tbuckley/cabot-search huggingface dataset:
Hepatic lipopolysaccharide binding protein partially uncouples inflammation from fibrosis in MAFLD
Authors: Dan Wang, Ania Baghoomian, Zhengyi Zhang, Ya Cui, Emily C. Whang, Xiang Li, Josue Fraga, Rachel Ariana Spellman, Tien S. Dong, Wei Li, Arpana Gupta, Jihane N. Benhammou, Tamer Sallam
Journal: Journal of Clinical Investigation (2024)
CRISPR-mediated ablation of TP53 and EGFR mutations enhances gefitinib sensitivity and anti-tumor efficacy in a mouse model of lung cancer
Authors: A-Rum Yoon, Soyeon Lee, Ju Hee Kim, Yejin Park, Taeyoung Koo, Chae-Ok Yun
Journal: Molecular Therapy (2024)

Multiple pathogenic single-nucleotide polymorphisms (SNPs) have been identified as contributing factors in the aggravation of cancer prognosis and emergence of drug resistance in various cancers. Here, we targeted mutated EGFR and TP53 oncogenes harboring single-nucleotide missense mutations (EGFR-T790M and TP53-R273H) that are associated with gefitinib resistance. Co-delivery of adenine base editor (ABE) and EGFR- and TP53-SNP specific single-guide RNA via adenovirus (Ad) resulted in precise correction of the oncogenic mutations with high accuracy and efficiency in vitro and in vivo. Importantly, compared with a control group treated only with gefitinib, an EGFR inhibitor, co-treatment with Ad/ABE targeting SNPs in TP53 and EGFR in combination with gefitinib increased drug sensitivity and suppressed abnormal tumor growth more efficiently. Taken together, these results indicate that ABE-mediated correction of dual oncogenic SNPs can be an effective strategy for the treatment of drug-resistant cancers. Multiple pathogenic single-nucleotide polymorphisms (SNPs) have been identified as contributing factors in the aggravation of cancer prognosis and emergence of drug resistance in various cancers. Here, we targeted mutated EGFR and TP53 oncogenes harboring single-nucleotide missense mutations (EGFR-T790M and TP53-R273H) that are associated with gefitinib resistance. Co-delivery of adenine base editor (ABE) and EGFR- and TP53-SNP specific single-guide RNA via adenovirus (Ad) resulted in precise correction of the oncogenic mutations with high accuracy and efficiency in vitro and in vivo. Importantly, compared with a control group treated only with gefitinib, an EGFR inhibitor, co-treatment with Ad/ABE targeting SNPs in TP53 and EGFR in combination with gefitinib increased drug sensitivity and suppressed abnormal tumor growth more efficiently. Taken together, these results indicate that ABE-mediated correction of dual oncogenic SNPs can be an effective strategy for the treatment of drug-resistant cancers.
Specific targeting of cancer vaccines to antigen-presenting cells via an endogenous TLR2/6 ligand derived from cysteinyl-tRNA synthetase 1
Authors: Hyeong Yun Kim, Seongmin Cho, Sang Bum Kim, Ee Chan Song, Wonchul Jung, Yun Gyeong Shin, Ji Hun Suh, Jihye Choi, Ina Yoon, Uijoo Kim, Hamin Ban, Sunkyo Hwang, Jeongwon Mun, Joohee Park, Nayoung Kim, Youngjin Lee, Myung Hee Kim, Sunghoon Kim
Journal: Molecular Therapy (2024)

Cancer vaccines have been developed as a promising way to boost cancer immunity. However, their clinical potency is often limited due to the imprecise delivery of tumor antigens. To overcome this problem, we conjugated an endogenous Toll-like receptor (TLR)2/6 ligand, UNE-C1, to human papilloma virus type 16 (HPV-16)-derived peptide antigen, E7, and found that the UNE-C1-conjugated cancer vaccine (UCV) showed significantly enhanced antitumor activity in vivo compared with the noncovalent combination of UNE-C1 and E7. The combination of UCV with PD-1 blockades further augmented its therapeutic efficacy. Specifically, the conjugation of UNE-C1 to E7 enhanced its retention in inguinal draining lymph nodes, the specific delivery to dendritic cells and E7 antigen-specific T cell responses, and antitumor efficacy in vivo compared with the noncovalent combination of the two peptides. These findings suggest the potential of UNE-C1 derived from human cysteinyl-tRNA synthetase 1 as a unique vehicle for the specific delivery of cancer antigens to antigen-presenting cells via TLR2/6 for the improvement of cancer vaccines. Cancer vaccines have been developed as a promising way to boost cancer immunity. However, their clinical potency is often limited due to the imprecise delivery of tumor antigens. To overcome this problem, we conjugated an endogenous Toll-like receptor (TLR)2/6 ligand, UNE-C1, to human papilloma virus type 16 (HPV-16)-derived peptide antigen, E7, and found that the UNE-C1-conjugated cancer vaccine (UCV) showed significantly enhanced antitumor activity in vivo compared with the noncovalent combination of UNE-C1 and E7. The combination of UCV with PD-1 blockades further augmented its therapeutic efficacy. Specifically, the conjugation of UNE-C1 to E7 enhanced its retention in inguinal draining lymph nodes, the specific delivery to dendritic cells and E7 antigen-specific T cell responses, and antitumor efficacy in vivo compared with the noncovalent combination of the two peptides. These findings suggest the potential of UNE-C1 derived from human cysteinyl-tRNA synthetase 1 as a unique vehicle for the specific delivery of cancer antigens to antigen-presenting cells via TLR2/6 for the improvement of cancer vaccines.
Real-world acute toxicity and 90-day mortality in patients with stage I non-small cell lung cancer treated with stereotactic body radiotherapy.
Authors: Peter S N van Rossum, Nienke Wolfhagen, Liselotte W van Bockel, Ida E M Coremans, Corine A van Es, Annelies M van der Geest, Katrien E A De Jaeger, Barbara Wachters, Hans P Knol, Friederike L A Koppe, Jacqueline Pomp, Bart J T Reymen, Dominic A X Schinagl, Femke O B Spoelstra, Caroline J A Tissing-Tan, Max Peters, Noëlle C M G van der Voort van Zijp, Antoinet M van der Wel, Erwin M Wiegman, Robin Wijsman, Ronald A M Damhuis, José S A Belderbos
Journal: Journal of Thoracic Oncology (2024)
VAV1 as a putative therapeutic target in autoimmune and chronic inflammatory diseases
Authors: Markus F. Neurath, Leslie J. Berg
Journal: Trends in Immunology (2024)

The guanine nucleotide exchange factor (GEF) VAV1, a previously 'undruggable' protein integral to T/B lymphocyte antigen-receptor signaling, promotes actin polymerization, immunological synapse formation, T cell activation and differentiation, and cytokine production. With the development of novel modalities for targeting proteins, we hypothesize that interventions targeting VAV1 will have therapeutic potential in T and T/B cell-mediated autoimmune and chronic inflammatory diseases. This opinion is supported by recent CRISPR-Cas9 studies showing VAV1 as a key positive regulator of T cell receptor (TCR) activation and cytokine production in primary human CD4
Safety and immunogenicity of the live-attenuated hRVFV-4s vaccine against Rift Valley fever in healthy adults: a dose-escalation, placebo-controlled, first-in-human, phase 1 randomised clinical trial
Authors: Isabel Leroux-Roels, Chittappen Kandiyil Prajeeth, Amare Aregay, Niranjana Nair, Guus F Rimmelzwaan, Albert D M E Osterhaus, Simone Kardinahl, Sabrina Pelz, Stephan Bauer, Valentino D'Onofrio, Azhar Alhatemi, Bart Jacobs, Fien De Boever, Sharon Porrez, Gwenn Waerlop, Carine Punt, Bart Hendriks, Ellemieke von Mauw, Sandra van de Water, Jose Harders-Westerveen, Barry Rockx, Lucien van Keulen, Jeroen Kortekaas, Geert Leroux-Roels, Paul J Wichgers Schreur
Journal: The Lancet Infectious Diseases (2024)
Moving Forward on Understanding the Public Health Implications of Mass Violence Incidents
Authors: Erika D. Felix
Journal: JAMA Network Open (2024)

Angela D. Moreland, PhD; Caitlin Rancher, PhD; Faraday Davies, MS; Jamison Bottomley, PhD; Sandro Galea, MD, MPH, DrPH; Mohammed Abba-Aji, MBBS, MPH; Salma M. Abdalla, MBBS, MPH; Michael G. Schmidt, PhD; John E. Vena, PhD; Dean G. Kilpatrick, PhD
COVID-19 Vaccination in Early Pregnancy Not Linked to Birth Defects
Authors: Emily Harris
Journal: JAMA (2024)

Elyse O. Kharbanda, MD, MPH; Malini B. DeSilva, MD, MPH; Heather S. Lipkind, MD, MS; Paul A. Romitti, PhD; Jingyi Zhu, PhD; Kimberly K. Vesco, MD, MPH; Thomas G. Boyce, MD, MPH; Matthew F. Daley, MD; Candace C. Fuller, PhD; Darios Getahun, MD, PhD; Lisa A. Jackson, MD, MPH; Joshua T. B. Williams, MD; Ousseny Zerbo, PhD; Eric S. Weintraub, MPH; Gabriela Vazquez-Benitez, PhD
Readability and Information Quality in Cancer Information From a Free vs Paid Chatbot
Authors: David Musheyev, Alexander Pan, Preston Gross, Daniel Kamyab, Peter Kaplinsky, Mark Spivak, Marie A. Bragg, Stacy Loeb, Abdo E. Kabarriti
Journal: JAMA Network Open (2024)

Importance The mainstream use of chatbots requires a thorough investigation of their readability and quality of information. Objective To identify readability and quality differences in information between a free and paywalled chatbot cancer-related responses, and to explore if more precise prompting can mitigate any observed differences. Design, Setting, and Participants This cross-sectional study compared readability and information quality of a chatbot’s free vs paywalled responses with Google Trends’ top 5 search queries associated with breast, lung, prostate, colorectal, and skin cancers from January 1, 2021, to January 1, 2023. Data were extracted from the search tracker, and responses were produced by free and paywalled ChatGPT. Data were analyzed from December 20, 2023, to January 15, 2024. Exposures Free vs paywalled chatbot outputs with and without prompt: “Explain the following at a sixth grade reading level: [nonprompted input].” Main Outcomes and Measures The primary outcome measured the readability of a chatbot’s responses using Flesch Reading Ease scores (0 [graduate reading level] to 100 [easy fifth grade reading level]). Secondary outcomes included assessing consumer health information quality with the validated DISCERN instrument (overall score from 1 [low quality] to 5 [high quality]) for each response. Scores were compared between the 2 chatbot models with and without prompting. Results This study evaluated 100 chatbot responses. Nonprompted free chatbot responses had lower readability (median [IQR] Flesh Reading ease scores, 52.60 [44.54-61.46]) than nonprompted paywalled chatbot responses (62.48 [54.83-68.40]) ( P &amp;amp;lt; .05). However, prompting the free chatbot to reword responses at a sixth grade reading level was associated with increased reading ease scores than the paywalled chatbot nonprompted responses (median [IQR], 71.55 [68.20-78.99]) ( P &amp;amp;lt; .001). Prompting was associated with increases in reading ease in both free (median [IQR], 71.55 [68.20-78.99]; P &amp;amp;lt; .001)and paywalled versions (median [IQR], 75.64 [70.53-81.12]; P &amp;amp;lt; .001). There was no significant difference in overall DISCERN scores between the chatbot models, with and without prompting. Conclusions and Relevance In this cross-sectional study, paying for the chatbot was found to provide easier-to-read responses, but prompting the free version of the chatbot was associated with increased response readability without changing information quality. Educating the public on how to prompt chatbots may help promote equitable access to health information.
16α-<sup>18</sup>F-Fluoro-17β-Estradiol PET/CT—A Tool for Staging Estrogen Receptor–Expressing Breast Cancer?
Authors: Sophia R. O’Brien, Austin R. Pantel, David A. Mankoff
Journal: JAMA Network Open (2024)

Gary A. Ulaner, MD, PhD; Mel Silverstein, MD; Chaitali Nangia, MD; Merry Tetef, MD; Louis Vandermolen, MD; Colleen Coleman, MD; Sadia Khan, MD; Heather MacDonald, MD; Trushar Patel, MD; Tust Techasith, MD; Audrey Mauguen, PhD
CITED4 gene therapy protects against maladaptive cardiac remodeling after ischemia/reperfusion injury in mice
Authors: Carolin Lerchenmüller, Margaret H Hastings, Charles P Rabolli, Fynn Betge, Mani Roshan, Laura X Liu, Xiaojun Liu, Chiara Heß, Jason D Roh, Colin Platt, Vassilios Bezzerides, Martin Busch, Hugo A Katus, Norbert Frey, Patrick Most, Anthony Rosenzweig
Journal: Molecular Therapy (2024)
Altmetric Attention Scores and Citations of Published Research With or Without Preprints
Authors: Seth Zissette, Anant Gautam, Harlan M. Krumholz, Joseph S. Ross, Joshua D. Wallach
Journal: JAMA Network Open (2024)

This cross-sectional study assesses how frequently research articles published in the clinical journals with high impact factors are preprinted and whether preprinting is associated with changes in media attention and citation counts.
Monetary Incentives May Improve Chances of Quitting Smoking
Authors: Emily Harris
Journal: JAMA (2024)

Darla E. Kendzor, PhD; Michael S. Businelle, PhD; Summer G. Frank-Pearce, PhD; Joseph J. C. Waring, MPH; Sixia Chen, PhD; Emily T. Hébert, DrPH; Michael D. Swartz, PhD; Adam C. Alexander, PhD; Munjireen S. Sifat, PhD; Laili Kharazi Boozary, PhD; David W. Wetter, PhD
Designing Prefaculty Competencies for Diverse Learners Through a Modified Delphi Process
Authors: Rosa Lee, Raymond Lucas, Joel Dickerman, Lukejohn W. Day, Daniel Guzman, Pooja Kothari, LaTanya Love, William McDade, Ashley Rodgers, Monica Verduzco-Gutierrez, Lindy Zhang, John Paul Sánchez
Journal: JAMA Network Open (2024)

Faculty diversity in academic medicine may better prepare the next generation of equity-minded health care practitioners and leaders. Prefaculty development is an emerging concept to support trainees in achieving key knowledge, skills, and experiences to become successful faculty.
Lowering Nicotine Levels to Reduce Dependence on E-Cigarettes—Promising yet Complicated
Authors: Mark W. Vander Weg
Journal: JAMA Network Open (2024)

Tarana Ferdous, MPH; Simanta Roy, MPH; Sreshtha Chowdhury, MPH; Rime Jebai, PhD; Leonardo Maya, MS; Anthony P. DeCaprio, PhD; Zoran Bursac, PhD; Wasim Maziak, PhD
Site-specific therapy guided by a 90-gene expression assay versus empirical chemotherapy in patients with cancer of unknown primary (Fudan CUP-001): a randomised controlled trial
Authors: Xin Liu, Xiaowei Zhang, Shiyu Jiang, Miao Mo, Qifeng Wang, Yanli Wang, Liangping Zhou, Silong Hu, Huijuan Yang, Yifeng Hou, Yong Chen, Xueguan Lu, Yu Wang, Xiaoyan Zhou, Wentao Li, Cai Chang, Xiujiang Yang, Ke Chen, Jun Cao, Qinghua Xu, Yifeng Sun, Jianfeng Luo, Zhiguo Luo, Xichun Hu
Journal: The Lancet Oncology (2024)
Feasibility of a Serious Illness Communication Program for Pediatric Advance Care Planning
Authors: Danielle D. DeCourcey, Rachelle E. Bernacki, Brett Nava-Coulter, Sithya Lach, Niya Xiong, Joanne Wolfe
Journal: JAMA Network Open (2024)

Importance Pediatric advance care planning (ACP), which aims to ensure care is aligned with family goals and values, is associated with better end-of-life outcomes; however, ACP in pediatrics remains uncommon. Objectives To determine the feasibility and acceptability of the Pediatric Serious Illness Communication Program (PediSICP) and explore family-centered outcomes. Design, Setting, and Participants This cohort study was a single-group pilot study of the PediSICP in adolescents and young adults (AYAs; age ≥13 y) with serious illness, parents of seriously ill children, and interprofessional clinicians from April 2021 to March 2023 in a quaternary care pediatric hospital. Duration of follow-up was 1 month. Data were analyzed from January 2022 to March 2023. Exposure The PediSICP includes clinician training preceding an ACP communication occasion supported by communication guides and a template for electronic medical record documentation. Main Outcomes and Measures Outcomes of interest were parent, patient, and clinician experiences with and perceptions of the PediSICP. Feasibility was defined a priori as at least 70% clinician intervention completion rates. Results A total of 10 virtual trainings were conducted among 40 clinicians, including 27 physicians, 7 nurse practitioners, 5 nurses, and 1 respiratory therapist, and 30 trained clinicians (75%) conducted and documented 42 ACP conversations with 33 parents (median [IQR] age, 43 [35-51] years; 25 [76%] female) and 5 AYAs (median [IQR] age, 19 [17-19] years; 3 [60%] female) who completed the intervention. The median (IQR) conversation duration was 27 (10-45) minutes. Most clinicians (29 clinicians [97%]) agreed that they felt prepared for the conversation, and all clinicians recommended the PediSICP. Parents reported participation was worthwhile (27 parents [84%]), they felt listened to (31 parents [94%]), and would recommend the PediSICP (28 parents [85%]). Parents endorsed higher therapeutic alliance after the PediSICP intervention compared with before (The Human Connection scale mean [SD] score, 57.6 [6.4] vs 55.3 [7.8]; P = .03) and decreased anxiety immediately after the intervention (Generalized Anxiety Disorder–7-item mean [SD] score, 10.1 [7.3] vs 8.4 [6.9]; P = .003), which persisted at the 1-month follow-up (mean [SD] score, 7.7 [6.8]; P = .03). Conclusions and Relevance This pilot cohort study found that the PediSICP was feasible, acceptable, and highly valued by clinicians and parents of children with serious illness. These findings suggest that the PediSICP may empower interprofessional clinicians and improve ACP with families of children and AYAs who are seriously ill.
ER-Targeted PET for Initial Staging and Suspected Recurrence in ER-Positive Breast Cancer
Authors: Gary A. Ulaner, Mel Silverstein, Chaitali Nangia, Merry Tetef, Louis Vandermolen, Colleen Coleman, Sadia Khan, Heather MacDonald, Trushar Patel, Tust Techasith, Audrey Mauguen
Journal: JAMA Network Open (2024)

Importance There are insufficient data comparing 16α- 18 F-fluoro-17β-estradiol (FES) positron emission tomography (PET) computed tomography (CT) with standard-of-care imaging (SOC) for staging locally advanced breast cancer (LABC) or evaluating suspected recurrence. Objective To determine the detection rate of FES PET/CT and SOC for distant metastases in patients with estrogen receptor (ER)-positive LABC and recurrences in patients with ER-positive BC and suspected recurrence. Design, Setting, and Participants This diagnostic study was conducted as a single-center phase 2 trial, from January 2021 to September 2023. The study design provided 80% power to find a 20% detection rate difference. Participants included patients with ER-positive LABC (cohort 1) or suspected recurrence (cohort 2). Data were analyzed from September 2023 to February 2024. Exposure Participants underwent both SOC imaging and experimental FES PET/CT. When there were suspicious lesions on imaging, 1 was biopsied for histopathological reference standard to confirm presence (true positive) or absence (false positive) of malignant neoplasm. Main Outcomes and Measures The outcome of interest was the detection rate of FES PET CT vs SOC for distant metastases and recurrences. Results A total of 124 patients were accrued, with 62 in cohort 1 (median [IQR] age, 52 [32-84] years) and 62 in cohort 2 (median [IQR] age, 66 [30-93] years). In cohort 1, of 14 true-positive findings, SOC imaging detected 12 and FES detected 11 ( P &amp;amp;gt; .99). In cohort 2, of 23 true-positive findings, SOC detected 16 and FES detected 18 ( P = .77). In 30 patients with lobular histology, of 11 true-positive findings, SOC detected 5 and FES detected 9 ( P = .29). There were 6 false-positive findings on SOC and 1 false-positive finding on FES PET/CT ( P = .13). Conclusions and Relevance In this diagnostic study with pathological findings as the reference standard, no difference was found between FES PET/CT and current SOC imaging for detecting distant metastases in patients with ER-positive LABC or recurrences in patients with ER-positive tumors and suspected recurrence. FES PET/CT could be considered for both clinical indications, which are not part of current Appropriate Use Criteria for FES PET. The findings regarding FES PET/CT in patients with lobular tumors, and for lower false positives than current SOC imaging, warrant further investigation.
Posttraumatic Stress Disorder Among Adults in Communities With Mass Violence Incidents
Authors: Angela D. Moreland, Caitlin Rancher, Faraday Davies, Jamison Bottomley, Sandro Galea, Mohammed Abba-Aji, Salma M. Abdalla, Michael G. Schmidt, John E. Vena, Dean G. Kilpatrick
Journal: JAMA Network Open (2024)

Mass violence incidents (MVIs) are prevalent in the US and can have profound and long-lasting psychological consequences on direct survivors, but their outcomes among the broader communities where the MVI occurred are unknown.
Ipatasertib plus Paclitaxel for patients with <i>PIK3CA</i>/<i>AKT1</i>/<i>PTEN</i>-Altered Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer in the IPATunity130 Phase III Trial
Authors: Rebecca A. Dent, Sung-Bae Kim, Mafalda Oliveira, Carlos Barrios, Joyce O’Shaughnessy, Steven J. Isakoff, Shigehira Saji, Ruffo Freitas-Junior, Manuel Philco, Igor Bondarenko, Qinshu Lian, Denise Bradley, Heather Hinton, Matthew J. Wongchenko, Sarah-Jayne Reilly, Nicholas Turner
Journal: Clinical Cancer Research (2024)

Abstract Purpose: In the randomized phase II LOTUS trial, combining ipatasertib with first-line paclitaxel for triple-negative breast cancer (TNBC) improved progression-free survival (PFS), particularly in patients with PIK3CA/AKT1/PTEN-altered tumors. We aimed to validate these findings in a biomarker-selected TNBC population. Patients and Methods: In Cohort A of the randomized double-blind placebo-controlled phase III IPATunity130 trial, taxane-eligible patients with PIK3CA/AKT1/PTEN-altered measurable advanced TNBC and no prior chemotherapy for advanced disease were randomized 2:1 to ipatasertib (400 mg, days 1–21) or placebo, both plus paclitaxel (80 mg/m2, days 1, 8, and 15), every 28 days until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed PFS. Results: Between February 2018 and April 2020, 255 patients were randomized (168 to ipatasertib, 87 to placebo). At the primary analysis, there was no significant difference between treatment arms in PFS [hazard ratio 1.02, 95% confidence interval (CI), 0.71–1.45; median 7.4 months with ipatasertib vs. 6.1 months with placebo]. The final analysis showed no difference in overall survival between treatment arms (hazard ratio 1.08, 95% CI, 0.73–1.58; median 24.4 vs. 24.9 months, respectively). Ipatasertib was associated with more grade ≥3 diarrhea (9% vs. 2%) and adverse events leading to dose reduction (39% vs. 14%) but similar incidences of grade ≥3 adverse events (51% vs. 46%). Exploratory subgroup analyses by PAM50 and Burstein gene expression showed inconsistent results. Conclusions: Adding ipatasertib to paclitaxel did not improve efficacy in PIK3CA/AKT1/PTEN-altered advanced TNBC. Biomarkers for benefit from PI3K/AKT pathway inhibition in TNBC remain poorly understood.