tbuckley/cabot-search huggingface dataset:
Exploiting LRRC15 as a Novel Therapeutic Target in Cancer
Authors: Upasana Ray, Christopher L. Pathoulas, Prabhu Thirusangu, James W. Purcell, Nagarajan Kannan, Viji Shridhar
Journal: Cancer Research (2022)

Abstract Abundant fibrotic stroma is a typical feature of most solid tumors, and stromal activation promotes oncogenesis, therapy resistance, and metastatic dissemination of cancer cells. Therefore, targeting the tumor stroma in combination with standard-of-care therapies has become a promising therapeutic strategy in recent years. The leucine-rich repeat-containing protein 15 (LRRC15) is involved in cell–cell and cell–matrix interactions and came into focus as a promising anticancer target owing to its overexpression in mesenchymal-derived tumors such as sarcoma, glioblastoma, and melanoma and in cancer-associated fibroblasts in the microenvironment of breast, head and neck, lung, and pancreatic tumors. Effective targeting of LRRC15 using specific antibody–drug conjugates (ADC) has the potential to improve the outcome of patients with LRRC15-positive (LRRC15+) cancers of mesenchymal origin or stromal desmoplasia. Moreover, LRRC15 expression may serve as a predictive biomarker that could be utilized in the preclinical assessment of cancer patients to support personalized clinical outcomes. This review focuses on the role of LRRC15 in cancer, including clinical trials involving LRRC15-targeted therapies, such as the ABBV-085 ADC for patients with LRRC15+ tumors. This review spans perceived knowledge gaps and highlights the clinical avenues that need to be explored to provide better therapeutic outcomes in patients.
Detection of Barrett’s neoplasia with a near-infrared fluorescent heterodimeric peptide
Authors: Jing Chen, Yang Jiang, Tse-Shao Chang, Joel H. Rubenstein, Richard S. Kwon, Erik J. Wamsteker, Anoop Prabhu, Lili Zhao, Henry D. Appelman, Scott R. Owens, David G. Beer, D. Kim Turgeon, Eric J. Seibel, Thomas D. Wang
Journal: Endoscopy (2022)

Esophageal adenocarcinoma (EAC) is a molecularly heterogeneous disease with poor prognosis that is rising rapidly in incidence. We aimed to demonstrate specific binding by a peptide heterodimer to Barrett's neoplasia in human subjects.Peptide monomers specific for EGFR and ErbB2 were arranged in a heterodimer configuration and labeled with IRDye800. This near-infrared (NIR) contrast agent was topically administered to patients with Barrett's esophagus (BE) undergoing either endoscopic therapy or surveillance. Fluorescence images were collected using a flexible fiber accessory passed through the instrument channel of an upper gastrointestinal endoscope. Fluorescence images were collected from 31 BE patients. A deep learning model was used to segment the target (T) and background (B) regions.The mean target-to-background (T/B) ratio was significantly greater for high grade dysplasia (HGD) and EAC versus BE, low grade dysplasia (LGD), and squamous epithelium. At a T/B ratio of 1.5, sensitivity and specificity of 94.1 % and 92.6 %, respectively, were achieved for the detection of Barrett's neoplasia with an area under the curve of 0.95. No adverse events attributed to the heterodimer were found. EGFR and ErbB2 expression were validated in the resected specimens.This "first-in-human" clinical study demonstrates the feasibility of detection of early Barrett's neoplasia using a NIR-labeled peptide heterodimer.
A Different Case of Penumbra
Authors: Haruko Yamamoto, Tetsuya Kusakabe, Mimei Takahashi
Journal: JAMA Internal Medicine (2022)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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 Internal Medicine journal
FDG PET/MRI of Acute Myocarditis After mRNA COVID-19 Vaccination
Authors: Chan-Hee Lee, Eun-Jung Kong
Journal: Clinical Nuclear Medicine (2022)

A 22-year-old man visited the emergency department with chest pain. He had received a second dose of the coronavirus disease 2019 (COVID-19) mRNA (Moderna) vaccine 5 days prior. 18F-FDG PET/MR revealed a focal FDG uptake and late gadolinium enhancement on the basal posterolateral wall of the left ventricle. Myocarditis after a COVID-19 vaccination has been reported predominantly after the second dose of mRNA vaccines in young men. This was a case of acute focal myocarditis after a COVID-19 mRNA vaccination, which was well-visualized by FDG PET/MRI.
Association of Early Adulthood 25-Year Blood Pressure Trajectories With Cerebral Lesions and Brain Structure in Midlife
Authors: Yi-Han Hu, Michael R. Halstead, R. Nick Bryan, Pamela J. Schreiner, David R. Jacobs, Stephen Sidney, Cora E. Lewis, Lenore J. Launer
Journal: JAMA Network Open (2022)

Midlife elevated blood pressure (BP) is an important risk factor associated with brain structure and function. Little is known about trajectories of BP that modulate this risk.To identify BP trajectory patterns from young adulthood to midlife that are associated with brain structure in midlife.This cohort study used data of US adults from Coronary Artery Risk Development in Young Adults (CARDIA), a prospective longitudinal study of Black and White men and women (baseline age 18 to 30 years) examined up to 8 times over 30 years (1985-1986 to 2015-2016). There were 885 participants who underwent brain magnetic resonance imaging (MRI) in the 25th or 30th year examinations. Analyses were conducted November 2019 to December 2020.Using group-based trajectory modeling, 5 25-year BP trajectories for 3 BP traits were identified in the total CARDIA cohort of participants with 3 or more BP measures, which were then applied to analyses of the subset of 853 participants in the Brain MRI substudy. Mean arterial pressure (MAP) was examined as an integrative measure of systolic and diastolic BP. With linear regression, the associations of the BP trajectories with brain structures were examined, adjusting sequentially for demographics, cardiovascular risk factors, and antihypertensive medication use.Brain MRI outcomes include total brain, total gray matter, normal-looking and abnormal white matter volumes, gray matter cerebral blood flow, and white matter fractional anisotropy.Brain MRI analyses were conducted on 853 participants (mean [SD] age, 50.3 [3.6] years; 399 [46.8%] men; 354 [41.5%] Black and 499 [58.5%] White individuals). The MAP trajectory distribution was 187 individuals (21.1%) with low-stable, 385 (43.5%) with moderate-gradual, 71 (8.0%) with moderate-increasing, 204 (23.1%) with elevated-stable, and 38 (4.3%) with elevated-increasing. Compared with the MAP low-stable trajectory group, individuals in the moderate-increasing and elevated-increasing groups were more likely to have higher abnormal white matter volume (moderate: β, 0.52; 95% CI, 0.23 to 0.82; elevated: β, 0.57; 95% CI, 0.19 to 0.95). Those in the MAP elevated-increasing group had lower gray matter cerebral blood flow (β, -0.42; 95% CI, -0.79 to -0.05) after adjusting for sociodemographics and cardiovascular risk factors. After adjustment for antihypertensive medication use, the difference was consistent for abnormal white matter volume, but results were no longer significant for gray matter cerebral blood flow.Among young adults with moderate to high levels of BP, a gradual increase in BP to middle-age may increase the risk in diffuse small vessel disease and lower brain perfusion.
Provocative Hyperventilation in a Patient With Stroke-Like Migraine Attacks After Radiation Therapy
Authors: Yonatan Serlin, Mohammed Alshahrani, Birgit Frauscher
Journal: JAMA Neurology (2022)

This case report describes a patient with stroke-like migraine attacks after radiation therapy with recurrent and transient neurological deficits in whom provocative hyperventilation during routine electroencephalography was key for the diagnosis of seizures.
UNEXPLAINED LEFT VENTRICULAR DYSFUNCTION: HOW IS CORONARY ANGIOGRAPHY USEFUL TODAY?
Authors: Louis-Marie Desroche, Thiziri Si Moussi, Gregory Ducrocq, Damien Mandry, Isabelle Zaleski, Damien Millischer, Olivier Milleron, Olivier Huttin, Mathieu Valla, Loic Belle, Yoan Lavie-Badie, Bruno Farah, Christelle Diakov, Damien Logeart, Reza Rossanaly Vasram, Benjamin Safar, Jean-Yves Travers, Arthur Darmon, Toni Alfaiate, Charles Burdet, Guillaume Jondeau
Journal: Journal of the American College of Cardiology (2022)
Assessment of Myocardial Stiffness in Patients With Left Ventricular Hypertrophy
Authors: Emma Burnhope, Alessandro Polcaro, Jurgen H. Runge, Inka Granlund, Filippo Bosio, Marian A. Troelstra, Adriana D.M. Villa, Amedeo Chiribiri, Gerald Carr-White, Jessica Webb, Reza Razavi, Jordi Martorell, Ralph Sinkus, Tevfik F. Ismail
Journal: JACC. Cardiovascular imaging (2022)
Associations between ambient temperature and enteric infections by pathogen: a systematic review and meta-analysis
Authors: Paul L C Chua, Chris Fook Sheng Ng, Aurelio Tobias, Xerxes T Seposo, Masahiro Hashizume
Journal: The Lancet Planetary Health (2022)

BackgroundNumerous studies have quantified the associations between ambient temperature and enteric infections, particularly all-cause enteric infections. However, the temperature sensitivity of enteric infections might be pathogen dependent. Here, we sought to identify pathogen-specific associations between ambient temperature and enteric infections.MethodsWe did a systematic review and meta-analysis by searching PubMed, Web of Science, and Scopus for peer-reviewed research articles published from Jan 1, 2000, to Dec 31, 2019, and also hand searched reference lists of included articles and excluded reviews. We included studies that quantified the effects of ambient temperature increases on common pathogen-specific enteric infections in humans. We excluded studies that expressed ambient temperature as a categorical or diurnal range, or in a standardised format. Two authors screened the search results, one author extracted data from eligible studies, and four authors verified the data. We obtained the overall risks by pooling the relative risks of enteric infection by pathogen for each 1°C temperature rise using random-effects modelling and robust variance estimation for the correlated effect estimates. Between-study heterogeneity was measured using I2, τ2, and Q-statistic. Publication bias was determined using funnel plot asymmetry and the trim-and-fill method. Differences among pathogen-specific pooled estimates were determined using subgroup analysis of taxa-specific meta-analysis. The study protocol was not registered but followed the PRISMA guidelines.FindingsWe identified 2981 articles via database searches and 57 articles from scanning reference lists of excluded reviews and included articles, of which 40 were eligible for pathogen-specific meta-analyses. The overall increased risks of incidence per 1°C temperature rise, expressed as relative risks, were 1·05 (95% CI 1·04–1·07; I2 97%) for salmonellosis, 1·07 (1·04–1·10; I2 99%) for shigellosis, 1·02 (1·01–1·04; I2 98%) for campylobacteriosis, 1·05 (1·04–1·07; I2 36%) for cholera, 1·04 (1·01–1·07; I2 98%) for Escherichia coli enteritis, and 1·15 (1·07–1·24; I2 0%) for typhoid. Reduced risks per 1°C temperature increase were 0·96 (95% CI 0·90–1·02; I2 97%) for rotaviral enteritis and 0·89 (0·81–0·99; I2 96%) for noroviral enteritis. There was evidence of between-pathogen differences in risk for bacterial infections but not for viral infections.InterpretationTemperature sensitivity of enteric infections can vary according to the enteropathogen causing the infection, particularly for bacteria. Thus, we encourage a pathogen-specific health adaptation approach, such as vaccination, given the possibility of increasingly warm temperatures in the future.FundingJapan Society for the Promotion of Science (Kakenhi) Grant-in-Aid for Scientific Research.
RACE-IT- RAPID MYOCARDIAL INFARCTION EXCLUSION USING AN ACCELERATED HIGH-SENSITIVITY CARDIAC TROPONIN I PROTOCOL: A PROSPECTIVE TRIAL
Authors: James K. McCord, Bernard Cook, Chaun Gandolfo, Sachin Parikh, Howard Klausner, Khaled Abdul-Nour, Aaron Lewandowski, Michael Peter Hudson, Giuseppe S. Perrotta, Bryan Zweig, Satheesh Gunaga, David E. Lanfear, Ryan Gindi, Phillip David Levy, Nicholas L. Mills, Simon Mahler, Henry E. Kim, Shooshan Danagoulian, Amy Tang, Hashem Nassereddine, Ahmed Oudeif, Kelly Malette, Seth Krupp, Catriona Keerie, Joseph Miller
Journal: Journal of the American College of Cardiology (2022)
PULMONARY HYPERTENSION IS MORE PREVALENT IN WOMEN WITH APICAL HYPERTROPHIC CARDIOMYOPATHY
Authors: Vidhu Anand, Megan K. Covington, Ushasi Saraswati, Christopher Scott, Nandan Sadanand Anavekar, Jeffrey Benjamin Geske, Adelaide Maria Arruda-Olson, Kyle W. Klarich
Journal: Journal of the American College of Cardiology (2022)
Therapeutic targets for cardiac fibrosis: from old school to next-gen
Authors: Joshua G. Travers, Charles A. Tharp, Marcello Rubino, Timothy A. McKinsey
Journal: Journal of Clinical Investigation (2022)

Cardiovascular diseases remain the leading cause of death worldwide, with pathological fibrotic remodeling mediated by activated cardiac myofibroblasts representing a unifying theme across etiologies. Despite the profound contributions of myocardial fibrosis to cardiac dysfunction and heart failure, there currently exist limited clinical interventions that effectively target the cardiac fibroblast and its role in fibrotic tissue deposition. Exploration of novel strategies designed to mitigate or reverse myofibroblast activation and cardiac fibrosis will likely yield powerful therapeutic approaches for the treatment of multiple diseases of the heart, including heart failure with preserved or reduced ejection fraction, acute coronary syndrome, and cardiovascular disease linked to type 2 diabetes. In this Review, we provide an overview of classical regulators of cardiac fibrosis and highlight emerging, next-generation epigenetic regulatory targets that have the potential to revolutionize treatment of the expanding cardiovascular disease patient population.
DIRECT ORAL ANTICOAGULANTS VERSUS VITAMIN K ANTAGONISTS FOR THE TREATMENT OF CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Cameron Burmeister, Sami Ghazaleh, Neha Patel, Omar Sajdeya, Mohammed Mhanna, Clarissa Pena, Waleed Khokher, Sapan Bhuta, Ragheb Assaly, Ehab Ahmed Eltahawy
Journal: Journal of the American College of Cardiology (2022)
CONSCIOUSNESS EQUALS LIFE: SURVIVAL IN CARDIAC ARREST PATIENTS UNDERGOING PCI IS MARKEDLY ASSOCIATED WITH NEUROLOGICAL STATUS
Authors: Daniel Kobe, Milan Seth, David Hamilton, Manoj Sharma, Douglas J. Wunderly, David Alan Sutter, Ronald V. Miller, Thomas A. LaLonde, Hitinder S. Gurm, Devraj Sukul
Journal: Journal of the American College of Cardiology (2022)
Mantle cell lymphoma in 2022—A comprehensive update on molecular pathogenesis, risk stratification, clinical approach, and current and novel treatments
Authors: Preetesh Jain, Michael L. Wang
Journal: American Journal of Hematology (2022)

The field of mantle cell lymphoma (MCL) has witnessed remarkable progress due to relentless advances in molecular pathogenesis, prognostication, and newer treatments. MCL consists of a spectrum of clinical subtypes. Rarely, atypical cyclin D1-negative MCL and in situ MCL neoplasia are identified. Prognostication of MCL is further refined by identifying somatic mutations (such as TP53, NSD2, KMT2D), methylation status, chromatin organization pattern, SOX-11 expression, minimal residual disease (MRD), and genomic clusters. Lymphoid tissue microenvironment studies demonstrated the role of B-cell receptor signaling, nuclear factor kappa B (NF-kB), colony-stimulating factor (CSF)-1, the CD70-SOX-11 axis. Molecular mechanism of resistance, mutation dynamics, and pathogenic pathways (B-cell receptor (BCR), oxidative phosphorylation, and MYC) were identified in mediating resistance to various treatments (bruton tyrosine kinase (BTK) inhibitors [ibrutinib, acalabrutinib]. Treatment options range from conventional chemoimmunotherapy and stem cell transplantation (SCT) to targeted therapies against BTK (covalent and noncovalent), Bcl2, ROR1, cellular therapy such as anti-CD19 chimeric antigen receptor therapy (CAR-T), and most recently bispecific antibodies against CD19 and CD20. MCL patients frequently relapse. Complex pathogenesis and the management of patients with progression after treatment with BTK/Bcl2 inhibitors and CAR-T (triple-resistant MCL) remain a challenge. Next-generation clinical trials incorporating newer agents and concurrent translational and molecular investigations are ongoing.
Ruxolitinib in addition to standard of care for the treatment of patients admitted to hospital with COVID-19 (RUXCOVID): a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: MeiLan K Han, Martti Antila, Joachim H Ficker, Ivan Gordeev, Alfredo Guerreros, Amparo Lopez Bernus, Antoine Roquilly, José Sifuentes-Osornio, Fehmi Tabak, Ricardo Teijeiro, Lorraine Bandelli, Diane S Bonagura, Xu Shu, James M Felser, Barbara Knorr, Weihua Cao, Peter Langmuir, Thomas Lehmann, Michael Levine, Sinisa Savic
Journal: The Lancet Rheumatology (2022)
Association of Persistent Rubella Virus With Idiopathic Skin Granulomas in Clinically Immunocompetent Adults
Authors: Karolyn A. Wanat, Ludmila Perelygina, Min-hsin Chen, LiJuan Hao, Emily Abernathy, Nicole R. Bender, Bridget E. Shields, Barbara D. Wilson, David Crosby, John Routes, Sara S. Samimi, Paul L. Haun, Olayemi Sokumbi, Joseph P. Icenogle, Kathleen E. Sullivan, Misha Rosenbach, Beth A. Drolet
Journal: JAMA Dermatology (2022)

<h3>Importance</h3> Vaccine-derived and wild-type rubella virus (RuV) has been identified within granulomas in patients with inborn errors of immunity, but has not been described in granulomas of healthy adults. <h3>Objective</h3> To determine the association between RuV and atypical granulomatous inflammation in immune-competent adults. <h3>Design, Setting, and Participants</h3> This case series, conducted in US academic dermatology clinics from January 2019 to January 2021, investigated the presence of RuV in skin specimens using RuV immunofluorescent staining of paraffin-embedded tissue sections, real-time reverse-transcription polymerase chain reaction, whole-genome sequencing with phylogenetic analyses, and cell culture by the US Centers for Disease Control and Prevention. Rubella immunoglobulin G, immunoglobulin M enzyme-linked immunoassay, and viral neutralization assays were performed for the sera of immunocompetent individuals with treatment refractory cutaneous granulomas and histopathology demonstrating atypical palisaded and necrotizing granulomas. Clinical immune evaluation was performed. <h3>Main Outcomes and Measures</h3> Identification, genotyping, and culture of vaccine-derived and wild-type RuV within granulomatous dermatitis of otherwise clinically immune competent adults. <h3>Results</h3> Of the 4 total immunocompetent participants, 3 (75%) were women, and the mean (range) age was 61.5 (49.0-73.0) years. The RuV capsid protein was detected by immunohistochemistry in cutaneous granulomas. The presence of RuV RNA was confirmed by real-time reverse-transcription polymerase chain reaction in fresh-frozen skin biopsies and whole-genome sequencing. Phylogenetic analysis of the RuV sequences showed vaccine-derived RuV in 3 cases and wild-type RuV in 1. Live RuV was recovered from the affected skin in 2 participants. Immunology workup results demonstrated no primary immune deficiencies. <h3>Conclusions and Relevance</h3> The case series study results suggest that RuV (vaccine derived and wild type) can persist for years in cutaneous granulomas in clinically immunocompetent adults and is associated with atypical (palisaded and necrotizing type) chronic cutaneous granulomas. These findings represent a potential paradigm shift in the evaluation, workup, and management of atypical granulomatous dermatitis and raises questions regarding the potential transmissibility of persistent live RuV.
Diversity in Surgery Residents and Unwanted Mistreatment—Reply
Authors: Cary Jo R. Schlick, Evan A. Heiderscheit, Yue-Yung Hu
Journal: JAMA Surgery (2022)

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 Surgery 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 Surgery journal
2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary
Authors: Paul A. Heidenreich, Biykem Bozkurt, David Aguilar, Larry A. Allen, Joni J. Byun, Monica M. Colvin, Anita Deswal, Mark H. Drazner, Shannon M. Dunlay, Linda R. Evers, James C. Fang, Savitri E. Fedson, Gregg C. Fonarow, Salim S. Hayek, Adrian F. Hernandez, Prateeti Khazanie, Michelle M. Kittleson, Christopher S. Lee, Mark S. Link, Carmelo A. Milano, Lorraine C. Nnacheta, Alexander T. Sandhu, Lynne Warner Stevenson, Orly Vardeny, Amanda R. Vest, Clyde W. Yancy
Journal: Journal of the American College of Cardiology (2022)
ONE-YEAR OUTCOME IN HYPOKINETIC NON-DILATED CARDIOMYOPATHY DETECTED BY CARDIAC MAGNETIC RESONANCE: IDIOPATHIC DILATED CARDIOMYOPATHY COMPARISON
Authors: Nozomu Yukimitsu, Naoyuki Yokoyama, Yoshiyuki Ikeda, Ruri Ishibashi, Shintaro Takamura, Ken Kozuma, Mina Hatsuno
Journal: Journal of the American College of Cardiology (2022)