tbuckley/cabot-search huggingface dataset:
Abstract B17: Interleukin-17 and -22 expression in non-small cell lung cancer
Authors: Julia Stump, Yue Jiang, Clara Karches, Javier Suárez Gosálvez, Jens Neumann, Sebastian Kobold, Rudolf Hatz, Hauke Winter, Amanda Tufman, Rudolf M. Huber, Simone Reu
Journal: Clinical Cancer Research (2018)

Abstract Background: In non-small cell lung cancer (NSCLC) the TNM staging remains standard for prognostic assessment and therapy decisions. Nevertheless, stage-specific outcomes vary significantly, indicating a need for additional prognosticators. In this retrospective study we wanted to assess the role of the mediator interleukin-22 (IL-22), as IL-22 is known to be involved in various lung diseases and to be elevated in lung cancer patients. Moreover, we evaluated interleukin-17 (IL-17), which also depicts a proinflammatory cytokine, but seems to play a dual role in antitumor immunity. We asked the question of their link to prognosis, therapy response and recurrence. Methods: Tissue microarrays (TMAs) were generated from formalin-fixed, paraffin embedded tissue of 138 curatively resected patients with stage IA-IV NSCLC. TMAs included each three cores from the tumor center (CT) and invasive margin (IM), selected from areas with the most dense lymphocytic infiltrates. IL-22 and IL-17 expression of the tissue was analyzed by immunohistochemistry via cytoplasmic staining (double-staining: IL-22, CD3 resp. IL-17, CD3). Results: IL-22 expression status in adeno and SCC does not seem to have a prognostic impact on survival, regardless of the localization. However, a high IL-22 CT/IM ratio in adenocarcinoma is clearly linked to longer overall survival; this cannot be seen in SCC. For IL-17 a distinct tendency is visible for adeno and SCC in the invasive margin as well as in the tumor center—interestingly, this is more clear for SCC. In SCC a high CT/IM ratio for IL-17 seems to have a positive prognostic impact on overall survival. Patient numbers will be enlarged to validate these findings. Conclusion: The cytokines IL-22 and IL-17 seem—depending on histology and location—to have a prognostic impact on overall survival in NSCLC. In previous experiments we showed that multispectral assessment of CD8 and PD-L1 has a clear correlation with clinical outcome. Adding cytokines to this method might open novel avenues for predicting clinical outcome and therapeutic efficacy in NSCLC. Citation Format: Julia Stump, Yue Jiang, Clara Karches, Javier Suárez Gosálvez, Jens Neumann, Sebastian Kobold, Rudolf Hatz, Hauke Winter, Amanda Tufman, Rudolf M. Huber, Simone Reu. Interleukin-17 and -22 expression in non-small cell lung cancer [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr B17.
Toxicity‐Attenuated Glycol Chitosan Adhesive Inspired by Mussel Adhesion Mechanisms
Authors: Eunsook Park, Jeehee Lee, Kang Moo Huh, Soo Hyeon Lee, Haeshin Lee
Journal: Advanced Healthcare Materials (2019)

Abstract Chitosan‐catechol, inspired from mussel‐adhesive‐proteins, is characterized by the formation of an adhesive membrane complex through instant bonding with serum proteins not found in chitosan. Using this intrinsic property, chitosan‐catechol is widely applied for hemostatic needles, general hemostatic materials, nanoparticle composites, and 3D printing. Despite its versatility, the practical use of chitosan‐catechol in the clinic is limited due to its undesired immune responses. Herein, a catechol‐conjugated glycol chitosan is proposed as an alternative hemostatic hydrogel with negligible immune responses enabling the replacement of chitosan‐catechol. Comparative cellular toxicity and in vivo skin irritation between chitosan‐catechol and glycol chitosan‐catechol are evaluated. Their immune responses are also assessed using histological analysis after subcutaneous implantation into mice. The results show that glycol chitosan‐catechol significantly attenuates the immune response compared with chitosan‐catechol; this finding is likely due to the antibiofouling effect of ethylene glycol groups and the reduced adhesion of immune cells. Finally, the tissue adhesion and hemostatic ability of glycol chitosan‐catechol hydrogels reveal that these ethylene glycol groups do not dramatically modify the adhesiveness and hemostatic ability compared with nonglycol chitosan‐catechol. This study suggests that glycol chitosan‐catechol can be a promising alternative to chitosan‐catechol in various biomedical fields such as hemostatic agents.
ENDOSCOPIC CRYOBALLOON ABLATION IS SAFE, WELL-TOLERATED AND HIGHLY EFFECTIVE IN THE ERADICATION OF ESOPHAGEAL SQUAMOUS CELL NEOPLASIA
Authors: S van Munster, Y Ke, S He, Y Zhang, L Xue, N Lv, S Dawsey, B Weusten, J Bergman, G Wang
Journal: Endoscopy (2019)

Globally, 80% of all esophageal cancers are squamous cell cancer (ESCC), arising from squamous cell neoplasia (ESCN). Although patients with ESCC have poor prognosis, curative endoscopic treatment can be performed for ESCN. ESCN mainly occurs in developing countries, with limited endoscopic expertise and resources. Hence, an easy-to-use, low-cost treatment would be of great value. The cryoballoon focal ablation system (CbFAS) is a novel endoscopic ablation therapy that comprises a portable handle with a through-the-scope catheter containing a conformable balloon. The balloon is simultaneously inflated and cooled, resulting in ice patches of ± 2 cm2. CbFAS is easy to use and requires no capital equipment. We aimed to assess the safety, tolerability and efficacy of CbFAS for eradicating ESCN.
Early Sedation with Dexmedetomidine in Critically Ill Patients
Authors: Yahya Shehabi, Belinda D. Howe, Rinaldo Bellomo, Yaseen M. Arabi, Michael Bailey, Frances E. Bass, Suhaini Bin Kadiman, Colin J. McArthur, Lynnette Murray, Michael C. Reade, Ian M. Seppelt, Jukka Takala, Matt P. Wise, Steven A. Webb
Journal: New England Journal of Medicine (2019)

Dexmedetomidine produces sedation while maintaining a degree of arousability and may reduce the duration of mechanical ventilation and delirium among patients in the intensive care unit (ICU). The use of dexmedetomidine as the sole or primary sedative agent in patients undergoing mechanical ventilation has not been extensively studied.
81. Insulated Retroviral Vectors towards Safe and Efficient Genetic Modification of Stem Cells
Journal: Molecular Therapy (2009)

In otherwise successful gene therapy trials for the treatment
of SCID patients and others, insertional mutagenesis
has resulted in leukemia development. Besides the integration
of vectors that including strong enhancers, more recently,
SIN-vectors have been shown to partially retain oncogenic
potential. The identification of genetic elements which would
both prevent such activation effects and shield the transgene
from silencing, is a main challenge. Previous attempts met
with difficulties in producing the vectors and poor efficacy of
the insulators (GIE). The improvement of integrating vectors
safety has been investigated using new candidate synthetic
GIEs. The latter have been introduced in retroviral and lentiviral
vectors. Native LTRs, SIN-LTRs, and SIN-insulated
constructs have been designed and compared, using two sets
of internal promoter, i.e. strong and housekeeping. We could
establish that a specific insulator translates at best into functional
activity and boundary effect in both vector types. We
could also determine that other genetic elements are key determinants
in order to achieve accurate expression and viral
titre, from these insulated vectors. A dramatic shift in the expression
profile is observed in target cells, with a homogenous
pattern including data on both cell-lines and primary HSCs
from cord blood. The assessment of potential genotoxicity will
be presented, based on the comparison of the integration
patterns ingenuity in human target cells sampled over a three
months period with both reference LTRs and SIN versus test
insulated vectors, using high-throughput pyro-sequencing.
Non-vigorous physical activity and the risk of breast cancer among Nigerian women
Authors: S.O. Azubuike, L. Hayes, R. McNally
Journal: Annals of Oncology (2019)

Background: Breast cancer incidence in Nigeria has risen by > 120% since 2000. Its mortality rate (18.8 / 100 000 women / year) ranks highest in Africa. Studies have suggested that non-vigorous physical activity is associated with reduced risk of breast cancer. However, its role in breast cancer risk is yet to be established in sub-Saharan Africa. Increasing prevalence of behaviours associated with reduced non-vigorous physical activity has been reported across several countries in sub-Saharan Africa, including Nigeria. The purpose of this study was to investigate if there is an association between non-vigorous physical activity and breast cancer risk among Nigerian women. Methods: The study was a multisite hospital based case-control design involving 379 histologically confirmed breast cancer cases and 403 controls. The participants were interviewed in-person between October 2016 and May 2017. Cases were selected from the oncology wards and controls from ophthalmology wards. Self-reported non vigorous physical activity (sum of occupational, household and transport physical activities) was summarised as both hours per week and metabolic equivalents hours per week (MET-hr / wk). Data were analyzed using multivariable logistic regression, adjusting for known confounders. Results: The result (in MET-hr/wk) showed a 40% [95 % confidence interval (CI): 0.40 - 0.89, p for trend = 0.032] reduction in breast cancer risk among women in the upper tertile of total non-vigorous physical activity compared to those in the lowest tertile of non-vigorous physical activity. This was stronger among younger [ odds ratio (OR) 0. 54, 95 % CI: 0.32 - 0.92], premenopausal (OR 0.46, 95% CI: 0.24 - 0.89) and lean women (OR 0.47; 95% CI: 0.25 - 0.88) compared to older, postmenopausal and overweight/obese women respectively. Conclusions: Non-vigorous physical activity was associated with reduced risk of breast cancer among Nigerian women. This risk reduction was modified by age, menopausal status and body mass index. Conditions that promote increased participation in non-vigorous physical activity among women should therefore be encouraged with respect to breast cancer prevention in Nigeria. Legal entity responsible for the study: Samuel Onyinyechukwu Azubuike. Funding: National Open University of Nigeria. Disclosure: All authors have declared no conflicts of interest.
Résection endoscopique par mucosectomie à l'anse froide de polypes coliques
Authors: C Leandri, B Brieau, B Bordacahar, S Ribière, MA Guillaumot, S Leblanc, F Prat, S Chaussade
Journal: Endoscopy (2019)

La résection à l'anse froide est une technique de polypectomie sûre et recommandée en première intention pour les polypes de moins de 10 mm. L'ESGE recommande une résection par mucosectomie à l'anse chaude des lésions de 10 – 19 mm et lésions de plus de 20 mm, fragmentée si nécessaire, en l'absence de suspicion d'envahissement en profondeur. L'utilisation de l'anse froide pour la résection fragmentée si nécessaire de lésions plus volumineuses notamment planes n'est pas utilisée en pratique courante et reste à évaluer (1). La résection optimale de lésions de type sessile serrated adenoma (SSA/P) n'est par ailleurs pas encore connu. Une étude semble montrer que la mucosectomie à l'anse froide est une technique de résection sûre et efficace des lésions SSA/P de plus de 10 mm (2). L'objectif de cette série de cas était de confirmer ces données en évaluant la faisabilité et la sûreté de la résection de lésions coliques volumineuses adénomateuses ou SSA/P par mucosectomie à l'anse froide.
EVALUATION OF DOSE RADIATION IN ENDOSCOPIC UNIT
Authors: C Lefort, B Napoléon, R Gincul, F Fumex, V Lepilliez
Journal: Endoscopy (2019)

We randomized between september 2017 and june 2018, 255 endoscopic procedures realized under fluoroscopy. 5 experienced endoscopist work in 2 rooms (one with GE system, the other with Siemens system). The Kerma-area product (KAP) was retrospectively evaluated and classified according to the type of procedure.
Abstract A29: Heterogeneity of androgen receptor dynamics and drug response in prostate cancer cells
Authors: Katherin Patsch, Anjana Soundararajan, Mark Engeln, Mitchell E. Gross, Shannon M. Mumenthaler, Daniel Ruderman
Journal: Cancer Research (2017)

Abstract Background: Recent studies suggest that the spatio-temporal dynamics of critical signaling molecules can mediate heterogeneous response to therapeutic intervention. Here, we set out to apply live cell imaging of single cells in high throughput to correlate the dynamics of androgen receptor (AR) with response to taxane chemotherapy in heterogeneous prostate cancer (PCa) cell populations. Methods: We previously developed a 3-step high throughput imaging and data analysis workflow to improve measurements of the dynamic phenotype in heterogeneous populations. We treated PCa cells stably expressing GFP-AR with AR ligand and quantified nuclear/cytoplasmic GFP intensity to measure nuclear translocation of AR over a 30 min time course. Then we treated cells with paclitaxel and tracked cells' response for 24h. Results: Applied to PCa cell lines stably expressing GFP-AR, we measured considerable heterogeneity of AR translocation in response to ligand stimulation. We quantified populations of non-responders and classified responding cells based on the dynamics of AR. Evaluation of cell morphology revealed a fraction of relatively large cells to be exclusively slow responders to AR ligand. We measured heterogeneous response to treatment with paclitaxel that correlated with cell phenotype. Conclusion: We conclude that cell morphology features in heterogeneous PCa cell populations correlate with AR translocation dynamics and drug response. Future experiments will include expression of the constitutively active AR variant AR-v7 to analyze its effect on the dynamics of wild-type AR and on single cell response to paclitaxel chemotherapy. Note: This abstract was not presented at the conference. Citation Format: Katherin Patsch, Anjana Soundararajan, Mark Engeln, Mitchell E. Gross, Shannon M. Mumenthaler, Daniel Ruderman. Heterogeneity of androgen receptor dynamics and drug response in prostate cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A29.
Use of the national electronic maternal and child health registry (MCH eRegistry) in primary care clinics in occupied Palestinian territory: a pilot time-motion study
Authors: Tamara Awwad, Mahima Venkateswaran, Marie Hella Lindberg, Khadija Abu Khader, Taghreed Hijaz, Buthaina Ghanem, Kjersti Mørkrid, Asad Ramlawi, Rand Salman, J Frederik Frøen
Journal: The Lancet (2019)
Double sténose tumorale biliaire et duodénale concomitante: influence du timing et des modalités de drainage endoscopique sur le pronostic
Authors: A Debourdeau, F Caillol, JP Ratone, J Winkler, C Decoster, C Pesenti, E Bories, M Giovannini
Journal: Endoscopy (2019)

L'association d'une sténose duodénale et biliaire néoplasique est une situation problématique rendant la prise en charge endoscopique compliquée avec un accès biliaire plus difficile et la nécessité de réaliser deux procédures: biliaire et duodénal. Le but de cette étude est d'analyser les facteurs qui influencent l'évolution après double drainage endoscopique des patients présentant une sténose bilio-duodénale concomitante.
Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial
Authors: Erik A Imel, Francis H Glorieux, Michael P Whyte, Craig F Munns, Leanne M Ward, Ola Nilsson, Jill H Simmons, Raja Padidela, Noriyuki Namba, Hae Il Cheong, Pisit Pitukcheewanont, Etienne Sochett, Wolfgang Högler, Koji Muroya, Hiroyuki Tanaka, Gary S Gottesman, Andrew Biggin, Farzana Perwad, Meng Mao, Chao-Yin Chen, Alison Skrinar, Javier San Martin, Anthony A Portale
Journal: The Lancet (2019)
DUODENAL NEUROENDOCRINE TUMOUR RESECTION WITH A NEW DUODENAL FULL THICKNESS RESECTION DEVICE
Authors: J Cortez Pinto, S Mão de Ferro, J Castela, I Claro, P Chaves, A Dias Pereira
Journal: Endoscopy (2019)

Most well-differentiated, non-functional duodenal NETs limited to the mucosa/submucosa can be treated effectively with endoscopic resection.
Mechanotransduction, immunoregulation, and metabolic functions of CD31 in cardiovascular pathophysiology
Authors: Giuseppina Caligiuri
Journal: Cardiovascular Research (2019)

Biomechanical changes in the heart and vessels drive rapid and dynamic regulation of blood flow, a vital process for meeting the changing metabolic needs of the peripheral tissues at any given point in time. The fluid movement of the blood exerts haemodynamic stress upon the solid elements of the cardiovascular system: the heart, vessels, and cellular components of the blood. Cardiovascular diseases can lead to prolonged mechanical stress, such as cardiac remodelling during heart failure or vascular stiffening in atherosclerosis. This can lead to a significantly reduced or increasingly turbulent blood supply, inducing a shift in cellular metabolism that, amongst other effects, can trigger the release of reactive oxygen species and initiate a self-perpetuating cycle of inflammation and oxidative stress. CD31 is the most abundant constitutive co-signalling receptor glycoprotein on endothelial cells, which line the cardiovascular system and form the first-line of cellular contact with the blood. By associating with most endothelial receptors involved in mechanosensing, CD31 regulates the response to biomechanical stimuli. In addition, by relocating in the lipid rafts of endothelial cells as well as of cells stably interacting with the endothelium, including leucocytes and platelets, CD31-CD31 trans-homophilic engagement guides and restrains platelet and immune cell accumulation and activation and at sites of damage. In this way, CD31 is at the centre of mediating mechanical, metabolic, and immunological changes within the circulation and provides a single target that may have pleiotropic beneficial effects.
SUCCESSFUL COMPLETE ERADICATION OF BARRETT'S ADENOCARCINOMA WITH UNDERLYING ESOPHAGEAL VARICES WITH MODIFIED EMR TECHNIQUE AND RADIOFREQUENCY ABLATION
Authors: H Uchima, D Busquets, I Serra, C Lopez, L Gutierrez, L Torrealba, M Figa, C Huertas, M Hombrados, V Piñol, X Aldeguer
Journal: Endoscopy (2019)

We present the case of a 63-year-old patient with alcohol liver cirrhosis, with portal hypertension and esophageal varices in prophylaxis with beta-blocker.
Para-necrotic expression of VEGFA metagene signature identified by single-cell profiling
Authors: T. Karn, C. Denkert, K.E. Weber, P. Jank, A. El-Balat, A. Rody, M. Untch, S. Loibl, L. Pusztai, U. Holtrich
Journal: Annals of Oncology (2019)

Background: We previously identified a VEGFA metagene in TNBC which is associated with poor prognosis and eliminates the good prognostic effect of TILs (PMID 21978456, 28750120). But high pretreatment values of this signature predicted pCR in the neoadjuvant GeparQuinto trial (OR 2.40, P = 0.006) showing an interaction with bevacizumab treatment (P = 0.020). The main cellular sources of the transcripts that comprise the VEGFA metagene are unknown since mRNA profiling of bulk biopsies contains signals from different cell types. The individual genes have been reported to be expressed both in endothelial cells, fibroblasts, and epithelial cancer cells. Methods: We analyzed single-cell sequencing RNA-Seq (sc-RNA-Seq) data of n = 772 single cells from TNBC and 52,698 single cells from lung cancer and non-malignant lung to identify the cellular source of the metagene expression. We then established and validated single marker IHC assays for the VEGFA metagene and applied them to tissue micro arrays (TMA). Results: sc-RNA-Seq from TNBC revealed co-expression of core genes of the VEGFA metagene (NDRG1, VEGFA, and DDIT4) in different cell types with highest expression in basal-like cancer cells. Strong co-expression in a subset of carcinoma cells was also seen in lung cancer sc-RNA-Seq, but only limited expression in endothelial cells. An IHC assay revealed strong para-necrotic expression in line with functions in cellular stress and hypoxia. Whole-slide-IHC showed good correlation to mRNA expression even in core biospies (Kappa=0.864, P < 0.001). However, comparison of whole-slide and TMA demonstrated a profound loss of sensitivity, while specificity remained high. Loss of sensitivity was mainly due to heterogeneity in expression and the small sized TMA cores from pretreatment biopsies. Nevertheless, still a predictive value for pCR was detected in the TMA dataset (P = 0.025). Conclusions: The cellular source of the VEGFA metagene are peri-necrotic carcinoma cells. Thus, necrosis detection may help in response prediction and as stratification factor in trials. Since the signature indicates an immunosuppressive environment it should also be further studied in the context of combination therapies of anti-angiogenic and immune treatments. Legal entity responsible for the study: University of Frankfurt. Funding: H.W. & J. Hector-Stiftung, Mannheim, Germany. Disclosure: All authors have declared no conflicts of interest.
Abstract 16971: Engineering MicroMyocardium With Tunable Cell-Matrix and Cell-Cell Interactions and an Integrated Contractility Assay
Authors: Nethika Ariyasinghe, Caitlin H Reck, Alyssa A Viscio, Andrew P Petersen, Davi M Lyra-Leite, Nathan Cho, Megan L McCain
Journal: Circulation (2017)

Introduction: The myocardium consists of cardiac myocytes, fibroblasts, and a supportive extracellular matrix (ECM) with defined mechanical and biochemical properties. In many pathological settings...
ACUTE GASTROINTESTINAL BLEEDING IN THIRD WORLD COUNTRIES WITH FEW RESOURCES: A STUDY OF 1347 PATIENTS IN SPECIALIZED CENTRE
Authors: N Arabi Mohammad, A Musaad, E Ahmed, MA Aziz
Journal: Endoscopy (2019)

Acute gastrointestinal blood loss presents a management challenge and a crucial threat to the patients. The bleeding lesion cannot be easily controlled by endoscopy for unexperienced hand, but it is necessary for definitive diagnosis and management. The aim of this study is to reflect the causes, and management of acute gastrointestinal bleeding in Sudanese patients.
An Evolutionarily Conserved uORF Regulates PGC1α and Oxidative Metabolism in Mice, Flies, and Bluefin Tuna
Authors: Phillip A. Dumesic, Daniel F. Egan, Philipp Gut, Mei T. Tran, Alice Parisi, Nirmalya Chatterjee, Mark Jedrychowski, Margherita Paschini, Lawrence Kazak, Sarah E. Wilensky, Florence Dou, Dina Bogoslavski, Jeffrey A. Cartier, Norbert Perrimon, Shingo Kajimura, Samir M. Parikh, Bruce M. Spiegelman
Journal: Cell Metabolism (2019)
Revised Acute Myeloid Leukemia Composite Model Using the 2017 European LeukemiaNet Risk Classification
Authors: Mohamed L. Sorror, Barry E. Storer, Jennifer Nyland, Elihu H. Estey
Journal: JAMA Oncology (2019)

In this cohort modeling study, the acute myeloid leukemia composite model is updated using the European LeukemiaNet 2017 classification for cytogenetic and/or molecular risks.
CAPNOGRAPHY DURING ENDOSCOPY – A VALUE-BASED HEALTHCARE PILOT IN A HIGH-VOLUME GASTROENTEROLOGY PRACTICE
Authors: R Bisschops, I Demedts, P Roelandt, C Dooms, I Hoffman, R Weissbrod, R Saunders, K Buysschaert, M Hiele, G Van Assche
Journal: Endoscopy (2019)

As part of a quality-improvement initiative in a high-volume university hospital GI department, the study evaluated the incidence of respiratory-related adverse events (AEs) and interventions occurring during sedation using World SIVA task force consensus definitions and the impact of capnography monitoring on these.