tbuckley/cabot-search huggingface dataset:
Abstract 11531: Exploring Associative Pathways and Gender Effects of Racial and Weight Discrimination with Sleep Quality, Physical Activity, and Dietary Behavior in Adults with Higher Body Mass Index and Elevated Cardiovascular Disease Risk
Authors: Sandra Wittleder, Linda Lee, Nikhil Patel, Jinhee Chang, Emilie Geesey, Sreejan Saha, Ericka Merriwether, Stephanie L Orstad, Binhuan Wang, Azizi Seixas, Melanie Jay
Journal: Circulation (2021)

Introduction: Racial disparities in obesity and cardiovascular disease can partly be attributed discrimination. Racial discrimination (RD) and weight discrimination (WD) have been linked to higher psychological distress, lower sleep quality, less physical activity, and unhealthy diet, which can negatively impact weight. Better understanding the processes by which discrimination influences weight-loss factors would help create strategies for mitigating obesity disparities. Methods: This is a cross-sectional study of 745 primary care patients with a BMI ≥ 25 kg/m 2 (43.1% Female, M age =51 years) who were enrolled in a weight-loss trial. To investigate the direct and indirect (via psychological distress) pathways by which RD and WD may be associated with sleep quality, physical activity, and diet, and to explore gender as a moderator, we used Ordinary Least Square regression with bootstrapping. Validated surveys included EOD, PROMIS-29, LDBQ, REAP-S, IPAQ-SF. Results: We found that RD and WD were indirectly associated with lower sleep quality via psychological distress (WD: indirect=2.11, CI[1.218;3.092]; RD: indirect=0.93, CI[0.057;0.134]). Further, we found that for men, RD and WD were indirectly associated with less physical activity via psychological distress (WD: moderated mediation=491.67, CI[75.565;1040.877]; RD: moderated mediation=22.60, CI[0.080;51.828]). Finally, we found that RD and WD were directly associated with unhealthy diet (WD: direct=0.195, CI[0.076;0.314]; RD: direct=0.007; CI[0.001;0.012]). Conclusions: Weight-loss factors were associated with both racial and weight discrimination through different pathways depending on gender and type of outcome. Lower sleep quality was associated with discrimination via psychological distress for both gender groups. Lower physical activity was also linked to discrimination via psychological distress, however for men only. Associations between unhealthy diet and discrimination were direct and could not be explained by increases in psychological distress. Although more research is needed, our findings suggest that interventions to address discrimination and its psychological impacts could mitigate obesity disparities and improve cardiovascular health.
Abstract 9770: Endothelial Loss of Amphiregulin Drives Inflammation and Endothelial Apoptosis in Pulmonary Hypertension
Authors: Jonathan Florentin, Jingsi Zhao, Yi-Yin Tai, Wei Sun, Lee Ohayon, Scott O'Neil, anagha arunkumar, xinyi zhang, Yassmin Al Aaraj, Annie Watson, John C Sembrat, mauricio rojas, Stephen Y Chan, Partha Dutta
Journal: Circulation (2021)

Pulmonary hypertension (PH) is a vascular disease characterized by elevated pulmonary arterial pressure (PAP), leading to right ventricular failure and death. Pathogenic features of PH include endothelial apoptosis and vascular inflammation, which drive vascular remodeling and increased PAP. Re-analysis of the whole transcriptome sequencing comparing human pulmonary arterial endothelial cells (PAECs) isolated from PH and control patients identified AREG , which encodes amphiregulin, as a key endothelial survival factor. PAECs from PH patients and mice exhibited downregulation of AREG and its receptor epidermal growth factor receptor (EGFR). Moreover, the deficiency of AREG and EGFR in ECs in vivo and in vitro heightened inflammatory leukocyte recruitment, cytokine production and endothelial apoptosis, and diminished angiogenesis. Correspondingly, hypoxic mice lacking Egfr in ECs ( cdh5 cre/+ Egfr fl/fl ) displayed elevated RVSP, Fulton index, and pulmonary remodeling. Computational analysis identified NCOA6, PHB2, and RRP1B as putative genes regulating AREG in endothelial cells. The master transcription factor of hypoxia HIF-1αbinds to the promoter regions of these genes and upregulate their expression in hypoxia. Silencing of these genes in cultured PAECs decreased inflammation and apoptosis, and increased angiogenesis in hypoxic conditions. Our pathway analysis and gene silencing experiments revealed that BCL2-associated agonist of cell death (BAD) is a downstream mediator of AREG . BAD silencing in ECs lacking AREG , mitigated inflammation and apoptosis and suppressed tube formation. In conclusion, loss of amphiregulin and its receptor EGFR in PH is a crucial step in the pathogenesis of PH, promoting pulmonary endothelial cell death, vascular recruitment of inflammatory myeloid cells, and vascular remodeling.
EPCO-23. A SINGLE-CELL BASED PRECISION MEDICINE APPROACH USING GLIOBLASTOMA PATIENT-SPECIFIC MODELS
Authors: Abdullah Feroze, James Park, Samuel Emerson, Anca Mihalas, Dirk Keene, Patrick Cimino, Adrian Lopez Garcia de Lomana, Kavya Kannan, Wei-Ju Wu, Serdar Turkarslan, Nitin Baliga, Anoop Patel
Journal: Neuro-Oncology (2021)

Abstract Glioblastoma is a heterogeneous tumor made up of cell states that evolve over time. We modeled tumor evolutionary trajectories during standard-of-care treatment using multimodal single-cell analysis of a primary tumor sample, corresponding mouse xenografts subjected to standard of care therapy, and recurrent tumor at autopsy. We mined the multimodal data with single cell SYstems Genetics Network AnaLysis (scSYGNAL) to identify a network of 52 regulators that mediate treatment-induced shifts in xenograft tumor-cell states that were also reflected in recurrence. By integrating scSYGNAL-derived regulatory network information with transcription factor accessibility deviations derived from single-cell ATAC-seq data, we developed consensus networks that regulate subpopulations of primary and recurrent tumor cells. Finally, by matching targeted therapies to active regulatory networks underlying tumor evolutionary trajectories, we provide a framework for applying single-cell-based precision medicine approaches in a concurrent, neo-adjuvant, or recurrent setting. Our proof-of-concept work herein provides the basis for the development of a modeling and analytical system that enables single-cell characterization of an individual patient’s tumor and inferred therapeutic vulnerabilities. Although further validation is required, in the form of in vivo studies of these putative druggable targets, our preliminary analysis and results suggest that systems biology techniques can be used to infer and predict therapeutic vulnerabilities that are either selected or induced during standard-of-care treatment. Ultimately, the information gathered from such systematic modeling and analysis of individual tumors may inform clinical treatment in a more targeted manner and enable a rational, tailored precision medicine that accounts for intratumoral cell heterogeneity.
CTNI-19. CONCURRENT CHEMORADIATION AND TUMOR TREATING FIELDS (TTFields, 200 kHz) FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA MAY INCREASE THE RATE OF DISTANT RECURRENCE
Authors: Ayesha S Ali, Muneeb Niazi, Voichita Bar-Ad, Maria Werner-Wasik, David Andrews, Christopher Farrell, James Evans, Kevin Judy, Jon Glass, L Martinez Nina, Iyad Alnahhas, Inna Chervoneva, Wenyin Shi
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION: Current standard of care for glioblastoma (GBM) includes concurrent chemoradiation and maintenance temozolomide (TMZ) along with Tumor Treating Fields (TTFields). Preclinical studies suggest TTFields and radiation treatment have synergistic effects. Secondary analysis of EF14 trial demonstrated TTFields treatment may increase the rate of distant recurrence. We report our experience evaluating areas of progression in our pilot clinical trial of concurrent chemoradiation with TTFields. METHODS: This is a single arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Adult patients (age ≥ 18 years) with KPS ≥ 60 with newly diagnosed GBM were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions), standard concurrent TMZ (75 mg/m2 daily), and TTFields. Maintenance therapy included standard TMZ and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. Incidence and location of progression was documented. Distant recurrence was defined as recurrence more than 2 cm from primary enhancing lesion. RESULTS: A total of 30 patients were enrolled on the trial. Twenty were male, and ten were female, with median age 58 years (19-77 years). Median KPS was 90 (70-100). Median follow-up was 11.6 months (1.7-22.1 months). Twenty (66.7%) patients had an unmethylated MGMT promotor status and ten (33.3%) patients had a methylated promoter status. Twenty patients (66.7%) had progression, with median PFS of 9.1 months (range 1.6 to 12.9 months). Five patients (26%) of patient presented with distant recurrence, with median distance from primary lesion of 5.1 cm (2.26-9.12 cm). One infratentorial progression was noted. Another patient transferred care and location of progression is unknown. CONCLUSIONS: Concurrent chemoradiation with TTFields for patients with newly diagnosed glioblastoma may have increased incidence of distant recurrence. This finding is suggestive of improved local control of primary site. Further data are needed to validate this finding.
Abstract 13889: Impact Of Acute Hypoxia On Left Ventricular Relaxation Time In Healthy Men
Authors: Vladimir N Melnikov, Irina V Karmakulova, Tamara G Komlyagina, Sergey G Krivoschekov
Journal: Circulation (2021)

Introduction: The oxygen-dependence of myocardial contractility is known but it is not the case for ventricular distension in humans. It has been shown that acute ischemia causes incomplete and retarded relaxation through the decrease in intracellular pH and ATP content. Purpose: to verify whether hypoxemia changes the left ventricular relaxation time (LVRT). Methods: Overall, 37 physically active normotensive men (age 19-42 years, 20.4±2.3 yrs., M±SD) constituted the study sample. The LVRT was derived from aortic pulse wave analysis (SphygmoCor) and measured as difference between the end of systole (ejection duration point, ED, corresponding to the closure of aortic valve) and the time of peak pressure (T1), generated by LV in the aortic root and corresponding to the first incisura [LVRT,%=(ED-T1)/length of cardiac cycle*100]. Subjects inhaled hypoxic mixture with 10%O2 over 10 min for mean blood SpO2 of 80%. Associations were assessed by partial correlation (age, SBP=const.), multiple linear regression analyses (GLM option in SPSS), and t-test for dependent samples. Results: At baseline, the longer length of LVR was associated with lower end systolic blood pressure (r=-0.56, p&lt;0.001). The regression model combining heart rate, augmentation pressure, and aortic-to-radial pulse pressure amplification explained 98.6% of total LVRT variation with significant effects of all covariates. Hypoxia increased LVRT from 19.0±2.8% to 23.1±4.2%, p&lt;0.001. The response of LVRT to hypoxic exposure (range for Δ, -0.7%, +9.1%) was directly correlated with the extent of blood oxygen desaturation (r=0.53, p=0.016). Conclusion: The results show that cardiomyocytes retard their relaxation in hypoxic conditions. Cardiomyocytes happened to be quite sensitive to hypoxemia since even 10-min hypoxia was sufficient for elongation of the ventricular relaxation.
Reducing Central Line Associated Bloodstream Infections in Allogeneic Hematopoietic Stem Cell Transplant Patients
Authors: Nataly Valeria Torrejon, Tiffany Onger, Ronald M. Sobecks, Megan Corrao, Debra Scott, Alexandria Farrell, Christina Colvin, Steve Booth, Silvana Began, Jeanne Ferraro, Donna Corrigan, Tori Nelson, Nicholas Rinaldi, Susan McInnes
Journal: Blood (2021)
Clinical Activity of CC-99282, a Novel, Oral Small Molecule Cereblon E3 Ligase Modulator (CELMoD) Agent, in Patients (Pts) with Relapsed or Refractory Non-Hodgkin Lymphoma (R/R NHL) - First Results from a Phase 1, Open-Label Study
Authors: Jean-Marie Michot, Julio C. Chavez, Cecilia Carpio, Silvia Ferrari, Tatyana A. Feldman, Daniel Morillo, John Kuruvilla, Antonio Pinto, Vincent Ribrag, Emmanuel Bachy, Tonia J Buchholz, Soraya Carrancio, Carla Guarinos, Fan Wu, Shaoyi Li, Poliana Patah, Michael Pourdehnad, Loretta Nastoupil
Journal: Blood (2021)
CTNI-45. RESPONSE EVALUATION OF AR-67 FROM A PHASE-2 RECURRENT GLIOBLASTOMA TRIAL BY ARTIFICIAL INTELLIGENCE ASSISTED TUMOR VOLUMETRIC ESTIMATION: COMPARISON WITH THE SUM OF THE PERPENDICULAR DIAMETERS PRODUCT
Authors: Sotirios Bisdas, Jai Grewal, Volker Stieber, Robert Cavaliere, Craig Devoe, Randy Jensen, Elise Brownell, Tina Runk, Diana Dupont-Roettger
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Modified Radiographic Response Assessment in Neuro-Oncology (“mRANO”) criteria based on SPDP form the basis for assessing treatment response in Glioblastoma but are subject to sampling bias and difficulty in differentiating between pseudo- and true disease progression. Volumetric image analysis using AI may overcome these limitations of standard techniques and improve our ability to detect changes earlier and more accurately. METHODS Images from eight reGBM patients enrolled in a Phase-2 reGBM study of Vivacitas Oncology’s drug, AR-67, were re-assessed using IAG’s AI-assisted volumetric measurements. A median of five MRI time points from each patient were included. The mRANO response was determined by central reading and tumor volumetric measurement using IAG’s proprietary platform. Statistical significance was set at p&amp;lt; .0001. RESULTS Four patients showed responses, two patients showed stable disease, and two patients showed progressive disease. Tumor volume was correlated (r=0.97) with SPDP, but was driven by high coefficients in large lesions. Standard SPDP overestimated tumor size in larger tumors using the Bland-Altman analysis (mean difference: 829; 95% CI: 704 to -2362) leading to discrepancies in response rates. For example, the mean response rate based on IAG’s volumetric criteria was +22% (1.29) compared with +17% using SPDP (0.81). Eight out of 45 time-points also differed in the directionality of responses (e.g., increase vs. decrease) with SPDP underestimating the positive effects of AR-67 compared to AI analysis. CONCLUSIONS IAG’s AI-assisted tumor volumetric analysis is feasible for clinical trials and may be more sensitive for evaluating treatment-related response rates vs. SPDP methodology. This is particularly true for measuring large lesions, and may also allow for more accurately differentiating between pseudo- and true disease progression. The data included eight patients’ MRI images from a Phase-2 reGBM study, showing that five patients achieved the primary end-point of six months Progression-Free Survival, suggesting AR-67’s therapeutic potential.
Why I don’t support GPs taking industrial action
Authors: Azeem Majeed
Journal: BMJ (2021)

<h3>Background</h3> <i>Panax ginseng</i> (ginseng) is a therapeutic herb which might be beneficial in COPD. The study investigated if ginseng, compared with placebo, is effective and safe for people with moderate COPD. <h3>Methods</h3> This multicentre, randomised, double-blind, placebo-controlled trial compared 24 weeks of ginseng capsules (100 mg twice daily) with placebo. Participants were followed up for a further 24 weeks. Participants were aged 40 years and over and had airflow limitation in the moderate (Global Initiative for Chronic Obstructive Lung Disease 2) COPD range. The coprimary endpoints were the St George’s Respiratory Questionnaire, the COPD Assessment Test and the Short Form Health Survey. Secondary outcomes included lung function, exacerbation rate and use of relief medication. <h3>Findings</h3> 168 participants were randomised 1:1 from five centres in Australia and China. Baseline characteristics were balanced between groups. There were no significant differences between ginseng and placebo, with overall results improving in both groups. Ginseng seemed safe for, and well tolerated by, people with COPD. <h3>Interpretation</h3> There was no significant difference in improvement in health-related quality of life (primary outcome) between the ginseng and placebo groups. <h3>Trial registration number</h3> ACTRN12610000768099.
Effect of an artificial intelligence-based quality improvement system on efficacy of a computer-aided detection system in colonoscopy: a four-group parallel study
Authors: Liwen Yao, Lihui Zhang, Jun Liu, Wei Zhou, Chunping He, Jun Zhang, Lianlian Wu, Hongguang Wang, Youming Xu, Dexin Gong, Ming Xu, Xun Li, Yutong Bai, Rongrong Gong, Prateek Sharma, Honggang Yu
Journal: Endoscopy (2021)

Background Tandem colonoscopy studies have found that about one in five adenomas are missed at colonoscopy. It remains debatable whether the combination of a computer-aided polyp detection (CADe) system with a computer-aided quality improvement (CAQ) system for real-time monitoring of withdrawal speed results in additional benefits in adenoma detection or if the synergetic effect may be harmed due to excessive visual burden resulting from information overload. This study aimed to evaluate the interaction effect on improving the adenoma detection rate (ADR). Methods This single-center, randomized, four-group, parallel, controlled study was performed at Renmin Hospital of Wuhan University. Between 1 July and 15 October 2020, 1076 patients were randomly allocated into four treatment groups: control 271, CADe 268, CAQ 269, and CADe plus CAQ (COMBO) 268. The primary outcome was ADR. Results The ADR in the control, CADe, CAQ, and COMBO groups was 14.76 % (95 % confidence interval [CI] 10.54 to 18.98), 21.27 % (95 %CI 16.37 to 26.17), 24.54 % (95 %CI 19.39 to 29.68), and 30.60 % (95 %CI 25.08 to 36.11), respectively. The ADR was higher in the COMBO group compared with the CADe group (21.27 % vs. 30.6 %, P = 0.024, odds ratio [OR] 1.284, 95 %CI 1.033 to 1.596) but not compared with the CAQ group (24.54 % vs. 30.6 %, P = 0.213, OR 1.309, 95 %CI 0.857 to 2.000, respectively). Conclusions CAQ significantly improved the efficacy of CADe in a four-group, parallel, controlled study. No significant difference in the ADR or polyp detection rate was found between CAQ and COMBO.
Abstract 11328: Risk Analytics and Clinical Decision Support System Role in Identifying Elevated Serum Lactate Level for Pediatric Cardiac Patients
Authors: Ahmed Asfari, Kristal Hock, Jordan Huskey, Adam Tomczak, Evan Butler, Santiago Borasino, Hayden Zaccagni
Journal: Circulation (2021)

Introduction: Pediatric patients with congenital heart defect are predisposed for low cardiac output syndrome (LCOS). Serum lactate is a well-defined marker of LCOS. To improve the quality and safety of care, new tools that are less invasive, more sensitive and specific are needed. Hypothesis: We hypothesize that analytics algorithms can compute risk indices that are associated with elevated lactate. Methods: Quality improvement project in tertiary pediatric cardiac intensive care unit. Data used were collected retrospectively throughout 6/2019-8/2020. The risk analytics algorithm uses a model of patient physiology with vitals and lab data to compute probability density curves for various physiologic variables in real-time. These densities are used to calculate the Hyperlactatemia Index (HLA) and Inadequate Delivery of Oxygen Index (IDO2) [Etiometry Inc., Boston, MA]. HLA and IDO2 represent the integrated probabilities that the current lactate is greater than 4 mmol/L and that the current SvO2 is less than 40% respectively. The minimum data required to calculate HLA and IDO2 is heart rate every 60 seconds, oxygen saturation via pulse oximetry, blood pressures every ten minutes, and at least one lactate lab per day (HLA only). The reported lactates were categorized in four groups. We subdivided the preceding three hours period before the lactate into 30 minutes windows. Subsequently, we calculated the mean IDO2 and HLA and compared the positive predictive value (PPV) of lactate &gt; 4 for both. Results: We included 484 patients in our analysis, 20% of which were neonates. The median patient age was 7.7 months (IQR:2,46). IDO2 and HLA trended higher when lactate levels were elevated, especially in the 30 minutes immediately preceding the lactate check. When the individual probability &gt; 50%, lactate was &gt; 4 in 44% ( + 10%) for HLA and 3% for IDO2. Conclusions: HLA shows a strong association with lactate and is superior to IDO2 across all time points. Performance of the indices was better in the 30min prior to the elevated lactate. Future studies validating this new tool prospectively are critical before its usage in the clinical setting.
EPCO-11. SINGLE-NUCLEI TRANSCRIPTOMICS RELATES GLIOBLASTOMA INFILTRATION TO DISTINCT GLIAL PROGENITOR STATES
Authors: Zarmeen Mussa, Susana Ramos, Kristin Beaumont, Robert Sebra, Alexander Tsankov, Nadejda Tsankova
Journal: Neuro-Oncology (2021)

Abstract Our understanding of glioblastoma (GBM) intratumoral heterogeneity, particularly in the context of neurodevelopment, has thus far been primarily focused on the more surgically accessible tumor core niche. In contrast, the biology of GBM cells at the infiltrative edge, which evade surgical resection and drive tumor recurrence, remains poorly characterized. To this end, we microdissected and performed single-nuclei RNA sequencing (snRNA-seq) on approximately 62,000 nuclei taken from the tumor core and from the infiltrative edge of six GBM tumors with diverse genomic drivers, including IDH1, EGFR, PDGFRA, FGFR3, and NF1. Unbiased clustering reveals distinct neoplastic and non-neoplastic populations, further distinguished using copy number variation analysis. After projecting previously defined signatures taken from snRNA-seq analysis of human adult neocortex/subventricular zone and prenatal germinal matrix, we find that approximately 90% of tumor cells recapitulate a neurodevelopment-like molecular phenotype, reprising gene expression signatures of prenatal astrocytes and of a distinct glial intermediate progenitor cell population (g-IPC) that precedes both astrocyte and oligodendrocyte lineage differentiation. Examining the infiltrative edge of samples with the most confident microdissection (n=4), we see that while distinct populations of tumor cells in this niche express proneural and classical signatures, these cells are overall enriched for a g-IPC-like phenotype, relative to the tumor core, irrespective of the tumors’ genomic alterations. A subset of cells at the infiltrative edge, in particular, recapitulates the signature of an uncommitted g-IPC subtype, expressing both astroglial and oligodendroglial markers. Trajectory analyses also reveal distinct branches of core and edge tumor cells, which are predominantly astrocyte- and g-IPC-like, respectively. Differential gene expression analysis of GBM cells at the infiltrative edge vs. tumor core reveals a migration signature, dominated by EGFR, ERBB4, PCDH9, and PCDH15. Ultimately, this high resolution analysis of heterogeneity at the infiltrative edge allows us to uncover potentially targetable drivers of invasion in GBM.
Determining the Benefits of Gender-Affirming Surgery—A Call for Action
Authors: Nnenaya Agochukwu-Mmonu, Asa Radix, A. Mark Fendrick
Journal: JAMA Surgery (2021)

This Viewpoint discusses how coverage with evidence development may be warranted to develop a rigorous evidence base for gender-affirming interventions and surgery while simultaneously allowing access and provisional coverage for these services.
Investigating Erythrocytosis: Changing Practice Patterns in the Era of Molecular Diagnostics
Authors: Benjamin Chin-Yee, Maxim Matyashin, Pratibha Bhai, Ian Cheong, Alan Stuart, Eri Kawata, Sean Cuninghame, Michael A. Levy, Alejandro Lazo-Langner, Hanxin Lin, Ian Chin-Yee, Bekim Sadikovic, Cyrus C. Hsia
Journal: Blood (2021)