tbuckley/cabot-search huggingface dataset:
Chromatin accessibility and gene expression vary between a new and evolved autopolyploid <i>Arabidopsis arenosa</i>
Authors: Thanvi Srikant, Adrián Gonzalo, Kirsten Bomblies
Journal: Molecular Biology and Evolution (2024)

Abstract Polyploids arise from whole-genome duplication (WGD) events, which have played important roles in genome evolution across eukaryotes. WGD can increase genome complexity, yield phenotypic novelty, and influence adaptation. Neo-polyploids have been reported to often show seemingly stochastic epigenetic and transcriptional changes, but this leaves open the question whether these changes persist in evolved polyploids. A powerful approach to address this is to compare diploids, neo-polyploids, and evolved polyploids of the same species. Arabidopsis arenosa is a species that allows us to do this—natural diploid and autotetraploid populations exist, while neo-tetraploids can be artificially generated. Here, we use ATAC-seq to assay local chromatin accessibility, and RNA-seq to study gene expression on matched leaf and petal samples from diploid, neo-tetraploid and evolved tetraploid A. arenosa. We found over 8,000 differentially accessible chromatin regions across all samples. These are largely tissue specific and show distinct trends across cytotypes, with roughly 70% arising upon WGD. Interestingly, only a small proportion is associated with expression changes in nearby genes. However, accessibility variation across cytotypes associates strongly with the number of nearby transposable elements. Relatively few genes were differentially expressed upon genome duplication, and ∼60% of these reverted to near-diploid levels in the evolved tetraploid, suggesting that most initial perturbations do not last. Our results provide new insights into how epigenomic and transcriptional mechanisms jointly respond to genome duplication and subsequent evolution of autopolyploids, and importantly, show that one cannot be directly predicted from the other.
Autologous platelet concentrates in root coverage procedures
Authors: Shayan Barootchi, Lorenzo Tavelli, Maria Elisa Galarraga Vinueza, Hamoun Sabri, Catherine Andrade, Nelson Pinto, Antonio Sanz, Hom‐Lay Wang
Journal: Periodontology 2000 (2024)

Gingival recessions are vastly prevalent among the general population. With regards to their treatment, recent advancements in periodontal and microsurgical procedures, focusing on minimal invasiveness and patient-centered therapies, have propelled a shift in their contemporary treatment, highlighting the field of biologics and bioactive mediators. Among different classes and types of biologics, autologous platelet concentrates (APCs), also referred to as autologous blood-derived products, are commonly used and preferred among many clinicians. These are essentially obtained via venipuncture (intravenous access) followed by centrifugation, for which numerous protocols and preparation methods have been used, leading to varieties of blood-derived products. In this review, via a systematic search, we explored the efficacy of the different utilized preparation methods and centrifugation protocols of APCs (e.g., platelet-rich plasma (PRP), platelet-rich fibrin (PRF), leucocyte-PRF, advanced-PRF, concentrated growth factor (CGF), etc.) for the treatment of type 1 gingival recessions (RT1, without interproximal attachment loss or noticeable tooth displacement), as well as their effectiveness relative to a common control (treatment with flap advancement alone without any additional material). Based on the available literature from randomized trials found in our systematic search, we observed that utilization of PRF can significantly enhance treatment outcomes when performing a coronally advanced flap, in terms of the amount of root coverage. The improvement in root coverage was further enhanced in the presence of baseline keratinized tissue width, and with an increasing relative magnitude (the more the baseline keratinized tissue width, the better the root coverage outcomes when using PRF). The efficacy of these products needs to be further explored with different graft substitutes and matrices, as well as relative to other commonly applied biologics, through well-conducted and adequately-powered randomized clinical trials.
Machine learning reveals the diversity of human 3D chromatin contact patterns
Authors: Erin N Gilbertson, Colin M Brand, Evonne McArthur, David C Rinker, Shuzhen Kuang, Katherine S Pollard, John A Capra
Journal: Molecular Biology and Evolution (2024)

Abstract Understanding variation in chromatin contact patterns across diverse humans is critical for interpreting noncoding variants and their effects on gene expression and phenotypes. However, experimental determination of chromatin contact patterns across large samples is prohibitively expensive. To overcome this challenge, we develop and validate a machine learning method to quantify the variation in 3D chromatin contacts at 2 kilobase resolution from genome sequence alone. We apply this approach to thousands of human genomes from the 1000 Genomes Project and the inferred hominin ancestral genome. While patterns of 3D contact divergence genome wide are qualitatively similar to patterns of sequence divergence, we find substantial differences in 3D divergence and sequence divergence in local 1 megabase genomic windows. In particular, we identify 392 windows with significantly greater 3D divergence than expected from sequence. Moreover, for 31% of genomic windows, a single individual has a rare divergent 3D contact map pattern. Using in silico mutagenesis, we find that most single nucleotide sequence changes do not result in changes to 3D chromatin contacts. However, in windows with substantial 3D divergence just one or a few variants can lead to divergent 3D chromatin contacts without the individuals carrying those variants having high sequence divergence. In summary, inferring 3D chromatin contact maps across human populations reveals variable contact patterns. We anticipate that these genetically diverse maps of 3D chromatin contact will provide a reference for future work on the function and evolution of 3D chromatin contact variation across human populations.
Immunotherapy for glioblastoma: current state, challenges, and future perspectives
Authors: Yang Liu, Fei Zhou, Heba Ali, Justin D. Lathia, Peiwen Chen
Journal: Cellular and Molecular Immunology (2024)

Glioblastoma (GBM) is an aggressive and lethal type of brain tumor in human adults. The standard of care offers minimal clinical benefit, and most GBM patients experience tumor recurrence after treatment. In recent years, significant advancements have been made in the development of novel immunotherapies or other therapeutic strategies that can overcome immunotherapy resistance in many advanced cancers. However, the benefit of immune-based treatments in GBM is limited because of the unique brain immune profiles, GBM cell heterogeneity, and immunosuppressive tumor microenvironment. In this review, we present a detailed overview of current immunotherapeutic strategies and discuss the challenges and potential molecular mechanisms underlying immunotherapy resistance in GBM. Furthermore, we provide an in-depth discussion regarding the strategies that can overcome immunotherapy resistance in GBM, which will likely require combination therapies.
Lung Cancer Research and Treatment: Global Perspectives and Strategic Calls to Action
Authors: M-L Meyer, S Peters, T S Mok, S Lam, P-C Yang, C Aggarwal, J Brahmer, R Dziadziuszko, E Felip, A Ferris, P M Forde, J Gray, L Gros, B Halmos, R Herbst, P A Jänne, B E Johnson, K Kelly, N B Leighl, S Liu, I Lowy, T U Marron, L Paz-Ares, N Rizvi, C M Rudin, E Shum, R Stahel, N Trunova, P Ujhazy, P A Bunn, F R Hirsch
Journal: Annals of Oncology (2024)
A cross-disease resource of living human microglia identifies disease-enriched subsets and tool compounds recapitulating microglial states
Authors: John F. Tuddenham, Mariko Taga, Verena Haage, Victoria S. Marshe, Tina Roostaei, Charles White, Annie J. Lee, Masashi Fujita, Anthony Khairallah, Ya Zhang, Gilad Green, Bradley Hyman, Matthew Frosch, Sarah Hopp, Thomas G. Beach, Geidy E. Serrano, John Corboy, Naomi Habib, Hans-Ulrich Klein, Rajesh Kumar Soni, Andrew F. Teich, Richard A. Hickman, Roy N. Alcalay, Neil Shneider, Julie Schneider, Peter A. Sims, David A. Bennett, Marta Olah, Vilas Menon, Philip L. De Jager
Journal: Nature Neuroscience (2024)
Developmental mosaicism underlying EGFR-mutant lung cancer presenting with multiple primary tumors
Authors: Risa Burr, Ignaty Leshchiner, Christina L. Costantino, Martin Blohmer, Tilak Sundaresan, Justin Cha, Karsen Seeger, Sara Guay, Brian P. Danysh, Ira Gore, Raquel A. Jacobs, Kara Slowik, Filippo Utro, Kahn Rhrissorrakrai, Chaya Levovitz, Jaimie L. Barth, Taronish Dubash, Brian Chirn, Laxmi Parida, Lecia V. Sequist, Jochen K. Lennerz, Mari Mino-Kenudson, Shyamala Maheswaran, Kamila Naxerova, Gad Getz, Daniel A. Haber
Journal: Nature Cancer (2024)

Abstract Although the development of multiple primary tumors in smokers with lung cancer can be attributed to carcinogen-induced field cancerization, the occurrence of multiple tumors at presentation in individuals with EGFR -mutant lung cancer who lack known environmental exposures remains unexplained. In the present study, we identified ten patients with early stage, resectable, non-small cell lung cancer who presented with multiple, anatomically distinct, EGFR -mutant tumors. We analyzed the phylogenetic relationships among multiple tumors from each patient using whole-exome sequencing (WES) and hypermutable poly(guanine) (poly(G)) repeat genotyping as orthogonal methods for lineage tracing. In four patients, developmental mosaicism, assessed by WES and poly(G) lineage tracing, indicates a common non-germline cell of origin. In two other patients, we identified germline EGFR variants, which confer moderately enhanced signaling when modeled in vitro. Thus, in addition to germline variants, developmental mosaicism defines a distinct mechanism of genetic predisposition to multiple EGFR -mutant primary tumors, with implications for their etiology and clinical management.
A genome-wide association analysis reveals new pathogenic pathways in gout*
Authors: Tanya J. Major, Riku Takei, Hirotaka Matsuo, Megan P. Leask, Nicholas A. Sumpter, Ruth K. Topless, Yuya Shirai, Wei Wang, Murray J. Cadzow, Amanda J. Phipps-Green, Zhiqiang Li, Aichang Ji, Marilyn E. Merriman, Emily Morice, Eric E. Kelley, Wen-Hua Wei, Sally P. A. McCormick, Matthew J. Bixley, Richard J. Reynolds, Kenneth G. Saag, Tayaza Fadason, Evgenia Golovina, Justin M. O’Sullivan, Lisa K. Stamp, Nicola Dalbeth, Abhishek Abhishek, Michael Doherty, Edward Roddy, Lennart T. H. Jacobsson, Meliha C. Kapetanovic, Olle Melander, Mariano Andrés, Fernando Pérez-Ruiz, Rosa J. Torres, Timothy Radstake, Timothy L. Jansen, Matthijs Janssen, Leo A. B. Joosten, Ruiqi Liu, Orsolya I. Gaal, Tania O. Crişan, Simona Rednic, Fina Kurreeman, Tom W. J. Huizinga, René Toes, Frédéric Lioté, Pascal Richette, Thomas Bardin, Hang Korng Ea, Tristan Pascart, Geraldine M. McCarthy, Laura Helbert, Blanka Stibůrková, Anne-K. Tausche, Till Uhlig, Véronique Vitart, Thibaud S. Boutin, Caroline Hayward, Philip L. Riches, Stuart H. Ralston, Archie Campbell, Thomas M. MacDonald, Akiyoshi Nakayama, Tappei Takada, Masahiro Nakatochi, Seiko Shimizu, Yusuke Kawamura, Yu Toyoda, Hirofumi Nakaoka, Ken Yamamoto, Keitaro Matsuo, Nariyoshi Shinomiya, Kimiyoshi Ichida, Chaeyoung Lee, Linda A. Bradbury, Matthew A. Brown, Philip C. Robinson, Russell R. C. Buchanan, Catherine L. Hill, Susan Lester, Malcolm D. Smith, Maureen Rischmueller, Hyon K. Choi, Eli A. Stahl, Jeff N. Miner, Daniel H. Solomon, Jing Cui, Kathleen M. Giacomini, Deanna J. Brackman, Eric M. Jorgenson, Hongbo Liu, Katalin Susztak, Suyash Shringapure, Suyash Shringarpure, Alexander So, Yukinori Okada, Changgui Li, Yongyong Shi, Tony R. Merriman
Journal: Nature Genetics (2024)
Itaconate drives mtRNA-mediated type I interferon production through inhibition of succinate dehydrogenase
Authors: Shane M. O’Carroll, Christian G. Peace, Juliana E. Toller-Kawahisa, Yukun Min, Alexander Hooftman, Sara Charki, Louise Kehoe, Maureen J. O’Sullivan, Aline Zoller, Anne F. Mcgettrick, Emily A. Day, Maria Simarro, Neali Armstrong, Justin P. Annes, Luke A. J. O’Neill
Journal: Nature Metabolism (2024)
HBI: a hierarchical Bayesian interaction model to estimate cell-type-specific methylation quantitative trait loci incorporating priors from cell-sorted bisulfite sequencing data
Authors: Youshu Cheng, Biao Cai, Hongyu Li, Xinyu Zhang, Gypsyamber D’Souza, Sadeep Shrestha, Andrew Edmonds, Jacquelyn Meyers, Margaret Fischl, Seble Kassaye, Kathryn Anastos, Mardge Cohen, Bradley E. Aouizerat, Ke Xu, Hongyu Zhao
Journal: Genome biology (2024)

Methylation quantitative trait loci (meQTLs) quantify the effects of genetic variants on DNA methylation levels. However, most published studies utilize bulk methylation datasets composed of different cell types and limit our understanding of cell-type-specific methylation regulation. We propose a hierarchical Bayesian interaction (HBI) model to infer cell-type-specific meQTLs, which integrates a large-scale bulk methylation data and a small-scale cell-type-specific methylation data. Through simulations, we show that HBI enhances the estimation of cell-type-specific meQTLs. In real data analyses, we demonstrate that HBI can further improve the functional annotation of genetic variants and identify biologically relevant cell types for complex traits.
Multi-omics reveals lactylation-driven regulatory mechanisms promoting tumor progression in oral squamous cell carcinoma
Authors: Fengyang Jing, Lijing Zhu, Jianyun Zhang, Xuan Zhou, Jiaying Bai, Xuefen Li, Heyu Zhang, Tiejun Li
Journal: Genome biology (2024)

Lactylation, a post-translational modification, is increasingly recognized for its role in cancer progression. This study investigates its prevalence and impact in oral squamous cell carcinoma (OSCC).
HLA-DRB1*01:03 and Severe Ulcerative Colitis
Authors: Marie Vibeke Vestergaard, Anne Krogh Nøhr, Kristine Højgaard Allin, Henrik Krarup, Lone Larsen, Aleksejs Sazonovs, Tine Jess
Journal: JAMA (2024)

This Danish nationwide genome-wide association study aims to identify biomarkers of severe vs less severe ulcerative colitis.
The Immune Landscape in Brain Metastasis
Authors: Luca D Schreurs, Alexander F vom Stein, Stephanie T Jünger, Marco Timmer, Ka-Won Noh, Reinhard Buettner, Hamid Kashkar, Volker Neuschmelting, Roland Goldbrunner, Phuong-Hien Nguyen
Journal: Neuro-Oncology (2024)

Abstract The prognosis for patients with brain metastasis remains dismal despite intensive therapy including surgical resection, radiotherapy, chemo-, targeted, and immunotherapy. Thus, there is a high medical need for new therapeutic options. Recent advances employing high-throughput and spatially resolved single-cell analyses have provided unprecedented insights into the composition and phenotypes of the diverse immune cells in the metastatic brain, revealing a unique immune landscape starkly different from that of primary brain tumors or other metastatic sites. This review summarizes the current evidence on the composition and phenotypes of the most prominent immune cells in the brain metastatic niche, along with their dynamic interactions with metastatic tumor cells and each other. As the most abundant immune cell types in this niche, we explore in detail the phenotypic heterogeneity and functional plasticity of tumor-associated macrophages, including both resident microglia and monocyte-derived macrophages, as well as the T-cell compartment. We also review preclinical and clinical trials evaluating the therapeutic potential of targeting the immune microenvironment in brain metastasis. Given the substantial evidence highlighting a significant role of the immune microenvironmental niche in brain metastasis pathogenesis, a comprehensive understanding of the key molecular and cellular factors within this niche holds great promise for developing novel therapeutic approaches as well as innovative combinatory treatment strategies for brain metastasis.
Successful Use of a GLP-1 Receptor Agonist as Add-on Therapy to Glibenclamide in a Young Adult With <i>KCNJ11</i> Permanent Neonatal Diabetes
Authors: Mairéad T. Crowley, Sarah Roarty, Helen O’Shea, Andrew T. Hattersley, Maria M. Byrne
Journal: Diabetes Care (2024)
The USP1 Inhibitor KSQ-4279 Overcomes PARP Inhibitor Resistance in Homologous Recombination–Deficient Tumors
Authors: Louise Cadzow, Jehrod Brenneman, Erica Tobin, Pamela Sullivan, Sumeet Nayak, Janid A. Ali, Sol Shenker, Jim Griffith, Michael McGuire, Paula Grasberger, Yuji Mishina, Morgan Murray, Anne E. Dodson, Hugh Gannon, Elsa Krall, Jeff Hixon, Edmond Chipumuro, Kerstin Sinkevicius, Prafulla C. Gokhale, Suthakar Ganapathy, Ursula A. Matulonis, Joyce F. Liu, Andrew Olaharski, Dipen Sangurdekar, Hanlan Liu, Jeremy Wilt, Michael Schlabach, Frank Stegmeier, Andrew A. Wylie
Journal: Cancer Research (2024)

Abstract Defects in DNA repair pathways play a pivotal role in tumor evolution and resistance to therapy. At the same time, they create vulnerabilities that render tumors dependent on the remaining DNA repair processes. This phenomenon is exemplified by the clinical activity of PARP inhibitors in tumors with homologous recombination (HR) repair defects, such as tumors with inactivating mutations in BRCA1 or BRCA2. However, the development of resistance to PARP inhibitors in BRCA-mutant tumors represents a high unmet clinical need. In this study, we identified deubiquitinase ubiquitin-specific peptidase-1 (USP1) as a critical dependency in tumors with BRCA mutations or other forms of HR deficiency and developed KSQ-4279, the first potent and selective USP1 inhibitor to enter clinical testing. The combination of KSQ-4279 with a PARP inhibitor was well tolerated and induced durable tumor regression across several patient-derived PARP-resistant models. These findings indicate that USP1 inhibitors represent a promising therapeutic strategy for overcoming PARP inhibitor resistance in patients with BRCA-mutant/HR-deficient tumors and support continued testing in clinical trials. Significance: KSQ-4279 is a potent and selective inhibitor of USP1 that induces regression of PARP inhibitor–resistant tumors when dosed in combination with PARP inhibitors, addressing an unmet clinical need for BRCA-mutant tumors.
Retraction: Variable Inhibition of Thrombospondin 1 against Liver and Lung Metastases through Differential Activation of Metalloproteinase ADAMTS1
Authors: Yoon-Jin Lee, Moritz Koch, Daniel Karl, Antoni X. Torres-Collado, Namali T. Fernando, Courtney Rothrock, Darshini Kuruppu, Sandra Ryeom, M. Luisa Iruela-Arispe, Sam S. Yoon
Journal: Cancer Research (2024)
Breast Cancer Disseminated Tumor Cells: Do They Stay and Fight or Run and Hide?
Authors: Frank C. Cackowski, Hasan Korkaya
Journal: Cancer Research (2024)

Many solid tumors including breast cancer can exhibit early dissemination and dormancy—in which cancer cells spread early in the disease process and survive long periods without detectable growth. These early disseminated tumor cells sometimes reactivate and lead to incurable metastatic disease years or even decades after curative-intent therapy for the primary tumor. We are just beginning to understand the role of the immune system in this process in part because of improvements in immunocompetent models as well as technological advances such as single-cell genomics and spatial transcriptomics. In this issue of Cancer Research, Bushnell and colleagues showed that NK cells are important in this context. The authors found that disseminated tumor cells and quiescent cells express higher levels of MHC 1 but are resistant to NK-cell–mediated immunity. The proposed mechanism involves the STING pathway and transcription factors Sox2 and Bach1. As other studies have highlighted the importance of T-cell immunity, this work reaffirms the importance and diversity of immune regulation of dormancy and suggests the need for future studies to flesh out mechanistic details and predict when each type of immunity is most important. See related article by Bushnell et al., p. 3337
Retraction: Differential Effects of VEGFR-1 and VEGFR-2 Inhibition on Tumor Metastases Based on Host Organ Environment
Authors: Yoon-Jin Lee, Daniel L. Karl, Ugwuji N. Maduekwe, Courtney Rothrock, Sandra Ryeom, Patricia A. D’Amore, Sam S. Yoon
Journal: Cancer Research (2024)
Editor’s Note: Tumor Escape from Endogenous, Extracellular Matrix–Associated Angiogenesis Inhibitors by Up-Regulation of Multiple Proangiogenic Factors
Authors: Namali T. Fernando, Moritz Koch, Courtney Rothrock, Lila K. Gollogly, Patricia A. D’Amore, Sandra Ryeom, Sam S. Yoon
Journal: Clinical Cancer Research (2024)
Retraction: CD44 Expression Denotes a Subpopulation of Gastric Cancer Cells in Which Hedgehog Signaling Promotes Chemotherapy Resistance
Authors: Changhwan Yoon, Do Joong Park, Benjamin Schmidt, Nicholas J. Thomas, Hae-June Lee, Teresa S. Kim, Yelena Y. Janjigian, Deirdre J. Cohen, Sam S. Yoon
Journal: Clinical Cancer Research (2024)
Retraction: Chemotherapy Resistance in Diffuse-Type Gastric Adenocarcinoma Is Mediated by RhoA Activation in Cancer Stem-Like Cells
Authors: Changhwan Yoon, Soo-Jeong Cho, Bülent Arman Aksoy, Do Joong Park, Nikolaus Schultz, Sandra W. Ryeom, Sam S. Yoon
Journal: Clinical Cancer Research (2024)
Retraction: <i>KMT2C</i> Mutations in Diffuse-Type Gastric Adenocarcinoma Promote Epithelial-to-Mesenchymal Transition
Authors: Soo-Jeong Cho, Changhwan Yoon, Jun Ho Lee, Kevin K. Chang, Jian-xian Lin, Young-Ho Kim, Myeong-Cherl Kook, Bülent Arman Aksoy, Do Joong Park, Hassan Ashktorab, Duane T. Smoot, Nikolaus Schultz, Sam S. Yoon
Journal: Clinical Cancer Research (2024)