tbuckley/cabot-search huggingface dataset:
Safety, Activity, and Long-term Outcomes of Pomalidomide in the Treatment of Kaposi Sarcoma among Individuals with or without HIV Infection
Authors: Ramya Ramaswami, Mark N. Polizzotto, Kathryn Lurain, Kathleen M. Wyvill, Anaida Widell, Jomy George, Priscila Goncalves, Seth M. Steinberg, Denise Whitby, Thomas S. Uldrick, Robert Yarchoan
Journal: Clinical Cancer Research (2021)

Kaposi sarcoma (KS) is caused by Kaposi sarcoma herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8). KS, which develops most frequently among people with HIV, is generally treated with chemotherapy, but these drugs have acute and cumulative toxicities. We previously described initial results of a trial of pomalidomide, an oral immunomodulatory derivative of thalidomide, in patients with KS. Here, we present results on the full cohort and survival outcomes.
2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Kawasaki Disease
Authors: Mark Gorelik, Sharon A. Chung, Kaveh Ardalan, Bryce A. Binstadt, Kevin Friedman, Kristen Hayward, Lisa F. Imundo, Sivia K. Lapidus, Susan Kim, Mary Beth Son, Sangeeta Sule, Adriana H. Tremoulet, Heather Van Mater, Cagri Yildirim‐Toruner, Carol A. Langford, Mehrdad Maz, Andy Abril, Gordon Guyatt, Amy M. Archer, Doyt L. Conn, Kathy A. Full, Peter C. Grayson, Maria F. Ibarra, Peter A. Merkel, Rennie L. Rhee, Philip Seo, John H. Stone, Robert P. Sundel, Omar I. Vitobaldi, Ann Warner, Kevin Byram, Anisha B. Dua, Nedaa Husainat, Karen E. James, Mohamad Kalot, Yih Chang Lin, Jason M. Springer, Marat Turgunbaev, Alexandra Villa‐Forte, Amy S. Turner, Reem A. Mustafa
Journal: Arthritis & Rheumatology (2022)

Objective To provide evidence‐based recommendations and expert guidance for the management of Kawasaki disease (KD), focusing on clinical scenarios more commonly addressed by rheumatologists. Methods Sixteen clinical questions regarding diagnostic testing, treatment, and management of KD were developed in the Patient/Population, Intervention, Comparison, and Outcomes (PICO) question format. Systematic literature reviews were conducted for each PICO question. We used the Grading of Recommendations, Assessment, Development and Evaluation method to assess the quality of evidence and formulate recommendations. Each recommendation required consensus from at least 70% of the Voting Panel. Results We present 1 good practice statement, 11 recommendations, and 1 ungraded position statement to guide the management of KD and clinical scenarios of suspected KD. These recommendations for KD are focused on situations in which input from rheumatologists may be requested by other managing specialists, such as in cases of treatment‐refractory, severe, or complicated KD. The good practice statement affirms that all patients with KD should receive initial treatment with intravenous immunoglobulin (IVIG). In addition, we developed 7 strong and 4 conditional recommendations for the management of KD or suspected KD. Strong recommendations include prompt treatment of incomplete KD, treatment with aspirin, and obtaining an echocardiogram in the setting of unexplained macrophage activation syndrome or shock. Conditional recommendations include use of IVIG with other adjuvant agents for patients with KD and high‐risk features of IVIG resistance and/or coronary artery aneurysms. These recommendations endorse minimizing risk to the patient by using established therapy promptly at disease onset and identifying situations in which adjunctive therapy may be warranted. Conclusion These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and use of echocardiography in patients with suspected or confirmed KD.
Frequency of transmission, asymptomatic shedding, and airborne spread of Streptococcus pyogenes in schoolchildren exposed to scarlet fever: a prospective, longitudinal, multicohort, molecular epidemiological, contact-tracing study in England, UK
Authors: Rebecca Cordery, Amrit K Purba, Lipi Begum, Ewurabena Mills, Mia Mosavie, Ana Vieira, Elita Jauneikaite, Rhoda C Y Leung, Matthew K Siggins, Derren Ready, Peter Hoffman, Theresa Lamagni, Shiranee Sriskandan
Journal: The Lancet Microbe (2022)
PROGNOSTIC VALUE OF CORONARY ARTERY CALCIUM AND MYOCARDIAL FLOW RESERVE FROM 82RB PET MPI IN HEART TRANSPLANT PATIENTS
Authors: Ramyashree Tummala, Konrad Pieszko, Donghee Han, Robert JH Miller, Damini Dey, Jon A. Kobashigawa, Piotr Slomka, Daniel S. Berman
Journal: Journal of the American College of Cardiology (2022)
Inhibition of Tau seeding by targeting Tau nucleation core within neurons with a single domain antibody fragment
Authors: Clément Danis, Elian Dupré, Orgeta Zejneli, Raphaëlle Caillierez, Alexis Arrial, Séverine Bégard, Justine Mortelecque, Sabiha Eddarkaoui, Anne Loyens, François-Xavier Cantrelle, Xavier Hanoulle, Jean-Christophe Rain, Morvane Colin, Luc Buée, Isabelle Landrieu
Journal: Molecular Therapy (2022)

Tau proteins aggregate into filaments in brain cells in Alzheimer's disease and related disorders referred to as tauopathies. Here, we used fragments of camelid heavy-chain-only antibodies (VHHs or single domain antibody fragments) targeting Tau as immuno-modulators of its pathologic seeding. A VHH issued from the screen against Tau of a synthetic phage-display library of humanized VHHs was selected for its capacity to bind Tau microtubule-binding domain, composing the core of Tau fibrils. This parent VHH was optimized to improve its biochemical properties and to act in the intra-cellular compartment, resulting in VHH Z70. VHH Z70 precisely binds the PHF6 sequence, known for its nucleation capacity, as shown by the crystal structure of the complex. VHH Z70 was more efficient than the parent VHH to inhibit in vitro Tau aggregation in heparin-induced assays. Expression of VHH Z70 in a cellular model of Tau seeding also decreased the aggregation-reporting fluorescence signal. Finally, intra-cellular expression of VHH Z70 in the brain of an established tauopathy mouse seeding model demonstrated its capacity to mitigate accumulation of pathological Tau. VHH Z70, by targeting Tau inside brain neurons, where most of the pathological Tau resides, provides an immunological tool to target the intra-cellular compartment in tauopathies. Tau proteins aggregate into filaments in brain cells in Alzheimer's disease and related disorders referred to as tauopathies. Here, we used fragments of camelid heavy-chain-only antibodies (VHHs or single domain antibody fragments) targeting Tau as immuno-modulators of its pathologic seeding. A VHH issued from the screen against Tau of a synthetic phage-display library of humanized VHHs was selected for its capacity to bind Tau microtubule-binding domain, composing the core of Tau fibrils. This parent VHH was optimized to improve its biochemical properties and to act in the intra-cellular compartment, resulting in VHH Z70. VHH Z70 precisely binds the PHF6 sequence, known for its nucleation capacity, as shown by the crystal structure of the complex. VHH Z70 was more efficient than the parent VHH to inhibit in vitro Tau aggregation in heparin-induced assays. Expression of VHH Z70 in a cellular model of Tau seeding also decreased the aggregation-reporting fluorescence signal. Finally, intra-cellular expression of VHH Z70 in the brain of an established tauopathy mouse seeding model demonstrated its capacity to mitigate accumulation of pathological Tau. VHH Z70, by targeting Tau inside brain neurons, where most of the pathological Tau resides, provides an immunological tool to target the intra-cellular compartment in tauopathies.
YIA22-007: Adaptive Nutrition and Exercise Weight loss (A-NEW) Study for Breast Cancer Survivors With Overweight or Obesity
Authors: Jennifer Yeong-shin Sheng, Amanda Montanari, Faith Too, Marianna Zahurak, Gary L Rosner, Kimberly A Gudzune, Janelle W Coughlin, Vered Stearns
Journal: Journal of the National Comprehensive Cancer Network (2022)
IMPACT OF INPATIENT INITIATION OF SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITORS ON GUIDELINE-DIRECTED MEDICAL THERAPY FOR HEART FAILURE WITH REDUCED EJECTION FRACTION PATIENTS
Authors: Henry C. Okoroike, Sajni V. Patel, Pamela Simone, Rachel I. Lavelle, Jennifer Austin Szwak
Journal: Journal of the American College of Cardiology (2022)
REFRACTORY CORONARY SPASM IN A 37-YEAR-OLD FEMALE: A DIAGNOSIS BY INTRAVASCULAR ULTRASOUND, TREATED WITH RANOLAZINE &amp; DILTIAZEM
Authors: Krishna Theja Reddy, Srivaibhav Reddy, Humera Syeda, Sina Bakhshaei, Darren Nguyen, Andrew T. Ho
Journal: Journal of the American College of Cardiology (2022)
Abstract P2-13-15: VRN101396, a brain-permeable HER2 inhibitor, shows the anti-tumor activity in preclinical HER2-positive cancer models
Authors: Hong-ryul Jung, Sunghwan Kim, Jihye Yoo, Chan mi Park, Somi Lee, Hyoju Lee, Youngyi Lee, Jinhee Park, Kyungah Seo, Dong-Hyuk Seo, Eunhwa Ko, Jung Beom Son, Deakwon Kim, Hwan Geun Choi, Nam Doo Kim
Journal: Cancer Research (2022)

Abstract Breast cancer (BC) is the second most common cancer associated with brain metastasis (BM) and among patients with breast cancer brain metastasis (BCBM), human epidermal growth factor receptor 2 (HER2)-positive breast cancer is most likely to develop BM. The overall prognosis of HER2-positive BCBM remains dismal with median survival time after BM of less than a year. Drugs like T-DM1, T-DXd and Tucatinib are reported to deliver a progression-free survival benefit in HER2-positive BCBM patients, but there are still unmet needs for a drug that crosses the blood brain barrier more effectively. We develop VRN101396, a brain penetrant, orally available, and irreversible small molecule inhibitor targeting HER2 to offer a new therapeutic option for the treatment of HER2-positive BCBM. VRN101396 potently inhibits catalytic activity of HER2 but spares wild-type EGFR. In HER2-positive breast cancer cell lines BT474 and SK-BR3 and gastric cancer cell line NCI-N87, VRN101396 inhibited the cell proliferation and phosphorylation of HER2 with single- or double-digit nanomolar IC50 values while inhibiting wild type EGFR with an IC50 value of &amp;gt;100 nM. In both subcutaneous and intracranial efficacy mouse models, once-daily oral dose of VRN101396 significantly inhibited tumor growth and achieved tumor regression. In N87 subcutaneous xenograft model, VRN101396 alone showed superior efficacy to the combination of Tucatinib and Trastuzumab. Additionally, in intracranial xenograft model, VRN101396 showed superior efficacy to Tucatinib. Pharmacokinetics of VRN101396 displayed higher brain exposure than tucatinib and lapatinib, indicating better target engagement in the brain. Pharmacodynamic analysis revealed that VRN101396 reduced phosphorylation of HER2, HER3, AKT, and ERK compared to vehicle group after administration up to 24 hours. In conclusion, VRN101396 is a therapeutic candidate for the treatment of HER2-positive BC, BCBM and gastric cancer. Citation Format: Hong-ryul Jung, Sunghwan Kim, Jihye Yoo, Chan mi Park, Somi Lee, Hyoju Lee, Youngyi Lee, Jinhee Park, Kyungah Seo, Dong-Hyuk Seo, Eunhwa Ko, Jung Beom Son, Deakwon Kim, Hwan Geun Choi, Nam Doo Kim. VRN101396, a brain-permeable HER2 inhibitor, shows the anti-tumor activity in preclinical HER2-positive cancer models [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-15.
An unequivocal call to climate action for the health sector
Authors: Naomi Beyeler, Renee N Salas
Journal: BMJ (2022)

The word unequivocal is rare in medicine and stands out in the latest report of the United Nations (UN) Intergovernmental Panel on Climate Change (IPCC), which states that "the human toll of climate change is unequivocal and growing." 1 The report issues three clear warnings and a call to action for everyone in the health sector.
Immunogenicity and safety of booster CYD-TDV dengue vaccine after alternative primary vaccination schedules in healthy individuals aged 9–50 years: a randomised, controlled, phase 2, non-inferiority study
Authors: Diana Leticia Coronel-Martinez, Juliana Park, Eduardo López-Medina, María Rosario Capeding, Andrés Angelo Cadena Bonfanti, María Cecilia Montalbán, Isabel Ramírez, María Liza Antoinette Gonzales, Betzana Zambrano, Gustavo Dayan, Zhenghong Chen, Hao Wang, Matthew Bonaparte, Andrey Rojas, Jenny Carolina Ramírez, Mae Ann Verdan, Fernando Noriega
Journal: The Lancet Infectious Diseases (2022)
DAPAGLIFLOZIN ASSOCIATED TO SACUBITRIL/VALSARTAN (LCZ696) EXERTS ADDITIVE CARDIOPROTECTION IN HUMAN CARDIOMYOCYTES EXPOSED SEQUENTIALLY TO DOXORUBICIN AND TRASTUZUMAB THROUGH MYD88, NLRP3 MEDIATED PATHWAYS AND PRO-INFLAMMATORY CYTOKINES
Authors: Nicola Maurea, Marino Scherillo, Annamaria Bonelli, Simona Buccolo, Martina Iovine, Carlo Maurea, Andrea Paccone, Irma Bisceglia, Vincenzo Quagliariello
Journal: Journal of the American College of Cardiology (2022)
The relapse doesn’t fall far from the radiotherapy field: Lessons to be learned for the future of radiotherapy in medulloblastoma from the relapse patterns of SJMB03
Authors: Frank Saran, David D Eisenstat
Journal: Neuro-Oncology (2022)

“Revised clinical and molecular risk strata define the incidence and failure type in medulloblastoma following risk-adapted radiotherapy and chemotherapy” is a secondary analysis of the pattern of failure in relationship to radiotherapy quality assurance (RTQA) and currently accepted molecular stratification criteria.1 SJMB03 was the first study to enroll patients with medulloblastoma (MB) of all stages in a unified protocol.2 At inception, the protocol’s design was considered visionary. Subsequently, the study investigators have interrogated long-term outcome data to inform future international studies in MB. The data presented are highly relevant; however, SJMB03 should be evaluated in its historic context. The trial developed in the late 1990s was open to recruitment between 2003 and 2013. For the first time, biological data were prospectively collected along with risk stratification and treatment paradigms based on preexisting concepts for average risk (AR) and high risk (HR) disease. The accepted RT standard of care for AR MB at the time was craniospinal irradiation (CSI) followed by a boost to the whole posterior fossa (CCG-9892, COG-A9961, and SIOP PNET-4) using a two-dimensional (2D) planning approach with direct and parallel opposed fields. However, the impact of RTQA on outcome was increasingly recognised3 as well as the impact of late toxicity related to high dose and large volume RT.4 The availability of CT-based three-dimensional (3D) conformal approaches in the early 2000s was the exception, and the team from St. Jude Children’s Research Hospital (St. Jude’s) as well as the French group,5 were early adopters. However, 3D conformal planning was non-mandatory and limited to the primary tumor bed boost in the SJMB03 protocol. Boost target volume definitions for patients with HR features at the time were empirically derived and pragmatic, thereby open to individual local interpretation even in the context of a formal trial. The investigators demonstrated that changing either dose prescriptions and/or boost target volume definitions can lead to a significant reduction in integral dose and, in turn, should lead to reduced late toxicity if the same overall survival (OS) can be achieved.6
Abstract P5-05-01: Metabolite profiling and RNA-seq identifies novel metabolomic-genomic biomarker and therapeutic options for rapidly proliferating breast cancers
Authors: Cherise R Glodowski, Chengheng Liao, Cheng Fan, Juan Liu, Kevin R Mott, Akash Kaushik, Hieu Vu, Jason W Locasale, Samuel K McBrayer, Ralph J DeBerardinis, Charles M Perou, Qing Zhang
Journal: Cancer Research (2022)

Abstract Metabolic dysregulation is one of the distinctive features of breast cancer, yet remains under-characterized in different subtypes of breast cancer. In this study, we performed full metabolome profiling and RNA-seq gene expression analyses on patient samples comprised of Triple Negative Breast Cancer (TNBC) and Estrogen Receptor (ER) positive breast cancers, as well as TNBC patient-derived xenografts (PDX). We identified two major metabolic groups using hierarchical clustering analysis of global metabolite levels: a Nucleotide/Carbohydrate-Enriched group and a Lipid/Fatty Acid-Enriched group. The Nucleotide/Carbohydrate-Enriched group is populated by the majority of TNBCs and all TNBC PDX samples, and shows high levels of energy consumption and nucleotide biosynthesis related metabolites, while the Lipid/Fatty Acid-Enriched group contained all ER+ cancers (and normal breast tissues) and showed high levels of lipids and fatty acids. Using these two metabolite-defined groups, we compared metabolic signatures to RNA-seq expression data and identified gene expression signatures that correlated with each metabolic group. This novel integrated signature identified classic proliferation-associated genes as highly expressed in the Nucleotide/Carbohydrate-Enriched metabolomics group. We next sought to therapeutically target the Nucleotide/Carbohydrate-Enriched group through targeting of nucleotide metabolism using a pyrimidine biosynthesis inhibitor (DHODH inhibitor, Brequinar), and/or a glutaminase inhibitor (CB-839), and observed tumor volume reductions and improved survival times using the TNBC PDX models. Notably,. when the DHODH inhibitor Brequinar was tested on four different immune-competent TNBC mouse models, it showed significant single agent activity, and in 3/4 cases had better activity than carboplatin/paclitaxel combination, and with less toxicity. Our study reveals a new molecularly targeted therapy for rapidly proliferating TNBCs, guided by a novel set of metabolic-genomic biomarkers, which might be translated quickly as DHODH inhibitors are already FDA approved for use in other diseases. Citation Format: Cherise R Glodowski, Chengheng Liao, Cheng Fan, Juan Liu, Kevin R Mott, Akash Kaushik, Hieu Vu, Jason W Locasale, Samuel K McBrayer, Ralph J DeBerardinis, Charles M Perou, Qing Zhang. Metabolite profiling and RNA-seq identifies novel metabolomic-genomic biomarker and therapeutic options for rapidly proliferating breast cancers [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-05-01.
DELINEATION OF RIGHT AND LEFT REGIONAL VENTRICULAR FUNCTION WITH SELECTIVE MICROVASCULAR ENHANCEMENT FOLLOWING PERFLUOROPRANE DROPLET ACTIVATION IMAGING
Authors: Thomas Richard Porter, Shouqiang Li, Ping Zeng, Chen Cheng, John Lof, Elizabeth Stolze, Xucai Chen, John J. Pacella, Flordeliza S. Villanueva, Terry Matsunaga, Carr Everbach, Hongwen Fei, Feng Xie
Journal: Journal of the American College of Cardiology (2022)
Loss of mouse Stmn2 function causes motor neuropathy
Authors: Irune Guerra San Juan, Leslie A. Nash, Kevin S. Smith, Marcel F. Leyton-Jaimes, Menglu Qian, Joseph R. Klim, Francesco Limone, Alexander B. Dorr, Alexander Couto, Greta Pintacuda, Brian J. Joseph, D. Eric Whisenant, Caroline Noble, Veronika Melnik, Deirdre Potter, Amie Holmes, Aaron Burberry, Matthijs Verhage, Kevin Eggan
Journal: Neuron (2022)
Shared Decision-making—It’s Not for Everyone
Authors: Anne P. Ehlers, Dana A. Telem
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
DETAILED PSYCHOSOCIAL CHARACTERISTICS OF PATIENTS WITH RECURRENT TAKOTSUBO SYNDROME COMPARED TO PATIENTS WITH SINGLE EVENT
Authors: Paul Marano, Jenna Maughan, Okezi Obrutu, Marie Lauzon, Benita Tjoe, Romana Herscovici, Prizzi Moy, Natalie Rojas, Chrisandra Shufelt, Thomas Rutledge, Janet Wei, C. Noel Bairey Merz
Journal: Journal of the American College of Cardiology (2022)
IMPROVED OR STABLE LEFT VENTRICULAR EJECTION FRACTION IN PATIENTS WITH TRANSTHYRETIN CARDIAC AMYLOIDOSIS AND REDUCED EJECTION FRACTION PORTEND BETTER LONG-TERM OUTCOMES
Authors: Joshua Saef, Trejeeve Martyn, Anusha Ray Dey, Lauren Ives, Mazen A. Hanna, Wai Hong Wilson Tang
Journal: Journal of the American College of Cardiology (2022)
LOW PT AND APTT PREDICT STROKE RISK IN ATRIAL FIBRILLATION PATIENTS
Authors: Abdel Hadi El Hajjar, Yichi Zhang, Mario Mekhael, Charbel Noujaim, Tarek Hassan Ayoub, Christopher Pottle, Arezu Bhatnagar, Chao Huang, Chan Ho Lim, Shadi Razipour, Lilas Dagher, Nassir F. Marrouche
Journal: Journal of the American College of Cardiology (2022)
Longitudinal Outcomes of Subcutaneous or Transvenous Implantable Cardioverter-Defibrillators in Older Patients
Authors: Daniel J. Friedman, Li Qin, Craig Parzynski, E. Kevin Heist, Andrea M. Russo, Isuru Ranasinghe, Emily P. Zeitler, Karl E. Minges, Joseph G. Akar, James V. Freeman, Jeptha P. Curtis, Sana M. Al-Khatib
Journal: Journal of the American College of Cardiology (2022)
LA FUNCTION PROVIDES INCREMENTAL RISK STRATIFICATION IN PATIENTS WITH NON-ISCHEMIC CARDIOMYOPATHY AND FUNCTIONAL MITRAL REGURGITATION
Authors: Tom Kai Ming Wang, Donna Salam, Mustafa Turkmani, Samir R. Kapadia, Amar Krishnaswamy, Brian P. Griffin, Scott D. Flamm, Wai Hong Wilson Tang, Deborah Kwon
Journal: Journal of the American College of Cardiology (2022)
CLO22-088: Phase II Trial of Trifluridine/Tipiracil in Combination With Irinotecan in Advanced Biliary Tract Cancers (BTCs)
Authors: Sri Harsha Tella, Jaclynn Wessling, Foster Nathan, Shi Qian, Tran Nguyen, Robert McWillimas, Alberts Steven, Minetta Liu, Mitesh Borad, Wen Wee Ma, Mindy Hartgers, Leslie Washburn, Fruth Briant, Martin Fernandezzapico, Tara L Hogenson, Henry Pitot, Zhaohui Jin, Amit Mahipal
Journal: Journal of the National Comprehensive Cancer Network (2022)