tbuckley/cabot-search huggingface dataset:
Diagnosis and management of Non‐IgE gastrointestinal allergies in breastfed infants—An EAACI Position Paper
Authors: Rosan Meyer, Adriana Chebar Lozinsky, David M. Fleischer, Mario C. Vieira, George Du Toit, Yvan Vandenplas, Christophe Dupont, Rebecca Knibb, Piınar Uysal, Ozlem Cavkaytar, Anna Nowak‐Wegrzyn, Neil Shah, Carina Venter
Journal: Allergy (2019)

It is well-established that food proteins, such as egg, soya, cow's milk and wheat, are detectable in breastmilk for many hours or days after ingestion. Exposure to these proteins is important to the process of developing tolerance but can also sometimes elicit IgE-mediated and non-IgE-mediated allergic symptoms in breastfed infants. Non-IgE-mediated allergy, outside of food protein-induced allergic proctocolitis and eosinophilic oesophagitis, is not well understood, leading to variations in the diagnosis and management thereof. A primary objective of the European Academy for Allergy and Clinical Immunology is to support breastfeeding in all infants, including those with food allergies. A Task Force was established, to explore the clinical spectrum of non-IgE-mediated allergies, and part of its objectives was to establish diagnosis and management of non-IgE-mediated allergies in breastfed infants. Eight questions were formulated using the Patient, Intervention, Comparison, Outcome (PICO) system and Scottish Intercollegiate Guideline Network (SIGN) criteria for data inclusion, and consensus was achieved on practice points through the Delphi method. This publication aims to provide a comprehensive overview on this topic with practice points for healthcare professionals.
THU0637 ACADEMIC ACHIEVEMENT, EMPLOYMENT STATUS, WORK PRODUCTIVITY AND ACTIVITY IMPAIRMENT IN ADULTS WITH JUVENILE IDIOPATHIC ARTHRITIS (JIA): DETERMINANTS AND CONSEQUENCES
Authors: Chengappa Kavadichanda, Karunya Ravi, Vir Negi
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Changes occurring in childhood due to JIA leads to activity and work impairment during their transition to adulthood. The factors impairing work and overall activity among adults with JIA need to be explored to formulate policy decisions and rehabilitation measures. <h3>Objectives:</h3> · To assess the level of academic achievement, employment, work productivity and activity impairment among adults suffering from JIA · To identify factors determining activity impairment among adults with JIA <h3>Methods:</h3> Consecutive adults classified as JIA (1) were included. Consenting patients filled a questionnaire comprising of demographic details, occupational/educational status, Indian health associated questionnaire (iHAQ), Work Productivity and Activity Impairment score (WPAI) (2)in the language of their choice. Clinical evaluation for disease activity and damage was done and remission was assessed by Wallace criteria. Remission was defined as ever remission: &gt;3 months and sustained remission: &gt; 6 months of disease control. Appropriate statistical tests to assess association and correlation of various factors with WPAI were used. <h3>Results:</h3> Demography (n=51) is depicted in table 1. Never attaining remission resulted in significantly higher college dropouts (8 vs 17, p&lt;0.05), functional impairment (mean iHAQ 1.08 vs 0.5, p&lt;0.05) and articular damage (mean JADI A 3 vs 8, p&lt;0.01). Disease duration, JADI A and iHAQ correlated well (r<sup>2</sup> &gt;.400, p&lt;0.05) with measures of WPAI (table 2). Assessment of patient variables like gender, occupation, disease activity and remission status (figure 1) showed that women, especially the homemakers and individuals with moderate to high disease activity had significant activity impairment (P&lt;0.05). <h3>Conclusion:</h3> Early effective treatment directly impacts employment levels and activity in adults with JIA. Homemakers in middle- and low-income countries have the most impairment in activity as they cannot alter their work. Replacement costs for homemakers would be an added financial burden to the family and is seldom captured by studies. Our study highlights the need to look further into the indirect and intangible costs involving women that will help policy makers formulate effective economic policies for individuals with JIA. <h3>References:</h3> [1] Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004Feb;31(2):390–2. [2] Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and activity impairment instrument. Pharmacoeconomics. 1993Nov;4(5):353–65. <h3>Disclosure of Interests:</h3> None declared
Abstract O.48: Intravenous Immunoglublin-Associated Hemolysis in Kawasaki Disease
Authors: Rae S Yeung, Fiona Almeida, Vahid Khajoee, Nita Chahal, Trent Mizzi, Sarah Schwartz, Brian W McCrindle, Wendy Lau
Journal: Circulation (2015)

Background: Intravenous immunoglobulin (IVIG) is the mainstay of treatment for Kawasaki Disease (KD). Due to the consolidation of IVIG manufacturers in 2008, different preparations of IVIG are currently available in Canada. An increase in adverse effects, especially hemolytic anemia, has been observed. Objective: To characterize the natural history of IVIG-associated hemolytic anemia in KD. Methods: A single-centre retrospective study was conducted at Toronto’s SickKids Hospital between January 2002 and December 2012. Medical records of all KD patients were reviewed and hemolytic anemia identified (drop in hemoglobin ≥20mg/dl post-IVIG treatment with 2 or more of the following criteria: reticulocytosis, positive direct anti-globulin test (DAT), and morphological changes on blood film). For statistical analysis, Chi-square tests and ANOVA with Tukey’s post-hoc correction for multiple comparisons were utilized. Results: Between 2002 and 2008, 2 of 370 patients diagnosed with KD who received Iveegam had hemolytic anemia (0.5%). After 2008, the rates of IVIG-associated hemolysis were as follows: Privigen 17% (8/48, p&lt;0.001), Gammagard 3.3% (4/121) and Gamunex 2.3% (3/130). Retreatment rates were significantly higher in the hemolysis group (64% vs. 22%, p&lt;0.001), and there was a trend showing more patients with larger aneurysms (Z-score &gt;5) in the hemolysis group (17% vs. 5.3%). All patients who hemolyzed had non-O+ blood types. Out of the 17 patients with hemolysis, 9 required red cell transfusions (60%). Starting in 2012, a detailed hemolysis work-up was included as standard protocol for all KD patients. Hemolysis was mediated by anti-blood group A &amp; B antibodies resulting in DAT positivity, but no complement fixation. This extravascular hemolysis was maximal at 72 hours post-IVIG infusion and appeared to be dose dependent. Conclusions: Hemolysis is seen in up to 17% of those receiving new IVIG preparations, which also appear to be less efficacious - associated with treatment failure and, possibly, poor coronary outcome. There are important implications for patient safety. Further study is required to develop evidence-based guidelines to improve our management of these children.
PS978 DISCOVERY OF NOVEL C/D BOX SNORNAS THAT ARE REQUIRED FOR LEUKEMIA CELL PROLIFERATION
Authors: A. Kienast, C. Rohde, F. Zhou, Y. Liu, D. Gerloff, C. Thiede, C. Pabst, F. Radtke, J. Zoller, C. Müller‐Tidow
Journal: HemaSphere (2019)

Background: The vast majority of the human genome is transcribed, but the function of many transcripts remain obscure. It is likely, that cancer specific transcripts exist that are overlooked by conventional pipeline analysis. Aims: We tried to identify novel non coding RNA transcripts with C/D box snoRNA properties based on sequence homology. We specifically analysed AML patient samples Methods: To understand the role of snoRNAs in leukemogenesis, we analyzed the snoRNA expression pattern in an initial cohort of 63 AML patients (Zhou, 2017) and an additional cohort of 90 AML patients. Abundant regions with coverage were annotated using snoRNABase (LBME), the recently published updated snoRNAome (Jorjani, 2016) and tracks from ENSEMBL, UCSC, RNAcentral and DASHR databases. Regions without annotation were analyzed for C/D box motifs to discover putative C/D box snoRNAs. For further analysis only regions with at least one reads per million (RPM) in at least one patient sample were included. Results: Next generation sequencing data revealed that 248 of the 269 known C/D box snoRNAs (92%) were expressed in one or more patient samples. For the H/ACA box snoRNAs we could identify 103 of 112 (92%). In addition to this established functionally well annotated core‐set of C/D box snoRNA we confirmed another set of 76 C/D box snoRNA to be expressed in AML patient samples. These 76 snoRNA recently have been described as novel C/D‐box snoRNA based on the analysis of ENCODE small RNA‐seq data. Importantly, our in silico analysis identified 45 novel putative C/D box snoRNAs which had not been described so far. All of these putative C/D box snoRNAs contain the box C/D motifs and were mostly located in introns of known genes. In further analyses, we observed increased expression of putative snoRNAs was found in patients with intermediate molecular risk (7 snoRNAs, p≤0.05) and in patients with a poor response to chemotherapy (9 snoRNAs, p≤0.05). The novel snoRNAs were more prominently expressed in in NPM1 wildtype AML compared to NPM1 mutant AML. Overall, 13 putative C/D box snoRNA were downregulated during myeloid differentiation of HL60 cells. To study the function of the snoRNA we performed a CRISPR/Cas9 knockout of five regions in Kasumi1 and U937 cell lines. The knockout of four out of five novel snoRNAs impaired proliferation and colony growth. Summary/Conclusion: Multiple novel C/D box snoRNAs were identified from primary AML specimens. These show a specific expression pattern in myeloid differentiation in distinct AML subtypes. The functional relevance of these snoRNAs suggests that so far overlooked non coding RNA sequences are of high importance in AML.
FRI0308 HIGH LEVEL OF SERUM NEOPTERIN IS ASSOCIATED WITH RAPIDLY PROGRESSIVE INTERSTITIAL LUNG DISEASE AND REDUCED SURVIVAL IN DERMATOMYOSITIS
Authors: Qinglin Peng, Yamei Zhang, Lin Liang, Xin Lu, Guochun Wang
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Neopterin is primarily synthesized and released by activated macrophages/monocytes upon stimulation with interferon-γ and is considered as a marker for macrophage activation. <h3>Objectives</h3> This study aimed to analyze the serum levels of neopterin in patients with dermatomyositis (DM) in association with clinical manifestations, laboratory data and patient prognosis. <h3>Methods</h3> One hundred and eighty-two consecutive DM patients and 30 healthy controls were retrospectively enrolled in the study. Serum levels of neopterin were detected by using the ELISA method. Clinical and laboratory data and patient prognosis were obtained and analyzed in association with serum neopterin. <h3>Results</h3> Serum levels of neopterin were significantly increased in DM patients (median 21.2 nmol/L, IQR 13.9-35.2 nmol/L) compared to healthy controls (median 4.3 nmol/L, IQR 2.9-5.6 nmol/L, P&lt;0.01). High serum neopterin levels were associated with anti-MDA5 antibody, rapidly progressive interstitial lung disease (RP-ILD), and cutaneous involvement including skin ulcer and heliotrope rash. Longitudinal assessment of serum samples revealed that the serum neopterin levels were closely correlated with disease severity. In addition, a significant increase in serum neopterin concentration of non-survivors (median 38.7 nmol/L, IQR 23.5-65.3 nmol/L) was observed when compared to that of survivors (median 19.0 nmol/L, IQR 12.5-29.0 nmol/L) (P&lt;0.01). ROC curves showed that serum neopterin could distinguish non-survivors and survivors at an optimal cut-off level of 22.1 nmol/L with a sensitivity and specificity of 0.804 and 0.625 respectively (P&lt;0.01). Kaplan-Meier survival curves revealed that DM patients with serum neopterin &gt; 22.1 nmol/L had a significantly higher mortality compared to patient group with serum neopterin &lt;22.1 nmol/L (logrank P&lt;0.01). Multivariate Cox regression analysis identified high serum neopterin concentration to be an independent risk factor for poor prognosis in DM (adjusted HR=4.619, 95%CI: 2.092-10.195, P&lt;0.01). <h3>Conclusion</h3> Increased serum levels of neopterin were significantly associated with RP-ILD and reduced survival in DM patients, suggesting it as a promising biomarker in the disease evaluation of DM. These findings highlight the role of cellular immune activation and macrophage activity in the pathogenesis of DM. <h3>Reference:</h3> [1] Murr C, Widner B, Wirleitner B, et al. Neopterin as a marker for immune system activation. Current drug metabolism2002; 3: 175-87. <h3>Disclosure of Interests</h3> None declared
Bioresorbable Electrode Array for Electrophysiological and Pressure Signal Recording in the Brain
Authors: Kedi Xu, Shijian Li, Shurong Dong, Shaomin Zhang, Gang Pan, Guangming Wang, Lin Shi, Wei Guo, Chaonan Yu, Jikui Luo
Journal: Advanced Healthcare Materials (2019)

Medical implantation of an electrocorticography (ECoG) recording system for brain monitoring is an effective clinical tool for seizure focus location and brain disease diagnosis. Planar and flexible ECoG electrodes can minimize the risks of infection and serious inflammatory response, and their good shape adaptability allows the device to fit complex cortex shape and structure to record brain signals with high spatial and temporal resolution. However, these ECoG electrodes require an additional surgery to remove the implant, which imposes potential medical risks. Here, a novel flexible and bioresorbable ECoG device integrated with an intracortical pressure sensor for monitoring swelling of the cortex during operation is reported. The ECoG device is fabricated with poly( l ‐lactide) and polycaprolactone composite and transient metal molybdenum. In vivo tests on rats show that the ECoG system can record the dynamic changes in brain signals for the different epilepsy stages with high resolution, while the malleable pressure sensor shows a linear relationship between the pressure and resistance in in vitro tests. In vitro degradation experiments show that the ECoG system can work stably for about five days before loss of efficacy, and the whole ECoG system degrades completely in a phosphate buffer solution in about 100 days.
Abstract 2489: Physical Activity is Associated With Neurally Mediated Responses During Head Up Tilt Table Testing and Carotid Sinus Massage
Authors: Shishir Mathur, Danette Guertin, Craig Coleman, Jeffrey Kluger
Journal: Circulation (2009)

AIMS: Endurance athletes are known to have poor tolerance to orthostatic stress and increased chances of neurocardiogenic syncope. The aim of this study was to identify association between regular ...
Abstract 16123: D-Dimer Levels and Clinical Outcomes in Acute Coronary Syndrome Patients: An ATLAS ACS TIMI 46 Trial Substudy
Authors: Fahad Alkhalfan, Mathieu Kerneis, Tarek Nafee, Megan K Yee, Gerald Chi, Alexei Plotnikov, Eugene M Braunwald, C. Michael Gibson
Journal: Circulation (2018)

Introduction: The prognostic value of D-dimer in the setting of acute coronary syndromes (ACS) and the ability of pharmacotherapy to reduce D-dimer in ACS has not been previously explored. Methods:...
The S52F FOXF1 Mutation Inhibits STAT3 Signaling and Causes Alveolar Capillary Dysplasia
Authors: Arun Pradhan, Andrew Dunn, Vladimir Ustiyan, Craig Bolte, Guolun Wang, Jeffrey A. Whitsett, Yufang Zhang, Alexey Porollo, Yueh-Chiang Hu, Rui Xiao, Przemyslaw Szafranski, Donglu Shi, Pawel Stankiewicz, Tanya V. Kalin, Vladimir V. Kalinichenko
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal congenital disorder causing respiratory failure and pulmonary hypertension shortly after birth. There are no effective treatments for ACDMPV other than lung transplant, and new therapeutic approaches are urgently needed. Although ACDMPV is linked to mutations in the
Screening for HIV Infection in Asymptomatic, Nonpregnant Adolescents and Adults
Authors: Roger Chou, Tracy Dana, Sara Grusing, Christina Bougatsos
Journal: JAMA (2019)

Untreated HIV infection can result in significant morbidity, mortality, and HIV transmission. A 2012 review for the US Preventive Services Task Force (USPSTF) found antiretroviral therapy (ART) associated with improved clinical outcomes and decreased transmission risk in persons with CD4 cell counts less than 500/mm3.To update the 2012 review on HIV screening to inform the USPSTF.Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from 2012 to June 2018, with surveillance through January 2019.Nonpregnant individuals 12 years and older; randomized clinical trials (RCTs) and controlled observational studies of screening vs no screening, alternative screening strategies, earlier vs later initiation of ART, and long-term harms of ART.One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality.Mortality, AIDS events, quality of life, function, and HIV transmission; harms of screening and long-term (≥2 years) harms of ART; screening yield.Eighteen new studies (5 RCTs, 11 cohort studies, and 2 systematic reviews; N = 266 563) were included, and 11 studies (2 RCTs and 9 cohort studies; N = 218 542) were carried forward from the prior USPSTF report. No study directly evaluated effects of HIV screening vs no screening on clinical outcomes or harms, or the yield of alternative screening strategies. Two newly identified RCTs conducted completely or partially in low-resource settings found ART initiation at CD4 cell counts greater than 500/mm3 associated with lower risk of a composite outcome of mortality, AIDS-defining events, or serious non-AIDS events (relative risk [RR], 0.44 [95% CI, 0.31-0.63] and RR, 0.57 [95% CI, 0.35-0.95]); results were consistent with those from a large observational study. Early ART was not associated with increased risk of cardiovascular events. Early ART initiation was associated with sustained reduction in risk of HIV transmission at 5.5 years (RR, 0.07 [95% CI, 0.02-0.22] for linked transmission). New evidence regarding the association between abacavir use and risk of cardiovascular events was inconsistent. Certain antiretroviral regimens were associated with increased risk of long-term neuropsychiatric, renal, hepatic, and bone adverse events.In nonpregnant adolescents and adults there was no direct evidence on the clinical benefits and harms of screening for HIV infections vs no screening, or the yield of repeat or alternative screening strategies. New evidence extends effectiveness of ART to asymptomatic individuals with CD4 cell counts greater than 500/mm3 and shows sustained reduction in risk of HIV transmission at longer-term follow-up, although certain ART regimens may be associated with increased risk of long-term harms.
Abstract 12478: Hypertension-related Left Ventricular Hypertrophy is Assossiated With Right Ventricular Dysfunction
Authors: Vasiliki Katsi, Constantina Aggeli, Ioannis Felekos, George Souretis, Ioannis Vlasseros, Dimitrios Tousoulis, Christodoulos Stefanadis, Ioannis Kallikazaros
Journal: Circulation (2012)

Introduction: In the setting of essential hypertension, left ventricular hypertrophy is a common echocardiographic finding. The functional interdependance of the two ventrincles often leads to righ...
Non-medical colonoscopists are safe and effective: results from randomised controlled trial
Authors: A Gardiner, E Skinn, S Maslekar, Graeme Duthie
Journal: Gut (2006)

Introduction: There is an increasing demand for colonoscopy, especially with introduction of screening programmes. Though it is performed by doctors and nurses, there is an acute shortage of trained colonoscopists. Non-medical personnel were therefore trained to perform colonoscopy. The aim of this study was to prospectively compare the outcome and efficacy of non-medical colonoscopists (NMC), with both medical (MEC) and nurse colonoscopists (NC). MethodsThis study was drawn from a randomised controlled trial of sedation for colonoscopy. Randomisation was stratified by endoscopist grade: MEC or NMC or NC. Patients undergoing elective colonoscopy completed anxiety questionnaires, and baseline letter cancellation test and pain score on visual analogue scale (VAS). Post-procedure all patients marked assessment of pain and satisfaction on VAS and completed letter cancellation test. Secondary outcome variables included completion rates,nurse satisfaction and rate of complications. ResultsOut of 110 patients, 40 were randomised to MEC and NC group each and 30 patients to the NMC group. Demographic characteristics of all groups were similar. Completion rate was 95%, 97.5%, and 91% in MEC, NC, and NMC groups respectively (p=0.3). There was no statistically significant difference between the groups in terms of median pain scores (p=0.1), patient satisfaction (p=0.8), nurse satisfaction (p=0.6), and time to discharge (p=0.08). No complications occurred. ConclusionThis first prospective randomised controlled trial on non-medical colonoscopy has shown that NMC is safe, feasible, and therapeutic as well as diagnostic procedures can be performed with comparable completion rates and patient satisfaction. We conclude that this is a viable and effective option that complements and reduces clinician's workload.
Esophageal Squamous Cell Carcinoma Involving the Lip, Back and Hip
Authors: Shugeng Gao, Yalong Wang, Qi Xue, Juwei Mu, Yushun Gao, Fengwei Tan, Yousheng Mao, Dali Wang, Jun Zhao, Yin Li, Jie He
Journal: Journal of Thoracic Oncology (2019)
Connecting the Sequence-Space of Bacterial Signaling Proteins to Phenotypes Using Coevolutionary Landscapes
Authors: R. R. Cheng, O. Nordesjö, R. L. Hayes, H. Levine, S. C. Flores, J. N. Onuchic, F. Morcos
Journal: Molecular Biology and Evolution (2016)

Two-component signaling (TCS) is the primary means by which bacteria sense and respond to the environment. TCS involves two partner proteins working in tandem, which interact to perform cellular functions whereas limiting interactions with non-partners (i.e., cross-talk). We construct a Potts model for TCS that can quantitatively predict how mutating amino acid identities affect the interaction between TCS partners and non-partners. The parameters of this model are inferred directly from protein sequence data. This approach drastically reduces the computational complexity of exploring the sequence-space of TCS proteins. As a stringent test, we compare its predictions to a recent comprehensive mutational study, which characterized the functionality of 204 mutational variants of the PhoQ kinase in Escherichia coli. We find that our best predictions accurately reproduce the amino acid combinations found in experiment, which enable functional signaling with its partner PhoP. These predictions demonstrate the evolutionary pressure to preserve the interaction between TCS partners as well as prevent unwanted cross-talk. Further, we calculate the mutational change in the binding affinity between PhoQ and PhoP, providing an estimate to the amount of destabilization needed to disrupt TCS.