tbuckley/cabot-search huggingface dataset:
Developing and Evaluating Large Language Model–Generated Emergency Medicine Handoff Notes
Authors: Vince Hartman, Xinyuan Zhang, Ritika Poddar, Matthew McCarty, Alexander Fortenko, Evan Sholle, Rahul Sharma, Thomas Campion, Peter A. D. Steel
Journal: JAMA Network Open (2024)

Importance An emergency medicine (EM) handoff note generated by a large language model (LLM) has the potential to reduce physician documentation burden without compromising the safety of EM-to-inpatient (IP) handoffs. Objective To develop LLM-generated EM-to-IP handoff notes and evaluate their accuracy and safety compared with physician-written notes. Design, Setting, and Participants This cohort study used EM patient medical records with acute hospital admissions that occurred in 2023 at NewYork-Presbyterian/Weill Cornell Medical Center. A customized clinical LLM pipeline was trained, tested, and evaluated to generate templated EM-to-IP handoff notes. Using both conventional automated methods (ie, recall-oriented understudy for gisting evaluation [ROUGE], bidirectional encoder representations from transformers score [BERTScore], and source chunking approach for large-scale inconsistency evaluation [SCALE]) and a novel patient safety-focused framework, LLM-generated handoff notes vs physician-written notes were compared. Data were analyzed from October 2023 to March 2024. Exposure LLM-generated EM handoff notes. Main Outcomes and Measures LLM-generated handoff notes were evaluated for (1) lexical similarity with respect to physician-written notes using ROUGE and BERTScore; (2) fidelity with respect to source notes using SCALE; and (3) readability, completeness, curation, correctness, usefulness, and implications for patient safety using a novel framework. Results In this study of 1600 EM patient records (832 [52%] female and mean [SD] age of 59.9 [18.9] years), LLM-generated handoff notes, compared with physician-written ones, had higher ROUGE (0.322 vs 0.088), BERTScore (0.859 vs 0.796), and SCALE scores (0.691 vs 0.456), indicating the LLM-generated summaries exhibited greater similarity and more detail. As reviewed by 3 board-certified EM physicians, a subsample of 50 LLM-generated summaries had a mean (SD) usefulness score of 4.04 (0.86) out of 5 (compared with 4.36 [0.71] for physician-written) and mean (SD) patient safety scores of 4.06 (0.86) out of 5 (compared with 4.50 [0.56] for physician-written). None of the LLM-generated summaries were classified as a critical patient safety risk. Conclusions and Relevance In this cohort study of 1600 EM patient medical records, LLM-generated EM-to-IP handoff notes were determined superior compared with physician-written summaries via conventional automated evaluation methods, but marginally inferior in usefulness and safety via a novel evaluation framework. This study suggests the importance of a physician-in-loop implementation design for this model and demonstrates an effective strategy to measure preimplementation patient safety of LLM models.
Acceptability of Guidelines to Stop Colon Cancer Screening by Estimated Life Expectancy
Authors: Laura E. Brotzman, Brian J. Zikmund-Fisher, Eve A. Kerr, Mohammed Kabeto, Jeffrey T. Kullgren
Journal: JAMA Network Open (2024)

This cross-sectional study examines whether older adults with limited vs longer estimated life expectancy accept guideline recommendations that patients stop getting screened for colon cancer once they reach age 75 years.
Learning Curves for Robotic-Assisted Ventral Hernia Repair
Authors: Wei San Loh, Ryan A. Howard, Brian T. Fry, Jyothi R. Thumma, Edward C. Norton, Justin B. Dimick, Kyle H. Sheetz
Journal: JAMA Network Open (2024)

Importance Although the use of robotic-assisted ventral hernia repairs has increased significantly over the last decade, the experience surgeons need to achieve comparable outcomes with more established laparoscopic and open approaches has not been well characterized. Objective To estimate the learning curves for robotic-assisted ventral (incisional and umbilical) hernia repair. Design, Setting, and Participants This retrospective cohort study included Medicare fee-for-service patients (≥18 years) enrolled in Medicare Part A and Part B with no managed care undergoing ventral hernia repairs between 2010 and 2020. Multivariate logistic regression was used to estimate reoperation rates for hernia recurrence, adjusting for patient demographics, comorbidities, mesh placement, and hospital characteristics. Analyses were conducted from October 2023 to July 2024. Exposure Incremental robotic-assisted hernia repair volume. Main Outcome and Measure Reoperation for hernia recurrence within 7 years of index hernia repair. Results This study comprised 160 379 Medicare patients (mean [SD] age, 69 [11] years), of whom 93 272 (58.2%) were female, 13 799 (8.6%) were Black, 3124 (2.0%) were Hispanic, and 138 311 (86.2%) were White. Among these patients, 12 609 (7.9%) underwent robotic-assisted hernia repairs, 32 337 (20.2%) laparoscopic repairs, and 115 433 (71.9%) open repairs. This study also included 23 580 surgeons, with 5074 performing robotic-assisted hernia repairs. The national reoperation rates for hernia recurrence after laparoscopic and open repairs were 12.5% (95% CI, 12.06%-12.94%) and 12.9% (95% CI, 12.70%-13.15%), respectively. Reoperation rates decreased as the number of robotic-assisted cases increased, from 14.2% (95% CI, 13.34%-14.97%) at 10 cases to 7.6% (95% CI, 6.75-8.37) at 50 cases. Surgeons needed at least 19 (95% CI, 16-22) robotic-assisted hernia repairs or 16 (95% CI, 13-19) repairs to achieve outcomes equivalent to those of laparoscopic and open procedures. Few surgeons (285 surgeons [5.7%]) performed enough robotic-assisted ventral hernia repairs to achieve necessary volume nationally to overcome the learning curve. Conclusions and Relevance In this cohort study of 23 580 surgeons who performed ventral hernia repairs between 2010 and 2020, increasing experience with robotic-assisted hernia repairs was associated with improved long-term reoperation rates for hernia recurrence. However, the majority of surgeons did not perform enough cases to reach reoperation rates equivalent to more established laparoscopic and open approaches.
Single-nucleus multi-omics analyses reveal cellular and molecular innovations in the anterior cingulate cortex during primate evolution
Authors: Jiamiao Yuan, Kangning Dong, Haixu Wu, Xuerui Zeng, Xingyan Liu, Yan Liu, Jiapei Dai, Jichao Yin, Yongjie Chen, Yongbo Guo, Wenhao Luo, Na Liu, Yan Sun, Shihua Zhang, Bing Su
Journal: Cell Genomics (2024)
Genetic and microenvironmental evolution of colorectal liver metastases under chemotherapy
Authors: Min Shi, Yingxi Yang, Na Huang, Dongqiang Zeng, Zongchao Mo, Jiao Wang, Xiaomeng Zhang, Ran Liu, Chunlin Wang, Xiaoxiang Rong, Zhenzhen Wu, Qiong Huang, Haixia Shang, Jihong Tang, Zhaojun Wang, Jianan Cai, Genjie Huang, Yijin Guan, Jian Guo, Quanhua Mu, Jiguang Wang, Wangjun Liao
Journal: Cell Reports Medicine (2024)
Understanding the Older Patient Perspective on Colorectal Cancer Screening Cessation
Authors: Leigh H. Simmons, Folasade P. May, Meredith A. Gilliam
Journal: JAMA Network Open (2024)

Laura E. Brotzman, MPH; Brian J. Zikmund-Fisher, PhD; Eve A. Kerr, MD, MPH; Mohammed Kabeto, MS; Jeffrey T. Kullgren, MD, MS, MPH
Altered Empathy Processing in Frontotemporal Dementia
Authors: Olof Lindberg, Tie-Qiang Li, Cecilia Lind, Susanna Vestberg, Ove Almkvist, Mikael Stiernstedt, Anita Ericson, Nenad Bogdanovic, Oskar Hansson, Luke Harper, Eric Westman, Caroline Graff, Theofanis Tsevis, Peter Mannfolk, Håkan Fischer, Gustav Nilsonne, Predrag Petrovic, Lars Nyberg, Lars-Olof Wahlund, Alexander F. Santillo
Journal: JAMA Network Open (2024)

This case-control study examines differences in empathetic response of patients experiencing behavioral variant frontotemporal dementia using functional magnetic resonance imaging.
Using multiplexed functional data to reduce variant classification inequities in underrepresented populations
Authors: Moez Dawood, Shawn Fayer, Sriram Pendyala, Mason Post, Divya Kalra, Karynne Patterson, Eric Venner, Lara A Muffley, Douglas M Fowler, Alan F Rubin, Jennifer E Posey, Sharon E Plon, James R Lupski, Richard A Gibbs, Lea M Starita, Carla Daniela Robles-Espinoza, Willow Coyote-Maestas, Irene Gallego Romero
Journal: Genome Medicine (2024)

Multiplexed Assays of Variant Effects (MAVEs) can test all possible single variants in a gene of interest. The resulting saturation-style functional data may help resolve variant classification disparities between populations, especially for Variants of Uncertain Significance (VUS). We analyzed clinical significance classifications in 213,663 individuals of European-like genetic ancestry versus 206,975 individuals of non-European-like genetic ancestry from All of Us and the Genome Aggregation Database. Then, we incorporated clinically calibrated MAVE data into the Clinical Genome Resource's Variant Curation Expert Panel rules to automate VUS reclassification for BRCA1, TP53, and PTEN. Using two orthogonal statistical approaches, we show a higher prevalence (p ≤ 5.95e − 06) of VUS in individuals of non-European-like genetic ancestry across all medical specialties assessed in all three databases. Further, in the non-European-like genetic ancestry group, higher rates of Benign or Likely Benign and variants with no clinical designation (p ≤ 2.5e − 05) were found across many medical specialties, whereas Pathogenic or Likely Pathogenic assignments were increased in individuals of European-like genetic ancestry (p ≤ 2.5e − 05). Using MAVE data, we reclassified VUS in individuals of non-European-like genetic ancestry at a significantly higher rate in comparison to reclassified VUS from European-like genetic ancestry (p = 9.1e − 03) effectively compensating for the VUS disparity. Further, essential code analysis showed equitable impact of MAVE evidence codes but inequitable impact of allele frequency (p = 7.47e − 06) and computational predictor (p = 6.92e − 05) evidence codes for individuals of non-European-like genetic ancestry. Generation of saturation-style MAVE data should be a priority to reduce VUS disparities and produce equitable training data for future computational predictors.
Use of Artificial Intelligence in Peer Review Among Top 100 Medical Journals
Authors: Zhi-Qiang Li, Hui-Lin Xu, Hui-Juan Cao, Zhao-Lan Liu, Yu-Tong Fei, Jian-Ping Liu
Journal: JAMA Network Open (2024)

This cross-sectional study of 100 top medical journals examines policies for use of artificial intelligence (AI) and generative AI in peer review.
Duvelisib with docetaxel for patients with anti-PD-1 refractory, recurrent or metastatic head and neck squamous cell carcinoma
Authors: G. J. Hanna, L. B. Oakley, R. Shi, A. ONeill, K.Y. Shin, N. Scarfo, K/ Sehgal, M. J. Dennis, N. Quinn, V. Y. Jo, K. Wong, A. Shvyrkova, V. Kushnarev, B. U. Shanthappa, A. Tkachuk, K. Kryukov, A. Sarachakov, V. Svekolkin, J. Lennerz, S. Waters, R. I. Haddad
Journal: Clinical Cancer Research (2024)

Abstract Background: Treatments after anti-PD-1 therapy for patients with recurrent, metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) are limited. Blocking phosphatidylinositol 3-kinase (PI3K) signaling may lead to tumor immunomodulation and enhanced taxane sensitivity. This phase 2 trial evaluated dual, selective PI3Kδ/γ inhibition with docetaxel in patients with anti-PD-1 refractory R/M HNSCC. Design: Patients received duvelisib (25 mg orally twice daily) with docetaxel (75 mg/m2 IV) every 21-days. The primary endpoint was overall response rate (ORR) (RECISTv1.1), employing a Simon two-stage design. Secondary endpoints: safety, progression-free survival (PFS), overall survival (OS); exploratory endpoints: correlating immunologic and genomic parameters with outcomes. Results: From 11/1/21 to 10/10/23, 26 patients enrolled (median age: 64, 96% men, 54% with HPV+ disease; primary site: 12 oropharynx, 11 oral cavity, 3 larynx/hypopharynx. Best ORR was 19% (5/26) (95%CI: 6.8-40.7%), all were partial responses (median duration: 5.1 months [0.7-15.5]); 46% (12/26) exhibited stable disease and 32% (8/26) progression (1 unevaluable). Two patients remain on-treatment at data cutoff; 25% (6/24) came off for toxicity. Grade 3+ treatment-related adverse events were observed in 50% (13/26), most often elevated liver function tests (6, 23%). No deaths were treatment related. At median follow-up of 6.5 months (0.7-26), median PFS: 2.8 months (95%CI: 1.9-7.0); 17/26 patients had died. Median OS: 10.2 months (95%CI: 6.7-15.9), favoring HPV-negative patients. Greater tumor CD3+/CD8+ T cell infiltration trended with improved outcomes. Conclusion(s): We report a favorable response rate when combining a selective PI3K pathway inhibitor and taxane in patients with anti-PD-1 refractory HNSCC. ClinicalTrials.gov: NCT05057247
Oral probiotic extracellular vesicle therapy mitigates Influenza A Virus infection via blunting IL-17 signaling
Authors: Hongxia Zhou, Wenbo Huang, Jieting Li, Peier Chen, Lihan Shen, Wenjing Huang, Kailin Mai, Heyan Zou, Xueqin Shi, Yunceng Weng, Yuhua Liu, Zifeng Yang, Caiwen Ou
Journal: Bioactive Materials (2024)
Lung adenocarcinomas with mucinous histology: clinical, genomic, and immune microenvironment characterization and outcomes to immunotherapy-based treatments and KRASG12C inhibitors
Authors: A Di Federico, L Hong, A Elkrief, R Thummalapalli, A J Cooper, B Ricciuti, S Digumarthy, J V Alessi, P Gogia, F Pecci, M Makarem, M M Gandhi, E Garbo, A Saini, A De Giglio, V Favorito, S Scalera, L Cipriani, D Marinelli, D Haradon, T Nguyen, J Haradon, E Voligny, V Vaz, F Gelsomino, F Sperandi, B Melotti, M Ladanyi, J Zhang, D L Gibbons, J V Heymach, M Nishino, J Lindsay, S J Rodig, K Pfaff, L M Sholl, X Wang, B E Johnson, P A Jänne, N Rekhtman, M Maugeri-Saccà, R S Heist, A Ardizzoni, M M Awad, K C Arbour, A J Schoenfeld, N I Vokes, J Luo
Journal: Annals of Oncology (2024)
Evidence for a causal link between intra-pancreatic fat deposition and pancreatic cancer: A prospective cohort and Mendelian randomization study
Authors: Hajime Yamazaki, Samantha A. Streicher, Lang Wu, Shunichi Fukuhara, Róbert Wagner, Martin Heni, Steven R. Grossman, Heinz-Josef Lenz, Veronica Wendy Setiawan, Loïc Le Marchand, Brian Z. Huang
Journal: Cell Reports Medicine (2024)
Parallel gut-to-brain pathways orchestrate feeding behaviors
Authors: Hongyun Wang, Runxiang Lou, Yunfeng Wang, Liufang Hao, Qiushi Wang, Rui Li, Jiayi Su, Shuhan Liu, Xiangyu Zhou, Xinwei Gao, Qianxi Hao, Zihe Chen, Yibo Xu, Chongwei Wu, Yang Zheng, Qingchun Guo, Ling Bai
Journal: Nature Neuroscience (2024)
Discovering geroprotectors through the explainable artificial intelligence-based platform AgeXtend
Authors: Sakshi Arora, Aayushi Mittal, Subhadeep Duari, Sonam Chauhan, Nilesh Kumar Dixit, Sanjay Kumar Mohanty, Arushi Sharma, Saveena Solanki, Anmol Kumar Sharma, Vishakha Gautam, Pushpendra Singh Gahlot, Shiva Satija, Jeet Nanshi, Nikita Kapoor, Lavanya CB, Debarka Sengupta, Parul Mehrotra, Tarini Shankar Ghosh, Gaurav Ahuja
Journal: Nature Aging (2024)
Single-cell RNA sequencing of peripheral blood links cell-type-specific regulation of splicing to autoimmune and inflammatory diseases
Authors: Chi Tian, Yuntian Zhang, Yihan Tong, Kian Hong Kock, Donald Yuhui Sim, Fei Liu, Jiaqi Dong, Zhixuan Jing, Wenjing Wang, Junbin Gao, Le Min Tan, Kyung Yeon Han, Yoshihiko Tomofuji, Masahiro Nakano, Eliora Violain Buyamin, Radhika Sonthalia, Yoshinari Ando, Hiroaki Hatano, Kyuto Sonehara, Xin Jin, Marie Loh, John Chambers, Chung-Chau Hon, Murim Choi, Jong-Eun Park, Kazuyoshi Ishigaki, Tomohisa Okamura, Keishi Fujio, Yukinori Okada, Woong-Yang Park, Jay W Shin, Xavier Roca, Shyam Prabhakar, Boxiang Liu
Journal: Nature Genetics (2024)

Alternative splicing contributes to complex traits, but whether this differs in trait-relevant cell types across diverse genetic ancestries is unclear. Here we describe cell-type-specific, sex-biased and ancestry-biased alternative splicing in ~1 M peripheral blood mononuclear cells from 474 healthy donors from the Asian Immune Diversity Atlas. We identify widespread sex-biased and ancestry-biased differential splicing, most of which is cell-type-specific. We identify 11,577 independent cis-splicing quantitative trait loci (sQTLs), 607 trans-sGenes and 107 dynamic sQTLs. Colocalization between cis-eQTLs and trans-sQTLs revealed a cell-type-specific regulatory relationship between HNRNPLL and PTPRC. We observed an enrichment of cis-sQTL effects in autoimmune and inflammatory disease heritability. Specifically, we functionally validated an Asian-specific sQTL disrupting the 5′ splice site of TCHP exon 4 that putatively modulates the risk of Graves' disease in East Asian populations. Our work highlights the impact of ancestral diversity on splicing and provides a roadmap to dissect its role in complex diseases at single-cell resolution. This analysis of single-cell RNA sequencing data from peripheral blood mononuclear cells for 474 individuals of diverse Asian ancestries in the Asian Immune Diversity Atlas links cell-type-specific splicing variation with autoimmune and inflammatory disease risk.
Molecular connectomics reveals a glucagon-like peptide 1-sensitive neural circuit for satiety
Authors: Addison N. Webster, Jordan J. Becker, Chia Li, Dana C. Schwalbe, Damien Kerspern, Eva O. Karolczak, Catherine B. Bundon, Roberta A. Onoharigho, Maisie Crook, Maira Jalil, Elizabeth N. Godschall, Emily G. Dame, Adam Dawer, Dylan Matthew Belmont-Rausch, Tune H. Pers, Andrew Lutas, Naomi Habib, Ali D. Güler, Michael J. Krashes, John N. Campbell
Journal: Nature Metabolism (2024)
Unique structural configuration of EV-DNA primes Kupffer cell-mediated antitumor immunity to prevent metastatic progression
Authors: Inbal Wortzel, Yura Seo, Ife Akano, Lee Shaashua, Gabriel Cardial Tobias, Jakob Hebert, Kyung-A Kim, DooA Kim, Shani Dror, Yanshen Liu, Griffin Campbell Azrak, Michele Cioffi, Kofi Ennu Johnson, Tammy Hennika, Meshulam Zisha Twerski, Alexis Kushner, Robert Math, Yoon Dae Han, Dai Hoon Han, Minsun Jung, Juyeong Park, Soonmyung Paik, Jeon-Soo Shin, Min Goo Lee, Marco Vincenzo Russo, Daniel Zakheim, Jesse Barnes, Sunjoy Mehta, Katia Manova, Robert E Schwartz, Basant Kumar Thakur, Nancy Boudreau, Irina Matei, Haiying Zhang, Simone Sidoli, Jacqueline Bromberg, Yael David, Han Sang Kim, David Lyden
Journal: Nature Cancer (2024)
CD33-CD123 IF-THEN gating reduces toxicity while enhancing the specificity and memory phenotype of AML-targeting CAR-T cells
Authors: Samy Jambon, Jianping Sun, Shawn Barman, Sakunthala Muthugounder, Xue Rachel. Bito, Armita Shadfar, Alexandra E. Kovach, Brent L. Wood, Varsha Thoppey Manoharan, A. Sorana Morrissy, Deepa Bhojwani, Alan S. Wayne, Michael A. Pulsipher, Yong-Mi Kim, Shahab Asgharzadeh, Chintan Parekh, Babak Moghimi
Journal: Blood Cancer Discovery (2024)

Abstract CAR T-cell therapy has remarkably succeeded in treating lymphoblastic leukemia. However, its success in AML remains elusive due to the risk of on-target off-tumor toxicity to hematopoietic stem and progenitor cells (HSPC) and insufficient T-cell persistence and longevity. Using a SynNotch circuit, we generated a high-precision “IF-THEN” gated logical circuit against the combination of CD33 and CD123 AML antigens and demonstrated anti-tumor efficacy against AML cell lines and patient-derived xenografts. Unlike constitutively expressed CD123 CAR-T cells, those expressed through the CD33 SynNotch circuit could preserve HSPCs and lower the risk of on-target off-tumor hematopoietic toxicity. These gated CAR-T cells exhibited lower expression of exhaustion markers (PD1, Tim3, LAG3, and CD39), higher frequency of memory T cells (CD62L+CD45RA+), and enhanced expansion. While targeting AML, the moderated circuit CAR signal also helped to mitigate cytokine release syndrome, potentially addressing one of the ongoing challenges in CAR-T immunotherapy.
Clinical features in patients with severe Alpha-1 antitrypsin deficiency due to rare genotypes
Authors: Ilaria Ferrarotti, Davide Piloni, Asia Filosa, Stefania Ottaviani, Valentina Barzon, Alice Maria Balderacchi, Luciano Corda, Christine Seebacher, Sara Magni, Francesca Mariani, Paolo Baderna, Paola Confalonieri, Leonardo Iannacci, Silvia Mancinelli, Paola Putignano, Carlo Albera, Giulia Maria Stella, Maria Cristina Monti, Angelo Guido Corsico
Journal: Pulmonology (2024)

Alpha-1 Antitrypsin Deficiency (AATD) is a co-dominant condition associated with an increased risk of lung and liver disease. Since it is commonly thought that 95% of severe cases of AATD have PI*ZZ genotype, most studies about AATD have been focused on the Z variant. Nevertheless, over 500 single nucleotide variations in the SERPINA1 gene have been identified. We investigated the clinical presentation of subjects with severe AAT deficiency due to rare genotypes of the SERPINA1 gene. We enrolled patients from the Italian Registry for AATD (RIDA1) with the following inclusion criteria: diagnosis of severe AATD; age >18 years; full clinical data available at diagnosis; three years of follow-up respiratory function data. A total of 281 patients were enrolled from the RIDA1 Registry and subdivided into 3 cohorts: PI*ZZ genotype (n = 160), PI*SZ genotype (n = 54), and rare genotypes PI*R (n = 67). We did not observe any statistical differences among the cohorts regarding sex, smoking habits, occupational exposure and age at diagnosis. Patients with severe AATD due to rare genotypes have clinical characteristics and respiratory profiles similar to PI*ZZ subjects, and differed from the PI*SZ patient group. Early and accurate diagnosis of PI*R subjects is therefore important for their appropriate clinical management.
Impact of Smokeless Oral Nicotine Products on Cardiovascular Disease: Implications for Policy, Prevention, and Treatment: A Policy Statement From the American Heart Association
Authors: Cheryl R. Dennison Himmelfarb, Neal L. Benowitz, Melissa D. Blank, Aruni Bhatnagar, Paul J. Chase, Esa M. Davis, Jessica L. Fetterman, Brittney Keller-Hamilton, Oluwabunmi Ogungbe, Robert L. Page, Mary Rezk-Hanna, Rose Marie Robertson, Laurie P. Whitsel
Journal: Circulation (2024)

Smokeless oral nicotine products are addictive, and their use has potential adverse effects on some but not all biomarkers of cardiovascular risk. The use of some types of these products, for instance, is associated with an increased mortality risk in those with ischemic heart or cerebrovascular disease. Similarly, smokeless tobacco has the potential to increase the risk of oral cancer, but the risks depend on the chemical composition of the product. The market of smokeless oral nicotine products has transformed since the last American Heart Association smokeless tobacco policy statement. Several varieties of tobacco-free oral nicotine products—including oral nicotine pouches; nontherapeutic nicotine gums, lozenges, and tablets; and nicotine gummies—have rapidly proliferated. The sales of oral nicotine pouches, in particular, have increased substantially; however, no data are available on their cardiovascular or health risks. In addition, synthetic (compared with tobacco-derived) nicotine has been used in some brands of oral nicotine products, but its cardiovascular and health effects have been inadequately studied. Robust public policy levers are identified to support ending addiction to all commercial tobacco products. Critical components and policy initiatives include clinicians emphasizing the prevention of tobacco product initiation and supporting cessation with established pharmacological and behavioral tobacco dependence treatment therapies as primary goals for achieving an end to commercial tobacco and nicotine addiction.