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151. Experience Report on the Challenges and Opportunities in Securing Smartphones Against Zero-Click Attacks

Author

Shafqat, Narmeen, Topcuoglu, Cem, Kirda, Engin, and Ranganathan, Aanjhan

Subjects
Computer Science - Cryptography and Security
Abstract

Zero-click attacks require no user interaction and typically exploit zero-day (i.e., unpatched) vulnerabilities in instant chat applications (such as WhatsApp and iMessage) to gain root access to the victim's smartphone and exfiltrate sensitive data. In this paper, we report our experiences in attempting to secure smartphones against zero-click attacks. We approached the problem by first enumerating several properties we believed were necessary to prevent zero-click attacks against smartphones. Then, we created a security design that satisfies all the identified properties, and attempted to build it using off-the-shelf components. Our key idea was to shift the attack surface from the user's smartphone to a sandboxed virtual smartphone ecosystem where each chat application runs in isolation. Our performance and usability evaluations of the system we built highlighted several shortcomings and the fundamental challenges in securing modern smartphones against zero-click attacks. In this experience report, we discuss the lessons we learned, and share insights on the missing components necessary to achieve foolproof security against zero-click attacks for modern mobile devices.

Published
2022

158. Atmospheric retrievals for LIFE and other future space missions: the importance of mitigating systematic effects

Author

Alei, Eleonora, Konrad, Björn S., Mollière, Paul, Quanz, Sascha P., Angerhausen, Daniel, Ranganathan, Mohanakrishna, and collaboration, the LIFE

Subjects
Astrophysics - Earth and Planetary Astrophysics, Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

Atmospheric retrieval studies are essential to determine the science requirements for future generation missions, such as the Large Interferometer for Exoplanets (LIFE). The use of heterogeneous absorption cross-sections might be the cause of systematic effects in retrievals, which could bias a correct characterization of the atmosphere. In this contribution we quantified the impact of differences in line list provenance, broadening coefficients, and line wing cut-offs in the retrieval of an Earth twin exoplanet orbiting a Sun-like star at 10 pc from the observer, as it would be observed with LIFE. We ran four different retrievals on the same input spectrum, by varying the opacity tables that the Bayesian retrieval framework was allowed to use. We found that the systematics introduced by the opacity tables could bias the correct estimation of the atmospheric pressure at the surface level, as well as an accurate retrieval of the abundance of some species in the atmosphere (such as CO$_2$ and N$_2$O). We argue that differences in the line wing cut-off might be the major source of errors. We highlight the need for more laboratory and modeling efforts, as well as inter-model comparisons of the main radiative transfer models and Bayesian retrieval frameworks. This is especially relevant in the context of LIFE and future generation missions, to identify issues and critical points for the community to jointly work together to prepare for the analysis of the upcoming observations., Comment: 24 pages, 12 figures. Proceedings SPIE Volume 12180, Space Telescopes and Instrumentation 2022: Optical, Infrared, and Millimeter Wave; 121803L (2022)

Published
2022
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159. Superparamagnetic and metal-like Ru2TiGe: a propitious thermoelectric material

Author

Mondal, Sanchayita, Ghosh, Krishanu, Ranganathan, R., Alleno, Eric, and Mazumdar, Chandan

Subjects
Condensed Matter - Strongly Correlated Electrons
Abstract

We report a study of structural, magnetic, heat capacity and thermoelectric properties of a Rubased Heusler alloy, Ru2TiGe. The magnetic measurements reveal that at higher temperatures, diamagnetic and Pauli paramagnetic contributions dominate the magnetic behaviour whereas, at lower temperatures (T<= 20 K), superparamagnetic interaction among clusters is observed. Effect of such magnetic defects is also evident in the electrical resistivity behaviour at lower temperatures. Though the temperature dependence of resistivity exhibits a metal-like nature, the large value of Seebeck coefficient leads to an appreciable power factor of the order of 1 mW/mK2 at 300 K. Large power factor as well as low thermal conductivity results in a value of ZT = 0.025 at 390 K for Ru2TiGe that is orders of magnitude higher than that of the other pure Heusler alloys and point towards its high potential for practical thermoelectric applications.

Published
2022
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160. Neighborhood VAR: Efficient estimation of multivariate timeseries with neighborhood information

Author

Hu, Zhihao, Ranganathan, Shyam, Shao, Yang, and Deng, Xinwei

Subjects
Statistics - Methodology, Statistics - Applications
Abstract

In data science, vector autoregression (VAR) models are popular in modeling multivariate time series in the environmental sciences and other applications. However, these models are computationally complex with the number of parameters scaling quadratically with the number of time series. In this work, we propose a so-called neighborhood vector autoregression (NVAR) model to efficiently analyze large-dimensional multivariate time series. We assume that the time series have underlying neighborhood relationships, e.g., spatial or network, among them based on the inherent setting of the problem. When this neighborhood information is available or can be summarized using a distance matrix, we demonstrate that our proposed NVAR method provides a computationally efficient and theoretically sound estimation of model parameters. The performance of the proposed method is compared with other existing approaches in both simulation studies and a real application of stream nitrogen study.

Published
2022

161. Learning to Improve Code Efficiency

Author

Chen, Binghong, Tarlow, Daniel, Swersky, Kevin, Maas, Martin, Heiber, Pablo, Naik, Ashish, Hashemi, Milad, and Ranganathan, Parthasarathy

Subjects
Computer Science - Software Engineering, Computer Science - Machine Learning
Abstract

Improvements in the performance of computing systems, driven by Moore's Law, have transformed society. As such hardware-driven gains slow down, it becomes even more important for software developers to focus on performance and efficiency during development. While several studies have demonstrated the potential from such improved code efficiency (e.g., 2x better generational improvements compared to hardware), unlocking these gains in practice has been challenging. Reasoning about algorithmic complexity and the interaction of coding patterns on hardware can be challenging for the average programmer, especially when combined with pragmatic constraints around development velocity and multi-person development. This paper seeks to address this problem. We analyze a large competitive programming dataset from the Google Code Jam competition and find that efficient code is indeed rare, with a 2x runtime difference between the median and the 90th percentile of solutions. We propose using machine learning to automatically provide prescriptive feedback in the form of hints, to guide programmers towards writing high-performance code. To automatically learn these hints from the dataset, we propose a novel discrete variational auto-encoder, where each discrete latent variable represents a different learned category of code-edit that increases performance. We show that this method represents the multi-modal space of code efficiency edits better than a sequence-to-sequence baseline and generates a distribution of more efficient solutions.

Published
2022

162. Outcomes of Patients Treated for Hepatoblastoma with Low Alpha-Fetoprotein and/or Small Cell Undifferentiated Histology: A Report from the Children's Hepatic Tumors International Collaboration (CHIC).

Author

Trobaugh-Lotrario, Angela D, Maibach, Rudolf, Aronson, Daniel C, Rangaswami, Arun, Häberle, Beate, O'Neill, Allison F, Schmid, Irene, Ansari, Marc, Hishiki, Tomoro, Ranganathan, Sarangarajan, Alaggio, Rita, de Krijger, Ronald R, Tanaka, Yukichi, Cho, Soo-Jin, Vokuhl, Christian, Maxwell, Rebecca, Krailo, Mark, Hiyama, Eiso, Czauderna, Piotr, Finegold, Milton, Feusner, James H, Malogolowkin, Marcio H, Meyers, Rebecka L, and Lopez-Terrada, Dolores

Subjects
AFP, Hepatoblastoma, SCU, SMARCB1, rhabdoid, Cancer, Digestive Diseases, Liver Disease, Oncology and Carcinogenesis
Abstract

Small cell undifferentiated (SCU) histology and alpha-fetoprotein (AFP) levels below 100 ng/mL have been reported as poor prognostic factors in hepatoblastoma (HB); subsequent studies reported SMARCB1 mutations in some SCU HBs confirming the diagnosis of rhabdoid tumor. The Children's Hepatic tumors International Collaboration (CHIC) database was queried for patients with HB who had AFP levels less than 100 ng/mL at diagnosis or were historically diagnosed as SCU HBs. Seventy-three of 1605 patients in the CHIC database were originally identified as SCU HB, HB with SCU component, or HB with low AFP levels. Upon retrospective review, they were re-classified as rhabdoid tumors (n = 11), HB with SCU component (n = 41), and HB with low AFP (n = 14). Seven were excluded for erroneously low AFP levels. Overall survival was 0% for patients with rhabdoid tumors, 76% for patients with HB with SCU component, and 64% for patients with HB with AFP less than 100 ng/mL. Patients with HB with SCU component or low AFP should be assessed for SMARCB1 mutations and, if confirmed, treated as rhabdoid tumors. When rhabdoid tumors are excluded, the presence of SCU component and low AFP at diagnosis were not associated with poor prognosis in patients diagnosed with HB.

Published
2023

163. Young people's data governance preferences for their mental health data: MindKind Study findings from India, South Africa, and the United Kingdom.

Author

Sieberts, Solveig K, Marten, Carly, Bampton, Emily, Björling, Elin A, Burn, Anne-Marie, Carey, Emma Grace, Carlson, Sonia, Fernandes, Blossom, Kalha, Jasmine, Lindani, Simthembile, Masomera, Hedwick, Neelakantan, Lakshmi, Pasquale, Lisa, Ranganathan, Swetha, Joy Scanlan, Erin, Shah, Himani, Sibisi, Refiloe, Sumant, Sushmita, Suver, Christine, Thungana, Yanga, Tummalacherla, Meghasyam, Velloza, Jennifer, Collins, Pamela Y, Fazel, Mina, Ford, Tamsin, Freeman, Melvyn, Pathare, Soumitra, Zingela, Zukiswa, MindKind Consortium, and Doerr, Megan

Subjects
MindKind Consortium, Humans, Mental Health, Qualitative Research, Adolescent, Adult, South Africa, India, Young Adult, United Kingdom, Clinical Research, Clinical Trials and Supportive Activities, Behavioral and Social Science, Pediatric, 7.1 Individual care needs, Management of diseases and conditions, Mental health, Good Health and Well Being, General Science & Technology
Abstract

Mobile devices offer a scalable opportunity to collect longitudinal data that facilitate advances in mental health treatment to address the burden of mental health conditions in young people. Sharing these data with the research community is critical to gaining maximal value from rich data of this nature. However, the highly personal nature of the data necessitates understanding the conditions under which young people are willing to share them. To answer this question, we developed the MindKind Study, a multinational, mixed methods study that solicits young people's preferences for how their data are governed and quantifies potential participants' willingness to join under different conditions. We employed a community-based participatory approach, involving young people as stakeholders and co-researchers. At sites in India, South Africa, and the UK, we enrolled 3575 participants ages 16-24 in the mobile app-mediated quantitative study and 143 participants in the public deliberation-based qualitative study. We found that while youth participants have strong preferences for data governance, these preferences did not translate into (un)willingness to join the smartphone-based study. Participants grappled with the risks and benefits of participation as well as their desire that the "right people" access their data. Throughout the study, we recognized young people's commitment to finding solutions and co-producing research architectures to allow for more open sharing of mental health data to accelerate and derive maximal benefit from research.

Published
2023

167. CONTRIBUTORS

Author

Abahuje, Egide, primary, Abrahim, Orit, additional, Adetifa, Ifedayo M.O., additional, Ajjampur, Sitara S.R., additional, Alexander, Suceena, additional, PhD, Chiara Altare,, additional, Alves, Fabiana, additional, Andrianaivoarimanana, Voahangy, additional, Angelakis, Emmanouil, additional, Aronson, Jeffrey K., additional, Atukorala, Inoshi G., additional, Baily, Guy, additional, Baker, Stephen, additional, Barrett, Alan D.T., additional, Basnyat, Buddha, additional, Bastawrous, Andrew, additional, Bates, Imelda, additional, Bausch, Daniel G., additional, Baxter, Cheryl, additional, Beare, Nicholas A.V., additional, Beeching, Nick J., additional, Bekker, Linda-Gail, additional, Berlin, Anita, additional, FRS, Zulfiqar A. Bhutta, additional, Bloom, David E., additional, Blumberg, Lucille, additional, Boelaert, Marleen, additional, Brett-Major, David, additional, Brooker, Simon J., additional, Brouwer, Matthijs C., additional, Brunetti, Enrico, additional, Bull, Susan, additional, Bundy, Donald A.P., additional, Burri, Christian, additional, Bustinduy, Amaya L., additional, Caillet, Céline, additional, Chai, Jong Yil, additional, Chang, Thashi, additional, Chappuis, François, additional, Chibi, Buyisile, additional, Chiodini, Peter L., additional, Chowdhury, Rajiv, additional, Chowdhury, Sudipta Dhar, additional, Clemens, John D., additional, Cooke, Graham S., additional, Cotton, Mark F., additional, Currie, Bart J., additional, Cusack, Tomas-Paul, additional, Dance, David A.B., additional, Davis, Emily H., additional, Day, Nicholas P.J., additional, Deen, Jacqueline, additional, Dondorp, Arjen M., additional, Dünser, Martin W., additional, Eitzen, Edward, additional, Chebib, Hassan El, additional, Enria, Delia, additional, Faust, Christina, additional, Fekadu, Abebaw, additional, Fink, Günther, additional, Fischer, Peter U., additional, Fletcher, Tom, additional, Franco-Paredes, Carlos, additional, French, Neil, additional, Frumkin, Howard, additional, Garcia, Hector H., additional, Gerada, Alessandro, additional, Glass, Roger I., additional, Gordon, Stephen B., additional, Gottstein, Bruno, additional, Goyal, Alpesh, additional, Grey, Jonathan, additional, Gupta, Yashdeep, additional, Haines, Andy, additional, Hampson, Katie, additional, Hanlon, Charlotte, additional, Harrison, Mark, additional, Haswell, Melissa R., additional, Hawkesworth, Sophie, additional, Hay, Roderick J., additional, Heckmann, Jeannine M., additional, Heimesaat, Markus M., additional, Henao-Martínez, Andrés F., additional, Hien, Tran Tinh, additional, Hoerauf, Achim, additional, Irfan, Omar, additional, PhD, Euzebiusz Jamrozik, additional, Jobe, Modou, additional, John, George T., additional, Jones, Nick K., additional, Jones, Malcolm K., additional, Junghanss, Thomas, additional, Kaewkes, Sasithorn, additional, Karim, Quarraisha Abdool, additional, Keiser, Jennifer, additional, Kelly, Paul, additional, Khan, Amira M., additional, King, Charles H., additional, Kishore, Sandeep P., additional, Lang, Trudie, additional, Le, Thuy, additional, Liesenfeld, Oliver, additional, Lockwood, Diana N.J., additional, Mabey, David C.W., additional, Madkour, M. Monir, additional, Manesh, Abi, additional, Masekela, Refiloe, additional, Mäser, Pascal, additional, Mayaud, Philippe, additional, Mbanya, Dora, additional, McCarthy, James S., additional, McCartney, Daniel J., additional, McGready, Rose, additional, McKee, Martin, additional, Mc, Namara, Paul S., additional, Meara, John G., additional, Meintjes, Graeme, additional, Merson, Laura, additional, Mola, Glen, additional, Morassutti, Alessandra L., additional, Morris-Jones, Rachael, additional, Mortimer, Kevin J., additional, Muliyil, Divya Elizabeth, additional, Mumcuoglu, Kosta Y., additional, Munoz, Flor M., additional, Murphy, Adrianna, additional, Mutabingwa, Theonest, additional, Nawa, Yukifumi, additional, Newton, Paul N., additional, Nightingale, Sam, additional, Nokes, D. James, additional, Nosten, François H., additional, O’Hea, Jennifer, additional, Olliaro, Piero, additional, Ong, Jason J., additional, Oommen, Anu Mary, additional, Parashar, Umesh D., additional, Paris, Daniel H., additional, Parker, Michael, additional, Pluschke, Gerd, additional, Preidis, Geoffrey A., additional, Prentice, Andrew M., additional, Quail, Geoffrey, additional, Quinn, Thomas C., additional, Rabie, Helena, additional, Rajashekharaiah, Harsha, additional, Rajerison, Minoarisoa, additional, Ranganathan, Kannan, additional, Raoult, Didier, additional, Rassi,, Anis, additional, Ravi, Vasanthapuram, additional, Reddy, K. Srinath, additional, Rees, Claire, additional, Reynolds, Steven J., additional, Richter, Joachim, additional, Rijken, Marcus J., additional, Riviello, Robert, additional, Robinson, Janet, additional, Salazar, Juan C., additional, Schultz, Marcus J., additional, Schwarz, Dan, additional, Sendagire, Ibrahim, additional, Sharma, Savitri, additional, Shawon, Shajedur Rahman, additional, Singh, Bhagteshwar, additional, Sithithaworn, Paiboon, additional, Siwila, Joyce, additional, Solomon, Tom, additional, Spiegel, Paul, additional, Sridhar, Devi, additional, Sripa, Banchob, additional, Srour, M. Leila, additional, Stojković, Marija, additional, Strader, Christopher, additional, Suárez, Jose A., additional, Sundar, Shyam, additional, Tamarozzi, Francesca, additional, Tandon, Nikhil, additional, Tate, Jacqueline E., additional, Thachil, Jecko, additional, Thomson, Madeleine C., additional, Thwaites, Guy, additional, Thwaites, C. Louise, additional, van Daalen, Kim R., additional, Beek, Diederik van de, additional, van Doorn, H. Rogier, additional, Vega-Lopez, Francisco, additional, von Seidlein, MD, PhD, Lorenz, additional, Wakeham, Katie, additional, Walker, Stephen L., additional, Wallace, Ryan M., additional, Ward, Honorine, additional, Warrell, David A., additional, Weber, Tim Frederik, additional, Weil, Gary J., additional, White, Nicholas J., additional, White, MB Ch, B, Graham B., additional, Wong, Vanessa, additional, Wood, Robin, additional, Wood, Georgina, additional, Wyllie, Sarah, additional, Yacoub, Sophie, additional, Yen, Lam Minh, additional, Young, Paul R., additional, and Zafren, Ken, additional

Published
2024
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168. Exploring the clinical utility of liquid biopsy with cfDNA in cancer: A systematic review

Author

Keerthi Ranganathan, Neethu Sheri Kurian, Hitesh M. Goswami, Kshitij D. Rishi, and Vidya H. Veldore

Subjects
Tumor, Tumor heterogeneity, Liquid biopsy, Cell-free DNA (cfDNA), Circulating tumor DNA (ctDNA), Minimal residual disease (MRD), Medicine
Abstract

Various tumor cells may exhibit different genetic or phenotypic characteristics. This phenomenon of cancer cells, known as Tumor Heterogeneity, is responsible for multiple cancer sites caused in a single patient through metastases. It is possible that the biopsy of the most accessible metastasis will not provide enough information to reexamine tumor features and make therapeutic recommendations. Liquid biopsy is a diagnostic technique that probes metastatic deposits from biofluids like peripheral blood for cell-free DNA (cfDNA)/circulating tumor DNA (ctDNA) from cancer patients. This analysis provides researchers and oncologists a comprehensive insight into therapeutic targets and treatment resistance-causing gene alterations.Various studies have validated that cfDNA/ctDNA may be essential in tumor analysis, constituting the need for the identification of cancer cells that may reactivate and proliferate, causing the disease to reoccur. This detection is also called Minimal Residual Disease (MRD) and shares insights on the efficiency of the treatment regimen and if the cancer cells have developed resistance to a specific treatment regimen.In this review, the significance of cfDNA/ctDNA as a possible diagnostic, prognostic, or monitoring biomarker for solid tumors has been evaluated in recent studies, and its clinical relevance in routine cancer clinics in India has been reviewed.

Published
2024
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169. OPTIMIZED DEEP LEARNING FOR CYBER INTRUSION DETECTION AND SECURED COMMUNICATION IN MANET

Author

Ramakrishnan Ramamoorthy, Sivakumar Ramu, and Ramesh Kumar Ranganathan

Subjects
Technology, Science
Abstract

The popularity of the Mobile Ad-Hoc Network increases with low expense solutions to the real time applications. The dynamic nature, limited centralized system with low bandwidth often susceptible to the security threads and became the hot topic. To protect the MANET system it is essential to implement a secured system. The purpose of this work is to design an intelligent Cyber Security System (CSS) by collecting the threads data from the MANET system. Initially, the data is pre-processed using the Min-Max normalization technique, followed by the feature selection with the newly approached Mother Optimization algorithm (MOA). The feature selection is effectuated for speedy classification of intrusions and prevent the attacks and therein significantly enhances the security. To provide the security to the MANET system the work proposes a novel Adaptive Deep Belief Network (ADBN). This classifies the attacks and normal data and prevents the system from falling for the threat. Simulation is performed in NS2 and analyzed the effectiveness of the proposed work with existing systems. Our proposed work effectively enhances the security of the MANET system and surpasses all the other works.

Published
2024
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177. Pluricanonical cycles and tropical covers

Author

Cavalieri, Renzo, Markwig, Hannah, and Ranganathan, Dhruv

Subjects
Mathematics - Algebraic Geometry
Abstract

We extract a system of numerical invariants from logarithmic intersection theory on pluricanonical double ramification cycles, and show that these invariants exhibit a number of properties that are enjoyed by double Hurwitz numbers. Among their properties are (i) the numbers can be efficiently calculated by counts of tropical curves with a modified balancing condition, (ii) they are piecewise polynomial in the entries of the ramification vector, and (iii) they are matrix elements of operators on the Fock space. The numbers are extracted from the logarithmic double ramification cycle, which is a lift of the standard double ramification cycle to a blowup of the moduli space of curves. The blowup is determined by tropical geometry. We show that the traditional double Hurwitz numbers are intersections of the refined cycle with the cohomology class of a piecewise polynomial function on the tropical moduli space of curves. This perspective then admits a natural, combinatorially motivated, generalization to the pluricanonical setting. Tropical correspondence results for the new invariants lead immediately to the structural results for these numbers., Comment: 40 pages, 14 figures. v3: Minor changes. Final version to appear in Transactions of the AMS

Published
2022

178. On the Running Time of Hypergraph Bootstrap Percolation

Author

Noel, Jonathan A. and Ranganathan, Arjun

Subjects
Mathematics - Combinatorics, 05C35, 05C65, 05D99, 82B43
Abstract

Given $r\geq2$ and an $r$-uniform hypergraph $F$, the $F$-bootstrap process starts with an $r$-uniform hypergraph $H$ and, in each time step, every hyperedge which "completes" a copy of $F$ is added to $H$. The maximum running time of this process has been recently studied in the case that $r=2$ and $F$ is a complete graph by Bollob\'as, Przykucki, Riordan and Sahasrabudhe [Electron. J. Combin. 24(2) (2017), Paper No. 2.16], Matzke [arXiv:1510.06156v2] and Balogh, Kronenberg, Pokrovskiy and Szab\'o [arXiv:1907.04559v1]. We consider the case that $r\geq3$ and $F$ is the complete $r$-uniform hypergraph on $k$ vertices. Our main results are that the maximum running time is $\Theta\left(n^r\right)$ if $k\geq r+2$ and $\Omega\left(n^{r-1}\right)$ if $k=r+1$. For the case $k=r+1$, we conjecture that our lower bound is optimal up to a constant factor when $r=3$, but suspect that it can be improved by more than a constant factor for large $r$., Comment: 20 pages, 3 figures

Published
2022
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179. Cryptography Is Not Enough: Relay Attacks on Authenticated GNSS Signals

Author

Motallebighomi, Maryam, Sathaye, Harshad, Singh, Mridula, and Ranganathan, Aanjhan

Subjects
Computer Science - Cryptography and Security
Abstract

Civilian-GNSS is vulnerable to signal spoofing attacks, and countermeasures based on cryptographic authentication are being proposed to protect against these attacks. Both Galileo and GPS are currently testing broadcast authentication techniques based on the delayed key disclosure to validate the integrity of navigation messages. These authentication mechanisms have proven secure against record now and replay later attacks, as navigation messages become invalid after keys are released. This work analyzes the security guarantees of cryptographically protected GNSS signals and shows the possibility of spoofing a receiver to an arbitrary location without breaking any cryptographic operation. In contrast to prior work, we demonstrate the ability of an attacker to receive signals close to the victim receiver and generate spoofing signals for a different target location without modifying the navigation message contents. Our strategy exploits the essential common reception and transmission time method used to estimate pseudorange in GNSS receivers, thereby rendering any cryptographic authentication useless. We evaluate our attack on a commercial receiver (ublox M9N) and a software-defined GNSS receiver (GNSS-SDR) using a combination of open-source tools, commercial GNSS signal generators, and software-defined radio hardware platforms. Our results show that it is possible to spoof a victim receiver to locations around 4000 km away from the true location without requiring any high-speed communication networks or modifying the message contents. Through this work, we further highlight the fundamental limitations in securing a broadcast signaling-based localization system even if all communications are cryptographically protected.

Published
2022

186. Outcomes of children with well-differentiated fetal hepatoblastoma treated with surgery only: Report from Childrens Oncology Group Trial, AHEP0731.

Author

Vasudevan, Sanjeev, Meyers, Rebecka, Finegold, Milton, López-Terrada, Dolores, Ranganathan, Sarangarajan, Dunn, Stephen, Langham, Max, McGahren, Eugene, Tiao, Greg, Weldon, Christopher, Krailo, Mark, Piao, Jin, Randazzo, Jessica, Towbin, Alexander, BethMcCarville, M, ONeill, Allison, Furman, Wayne, Rodriguez-Galindo, Carlos, Katzenstein, Howard, and Malogolowkin, Marcio

Subjects
Fetal, Hepatoblastoma, Resection, Well-differentiated, Chemotherapy, Adjuvant, Child, Hepatectomy, Hepatoblastoma, Humans, Infant, Liver Neoplasms, Prognosis, Treatment Outcome
Abstract

BACKGROUND: Hepatoblastoma (HB) requires surgical resection for cure, but only 20-30% of patients have resectable disease at diagnosis. Patients who undergo partial hepatectomy at diagnosis have historically received 4-6 cycles of adjuvant chemotherapy; however, those with 100% well-differentiated fetal histology (WDF) have been observed to have excellent outcomes when treated with surgery alone. PATIENTS AND METHODS: Patients on the Childrens Oncology Group non randomized, multicenter phase III study, AHEP0731, were stratified based on Evans stage, tumor histology, and serum alpha-fetoprotein level at diagnosis. Patients were eligible for the very low risk stratum of surgery and observation if they had a complete resection at diagnosis and rapid central histologic review demonstrated HB with 100% WDF histology. RESULTS: A total of 8 eligible patients were enrolled on study between September 14, 2009 and May 28, 2014. Outcome current to 06/30/2020 was used in this analysis. The median age at enrollment was 22.5 months (range: 8-84 months) and the median AFP at enrollment was 714 ng/ml (range: 18-77,747 ng/mL). With a median follow-up of 6.6 years (range: 3.6-9.8 years), the 5-year event-free (EFS) and overall survival (OS) were both 100%. CONCLUSION: This report supports that HB with 100% WDF histology completely resected at diagnosis is curable with surgery only. The development of evidence-based surgical guidelines utilizing criteria based on PRETEXT group, vascular involvement (annotation factors), tumor-specific histology and corresponding biology will be crucial for optimizing which patients are candidates for resection at diagnosis followed by observation. LEVEL OF EVIDENCE: Prognosis study, Level I evidence.

Published
2022

187. Hepatoblastomas with carcinoma features represent a biological spectrum of aggressive neoplasms in children and young adults

Author

Sumazin, Pavel, Peters, Tricia L, Sarabia, Stephen F, Kim, Hyunjae R, Urbicain, Martin, Hollingsworth, Emporia Faith, Alvarez, Karla R, Perez, Cintia R, Pozza, Alice, Panah, Mohammad Javad Najaf, Epps, Jessica L, Scorsone, Kathy, Zorman, Barry, Katzenstein, Howard, O’Neill, Allison F, Meyers, Rebecka, Tiao, Greg, Geller, Jim, Ranganathan, Sarangarajan, Rangaswami, Arun A, Woodfield, Sarah E, Goss, John A, Vasudevan, Sanjeev A, Heczey, Andras, Roy, Angshumoy, Fisher, Kevin E, Alaggio, Rita, Patel, Kalyani R, Finegold, Milton J, and López-Terrada, Dolores H

Subjects
Rare Diseases, Pediatric, Liver Cancer, Genetics, Digestive Diseases, Cancer, Liver Disease, Pediatric Cancer, Carcinoma, Hepatocellular, Child, Chromosome Aberrations, Hepatoblastoma, Humans, Liver Neoplasms, Mutation, Young Adult, Cancer heterogeneity, liver cancer, pediatric cancer, hepatoblastoma, HCN NOS, cancer etiology, diagnostic biomarker, HB FPAHBs that demonstrate focal macrotrabecular pattern, pleomorphism or anaplasia, HB FPAHBs that demonstrate focal macrotrabecular pattern, pleomorphism or anaplasia, Clinical Sciences, Public Health and Health Services, Gastroenterology & Hepatology
Abstract

Background & aimsHepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the predominant liver cancers in children, though their respective treatment options and associated outcomes differ dramatically. Risk stratification using a combination of clinical, histological, and molecular parameters can improve treatment selection, but it is particularly challenging for tumors with mixed histological features, including those in the recently created hepatocellular neoplasm not otherwise specified (HCN NOS) provisional category. We aimed to perform the first molecular characterization of clinically annotated cases of HCN NOS.MethodsWe tested whether these histological features are associated with genetic alterations, cancer gene dysregulation, and outcomes. Namely, we compared the molecular features of HCN NOS, including copy number alterations, mutations, and gene expression profiles, with those in other pediatric hepatocellular neoplasms, including HBs and HCCs, as well as HBs demonstrating focal atypia or pleomorphism (HB FPAs), and HBs diagnosed in older children (>8).ResultsMolecular profiles of HCN NOS and HB FPAs revealed common underlying biological features that were previously observed in HCCs. Consequently, we designated these tumor types collectively as HBs with HCC features (HBCs). These tumors were associated with high mutation rates (∼3 somatic mutations/Mb) and were enriched with mutations and alterations in key cancer genes and pathways. In addition, recurrent large-scale chromosomal gains, including gains of chromosomal arms 2q (80%), 6p (70%), and 20p (70%), were observed. Overall, HBCs were associated with poor clinical outcomes.ConclusionsOur study indicates that histological features seen in HBCs are associated with combined molecular features of HB and HCC, that HBCs are associated with poor outcomes irrespective of patient age, and that transplanted patients are more likely to have good outcomes than those treated with chemotherapy and surgery alone. These findings highlight the importance of molecular testing and early therapeutic intervention for aggressive childhood hepatocellular neoplasms.Lay summaryWe molecularly characterized a class of histologically aggressive childhood liver cancers and showed that these tumors are clinically aggressive and that their observed histological features are associated with underlying recurrent molecular features. We proposed a diagnostic algorithm to identify these cancers using a combination of histological and molecular features, and our analysis suggested that these cancers may benefit from specialized treatment strategies that may differ from treatment guidelines for other childhood liver cancers.

Published
2022

191. Targeting host inducible-heat shock protein 70 with PES-Cl is a promising antiviral strategy against SARS-CoV-2 infection and pathogenesis

Author

Joshi, Prerna, Garg, Swati, Mani, Shailendra, Shoaib, Rumaisha, Jakhar, Kamini, Almuqdadi, Haider Thaer Abdulhameed, Sonar, Sudipta, Marothia, Manisha, Behl, Ankita, Biswas, Shreeja, Singhal, Jhalak, Kahlon, Amandeep Kaur, Shevtsov, Maxim, Abid, Mohammad, Garg, Pramod, Ranganathan, Anand, and Singh, Shailja

Published
2024
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193. Return of genetic research results in 21,532 individuals with autism

Author

Aarrestad, Alexandria, Abbeduto, Leonard, Aberbach, Gabriella, Aberle, Shelley, Adegbite, Adediwura, Adeniji, Debbie, Aguilar, Maria, Ahlers, Kaitlyn, Albright, Charles, Alessandri, Michael, Algaze, Zach, Alkazi, Jasem, Amador, Raquel, Amaral, David, Amon, Logan, Amundsen, Leonor, Andrus, Alicia, Anglo, Claudine, Annett, Robert, Arar, Adam, Arnold, Jonathan, Arriaga, Ivette, Arzate, Eduardo, Ashley, Raven, Aslamy, Leilemah, Baalman, Kelli, Baer, Melissa, Bahi, Ethan, Bailey, Joshua, Baldlock, Zachary, Banks, Grabrielle, Baraghoshi, Gabriele, Bardett, Nicole, Barrett, Mallory, Bartholomew, Yan, Bates, Heidi, Beard, Katie, Becerra, Juana, Beckwith, Malia, Beechan, Paige, Beeson, Landon, Beeson, Josh, Bell, Brandi, Belli, Monica, Bentley, Dawn, Berger, Natalie, Berman, Anna, Bernier, Raphael, Berry-Kravis, Elizabeth, Berwanger, Mary, Birdwell, Shelby, Blank, Elizabeth, Bond, Rebecca, Booker, Stephanie, Bordofsky, Aniela, Bower, Erin, Bowers, Lukas, Bradley, Catherine, Brayer, Heather, Brewster, Stephanie, Brown, Hallie, Brown, Alison, Brown, Melissa, Buck, Catherine, Buescher, Cate, Bullon, Kayleigh, Buraima, Joy, Butter, Eric, Caamano, Amalia, Cacciato, Nicole, CaI, Wenteng, Calderon, Norma, Callahan, Kristen, Camba, Alexies, Campo-Soria, Claudia, Caprara, Giuliana, Carbone, Paul, Carpenter, Laura, Carpenter, Sarah, Casseus, Myriam, Casten, Lucas, Catherine, Sullivan, Chappo, Ashley, Chavez, Kimberly, Cheathem-Johnson, Randi, Chen, Tia, Chintalapalli, Sharmista, Cho, Daniel, Choi, Y.B., Clark, Nia, Clark, Renee, Coffman, Marika, Coleman, Laura, Coleman, Kendra, Collins, Alister, Columbi, Costanza, Comitre, Joaquin, Constant, Stephanie, Contra, Arin, Conyers, Sarah, Cooper, Lindsey, Cooper, Cameron, Coppola, Leigh, Corlett, Allison, Corrales, Lady, Correa, Dahriana, Cottrell, Hannah, Coughlin, Michelle, Courchesne, Eric, Coury, Dan, Crocetti, Deana, Croson, Carrie, Crowell, Judith, Cubells, Joseph, Cunningham, Sean, Currin, Mary, Cutri, Michele, D'Ambrosi, Sophia, David, Giancarla, Davis, Ayana, Davis, Sabrina, Decius, Nickelle, Delaporte, Jennifer, DeMarco, Lindsey, Dennis, Brandy, Deronda, Alyssa, Dhawan, Esha, Dichter, Gabriel, Doan, Ryan, Dominick, Kelli, Ortega, Leonardo Dominquez, Doyle, Erin, Drayton, Andrea, DuBois, Megan, Dudley, Johnny, Duhon, Gabrielle, Duncan, Grabrielle, Duncan, Amie, Dunlevy, Megan, Dyer, Meaghan, Earl, Rachel, Edmonson, Catherine, Eldred, Sara, Elliott, Nelita, Emery, Brooke, Enright, Barbara, Erb, Sarah, Erickson, Craig, Esler, Amy, Estevez, Liza, Fanta, Anne, Fassler, Carrie, Fatemi, Ali, Fazal, Faris, Featherston, Marilyn, Ferguson, Jonathan, Fish, Angela, Fitzgerald, Kate, Flores, Kathleen, Fombonne, Eric, Foster, Margaret, Fowler, Tiffany, Fox, Emma, Fox, Emily, Francis, Sunday, Frayne, Margot, Froman, Sierra, Fuller, Laura, Galbraith, Virginia, Gallimore, Dakota, Gambrell, Ariana, Gazestani, Vahid, Geisheker, Madeleine R., Gerdts, Jennifer, Geschwind, Daniel, Ghaziuddin, Mohammad, Ghina, Haidar, Given, Erin, Goetz, Mykayla, Gong, Jared, Gonring, Kelsey, Gonzalez, Natalia, Gonzalez, Antonio, Goodwill, Ellie, Gordon, Rachel, Graham, Carter, Gray, Catherine, Grimes, Ellen, Griswold, Anthony, Gu, Pan, Guilfoyle, Janna, Gulsrud, Amanda, Gunderson, Jaclyn, Gunter, Chris, Gupta, Sanya, Gupta, Abha, Gutierrez, Anibal, Gwynette, Frampton, Haidar, Ghina, Hale, Melissa, Haley, Monica, Hall, Lauren K., Hamer, Kira, Hamilton, Piper, Hanna, Nathan, Hardan, Antonio, Harkins, Christina, Harrell, Eldric, Harris, Jill, Harris, Nina, Hayes, Caitlin, Hayse, Braden, Heckers, Teryn, Heerwagen, Kathryn, Hennelly, Daniela, Herbert, Lynette, Hermle, Luke, Hernandez, Briana, Herrera, Clara, Hess, Amy, Heyman, Michelle, Higgins, Lorrin, Phillips, Brittani Hilscher, Hirst, Kathy, Ho, Theodore, Hoffman, Emily, Hojlo, Margaret, Honaker, Makayla, Hong, Michael, Hooks, Gregory, Horner, Susannah, Horton, Danielle, Hounchell, Melanie, Howes, Dain, Huang-Storm, Lark, Hunter, Samantha, Hutter, Hanna, Hyde, Emily, Ibanez, Teresa, Ingram, Kelly, Istephanous, Dalia, Jacob, Suma, Jarratt, Andrea, Jelinek, Anna, Johnson, Mary, Jones, Mya, Jones, Garland, Jones, Mark, Jorgenson, Alissa, Judge, Jessyca, Kalb, Luther, Kalmus, Taylor, Kang, Sungeun, Kangas, Elizabeth, Kanne, Stephen, Kaplan, Hannah, Khan, Sara, Kim, Sophy, Kim, Annes, Kitaygordsky, Alex, Klaiman, Cheryl, Klever, Adam, Koene, Hope, Koomar, Tanner, Koza, Melinda, Kramer, Sydney, Krushena, Meghan, Kurtz-Nelson, Eva, Lamarche, Elena, Lampert, Erica, Lamy, Martine, Landa, Rebecca, Lebron-Cruz, Alexa, Lechniak, Holly, Lee, Soo, Leight, Bruce, Lerner, Matthew, Lesher, Laurie, Lewis, Courtney, Li, Hai, Li, Deana, Libove, Robin, Lillie, Natasha, Limon, Danica, Limpoco, Desi, Lin, Melody, Littlefield, Sandy, Lobisi, Brandon, Locarno, Laura, Long, Nancy, Long, Bailey, Long, Kennadie, Lopez, Marilyn, Lovering, Taylor, Lozano, Ivana, Lucio, Daniella, Luo, Addie, Luu, My-Linh, Lyon, Audrey, Ma, Julia, Madi, Natalie, Malloch, Lacy, Mankaryous, Reanna, Manning, Patricia, Mantey, Alvin, Marini, Richard, Marsden, Alexandra, Marwali, Clarissa, Marzano, Gabriela, Mason, Andrew, Mastel, Sarah, Mathai, Sheena, Matthews, Emily, Matusoff, Emma, Maxim, Clara, McCarthy, Caitlin, McClellen, Lynn, Mccoy, Nicole, McCullough, Kaylen, McDonald, Brooke, McGalliard, Julie, McIntyre, Anne-Marie, McKenna, Brooke, McKenzie, Alexander, McTaggart, Megan, Meinen, Hannah, Melnyk, Sophia, Miceli, Alexandra, Michaels, Sarah, Michaelson, Jacob, Milan, Estefania, Miller, Melissa, Milliken, Anna, Minton, Kyla, Mitchell, Terry, Gunn, Amanda Moffitt, Mohiuddin, Sarah, Money, Gina, Montezuma, Jessie, Mooney, Lindsey, Moore, Margo, Morales-Lara, Amy, Morgan, Kelly, Morotti, Hadley, Morrier, Michael, Munoz, Maria, Lavanderos, Ambar Munoz, Murali, Shwetha, Murillo, Karla, Murray, Kailey, Myhre, Erin, Neely, Jason, Neuhaus, Emily, Newman, Olivia, Nguyen, Richard, Nguyen, Victoria, Nichols, Evelyn, Nicholson, Amy, Niederhauser, Melanie, Norris, Megan, Norton, Shai, Nowell, Kerri, O’Brien, Kaela, O’Meara, Mitchell, O’Neil, Molly, O'Roak, Brian, Ocampo, Edith, Ochoa-Lubinoff, Cesar, Oft, Anna, Orobio, Jessica, Ortiz, Crissy, Ousley, Opal, Oyeyemi, Motunrayo, Pacheco, Lillian, Palacios, Valeria, Palmer, Samiza, Palmeri, Isabella, Pama, Katrina, Pandey, Juhi, Paolicelli, Anna Marie, Parker, Jaylaan, Patterson, Morgan, Pawlowski, Katherine, Pedapati, Ernest, Pepper, Michah, Perrin, Jeremy, Peura, Christine, Phillips, Diamond, Pierce, Karen, Piven, Joseph, Plate, Juhi, Polanco, Jose, Pott-Schmidt, Natalie, Pramparo, Tiziano, Pratt, Taleen, Prock, Lisa, White, Stormi Pulver, Qi, Hongjian, Qiu, Shanping, Queen, Eva, Questel, Marcia, Quinones, Ashley, Rambeck, Desiree, Randall, Shelley, Ranganathan, Vaikunt, Raymond, Laurie, Rayos, Madelyn, Real, Kelly, Rhea, Anna, Rice, Catherine, Richardson, Harper, Riffle, Stacy, Robertson, Tracy, Roby, Erin, Rocha, Ana, Roche, Casey, Rodriguez, Nicki, Rodriguez, Bianca, Roeder, Katherine, Rojas, Daniela, Rosewater, Jacob, Rosselott, Hilary, Runyan, Payton, Russo, Nicole, Rutter, Tara, Ruzzo, Elizabeth, Sahin, Mustafa, Salem, Fatima, Sanchez, Rebecca, Sanders, Muave, Sanderson, Tayler, Sandhu, Sophie, Sanford, Katelyn, Santangelo, Susan, Santulli, Madeline, Sarver, Dustin, Savage, Madeline, Scherr, Jessica, Schneider, Hoa, Schools, Hayley, Schoonover, Gregory, Schultz, Robert, Sebolt, Cheyanne, Shaffer, Rebecca, Shameen, Sana, Sherard, Curry, Shikov, Roman, Shillington, Amelle, Shir, Mojeeb, Shocklee, Amanda, Shrier, Clara, Shulman, Lisa, Siegel, Matt, Simon, Andrea, Simon, Laura, Singh, Arushi, Singh, Vini, Smalley, Devin, Smith, Kaitlin, Smith, Chris, Smith, Ashlyn, Soorya, Latha, Soscia, Julia, Soucy, Aubrie, Stchur, Laura, Steele, Morgan, Srishyla, Diksha, Stamps, Danielle, Sussman, Nicole, Swanson, Amy, Sweeney, Megan, Sziklay, Anthony, Tafolla, Maira, Taiba, Jabeen, Takahashi, Nicole, Terroso, Sydney, Strathearn, Camilla, Thomas, Taylor, Thompson, Samantha, Touchette, Ellyn, Townsend, Laina, Trog, Madison, Tsai, Katherine, Tseng, Angela, Tshering, Paullani, Tso, Ivy, Valicenti-Mcdermott, Maria, VanMetre, Bonnie, VanWade, Candace, Turecki, Samuel, Vargo, Kerrigan, Vattuone, Cristiana, Veenstra-Vanderweele, Jeremy, Vehorn, Alison, Benitez Velazquez, Alan Jesus, Verdi, Mary, Villalobos, Michele, Vrittamani, Lakshmi, Wainer, Allison, Wallace, Jermel, Walston, Corrie, Wang, Jiayaho, Ward, Audrey, Warren, Zachary, Washington, Katherine, Westerkamp, Grace, White, Sabrina, Wink, Logan, Winoto, Fiona, Winters, Sarah, Wodka, Ericka, Xavier, Samantha, Xu, Sidi, Yang, Yi, Yang, WhaJames, Yang, Amy, Yinger, Meredith, Yu, Timothy, Zaro, Christopher, Zha, Cindy, Zhang, Haicang, Zhao, Haoquan, Zick, Allyson, Salmon, Lauren Ziegelmayer, Wright, Jessica R., Astrovskaya, Irina, Barns, Sarah D., Goler, Alexandra, Zhou, Xueya, Shu, Chang, Snyder, LeeAnne Green, Han, Bing, Shen, Yufeng, Volfovsky, Natalia, Hall, Jacob B., Feliciano, Pamela, and Chung, Wendy K.

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2024
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