tbuckley/cabot-search huggingface dataset:
Factors Associated With Age Disparities Among Cancer Clinical Trial Participants
Authors: Ethan B. Ludmir, Walker Mainwaring, Timothy A. Lin, Austin B. Miller, Amit Jethanandani, Andres F. Espinoza, Jacob J. Mandel, Steven H. Lin, Benjamin D. Smith, Grace L. Smith, Noam A. VanderWalde, Bruce D. Minsky, Albert C. Koong, Thomas E. Stinchcombe, Reshma Jagsi, Daniel R. Gomez, Charles R. Thomas, C. David Fuller
Journal: JAMA Oncology (2019)

Seminal investigation 2 decades ago alerted the oncology community to age disparities in participation in cooperative group trials; less is known about whether these disparities persist in industry-funded research.To characterize the age disparities among trial enrollees on randomized clinical trials (RCTs) of common cancers in clinical oncology and identify factors associated with wider age imbalances.Phase 3 clinical oncology RCTs were identified through ClinicalTrials.gov.Multiarm RCTs assessing a therapeutic intervention for patients with breast, prostate, colorectal, or lung cancer (the 4 most common cancer disease sites) were included.Trial data were extracted from ClinicalTrials.gov. Trial screening and parameter identification were independently performed by 2 individuals. Data were analyzed in 2018.The difference in median age (DMA) between the trial participant median age and the population-based disease-site-specific median age was determined for each trial.Three hundred two trials met inclusion criteria. The trials collectively enrolled 262 354 participants; 249 trials (82.5%) were industry-funded. For all trials, the trial median age of trial participants was a mean of 6.49 years younger than the population median age (95% CI, -7.17 to -5.81 years; P < .001). Age disparities were heightened among industry-funded trials compared with non-industry-funded trials (mean DMA, -6.84 vs -4.72 years; P = .002). Enrollment criteria restrictions based on performance status or age cutoffs were associated with age disparities; however, industry-funded trials were not more likely to use these enrollment restrictions than non-industry-funded trials. Age disparities were also larger among trials that evaluated a targeted systemic therapy and among lung cancer trials. Linear regression modeling revealed a widening gap between trial and population median ages over time at a rate of -0.19 years annually (95% CI, -0.37 to -0.01 years; P = .04).Age disparities between trial participants and the incident disease population are pervasive across trials and appear to be increasing over time. Industry sponsorship of trials is associated with heightened age imbalances among trial participants. With an increasing role of industry funding among cancer trials, efforts to understand and address age disparities are necessary to ensure generalizability of trial results as well as equity in trial access.
Sexual behaviour and incidence of HIV and sexually transmitted infections among men who have sex with men using daily and event-driven pre-exposure prophylaxis in AMPrEP: 2 year results from a demonstration study
Authors: Elske Hoornenborg, Liza Coyer, Roel C A Achterbergh, Amy Matser, Maarten F Schim van der Loeff, Anders Boyd, Yvonne T H P van Duijnhoven, Sylvia Bruisten, Paul Oostvogel, Udi Davidovich, Arjan Hogewoning, Maria Prins, Henry J C de Vries
Journal: The Lancet HIV (2019)
Successful closure of a rare tracheogastroesophageal fistula with an endoloop and endoclips
Authors: Chaojun Zhu, Panpan Liu, Weiqing Ruan, Tongyin Xing, Ying Huang, Yue Li, Side Liu
Journal: Endoscopy (2019)

Tracheoesophageal fistula after esophagectomy is a rare complication with a high mortality rate. Conventional treatment of tracheoesophageal fistulas includes surgical re-exploration, or endoscopic and bronchoscopic techniques with stent implantation or fibrin glue application [1] [2]. Here we report the successful treatment of a tracheogastroesophageal fistula with an endoloop-aided purse-string suture.
Abstract 19865: Transcriptional Landscape of Cardiomyocyte Maturation
Authors: Hideki Uosaki, Patrick Cahan, Dong I Lee, Songnan Wang, Matthew Miyamoto, Laviel Fernandez, David A kass, Chulan Kwon
Journal: Circulation (2015)

Introduction: The term “development” refers to the process of growing to maturity. While decades of progress in developmental cardiology contributed to our understanding of heart development, the efforts were mostly focused on early aspects of development such as cardiomyocyte (CM) differentiation, which is completed at mid-gestation. However, CM maturation, a later developmental process required to generate adult CMs, remains largely unknown. The lack of the knowledge may be attributed to the fact that the process typically takes place over a long period of time after terminal differentiation. Results: Here, we analyzed over 200 microarray datasets from early embryonic to adult hearts and found a large number of genes whose expression shifts gradually and continuously throughout the stages. Based on the datasets, we generated an atlas of integrated gene expression, biological pathways, transcriptional regulators, and gene regulatory networks (GRNs). This analysis revealed discrete sets of key transcriptional regulators and pathways that are temporally activated or suppressed over the course of CM maturation. We developed a GRN-based program named MatStatCM that informs the status of CM maturation at the molecular level. The MatStatCM demonstrated that pluripotent stem cell-derived CMs undergo maturation early in culture, but are arrested at the late embryonic stage, accompanied by aberrant expression of key transcription factors. Conclusions: Our study provides a foundation for understanding CM maturation.
Lymphocyte-driven regional immunopathology in pneumonitis caused by impaired central immune tolerance
Authors: Elise M. N. Ferré, Timothy J. Break, Peter D. Burbelo, Michael Allgäuer, David E. Kleiner, Dakai Jin, Ziyue Xu, Les R. Folio, Daniel J. Mollura, Muthulekha Swamydas, Wenjuan Gu, Sally Hunsberger, Chyi-Chia R. Lee, Anamaria Bondici, Kevin W. Hoffman, Jean K. Lim, Kerry Dobbs, Julie E. Niemela, Thomas A. Fleisher, Amy P. Hsu, Laquita N. Snow, Dirk N. Darnell, Samar Ojaimi, Megan A. Cooper, Martin Bozzola, Gary I. Kleiner, Juan C. Martinez, Robin R. Deterding, Douglas B. Kuhns, Theo Heller, Karen K. Winer, Arun Rajan, Steven M. Holland, Luigi D. Notarangelo, Kevin P. Fennelly, Kenneth N. Olivier, Michail S. Lionakis
Journal: Science Translational Medicine (2019)

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a monogenic disorder caused by
Abstract 14296: Site-targeting Nitroglycerin Nanotherapeutic for Local Immunosuppression Without Induction of Tolerance
Authors: Soroush Ardekani, Shane Eum, Harry A Scott, Sharad Gupta, Xiao Yang, Alex R Brunelle, Sean M Wilson, Umar Mohideen, Kaustabh Ghosh
Journal: Circulation (2015)

Nitroglycerin (NTG) markedly enhances nitric oxide (NO) bioavailability. However, its ability to mimic the anti-inflammatory properties of NO remains unknown. Here, we examined whether NTG can suppress endothelial cell (EC) activation during inflammation and developed NTG nanoformulation to simultaneously amplify its anti-inflammatory effects and ameliorate adverse effects associated with high-dose NTG administration. Our findings reveal that NTG significantly inhibits human monocyte adhesion to NO-deficient human microvascular ECs in vitro (EC50 = 0.64 uM) through an increase in endothelial NO and decrease in endothelial ICAM-1 clustering, as determined by NO analyzer, microfluorimetry, and immunofluorescence staining. Nanoliposomal NTG (NTG-NL) was formulated by encapsulating NTG within unilamelar lipid nanoparticles that were ~150 nm in diameter and readily uptaken by ECs, as determined by dynamic light scattering and quantitative fluorescence microscopy, respectively. More importantly, NTG-NL produced an approximately two orders of magnitude greater anti-inflammatory effect than free NTG while preventing excessive mitochondrial superoxide production and loss of arterial vasorelaxation associated with high NTG doses. Finally, to facilitate targeting of NTG-NL to inflamed ICAM-1-expressing vessels, we have tethered a non-immunogenic fragment of ICAM-1 antibody to the surface of NTG-NL. Our preliminary in vitro studies show that NTG-NL modified with anti-ICAM-1 fragment exhibits 6-fold greater binding to inflamed (ICAM-1-expressing) ECs than to normal ECs. Thus, by identifying the superior therapeutic effects of NTG nanoformulation and conferring potent site-targeting capability to it, this study provides the rationale for detailed investigation of NTG nanotherapeutic as a potentially superior anti-inflammatory therapy.
Promoter Methylation Profiles of Six Tumor-Related Genes in Various Brain Tumors
Authors: 郭律廷, 郭冠廷, 蔡瑞章, 曾漢民, 杜永光, Lu-Ting Kuo, Kuan-Ting Kuo, Jui-Chang Tsai, Han-Min Tseng, Yong-Kwang Tu
Journal: Neuro-Oncology (2009)
Effect of a Self-management Support Intervention on Asthma Outcomes in Older Adults
Authors: Alex D. Federman, Rachel O’Conor, Irina Mindlis, Jamillah Hoy-Rosas, Diane Hauser, Joseph Lurio, Nandini Shroff, Ray Lopez, Joel Erblich, Michael S. Wolf, Juan P. Wisnivesky
Journal: JAMA Internal Medicine (2019)

Older adults with asthma have worse control and outcomes than younger adults. Interventions to address suboptimal self-management among older adults with asthma are typically not tailored to the specific needs of the patient.To test the effect of a comprehensive, patient-tailored asthma self-management support intervention for older adults on clinical and self-management outcomes.Three-arm randomized clinical trial conducted between February 2014 and December 2017 at primary care practices and personal residences in New York City. Adults 60 years and older with persistent, uncontrolled asthma were identified from electronic medical records at an academic medical center and a federally qualified health center. Of 1349 patients assessed for eligibility, 406 met eligibility criteria, consented to participate, and were randomized to 1 of 3 groups: home-based intervention, clinic-based intervention, or control (usual care). A total of 391 patients received the allocated treatment.Screening for psychosocial, physical, cognitive, and environmental barriers to asthma control and self-management with actions to address identified barriers. The intervention was delivered in the home or primary care practices by asthma care coaches.Primary outcomes were the Asthma Control Test, Mini Asthma Quality of Life Questionnaire, Medication Adherence Rating Scale, metered dose inhaler technique, and emergency department visits for asthma care. Primary analyses compared intervention (home or clinic based) with usual care.Of the 391 patients who received treatment, 58 (15.1%) were men, and the mean (SD) age was 67.8 (7.4) years. After accounting for baseline scores, scores on the asthma control test were better in the intervention groups vs the control group (difference-in-differences at 3 months, 1.2; 95% CI, 0.2-2.2; P = .02; 6 months, 1.0; 95% CI, 0.0-2.1; P = .049; 12 months, 0.6; 95% CI, -0.5 to 1.8; P = .28; and overall, χ2 = 13.4, with 4 degrees of freedom; P = .01). Emergency department visits were lower at 12 months for the intervention groups vs the control group (16 [6.2%] vs 17 [12.7%]; P = .03; adjusted odds ratio, 0.8; 95% CI, 0.6-0.99; P = .03). Statistically significant improvements were observed for the intervention vs control patients in quality of life (overall effect: χ2 = 10.5, with 4 degrees of freedom; P = .01), medication adherence (overall effect: χ2 = 9.5, with 4 degrees of freedom; P = .049), and inhaler technique (metered-dose inhaler technique, correctly completed steps at 12 months, median [range]: 75% [0%-100%] vs 58% [0%-100%]). No significant differences in outcomes were observed between patients receiving the intervention in home vs practice settings.An intervention directed by patients' needs and barriers improved asthma outcomes and self-management behaviors among older adults.ClinicalTrials.gov identifier: NCT02316223.
Codes, communication and cognition
Authors: Stevan Harnad
Journal: Behavioral and Brain Sciences (2019)

Abstract Brette criticizes the notion of neural coding because it seems to entail that neural signals need to “decoded” by or for some receiver in the head. If that were so, then neural coding would indeed be homuncular (Brette calls it “dualistic”), requiring an entity to decipher the code. But I think Brette's plea to think instead in terms of complex, interactive causal throughput is preaching to the converted. Turing (not Shannon) has already shown the way. In any case, the metaphor of neural coding has little to do with the symbol grounding problem.
Overall survival (OS) results of a phase III randomized trial of standard-of-care therapy with or without enzalutamide for metastatic hormone-sensitive prostate cancer (mHSPC): ENZAMET (ANZUP 1304), an ANZUP-led international cooperative group trial.
Authors: Christopher Sweeney, Andrew James Martin, Robert Richard Zielinski, Alastair Thomson, Thean Hsiang Tan, Shahneen Kaur Sandhu, M. Neil Reaume, David William Pook, Francis Parnis, Scott A. North, Ray McDermott, John McCaffrey, Gavin M. Marx, Nicola Jane Lawrence, Lisa Horvath, Mark Frydenberg, Simon Chowdhury, Kim N. Chi, Martin R. Stockler, Ian D. Davis
Journal: Journal of Clinical Oncology (2019)

LBA2 Background: Testosterone suppression (TS) is the backbone of treatment for mHSPC. OS is improved by the addition of early docetaxel (DOC) or abiraterone to TS. ENZAMET assessed the effects of enzalutamide (ENZA), a potent androgen receptor (AR) inhibitor, versus a nonsteroidal anti-androgen (NSAA: bicalutamide, nilutamide, or flutamide) in addition to SOC (TS with or without DOC) in mHSPC. Methods: Men with mHSPC were randomly assigned 1:1 to receive TS plus either ENZA or NSAA. Randomization was stratified by: volume of disease (high vs low, according to CHAARTED); planned early DOC; planned anti-resorptive therapy, comorbidity score (ACE-27), and study site. The primary endpoint was overall survival. Accrual of 1100 men provided 80% power to detect a 25% reduction in the hazard of death (HR 0.75) with up to 4 interim analyses (IA), the first planned to occur after 235 deaths (50% of total information with a critical p-value threshold &lt;0.0031 by the Lan-DeMets alpha-spending approach with O’Brien-Fleming type shape). Subgroup analyses to assess possible modulation of the treatment effect were specified a priori and included planned early docetaxel (yes vs no) and volume of disease (high vs low). Results: We randomly assigned 1125 patients from 31MAR14 to 24MAR17. The treatment groups were well balanced for all important baseline factors. Criteria for early reporting were met at the first IA (28FEB2019) after a median follow-up of 33 months. Overall survival was prolonged by ENZA (see below). At 3 years, 36% NSAA vs 64% ENZA were still on their assigned study treatment. Serious adverse events (regardless of attribution) within 30 days of study treatment occurred in 42% ENZA vs 34% NSAA, commensurate with the different durations of study treatment. Conclusions: ENZA significantly improved OS when added to SOC in mHSPC. The benefits appeared lower in those planned to receive early DOC. Results of analyses with updated follow-up triggered by this IA will be presented. Clinical trial information: NCT02446405. [Table: see text]
Abstract 16998: Ventricular Systolic and Diastolic Dyssynchrony and Their Relationship with Ventricular Function in Patients with Single Ventricular Circulation
Authors: Mitsuru Seki, Hirofumi Saiki, Satoshi Masutani, Hideaki Senzaki
Journal: Circulation (2011)

BACKGROUND: Recent studies highlighted importance of ventricular diastolic dyssynchrony as well as systolic dyssynchrony in the pathophysiology of adult heart failure. However, little is known about interaction between diastolic and systolic dyssynchrony and their impacts on ventricular function in pediatric patients with single ventricular circulation. METHODS: We studied 24 pediatric patients (mean age; 2.1±1.3 years) with single ventricular circulation and 12 age-matched control subjects. Transthoracic two-demensional speckle tracking echocardiography (Vivid 7, GE) was performed to assess ventricular dyssynchrony (EchoPac workstation, GE). Systolic and diastolic dyssynchrony was measured as a maximal time delay in peak systolic and early diastolic velocities of longitudinal strain at four segments. Comprehensive ventricular systolic and diastolic function was assessed by employing pressure-area relationships during preload varied by transient inferior vena caval balloon obstruction. RESULTS: Systolic and diastolic time delay were 31.8±14.5 ms and 29.2±14.6 ms respectively in single ventricular patients, and were significantly larger than in the controls (16.2±11.9 ms for systolic and 15.8±11.2 ms for diastolic, both p&lt;0.01). There was no significant correlation between systolic and diastolic dyssynchrony in the patient group. Systolic dyssynchrony was negatively correlated with ventricular contractility indexes of end-systolic elastance (r=0.34, p&lt;0.05) and maximum rate of pressure rise (r=0.585, p&lt;0.05). Diastolic dyssynchrony was positively correlated with end-diastolic pressure (r=0.719, p&lt;0.05), but not with time constant of ventricular relaxation. CONCLUSIONS: Not only systolic but also diastolic dyssynchrony has important impacts on ventricular function in patients with single ventricular circulation. These data suggest important notion that diastolic as well as systolic dyssynchrony is an important therapeutic target when considering cardiac resynchronization therapy for patients with single ventricular circulation.
Survey of sexual harassment and gender disparities among gynecologic oncologists.
Authors: Marina Stasenko, Christopher M. Tarney, Mitchell Veith, Kenneth Seier, Yovanni Casablanca, Carol L. Brown
Journal: Journal of Clinical Oncology (2019)

LBA10502 Background: Sexual harassment is a problem in the workplace, with a third of U.S. women reporting experiencing unwanted sexual advances in their careers. Moreover, gender disparities have persisted in medicine, despite over half of U.S. physicians under age 44 being female. The purpose of this study is to evaluate perceived gender biases, prevalence of sexual harassment, and how these affect physician growth and advancement in gynecologic oncology (Gyn-Onc). Methods: We conducted a survey study of U.S.-based physician members of the Society of Gynecologic Oncology: full, senior, and fellow members. Participants reported: demographics; experiences with sexual harassment in training/practice; perceptions of gender disparities in Gyn-Onc. Survey was anonymized and collected using RedCap data capture tool. Dichotomous outcomes were compared using Fisher’s exact test. Results: The survey was sent to 1,566 members; 402 responses were received (26% response rate: 255 females (F), 147 males (M)). Female responders were younger, non-white (28% F, 11% M), not married (16% F, 3% M), and had fewer years in practice than males (p≤0.001, each). Six of every 10 responders (64%) reported experiencing sexual harassment during training/practice; 7 of every 10 women (71%) experienced sexual harassment in training/practice. One in 10 responders openly reported this behavior (15% responders; 17%F, 10% M, p=0.210); most common reasons for lack of reporting were: incident did not seem important enough (40%), did not think anything would be done about it (37%), and fear of reprisal (34%). Female responders were more likely to report that they felt gender affected their career advancement (34% F, 10% M; p≤0.001) and that gender played a role in setting their salary (42% F, 6% M; p≤0.001). Of note, 91% male responders did not feel that there is a gender pay gap in Gyn-Onc, compared to 57% females (p≤0.001). Conclusions: This report is the first to show that experience of sexual harassment is common among Gyn-Onc physicians. Importantly, only few report these occurrences, often for fear of reprisal or concern that nothing will be done. Further, female Gyn-Oncologists report feeling that gender influences salaries and career advancement. Awareness and acknowledgement of sexual harassment and gender inequalities within Gyn-Onc can lead to interventions to address these disparities.
Erratum: Integrating genotypic and expression data in a segregating mouse population to identify 5-lipoxygenase as a susceptibility gene for obesity and bone traits
Authors: M Mehrabian, H Allayee, J Stockton, P Y Lum, T A Drake, L W Castellani, M Suh, C Armour, S Edwards, J Lamb, A J Lusis, E E Schadt
Journal: Nature Genetics (2005)
Proteolytic, lipidergic and polysaccharide molecular recognition shape innate responses to house dust mite allergens
Authors: Alain Jacquet, Clive Robinson
Journal: Allergy (2019)

Abstract House dust mites (HDMs) are sources of an extensive repertoire of allergens responsible for a range of allergic conditions. Technological advances have accelerated the identification of these allergens and characterized their putative roles within HDMs. Understanding their functional bioactivities is illuminating how they interact with the immune system to cause disease and how interrelations between them are essential to maximize allergic responses. Two types of allergen bioactivity, namely proteolysis and peptidolipid/lipid binding, elicit IgE and stimulate bystander responses to unrelated allergens. Much of this influence arises from Toll‐like receptor (TLR) 4 or TLR2 signalling and, in the case of protease allergens, the activation of additional pleiotropic effectors with strong disease linkage. Of related interest is the interaction of HDM allergens with common components of the house dust matrix, through either their binding to allergens or their autonomous modulation of immune receptors. Herein, we provide a contemporary view of how proteolysis, lipid‐binding activity and interactions with polysaccharides and polysaccharide molecular recognition systems coordinate the principal responses which underlie allergy. The power of the catalytically competent group 1 HDM protease allergen component is demonstrated by a review of disclosures surrounding the efficacy of novel inhibitors produced by structure‐based design.
Diabetes in humanitarian crises: the Boston Declaration
Authors: Sylvia Kehlenbrink, Lindsay M Jaacks, Sigiriya Aebischer Perone, Éimhín Ansbro, Elizabeth Ashbourne, Carol Atkinson, Mark Atkinson, Rifat Atun, Stéphane Besançon, Philippa Boulle, Helen Bygrave, Enrique Caballero, Katy Cooper, Angelica Cristello, Katy Digovich, Shannon Doocy, Senan Ebrahim, Margaret Ewen, Dina Goodman, Lena Hamvas, Saria Hassan, Meredith A. Hawkins, Arjan Hehenkamp, Ruth F. Hunter, Lindsay M. Jaacks, Dlorah Jenkins, Kiran Jobanputra, Stephanie Kayden, Yasmin Khan, Sylvia Kehlenbrink, Farah Kidy, Emma Klatman, Lydje Lahens, Richard Laing, Jennifer Leaning, Peter Le Feuvre, Eric Lontchi-Yimagou, Jing Luo, Gemma Lyons, Marie E. McDonnell, James Meigs, Christina Meyer, Laura Miller, Joy Moy, Kelly Mueller, Graham Ogle, Kelli O'Laughlin, Paul Park, Preeti Patel, Elizabeth Pfiester, Ruwan Ratnayake, Amulya Reddy, Tim Reed, Bayard Roberts, Paul Robinson, Khrist Roy, Nisreen Salti, Jacqueline Seiglie, Akihiro Seita, Vera Siesjö, Slim Slama, Katherine J. Souris, Bram Wispelwey, Sydney Yovic, Ossama Zaqqout, Matthew Zhao
Journal: The Lancet Diabetes & Endocrinology (2019)