tbuckley/cabot-search huggingface dataset:
Ten-Year Follow-up of Persons With Sun-Damaged Skin Associated With Subsequent Development of Cutaneous Squamous Cell Carcinoma
Authors: Shabnam Madani, Sangeeta Marwaha, Jennifer R. Dusendang, Stacey Alexeeff, Ngoc Pham, Elbert H. Chen, Sandra Han, Lisa J. Herrinton
Journal: JAMA Dermatology (2021)

Risk of cutaneous squamous cell carcinoma (cSCC) after the diagnosis of actinic keratosis (AK) has not been studied during long follow-up periods.To estimate the risk up to 10 years and identify risk factors for cSCC development.This longitudinal cohort study, performed from January 1, 2009, to February 29, 2020, examined Kaiser Permanente Northern California patients with AK and control patients matched 1:1 on age, sex, race/ethnicity, medical center, and date of the initial diagnosis plus 30 days in the patients with AK.Patients with AK and control participants were followed up for up to 10 years for incidence of cSCC.Incident cSCC was obtained from pathologic data, and subdistribution hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression analysis, accounting for competing risks, calendar year, demographic factors, and number of AKs.The study included 220 236 patients with AK and 220 236 matched control patients (mean [SD] age, 64.1 [12.2] years; 231 248 [52.5%] female). After losses to follow-up were accounted for, risk of cSCC increased with each year of follow-up by 1.92% (95% CI, 1.89%-1.95%) in patients with AK and 0.83% (95% CI, 0.81%-0.85%) in matched control patients (subdistribution HR, 1.90; 95% CI, 1.85-1.95). However, among patients 49 years or younger, those diagnosed with AK were nearly 7 times more likely to be diagnosed with cSCC than those without AK (HR, 6.77; 95% CI, 5.50-8.32). At 10 years, the cumulative incidence of cSCC reached 17.1% (95% CI, 16.9%-17.4%) in patients with AK and 5.7% (95% CI, 5.5%-5.9%) in control patients. Increased numbers of AKs were modestly associated with increased cSCC risk (≥15 AKs vs 1 AK: subdistribution HR, 1.89; 95% CI, 1.75-2.04). Older patients had much higher risk of cSCC than younger patients (compared with those ≤49 years of age at AK diagnosis; ≥80 years of age: subdistribution HR, 8.18; 95% CI, 7.62-8.78). Other than AK, risk factors for cSCC included older age, White race (a proxy for skin type), history of basal cell carcinoma, and male sex. Risk decreased between 2009 and 2019 (2018-2019 vs 2009-2010: subdistribution HR, 0.67; 95% CI, 0.63-0.72).The results of this longitudinal cohort study can be used to develop recommendations to increase early detection of cSCC. Additional research is needed to understand the effect of AK treatment on cSCC risk and outcomes of cSCC.
T cell and antibody kinetics delineate SARS-CoV-2 peptides mediating long-term immune responses in COVID-19 convalescent individuals
Authors: Tatjana Bilich, Annika Nelde, Jonas S. Heitmann, Yacine Maringer, Malte Roerden, Jens Bauer, Jonas Rieth, Marcel Wacker, Andreas Peter, Sebastian Hörber, David Rachfalski, Melanie Märklin, Stefan Stevanović, Hans-Georg Rammensee, Helmut R. Salih, Juliane S. Walz
Journal: Science Translational Medicine (2021)

Longitudinal analysis identifies SARS-CoV-2 peptide targets of durable memory T cell responses in COVID-19 convalescent individuals.
MA02.04 Initial Experience of Hybrid Operating Room Cone-Beam CT Guided Bronchoscopic Microwave Thermal Ablation of Peripheral Small Lung Lesions
Authors: J. Chan, C. Ng, P. Yu, K. Lim, I. Siu, E. Yuan, S. Liu, J. Choi, C.M. Chu, R. Lau
Journal: Journal of Thoracic Oncology (2021)
Another Piece of the Puzzle
Authors: William F. Jackson
Journal: Circulation Research (2021)

oronary blood flow is exquisitely regulated to match the oxidative metabolic needs of the rhythmically contracting cardiac myocytes. 1Because most of the oxygen delivered to the heart at rest is consumed by the heart in many species, increases in cardiac metabolism, over a broad range of cardiac workloads, must be met by a linear increase in blood flow. 1 The effectors of this increase in coronary blood flow are coronary resistance arteries and arterioles that progressively dilate as cardiac metabolism increases, reducing the hemodynamic resistance of the coronary circulation and producing the observed increase in coronary blood flow (supply) to meet the increased metabolic demands of the heart. 1 Despite >50 years of intense research, the details of the signaling pathways that couple myocardial oxygen demand to regulation of vascular smooth muscle tone in coronary resistance arteries and arterioles remain unclear.The studies by Ohanyan et al 2 in this issue of Circulation Research add a new piece to this puzzle by showing that coronary resistance vessel smooth muscle cell expression of functional KVβ2 (accessory units) coupled to KV1.5 voltage-gated K + channels is essential for normal metabolic regulation of blood flow in the murine heart.
MA07.04 Breathe Anew: Designing and Testing the Feasibility of a Novel Intervention for Lung Cancer Survivorship
Authors: Y. Patel, I. Churchill, K. Sullivan, M. Beauchamp, J. Wald, L. Mbuagbaw, B. Key, S. Green, P. Bieling, J. Agzarian, C. Finley, Y. Shargall, C. Fahim, W. Hanna
Journal: Journal of Thoracic Oncology (2021)
P54.02 Urethane-Induced Lung Carcinogenesis in Genetically Edited C57Bl/6 Mice with CHEK2 and GPRC5A Heterozygous Inactivating Mutations
Authors: E. Imyanitov, A. Panchenko, O. Permyakov, M. Maydin, M. Yurova, S. Aleksakhina, O. Averina, O. Grigoryeva, P. Sergiev
Journal: Journal of Thoracic Oncology (2021)
A first-generation pediatric cancer dependency map
Authors: Neekesh V. Dharia, Guillaume Kugener, Lillian M. Guenther, Clare F. Malone, Adam D. Durbin, Andrew L. Hong, Thomas P. Howard, Pratiti Bandopadhayay, Caroline S. Wechsler, Iris Fung, Allison C. Warren, Joshua M. Dempster, John M. Krill-Burger, Brenton R. Paolella, Phoebe Moh, Nishant Jha, Andrew Tang, Philip Montgomery, Jesse S. Boehm, William C. Hahn, Charles W. M. Roberts, James M. McFarland, Aviad Tsherniak, Todd R. Golub, Francisca Vazquez, Kimberly Stegmaier
Journal: Nature Genetics (2021)
Tricuspid Annulus Disjunction
Authors: Eivind W. Aabel, Monica Chivulescu, Lars A. Dejgaard, Margareth Ribe, Erik Gjertsen, Einar Hopp, Tove E. Hunt, Øyvind H. Lie, Kristina H. Haugaa
Journal: JACC. Cardiovascular imaging (2021)

This study aimed to assess whether patients with MAD also have disjunction of the tricuspid annulus. Mitral annulus disjunction (MAD) is an abnormal atrial displacement of the mitral annulus. Whether the disjunction extends to the right side of the heart is not known. In a cohort of patients with MAD, we assessed the presence of tricuspid annulus disjunction (TAD) with the use of cardiac magnetic resonance. We explored the associations between TAD and MAD characteristics and the relationship to ventricular arrhythmias (nonsustained/sustained ventricular tachycardias and aborted cardiac arrest). We included 84 patients (mean age: 48 ± 16 years; 63% female). We observed TAD in 42 (50%). Patients with TAD were older (age 52 ± 16 years vs. 43 ± 15 years; p = 0.02), had greater circumferential extent of MAD (164 ± 57° vs. 115 ± 58°; p = 0.002), greater maximum longitudinal MAD distance (9.4 ± 2.9 mm vs. 6.2 ± 2.8 mm; p < 0.001), and more frequent mitral valve prolapse (n = 39 [92%] vs. n = 24 [57%]; p < 0.001). Ventricular arrhythmias had occurred in 34 patients (41%), who were younger (age 39 ± 14 years vs. 54 ± 14 years; p < 0.001) and had lower prevalence of TAD (n = 22 [29%] vs. n = 12 [52%]; p = 0.03). TAD was not associated with ventricular arrhythmias when adjusted for age (odds ratio adjusted for age: 0.54; 95% confidence interval: 0.20 to 1.45; p = 0.22). We report for the first time the existence of right-sided annulus disjunction as a common finding in patients with MAD. TAD was associated with more severe left-sided annulus disjunction and mitral valve prolapse, but not with ventricular arrhythmias.
Performance of intensive care unit severity scoring systems across different ethnicities in the USA: a retrospective observational study
Authors: Rahuldeb Sarkar, Christopher Martin, Heather Mattie, Judy Wawira Gichoya, David J Stone, Leo Anthony Celi
Journal: The Lancet Digital Health (2021)

BackgroundDespite wide use of severity scoring systems for case-mix determination and benchmarking in the intensive care unit (ICU), the possibility of scoring bias across ethnicities has not been examined. Guidelines on the use of illness severity scores to inform triage decisions for allocation of scarce resources, such as mechanical ventilation, during the current COVID-19 pandemic warrant examination for possible bias in these models. We investigated the performance of the severity scoring systems Acute Physiology and Chronic Health Evaluation IVa (APACHE IVa), Oxford Acute Severity of Illness Score (OASIS), and Sequential Organ Failure Assessment (SOFA) across four ethnicities in two large ICU databases to identify possible ethnicity-based bias.MethodsData from the electronic ICU Collaborative Research Database (eICU-CRD) and the Medical Information Mart for Intensive Care III (MIMIC-III) database, built from patient episodes in the USA from 2014–15 and 2001–12, respectively, were analysed for score performance in Asian, Black, Hispanic, and White people after appropriate exclusions. Hospital mortality was the outcome of interest. Discrimination and calibration were determined for all three scoring systems in all four groups, using area under receiver operating characteristic (AUROC) curve for different ethnicities to assess discrimination, and standardised mortality ratio (SMR) or proxy measures to assess calibration.FindingsWe analysed 166 751 participants (122 919 eICU-CRD and 43 832 MIMIC-III). Although measurements of discrimination were significantly different among the groups (AUROC ranging from 0·86 to 0·89 [p=0·016] with APACHE IVa and from 0·75 to 0·77 [p=0·85] with OASIS), they did not display any discernible systematic patterns of bias. However, measurements of calibration indicated persistent, and in some cases statistically significant, patterns of difference between Hispanic people (SMR 0·73 with APACHE IVa and 0·64 with OASIS) and Black people (0·67 and 0·68) versus Asian people (0·77 and 0·95) and White people (0·76 and 0·81). Although calibrations were imperfect for all groups, the scores consistently showed a pattern of overpredicting mortality for Black people and Hispanic people. Similar results were seen using SOFA scores across the two databases.InterpretationThe systematic differences in calibration across ethnicities suggest that illness severity scores reflect statistical bias in their predictions of mortality.FundingThere was no specific funding for this study.
Computed Tomography–Derived 3D Modeling to Guide Sizing and Planning of Transcatheter Mitral Valve Interventions
Authors: Joris F Ooms, Dee Dee Wang, Ronak Rajani, Simon Redwood, Stephen H Little, Michael L Chuang, Jeffrey J Popma, Gry Dahle, Michael Pfeiffer, Brinder Kanda, Magali Minet, Alexander Hirsch, Ricardo P Budde, Peter P De Jaegere, Bernard Prendergast, William O'Neill, Nicolas M Van Mieghem
Journal: JACC. Cardiovascular imaging (2021)
P37.21 Improvement of PCR-Based Detection of ALK Rearrangements
Authors: N. Mitiushkina, V. Tiurin, A. Romanko, E. Preobrazhenskaya, A. Martianov, A. Ivantsov, O. Yatsuk, T. Laidus, A. Iyevleva, A. Togo, E. Imyanitov
Journal: Journal of Thoracic Oncology (2021)
Microglial PGC-1α protects against ischemic brain injury by suppressing neuroinflammation
Authors: Bin Han, Wei Jiang, Pan Cui, Kai Zheng, Chun Dang, Junjie Wang, He Li, Lin Chen, Rongxin Zhang, Qing Mei Wang, Zhenyu Ju, Junwei Hao
Journal: Genome Medicine (2021)

Abstract Background Neuroinflammation and immune responses occurring minutes to hours after stroke are associated with brain injury after acute ischemic stroke (AIS). PPARγ coactivator-1α (PGC-1α), as a master coregulator of gene expression in mitochondrial biogenesis, was found to be transiently upregulated in microglia after AIS. However, the role of microglial PGC-1α in poststroke immune modulation remains unknown. Methods PGC-1α expression in microglia from human and mouse brain samples following ischemic stroke was first determined. Subsequently, we employed transgenic mice with microglia-specific overexpression of PGC-1α for middle cerebral artery occlusion (MCAO). The morphology and gene expression profile of microglia with PGC-1α overexpression were evaluated. Downstream inflammatory cytokine production and NLRP3 activation were also determined. ChIP-Seq analysis was performed to detect PGC-1α-binding sites in microglia. Autophagic and mitophagic activity was further monitored by immunofluorescence staining. Unc-51-like autophagy activating kinase 1 (ULK1) expression was evaluated under the PGC-1α interaction with ERRα. Finally, pharmacological inhibition and genomic knockdown of ULK1 were performed to estimate the role of ULK1 in mediating mitophagic activity after ischemic stroke. Results PGC-1α expression was shortly increased after ischemic stroke, not only in human brain samples but also in mouse brain samples. Microglia-specific PGC-1α overexpressing mice exhibited significantly decreased neurologic deficits after ischemic injury, with reduced NLRP3 activation and proinflammatory cytokine production. ChIP-Seq analysis and KEGG pathway analysis revealed that mitophagy was significantly enhanced. PGC-1α significantly promoted autophagic flux and induced autolysosome formation. More specifically, the autophagic clearance of mitochondria was enhanced by PGC-1α regulation, indicating the important role of mitophagy. Pharmacological inhibition or knockdown of ULK1 expression impaired autophagic/mitophagic activity, thus abolishing the neuroprotective effects of PGC-1α. Conclusions Mechanistically, in AIS, PGC-1α promotes autophagy and mitophagy through ULK1 and reduces NLRP3 activation. Our findings indicate that microglial PGC-1α may be a promising therapeutic target for AIS.
P65.03 A Circle RNA Regulatory Axis Promotes Lung Squamous Metastasis via CDR1 Regulation of Golgi Trafficking
Authors: E. Harrison, A. Porrello, B. Bowman, A. Belanger, G. Yacovone, S. Azam, I. Windham, S. Ghosh, N. Mckenzie, T. Waugh, A. Van Swearingen, S. Cohen, J. Bear, S. Cohen, P. Massion, M. Major, C. Pecot
Journal: Journal of Thoracic Oncology (2021)
P01.04 Dynamics of Molecular Markers in EGFR-Mutated NSCLC Patients Treated with Patritumab Deruxtecan (HER3-DXd; U3-1402)
Authors: P. Jänne, C. Baik, H. Hayashi, W. Su, Z. Qi, K. Enomoto, M. Karnoub, C. Yu, Y. Qiu, H.A. Yu
Journal: Journal of Thoracic Oncology (2021)
P20.05 Oesophageal Dose Predicts on Treatment Toxicity in Patients Receiving Concurrent Chemo-Radiotherapy for Non-Small Cell Lung Cancer
Authors: C. Keogh, I. Phillips, A. Horne, K. Maclennan, A. Tufail, T. Evans, S. Campbell, D. Finn, C. Smith
Journal: Journal of Thoracic Oncology (2021)
Hsa_circ_0030042 regulates abnormal autophagy and protects atherosclerotic plaque stability by targeting eIF4A3
Authors: Fangpu Yu, Ya Zhang, Zunzhe Wang, Weigang Gong, Cheng Zhang
Journal: Theranostics (2021)

Rationale: Abnormal autophagic death of endothelial cells is detrimental to plaque structure as endothelial loss promotes lesional thrombosis. As emerging functional biomarkers, circular RNAs (circRNAs) are involved in various diseases, including cardiovascular. This study is aimed to determine the role of hsa_circ_0030042 in abnormal endothelial cell autophagy and plaque stability. Methods: circRNA sequencing and quantitative polymerase chain reaction were performed to detect hsa_circ_0030042 expression in coronary heart disease (CHD) and human umbilical vein endothelial cells (HUVECs). Transfection of stubRFP-sensGFP-LC3 adenovirus, flow cytometry, and electron microscopy were used to identify the role of hsa_circ_0030042 in ox-LDL‒induced abnormal autophagy in vitro. Bioinformatic analysis, RNA immunoprecipitation, immunofluorescence assay and other in vitro experiments were performed to elucidate the mechanism underlying hsa_circ_0030042-mediated regulation of autophagy. To evaluate the role of hsa_circ_0030042 in atherosclerotic plaques and endothelial function, we measured the carotid artery tension and performed histopathology and immunohistochemistry analysis. Results: hsa_circ_0030042 was significantly downregulated in CHD, while upon overexpression, it acted as an endogenous eukaryotic initiation factor 4A-III (eIF4A3) sponge to inhibit ox-LDL-induced abnormal autophagy of HUVECs and maintain plaque stability in vivo. Furthermore, hsa_circ_0030042 influenced autophagy by sponging eIF4A3 and blocking its recruitment to beclin1 and forkhead box O1 (FOXO1) mRNA, while hsa_circ_0030042-induced inhibition of beclin1 and FOXO1 was counteracted by eIF4A3 overexpression or decreased hsa_circ_0030042 binding. In high-fat-diet fed ApoE-/- mice, hsa_circ_0030042 also ameliorated plaque stability and counteracted eIF4A3-induced plaque instability. Conclusions: These results demonstrate a novel pathway involving hsa_circ_0030042, eIF4A3, FOXO1, and beclin1; hence, modulating their levels may be a potential therapeutic strategy against CHD.
Administering Thrombolysis for Acute Ischemic Stroke in Patients Taking Direct Oral Anticoagulants
Authors: David J. Seiffge, Duncan Wilson, Teddy Yuan-Hao Wu
Journal: JAMA Neurology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Phase I/II Trial of Exemestane, Ribociclib, and Everolimus in Women with HR+/HER2− Advanced Breast Cancer after Progression on CDK4/6 Inhibitors (TRINITI-1)
Authors: Aditya Bardia, Sara A. Hurvitz, Angela DeMichele, Amy S. Clark, Amelia Zelnak, Denise A. Yardley, Meghan Karuturi, Tara Sanft, Sibel Blau, Lowell Hart, Cynthia Ma, Hope S. Rugo, Das Purkayastha, Stacy Moulder
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Standard-of-care treatment for metastatic hormone receptor–positive (HR+), HER2-negative (HER2−) breast cancer includes endocrine therapy (ET) combined with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i). Optimal treatment after progression on CDK4/6i is unknown. The TRINITI-1 trial investigated ribociclib, a CDK4/6i that has recently demonstrated significant overall survival benefit in two phase III trials, in combination with everolimus and exemestane in patients with HR+, HER2− advanced breast cancer (ABC) after progression on a CDK4/6i. Patients and Methods: This multicenter, open-label, single-arm, phase I/II study included patients with locally advanced/metastatic HR+/HER2− breast cancer. The primary endpoint was clinical benefit rate (CBR) at week 24 among patients with ET-refractory disease with progression on a CDK4/6i. Other endpoints included safety and biomarker analysis. Results: Of 104 patients enrolled (phases I and II), 96 had prior CDK4/6i. Recommended phase II doses (all once daily days 1–28 of 28-day cycle) were ribociclib 300 mg, everolimus 2.5 mg, and exemestane 25 mg (group 1) and ribociclib 200 mg, everolimus 5 mg, and exemestane 25 mg (group 2). CBR among 95 efficacy-evaluable patients (phases I and II) at week 24 was 41.1% (95% confidence interval, 31.1–51.6), which met the primary endpoint (predetermined threshold: 10%). Common adverse events included neutropenia (69.2%) and stomatitis (40.4%). No new safety signals were observed; no grade 3/4 QTc prolongation was reported. Conclusions: Preliminary TRINITI-1 safety and efficacy results support further investigation of CDK4/6 blockade and targeting of the PI3K/AKT/mTOR signaling pathway in patients with ET-refractory HR+/HER2− ABC after progression on a CDK4/6i.
Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study
Authors: John Kuruvilla, Radhakrishnan Ramchandren, Armando Santoro, Ewa Paszkiewicz-Kozik, Robin Gasiorowski, Nathalie A Johnson, Laura Maria Fogliatto, Iara Goncalves, Jose S R de Oliveira, Valeria Buccheri, Guilherme F Perini, Neta Goldschmidt, Iryna Kriachok, Michael Dickinson, Mieczyslaw Komarnicki, Andrew McDonald, Muhit Ozcan, Naohiro Sekiguchi, Ying Zhu, Akash Nahar, Patricia Marinello, Pier Luigi Zinzani
Journal: The Lancet Oncology (2021)
Novel ultra-rare exonic variants identified in a founder population implicate cadherins in schizophrenia
Authors: Todd Lencz, Jin Yu, Raiyan Rashid Khan, Erin Flaherty, Shai Carmi, Max Lam, Danny Ben-Avraham, Nir Barzilai, Susan Bressman, Ariel Darvasi, Judy H. Cho, Lorraine N. Clark, Zeynep H. Gümüş, Joseph Vijai, Robert J. Klein, Steven Lipkin, Kenneth Offit, Harry Ostrer, Laurie J. Ozelius, Inga Peter, Anil K. Malhotra, Tom Maniatis, Gil Atzmon, Itsik Pe’er
Journal: Neuron (2021)
Review of Hearing Loss in Children
Authors: Daniel Fink
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal