tbuckley/cabot-search huggingface dataset:
Incidence and risk factors associated with injuries during static line parachute training in Royal Thai Army
Authors: Watcharaphat Maneechaeye, Kathawoot Deepreecha, Wiroj Jiamjarasrangsi
Journal: Military Medical Research (2020)

Abstract Background Incidence and risk factors of parachute injuries has been studied in developed countries, but not in trainees of the airborne forces in the Royal Thailand Army. Methods A prospective cohort study was conducted among 992 military personnel who attended the basic airborne training program from February to July 2018. Information sheets were used to collect data about (a) personal demographics; (b) environmental conditions surrounding the parachute practice; and (c) parachute-related injuries. The incidence rate of injury was then calculated. Risk factors were examined using multilevel Poisson regression analysis and presented as incidence rate ratio (IRR) and 95% confidence interval (95% CI). Results A total of 166 parachute-related injuries occurred in 4677 jumps. The incidence rate of injury was 35.50 per 1000 jumps (95%CI: 30.04–41.21). Factors significantly related to parachute injury included: jumping with equipment versus without equipment [adjusted IRR (95% CI): 1.28 (0.88–1.87)], higher wind speed [1.54 (1.27–1.87) per knot], airplane versus helicopter exit [1.75(0.68–4.55)], side versus rear exit [2.13 (1.43–3.23)], night versus day jumping [2.19 (0.81–5.90)], and presence of motion sickness [3.43 (1.93–6.92)]. Conclusions To prevent military static line parachute injuries, the following factors should be taken into consideration: type of aircraft, aircraft exit, time of the day, equipment, motion sickness and wind speed. Trial registration The project was certified by the Research Ethics Committee, Faculty of Medicine, Chulalongkorn University (IRB No. 697/60).
The Tumor Microenvironment in Cholangiocarcinoma Progression
Authors: Luca Fabris, Keisaku Sato, Gianfranco Alpini, Mario Strazzabosco
Journal: Hepatology (2020)

Cholangiocarcinoma (CCA) is an aggressive and heterogeneous malignancy of the biliary tree.A typical hallmark of CCA is that cancer cells are embedded into a dense stroma containing fibrogenic cells, lymphatics and a variety of immune cells.Functional roles of the reactive tumor stroma are not fully elucidated; however, recent studies suggest that the tumor microenvironment plays a key role in the progression and invasiveness of CCA.CCA cells exchange autocrine/ paracrine signals with other cancer cells and the infiltrating cell types that populate the microenvironment.This crosstalk is under the control of signals mediated by various cytokines, chemokines, and growth factors.In addition, extracellular vesicles (EVs), exosomes and microvesicles, containing cargo mediators, such as proteins and RNAs, play a key role in cell-tocell communication, and particularly in epigenetic regulation thanks to their content in miRNAs.Both cytokine-and EV-mediated communications between CCA cells and other liver cells provide a potential novel target for the management of CCA.This review summarizes current understandings of the tumor microenvironment and intercellular communications in CCA and their role in tumor progression.
Dysautonomia Is Linked to Striatal Dopamine Deficits and Regional Cerebral Perfusion in Early Parkinson Disease
Authors: Hae-Won Shin, Seok Jong Chung, Sangwon Lee, Jungho Cha, Young H. Sohn, Mijin Yun, Phil Hyu Lee
Journal: Clinical Nuclear Medicine (2020)

Purpose The aim of this study was to investigate the association between autonomic dysfunction and striatal dopamine depletion or metabolic changes in de novo Parkinson disease (PD). Methods Based on the Composite Autonomic Severity Score (CASS), patients with de novo PD were classified into PD with (PD-AUT+) and without autonomic dysfunction (PD-AUT−) groups. We compared the dopamine transporter (DAT) availability in the striatum by quantitatively measuring 18 F-FP-CIT PET between both groups. We also assessed the association between DAT availability and the CASS. In addition, we compared regional uptake in early-phase images of 18 F-FP-CIT PET as well as cortical thickness between the PD-AUT+ and PD-AUT− groups. Results The PD-AUT+ group had significantly lower DAT availability in all striatal subregions than did the PD-AUT− group. The total CASS was significantly correlated with DAT availability in all striatal subregions. In addition, the subscores of the adrenergic component were correlated with DAT availability in all striatal subregions. The subscores of the cardiovagal component were negatively correlated with DAT availability in the caudate and ventral striatum. In early-phase 18 F-FP-CIT PET, the PD-AUT+ group exhibited decreased regional perfusion in the parieto-occipital areas and increased regional perfusion in the pallidothalamic, pontocerebellar, inferior frontal, and primary motor areas compared with the PD-AUT− group. There were no regions of different cortical thickness between the PD groups. Conclusions The present study revealed that autonomic dysfunction is closely linked to striatal dopamine depletion and prominent PD-related perfusion patterns in de novo PD, suggesting a greater pathological burden in patients with dysautonomia.
Abstract B41: Piritramide analgesia reduces CEA mRNA-positive circulating tumor cells’ presence compared to morphine and epidural analgesia following radical colon cancer surgery
Authors: Josef Srovnal, Emil Berta, Alona Rehulkova, Monika Vidlarova, Petr Prasil, Lubomir Vecera, Petr Stourac, Pavla Kourilova, Marian Hajduch
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Piritramide is a strong opioid widely used for postoperative analgesia (PA) in Europe while morphine and epidural PA are well established worldwide. Our retrospective analysis revealed that compared to morphine, piritramide improved cancer-specific survival in patients undergoing radical colon cancer surgery. Since circulating tumor cells’ (CTCs) presence has negative effect on colon cancer survival, we hypothesized that different types of PA could affect postoperative CTCs levels. Patients and Methods: In total, 60 patients undergoing radical colon cancer surgery were enrolled in this prospective, randomized, two-center pilot study. Patients were randomized to receive either piritramide, morphine, or epidural PA. The presence of carcinoembryonic antigen (CEA) and cytokeratin 20 (CK-20) mRNA positive CTCs in peripheral blood was measured at four points (before and immediately after surgery, on postoperative day 2, and one month after surgery) using quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). Perioperative treatment was standardized. Results: In piritramide-treated patients, the levels of CEA mRNA positive cells were significantly lower on postoperative day 2 compared to other patients (p=0.04). CK-20 mRNA positive cells levels remained similar. In all groups, CTCs levels returned to preoperative baseline one month after surgery. Groups were similar regarding age, sex, ASA status, TNM, and grading. Conclusion: Compared to morphine and epidural analgesia, piritramide reduces postoperative CEA mRNA-positive circulating tumor cells’ presence following radical colon cancer surgery. Further trials enrolling larger numbers of patients are needed. Acknowledgments: This study was supported by Ministry of Health of the Czech Republic (NV18-03-00470), Ministry of Education, Youth and Sport of the Czech Republic (LO1304, LM2015089), European Regional Development Fund (ENOCH CZ.02.1.01/0.0/0.0/16_019/0000868) and Cancer Research Czech Republic. Citation Format: Josef Srovnal, Emil Berta, Alona Rehulkova, Monika Vidlarova, Petr Prasil, Lubomir Vecera, Petr Stourac, Pavla Kourilova, Marian Hajduch. Piritramide analgesia reduces CEA mRNA-positive circulating tumor cells’ presence compared to morphine and epidural analgesia following radical colon cancer surgery [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B41.
Factors associated with non-completion of latent tuberculosis infection treatment in Rio de Janeiro, Brazil: A non-matched case control study
Authors: R.M. de Aguiar, M.A.M. da Silva Vieira, I.N. de Almeida, D.M. de Paula Ramalho, A. Ruffino-Netto, A.C.C. Carvalho, A.L. Kritski
Journal: Pulmonology (2020)

There are scarce data on the routine latent tuberculosis infection treatment (LTBIT) and factors associated with a non-completion in high tuberculosis burden countries. Therefore, in this study we aimed to evaluate the factors associated with non-completion of LTBIT.This was a non-matched case control study conducted at a University Hospital in Rio de Janeiro, Brazil. A total of 114 cases and 404 controls were enrolled between January/1999 and December/2009. Cases were close contacts who did not complete the LTBIT and controls were the contacts that completed it. Multivariate analysis was used to investigate risk factors associated with non-completion of LTBIT among contacts in two different periods of recruitment.Factors associated with non-completion LTBIT included: drug use (OR 23.33, 95% CI 1.83-296.1), TB treatment default by the index case (OR 16.97, 95% CI 3.63-79.24) and drug intolerance. TB disease rates after two years of follow up varied from 0.4% to 1.9%. The number necessary to treat to prevent one TB case among contacts was 116.Non-completion treatment by the index case and illicit drug use were associated with not completing latent tuberculosis infection treatment and no tuberculosis disease was identified among those who completed latent tuberculosis infection treatment.
Applying cascaded convolutional neural network design further enhances automatic scoring of arthritis disease activity on ultrasound images from rheumatoid arthritis patients
Authors: Anders Bossel Holst Christensen, Søren Andreas Just, Jakob Kristian Holm Andersen, Thiusius Rajeeth Savarimuthu
Journal: Annals of the Rheumatic Diseases (2020)

We have previously shown that neural network technology can be used for scoring arthritis disease activity in ultrasound images from rheumatoid arthritis (RA) patients, giving scores according to the EULAR-OMERACT grading system. We have now further developed the architecture of this neural network and can here present a new idea applying cascaded convolutional neural network (CNN) design with even better results. We evaluate the generalisability of this method on unseen data, comparing the CNN with an expert rheumatologist.The images were graded by an expert rheumatologist according to the EULAR-OMERACT synovitis scoring system. CNNs were systematically trained to find the best configuration. The algorithms were evaluated on a separate test data set and compared with the gradings of an expert rheumatologist on a per-joint basis using a Kappa statistic, and on a per-patient basis using a Wilcoxon signed-rank test.With 1678 images available for training and 322 images for testing the model, it achieved an overall four-class accuracy of 83.9%. On a per-patient level, there was no significant difference between the classifications of the model and of a human expert (p=0.85). Our original CNN had a four-class accuracy of 75.0%.Using a new network architecture we have further enhanced the algorithm and have shown strong agreement with an expert rheumatologist on a per-joint basis and on a per-patient basis. This emphasises the potential of using CNNs with this architecture as a strong assistive tool for the objective assessment of disease activity of RA patients.
Micromechanobiology: Focusing on the Cardiac Cell–Substrate Interface
Authors: Erica A. Castillo, Kerry V. Lane, Beth L. Pruitt
Journal: Annual Review of Biomedical Engineering (2020)

Engineered, in vitro cardiac cell and tissue systems provide test beds for the study of cardiac development, cellular disease processes, and drug responses in a dish. Much effort has focused on improving the structure and function of engineered cardiomyocytes and heart tissues. However, these parameters depend critically on signaling through the cellular microenvironment in terms of ligand composition, matrix stiffness, and substrate mechanical properties—that is, matrix micromechanobiology. To facilitate improvements to in vitro microenvironment design, we review how cardiomyocytes and their microenvironment change during development and disease in terms of integrin expression and extracellular matrix (ECM) composition. We also discuss strategies used to bind proteins to common mechanobiology platforms and describe important differences in binding strength to the substrate. Finally, we review example biomaterial approaches designed to support and probe cell–ECM interactions of cardiomyocytes in vitro, as well as open questions and challenges.
ET-20. NIGELLA SATIVA AND THYMOQUINONE INDUCE CASPASE-9/3 ACTIVATION AND GLIOBLASTOMA CELL DEATH
Authors: Isa Hussaini, Samson Amos, Kendra Simpson, Gerard Redpath, Charles Lyons, Charles Dipierro
Journal: Neuro-Oncology (2011)

The seeds of Nigella sativa have been used for centuries by various cultures for the treatment of a host of illnesses and symptoms, including asthma, inflammation, and fever. Recently, N. sativa seed oil was shown to exhibit anticonvulsant and anti-prostate cancer activities. We investigated the eff
Abstract IA01: Modeling and understanding tumor biologic mechanisms
Authors: Adam Boutin, Peiwen Chen, Prasenjit Dey, Pingping Hou, Wen-Ting Liao, Xin Lu, Haoqiang Ying, Di Zhao, Ronald A. DePinho
Journal: Cancer Research (2020)

Abstract This presentation will highlight our use of mouse models to dissect molecular and cellular interactions in the tumor microenvironment, including (i) the illumination of the role of myeloid cells in driving immune suppression in prostate cancer, and the impact of combined MDSC-targeted and immune checkpoint blockade therapies in the treatment of metastatic castration-resistant prostate cancer; (ii) the generation and analysis of oncogenic Kras in an inducible colorectal cancer mouse model, revealing the role of IRF2 in the recruitment of myeloid cells into the tumor microenvironment and informing patient selection for more effective ICB therapy in CRC; (iii) the concept of “synthetic essentiality” (a means by which to target specific tumor-suppressor gene deficiencies in cancer), exemplified by the identification of the role of CHD1 in modulation of the tumor microenvironment in Pten-deficient prostate cancer; (iv) the discovery of a symbiotic interaction between glioma cell (LOX) and macrophage (SPP1) in PTEN-null glioma, as well as macrophage reprogramming in immune suppression in glioblastoma; and (v) the role of KRAS in cancer metabolism, in particular how the tumor microenvironment may support KRAS-directed cancer cell metabolism and provide a nonautonomous mechanism enabling escape from Kras-dependent tumor growth. These illustrative examples provide translational opportunities to improve cancer patient treatment and survival. Citation Format: Adam Boutin, Peiwen Chen, Prasenjit Dey, Pingping Hou, Wen-Ting Liao, Xin Lu, Haoqiang Ying, Di Zhao, Ronald A. DePinho. Modeling and understanding tumor biologic mechanisms [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr IA01.
BCI-based sensorimotor rhythm training can affect individuated finger movements
Authors: D.J. McFarland, S.L. Norman, W.A. Sarnacki, E.T. Wolbrecht, D.J. Reinkensmeyer, J.R. Wolpaw
Journal: Brain-Computer Interfaces (2020)

ABSTRACT Brain-computer interface (BCI) technology can restore communication and control to people who are severely paralyzed. BCI technology might also be able to enhance rehabilitation of motor function. We have previously shown that pre-movement sensorimotor rhythm (SMR) amplitude affects reaction time and performance on a joystick-based cursor movement task. The present study explores in adults without motor impairment the possibility that pre-movement SMR amplitude affects performance of individuated finger movements. In Phase 1, 8 individuals performed a finger flexion task that was monitored by an exoskeleton. During a 1-sec preparatory period, two colored targets on a video monitor cued flexion of the index finger, middle finger, both fingers, or neither finger; sudden color change then triggered the movement (or non-movement). SMR features (i.e. EEG amplitudes in specific frequency bands at specific scalp locations) in the pre-movement EEG that correlated with movement versus no movement were identified. In Phase 2, the participants learned to increase or decrease these SMR features to control a two-target BCI task. Finally, in Phase 3, they were asked to increase or decrease the SMR features to initiate the finger flexion task of Phase 1 and the impact on finger flexion performance was assessed. After BCI training, pre-movement SMR feature amplitude affected performance in a subset of individuals: lower amplitude was associated with shorter movement onset. In a subset of individuals, the beneficial effect on performance of lower SMR amplitude was greater when both fingers were flexed than when one was flexed and the other remained extended; thus, the impact of SMR amplitude modulation depended on the specificity of the subsequent motor task. These results indicate that BCI-based training of SMR activity in the pre-movement preparatory period can affect finger movements in a subset of individuals. They encourage studies that integrate such training into rehabilitation protocols and examine its capacity to enhance restoration of useful hand function.
Peptide Receptor Radionuclide Therapy in Patients With Differentiated Thyroid Cancer
Authors: Dong Yun Lee, Yong-il Kim
Journal: Clinical Nuclear Medicine (2020)

Purpose As patients with progressive medullary thyroid cancer (MTC) and radioiodine-refractory metastatic differentiated nonmedullary thyroid cancer (DTC) have poor prognoses and present therapeutic challenges, peptide receptor radionuclide therapy (PRRT) targeting the somatostatin receptor provides a promising option. This meta-analysis evaluated the therapeutic effects and outcomes of PRRT in differentiated thyroid cancer. PATIENTS AND METHODS PUBMED, EMBASE, CINAHL, SCOPUS, and COCHRANE were systematically searched using appropriate key words. The primary therapeutic effect was the radiological response after PRRT, and the objective response rate (ORR) and disease control rate (DCR) were identified in MTC and DTC, respectively. The outcome of serious adverse events (grade 3 or 4), additional therapeutic effects of 18 F-FDG PET/CT and biochemical (calcitonin and thyroglobulin) responses, and radionuclides for PRRT were assessed as subgroup analyses. The parameters were generated as pooled proportions. Results Eleven articles with 165 patients were included (98 patients with MTC and 67 patients with DTC). PRRT achieved pooled proportions of ORR in 8.53% to 15.61%, DCR in 53.95% to 59.99%, and serious adverse events in 2.79% to 2.82% in MTC and DTC patients. 18 F-FDG PET/CT and biochemical responses revealed similar results as the radiological response. 177 Lu-based PRRT (ORR, 11.48%–24.52%; DCR, 61.47%–67.26%) showed better therapeutic effects than 90 Y-based PRRT (ORR, 6.98%–13.82%; DCR, 50.86%–57.29%). Conclusions This meta-analysis suggests that PRRT could be a potential and safe strategy for MTC and DTC. In particular, PRRT with 177 Lu exhibited improved therapeutic effects relative to PRRT with 90 Y.
Freeze-dried fecal samples are biologically active after long-lasting storage and suited to fecal microbiota transplantation in a preclinical murine model of<i>Clostridioides difficile</i>infection
Authors: Julie Reygner, Christine Charrueau, Johanne Delannoy, Camille Mayeur, Véronique Robert, Céline Cuinat, Thierry Meylheuc, Aurélie Mauras, Jérémy Augustin, Ioannis Nicolis, Morgane Modoux, Francisca Joly, Anne-Judith Waligora-Dupriet, Muriel Thomas, Nathalie Kapel
Journal: Gut Microbes (2020)

Fecal microbiota transplantation is now recommended for treating recurrent forms of Clostridioides difficile infection. Recent studies have reported protocols using capsules of either frozen or freeze-dried stool allowing oral administration in in- and out-patient settings. However, a central question remains the viability, engraftment, and efficacy of the microbiome over time during storage life. This study shows that both the freeze-drying and freezing procedures for fecal samples allowed preserving viability, short-chain fatty acids concentration, and anti-Clostridioides difficile properties of microbiota without significant alteration after storage for 12 months. Fecal transplantation with freeze-dried microbiota allowed engraftment of microbiota leading to clearance of Clostridioides difficile infection in a preclinical murine model with a survival rate of 70% versus 53-60% in mice treated with frozen inocula, and 20% in the untreated group. Moreover, the freeze-dried powder can be used to fill oral hard capsules using a very low amount (0.5%) of glidant excipient, allowing oral formulation. Altogether, this study showed that freeze-dried inocula can be used for the treatment of Clostridioides difficile infection with long-lasting stability of the fecal microbiota. This formulation facilitates biobanking and allows the use of hard capsules, an essential step to simplify patient access to treatment.
Abstract B02: Association of APC, BRAF, and TCF7L2 mutations with tumor mutation load and survival outcomes in patients with metastatic colorectal cancer
Authors: Liang Xu, Xiao-Sheng He, Ping Lan
Journal: Cancer Research (2020)

Abstract Objective: To investigate whether APC, BRAF, and TCF7L2 mutations are associated with prognosis in patients with mCRC. Methods: Statistical analysis of genomic data from 980 metastatic colorectal cancer samples obtained from the cbioportal database was performed. The cbioportal cohort was used as a discovery set. Logistic regression models and Kaplan-Meier survival analysis and multivariate analysis and nomogram analysis were applied. The lasso regression was used to identify significantly mutant genes. Results: We identified 25 mutant genes related to survival outcomes by using lasso regression. These mutated genes were generated to classify mCRC patients into high-risk and low-risk groups. Patients with high-risk scores in the training cohort had shorter survival (hazard ratio [HR] 2.735, 95% CI 2.206-3.390; p&amp;lt;0.0001) than patients with low-risk scores. These 25 genes and mutant gene with mutation frequencies more than 5% were analyzed by univariate and multivariate analysis. Three mutant genes could be regarded as independent prognostic factors for overall survival in mCRC patients: APC, BRAF, and TCF7L2. APC and TCF7L2 mutation were favorable factors, while BRAF mutation was an unfavorable factor. The combined Kaplan-Meier analysis showed 5 groups were significantly associated with prognosis in mCRC and found that these 5 groups were associated with tumor location, molecular subtype, survival, tumor grade, and hypermutation. In TCF7L2 and BRAF mutant group, other mutant gene had a much higher mutation frequency than wild-type group. We speculated that BRAF and TCF7L2 mutation were two important mutation points during CRC metastasis. Conclusions: These findings indicate that APC, BRAF, and TCF7L2 mutations were associated with tumor mutation load and survival outcomes. These findings may be applicable for patients with mCRC. Note: This abstract was not presented at the conference. Citation Format: Liang Xu, Xiao-Sheng He, Ping Lan. Association of APC, BRAF, and TCF7L2 mutations with tumor mutation load and survival outcomes in patients with metastatic colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr B02.