tbuckley/cabot-search huggingface dataset:
Utilization of recurrent laryngeal nerve monitoring during thyroid surgery in china: a point prevalence survey (2015–2023)
Authors: Yishen Zhao, Peiyao Wang, Gianlorenzo Dionigi, Jiedong Kou, Changlin Li, Fang Li, Tie Wang, Wen Tian, Kewei Jiang, Ping Wang, Hao Zhang, Hui Sun
Journal: International Journal of Surgery (2024)
Identification of genomic alteration and prognosis using pathomics-based artificial intelligence in oral leukoplakia and head and neck squamous cell carcinoma: A multicenter experimental study
Authors: Xin-Jia Cai, Chao-Ran Peng, Ying-Ying Cui, Long Li, Ming-Wei Huang, He-Yu Zhang, Jian-Yun Zhang, Tie-Jun Li
Journal: International Journal of Surgery (2024)
Mirtazapine to alleviate severe breathlessness in patients with COPD or interstitial lung diseases (BETTER-B): an international, multicentre, double-blind, randomised, placebo-controlled, phase 3 mixed-method trial
Authors: Irene J Higginson, Sarah T Brown, Adejoke O Oluyase, Peter May, Matthew Maddocks, Massimo Costantini, Sabrina Bajwah, Charles Normand, Claudia Bausewein, Steffen T Simon, Karen Ryan, David C Currow, Miriam J Johnson, Simon P Hart, Hannah Mather, Malgorzata Krajnik, Silvia Tanzi, Luca Ghirotto, Charlotte E Bolton, Piotr Janowiak, Elena Turola, Caroline J Jolley, Geraldine Murden, Andrew Wilcock, Bobbie Farsides, Julia M Brown
Journal: The Lancet Respiratory Medicine (2024)

Breathlessness frequently becomes severe among people with respiratory disease. Mirtazapine, a widely used antidepressant, has shown promise in the modulation of respiratory sensation and the response to it, as well as reducing feelings of panic, which often accompanies breathlessness. We aimed to determine the effectiveness of mirtazapine to alleviate severe persisting breathlessness.
Cognitive phenotypes: Unraveling the heterogeneity in cognitive dysfunction among patients with primary brain tumors receiving radiotherapy
Authors: Anny Reyes, Alena Stasenko, Austin Hopper, Jiwandeep S Kohli, Jonathan L Helm, Mia Salans, Divya Prabhakaran, Lily Kamalyan, Molly Wilkinson, Soumya Unnikrishnan, Roshan Karunamuni, Jona Hattangadi-Gluth, Carrie R McDonald
Journal: Neuro-Oncology (2024)

Abstract Background Patients with primary brain tumors demonstrate heterogeneous patterns of cognitive dysfunction, which we explore using latent profile analysis (LPA) to identify cognitive phenotypes and their trajectories in patients receiving radiotherapy (RT). Methods Ninety-six patients completed neuropsychological testing before and post-RT (3, 6, 12-months) on a prospective longitudinal trial, including measures of processing speed, executive function, language, and verbal and visual memory. Models with 2-4 classes were examined. Demographic and clinical data were examined across phenotypes and post-RT cognitive change was evaluated. Results The optimal model identified three unique cognitive phenotypes including a group of patients with generalized impairments (11.5%), a group with isolated verbal memory impairments (21.9%), and a group with minimal impairments (66.7%). The Verbal Memory phenotype had fewer years of education (p=.007) and a greater proportion of males (p&amp;lt;.001); the Generalized group had a greater proportion of patients with IDH-wild type gliomas and showed greater symptoms of anxiety and poorer quality of life (p-values&amp;lt;.05); and the Minimal Impairment phenotype had higher rates of IDH-Mutant gliomas. Approximately 50% of patients declined on at least one cognitive domain with memory the most vulnerable. Patients that declined reported greater symptoms of depression (p=.007) and poorer quality of life (p=.025). Conclusions We identified three distinct cognitive phenotypes in patients with primary brain tumors receiving RT, each associated with unique demographic and clinical (e.g., IDH mutational status) profiles, with mood symptoms associated with late cognitive decline. This patient-centered approach enhances our understanding of clinical profiles associated with cognitive dysfunction and treatment-related neurotoxicity.
Tumor-infiltrating lymphocytes in necrotic tumors after melanoma neoadjuvant anti-PD1 therapy correlate with pathological response and recurrence-free survival
Authors: Kevin L. Ma, Tara C. Mitchell, Meaghan Dougher, Cimarron E. Sharon, Gabriella N. Tortorello, David E. Elder, Eric E. Morgan, Phyllis A. Gimotty, Alexander C. Huang, Ravi K. Amaravadi, Lynn M. Schuchter, Ahron Flowers, John T. Miura, Giorgos C. Karakousis, Xiaowei Xu
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Neoadjuvant anti-PD1 therapy in melanoma may increase tumor-infiltrating lymphocytes (TILs), and more TILs are associated with better treatment response. A major pathological response (MPR) in melanoma after neoadjuvant anti-PD1 therapy usually comprises tumor necrosis and fibrosis. The role of TILs in necrotic tumor necrosis (nTILs) has not been explored. Experimental Design: We performed CD3 and CD8 immunohistochemical stains on 41 melanomas with geographic necrosis. 14 were immunotherapy-naïve, and 27 had been treated with one dose of neoadjuvant anti-PD-1 in two clinical trials. CD3+ and CD8+ nTILs were graded as absent/minimal or moderate/brisk. The percentage of necrotic areas in the tumor bed before and after treatment was quantified. Endpoints were MPR and 5-year recurrence-free survival (RFS). Results: In the immunotherapy-naïve cohort, 3/14 (21%) specimens had moderate/brisk CD3+, and 2/14 (14%) had moderate/brisk CD8+ nTILs. In the treated cohort, 16/27 (59%) specimens had moderate/brisk CD3+, and 15/27 (56%) had moderate/brisk CD8+ nTILs, higher than the naïve cohort (CD3, p=0.046; CD8, p=0.018). Tumor necrosis was significantly increased after anti-PD1 therapy (p=0.007). In the treated cohort, moderate/brisk CD3+ and CD8+ nTILs correlated with MPR (p=0.042, p=0.019, respectively). Treated patients with moderate/brisk CD3+ nTILs had higher 5-year RFS than those with absent/minimal nTILs (69% versus 0%; p=0.006). This persisted on multivariate analysis (HR 0.16, 95% CI 0.03-0.84, p=0.03), adjusted for pathologic response, which was borderline significant (HR 0.26, 95% CI 0.07-1.01, p=0.051). Conclusions: CD3+ and CD8+ nTILs are associated with pathological response and 5-year RFS in melanoma patients after neoadjuvant anti-PD1 therapy.
Haploidentical hematopoietic cell transplantation as a platform for natural killer cell immunotherapy
Authors: Rémy Duléry, Sara Piccinelli, Mohmad Shahnawaz Beg, Ji Eun Jang, Rizwan Romee
Journal: American Journal of Hematology (2024)

Abstract An innovative approach is crucially needed to manage relapse after allogeneic hematopoietic cell transplantation (HCT) in patients with advanced hematological malignancies. This review explores key aspects of haploidentical HCT with post‐transplant cyclophosphamide, highlighting the potential and suitability of this platform for natural killer (NK) cell immunotherapy. NK cells, known for their unique abilities to eliminate cancer cells, can also exhibit memory‐like features and enhanced cytotoxicity when activated by cytokines. By discussing promising results from clinical trials, the review delves into the recent major advances: donor‐derived NK cells can be expanded ex vivo in large numbers, cytokine activation may enhance NK cell persistence and efficacy in vivo, and post‐HCT NK cell infusion can improve outcomes in high‐risk and/or relapsed myeloid malignancies without increasing the risk of graft‐versus‐host disease, severe cytokine release syndrome, or neurotoxicity. Looking ahead, cytokine‐activated NK cells can be synergized with immunomodulatory agents and/or genetically engineered to enhance their tumor‐targeting specificity, cytotoxicity, and persistence while preventing exhaustion. The ongoing exploration of these strategies holds promising preliminary results and could be rapidly translated into clinical applications for the benefit of the patients.
Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype
Authors: David J. Jackson, Michael E. Wechsler, Daniel J. Jackson, David Bernstein, Stephanie Korn, Paul E. Pfeffer, Ruchong Chen, Junpei Saito, Gustavo de Luíz Martinez, Lucyna Dymek, Loretta Jacques, Nicholas Bird, Stein Schalkwijk, Douglas Smith, Peter Howarth, Ian D. Pavord
Journal: New England Journal of Medicine (2024)

Depemokimab is an ultra-long-acting biologic therapy with enhanced binding affinity for interleukin-5 that may enable effective 6-month dosing intervals.
EGFR and EGFRvIII coopt host defense pathways, promoting progression in glioblastoma
Authors: Zhenyi An, Qi-Wen Fan, Linyu Wang, Hiroyuki Yoda, Megumi J Barata, David Jimenez-Morales, Joanna J Phillips, Danielle L Swaney, Erica Stevenson, Ethan Lee, Nevan Krogan, William A Weiss
Journal: Neuro-Oncology (2024)

Abstract Background Co-amplification of EGFR and EGFRvIII, a tumor-specific truncation mutant of EGFR, represent hallmark genetic lesions in glioblastoma. Methods We used phospho-proteomics, RNA-sequencing, TCGA data and glioblastoma cell culture and mouse models to study the signal transduction mediated by EGFR and EGFRvIII. Results We report that EGFR and EGFRvIII stimulate the innate immune defense receptor Toll-like Receptor 2 (TLR2); and that knockout of TLR2 dramatically improved survival in orthotopic glioblastoma xenografts. EGFR and EGFRvIII activated TLR2 in a ligand-independent manner, promoting tumor growth and immune evasion. We show that EGFR and EGFRvIII cooperate to activate the Rho-associated protein kinase ROCK2, which modulated malignant progression both by activating TLR2 and WNT signaling, and through remodeling the tumor microenvironment. Conclusion Together, our findings show that EGFR and EGFRvIII cooperate to drive tumor progression through ROCK2 and downstream WNT-β-catenin/TLR2 signaling pathways.
Effect of immunochemotherapy infusion timing, sequence, and interval on prognosis of advanced esophageal cancer: A retrospective cohort study
Authors: Shujie Huang, Zijie Li, Zhen Gao, Sichao Wang, Jiating Sun, Hansheng Wu, Jixian Liu, Patrick Ming-Kuen Tang, Rixin Chen, Guibin Qiao
Journal: International Journal of Surgery (2024)
Translational evaluation of metabolic risk factors impacting DBS efficacy for PD-Related sleep and depressive disorders: preclinical, prospective and cohort studies
Authors: Longping Yao, Rui Chen, Zijian Zheng, Maryam Hatami, Sumeyye Koc, Xu Wang, Yang Bai, Chen Yao, Guohui Lu, Thomas Skutella
Journal: International Journal of Surgery (2024)
Malignant transformation and tumour recurrence in sacrococcygeal teratoma: a global, retrospective cohort study
Authors: LJ van Heurn, JPM Derikx, N Hall, JH Aldrink, MM Bailez, LB Chirdan, S Fumino, A Hesse, T Soyer, S StPeter, J Twisk, T Yang, LWE van Heurn
Journal: International Journal of Surgery (2024)
RBPMS promotes contractile phenotype splicing in human embryonic stem cell derived vascular smooth muscle cells
Authors: Aishwarya G Jacob, Ilias Moutsopoulos, Alex Petchey, Rafael Kollyfas, Vincent R Knight-Schrijver, Irina Mohorianu, Sanjay Sinha, Christopher W J Smith
Journal: Cardiovascular Research (2024)

Differentiated Vascular Smooth Muscle Cells (VSMCs) express a unique network of mRNA isoforms via smooth muscle specific alternative splicing (SM-AS) in functionally critical genes, including those comprising the contractile machinery. We previously described RNA Binding Protein Multiple Splicing (RBPMS) as a potent driver of differentiated SM-AS in the rat PAC1 VSMC cell line. What is unknown is how RBPMS affects VSMC phenotype and behaviour. Here, we aimed to dissect the role of RBPMS in SM-AS in human cells and determine the impact on VSMC phenotypic properties.
Evolution of the correlated genomic variation landscape across a divergence continuum in the genus <i>Castanopsis</i>
Authors: Xue-Yan Chen, Biao-Feng Zhou, Yong Shi, Hui Liu, Yi-Ye Liang, Pär K Ingvarsson, Baosheng Wang
Journal: Molecular Biology and Evolution (2024)

The heterogeneous landscape of genomic variation has been well documented in population genomic studies. However, disentangling the intricate interplay of evolutionary forces influencing the genetic variation landscape over time remains challenging. In this study, we assembled a chromosome-level genome for Castanopsis eyrei and sequenced the whole genomes of 276 individuals from 12 Castanopsis species, spanning a broad divergence continuum. We found highly correlated genomic variation landscapes across these species. Furthermore, variations in genetic diversity and differentiation along the genome were strongly associated with recombination rates and gene density. These results suggest that long-term linked selection and conserved genomic features have contributed to the formation of a common genomic variation landscape. By examining how correlations between population summary statistics change throughout the species divergence continuum, we determined that background selection alone does not fully explain the observed patterns of genomic variation; the effects of recurrent selective sweeps must be considered. We further revealed that extensive gene flow has significantly influenced patterns of genomic variation in Castanopsis species. The estimated admixture proportion correlated positively with recombination rate and negatively with gene density, supporting a scenario of selection against gene flow. Additionally, putative introgression regions exhibited strong signals of positive selection, an enrichment of functional genes, and reduced genetic burdens, indicating that adaptive introgression has played a role in shaping the genomes of hybridizing species. This study provides insights into how different evolutionary forces have interacted in driving the evolution of the genomic variation landscape.
Oligodendroglial fatty acid metabolism as a central nervous system energy reserve
Authors: Ebrahim Asadollahi, Andrea Trevisiol, Aiman S Saab, Zoe J Looser, Payam Dibaj, Reyhane Ebrahimi, Kathrin Kusch, Torben Ruhwedel, Wiebke Möbius, Olaf Jahn, Jun Yup Lee, Anthony S Don, Michelle-Amirah Khalil, Karsten Hiller, Myriam Baes, Bruno Weber, E Dale Abel, Andrea Ballabio, Brian Popko, Celia M Kassmann, Hannelore Ehrenreich, Johannes Hirrlinger, Klaus-Armin Nave
Journal: Nature Neuroscience (2024)
Defining and pursuing diversity in human genetic studies
Authors: Maili C Raven-Adams, Tina Hernandez-Boussard, Yann Joly, Bartha Maria Knoppers, Subhashini Chandrasekharan, Adrian Thorogood, Judit Kumuthini, Calvin Wai Loon Ho, Ariana Gonzlez, Sarah C Nelson, Yvonne Bombard, Donrich Thaldar, Hanshi Liu, Alessia Costa, Vijaytha Muralidharan, Sasha Henriques, Jamal Nasir, Aimé Lumaka, Beatrice Kaiser, Saumya Shekhar Jamuar, Anna C F Lewis
Journal: Nature Genetics (2024)
Spatial single-cell isotope tracing reveals heterogeneity of de novo fatty acid synthesis in cancer
Authors: Elena Buglakova, Måns Ekelöf, Michaela Schwaiger-Haber, Lisa Schlicker, Martijn R Molenaar, Mohammed Shahraz, Lachlan Stuart, Andreas Eisenbarth, Volker Hilsenstein, Gary J Patti, Almut Schulze, Marteinn T Snaebjornsson, Theodore Alexandrov
Journal: Nature Metabolism (2024)
A pan-cancer dye for solid-tumour screening, resection and wound monitoring via short-wave and near-infrared fluorescence imaging
Authors: Benedict Edward Mc Larney, Ali Yasin Sonay, Elana Apfelbaum, Nermin Mostafa, Sébastien Monette, Dana Goerzen, Nicole Aguirre, Rüdiger M Exner, Christine Habjan, Elizabeth Isaac, Ngan Bao Phung, Magdalena Skubal, Mijin Kim, Anuja Ogirala, Darren Veach, Daniel A Heller, Jan Grimm
Journal: Nature Biomedical Engineering (2024)
Atomic Artificial Enzyme for Acute and Chronic Pneumonia
Authors: Wei Liu, Di Liu, Tianyi Cui, Yili Wang, Sufei Zhou, Fangzhen Tian, Ke Yang, Wei Wang, Lewei Bi, Kelong Fan, Lan Li, Hao Wang, Xiao‐Dong Zhang
Journal: Advanced Healthcare Materials (2024)

Abstract Pneumonia involves complex immunological and pathological processes leading to pulmonary dysfunction, which can be life‐threatening yet lacks effective specialized medications. Natural enzymes can be used as biological agents for the treatment of oxidative stress‐related diseases, but limiting to catalytic and environmental stability as well as high cost. Herein, an artificial enzyme, gold nanoclusters (Au NCs) with excellent stability, bioactivity, and renal clearance can be used as the next‐generation biological agents for acute lung injury (ALI) and allergic lung disease (ALD). The Au 25 clusters can mimic catalase (CAT) and glutathione peroxidase (GPx), and the K m of Au 24 Er 1 with H 2 O 2 reaches 1.28 mM, about 22 times higher than natural CAT (≈28.8 mM). The clusters inhibit the oxidative stress in the mitochondria and promote the synthesis of adenosine triphosphate (ATP). The molecular mechanism shows that the TLR4/MyD88/NF‐κB pathway and M1 macrophage‐mediated inflammatory response are suppressed in ALI and the Th1/Th2 imbalance in ovalbumin (OVA)‐induced ALD is rescued. Further, the clusters can notably improve lung function in both ALI and ALD models which paves the way for immunomodulation and intervention for lung injury and can be used as a substitute for natural enzymes and potential biopharmaceuticals in the treatment of various types of pneumonia.
Identification of diagnostic candidates in Mendelian disorders using an RNA sequencing-centric approach
Authors: Carolina Jaramillo Oquendo, Htoo A Wai, Wil I Rich, David J Bunyan, N Simon Thomas, David Hunt, Jenny Lord, Andrew G L Douglas, Diana Baralle
Journal: Genome Medicine (2024)

Abstract Background RNA sequencing (RNA-seq) is increasingly being used as a complementary tool to DNA sequencing in diagnostics where DNA analysis has been uninformative. RNA-seq enables the identification of aberrant splicing and aberrant gene expression, improving the interpretation of variants of unknown significance (VUSs), and provides the opportunity to scan the transcriptome for aberrant splicing and expression in relevant genes that may be the cause of a patient’s phenotype. This work aims to investigate the feasibility of generating new diagnostic candidates in patients without a previously reported VUS using an RNA-seq-centric approach. Methods We systematically assessed the transcriptomic profiles of 86 patients with suspected Mendelian disorders, 38 of whom had no candidate sequence variant, using RNA from blood samples. Each VUS was visually inspected to search for splicing abnormalities. Once aberrant splicing was identified in cases with VUS, multiple open-source alternative splicing tools were used to investigate if they would identify what was observed in IGV. Expression outliers were detected using OUTRIDER. Diagnoses in cases without a VUS were explored using two separate strategies. Results RNA-seq allowed us to assess 71% of VUSs, detecting aberrant splicing in 14/48 patients with a VUS. We identified four new diagnoses by detecting novel aberrant splicing events in patients with no candidate sequence variants from prior DNA testing ( n = 32) or where the candidate VUS did not affect splicing ( n = 23). An additional diagnosis was made through the detection of skewed X-inactivation. Conclusion This work demonstrates the utility of an RNA-centric approach in identifying novel diagnoses in patients without candidate VUSs. It underscores the utility of blood-based RNA analysis in improving diagnostic yields and highlights optimal approaches for such analyses.
Dimension reduction, cell clustering, and cell–cell communication inference for single-cell transcriptomics with DcjComm
Authors: Qian Ding, Wenyi Yang, Guangfu Xue, Hongxin Liu, Yideng Cai, Jinhao Que, Xiyun Jin, Meng Luo, Fenglan Pang, Yuexin Yang, Yi Lin, Yusong Liu, Haoxiu Sun, Renjie Tan, Pingping Wang, Zhaochun Xu, Qinghua Jiang
Journal: Genome biology (2024)

Advances in single-cell transcriptomics provide an unprecedented opportunity to explore complex biological processes. However, computational methods for analyzing single-cell transcriptomics still have room for improvement especially in dimension reduction, cell clustering, and cell-cell communication inference. Herein, we propose a versatile method, named DcjComm, for comprehensive analysis of single-cell transcriptomics. DcjComm detects functional modules to explore expression patterns and performs dimension reduction and clustering to discover cellular identities by the non-negative matrix factorization-based joint learning model. DcjComm then infers cell-cell communication by integrating ligand-receptor pairs, transcription factors, and target genes. DcjComm demonstrates superior performance compared to state-of-the-art methods.
NSD2 is a requisite subunit of the AR/FOXA1 neo-enhanceosome in promoting prostate tumorigenesis
Authors: Abhijit Parolia, Sanjana Eyunni, Brijesh Kumar Verma, Eleanor Young, Yihan Liu, Lianchao Liu, James George, Shweta Aras, Chandan Kanta Das, Rahul Mannan, Reyaz Ur Rasool, Erick Mitchell-Velasquez, Somnath Mahapatra, Jie Luo, Sandra E Carson, Lanbo Xiao, Prathibha R Gajjala, Sharan Venkatesh, Mustapha Jaber, Xiaoju Wang, Tongchen He, Yuanyuan Qiao, Matthew Pang, Yuping Zhang, Jean Ching-Yi Tien, Micheala Louw, Mohammed Alhusayan, Xuhong Cao, Fengyun Su, Omid Tavana, Caiyun Hou, Zhen Wang, Ke Ding, Arul M Chinnaiyan, Irfan A Asangani
Journal: Nature Genetics (2024)
Preexisting senescent fibroblasts in the aged bladder create a tumor-permissive niche through CXCL12 secretion
Authors: Satoru Meguro, Yoshikazu Johmura, Teh-Wei Wang, Satoshi Kawakami, Shota Tanimoto, Satotaka Omori, Yuki T Okamura, Seiji Hoshi, Emina Kayama, Kiyoshi Yamaguchi, Seira Hatakeyama, Satoshi Yamazaki, Eigo Shimizu, Seiya Imoto, Yoichi Furukawa, Yoshiyuki Kojima, Makoto Nakanishi
Journal: Nature Aging (2024)
High-quality genome of a modern soybean cultivar and resequencing of 547 accessions provide insights into the role of structural variation
Authors: Caiying Zhang, Zhenqi Shao, Youbin Kong, Hui Du, Wenlong Li, Zhanwu Yang, Xiangkong Li, Huifeng Ke, Zhengwen Sun, Jiabiao Shao, Shiliang Chen, Hua Zhang, Jiahao Chu, Xinzhu Xing, Rui Tian, Ning Qin, Junru Li, Meihong Huang, Yaqian Sun, Xiaobo Huo, Chengsheng Meng, Guoning Wang, Yuan Liu, Zhiying Ma, Shilin Tian, Xihuan Li
Journal: Nature Genetics (2024)
Increased RNA and protein degradation is required for counteracting transcriptional burden and proteotoxic stress in human aneuploid cells
Authors: Marica Rosaria. Ippolito, Johanna Zerbib, Yonatan Eliezer, Eli Reuveni, Sonia Vigano, Giuseppina De Feudis, Eldad D. Shulman, Anouk Savir Kadmon, Rachel Slutsky, Tiangen Chang, Emma M. Campagnolo, Silvia Taglietti, Simone Scorzoni, Sara Gianotti, Sara Martin, Julia Muenzner, Michael Mulleder, Nir Rozenblum, Carmela Rubolino, Tal Ben-Yishay, Kathrin Laue, Yael Cohen-Sharir, Ilaria Vigorito, Francesco Nicassio, Eytan Ruppin, Markus Ralser, Francisca Vazquez, Stefano Santaguida, Uri Ben-David
Journal: Cancer Discovery (2024)

Abstract Aneuploidy results in a stoichiometric imbalance of protein complexes that jeopardizes cellular fitness. Aneuploid cells thus need to compensate for the imbalanced DNA levels by regulating their RNA and protein levels, but the underlying molecular mechanisms remain unknown. Here, we dissected multiple diploid vs. aneuploid cell models. We found that aneuploid cells cope with transcriptional burden by increasing several RNA degradation pathways, and are consequently more sensitive to the perturbation of RNA degradation. At the protein level, aneuploid cells mitigate proteotoxic stress by reducing protein translation and increasing protein degradation, rendering them more sensitive to proteasome inhibition. These findings were recapitulated across hundreds of human cancer cell lines and primary tumors, and aneuploidy levels were significantly associated with the response of multiple myeloma patients to proteasome inhibitors. Aneuploid cells are therefore preferentially dependent on several key nodes along the gene expression process, creating clinically-actionable vulnerabilities in aneuploid cells.