tbuckley/cabot-search huggingface dataset:
Risk of adult‐onset asthma increases with the number of allergic multimorbidities and decreases with age
Authors: Sanna Toppila‐Salmi, Sebastien Chanoine, Jussi Karjalainen, Juha Pekkanen, Jean Bousquet, Valérie Siroux
Journal: Allergy (2019)

The aim was to study the association between allergic multimorbidity and adult-onset asthma considering the number of allergic diseases and the age effect.We used population-based data from Finnish national registers including 1205 adults over 30 years of age with recently diagnosed asthma (age range: 30-93), matched for gender, age, and living region with one or two controls (n = 2050). Allergic rhinitis (AR), allergic conjunctivitis (AC), and allergic dermatitis (AD) were defined from self-completed questionnaire. Conditional logistic regression adjusted on potential confounders (smoking, growing in countryside, childhood hospitalized infection/pneumonia, parental asthma/allergy, parental smoking, education level, professional training, number of siblings, and birth order) was applied to estimate the asthma risk associated with allergic multimorbidity.A total of 1118 cases with asthma and 1772 matched controls were included [mean (SD, min-max) 53 (11, 31-71) years, 37% men)]. AR, AC, and AD were reported by 50.2%, 39.6%, and 33.8%, respectively, among subjects with asthma and 26.1%, 20.0%, and 23.5%, respectively, among controls. Compared to nonatopics, adult-onset asthma increased with the number of allergic diseases; adjusted OR for asthma [95% CI] associated with 1, 2, and 3 allergic diseases was 1.95 [1.52-2.49], 2.87 [2.19-3.77], and 4.26 [3.07-5.90], respectively. The association between adult-onset asthma and ≥ 1 allergic multimorbidity decreased with increasing age (3.52 [2.51-4.94], 2.44 [1.74-3.42], and 1.68 [1.04-2.71]) in subjects < 50 years, 50-62 years, and > 62 years, respectively (p for age*≥1 allergic multimorbidity interaction, 0.002).Adult-onset asthma was positively associated with the number of allergic diseases, and this association decreases with age.
Compulsory vaccination would exacerbate resistance
Authors: Giuseppe Vetrugno, Michela Cicconi, Federica Foti, Angelico Spagnolo, Fabio De-Giorgio
Journal: BMJ (2019)

Vaccination programmes are an extension of the solidarity principle on which the foundations of living in a community are based. Health is a fundamental right of the individual, but it is also the expression of a collective interest in all community members having this right.

If vaccination is needed to protect collective health, then being part of a community should …
Dietary Supplements for Brain Health
Authors: A. David Smith, Helga Refsum, Joshua W. Miller
Journal: JAMA (2019)

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Abstract 3492: A targeted semi-conductor based next-generation sequencing (NGS) test to characterize microsatellite instability in FFPE tumor samples
Authors: Anelia Kraltcheva, Sameh El-Difrawy, Asha Kamat, Janice Au-Young, Simon Cawley, Seth Sadis
Journal: Cancer Research (2019)

Abstract Microsatellite instability (MSI) arises from defects in the mismatch repair (MMR) system and is associated with hypermutability of short DNA sequence repeats. Defects in MMR are observed in diverse cancer types but are common in colorectal, gastric and endometrial cancers. MSI testing is increasingly important for patient management. For example, in diverse cancer types, MSI is associated with favorable response to immune checkpoint inhibitors. The mainstay of MSI testing has been PCR/fragment analysis or IHC to monitor loss of expression of MMR proteins. Although generally robust, these methods are single biomarker tests that may consume limited biopsy samples. For this reason, MSI testing has been recently incorporated into NGS tests. However, targeted amplicon based NGS tests for MSI that consume limited sample input and provide fast turn-around time remain an unmet need. Herein, we describe a targeted NGS-based method to assess MSI that leverages Ion AmpliSeq™ or Ion AmpliSeq™ HD multiplex PCR and Ion GeneStudio™ S5 next-generation sequencing. The test is comprised of diverse microsatellite markers including mono- and di-nucleotide repeats that range from 10 to 40 bp. A novel algorithm was developed that leverages the unique signal processing properties inherent in semi-conductor sequencing and workflows were developed for tumor only samples as well as paired tumor-normal samples. The test provides results for individual microsatellites and generates an MSI score for the sample. The performance of the assay was verified over a large cohort of colorectal, gastric and endometrial cancer samples with MSI status independently assigned by orthogonal on-market tests. The MSI panel can be used by itself or integrated into larger targeted sequencing panels. MSI tests that leverage the inherent advantages of targeted semiconductor sequencing, low sample input and fast turn-around time, will support expanded research opportunities into the association of MSI with other targeted alterations and help elucidate the interaction of MSI, DNA repair defects, and the response to immune checkpoint inhibition. Citation Format: Anelia Kraltcheva, Sameh El-Difrawy, Asha Kamat, Janice Au-Young, Simon Cawley, Seth Sadis. A targeted semi-conductor based next-generation sequencing (NGS) test to characterize microsatellite instability in FFPE tumor samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3492.
Abstract 5111: HuPharm: An interactive data analysis platform for preclinical studies
Authors: Binchen Mao, Sheng Guol, Qixiang Li
Journal: Cancer Research (2019)

Abstract Background: Preclinical studies, the first stage of the drug development process, must always have proper planning, execution, analysis and reporting in order to preserve scientific integrity. The decision to advance to human clinical trials depends heavily on results of these studies. For To facilitateing in vivo pharmacology data analysis and interpretation, we developed a web platform (HuPharm) that automates statistical pipelines and report generation. Its intuitive and interactive interface will greatly help researchers, who more often than not are non-statisticians, on data validation, exploratory data analysis and statistical analysis. Methods: We use RStudio’s shiny package to build an interactive web application (HuPharm), and we use knitr and rmarkdown packages to generate a highly informative data analysis report. HuPharm is deployed on the web using Shinyapps.io developed by RStudio. Based on the distribution of input data, HuPharm will automatically performs parametric tests such as ANOVA and Welch’s t-test or non-parametric tests such as Kruskal-Wallis test and Mann-Whitney U test. Additionally, HuPharm is capable of conducting survival analysis, including both non-parametric Kaplan-Meier analysis and Ccox regression. Aside from classical tests, we have also implemented a number of state-of-the-art analytics on HuPharm, such as multilevel/hierarchical linear models, frailty analysis and joint modeling of longitudinal and survival data. Last by not the least, power analysis module in HuPharm can help researchers with their study design by power and sample size calculation. Results: Based upon user inputs, HuPharm will dynamically generate a series of tables and figures to facilitate preclinical data analysis, such as tumor volume summary statistic table and plots, tumor growth curves, omnibus group comparison plots, all pairwise group comparison table and post hoc analysis results table. In addition, HuPharm can generate one nicely formatted study report including all those aforementioned figures and tables in both html and pdf format. Powered by shiny server’s interactive design, users can easily adjust the parameters to explore their data in a highly flexible and responsive way. Conclusions: HuPharm is a convenient and powerful tool to aid researchers in the field of preclinical trials studies for their study design and data analysis. It will help to add rigor and improve the quality of preclinical studies. Citation Format: Binchen Mao, Sheng Guol, Qixiang Li. HuPharm: An interactive data analysis platform for preclinical studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5111.
Abstract 19384: Catheter Ablation of Scar-Based Ventricular Tachycardia: Impact of Procedural Duration on Outcomes
Authors: Roderick Tung, Ricky Yu, Justin Hayase, Noel Boyle, Kalyanam Shivkumar
Journal: Circulation (2012)

Background: The relationship of procedural duration with efficacy and complication rate in ventricular tachycardia (VT) ablation has not been well studied. The aim of this report is to examine the relationship between procedural duration and VT ablation outcomes. Methods: All patients referred for VT ablation between 6/04-6/11 were included in the present study. Procedural duration was defined as the time from the insertion of catheter sheaths through the femoral vein to the time of their withdrawal. Variables that were recorded and analyzed for relationship to procedural duration included: number of induced VTs, in-hospital mortality, and 6-month outcomes. Results: 148 patients with scar-mediated VT were available for analysis. The mean procedural duration for cases with endocardial, epicardial, and combined epicardial-endocardial VT mapping were: 5.1 ± 1.7, 5.0 ± 1.6, and 6.4 ± 1.7 hours, respectively. Longer procedural duration was associated with a greater number of VT morphologies induced (range 1.5- 3.7 mean VTs induced). The six month freedom from VT for the overall cohort was 53% (ICM=66% (49/74), NICM=39% (27/69)). The duration of the procedure did not impact success rates. An increase in in-hospital mortality was observed for procedures longer than eight hours. Conclusion: While longer procedural duration was associated with comparable 6 month freedom from VT recurrence, an escalating risk for in-hospital mortality was seen in patients who underwent procedures longer than eight hours.
Outcomes in large B-cell lymphoma progressing after axicabtagene ciloleucel (Axi-cel): Results from the U.S. Lymphoma CAR-T Consortium.
Authors: Jay Y. Spiegel, Saurabh Dahiya, Michael D. Jain, Loretta J. Nastoupil, Armin Ghobadi, Yi Lin, Matthew Alexander Lunning, Patrick Michael Reagan, Joseph McGuirk, Abhinav Deol, Javier Munoz, Frederick Lundry Locke, Sattva Swarup Neelapu, John S Tamaresis, Aaron Rapoport, David Bernard Miklos, Brian Thomas Hill
Journal: Journal of Clinical Oncology (2019)

7517 Background: Axi-cel, an anti-CD19 CART cell therapy, achieved 83% ORR, 58% CR rate, with 39% PFS at 2 years in patients (pts) with relapsed refractory large B-cell lymphoma (LBCL) on the ZUMA-1 study (Locke, Lancet Oncology 2018). Data from a 17-center consortium showed response rates were similar in 274 pts treated with commercial axi-cel (Nastoupil, ASH 2018). Here, we performed retrospective analysis of outcomes in pts with progressive disease (PD) after axi-cel. Methods: Response status was determined by Cheson 2014 and reported as date of radiologic relapse. 274 pts were infused by December 26, 2018 with maximum follow-up of 14 months; 116 pts had PD as of Feb 1, 2019. Twelve sites provided additional data, detailing 85% of PD pts (n=99) with a median time to relapse of 54 days (IQR 16-120). Results: Pre axi-cel pt characteristics: median lines of therapy were 4 (range 2-11), 86% were Stage III/IV and 22% were ECOG &gt;1. Following relapse, 60% (n=61) were biopsied and 70% (43/61) had CD19 expression measured. Thirty percent (13/43) were CD19 negative by: IHC (3/13), flow (2/13) or both (8/13). Seventy percent (n=71) received salvage therapy for PD. Median lines of salvage therapy was 1 (range 0-4). The most common therapies were Lenalidomide-based (30%), checkpoint inhibitors (30%), chemotherapy (20%) and radiation (10%). First salvage therapy ORR by regimen: checkpoint inhibitors = 24%, lenalidomide regimens = 20% and chemotherapy = 11%. One patient received allogeneic transplant. Twelve pts enrolled on clinical trial, with one receiving 2 nd CAR-T. Median OS following relapse was 108 days (95% LCL 71). Nineteen pts relapsed &lt;3 months after axi-cel and did not receive therapy with median OS 17 days (95% CI 7-49); 33 pts relapsed &lt;3 months and received therapy with 114 day median OS (95% LCL 82). In contrast, 30 pts who relapsed &gt;3 months post axi-cel and received therapy had estimated median OS &gt;220 days (95% LCL 81). Conclusions: Patients with LBCL relapsing less than 3 months following axi-cel have extremely poor outcomes supporting the development of novel therapies. Therapy for relapse &gt;3 months appears promising. JYS and SD contributed equally; APR, DBM and BTH contributed equally.
Abstract 1956: ICG pHLIP: A novel agent for fluorescence-guided surgery
Authors: Troy Crawford, Anna Moshnikova, Sean Roles, Lukas M. Carter, Jason S. Lewis, Donald M. Engelman, Oleg A. Andreev, Yana K. Reshetnyak
Journal: Cancer Research (2019)

Abstract Introduction: Fluorescence imaging has applications in medicine for many image-guided procedures such as mapping and visualization of lymph nodes, targeting and marking cancerous lesions and assessment of tumor margins. Several fluorescent molecules are approved for clinical use including the ICG (indocyanine green) near infrared (NIR) fluorescent dye. We conjugated ICG to a pH Low Insertion Peptide (pHLIP®), which senses and targets the acidity at the surfaces of cancer cells, and evaluated ICG pHLIP® as a targeted imaging agent for tumor visualization. Our construct is progressing toward clinical trials. Experimental Procedures: ICG pHLIP® was manufactured for proof-of-concept tumor-targeting imaging studies in mice, and toxicity evaluation in mice, dogs and rats. Tumor targeting was assessed in various human and murine tumor models. Biodistribution was evaluated at different time points from 5 min to 48 hours after a single intravenous administration of 0.5 mg/kg of ICG pHLIP®. The distribution of the agent within tumors was evaluated in tumor sections. Results: The fluorescence of ICG is enhanced about 15 times when pHLIP® tethers it to a cell membrane, significantly improving the contrast index. No toxicity is seen at 25-30x of the proposed human dose, evaluated in mice and dogs. ICG pHLIP® demonstrates excellent tumor targeting, including targeting of 1-3 mm sized tumors in breast. About 10-15% ID/g was observed within tumors at 4 hours p.i., and the signal persists for up to 24 hours with a slight decline at 48 hours. The background signal in major organs decayed after agent administration. The highest uptake, of about 50% ID/g, was observed in liver at 4 hrs p.i. and decayed after that. An excellent correlation was established between ICG pHLIP® NIRF imaging and H&amp;E histopathology at the indicated tumor location. Conclusions: ICG pHLIP® is a promising new imaging agent for fluorescence-guided surgical applications. It is on the path to clinical translation for accurate resection of breast tumors. Since pHLIP® targeting of tumors is based on the general principle of cancer cell surface acidity, ICG pHLIP® is an agent that may be used in a range of fluorescence-guided surgical interventions. Citation Format: Troy Crawford, Anna Moshnikova, Sean Roles, Lukas M. Carter, Jason S. Lewis, Donald M. Engelman, Oleg A. Andreev, Yana K. Reshetnyak. ICG pHLIP: A novel agent for fluorescence-guided surgery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1956.
Long-term follow-up of patients (pts) with relapsed or refractory (r/r) follicular lymphoma (FL) treated with copanlisib.
Authors: Sirpa Leppä, Armando Santoro, Judit Demeter, George Follows, Georg Lenz, Won Seog Kim, Luigina Mollica, Arnon Nagler, Colin Phipps Diong, Mariano Provencio, Don A. Stevens, David R. Trevarthen, MingLu Wang, Oliver Wirtz, Ashok Miriyala, Jose Garcia Vargas, Barrett H. Childs, Pier Luigi Zinzani, Martin H. Dreyling
Journal: Journal of Clinical Oncology (2019)

7553 Background: The pan-class I phosphatidylinositol 3-kinase inhibitor copanlisib was approved by the FDA in September 2017 for treatment of relapsed FL based on results from the CHRONOS-1 study in pts with indolent non-Hodgkin lymphoma. We report efficacy and safety results of a 2-year (yr) follow-up of FL pts. Methods: Pts with indolent FL (grade [G] 1-3a) r/r to ≥2 prior lines of treatment received copanlisib (60 mg i.v. infusion) on days 1, 8, and 15 of a 28-day cycle. The primary endpoint was objective tumor response rate (ORR) per independent radiologic review (Cheson et al. 2007). Adverse events were reported using MedDRA (v20.1). Data cut-off: February 20, 2018. Results: 104 FL pts were enrolled. Median age was 62 yr (39% &gt;65 yr), the median number of prior lines of anti-cancer therapy was 3 (range 2-8), and 27 pts (26%) were classified as having G3a disease. The ORR was 59%, with complete responses (CR) in 20% ( n=21); 14 pts had a CR at the primary analysis in June 2016. The median duration of response (mDoR) was 12.2 months (mo) (range 0.03-43 mo). Stable disease (SD) was observed in 33% of pts; median duration of SD was 7.8 mo (range 1.3-23 mo). Median progression-free survival (mPFS) was 11.2 mo (range 0.03-44 mo) with 33% alive and progression-free at 2 yrs. Median overall survival (mOS) was 3.2 yr (range 0.06-4.2 yr) with 67% alive at 2 yrs. Median duration of treatment was 26 weeks (wk) (range 1-192 wk); median duration of safety follow-up was 29 wk. In the G3a subset, the ORR was 67% (26% CR), mDoR was 10.9 mo, mPFS was 12.5 mo, and mOS was 2.5 yr. The most common treatment-emergent adverse events occurring in &gt;25% of pts included (all grade/G3+): diarrhea (37%/9%), neutropenia (26%/23%), and pyrexia (28%/5%). Hyperglycemia (49%/40%) and hypertension (29%/23%) were transient. Incidences of pneumonitis (6.7%/1.9%) and colitis (1.0% G4) were low. Conclusions: Long-term follow-up of r/r FL pts treated with copanlisib revealed robust and durable responses with CRs exceeding 20%, including in pts with higher grade disease. The safety profile continues to be both manageable and favorable, with no evidence of late-onset severe toxicities. Clinical trial information: NCT01660451.
Abstract 4532: Differential protein and metabolite regulation in urothelial carcinoma highlights changes in immunity and receptor signaling pathways
Authors: Lee Gethings, Adam King, Andrew J. Peck, Robert S. Plumb
Journal: Cancer Research (2019)

Abstract Bladder cancer is ranked as one of the tumours posing high morbidity and mortality, with a pathogenesis which is still not well understood. A combination of genetic and lifestyle factors, including smoking, are known to contribute towards increasing the probability of encountering cancer. Here, we describe a multi-omic approach to reveal molecular factors that may be involved in these biomolecular processes. Plasma samples consisting of healthy controls and those from patients diagnosed with bladder cancer were prepared for proteomic, metabolomic and lipidomic analyses. Label-free LC-MS data were acquired using a QTof platform utilizing a data independent (DIA) workflow termed SONAR. Small molecule analysis consisted of using Progenesis QI for data processing to provide normalised values prior to statistical analysis. Unsupervised MVA of the data showed clear distinction between cohorts. OPLS-DA was used to filter for features of significant correlation and covariance prior to identification using metabolite and lipid specific databases. Identifications matching the following criteria, mass accuracy &amp;lt;5 ppm, ANOVA p &amp;lt;0.05, %CV &amp;lt;30 and fold change &amp;gt;2 were considered for further interrogation. SONAR-based analysis indicates that this method of data acquisition enabled over an order of magnitude more specificity than equivalent methodologies with the same resolution. Proteomic data were processed and searched against a Uniprot Homo sapien database, containing reviewed entries and limited to 1% FDR. Additionally, we also searched the data against a spectral library and comparatively analysed the results from both workflows. A number of significant proteins with differential regulation were exhibited for a number of protein groups involved in antigen and lipid binding. Proteins occurring in a minimum of two out of three replicates and with ANOVA p &amp;lt;0.05 were considered. Biological significance of the results was established by merging data from all three omic experiments and performing pathway analysis. A number of significant pathways including complement activation, B cell mediated immunity and receptor signalling were identified as key pathways. Citation Format: Lee Gethings, Adam King, Andrew J. Peck, Robert S. Plumb. Differential protein and metabolite regulation in urothelial carcinoma highlights changes in immunity and receptor signaling pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4532.