tbuckley/cabot-search huggingface dataset:
Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program
Authors: Murray B. Stein, Daniel F. Levey, Zhongshan Cheng, Frank R. Wendt, Kelly Harrington, Gita A. Pathak, Kelly Cho, Rachel Quaden, Krishnan Radhakrishnan, Matthew J. Girgenti, Yuk-Lam Anne Ho, Daniel Posner, Mihaela Aslan, Ronald S. Duman, Hongyu Zhao, Murray B. Stein, Daniel F. Levey, Zhongshan Cheng, Frank R. Wendt, Gita A. Pathak, Krishnan Radhakrishnan, Mihaela Aslan, Hongyu Zhao, Renato Polimanti, John Concato, Joel Gelernter, Murray B. Stein, Daniel F. Levey, Zhongshan Cheng, Frank R. Wendt, Kelly Harrington, Gita A. Pathak, Kelly Cho, Rachel Quaden, Yuk-Lam Anne Ho, Daniel Posner, Renato Polimanti, John Concato, Joel Gelernter, Renato Polimanti, John Concato, Joel Gelernter
Journal: Nature Genetics (2021)
Abstract 14907: Inconclusive CT Angiography Test Results Are Less Frequent but Lead to More Testing and Have Higher 24-Month Medical Costs in Stable Patients With Suspected Coronary Artery Disease: Insights From the PROMISE Trial
Authors: Akash Goyal, Neha Pagidipati, Daniel B Mark, Larry Hill, Brooke Alhanti, James E Udelson, Michael Picard, Patricia A Pellikka, Udo Hoffmann, Pamela S Douglas
Journal: Circulation (2019)

Introduction: Inconclusive noninvasive diagnostic tests (NIT) are not uncommonly encountered in patients with suspected coronary artery disease, but their relative frequencies and attributable medi...
Abstract 14693: Incremental Utility of BNP and LV Global Longitudinal Strain in Predicting Post-operative LV Systolic Dysfunction and Outcomes in Asymptomatic Patients With Significant Primary Mitral Regurgitation Undergoing Mitral Valve Surgery
Authors: Alaa Alashi, Amgad Mentias, Krishna Patel, A Marc Gillinov, Zoran B Popovic, Tomislav Mihaljevic, L Leonardo Rodriguez, Joseph F Sabik, Brian P Griffin, Milind Y Desai
Journal: Circulation (2015)

Background: Outcomes after mitral valve (MV) surgery for primary mitral regurgitation (PMR) are excellent. However, some patients have a drop in post-op left ventricular ejection fraction (LVEF), despite preserved pre-op LVEF. In asymptomatic patients with ≥3+ PMR with preserved pre-op LVEF (≥60%) who underwent MV surgery for class IIa indications, we assessed the incremental ability of brain natriuretic peptide (BNP) &amp; LV-global longitudinal strain (LV-GLS) to predict a) a reduction in post-op LVEF &amp; b) long-term mortality. Methods: We included 448 such patients (61±12 years, 69% men) who had MV surgery between 2005-08. Clinical (including logBNP), baseline (including LV-GLS using Velocity Vector Imaging) &amp; follow up echo (LVEF) data were recorded. Post-op LVEF &lt;50% was considered abnormal. Society of Thoracic Surgeons (STS) score was calculated. Death during follow-up was recorded. Results: At baseline, atrial fibrillation, angiotensin inhibitors and betablockers &amp; MV flail were observed in 21%, 55%, 40% &amp; 45%, while mean STS score, logBNP, MV efective regurgitant orifice, LVEF, right ventricular systolic pressure &amp; LV-GLS were 4.1±1, 4.1±1, 0.55±0.2 cm2, 62±2%, 37±15 mm Hg &amp; -20.6±2%. 92% underwent MV repair (11% with coronary bypass) &amp; 94 (21%) had abnormal post-op LVEF. At 7.7±2 years, there were 30 (7%) deaths. Figure 1a shows logistic regression of association between abnormal post-op LVEF &amp; various factors. On multivariable Cox survival analysis, higher STS score (Hazard ratio or HR 1.55), lower LV-GLS (HR 1.17) &amp; higher logBNP (HR 2.26) were independent predictors of long-term mortality (all p&lt;0.05). Figure 1 b-c shows curves for long-term survival, based on LV-GLS &amp; log-BNP better or worse than median. Conclusions: In asymptomatic patients with ≥3+ PMR &amp; baseline LVEF ≥60% who underwent MV surgery, lower baseline LV-GLS &amp; higher logBNP were associated with abnormal post-op LVEF. Both, higher logBNP &amp; LV-GLS were associated with higher long-term mortality.
Claudi Bockting: preventing common mental health conditions
Authors: Tony Kirby
Journal: The Lancet Psychiatry (2021)

Growing up in a small town an hour's drive from Arnhem in The Netherlands, virtually every family that Claudi Bockting knew was touched by mental illness, including her own. "I saw at a young age the profound effect these conditions had on quality of life", Bockting tells The Lancet Psychiatry. "Without good mental health, nothing material matters."
Chromatin Accessibility of Human Mitral Valves and Functional Assessment of MVP Risk Loci
Authors: Sergiy Kyryachenko, Adrien Georges, Mengyao Yu, Takiy Barrandou, Lilong Guo, Patrick Bruneval, Tony Rubio, Judith Gronwald, Hassina Baraki, Ingo Kutschka, Kedar K. Aras, Igor R. Efimov, Russel A. Norris, Niels Voigt, Nabila Bouatia-Naji
Journal: Circulation Research (2021)

Mitral valve prolapse (MVP) is a common valvopathy that leads to mitral insufficiency, heart failure, and sudden death. Functional genomic studies in mitral valves are needed to better characterize MVP-associated variants and target genes.
Natural Language Processing to Assess Frequency of Functional Status Documentation for Patients Newly Diagnosed With Colorectal Cancer
Authors: Lin Sun
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Suicide Deaths During the COVID-19 Stay-at-Home Advisory in Massachusetts, March to May 2020
Authors: Jeremy Samuel Faust, Sejal B. Shah, Chengan Du, Shu-Xia Li, Zhenqiu Lin, Harlan M. Krumholz
Journal: JAMA Network Open (2021)

Mortality From Drug Overdose, Homicide, Unintentional Injuries, Motor Vehicle Crashes, and Suicide During the COVID-19 Pandemic
A novel protein encoded by circular SMO RNA is essential for Hedgehog signaling activation and glioblastoma tumorigenicity
Authors: Xujia Wu, Songhua Xiao, Maolei Zhang, Lixuan Yang, Jian Zhong, Bo Li, Fanying Li, Xin Xia, Xixi Li, Huangkai Zhou, Dawei Liu, Nunu Huang, Xuesong Yang, Feizhe Xiao, Nu Zhang
Journal: Genome biology (2021)

Abstract Background Aberrant activation of the Hedgehog pathway drives tumorigenesis of many cancers, including glioblastoma. However, the sensitization mechanism of the G protein-coupled-like receptor smoothened (SMO), a key component of Hedgehog signaling, remains largely unknown. Results In this study, we describe a novel protein SMO-193a.a. that is essential for Hedgehog signaling activation in glioblastoma. Encoded by circular SMO (circ-SMO), SMO-193a.a. is required for sonic hedgehog (Shh) induced SMO activation, via interacting with SMO, enhancing SMO cholesterol modification, and releasing SMO from the inhibition of patched transmembrane receptors. Deprivation of SMO-193a.a. in brain cancer stem cells attenuates Hedgehog signaling intensity and suppresses self-renewal, proliferation in vitro, and tumorigenicity in vivo. Moreover, circ-SMO/SMO-193a.a. is positively regulated by FUS, a direct transcriptional target of Gli1. Shh/Gli1/FUS/SMO-193a.a. form a positive feedback loop to sustain Hedgehog signaling activation in glioblastoma. Clinically, SMO-193a.a. is more specifically expressed in glioblastoma than SMO and is relevant to Gli1 expression. Higher expression of SMO-193a.a. predicts worse overall survival of glioblastoma patients, indicating its prognostic value. Conclusions Our study reveals that SMO-193a.a., a novel protein encoded by circular SMO, is critical for Hedgehog signaling, drives glioblastoma tumorigenesis and is a novel target for glioblastoma treatment.
Mitochondrial and Metabolic Pathways Regulate Nuclear Gene Expression to Control Differentiation, Stem Cell Function, and Immune Response in Leukemia
Authors: Grace Egan, Dilshad H. Khan, Jong Bok Lee, Sara Mirali, Li Zhang, Aaron D. Schimmer
Journal: Cancer Discovery (2021)

Mitochondria are involved in many biological processes including cellular homeostasis, energy generation, and apoptosis. Moreover, mitochondrial and metabolic pathways are interconnected with gene expression to regulate cellular functions such as cell growth, survival, differentiation, and immune recognition. Metabolites and mitochondrial enzymes regulate chromatin-modifying enzymes, chromatin remodeling, and transcription regulators. Deregulation of mitochondrial pathways and metabolism leads to alterations in gene expression that promote cancer development, progression, and evasion of the immune system. This review highlights how mitochondrial and metabolic pathways function as a central mediator to control gene expression, specifically on stem cell functions, differentiation, and immune response in leukemia. SIGNIFICANCE: Emerging evidence demonstrates that mitochondrial and metabolic pathways influence gene expression to promote tumor development, progression, and immune evasion. These data highlight new areas of cancer biology and potential new therapeutic strategies.
First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy in Advanced NSCLC With 1% or Greater Tumor PD-L1 Expression: Patient-Reported Outcomes From CheckMate 227 Part 1
Authors: Martin Reck, Tudor-Eliade Ciuleanu, Jong-Seok Lee, Michael Schenker, Clarisse Audigier-Valette, Bogdan Zurawski, Helena Linardou, Gregory A. Otterson, Pamela Salman, Makoto Nishio, Emmanuel de la Mora Jimenez, Krysztof Lesniewski-Kmak, István Albert, Samreen Ahmed, Konstantinos Syrigos, John R. Penrod, Yong Yuan, Steven I. Blum, Faith E. Nathan, Xiaowu Sun, Alejandro Moreno-Koehler, Fiona Taylor, Kenneth John O'Byrne
Journal: Journal of Thoracic Oncology (2021)

In CheckMate 227 (NCT02477826), patients with treatment-naive stage IV or recurrent NSCLC and 1% or greater tumor programmed death ligand 1 expression had significantly improved overall survival with nivolumab plus ipilimumab versus chemotherapy. We present the patient-reported outcomes (PROs).Patients (N = 1189) were randomized to nivolumab plus ipilimumab, nivolumab, or chemotherapy. PROs were exploratory. Changes in Lung Cancer Symptom Scale (LCSS) average symptom burden index, LCSS 3-item global index, EQ-5D visual analog scale (VAS), and EQ-5D utility index were analyzed descriptively. Mixed-effect model repeated measures and time-to-first deterioration and improvement analyses were conducted.PRO completion rates were generally greater than 80%. On-treatment improvements from baseline in LCSS measures of symptom burden and global health status with nivolumab plus ipilimumab generally met or exceeded the minimal important difference (smallest clinically meaningful change) from weeks 24 and 30, respectively; improvements with chemotherapy generally remained below the minimal important difference. Mean on-treatment EQ-5D VAS scores for both treatments approached the U.K. population norm at week 24, remaining so throughout the treatment period. Mixed-effect model repeated measures analyses revealed numerically greater improvements from baseline with nivolumab plus ipilimumab versus chemotherapy across LCSS average symptom burden index and 3-item global index, and EQ-5D VAS and utility index. Nivolumab plus ipilimumab had delayed time-to-first deterioration (hazard ratio [95% confidence interval] 0.74 [0.56 to 0.98]) and a trend for more rapid time-to-first improvement (1.24 [0.98 to 1.59]) versus chemotherapy.Nivolumab plus ipilimumab revealed delayed deterioration and numerical improvement in symptoms and health-related quality of life versus chemotherapy in patients with advanced NSCLC and 1% or greater programmed death ligand 1 expression.
Abstract 14743: Usefulness of Estimated Coronary Flow Velocity Using Quantitative Flow Ratio for Intermediate Coronary Stenosis
Authors: Eiji Ichimoto, Nao Konagai, Sawako Horie, Atsushi Hasegawa, Hirofumi Miyahara, Toshihisa Inoue, Yoshitake Nakamura
Journal: Circulation (2020)

Introduction: Quantitative flow ratio (QFR) is a diagnostic modality for functional assessment for intermediate coronary stenosis without the use of pressure wire. QFR is calculated from 3-dimensional quantitative CAG (3D-QCA) using an advanced algorithm that enables fast computation of the pressure drop caused by coronary stenosis. Hypothesis: We assessed the usefulness of QFR and the association with an estimated coronary flow velocity (eCFV) for intermediate coronary stenosis. Methods: A total of 100 lesions in 80 consecutive patients were assessed Fractional Flow Reserve (FFR) for intermediate coronary stenosis between January 2011 and April 2019. Of these, 97 lesions in 77 patients who underwent QFR were included in this study. Patients were classified into two groups (FFR ≤ 0.80 or FFR &gt; 0.80). QFR and eCFV using contrast were measured by Thrombolysis in Myocardial Infarction (TIMI) frame counts. Results: There was no significant differences in target vessels (p = 0.90) and diffuse lesions (p = 0.06) between the two groups (FFR ≤ 0.80 or FFR &gt; 0.80). Mean FFR and QFR values were 0.78 ± 0.12 and 0.77 ± 0.11, respectively. QFR had a good correlation with FFR values (r = 0.86, p &lt; 0.0001). The diagnostic accuracy, sensitivity, and specificity on QFR ≤ 0.80 were 91.8%, 92.7% and 90.5%, respectively. The eCFV of FFR ≤ 0.80 was greater than that of FFR &gt; 0.80 (0.19 ± 0.08 m/s vs. 0.14 ± 0.06 m/s, p&lt;0.001). Figure showed that the eCFV correlated with FFR values (r = -0.29, p &lt; 0.01). Moreover, the eCFV had a high area under the curve (AUC = 0.71, p &lt; 0.01) on Receiver operating characteristics curve (ROC) analysis with FFR ≤ 0.80. Conclusions: QFR was useful for the assessment of functional stenosis severity. As eCFV was faster, FFR was lower for intermediate coronary stenosis. The eCFV had a good correlation with FFR and may become one of the evaluations for ischemia.
Abstract 15292: Bradykinin Increases Cytosolic Ca2+ by Activating IP3Rs and TRPC1 Channels in Human Cardiac C-kit+ Progenitor Cells
Authors: Gang Li, Wei-Yin Wu, Ling-Jun Jie, Yan Wang, Gui-Rong Li
Journal: Circulation (2016)

Introduction: Bradykinin is an endogenous protective peptide. In a previous study we demonstrated that bradykinin regulates cell proliferation and migration by activating B2Rs and pAkt/pERK1/2 sign...
Abstract 15632: Renal Sympathetic Denervation in Addition to Pulmonary Vein Isolation Reduces the Recurrence Following Atrial Fibrillation Ablation: Meta-Analysis of Randomized Control Trials
Authors: Pattara Rattanawong, Narut Prasitlumkum, Nath Limpruttidham, Tanawan Riangwiwat, Wasawat Vutthikraivit
Journal: Circulation (2018)

Introduction: Atrial fibrillation (AF) is the most common arrhythmia among adults worldwide. The sympathetic nervous system plays an important role in precipitating and maintenance AF. Recent studi...
BMI1 enables extensive expansion of functional erythroblasts from human peripheral blood mononuclear cells
Authors: Senquan Liu, Mengyao Wu, Moira Lancelot, Jiusheng Deng, Yongxing Gao, John D. Roback, Tong Chen, Linzhao Cheng
Journal: Molecular Therapy (2021)

Transfusion of red blood cells (RBCs) from ABO-matched but genetically unrelated donors is commonly used for treating anemia and acute blood loss. Increasing demand and insufficient supply for donor RBCs, especially those of universal blood types or free of known and unknown pathogens, has called for ex vivo generation of functional RBCs by large-scale cell culture. However, generating physiological numbers of transfusable cultured RBCs (cRBCs) ex vivo remains challenging, due to our inability to either extensively expand primary RBC precursors (erythroblasts) or achieve efficient enucleation once erythroblasts have been expanded and induced to differentiation and maturation. Here, we report that ectopic expression of the human BMI1 gene confers extensive expansion of human erythroblasts, which can be derived readily from adult peripheral blood mononuclear cells of either healthy donors or sickle cell patients. These extensively expanded erythroblasts (E3s) are able to proliferate exponentially (>1 trillion-fold in 2 months) in a defined culture medium. Expanded E3 cells are karyotypically normal and capable of terminal maturation with approximately 50% enucleation. Additionally, E3-derived cRBCs can circulate in a mouse model following transfusion similar to primary human RBCs. Therefore, we provide a facile approach of generating physiological numbers of human functional erythroblasts ex vivo.
The hospital admission profile of people presenting to specialist addiction services with problematic use of alcohol or opioids: A national retrospective cohort study in England
Authors: Emmert Roberts, Matthew Hotopf, John Strang, John Marsden, Martin White, Brian Eastwood, Colin Drummond
Journal: The Lancet Regional Health - Europe (2021)

Over the past decade in England the rate of alcohol and opioid-related hospitalisation has increased alongside a simultaneous reduction in people accessing specialist addiction treatment. We aimed to determine the hospitalisation patterns of people presenting to addiction treatment with problematic use of alcohol or opioids, and estimate how individual sociodemographic characteristics and hospital admission diagnoses are associated with the rate of hospitalisation, death and successful completion of addiction treatment.A national record linkage between Hospital Episode Statistics (HES) and the National Drug Treatment Monitoring System (NDTMS) captured lifetime hospital admission profiles of people presenting to addiction services in England in 2018/19. Latent class analysis assigned individuals to clusters based on the ICD-10 diagnosis coded as primary reason for admission. Negative binomial, and multilevel logistic regression models determined if outcomes differed due to sociodemographic characteristics or assigned diagnostic clusters.Inpatient data were available for 64,840 alcohol patients, and 107,296 opioid patients. The most common reasons for admission were alcohol withdrawal (n = 20,024 (5.3% of alcohol-cohort admissions)), and unspecified illness (n = 11,387 (2.1% of opioid-cohort admissions)). Seven diagnostic clusters were identified for each substance cohort. People with admissions predominantly relating to mental and behavioural disorders, and injuries or poisonings had significantly higher hospitalisation rates (adjusted IRR 7.06 (95%CI 6.72-7.42);p < 0.001), higher odds of death during addiction treatment (adjusted OR 2.71 (95%CI 2.29-3.20);p < 0.001) and lower odds of successful treatment completion (adjusted OR 0.72 (95%CI 0.68-0.76);p < 0.001).This is the first study to interrogate national hospitalisation patterns within people presenting to addiction services with problematic use of alcohol or opioids. Having identified high-risk, high-cost individuals with increased hospital usage, and increased odds of death, future work should focus on targeting appropriate interventions, to improve their health outcomes and prevent unnecessary hospital readmission.The work was funded by the Medical Research Council (MRC).
THU0057 Disturbed peripheral b cell homeostais in sle
Authors: T Dörner, M Odendahl, A Jacobi, A Hansen, F Hiepe, GR Burmester, PE Lipsky, A Radbruch
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The distribution of peripheral B cell subpopulations in SLE is unknown, although a variety of humoral abnormalities are known. <h3>Objectives</h3> The phenotype and Ig heavy chain gene usage of peripheral B cell subpopulations of patients with active systemic lupus erythematosus (SLE) were examined. <h3>Methods</h3> Peripheral B cells were characterised by FACS analysis and B cell subpopulations of one patient were characterised for V(D) J gene rearrangements. <h3>Results</h3> In patients with SLE, there was a marked B lymphocytopenia that affected CD19<sup>+</sup>/CD27- naïve B cells more than CD19<sup>+</sup>/CD27<sup>+</sup> memory B cells leading to a relative predominance of CD27 expressing peripheral B cells. In contrast, CD27high/CD38<sup>+</sup>/CD19dim/surface Iglow/CD20-/syndecan-1+plasma cells were found at an enhanced frequency in active but not inactive SLE patients. Upon immunosuppressive therapy, CD27high plasma cells and naïve CD27- B cells were markedly decreased in the peripheral blood. Mutational analysis of V gene rearrangements of individual B cells confirmed that CD27<sup>+</sup> B cells coexpressing IgD were memory B cells preferentially using VH3 family members with multiple somatic mutations. CD27high plasma cells showed a similar degree of somatic hypermutation, but preferentially employed VH4 family members. <h3>Conclusion</h3> These results indicate that there are profound abnormalities in the various B cell compartments in SLE that respond differently to immunosuppressive therapy.
Identification and characterization of ERAP1 as a novel molecular target for breast cancer therapy
Authors: Jung-Won Kim, Miki Akiyama, Toyomasa Katagiri, Toshihiko Nishidate, Yusuke Nakamura
Journal: Cancer Research (2008)

2357  To discover novel therapeutic targets for breast cancer, we previously analyzed genome-wide expression profiles of 81 breast cancers by using cDNA microarray. Among the transactivated genes, we identified ERAP1 (Estrogen Receptor-Associated Protein1) as a candidate molecule for development of drugs for breast cancer. Semiquantitative RT-PCR and northern analyses confirmed that expression of ERAP1 was up-regulated in the great majority of breast cancer samples. Knockdown of ERAP1 expression with specific small-interfering RNA significantly suppressed the growth of breast cancer cell lines, BT-549 and BT-474 cells. In addition, introduction of ERAP1 into NIH3T3 cells significantly enhanced cell growth at in vitro, suggesting an oncogenic role of ERAP1 for development of breast cancer. Furthermore, we found the interaction of ERAP1 and prohibitin 2/repressor of estrogen receptor activity (PHB2/REA) by co-immunoprecipitation and immunoblotting assays. Interestingly, in an absence of ERAP1 protein, PHB2/REA translocated together with ERα to the nucleus by the stimulation of 17β-estradiol (E2), but in the presence of exogenously expressed ERAP1 protein it remained in cytoplasm. Introduction of ERAP1 protein enhanced of ER transcriptional activity in MCF7 (ERα-positive) cells after E2 treatment, while did not enhance ER transcriptional activity in SK-BR-3 (ERα-negative) cells, implying that ERAP1 is likely to be involved in breast tumorigenesis by the regulation of ERα transcriptional activity through the inhibition of interaction between ERα and PHB2/REA. Taken together, our findings suggest that ERAP1 may play key roles in breast tumor cell growth.