tbuckley/cabot-search huggingface dataset:
Impact of Cancer Therapy-Related Cardiac Dysfunction on Risk of Heart Failure in Pregnancy
Authors: Mark Nolan, Evangelos K. Oikonomou, Candice K. Silversides, Melissa R. Hines, Kara A. Thompson, Belinda A. Campbell, Eitan Amir, Cynthia Maxwell, Paaladinesh Thavendiranathan
Journal: JACC CardioOncology (2020)

Cancer treatment can lead to left ventricular (LV) dysfunction in female cancer survivors of reproductive age, and pregnancy-related hemodynamic stress may result in LV dysfunction or heart failure (HF).We performed a systematic review and meta-analysis to determine the incidence of LV systolic dysfunction or HF during or soon after pregnancy in cancer survivors and evaluated the impact of history of cancer therapeutics-related cardiac dysfunction (CTRCD).We systematically searched electronic databases (MEDLINE and EMBASE) from inception to January 2020 to identify cohort studies that examined cardiac disease in pregnant cancer survivors. Meta-analysis was performed using the inverse-variance fixed effects method. Potential sources of heterogeneity were explored using subgroup analyses and meta-regression.Of 13,782 identified articles, 6 studies consisting of 2,016 pregnancies, predominantly in childhood cancer survivors, were included. Overall, there were 33 cardiac events. The total weighted incidence of LV dysfunction or HF with pregnancy was 1.7% (95% confidence interval [CI]: 0.9% to 2.7%) overall; 28.4% (95% CI: 14.6% to 43.9%) in those with a history of CTRCD and 0.24% (95% CI: 0% to 0.81%) in those without, translating into an odds ratio of 47.4 (95% CI: 17.9 to 125.8). Interstudy heterogeneity was low (I2 = 17.5%). Metaregression did not reveal significant sources of heterogeneity.The incidence of LV dysfunction or HF during pregnancy in cancer survivors was low. Although risk estimates are limited by the small number of events, women with a history of CTRCD compared to those without had a 47.4-fold higher odds of experiencing pregnancy-related LV dysfunction or HF.
John Lennon’s Elbow
Authors: Robert E Hirschtick
Journal: JAMA (2012)

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
Neuroregeneration and plasticity: a review of the physiological mechanisms for achieving functional recovery postinjury
Authors: Palaniappan Ganesh Nagappan, Hong Chen, De-Yun Wang
Journal: Military Medical Research (2020)

Abstract Neuronal networks, especially those in the central nervous system (CNS), evolved to support extensive functional capabilities while ensuring stability. Several physiological “brakes” that maintain the stability of the neuronal networks in a healthy state quickly become a hinderance postinjury. These “brakes” include inhibition from the extracellular environment, intrinsic factors of neurons and the control of neuronal plasticity. There are distinct differences between the neuronal networks in the peripheral nervous system (PNS) and the CNS. Underpinning these differences is the trade-off between reduced functional capabilities with increased adaptability through the formation of new connections and new neurons. The PNS has “facilitators” that stimulate neuroregeneration and plasticity, while the CNS has “brakes” that limit them. By studying how these “facilitators” and “brakes” work and identifying the key processes and molecules involved, we can attempt to apply these theories to the neuronal networks of the CNS to increase its adaptability. The difference in adaptability between the CNS and PNS leads to a difference in neuroregenerative properties and plasticity. Plasticity ensures quick functional recovery of abilities in the short and medium term. Neuroregeneration involves synthesizing new neurons and connections, providing extra resources in the long term to replace those damaged by the injury, and achieving a lasting functional recovery. Therefore, by understanding the factors that affect neuroregeneration and plasticity, we can combine their advantages and develop rehabilitation techniques. Rehabilitation training methods, coordinated with pharmacological interventions and/or electrical stimulation, contributes to a precise, holistic treatment plan that achieves functional recovery from nervous system injuries. Furthermore, these techniques are not limited to limb movement, as other functions lost as a result of brain injury, such as speech, can also be recovered with an appropriate training program.
Layilin augments integrin activation to promote antitumor immunity
Authors: Kelly M. Mahuron, Joshua M. Moreau, Jeff E. Glasgow, Devi P. Boda, Mariela L. Pauli, Victoire Gouirand, Luv Panjabi, Robby Grewal, Jacob M. Luber, Anubhav N. Mathur, Renny M. Feldman, Eric Shifrut, Pooja Mehta, Margaret M. Lowe, Michael D. Alvarado, Alexander Marson, Meromit Singer, Jim Wells, Ray Jupp, Adil I. Daud, Michael D. Rosenblum
Journal: The Journal of Experimental Medicine (2020)

Tumor-infiltrating CD8+ T cells mediate antitumor immune responses. However, the mechanisms by which T cells remain poised to kill cancer cells despite expressing high levels of inhibitory receptors are unknown. Here, we report that layilin, a C-type lectin domain–containing membrane glycoprotein, is selectively expressed on highly activated, clonally expanded, but phenotypically exhausted CD8+ T cells in human melanoma. Lineage-specific deletion of layilin on murine CD8+ T cells reduced their accumulation in tumors and increased tumor growth in vivo. Congruently, gene editing of LAYN in human CD8+ T cells reduced direct tumor cell killing ex vivo. On a molecular level, layilin colocalized with integrin αLβ2 (LFA-1) on T cells, and cross-linking layilin promoted the activated state of this integrin. Accordingly, LAYN deletion resulted in attenuated LFA-1–dependent cellular adhesion. Collectively, our results identify layilin as part of a molecular pathway in which exhausted or “dysfunctional” CD8+ T cells enhance cellular adhesiveness to maintain their cytotoxic potential.
Single-Cell RNA-Seq Mapping of Human Thymopoiesis Reveals Lineage Specification Trajectories and a Commitment Spectrum in T Cell Development
Authors: Justin Le, Jeong Eun Park, Vi Luan Ha, Annie Luong, Sergio Branciamore, Andrei S. Rodin, Grigoriy Gogoshin, Fan Li, Yong-Hwee Eddie Loh, Virginia Camacho, Sweta B. Patel, Robert S. Welner, Chintan Parekh
Journal: Immunity (2020)
Risk factors for death in 1859 subjects with COVID-19
Authors: Lei Chen, Jianming Yu, Wenjuan He, Li Chen, Guolin Yuan, Fang Dong, Wenlan Chen, Yulin Cao, Jingyan Yang, Liling Cai, Di Wu, Qijie Ran, Lei Li, Qiaomei Liu, Wenxiang Ren, Fei Gao, Hongxiang Wang, Zhichao Chen, Robert Peter Gale, Qiubai Li, Yu Hu
Journal: Leukemia (2020)
Facing the Monster in Haiti
Authors: Vanessa Rouzier, Bernard Liautaud, Marie Marcelle Deschamps
Journal: New England Journal of Medicine (2020)

Who we are CREDThe Centre for Research on the Epidemiology of Disasters (CRED) is the world's foremost agency for the study of public health during mass emergencies, including the epidemiology of diseases, plus the structural and socio-economic impacts of natural and technological disasters and human conflicts.
Efficacy of lifestyle and psychosocial interventions in reducing cognitive decline in older people: Systematic review
Authors: Emma Whitty, Hassan Mansour, Elisa Aguirre, Marina Palomo, Georgina Charlesworth, Serena Ramjee, Michaela Poppe, Henry Brodaty, Helen C. Kales, Sarah Morgan-Trimmer, Samuel R. Nyman, Iain Lang, Kate Walters, Irene Petersen, Jennifer Wenborn, Anne -Marie Minihane, Karen Ritchie, Jonathan Huntley, Zuzana Walker, Claudia Cooper
Journal: Ageing Research Reviews (2020)
Cardiovascular Effects of CAR T Cell Therapy
Authors: Bénédicte Lefebvre, Yu Kang, Amanda M. Smith, Noelle V. Frey, Joseph R. Carver, Marielle Scherrer-Crosbie
Journal: JACC CardioOncology (2020)

Anti-CD19 chimeric antigen receptor (CAR) T cell therapy holds great promise in the treatment of patients with hematologic malignancies. A high occurrence of cardiac dysfunction has been noted in children treated with CAR T cell therapy. The aim of this study was to define the occurrence of major adverse cardiovascular events (MACE) in adult patients treated with CAR T cell therapy and assess the relationships among clinical factors, echocardiographic parameters, laboratory values, and cardiovascular outcomes. Baseline clinical, laboratory, and echocardiographic parameters were collected in 145 adult patients undergoing CAR T cell therapy. MACE included cardiovascular death, symptomatic heart failure, acute coronary syndrome, ischemic stroke, and de novo cardiac arrhythmia. Baseline parameters associated with MACE were identified using Cox proportional cause-specific hazards regression analysis. Thirty-one patients had MACE (41 events) at a median time of 11 days (interquartile range: 6 to 151 days) after CAR T cell infusion. The median follow-up period was 456 days (interquartile range: 128 to 1,214 days). Sixty-one patients died. Cytokine release syndrome (CRS) occurred 176 times in 104 patients; the median time to CRS was 6 days (interquartile range: 1 to 8 days). The Kaplan-Meier estimates for MACE and CRS at 30 days were 17% and 53%, respectively. The Kaplan-Meier estimates for survival at 1 year was 71%. Multivariable Cox proportional cause-specific hazards regression analysis determined that baseline creatinine and grade 3 or 4 CRS were independently associated with MACE. Patients treated with CAR T cell therapy are at an increased risk for MACE and may benefit from cardiovascular surveillance. Further large prospective studies are needed to confirm the incidence and risk factors predictive of MACE.
SAT-483-Hepatic epithelioid hemangioendotelioma: An international multicenter study
Authors: Marco Sanduzzi Zamparelli, Jordi Rimola, Carla Montironi, Vinicius Nunes, Venancio Avancini Ferreira Alves, Víctor Sapena, Alejandro Forner, Flair Jose Carrilho, Alba Díaz, Carla Fuster, Joana Ferrer, Josep Fuster, Carmen Ayuso, Manel Sole, Jordi Bruix, María Reig
Journal: Journal of Hepatology (2019)
3D genome architecture coordinates trans and cis regulation of differentially expressed ear and tassel genes in maize
Authors: Yonghao Sun, Liang Dong, Ying Zhang, Da Lin, Weize Xu, Changxiong Ke, Linqian Han, Lulu Deng, Guoliang Li, David Jackson, Xingwang Li, Fang Yang
Journal: Genome biology (2020)

Abstract Background Maize ears and tassels are two separate types of inflorescence which are initiated by similar developmental processes but gradually develop distinct architectures. However, coordinated trans and cis regulation of differentially expressed genes determining ear and tassel architecture within the 3D genome context is largely unknown. Results We identify 56,055 and 52,633 open chromatin regions (OCRs) in developing maize ear and tassel primordia using ATAC-seq and characterize combinatorial epigenome features around these OCRs using ChIP-seq, Bisulfite-seq, and RNA-seq datasets. Our integrative analysis of coordinated epigenetic modification and transcription factor binding to OCRs highlights the cis and trans regulation of differentially expressed genes in ear and tassel controlling inflorescence architecture. We further systematically map chromatin interactions at high-resolution in corresponding tissues using in situ digestion-ligation-only Hi-C (DLO Hi-C). The extensive chromatin loops connecting OCRs and genes provide a 3D view on cis- and trans -regulatory modules responsible for ear- and tassel-specific gene expression. We find that intergenic SNPs tend to locate in distal OCRs, and our chromatin interaction maps provide a potential mechanism for trait-associated intergenic SNPs that may contribute to phenotypic variation by influencing target gene expression through chromatin loops. Conclusions Our comprehensive epigenome annotations and 3D genome maps serve as valuable resource and provide a deep understanding of the complex regulatory mechanisms of genes underlying developmental and morphological diversities between maize ear and tassel.
ICU Resource Use in Critically III Patients following Chimeric Antigen Receptor T-Cell Therapy
Authors: Anne Rain T. Brown, Irfan Jindani, Judd Melancon, Rose Erfe, Jason Westin, Lei Feng, Cristina Gutierrez
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

"ICU Resource Use in Critically III Patients following Chimeric Antigen Receptor T-Cell Therapy." American Journal of Respiratory and Critical Care Medicine, 202(8), pp. 1184–1187
THU0591 CENTRAL NERVOUS SYSTEM VASCULITIS IN WHIPPLE DISEASE: A CASE REPORT
Authors: A. Giollo, C. Zivelonghi, D. Cardellini, G. M. Schiavi, G. Vattemi, O. Viapiana, M. Rossini
Journal: Annals of the Rheumatic Diseases (2020)

Background: Whipple disease (WD) is a rare systemic infection with possible involvement of the central nervous system (CNS). The neurological manifestations of the disease are various and can mimic any neurologic condition. Objectives: To describe the severe neurological complications occurred in a patient with WD misdiagnosed as a chronic inflammatory immune-mediated disorder. Methods: Case report Results: A 46-year-old woman developed acute right-sided hemiparesis and dysarthria. She had a 10-year history of ill-defined rheumatic condition (defined as seronegative rheumatoid arthritis, spondyloarthritis, and adult onset Still’s disease) presenting with polyarthritis, episodic fever &gt; 38°C and rash of unclear etiology poorly responsive to different immunotherapies including methotrexate, anti-IL6 and anti-IL1 inhibitors. Brain MRI demonstrated multiple anterior circulation infarctions and stenosis of the bilateral M1 segments of the middle cerebral artery on MR angiography. Black blood sequences revealed contrast enhancement of the vessel walls consistent with vasculitis (Figure 1). Cerebrospinal fluid (CSF) analysis was unrevealing, including PCR for viruses and bacteria. A working diagnosis of primary CNS vasculitis and progressive neurologic deterioration with abnormal behavior and altered mental status prompted the initiation of intravenous (IV) methylprednisolone followed by cyclophosphamide without significant improvement. Re-evaluation of the long-standing history of joint symptoms unresponsive to immunotherapy, along with recurrent fevers and chronic diarrhea raised the suspicion of unrecognized Whipple’s disease. PCR for Tropheryma Whippleii was positive in stool, urine, blood and CSF, and duodenal mucosal biopsies confirmed the diagnosis. A combination of ceftriaxone, doxycycline, and hydroxychloroquine was initiated. Three days later the patient developed periocular burning pain and cutaneous vesicles consistent with shingles. Varicella-zoster virus DNA was detected in CSF and IV acyclovir was started. At 3 months follow-up neurologic examination was unremarkable except for a slightly fatuous behavior. Conclusion: Recognition of rare manifestations of WD is important to avoid diagnostic delay and inappropriate, potentially harmful treatments. Disclosure of Interests: Alessandro Giollo: None declared, Cecilia Zivelonghi: None declared, Davide Cardellini: None declared, Gian Marco Schiavi: None declared, Gaetano Vattemi: None declared, Ombretta Viapiana: None declared, Maurizio Rossini Speakers bureau: AbbVie, Abiogen, Amgen, BMS, Eli-Lilly, Novartis, Pfizer, Sanofi, Sandoz and UCB
Psychiatric Comorbidity and Outcomes After Left Ventricular Assist Device Implantation for End-Stage Heart Failure
Authors: Clancy Mullan, Cesar Caraballo, Neal G. Ravindra, P. Elliott Miller, Megan McCullough, Kelly Brown, Tsung Wai Aw, Jadry Gruen, John-Ross D. Clarke, Eric J. Velazquez, Arnar Geirsson, Makoto Mori, Nihar R. Desai, Tariq Ahmad
Journal: JACC Heart Failure (2020)
AB0447 IRREVERSIBLE ORGAN DAMAGE IN PERI- AND POSTMENOPAUSAL WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS IN REMISSION
Authors: S. Shkireeva, E. Zotkin, O. Lesnyak
Journal: Annals of the Rheumatic Diseases (2020)

Background: Although the survival of patients with systemic lupus erythematosus (SLE) has improved, irreversible organ damage remains a critical concern. Long-standing inflammation, drug-related side effects and comorbidities may eventually cause permanent organ damage even in remission [1]. Objectives: To describe irreversible organ damage in peri- and postmenopausal women with SLE in remission and low disease activity, to find predictors of damage progression. Methods: 234 peri- and postmenopausal women with SLE were included (mean age 49,94±9,1 years) in our study. All women were under outpatient observation in St.Petersburg State Clinical Rheumatology Hospital #25 (Russia). Mean disease duration was 8,9±7,5 years. We analyzed treatment regimens and doses of glucocorticoids (GC) based on source medical documents. To assess disease activity, we used SLEDAI-2K and LLDAS. To assess organ damage, we used SLICC damage index (SDI). Results: 94,3% of women have been taking GC during our study. Median of maintenance dose was 12,5 mg per day. Almost a half of all women (44,8%, n=105) in our study were postmenopausal (mean duration of menopause was 11,1±7,1 years). A half of all patients had low disease activity (44,4%, n=111) or were in remission (18,8%, n=44) according to SLEDAI-2K. 26,5% (n=65) of patients had all 5 criteria and 45,1 % (n=115) of patients had 4 of 5 criteria according to LLDAS. Critical organ damage (SDI&gt;4) was observed in 68,8% (n=161) of women with SLE. Moderate (1≤SDI≤4) and low (SDI=1) damage had 25,6% (n=60) and 6,4% (n=15) of patients respectively. Musculoskeletal damage was on the first place among others: 37,6% (n=88) of patients had osteoporosis with fractures and 34,2% (n=80) had muscle weakness. In 75 women with SLE of osteoporotic fractures occurred in remission or low disease activity (LLDAS). Progression of irreversible organ damage in remission or low disease activity (LLDAS) had 62% (n=145) of women with SLE. Multifactorial logistic regression analysis of factors associated with organ damage in SLE showed that only patients age (р=0.013215), cumulative dose of GC (р=0.000047) and therapy with cyclophosphamide (р=0.041505) were statistically significant. Conclusion: Progression of irreversible organ damage in peri- and postmenopausal women with SLE may occur despite remission or low disease activity. There are no doubts that organ damage accrual is associated with CG therapy. Correction of GC dose or discontinuation of GC treatment in remission can predict organ damage accrual in SLE including osteoporosis and osteoporotic fractures. References: [1]Frodlund M, Reid S, Wetterö J, Dahlström Ö, Sjöwall C, Leonard D. The majority of Swedish systemic lupus erythematosus patients are still affected by irreversible organ impairment: factors related to damage accrual in two regional cohorts. Lupus. 2019;28(10):1261–1272. doi:10.1177/0961203319860198 Disclosure of Interests: None declared
Abstract A03: Isolation, characterization, and expansion of circulating tumor cells in head and neck cancers
Authors: Arutha Kulasinghe, Joanna Kapeleris, Liz Kenny, Majid Warkiani, Ian Vela, Jean Paul Thiery, Ken O’Byrne, Chamindie Punyadeera
Journal: Clinical Cancer Research (2020)

Abstract Metastasis in head and neck cancer (HNC) patients is reflected by measurable levels of circulating tumor cells (CTCs) in the blood of patients. CTCs represent cancer cells from the primary and metastatic sites, thereby providing a comprehensive representation of the tumor burden of an individual patient. Recent advancements have shown that PD-1/PD-L1 immune checkpoint therapies have durable responses in HNC. Our study was designed to use multiple CTC enrichment platforms for the capture of CTCs and novel culture formulations for the ex vivo expansion of CTCs. n=300 head and neck cancer patients were recruited to investigate the prognostic role of CTCs. We evaluated multiple CTC isolation technologies (CellSearch, filtration, CD45 depletion, inertial microfluidics) using matched patient samples, which showed that epitope-independent CTC isolation captured a greater proportion of CTCs. Molecular alterations present in the primary tissue were confirmed in the CTCs by 3D-DNA FISH (EGFR-amplification). The presence of CTC clusters was associated with the development of distant metastatic disease (P=0.0313). HNC CTC-positive patients had shorter progression-free survival (PFS) (Hazard ratio [HR]: 4.946; 95% confidence interval [CI]:1.571-15.57; P=0.0063) and PD-L1-positive CTCs were found to be significantly associated with worse outcome ([HR]:5.159; 95% [CI]:1.011-26.33; P=0.0485). In a proof-of-principle study, we were able to demonstrate for the first time short-term patient-derived CTC cultures outside the patient’s body from 7/18 HNC samples (4/7 HPV-positive). Recently, we have preliminary data that suggest that PD-L1 is frequently expressed on CTCs in HNC and an immunoscore may be able to identify patients likely to benefit from immunotherapy—a current unmet clinical need. Expanding CTCs outside the patient’s body allows for the recapitulation of the molecular diversity present within the tumor, understanding of the disease progression, and testing of therapies. Citation Format: Arutha Kulasinghe, Joanna Kapeleris, Liz Kenny, Majid Warkiani, Ian Vela, Jean Paul Thiery, Ken O’Byrne, Chamindie Punyadeera. Isolation, characterization, and expansion of circulating tumor cells in head and neck cancers [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A03.