tbuckley/cabot-search huggingface dataset:
Abstract P497: Association Between Accelerometer-estimated Physical Activity Intensity and Heart Rate Variability: Mediation by Glycemic Measures and Triglycerides (from The Cardia Study)
Authors: Zachary C Pope, Kelley P Gabriel, Kara M Whitaker, Lin Y Chen, Pamela J Schreiner, David R Jacobs, Barbara Sternfeld, Jeffrey Carr, Donald M Lloyd-Jones, Mark A Pereira
Journal: Circulation (2020)

Introduction: We estimated cross-sectional associations between accelerometer-estimated light (LPA), moderate (MPA), and vigorous (VPA) intensity physical activity (PA) and heart rate variability (HRV), and tested mediation of these associations by glycemic control indices, blood lipids, and blood pressure. Hypothesis: PA is positively and independently associated with higher (improved) HRV. Glycemic measures are partial physiological mediators of these associations. Methods: Data were from 1,668 participants (X -age = 46 ± 4 yrs, 58% F, 40% black) in Year 20 (2005-06) of the Coronary Artery Risk Development in Young Adults (CARDIA) Fitness Study. The ActiGraph 7164 estimated participants’ mean min/d of LPA, MPA, and VPA over 7d. Three sequential 10-sec 12-lead ECG strips provided standard deviation of all normal RR intervals (SDNN) and root mean square of all successive RR intervals (rMSSD) HRV. Physiological mediators included fasting glucose and insulin as well as 2-hr oral glucose tolerance (OGTT), fasting triglycerides (TG), HDL-C, and systolic blood pressure (BP). Multiple linear regression, controlling for demographic and lifestyle confounders, assessed independent associations of PA with SDNN and rMSSD HRV per 1-SD. Mediation analyses computed the proportion of the PA-HRV associations attributable to physiological mediators. Results: Participants averaged 360.2 ± 83.8, 33.0 ± 22.0, and 2.7 ± 6.2 min/d of LPA, MPA, and VPA, respectively, with mean values for SDNN (32.6 ± 22.4 ms) and rMSSD (34.0 ± 24.8 ms) similar. VPA was associated with both HRV metrics (SDNN: std = .06 [.03, .10]; rMSSD: std = .08, [.05, .12]) and LPA with rMSSD only (std = .05, [.01, .08]). Fasting glucose and insulin mediated between 11.6%-20.7% of the association of VPA and LPA with HRV (Table). Triglycerides also mediated these associations (range: 9.6%-13.4%; Table). Conclusions: Accelerometer-estimated VPA and LPA were positively associated with higher HRV. These associations may be due most to glycemia and insulinemia.
Abstract 15867: Contemporary Percutaneous Treatment of In-Stent Restenosis in the United States: Insights From a Large Single-Center Registry
Authors: Bimmer E Claessen, George D Dangas, Usman Baber, Sabato Sorrentino, Paul Guedeney, Melissa Aquino, Jason Kovacic, Prakash Krishnan, Pedro Moreno, Joseph Sweeney, Nitin Barman, Pooja Vijay, Annapoorna S Kini, Samin K Sharma, Roxana Mehran
Journal: Circulation (2018)

Introduction: Treatment of in-stent restenosis (ISR) remains challenging in contemporary clinical practice. Coronary drug-eluting balloons are not available in the United States and technical appro...
<i>Ex vivo</i> confocal microscopy: revolution in fast pathology in dermatology
Authors: J. Malvehy, J. Pérez‐Anker, A. Toll, R. Pigem, A. Garcia, L.L. Alos, S. Puig
Journal: British Journal of Dermatology (2020)

Confocal microscopy with in vivo and ex vivo modalities has been used in the evaluation of skin cancer and other dermatological disorders. Recent developments in ex vivo confocal microscopy allow for faster pathology assessment with greater accuracy by the visualization of cellular and architectural details, similarly to standard pathology, in either paraffin-embedded or frozen samples. They include the possibility of multimodal confocal microscopy using different lasers and fusion images. New staining protocols including immunostaining, with no damage to conventional histopathology preparation, have been recently described in melanocytic tumours and inflammatory skin diseases. Digital staining with haematoxylin and eosin is also incorporated in the new devices. In this review the applications of ex vivo confocal microscopy will be presented with the description of the technique and the technology, clinical evidence in dermatology and other fields, and further applications.
Booster vaccination of non-small cell lung cancer (NSCLC) patients with MAGEA3 protein and AS02B adjuvant
Authors: D. Atanackovic, N. K. Altorki, Y. Cao, E. Ritter, C. Ferrara, G. Ritter, E. W. Hoffman, C. Bokemeyer, L. J. Old, S. Gnjatic
Journal: Journal of Clinical Oncology (2007)

3015 Background: We have previously reported results of a phase II trial of recombinant ProtD/MAGE-3/His (MAGEA3) protein 300μg administered IM every three weeks for 4 doses with or without adjuvant AS02B to NSCLC patients following resection of MAGEA3 positive disease (JI, 172:3289, 2004). We found that the presence of adjuvant was essential for the development of strong humoral and cellular responses against selected MAGEA3 epitopes. Methods: 14 of the original 18 patients received booster vaccinations. Patients who still had no evidence of disease for up to two years after receiving their original MAGEA3 protein regimen (7 in cohort 1 without adjuvant, 7 in cohort 2 with adjuvant), received 4 additional doses of MAGEA3 protein with adjuvant. T cell immunomonitoring was extended to encompass any MAGEA3 epitope using full length antigen, and the scope of analysis of humoral responses was widened. Results: After just one boost injection, 6 of the 7 patients originally vaccinated with MAGEA3 protein plus adjuvant reached the peak of antibody titers to MAGEA3 attained during the first vaccination and went on to develop a stronger response than during the first cycle. In addition, the spectrum of CD4+ and CD8+ T cells against various new and known epitopes widened with booster vaccination. In contrast, only 3/7 patients originally vaccinated with MAGEA3 protein alone seroconverted to low-titered MAGEA3 responses and showed very limited CD4+ and no CD8+ T cell reactivity, despite now receiving antigen in the presence of adjuvant. Conclusions: These results underscore the importance of proper antigen priming using an adjuvant for generating persistent B and T cell memory, allowing for typical booster responses with re-immunization. In contrast, absence of adjuvant at priming may compromise further immunization attempts. These data provide immunological rationale for vaccine design in light of recently reported favorable clinical findings in NSCLC patients following vaccination with MAGEA3 protein plus adjuvant AS02B (GSK, ASCO 2005). No significant financial relationships to disclose.
The Heart Failure Association Atlas: rationale, objectives, and methods
Authors: Petar M. Seferović, Ewa Jankowska, Andrew J.S. Coats, Aldo P. Maggioni, Yuri Lopatin, Ivan Milinković, Marija Polovina, Mitja Lainščak, Adam Timmis, Radu Huculeci, Panos Vardas
Journal: European Journal of Heart Failure (2020)
Mepolizumab effectiveness and identification of super-responders in severe asthma
Authors: Erin S. Harvey, David Langton, Constance Katelaris, Sean Stevens, Claude S. Farah, Andrew Gillman, John Harrington, Mark Hew, Vicky Kritikos, Naghmeh Radhakrishna, Philip Bardin, Matthew Peters, Paul N. Reynolds, John W. Upham, Melissa Baraket, Simon Bowler, Jeffrey Bowden, Jimmy Chien, Li Ping Chung, Christopher Grainge, Christine Jenkins, Gregory P. Katsoulotos, Joy Lee, Vanessa M. McDonald, Helen K. Reddel, Janet Rimmer, Peter A.B. Wark, Peter G. Gibson
Journal: European Respiratory Journal (2020)

Severe asthma is a high-burden disease. Real-world data on mepolizumab in patients with severe eosinophilic asthma is needed to assess whether the data from randomised controlled trials are applicable in a broader population. The Australian Mepolizumab Registry (AMR) was established with an aim to assess the use, effectiveness and safety of mepolizumab for severe eosinophilic asthma in Australia. Patients (n=309) with severe eosinophilic asthma (median age 60 years, 58% female) commenced mepolizumab. They had poor symptom control (median Asthma Control Questionnaire (ACQ)-5 score of 3.4), frequent exacerbations (median three courses of oral corticosteroids (OCS) in the previous 12 months), and 47% required daily OCS. Median baseline peripheral blood eosinophil level was 590 cells·µL −1 . Comorbidities were common: allergic rhinitis 63%, gastro-oesophageal reflux disease 52%, obesity 46%, nasal polyps 34%. Mepolizumab treatment reduced exacerbations requiring OCS compared with the previous year (annualised rate ratio 0.34 (95% CI 0.29–0.41); p&lt;0.001) and hospitalisations (rate ratio 0.46 (95% CI 0.33–0.63); p&lt;0.001). Treatment improved symptom control (median ACQ-5 reduced by 2.0 at 6 months), quality of life and lung function. Higher blood eosinophil levels (p=0.003) and later age of asthma onset (p=0.028) predicted a better ACQ-5 response to mepolizumab, whilst being male (p=0.031) or having body mass index ≥30 (p=0.043) predicted a lesser response. Super-responders (upper 25% of ACQ-5 responders, n=61, 24%) had a higher T2 disease burden and fewer comorbidities at baseline. Mepolizumab therapy effectively reduces the significant and long-standing disease burden faced by patients with severe eosinophilic asthma in a real-world setting.
Abstract P215: Medical Lifestyle Residential Program Reduces Anxiety In 10 Days
Authors: Francisco E Ramirez, Payton Heisler, Neil Nedley
Journal: Circulation (2020)

Introduction: Anxiety is a condition that can lower the quality of life of an individual. Hypothesis: It is proposed that after going through a residential depression and anxiety program, patients could decrease in their anxiety levels. Methods: Participants (n=181), completed a 10-day residential depression and anxiety recovery program in the town of Weimar California. At the beginning of the program, the participants were given different mental condition tests including the Beck Anxiety Inventory Version II (BAI-II) to determine baseline conditions. The BAI-II test refers to levels of depression in four categories: Minimal(0-7), Mid(8-15), Moderate(16-25), Severe(26-63). While participating in the program, the patients partook of exercise therapy, light therapy, interactive lectures with health professionals, plant based healthy meals, and one on one consultations with appropriate physicians and cognitive behavioral therapy from clinical counselors as well as chaplaincy care to deal with other stress sources. Patients also read books on cognitive behavioral therapy. Results: At baseline mean Beck Anxiety was 18.22, SD 11.86, median 16, mode 11. At the end of the program the mean Beck Anxiety score was 7.4, SD 7.7, median 4, mode 0. The change was significant with a t(180) = 13.8 p&lt;.001. Conclusion: The residential medical residential program was very effective in decreasing anxiety. Long term follow up is being done at the moment.
Absence of brain metastases in late relapse of HER2-overexpressed breast carcinoma
Authors: Z. I. Tomasevic, D. Jovanovic, L. Radosevic Jelic, Z. M. Tomasevic, S. Vasovic, L. Stamatovic, S. Jelic, J. Spasic
Journal: Journal of Clinical Oncology (2007)

1014 Background: The incidence of brain metastases (BM) in HER2 3+ breast carcinoma (BC) reported in the literature is between 20–34%, usually during first 2 years of metastatic disease. However, there are limited data about BM as a late relapse in HER2 over expressed BC. Therefore, the aim of this paper is to analyze BM as a late relapse in patients with HER2 over expressed and non over expressed BC. Late relapse is defined as relapse at least five years after initial diagnose. Methods: Medical documentation of all patients with late relapse was analyzed for DFI and development of BM at any time point during metastatic disease. IHH (Herceptest DAKO) HER-2 status was determined on the archived pathological specimens of the primary BC Results: Among 1,256 BC patients diagnosed during 6 months period (June-November, 2005 at the Institute for Oncology and Radiology of Serbia), 111 (8,8%) were diagnosed with late relapse. Median age at the initial diagnose was 50 years (33–74), median time to relapse was 7 years, (range 5–29). Archived pathological specimens is identified for 64% of patients and HER-2 status of the primary BC was: 76,3% 0 or1+; 9,5% 2+; and 14,2% 3+; Only 5 patients have been treated with trastuzumab in metastatic setting. None of the patients with HER2 3+ BC had BM either as a first relapse site or later during metastatic disease. Two patients who had late relapse of HER2 0+ BC, developed BM as a first site of relapse, after 5 and 7 years of the initial diagnose. Conclusions: Although the number of presented patients is small, the absence of BM in late relapse of HER2 3+ BC, could represent the specific biological characteristic of HER 2 3+ carcinomas to develop BM mostly in the early course of metastatic disease. No significant financial relationships to disclose.
Abstract MP77: Associations Between Atrial Cardiopathy and Cerebral Amyloid: The Aric Pet Study
Authors: Michelle C JOHANSEN, Thomas Mosley, David Knopman, Dean Wong, Lynne E Wagenknecht, Chiadi E Ndumele, Amil M Shah, Scott Solomon, Rebecca F Gottesman
Journal: Circulation (2020)

Background: Atrial fibrillation (AF) is a risk factor for cognitive decline, perhaps due to silent cerebral infarction, but it is unknown if it also acts on Alzheimer’s Disease (AD)-specific mechanisms, such as deposition of β-amyloid (Aβ). Left atrial changes in structure or function, or atrial cardiopathy, can lead to AF but may cause infarcts independently, and thus might also impact cognition. We hypothesize that Aβ is associated with AF and atrial cardiopathy, independent of AF, when defined similarly to an ongoing clinical trial (ARCADIA). Methods: 321 participants without dementia from the Atherosclerosis Risk in Communities study underwent florbetapir (FBP) PET, electrocardiogram and 2D echocardiography. Atrial cardiopathy was defined as ≥1 of: 1) left atrial volume index (LAVI) &gt;34 ml/m2; 2) P-wave terminal force &gt;5000 uV x ms and 3) serum NT proBNP&gt;250 pg/mL. Cross-sectional associations between global cortical Aβ (&gt;1.2 standardized uptake value ratio (SUVR)) and adjudicated history of atrial fibrillation and atrial cardiopathy, each, were evaluated using multivariable logistic regression. Results: Participants, with mean age 76 y, were 56% female and 42% black. Odds of elevated FBP SUVR was increased for those with atrial cardiopathy (Model 3) and nearly doubled among those with enlarged LAVI that remained significant after sequential adjustment, including AF (Table). There was no significant association between either P-wave terminal force or NT proBNP and elevated FBP SUVR (Table), nor between elevated SUVR and AF. Conclusions: In this cross-sectional analysis of a cohort of healthy, nondemented community-dwelling older individuals, we report a significant association between atrial cardiopathy as well as LAVI and elevated amyloid, by PET, without a similar association in individuals with AF. Potential limitations include reverse causation and survival bias. Ongoing work will help determine if changes in cardiac structure and function precede, or occur simultaneously with amyloid deposition.
CA-125 response as a marker of clinical benefit in patients with recurrent ovarian cancer treated with gemcitabine and sorafenib—A trial of the PMH Phase II Consortium
Authors: S. Welch, H. Hirte, L. Elit, R. J. Schilder, G. Pond, J. Kovacs, J. Wright, A. M. Oza
Journal: Journal of Clinical Oncology (2007)

5519 Background: Molecularly targeted agents are expected to have a cytostatic effect on cancers, thus traditional radiographic criteria for objective response may not be optimal in evaluating these agents. There is considerable preclinical rationale for the use of angiogenesis inhibitors in ovarian cancer (OC), and early phase trials of these agents have suggested activity. We have completed a phase II trial evaluating the efficacy of the combination of gemcitabine (GEM), a cytotoxic agent with activity in OC, and sorafenib (SOR), a novel mutitargeted kinase inhibitor with antiangiogenic activity, in patients (pts) with recurrent OC. Methods: Eligible pts had recurrent OC after platinum-based therapy and received up to 2 prior lines of chemotherapy for recurrence. All pts were gemcitabine-naive. GEM (1,000 mg/m 2 i.v.) was given weekly for 7 weeks out of 8 weeks in the first cycle, then weekly for the first 3 weeks of each subsequent 4-week cycle. SOR (400 mg p.o. bid) was given continuously. The primary endpoint was objective response rate by RECIST criteria. Secondary endpoints included CA-125 response, time to progression (TTP), overall survival (OS) and toxicity. Results: 43 pts were accrued to this study. 137 (median 3; range: 1–19) cycles of treatment were given to 38 evaluable pts. 26 were evaluable for CA-125 response. Median age was 60 (range: 37–78). 44% of pts were ECOG PS 0 and 56% were PS 1. Using RECIST criteria, 2 pts (4.7%) had a confirmed partial response and 26 pts (60.4%) had a best response of stable disease. 9/26 pts (36.6%) with abnormal baseline CA-125 level achieved a CA-125 response using GCIG criteria. The median TTP was 5.4 months (95% CI: 3.5–9.5) and the median OS was 13.3 months (95% CI: 9.0-NR). The most frequent grade 3 or 4 adverse events were lymphopenia (32%), neutropenia (21%), thrombocytopenia (21%), hand-foot syndrome (21%), fatigue (16%), and hypokalemia (16%). Conclusions: The combination of GEM and SOR is well tolerated and associated with encouraging rates of disease stability. This trial illustrates the need for novel clinical trial design and response endpoints in order to more clearly identify the activity of targeted therapies in recurrent OC. No significant financial relationships to disclose.
Abstract P455: Epistatic Regulation of Hematological-related Traits and Gene Expression in Mice Reveals Additional Heritability Missed by Standard GWAS-type Analyses
Authors: Anna Miller, Anlu Chen, David Buchner, Scott Williams
Journal: Circulation (2020)

The genetic contribution of additive versus non-additive (epistasis) effects in the regulation of hematologic and other complex traits is unclear. Although many variants have been associated with a range of complex traits via genome wide association studies (GWAS), these loci combined in additive models do not account for most of the trait heritability. GWAS-type analyses typically ignore gene-gene interactions, in part because of the difficulty in detecting them in complex multicellular organisms, especially humans. We have previously shown that mouse chromosome substitution strains (CSSs) are a powerful model for detecting epistasis, and that for certain complex traits the relative contribution of epistasis to heritability is as important as additivity. We have now applied the use of these CSSs to identify and map additive and epistatic loci that regulate a range of hematological-related traits and hepatic gene expression levels. A modified backcross was performed with CSS strains carrying the A/J-derived substituted chromosomes 4 and 6 on an otherwise C57BL/6J genetic background. By analyzing the transcriptomes of offspring from this cross, we identified and mapped additive quantitative trait loci (QTLs) that regulated the expression of 770 genes, and epistatic QTLs for 802 genes. Similarly we performed a complete blood analysis of offspring from the cross and identified additive QTLs for platelets and percentage of granulocyte in the blood as well as epistatic QTLs controlling the percentage of lymphocytes in the blood (rs13477644, rs13478739; LOD = 3.4) and red cell distribution width (rs13477864, rs13478802; LOD = 3.7). The variance attributable to the epistatic QTLs was approximately equal to that of the additive QTLs, highlighting the importance of identifying genetic interactions. Of note, even the SNPs associated with the most significant epistatic interactions were undetected in our single loci GWAS-like association analyses, demonstrating the need to specifically test for gene-gene interactions in studies of complex traits. In summary, our studies identified epistatic loci in mice that are important regulators of hematological-related traits and gene expression. Additionally, our studies call attention to the importance of extending single loci GWAS-type analyses to include analyses of gene-gene interactions to improve our ability to identify genetic variants that regulate complex traits.
Cirrhosis of the liver.
Authors: B. L. Agarwal
Journal: BMJ (1968)

gations: chest x-ray normal; Hb 55%; W.B.C. 7,100 with normal diffierential; iron deficiency on the blood film; E.S.R. 138 mm. in one hour; Paul-Bunnell test negative.Blood culture revealed Haemophilus influenzae type B sensitive to all the usual antibiotics except sulphonamide.This child was treated with ampicillin and made a good recovery.My point in recording this case history is to emphasize that septicaemia due to Haemo- philus influenzae may not be as rare as we had thought and one can easily envisage such a child as I have mentioned developing osteomyelitis due to this organism.-Iam, etc.,
Pathogenic DDX3X Mutations Impair RNA Metabolism and Neurogenesis during Fetal Cortical Development
Authors: Ashley L. Lennox, Mariah L. Hoye, Ruiji Jiang, Bethany L. Johnson-Kerner, Lindsey A. Suit, Srivats Venkataramanan, Charles J. Sheehan, Fernando C. Alsina, Brieana Fregeau, Kimberly A. Aldinger, Ching Moey, Iryna Lobach, Alexandra Afenjar, Dusica Babovic-Vuksanovic, Stéphane Bézieau, Patrick R. Blackburn, Jens Bunt, Lydie Burglen, Philippe M. Campeau, Perrine Charles, Brian H.Y. Chung, Benjamin Cogné, Cynthia Curry, Maria Daniela D’Agostino, Nataliya Di Donato, Laurence Faivre, Delphine Héron, A. Micheil Innes, Bertrand Isidor, Boris Keren, Amy Kimball, Eric W. Klee, Paul Kuentz, Sébastien Küry, Dominique Martin-Coignard, Ghayda Mirzaa, Cyril Mignot, Noriko Miyake, Naomichi Matsumoto, Atsushi Fujita, Caroline Nava, Mathilde Nizon, Diana Rodriguez, Lot Snijders Blok, Christel Thauvin-Robinet, Julien Thevenon, Marie Vincent, Alban Ziegler, William Dobyns, Linda J. Richards, A. James Barkovich, Stephen N. Floor, Debra L. Silver, Elliott H. Sherr
Journal: Neuron (2020)