tbuckley/cabot-search huggingface dataset:
Abstract 19: Progressive Metabolic Derangement During Prolonged Resuscitation for Refractory VT/VF Cardiac Arrest and the Relationship to Neurologically Intact Survival With Extracorporeal Cardiopulmonary Resuscitation
Authors: Jason A Bartos, Claire Carlson, Ganesh Raveendran, Ranjit John, Tom P Aufderheide, Demetris Yannopoulos
Journal: Circulation (2018)

Background: Multiple studies have shown declining likelihood of neurologically intact survival with prolonged resuscitation with standard CPR. With standard CPR, survival after VT/VF arrest declines from 35-45% at initiation of CPR to 10-20% survival at 30 min. Objective: The aim of this study was to examine the effects of resuscitation duration on neurologically intact survival in the Minnesota Resuscitation Consortium ECPR protocol. Further, the progressive metabolic derangement of prolonged resuscitation was observed for the first time in this population. Methods: Between December 1, 2015 and May 1, 2018, 115 consecutive adult patients with refractory out-of-hospital VT/VF cardiac arrest requiring ongoing CPR were transported to the cardiac catheterization laboratory where ECLS was initiated and coronary angiography and PCI were performed as needed. Patients achieving an organized cardiac rhythm were admitted for further treatment. Results: Overall, 41% of patients receiving full resuscitative efforts were discharged neurologically intact. Neurologically intact survival declined with increasing duration of CPR with 100% survival in patients placed on ECLS within 30 min. Survival declined to 50% within 50 min and 20% within 70 min. Lactic acid and paCO2 increased over time peaking at 15 mmol/L and 72 mmHg, respectively. pH declined accordingly reaching 6.92 at its nadir. paO2 was stable over time but variable between patients. Conclusions: Likelihood of neurologically intact survival declined with increasing duration of CPR for patients going on to receive ECLS. The metabolic profile worsened during prolonged CPR with increasing lactic acidemia and hypercapnia but survival could be achieved with the hemodynamic support provided by ECLS. Together these findings support the need for rapid transport of patients to teams prepared to place ECLS. Substantial decline in survival begins at 30 min of CPR.
Environmental risk factors and biomarkers for autism spectrum disorder: an umbrella review of the evidence
Authors: Jong Yeob Kim, Min Ji Son, Chei Yun Son, Joaquim Radua, Michael Eisenhut, Florence Gressier, Ai Koyanagi, Andre F Carvalho, Brendon Stubbs, Marco Solmi, Theodor B Rais, Keum Hwa Lee, Andreas Kronbichler, Elena Dragioti, Jae Il Shin, Paolo Fusar-Poli
Journal: The Lancet Psychiatry (2019)
Transcription factors orchestrate dynamic interplay between genome topology and gene regulation during cell reprogramming
Authors: Ralph Stadhouders, Enrique Vidal, François Serra, Bruno Di Stefano, François Le Dily, Javier Quilez, Antonio Gomez, Samuel Collombet, Clara Berenguer, Yasmina Cuartero, Jochen Hecht, Guillaume J. Filion, Miguel Beato, Marc A. Marti-Renom, Thomas Graf
Journal: Nature Genetics (2018)
How do the costs of physical therapy and arthroscopic partial meniscectomy compare? A trial-based economic evaluation of two treatments in patients with meniscal tears alongside the ESCAPE study
Authors: Victor A van de Graaf, Johanna M van Dongen, Nienke W Willigenburg, Julia C A Noorduyn, Ise K Butter, Arthur de Gast, Daniel B F Saris, Maurits W van Tulder, Rudolf W Poolman
Journal: British Journal of Sports Medicine (2019)

Objectives To examine whether physical therapy (PT) is cost-effective compared with arthroscopic partial meniscectomy (APM) in patients with a non-obstructive meniscal tear, we performed a full trial-based economic evaluation from a societal perspective. In a secondary analysis—this paper—we examined whether PT is non-inferior to APM. Methods We recruited patients aged 45–70 years with a non-obstructive meniscal tear in nine Dutch hospitals. Resource use was measured using web-based questionnaires. Measures of effectiveness included knee function using the International Knee Documentation Committee (IKDC) and quality-adjusted life-years (QALYs). Follow-up was 24 months. Uncertainty was assessed using bootstrapping techniques. The non-inferiority margins for societal costs, the IKDC and QALYs, were €670, 8 points and 0.057 points, respectively. Results We randomly assigned 321 patients to PT (n=162) or APM (n=159). PT was associated with significantly lower costs after 24 months compared with APM (−€1803; 95% CI −€3008 to −€838). The probability of PT being cost-effective compared with APM was 1.00 at a willingness to pay of €0/unit of effect for the IKDC (knee function) and QALYs (quality of life) and decreased with increasing values of willingness to pay. The probability that PT is non-inferior to APM was 0.97 for all non-inferiority margins for the IKDC and 0.89 for QALYs. Conclusions The probability of PT being cost-effective compared with APM was relatively high at reasonable values of willingness to pay for the IKDC and QALYs. Also, PT had a relatively high probability of being non-inferior to APM for both outcomes. This warrants further deimplementation of APM in patients with non-obstructive meniscal tears. Trial registration numbers NCT01850719 and NTR3908.
Exercise Effect on Risk Factor Score Differs Between Genders in a Rural Cohort
Authors: Herbert J. Marx, Tara Erb, Paul L. Jenkins, Anne N. Nafziger, Carol Lewis
Journal: Circulation (2001)

P95 Physical inactivity is classified as a predisposing risk factor (RF) in the AHA/ACC Scientific Statement on Assessment of Cardiovascular Risk. Whether the mechanism relates to intensification of “causal” RF or is independent is uncertain. Also, the quantity and intensity of exercise needed to reverse that risk effect remain unclear. The recent Harvard Alumni Study update suggests that in males (M) vigorous activity was associated with lower cardiovascular (CV) risk, but moderate to light activity was not. Whether the same applies to females (F) is not known. We evaluated the effect of exercise on the AHA/ACC risk factor score (RFS) in 173 M and 217 F (ages 20 to 69 years) with no known CV disease in 3 rural counties in New York State. Each subject completed a behavioral RF survey and had a physical exam plus laboratory tests at baseline and again 5 years later. Degree and frequency of work and recreational activity were assessed. Strenuous activity on ≥4 days/week was termed vigorous exercise (VE). In our cohort, 59% of M and 67% of F did not exercise vigorously compared to 60% of American adults nationally. M who did VE had significantly lower RFS at baseline than those who did not (No VE) and maintained this difference in RFS 5 years later. However, among F there was no difference in RFS between the VE and No VE groups at baseline or follow-up (see table). We conclude that the lower CV risk in M associated with VE may be mediated at least in part through influence on causal RF. However, if VE confers benefit in F, a different mechanism must be involved. Table 1.
S109 TRANSCEND CLL 004: MINIMAL RESIDUAL DISEASE NEGATIVE RESPONSES AFTER LISOCABTAGENE MARALEUCEL (LISO-CEL) IN PATIENTS WITH RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA OR SMALL LYMPHOCYTIC LYMPHOMA
Authors: T. Siddiqi, K. Dorritie, J. Soumerai, D. Stephens, J. Dubovsky, H. Gillenwater, L. Gong, J. Thorpe, L. Yang, W. Wierda
Journal: HemaSphere (2019)

Background: Eradication of minimal residual disease (MRD) in patients with chronic lymphocytic leukemia (CLL) may be necessary for deep and durable responses. Aims: To assess the safety, pharmacokinetics, and efficacy of lisocabtagene maraleucel (liso-cel, JCAR017), an investigational, anti-CD19 chimeric antigen receptor (CAR) T cell product administered as a defined composition of CD4+/CD8+ CAR T cells, in the ongoing phase 1/2 TRANSCEND CLL 004 study. Methods: Eligible patients had CLL or small lymphocytic lymphoma (SLL), had received ≥2 prior lines of therapy (including Bruton's tyrosine kinase inhibitors [BTKi] unless medically contraindicated), and had an Eastern Cooperative Oncology Group performance status of ≤1. After 3 days of lymphodepleting chemotherapy, patients received liso-cel infusion at either dose level 1 (50 × 106) or dose level 2 (100 × 106) total CAR+ T cells. Patients were monitored for dose-limiting toxicities. Response was assessed by International Workshop on CLL 2008 criteria. MRD was assessed by flow cytometry in blood (sensitivity, 10−4) and by Next-Generation Sequencing in bone marrow (BM; sensitivity, 10−6). Results: At data cutoff, 16 patients received liso-cel: n = 6 in dose level 1 and n = 10 in dose level 2. Of the patients, 75% had high-risk features (TP53 mutation, complex karyotype, or del17p); 100% had received prior ibrutinib and 50% had received prior venetoclax. Median (range) number of prior lines of therapy was 4.5 (2-11). There was 1 dose-limiting toxicity of grade 4 hypertension at dose level 2. The most common grade 3/4 treatment-emergent adverse events were cytopenias (thrombocytopenia, 75%; anemia, 69%; neutropenia, 63%; leukopenia, 56%). One patient had grade 3 cytokine release syndrome (CRS); 3 patients had grade 3 neurological events (NE). Best overall response rate (ORR) in 15 evaluable patients was 87% (13/15). Seven patients (47%) achieved complete remission with/without complete blood count recovery (CR/CRi). ORR at 6 mo was 83% (5/6). Undetectable MRD (uMRD) in blood was achieved in 10/15 patients (67%) by day 30, and in BM in 7/8 patients (88%). MRD-negative CRs were seen in patients who had failed both BTKi and venetoclax. Median (range) time to peak blood CAR+ T cell level was 16 (4–30) days. Summary/Conclusion: In this study of heavily pretreated patients with standard- and high-risk CLL/SLL and previous ibrutinib treatment, liso-cel-related toxicities (ie, CRS and NEs) were manageable. Patients rapidly achieved CR/CRi and uMRD. The phase 2 component of the study is currently enrolling patients for treatment at dose level 2. Additional follow-up will be presented.
Abstract 15665: Experimental Study for Elucidating Mechanism of Coronary Spasm Using Ipsc-derived Smooth Muscle Cells; Role of P122 Rhogap / Dlc-1 and Phospholipase C
Authors: Makoto Tanaka, Tomohiro Osanai, Ken Okumura, Hirofumi Tomita
Journal: Circulation (2017)

Background: We previously reported that phospholipase C (PLC) activity was enhanced in patients with coronary spastic angina (CSA) (JACC 2000) and that variant of PLC-δ1 (R257H) gene was found in 1...
Early release rules for prisoners at end of life may be “discriminatory,” say doctors
Authors: Gareth Iacobucci
Journal: BMJ (2019)

Doctors have called for changes to the rules governing when terminally ill prisoners can be released early on compassionate grounds, amid concern that the current approach is discriminatory.

Data obtained from the Ministry of Justice, shared with The BMJ , indicate that prisoners in England and Wales at the end of life are more likely to be granted early release on compassionate grounds if they have cancer than if they have other conditions, say clinical researchers who examined the data.

Under current legislation the secretary of state for justice can grant early release where there is a risk of harm to the prisoner from ongoing imprisonment, potential benefit through release, a low risk of recidivism, and adequate arrangements for safe care in the community. But, crucially, the prisoner’s death must be expected “very soon,” and HM Prisons and Probation Service considers this to be within three months.1

Jim Burtonwood, a palliative care specialist, GP, and MSc student at Cardiff University, who led the research, said the current rules meant that timescales often became too tight for a successful application for early release if an acknowledgment of terminal decline was delayed or there was prognostic uncertainty.

He told The BMJ , “The …
THU0409 PATTERN AND INFLUENTIAL FACTORS IN PROMOTING TREAT-TO-TARGET (T2T) FOR FOLLOW-UP ANKYLOSING SPONDYLITIS (AS) PATIENTS WITH A RHEUMATOLOGIST-PATIENT INTERACTIVE SMART SYSTEM OF DISEASE MANAGEMENT (SSDM): A COHORT STUDY FROM CHINA
Authors: Jing Xue, Hui Song, Jing Yang, Zhenchun Zhang, LI Hongbin, Junli Zhang, Zongwen Shuai, Zhenbiao Wu, Henglian Wu, Bei Wang, Hua Wei, LI Yasong, LI Zhijun, Lijun Liu, Yuhua Jia, Fei Xiao, Huaxiang Wu
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Ankylosing Spondylitis Disease Activity Score (ASDAS) is adopted to evaluate the degree of disease activity and the inflammatory response in AS patients. ASDAS score ≤ 1.3 represents inactive disease status and achievement of T2T. <h3>Objectives:</h3> To evaluate the patterns of T2T and related influential factors among AS patients after applying SSDM in the real world. <h3>Methods:</h3> SSDM is a mobile application for disease management. Patients were trained to master SSDM by healthcare professionals and to conduct ASDAS self-assessments. Patients were also required for repeating self-evaluation after leaving the hospital. After entry by patients, data can synchronized to the SSDM terminal of authorized rheumatologists. <h3>Results:</h3> From Jan 2015 to Jan 2019, 667 AS patients across China were followed up for more than 6 months through SSDM. The results at baseline and in final follow up were summarized in Table 1. The rate of T2T achievers were 28.49% (190/667) at baseline, and improved significantly to 41.38% (276/667) after 6 months follow up, p&lt;0.01. Among T2T achievers at baseline, 64.21% (122/190) maintained T2T, 35.79% (68/190) relapsed. Of patients who didn’ t achieve T2T at baseline, only 32.29% (154/477) of the other AS patients achieved T2T after 6 months follow up. We further analyzed the impact of the times of self-assessment for ASDAS on T2T. The patients were stratified according to their frequency of self-assessment: more than 3 times, less than or equal to 3 times self-assessments within 6 months follow-up. Results show that the more frequent of the self-assessment, the higher improvement of T2T rate (19.34% vs. 8.40%, Table 2). A linear regression analysis of variables in statistics and parameter estimation was conducted by least square method. The improvement of T2T rate(y) was positively correlated with times of self-assessment for ASDAS(x) independently (Figure 1). <h3>Conclusion:</h3> Significant improvement was observed under applying SSDM through empowering AS patients. After proactive disease management via SSDM for more than 6 months, Patients with ASDAS≤1.3 score at baseline had a significantly higher retention rate of disease activity. The patients who performed more self-assessments through SSDM had lower probability of relapse and higher rate of T2T. SSDM is a valuable tool for long term follow-up through empowering patients. <h3>Disclosure of Interests:</h3> None declared
Rapid Reconfiguration of the Functional Connectome after Chemogenetic Locus Coeruleus Activation
Authors: Valerio Zerbi, Amalia Floriou-Servou, Marija Markicevic, Yannick Vermeiren, Oliver Sturman, Mattia Privitera, Lukas von Ziegler, Kim David Ferrari, Bruno Weber, Peter Paul De Deyn, Nicole Wenderoth, Johannes Bohacek
Journal: Neuron (2019)
Impaired antioxidative activity of high-density lipoprotein is associated with more severe acute ischemic stroke
Authors: Konstantinos Tziomalos, Konstantina Katrini, Marianthi Papagianni, Konstantinos Christou, Christina Gkolfinopoulou, Stella-Maria Angelopoulou, Areti Sofogianni, Christos Savopoulos, Apostolos I. Hatzitolios, Angeliki Chroni
Journal: Metabolism (2019)
Platelet serotonin 2A (5-HT2A) receptor characteristics and parenting factors for boys at risk for delinquency: a preliminary report
Authors: D S Pine, G A Wasserman, J Coplan, J A Fried, Y Y Huang, S Kassir, L Greenhill, D Shaffer, B Parsons
Journal: American Journal of Psychiatry (1996)

This study examined the cross-sectional association between platelet membrane serotonin 2A (5-HT2A) receptor variables in children and characteristics of their parents that place these children at risk for antisocial behavior.As part of a larger prospective study investigating predictors of antisocial behavior, 38 younger brothers of convicted delinquents provided platelet samples; samples from 34 boys (mean age=8.3 years) were usable. The authors determined the density (Bmax) and affinity (Kd) of platelet membrane 5-HT2A receptors by using [3H]lysergic acid diethylamide. They also measured parental characteristics related to serotonergic dysfunction in prior studies, the quality of parent-child interactions, and psychiatric profiles of the boys who provided platelets.Bmax was significantly lower in boys whose parents had histories of substance abuse or incarceration. Bmax was also inversely related to harsh parenting; boys raised in environments characterized by frequent parental physical punishment and anger had a significantly lower Bmax. Bmax was not related to boys' disruptive behavior.In boys at risk for antisocial behavior, the density of 5-HT2A receptors on platelets is inversely related to parental factors known to place youth at risk for antisocial behavior.
Abstract 16152: Renal Function Impacts the Association Between HDL Particles and Incident Cardiovascular Events (Observations From the DHS)
Authors: Shahzad Chindhy, Colby Ayers, Amit Khera, Parag Joshi, Anand Rohatgi
Journal: Circulation (2017)

Background: High-density lipoprotein (HDL) has different biochemical properties in the setting of renal dysfunction. HDL particle concentration (HDL-P) has emerged as a cardiovascular risk biomarke...
Single-cell transcriptome conservation in cryopreserved cells and tissues
Authors: Amy Guillaumet-Adkins, Gustavo Rodríguez-Esteban, Elisabetta Mereu, Maria Mendez-Lago, Diego A. Jaitin, Alberto Villanueva, August Vidal, Alex Martinez-Marti, Enriqueta Felip, Ana Vivancos, Hadas Keren-Shaul, Simon Heath, Marta Gut, Ido Amit, Ivo Gut, Holger Heyn
Journal: Genome biology (2017)

A variety of single-cell RNA preparation procedures have been described. So far, protocols require fresh material, which hinders complex study designs. We describe a sample preservation method that maintains transcripts in viable single cells, allowing one to disconnect time and place of sampling from subsequent processing steps. We sequence single-cell transcriptomes from >1000 fresh and cryopreserved cells using 3'-end and full-length RNA preparation methods. Our results confirm that the conservation process did not alter transcriptional profiles. This substantially broadens the scope of applications in single-cell transcriptomics and could lead to a paradigm shift in future study designs.
A variant by any name: quantifying annotation discordance across tools and clinical databases
Authors: Jennifer L. Yen, Sarah Garcia, Aldrin Montana, Jason Harris, Stephen Chervitz, Massimo Morra, John West, Richard Chen, Deanna M. Church
Journal: Genome Medicine (2017)

Clinical genomic testing is dependent on the robust identification and reporting of variant-level information in relation to disease. With the shift to high-throughput sequencing, a major challenge for clinical diagnostics is the cross-identification of variants called on their genomic position to resources that rely on transcript- or protein-based descriptions.We evaluated the accuracy of three tools (SnpEff, Variant Effect Predictor, and Variation Reporter) that generate transcript and protein-based variant nomenclature from genomic coordinates according to guidelines by the Human Genome Variation Society (HGVS). Our evaluation was based on transcript-controlled comparisons to a manually curated set of 126 test variants of various types drawn from data sources, each with HGVS-compliant transcript and protein descriptors. We further evaluated the concordance between annotations generated by Snpeff and Variant Effect Predictor and those in major germline and cancer databases: ClinVar and COSMIC, respectively.We find that there is substantial discordance between the annotation tools and databases in the description of insertions and/or deletions. Using our ground truth set of variants, constructed specifically to identify challenging events, accuracy was between 80 and 90% for coding and 50 and 70% for protein changes for 114 to 126 variants. Exact concordance for SNV syntax was over 99.5% between ClinVar and Variant Effect Predictor and SnpEff, but less than 90% for non-SNV variants. For COSMIC, exact concordance for coding and protein SNVs was between 65 and 88% and less than 15% for insertions. Across the tools and datasets, there was a wide range of different but equivalent expressions describing protein variants.Our results reveal significant inconsistency in variant representation across tools and databases. While some of these syntax differences may be clear to a clinician, they can confound variant matching, an important step in variant classification. These results highlight the urgent need for the adoption and adherence to uniform standards in variant annotation, with consistent reporting on the genomic reference, to enable accurate and efficient data-driven clinical care.
SP0096 MRI OF LARGE JOINTS IN ARTHRITIS: HOW TO DO AND HOW THEY ARE DIFFERENT FROM SMALL JOINTS?
Authors: Iris Eshed
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> The appendicular skeleton is frequently involved in patients with rheumatic diseases. Involved joints are affected by inflammation of the synovium and joint"s entheses. Imaging depicts joint derangement and generally mirrors the pathophysiology of the disease. MRI is considered the imaging modality of choice for the detection of acute joint inflammation as well as its structural sequela. Thus, MRI plays an important role in identifying, monitoring disease activity and the patient follow-up. The MRI features of inflammatory arthritis are well described, especially in the small appendicular joints of the hands and feet and include synovitis, erosions, osteitis, tenosynovitis and erosions. In the current presentation, the typical MRI properties of large joints arthritis in different rheumatic entities will be presented with special focus on the difference from inflammatory findings in smaller appendicular joints.: <h3>Disclosure of Interests:</h3> None declared
Pharmacology and structure-activity relationships of bioactive polycyclic cage compounds: A focus on pentacycloundecane derivatives
Authors: Werner J. Geldenhuys, Sarel F. Malan, Jeffrey R. Bloomquist, Alan P. Marchand, Cornelis J. Van der Schyf
Journal: Medicinal Research Reviews (2004)

The chemistry of organic polycyclic cage compounds has intrigued medicinal chemists for over 50 years, yet little is published about their pharmacological profiles. Polycyclic cage compounds have important pharmaceutical applications, ranging from the symptomatic and proposed curative treatment of neurodegenerative diseases such as Parkinson's and Alzheimer's disease (e.g., amantadine and memantine), to use as anti-viral agents against influenza and the immunodeficiency virus (HIV). The polycyclic cage appears to be a useful scaffold to yield drugs with a wide scope of applications, and can be used also to modify and improve the pharmacokinetic and pharmacodynamic properties of drugs in current use. This review attempts to summarize the pharmacological profiles of polycyclic cage compounds with an emphasis on the lesser known pentacycloundecanes, homocubanes, and trishomocubanes.
Abstract 15555: Sex-Related Differences of Coronary Atherosclerosis Regression Following Maximally Intensive Statin Therapy: Insights From SATURN
Authors: Rishi Puri, Steven Nissen, Mingyuan Shao, Christie Ballantyne, Phillip Barter, M. John Chapman, Raimund Erbel, Peter Libby, Joel Raichlen, Kiyoko Uno, Yu Kataoka, Stephen Nicholls
Journal: Circulation (2013)

Background: Women are under-represented in clinical trials, leading to a gender-disparity for prescribing evidenced-based therapies. The efficacy of high-intensity statins in women is poorly unders...