tbuckley/cabot-search huggingface dataset:
Abstract B28: HPV-related oropharyngeal cancer: Knowledge and beliefs among staff at community-based HIV/AIDS service organizations (ASOs)
Authors: Aditi Tomar, Hannah Catherine Balcezak, Lisa Tisdale Wigfall
Journal: Clinical Cancer Research (2020)

Abstract This study explores knowledge and beliefs about HPV-related oropharyngeal cancer among ASO staff (n=51) from five ASOs located in South Carolina (N=3/5 ASOs; N=30/51 staff) and Texas (N=2/5 ASOs; N=21/51 staff). ASO staff completed a 118-item, self-administered needs assessment survey. Data were analyzed using Stata/SE 15.1. ASO staff (n=51) were 78% non-Hispanic Black [mean age (years): 44.2 ± 12.8 SD]; range 21.6-68.2. More than half (59%) were females and predominantly heterosexual (61%). Most (67%) had at least an undergraduate degree, and 65% had more than five years of experience working with HIV-positive clients. Only 18% had ever looked for information about oropharyngeal cancer. Almost half (48%) were not sure about the role of HPV in causing oropharyngeal cancer, and fewer (31%) thought that the HPV vaccine is pretty/very successful in preventing oropharyngeal cancer. Over half (53%) did not think that a woman can do much to reduce her chances of getting HPV, and 60% believed the same for men. Very few (16%) thought of smoking as a risk factor for HPV-related health problems such as genital warts and cancer. A large proportion (73%) thought that quitting smoking can have a huge impact in lowering its harmful effects. People living with HIV (PLWH) are disproportionately affected by HPV-related oropharyngeal cancer. ASO staff play an instrumental role in educating their clients about HIV/AIDS-related health topics, and therefore fostering their knowledge and beliefs about HPV-related oropharyngeal cancer could help improve outcomes for PLWH. Citation Format: Aditi Tomar, Hannah Catherine Balcezak, Lisa Tisdale Wigfall. HPV-related oropharyngeal cancer: Knowledge and beliefs among staff at community-based HIV/AIDS service organizations (ASOs) [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B28.
Abstract 4757: TNFAIP8 facilitates metabolic reprogramming in prostate cancer cells
Authors: Suryakant Niture, Minghui Lin, Joab O. Odera, John Moore, Deepak Kumar
Journal: Cancer Research (2020)

Abstract Tumor necrosis factor-α-induced protein 8 (TNFAIP8), a member of TIPE/TNFAIP8 family, has been associated with multiple oncogenic roles in human cancers. Here we investigated the role of TNFAIP8 in metabolic reprogramming in prostate cancer (PCa) cells. Ectopic expression of TNFAIP8 increased cell survival/proliferation by enhancing metabolic activity in PCa cells. TNFAIP8 activated the PI3K-AKT pathway and up-regulated the expression of cell proliferation markers, cell cycle-related proteins, and PCa stem cell markers. TNFAIP8 was also found to regulate the expression of glucose metabolizing enzymes, enhancing glucose consumption, and endogenous ATP production. Treatment with glycolysis inhibitor 2-deoxyglucose (2-DG) reduced TNFAIP8 mediated glucose consumption /ATP production and spheroid formation in PCa cells. Moreover, TNFAIP8 maintained mitochondrial membrane potential and increased glycolysis/oxidative phosphorylation. These changes were also consistent with an observed altered metabolomic profile in PCa cells transfected with TNFAIP8. Collectedly, our data suggest that TNFAIP8 exerts its oncogenic effects by enhancing glucose metabolism and by facilitating metabolic reprogramming in PCa cells. Citation Format: Suryakant Niture, Minghui Lin, Joab O. Odera, John Moore, Deepak Kumar. TNFAIP8 facilitates metabolic reprogramming in prostate cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4757.
Abstract 2596: Toll like receptor 4 as a potential DNA repair modulator in U87MG-GBM cells
Authors: Isabele F. Moretti, Antonio Lerario, Sueli M. Oba-Shinjo, Suely K. Marie, Marina Trombetta Lima
Journal: Cancer Research (2020)

Abstract Toll like receptor 4 (TLR4) has a dual role in cellular fate, depending on the stimuli and microenvironment context. Its activation may promotes cell survival and proliferative phenotype via MyD88 with NFkB activation, or leads to cell death via TRIF. Glioblastoma (GBM), grade IV astrocytoma, is the most common and aggressive primary malignancy in the brain. Surgical tumor cytoreduction followed by radiotherapy and adjunct chemotherapy with Temozolomide (TMZ) have been considered the standard of care for GBM. And, in spite of several combinatory rescue therapeutic trials, the median overall survival of GBM patients continue to be approximately 15 months. In this context, new therapeutic strategies are urgent, and immune modulation has demonstrated optimistic results in several tumor types. Therefore, the aim of this study was to analyze the role of TLR4 in human astrocytomas. First, we evaluated TLR4 expression in 140 human astrocytoma of different grades of malignancy, by qRT-PCR. TLR4 molecular signaling pathways were investigated through LPS stimuli in U87MG-GBM cell line. In astrocytoma samples, TLR4 was up-regulated when compared to brain non-neoplastic samples (p&amp;lt;0.05, Kruskall Wallis and Dunn tests), with increased expression in Mesenchymal compare to Classical and Proneural subtypes. U87MG cells stimulation with LPS (10ug/ml) lead to NF-kB (p65) nuclear translocation after 12hr through western blot and immunofluorescence, which was unexpected as such translocation through the MyD88/TRAF6 canonical pathway occurs within 30min to 2hr after LPS stimulation. TRIF, IL1B, RIPK1/3 expressions were increased after LPS stimulation, suggesting an activation of inflammasome and ripoptosome pathways. Moreover, the combined LPS treatment with TMZ showed a higher apoptotic rate after 48hr when compared to TMZ alone. However, the transcriptomic analysis by RNASeq of U87MG cells after LPS stimulation showed an upregulation of DNA repair genes, particularly MBD4 and PLAUR. Both genes are upregulated in mesenchymal GBM subtype in the TCGA RNASeq dataset, and they present correlated expression with TLR4 (r=0.406, p=0.004 and r=0.338, p=0.019 by Spearman's test). Our results suggest that the anti-tumoral effect by TLR4 pathway activation by enhancement of tumor apoptosis might be more efficient with combined inhibition of DNA repair cascade. In fact, OSI-296 and BKM-120 have shown to decrease MBD4 expression, and increased overall survival was observed in a phase II clinical trial for solid tumor. Citation Format: Isabele F. Moretti, Antonio Lerario, Sueli M. Oba-Shinjo, Suely K. Marie, Marina Trombetta Lima. Toll like receptor 4 as a potential DNA repair modulator in U87MG-GBM cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2596.
Trends in Diagnosis and Disparities in Initial Management of High-Risk Prostate Cancer in the US
Authors: Vishesh Agrawal, Xiaoyue Ma, Jim C. Hu, Christopher E. Barbieri, Himanshu Nagar
Journal: JAMA Network Open (2020)

This retrospective study uses data from the National Cancer Database of new cancer diagnoses across the US to examine trends in proportional diagnosis rates and management of patients with high-risk prostate cancer.
Imaging technology of the lymphatic system
Authors: Anna K. Polomska, Steven T. Proulx
Journal: Advanced Drug Delivery Reviews (2020)

The lymphatic system plays critical roles in tissue fluid homeostasis and immunity and has been implicated in the development of many different pathologies, ranging from lymphedema, the spread of cancer to chronic inflammation. In this review, we first summarize the state-of-the-art of lymphatic imaging in the clinic and the advantages and disadvantages of these existing techniques. We then detail recent progress on imaging technology, including advancements in tracer design and injection methods, that have allowed visualization of lymphatic vessels with excellent spatial and temporal resolution in preclinical models. Finally, we describe the different approaches to quantifying lymphatic function that are being developed and discuss some emerging topics for lymphatic imaging in the clinic. Continued advancements in lymphatic imaging technology will be critical for the optimization of diagnostic methods for lymphatic disorders and the evaluation of novel therapies targeting the lymphatic system.
Autoantibody-negative insulin-dependent diabetes mellitus after SARS-CoV-2 infection: a case report
Authors: Tim Hollstein, Dominik M. Schulte, Juliane Schulz, Andreas Glück, Anette G. Ziegler, Ezio Bonifacio, Mareike Wendorff, Andre Franke, Stefan Schreiber, Stefan R. Bornstein, Matthias Laudes
Journal: Nature Metabolism (2020)
Abstract 1542: Roles of extracellular ATP in inducing EMT and CSC-like changes to promote early steps of metastasis in non-small lung cancer cell lines
Authors: Jingwen Song, Maria Evers, Xiaozhuo Chen
Journal: Cancer Research (2020)

Abstract Cancer is a major death-causing disease worldwide, and metastasis, a hallmark of cancer, is associated with up to 90% of all cancer-related deaths. Metastasis requires ATP, and the tumor microenvironment (TME) has much higher concentrations of intratumoral and extracellular ATP (eATP) than healthy tissue, implying that eATP may have potential roles in tumor development and progression. Our previous ATP studies, cited by a Nature Review Cancer paper in 20181 showed that eATP is internalized by cancer cell through macropinocytosis, and it promotes cancer cell growth, survival, and drug resistance. However, how intratumoral eATP plays roles in metastasis remains largely unclear. Our 2019 published results show that eATP promotes cancer migration and invasion, initiates epithelial to mesenchymal transition (EMT), alters expression level of EMT related protein markers such as ZEB1, SNAIL, SLUG in human non-small lung cancer cell (NSCLC) lines2. It has been reported that the EMT and cancer stem cells (CSCs) share some molecular links, but the detailed mechanisms involved are still unknown. Recently, we have found the eATP significantly induces the gene expression level of CSC transcription factors (TFs): SOX2, NANOG and OCT4 in A549 cells in a time-dependent manner. We have also found that, after A549 cells were pretreated with 0.5mM for 6 hrs, the ATP-pretreated A549 cells were able to show significantly increased migration and invasion even in the absence of ATP addition. Based on all these results, we hypothesize that extracellular ATP functions as a messenger, a signal facilitator, an energy molecule, and a transcription cofactor to induce EMT and CSC-like features to promote metastasis in NSCLC. RNAseq and metabolomics studies are being used to determine the transcriptional and metabolic changes associated with the ATP induced EMT and CSC process in NSCLC. The completion of the project will not only unravel eATP's roles in EMT and CSC induction and early steps of tumor metastasis, but also potentially provide novel promising therapeutic targets for inhibiting tumor metastasis. Citation Format: Jingwen Song, Maria Evers, Xiaozhuo Chen. Roles of extracellular ATP in inducing EMT and CSC-like changes to promote early steps of metastasis in non-small lung cancer cell lines [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1542.
Gabapentin in pregnancy and the risk of adverse neonatal and maternal outcomes: A population-based cohort study nested in the US Medicaid Analytic eXtract dataset
Authors: Elisabetta Patorno, Sonia Hernandez-Diaz, Krista F. Huybrechts, Rishi J. Desai, Jacqueline M. Cohen, Helen Mogun, Brian T. Bateman
Journal: PLoS Medicine (2020)

Background Despite the widespread use, only sparse information is available on the safety of gabapentin during pregnancy. We sought to evaluate the association between gabapentin exposure during pregnancy and risk of adverse neonatal and maternal outcomes. Methods and findings Using the United States Medicaid Analytic eXtract (MAX) dataset, we conducted a population-based study of 1,753,865 Medicaid-eligible pregnancies between January 2000 and December 2013. We examined the risk of major congenital malformations and cardiac defects associated with gabapentin exposure during the first trimester (T1), and the risk of preeclampsia (PE), preterm birth (PTB), small for gestational age (SGA), and neonatal intensive care unit admission (NICUa) associated with gabapentin exposure early, late, or both early and late in pregnancy. Gabapentin-unexposed pregnancies served as the reference. We estimated relative risks (RRs) and 95% confidence intervals (CIs) using fine stratification on the propensity score (PS) to control for over 70 confounders (e.g., maternal age, race/ethnicity, indications for gabapentin, other pain conditions, hypertension, diabetes, use of opioids, and specific morphine equivalents). We identified 4,642 pregnancies exposed in T1 (mean age = 28 years; 69% white), 3,745 exposed in early pregnancy only (28 years; 67% white), 556 exposed in late pregnancy only (27 years; 60% white), and 1,275 exposed in both early and late pregnancy (29 years; 75% white). The reference group consisted of 1,744,447 unexposed pregnancies (24 years; 40% white). The adjusted RR for major malformations was 1.07 (95% CI 0.94–1.21, p = 0.33) and for cardiac defects 1.12 (0.89–1.40, p = 0.35). Requiring ≥2 gabapentin dispensings moved the RR to 1.40 (1.03–1.90, p = 0.03) for cardiac defects. There was a higher risk of preterm birth among women exposed to gabapentin either late (RR, 1.28 [1.08–1.52], p < 0.01) or both early and late in pregnancy (RR, 1.22 [1.09–1.36], p < 0.001), SGA among women exposed to gabapentin early (1.17 [1.02–1.33], p = 0.02), late (1.39 [1.01–1.91], p = 0.05), or both early and late in pregnancy (RR, 1.32 [1.08–1.60], p < 0.01), and NICU admission among women exposed to gabapentin both early and late in pregnancy (RR, 1.35 [1.20–1.52], p < 0.001). There was no higher risk of preeclampsia among women exposed to gabapentin after adjustment. Study limitations include the potential for residual confounding and exposure misclassification. Conclusions In this large population-based study, we did not find evidence for an association between gabapentin exposure during early pregnancy and major malformations overall, although there was some evidence of a higher risk of cardiac malformations. Maternal use of gabapentin, particularly late in pregnancy, was associated with a higher risk of PTB, SGA, and NICUa.
The times they are a-changin' (for NAFLD as well)
Authors: Vlad Ratziu, Mary Rinella, Ulrich Beuers, Rohit Loomba, Quentin M. Anstee, Stephen Harrison, Sven Francque, Arun Sanyal, Philip N. Newsome, Zobair Younossi
Journal: Journal of Hepatology (2020)
P-COSCA (Pediatric Core Outcome Set for Cardiac Arrest) in Children: An Advisory Statement From the International Liaison Committee on Resuscitation
Authors: Alexis A. Topjian, Barnaby R. Scholefield, Neethi P. Pinto, Ericka L. Fink, Corinne M.P. Buysse, Kirstie Haywood, Ian Maconochie, Vinay M. Nadkarni, Allan de Caen, Raffo Escalante-Kanashiro, Kee-Chong Ng, Gabrielle Nuthall, Amelia G. Reis, Patrick Van de Voorde, Stacy J. Suskauer, Stephen M. Schexnayder, Mary Fran Hazinski, Beth S. Slomine
Journal: Circulation (2020)

Studies of pediatric cardiac arrest use inconsistent outcomes, including return of spontaneous circulation and short-term survival, and basic assessments of functional and neurological status. In 2018, the International Liaison Committee on Resuscitation sponsored the COSCA initiative (Core Outcome Set After Cardiac Arrest) to improve consistency in reported outcomes of clinical trials of adult cardiac arrest survivors and supported this P-COSCA initiative (Pediatric COSCA). The P-COSCA Steering Committee generated a list of potential survival, life impact, and economic impact outcomes and assessment time points that were prioritized by a multidisciplinary group of healthcare providers, researchers, and parents/caregivers of children who survived cardiac arrest. Then expert panel discussions achieved consensus on the core outcomes, the methods to measure those core outcomes, and the timing of the measurements. The P-COSCA includes assessment of survival, brain function, cognitive function, physical function, and basic daily life skills. Survival and brain function are assessed at discharge or 30 days (or both if possible) and between 6 and 12 months after arrest. Cognitive function, physical function, and basic daily life skills are assessed between 6 and 12 months after cardiac arrest. Because many children have prearrest comorbidities, the P-COSCA also includes documentation of baseline (ie, prearrest) brain function and calculation of changes after cardiac arrest. Supplementary outcomes of survival, brain function, cognitive function, physical function, and basic daily life skills are assessed at 3 months and beyond 1 year after cardiac arrest if resources are available.
Abstract 16160: Female Cardiologists Are More Likely to Refer Patients With Coronary Heart Disease to Cardiac Rehabilitation Than Male Cardiologists
Authors: Lue Lao, Santiago R Nuño, Nainjot Bains, Michelle Hsu, Armando Gallegos, Yu-Xuan Dang, Kyle Udd-Garnica, Ignacio Zepeda, Luis R Castellanos
Journal: Circulation (2018)

Background: Cardiac rehabilitation (CR) improves quality of life and survival in patients with coronary heart disease (CHD). However, CR is often underutilized amongst patients with CHD, which may ...
Surgery of the Biliary Tract
Authors: Marshall K. Bartlett, William C. Quinby
Journal: New England Journal of Medicine (1957)

THE results of the treatment of acute and chronic cholecystitis at the Massachusetts General Hospital from 1943 to 1953 have been reported in two previous papers.1 , 2 Most patients who have symptoms from cholecystitis and cholelithiasis are relieved by cholecystectomy, accompanied by choledochostomy when indicated. A few have symptoms that continue or recur after a variable interval of good health. They present difficult problems of diagnosis and treatment, and the outcome is not always satisfactory.The purpose of the present study was to review our experience with patients who had two or more definitive operations on the biliary tract for symptoms . . .
Abstract 488: Establishing consistent methods for the generation of donor-derived iPSCs from T cell subsets
Authors: Mark Landon, Chad C. MacArthur, Melissa E. Hernandez, Uma Lakshmipathy, Jerry Guzman
Journal: Cancer Research (2020)

Abstract T cell-based immunotherapies offer a potent and specific solution to grievous diseases such as cancer and viral infections. Expansion and re-infusion of antigen specific T cells has seen success in the treatment of metastatic melanoma and prevention of viral infections such as CMV and EBV. Additionally, engineered T cell therapies, especially chimeric antigen receptor (CAR) T cells, have been met with great clinical success and spurred innovation within the field of cellular immunotherapies. While promising, these therapies rely on sourcing T cells from donor derived blood. This process is invasive to the patient, especially when multiple or prolonged blood draws are required to obtain sufficient T cell numbers. Additionally, T cells sourced from diseased patients are often exhausted and display significantly perturbed growth and dysfunctional responses to antigen stimulation. An appealing alternative is somatic reprogramming of T cells to generate induced pluripotent stem cells (iPSCs) and differentiated into rejuvenated T cells that retain the original TCR, particularly with tumor infiltrating lymphocytes or viral specific T cells. We had previously reported a Sendai-virus based CytoTune 2.1 Reprogramming specifically designed for translational and clinical research. In this study we examine the effect of various cellular phenotypes and optimize methods for consistent reprogramming of multiple donor T cell reprogramming. Additionally, pan CD3+ cells isolated using different methods and further enriched for CD4+ and CD8+ were successfully reprogrammed. The resulting iPSCs were extensively characterized to ensure that pluripotency was achieved and that TCR sequences were preserved. This approach of reprogramming T cells and specific cell subtypes to derive iPSC with a known TCR sequence enables their use for downstream application as a renewable source of T cells with known antigen specificity. Citation Format: Mark Landon, Chad C. MacArthur, Melissa E. Hernandez, Uma Lakshmipathy, Jerry Guzman. Establishing consistent methods for the generation of donor-derived iPSCs from T cell subsets [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 488.
Deletion 7q Is Associated with KLF2 and NOTCH2 Mutations and Is Strongly Correlated with Splenic Marginal Zone Lymphoma but Also Found in Lymphoplasmacytic Lymphoma and Hairy Cell Leukemia Variant
Authors: Alexander Höllein, Anna Stengel, Manja Meggendorfer, Annette Fasan, Wolfgang Kern, Torsten Haferlach, Claudia Haferlach
Journal: Blood (2017)
Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study
Authors: Jeremy S Abramson, M Lia Palomba, Leo I Gordon, Matthew A Lunning, Michael Wang, Jon Arnason, Amitkumar Mehta, Enkhtsetseg Purev, David G Maloney, Charalambos Andreadis, Alison Sehgal, Scott R Solomon, Nilanjan Ghosh, Tina M Albertson, Jacob Garcia, Ana Kostic, Mary Mallaney, Ken Ogasawara, Kathryn Newhall, Yeonhee Kim, Daniel Li, Tanya Siddiqi
Journal: The Lancet (2020)
Postmarket Clinical Evidence for High-Risk Therapeutic Medical Devices Receiving Food and Drug Administration Premarket Approval in 2010 and 2011
Authors: Vinay K. Rathi, Harlan M. Krumholz, Frederick A. Masoudi, Joseph S. Ross
Journal: JAMA Network Open (2020)

Our results suggest that patients and clinicians may have limited evidence available to inform treatment decisions about high-risk medical devices up to a decade after approval.Policy makers should consider measures to promote timely completion and reporting of postmarket studies.These approaches could include enforcing financial penalties for failure to report results on ClinicalTrials.govor funding independent comparative effectiveness research using milestone payments linked to study progress and publication.