tbuckley/cabot-search huggingface dataset:
REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics
Authors: R. L. Carhart-Harris, K. J. Friston
Journal: Pharmacological Reviews (2019)

This paper formulates the action of psychedelics by integrating the free-energy principle and entropic brain hypothesis. We call this formulation relaxed beliefs under psychedelics (REBUS) and the anarchic brain, founded on the principle that—via their entropic effect on spontaneous cortical activity—psychedelics work to relax the precision of high-level priors or beliefs, thereby liberating bottom-up information flow, particularly via intrinsic sources such as the limbic system. We assemble evidence for this model and show how it can explain a broad range of phenomena associated with the psychedelic experience. With regard to their potential therapeutic use, we propose that psychedelics work to relax the precision weighting of pathologically overweighted priors underpinning various expressions of mental illness. We propose that this process entails an increased sensitization of high-level priors to bottom-up signaling (stemming from intrinsic sources), and that this heightened sensitivity enables the potential revision and deweighting of overweighted priors. We end by discussing further implications of the model, such as that psychedelics can bring about the revision of other heavily weighted high-level priors, not directly related to mental health, such as those underlying partisan and/or overly-confident political, religious, and/or philosophical perspectives. <h3>Significance Statement</h3> Psychedelics are capturing interest, with efforts underway to bring psilocybin therapy to marketing authorisation and legal access within a decade, spearheaded by the findings of a series of phase 2 trials. In this climate, a compelling unified model of <i>how</i> psychedelics alter brain function to alter consciousness would have appeal. Towards this end, we have sought to integrate a leading model of global brain function, <i>hierarchical predictive coding</i>, with an often-cited model of the acute action of psychedelics, <i>the entropic brain hypothesis</i>. The resulting synthesis states that psychedelics work to relax high-level priors, sensitising them to liberated bottom-up information flow, which, with the right intention, care provision and context, can help guide and cultivate the revision of entrenched pathological priors.
PB2259 SIGNIFICANCE OF INCIDENTAL FINDINGS DETECTED ON PET‐CT SCANS PERFORMED IN HAEMATO‐ONCOLOGY: A SINGLE CENTRE EXPERIENCE
Authors: C. Mackintosh, R. Soutar, P. McCarthy, A.‐E. Koumpis
Journal: HemaSphere (2019)

Background: PET‐CTs scans are commonly used in haematological malignancies to stage disease and assess response to therapy. It is not uncommon for PET‐CT to reveal incidental findings, the significance of which is unclear. Aims: This study aimed to determine how common incidental findings are in patients with haematological malignancies, and assess the outcome of the investigations into these findings. Methods: Reports from 212 patients who had a PET‐CT scan reviewed at the departmental haematology‐radiology meeting of the Beatson Oncology Centre, Glasgow, Scotland between May 2015 and May 2018 were reviewed retrospectively. All scans were undertaken at the same site, the West of Scotland PET Centre. For each incidental finding, follow up, diagnosis and outcome was then reviewed. 57% (n = 121) of patients were male and the median age was 57 years. The majority of patients (93%, n = 196) underwent the PET‐CT scan due to underlying lymphoma, 122 (43%) of these were Non‐Hodgkin and 74 (35%) with Hodgkin lymphoma,16 of the patients had underlying myeloma or other suspected malignancies. Results: The study found that 13% (n = 28) of patients that underwent PET‐CT scanning had an incidental finding. The majority of these findings (82%, n = 23) were investigated further. No significant abnormal finding was revealed through further investigation for 43% (n = 10). A pathological finding was found in 57% (n = 13) of scans. Of these 69% (n = 9) had a pre‐malignant or malignant diagnosis: 2 adenocarcinomas and 4 precancerous polyps in the colon and 3 Thy3a in the thyroid. The remaining 4 were benign pathologies including gastric reflux, benign adenomas and a fistula. The incidental findings were in a variety of anatomical sites, the most common being the colon (n = 15 findings), followed by the thyroid (n = 4). Regarding outcome patients with pre‐malignant polyps and adenocarcinomas underwent complete surgical excision, with no disease remaining post operatively. No patient had evidence of progression / relapse of the incidental finding at time of follow up. Summary/Conclusion: Incidental findings on PET‐CT were shown to occur commonly in patients with haematological malignancies. Follow up of these incidental findings is indicated, and appropriate, as it often results in the diagnosis of a treatable, pathological condition. Further investigation in patients with haematological malignancy is particularly important in view of the potential high survival rate from the underlying haematological cancer.
Abstract 13355: The Characteristics and Outcomes of the Elderly Atrial Fibrillation Patients With or Without Oral Anticoagulants in Japanese Clinical Practice: The Fushimi AF Registry
Authors: Syuhei Ikeda, Moritake Iguchi, Yuya Aono, Kosuke Doi, Yoshimori An, Mitsuru Ishii, Nobutoyo Masunaga, Masahiro Esato, Hiromichi Wada, Koji Hasegawa, Hisashi Ogawa, Mitsuru Abe, Masaharu Akao
Journal: Circulation (2018)

Introduction: Atrial fibrillation (AF) increases the risk of thromboembolism, and oral anticoagulants (OAC) are highly effective in preventing it. However, the risk of bleeding is also high in the ...
SAT0069 PROTECTIVE EFFECT OF PROTOCATECHUIC ACID RICH FRACTION OF TRIANTHEMA PORTULACASTRUM AGAINST COLLAGEN INDUCED RHEUMATOID ARTHRITIS VIA GUT MICROBIOTA MODULATION
Authors: Ekta Yadav
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Rheumatoid arthritis, a chronic inflammatory joint disease affects people all over the world. Trianthema portulacastrum (TP) has been traditionally utilized for the treatment of rheumatism. <h3>Objectives</h3> The current study was envisaged to evaluate the effect of protocatechuic acid rich fraction of TP on type II collagen induced rheumatoid arthritis, inflammation and microbial population of gut by using rodent model. <h3>Methods</h3> Hydroethanolic extract of TP was fractionated with three different solvents (ethyl acetate, chloroform and n-butanol) and quantitatively analyzed with HPLC-DAD method which revealed n-butanol fraction of TP (BFTP) is rich in protocatechuic acid along with other phenolic compounds. Animals were randomly divided into five groups. Four groups were injected with bovine type-II collagen (BTC-II; 100μg) in Freund's complete adjuvant (0.1 ml) intradermally. On day 21, animals were again treated with BTC-II along with booster incomplete Freund's adjuvant injection. After 24 hrs, animal groups were administered intraperitoneally with their respective drug treatment, i.e., vehicle, BFTP (100, 200 and 400 mg/kg b.w.) and methotrexate (3 mg/kg b.w.), respectively once in a day for next 21 days. At the end of experiment serum level of pro-inflammatory cytokines was determined, and gut microbioata was analyzed by using Illumina HiSeq. <h3>Results</h3> Results revealed BFTP preadministered group exhibited significantly reduced level of paw swelling and arthritis score as compared to vehicle group. Inflammatory markers (IL-1β, IL-6, IL-7, IL-23 and TNF-α) of rheumatoid arthritis were also significantly alleviated by BFTP. Histological studies of mice ankle soft tissue also support the protective effect of BFTP. Additionally, BFTP repair altered gut microbial communities by reducing relative loads of inflammatory microbes such as Mucispirillum, Helicobacter and Lachnospiraceae. <h3>Conclusion</h3> The results conclude that BFTP possess beneficial anti-inflammatory response in arthritic model and can be used as a potential anti-arthritic agent for the management of arthiritis. <h3>Disclosure of Interests</h3> None declared
Orthotopic replacement of T-cell receptor α- and β-chains with preservation of near-physiological T-cell function
Authors: Kilian Schober, Thomas R. Müller, Füsun Gökmen, Simon Grassmann, Manuel Effenberger, Mateusz Poltorak, Christian Stemberger, Kathrin Schumann, Theodore L. Roth, Alexander Marson, Dirk H. Busch
Journal: Nature Biomedical Engineering (2019)
Cold stress induces enhanced chromatin accessibility and bivalent histone modifications H3K4me3 and H3K27me3 of active genes in potato
Authors: Zixian Zeng, Wenli Zhang, Alexandre P. Marand, Bo Zhu, C. Robin Buell, Jiming Jiang
Journal: Genome biology (2019)

Cold stress can greatly affect plant growth and development. Plants have developed special systems to respond to and tolerate cold stress. While plant scientists have discovered numerous genes involved in responses to cold stress, few studies have been dedicated to investigation of genome-wide chromatin dynamics induced by cold or other abiotic stresses.Genomic regions containing active cis-regulatory DNA elements can be identified as DNase I hypersensitive sites (DHSs). We develop high-resolution DHS maps in potato (Solanum tuberosum) using chromatin isolated from tubers stored under room (22 °C) and cold (4 °C) conditions. We find that cold stress induces a large number of DHSs enriched in genic regions which are frequently associated with differential gene expression in response to temperature variation. Surprisingly, active genes show enhanced chromatin accessibility upon cold stress. A large number of active genes in cold-stored tubers are associated with the bivalent H3K4me3-H3K27me3 mark in gene body regions. Interestingly, upregulated genes associated with the bivalent mark are involved in stress response, whereas downregulated genes with the bivalent mark are involved in developmental processes. In addition, we observe that the bivalent mark-associated genes are more accessible than others upon cold stress.Collectively, our results suggest that cold stress induces enhanced chromatin accessibility and bivalent histone modifications of active genes. We hypothesize that in cold-stored tubers, the bivalent H3K4me3-H3K27me3 mark represents a distinct chromatin environment with greater accessibility, which may facilitate the access of regulatory proteins required for gene upregulation or downregulation in response to cold stress.
Tumor necrosis factor-A polymorphisms and gastric cancer risk: A meta-analysis
Authors: Fariborz Gorouhi, Farin Kamangar, Hossein Bahrami
Journal: Cancer Research (2007)

4242  Inflammation is one of the early phases in the development of gastric cancer. Therefore, several studies have examined the association of polymorphisms in tumor necrosis factor-A gene (TNF-A) with gastric cancer risk. This meta-analysis reviews and summarizes published evidence for these associations. Searching the PubMed Database yielded 20 independent studies that reported on the associations between TNF-A -308 or TNF-A -238 G>A polymorphisms and gastric cancer risk. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were calculated in the random-effects model using the DerSimonian-Laird method. Q-statistics and I2 statistics were calculated to examine heterogeneity, and funnel plots were plotted to examine small study effects. For TNF-A -308 polymorphism, the overall OR (95% CI) for AG and AA genotypes versus GG genotype was 1.06 (0.90 - 1.26). I2 statistic for this association was 44% and the P-value for Q-statistic was 0.02. For TNF-A -238 polymorphism, the overall OR (95% CI) for AG and AA genotypes versus GG genotype was 1.15 (0.87 - 1.52). I2statistic for this association was equal to zero and the P-value for Q-statistic was 0.43. Limiting the analyses to noncardia gastric cancers, intestinal type cancers, H. pylori-positive subjects, Western or East-Asian populations, or studies in which genotype distributions were in Hardy-Weinberg equilibrium, the summary OR remained non-significant for both of these polymorphisms. In conclusion, the overall associations between TNF-A -308 and TNF-A -238 A carrying genotypes (GA and AA) and gastric cancer were null, but there might be some result heterogeneity.
PB1823 PROGNOSTIC FACTORS AND TREATMENT OUTCOME OF RELAPSING AND REFRACTORY MATURE B CELL NON HODGKIN LYMPHOMA CCHE EXPERIENCE
Authors: A. Hamoda, H. Abdelrahman, S. Fathy el semary, N. El Kinaai, I. Zaki, S. Salem, N. Naggy, O. Ahmed
Journal: HemaSphere (2019)

Background: Treatment of non‐Hodgkin lymphoma (NHL) is an example of successful therapy of cancer in children with a cure rate approximating 80%. Unfortunately, relapsed NHL has a dismal outcome, and customary treatment is by highly toxic chemotherapy followed by hematopoietic stem cell transplantation (HSCT). Aims: To analyze prognostic factors, and to report treatment outcome of relapsing/refractory mature B cell NHL. Methods: A retrospective analysis including all patients less than 18 years initially diagnosed as mature B cell NHL who were primary refractory to chemotherapy or relapsed during the period between July 2012 till end of 2017 at the Children Cancer Hospital Egypt (CCHE). Results: Out of 494 patients diagnosed during the study period, 34 (7%) were included in our study. Twenty‐three (67.6%) had Burrkitt lymphoma, while 5 (14.7%) had diffuse large B cell lymphoma. The majority were males (79.4%), with a median age 6.2 years. According to Modified Murphy Staging, 6 patients (17.6%) were stage II, 24 (70.6%) stage III, and 4 (11.8%) stage IV. Bone marrow (BM) involvement at presentation was detected in 2 patient, and 3 (8.8%) had CNS infiltration. Thirty patients (88.2%) received LMB protocol, and 4 (11.8%) R‐CHOP as primary chemotherapy. One patient (2.9%) was treated as low risk, 28 (82.4%) as intermediate, and 5 (14.7%) high risk. Median delay in 1st line treatment was 22 days (range 0 to 162).Twenty two patients (64.7%) relapsed, and 12 (35.3%) had tumor progression. Relapse was early in 15 (68.2%), and late in 7 patients (31.8%). It was documented by tissue biopsy in 30 patients (88.2%), and bone marrow aspirate in 3 (8.8%). Patients relapsed other than primary site were 6/34 (17.6%). CNS relapse was detected in 8 (23.5%), BM in 8 (20.5%), while combined BM and CNS in 2 (5.9%). R‐ICE was the 2 nd line of treatment in 29 patients (85.3%), and complete 2 nd remission (CR) was achieved in 7 patients (20.6%). Allogeneic HSCT was done for 2 patients (5.9%), and autologous HSCT for 3 patients (8.8%). Finally, 7/34 (20.5%) patients were alive in CR, and 24/37 (70.5%) died. The 3 years Overall survival (OS) 35.3%, with no statistical difference between relapsing and progression. The 3 years OS for patient who underwent HSCT was 80% compared 20% for no HSCT (p = 0.034). Summary/Conclusion: Our relapse rate is higher than the literature probably due to delay of chemotherapy with loss of dose intensity. For patients in second remission, HSCT markedly improves the outcome.
Abstract 15397: The Impact of Age on Ten Year Survival in a Large Contemporary Outpatient Cohort of Patients with Chronic Heart Failure
Authors: J M Arnold, Marie-Hélène Leblanc, Peter Liu, Andrew Ignaszewski, Jonathan Howlett, Annemarie Kaan, Michael Chan, Haissam Haddad, Miroslaw Rajda, Shelly Zieroth, Estrellita Estrella-Holder, Danielle Beaudoin, Gordon Marchiori
Journal: Circulation (2012)

Heart failure (HF) can occur at any stage of life but is generally considered to be predominantly a disease of the elderly. Currently, it has been referred to as an epidemic as hospitalizations and...
Injury from E-Cigarette Explosion
Authors: Micah G Katz, Katie W Russell
Journal: New England Journal of Medicine (2019)

A 17-year-old boy presented to the ED with pain and swelling in his jaw 2 hours after an e-cigarette exploded during use. He had extensive lacerations in his mouth, multiple disrupted lower incisors, and bony incongruity of his left mandible.
SCALE: modeling allele-specific gene expression by single-cell RNA sequencing
Authors: Yuchao Jiang, Nancy R. Zhang, Mingyao Li
Journal: Genome biology (2017)

Allele-specific expression is traditionally studied by bulk RNA sequencing, which measures average expression across cells. Single-cell RNA sequencing allows the comparison of expression distribution between the two alleles of a diploid organism and the characterization of allele-specific bursting. Here, we propose SCALE to analyze genome-wide allele-specific bursting, with adjustment of technical variability. SCALE detects genes exhibiting allelic differences in bursting parameters and genes whose alleles burst non-independently. We apply SCALE to mouse blastocyst and human fibroblast cells and find that cis control in gene expression overwhelmingly manifests as differences in burst frequency.
AB1416-HPR A REVIEW OF PUBLIC PATIENT INVOLVEMENT AND ENGAGEMENT (PPI/E) AT THE ARTHRITIS RESEARCH UK CENTRE FOR ADOLESCENT RHEUMATOLOGY AT UCL, UCLH AND GOSH
Authors: James Wilton, Caitlin Clifford, Hema Chaplin, Despina Eleftheriou, Anna Radziszewska, Coziana Ciurtin, George Robinson, Lucia Martin-Gutierrez, Debajit Sen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The adolescent and young adult (AYA) rheumatology clinical service has a well established culture of involving our users in shaping how services are delivered. Since its inception in 2012 the Arthritis Research UK Centre for Adolescent Rheumatology has worked to offer every patient within the clinical service the opportunity to participate in research <h3>Objectives</h3> This was achieved by 2015 and from 2014 we renewed our focus on an active involvementprogramme to promote the role of young people in prioritising and designing our research agenda and workstreams. We are currently developing our strategy for the next five years and reviewing our experience to date. <h3>Methods</h3> PPI/E activity records were searched for the period October 2014 to April 2018. This included number of patients involved, their age and diagnosis, and the type of activity along with the number of times they have been involved. <h3>Results</h3> 19 PPI/E activities were organised. From a total of 1554 adolescent and young adult patients 150 patients having been involved in PPI/E, the age range was 11-27 and 118 were female. The activities consisted of focus groups (79%) and support days (11%) all but two of which were disease specific groups. The disease specific PPI/E activities have been focused on JIA, JSLE, and JDM. The number of patients involved in these activities were 24.62% (n=99), 24% (n=17) and 66% (n=25) respectively. The mean instances of involvement per disease were 2.09 for JIA, 2.53 for JSLE and 3.56 for JDM. <h3>Conclusion</h3> Our results show that many of our patients have taken part in PPI/E activities (11.19%) with over 65% of of our JDM patients having taken part in either a focus group or support day. The focus on inflammatory rheumatic disease is in keeping with the stated aims of our Centre. The mean instances of involvement ranging from 2.09 3.56 suggest that patients feel PPI/E is worthwhile. We aim to share our results with the young people who have driven this work and will consider how we might move forward. We aim to consult with the group of patients we serve who have not been part of this process to date. <h3>Disclosure of Interests</h3> None declared
Unusual Physiological Properties of Smooth Monostratified Ganglion Cell Types in Primate Retina
Authors: Colleen E. Rhoades, Nishal P. Shah, Michael B. Manookin, Nora Brackbill, Alexandra Kling, Georges Goetz, Alexander Sher, Alan M. Litke, E.J. Chichilnisky
Journal: Neuron (2019)
Abstract 14649: Transient Receptor Potential Channel of the Ankyrin Subtype-1 Stimulation Enhances Cardiomyocyte Contractile Function via a CaMKII-dependent Pathway
Authors: Monica Ghosh, Michael A Garrison, Spencer R Andrei, Derek S Damron
Journal: Circulation (2017)

Introduction: Transient receptor potential channels of the ankyrin subtype-1 (TRPA1) are non-selective cation channels that show high permeability to calcium. Previous studies from our laboratory h...
Genetic Risk Score for Coronary Disease Identifies Predispositions to Cardiovascular and Noncardiovascular Diseases
Authors: Ioanna Ntalla, Stavroula Kanoni, Lingyao Zeng, Olga Giannakopoulou, John Danesh, Hugh Watkins, Nilesh J. Samani, Panos Deloukas, Heribert Schunkert
Journal: Journal of the American College of Cardiology (2019)
Impacts of particle shapes on the oral delivery of drug nanocrystals: Mucus permeation, transepithelial transport and bioavailability
Authors: Mengran Guo, Mengdi Wei, Wen Li, Meichen Guo, Chunlin Guo, Minchao Ma, Yu Wang, Zimeng Yang, Mo Li, Qiang Fu, Li Yang, Zhonggui He
Journal: Journal of Controlled Release (2019)
In Vivo Magnetic Recording of Neuronal Activity
Authors: Laure Caruso, Thomas Wunderle, Christopher Murphy Lewis, Joao Valadeiro, Vincent Trauchessec, Josué Trejo Rosillo, José Pedro Amaral, Jianguang Ni, Patrick Jendritza, Claude Fermon, Susana Cardoso, Paulo Peixeiro Freitas, Pascal Fries, Myriam Pannetier-Lecoeur
Journal: Neuron (2017)
Особливості застосування урсодезоксихолевої кислоти при широкому спектрі патології гепатобіліарного тракту та інших органів та систем
Authors: Yu.M. Stepanov, S.V. Kosynska
Journal: GASTROENTEROLOGY (2014)

У статті викладено обґрунтування та особливості застосування урсодезоксихолевої кислоти (УДХК) при широкому спектрі гепатобіліарної та позапечінкової патології. Наведено літературні дані та власні спостереження ефективності УДХК при багатьох захворюваннях. Окреслені перспективи застосування УДХК
FRI0593 PATHOLOGICAL FEATURES OF LYMPH NODE IN JAPANESE PATIENTS WITH ADULT-ONSET STILL’S DISEASE
Authors: Masahiro Iida, Yoshiki Nagai, Naoto Yokogawa, Kota Shimada, Shoji Sugii
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Adult-onset Still's disease (AOSD) rarely occurs in adults and no specific serological or pathological findings have ever been reported. Although multiple lymphadenopathy often develops in AOSD patients, only few reports have described their pathology so far.<sup>1,2</sup> <h3>Objectives</h3> To examine pathological features of lymph node (LN) in AOSD patients and their usefulness in diagnosis in Japan. <h3>Methods</h3> This is a single center, retrospective study. The subjects were 115 Japanese patients who visited our department and received LN biopsy from April 2010 to July 2018. Of these, 12 patients, in whom AOSD was suspected by clinicians at the time of biopsy, were analyzed. AOSD patients were diagnosed according to the Yamaguchi's criteria<sup>3</sup>, except the item "excluding malignant lymphoma". <h3>Results</h3> The median age of the 12 cases (2 males, 10 females) was 60.5 years old (range: 18-81). Paracortical hyperplasia was shown in 7, follicular hyperplasia in 1, histiocytic necrotizing lymphadenitis (HNL) in 3, and diffuse large B cell lymphoma (DLBCL) in 1. Of 9 who fulfilled Yamaguchi's criteria, TAFRO syndrome was diagnosed in one. As for the other 8, diagnosis of AOSD was made and successfully treated as AOSD. Although 1 of the 8 had pathological features of HNL, we treated her as AOSD because her clinical feature and laboratory data were not compatible with HNL. As for the 3 who did not meet the criteria, their clinicopathological diagnosis was HNL in 2 and DLBCL in 1. We could find no associations between the clinical features and lymph node patterns in AOSD as previously reported. <h3>Conclusion</h3> In patient who fulfilled the criteria, most cases showed paracortical hyperplasia in LN as previously reported from outside Japan and no cases had malignant lymphoma. However, in diagnosing AOSD, LN biopsy is needed to exclude AOSD-mimicking malignant lymphoma especially in the case that does not fulfill the criteria. <h3>References</h3> [1] Kim HA, et al. Medicine (Baltimore). 2015;94:e787. [2] Jeon YK, et al. J Clin Pathol. 2004;57:1052. [3] Yamaguchi M, et al. J Rheumatol1992;19:424–30. <h3>Disclosure of Interests</h3> None declared