tbuckley/cabot-search huggingface dataset:
Etomidate versus ketamine for emergency endotracheal intubation: a randomized clinical trial
Authors: Gerald Matchett, Irina Gasanova, Christina A. Riccio, Dawood Nasir, Mary C. Sunna, Brian J. Bravenec, Omaira Azizad, Brian Farrell, Abu Minhajuddin, Jesse W. Stewart, Lawrence W. Liang, Tiffany Sun Moon, Pamela E. Fox, Callie G. Ebeling, Miakka N. Smith, Devin Trousdale, Babatunde O. Ogunnaike, Anand M. Abraham, Robert S. Ackerman, Oluwafunmilayo B. Adebayo-Adonis, Venkatesh Aiyagari, Aditee P. Ambardekar, Kelechi B. Anyaehie, David M. Bashover, Matthew Burke Bourneuf, James R. Brann II, Grace Wilkowski Bryant, Matthew P. Bunker, Leigh Anne Catoe, Catherine Chen, Jeffrey S. Chen, Joy Lo Chen, Gloria S. Cheng, Ivan Nicholas Chew, Jeanette L. Chin, Samuel M. Cohen, Mary Abigail Cowlishaw, Janice Davis II, Jennifer Lynn Davis, TomMario Alando Davis, David G. DePinto, Paul E. Dilfer, Renee D. Doherty, Philip James DuChamp, Katherine L. Duncan, Colin C. Ehlenbach, Ahmad Elsharydah, Sonia D. Estes, Akil Farishta, William Eric Foster, David G. Francis, Shannon Garitty, Nicholas W. Gill, Louise A. Gliga, Joseph Arthur Graham, Nancy B. Greilich, Jessica E. Grundt, Allan J. Hamilton, Hooman Heravi, Douglas C. Huynh, Ray K. Hwong, Rachel E. Jacobs, Syed Jaffery, Aveline P. Jerome, Suja John, Enas Kandil, Asif Khan, Sarah M. Khorsand, Jennifer Meeyun Kim, Elena J. Koepke, Grayson Jeffrey Koval, Brian Kurtz, Xuan T. Langridge, Gene W. Lee, Simon J. Craddock Lee, Matthew J. Leveno, Dawn Lewellen, Frederick C. Li, Nathaniel Loo, Xi Luo, Rachelle A. Makinde, Anna E. Martin, Evan Z. Mayes, Diane E. McCune, John McGrimley, Jennifer J. McGuire, Kyle Meinhardt, Akeel M. Merchant, Zahid Merchant, David W. Mercier, Brandon C. Mitchell, Andrea J. Murray, Shamsideen O. Musa, Geoffrey Edward Nelson, Seth Nelson, Le H. Nguyen, Linsey Nohrn, Osamudiamen O. Obanor, Chinwe C. Ononogbu, Mihir Parikh, Hetal J. Patel, John H. Pennant, Paul E. Pepe, David Quang-Nam Pham, Jenny Ringqvist, John A. Rosener, Timothy J. Ryan, Stephen Andrew Sarmiento, Stephen W. Sawyer, Nicholas A. Schilling, Levi J. Schlegel, Brady P. Selig, Ben R. Sessions, Mohammad-Ali Shaikh, Eric Y. Siu, Joseph T. Sofia, Tristyn V. St. Thomas-Achoja, Jonathan D. Stubblefield, Ivy A. Taylor, Stephen M. Topper, Coby Tran, Michael Panganiban Tulio, Emily R. Turner, Steven Vela, Hayley Vickers, Daren Walters, Juliana Watson, Noel F. White, Charles W. Whitten, Brian H. Williams, Willis T. Williams, Casey Wollenman, Isabel Q. Wu, Alla Yarmosh, Leila W. Zuo
Journal: Intensive Care Medicine (2021)
Longitudinal SARS-CoV-2 mRNA Vaccine-Induced Humoral Immune Responses in Patients with Cancer
Authors: Jane C. Figueiredo, Noah M. Merin, Omid Hamid, So Yung Choi, Tucker Lemos, Wendy Cozen, Nathalie Nguyen, Laurel J. Finster, Joslyn Foley, Justin Darrah, Jun Gong, Ronald Paquette, Alain C. Mita, Robert Vescio, Inderjit Mehmi, Reva Basho, Warren G. Tourtellotte, Carissa A. Huynh, Gil Y. Melmed, Jonathan Braun, Dermot P.B. McGovern, Emebet Mengesha, Greg Botwin, John C. Prostko, Edwin C. Frias, James L. Stewart, Sandy Joung, Jennifer Van Eyk, Joseph E. Ebinger, Susan Cheng, Kimia Sobhani, Karen L. Reckamp, Akil Merchant
Journal: Cancer Research (2021)

Abstract Longitudinal studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced immune responses in patients with cancer are needed to optimize clinical care. In a prospective cohort study of 366 (291 vaccinated) patients, we measured antibody levels [anti-spike (IgG-(S-RBD) and anti-nucleocapsid immunoglobulin] at three time points. Antibody level trajectories and frequency of breakthrough infections were evaluated by tumor type and timing of treatment relative to vaccination. IgG-(S-RBD) at peak response (median = 42 days after dose 2) was higher (P = 0.002) and remained higher after 4 to 6 months (P = 0.003) in patients receiving mRNA-1273 compared with BNT162b2. Patients with solid tumors attained higher peak levels (P = 0.001) and sustained levels after 4 to 6 months (P &amp;lt; 0.001) compared with those with hematologic malignancies. B-cell targeted treatment reduced peak (P = 0.001) and sustained antibody responses (P = 0.003). Solid tumor patients receiving immune checkpoint inhibitors before vaccination had lower sustained antibody levels than those who received treatment after vaccination (P = 0.043). Two (0.69%) vaccinated and one (1.9%) unvaccinated patient had severe COVID-19 illness during follow-up. Our study shows variation in sustained antibody responses across cancer populations receiving various therapeutic modalities, with important implications for vaccine booster timing and patient selection. Significance: Long-term studies of immunogenicity of SARS-CoV-2 vaccines in patients with cancer are needed to inform evidence-based guidelines for booster vaccinations and to tailor sequence and timing of vaccinations to elicit improved humoral responses.
A Phase 1b Study of Blinatumomab Including Subcutaneous Administration in Relapsed / Refractory (R/R) Indolent Non Hodgkin's Lymphoma (NHL)
Authors: Giuseppe Rossi, Henry Miles Prince, Constantine S. Tam, Matthew Ku, Catherine Thieblemont, Leslie L. Popplewell, Martin Wermke, Corinne Haioun, Nicole Wong Doo, Andreas Viardot, Andrés J M Ferreri, Silvia Ferrari, Hansen L. Wong, Priti Kadu, Gerhard Zugmaier, Yi Zeng, Alessandro Rambaldi
Journal: Blood (2021)
Navigating Cancer Care in the COVID-19 Era
Journal: Cancer Discovery (2021)

With the COVID-19 pandemic, clinicians, researchers, industry leaders, and federal regulators in oncology have had to adapt to an evolving landscape of patient care and trial management. At the 2021 Society for Immunotherapy of Cancer Annual Meeting, several experts discussed some of the lessons learned along the way, and advocated for more decentralized, or virtual, clinical trials.
Identification of Similarities Between Skin Lesions in Patients With Antisynthetase Syndrome and Skin Lesions in Patients With Dermatomyositis by Highly Multiplexed Imaging Mass Cytometry
Authors: Jay Patel, Adarsh Ravishankar, Spandana Maddukuri, Thomas Vazquez, Madison Grinnell, Victoria P. Werth
Journal: Arthritis & Rheumatology (2021)

Antisynthetase syndrome (ASyS) and dermatomyositis (DM) are autoimmune disorders that overlap clinically. Given the presence of DM-like skin lesions in ASyS patients, there is debate about whether ASyS is a distinct disease or a subclassification of DM. Recent studies identified differences in type I interferon (IFN) expression between ASyS and DM muscle and finger eruptions. This study was undertaken to elucidate similarities and differences in the pathogenesis of cutaneous disease in ASyS and DM at the single-cell level.Five ASyS patients and 7 DM patients were recruited from a prospectively collected database of well-characterized DM patients. ASyS patients were clinically confirmed as having ASyS according to the Connors et al criteria and the Solomon et al criteria and the presence of aminoacyl-transfer RNA synthetase antibodies. Immunophenotyping was conducted using immunofluorescence (IF) and imaging mass cytometry (IMC).IF staining for MxA and IFNβ expression revealed up-regulation of type I IFN in ASyS and DM samples compared to healthy control samples (P < 0.05). IMC showed similar numbers of macrophages, T cells, B cells, and dendritic cells in ASyS and DM samples, with no differences in counts (P > 0.05), but an increase in myeloid dendritic cell percentage in DM samples (P < 0.05). Key type I IFN, cytokine, and JAK/STAT pathways were similarly expressed in both ASyS and DM (P > 0.05). At the single-cell level, macrophages positive for phosphorylated stimulator of IFN genes in ASyS samples expressed increased levels of tumor necrosis factor, interluekin-17 (IL-17), and IFNβ (P < 0.001).IMC is a powerful tool that identifies a role for the type I IFN system in DM-like skin lesions in ASyS and DM with some differences at the cellular level, but overall significant overlap, supporting similar therapeutic decision making.
NADH inhibition of SIRT1 links energy state to transcription during time-restricted feeding
Authors: Daniel C. Levine, Hsin-Yu Kuo, Hee-Kyung Hong, Jonathan Cedernaes, Chelsea Hepler, Alexandra G. Wright, Meredith A. Sommars, Yumiko Kobayashi, Biliana Marcheva, Peng Gao, Olga R. Ilkayeva, Chiaki Omura, Kathryn M. Ramsey, Christopher B. Newgard, Grant D. Barish, Clara Bien Peek, Navdeep S. Chandel, Milan Mrksich, Joseph Bass
Journal: Nature Metabolism (2021)

In mammals, circadian rhythms are entrained to the light cycle and drive daily oscillations in levels of NAD
Uncovering Tumorigenesis Circuitry with Combinatorial CRISPR
Authors: Samson H. Fong, Brenton P. Munson, Trey Ideker
Journal: Cancer Research (2021)

Abstract Oncogenesis relies on the alteration of multiple driver genes, but precisely which groups of alterations lead to cancer is not well understood. To chart these combinations, Zhao and colleagues use the CRISPR-Cas9 system to knockout all pairwise combinations among 52 tumor suppressor genes, with the goal of identifying groups of alterations that collaborate to promote cell growth. Interaction screens are performed across multiple models of tumorigenesis in cell cultures and mice, revealing clear cooperation among NF2, PTEN, and TP53 in multiple models. These and other strongly synergistic interactions are characterized further by single-cell transcriptomic profiling. This methodology presents a scalable approach to move beyond single-gene drivers to map the complex gene networks that give rise to tumorigenesis. See related article by Zhao et al., p. 6090
Multiple-Timescale Representations of Space: Linking Memory to Navigation
Authors: Wenbo Tang, Shantanu P. Jadhav
Journal: Annual Review of Neuroscience (2021)

When navigating through space, we must maintain a representation of our position in real time; when recalling a past episode, a memory can come back in a flash. Interestingly, the brain's spatial representation system, including the hippocampus, supports these two distinct timescale functions. How are neural representations of space used in the service of both real-world navigation and internal mnemonic processes? Recent progress has identified sequences of hippocampal place cells, evolving at multiple timescales in accordance with either navigational behaviors or internal oscillations, that underlie these functions. We review experimental findings on experience-dependent modulation of these sequential representations and consider how they link real-world navigation to time-compressed memories. We further discuss recent work suggesting the prevalence of these sequences beyond hippocampus and propose that these multiple-timescale mechanisms may represent a general algorithm for organizing cell assemblies, potentially unifying the dual roles of the spatial representation system in memory and navigation.
101P Nivolumab outcomes in interstitial lung disease patients with advanced non-small cell lung cancer in French real-world setting
Authors: J-B. Assie, C. Chouaid, H. Nunes, D. Reynaud, A-F. Gaudin, V. Grumberg, R. Jolivel, B. Jouaneton, F-E. Cotté, B. Duchemann
Journal: Annals of Oncology (2021)
5-aza-2′-deoxycytidine potentiates anti-tumor immunity in colorectal peritoneal metastasis by modulating ABC A9-mediated cholesterol accumulation in macrophages
Authors: Rongchen Shi, Kun Zhao, Teng Wang, Jing Yuan, Dapeng Zhang, Wei Xiang, Jin Qian, Na Luo, Yong Zhou, Bo Tang, Chuan Li, Hongming Miao
Journal: Theranostics (2021)

Background: 5-aza-2'-deoxycytidine (5Aza), a DNA methyltransferase (DNMT) inhibitor, could activate tumor adaptive immunity to inhibit tumor progression. However, the molecular mechanisms by which 5Aza regulates tumor immune microenvironment are still not fully understood. Methods: The role of 5Aza in immune microenvironment of peritoneal carcinomatosis (PC) of colorectal cancer (CRC) was investigated. The effects of 5Aza on macrophage activation were studied by flow cytometry, real-time PCR, Western blotting assays, and Drug Affinity Responsive Target Stability (DARTS). The effects of 5Aza on tumor immunity were validated in stromal macrophages and T cells from CRC patients. Results: 5Aza could stimulate the activation of macrophages toward an M1-like phenotype and subsequent activation of T cells in premetastatic fat tissues, and ultimately suppress CRC-PC in immune-competent mouse models. Mechanistically, 5Aza stimulated primary mouse macrophages toward to a M1-like phenotype characterized by the increase of p65 phosphorylation and IL-6 expression. Furthermore, we screened and identified ATP-binding cassette transporter A9 (ABC A9) as a binding target of 5Aza. 5Aza induced cholesterol accumulation, p65 phosphorylation and IL-6 expression in an ABC A9-dependent manner. Pharmacological inhibition of NF-κB, or genetic depletion of IL-6 abolished the antitumor effect of 5Aza in mice. In addition, the antitumor effect of 5Aza was synergistically potentiated by conventional chemotherapeutic drugs 5-Fu or OXP. Finally, we validated the reprogramming role of 5Aza in antitumor immunity in stromal macrophages and T cells from CRC patients. Conclusions: Taken together, our findings showed for the first time that 5Aza suppressed CRC-PC by regulating macrophage-dependent T cell activation in premetastatic microenvironment, meanwhile uncovered a DNA methylation-independent mechanism of 5Aza in regulating ABC A9-associated cholesterol metabolism and macrophage activation.
Missing Additional Information
Authors: Werner Stenzel
Journal: JAMA Neurology (2021)

Colin B. Josephson, MD, MSc; Samuel Wiebe, MD, MSc; Guillermo Delgado-Garcia, MD, MSc; Arturo Gonzalez-Izquierdo, PhD; Spiros Denaxas, PhD; Tolulope T. Sajobi, PhD; Mubasiru Lamidi, MSc; Meng Wang, MSc; Mark R. Keezer, MDCM, PhD
Covid-19: Coroners call for changes after highlighting avoidable deaths during pandemic
Authors: Clare Dyer
Journal: BMJ (2021)

<h3>Abstract</h3> Interferons play a critical role in regulating host immune responses to SARS-CoV-2, but the interferon (IFN)-stimulated gene (ISG) effectors that inhibit SARS-CoV-2 are not well characterized. The IFN-inducible short isoform of human nuclear receptor coactivator 7 (NCOA7) inhibits endocytic virus entry, interacts with the vacuolar ATPase, and promotes endo-lysosomal vesicle acidification and lysosomal protease activity. Here, we used ectopic expression and gene knockout to demonstrate that NCOA7 inhibits infection by SARS-CoV-2 as well as by lentivirus particles pseudotyped with SARS-CoV-2 Spike in lung epithelial cells. Infection with the highly pathogenic, SARS-CoV-1 and MERS-CoV, or seasonal, HCoV-229E and HCoV-NL63, coronavirus Spike-pseudotyped viruses was also inhibited by NCOA7. Importantly, either overexpression of TMPRSS2, which promotes plasma membrane fusion versus endosomal fusion of SARS-CoV-2, or removal of Spike’s polybasic furin cleavage site rendered SARS-CoV-2 less sensitive to NCOA7 restriction. Collectively, our data indicate that furin cleavage sensitizes SARS-CoV-2 Spike to the antiviral consequences of endosomal acidification by NCOA7, and suggest that the acquisition of furin cleavage may have favoured the co-option of cell surface TMPRSS proteases as a strategy to evade the suppressive effects of IFN-induced endo-lysosomal dysregulation on virus infection.
One-step synthesis of site-specific antibody–drug conjugates by reprograming IgG glycoengineering with LacNAc-based substrates
Authors: Wei Shi, Wanzhen Li, Jianxin Zhang, Tiehai Li, Yakai Song, Yue Zeng, Qian Dong, Zeng Lin, Likun Gong, Shuquan Fan, Feng Tang, Wei Huang
Journal: Acta Pharmaceutica Sinica B (2021)

Glycosite-specific antibody‒drug conjugatess (gsADCs), harnessing Asn297 N-glycan of IgG Fc as the conjugation site for drug payloads, usually require multi-step glycoengineering with two or more enzymes, which limits the substrate diversification and complicates the preparation process. Herein, we report a series of novel disaccharide-based substrates, which reprogram the IgG glycoengineering to one-step synthesis of gsADCs, catalyzed by an endo-N-acetylglucosaminidase (ENGase) of Endo-S2. IgG glycoengineering via ENGases usually has two steps: deglycosylation by wild-type (WT) ENGases and transglycosylation by mutated ENGases. But in the current method, we have found that disaccharide LacNAc oxazoline can be efficiently assembled onto IgG by WT Endo-S2 without hydrolysis of the product, which enables the one-step glycoengineering directly from native antibodies. Further studies on substrate specificity revealed that this approach has excellent tolerance on various modification of 6-Gal motif of LacNAc. Within 1 h, one-step synthesis of gsADC was achieved using the LacNAc-toxin substrates including structures free of bioorthogonal groups. These gsADCs demonstrated good homogeneity, buffer stability, in vitro and in vivo anti-tumor activity. This work presents a novel strategy using LacNAc-based substrates to reprogram the multi-step IgG glycoengineering to a one-step manner for highly efficient synthesis of gsADCs.
Abstract 17133: Complete Inferior Vena Cava Thrombosis In A Sickle Cell Patient With Suspected May Thurner Syndrome
Authors: Matthew T Finn, Erika Rosenzweig, Mariel Turner, Ajay J Kirtane, Sahil Parikh, Sanjum S Sethi
Journal: Circulation (2021)

Case Presentation: 19 year old woman with sickle cell anemia and nephrotic syndrome presented with leg and back pain. While treated for vaso-occlusive crisis, patient developed dyspnea and chest pain. She underwent CT chest which revealed a right lower lobe pulmonary embolism. The patient was started on anticoagulation. Her transthoracic echocardiography revealed normal right heart function but nearly occlusive inferior vena cava (IVC) thrombus just distal to the right atrium. Subsequently a CT venogram demonstrated extensive thrombus from the left external iliac vein to the right atrium as well as compression of the left common iliac vein. Multidisciplinary discussion was performed to discuss options including medical therapy, surgical removal, or catheter-based removal. Given concern for further pulmonary embolization, patient underwent catheter based thrombus removal. A 26 french access was obtained in the right internal jugular vein and a 17 french access was obtained in the right femoral vein. Using the Angiovac system, mechanical thrombectomy was performed in the IVC. The angiovac system is a 24 french suction catheter with filtration and reperfusion through the right femoral vein. Limited thrombus removal was achieved. Next,14 french left femoral vein access was obtained and the Inari Clottriever device was used to mechanically score and remove a significant amount of thrombus (Figure 1). Post removal angiography revealed a patent IVC with minimal residual thrombus. Discussion: IVC thrombosis is a rare presentation of venous thromboembolism (VTE). This patient had multiple reasons for VTE including nephrotic syndrome and likely May Thurner Syndrome (MTS). MTS is an underdiagnosed entity resulting in mechanical compression of the left iliac vein in upto 50% of patients presenting with left lower extremity VTE. While proximal extension of thrombus is rare as seen in this case, high clinical suspicion is warranted for accurate diagnosis and treatment.
Chromosomal Fusions Facilitate Adaptation to Divergent Environments in Threespine Stickleback
Authors: Zuyao Liu, Marius Roesti, David Marques, Melanie Hiltbrunner, Verena Saladin, Catherine L Peichel
Journal: Molecular Biology and Evolution (2021)

Chromosomal fusions are hypothesized to facilitate adaptation to divergent environments, both by bringing together previously unlinked adaptive alleles and by creating regions of low recombination that facilitate the linkage of adaptive alleles; but, there is little empirical evidence to support this hypothesis. Here, we address this knowledge gap by studying threespine stickleback (Gasterosteus aculeatus), in which ancestral marine fish have repeatedly adapted to freshwater across the northern hemisphere. By comparing the threespine and ninespine stickleback (Pungitius pungitius) genomes to a de novo assembly of the fourspine stickleback (Apeltes quadracus) and an outgroup species, we find two chromosomal fusion events involving the same chromosomes have occurred independently in the threespine and ninespine stickleback lineages. On the fused chromosomes in threespine stickleback, we find an enrichment of quantitative trait loci underlying traits that contribute to marine versus freshwater adaptation. By comparing whole-genome sequences of freshwater and marine threespine stickleback populations, we also find an enrichment of regions under divergent selection on these two fused chromosomes. There is elevated genetic diversity within regions under selection in the freshwater population, consistent with a simulation study showing that gene flow can increase diversity in genomic regions associated with local adaptation and our demographic models showing gene flow between the marine and freshwater populations. Integrating our results with previous studies, we propose that these fusions created regions of low recombination that enabled the formation of adaptative clusters, thereby facilitating freshwater adaptation in the face of recurrent gene flow between marine and freshwater threespine sticklebacks.
Error in Author Affiliations and Supplement
Authors: Wenjie Ma, Mingyang Song, Andrew Chan, Arpit Chhabra
Journal: JAMA Oncology (2021)

Antonio Llombart-Cussac, MD; José Manuel Pérez-García, MD; Meritxell Bellet, MD; Florence Dalenc, MD; Miguel Gil-Gil, MD; Manuel Ruíz-Borrego, MD; Joaquín Gavilá, MD; Miguel Sampayo-Cordero, MSc; Elena Aguirre, MD; Peter Schmid, MD; Frederik Marmé, MD; Serena Di Cosimo, MD; Joseph Gligorov, MD; Andreas Schneeweiss, MD; Joan Albanell, MD; Pilar Zamora, MD; Duncan Wheatley, MD; Eduardo Martínez-de Dueñas, MD; Kepa Amillano, MD; Andrea Malfettone, PhD; Javier Cortés, MD; PARSIFAL Steering Committee and Trial Investigators; Antonio Antón; Vladimir Moiseyenko; Paul Cottu; Gemma Viñas; Thierry Petit; Petra Tesarova; Vladimir Vladimirov; Juan Cueva Bañuelos; Marco Colleoni; Gianfilippo Bertelli; Purificación Martínez; Raquel Andres; Tatiana Barannikova; Sonia Servitja; Jacques Medioni; Saverio Cinieri; Juan Bayo; Santiago González; Bohuslav Melichar; Vicente Caranyana; Francesco Atzori; Mark Beresford; Steven Chan; Maria Luque-Cabal; Juan de la Haba; Joachim Bischoff; Guzel Mukhametsina; Maria Cazzaniga; Daniele Generali; Andrew Wardley; Laura Cortesi; Luigi Cavanna; Mario Airoldi
Multiomic analysis identifies CPT1A as a potential therapeutic target in platinum-refractory, high-grade serous ovarian cancer
Authors: Dongqing Huang, Shrabanti Chowdhury, Hong Wang, Sara R. Savage, Richard G. Ivey, Jacob J. Kennedy, Jeffrey R. Whiteaker, Chenwei Lin, Xiaonan Hou, Ann L. Oberg, Melissa C. Larson, Najmeh Eskandari, Davide A. Delisi, Saverio Gentile, Catherine J. Huntoon, Uliana J. Voytovich, Zahra J. Shire, Qing Yu, Steven P. Gygi, Andrew N. Hoofnagle, Zachary T. Herbert, Travis D. Lorentzen, Anna Calinawan, Larry M. Karnitz, S. John Weroha, Scott H. Kaufmann, Bing Zhang, Pei Wang, Michael J. Birrer, Amanda G. Paulovich
Journal: Cell Reports Medicine (2021)

Resistance to platinum compounds is a major determinant of patient survival in high-grade serous ovarian cancer (HGSOC). To understand mechanisms of platinum resistance and identify potential therapeutic targets in resistant HGSOC, we generated a data resource composed of dynamic (±carboplatin) protein, post-translational modification, and RNA sequencing (RNA-seq) profiles from intra-patient cell line pairs derived from 3 HGSOC patients before and after acquiring platinum resistance. These profiles reveal extensive responses to carboplatin that differ between sensitive and resistant cells. Higher fatty acid oxidation (FAO) pathway expression is associated with platinum resistance, and both pharmacologic inhibition and CRISPR knockout of