tbuckley/cabot-search huggingface dataset:
Rotavirus and autoimmunity
Authors: J. Gómez-Rial, I. Rivero-Calle, A. Salas, F. Martinón-Torres
Journal: Journal of Infection (2020)

Rotavirus, a major etiological agent of acute diarrhea in children worldwide, has historically been linked to autoimmunity. In the last few years, several physiopathological approaches have been proposed to explain the leading mechanism triggering autoimmunity, from the old concept of molecular mimicry to the emerging theory of bystander activation and break of tolerance. Epidemiological and immunological data indicate a strong link between rotavirus infection and two of the autoimmune pathologies with the highest incidence: celiac disease and diabetes. The role for current oral rotavirus vaccines is now being elucidated, with a so far positive protective association demonstrated.
Early Response to Induction Is Predictive of Survival in Childhood Philadelphia Chromosome Positive Acute Lymphoblastic Leukaemia: Results of the Medical Research Council ALL 97 Trial.
Authors: Anindita Roy, Mike Bradburn, Anthony V. Moorman, Julie Burrett, Chris Mitchell, Sally E. Kinsey, Ajay J. Vora, John Lilleyman, Osborn Eden, Ian Hann, Vaskar Saha
Journal: Blood (2004)
The effect of lactoferrin supplementation on death or major morbidity in very low birthweight infants (LIFT): a multicentre, double-blind, randomised controlled trial
Authors: William O Tarnow-Mordi, Mohamed E Abdel-Latif, Andrew Martin, Mohan Pammi, Kristy Robledo, Paolo Manzoni, David Osborn, Kei Lui, Anthony Keech, Wendy Hague, Alpana Ghadge, Javeed Travadi, Rebecca Brown, Brian A Darlow, Helen Liley, Margo Pritchard, Anu Kochar, David Isaacs, Adrienne Gordon, Lisa Askie, Melinda Cruz, Tim Schindler, Kelly Dixon, Girish Deshpande, Mark Tracy, Deborah Schofield, Nicola Austin, John Sinn, R John Simes, R. Black, W. Nie, S. Reid, J. Michalowski, L. McKeown, P. Koorts, M. Broom, P. Kwan, S. Morris, K. Cornthwaite, R. Tobiansky, D. Darcy, L. Goodchild, C. Collins, E. Noble, A. Lewis, E. Yeomans, C. Hua, M. Hinder, A. Bhaskaracharya, P. Graham, H. Patel, N Wilkes, N. Marlow, R. Soll, C. McKinlay, N. Modi, I. Marschner, B. Stenson, D. Espinoza
Journal: The Lancet Child & Adolescent Health (2020)
Real-time tracking of self-reported symptoms to predict potential COVID-19
Authors: Cristina Menni, Ana M. Valdes, Maxim B. Freidin, Carole H. Sudre, Long H. Nguyen, David A. Drew, Sajaysurya Ganesh, Thomas Varsavsky, M. Jorge Cardoso, Julia S. El-Sayed Moustafa, Alessia Visconti, Pirro Hysi, Ruth C. E. Bowyer, Massimo Mangino, Mario Falchi, Jonathan Wolf, Sebastien Ourselin, Andrew T. Chan, Claire J. Steves, Tim D. Spector
Journal: Nature Medicine (2020)

A total of 2,618,862 participants reported their potential symptoms of COVID-19 on a smartphone-based app. Among the 18,401 who had undergone a SARS-CoV-2 test, the proportion of participants who reported loss of smell and taste was higher in those with a positive test result (4,668 of 7,178 individuals; 65.03%) than in those with a negative test result (2,436 of 11,223 participants; 21.71%) (odds ratio = 6.74; 95% confidence interval = 6.31-7.21). A model combining symptoms to predict probable infection was applied to the data from all app users who reported symptoms (805,753) and predicted that 140,312 (17.42%) participants are likely to have COVID-19.
Abstract 19882: Incidence, Clinical Outcomes and Factors Influencing Permanent Pacemaker Implantation after Transcatheter Aortic Valve Replacement - A Meta-Analysis of 93 Studies including 37,836 Patients
Authors: Tarun Chakravarty, Richard Cheng, Yigal Abramowitz, Amit Noheria, Hasan Jilaihawi, Niraj Doctor, Wen Cheng, Raj R Makkar
Journal: Circulation (2014)

Background: The impact of transcatheter aortic valve replacement (TAVR) strategy, valve type (balloon-expandable Edwards (ES) valve or self-expanding Medtronic CoreValve (MCV)) and geographical differences (USA or Europe) on new permanent pacemaker (PPM) implantation is unclear. Similarly, the impact of PPM implantation on mortality after TAVR is unclear. We perform the first meta-analysis of incidence, clinical outcomes and factors influencing PPM implantation after TAVR.

Methods and Results: A total of 93 non-overlapping studies including 37,836 patients reporting 30-day PPM implantation rates post-TAVR were included. Random-effects model was used to calculate pooled estimates and risk ratios, summarized in Table 1. MCV (n=8076) was associated with increased PPM implantation rates compared to ES valve (n=20,280) (22.5%, 95% CI 19.4-25.9% vs. 6.5%, 95% CI 5.7-7.4%, p < 0.01). Among patients undergoing ES valve implantation, transapical (TA) approach was associated with increased PPM implantation rates compared to transfemoral (TF) approach (9.1%, 95% CI 6.5-11.5% vs. 4.8%, 95% CI 2.9-7.4%; p=0.02). Among patients undergoing TAVR by TF approach, MCV implantation was associated with increased PPM rates, compared to ES valve (22.51%, 95% CI 18.7-25.9% vs. 4.8%, 95% CI 2.9-7.4%; p<0.01). PPM implantation rates associated with ES or MCV were not statistically different between US or European studies. Compared to patients not requiring PPM post-TAVR, the need for new PPM implantation was not associated with increased 30-day mortality (Risk-ratio 0.84 95% CI 0.61-1.15, p=0.27) or 1-year mortality (Risk-ratio 0.94 95% CI 0.74-1.19, p=0.60).

Conclusions: PPM implantation is a frequent complication after TAVR. This is more commonly associated with MCV and TA approach for ES valve and is not influenced by geographical zones. Despite the high incidence of PPM implantation associated with TAVR, the need for new PPM does not influence 30-day or 1-year mortality.

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Effect of Carvedilol on Survival in Severe Chronic Heart Failure
Authors: Milton Packer, Andrew J.S. Coats, Michael B. Fowler, Hugo A. Katus, Henry Krum, Paul Mohacsi, Jean L. Rouleau, Michal Tendera, Alain Castaigne, Ellen B. Roecker, Melissa K. Schultz, Christoph Staiger, Ellen L. Curtin, David L. DeMets
Journal: New England Journal of Medicine (2001)

Beta-blocking agents reduce the risk of hospitalization and death in patients with mild-to-moderate heart failure, but little is known about their effects in severe heart failure.
A large-scale analysis of racial disparities in police stops across the United States
Authors: Emma Pierson, Camelia Simoiu, Jan Overgoor, Sam Corbett-Davies, Daniel Jenson, Amy Shoemaker, Vignesh Ramachandran, Phoebe Barghouty, Cheryl Phillips, Ravi Shroff, Sharad Goel
Journal: Nature Human Behaviour (2020)
Azithromycin Reduces Exacerbations In Adults With Persistent Symptomatic Eosinophilic Asthma
Authors: P. G. Gibson, I. A. Yang, J. W. Upham, P. N. Reynolds, S. Hodge, A. L. James, C. Jenkins, M. Peters, G. B. Marks, M. Baraket, J. L. Simpson, H. Powell
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Combination therapy of intra-arterial 5-fluorouracil and systemic pegylated interferon alpha-2b for advanced hepatocellular carcinoma.
Authors: Kazuhiro Kasai, Kei Sawara, Kazuyuki Suzuki
Journal: Journal of Clinical Oncology (2013)

216 Background: Two recent phase III clinical trials have shown that sorafenib improves the survival in patients with advanced hepatocellular carcinoma (HCC). However, patients with HCC and portal vein tumor thrombosis (PVTT) usually have very short survival even when treated with sorafenib. On the other hand, recent advances in implantable drug delivery systems have made it possible to administer repeated hepatic arterial infusion chemotherapy (HAIC) agent. Since 2006, we have treated the patients displaying advanced HCC with PVTT by combined HAIC of 5-fluorouracil (5-FU) and systemic pegylated interferon (PEG-IFN)α-2b, and reported favorable results. In this article, we evaluated the efficacy of combined 5-FU and PEG-IFN α-2b, and compared outcomes between advanced HCC patients with PVTT treated using sorafenib. Methods: Forty patients with HCC and PVTT were enrolled. Of these, 21 patients were treated using subcutaneous administration of PEG-IFNα-2b and intra-arterial infusion of 5-FU [5-FU / PEG-IFN group], 19 patients were treated using continuous oral treatment with 400-800 mg of sorafenib [Sorafenib group]. We compared the early response to the therapy and the cumulative survival rate between these two groups. Results: The objective early response rate in the 5-FU / PEG-IFN group was significantly higher than that in the Sorafenib group (71.4 vs. 10.5%, P&lt;0.01). The cumulative survival rates at 6, 12, 18, and 24 months, respectively, were 83.8, 77.8, 55.6, and 55.6% in the 5FU / PEG-IFN group, and 68.4, 37.7, 16.2, and 16.2% in the Sorafenib group. The cumulative survival rates was significantly higher in the 5FU / PEG-IFN group than in the Sorafenib group (P=0.03). Serious complications and treatment-related deaths were not observed in the 5FU / PEG-IFN group. On the other hand, the rate of discontinuation of treatment due to adverse events was 36.8% of the patients who were treated sorafenib. Conclusions: Based on our findings, this newly developed combination therapy may be useful for patients with advanced HCC, although a large-scale randomized controlled study by comparison with sorafenib is needed.
Initial combination therapy of macitentan and tadalafil in pulmonary arterial hypertension
Authors: Olivier Sitbon, Vincent Cottin, Matthieu Canuet, Pierre Clerson, Virginie Gressin, Loïc Perchenet, Laurent Bertoletti, Hélène Bouvaist, François Picard, Grégoire Prévot, Emmanuel Bergot, Gérald Simonneau
Journal: European Respiratory Journal (2020)

<b>Initial combination therapy with macitentan and tadalafil is well tolerated and improves cardiopulmonary haemodynamics and functional capacity in newly diagnosed PAH patients</b>https://bit.ly/3aWZagH
Phase II trial of neoadjuvant pemetrexed plus cisplatin followed by surgery and radiation in the treatment of malignant pleural mesothelioma (MPM).
Authors: F. Rea, A. G. Favaretto, G. Marulli, L. Spaggiari, T. M. De Pas, A. Ceribelli, A. Paccagnella, G. Crivellari, F. Russo, M. Ceccarelli, F. Facciolo
Journal: Journal of Clinical Oncology (2011)

7090 Background: Combined modality approaches to therapy, including surgery (S) and radiation, have proved feasible and are becoming one of the standards of care in MPM. This study was designed to assess the efficacy of the combination of neoadjuvant pemetrexed+cisplatin, extrapleural pneumonectomy (EPP) and hemithoracic radiation (HTR) (trimodality [TM] therapy) in MPM. Methods: This was a multicenter, phase II, open-label study with event-free survival (EFS) (defined as time from enrollment to first observation of disease progression, death due to any cause or early treatment discontinuation) as the primary endpoint. Between 2005 and 2008, 56 patients (pts) with MPM (T1-3, N0-2) were screened, of whom 54 were enrolled (87% male; median age 63 [range 39-75] years; ECOG PS 0-1; adequate organ function). Pre-operative pemetrexed 500 mg/m2+cisplatin 75 mg/m2 IV was given every 21 days x 3 cycles, plus folic acid, vitamin B12 and dexamethasone, followed by EPP and HTR (total dose 54 Gy). After 2 deaths due to cardiopulmonary failure, occurred after HTR therapy (21 [38.8%] pts out of 54 were already enrolled in the study at this time), the protocol was amended reducing HTR dose to 50.4 Gy. Results: Of the 54 pts enrolled, 52 (96.3%) completed chemotherapy (CT), 45 (83.3%) underwent S, 22 (40.7%) completed the whole treatment including 90 day follow up. The median EFS was 6.9 months (95%CI: 5.0–10.5) and the median progression-free survival was 8.6 months (95%CI: 6.3-14.4). A total of 18 (33.3%) and 13 (24.1%) pts were still event free after 1 and 2 years respectively. Of the 54 pts, 16 (29.6%) showed partial response to CT, 31 (57.4%) showed stable disease, 4 (7.4%) showed progression, responses in 3 (5.6%) pts were unknown (overall response before S). During the whole study 36 (66.7%) pts experienced ≥1 grade 3-4 toxicity (the most frequent were hematological and gastrointestinal) but no statistically significant differences were observed before and after amendment. Conclusions: These results are aligned with the available scientific literature related to the TM approach on MPM, showing that the adopted multidisciplinary treatment is effective with a manageable toxicity profile.
Association between tax on sugar sweetened beverages and soft drink consumption in adults in Mexico: open cohort longitudinal analysis of Health Workers Cohort Study
Authors: Luz María Sánchez-Romero, Francisco Canto-Osorio, Romina González-Morales, M Arantxa Colchero, Shu-Wen Ng, Paula Ramírez-Palacios, Jorge Salmerón, Tonatiuh Barrientos-Gutiérrez
Journal: BMJ (2020)

To examine changes in categories of soft drink consumption in a cohort of Mexican adults, three years after the implementation of the sugar sweetened beverage tax.Open cohort longitudinal analysis.Three waves of the Health Workers Cohort Study, Mexico, spanning 2004 to 2018.1770 people aged 19 years or older with information on drinks consumption available in at least one of the three cohort waves.Change in probability of belonging to one of four categories of soft drinks consumption (non, low, medium, high) after the tax was implemented. Heterogeneity of associations by income and education was also assessed.Before the implementation of the tax, more than 50% of the participants were medium and high consumers of soft drinks and less than 10% were in the non-consumer category. After the tax was implemented, 43% of the population was categorised as medium or high consumers and the prevalence of non-consumers increased to 14%. Three years after implementation of the tax on 1 January 2014, the probability of being a non-consumer of soft drinks increased by 4.7 (95% confidence interval 0.3 to 9.1) percentage points and that of being a low consumer increased by 8.3 (0.6 to 16.0) percentage points compared with the pre-tax period. Conversely, the probability of being in the medium and high levels of soft drinks consumption decreased by 6.8 (0.5 to 13.2) percentage points and 6.1 (0.4 to 11.9) percentage points, respectively. No significant heterogeneity of the tax across income levels was observed, but stronger effects of the tax were seen in participants with secondary school education or higher, compared with those with elementary school or less.The Mexican sugar sweetened beverage tax was associated with a reduction in the probability of consuming soft drinks in this cohort of employees from a healthcare provider. The results cannot be extrapolated to the Mexican population, but they suggest that three years after implementation, the tax had helped to increase the proportion of people who do not consume soft drinks while decreasing the proportion of high and medium consumers.
Genetic Changes in the Pathogenesis of Lung Cancer
Authors: M J Birrer, J D Minna
Journal: Annual Review of Medicine (1989)

Human lung cancer is a complex genetic disease resulting from a series of inherited and somatically occurring defects in a number of critical genes. These genetic events, produced in part by carcinogen exposure, include chromosomal deletion, rearrangement, and mutation, and lead to inactivation or activation of certain target genes. Recent data showed these genes to include both recessive oncogenes such as the retinoblastoma gene and dominantly acting oncogenes such as the myc and ras family members.
A new paradigm for drug development
Authors: Talha Burki
Journal: The Lancet Digital Health (2020)

In January, 2020, British pharmaceutical company Exscientia announced that its compound DSP-1181, which is intended to treat obsessive compulsive disorder, was starting a phase 1 clinical trial. DSP-1181 was created using an artificial intelligence (AI) platform to trawl through chemical libraries and identify the most relevant compounds. Reportedly, DSP-1181 is the first such drug to enter clinical trials.
Survival and course of lung function in the presence or absence of antifibrotic treatment in patients with idiopathic pulmonary fibrosis: long-term results of the INSIGHTS-IPF registry
Authors: Jürgen Behr, Antje Prasse, Hubert Wirtz, Dirk Koschel, David Pittrow, Matthias Held, Jens Klotsche, Stefan Andreas, Martin Claussen, Christian Grohé, Henrike Wilkens, Lars Hagmeyer, Dirk Skowasch, Joachim F. Meyer, Joachim Kirschner, Sven Gläser, Nicolas Kahn, Tobias Welte, Claus Neurohr, Martin Schwaiblmair, Thomas Bahmer, Tim Oqueka, Marion Frankenberger, Michael Kreuter
Journal: European Respiratory Journal (2020)

There is a paucity of observational data on antifibrotic therapy for idiopathic pulmonary fibrosis (IPF). We aimed to assess the course of disease of IPF patients with and without antifibrotic therapy under real-life conditions.We analysed data from a non-interventional, prospective cohort study of consecutively enrolled IPF patients from 20 interstitial lung disease expert centres in Germany. Data quality was ensured by automated plausibility checks, on-site monitoring, and source data verification. Propensity scores were applied to account for known differences in baseline characteristics between patients with and without antifibrotic therapy.Among the 588 patients suitable for analysis, the mean±sd age was 69.8±9.1 years, and 81.0% were male. The mean±sd duration of disease since diagnosis was 1.8±3.4 years. The mean±sd value at baseline for forced vital capacity (FVC) and diffusion capacity (DLCO) were 68.6±18.8% predicted and 37.8±18.5% predicted, respectively. During a mean±sd follow-up of 1.2±0.7 years, 194 (33.0%) patients died. The 1-year and 2-year survival rates were 87% versus 46% and 62% versus 21%, respectively, for patients with versus without antifibrotic therapy. The risk of death was 37% lower in patients with antifibrotic therapy (hazard ratio 0.63, 95% CI 0.45; 0.87; p=0.005). The results were robust (and remained statistically significant) on multivariable analysis. Overall decline of FVC and DLCO was slow and did not differ significantly between patients with or without antifibrotic therapy.Survival was significantly higher in IPF patients with antifibrotic therapy, but the course of lung function parameters was similar in patients with and without antifibrotic therapy. This suggests that in clinical practice, premature mortality of IPF patients eventually occurs despite stable measurements for FVC and DLCO.
Abstract 177: A Multimodal Neuroprotection Strategy Using Ketamine, Melatonin, and Limited Initial Reoxygenation Following Cardiac Arrest Does Not Improve MRI Cytotoxic Injury in a Swine Model: A Pilot Study
Authors: Miriam Peckham, Adam DeHavenon, Matthew D Alexander, Scott McNally, Jeffrey Anderson, Stephen H McKellar, Joseph Tonna, Jacob Steenblik, Ka-ho Wong, Scott T Youngquist
Journal: Circulation (2019)

Introduction: Reperfusion/ischemic brain injury following arrest is a major cause of death/disability among patients surviving to admission. Aside from targeted temperature management, no proven neuroprotective strategies exist. Melatonin (anti-epileptic/antioxidant) and ketamine (glutamate inhibitor), along with controlled reintroduction of oxygenated blood have been proposed to reduce secondary injury. Hypothesis: We hypothesized that a combination of above therapies would reduce the ischemic burden measured on MRI following cardiac arrest if administered upon initial reperfusion. Methods: 6 swine underwent isoflurane anesthesia and control MRI (DTI b2000/20 directions, DSC). Swine were randomized to fixed periods of cardiac arrest (2 swine to 20 min and 1 to 30 min in both control and treated groups), and ECMO catheters placed in the distal aorta and right atrium, then ventricular fibrillation induced by a bipolar pacing catheter. Following ischemia, swine were reperfused at 2.8-3.5 L/min with either unblended oxygenated blood in the control group, or 21% oxygenated blood increased to 30% after 4 minutes and then titrated to maintain PaO2 of 80-100 mm Hg, melatonin 5 mg/kg bolus then 5 mg/kg/hr and ketamine 4 mg/kg/hr for 2 hours in the treated group. After 4 min swine were defibrillated until return of heartbeat. Animals were weaned from pump, decannulated, and epinephrine and fluid boluses administered for hemodynamic support, then re-imaged within 2 hours post-resuscitation using same protocol. Whole brain ADC measurements were performed on gray and white matter. Frontal lobe regions of interest drawn for DSC perfusion parameters. Results: Baseline hemodynamic parameters: BP, Heart Rate, End-Tidal CO2, and SpO2 were similar between animals. There was no difference in percent change ADC in gray or white matter between treated and untreated swine (p=0.9), or difference in CBV (p=0.67). CBF showed an upward trend in treated animals (p=0.17). Conclusions: A multimodal neuroprotective strategy of melatonin, ketamine, and controlled reoxygenation failed to demonstrate measurable impact on MRI markers of ischemia-reperfusion injury in this pilot study. The translation of promising neuroprotectants might be triaged using the employed model.
OP0127 DISEASE PRESENTATION OF 1,312 CHILDHOOD-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS: INFLUENCE OF ETHNICITY
Authors: Lucia Campos, Fernanda Fiorot, Aline G. Islabão, Rosa M. Pereira, Maria T. Tererri, Claudia Saad-Magalhães, Glaucia V. Novak, Beatriz Molinari, Ana Paula Sakamoto, Nadia Aikawa, Octávio Peracchi, Simone Appenzeller, Virginia Ferriani, Marco Felipe Silva, Adriana Fonseca, Flávio R. Sztajnbok, Luciana Paim, Melissa Fraga, Eunice M. Okuda, Blanca Bica, Evaldo Sena, Ana Julia Moraes, Ana M. Rolim, Paulo F. Spelling, Iloite M. Scheibel, Andre S. Cavalcanti, Erica Naka, Teresa C Robazzi, Luciano Junqueira, Flávia P. Santos, Valeria C. Ramos, Magda Carneiro-Sampaio, Eloisa Bonfa, Clovis A. Silva
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> To our knowledge the influence of ethnic background in childhood-onset SLE (cSLE) presentation was not evaluated in a large population of Latin American country. <h3>Objectives</h3> To assess demographic data, clinical manifestations, laboratory abnormalities and disease activity score in cSLE patients according to ethnic groups at diagnosis <h3>Methods</h3> This multicenter study included cSLE patients(ACR criteria) followed in 27 Pediatric Rheumatology services of Brazil. Ethnicities were classified in four groups according to the parents’ and all four grandparents’ self-reported ethnicity. The statistical analysis was performed using the Bonferroni’s correction(p&lt;0.0027). <h3>Results</h3> According to ethnic groups, 1,537 cSLE patients were classified in: Caucasian (n=786), African-Latin American(n=526), Asian(n=8) and others/unknown(n=217). Comparisons between 1,312 African-Latin American and Caucasian revealed similar median age at cSLE diagnosis[12.2(2.6-18) vs. 12.1(0.3-18) years,p=0.234], time interval to diagnosis[0.25(0-12) vs. 0.3(0-10) years,p=0.034] and SLEDAI-2K score[14(0-55) vs. 14(0-63),p=0.781] in both groups. The mean number of diagnostic criteria according to SLICC(6.47±1.911 vs. 5.81±1.631, p&lt;0.0001) and frequencies of maculopapular lupus rash (8% vs. 3%, p&lt;0.0001), palate oral ulcers(17% vs. 11%,p=0.001), tongue oral ulcers (4% vs. 1%, p=0.001) and nonscarring alopecia(29% vs. 16%,p&lt;0.0001) were significantly higher in African-Latin American, whereas malar rash(45% vs. 58%,p&lt;0.0001) was more frequent in Caucasian. The presence of antiphospholipid antibody(23% vs. 12%,p&lt;0.0001), low complement levels(58% vs. 41%, p&lt;0.0001) and isolated direct Coombs test (10% vs. 5%,p=0.001) were also significantly higher in the former group. <h3>Conclusion</h3> Our study demonstrated that disease presentation severity of African-Latin American cSLE patients is comparable to Caucasian. Mucocutaneous manifestations and autoantibodies profile were the only distinctive features of the former group. The unique mixed background of Brazilian patients probably minimized race diversity spectrum of these patients. <h3>Disclosure of Interests</h3> None declared