tbuckley/cabot-search huggingface dataset:
Abstract LB-154: Differential predictive modeling to grasp disparities among sub-populations
Authors: Wonsuk Yoo
Journal: Cancer Research (2019)

Abstract Background: Many of these practical applications typically produce huge data sets that contain several thousands of objects with hundreds (or even thousands) of features that describe each object. Automatic modeling, organizingand interpreting these large-scale data sets is increasingly part of various disciplines, such as health, medicine, and biology. The study aims to propose a new framework for constrained learning of predictive models where we enforce additional constraints for the models to be as similar as possible. Methods: We develop a new task of differential predictive modeling to solve the problem of differences in the data distributions by developing a continuum of predictive models. To achieve this, we construct a new framework for constrained learning of predictive models where we enforce additional constraints for the models to be as similar as possible. The major distinction of our approach with the existing methods is that none of the existing methods explore the model distance based on building the similar tree concept. We compute the distance between two datasets from the structural information about the induced trees without referring back to the original data statistics or the model statistics. Our 29-state Medicaid dataset, which contains 100% of the claims for 90% of all African American and 90% of all Hispanic and Latino Medicaid enrollees in the entire U.S. geo-coded at the zip code and county levels. Principal Findings: The goal of the disparities work is to capture the differences across different population groups and provide a better understanding that can explain these differences. Using this model, we could be able to measure the group difference in a particular minority group and compare these differences across the other subgroups. This is useful in ranking the groups where the disparity varies from the highest to the lowest. The novelty of our approach is that it captures the disparity of groups through a systematic comparison of multivariate models which cannot be done using any of the existing methods available in the machine learning methods. Conclusions: This model has the potential to dictate more aggressive new therapeutic treatments for specific subsets of high-risk patients. This project proposes new research directions in exploratory tools needed by the domain experts analyzing their data. It will provide significant insights for data analysis that can be utilized in various domains of science. One of the ultimate goals of the proposed research is the development of a clinician-friendly software and web-based analysis tool to analyze the health disparity multivariate data using the prediction models. Citation Format: Wonsuk Yoo. Differential predictive modeling to grasp disparities among sub-populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-154.
Abstract P076: Racial Differences in Maintaining Optimal Healthy Lifestyles Until 50 Years of Age: Prospective Data From the Coronary Artery Risk Development in Young Adults Study
Authors: John N Booth, Norrina B Allen, David Calhoun, April P Carson, Luqin Deng, David C Goff, David T Redden, Jared P Reis, Daichi Shimbo, James M Shikany, Stephen Sidney, Bonnie J Spring, Cora E Lewis, Paul Muntner
Journal: Circulation (2017)

Introduction: Racial disparities in healthy lifestyles may begin in youth and increase over the lifespan. Hypothesis: Maintaining healthy lifestyles until 50 years of age will be lower in blacks compared with whites. Methods: The population-based Coronary Artery Risk Development in Young Adults (CARDIA) study enrolled 5115 blacks and whites aged 18-30 years in 1985-1986. Eight exams were completed over 25 years of follow-up. At each exam, optimal lifestyles were defined as body mass index (BMI) &lt; 25 kg/m 2 , never smoking status, moderate or vigorous physical activity ≥ 150 minutes per week, no or moderate alcohol intake (drinks per week [women / men]: 0-7 / 0-14) and Dietary Approaches to Stop Hypertension (DASH) adherence score ≥ 15. Optimal cardiovascular health (CVH) was defined as having ≥ 4 optimal lifestyles. The age-specific percentage of blacks and whites maintaining optimal lifestyles was calculated using a modified Kaplan Meier method. Hazard ratios (HR) were calculated for maintaining optimal lifestyles over 25 years in blacks compared with whites. Results: At the baseline exam, 4900 participants (mean age: 26 years; black: 51%) had ≥ 1 optimal lifestyle. By 50 years of age, maintaining BMI &lt; 25 kg/m 2 , never smoking status, moderate or vigorous physical activity ≥ 150 minutes per week, DASH diet adherence and optimal CVH were lower in blacks versus whites while maintaining no or moderate alcohol intake was higher ( Table ). The multivariable adjusted HR (95% confidence interval) comparing blacks to whites for maintaining BMI &lt; 25 kg/m 2 was 0.57 (0.52-0.63), never smoking status was 0.82 (0.66-1.01), moderate or vigorous physical activity ≥ 150 minutes per week was 0.83 (0.76-0.91), no or moderate alcohol intake was 1.19 (1.03-1.37), DASH diet adherence was 0.71 (0.61-0.82) and optimal CVH was 0.63 (0.56-0.72). Conclusion: Blacks were less likely to maintain optimal lifestyles until 50 years of age. Reducing racial differences in the maintenance of optimal CVH may help prevent racial disparities in cardiovascular disease.
Peripheral TREM1 responses to brain and intestinal immunogens amplify stroke severity
Authors: Qingkun Liu, Emily M. Johnson, Rachel K. Lam, Qian Wang, Hong Bo Ye, Edward N. Wilson, Paras S. Minhas, Ling Liu, Michelle S. Swarovski, Stephanie Tran, Jing Wang, Swapnil S. Mehta, Xi Yang, Joshua D. Rabinowitz, Samuel S. Yang, Mehrdad Shamloo, Christoph Mueller, Michelle L. James, Katrin I. Andreasson
Journal: Nature Immunology (2019)
Abstract 4115: Naturally circulating anti-LAG3 antibodies exist in cancer patients
Authors: Ilya Tsimafeyeu, Pavel Ershov, Leonid Kaluzhskiy, Jean-Philippe Couture, Hugo Gagnon, Vladimir Kuznetsov, Aleksei Kalachev, Alexis Ivanov, Gennady Bratslavsky
Journal: Cancer Research (2019)

Abstract To date there was no evidence of existence of the naturally circulating antibodies to checkpoint receptors in humans. LAG3 checkpoint is crucial in modulation of immune response that is altered in humans with inflammatory and malignant conditions. We have previously described novel methodology in identification of diagnostic and therapeutic antibodies (US Patent #9810694). Here we report identification of novel potentially therapeutic fully human anti-LAG3 antibodies in cancer patients. Anti-LAG3 antibody presence was evaluated in 25 individuals: 11 healthy donors (controls) and 14 cancer patients in two different laboratories blinded to clinical information. Surface plasmon resonance analysis was done using the optical biosensor BiacoreT200 where LAG3 protein was covalently immobilized on the optical chip and biosensor signals from human serum samples were analyzed. Western Blotting used recombinant LAG3 loaded on a 10% SDS PAGE followed by blotting with plasma samples followed by biotinylated anti-human IgA/IgG/IgM and IrDye 800 streptavidin. Plasma anti-LAG3 IP utilized recombinant LAG3 crosslinked to MagResyn Carboxyl beads followed by incubation with plasma, followed by a biotinylated anti human IgA/IgG/IgMand IrDye streptavidin. No anti-LAG3 antibodies were detected in control group. Among three assays there was complete correlation for presence of anti-LAG3 antibody in 3 cancer patients. One of these patients had sufficient plasma quantity and anti-LAG3 concentration (21 - 33 µg/ml) that should allow for the antibody purification and de novo sequencing. The novel fully human anti-LAG3 antibody will be identified, purified, and the sequence will be determined.To our knowledge this is the first report of checkpoint antibody presence in humans. Further study with cloning and evaluation of therapeutic properties of novel fully human anti-LAG3 antibody in xenograft models will be performed. Citation Format: Ilya Tsimafeyeu, Pavel Ershov, Leonid Kaluzhskiy, Jean-Philippe Couture, Hugo Gagnon, Vladimir Kuznetsov, Aleksei Kalachev, Alexis Ivanov, Gennady Bratslavsky. Naturally circulating anti-LAG3 antibodies exist in cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4115.
Abstract 3935: PLK4 inhibition as a strategy for non-small cell lung cancer radiosensitization
Authors: Thomas J. Hayman, Mark R. Bray, Jacqueline M. Mason, Tak W. Mak, Joseph N. Contessa
Journal: Cancer Research (2019)

Abstract Background/Purpose: Lung cancer remains the leading cause of cancer-related death. Concurrent chemoradiation is the standard of care for locally advanced non-small cell lung cancer (NSCLC). Despite advancements in treatment, local control remains an issue and survival is suboptimal, highlighting the need for novel therapeutic approaches. Polo-like kinase 4 (PLK4) is a serine/threonine kinase that controls centriole duplication. PLK4 is highly expressed in multiple malignancies including lung cancer. CFI-400945 is a specific PLK4 inhibitor currently undergoing clinical trial evaluation. As radiation causes cell death primarily via a mitotic death, we hypothesized that disruption of the mitotic machinery by inhibition of PLK4 would enhance the effects of radiation. Methods: The effects of CFI-400945 on cell survival and radiation sensitivity were examined using the clonogenic survival assay in two KRAS-mutant lung cancer cell lines (H460 and A549). Confocal microscopy was utilized to determine the effects of PLK4 inhibition on radiation-induced mitotic catastrophe (defined as the presence of 2 or more distinct nuclear lobes within a single cell). Cell cycle distribution by flow cytometry was determined after treatment with CFI-400945 and radiation. Results: Exposure of H460 and A549 lung cancer cell lines to 10nM CFI-400945 for 48h reduced clonogenic survival to 63.9% and 83.1% respectively. CFI-400945 treatment of H460 and A549 cells resulted in radiosensitization of both cell lines with dose enhancement factors (DEF) of 1.60 and 1.31. To understand the mechanism of enhanced radiosensitivity with CFI-400945 treatment the effects on radiation-induced mitotic catastrophe were determined. In both H460 and A549 cells the combination of radiation and PLK4 inhibition enhanced the proportion of cells undergoing mitotic catastrophe. The combination of CFI-400945 and radiation resulted in increased G2/M arrest and appearance of &amp;gt;4N populations by flow cytometric analysis when compared to drug or radiation treatment alone. Conclusion: PLK4 inhibition with CFI-400945 enhances the radiosensitivity of lung cancer cell lines via mitotic catastrophe and G2/M arrest and these data support additional pre-clinical testing. Citation Format: Thomas J. Hayman, Mark R. Bray, Jacqueline M. Mason, Tak W. Mak, Joseph N. Contessa. PLK4 inhibition as a strategy for non-small cell lung cancer radiosensitization [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3935.
Abstract 2833: Alterations in intestinal microbiota of colorectal cancer patients receiving radical surgery combined with adjuvant CapeOx therapy
Authors: Cheng Kong, Renyuan Gao, Huanlong Qin
Journal: Cancer Research (2019)

Abstract Background: An intricate relationship exists and interactions occur between gut microbiota and colorectal cancer (CRC). Radical surgery combined with adjuvant chemotherapy (AC) serves as the mainstream therapeutic scheme for most CRC patients. However, the impact of surgery or chemotherapy on gut microbiota remains elusive. Methods: Forty-three CRC patients who received radical surgery and AC were enrolled in the present study. Fecal samples of these patients were collected preoperatively, postoperatively, and after the first to fifth cycles of postoperative chemotherapy. The microbial community of each sample was analyzed using high throughput 16S rRNA amplicon sequencing. Results: Compared with preoperative samples, fecal samples collected postoperatively exhibited a significant decrease of obligate anaerobes (Bacteroides, Parabacteroides, Faecalibacterium, Prevotella_9 and Bifidobacterium), tumor-related bacteria (Enterococcus and Fusobacterium), and butyric acid-producing bacteria (Bacillus, Bilophila, Barnesiella and Enterococcus). However, a significant increase of some conditional pathogens was observed (Escherichia-Shigella, Enterobacteriaceae_unclassified, Veillonella, Morganella, Streptococcus, and Proteus). In addition, the AC regimen (CapeOx) was found to alter intestinal microbiota dramatically. In particular, several changes were observed after chemotherapy including an increase of pathogenic bacteria (Collinsella, Anaerostipes, Bilophila, Comamonas, Weissella, and Eggerthella), the “rebound effect” of chemotherapy-adapted bacteria (Dorea, Ruminococcaceae_UCG-010, Streptococcus, Prevotella_9, Mogibacterium and Roseburia), the shift of lactate-utilizing microbiota from Veillonella to Butyricimonas and Butyricicoccus, as well as the decrease of probiotics (such as Lactobacillus). Conclusions: Both radical surgery and CapeOx chemotherapy exert a non-negligible effect on the gut microbiota of CRC patients. Microbiota-based intervention may be beneficial for these patients during postoperative clinical management. Citation Format: Cheng Kong, Renyuan Gao, Huanlong Qin. Alterations in intestinal microbiota of colorectal cancer patients receiving radical surgery combined with adjuvant CapeOx therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2833.
Induction gemcitabine and cisplatin in locoregionally advanced nasopharyngeal carcinoma
Authors: Yuan Zhang, Ying Sun, Jun Ma
Journal: Cancer Communications (2019)

The standard of care for patients with locoregionally advanced nasopharyngeal carcinoma is concurrent platinum-based chemoradiotherapy. Existing literature have demonstrated that the addition of gemcitabine and cisplatin as induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma may have promising efficacy but were from phase 2 clinical trials. Stronger evidence-based data in forms of phase 3 clinical trial investigating the survival benefits of adding gemcitabine and cisplatin induction chemotherapy for such patients have been urgently warranted. In one of our recent studies published in the New England Journal of Medicine, "Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma", 480 locoregionally advanced nasopharyngeal carcinoma patients from 12 hospitals across China were randomly assigned in a 1:1 ratio to receive either chemoradiotherapy alone or gemcitabine plus cisplatin and chemoradiotherapy. Our findings evinced that, as compared to chemoradiotherapy alone, the addition of induction chemotherapy comprising of gemcitabine plus cisplatin to concurrent cisplatin-radiotherapy to patients with locoregionally advanced nasopharyngeal carcinoma was safe, demonstrated improved recurrence-free survival, overall survival, and distant recurrence-free survival, and marginally superior locoregional recurrence-free survival.
Peeking under the Hood of Acute Respiratory Distress Syndrome Phenotypes: Deeper Insights into Biological Heterogeneity
Authors: Pratik Sinha, Carolyn S. Calfee
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

microbiology identifies organisms that are viable using the appropriate media and culture conditions, and the load can be easily quantified.2. The greater the viable load, the more likely it is that secondary defense systems, including neutrophilic recruitment, will be activated.This turns the sputum green and is associated with airway inflammation and destructive neutrophil products that may also impede host defenses (9). 3. The presence of inflammation and the response to it can be monitored even by simple observation of sputum purulence, and a change to mucoid sputum with a reduction in microbial load or clearance reflects a successful intervention.4. If that is the aim, those are the patients! 5.The persistent production of purulent sputum should be investigated and, when possible, treated to decrease airway neutrophilia and the accompanying damaging neutrophil products, as this also improves the patient's well-being.This can be achieved with long-term inhaled therapy.The wheel is rediscovered: it is still a wheel, but certainly a more robust one.6.Such a strategy points the way not only to a more personalized approach to patient management but also to a more focused clinical trial design.7. Sometimes simple methodologies and clinical understanding outrank modern technological approaches.The authors conclude that "molecular techniques may be better" at identifying all airway bacteria (alive or dead).However, it remains to be seen whether such information will lead to better focused management strategies, as the load of the dominant species will likely remain the critical clinical factor in driving inflammation, as was confirmed in a previous study that used such a methodology in COPD (10).
Abstract 4104: Expression of the immune checkpoint receptor TIGIT in seminoma
Authors: Maximillian Lennartz, Niclas C. Blessin, Andrea Hinsch, Ronald Simon, Martina Kluth, Kristine Fischer, Claudia Hube-Magg, Wenchao Li, Tim Mandelkow, Nicolaus F. Debatin, Doris Höflmayer, Guido Sauter, Jakob R. Izbicki, Sarah Minner, Franziska Büscheck, Ria Uhlig, David Dum, Till Krech, Andreas M. Luebke, Corinna Wittmer, Frank Jacbosen, Eike Burandt, Stefan Steurer, Waldemar Wilczak
Journal: Cancer Research (2019)

Abstract A characteristic feature of testicular seminoma is the abundance of immune cells in the tumor microenvironment, raising the possibility that immune checkpoint inhibitors could be a therapeutic option in these tumors. TIGIT (T cell immunoreceptor with Ig and ITIM domains) is an inhibitory immune checkpoint receptor in analogy to PD-1 and drugs targeting TIGIT are currently tested in clinical trials. Little is known about the expression of these proteins in testicular seminomas. Here, we employed immunohistochemistry to determine the relative abundance of TIGIT and PD-1 in relation to the total CD3+immune cell infiltration in a tissue microarray (TMA) constructed from 78 seminoma patients. The fraction of TIGIT+and PD-1+lymphocytes was highly variable in individual cancers and ranged from 2.3% to 69.4% (mean:32.2±14.7%) for TIGIT and from 0.8% to 56.5% (mean:21.6±13.2%) for PD-1. The same high degree of variability was also found for the ratio of PD-1 to TIGITpositive cells that varied from a dominance of TIGIT (PD-1:TIGIT ratio=0.02) in 74% of patients to a predominance of PD-1 (PD-1:TIGIT ratio=12.5) in 23% of patients. In summary, the immune checkpoint receptors TIGIT and PD-1 are abundantly expressed in human seminomas. Once available, anti-TIGIT antibodies, possibly in combination with anti-PD-1 drugs, may be a promising therapeutic option for clinical studies in this cancer type. Citation Format: Maximillian Lennartz, Niclas C. Blessin, Andrea Hinsch, Ronald Simon, Martina Kluth, Kristine Fischer, Claudia Hube-Magg, Wenchao Li, Tim Mandelkow, Nicolaus F. Debatin, Doris Höflmayer, Guido Sauter, Jakob R. Izbicki, Sarah Minner, Franziska Büscheck, Ria Uhlig, David Dum, Till Krech, Andreas M. Luebke, Corinna Wittmer, Frank Jacbosen, Eike Burandt, Stefan Steurer, Waldemar Wilczak. Expression of the immune checkpoint receptor TIGIT in seminoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4104.
Abstract 479: <i>BRAF</i> and <i>KRAS m</i>utation define distinct subtypes of the CpG island methylator phenotype in colorectal cancers
Authors: Vicki L. Whitehall, Lochlan Fennell, Troy Dumenil, Gunter Hartel, Katia Nones, Catherine Bond, Diane McKeone, Ann-Marie Patch, Stephen Kazakoff, John Pearson, Nicola Waddell, Pratyaksha Wirapati, Paul Lochead, Shuji Ogino, Sabine Tejpar, Barbara Leggett
Journal: Cancer Research (2019)

Abstract BACKGROUND AND AIMS: Colorectal cancer is an epigenetically heterogeneous disease, however the extent and spectrum of the CpG Island Methylator Phenotype (CIMP) is not clear.METHODS: Genome scale methylation and transcript expression were measured using the Illumina HM450 DNA methylation and HT12 V3 expression microarrays in 216 unselected colorectal cancers. Mutations in epigenetic regulators were assessed using CIMP-classified Cancer Genome Atlas exomes.RESULTS: CIMP-High cancers dichotomised into CIMP-H1 and CIMP-H2 based on methylation profile, which was supported by over-representation of BRAF (74%, P&amp;lt;0.0001) or KRAS (55%, P&amp;lt;0.0001) mutation. Congruent with increasing methylation, there was a stepwise increase in patient age from 62 years in the CIMP-Negative subgroup to 75 years in the CIMP-H1 subgroup (P&amp;lt;0.0001). CIMP-H1 were predominantly comprised of consensus molecular subtype 1 (CMS1) cancers (70%) whilst CMS3 was over-represented in the CIMP-H2 subgroup (55%). PRC2-marked loci were subjected to significant gene body methylation in CIMP cancers (P&amp;lt;1.6x10-78). We identified oncogenes susceptible to gene body methylation and Wnt pathway antagonists resistant to gene body methylation. CIMP cluster specific mutations were observed for in chromatin remodeling genes, such as in the SWI/SNF and NuRD complexes, suggesting synthetic lethality.CONCLUSION: There are five clinically and molecularly distinct subgroups of colorectal cancer. We show a striking association between CIMP and age, gender and tumor location and identify an unidentified role for gene body methylation in progression of serrated neoplasia. These data support our recent findings that CIMP is uncommon in young patients and that BRAF mutant polyps in young patients may have limited potential for malignant progression. Citation Format: Vicki L. Whitehall, Lochlan Fennell, Troy Dumenil, Gunter Hartel, Katia Nones, Catherine Bond, Diane McKeone, Ann-Marie Patch, Stephen Kazakoff, John Pearson, Nicola Waddell, Pratyaksha Wirapati, Paul Lochead, Shuji Ogino, Sabine Tejpar, Barbara Leggett. BRAF and KRAS mutation define distinct subtypes of the CpG island methylator phenotype in colorectal cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 479.