraju, Aitken, Sarah J., Hackshaw, Allan, Nicholson, Andrew G., Jamal-Hanjani, Mariam, Swanton, Charles, Yuan, Yinyin, Le Quesne, John, and Moore, David A.

Published
2024
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4. Cross-Stream Interactions: Segmentation of Lung Adenocarcinoma Growth Patterns

Author

Pan, Xiaoxi, Zhang, Hanyun, Grapa, Anca-Ioana, AbdulJabbar, Khalid, Raza, Shan E Ahmed, Cheung, Ho Kwan Alvin, Karasaki, Takahiro, Quesne, John Le, Moore, David A., Swanton, Charles, Yuan, Yinyin, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Qin, Wenjian, editor, Zaki, Nazar, editor, Zhang, Fa, editor, Wu, Jia, editor, and Yang, Fan, editor

Published
2022
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5. A clinician's perspective on boron neutron capture therapy: promising advances, ongoing trials, and future outlook.

Author

Shen, Shumin, Wang, Shanghu, Zhou, Dachen, Wu, Xiuwei, Gao, Mingzhu, Wu, Jinjin, Yang, Yucai, Pan, Xiaoxi, and Wang, Nianfei

Abstract

This comprehensive review aims to provide a unique clinical perspective on the latest advances and ongoing boron neutron capture therapy (BNCT) trials for various cancers. We critically analyzed clinical data from BNCT trials for head and neck cancer, glioblastoma, melanoma, meningioma, breast cancer, and liver tumors. We investigated differences in tumor responses and normal tissue toxicities among trials and discussed potential contributing factors. We also identified the limitations of early BNCT trials and proposed strategies to optimize future trial design. BNCT has shown promising results in treating head and neck cancer, with high response rates and improved survival in patients with recurrent disease. In glioblastoma, BNCT combined with surgery and chemotherapy has demonstrated survival benefits compared to standard treatments. BNCT has also been successfully used for recurrent high-grade meningiomas and shows potential for melanomas, extramammary Paget's disease, and liver tumors. However, differences in tumor responses and toxicities were observed among trials, potentially attributable to variations in treatment protocols, patient characteristics, and evaluation methods. BNCT is a promising targeted radiotherapy for various cancers. Further optimization and well-designed randomized controlled trials are needed to establish its efficacy and safety. Future studies should focus on standardizing treatment protocols and addressing limitations to guide clinical decision-making and research priorities. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Fibrin clot structure alterations after particulate matter exposure

Author

Pan, Xiaoxi, Routledge, Michael, Ariens, Robert, and Gong, Yun Yun

Subjects
616.1
Abstract

Particulate matter (PM) as an important part of ambient air pollution has been associated with increased risks of cardiovascular diseases. Fibrin clot structure alteration is an emerging risk factor of many cardiovascular diseases, especially thrombosis. Therefore, the aim of this study was to investigate whether and how air particulate matter affects fibrin clot structure and endothelial cell behaviour. Turbidity assay, turbidity lysis assay and laser scanning confocal microscopy were used to analyse clots formed from normal pooled plasma or purified fibrinogen, in the presence of varying concentrations of PM. It was found that clots formed from plasma with higher concentrations of particles led to prolonged lysis time compared to control. No differences were seen for clots formed from fibrinogen. In a study of clots formed from plasma samples collected as part of a previous study on the effects of air pollution on deep vein thrombosis (DVT), alterations were observed in clots formed from plasma of DVT patients exposed to high levels of PM compared to those exposed to low levels, but the same differences were not observed in clots formed from plasma of control subjects. To investigate the potential role of venous endothelial cells in moderating clot structure following exposure to PM, human umbilical vein endothelial cells (HUVEC) were treated with PM for 24 hours and clots subsequently formed on the cells. Clots formed from plasma on the treated cells were altered compared to controls. RT-PCR and ELISA results showed increased gene expression of tissue factor (TF), protein expression of von Willebrand Factor (VWF) and plasminogen activation inhibitor-1 (PAI-1) and decreased thrombomodulin mRNA expression which were consistent with changes observed in clot structure. Engineered SiO2 nanoparticles caused denser clot structure in clots formed from normal pooled plasma. The gene expression of thrombomodulin was inhibited by SiO2 nanoparticles, but there were no significant difference in the TF mRNA expression between control and treated cells. Silica NPs caused increased concentrations of VWF, but not PAI-1 produced by endothelial cells. The results presented here show that PM can induce changes to clot structure and function, and that changes in gene expression induced in endothelial cells may be a mechanism by which a prothrombotic state is induced in response to PM exposure. Furthermore, some, but not all, similar changes were observed in clots and cells exposed to SiO2 nanoparticles, raising the possibility that such engineered nanoparticles may also have the potential to contribute to cardiovascular toxicity.

Published
2016

10. Concordance of genomic mutations between tissue and ctDNA in non-small cell lung cancer: impact of time interval stratified by stage, smoking history and treatment

Author

Li, Kun, primary, Zhang, Nana, additional, Xu, Bing, additional, Liu, Zichen, additional, Zhao, Dan, additional, Dong, Yujie, additional, Mu, Jing, additional, Lin, Haifeng, additional, Shan, Guangyu, additional, Gao, Sihang, additional, Yu, Bo, additional, Pan, Xiaoxi, additional, Wang, Yanrong, additional, Zhang, Dongxing, additional, Che, Nanying, additional, and Ji, Xiaoyong, additional

Published
2023
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17. Body composition and lung cancer-associated cachexia in TRACERx

Author

Al-Sawaf, Othman, Weiss, Jakob, Skrzypski, Marcin, Lam, Jie Min, Karasaki, Takahiro, Zambrana, Francisco, Kidd, Andrew C, Frankell, Alexander M, Watkins, Thomas BK, Martinez-Ruiz, Carlos, Puttick, Clare, Black, James RM, Huebner, Ariana, Al Bakir, Maise, Sokac, Mateo, Collins, Susie, Veeriah, Selvaraju, Magno, Neil, Naceur-Lombardelli, Cristina, Prymas, Paulina, Toncheva, Antonia, Ward, Sophia, Jayanth, Nick, Salgado, Roberto, Bridge, Christopher P, Christiani, David C, Mak, Raymond H, Bay, Camden, Rosenthal, Michael, Sattar, Naveed, Welsh, Paul, Liu, Ying, Perrimon, Norbert, Popuri, Karteek, Beg, Mirza Faisal, McGranahan, Nicholas, Hackshaw, Allan, Breen, Danna M, O'Rahilly, Stephen, Birkbak, Nicolai J, Aerts, Hugo JWL, Jamal-Hanjani, Mariam, Swanton, Charles, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Fennell, Dean A, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Price, Gillian, Kerr, Keith M, Benafif, Sarah, Gilbert, Kayleigh, Naidu, Babu, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Middleton, Gary, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Blackhall, Fiona H, Krebs, Matthew G, Summers, Yvonne, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Dive, Caroline, Schwarz, Roland F, Kaufmann, Tom L, Wilson, Gareth A, Rosenthal, Rachel, Van Loo, Peter, Szallasi, Zoltan, Kisistok, Judit, Diossy, Miklos, Demeulemeester, Jonas, Bunkum, Abigail, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Bailey, Chris, Abbosh, Christopher, Weeden, Clare E, Lee, Claudia, Richard, Corentin, Hiley, Crispin T, Moore, David A, Pearce, David R, Karagianni, Despoina, Biswas, Dhruva, Levi, Dina, Hoxha, Elena, Cadieux, Elizabeth Larose, Lim, Emilia L, Colliver, Emma, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran, Lowe, Helen L, Matos, Ignacio Garcia, Goldman, Jacki, Reading, James L, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Hartley, John A, Peggs, Karl S, Enfield, Katey SS, Selvaraju, Kayalvizhi, Thol, Kerstin, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Grigoriadis, Kristiana, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Duran, Marcos Vasquez, Litovchenko, Maria, Sunderland, Mariana Werner, Hill, Mark S, Dietzen, Michelle, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Pich, Oriol, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Quezada, Sergio A, Vanloo, Sharon, Zaccaria, Simone, Hessey, Sonya, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Marafioti, Teresa, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Forster, Martin D, Lee, Siow Ming, Borg, Elaine, Falzon, Mary, Papadatos-Pastos, Dionysis, Wilson, James, Ahmad, Tanya, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Lawrence, David, Patrini, Davide, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Hoogenboom, Emilie Martinoni, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Cave, Judith, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Nicholson, Andrew G, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Blyth, Kevin G, Dick, Craig, Le Quesne, John, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew

Subjects
Male, Proteomics, Cachexia, Lung Neoplasms, Antigens, Neoplasm, Carcinoma, Non-Small-Cell Lung, Body Weight, Body Composition, Humans, Neoplasm Recurrence, Local, Muscle, Skeletal, Neoplasm Proteins
Abstract

Cancer-associated cachexia (CAC) is a major contributor to morbidity and mortality in individuals with non-small cell lung cancer. Key features of CAC include alterations in body composition and body weight. Here, we explore the association between body composition and body weight with survival and delineate potential biological processes and mediators that contribute to the development of CAC. Computed tomography-based body composition analysis of 651 individuals in the TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study suggested that individuals in the bottom 20th percentile of the distribution of skeletal muscle or adipose tissue area at the time of lung cancer diagnosis, had significantly shorter lung cancer-specific survival and overall survival. This finding was validated in 420 individuals in the independent Boston Lung Cancer Study. Individuals classified as having developed CAC according to one or more features at relapse encompassing loss of adipose or muscle tissue, or body mass index-adjusted weight loss were found to have distinct tumor genomic and transcriptomic profiles compared with individuals who did not develop such features. Primary non-small cell lung cancers from individuals who developed CAC were characterized by enrichment of inflammatory signaling and epithelial-mesenchymal transitional pathways, and differentially expressed genes upregulated in these tumors included cancer-testis antigen MAGEA6 and matrix metalloproteinases, such as ADAMTS3. In an exploratory proteomic analysis of circulating putative mediators of cachexia performed in a subset of 110 individuals from TRACERx, a significant association between circulating GDF15 and loss of body weight, skeletal muscle and adipose tissue was identified at relapse, supporting the potential therapeutic relevance of targeting GDF15 in the management of CAC. ispartof: NATURE MEDICINE vol:29 issue:4 ispartof: location:United States status: Published online

Published
2023

18. The evolution of non-small cell lung cancer metastases in TRACERx

Author

Al Bakir, Maise, Huebner, Ariana, Martinez-Ruiz, Carlos, Grigoriadis, Kristiana, Watkins, Thomas BK, Pich, Oriol, Moore, David A, Veeriah, Selvaraju, Ward, Sophia, Laycock, Joanne, Johnson, Diana, Rowan, Andrew, Razaq, Maryam, Akther, Mita, Naceur-Lombardelli, Cristina, Prymas, Paulina, Toncheva, Antonia, Hessey, Sonya, Dietzen, Michelle, Colliver, Emma, Frankell, Alexander, Bunkum, Abigail, Lim, Emilia L, Karasaki, Takahiro, Abbosh, Christopher, Hiley, Crispin T, Hill, Mark S, Cook, Daniel E, Wilson, Gareth A, Salgado, Roberto, Nye, Emma, Stone, Richard Kevin, Fennell, Dean A, Price, Gillian, Kerr, Keith M, Naidu, Babu, Middleton, Gary, Summers, Yvonne, Lindsay, Colin R, Blackhall, Fiona H, Cave, Judith, Blyth, Kevin G, Nair, Arjun, Ahmed, Asia, Taylor, Magali N, Procter, Alexander James, Falzon, Mary, Lawrence, David, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Papadatos-Pastos, Dionysis, Forster, Martin D, Lee, Siow Ming, Ahmad, Tanya, Quezada, Sergio, Peggs, Karl S, Van Loo, Peter, Dive, Caroline, Hackshaw, Allan, Birkbak, Nicolai J, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, Swanton, Charles, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Benafif, Sarah, Gilbert, Kayleigh, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Krebs, Matthew G, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Aerts, Hugo JWL, Schwarz, Roland F, Kaufmann, Tom L, Rosenthal, Rachel, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Demeulemeester, Jonas, Stewart, Aengus, Magness, Alastair, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Bailey, Chris, Puttick, Clare, Weeden, Clare E, Lee, Claudia, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Biswas, Dhruva, Levi, Dina, Hoxha, Elena, Larose Cadieux, Elizabeth, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran, Lowe, Helen L, Matos, Ignacio, Goldman, Jacki, Reading, James L, Black, James RM, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Lam, Jie Min, Hartley, John A, Enfield, Katey SS, Selvaraju, Kayalvizhi, Thol, Kerstin, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Vasquez, Marcos, Litovchenko, Maria, Werner Sunderland, Mariana, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Hobson, Philip, Pawlik, Piotr, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Marafioti, Teresa, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Borg, Elaine, Wilson, James, Patrini, Davide, Martinoni Hoogenboom, Emilie, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Nicholson, Andrew G, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Dick, Craig, Le Quesne, John, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew

Subjects
Clonal Evolution, Cohort Studies, Evolution, Molecular, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Disease Progression, Humans, Neoplasm Metastasis, Neoplasm Recurrence, Local, Clone Cells
Abstract

Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse. ispartof: NATURE vol:616 issue:7957 ispartof: location:England status: Published online

Published
2023

19. The evolution of lung cancer and impact of subclonal selection in TRACERx

Author

Frankell, Alexander M, Dietzen, Michelle, Al Bakir, Maise, Lim, Emilia L, Karasaki, Takahiro, Ward, Sophia, Veeriah, Selvaraju, Colliver, Emma, Huebner, Ariana, Bunkum, Abigail, Hill, Mark S, Grigoriadis, Kristiana, Moore, David A, Black, James RM, Liu, Wing Kin, Thol, Kerstin, Pich, Oriol, Watkins, Thomas BK, Naceur-Lombardelli, Cristina, Cook, Daniel E, Salgado, Roberto, Wilson, Gareth A, Bailey, Chris, Angelova, Mihaela, Bentham, Robert, Martinez-Ruiz, Carlos, Abbosh, Christopher, Nicholson, Andrew G, Le Quesne, John, Biswas, Dhruva, Rosenthal, Rachel, Puttick, Clare, Hessey, Sonya, Lee, Claudia, Prymas, Paulina, Toncheva, Antonia, Smith, Jon, Xing, Wei, Nicod, Jerome, Price, Gillian, Kerr, Keith M, Naidu, Babu, Middleton, Gary, Blyth, Kevin G, Fennell, Dean A, Forster, Martin D, Lee, Siow Ming, Falzon, Mary, Hewish, Madeleine, Shackcloth, Michael J, Lim, Eric, Benafif, Sarah, Russell, Peter, Boleti, Ekaterini, Krebs, Matthew G, Lester, Jason F, Papadatos-Pastos, Dionysis, Ahmad, Tanya, Thakrar, Ricky M, Lawrence, David, Navani, Neal, Janes, Sam M, Dive, Caroline, Blackhall, Fiona H, Summers, Yvonne, Cave, Judith, Marafioti, Teresa, Herrero, Javier, Quezada, Sergio A, Peggs, Karl S, Schwarz, Roland F, Van Loo, Peter, Miedema, Daniel M, Birkbak, Nicolai J, Hiley, Crispin T, Hackshaw, Allan, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, Swanton, Charles, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joa, Primrose, Lindsay, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Gilbert, Kayleigh, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Aerts, Hugo JWL, Kaufmann, Tom L, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Demeulemeester, Jonas, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Weeden, Clare E, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Levi, Dina, Hoxha, Elena, Larose Cadieux, Elizabeth, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran L, Lowe, Helen L, Matos, Ignacio, Goldman, Jacki, Reading, James L, Rane, Jayant K, Lam, Jie Min, Hartley, John A, Enfield, Katey SS, Selvaraju, Kayalvizhi, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Vasquez, Marcos, Litovchenko, Maria, Werner Sunderland, Mariana, Leung, Michelle, Escudero, Mickael, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Borg, Elaine, Wilson, James, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Patrini, Davide, Martinoni Hoogenboom, Emilie, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Danson, Sarah, Robinson, Lily, Dick, Craig, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew

Subjects
Lung Neoplasms, Treatment Outcome, DNA Copy Number Variations, Mutagenesis, Carcinoma, Non-Small-Cell Lung, Mutation, Smoking, Humans, Adenocarcinoma of Lung, Neoplasm Recurrence, Local, Phylogeny
Abstract

Lung cancer is the leading cause of cancer-associated mortality worldwide1. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource. ispartof: NATURE vol:616 issue:7957 ispartof: location:England status: Published online

Published
2023

20. Evolutionary characterization of lung adenocarcinoma morphology in TRACERx

Author

Karasaki, Takahiro, Moore, David A, Veeriah, Selvaraju, Naceur-Lombardelli, Cristina, Toncheva, Antonia, Magno, Neil, Ward, Sophia, Al Bakir, Maise, Watkins, Thomas BK, Grigoriadis, Kristiana, Huebner, Ariana, Hill, Mark S, Frankell, Alexander M, Abbosh, Christopher, Puttick, Clare, Zhai, Haoran, Gimeno-Valiente, Francisco, Saghafinia, Sadegh, Kanu, Nnennaya, Dietzen, Michelle, Pich, Oriol, Lim, Emilia L, Martinez-Ruiz, Carlos, Black, James RM, Biswas, Dhruva, Campbell, Brittany B, Lee, Claudia, Colliver, Emma, Enfield, Katey SS, Hessey, Sonya, Hiley, Crispin T, Zaccaria, Simone, Litchfield, Kevin, Birkbak, Nicolai J, Cadieux, Elizabeth Larose, Demeulemeester, Jonas, Van Loo, Peter, Adusumilli, Prasad R, Tan, Kay See, Cheema, Waseem, Sanchez-Vega, Francisco, Jones, David R, Rekhtman, Natasha, Travis, William D, Hackshaw, Allan, Marafioti, Teresa, Salgado, Roberto, Le Quesne, John, Nicholson, Andrew G, McGranahan, Nicholas, Swanton, Charles, Jamal-Hanjani, Mariam, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Fennell, Dean A, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Price, Gillian, Kerr, Keith M, Benafif, Sarah, Gilbert, Kayleigh, Naidu, Babu, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Middleton, Gary, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Blackhall, Fiona H, Krebs, Matthew G, Summers, Yvonne, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Dive, Caroline, Aerts, Hugo JWL, Schwarz, Roland F, Kaufmann, Tom L, Wilson, Gareth A, Rosenthal, Rachel, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Bunkum, Abigail, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Castignani, Carla, Bailey, Chris, Weeden, Clare E, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Levi, Dina, Hoxha, Elena, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Lowe, Helen L, Matos, Ignacio Garcia, Goldman, Jacki, Reading, James L, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Lam, Jie Min, Hartley, John A, Peggs, Karl S, Selvaraju, Kayalvizhi, Thol, Kerstin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Duran, Marcos Vasquez, Litovchenko, Maria, Sunderland, Mariana Werner, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Prymas, Paulina, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Quezada, Sergio A, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Forster, Martin D, Lee, Siow Ming, Borg, Elaine, Falzon, Mary, Papadatos-Pastos, Dionysis, Wilson, James, Ahmad, Tanya, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Lawrence, David, Patrini, Davide, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Hoogenboom, Emilie Martinoni, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Cave, Judith, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Blyth, Kevin G, Dick, Craig, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew

Subjects
TRACERx Consortium
Abstract

Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions in predominantly high-grade pattern tumors exhibited higher proliferation and lower clonal diversity, potentially reflecting large recent subclonal expansions. Co-occurrence of truncal loss of chromosomes 3p and 3q was enriched in predominantly low-/mid-grade tumors, while purely undifferentiated solid-pattern tumors had a higher frequency of truncal arm or focal 3q gains and SMARCA4 gene alterations compared with mixed-pattern tumors with a solid component, suggesting distinct evolutionary trajectories. Clonal evolution analysis revealed that tumors tend to evolve toward higher-grade patterns. The presence of micropapillary pattern and 'tumor spread through air spaces' were associated with intrathoracic recurrence, in contrast to the presence of solid/cribriform patterns, necrosis and preoperative circulating tumor DNA detection, which were associated with extra-thoracic recurrence. These data provide insights into the relationship between LUAD morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk. ispartof: NATURE MEDICINE vol:29 issue:4 ispartof: location:United States status: Published online

Published
2023

21. Abstract LB153: Clinical relevance of spatial intermixing of growth patterns and immune infiltration in lung adenocarcinoma-from TRACERx to LATTICe-A

Author

Grapa, Anca-Ioana, primary, Zhang, Hanyun, additional, Pan, Xiaoxi, additional, AbdulJabbar, Khalid, additional, Coelho-Lima, Jose, additional, Cheung, Ho Kwan Alvin, additional, Aitken, Sarah J., additional, Moore, David A., additional, Swanton, Charles, additional, Quesne, John Le, additional, and Yuan, Yinyin, additional

Published
2022
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25. RHD Genotypes in a Chinese Cohort of Pregnant Women

Author

Zhang, Jianjun, Zeng, Yan, Wang, Yuefeng, Fan, Jiaming, Chen, Haijiang, Yang, Dan, Shi, Xiaoliang, Xu, Hualin, Fu, Zimu, Sheng, Fang, Xuan, Jie, Pan, Xiaoxi, Zhang, Zhiming, Ai, Liping, Zhang, Yue, Pan, Jingjing, Zhao, Jing, and Wang, Mingming

Subjects
RHD, genotyping, intron, Genetics, Molecular Medicine, splice mutation, sequencing, QH426-470, Genetics (clinical), Original Research
Abstract

RHD variants in D¯ Chinese pregnant women arose difficulties in management during pregnancy. Therefore, this study aims to precisely manage D¯ pregnant women by evaluating the spectrum of RHD mutations in D¯ pregnant women and getting insight into the possible rare alleles of RHD. A total of 76 D¯ pregnant women were analyzed by performing polymerase chain reactions with sequence-specific primers (PCR-SSP), the 10 RHD exons Sanger sequencing, RHD zygosity detection, and mRNA sequencing (mRNA-seq). About 40% of alleles are variations of RHD, including RHD 1227A homozygous, RHD-CE(2-9)-D, et al. Therefore, we developed a molecular diagnostic strategy for Chinese women, and most D¯ pregnant women can be diagnosed with this simple decision tree. After RHD genotyping for D¯ pregnancy women, we eliminated at least 15% unnecessary ante- and postpartum injections of Rh immunoglobulin (RhIG). As the first pedigree study and the first functional analysis under physiological conditions, mRNA-seq revealed that c.336-1G>A mutation mainly led to the inclusion of the intron 2, which indirectly explained the D¯ phenotype in this family. We also developed a robust protocol for determining fetal RhD status from maternal plasma. All 31 fetuses were predicted as RhD positive and confirmed the RhD status after birth.

Published
2021

27. Pour la caractérisation et la classification des images TEP-FDG : application du diagnostic assisté par ordinateur de la maladie d'Alzheimer

Author

Pan, Xiaoxi, Institut FRESNEL (FRESNEL), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Ecole Centrale Marseille, Mouloud Adel, Caroline Fossati, STAR, ABES, and Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[PHYS.PHYS.PHYS-OPTICS] Physics [physics]/Physics [physics]/Optics [physics.optics], Diagnostic assisté par ordinateur, [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], Feature extraction, TEP-FDG, Extraction de caractéristiques, Computer-aided diagnosis, Alzheimer's disease, Maladie d’Alzheimer
Abstract

Alzheimer's disease (AD) is becoming the dominant type of neurodegenerative brain disease in elderly people, which is incurable and irreversible for now. It is expected to diagnose its early stage, Mild Cognitive Impairment (MCI), then interventions can be applied to delay the onset. Fluorodeoxyglucose positron emission tomography (FDG-PET) is considered as a significant and effective modality to diagnose AD and the corresponding early phase since it can capture metabolic changes in the brain thereby indicating abnormal regions. Therefore, this thesis is devoted to identify AD from Normal Control (NC) and predict MCI conversion under FDG-PET modality. For this purpose, three independent novel methods are proposed. The first method focuses on developing connectivities among anatomical regions involved in FDG-PET images which are rarely addressed in previous methods. Such connectivities are represented by either similarities or graph measures among regions. Then combined with each region's properties, these features are fed into a designed ensemble classification framework to tackle problems of AD diagnosis and MCI conversion prediction. The second method investigates features to characterize FDG-PET images from the view of spatial gradients, which can link the commonly used features, voxel-wise and region-wise features. The spatial gradient is quantified by a 2D histogram of orientation and expressed in a multiscale manner. The results are given by integrating different scales of spatial gradients within different regions. The third method applies Convolutional Neural Network (CNN) techniques to three views of FDG-PET data, thereby designing the main multiview CNN architecture. Such an architecture can facilitate convolutional operations, from 3D to 2D, and meanwhile consider spatial relations, which is benefited from a novel mapping layer with cuboid convolution kernels. Then three views are combined and make a decision jointly. Experiments conducted on public dataset show that the three proposed methods can achieve significant performance and moreover, outperform most state-of-the-art approaches., La maladie d’Alzheimer (MA) est la maladie neurodégénérative--incurable et irréversible pour le moment--la plus répandue chez les personnes âgées. On s’attend à ce qu’elle soit diagnostiquée à son stade précoce, Mild Cognitive Impairment (MCI), pour pouvoir intervenir et retarder son apparition. La tomographie par émission de positons au fluorodésoxyglucose (TEP-FDG) est considérée comme une modalité efficace pour diagnostiquer la MA et la phase précoce correspondante, car elle peut capturer les changements métaboliques dans le cerveau, indiquant ainsi des régions anormales. Cette thèse est consacrée à identifier et distinguer, sur des images TEP, les sujets atteints de MA de ceux qui sont sains. Ce travail vise également à prédire la conversion de MCI sous la modalité d’imagerie TEP-FDG. A cette fin, trois nouvelles méthodes indépendantes sont proposées.La première méthode est axée sur le développement de connectivités entre les régions anatomiques impliquées dans les images au TEP-FDG, qui sont rarement abordées dans les méthodes déjà publiées. Ces connectivités sont représentées par des similarités ou des mesures graphiques entre régions. Combinées ensuite aux propriétés de chaque région, ces caractéristiques sont intégrées dans un cadre de classification d’ensemble conçu pour résoudre les problèmes de diagnostic MA et de prédiction de conversion MCI.La seconde méthode étudie les caractéristiques permettant de caractériser les images au TEP-FDG à partir de gradients spatiaux, ce qui permet de lier les caractéristiques couramment utilisées, voxel ou régionales. Le gradient spatial est quantifié par un histogramme 2D d’orientation et exprimé sous forme multi-échelle. Les résultats sont obtenus en intégrant différentes échelles de gradients spatiaux dans différentes régions.La troisième méthode applique le Convolutional Neural Network (CNN) sur les trois axes des données 3D de TEP-FDG, proposant ainsi la principale architecture CNN à vues multiples. Une telle architecture peut faciliter les opérations de convolution, de la 3D à la 2D, tout en tenant compte des relations spatiales, qui bénéficient d’une nouvelle couche de cartographie. Ensuite, le traitement sur les trois axes sont combinées et prennent une décision conjointement.Les expériences menées sur des ensembles de données publics montrent que les trois méthodes proposées peuvent atteindre des performances significatives et, de surcroît, dépasser les approches les plus avancées.

Published
2019

29. Brain Concentration of Ginsenosides and Pharmacokinetics after Oral Administration of Mountain-cultivated Ginseng

Author

Guan Yiming, Li Meijia, Liu Ning, Hai Sun, Qiuxia Wang, Shao Cai, Yayu Zhang, Chen Jianbo, Liu Zhengbo, and Pan Xiaoxi

Subjects
010401 analytical chemistry, General Chemistry, Pharmacology, 030226 pharmacology & pharmacy, 01 natural sciences, 0104 chemical sciences, Bioavailability, 03 medical and health sciences, chemistry.chemical_compound, Ginseng, 0302 clinical medicine, chemistry, Pharmacokinetics, Ginsenoside, Oral administration
Published
2017

30. Silicon application and related changes in soil bacterial community dynamics reduced ginseng black spot incidence in Panax ginseng in a short-term study

Author

Pan Xiaoxi, Qiuxia Wang, Zhang Yayu, Liu Zhengbo, and Li Meijia

Subjects
0106 biological sciences, Microbiology (medical), Silicon, Alternaria panax, lcsh:QR1-502, Panax, Ginseng black spot, 01 natural sciences, Microbiology, complex mixtures, lcsh:Microbiology, 03 medical and health sciences, Ginseng, Soil, RNA, Ribosomal, 16S, Soil bacterial community, Illumina HiSeq sequencing, Relative species abundance, Phylogeny, Soil Microbiology, 030304 developmental biology, Plant Diseases, 0303 health sciences, Rhizosphere, biology, Bacteria, Inoculation, Incidence, Microbiota, Panax ginseng, food and beverages, Alternaria, biology.organism_classification, Horticulture, Microbial population biology, Soil water, 010606 plant biology & botany, Black spot, Research Article
Abstract

Background This study analyzed the effect of silicon (Si) application on the occurrence of ginseng black spot caused by Alternaria panax. We explored the differences in soil physical and chemical factors and microbial community structure following Si application as well as the key factors that affected the occurrence of ginseng black spot in soil. Potted Panax ginseng plants were used to assess the effect of Si treatment on ginseng black spot. Soil physical and chemical properties were comprehensively analyzed. Bacterial communities were analyzed using Illumina HiSeq sequencing targeting the 16S rRNA gene. Results After inoculation with A. panax, the morbidity (and morbidity index) of ginseng with and without Si was 52% (46) and 83% (77), respectively. Soil physical and chemical analysis showed that under the ginseng black spot inoculation, bacterial communities were mainly affected by pH and available potassium, followed by ammonium nitrogen and available Si. NMDS and PLS-DA analyses and the heat maps of relative abundance revealed that Si application elevated the resistance of ginseng black spot as regulated by the abundance and diversity of bacterial flora in rhizosphere soils. Heatmap analysis at the genus level revealed that A. panax + Si inoculations significantly increased the soil community abundance of Sandaracinus, Polycyclovorans, Hirschia, Haliangium, Nitrospira, Saccharothrix, Aeromicrobium, Luteimonas, and Rubellimicrobium and led to a bacterial community structure with relative abundances that were significantly similar to that of untreated soil. Conclusions Short-term Si application also significantly regulated the structural impact on soil microorganisms caused by ginseng black spot. Our findings indicated that Si applications may possibly be used in the prevention and treatment of ginseng black spot.

Published
2019

31. Arbuscular mycorrhizal fungi biofertilizer improves American ginseng (Panax quinquefolius L.) growth under the continuous cropping regime

Author

Zhang Linlin, Liu Ning, Zhang Zhenghai, Liu Zhengbo, Sun Hai, Zhang Yayu, Guan Yiming, Pan Xiaoxi, Shao Cai, Bing Zhang, and Wu Lianju

Subjects
Rhizosphere, biology, Biofertilizer, fungi, food and beverages, Soil Science, 04 agricultural and veterinary sciences, 010501 environmental sciences, biology.organism_classification, complex mixtures, 01 natural sciences, Actinobacteria, Horticulture, Soil pH, Fusarium oxysporum, Shoot, 040103 agronomy & agriculture, Root rot, 0401 agriculture, forestry, and fisheries, American ginseng, 0105 earth and related environmental sciences
Abstract

Continuous cropping of American ginseng (Panax quinquefolius L.) is often associated with the scarcity or unavailability of soil nutrients and an imbalance of rhizosphere microbiota, resulting in low yield and poor plant quality. Inoculation with arbuscular mycorrhizal fungi (AMF) improves plant growth and production by facilitating nutrient acquisition and by modifying the abundance and diversity of rhizosphere microorganisms. In the present study, we investigated the mechanisms by which continuous cropping of American ginseng caused growth inhibition and how AMF biofertilizer application relieved these cropping obstacles. The results showed that: 1) continuous cropping of American ginseng significantly decreased the emergence rate, shoot and root dry weight, rhizosphere soil pH, the contents of ammonium, available phosphorus (P), and available potassium (K) in the rhizosphere, while increasing the root rot disease index and the soil content of nitrate; 2) continuous cropping of American ginseng decreased the diversity of bacteria, while increasing the diversity of fungi, and increased the relative abundances of Acidobacteria and Ascomycota, while decreasing the relative abundances of Actinobacteria, Firmicutes and Zygomycota; 3) in contrast, the application of AMF biofertilizer relieved the negative effects of continuous cropping American ginseng; 4) significant positive correlations were found between Pseudarthrobacter, Streptomyces and the content of ammonium, between Bacillus and the content of available K, and between Mortierella elongata and the content of available P, suggesting that the increase of rhizosphere plant-beneficial bacteria and fungi promoted the contents of available nutrients in the rhizosphere; 5) application of AMF biofertilizer significantly decreased the abundances of soil-borne pathogenic fungi Fusarium oxysporum, F. solani and the deleterious bacteria Candidatus Solibacter. In summary, our results suggest that AMF biofertilizer application improved the continuous cropping of American ginseng growth by increasing the AMF inoculation rate, by recruiting rhizosphere beneficial bacteria and fungi that promote plant-uptake of nitrogen (N) and P, and by suppressing soil-borne pathogens. Therefore, AMF biofertilizer is a probiotic agent that prevents microbial imbalances and nutrient deficiencies during continuous cropping of American ginseng.

Published
2020

43. Developing a pH-sensitive Al(OH)3 layer-mediated UCNP@Al(OH)3/Au nanohybrid for photothermal therapy and fluorescence imaging in vivo.

Author

Chen, Jian, Zhang, Dongya, Zou, Yan, Wang, Zhongjie, Hao, Mingcong, Zheng, Meng, Xue, Xue, Pan, Xiaoxi, Lu, Yiqing, Wang, Jiefei, and Shi, Bingyang

Abstract

Nanohybrids fabricated with upconversion nanoparticles (UCNPs) and gold nanoparticles (NPs) hold great promise for near-infrared photothermal therapy (NIR-PTT) and upconversion fluorescence imaging. However, the obstacles of poor solubility in water and finite hydrophilic modification method for UCNPs limit their application in biological fields. Herein, we report a novel UCNP@Al(OH)3/Au nanohybrid mediated by a highly hydrophilic and biocompatible Al(OH)3 layer to realize a synergistic targeted PTT and fluorescence imaging capability to U87MG tumor-bearing mice under NIR light irradiation. The modification with Al(OH)3 layers can improve the water solubility of UCNPs. And cytotoxicity assays and hemolysis assay showed that the modification with Al(OH)3 layers makes UCNPs have low cytotoxicity and good biocompatibility. In addition, the Al(OH)3 layers are thin enough to allow fluorescence resonance energy transfer (FRET) between UCNPs and gold NPs to occur, giving the NPs a good PTT effect for tumor-bearing mice. Meanwhile, as the pH-sensitive Al(OH)3 layers decompose in acidic tumor microenvironments with Au NPs detached from their surface, the FRET effect no longer occurred, subsequently leading to the fluorescence intensity of naked UCNPs being recovered for good imaging effects. The study suggests that Al(OH)3 mediation layer as a promising hydrophilic nanoplatform can potentially be used for the preparation of superior hydrophilic NPs and pH-stimulated drug release carriers for theranostic application in vivo. [ABSTRACT FROM AUTHOR]

Published
2018
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46. Connotation of failure mechanism consistency and identification method for accelerated testing

Author

Pan Xiaoxi, Wang Yalan, Kang Rui, Chen Yunxia, and Huang Xiaokai

Subjects
Identification (information), Engineering, Product life-cycle management, business.industry, Consistency (statistics), Key (cryptography), Systems design, Failure mechanism, business, Connotation, Statistical hypothesis testing, Reliability engineering
Abstract

Failure mechanism consistency means products failure mechanisms maintain unchanged at different stress levels, which is essential for estimated lives conversion between different stresses. In engineering, it is very popular to derive usage life from high stress accelerated tests for long life products, and identification of failure mechanism consistency is a key approach to solve this problem. In this paper, connotation and the identification methods of failure mechanism consistency are introduced and other related problems are discussed. The conclusion of this paper can provide a theoretical foundation for the modeling and validation of PoF in PHM system design.

Published
2011

47. Brain Concentration of Ginsenosides and Pharmacokinetics after Oral Administration of Mountain-cultivated Ginseng.

Author

Li, Meijia, Guan, Yiming, Liu, Ning, Shao, Cai, Liu, Zhengbo, Chen, Jianbo, Wang, Qiuxia, Pan, Xiaoxi, Sun, Hai, and Zhang, Yayu

Subjects
GINSENOSIDES, PHARMACOKINETICS, GINSENG, ORAL medication, LIQUID chromatography-mass spectrometry
Abstract

Mountain-cultivated ginseng ( MCG) can be considered a mimic of wild ginseng, whose seeds are sowed artificially, cultivated in the natural environment, and returned to the wild state before being used clinically. Cultivated ginseng ( CG) and MCG are mainly used as the commercial material for clinical applications. However, MCG is much more expensive but effective than CG. The aim of this study is to explore the differences in the pharmacokinetics and brain concentration of Rg1, Re, Rb1, and Rd after oral administration of MCG, CG, and pure ginsenosides. An ultra-performance liquid chromatography-tandem mass spectrometry method was developed and validated to determine the concentration of the four ginsenosides in rat plasma and brain tissue. Compared with the pure group, the area under the curve ( AUC) of all the four ginsenosides for CG and MCG increased. The mean brain concentrations of the four ginsenosides were found to be 10- to 15-fold lower than the corresponding contents in the plasma, and the poor permeability of ginsenosides into blood-brain barrier was indicated by the low concentrations of the four ginsenosides. [ABSTRACT FROM AUTHOR]

Published
2017
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48. Multi-View Separable Pyramid Network for AD Prediction at MCI Stage by 18 F-FDG Brain PET Imaging.

Author

Pan X, Phan TL, Adel M, Fossati C, Gaidon T, Wojak J, and Guedj E

Subjects
Aged, Brain diagnostic imaging, Disease Progression, Fluorodeoxyglucose F18, Humans, Positron-Emission Tomography, Alzheimer Disease diagnostic imaging, Cognitive Dysfunction diagnostic imaging
Abstract

Alzheimer's Disease (AD), one of the main causes of death in elderly people, is characterized by Mild Cognitive Impairment (MCI) at prodromal stage. Nevertheless, only part of MCI subjects could progress to AD. The main objective of this paper is thus to identify those who will develop a dementia of AD type among MCI patients. 18 F-FluoroDeoxyGlucose Positron Emission Tomography ( 18 F-FDG PET) serves as a neuroimaging modality for early diagnosis as it can reflect neural activity via measuring glucose uptake at resting-state. In this paper, we design a deep network on 18 F-FDG PET modality to address the problem of AD identification at early MCI stage. To this end, a Multi-view Separable Pyramid Network (MiSePyNet) is proposed, in which representations are learned from axial, coronal and sagittal views of PET scans so as to offer complementary information and then combined to make a decision jointly. Different from the widely and naturally used 3D convolution operations for 3D images, the proposed architecture is deployed with separable convolution from slice-wise to spatial-wise successively, which can retain the spatial information and reduce training parameters compared to 2D and 3D networks, respectively. Experiments on ADNI dataset show that the proposed method can yield better performance than both traditional and deep learning-based algorithms for predicting the progression of Mild Cognitive Impairment, with a classification accuracy of 83.05%.

Published
2021
Full Text
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49. Developing a pH-sensitive Al(OH) 3 layer-mediated UCNP@Al(OH) 3 /Au nanohybrid for photothermal therapy and fluorescence imaging in vivo.

Author

Chen J, Zhang D, Zou Y, Wang Z, Hao M, Zheng M, Xue X, Pan X, Lu Y, Wang J, and Shi B

Abstract

Nanohybrids fabricated with upconversion nanoparticles (UCNPs) and gold nanoparticles (NPs) hold great promise for near-infrared photothermal therapy (NIR-PTT) and upconversion fluorescence imaging. However, the obstacles of poor solubility in water and finite hydrophilic modification method for UCNPs limit their application in biological fields. Herein, we report a novel UCNP@Al(OH) 3 /Au nanohybrid mediated by a highly hydrophilic and biocompatible Al(OH) 3 layer to realize a synergistic targeted PTT and fluorescence imaging capability to U87MG tumor-bearing mice under NIR light irradiation. The modification with Al(OH) 3 layers can improve the water solubility of UCNPs. And cytotoxicity assays and hemolysis assay showed that the modification with Al(OH) 3 layers makes UCNPs have low cytotoxicity and good biocompatibility. In addition, the Al(OH) 3 layers are thin enough to allow fluorescence resonance energy transfer (FRET) between UCNPs and gold NPs to occur, giving the NPs a good PTT effect for tumor-bearing mice. Meanwhile, as the pH-sensitive Al(OH) 3 layers decompose in acidic tumor microenvironments with Au NPs detached from their surface, the FRET effect no longer occurred, subsequently leading to the fluorescence intensity of naked UCNPs being recovered for good imaging effects. The study suggests that Al(OH) 3 mediation layer as a promising hydrophilic nanoplatform can potentially be used for the preparation of superior hydrophilic NPs and pH-stimulated drug release carriers for theranostic application in vivo.

Published
2018
Full Text
View/download PDF

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