tbuckley/cabot-search huggingface dataset:
Evaluating and manipulating the immune landscape in hepatic verses peritoneal metastases arising from colorectal primary tumors.
Authors: Robert George Ramsay, Rosemary Millen, Vignesh Narasimhan, Sara Roth, Toan Pham, Joseph Kong, Glen Guerra, Wayne A Phillips, Alexander Graham Heriot
Journal: Journal of Clinical Oncology (2019)

568 Background: Colorectal metastases arise predominantly in the liver, lung and peritoneum. It is becoming increasingly clear that these locations might be distinct in terms of tumor cell tropism and genetics. We explored the immunological landscape in primary colorectal tumors along with hepatic and peritoneal metastases. The ultimate intent is to identify opportunities to implore immunomodulatory strategies to improve patient outcomes. Methods: Cancer biopsies were processed to generate tumor-derived organoids and TILs from patients with primary and/or metastatic tumors. These were co-cultured with patient matched TILs to assess immune competency and opportunities to employ checkpoint blockade using an in vitro platform we recently developed to explore TIL activity in patients with rectal cancer prior to standard of care therapy. Results: We found substantively different levels of TILs, their sub-set composition and most importantly their capacity to kill tumor cells. The nature of the metastatic peritoneal and hepatic tumor TILs were distinct. Where high programmed cell death 1 (PD-1) expression was high on TILs there was an opportunity to test PD-1 receptor function with blocking antibodies whereby some TILs showed enhanced cytotoxicity while others did not. Conclusions: Using our immune function assay we have demonstrated the distinct activities of patient-matched TILs in terms of killing at different organ sites of metastases. We also found differences in response to checkpoint inhibition blockade and de novo immune resistance.
Sphingolipid Perturbation Activates Proteostasis Programs to Govern Human Hematopoietic Stem Cell Self-Renewal
Authors: Stephanie Zhi-Juan Xie, Laura Garcia Prat, Veronique Voisin, Alex Murison, Olga I. Gan, Robin Ferrari, Naoya Takayama, Kerstin B. Kaufmann, Ishita Patel, Esther Lee, Gareth Holmes, Tiago Medina, Aditi Vedi, Chiara Luberto, Gary D Bader, Elisa Laurenti, Mathieu Lupien, John E. Dick
Journal: Blood (2018)
Risk factors for keratinocyte carcinoma skin cancer in nonwhite individuals: A retrospective analysis
Authors: Kumar S. Nadhan, Christina L. Chung, Erin M. Buchanan, Christine Shaver, Scott Shipman, Rina M. Allawh, Melissa L. Hoffman, Geoffrey Lim, Mark Abdelmalek, Carrie Ann Cusack
Journal: Journal of the American Academy of Dermatology (2019)
Abstract P4-04-12: TZAP mutation leads to poor prognosis of patients with breast cancer
Authors: J-H Lee
Journal: Cancer Research (2019)

Abstract The zinc finger protein ZBTB48 is a telomere-associated factor that has been renamed as telomeric zinc finger-associated protein (TZAP). It binds preferentially to long telomeres, competing with telomeric repeat factors 1 and 2. However, its expression in cancers has not been investigated. In the present study, we analyzed the TZAP mutation in 128 breast carcinomas (BCs). In addition, its association with telomere length was investigated. The TZAP mutation (c.1272G&amp;gt;A, L424L) was found in 7.8% (10/128) of the BCs and was associated with the N0 stage (p = 0.035). BCs with the TZAP mutation had longer telomeres than those without this mutation (2.62 ± 1.71 vs. 0.98 ± 0.37, p = 0.009). Telomere elongation was shown in 29.7% (38/128) of BCs and was significantly higher in luminal A and triple negative BCs (p &amp;lt; 0.001). Other characteristics were not associated with TZAP mutations and telomere length. Survival analysis showed that the TZAP mutation resulted in a poorer overall survival (52.8 vs. 87.3 months, χ2 = 4.37, P = 0.037). However, telomeres did not have any prognostic value for BCs (P = 0.908). These results suggest that the TZAP mutation is a possible prognostic marker in BC. Citation Format: Lee J-H. TZAP mutation leads to poor prognosis of patients with breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-04-12.
Parapharyngeal Ganglioneuroma Detected by 18F-FDG PET/CT in a Patient With Hodgkin Lymphoma
Authors: Wan-Ling Yi, Tzu-Pai Chen, Nan-Tsing Chiu, Chiang-Shin Liu, Yu-Hsuan Lin
Journal: Clinical Nuclear Medicine (2019)

Abstract A 38-year-old woman with anterior mediastinal Hodgkin lymphoma underwent 18 F-FDG PET/CT, revealing abnormal uptake at the left retrostyloid parapharyngeal space. After chemotherapy, follow-up PET/CT showed regression of previously avid lesions but not the left retropharyngeal mass. Subsequent MRI revealed findings suggestive of neurogenic tumor. Transoral biopsy revealed ganglioneuroma, which is uncommon in the parapharyngeal space, although usually of benign nature. This case therefore highlights the importance of PET/CT in both initial diagnostic screening for tumor development and posttreatment evaluation of ambiguous lesions.
The Xolair Pregnancy Registry (EXPECT): Perinatal outcomes among pregnant women with asthma treated with omalizumab (Xolair) compared against those of a cohort of pregnant women with moderate-to-severe asthma
Authors: Jennifer A. Namazy, Lucie Blais, Elizabeth B. Andrews, Angela E. Scheuerle, Michael D. Cabana, John M. Thorp, Joachim H. Veith, Dale T. Umetsu, Diana Sun, Derrick G. Kaufman, Deborah L. Covington, Santanu Mukhopadhyay, Robert B. Fogel, Sandra Lopez-Leon, Vic Spain
Journal: Journal of Allergy and Clinical Immunology (2019)
Apoptotic Blocks in Primary Non-Hodgkin B-Cell Lymphomas Identified By BH3 Profiling
Authors: Nathalie A Johnson, Claudia M Wever, Dominique Geoffrion, Ghassemian Artin, Brailovski Eugene, Pierre Sesques, Jeremy A. Ryan, Liliana Stoica, Josee Hebert, Tina Petrogiannis-Haliotis, Svetlana Dmitrienko, Frenkiel Saul, German Ott, Annette Staiger, Christian Steidl, David W. Scott, Koren Kathleen Mann, Anthony Letai
Journal: Blood (2018)
An Assessor-Blinded, Left-Right Comparison Study Of Washing With Water Alone Versus Soap In Maintaining Remission Of Eczema In Fall-Winter
Authors: Yusuke Inuzuka, Yoko Monna, Mayumi Matsunaga, Yukiko Kato, Tomohide Taguchi, Osamu Natsume
Journal: Journal of Allergy and Clinical Immunology (2019)
<i>Notes from the Field:</i> Circulating Vaccine-Derived Poliovirus Type 1 and Outbreak Response — Papua New Guinea, 2018
Authors: Mathias Bauri, Amanda L. Wilkinson, Berry Ropa, Keith Feldon, Cynthia J. Snider, Abhijeet Anand, Graham Tallis, Liliane Boualam, Varja Grabovac, Tigran Avagyan, Mohammad S. Reza, Dessie Mekonnen, Zaixing Zhang, Bruce R. Thorley, Hiroyuki Shimizu, Lea Necitas G. Apostol, Yoshihiro Takashima
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

On June 22, 2018, the Papua New Guinea National Department of Health confirmed an outbreak of poliomyelitis caused by circulating vaccine-derived poliovirus type 1 following isolation of genetically linked virus from a patient with paralysis and nonhousehold community contacts.
Changing causes of death for patients with chronic respiratory disease in England, 2005-2015
Authors: Alicia V Gayle, Eleanor L Axson, Chloe I Bloom, Vidya Navaratnam, Jennifer K Quint
Journal: Thorax (2019)

Background Chronic respiratory diseases (CRD) are common, are increasing in prevalence, and cause significant morbidity and mortality worldwide. However, we have limited knowledge on causes of death of patients with CRD in the general population. Objective We evaluated mortality rates and causes of death over time in patients with CRD. Methods We used linked primary care and mortality data to determine mortality rates and the most common causes of death in people with CRD (including asthma, bronchiectasis, COPD and interstitial lung diseases (ILD)) during 2005–2015 in England. Results We identified 558 888 patients with CRD (451 830 asthma, 137 709 COPD, 19 374 bronchiectasis, 10 745 ILD). The age-standardised mortality rate of patients with CRD was 1607 per 100 000 persons (asthma=856, COPD=1503, ILD=2609, bronchiectasis=1463). CRD mortality was overall 54% higher than the general population. A third of patients with CRD died from respiratory-related causes. Respiratory-related mortality was constant, while cardiovascular-related mortality decreased significantly over time. COPD accounted for the majority of respiratory-related deaths (66% overall) in all patient groups except ILD. Conclusions Patients with CRD continue to experience substantial morbidity and mortality due to respiratory diseases. Disease-modifying intervention strategies are needed to improve outcomes for patients with CRD.
Financial Hardship From Medical Bills Among Nonelderly U.S. Adults With Atherosclerotic Cardiovascular Disease
Authors: Javier Valero-Elizondo, Rohan Khera, Anshul Saxena, Gowtham R. Grandhi, Salim S. Virani, Javed Butler, Zainab Samad, Nihar R. Desai, Harlan M. Krumholz, Khurram Nasir
Journal: Journal of the American College of Cardiology (2019)
Provider-volume associated with variable receipt of therapy and outcomes for noncurative pancreas adenocarcinoma: A population-based analysis.
Authors: Julie I. Hallet, Laura Davis, Michail Mavros, Alyson L. Mahar, Kaitlyn Beyfuss, Ying Liu, Erin Diane Kennedy, Craig Earle, Natalie G. Coburn
Journal: Journal of Clinical Oncology (2019)

352 Background: While high-volume providers for pancreatic adenocarcinoma (PA) surgery yield better outcomes, variation in practice and the role of provider-volume has not been investigated for systemic therapy. We examined variation in practice and outcomes in the management of non-curative PA, based on medical oncology provider-volume. Methods: We conducted a population based retrospective cohort study of non-resected PA over 2005-2016 by linking administrative healthcare datasets. High-volume (HV) medical-oncology providers were defined as the 5th quintile of number of PA seen per provider per year. Outcomes were receipt of chemotherapy and overall survival (OS). Brown Forsythe Levene (BFL) test for equality of variances assessed outcomes variability between provider-volume quintiles (Q1 to 5). Multivariate regressions examined the association between management by HV provider and receipt of systemic therapy and OS. Results: Of 10,881 non-curative PA patients, 7,062 consulted with medical oncology. Among 341 medical oncology providers, 3% were HV, defined as &gt; 16 patients/year. There was variability in receipt of chemotherapy based on provider-volume, with 44% (IQR: 25-54) for Q1 and 47% (IQR: 43-54) for Q5, and in median survival, with 4.1 months (IQR: 2.7-6.2) for Q1 and 7.5 months (IQR: 6.6-8.0) for Q5. Variability between provider-volume quintiles was significant for receipt of chemotherapy and median survival (both BFL p &lt; 0.001). After adjusting for age, sex, comorbidity burden, rurality, income quintile, and diagnosis year, HV provider was independently associated with higher odds of receiving chemotherapy (OR 1.19 [1.05-1.34]), and superior OS (HR 0.79 [0.74-0.84]). Conclusions: There was significant variation in non-curative management and outcomes of PA based on provider-volume. Management by a HV provider was independently associated with higher odds of receiving chemotherapy and superior OS, after adjusting for case-mix. This information is important to inform disease care pathways and care organization. Cancer care systems could consider initiatives to increase the number of HV providers to reduce variation and improve outcomes.
Genome-wide identification of circulating-miRNA expression quantitative trait loci reveals the role of several miRNAs in the regulation of cardiometabolic phenotypes
Authors: Majid Nikpay, Kaitlyn Beehler, Armand Valsesia, Jorg Hager, Mary-Ellen Harper, Robert Dent, Ruth McPherson
Journal: Cardiovascular Research (2019)

To identify genetic variants that have a regulatory impact on circulating microRNAs (miRNAs) and to connect genetic risk to blood traits/biomarkers through the circulating miRNAs.Leveraging miRNA-Seq data and the 1000 Genomes imputed genotypes, we carried out genome-wide association analysis for SNPs that regulate the expression of circulating miRNAs in a sample of 710 unrelated subjects of European ancestry. Wherever possible, we used data from the Framingham and the Geuvadis studies to replicate our findings. We found at least one genome-wide significant (P < 5e-8) miRNA-eQTL (mirQTL) for 143 circulating miRNAs. Overall each mirQTL explained a small portion (<1%) of variation in miRNA levels; however, we identified a few mirQTLs that explained 4% to 20% of variation in miRNA levels in plasma. Unlike trans-mirQTLs (P = 0.7), cis-mirQTLs tend to be also associated with their counterpart mature miRNAs (P < 0.0001), this suggests trans-mirQTLs exert their effect through processes that affect the stability of mature miRNAs; whereas, cis-mirQTLs mainly regulate the expression of primary-miRNAs. Next, we used the identified mirQTLs to investigate the links between circulating miRNAs with blood traits/biomarkers through Mendelian randomization analysis. We found miR-1908-5p plays an important role in regulating low-density lipoprotein (LDL), total cholesterol (TC), fasting glucose, HbA1c, and several lipid-metabolites in blood, whereas, miR-10b-5p mediates the trans-regulatory effect of the ABO locus on several blood proteins, coronary artery disease, and TC. Moreover, we demonstrated that a higher plasma level of miR-199a is causally associated with lower levels of LDL and TC. Finally, we found miR-143-3p and miR-145-5p are functionally related and mediate the effect of ZFPM2 on a number of its protein targets in blood including VEGFA, SERPINE1, and PDGFs.This study identifies SNPs that have a regulatory impact on circulating miRNAs, and underlines the role of several circulating miRNAs in mediating the effect of a number of GWAS loci on cardiometabolic phenotypes.
Increased Response to Higher Dose Lanadelumab in Hereditary Angioedema Patients: Exploratory Findings From the HELP and HELP OLE Studies
Authors: Joshua S. Jacobs, Jonathan Bernstein, Mark Davis-Lorton, H. Henry Li, Daniel F. Soteres, Christina Nurse, Kim Paes, Daniel J. Sexton, Hilary Longhurst
Journal: Journal of Allergy and Clinical Immunology (2019)
Inhibition of the dipeptidyl peptidase DPP4 (CD26) reveals IL-33-dependent eosinophil-mediated control of tumor growth
Authors: Clémence Hollande, Jeremy Boussier, James Ziai, Tamaki Nozawa, Vincent Bondet, Wilson Phung, Binfeng Lu, Darragh Duffy, Valerie Paradis, Vincent Mallet, Gérard Eberl, Wendy Sandoval, Jill M. Schartner, Stanislas Pol, Rosa Barreira da Silva, Matthew L. Albert
Journal: Nature Immunology (2019)
Etanercept and Methotrexate as Monotherapy or in Combination for Psoriatic Arthritis: Primary Results From a Randomized, Controlled Phase <scp>III</scp> Trial
Authors: Philip J. Mease, Dafna D. Gladman, David H. Collier, Christopher T. Ritchlin, Philip S. Helliwell, Lyrica Liu, Gregory Kricorian, James B. Chung
Journal: Arthritis & Rheumatology (2019)

To examine the efficacy of methotrexate monotherapy relative to etanercept monotherapy and the value of combining methotrexate and etanercept for the treatment of patients with psoriatic arthritis (PsA).In this double-blind study, 851 patients with PsA were randomized to 1 of 3 treatment arms, as follows: oral methotrexate (20 mg) plus subcutaneous placebo given weekly (n = 284), subcutaneous etanercept (50 mg) plus oral placebo given weekly (n = 284), or subcutaneous etanercept (50 mg) plus oral methotrexate (20 mg) given weekly (combination therapy; n = 283). The American College of Rheumatology 20% improvement (ACR20) response and Minimal Disease Activity (MDA) response at week 24 were the primary end point and key secondary end point, respectively. Other measures of inflammatory arthritis, radiographic progression, and nonarticular disease manifestations were also assessed.Patients with PsA had a mean ± SD age of 48.4 ± 13.1 years, and the mean ± SD duration of PsA was 3.2 ± 6.3 years (median 0.6 years). ACR20 and MDA response rates at week 24 were significantly greater in patients who received etanercept monotherapy compared with those who received methotrexate monotherapy (ACR20, 60.9% versus 50.7% of patients [P = 0.029]; MDA, 35.9% versus 22.9% of patients [P = 0.005]), and both were significantly greater in the combination therapy group compared with the methotrexate monotherapy group at week 24 (ACR20, 65.0% versus 50.7% of patients [P = 0.005]; MDA, 35.7% versus 22.9% of patients [P = 0.005]). Other secondary outcomes (ACR50 and ACR70 response rates, proportions of patients achieving a Very Low Disease Activity score, and PsA disease activity scores) showed between-group differences that were consistent with the primary and key secondary end point results. Furthermore, patients in both etanercept treatment arms showed less radiographic progression at week 48 compared with patients who received methotrexate monotherapy. Outcomes were similar in the combination therapy and etanercept monotherapy groups, except for some skin end points. No new safety signals were seen.Etanercept monotherapy and combination therapy with etanercept and methotrexate showed greater efficacy than methotrexate monotherapy in patients with PsA, according to the ACR and MDA response rates and extent of radiographic progression at follow-up. Overall, combining methotrexate and etanercept did not improve the efficacy of etanercept.
Continuous adaptation of the HA and NA gene of H3N2 subtypes of avian influenza virus in South China, 2017–2018
Authors: Jingkai Hu, Yunfeng Zha, Xuanjiang Jin, Xiaohui Wen, Zhixian Li, Xiao Wang, Yixue Dai, Xiao Li, Ming Liao, Weixin Jia
Journal: Journal of Infection (2019)
Characteristics of School-Associated Youth Homicides — United States, 1994–2018
Authors: Kristin M. Holland, Jeffrey E. Hall, Jing Wang, Elizabeth M. Gaylor, Linda L. Johnson, Daniel Shelby, Thomas R. Simon
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

To understand trends and characteristics in school-associated homicides involving youths, data from CDC's School-Associated Violent Death Surveillance System were analyzed for 393 single-victim incidents that occurred during July 1994-June 2016 and 38 multiple-victim incidents (resulting in 121 youth homicides) during July 1994-June 2018. School-associated homicides consistently represent <2% of all youth homicides in the United States (1,2). The overall 22-year trend for single-victim homicide rates did not change significantly. However, multiple-victim incidence rates increased significantly from July 2009 to June 2018. Many school-associated homicides, particularly single-victim incidents, are similar to youth homicides unrelated to schools, often involving male, racial/ethnic minority youth victims, and occurring in urban settings. The majority of both single-victim (62.8%) and multiple-victim (95.0%) homicides were from a firearm-related injury. A comprehensive approach to violence prevention is needed to reduce risk for violence on and off school grounds.
l-Ornithine l-Aspartate (LOLA) for Hepatic Encephalopathy in Cirrhosis: Results of Randomized Controlled Trials and Meta-Analyses
Authors: Roger F. Butterworth, Mark J. W. McPhail
Journal: Drugs (2019)

This manuscript represents an appraisal of the evidence in support of L-ornithine-L-aspartate (LOLA) for the management and treatment of hepatic encephalopathy (HE) in cirrhosis. Meta-analyses of randomized controlled trials (RCTs) conducted over the last two decades generally reveal evidence of benefit of LOLA in a range of clinical presentations. This included improvement of mental state grade in overt HE (OHE) assessed by West Haven criteria as well as in minimal HE (MHE) assessed by psychometric testing where the oral formulation of LOLA was determined to be particularly effective. However, concerns over study quality were noted in one meta-analysis. Nevertheless, the concomitant lowering of fasting blood ammonia was reported in all RCTs using this endpoint. Network meta-analyses showed that LOLA appears to be comparable (or superior) in efficacy to non-absorbable disaccharides or probiotics. Emerging evidence from single RCTs show efficacy of LOLA for the treatment of post-transjugular intrahepatic portosystemic shunt (TIPSS) HE as well as for secondary HE prophylaxis. These findings provide support for the use of LOLA in the treatment of HE and future trials should focus on the use of LOLA for prophylaxis.
Meeting report from the joint IARC–NCI international cancer seminar series: a focus on colorectal cancer
Authors: M.J. Gunter, S. Alhomoud, M. Arnold, H. Brenner, J. Burn, G. Casey, A.T. Chan, A.J. Cross, E. Giovannucci, R. Hoover, R. Houlston, M. Jenkins, P. Laurent-Puig, U. Peters, D. Ransohoff, E. Riboli, R. Sinha, Z.K. Stadler, P. Brennan, S.J. Chanock
Journal: Annals of Oncology (2019)

Despite significant progress in our understanding of the etiology, biology and genetics of colorectal cancer, as well as important clinical advances, it remains the third most frequently diagnosed cancer worldwide and is the second leading cause of cancer death. Based on demographic projections, the global burden of colorectal cancer would be expected to rise by 72% from 1.8 million new cases in 2018 to over 3 million in 2040 with substantial increases anticipated in low- and middle-income countries. In this meeting report, we summarize the content of a joint workshop led by the National Cancer Institute and the International Agency for Research on Cancer, which was held to summarize the important achievements that have been made in our understanding of colorectal cancer etiology, genetics, early detection and treatment and to identify key research questions that remain to be addressed.
Combination Therapy as First-Line Treatment in Metastatic Renal-Cell Carcinoma
Authors: Bernard Escudier
Journal: New England Journal of Medicine (2019)

The treatment of metastatic renal-cell carcinoma has been revolutionized twice in the past 12 years by data showing that vascular endothelial growth factor (VEGF) inhibition can induce tumor shrinkage and increase progression-free survival and that immune checkpoint inhibitors can induce durable responses and increase overall survival among patients with this form of cancer. Guidelines for the treatment of metastatic renal-cell carcinoma have changed dramatically to recommend agents that target these two major pathways. In 2007, a trial showed that sunitinib, a tyrosine kinase inhibitor with potent VEGF inhibition, was superior to interferon alfa, and sunitinib became a new standard of . . .
Quality of life in men living with advanced and localised prostate cancer in the UK: a population-based study
Authors: Amy Downing, Penny Wright, Luke Hounsome, Peter Selby, Sarah Wilding, Eila Watson, Richard Wagland, Paul Kind, David W Donnelly, Hugh Butcher, James W F Catto, William Cross, Malcolm Mason, Linda Sharp, David Weller, Galina Velikova, Eilis McCaughan, Rebecca Mottram, Majorie Allen, Therese Kearney, Oonagh McSorley, Dyfed W Huws, David H Brewster, Emma McNair, Anna Gavin, Adam W Glaser
Journal: The Lancet Oncology (2019)