tbuckley/cabot-search huggingface dataset:
Pocket-creation method using a new technique of single-clip traction for colorectal endoscopic submucosal dissection
Authors: Tatsuma Nomura, Yoshikazu Hayashi, Ralph F. Lee, Takahito Takezawa, Keijiro Sunada, Hironori Yamamoto
Journal: Endoscopy (2019)

Colorectal endoscopic submucosal dissection (ESD) is a challenging procedure used in the removal of colorectal neoplasms and various methods have been developed to improve its performance [1] [2] [3]. Among these, the pocket-creation method (PCM) allows the safe and efficient removal of neoplastic lesions, using precise submucosal dissection just above the muscularis propria [4] [5]. However, the pocket-opening phase of PCM is often cumbersome and time-consuming. We have invented a new technique using single-clip traction that we have called PCM with clip traction (PCM-CT), which we believe improves the speed and safety of the pocket-opening phase.
Abstract 15109: Afterload Is a Determinant of Persistence of Myocardial Ischemic Memory Assessed by Post-Systolic Thickening
Authors: Kasumi Masuda, Toshihiko Asanuma, Daisuke Sakurai, Ayana Hioki, Satoshi Nakatani
Journal: Circulation (2011)

Background Post-systolic thickening (PST), which is defined as myocardial contraction after aortic valve closure, is a sensitive marker of ischemia and remains even after restoration of perfusion (...
Frequency of MRI changes suggestive of axial spondyloarthritis in the axial skeleton in a large population-based cohort of individuals aged &lt;45 years
Authors: Konstantinos Parperis
Journal: Annals of the Rheumatic Diseases (2019)

I read with great interest the recent report by Baraliakos et al published in the Annals of Rheumatic Disease, about a general population cohort study of healthy volunteers that examined the presence of bone marrow oedema and fatty lesions on MRI of the spine and sacroiliac joints.1 Over the past decade, imaging techniques such as the MRI have revolutionised the application of radiographic findings in the early diagnosis of axial spondyloarthritis (axSpA).2

In this study, the authors elegantly identified an increased frequency of fatty lesions as well as bone marrow oedema in the vertebral …
Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis
Authors: Catherine de Martel, Damien Georges, Freddie Bray, Jacques Ferlay, Gary M Clifford
Journal: The Lancet Global Health (2019)

BackgroundInfectious pathogens are strong and modifiable causes of cancer. The aim of this study was to improve estimates of the global and regional burden of infection-attributable cancers to inform research priorities and facilitate prevention efforts.MethodsWe used the GLOBOCAN 2018 database of cancer incidence and mortality rates and estimated the attributable fractions and global incidence for specific anatomical cancer sites, subsites, or histological subtypes known to be associated with ten infectious pathogens classified as human carcinogens. We calculated absolute numbers and age-standardised incidence rates (ASIR) of infection-attributable cancers at the country level. Estimates were stratified for sex, age group, and country, and were aggregated according to geographical regions and World Bank income groups.FindingsWe found that, for 2018, an estimated 2·2 million infection-attributable cancer cases were diagnosed worldwide, corresponding to an infection-attributable ASIR of 25·0 cases per 100 000 person-years. Primary causes were Helicobacter pylori (810 000 cases, ASIR 8·7 cases per 100 000 person-years), human papillomavirus (690 000, 8·0), hepatitis B virus (360 000, 4·1) and hepatitis C virus (160 000, 1·7). Infection-attributable ASIR was highest in eastern Asia (37·9 cases per 100 000 person-years) and sub-Saharan Africa (33·1), and lowest in northern Europe (13·6) and western Asia (13·8). China accounted for a third of worldwide cancer cases attributable to infection, driven by high ASIR of H pylori (15·6) and hepatitis B virus (11·7) infection. The cancer burden attributed to human papillomavirus showed the clearest relationship with country income level (from ASIR of 6·9 cases per 100 000 person-years in high-income countries to 16·1 in low-income countries).InterpretationInfection-attributable cancer incidence, in addition to the absolute number of cases, allows for refined geographic analyses and identification of populations with a high infection-associated cancer burden. When cancer prevention is largely considered in a non-communicable disease context, there is a crucial need for resources directed towards cancer prevention programmes that target infection, particularly in high-risk populations. Such interventions can markedly reduce the increasing cancer burden and associated mortality.FundingInternational Agency for Research on Cancer.
Abstract 13349: The Endothelial-Enriched lncRNA NTRAS Regulates Vessel Permeability and Endothelial Tight Junctions by Alternative Splicing
Authors: Nicolas Jaé, Youssef Fouani, David John, Ilka Wittig, Oliver Rossbach, Albrecht Bindereif, Stefan Liebner, Stefanie Dimmeler
Journal: Circulation (2018)

The discovery of long noncoding RNAs (lncRNAs), together with evidence for a predominantly noncoding human transcriptome, initiated a new era in RNA biology. LncRNAs exhibit various mechanisms of a...
Effect of Rocuronium vs Succinylcholine on Endotracheal Intubation Success Rate Among Patients Undergoing Out-of-Hospital Rapid Sequence Intubation
Authors: Bertrand Guihard, Charlotte Chollet-Xémard, Philippe Lakhnati, Benoit Vivien, Claire Broche, Dominique Savary, Agnes Ricard-Hibon, Pierre-Jean Marianne dit Cassou, Frédéric Adnet, Eric Wiel, Juliette Deutsch, Cindy Tissier, Thomas Loeb, Vincent Bounes, Emmanuel Rousseau, Patricia Jabre, Laetitia Huiart, Cyril Ferdynus, Xavier Combes
Journal: JAMA (2019)

<h3>Importance</h3> Rocuronium and succinylcholine are often used for rapid sequence intubation, although the comparative efficacy of these paralytic agents for achieving successful intubation in an emergency setting has not been evaluated in clinical trials. Succinylcholine use has been associated with several adverse events not reported with rocuronium. <h3>Objective</h3> To assess the noninferiority of rocuronium vs succinylcholine for tracheal intubation in out-of-hospital emergency situations. <h3>Design, Setting and Participants</h3> Multicenter, single-blind, noninferiority randomized clinical trial comparing rocuronium (1.2 mg/kg) with succinylcholine (1 mg/kg) for rapid sequence intubation in 1248 adult patients needing out-of-hospital tracheal intubation. Enrollment occurred from January 2014 to August 2016 in 17 French out-of-hospital emergency medical units. The date of final follow-up was August 31, 2016. <h3>Interventions</h3> Patients were randomly assigned to undergo tracheal intubation facilitated by rocuronium (n = 624) or succinylcholine (n = 624). <h3>Main Outcomes and Measures</h3> The primary outcome was the intubation success rate on first attempt. A noninferiority margin of 7% was chosen. A per-protocol analysis was prespecified as the primary analysis. <h3>Results</h3> Among 1248 patients who were randomized (mean age, 56 years; 501 [40.1%] women), 1230 (98.6%) completed the trial and 1226 (98.2%) were included in the per-protocol analysis. The number of patients with successful first-attempt intubation was 455 of 610 (74.6%) in the rocuronium group vs 489 of 616 (79.4%) in the succinylcholine group, with a between-group difference of −4.8% (1-sided 97.5% CI, −9% to ∞), which did not meet criteria for noninferiority. The most common intubation-related adverse events were hypoxemia (55 of 610 patients [9.0%]) and hypotension (39 of 610 patients [6.4%]) in the rocuronium group and hypoxemia (61 of 616 [9.9%]) and hypotension (62 of 616 patients [10.1%]) in the succinylcholine group. <h3>Conclusions and Relevance</h3> Among patients undergoing endotracheal intubation in an out-of-hospital emergency setting, rocuronium, compared with succinylcholine, failed to demonstrate noninferiority with regard to first-attempt intubation success rate. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02000674
The Cytosolic DNA-Sensing cGAS–STING Pathway in Cancer
Authors: John Kwon, Samuel F. Bakhoum
Journal: Cancer Discovery (2019)

The recognition of DNA as an immune-stimulatory molecule is an evolutionarily conserved mechanism to initiate rapid innate immune responses against microbial pathogens. The cGAS-STING pathway was discovered as an important DNA-sensing machinery in innate immunity and viral defense. Recent advances have now expanded the roles of cGAS-STING to cancer. Highly aggressive, unstable tumors have evolved to co-opt this program to drive tumorigenic behaviors. In this review, we discuss the link between the cGAS-STING DNA-sensing pathway and antitumor immunity as well as cancer progression, genomic instability, the tumor microenvironment, and pharmacologic strategies for cancer therapy. SIGNIFICANCE: The cGAS-STING pathway is an evolutionarily conserved defense mechanism against viral infections. Given its role in activating immune surveillance, it has been assumed that this pathway primarily functions as a tumor suppressor. Yet, mounting evidence now suggests that depending on the context, cGAS-STING signaling can also have tumor and metastasis-promoting functions, and its chronic activation can paradoxically induce an immune-suppressive tumor microenvironment.
Abstract B58: A phase I/II study of durvalumab and stereotactic radiotherapy in locally advanced pancreatic cancer
Authors: Richard Tuli, Nicholas Nissen, Simon Lo, Mourad Tighiouart, Veronica Placencio, Andrew Hendifar
Journal: Cancer Research (2019)

Abstract Purpose/Objective: Blockade of the PD-1/PD-L1 pathway with radiotherapy (RT) can enhance both local and systemic control in varying tumor types. Yet, no significant responses have been seen in pancreatic cancer (PC). We have previously shown that RT induces PD-1 and PD-L1 in PC following upregulation of interferon-gamma. This mechanism of adaptive immune resistance by PC may serve as an ideal therapeutic target for combined RT and PD-L1 blockade. We report interim results of an ongoing phase 1/2 clinical trial in locally advanced (LA) and borderline resectable (BR) PC (NCT03245541). Materials/Methods: Patients with LA or BR PC treated with standard-of-care gemcitabine and nab-paclitaxel for 3 to 6 cycles were enrolled. Treatment consisted of durvalumab (750 mg Q14 days) on D1. Stereotactic ablative radiotherapy (SABR; 6.6 Gy/fraction) was delivered every other day x 5 fractions beginning D8. Durvalumab continued as maintenance Q14 days until resection or progression. The run-in phase I utilized a standard 3+3 design prior to phase 2 expansion. Dose-limiting toxicities (DLTs), adverse events (AEs), and serious adverse events (SAEs) were assessed during the first 10 weeks of study treatment. CT scans were obtained every 2 months for response assessment. Endoscopic research biopsies were obtained pre- and 6-8 weeks post-SABR, and weekly blood samples were obtained on D1, weekly for 10 weeks, and then every 2 months until resection or progression to assess for immune correlates of response. Results: From 8/2017-5/2019, 18 of 30 planned patients were enrolled of whom 13 (72%) were LA and 5 (28%) were BR. Median age was 70 and 44% were female. No DLTs were identified in the phase 1 run in, and enrollment in the phase 2 study continues. Median follow-up from diagnosis is 14 months (range 6-26 months). Median cycles of chemotherapy received prior to enrollment were 4. Grade 3 toxicities have been identified in 2 patients (nausea, anorexia). No patients experienced dose-limiting toxicities. Median PFS was 14 months with median OS not reached. 9 of 18 patients have undergone resection and all were margin negative. BOR: PR (54%); CR (6%), SD (34%), PD (6%). Conclusion: To our knowledge, this is the first report of a PD-L1 inhibitor-RT combination in LA PC. The regimen was safe, well tolerated and appears to be clinically active with high rates of margin-negative resection. Citation Format: Richard Tuli, Nicholas Nissen, Simon Lo, Mourad Tighiouart, Veronica Placencio, Andrew Hendifar. A phase I/II study of durvalumab and stereotactic radiotherapy in locally advanced pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B58.
c-Maf regulates the plasticity of group 3 innate lymphoid cells by restraining the type 1 program
Authors: Morgan E. Parker, Alejandro Barrera, Joshua D. Wheaton, Matthew K. Zuberbuehler, David S.J. Allan, James R. Carlyle, Timothy E. Reddy, Maria Ciofani
Journal: The Journal of Experimental Medicine (2019)

CCR6- group 3 innate lymphoid cells (ILC3s) are mediators of intestinal immunity and barrier function that possess the capacity to acquire type 1 effector features and fully convert into ILC1s. The molecular mechanisms governing such plasticity are undefined. Here, we identified c-Maf as an essential regulator of ILC3 homeostasis and plasticity that limits physiological ILC1 conversion. Phenotypic analysis of effector status in Maf-deficient CCR6- ILC3s, coupled with evaluation of global changes in transcriptome, chromatin accessibility, and transcription factor motif enrichment, revealed that c-Maf enforces ILC3 identity. c-Maf promoted ILC3 accessibility and supported RORγt activity and expression of type 3 effector genes. Conversely, c-Maf antagonized type 1 programming, largely through restraint of T-bet expression and function. Mapping of the dynamic changes in chromatin landscape accompanying CCR6- ILC3 development and ILC1 conversion solidified c-Maf as a gatekeeper of type 1 regulatory transformation and a controller of ILC3 fate.
<i>Notes from the Field:</i> Hospital Water Contamination Associated with a Pseudo-Outbreak of <i>Mycobacterium porcinum</i> — Wisconsin, 2016–2018
Authors: Heather Kloth, Lina I. Elbadawi, Allen Bateman, Laura Louison, Nijika Shrivastwa
Journal: MMWR Morbidity and Mortality Weekly Report (2019)
First case of endoscopic ultrasound-guided gastrojejunal anastomosis for duodenal stricture in refractory Crohn’s disease: a bridge toward inflammation control
Authors: Laurent Monino, Jean-Michel Gonzalez, Melanie Serrero, Marc Barthet
Journal: Endoscopy (2019)

Endoscopic ultrasonography-guided gastrojejunal anastomosis (EUS-GJA) was developed in 2015 using a lumen-apposing metal stent (LAMS) [1] [2]. Its application was described for malignant bowel obstruction and a few cases of benign obstruction [3] [4]. Crohn's disease is an inflammatory bowel disease that could induce inflammatory or fibrotic bowel strictures, the management of which includes medical therapy, endoscopic dilation or surgical resection [5]. We report a case of duodenal stricture in severe Crohn's disease and short bowel syndrome.
Abstract 12139: The Mutation R94C InTNNT2-encoded Troponin T Predisposes to Restrictive Cardiomyopathy and Pediatric Sudden Death Through Impaired Thin Filament Relaxation Resulting in Myocardial Diastolic Dysfunction
Authors: Jordan E Ezekian, Sarah R Clippinger, Jackie Garcia, Susan W Denfield, Aamir Jeewa, William Dreyer, Wenxin Zou, Yuxin Fan, Hugh D Allen, Jeffrey Kim, Michael Greenberg, Andrew P Landstrom
Journal: Circulation (2019)

Introduction: Pediatric-onset restrictive cardiomyopathy (RCM) carries a high risk of death, yet the underlying mechanisms of disease remain relatively unknown. Though TNNT2-encoded cardiac troponi...
Abstract 12159: Red Cell Width is Associated With All-cause and Cardiovascular Mortality in Patients With Diabetes
Authors: Sadeer Al-Kindi, Amin Jayyousi, Nidal Asaad, Jassim Al Suwaidi, Abi Khalil Charbel
Journal: Circulation (2017)

Introduction: Red cell distribution width (RDW), a measure of variability in red blood cell size, is routinely measured in complete blood counts. RDW has emerged as a prognostic marker in patients ...
Influence of nivolumab on epidemiology of infectious complications in patients with relapse or refractory Hodgkin’s lymphoma
Authors: Y. Rogacheva, M. Popova, K. Lepik, E. Kondakova, Y. Zalyalov, L. Stelmah, A. Volkova, I. Nikolaev, O. Goloshchapov, I. Barhatov, S. Bondarenko, I. Moiseev, V. Baykov, N. Mikhailova, N. Klimko, B. Afanasyev
Journal: Annals of Oncology (2019)
Microbiome changes: an indicator of Parkinson’s disease?
Authors: Caroline Haikal, Qian-Qian Chen, Jia-Yi Li
Journal: Translational Neurodegeneration (2019)

Abstract Parkinson’s disease is characterized by dopaminergic neuron loss and intracellular inclusions composed mainly of alpha synuclein (α-syn), but the mechanism of pathogenesis is still obscure. In recent years, more attention has been given to the gut as a key player in the initiation and progression of PD pathology. Several studies characterizing changes in the microbiome, particularly the gut microbiome, have been conducted. Although many studies found a decrease in the bacterial family Prevotellaceae and in butyrate-producing bacterial genera such as Roseburia and Faecalibacteria, and an increase in the genera Akkermansia many of the studies reported contradictory findings. In this review, we highlight the findings from the different studies and reflect on the future of microbiome studies in PD research.
Exercise Window Trial in Newly Diagnosed Breast Cancer–Letter
Authors: Andrew H. Sims, Melanie Leggate, Anna Campbell
Journal: Clinical Cancer Research (2019)

We read with great interest the article by Ligibel and colleagues (1), of the Pre-Operative Health and Body (PreHAB) study looking at the molecular effects of exercise on breast tumors between diagnosis and surgery. The reported upregulation of pathways related to inflammation and immunity is consistent with the expected role of the tumor microenvironment in response to exercise (2). Sequentially sampled window studies have great potential to inform by minimizing patient–patient variation, but are a very challenging way to examine the effects of treatment or other interventions. Assessment of proliferation is a natural endpoint for response, but measurement of Ki67 is notoriously unreliable.There are many different gene expression analysis approaches and numerous breast cancer signatures (3). The current drive for reproducible research has led to expectations that datasets and analysis software are made freely available. With this in mind and our desire to perform similar studies, we reanalyzed the PreHAB study gene expression data (GSE129508) using the GeneFu package (4) to calculate estimations of the established genomic grade index, PAM50 and Mammaprint risk of relapse prognosis prediction algorithms of the samples taken at diagnosis and excision from patients randomized to the exercise and control groups.The majority of exercising patients (12/16) had significantly reduced predicted PAM50 risk of relapse scores (P = 0.03), whereas half of the control group had smaller nonsignificant (P = 0.81) reductions in predicted risk of relapse. Trends (P = 0.08 and P = 0.09) for reductions in genomic grade index and Mammaprint scores in most exercising patients were not evident in controls (Fig. 1). These prognostic signatures were derived from different analytic approaches and represent different facets of breast tumor biology including proliferation, immune response, and estrogen signaling.Whole-tumor gene expression profiling captures information on all cell types, whereas deconvolution approaches can generate in silico predictions of the proportions of immune cell types present in samples. As above, we used the ImSig package (5) to assess changes in immune cell content changes in the PreHAB data. Increases in several immune cell types were observed including macrophages and B cells, alongside a reduction in proliferation, but these changes were not statistically significant.Our analysis highlights different analysis approaches and supports the findings of the original study. We strongly encourage further studies in this area to examine the biological consequences of exercise on tumors along with assessments of the feasibility of introducing optimal and tolerable exercise regimens into routine clinical care for patients with cancer.No potential conflicts of interest were disclosed.A.H. Sims is grateful for funding from Breast Cancer Now and Cancer Research UK.
Interleukin-15 in cancer immunotherapy: IL-15 receptor complex versus soluble IL-15 in a cancer cell-delivered murine leukemia model
Authors: Alexandra Berger, Sarah J. Colpitts, Melanie S. S. Seabrook, Caren L. Furlonger, Maura B. Bendix, Joshua M. Moreau, William M. McKillop, Jeffrey A. Medin, Christopher J. Paige
Journal: Journal for ImmunoTherapy of Cancer (2019)

Cytokines of the common γ-chain receptor family such as IL-15 are vital with respect to activating immune cells, sustaining healthy immune functions, and augmenting the anti-tumor activity of effector cells, making them ideal candidates for cancer immunotherapy. IL-15, either in its soluble form (IL-15sol) or complexed with IL-15Rα (IL-15Rc), has been shown to exhibit potent anti-tumor activities in various experimental cancer studies. Here we describe the impact of intraperitoneal IL-15 in a cancer cell-delivered IL-15 immunotherapy approach using the 70Z/3-L leukemia mouse model. Whereas both forms of IL-15 led to significantly improved survival rates compared to the parent cell line, there were striking differences in the extent of the improved survival: mice receiving cancer cells secreting IL-15sol showed significantly longer survival and protective long-term immunity compared to those producing IL-15Rc. Interestingly, injection of leukemia cells secreting IL-15sol lead to heightened expansion of CD4<sup>+</sup> and CD8<sup>+</sup> T-cell populations in the peritoneum compared to IL-15Rc. Cell-secreted IL-15Rc resulted in an influx and/or expansion of NK1.1<sup>+</sup> cells in the peritoneum which was much less pronounced in the IL-15sol model. Furthermore, IL-15Rc but not IL-15sol lead to T-cell exhaustion and disease progression. To our knowledge, this is the first study detailing a significantly different biological effect of cell-delivered IL-15sol versus IL-15Rc in a mouse cancer immunotherapy study.
Closing the symbolic reference gap to support flexible reasoning about the passage of time
Authors: Danielle DeNigris, Patricia J. Brooks
Journal: Behavioral and Brain Sciences (2019)

Abstract This commentary relates Hoerl &amp; McCormack's dual systems perspective to models of cognitive development emphasizing representational redescription and the role of culturally constructed tools, including language, in providing flexible formats for thinking. We describe developmental processes that enable children to construct a mental time line, situate themselves in time, and overcome the primacy of the here and now.
Open source automated insulin delivery: addressing the challenge
Authors: Nick Oliver, Monika Reddy, Claire Marriott, Tomas Walker, Lutz Heinemann
Journal: npj Digital Medicine (2019)

Abstract Do-it-yourself automated insulin delivery systems for people living with type 1 diabetes use commercially available continuous glucose sensors and insulin pumps linked by unregulated open source software. Uptake of these systems is increasing, with growing evidence suggesting that positive glucose outcomes may be feasible. Increasing interest from people living with, or affected by, type 1 diabetes presents challenges to healthcare professionals, device manufacturers and regulators as the legal, governance and risk frameworks for such devices are not defined. We discuss the data, education, policy, technology and medicolegal obstacles to wider implementation of DIY systems and outline the next steps required for a co-ordinated approach to reducing variation in access to a technology that has potential to enable glucose self-management closer to target.