tbuckley/cabot-search huggingface dataset:
Ripple-selective GABAergic projection cells in the hippocampus
Authors: Gergely G. Szabo, Jordan S. Farrell, Barna Dudok, Wen-Hsien Hou, Anna L. Ortiz, Csaba Varga, Prannath Moolchand, Cafer Ikbal Gulsever, Tilo Gschwind, Jordane Dimidschstein, Marco Capogna, Ivan Soltesz
Journal: Neuron (2022)

Ripples are brief high-frequency electrographic events with important roles in episodic memory. However, the in vivo circuit mechanisms coordinating ripple-related activity among local and distant neuronal ensembles are not well understood. Here, we define key characteristics of a long-distance projecting GABAergic cell group in the mouse hippocampus that selectively exhibits high-frequency firing during ripples while staying largely silent during theta-associated states when most other GABAergic cells are active. The high ripple-associated firing commenced before ripple onset and reached its maximum before ripple peak, with the signature theta-OFF, ripple-ON firing pattern being preserved across awake and sleep states. Controlled by septal GABAergic, cholinergic, and CA3 glutamatergic inputs, these ripple-selective cells innervate parvalbumin and cholecystokinin-expressing local interneurons while also targeting a variety of extra-hippocampal regions. These results demonstrate the existence of a hippocampal GABAergic circuit element that is uniquely positioned to coordinate ripple-related neuronal dynamics across neuronal assemblies.
Mutations in the SARS-CoV-2 RNA-dependent RNA polymerase confer resistance to remdesivir by distinct mechanisms
Authors: Laura J. Stevens, Andrea J. Pruijssers, Hery W. Lee, Calvin J. Gordon, Egor P. Tchesnokov, Jennifer Gribble, Amelia S. George, Tia M. Hughes, Xiaotao Lu, Jiani Li, Jason K. Perry, Danielle P. Porter, Tomas Cihlar, Timothy P. Sheahan, Ralph S. Baric, Matthias Götte, Mark R. Denison
Journal: Science Translational Medicine (2022)

The nucleoside analog remdesivir (RDV) is a Food and Drug Administration-approved antiviral for treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Thus, it is critical to understand factors that promote or prevent RDV resistance. We passaged SARS-CoV-2 in the presence of increasing concentrations of GS-441524, the parent nucleoside of RDV. After 13 passages, we isolated three viral lineages with phenotypic resistance as defined by increases in half-maximal effective concentration from 2.7- to 10.4-fold. Sequence analysis identified nonsynonymous mutations in nonstructural protein 12 RNA-dependent RNA polymerase (
Tailoring combinatorial lipid nanoparticles for intracellular delivery of nucleic acids, proteins, and drugs
Authors: Yamin Li, Zhongfeng Ye, Hanyi Yang, Qiaobing Xu
Journal: Acta Pharmaceutica Sinica B (2022)

Lipid nanoparticle (LNP)-based drug delivery systems have become the most clinically advanced non-viral delivery technology. LNPs can encapsulate and deliver a wide variety of bioactive agents, including the small molecule drugs, proteins and peptides, and nucleic acids. However, as the physicochemical properties of small- and macromolecular cargos can vary drastically, every LNP carrier system needs to be carefully tailored in order to deliver the cargo molecules in a safe and efficient manner. Our group applied the combinatorial library synthesis approach and
A multi-centre prospective cohort study of patients on the elective waiting list for cardiac surgery during the COVID-19 pandemic
Authors: Martin T Yates, Damian Balmforth, Bilal H Kirmani, Metesh Acharya, Reuben Jeganathan, Dumbor Ngaage, Mayzar Kanani, Indu Deglurkar, Ana Lopez-Marco, Julie Sanders, Aung Ye Oo
Journal: Journal of the Royal Society of Medicine (2022)

During the worldwide COVID-19 pandemic, elective cardiac surgery was suspended to provide ICU beds for COVID-19 patients and those requiring urgent cardiac surgery. The aim of this study is to assess the effect of the pandemic on outcomes of patients awaiting elective cardiac surgery.A multi-centre prospective cohort study.The elective adult cardiac surgery waiting list as of 1 March 2020 across seven UK cardiac surgical centres.Patients on the elective adult cardiac surgery waiting list as of 1 March 2020 across seven UK cardiac surgical centres.Primary outcome was surgery, percutaneous therapy or death at one year.Data were collected prospectively on patients on the elective adult cardiac surgery waiting list as of 1 March 2020 across seven UK cardiac surgical centres. Primary outcome was surgery, percutaneous therapy or death at one year. Demographic data and outcomes were obtained from local electronic records, anonymised and submitted securely to the lead centre for analysis.On 1 March 2020, there were 1099 patients on the elective waiting list for cardiac surgery. On 1 March 2021, 83% (n = 916) had met a primary outcome. Of these, 840 (92%) had surgery after a median of 195 (118-262) days on waiting list, 34 (3%) declined an offer of surgery, 23 (3%) had percutaneous intervention, 12 (1%) died, 7 (0.6%) were removed from the waiting list. The remainder of patients, 183 (17%) remained on the elective waiting list.This study has shown, for the first time, significant delays to treatment of patients awaiting elective cardiac surgery. Although there was a low risk of mortality or urgent intervention, important unmeasured adverse outcomes such as quality of life or increased perioperative risk may be associated with prolonged waiting times.
Postoperative complications on pancreaticoduodenectomy with total mesopancreas excision in pancreatic head cancer
Authors: Alejandro Serrablo-Requejo, Sandra Paterna-López, Marta Gutiérrez-Díez, María Teresa Abadía-Forcén, Mario Serradilla-Requejo, Pablo Sancho-Pardo, Consuelo Artigas-Marco
Journal: International Journal of Surgery (2022)
Combinatorial Use of Therapeutic ELP‐Based Micelle Particles in Tissue Engineering
Authors: Beyza Bulutoglu, Aylin Acun, Sarah L. Deng, Safak Mert, Elise Lupon, Alexandre G. Lellouch, Curtis L. Cetrulo, Basak E. Uygun, Martin L. Yarmush
Journal: Advanced Healthcare Materials (2022)

Elastin-like peptides (ELPs) are a versatile platform for tissue engineering and drug delivery. Here, micelle forming ELP chains are genetically fused to three therapeutic molecules, keratinocyte growth factor (KGF), stromal cell-derived growth factor 1 (SDF1), and cathelicidin (LL37), to be used in wound healing. Chronic wounds represent a growing problem worldwide. A combinatorial therapy approach targeting different aspects of wound healing would be beneficial, providing a controlled and sustained release of active molecules, while simultaneously protecting these therapeutics from the surrounding harsh wound environment. The results of this study demonstrate that the conjugation of the growth factors KGF and SDF1 and the antimicrobial peptide LL37 to ELPs does not affect the micelle structure and that all three therapeutic moieties retain their bioactivity in vitro. Importantly, when the combination of these micelle ELP nanoparticles are applied to wounds in diabetic mice, over 90 % wound closure is observed, which is significantly higher than when the therapeutics are applied in their naked forms. The application of the nanoparticles designed here is the first report of targeting different aspect of wound healing synergistically.
Annals Story Slam - A Two-Year Long Blackjack Game: Decisions During COVID
Authors: Marion Mull McCrary
Journal: Annals of Internal Medicine (2022)

Web ExclusivesJune 2022Annals Story Slam - A Two-Year Long Blackjack Game: Decisions During COVIDFREEMarion Mull McCrary, MDMarion Mull McCrary, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W22-0007 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - A Two-Year Long Blackjack Game: Decisions During COVID "A Two-Year Long Blackjack Game: Decisions During COVID," by Dr. Marion Mull McCrary (Duration 5:00)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Marion Mull McCrary, MDCorresponding Author: Marion Mull McCrary, MD; e-mail, mlmmccrary@gmail.com.This article was published at Annals.org on 29 April 2022. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics June 2022Volume 175, Issue 6Page: SS1 ePublished: 29 April 2022 Issue Published: June 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.Loading ...
Improved risk stratification of nasopharyngeal cancer by targeted sequencing of Epstein–Barr virus DNA in post-treatment plasma
Authors: D.C.T. Chan, W.K.J. Lam, E.P. Hui, B.B.Y. Ma, C.M.L. Chan, V.C.T. Lee, S.H. Cheng, W. Gai, P. Jiang, K.C.W. Wong, F. Mo, B. Zee, A.D. King, Q.T. Le, A.T.C. Chan, K.C.A. Chan, Y.M.D. Lo
Journal: Annals of Oncology (2022)

Quantitative measurement of plasma Epstein-Barr virus (EBV) DNA by real-time PCR at the end of primary treatment is a robust prognostic marker for nasopharyngeal carcinoma (NPC) patients. However, up to 40% of patients who would later develop disease recurrence had undetectable post-treatment plasma EBV DNA. Targeted sequencing for the entire EBV genome potentially allows a more comprehensive and unbiased detection of plasma EBV DNA and enables the use of other parameters such as fragment size as biomarkers. Hence, we explored if plasma EBV DNA sequencing might allow more accurate prognostication of NPC patients.Plasma samples collected from 769 patients with stage IIB-IVB NPC at 6-8 weeks after radiotherapy were analysed using targeted sequencing for EBV DNA.The sensitivities of the PCR-based analysis, at a cut-off of any detectable levels of plasma EBV DNA, for prediction of local and distant recurrences were 42.3% and 85.3%, respectively. The sequencing-based analysis (involving quantitation and size profiling) achieved better performance for both local and distant recurrences than PCR. Using a cut-off of the proportion of plasma EBV DNA deduced by sequencing at 0.01%, the sensitivities of the sequencing-based analysis for local and distant recurrences were 88.5% and 97.1%, with the resultant negative predictive values of 99.1% and 99.4%, respectively. Among patients with undetectable EBV DNA on quantitative PCR, sequencing could further define a subgroup that enjoyed superior survival outcomes based on the proportion of plasma EBV DNA, with a 5-year progression-free survival (PFS) approaching 90%. On multivariate analysis, sequencing-based quantitative level of plasma EBV DNA was the independent prognostic factor with the highest hazard ratio for prediction of overall survival and PFS.NPC prognostication using post-treatment plasma EBV DNA could be enhanced through sequencing.
Effects of traditional mind–body movement therapy on chronic cardiopulmonary dyspnoea: a systematic review and meta-analysis
Authors: Tiange Zhang, Rui Zhou, Ting Wang, Yijun Xin, Xiaohong Liu, Huiting Huang
Journal: Thorax (2022)

Purpose To evaluate whether traditional mind–body movement therapy (TMBM) can be used as a complementary or alternative therapy for exercise-based cardiopulmonary rehabilitation (EBCR) on chronic cardiopulmonary dyspnoea. Methods PubMed, Embase, Scopus, Web of Science and China National Knowledge Infrastructure were searched from their inception to 2 July 2021. Randomised clinical trials evaluating the effectiveness of TMBM versus EBCR, and TMBM +EBCR versus TMBM in the treatment of chronic cardiopulmonary dyspnoea were selected. The outcomes were exercise capacity (6 min walk distance, 6MWD) and quality of life (QoL). Results Thirty-four randomised clinical trials with 2456 patients were included. For TMBM vs EBCR alone, statistically significant improvements in the 6MWD favoured the TMBM for chronic obstructive pulmonary disease (COPD) (mean difference(MD)=12.22 m; 95% CI 5.94 to 18.50; I 2 =56%) and heart failure (HF) patients (MD=43.65 m; 95% CI 7.91 to 79.38; I 2 =0%). Statistically significant improvements in QoL also favoured TMBM over EBCR for patients with HF(MD=−9.19; 95% CI −11.05 to −7.32; I 2 =0%) but non-significant trend for COPD (standardised mean difference (SMD)=−0.31; 95% CI −0.62 to 0.01; I 2 =78%). Comparisons of TMBM +EBCR versus EBCR alone revealed significant improvements in the QoL for COPD (SMD=−0.52; 95% CI −0.94 to −0.10; I 2 =86%) and patients with HF (MD=−2.82; 95% CI −4.99 to −0.64; I 2 =0%). The 6MWD results favoured the TMBM +EBCR for patients with COPD (MD=16.76 m; 95% CI 10.24 to 23.29; I 2 =0%), but only showed a slight trend towards additional benefits of TMBM +EBCR in the HF studies (MD=13.77 m; 95% CI −1.01 to 28.54; I2=65%) . Conclusions TMBM has positive effects on patients’ 6MWD and QoL, with similar or even better effects than EBCR. It may be beneficial to use TMBM as a supplementary or alternative strategy for EBCR in treatment plans. PROSPERO registration number CRD42021241181.
Cardiac remodelling – Part 2: Clinical, imaging and laboratory findings. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology
Authors: Alberto Aimo, Giuseppe Vergaro, Arantxa González, Andrea Barison, Josep Lupón, Victoria Delgado, A Mark Richards, Rudolf A. de Boer, Thomas Thum, Henrike Arfsten, Martin Hülsmann, Inês Falcao‐Pires, Javier Díez, Roger S.Y. Foo, Mark Yan Yee Chan, Chukwuemeka G. Anene‐Nzelu, Magdy Abdelhamid, Stamatis Adamopoulos, Stefan D. Anker, Yuri Belenkov, Tuvia Ben Gal, Alain Cohen‐Solal, Michael Böhm, Ovidiu Chioncel, Ewa A. Jankowska, Finn Gustafsson, Loreena Hill, Tiny Jaarsma, James L. Januzzi, Pardeep Jhund, Yuri Lopatin, Lars H. Lund, Marco Metra, Davor Milicic, Brenda Moura, Christian Mueller, Wilfried Mullens, Julio Núñez, Massimo F. Piepoli, Amina Rakisheva, Arsen D. Ristić, Patrick Rossignol, Gianluigi Savarese, Carlo G. Tocchetti, Sophie van Linthout, Maurizio Volterrani, Petar Seferovic, Giuseppe Rosano, Andrew J.S. Coats, Michele Emdin, Antoni Bayes‐Genis
Journal: European Journal of Heart Failure (2022)
Implication of stereotactic body radiotherapy (SBRT) as a neoadjuvant treatment in hepatobiliary malignancies – A single centre experience
Authors: Namita Chavan, Pritik A. Shah, Shivkumar Swamy Shivalingappa, Sridhar Papaiah Susheela, G. Lohith, Raghavendra Babu Jayaram
Journal: International Journal of Surgery (2022)
Identification of coronavirus particles by electron microscopy requires demonstration of specific ultrastructural features
Authors: Carsten Dittmayer, Michael Laue
Journal: European Respiratory Journal (2022)

With interest we read the publication of Evangelou et al ., which studied SARS-CoV-2 induced senescence in severe COVID-19 [1]. Immunohistochemistry (IHC) and electron microscopy (EM) were used for in situ detection of SARS-CoV-2 in autopsy tissues. The authors used formalin-fixed and paraffin-embedded (FFPE) autopsy lung of COVID-19 and non-COVID-19 patients to perform re-embedding for EM and ultrastructural analysis. They report detection of SARS-CoV-2 virions within alveolar type 2 (AT2) cells of representative COVID-19 cases (fig. 1c). Three electron micrographs show putative virus particles, indicated by arrows, to document their findings.
How to prepare the patients with acute-on-chronic liver failure with deep hepatic coma to living donor liver transplantation?
Authors: Teng-Yuan Hou, Yu-Cheng Lin, Cheng-Hsi Yeh, Wei-Feng Lee, Kuo-Chen Hung, Chee-Chien Yong, Chih-Che Lin, Chao-Long Chen, Chih-Chi Wang
Journal: International Journal of Surgery (2022)
Low-affinity CAR T cells exhibit reduced trogocytosis, preventing rapid antigen loss, and increasing CAR T cell expansion
Authors: Michael L. Olson, Erica R. Vander Mause, Sabarinath V. Radhakrishnan, Joshua D. Brody, Aaron P. Rapoport, Alana L. Welm, Djordje Atanackovic, Tim Luetkens
Journal: Leukemia (2022)
Xanthogranulomatous Cholecystitis Masquerading as Gallbladder Carcinoma on 68Ga-FAPI-04 PET
Authors: Zeyu Zhang, Hui Dong, Lu Zhang, Chao Cheng, Changjing Zuo
Journal: Clinical Nuclear Medicine (2022)

68 Ga-FAPI-04 has great potential for the detection and staging evaluation of a variety of tumors. We report a case of suspected gallbladder carcinoma that was enrolled in a prospective study of 68 Ga-FAPI-04 imaging at our institution. This case was later histopathologically confirmed as xanthogranulomatous cholecystitis. This demonstrates that xanthogranulomatous cholecystitis might be disguised as gallbladder carcinoma in 68 Ga-FAPI-04 imaging. Thus, we suggest that nuclear clinicians evaluating 68 Ga-FAPI-04 imaging should be aware of this possibility.
Institutional experience as a hallmark of progress in the treatment of pancreatic head cancer
Authors: Radoslav Kostadinov, Nikola Vladov, Vassil Mihaylov, Tsvetan Trichkov, Maria Yakova, Ivan Ivanov, Stefan Marvakov, Krum Katzarov, Edlir Gruda, Aneliya Hartova
Journal: International Journal of Surgery (2022)
Mammalian target of rapamycin inhibitor everolimus reduces the risk of late biliary stenosis in adult to adult liver transplantation
Authors: Tevfik Tolga Sahin, Koray Kutluturk, Yunus Karipkiz, Sait Murat Dogan, Yasuharu Onishi, Sezai Yilmaz
Journal: International Journal of Surgery (2022)
Time Spent Engaging in Health Care Among Patients With Left Ventricular Assist Devices
Authors: Sarah Chuzi, Faraz S. Ahmad, Tingqing Wu, Salem Argaw, Rebecca Harap, Kathleen L. Grady, Jonathan D. Rich, Duc Thinh Pham, Sadiya S. Khan, Jane E. Wilcox, Larry A. Allen, Anjan Tibrewala
Journal: JACC Heart Failure (2022)
Annals Story Slam - A Story About Women Empowerment
Authors: Grace Nassim
Journal: Annals of Internal Medicine (2022)

Web ExclusivesJune 2022Annals Story Slam - A Story About Women EmpowermentFREEGrace Nassim, MD, MPHGrace Nassim, MD, MPHSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W22-0008 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - A Story About Women Empowerment "A Story About Women Empowerment," by Dr. Grace Nassim (Duration 4:11)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Corresponding Author: Grace Nassim, MD, MPH; e-mail, grace.[email protected]com.This article was published at Annals.org on 29 April 2022. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics June 2022Volume 175, Issue 6Page: SS1 ePublished: 29 April 2022 Issue Published: June 2022 CopyrightCopyright © 2022 by American College of Physicians. All Rights Reserved.Loading ...
Driving CAR T Cells against Solid Tumors
Journal: Cancer Discovery (2022)

Abstract During the American Association for Cancer Research Annual Meeting 2022, researchers discussed ways to improve chimeric antigen receptor T-cell therapy's efficacy in solid tumors. These included sussing out differences between solid and blood cancers in their susceptibility to CAR T cells’ cytotoxicity, taking a modular approach to engineering next-generation agents, and building in breaks for exhaustion-prone CAR T cells to restore their function.
Integrated analysis of single-cell and bulk RNA sequencing data reveals a pan-cancer stemness signature predicting immunotherapy response
Authors: Zhen Zhang, Zi-Xian Wang, Yan-Xing Chen, Hao-Xiang Wu, Ling Yin, Qi Zhao, Hui-Yan Luo, Zhao-Lei Zeng, Miao-Zhen Qiu, Rui-Hua Xu
Journal: Genome Medicine (2022)

Although immune checkpoint inhibitor (ICI) is regarded as a breakthrough in cancer therapy, only a limited fraction of patients benefit from it. Cancer stemness can be the potential culprit in ICI resistance, but direct clinical evidence is lacking.
Evaluation of the Efficacy of Neoadjuvant Radiation Twice a Day Fractionation Therapy in Patients with Resectable Pancreatic Head Cancer
Authors: L. I. Korytova, D. A. Sklyar, E. V. Vlasova, A. V. Pavlovskiy, A. A. Polikarpov, E. V. Moiseenko, O. V. Korytov
Journal: Radiology - Practice (2022)

The coronavirus of severe acute respiratory syndrome-2 (SARS-CoV-2) and the coronavirus infection caused by it, along with damage to the respiratory system, can lead to disorders of the central and peripheral nervous system. The article presents literature data and own observations of neurological disorders in patients with coronavirus disease in the superacute period. Pronounced neurological disorders are mainly observed in severe coronavirus disease and include acute ischemic stroke, subcortical micro- and macro— bleeding, acute necrotizing encephalopathy, Guillain-Barre syndrome. Factors potentially complicating the course of coronavirus disease and contributing to the development of neurological complications are hypertension, diabetes mellitus, chronic diseases of the heart and respiratory system. Based on existing publications and our own observations, we have systematized information about the relationship between coronavirus disease and neurological disorders, about possible factors contributing to the occurrence of stroke. The possibilities of using chest MSCT as the only method of radiation diagnostics for the early detection of viral pneumonia in patients receiving emergency and emergency care at the regional vascular center of BUZOO «GC BSMP No. 1» are considered. The use of this method, in the ultra-acute period of acute ischemic stroke, during the first 40 minutes from the moment of admission, can significantly reduce the time of diagnosis and mortality in patients with acute ischemic stroke and viral pneumonia.
Universal immunotherapeutic strategy for hepatocellular carcinoma with exosome vaccines that engage adaptive and innate immune responses
Authors: Bingfeng Zuo, Yang Zhang, Kangjie Zhao, Li Wu, Han Qi, Rong Yang, Xianjun Gao, Mengyuan Geng, Yingjie Wu, Renwei Jing, Qibing Zhou, Yiqi Seow, HaiFang Yin
Journal: Journal of Hematology & Oncology (2022)

Personalized immunotherapy utilizing cancer vaccines tailored to the tumors of individual patients holds promise for tumors with high genetic heterogeneity, potentially enabling eradication of the tumor in its entirety.Here, we demonstrate a general strategy for biological nanovaccines that trigger tailored tumor-specific immune responses for hepatocellular carcinoma (HCC). Dendritic cell (DC)-derived exosomes (DEX) are painted with a HCC-targeting peptide (P47-P), an α-fetoprotein epitope (AFP212-A2) and a functional domain of high mobility group nucleosome-binding protein 1 (N1ND-N), an immunoadjuvant for DC recruitment and activation, via an exosomal anchor peptide to form a "trigger" DEX vaccine (DEXP&A2&N).DEXP&A2&N specifically promoted recruitment, accumulation and activation of DCs in mice with orthotopic HCC tumor, resulting in enhanced cross-presentation of tumor neoantigens and de novo T cell response. DEXP&A2&N elicited significant tumor retardation and tumor-specific immune responses in HCC mice with large tumor burdens. Importantly, tumor eradication was achieved in orthotopic HCC mice when antigenic AFP peptide was replaced with the full-length AFP (A) to form DEXP&A&N. Supplementation of Fms-related tyrosine kinase 3 ligand greatly augmented the antitumor immunity of DEXP&A&N by increasing immunological memory against tumor re-challenge in orthotopic HCC mice. Depletion of T cells, cross-presenting DCs and other innate immune cells abrogated the functionality of DEXP&A&N.These findings demonstrate the capacity of universal DEX vaccines to induce tumor-specific immune responses by triggering an immune response tailored to the tumors of each individual, thus presenting a generalizable approach for personalized immunotherapy of HCC, by extension of other tumors, without the need to identify tumor antigens.