tbuckley/cabot-search huggingface dataset:
The moral obligations of conflict and resistance
Authors: Melanie Killen, Audun Dahl
Journal: Behavioral and Brain Sciences (2020)

Abstract Morality has two key features: (1) moral judgments are not solely determined by what your group thinks, and (2) moral judgments are often applied to members of other groups as well as your own group. Cooperative motives do not explain how young children reject unfairness, and assert moral obligations, both inside and outside their groups. Resistance and experience with conflicts, alongside cooperation, is key to the emergence and development of moral obligation.
Abstract PR10: <i>Candida albicans</i> infection mediates gastrointestinal track malignancy independently of Il17a in an APECED mouse model
Authors: Feng Zhu, Jami Willette-Brown, Trang Phan, Yongmei Zhao, Bao Tran, Scott G. Filler, Mihalis S. Lionakis, Yinling Hu
Journal: Cancer Research (2020)

Abstract The cytokine Il17a plays an important role in protection against fungal infection, yet it also serves as a pathogenic factor in several inflammation-related cancers. Previously we reported that fungal infection promotes the development of esophageal squamous cell carcinoma (ESCC) in the IKKalpha kinase-dead KA knock-in (KA) mice that mimic a human autoimmune disorder, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Our data showed that KA T cells failed to induce Il17a in response to fungal infection. However, the role of Il17a in fungal infection-mediated esophageal carcinogenesis remains to be further determined. In this study, we crossed KA mice with Il17a-/- mice to generate KA;Il17a-/- double mutant mice. We orally inoculated WT, Il17a-/-, KA, and KA;Il17a-/- mice with Candida albicans weekly for 3 months to investigate gastrointestinal (GI) track tumorigenesis, including the SCC development in the oral cavity, esophagus, and forestomach. We found that loss of Il17a leads to much earlier onset of GI track tumors in KA;Il17a-/- mice than that in KA mice. KA;Il17a-/- mice also died much earlier compared to KA mice, which is likely due to increased C. albicans burden in the absence of Il17a. The incidence of GI track tumors is comparable between KA and KA;Il17a-/- mice, suggesting that C. albicans infection-associated GI track tumorigenesis is independent of Il17a in KA mouse model. To further understand the underlying mechanism, we performed single-cell RNA sequencing analysis for CD45+ immune cells isolated from long-term C. alibicans-infected mouse esophagi of WT, Il17a-/-, KA, and KA;Il17a-/- mouse cohorts. Interestingly, the neutrophil population was significantly increased in the esophagi of KA and KA;Il17a-/- mice compared to WT and Il17a-/- mice. However, KA neutrophils exhibited reduced capacity in killing C. albicans with reduced NETs formation compared to WT neutrophils, suggesting that the defect in NETs formation may play a pivotal role in GI track tumorigenesis in the context of fungal infection. We are currently investigating how the interplay between C. albicans infection and host neutrophils regulates Candida infection-associated GI track tumorigenesis. This abstract is also being presented as Poster B01. Citation Format: Feng Zhu, Jami Willette-Brown, Trang Phan, Yongmei Zhao, Bao Tran, Scott G. Filler, Mihalis S. Lionakis, Yinling Hu. Candida albicans infection mediates gastrointestinal track malignancy independently of Il17a in an APECED mouse model [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr PR10.
Deep learning-enabled point-of-care sensing using multiplexed paper-based sensors
Authors: Zachary S. Ballard, Hyou-Arm Joung, Artem Goncharov, Jesse Liang, Karina Nugroho, Dino Di Carlo, Omai B. Garner, Aydogan Ozcan
Journal: npj Digital Medicine (2020)

Abstract We present a deep learning-based framework to design and quantify point-of-care sensors. As a use-case, we demonstrated a low-cost and rapid paper-based vertical flow assay (VFA) for high sensitivity C-Reactive Protein (hsCRP) testing, commonly used for assessing risk of cardio-vascular disease (CVD). A machine learning-based framework was developed to (1) determine an optimal configuration of immunoreaction spots and conditions, spatially-multiplexed on a sensing membrane, and (2) to accurately infer target analyte concentration. Using a custom-designed handheld VFA reader, a clinical study with 85 human samples showed a competitive coefficient-of-variation of 11.2% and linearity of R 2 = 0.95 among blindly-tested VFAs in the hsCRP range (i.e., 0–10 mg/L). We also demonstrated a mitigation of the hook-effect due to the multiplexed immunoreactions on the sensing membrane. This paper-based computational VFA could expand access to CVD testing, and the presented framework can be broadly used to design cost-effective and mobile point-of-care sensors.
Cyclodextrin Prevents Abdominal Aortic Aneurysm via Activation of Vascular Smooth Muscle Cell Transcription Factor EB
Authors: Haocheng Lu, Jinjian Sun, Wenying Liang, Ziyi Chang, Oren Rom, Yang Zhao, Guizhen Zhao, Wenhao Xiong, Huilun Wang, Tianqing Zhu, Yanhong Guo, Lin Chang, Minerva T. Garcia-Barrio, Jifeng Zhang, Y. Eugene Chen, Yanbo Fan
Journal: Circulation (2020)

Background: Abdominal aortic aneurysm (AAA) is a severe aortic disease with a high mortality rate in the event of rupture. Pharmacological therapy is needed to inhibit AAA expansion and prevent aneurysm rupture. Transcription factor EB (TFEB), a master regulator of autophagy and lysosome biogenesis, is critical to maintain cell homeostasis. In this study, we aim to investigate the role of vascular smooth muscle cell (VSMC) TFEB in the development of AAA and establish TFEB as a novel target to treat AAA. Methods: The expression of TFEB was measured in human and mouse aortic aneurysm samples. We used loss/gain-of-function approaches to understand the role of TFEB in VSMC survival and explored the underlying mechanisms through transcriptome and functional studies. Using VSMC-selective Tfeb knockout mice and different mouse AAA models, we determined the role of VSMC TFEB and a TFEB activator in AAA in vivo. Results: We found that TFEB is downregulated in both human and mouse aortic aneurysm lesions. TFEB potently inhibits apoptosis in VSMCs, and transcriptome analysis revealed that TFEB regulates apoptotic signaling pathways, especially apoptosis inhibitor B-cell lymphoma 2. B-cell lymphoma 2 is significantly upregulated by TFEB and is required for TFEB to inhibit VSMC apoptosis. We consistently observed that TFEB deficiency increases VSMC apoptosis and promotes AAA formation in different mouse AAA models. Furthermore, we demonstrated that 2-hydroxypropyl-β-cyclodextrin, a clinical agent used to enhance the solubility of drugs, activates TFEB and inhibits AAA formation and progression in mice. Last, we found that 2-hydroxypropyl-β-cyclodextrin inhibits AAA in a VSMC TFEB–dependent manner in mouse models. Conclusions: Our study demonstrated that TFEB protects against VSMC apoptosis and AAA. TFEB activation by 2-hydroxypropyl-β-cyclodextrin may be a promising therapeutic strategy for the prevention and treatment of AAA.
Naevoid basal cell carcinoma syndrome with a palmar epidermoid cyst, milia and maxillary cysts
Authors: K. Ogata, M. Ikeda, K. Miyoshi, Y. Yamamoto, T. Yamamoto, T. Osaki, E. Michimukai, Y. Tanaka, A. Sakamoto, T. Oakamoto, H. Kodama
Journal: British Journal of Dermatology (2008)

Journal Article Naevoid basal cell carcinoma syndrome with a palmar epidermoid cyst, milia and maxillary cysts Get access K. Ogata, K. Ogata Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar M. Ikeda, M. Ikeda Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar K. Miyoshi, K. Miyoshi Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar Y. Yamamoto, Y. Yamamoto Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar T. Yamamoto, T. Yamamoto Oral Surgery, Kochi Medical School, Okohcho, Nankoku, Kochi 783–8505, Japan Search for other works by this author on: Oxford Academic Google Scholar T. Osaki, T. Osaki Oral Surgery, Kochi Medical School, Okohcho, Nankoku, Kochi 783–8505, Japan Search for other works by this author on: Oxford Academic Google Scholar E. Michimukai, E. Michimukai Department of Oral and Maxillofacial Surgery I, School of Dentistry, Hiroshima University, Kasumi 1‐chome, Minami‐ku, Hiroshima 734–8553, Japan Correspondence: Dr Kimiko OgataE‐mail: ogata@med.kochi‐ms.ac.jp Search for other works by this author on: Oxford Academic Google Scholar Y. Tanaka, Y. Tanaka Department of Oral and Maxillofacial Surgery I, School of Dentistry, Hiroshima University, Kasumi 1‐chome, Minami‐ku, Hiroshima 734–8553, Japan Correspondence: Dr Kimiko OgataE‐mail: ogata@med.kochi‐ms.ac.jp Search for other works by this author on: Oxford Academic Google Scholar A. Sakamoto, A. Sakamoto Department of Oral and Maxillofacial Surgery I, School of Dentistry, Hiroshima University, Kasumi 1‐chome, Minami‐ku, Hiroshima 734–8553, Japan Correspondence: Dr Kimiko OgataE‐mail: ogata@med.kochi‐ms.ac.jp Search for other works by this author on: Oxford Academic Google Scholar T. Oakamoto, T. Oakamoto Department of Oral and Maxillofacial Surgery I, School of Dentistry, Hiroshima University, Kasumi 1‐chome, Minami‐ku, Hiroshima 734–8553, Japan Correspondence: Dr Kimiko OgataE‐mail: ogata@med.kochi‐ms.ac.jp Search for other works by this author on: Oxford Academic Google Scholar ... Show more H. Kodama H. Kodama Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 145, Issue 3, 1 September 2001, Pages 508–509, https://doi.org/10.1111/j.1365-2133.2001.04389.x Published: 01 September 2001
P074 The alarmin S100A9 hampers osteoclast differentiation from circulating precursors by reducing the expression of rank
Authors: MH van den Bosch, I Di Ceglie, AB Blom, C Logie, JH Martens, J Roth, T Vogl, CS Goodyear, PM van der Kraan, PL van Lent
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Post-doctoral fellow. <h3>Introduction</h3> The alarmin S100A8/A9 is produced in high levels in inflamed synovium during arthritic diseases and has been implicated in sterile inflammation-induced bone resorption. We have previously shown that this alarmin increases the bone-resorptive capacity of mature osteoclasts. However, the effects on osteoclast differentiation remains elusive. <h3>Objectives</h3> Here, we investigated the effects of S100A9 on osteoclast differentiation from CD14<sup>+</sup> circulating precursors. <h3>Methods</h3> CD14<sup>+</sup> monocytes were isolated from buffy coats of healthy donors and differentiated towards osteoclasts with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B (RANK) ligand in the presence or absence of S100A9. Differentiation state of osteoclasts was determined by tartrate-resistant acid phosphatase (TRAP) staining and resorption capacity using hydroxyapatite-like-coated plates. RNA expression was analyzed with RNA sequencing and qPCR. RANK expression was assessed using FACS. Underlying epigenetic programming was studied using chromatin immunoprecipitation. Secretion of pro-/anti-inflammatory mediators was analyzed with Luminex analysis. <h3>Results</h3> S100A9 stimulation during monocyte-to-osteoclast differentiation resulted in a strong decrease in the numbers of multinucleated osteoclasts, underlined by a decreased resorptive capacity. The thus differentiated cells showed a high production of pro-inflammatory factors, such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α (TNFα) after 16 hour of stimulation. In contrast, at day 4, the cells showed a decreased expression of the osteoclast-promoting factor TNFα. Interestingly, S100A9 stimulation during the first 16 hour of culture was sufficient to reduce osteoclastogenesis. We observed that within this time frame, S100A9 inhibited the M-CSF-mediated induction of RANK, which associated with changes in various histone marks at the epigenetic level. This S100A9-induced reduction in RANK could be partially reversed by blocking TNFα, but not interleukin-1 (IL-1). <h3>Conclusions</h3> Whereas S100A8/A9 was previously shown to stimulate the resorptive capacity of mature osteoclasts, we here show that early S100A9 stimulation impedes monocyte-to-osteoclast differentiation via reduction of RANK expression that is partially TNFα-mediated. This suggests that the timing of exposure to S100A8/A9 is an important determinant for monocyte-to-osteoclast differentiation. <h3>Disclosure of Interest</h3> None declared.
Combination therapy for non-alcoholic steatohepatitis: rationale, opportunities and challenges
Authors: Jean-François Dufour, Cyrielle Caussy, Rohit Loomba
Journal: Gut (2020)

Non-alcoholic steatohepatitis (NASH) is becoming a leading cause of cirrhosis with the burden of NASH-related complications projected to increase massively over the coming years. Several molecules with different mechanisms of action are currently in development to treat NASH, although reported efficacy to date has been limited. Given the complexity of the pathophysiology of NASH, it will take the engagement of several targets and pathways to improve the results of pharmacological intervention, which provides a rationale for combination therapies in the treatment of NASH. As the field is moving towards combination therapy, this article reviews the rationale for such combination therapies to treat NASH based on the current therapeutic landscape as well as the advantages and limitations of this approach.
Percutaneous left atrial appendage transcatheter occlusion (PLAATO) to prevent stroke in patients with atrial fibrillation: Initial results of the multicenter feasibility trial
Authors: Horst Sievert, Michael D. Lesh, Stefan Ostermayer, Kai Billinger, Thomas Trepels, Heyder Omran, Antonio L. Bartorelli, Paolo Della Bella, Toshiko Nakai, Mark Reisman, William Gray, Carlo DiMario, Peter C. Block, Paul Kramer, David O. Williams, Athena Poppas, Allan Skanes, Ulrike Krumsdorf, Detlef Scherer
Journal: Journal of the American College of Cardiology (2003)
P636T wave peak to t wave end interval is prolonged in patients with atrioventricular nodal reentry:
Authors: O C Yontar, A Tutuncu, K Karaagac, A Karakus, ONUR Yontar, M Melek
Journal: Cardiovascular Research (2014)

Background: Atrioventricular nodal reentry tachycardia (AVNRT) is known to be associated with increased risk of susceptibility for ventricular arrhythmias and sudden death. Studies indicate that prolongation of the interval between the peak and end of the T wave (Tpeak to Tend, Tp-e) on the 12-lead ECG, is a marker of ventricular arrhythmogenesis. The aim of this study was to assess ventricular repolarization in patients with AVNRT by using Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio. Method: Patient records were retrospectively analyzed. Electrocardiogram of 62 patients, who were diagnosed as AVNRT by electrophysiological study, were obtained and scanned. T wave peak to end interval, QT and corrected QT intervals were measured. Electrocardiograms of age and sex matched 34 healthy control individuals were also analyzed for comparison. Patients with critical coronary stenosis, moderate or severe valve disease, left and/or right heart failure, left and/or right ventricle hypertrophy, atrial fibrillation, right or left bundle block or patients who got pacemaker or ICD implanted were excluded. Results: Both groups did not differ in patient demography. Mean values for AVNRT patients and control group were: QT (362.7±43.7 vs 364.1± 34.1), QTc (417.8±43.2 vs 438.3±44.2) and Tp-e interval (83.5±16.6 vs 77.0±9.7). Tp-e/QT and Tp-e/QTc ratio were also higher in AVNRT group. Discussion: Tp-e is a measure of transmural dispersion of repolarization in the left ventricle and accepted as a surrogate for increased ventricular arrhythmogenesis risk. Tp-e/QT and Tp-e/QTc are relatively new markers which also indicate repolarization defects. Our results show that Tp-e (p=0.018), Tp-e/QT (0.23 vs 0.21; p=0,008) and Tp-e/QTc (0.20 vs 0.17; p=0.000) were significantly higher in AVNRT group which correspond to prior studies about strong relationship between AVNRT and ventricular arrhythmia. ECG measurements of both groups. Tp-e: T wave peak to end interval QTc: corrected QT interval ECG measurements of both groups. Tp-e: T wave peak to end interval QTc: corrected QT interval
Arthroscopic surgery for degenerative knee arthritis and meniscal tears: a clinical practice guideline
Authors: Reed A C Siemieniuk, Ian A Harris, Thomas Agoritsas, Rudolf W Poolman, Romina Brignardello-Petersen, Stijn Van de Velde, Rachelle Buchbinder, Martin Englund, Lyubov Lytvyn, Casey Quinlan, Lise Helsingen, Gunnar Knutsen, Nina Rydland Olsen, Helen Macdonald, Louise Hailey, Hazel M Wilson, Anne Lydiatt, Annette Kristiansen
Journal: British Journal of Sports Medicine (2018)

### What you need to know What is the role of arthroscopic surgery in degenerative knee disease? An expert panel produced these recommendations based on a linked systematic review triggered by a randomised trial published in The BMJ in June 2016, which found that, among patients with a degenerative medial meniscus tear, knee arthroscopy was no better than exercise therapy. The panel make a strong recommendation against arthroscopy for degenerative knee disease. Box 1 shows all of the articles and evidence linked in this Rapid Recommendation package. The infographic provides an overview of the absolute benefits and harms of arthroscopy in standard GRADE format. Table 1 below shows any evidence that has emerged since the publication of this article.Box 1 ### Linked articles in this BMJ Rapid Recommendations cluster
Abstract 10181: Natural History of Genotype Positive Phenotype Negative Patients with Hypertrophic Cardiomyopathy
Authors: Belinda Gray, Jodie Ingles, Christopher Semsarian
Journal: Circulation (2011)

Background: Hypertrophic cardiomyopathy (HCM) is a clinically and genetically heterogeneous disease. Commercially available genetic testing has resulted in the emergence of a new subgroup of patien...
Association of Professional Football Cumulative Head Impact Index Scores With All-Cause Mortality Among National Football League Players
Authors: Brittany L. Kmush, Madeline Mackowski, Justin Ehrlich, Bhavneet Walia, Arthur Owora, Shane Sanders
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Long-term adverse health outcomes, particularly those associated with repetitive head impacts, are of growing concern among US-style football players in the US and Canada. <h3>Objective</h3> To assess whether exposure to repetitive head impacts during a professional football career is associated with an increase in the risk of all-cause mortality. <h3>Design, Setting, and Participants</h3> This retrospective cohort study included 13 912 players in the 1969 to 2017 National Football League (NFL) seasons. All cause-mortality up until July 1, 2018, was included. Data collection was performed from July 13, 2017, to July 1, 2018, as reported in the Pro Football Reference. <h3>Exposures</h3> The main exposure was a professional football cumulative head impact index (pfCHII). The pfCHII was measured by combining cumulative padded practice time and games played summed during seasons of play reported in the Pro Football Reference and a player position risk adjustment from helmet accelerometer studies. <h3>Main Outcomes and Measures</h3> Demographic characteristics except for the pfCHII were calculated for 14 366 players with complete follow-up. The pfCHII was calculated for 13 912 players (eliminating the 454 specials teams players). Cox proportional hazards regression was used to compare hazard ratios (HRs) of death by repetitive head impacts. Analyses were unadjusted and adjusted for birth year, body mass index, and height. <h3>Results</h3> Among 14 366 NFL players who had follow-up for analysis, the mean (SD) age was 47.3 (14.8) years, the mean (SD) body mass index was 29.6 (3.9), and 763 of 14 366 players (5.3%) had died. Among 13 912 players in the pfCHII analysis, the median pfCHII was 32.63 (interquartile range, 13.71-66.12). A 1-log increase in pfCHII was significantly associated with an increased hazard of death for the 1969 to 2017 seasons (HR, 2.02; 95% CI, 1.21-3.37;<i>P</i> = .01) after adjustment. The quadratic pfCHII was also statistically significant (HR, 0.91; 95% CI, 0.85-0.98;<i>P</i> = .01), indicating that the hazard of death increased at a decreasing rate, whereas the pfCHII increased. <h3>Conclusions and Relevance</h3> The findings suggest that an increase in repetitive head impacts is associated with an increased hazard of death among NFL players. Reduction in repetitive head impacts from playing football or other activities through additional rule and equipment changes may be associated with reduced mortality.
OTU-06 Upper gastrointestinal bleeding in scotland: trends in demographics and outcomes 2000–2015
Authors: Sardar Chaudhary, Daniel Mackay, Jill P Pell, Allan J Morris, Nick Church, Andrew Fraser, Adrian J Stanley
Journal: Endoscopy (2019)

<h3>Introduction</h3> Upper gastrointestinal bleeding (UGIB) remains a common cause of presentation and admission to hospital in the UK, with the incidence in Scotland one of the highest in the world. Over the past 15 years there have been several developments to improve management of patients with UGIB. <h3>Methods</h3> Our aim was to investigate the number of patients presenting to Scottish hospitals with UGIB between 2000–2015 and assess the difference in demographics, aetiology of bleeding and clinical outcomes, including those for weekends and weekday presentations. Data were collected from SMR01 hospital admissions records and GRO death certificates for the period 1st January 2000 to 31st December 2015 and analysed in the national safe haven. All outputs were disclosure-checked for confidentiality purposes. Admission and death rates were computed for each year with trends over the study period estimated using Poisson regression. Standard errors were adjusted to account for any serial dependence. <h3>Results</h3> A total of 129,404 patients presented to Scottish hospitals with UGIB between January 2000 and December 2015. Mean age at admission increased over this period from 59.2 years to 61.4 years (P=0.049). There was no difference in the annual number of patients over the 15-year period. The incidence of UGIB was highest in the more deprived quintiles, although there was a reduction in incidence in the three most deprived quintiles over the study period (SIMD1; P&lt;0.001: SIMD2; P=0.002: SIMD3; P=0.001). There was a significant decrease in 30-day case-fatality from 10.1% in 2000 to 7.9% in 2015 (p&lt;0.001), which was significant across all the deprivation quintiles (P&lt;0.001). This reduction was seen for both variceal and non-variceal bleeding (IRR 0.967; P&lt;0.001 and IRR 0.980; P&lt;0.001 respectively) with deaths as a proportion of admissions declining fastest in the variceal compared to the non-variceal group (24.4% to 14.5%, and 9.8% to 7.8% respectively). The mean length of stay also fell from 3.9 days to 2.1 days, an average decline of 0.14 days per year (95% CI .15612 - .11723; P&lt;0.001). There was no difference in 30-day case-fatality between patients presenting at weekdays or weekends. <h3>Conclusions</h3> The number of patients presenting with UGIB to Scottish hospitals annually has remained similar over the 15-year study period. However, case-fatality and length of hospital stay has fallen, despite a rise in the mean age of patients.