tbuckley/cabot-search huggingface dataset:
The Meningioma Enhancer Landscape Delineates Novel Subgroups and Drives Druggable Dependencies
Authors: Briana C. Prager, Harish N. Vasudevan, Deobrat Dixit, Jean A. Bernatchez, Qiulian Wu, Lisa C. Wallace, Shruti Bhargava, Derrick Lee, Bradley H. King, Andrew R. Morton, Ryan C. Gimple, Melike Pekmezci, Zhe Zhu, Jair L. Siqueira-Neto, Xiuxing Wang, Qi Xie, Clark Chen, Gene H. Barnett, Michael A. Vogelbaum, Stephen C. Mack, Lukas Chavez, Arie Perry, David R. Raleigh, Jeremy N. Rich
Journal: Cancer Discovery (2020)

Abstract Meningiomas are the most common primary intracranial tumor with current classification offering limited therapeutic guidance. Here, we interrogated meningioma enhancer landscapes from 33 tumors to stratify patients based upon prognosis and identify novel meningioma-specific dependencies. Enhancers robustly stratified meningiomas into three biologically distinct groups (adipogenesis/cholesterol, mesodermal, and neural crest) distinguished by distinct hormonal lineage transcriptional regulators. Meningioma landscapes clustered with intrinsic brain tumors and hormonally responsive systemic cancers with meningioma subgroups, reflecting progesterone or androgen hormonal signaling. Enhancer classification identified a subset of tumors with poor prognosis, irrespective of histologic grading. Superenhancer signatures predicted drug dependencies with superior in vitro efficacy to treatment based upon the NF2 genomic profile. Inhibition of DUSP1, a novel and druggable meningioma target, impaired tumor growth in vivo. Collectively, epigenetic landscapes empower meningioma classification and identification of novel therapies. Significance: Enhancer landscapes inform prognostic classification of aggressive meningiomas, identifying tumors at high risk of recurrence, and reveal previously unknown therapeutic targets. Druggable dependencies discovered through epigenetic profiling potentially guide treatment of intractable meningiomas. This article is highlighted in the In This Issue feature, p. 1611
Intravascular Microaxial Left Ventricular Assist Device vs Intra-aortic Balloon Pump for Cardiogenic Shock—Reply
Authors: Sanket S. Dhruva, Bobak J. Mortazavi, Nihar R. Desai
Journal: JAMA (2020)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Dialectical Behavior Therapy for Posttraumatic Stress Disorder (DBT-PTSD) Compared With Cognitive Processing Therapy (CPT) in Complex Presentations of PTSD in Women Survivors of Childhood Abuse
Authors: Martin Bohus, Nikolaus Kleindienst, Christopher Hahn, Meike Müller-Engelmann, Petra Ludäscher, Regina Steil, Thomas Fydrich, Christine Kuehner, Patricia A. Resick, Christian Stiglmayr, Christian Schmahl, Kathlen Priebe
Journal: JAMA Psychiatry (2020)

Childhood abuse significantly increases the risk of developing posttraumatic stress disorder (PTSD), often accompanied by symptoms of borderline personality disorder (BPD) and other co-occurring mental disorders. Despite the high prevalence, systematic evaluations of evidence-based treatments for PTSD after childhood abuse are sparse.To compare the efficacy of dialectical behavior therapy for PTSD (DBT-PTSD), a new, specifically designed, phase-based treatment program, against that of cognitive processing therapy (CPT), one of the best empirically supported treatments for PTSD.From January 2014 to October 2016, women who sought treatment were included in a multicenter randomized clinical trial with blinded outcome assessments at 3 German university outpatient clinics. The participants were prospectively observed for 15 months. Women with childhood abuse-associated PTSD who additionally met 3 or more DSM-5 criteria for BPD, including affective instability, were included. Data analysis took place from October 2018 to December 2019.Participants received equal dosages and frequencies of DBT-PTSD or CPT, up to 45 individual sessions within 1 year and 3 additional sessions during the following 3 months.The predefined primary outcome was the course of the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) score from randomization to month 15. Intent-to-treat analyses based on dimensional CAPS-5 scores were complemented by categorical outcome measures assessing symptomatic remission, reliable improvement, and reliable recovery.Of 955 consecutive individuals assessed for eligibility, 193 were randomized (DBT-PTSD, 98; CPT, 95; mean [SD] age, 36.3 [11.1] years) and included in the intent-to-treat analyses. Analysis revealed significantly improved CAPS-5 scores in both groups (effect sizes: DBT-PTSD: d, 1.35; CPT: d, 0.98) and a small but statistically significant superiority of DBT-PTSD (group difference: 4.82 [95% CI, 0.67-8.96]; P = .02; d, 0.33). Compared with the CPT group, participants in the DBT-PTSD group were less likely to drop out early (37 [39.0%] vs 25 [25.5%]; P = .046) and had higher rates of symptomatic remission (35 [40.7%] vs 52 [58.4%]; P = .02), reliable improvement (53 [55.8%] vs 73 [74.5%]; P = .006), and reliable recovery (34 [38.6%] vs 52 [57.1%]; P = .01).These findings support the efficacy of DBT-PTSD and CPT in the treatment of women with childhood abuse-associated complex PTSD. Results pertaining to the primary outcomes favored DBT-PTSD. The study shows that even severe childhood abuse-associated PTSD with emotion dysregulation can be treated efficaciously.German Clinical Trials Register: DRKS00005578.
SAT0222 Total body and regional bone mineral and soft-tissue composition in hiv disease
Authors: J Bernard, E Bonnet, C Acquilina, R Hervé, P Massip, B Mazières
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Osteopenia and adipose tissue maldistribution are two complications of highly active anti-retroviral therapy (HAART: 1 protease inhibitor + 2 nucleoside reverse transcriptase inhibitors). Dual energy x-rays absorptiometry (DEXA) is a reliable tool to assess total body and regional bone mineral and soft-tissue composition. <h3>Objectives</h3> (1) To compare the results of DEXA in HIV-infected patients treated or not with HAART, with or without clinical lipodystrophy and (2) to evaluate DEXA as a tool for early diagnosis of body fat redistribution. <h3>Methods</h3> A cross-sectional analysis was performed on 220 men. All subjects gave written informed consent. Controls (C): 106 healthy uninfected volunteers without medical or surgical history, nor immobilisation and therapies which may modify bone mineral density, mean age 38 years. One hundred and fourteen HIV-infected patients at steady-state, without opportunist disease, nor prophylactic drugs? use were divided in 3 groups: (i) 20 naive HIV-patients (N: mean age 38 years, disease duration 43 mths, viral load 3.7 log, CD4<sup>+</sup> 417/mm<sup>3</sup>), (ii) 32 HIV-treated patients with no clinical lipodystrophy (n-CLD: mean age 35, disease duration 72 mths, HAART duration 15 mths, viral load 2.3 log, CD4<sup>+</sup> 524/mm<sup>3</sup>), and (iii) 62 HIV-treated patients with clinical lipodystrophy (CLD: mean age 42, disease duration 94 mths, HAART duration 26 mths, viral load 1.8 log, CD4<sup>+</sup> 483/mm<sup>3</sup>). Total body and regional soft-tissue composition were measured with DEXA (DPX-L, Lunar Corp. Acquisition and analysis software 4.6). The following parameters were studied: Fat Mass% (FM,%), Lean Mass (LM, kg), Bone Mineral Content (BMC, mg), and Fat Mass Index (FMI: trunk fat mass/legs fat mass). Statistics. Mean ± SD, ANOVA, Scheffe's F procedure for post-hoc comparison. <h3>Results</h3> Lean Mass was the same in the 4 groups. Despite 43 months of disease duration, Naive and Controls had the same fat mass, BMC and FMI. The two treated HIV-infected groups had lower Fat Mass and upper Fat Mass Index than Controls. Loss in Fat Mass at the expense of the legs was proportional to duration of HAART. The great variability of the FMI (SD) in these two groups suggested a poor clinical sensitivity to change. Decrease of BMC seemed treatment-dependent. Lipodystrophy appeared also age-related. <h3>Conclusion</h3> DEXA allows an early diagnosis of fat maldistribution. We propose to perform this exam to all HIV-infected patients once a year before treatment and every 6 months in patients under treatment.
THU0189 Pronostic value of serum bone markers and hand bone densitometry in very early rheumatoid arthritis: preliminary results of the vera study
Authors: O Vittecoq, A Daragon, M Brazier, O Mejjad, P Fardellone, K Krzanowska, P Boumier, C Zarnitsky, A Phan Van, A Gayet, JF Menard, X Le Loët
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To study the pronostic value of serum bone markers and hand bone densitometry in very early rheumatoid arthritis (RA). <h3>Methods</h3> From a population-based recruitment, 66 patients with very early (median duration: 4.3 months [1 – 6 mo]) peripheral arthritis (swelling &gt; = 2 joints for &gt; 4 weeks) were studied. Patients were steroid and DMARD naive. After a year, patients were classified as RA or non RA. Assessments were performed at entry (T1), after 9 (T2) and 12 (T3) months. Serum bone markers were C telopeptide (ICTP) by ELISA test, free pyridinoline (Pyr) and free deoxypyridinoline (DPyr) by HPLC. Other investigation: hand bone densitometry (DEXA), hands and feet X rays. Prognosis was defined as the progression of radiological damage from T1 to T3 (van der Heijde modified Sharp's method). <h3>Results</h3> At T3, 26 patients had radiological progressive disease, and 40 no progressive disease. 50/66 patients fulfilled ACR criteria for RA (75% in non progressive group, 77% in progressive group, NS). At T1, no difference was found between progressive group and non progressive group, excepted for rheumatoid factors more frequent in progressive group (p &lt; 0,03). Bone mineral density (BMD) of both hands decreased significantly from T1 to T3 in the progressive group (p &lt; 0,03), whereas it remains unchanged in the non progressive group. Furthermore, ICTP, Pyr and DPyr levels at T1 were negatively correlated to the evolution of hand BMD from T1 to T3 (p &lt; 0,001, p &lt; 0,02, and p &lt; 0,01 respectively). <h3>Conclusion</h3> In patients with early RA, a structural bone damage progression after 12 months duration is associated with a decrease of hand BMD. Moreover, this decrease was negatively correlated with levels of serum bone markers at entry. These preliminary results of the VERA study need to be confirmed on a larger population. Study granted by Fondation de la Recherche Médicale and by Pharmacia, France.
A Man With Widespread Arthritis and Ill-Defined Cutaneous Lesions
Authors: Débora de A. A. Lima, Andreza Vertuan, José Barreto Campello Carvalheira
Journal: JAMA Oncology (2020)

A man in his 30s presented with a 3-month history of fourth finger right hand articular heat, pain, redness, and swelling, which developed into widespread arthritis accompanied by ill-defined skin nodules. What is your diagnosis?
Chromatin remodeler Znhit1 preserves hematopoietic stem cell quiescence by determining the accessibility of distal enhancers
Authors: Shenfei Sun, Ning Jiang, Yamei Jiang, Qiuping He, Hua He, Xin Wang, Li Yang, Runsheng Li, Feng Liu, Xinhua Lin, Bing Zhao
Journal: Leukemia (2020)

Abstract Hematopoietic stem cell (HSC) utilizes its quiescence feature to combat exhaustion for lifetime blood cell supply. To date, how certain chromatin architecture and subsequent transcription profile permit HSC quiescence remains unclear. Here, we show an essential role of chromatin remodeler zinc finger HIT-type containing 1 (Znhit1) in maintaining HSC quiescence. We find that loss of Znhit1 leads to exhaustion of stem cell pool and impairment of hematopoietic function. Mechanically, Znhit1 determines the chromatin accessibility at distal enhancers of HSC quiescence genes, including Pten , Fstl1 , and Klf4 , for sustained transcription and consequent PI3K–Akt signaling inhibition. Moreover, Znhit1–Pten–PI3K–Akt axis also participates in controlling myeloid expansion and B-lymphoid specification. Our findings therefore identify a dominant role of Znhit1-mediated chromatin remodeling in preserving HSC function for hematopoietic homeostasis.
Radioiodinated Persistent Luminescence Nanoplatform for Radiation‐Induced Photodynamic Therapy and Radiotherapy
Authors: Qiang Wang, Nian Liu, Zhenyu Hou, Junpeng Shi, Xinhui Su, Xiaolian Sun
Journal: Advanced Healthcare Materials (2020)

Abstract Radionuclide with Cerenkov radiation (CR) can serve as an internal excitation source to activate photosensitizers for photodynamic therapy (PDT) in deep tumor. However, the low efficiency of CR limits its therapeutic efficacy. A 131 I labeled zinc tetra(4‐carboxyphenoxy) phthalocyaninate (ZnPcC4) conjugated Cr 3+ ‐doped zinc gallate (ZnGa 2 O 4 :Cr 3+ , ZGCs) nanoplatform ( 131 I‐ZGCs‐ZnPcC4) is developed for radiotherapy (RT) and radiation‐induced PDT. 131 I can not only activate ZGCs for long‐lasting luminescence via both Cerenkov luminescence (CL) and ionizing radiation, which further continuously activate photosensitizer ZnPcC4 for PDT, but also can directly kill cancerous cells. This 131 I‐ZGCs‐ZnPcC4 exhibits excellent tumor inhibition both in vitro and in vivo. Combining self‐activated PDT and RT, it is believed that the 131 I‐ZGCs‐ZnPcC4 can greatly benefit the deep tumor therapy.
Resveratrol inhibits phorbol ester-induced expression of COX-2 and activation of NF-κB in mouse skin in vivo: IκB kinase-β and mitogen-activated protein kinases as potential targets
Authors: Joydeb K. Kundu, Young-Joon Surh
Journal: Cancer Research (2005)

750  Recent progress in unraveling molecular basis of carcinogenesis suggests a causal link between inflammation and cancer. Inappropriate up-regulation of cyclooxygenase-2 (COX-2), a rate limiting enzyme in the biosynthesis of inflammatory mediators, has been implicated in malignant transformation of cells. Resveratrol, a phytoalexin with antioxidant and anti-inflammatory properties, was reported to inhibit chemically-induced carcinogenesis in mouse skin. The present study was aimed to investigate the effect of resveratrol on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced COX-2 expression in mouse skin and to elucidate underlying molecular mechanisms. Dorsal skin of female ICR mice was treated with resveratrol (0, 0.25, and 1 μmol) 30 min prior to topical application of 10 nmol TPA. Skin tissue homogenates were subjected to western blot analysis, the electrophoretic mobility shift assay, and the in vitro kinase assay to examine effects of resveratrol on TPA-induced expression of COX-2, and the activation of transcription factor and upstream kinases in mouse skin, respectively. Topical application of resveratrol significantly inhibited TPA-induced COX-2 expression in mouse skin. Resveratrol prevented TPA-induced DNA binding of nuclear factor-kappaB (NF-κB), which is known to regulate COX-2 gene transcription. Moreover, resveratrol blocked TPA-induced phosphorylation and degradation of IκBα, and also phosphorylation and nuclear translocation of p65. A kinetic study revealed that topical application of TPA on mouse skin caused a significant increase in the activity of IκB kinase (IKK)-β, an upstream enzyme known to activate NF-κB through phosphorylation of IκBα. Pretreatment with resveratrol attenuated the TPA-induced IKK-β activity. Previous studies from this laboratory have revealed that mitogen-activated protein (MAP) kinases regulate TPA-induced activation of NF-κB and subsequently COX-2 expression in mouse skin (Chun et al., Carcinogenesis, 24:1515-1524, 2003). Pretreatment with resveratrol suppressed the phosphorylation of extracellular signal-regulated protein kinase (ERK), p38 MAP kinase and c-Jun N-terminal kinase. In addition, catalytic activities of ERK and p38 MAP kinase were attenuated by resveratrol. Taken together, the above findings suggest that resveratrol suppresses TPA-induced COX-2 expression in mouse skin by blocking the activation of NF-κB and upstream kinases such as MAP kinases and IKK-β, lending mechanistic support to the previously reported anti-tumor promoting effect of this dietary phytochemical.
OP0067 CUMULATIVE ANTIBIOTIC USE AND THE RISK OF DEVELOPING ANKYLOSING SPONDYLITIS: A POPULATION-BASED CASE CONTROL STUDY
Authors: A. Pascual-Dapena, A. Prats-Uribe, D. Prieto-Alhambra
Journal: Annals of the Rheumatic Diseases (2020)

Background: Recent studies show possible mechanisms of microbiota alterations that lead to the development of Ankylosing spondylitis (AS). These disturbances in the microbiota can be caused by long-term and high dose intake of antibiotics Objectives: To analyze the association between antibiotic/s use and the risk of developing AS. Methods: Population based case-control study using electronic medical records data from SIDIAP, covering &gt;80% of the population in Catalonia, Spain. AS diagnoses with 2+ years data available were matched to up to 5:1 controls of same age, sex, and GP practice, and similar follow-up. Tracking of antibiotic use in the previous two years was done through pharmacy dispensation data standardized with ATC codes, and categorized in terms of recency of use and quartiles of cumulative dose. Adjusted odds ratios were estimated using conditional logistic regression analyzing antibiotic use (yes/no), recency of intake (current, recent, past, no use) and cumulative dose (quartiles of daily defined doses in the previous two years). All analyses were adjusted for age, body mass index, smoking, co-morbidity, socio-economic deprivation and number of GP visits as a proxy for healthcare resource use. Results: The study included 4,493 cases diagnosed with AS and 22,016 controls. 46.3% of cases and 28.2% of controls had taken antibiotics. An association between taking beta-lactams (OR 1.18 [95% CI: 1.09-1.28]) and taking macrolides (OR 1.34 [95% CI: 1.18-1.52]) and getting diagnosed with AS was found. This association was stronger with current/recent use (Figure 1), but no dose-response pattern was seen (Figure 2). Figure 1. Recency of use and AS diagnosis. Figure 2. Cumulative use and AS diagnosis Conclusion: There is an association between use of certain types of antibiotics and the diagnosis of AS, but no dose-response gradient. These data do not support a causal effect of cumulative antibiotic use on the development of AS. More research is needed on the impact of microbiome disturbance on the risk of developing AS. Acknowledgments: Partial support received from the Oxford NIHR Biomedical Research Centre (BRC) Disclosure of Interests: Ana Pascual-Dapena: None declared, Albert Prats-Uribe: None declared, Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen
Rapid roll out of SARS-CoV-2 antibody testing: even at high levels of specificity, an important proportion of test results will be false positives
Authors: Laurence Gruer, Raj Bhopal
Journal: BMJ (2020)

We have published a paper with 12 tables (in a supplementary file) with calculations of sensitivity, specificity, and the predictive power of a positive and negative test that will help people understand the concerns about the rapid roll-out of SARS-CoV-2 antibody tests expressed by Andersson and colleagues.1 With our colleagues we showed that even at high levels of specificity, an …
Emergence of a High-Plasticity Cell State during Lung Cancer Evolution
Authors: Nemanja Despot Marjanovic, Matan Hofree, Jason E. Chan, David Canner, Katherine Wu, Marianna Trakala, Griffin G. Hartmann, Olivia C. Smith, Jonathan Y. Kim, Kelly Victoria Evans, Anna Hudson, Orr Ashenberg, Caroline B.M. Porter, Alborz Bejnood, Ayshwarya Subramanian, Kenneth Pitter, Yan Yan, Toni Delorey, Devan R. Phillips, Nisargbhai Shah, Ojasvi Chaudhary, Alexander Tsankov, Travis Hollmann, Natasha Rekhtman, Pierre P. Massion, John T. Poirier, Linas Mazutis, Ruifang Li, Joo-Hyeon Lee, Angelika Amon, Charles M. Rudin, Tyler Jacks, Aviv Regev, Tuomas Tammela
Journal: Cancer Cell (2020)
Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma
Authors: Carlos A. Ramos, Natalie S. Grover, Anne W. Beaven, Premal D. Lulla, Meng-Fen Wu, Anastasia Ivanova, Tao Wang, Thomas C. Shea, Cliona M. Rooney, Christopher Dittus, Steven I. Park, Adrian P. Gee, Paul W. Eldridge, Kathryn L. McKay, Birju Mehta, Catherine J. Cheng, Faith B. Buchanan, Bambi J. Grilley, Kaitlin Morrison, Malcolm K. Brenner, Jonathan S. Serody, Gianpietro Dotti, Helen E. Heslop, Barbara Savoldo
Journal: Journal of Clinical Oncology (2020)

Chimeric antigen receptor (CAR) T-cell therapy of B-cell malignancies has proved to be effective. We show how the same approach of CAR T cells specific for CD30 (CD30.CAR-Ts) can be used to treat Hodgkin lymphoma (HL).