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https://www.readbyqxmd.com/read/28391773/kif13b-nrg1-gene-fusion-and-kras-amplification-in-a-case-of-natural-progression-of-lung-cancer
#1
Daniel Xia, Long Phi Le, Anthony John Iafrate, Jochen Lennerz
An 85-year-old woman with a history of several primary lung cancers presented with liver metastases. The primary lung cancers were all managed surgically and the patient did not receive adjuvant or neoadjuvant therapy prior to presenting with metastases. Comparison of molecular testing results from the most recent primary and the liver metastases demonstrated ( a) a clonal relationship between the 2 cancers and ( 2) the presence of a KIF13B-NRG1 fusion and KRAS amplification unique to the metastases. When integrated, the molecular surgical pathology findings in this case illustrate the extent of "oncogenic drive" in preterminal lung cancer...
May 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28360267/decoupling-genetics-lineages-and-microenvironment-in-idh-mutant-gliomas-by-single-cell-rna-seq
#2
Andrew S Venteicher, Itay Tirosh, Christine Hebert, Keren Yizhak, Cyril Neftel, Mariella G Filbin, Volker Hovestadt, Leah E Escalante, McKenzie L Shaw, Christopher Rodman, Shawn M Gillespie, Danielle Dionne, Christina C Luo, Hiranmayi Ravichandran, Ravindra Mylvaganam, Christopher Mount, Maristela L Onozato, Brian V Nahed, Hiroaki Wakimoto, William T Curry, A John Iafrate, Miguel N Rivera, Matthew P Frosch, Todd R Golub, Priscilla K Brastianos, Gad Getz, Anoop P Patel, Michelle Monje, Daniel P Cahill, Orit Rozenblatt-Rosen, David N Louis, Bradley E Bernstein, Aviv Regev, Mario L Suvà
Tumor subclasses differ according to the genotypes and phenotypes of malignant cells as well as the composition of the tumor microenvironment (TME). We dissected these influences in isocitrate dehydrogenase (IDH)-mutant gliomas by combining 14,226 single-cell RNA sequencing (RNA-seq) profiles from 16 patient samples with bulk RNA-seq profiles from 165 patient samples. Differences in bulk profiles between IDH-mutant astrocytoma and oligodendroglioma can be primarily explained by distinct TME and signature genetic events, whereas both tumor types share similar developmental hierarchies and lineages of glial differentiation...
March 31, 2017: Science
https://www.readbyqxmd.com/read/28296680/primitive-neuroectodermal-tumors-of-the-female-genital-tract-a-morphologic-immunohistochemical-and-molecular-study-of-19-cases
#3
Sarah Chiang, Matija Snuderl, Sakiko Kojiro-Sanada, Ariadna Quer Pi-Sunyer, Dean Daya, Tohru Hayashi, Luisanna Bosincu, Fumihiro Ogawa, Andrew E Rosenberg, Lars-Christian Horn, Lu Wang, A John Iafrate, Esther Oliva
Primary primitive neuroectodermal tumor (PNET) of the female genital tract is rare, and its proper classification remains unclear. The clinical, histologic, and immunophenotypic features as well as EWSR1 rearrangement status of 19 gynecologic PNETs, including 10 ovarian, 8 uterine, and 1 vulvar tumors, are herein reported. Patient age ranged from 12 to 68 years, with a median age of 20 and 51 years among those with ovarian and uterine PNETs, respectively. Morphologic features of central nervous system (CNS) tumors were seen in 15 PNETs, including 9 medulloblastomas, 3 ependymomas, 2 medulloepitheliomas, and 1 glioblastoma, consistent with central PNET...
March 14, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28266931/biliary-adenofibroma-of-liver-morphology-tumor-genetics-and-outcomes-in-6-cases
#4
Thomas Arnason, Darrell R Borger, Christopher Corless, Catherine Hagen, A John Iafrate, Hala Makhlouf, Joseph Misdraji, Heidi Sapp, Wilson M Tsui, Ian R Wanless, Tania Zuluaga Toro, Gregory Y Lauwers
Biliary adenofibroma is a rare primary hepatic neoplasm, recognized in the World Health Organization classification, although only 14 cases have been reported to date. This series includes extended follow-up from 2 of the early case reports and 4 novel cases. Clinical history and histology were reviewed in all 6 cases. Tumor DNA was analyzed for point mutations by multiplex polymerase chain reaction and copy number alterations by array comparative genomic hybridization. The patients included 4 females and 2 males presenting between 46 and 83 years of age, with tumors ranging from 7 to 16 cm in diameter...
April 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28236104/uterine-fibroid-therapy-using-interventional-radiology-mini-invasive-treatments-current-perspective
#5
REVIEW
Carlo Masciocchi, Francesco Arrigoni, Fabiana Ferrari, Aldo Victor Giordano, Sonia Iafrate, Ilaria Capretti, Ester Cannizzaro, Alfonso Reginelli, Anna Maria Ierardi, Chiara Floridi, Alessio Salvatore Angileri, Luca Brunese, Antonio Barile
Uterine fibroids are common benign tumors of unclear etiopathology that affect the female reproductive tract. They are responsible for considerable morbidity and deterioration of life quality, and may have a negative impact on the reproductive system as well. Besides surgery aided by uterus-saving techniques, several minimally invasive procedures are now available within the field of interventional radiology that represent a valid solution for women who desire pregnancy and relief from disease-specific symptomatology...
April 2017: Medical Oncology
https://www.readbyqxmd.com/read/28188106/analytical-validation-of-the-next-generation-sequencing-assay-for-a-nationwide-signal-finding-clinical-trial-molecular-analysis-for-therapy-choice-clinical-trial
#6
Chih-Jian Lih, Robin D Harrington, David J Sims, Kneshay N Harper, Courtney H Bouk, Vivekananda Datta, Jonathan Yau, Rajesh R Singh, Mark J Routbort, Rajyalakshmi Luthra, Keyur P Patel, Geeta S Mantha, Savitri Krishnamurthy, Karyn Ronski, Zenta Walther, Karin E Finberg, Sandra Canosa, Hayley Robinson, Amelia Raymond, Long P Le, Lisa M McShane, Eric C Polley, Barbara A Conley, James H Doroshow, A John Iafrate, Jeffrey L Sklar, Stanley R Hamilton, P Mickey Williams
The National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) trial is a national signal-finding precision medicine study that relies on genomic assays to screen and enroll patients with relapsed or refractory cancer after standard treatments. We report the analytical validation processes for the next-generation sequencing (NGS) assay that was tailored for regulatory compliant use in the trial. The Oncomine Cancer Panel assay and the Personal Genome Machine were used in four networked laboratories accredited for the Clinical Laboratory Improvement Amendments...
February 3, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28144970/pulmonary-adenocarcinoma-with-epidermal-growth-factor-receptor-mutations-in-asbestos-exposed-non-smokers-a-case-series
#7
Richard L Kradin, John Iafrate, David C Christiani
BACKGROUND: Cigarette smoke and asbestos are recognized causes of lung carcinoma and together promote carcinogenesis. Adenocarcinoma is currently the most common cause of lung cancer in the USA and it has been linked to both smoking and asbestos exposure. Mutations in the epidermal growth factor gene receptor (EGFR) occur predominantly in non-smokers with adenocarcinoma. Methods Mutations in the EGFR gene were investigated using next-generation sequencing. RESULTS: We report the presence of EGFR exon point mutations in the pulmonary adenocarcinomas of three never-smokers occupationally exposed to asbestos...
February 1, 2017: American Journal of Industrial Medicine
https://www.readbyqxmd.com/read/28088512/ros1-fusions-rarely-overlap-with-other-oncogenic-drivers-in-non-small-cell-lung-cancer
#8
Jessica J Lin, Lauren L Ritterhouse, Siraj M Ali, Mark Bailey, Alexa B Schrock, Justin F Gainor, Lorin A Ferris, Mari Mino-Kenudson, Vincent A Miller, Anthony J Iafrate, Jochen K Lennerz, Alice T Shaw
INTRODUCTION: Chromosomal rearrangements involving the gene ROS1 define a distinct molecular subset of NSCLCs with sensitivity to ROS1 inhibitors. Recent reports have suggested a significant overlap between ROS1 fusions and other oncogenic driver alterations, including mutations in EGFR and KRAS. METHODS: We identified patients at our institution with ROS1-rearranged NSCLC who had undergone testing for genetic alterations in additional oncogenes, including EGFR, KRAS, and anaplastic lymphoma receptor tyrosine kinase gene (ALK)...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28059100/a-tailored-approach-to-braf-and-mlh1-methylation-testing-in-a-universal-screening-program-for-lynch-syndrome
#9
Tomer Adar, Linda H Rodgers, Kristen M Shannon, Makoto Yoshida, Tianle Ma, Anthony Mattia, Gregory Y Lauwers, Anthony J Iafrate, Daniel C Chung
To determine the correlation between BRAF genotype and MLH1 promoter methylation in a screening program for Lynch syndrome (LS), a universal screening program for LS was established in two medical centers. Tumors with abnormal MLH1 staining were evaluated for both BRAF V600E genotype and MLH1 promoter methylation. Tumors positive for both were considered sporadic, and genetic testing was recommended for all others. A total 1011 colorectal cancer cases were screened for Lynch syndrome, and 148 (14.6%) exhibited absent MLH1 immunostaining...
January 6, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28034880/polyclonal-secondary-fgfr2-mutations-drive-acquired-resistance-to-fgfr-inhibition-in-patients-with-fgfr2-fusion-positive-cholangiocarcinoma
#10
Lipika Goyal, Supriya K Saha, Leah Y Liu, Giulia Siravegna, Ignaty Leshchiner, Leanne G Ahronian, Jochen K Lennerz, Phuong Vu, Vikram Deshpande, Avinash Kambadakone, Benedetta Mussolin, Stephanie Reyes, Laura Henderson, Jiaoyuan Elisabeth Sun, Emily E Van Seventer, Joseph M Gurski, Sabrina Baltschukat, Barbara Schacher-Engstler, Louise Barys, Christelle Stamm, Pascal Furet, David P Ryan, James R Stone, A John Iafrate, Gad Getz, Diana Graus Porta, Ralph Tiedt, Alberto Bardelli, Dejan Juric, Ryan B Corcoran, Nabeel Bardeesy, Andrew X Zhu
Genetic alterations in the fibroblast growth factor receptor (FGFR) pathway are promising therapeutic targets in many cancers, including intrahepatic cholangiocarcinoma (ICC). The FGFR inhibitor BGJ398 displayed encouraging efficacy in patients with FGFR2 fusion-positive ICC in a phase II trial, but the durability of response was limited in some patients. Here, we report the molecular basis for acquired resistance to BGJ398 in three patients via integrative genomic characterization of cell-free circulating tumor DNA (cfDNA), primary tumors, and metastases...
March 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28032319/religiosity-marital-quality-and-couple-generativity-in-italian-couples-belonging-to-a-catholic-spiritual-association-a-quali-quantitative-study
#11
Miriam Parise, Fabiana Gatti, Raffaella Iafrate
The current studies aimed, firstly, at exploring the relationship between the level of religiosity and marital outcomes, in terms of relationship quality and couple generativity; secondly, at gaining insight into which strategies the couples use to ensure their marital quality/couple generativity, and understanding if religious practices have a positive influence on the development of such strategies. The studies focused on a specific aspect of religiosity, that is the active involvement in a Catholic association, and compared couples with a high level of religious involvement (HRI) belonging to a Catholic international association (New Families) and couples with a low level of religious involvement (LRI)...
December 28, 2016: Journal of Religion and Health
https://www.readbyqxmd.com/read/27984905/outstanding-performance-of-configuration-interaction-singles-and-doubles-using-exact-exchange-kohn-sham-orbitals-in-real-space-numerical-grid-method
#12
Jaechang Lim, Sunghwan Choi, Jaewook Kim, Woo Youn Kim
To assess the performance of multi-configuration methods using exact exchange Kohn-Sham (KS) orbitals, we implemented configuration interaction singles and doubles (CISD) in a real-space numerical grid code. We obtained KS orbitals with the exchange-only optimized effective potential under the Krieger-Li-Iafrate (KLI) approximation. Thanks to the distinctive features of KLI orbitals against Hartree-Fock (HF), such as bound virtual orbitals with compact shapes and orbital energy gaps similar to excitation energies; KLI-CISD for small molecules shows much faster convergence as a function of simulation box size and active space (i...
December 14, 2016: Journal of Chemical Physics
https://www.readbyqxmd.com/read/27913435/idh2-mutations-define-a-unique-subtype-of-breast-cancer-with-altered-nuclear-polarity
#13
Sarah Chiang, Britta Weigelt, Huei-Chi Wen, Fresia Pareja, Ashwini Raghavendra, Luciano G Martelotto, Kathleen A Burke, Thais Basili, Anqi Li, Felipe C Geyer, Salvatore Piscuoglio, Charlotte K Y Ng, Achim A Jungbluth, Jörg Balss, Stefan Pusch, Gabrielle M Baker, Kimberly S Cole, Andreas von Deimling, Julie M Batten, Jonathan D Marotti, Hwei-Choo Soh, Benjamin L McCalip, Jonathan Serrano, Raymond S Lim, Kalliopi P Siziopikou, Song Lu, Xiaolong Liu, Tarek Hammour, Edi Brogi, Matija Snuderl, A John Iafrate, Jorge S Reis-Filho, Stuart J Schnitt
Solid papillary carcinoma with reverse polarity (SPCRP) is a rare breast cancer subtype with an obscure etiology. In this study, we sought to describe its unique histopathologic features and to identify the genetic alterations that underpin SPCRP using massively parallel whole-exome and targeted sequencing. The morphologic and immunohistochemical features of SPCRP support the invasive nature of this subtype. Ten of 13 (77%) SPCRPs harbored hotspot mutations at R172 of the isocitrate dehydrogenase IDH2, of which 8 of 10 displayed concurrent pathogenic mutations affecting PIK3CA or PIK3R1 One of the IDH2 wild-type SPCRPs harbored a TET2 Q548* truncating mutation coupled with a PIK3CA H1047R hotspot mutation...
December 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27880786/effects-of-pile-driving-on-the-residency-and-movement-of-tagged-reef-fish
#14
Joseph D Iafrate, Stephanie L Watwood, Eric A Reyier, Douglas M Scheidt, Georges A Dossot, Steven E Crocker
The potential effects of pile driving on fish populations and commercial fisheries have received significant attention given the prevalence of pile driving occurring in coastal habitats throughout the world. Behavioral impacts of sound generated from these activities on fish typically have a greater area of influence than physical injury, and may therefore adversely affect a greater portion of the local population. This study used acoustic telemetry to assess the movement, residency, and survival of 15 sheepshead (Archosargus probatocephalus) and 10 grey snapper (Lutjanus griseus) in Port Canaveral, Florida, USA, in response to 35 days of pile driving at a wharf complex...
2016: PloS One
https://www.readbyqxmd.com/read/27806376/single-cell-rna-seq-supports-a-developmental-hierarchy-in-human-oligodendroglioma
#15
Itay Tirosh, Andrew S Venteicher, Christine Hebert, Leah E Escalante, Anoop P Patel, Keren Yizhak, Jonathan M Fisher, Christopher Rodman, Christopher Mount, Mariella G Filbin, Cyril Neftel, Niyati Desai, Jackson Nyman, Benjamin Izar, Christina C Luo, Joshua M Francis, Aanand A Patel, Maristela L Onozato, Nicolo Riggi, Kenneth J Livak, Dave Gennert, Rahul Satija, Brian V Nahed, William T Curry, Robert L Martuza, Ravindra Mylvaganam, A John Iafrate, Matthew P Frosch, Todd R Golub, Miguel N Rivera, Gad Getz, Orit Rozenblatt-Rosen, Daniel P Cahill, Michelle Monje, Bradley E Bernstein, David N Louis, Aviv Regev, Mario L Suvà
Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures...
November 10, 2016: Nature
https://www.readbyqxmd.com/read/27698648/corrigendum-the-associations-of-dyadic-coping-and-relationship-satisfaction-vary-between-and-within-nations-a-35-nation-study
#16
Peter Hilpert, Ashley K Randall, Piotr Sorokowski, David C Atkins, Agnieszka Sorokowska, Khodabakhsh Ahmadi, Ahmad M Alghraibeh, Richmond Aryeetey, Anna Bertoni, Karim Bettache, Marta Błażejewska, Guy Bodenmann, Jessica Borders, Tiago S Bortolini, Marina Butovskaya, Felipe N Castro, Hakan Cetinkaya, Diana Cunha, Oana A David, Anita DeLongis, Fahd A Dileym, Alejandra D C Domínguez Espinosa, Silvia Donato, Daria Dronova, Seda Dural, Maryanne Fisher, Tomasz Frackowiak, Evrim Gulbetekin, Aslıhan Hamamcıoğlu Akkaya, Karolina Hansen, Wallisen T Hattori, Ivana Hromatko, Raffaella Iafrate, Bawo O James, Feng Jiang, Charles O Kimamo, David B King, Fırat Koç, Amos Laar, Fívia De Araújo Lopes, Rocio Martinez, Norbert Mesko, Natalya Molodovskaya, Khadijeh Moradi, Zahrasadat Motahari, Jean C Natividade, Joseph Ntayi, Oluyinka Ojedokun, Mohd S B Omar-Fauzee, Ike E Onyishi, Barış Özener, Anna Paluszak, Alda Portugal, Ana P Relvas, Muhammad Rizwan, Svjetlana Salkičević, Ivan Sarmány-Schuller, Eftychia Stamkou, Stanislava Stoyanova, Denisa Šukolová, Nina Sutresna, Meri Tadinac, Andero Teras, Edna L Tinoco Ponciano, Ritu Tripathi, Nachiketa Tripathi, Mamta Tripathi, Noa Vilchinsky, Feng Xu, Maria E Yamamoto, Gyesook Yoo
[This corrects the article on p. 1106 in vol. 7, PMID: 27551269.].
2016: Frontiers in Psychology
https://www.readbyqxmd.com/read/27647802/next-generation-sequencing-adds-value-to-the-preoperative-diagnosis-of-pancreatic-cysts
#17
Matthew W Rosenbaum, Martin Jones, Jonathan C Dudley, Long P Le, A John Iafrate, Martha B Pitman
BACKGROUND: The diagnosis of a pancreatic cyst as mucinous or high-risk dictates the need for follow-up or surgery. Molecular analysis of aspirated pancreatic cyst fluid (PCF) can provide valuable information not obtained by carcinoembryonic antigen (CEA) analysis or cytology. METHODS: All patients who underwent molecular analysis of PCF between March 2013 and June 2015 were reviewed, including pathology, imaging, and follow-up. Molecular testing was performed using a patented, anchored multiplex polymerase chain reaction next-generation sequencing (NGS) platform, which sequenced numerous hotspots in 39 genes linked with malignancy...
January 2017: Cancer
https://www.readbyqxmd.com/read/27556950/her2-expression-identifies-dynamic-functional-states-within-circulating-breast-cancer-cells
#18
Nicole Vincent Jordan, Aditya Bardia, Ben S Wittner, Cyril Benes, Matteo Ligorio, Yu Zheng, Min Yu, Tilak K Sundaresan, Joseph A Licausi, Rushil Desai, Ryan M O'Keefe, Richard Y Ebright, Myriam Boukhali, Srinjoy Sil, Maristela L Onozato, Anthony J Iafrate, Ravi Kapur, Dennis Sgroi, David T Ting, Mehmet Toner, Sridhar Ramaswamy, Wilhelm Haas, Shyamala Maheswaran, Daniel A Haber
Circulating tumour cells in women with advanced oestrogen-receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer acquire a HER2-positive subpopulation after multiple courses of therapy. In contrast to HER2-amplified primary breast cancer, which is highly sensitive to HER2-targeted therapy, the clinical significance of acquired HER2 heterogeneity during the evolution of metastatic breast cancer is unknown. Here we analyse circulating tumour cells from 19 women with ER(+)/HER2(-) primary tumours, 84% of whom had acquired circulating tumour cells expressing HER2...
September 1, 2016: Nature
https://www.readbyqxmd.com/read/27551269/the-associations-of-dyadic-coping-and-relationship-satisfaction-vary-between-and-within-nations-a-35-nation-study
#19
Peter Hilpert, Ashley K Randall, Piotr Sorokowski, David C Atkins, Agnieszka Sorokowska, Khodabakhsh Ahmadi, Ahmad M Aghraibeh, Richmond Aryeetey, Anna Bertoni, Karim Bettache, Marta Błażejewska, Guy Bodenmann, Jessica Borders, Tiago S Bortolini, Marina Butovskaya, Felipe N Castro, Hakan Cetinkaya, Diana Cunha, Oana A David, Anita DeLongis, Fahd A Dileym, Alejandra D C Domínguez Espinosa, Silvia Donato, Daria Dronova, Seda Dural, Maryanne Fisher, Tomasz Frackowiak, Evrim Gulbetekin, Aslıhan Hamamcıoğlu Akkaya, Karolina Hansen, Wallisen T Hattori, Ivana Hromatko, Raffaella Iafrate, Bawo O James, Feng Jiang, Charles O Kimamo, David B King, Fırat Koç, Amos Laar, Fívia De Araújo Lopes, Rocio Martinez, Norbert Mesko, Natalya Molodovskaya, Khadijeh Moradi, Zahrasadat Motahari, Jean C Natividade, Joseph Ntayi, Oluyinka Ojedokun, Mohd S B Omar-Fauzee, Ike E Onyishi, Barış Özener, Anna Paluszak, Alda Portugal, Ana P Relvas, Muhammad Rizwan, Svjetlana Salkičević, Ivan Sarmány-Schuller, Eftychia Stamkou, Stanislava Stoyanova, Denisa Šukolová, Nina Sutresna, Meri Tadinac, Andero Teras, Edna L Tinoco Ponciano, Ritu Tripathi, Nachiketa Tripathi, Mamta Tripathi, Noa Vilchinsky, Feng Xu, Maria E Yamamoto, Gyesook Yoo
OBJECTIVE: Theories about how couples help each other to cope with stress, such as the systemic transactional model of dyadic coping, suggest that the cultural context in which couples live influences how their coping behavior affects their relationship satisfaction. In contrast to the theoretical assumptions, a recent meta-analysis provides evidence that neither culture, nor gender, influences the association between dyadic coping and relationship satisfaction, at least based on their samples of couples living in North America and West Europe...
2016: Frontiers in Psychology
https://www.readbyqxmd.com/read/27551012/metastatic-breast-cancer-with-esr1-mutation-clinical-management-considerations-from-the-molecular-and-precision-medicine-map-tumor-board-at-massachusetts-general-hospital
#20
Aditya Bardia, John A Iafrate, Tilak Sundaresan, Jerry Younger, Valentina Nardi
UNLABELLED: : The last decade in oncology has witnessed impressive response rates with targeted therapies, largely because of collaborative efforts at understanding tumor biology and careful patient selection based on molecular fingerprinting of the tumor. Consequently, there has been a push toward routine molecular genotyping of tumors, and large precision medicine-based clinical trials have been launched to match therapy to the molecular alteration seen in a tumor. However, selecting the "right drug" for an individual patient in clinic is a complex decision-making process, including analytical interpretation of the report, consideration of the importance of the molecular alteration in driving growth of the tumor, tumor heterogeneity, the availability of a matched targeted therapy, efficacy and toxicity considerations of the targeted therapy (compared with standard therapy), and reimbursement issues...
September 2016: Oncologist
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