tbuckley/cabot-search huggingface dataset:
Immune precision medicine for cancer: a novel insight based on the efficiency of immune effector cells
Authors: Jean‐François Rossi, Patrice Céballos, Zhao‐Yang Lu
Journal: Cancer Communications (2019)

Cancer cell growth is associated with immune surveillance failure. Nowadays, restoring the desired immune response against cancer cells remains a major therapeutic strategy. Due to the recent advances in biological knowledge, efficient therapeutic tools have been developed to support the best bio-clinical approaches for immune precision therapy. One of the most important successes in immune therapy is represented by the applicational use of monoclonal antibodies, particularly the use of rituximab for B-cell lymphoproliferative disorders. More recently, other monoclonal antibodies have been developed, to inhibit immune checkpoints within the tumor microenvironment that limit immune suppression, or to enhance some immune functions with immune adjuvants through different targets such as Toll-receptor agonists. The aim is to inhibit cancer proliferation by the diminishing/elimination of cancer residual cells and clinically improving the response duration with no or few adverse effects. This effect is supported by enhancing the number, functions, and activity of the immune effector cells, including the natural killer (NK) lymphocytes, NKT-lymphocytes, γδ T-lymphocytes, cytotoxic T-lymphocytes, directly or indirectly through vaccines particularly with neoantigens, and by lowering the functions of the immune suppressive cells. Beyond these new therapeutics and their personalized usage, new considerations have to be taken into account, such as epigenetic regulation particularly from microbiota, evaluation of transversal functions, particularly cellular metabolism, and consideration to the clinical consequences at the body level. The aim of this review is to discuss some practical aspects of immune therapy, giving to clinicians the concept of immune effector cells balancing between control and tolerance. Immunological precision medicine is a combination of modern biological knowledge and clinical therapeutic decisions in a global vision of the patient.
Platelets attach to lung type 2 innate lymphoid cells (ILC2s) expressing P-selectin glycoprotein ligand 1 and influence ILC2 function
Authors: Maya R. Karta, Kellen Cavagnero, Marina Miller, Jana Badrani, Luay Naji, Taylor A. Doherty, David H. Broide
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 300: Long-Term Survival, Quality of Life and Health Care Costs in the Survivors of Pre-Hospital Cardiac Arrest
Authors: Hao Y Lin, Zui S Yen, Chih H Lin, Chih W Yang, Ming J Hsieh, Chia M Fu, Matthew H Ma
Journal: Circulation (2018)

Background: Understanding the prognosis of out-of-hospital cardiac arrest (OHCA) patients is vital to informing resuscitation and advanced care planning decisions. However, short-term outcomes such as survival to hospital discharge do not account for post-arrest quality of life and medical costs. Objective: To investigate the survival time, long-term health-related quality of life, and health care costs of OHCA survivors. Methods: We conducted a prospective cohort study of all adult OHCA survivors of cardiac origin between 1 August 2016 and 31 December 2017 in a tertiary medical center in Taiwan. Chinese version of EuroQol-5D-5L (EQ-5D-5L) was used for measuring health-related quality of life at 1 month, 6 month and 1 year post-discharge. Survival and health care costs data were collected. Descriptive statistics and Wilcoxon Signed-Ranks Test were used for data analysis. Results: During the study period, 30 of 163 (18.4%) OHCA of presumed cardiac origin survived to hospital discharge. The mean age for the survivors was 59 years. Most survivors were male (83.3%), and received bystander cardiopulmonary resuscitation (73.3%) and defibrillation (86.7%) in the prehospital settings. Of 30 survivors, 23 patients were cerebral performance category score (CPC) of 1 or 2 and 7 were CPC of 3 or 4. The median hospital stay and estimated median survival time for CPC 1-2 and CPC 3-4 were 17 days, 8.8 years and 34 days, 0.4 years, respectively. The mean EQ-5D-5L visual analogue scale score and index score (utility) for 13 CPC 1-2 survivors followed at 6 month post discharge were 75.58 ± 13.31 and 0.856 ± 0.125, respectively, and were significantly higher than the scores (65.38 ± 15.47, 0.689 ± 0.114) at 1 month. The median health care costs of the index admission and 6 month post-discharge for CPC 1-2 survivors were NT$ 655,866 and NT$ 46,550, respectively. Conclusion: The survival time and health related quality of life for OHCA survivors with good neurologic outcome is good and improves over time. It pays to save those lives.
The Structured Coalescent and Its Approximations
Authors: Nicola F. Müller, David A. Rasmussen, Tanja Stadler
Journal: Molecular Biology and Evolution (2017)

Phylogeographic methods can help reveal the movement of genes between populations of organisms. This has been widely done to quantify pathogen movement between different host populations, the migration history of humans, and the geographic spread of languages or gene flow between species using the location or state of samples alongside sequence data. Phylogenies therefore offer insights into migration processes not available from classic epidemiological or occurrence data alone. Phylogeographic methods have however several known shortcomings. In particular, one of the most widely used methods treats migration the same as mutation, and therefore does not incorporate information about population demography. This may lead to severe biases in estimated migration rates for data sets where sampling is biased across populations. The structured coalescent on the other hand allows us to coherently model the migration and coalescent process, but current implementations struggle with complex data sets due to the need to infer ancestral migration histories. Thus, approximations to the structured coalescent, which integrate over all ancestral migration histories, have been developed. However, the validity and robustness of these approximations remain unclear. We present an exact numerical solution to the structured coalescent that does not require the inference of migration histories. Although this solution is computationally unfeasible for large data sets, it clarifies the assumptions of previously developed approximate methods and allows us to provide an improved approximation to the structured coalescent. We have implemented these methods in BEAST2, and we show how these methods compare under different scenarios.
Sodium Transport in the Toad Bladder
Authors: HOWARD S. FRAZIER
Journal: Circulation Research (1971)

The isolated urinary bladder of the toad transports sodium actively across its epithelial layer and responds to the hormones vasopressin and aldosterone, properties which make it a useful model for the study of certain functions of the renal tubule. Sodium transport in the granular cells of the bladder is thought to involve first an energetically passive but selective entry step at the mucosal surface, the rate of which is increased after vasopressin administration. The second step in transport is considered to be active extrusion of the ion across the serosal boundary of the cell. Recent evidence concerning the cellular pool of sodium and the site and mode of action of vasopressin suggests that this description is at best incomplete. No equally simple alternative hypothesis for the organization of sodium transport in this system is available at present.
Abstract 15581: Nocturnal Blood Pressure is Associated With Localized Retinal Nerve Fiber Layer Defects on Optical Coherence Tomography
Authors: Hee Tae Yu, Jaewon Oh, Joo Youn Shin, Suk Ho Byeon, Sungha Park, Sang-Hak Lee, Seok-Min Kang, Donghoon Choi
Journal: Circulation (2015)

Introduction: Retinal damages have been suggested a surrogate marker of end-organ damage and prognostic marker in hypertensive patients. Recent study reported that localized retinal nerve fiber layer defects (RNFLDs) assessed by noninvasive optical coherence tomography (OCT) was related to the degree of hypertension severity and cerebrovascular disease. Purpose: We hypothesize that RNFLDs are related to the parameters of 24 hour ambulatory blood pressure monitoring (ABPM). Methods: RNFLDs were assessed by retinal OCT in 562 consecutive subjects enrolled in Cardiovascular and Metabolic Disease Etiology Research Center - HIgh Risk Cohort (CMERC-HI, NCT02003781). We excluded the patients with glaucoma, which known to be related to RNFLD independently of cardiovascular risk factors. Results: RNFLD was found in 129 (23.0%) patients. In patients with RNFLD, there were higher proportion of men, higher prevalence of hypertension, higher glucose levels and lower HDL-cholesterol levels. The RNFLD patients had higher 24 hour mean systolic and diastolic blood pressure (SBP/DBP, 133±16/80±9 vs. 129±13/78±8, p=0.022/p=0.015, respectively) and nocturnal mean SBP/DBP (124±19/74±9 vs. 120±15/72±9, p=0.013/p=0.010, respectively) compared to those without RNFLD. Multivariate stepwise linear regression analysis revealed that RNFLD was independently associated with nocturnal mean SBP after controlling for age, gender, diabetes mellitus, smoking, body mass index, brachial systolic blood pressure, heart rate, estimated glomerular filtration rate, heart to femoral pulse wave velocity (β=0.093, p=0.036, R2=0.263). Conclusion: We reported that RNFLD on OCT was related to nocturnal blood pressure in 24 hour ABPM for the first time. Further studies which validate RNFLD as a cardiovascular surrogate and risk marker should be warranted.
Lorna Tapper-Jones
Authors: Elizabeth Metcalf, Kamila Hawthorne, Andy Grant
Journal: BMJ (2019)

Lorna Tapper-Jones trained in dentistry before switching to medicine. She dedicated herself to developing her practice in Penylan, Cardiff, where she was a fantastic GP, respected GP trainer, and MRCGP examiner for many years. She relished her role as an undergraduate teacher and was senior partner at Roath House Surgery for many years, until her retirement in …
SAT0023 THE DIFFERENTIAL PRODUCTION OF REACTIVE OXYGEN SPECIES IN T CELL SUBSETS IN PERIPHERAL BLOOD OF RHEUMATOID ARTHRITIS PATIENTS
Authors: Ha-Reum Lee, Su-Jin Yoo, Jinhyun Kim, In Seol Yoo, Chan Keol Park, Seong Wook Kang
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> T cells play a regulatory role in rheumatoid arthritis (RA) through inducing the homeostasis maintenance and self-tolerance <sup>[1]</sup>. Specially, the production and the oxidation mechanism of reactive oxygen species (ROS) were out of balance. <h3>Objectives</h3> The aim of the study was to compare ROS productions in T cell subset, which are helper T (TH) cell, cytotoxic T (TC) cell, T helper 17 (TH17) cell and regulatory T (Treg) cell in peripheral blood mononuclear cells (PBMC) of RA patients with RA activity. <h3>Methods</h3> Blood samples were collected from 30 RA patients and 10 healthy adult volunteers under IRB approval. RA activity was divided according to clinical parameter DAS28 <sup>[2]</sup>. PBMC cells were obtained from the whole blood using lymphocyte separation medium density gradient centrifugation. For separation between the live and dead cell populations, PBMC was stained with Live/Dead stain dye. After PBS washing, cells were incubated with antibodies for CD3, CD4, CD8, and CD25. Following fixation and permeabilization, and further stained with antibodies for FoxP3 and IL-17A. For ROS staining, CellRox and MitoSox were used. <h3>Results</h3> The frequency of TH cell was increased and that of TC cell was decreased in the peripheral blood of RA patients. TH17 and Treg cell population were significantly increased more than about 2-3 folds in active and inactive RA than healthy control. When the whole of cellular ROS production was measured, only Treg cell population was significantly increased in RA than control. Although ROS level was steadily increased with RA activity, there was a slight decline in severe RA compared to moderate and low RA. This difference is lager in mitochondrial specific ROS than total cellular ROS. The mitochondrial complex inhibitor reduced Treg cell frequency in PBMC from RA patients. <h3>Conclusion</h3> Treg is the most sensitive to ROS production among T cell subsets in RA. These findings provide a novel approach to regulate Treg function in RA through mitochondrial metabolism related ROS production. <h3>References</h3> [1] Szekanecz, Z., et al., New insights in synovial angiogenesis. Joint Bone Spine, 2010. 77(1): p.13-9. [2] Prevoo, M.L., et al., Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum, 1995. 38(1): p.44-8. <h3>Disclosure of Interests</h3> None declared
WEE1 inhibition selectively kills histone H3K36me3-deficient cancers by dNTP starvation
Authors: S X Pfister, E Markkanen, Y Jiang, S Sarkar, M Woodcock, Zalmas L-P., G Orlando, N Drobnitzky, G Dianov, S Ying, N B La Thangue, V D'Angiolella, A Ryan, T C Humphrey
Journal: Cancer Research (2016)
Nigerian surgical outcomes – Report of a 7-day prospective cohort study and external validation of the African surgical outcomes study surgical risk calculator
Authors: Babatunde Osinaike, Omobolaji Ayandipo, Tonia Onyeka, Olubusola Alagbe-Briggs, Alhassan Mohammed, Olanrewaju Oyedepo, Ahmed Nuhu, Felicia Asudo, Olanrewaju Akanmu, Chris Nwokorie, Abdulrahman Mohammed, Mark Edubio, Kodilinye Izuora, Rabiu Mohammed, Onochie Nweze, Michael Efu, Stella Eguma, Abiodun Jasper, Richard Ewah, Irene Akhideno, Chimaobi Nnaji, Suleiman Ado, Elizabeth Ogboli-Nwasor, Mamuda Atiku, Ibrahim Salisu, Yakubu Adinoyi, Edith Agu, Ibironke Desalu, Luka Samuel, Yunus Olorode, Oluwabunmi Fatungase, Olugbenga Akinwonmi, Folayemi Faponle, Olusola Idowu, Erdoo Isamade, Abdulrahman Aliyu, Shanka Buba, Garba Hamza, Bisola Onajin-Obembe, Simbo Amanor-Boadu
Journal: International Journal of Surgery (2019)
Early intensive treatment normalises excess mortality in ACPA-negative RA but not in ACPA-positive RA
Authors: Xanthe ME Matthijssen, Tom WJ Huizinga, Ellis Niemantsverdriet, Annette HM van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2019)

With great interest, we read the recently published report by Poppelaars et al in which no excess mortality was observed in 155 patients with rheumatoid arthritis (RA) from the COmbinatie therapie Bij Rheumatoide Artritis (COBRA)-trial, who received early intensive treatment, compared with the general population (Standardised mortality rate (SMR) 0.80 (0.59–1.06)).1 The question whether mortality in RA has normalised is debated, as contradicting results have been published.2–8 In many of the studies on mortality, two important factors are not sufficiently taken into account: follow-up duration and disease subtypes. This might explain the conflicting results. Because thus far none of the reported studies incorporated both factors in the analyses, it is too soon to conclude that mortality is ‘normal’ again, as we will show here.

We compliment the authors on emphasising the importance of a long follow-up duration by showing in their meta-analysis that excess mortality in RA becomes fully apparent after >10 years. This implies that previous studies that reported on normalisation of mortality had insufficient follow-up to reach this conclusion.2–5 Some studies with a short follow-up duration even showed a seemingly decreased …
AB0450 METHOTREXATE ADHERENCE IN MOROCCAN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: hamza toufik, Julien Djossou, Mohamed A.Ghassem, Najlae EL Ouardi, Abderrahim Majjad, Abdellah EL Maghraoui
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Adherence to conventional DMARDs (disease-modifying anti-rheumatic drugs) is highly variable in rheumatoid arthritis (RA), ranging from 22 to 107%. Many studies have evaluated these drugs adherence, but only one single systematic review evaluated specifically methotrexate adhesion in patients with RA. <h3>Objectives:</h3> The aim of this study is to evaluate the adherence to methotrexate (MTX) in Moroccan patients with rheumatoid arthritis (RA) and to investigate factors that may influence it. <h3>Methods:</h3> A cross-sectional study enrolled subjects suffering from rheumatoid arthritis according to ACR/EULAR 2010 criteria, with a history of methotrexate treatment for more than 6 months, either as monotherapy or in combination with other conventional or biological DMARDs. The evaluation of therapeutic compliance with methotrexate was realized using two validated self-questionnaires; the Morisky-Green (MG) questionnaire consisting of 6 questions, and the CQR (Compliance Questionnaire on Rheumatology) consisting of 19 questions. Adherence levels were defined according to the validated thresholds of the questionnaires. The factors likely to influence the adhesion were researched by a standardized questionnaire. <h3>Results:</h3> A total of 61 subjects were studied. The mean age was 53.4±12.5 years, with a weekly methotrexate average dose of 18.2 ± 4.5 mg. In combination methotrexate 77% of patients were receiving corticosteroids, 21% biological DMARDs, 19.7% other conventional DMARDs, and 42% folic acid. The methotrexate adherence levels are presented in figure 1. Lack of resources and adverse effects were the main factors behind methotexate's low level adherence. The patients with these levels had a longer duration of disease progression and higher parameters of disease activity. <h3>Conclusion:</h3> This study shows that the methotrexate adherence level in Moroccan patients with RA is low. The patient's education should be improved in the Moroccan population for a better control of the disease. <h3>Disclosure of Interests:</h3> None declared
Response to anti-angiogenic therapy reflects tumor genotype and microenvironment
Authors: Timothy F Lane, Darren R Carpizo, Osnat Zmora-Beloosesky, Gustavo A Miranda, M. Luisa Iruela-Arisp
Journal: Cancer Research (2004)

58  Breast cancers progress through accumulation of genetic changes in epithelial-derived tumor cells. Expansion of specific populations of cells gives rise to clones that develop resistance to various anticancer agents. In contrast, tumor-supporting stromal elements such as the vasculature are thought to be less heterogeneous and potentially to provide a more consistent target for anti-tumor therapeutics. To test whether the microvasculature of mammary tumors was similar in the presence of diverse populations of tumor cells, we analyzed key aspects of the angiogenic phenotype in a series of mammary tumors that develop in transgenic mice. Specifically, we have examined capillary density, morphometry, gene expression profiles in wnt10b, erbB2, Brca1 and p53-dependent models that were developed in the inbred FVB background. We find that morphometric features of the tumor vasculature are quite distinct in tumors arising from diverse genetic insults. The phenotypes correlate with differences in gene expression profiles of genes known to regulate endothelial growth. To determine if these tumor cell genetic differences impart differences in response to various modes of anti-angiogenic therapy, primary cell lines from the erbB2, wnt10b, Brca1/erbB2, and Brca1/p53 -/- transgenic tumors were established and injected orthotopically into female nude mice. Vehicle control, anti-VEGF and endostatin therapy were initiated on day 1 and tumor growth kinetics were determined. Tumors derived from erbB2 and Brca1/erbB2 cell lines demonstrated a robust response to anti-VEGF therapy with the Brca1/erbB2 cell line responding to endostatin to a lesser degree. Interestingly, tumors derived from the wnt10b cell line demonstrated poor responses to both anti-VEGF and endostatin therapies. These results provide evidence that the molecular events that govern mammary epithelial transformation impact the extracellular environment, specifically the vascular compartment. Moreover, these differences have therapeutic consequences as they affect the tumor’s response to anti-angiogenic therapy. They also provide a basis for the development of criterion (based on angiogenic phenotype) for the prediction of tumor response to specific therapeutic strategies.
Abstract 16233: Trends in Primary Percutaneous Coronary Intervention (PPCI) in Patients Presenting to Non-PCI Capable Hospitals With STEMI in New York State
Authors: Sohah N Iqbal, Sripal Bangalore, Yu Guo, Matthew Schoenfeld, Norma Keller, James Slater
Journal: Circulation (2018)

Introduction: In patients presenting to non-PCI capable hospital with STEMI, the management options include transfer for primary PCI (PPCI) or administration of thrombolytics and transfer for PCI (...
Neurotrophic factor GDNF regulates intestinal barrier function in inflammatory bowel disease
Authors: Michael Meir, Natalie Burkard, Hanna Ungewiß, Markus Diefenbacher, Sven Flemming, Felix Kannapin, Christoph-Thomas Germer, Matthias Schweinlin, Marco Metzger, Jens Waschke, Nicolas Schlegel
Journal: Journal of Clinical Investigation (2019)

Impaired intestinal epithelial barrier (IEB) function with loss of desmosomal junctional protein desmoglein 2 (DSG2) is a hallmark in the pathogenesis of inflammatory bowel disease (IBD). While previous studies have reported that glial cell line–derived neurotrophic factor (GDNF) promotes IEB function, the mechanisms are poorly understood. We hypothesized that GDNF is involved in the loss of DSG2, resulting in impaired IEB function as seen in IBD. In the inflamed intestine of patients with IBD, there was a decrease in GDNF concentrations accompanied by a loss of DSG2, changes of the intermediate filament system, and increased phosphorylation of p38 MAPK and cytokeratins. DSG2-deficient and RET-deficient Caco2 cells revealed that GDNF specifically recruits DSG2 to the cell borders, resulting in increased DSG2-mediated intercellular adhesion via the RET receptor. Challenge of Caco2 cells and enteroids with proinflammatory cytokines as well as dextran sulfate sodium–induced (DSS-induced) colitis in C57Bl/6 mice led to impaired IEB function with reduced DSG2 mediated by p38 MAPK–dependent phosphorylation of cytokeratins. GDNF blocked all inflammation-induced changes in the IEB. GDNF attenuates inflammation-induced impairment of IEB function caused by the loss of DSG2 through p38 MAPK–dependent phosphorylation of cytokeratin. The reduced GDNF in patients with IBD indicates a disease-relevant contribution to the development of IEB dysfunction.
Abatacept for Severe Immune Checkpoint Inhibitor–Associated Myocarditis
Authors: Douglas B Johnson, Joe-Elie Salem, Yves Allenbach, Aurore Vozy, Nicolas Brechot, ; Douglas, B. Johnson, ; Javid, Javid J Moslehi, Mathieu Kerneis
Journal: New England Journal of Medicine (2019)

Abatacept for Nivolumab-Induced Myocarditis Autoimmune myocarditis is a rare but often fatal complication of immune checkpoint inhibitor therapy for cancer. A case of glucocorticoid-refractory myoc...
Learning Curve for Endoscopic Submucosal Dissection With an Untutored, Prevalence-Based Approach in the United States
Authors: Xiaocen Zhang, Erin K. Ly, Sagarika Nithyanand, Rani J. Modayil, Dmitriy O. Khodorskiy, Sivaram Neppala, Sriya Bhumi, Matthew DeMaria, Jessica L. Widmer, David M. Friedel, James H. Grendell, Stavros N. Stavropoulos
Journal: Clinical Gastroenterology and Hepatology (2019)
Sofosbuvir/ledipasvir plus ribavirin achieves high SVR12 in genotype‐3 patients with compensated cirrhosis and similar to sofosbuvir plus daclatasvir: a multicentre real life cohort
Authors: M. Riveiro-Barciela, Sonia Alonso, Inmaculada Fernández, Diego Rincón, Yolanda Real, Javier Crespo, Francisco Gea, Antonio Olveira, J.L. Calleja, B. Polo-Lorduy, J.A. Carrión, J. Arenas, M.J. Devesa, C. Baliellas, Ángeles Castro-Iglesias, Manuel Romero-Gómez, R. Granados, J.M. Pascasio, Xavier Forns, Juan Turnes, J.L. Montero, R. Esteban, Conrado M. Fernández-Rodríguez
Journal: Hepatology (2016)