tbuckley/cabot-search huggingface dataset:
Prevalence and outcomes of cancer and treatment-associated toxicities for patients with Ataxia Telangiectasia
Authors: Aimee Magnarelli, Qi Liu, Fan Wang, Xiao P Peng, Jennifer Wright, Ninad Oak, Valerie Natale, Cynthia Rothblum-Oviatt, Maureen A Lefton-Greif, Sharon McGrath-Morrow, Thomas O Crawford, Matthew J Ehrhardt, Howard M Lederman, Richa Sharma
Journal: Journal of Allergy and Clinical Immunology (2024)

Ataxia telangiectasia (A-T) is a DNA repair disorder with cancer predisposition. We sought to characterize the prevalence and outcomes of hematologic and solid cancers and treatment-associated toxicities in individuals with A-T. Data were retrospectively analyzed from the Johns Hopkins Ataxia Telangiectasia Clinical Center cohort. Cumulative incidence and standardized incidence ratios of cancer, survival probability after cancer diagnosis, and standardized mortality ratios were calculated. Cox regression estimated risk of death on the basis of chemotherapy (standard vs reduced) dosing, and multivariable logistic regression evaluated cancer risk associations with ataxia telangiectasia mutated (ATM) exons and variants. Eighty-four (16.5%) of 508 individuals were diagnosed with a primary cancer, of whom 62 (74%) were hematologic in origin and 22 (26%) were solid-organ cancers. The cumulative incidence of cancer was 29% by age 35 years. Non-Hodgkin lymphoma occurred most frequently (n = 39), whereas solid cancers disproportionately affected those 18 years and older (n = 22). The standardized mortality ratio was 24.6 (95% CI, 21.1-28.4) overall and 232.9 (95% CI,178.1-299.2) among individuals with cancer. Risk of death was higher when treated with standard/unknown versus modified chemotherapy (hazard ratio, 2.2; 95% CI, 1.1-4.4; P = .024). Chemotherapy-associated toxicities developed in 58% of individuals, predominantly neurologic (n = 14) and gastrointestinal (n = 10) systems. Three exons were enriched for cancer-associated variants. Individuals with A-T experience a wide array of blood and solid-organ malignancies, high mortality rates, and treatment-related toxicities, highlighting need for targeted therapies to mitigate toxicity and optimize survival.
Regulatory T cells in immune checkpoint blockade antitumor therapy
Authors: An Zhang, Tao Fan, Yixiao Liu, Guanhua Yu, Chunxiang Li, Zheng Jiang
Journal: Molecular Cancer (2024)

Regulatory T cells (Tregs), an essential component of the human immune system, are a heterogeneous group of T lymphocytes with the ability to suppress immune responses and maintain immune homeostasis. Recent evidence indicates that Tregs may impair antitumor immunity and facilitate cancer progression by weakening functions of effector T cells (Teffs). Consequently, targeting Tregs to eliminate them from tumor microenvironments to improve Teffs' activity could emerge as an effective strategy for cancer immunotherapy. This review outlines the biology of Tregs, detailing their origins, classification, and crucial markers. Our focus lies on the complex role of Tregs in cancer's development, progression and treatment, particularly on their suppressive role upon antitumor responses via multiple mechanisms. We delve into Tregs' involvement in immune checkpoint blockade (ICB) therapy, their dual effect on cancer immunotherapy and their potential biomarkers for ICB therapy effectiveness. We also summarize advances in the therapies that adjust Tregs to optimize ICB therapy, which may be crucial for devising innovative cancer treatment strategies.
Critical and differential roles of eIF4A1 and eIF4A2 in B-cell development and function
Authors: Ying Du, Jun Xie, Dewang Liu, Jiayi Zhao, Pengda Chen, Xiaoyu He, Peicheng Hong, Yubing Fu, Yazhen Hong, Wen-Hsien Liu, Changchun Xiao
Journal: Cellular and Molecular Immunology (2024)

Eukaryotic initiation factor 4 A (eIF4A) plays critical roles during translation initiation of cellular mRNAs by forming the cap-binding eIF4F complex, recruiting the 40S small ribosome subunit, and scanning the 5' untranslated region (5' UTR) for the start codon. eIF4A1 and eIF4A2, two isoforms of eIF4A, are highly conserved and exchange freely within eIF4F complexes. The understanding of their biological and molecular functions remains incomplete if not fragmentary. In this study, we showed that eIF4A1 and eIF4A2 exhibit different expression patterns during B-cell development and activation. Mouse genetic analyses showed that they play critical but differential roles during B-cell development and humoral immune responses. While eIF4A1 controls global protein synthesis, eIF4A2 regulates the biogenesis of 18S ribosomal RNA and the 40S ribosome subunit. This study demonstrates the distinct cellular and molecular functions of eIF4A1 and eIF4A2 and reveals a new role of eIF4A2 in controlling 40S ribosome biogenesis.
Umbrella review of meta-analyses on the risk factors, protective factors, consequences and interventions of cyberbullying victimization
Authors: K. T. A. Sandeeshwara Kasturiratna, Andree Hartanto, Crystal H. Y. Chen, Eddie M. W. Tong, Nadyanna M. Majeed
Journal: Nature Human Behaviour (2024)

The increasing prevalence of cyberbullying victimization has become a commonplace issue globally. Although research has explored various predictors and consequences of cyberbullying victimization, most focus on a narrow range of variables or contexts, highlighting the need to comprehensively review and synthesize the wealth of empirical findings. We conducted a systematic review of meta-analyses on cyberbullying victimization, incorporating 56 meta-analyses and 296 effect sizes (sample size range 421-1,136,080, sample size median 53,183; searched via EBSCOhost ERIC, EBSCOhost PsycInfo, PubMed, Scopus, Web of Science, 13 cyberbullying-related journals, Google Scholar and ProQuest Dissertations and Theses) to address the following critical questions: (1) What are the crucial sociodemographic and psychological profiles of cyberbullying victims? (2) What critical contextual and environmental factors are associated with cyberbullying victimization? (3) What are the key psychological and behavioural consequences of cyberbullying victimization? (4) How effective are existing interventions in mitigating impacts of cyberbullying? Included meta-analyses had to focus on cyberbullying victimization and report at least one predictor or consequence. A quality assessment was conducted using the Joanna Briggs Institute Critical Appraisal Instrument for Systematic Reviews and Research Syntheses. Findings suggest that females, school-aged populations, traditional bullying victims and frequent internet users were more likely to be cyberbullied. Unregulated school environments and unsupportive parental relationships were also associated with increased cyberbullying victimization. Cyberbullying victimization was consistently associated with negative psychological outcomes, lower school performance and maladaptive coping behaviours. More importantly, the current review found that cyberbullying intervention programmes show promising results. The current review underscores the importance of devoting adequate resources to mitigating cyberbullying victimization.
A stealthy neural recorder for the study of behaviour in primates
Authors: Saehyuck Oh, Janghwan Jekal, Jinyoung Won, Kyung Seob Lim, Chang-Yeop Jeon, Junghyung Park, Hyeon-Gu Yeo, Yu Gyeong Kim, Young Hee Lee, Leslie Jaesun Ha, Han Hee Jung, Junwoo Yea, Hyeokjun Lee, Jeongdae Ha, Jinmo Kim, Doyoung Lee, Soojeong Song, Jieun Son, Tae Sang Yu, Jungmin Lee, Sanghoon Lee, Jaehong Lee, Bong Hoon Kim, Ji-Woong Choi, Jong-Cheol Rah, Young Min Song, Jae-Woong Jeong, Hyung Jin Choi, Sheng Xu, Youngjeon Lee, Kyung-In Jang
Journal: Nature Biomedical Engineering (2024)

By monitoring brain neural signals, neural recorders allow for the study of neurological mechanisms underlying specific behavioural and cognitive states. However, the large brain volumes of non-human primates and their extensive range of uncontrolled movements and inherent wildness make it difficult to carry out covert and long-term recording and analysis of deep-brain neural signals. Here we report the development and performance of a stealthy neural recorder for the study of naturalistic behaviours in non-human primates. The neural recorder includes a fully implantable wireless and battery-free module for the recording of local field potentials and accelerometry data in real time, a flexible 32-electrode neural probe with a resorbable insertion shuttle, and a repeater coil-based wireless-power-transfer system operating at the body scale. We used the device to record neurobehavioural data for over 1 month in a freely moving monkey and leveraged the recorded data to train an artificial intelligence model for the classification of the animals' eating behaviours.
Inadequate foundational decoding skills constrain global literacy goals for pupils in low- and middle-income countries
Authors: Michael Crawford, Neha Raheel, Maria Korochkina, Kathleen Rastle
Journal: Nature Human Behaviour (2024)

Learning to read is the most important outcome of primary education. However, despite substantial improvements in primary school enrolment, most students in low- and middle-income countries (LMICs) fail to learn to read by age 10. We report reading assessment data from over half a million pupils from 48 LMICs tested primarily in a language of instruction and show that these pupils are failing to acquire the most basic skills that contribute to reading comprehension. Pupils in LMICs across the first three instructional years are not acquiring the ability to decode printed words fluently and, in most cases, are failing to master the names and sounds associated with letters. Moreover, performance gaps against benchmarks widen with each instructional year. Literacy goals in LMICs will be reached only by ensuring focus on decoding skills in early-grade readers. Effective literacy instruction will require rigorous systematic phonics programmes and assessments suitable for LMIC contexts.
AI-READI: rethinking AI data collection, preparation and sharing in diabetes research and beyond
Authors: Sally L. Baxter, Virginia R. de Sa, Kadija Ferryman, Prachee Jain, Cecilia S. Lee, Jennifer Li-Pook-Than, T. Y. Alvin Liu, Julia P. Owen, Bhavesh Patel, Qilu Yu, Linda M. Zangwill, Amir Bahmani, Christopher G. Chute, Jeffrey C. Edberg, Samantha Hurst, Hiroshi Ishikawa, Aaron Y. Lee, Gerald McGwin, Shannon McWeeney, Camille Nebeker, Cynthia Owsley, Sara J. Singer, Riddhiman Adib, Mohammad Adibuzzaman, Arash Alavi, Catherine Ashley, Adrienne Baer, Erik Benton, Marian Blazes, Aaron Cohen, Benjamin Cordier, Katie Crist, Colleen Cuddy, Aydan Gasimova, Nayoon Gim, Stephanie Hong, Trina Kim, Wei-Chun Lin, Jessica Mitchell, Caitlyn Ngadisastra, Victoria Patronilo, Jamie Shaffer, Sanjay Soundarajan, Kevin Zhao, Caroline Drolet, Abigail Lucero, Dawn Matthies, Hanna Pittock, Kate Watkins, Brittany York, Charles E. Amankwa, Monique Bangudi, Nada Haboudal, Shahin Hallaj, Anna Heinke, Lingling Huang, Fritz Gerald P. Kalaw, Apoorva Karsolia, Hadi Khazaei, Muna Mohammed, Kyongmi Simpkins, Xujing Wang
Journal: Nature Metabolism (2024)
Advancing osteosarcoma 3D modeling in vitro for novel tumor microenvironment-targeted therapies development
Authors: Sofia Costa, João Rodrigues, Carolina Vieira, Sofia Dias, Juliana Viegas, Flávia Castro, Bruno Sarmento, Catarina Leite Pereira
Journal: Journal of Controlled Release (2024)

Osteosarcoma (OS) represents one of the most common primary bone cancers affecting children and young adults. The available treatments have remained unimproved for the past decades, hampered by the poor knowledge of OS etiology/pathophysiology and the lack of innovative, predictive and biologically relevant in vitro models, that can recapitulate the 3D OS tumor microenvironment (TME). Here, we report the development and characterization of an innovative 3D model of OS, composed of OS tumor cells, immune cells (macrophages) and mesenchymal stem cells (MSCs), that formed a multicellular tissue spheroid (MCTS). This fully humanized 3D model was shown to accurately mimic the native histological features of OS, while innately leading to the polarization of macrophages towards an M2-like phenotype, highly aggressive and pro-tumor profile. Upon the exposure to immunomodulatory molecules, the MCTS were shown to be responsive by shifting macrophages polarization, and dramatically altering the TME secretome. In agreement, when treated with immunomodulatory/stimulatory nanoparticles (NPSs), we were able to revert the TME secretome towards an anti-inflammatory profile. This study establishes an advanced 3D OS model capable of shedding light on macrophages and MSCs contributions to disease progression, paving the way for the development of innovative therapeutic approaches targeting the OS TME, while providing a biologically relevant in vitro tool for the efficacy screening of novel OS therapeutic approaches.
Epigenetic training of human bronchial epithelium cells by repeated rhinovirus infections
Authors: Marua Abu Risha, Karosham D. Reddy, Sai Sneha Priya Nemani, Constanze Jakwerth, Carsten Schmidt‐Weber, Thomas Bahmer, Gesine Hansen, Erika von Mutius, Klaus F. Rabe, Anna‐Maria Dittrich, Ruth Grychtol, Nicole Maison, Bianca Schaub, Matthias V. Kopp, Folke Brinkmann, Silke Meiners, Uta Jappe, Markus Weckmann
Journal: Allergy (2024)

Humans are subjected to various environmental stressors (bacteria, viruses, pollution) throughout life. As such, an inherent relationship exists between the effect of these exposures with age. The impact of these environmental stressors can manifest through DNA methylation (DNAm). However, whether these epigenetic effects selectively target genes, pathways, and biological regulatory mechanisms remains unclear. Due to the frequency of human rhinovirus (HRV) infections throughout life (particularly in early development), we propose the use of HRV under controlled conditions can model the effect of multiple exposures to environmental stressors.
Sympathetic Neurons Promote Small Cell Lung Cancer Through the Beta-2 Adrenergic Receptor
Authors: Tala FNU, Peiguo Shi, Wanwei Zhang, Sanny S.W. Chung, Christopher B. Damoci, Yinshan Fang, Qi-Yue Chen, Anjali Saqi, Yuefeng Huang, Xuebing Wu, Chao Lu, Dian Yang, Timothy C. Wang, Jianwen Que
Journal: Cancer Discovery (2024)

SCLC is highly aggressive, with limited effective treatment options. We show that ablating sympathetic nerves or inhibiting the ADRB2 receptor slows SCLC progression and prolongs survival in mice. Additionally, ADRB2 inhibition reduces the growth of human SCLC organoids and xenografts by disrupting PKA signaling, identifying a new therapeutic target.
Exploring multi-omics and clinical characteristics linked to accelerated biological aging in Asian women of reproductive age: insights from the S-PRESTO study
Authors: Li Chen, Karen Mei-Ling Tan, Jia Xu, Priti Mishra, Sartaj Ahmad Mir, Min Gong, Kothandaraman Narasimhan, Bryan Ng, Jun Shi Lai, Mya Thway Tint, Shirong Cai, Suresh Anand Sadananthan, Navin Michael, Jadegoud Yaligar, Sambasivam Sendhil Velan, Melvin Khee Shing Leow, Kok Hian Tan, Jerry Chan, Michael J. Meaney, Shiao-Yng Chan, Yap Seng Chong, Johan G. Eriksson
Journal: Genome Medicine (2024)

Phenotypic age (PhenoAge), a widely used marker of biological aging, has been shown to be a robust predictor of all-cause mortality and morbidity in different populations. Existing studies on biological aging have primarily focused on individual domains, resulting in a lack of a comprehensive understanding of the multi-systemic dysregulation that occurs in aging.
Bridging immune-neurovascular crosstalk via the immunomodulatory microspheres for promoting neural repair
Authors: Tongtong Xu, Lin Gan, Wei Chen, Dandan Zheng, Hanlai Li, Shiyu Deng, Dongliang Qian, Tingting Gu, Qianyuan Lian, Gracie Shen, Qingzhu An, Wanlu Li, Zhijun Zhang, Guo-Yuan Yang, Huitong Ruan, Wenguo Cui, Yaohui Tang
Journal: Bioactive Materials (2024)
Targeting c-MET for Endoscopic Detection of Dysplastic Lesions Within Barrett’s Esophagus Using EMI-137 Fluorescence Imaging
Authors: Yi-Jhih Huang, Jonas Rieder, Kel Vin. Tan, Anna Tenditnaya, Borivoj Vojnovic, Dimitris Gorpas, Michael Quante, Katherine A. Vallis
Journal: Clinical Cancer Research (2024)

Esophageal cancer carries a poor prognosis with a 5-year overall survival of less than 20%. Barrett's esophagus increases the risk of esophageal adenocarcinoma. The aim of this study was to investigate the ability of EMI-137, a mesenchymal-epithelial transition factor (c-MET)-targeting optical imaging tracer, to detect dysplasia in Barrett's esophagus.
Re-irradiation plus pembrolizumab: Phase II study for recurrent glioblastoma patients
Authors: Fabio M. Iwamoto, Shyam K. Tanguturi, Lakshmi Nayak, Tony J. Wang, Arati Desai, Robert A. Lustig, Stephen Bagley, Eric T. Wong, Lauren M. Hertan, Christine McCluskey, Julia Hayden, Alona Muzikansky, Shreya Nakhawa, Julia Japo, Connor C. Bossi, Maxime Meylan, Ye Tian, Graham L. Barlow, Paul Speliakos, Georges Ayoub, David M. Meredith, Keith L. Ligon, Daphne Haas-Kogan, Kun Huang, Kai W. Wucherpfennig, Patrick Y. Wen, David A. Reardon
Journal: Clinical Cancer Research (2024)

Radiation therapy may enhance anti-tumor immune responses by several mechanisms including induction of immunogenic cell death. We performed a phase 2 study of pembrolizumab with re-irradiation in patients with recurrent glioblastoma.
Genomic, epigenomic and transcriptomic inter- and intra-tumor heterogeneity in desmoid tumors
Authors: Chelsea De Bellis, Sujay Vennam, Christopher Eeles, Pegah Rahimizadeh, Justin Cates, Thomas Stricker, Jenny Hoffman, Kristen Ganjoo, Gregory W. Charville, Benjamin Haibe-Kains, Matt van de Rijn, Joanna Przybyl
Journal: Clinical Cancer Research (2024)

Desmoid tumors are bland fibroblastic tumors that do not metastasize but have a high rate of local recurrence. Previously published studies proposed two different transcriptomic signatures to predict relapse. Molecular heterogeneity has been well established in high-grade sarcomas, but little is known about molecular variability within locally aggressive tumors such as desmoids.
Randomized Phase II Study of Durvalumab with or without Tremelimumab in Patients with Metastatic Castration Resistant Prostate Cancer.
Authors: Eric Winquist, Sebastien J. Hotte, Kim Chi, Srikala Sridhar, Susan Ellard, Michael Ong, Nayyer Iqbal, Muhammad Salim, Urban Emmenegger, Joel R. Gingerich, Aly-Khan Lalani, Pierre Major, Christian Kollmannsberger, Steven Yip, Aaron Hansen, Daygen Finch, Christina Canil, James Hutchenreuther, Francisco Vera-Badillo, Martin Smoragiewicz, Michael Cabanero, Ming-Sound Tsao, Elie Ritch, Alexander W. Wyatt, Lesley Seymour
Journal: Clinical Cancer Research (2024)

Abstract Purpose: PD-L1 is overexpressed by dendritic cells in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing on androgen receptor pathway inhibitors. We tested whether checkpoint blockade could enhance antitumor activity in mCRPC. Patients and Methods: In a multicenter open-label noncomparative randomized phase II study, patients with mCRPC treated with ≤1 prior cytotoxic chemotherapy, with measurable disease and progression on abiraterone and/or enzalutamide, were randomized to durvalumab 1,500 mg intravenously every 4 weeks ±4 doses of tremelimumab 75 mg intravenously. The primary endpoint was objective response (OR) by iRECIST using a Simon two-stage design. Correlative testing included PD-L1/cluster designation 8 IHC on baseline tumor biopsies and deep targeted sequencing of plasma cell–free DNA. Results: Fifty-two patients were enrolled. Median age was 70 years (range, 50–83 years), and 52% had prior taxane therapy for mCRPC. In stage I, 13 patients were randomized to durvalumab with no OR observed. Durvalumab + tremelimumab advanced to stage II with 39 patients enrolled (receiving a median three cycles, range 1–53). Durvalumab + tremelimumab–related adverse events were mainly ≤ grade 2 but led to discontinuation in seven patients. There were seven ORs [19.4% (95% confidence interval: 8.2%–36.0%); intention to treat 17.9% (95% confidence interval: 7.5%–33.5%)]. Five responding tumors were PD-L1–positive and two exhibited DNA damage repair defects. Responses were observed without high tumor mutational burden or other genomic indices of immunotherapy sensitivity. Conclusions: Durvalumab + tremelimumab is active in mCRPC, but patient selection remains a challenge. Further studies to develop predictive biomarkers are warranted.
Pathogenic variants in cancer susceptibility genes predispose to Ductal Carcinoma <i>In situ</i> of the breast
Authors: Huaizhi Huang, Ronan E. Couch, Rachid Karam, Chunling Hu, Nicholas Boddicker, Eric C. Polley, Jie Na, Christine B. Ambrosone, Song Yao, Amy Trentham-Dietz, A. Heather Eliassen, Kathryn Penney, Kristen Brantley, Clara Bodelon, Lauren R. Teras, James Hodge, Alpa Patel, Christopher A. Haiman, Esther M. John, Susan L. Neuhausen, Elena Martinez, James V. Lacey, Katie M. O'Brien, Dale P. Sandler, Clarice R. Weinberg, Julie R. Palmer, Kimberly A. Bertrand, Celine M. Vachon, Janet E. Olson, Kathryn E. Ruddy, Hoda Anton-Culver, Argyrios Ziogas, David E. Goldgar, Katherine L. Nathanson, Susan M. Domchek, Jeffrey N. Weitzel, Peter Kraft, Jill S. Dolinsky, Tina Pesaran, Marcy E. Richardson, Siddhartha Yadav, Fergus J. Couch
Journal: Clinical Cancer Research (2024)

To determine the relationship between germline pathogenic variants (PV) in cancer predisposition genes and the risk of ductal carcinoma in situ (DCIS).
A tumor-naive ctDNA assay detects minimal residual disease in resected stage II or III colorectal cancer and predicts recurrence: subset analysis from the GALAXY study in CIRCULATE-Japan
Authors: Yoshiaki Nakamura, Kristiyana Kaneva, Christine Lo, Daniel Neems, Jonathan E. Freaney, Hala Boulos, Seung Won Hyun, Farahnaz Islam, Jason Yamada-Hanff, Terri M. Driessen, Anne Sonnenschein, Dana F. DeSantis, Daisuke Kotani, Jun Watanabe, Masahito Kotaka, Saori Mishima, Hideaki Bando, Kentaro Yamazaki, Hiroya Taniguchi, Ichiro Takemasa, Takeshi Kato, Chithra Sangli, Robert Tell, Richard Blidner, Takayuki Yoshino, Kate Sasser, Eiji Oki, Halla Nimeiri
Journal: Clinical Cancer Research (2024)

Analysis of circulating tumor DNA (ctDNA) may enable early identification of patients likely to relapse, presenting an opportunity for early interventions and improved outcomes. Tumor-naïve plasma-only approaches for molecular residual disease (MRD) assessment accelerate turnaround time, enabling rapid treatment decisions and ongoing surveillance.
Utilizing Patient-derived Xenografts to Model Precision Oncology for Biliary Tract Cancer
Authors: Timothy P. DiPeri, Kurt W. Evans, Stephen Scott, Xiaofeng Zheng, Kaushik Varadarajan, Lawrence N. Kwong, Michael Kahle, Hop S. Tran Cao, Ching-Wei Tzeng, Thuy Vu, Sunhee Kim, Fei Su, Maria Gabriela Raso, Yasmeen Rizvi, Ming Zhao, Huamin Wang, Sunyoung S. Lee, Timothy A. Yap, Jordi Rodon, Milind Javle, Funda Meric-Bernstam
Journal: Clinical Cancer Research (2024)

Biliary tract cancers (BTCs), which are rare and aggressive malignancies, are rich in clinically actionable molecular alterations. A major challenge in the field is the paucity of clinically relevant BTC models which recapitulate the diverse molecular profiles of these tumors. The purpose of this study was to curate a collection of patient-derived xenograft (PDX) models that reflect the spectrum of genomic alterations present in BTCs to create a resource for modeling precision oncology.
<i>BRAF </i>deletion in adult patients with Langerhans cell histiocytosis correlates with multisystem disease and poor outcome
Authors: Min Lang, Long Chang, Hao Cai, He Lin, Zheng-zheng Liu, Ming-hui Duan, Dao-bin Zhou, Xin-xin Cao
Journal: Clinical Cancer Research (2024)

Langerhans cell histiocytosis (LCH) is a rare and highly heterogeneous histiocytosis. There are currently few studies examining the correlation between molecular profiling and clinical phenotype or outcomes in adult patients with LCH. The objective of this study was to characterize the genomic landscape of adult LCH and correlate molecular findings with clinical features and patient outcomes.