tbuckley/cabot-search huggingface dataset:
New Directions in Right Ventricular Assessment Using 3-Dimensional Echocardiography
Authors: Karima Addetia, Denisa Muraru, Luigi P. Badano, Roberto M. Lang
Journal: JAMA Cardiology (2019)

<h3>Importance</h3> Before the introduction of 3-dimensional echocardiography, estimations of right ventricular (RV) size and function by echocardiography were limited to regional approximations of global function. This review describes the novel application of 3-dimensional echocardiography in the assessment of RV size and function, in juxtaposition with what is currently available using 2-dimensional echocardiography. <h3>Observations</h3> Two-dimensional echocardiographic evaluation of RV size and function includes measures of systolic basal longitudinal excursion (tricuspid annular plane systolic excursion and peak systolic velocity), fractional area change, and free-wall strain, all of which are measured from a single tomographic imaging plane: the RV-focused view. Given this limitation, clinical situations in which more accurate assessment of the RV or close patient follow-up were required were resolved with the use of cardiovascular magnetic resonance, computed tomography, and other modalities to obtain global measures of size and function (ie, volume and ejection fraction). With 3-dimensional echocardiography, both volume and ejection fraction assessments of the RV are possible with an accuracy and reproducibility close to that of cardiovascular magnetic resonance imaging. Further, 3-dimensional RV data sets can be cropped, sliced, and rotated to assess device leads, tricuspid valve leaflets, and RV wall–motion abnormalities. The 3-dimensional RV data set opens the horizon to endless possibilities for further exploration of novel parameters, including 3-dimensional RV shape and 3-dimensional RV deformation analysis. <h3>Conclusions and Relevance</h3> The use of 3-dimensional echocardiography overcomes many of the limitations associated with conventional 2-dimensional echocardiography and has the potential to provide the detailed information required for the complex clinical decision-making that requires accurate, quantitative information about the RV.
Epidemiological Study of Aplastic Anemia in Algeria for 844 Cases over 10 Years (2007-2016)
Authors: F Mehdid, N Rekkab, S Oukid, MT Abad, M Bradai, S Hamdi, F Boukhemia, RM Hamladji, R Ahmed Nacer, M Allouda, H Ait Ali, S Benaichou, Z Zouaoui, S Boughrira, F Grifi, N Cherif, A Bensenouci, Z Kaci, M Belhani, N Boudjerra, F Serradj, MA Bekadja, M Kehal, H Touhami, D Saidi, B Gareh, M Saidi, L Sahraoui, Fz Ardjoun, SE Belakehal, S Chichoune, Y Ouarlhent, F Bendahmane, N Mesli, M Benhalilou, N Sidi Mansour, N Benmoufek, S Ladj, W Hadji, N Bensmaine, N Hendel, F Arbaoui, N Mehalhal, S Hadji, A Bachiri, L Touati, N Lakhdari, N Ferroudj, S Nekkal, H Boudiaf, M Achir, A Fafa, Malek Benakli
Journal: Blood (2018)
Results from the Hgb-207 (Northstar-2) Trial: A Phase 3 Study to Evaluate Safety and Efficacy of Lentiglobin Gene Therapy for Transfusion-Dependent β-Thalassemia (TDT) in Patients with Non-β0/β0 Genotypes
Authors: Mark C. Walters, Suradej Hongeng, Janet L. Kwiatkowski, Franco Locatelli, John B. Porter, Martin G. Sauer, Adrian J Thrasher, Isabelle Thuret, Evangelia Yannaki, Heidi Elliot, Marisa Gayron, Mohammed Asmal, Alexis A Thompson
Journal: Blood (2017)
Abstract 14805: Use of Dedicated Protocol and Implantable Loop Recorder to Evaluate for Atrial Fibrillation in Cryptogenic Stroke Patients: Real World Validation of Crystal AF
Authors: Amber Seiler, Sharon Biby, Pramod Sethi, James Allred
Journal: Circulation (2015)

Introduction: Embolic strokes related to atrial fibrillation (AF) carry significant morbidity and mortality. Identifying patients with asymptomatic AF following stroke is difficult. A protocol for incorporation of implantable loop recorders (ILR) in stroke management has not been established. Methods: We developed a protocol for evaluation of patients with cryptogenic embolic stroke using ILR for detection of AF (figure 1). Patients implanted with ILR were enrolled in an AF clinic with structured remote follow-up. The primary end point was time to first detected AF. Secondary end point was time to initiation of anticoagulation following identification of AF. Results: 95 patients underwent ILR placement. Baseline characteristics are shown in table 1. The median time between stroke and ILR placement was 6 days with a range of 1 to 496 days. The mean follow-up time was 169.4 +/- 103.1days. 18 patients (18.9%) had AF detected during the study period (Figure 2). Mean time to detection of AF was 95.7 +/- 93.6 days. 94.4% were anticoagulated (52.9% Rivaroxaban, 41.2% Apixaban, 5.9% Warfarin). The median time from detection of AF to initiation of anticoagulation was 2 days with a range of 1 to 28 days. Conclusions: A protocol for incorporating ILR in evaluation of embolic cryptogenic stroke can improve AF detection and time to initiation of anticoagulation.
Diverse and highly cross‐reactive T‐cell responses in ragweed allergic patients independent of geographical region
Authors: Peter A. Würtzen, Ilka Hoof, Lars H. Christensen, Zuzana Váczy, Helene Henmar, Guillermo Salamanca, Claus Lundegaard, Lise Lund, Tatiana Kráľova, Edwars G. Brooks, Peter S. Andersen
Journal: Allergy (2019)

Abstract Background Ragweed frequently causes seasonal allergies in North America and Europe. In the United States, several related ragweed species with diverse geographical distribution cause allergic symptoms. Cross‐reactivity towards related ragweed species of IgE and treatment‐induced IgG 4 has been demonstrated previously. However, less is known about the underlying T‐cell cross‐reactivity. Methods The allergen content of ragweed extracts was determined by mass spectrometry and related to T‐cell epitopes of Amb a allergens (group 1, 3, 4, 5, 8 and 11) in 20 American ragweed allergic patients determined by FluoroSpot and proliferation assays. T‐cell responses to 50 frequently recognized Amb a‐derived T‐cell epitopes and homologous peptides from western ragweed (Amb p), giant ragweed (Amb t) and mugwort (Art v) were investigated in an additional 11 American and 14 Slovakian ragweed allergic donors. Results Ragweed extracts contained all known allergens and isoallergens thereof. Donor T‐cell responses were diverse and directed against all Amb a 1 isoallergens and to most minor allergens investigated. Similar response patterns were seen in American and Slovakia donors. Several epitopes were cross‐reactive between isoallergens and ragweed species, some even including mugwort. T‐cell cross‐reactivity generally correlated with allergen sequence homology. Conclusion T‐cell epitopes of multiple allergens/isoallergens are involved in the diverse T‐cell responses in ragweed allergic individuals. T‐cell lines were highly cross‐reactive to epitopes of related ragweed species without any apparent geographical response bias. These data support that different ragweed species can be considered an allergen homology group with Amb a as the representative species regarding diagnosis as well as allergy immunotherapy.
Expanding the critique of the social motivation theory of autism with participatory and developmental research
Authors: Steven K. Kapp, Emily Goldknopf, Patricia J. Brooks, Bella Kofner, Maruf Hossain
Journal: Behavioral and Brain Sciences (2019)

Abstract We argue that understanding of autism can be strengthened by increasing involvement of autistic individuals as researchers and by exploring cascading impacts of early sensory, perceptual, attentional, and motor atypicalities on social and communicative developmental trajectories. Participatory action research that includes diverse participants or researchers may help combat stigma while expanding research foci to better address autistic people's needs.
High Prevalence and Disease Correlation of Autoantibodies Against p40 Encoded by Long Interspersed Nuclear Elements in Systemic Lupus Erythematosus
Authors: Victoria Carter, John LaCava, Martin S. Taylor, Shu Ying Liang, Cecilia Mustelin, Kennedy C. Ukadike, Anders Bengtsson, Christian Lood, Tomas Mustelin
Journal: Arthritis & Rheumatology (2019)

Long interspersed nuclear element 1 (LINE-1) encodes 2 proteins, the RNA binding protein p40 and endonuclease and reverse transcriptase (open-reading frame 2p [ORF2p]), which are both required for LINE-1 to retrotranspose. In cells expressing LINE-1, these proteins assemble with LINE-1 RNA and additional RNA binding proteins, some of which are well-known autoantigens in patients with systemic lupus erythematosus (SLE). This study was undertaken to investigate whether SLE patients also produce autoantibodies against LINE-1 p40.Highly purified p40 protein was used to quantitate IgG autoantibodies in serum from 172 SLE patients and from disease controls and age-matched healthy subjects by immunoblotting and enzyme-linked immunosorbent assay (ELISA). Preparations of p40 that also contained associated proteins were analyzed by immunoblotting with patient sera.Antibodies reactive with p40 were detected in the majority of patients and many healthy controls. Their levels were higher in patients with SLE, but not those with systemic sclerosis, compared to healthy subjects (P = 0.01). Anti-p40 reactivity was higher in patients during a flare than in patients with disease in remission (P = 0.03); correlated with the SLE Disease Activity Index score (P = 0.0002), type I interferon score (P = 0.006), decrease in complement C3 level (P = 0.0001), the presence of anti-DNA antibodies (P < 0.0001) and anti-C1q antibodies (P = 0.004), and current or past history of nephritis (P = 0.02 and P = 0.003, respectively); and correlated inversely with age (r = -0.49, P < 0.0001). SLE patient sera also reacted with p40-associated proteins.Autoantibodies reacting with LINE-1 p40 characterize a population of SLE patients with severe and active disease. These autoantibodies may represent an early immune response against LINE-1 p40 that does not yet by itself imply clinically significant autoimmunity, but may represent an early, and still reversible, step toward SLE pathogenesis.
Mind the Gap: The Ethics Void Created by the Rise of Citizen Science in Health and Biomedical Research
Authors: Bray Patrick-Lake, Jennifer C. Goldsack
Journal: The American Journal of Bioethics (2019)

The target article by Wiggins and Wilbanks (2019) reports on the history and typology of the models of citizen science emerging in health and biomedical research with the rapid dispersion and repur...
Prostate-specific antigen (PSA) screening in the United States: Patterns of use and PSA outcomes in screened versus unscreened men.
Authors: Ian M. Allen, Laura H Hendrix, Trevor Joseph Royce, William A. Stokes, Andrew Wang, Paul Alphonso Godley, Ronald C. Chen
Journal: Journal of Clinical Oncology (2012)

4658 Background: PSA screening is a subject of substantial controversy. We examined patterns of PSA screening using a recent cohort from the population-based National Health and Nutrition Examination Survey (NHANES) study and compared PSA levels of previously screened vs. never screened men. Methods: NHANES is a cross-sectional study which collects health-related information (including cancer screening history, family history and socioeconomic variables) and blood samples from nationally representative samples of the US population. We included 2,078 previously screened men and 1,902 never screened men surveyed from 2003-8. Statistical analysis accounted for sampling weights. Results: 25% of men age 40-49 years had prior PSA screening; 56% age 50-59, and 72% age 60-69. Screening rates were higher for men with family history (68% vs. 50% no history, p&lt;.001), health insurance (58% vs. 21% no insurance, p&lt;.001), and Caucasians (59% vs. 44% non-Caucasian, p&lt;.001). No significant differences were seen in the PSA values of screened vs. never screened men stratified by age (Table), or by race/ethnicity, insurance status, or family history. Conclusions: Rates of PSA screening in the US differ by age, family history, race/ethnicity and insurance status. However, no significant differences were seen in PSA values of screened vs. unscreened men, and very few patients under 60 years of age had PSA values ≥10. Despite questions about the appropriate role of PSA testing, population-based prostate cancer screening is routinely conducted among Caucasian and non-Caucasian men 50 years of age and older. [Table: see text]
Autoimmune pathways in mice and humans are blocked by pharmacological stabilization of the TYK2 pseudokinase domain
Authors: James R. Burke, Lihong Cheng, Kathleen M. Gillooly, Joann Strnad, Adriana Zupa-Fernandez, Ian M. Catlett, Yifan Zhang, Elizabeth M. Heimrich, Kim W. McIntyre, Mark D. Cunningham, Julie A. Carman, Xiadi Zhou, Dana Banas, Charu Chaudhry, Sha Li, Celia D’Arienzo, Anjaneya Chimalakonda, XiaoXia Yang, Jenny H. Xie, Jian Pang, Qihong Zhao, Shawn M. Rose, Jinwen Huang, Ryan M. Moslin, Stephen T. Wrobleski, David S. Weinstein, Luisa M. Salter-Cid
Journal: Science Translational Medicine (2019)

TYK2 is a nonreceptor tyrosine kinase involved in adaptive and innate immune responses. A deactivating coding variant has previously been shown to prevent receptor-stimulated activation of this kinase and provides high protection from several common autoimmune diseases but without immunodeficiency. An agent that recapitulates the phenotype of this deactivating coding variant may therefore represent an important advancement in the treatment of autoimmunity. BMS-986165 is a potent oral agent that similarly blocks receptor-stimulated activation of TYK2 allosterically and with high selectivity and potency afforded through optimized binding to a regulatory domain of the protein. Signaling and functional responses in human TH17, TH1, B cells, and myeloid cells integral to autoimmunity were blocked by BMS-986165, both in vitro and in vivo in a phase 1 clinical trial. BMS-986165 demonstrated robust efficacy, consistent with blockade of multiple autoimmune pathways, in murine models of lupus nephritis and inflammatory bowel disease, supporting its therapeutic potential for multiple immune-mediated diseases.
Association of germ-line genetic variation with failure of androgen ablation (AA) in hormone-sensitive advanced prostate cancer.
Authors: Manish Kohli, Shannon McDonnell, Graham H. Bevan, Shaun M. Riska, Brian Addis Costello, Sherri Longenbach, Roxana Stefania Dronca, Timothy Jerome Moynihan, Henry Clement Pitot, Fernando Quevedo, Winston Tan, James Robert Cerhan
Journal: Journal of Clinical Oncology (2013)

5082 Background: We evaluated the association of germ-line variation in 10 candidate genes important in prostate cancer biology (NKX3-1, JAK2, SLCO2B1, STAT3, CYP19A1, HSD17B4, TRMT11, PRMT3, HSD17B12, NCOA4) with failure of AA in advanced prostate cancer patients. Methods: Patients (N=619) were enrolled for genotyping at the time of AA failure. Candidate genes were selected from the literature and previous pilot studies in smaller cohorts which had identified variation in TRMT11 and HSD17B12 to be associated with AA failure. Genes were tagged using single nucleotide polymorphisms (SNPs) from HapMap with minor allele frequency of &gt;5% and r 2 ≥0.8. DNA was extracted from peripheral blood and genotyped using Illumina Veracode platform. The primary endpoint was time to failure on AA, defined as time from initiating continuous AA to two serial PSA increases over the nadir or clinical or imaging based progression, whichever came first. Principal component analysis was used for gene-levels tests. Association with the primary endpoint was assessed using proportional hazards regression models at the gene-level and at the SNP level. For SNP level results we estimated per allele (ordinal model) hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression, adjusted for Gleason score (GS). Results: We successfully genotyped 60 SNPs (from 10 genes) in 519 subjects. The median age of the cohort was 71 years (range 43, 92). The GS distribution was 51% subjects with GS≥8; 33% with GS=7 and 17% with GS&lt;7. Median time to AA failure for the cohort was 2.3 years (IQ range: 1.0-4.5). In gene level analyses adjusting for GS, TRMT11 (p=0.004), HSD17B12 (p=0.016), and JAK2 (p=0.044) genes were associated with time to AA failure. Four of the 18 genotyped SNPs in JAK2 were associated with AA failure after adjustment for GS (Table). Conclusions: Variation in the JAK2 gene is significantly associated with time to AA failure. Validation is needed to develop these as predictive biomarkers for AA in advanced prostate cancer. [Table: see text]
Identification of a selective and direct NLRP3 inhibitor to treat inflammatory disorders
Authors: Hua Jiang, Hongbin He, Yun Chen, Wei Huang, Jinbo Cheng, Jin Ye, Aoli Wang, Jinhui Tao, Chao Wang, Qingsong Liu, Tengchuan Jin, Wei Jiang, Xianming Deng, Rongbin Zhou
Journal: The Journal of Experimental Medicine (2017)

The NLRP3 inflammasome has been implicated in the pathogenesis of a wide variety of human diseases. A few compounds have been developed to inhibit NLRP3 inflammasome activation, but compounds directly and specifically targeting NLRP3 are still not available, so it is unclear whether NLRP3 itself can be targeted to prevent or treat diseases. Here we show that the compound CY-09 specifically blocks NLRP3 inflammasome activation. CY-09 directly binds to the ATP-binding motif of NLRP3 NACHT domain and inhibits NLRP3 ATPase activity, resulting in the suppression of NLRP3 inflammasome assembly and activation. Importantly, treatment with CY-09 shows remarkable therapeutic effects on mouse models of cryopyrin-associated autoinflammatory syndrome (CAPS) and type 2 diabetes. Furthermore, CY-09 is active ex vivo for monocytes from healthy individuals or synovial fluid cells from patients with gout. Thus, our results provide a selective and direct small-molecule inhibitor for NLRP3 and indicate that NLRP3 can be targeted in vivo to combat NLRP3-driven diseases.
A phase I study of oxaliplatin (OXA) and irinotecan (IRN) in pediatric patients with refractory solid tumors: A Children's Oncology Group study
Authors: L. M. McGregor, S. L. Spunt, W. L. Furman, C. F. Stewart, M. D. Krailo, R. Speights, P. J. Houghton, S. P. Ivy, S. M. Blaney, P. C. Adamson
Journal: Journal of Clinical Oncology (2007)

9546 Background: Platinum analogues in combination with topoisomerase 1 inhibitors have been shown in in vitro studies to have synergistic anti-tumor activity. This study estimated the maximum tolerated dose (MTD) of OXA in combination with a protracted schedule of IRN in children with refractory solid tumors. Methods: OXA was administered over 2 hrs on days 1 and 8 in combination with IRN iv over 1 hr on days 1–5 and 8–12 of a 21-day cycle. An oral cephalosporin was administered daily to ameliorate IRN-associated diarrhea. Pharmacokinetic studies of OXA and UGT1A1 genotyping were performed during course 1 in consenting patients. Results: 13 patients (median age 16 yrs, 4 M) were enrolled. Dose-limiting diarrhea (n=3), serum lipase elevation (n=3), serum amylase elevation (n=2), colitis (n=1), abdominal pain (n=1) and headache (n=1) occurred at the 1st dose level (60 mg/m 2 /dose OXA; 20 mg/m 2 /dose of IRN) in the first 3 patients. Only 1/7 patients treated with reduced doses of both agents (40 mg/m 2 /dose OXA; 15 mg/m 2 /dose IRN) experienced DLT, diarrhea. When the OXA dose (60 mg/m 2 ) was increased with the reduced IRN dose (15 mg/m 2 ) 2/3 patients had DLT (1 diarrhea, 1 hypokalemia). Myelosuppression was minimal at all dose levels. One patient with alveolar rhabdomyosarcoma previously treated with irinotecan (dose level 2: 40 mg/m 2 /dose OXA; 15 mg/m 2 /dose IRN) had an unconfirmed complete response of her breast metastases and one patient with refractory neuroblastoma had disease stabilization through 6 courses of therapy. The frequency of 6/6, 6/7, and 7/7 UGT1A1 promoter genotypes were 5/10, 4/10, and 1/10, respectively. Conclusions: The MTD using this schedule with oral cephalosporin support was oxaliplatin 40 mg/m 2 /dose with irinotecan 15 mg/m 2 /dose. There was some evidence of benefit but significant toxicity, both expected (diarrhea) and unexpected (elevation in pancreatic enzymes), was also observed. [Table: see text]
Country specific serum IgE reactivity profile and concordance with allergic history among acute lymphoblastic leukemia children and controls.
Authors: Maria Stella Lariou, Stavroula Dikalioti, Nick Dessypris, Apostolos Pourtsidis, Margarita Baka, Sophia Polychronopoulou, Fani Athanasiadou Piperopoulou, Maria Moschovi, Ioanna Fragandrea, Maria Kalmanti, Anastassios Germenis, Eleni Petridou
Journal: Journal of Clinical Oncology (2012)

e20002 Background: Allergy has been studied as a risk factor for several malignancies, including childhood leukemia; yet, the tentative etiological nature of this association needs to be further explored. Published studies suffer inappropriate study design and accuracy of exposure variables. In response to the latter need, this study aims to use country specific biological markers, namely levels of the most prevalent allergen-specific immunoglobulin E (IgE) antibodies in Greece as an alternative exposure measurement to history of allergy and compare their concordance with allergic history. Methods: Allergen-specific-IgEs against 24 most prevalent inhalant and food allergens were determined for 199 incident childhood acute lymphoblastic leukemia (ALL), newly diagnosed cases across Greece and registered in the Nationwide Registry for Childhood Hematological Malignancies (NARECHEM) and 113 hospital controls. K statistic was used to check the concordance between serum IgE specific allergens and allergic history overall, as well as among cases and controls. Results: Concordance between self-reported food allergy and food IgE levels in the same individual among both cases and controls was 87% and 83% for respiratory allergens. Among cases, concordance between self reported food allergies and food IgEs was 92% and 80% for controls (p-value 0.003) and the respective κ statistics were 0.28 for cases and 0.10 for controls. Concordance between self reported respiratory allergies and respiratory IgEs was 84% for cases and 81% for controls (p-value 0.57); κ statistics 0.09 for cases and 0.07 for controls. Conclusions: Much of the discordance among cases and controls (self-report false positives) might probably be a reflection of non allergic food hypersensitivity, an allergy that was surpassed or extended allergen avoidance. Other discordance (self-report false negatives) seems to be the result of food sensitization, either hypoclinical or not acknowledged as a type of allergy by mothers of the children. Nevertheless, these measurements jointly analyzed are valuable in exploring the stated hypothesis, especially in well designed prospective studies.
RaPID: ultra-fast, powerful, and accurate detection of segments identical by descent (IBD) in biobank-scale cohorts
Authors: Ardalan Naseri, Xiaoming Liu, Kecong Tang, Shaojie Zhang, Degui Zhi
Journal: Genome biology (2019)

While genetic relatedness, usually manifested as segments identical by descent (IBD), is ubiquitous in modern large biobanks, current IBD detection methods are not efficient at such a scale. Here, we describe an efficient method, RaPID, for detecting IBD segments in a panel with phased haplotypes. RaPID achieves a time and space complexity linear to the input size and the number of reported IBDs. With simulation, we showed that RaPID is orders of magnitude faster than existing method while offering competitive power and accuracy. In UK Biobank, RaPID identified 3,335,807 IBDs with a lenght ≥ 10 cM among 223,507 male X chromosomes in 11 min.
Immune Thrombocytopenia in US Clinical Practice: Incidence and Healthcare Utilization/Expenditures in the First 12 Months Following Diagnosis
Authors: Derek Weycker, Aaron Grossman, Ahuva Hanau, Hongsheng Wu, Mark Hatfield, Anjali Sharma, Mark E. Bensink, David Chandler, Michael D. Tarantino
Journal: Blood (2018)