tbuckley/cabot-search huggingface dataset:
Global implementation of the world health organization's International Classification of Diseases (ICD)‐11: The allergic and hypersensitivity conditions model
Authors: Luciana Kase Tanno, Robert Chalmers, Robert Jacob, Nenad Kostanjsek, Ana Luiza Bierrenbach, Bryan Martin, Nicolas Molinari, Isabella Annesi‐Maesano, Nikolaos G. Papadopoulos, Mario Sanchez‐Borges, Lanny J. Rosenwasser, Ignacio Ansontegui, Motohiro Ebisawa, Juan Carlos Sisul, Edgardo Jares, Maximiliano Gomez, Ioana Agache, Antonella Muraro, Gary W. K. Wong, Francis Thien, Ruby Pawankar, Todd A. Mahr, James L. Sublett, David M. Lang, Thomas Casale, Pascal Demoly
Journal: Allergy (2020)

The International Classification of Diseases (ICD) provides a common language for use worldwide as a diagnostic and classification tool for epidemiology, clinical purposes and health management. Since its first edition, the ICD has maintained a framework distributing conditions according to topography, with the result that some complex conditions, such as allergies and hypersensitivity disorders (A/H) including anaphylaxis, have been poorly represented. The change in hierarchy in ICD-11 permitted the construction of the pioneer section addressed to A/H, which may result in more accurate mortality and morbidity statistics, including more accurate accounting for mortality due to anaphylaxis, strengthen classification, terminology and definitions. The ICD-11 was presented and adopted by the 72nd World Health Assembly in May 2019, and the implementation is ongoing worldwide. We here present the outcomes from an online survey undertaken to reach out the allergy community worldwide in order to peer review the terminology, classification and definitions of A/H introduced into ICD-11 and to support their global implementation. Data are presented here for 406 respondents from 74 countries. All of the subsections of the new A/H section of the ICD-11 had been considered with good accuracy by the majority of respondents. We believe that, in addition to help during the implementation phase, all the comments provided will help to improve the A/H classification and to increase awareness by different disciplines of what actions are needed to ensure more accurate epidemiological data and better clinical management of A/H patients.
Abstract 15154: Reducing Wall Stress With a Trans-Ventricular Restraint Improves Systolic Function and Cardiac Energy Metabolism in a Rodent Ischemic Cardiomyopathy Model
Authors: Daisuke Onohara, Daniella Corporan, Takanori Kono, Roberto Hernandez-Merlo, Muralidhar Padala
Journal: Circulation (2019)

Introduction: Left ventricle (LV) dilatation after myocardial infarction increases wall stress (WS) which drives adverse LV remodeling to failure. LV reshaping to reduce WS is a promising strategy ...
Dexamethasone Intracanalicular Insert: A Review in Treating Post-Surgical Ocular Pain and Inflammation
Authors: Arnold Lee, Hannah A. Blair
Journal: Drugs (2020)

Dextenza®, an intracanalicular insert that is placed into the lower punctal opening of the eye, gradually releases dexamethasone for up to 30 days to alleviate pain and inflammation associated with ophthalmic surgery. A significantly higher proportion of patients treated with the dexamethasone intracanalicular insert than with the placebo insert had no pain at day 8 (co-primary endpoint, 7 days post-operation) across three pivotal phase III trials, and the inflammation co-primary endpoint (absence of anterior chamber cells) at day 14 (13 days post-operation) was met in two of three trials. Overall, the dexamethasone intracanalicular insert was effective and generally well tolerated for the treatment of post-surgical ocular pain and inflammation following cataract surgery. As low patient adherence is an issue for topical ophthalmic anti-inflammatory medications, the convenience (ease of insertion, single application with no patient input and typically no removal required) of the dexamethasone intracanalicular insert makes it a promising emerging option for the treatment of ocular inflammation and pain following ophthalmic surgery.
Sudden cardiac death in Japanese heart failure : results from a multicenter retrospective cohort study
Authors: N Kawashiro, Naoki Matuda, Kazuo Haze, Takashi Honda, Toshinobu Horie, Tetsuya Sumiyoshi, Yasuhiro Kawagoe, Masatoshi Kawana, Naohide Tanaka, Tatsuro Uchida, Takashi Nirei, Tetsurou Ueda, Naoya Fujita, Masao Kawaguchi, Yasuhiro Endoh, Toshiaki Oka, Ryo Koyanagi, Hiroshi Ogawa, Nobuhisa Hagiwara, Hiroshi Kasanuki
Journal: Circulation (2006)
Association Between Penicillin Allergy Documentation and Antibiotic Use
Authors: Kimberly G. Blumenthal, Kristi Kuper, Lucas T. Schulz, Tanaya Bhowmick, Michael Postelnick, Francesca Lee, Rochelle P. Walensky
Journal: JAMA Internal Medicine (2020)

that legalization of recreational marijuana is associated with increased traffic fatality rates.Applying these results to national driving statistics, nationwide legalization would be associated with 6800 (95% CI, 4200-9700) excess roadway deaths each year.Despite certain methodological differences, we found an increase similar to that reported by Aydelotte et al. 4 They reported an increase of 1.8 fatal crashes (equivalent to 2.0 fatalities) per BVMT.We concur with their opinion that changes may not be detected immediately after legalization but only after a longer time period or after commercial sales begin.We chose a control group consisting of all states with neither legal recreational nor medical marijuana to isolate the effects of marijuana.We did not require that control states have baseline attributes similar to the experimental states because the difference-in-difference technique removes biases in comparisons between experimental and control groups that result from permanent differences between those groups.Our conclusions, nonetheless, are limited by adjusting for only 3 state-specific factors that may have changed during the study period.It is possible that another confounder, rather than marijuana legalization and commercialization, caused the observed increase in roadway deaths.
Epidemiology of injury and illness in 153 Australian international-level rowers over eight international seasons
Authors: Larissa Trease, Kellie Wilkie, Greg Lovell, Michael Drew, Ivan Hooper
Journal: British Journal of Sports Medicine (2020)

Aim To report the epidemiology of injury and illness in elite rowers over eight seasons (two Olympiads). Methods All athletes selected to the Australian Rowing Team between 2009 and 2016 were monitored prospectively under surveillance for injury and illness. The incidence and burden of injury and illness were calculated per 1000 athlete days (ADs). The body area, mechanism and type of all injuries were recorded and followed until the resumption of full training. We used interrupted time series analyses to examine the association between fixed and dynamic ergometer testing on rowers’ injury rates. Time lost from illness was also recorded. Results All 153 rowers selected over eight seasons were observed for 48 611 AD. 270 injuries occurred with an incidence of 4.1–6.4 injuries per 1000 AD. Training days lost totalled 4522 (9.2% AD). The most frequent area injured was the lumbar region (84 cases, 1.7% AD) but the greatest burden was from chest wall injuries (64 cases, 2.6% AD.) Overuse injuries (n=224, 83%) were more frequent than acute injuries (n=42, 15%). The most common activity at the time of injury was on-water rowing training (n=191, 68). Female rowers were at 1.4 times the relative risk of chest wall injuries than male rowers; they had half the relative risk of lumbar injuries of male rowers. The implementation of a dynamic ergometers testing policy (Concept II on sliders) was positively associated with a lower incidence and burden of low back injury compared with fixed ergometers (Concept II). Illness accounted for the greatest number of case presentations (128, 32.2% cases, 1.2% AD). Conclusions Chest wall and lumbar injuries caused training time loss. Policy decisions regarding ergometer testing modality were associated with lumbar injury rates. As in many sports, illness burden has been under-recognised in elite Australian rowers.
Intestinal permeability, microbial translocation, changes in duodenal and fecal microbiota, and their associations with alcoholic liver disease progression in humans
Authors: Luca Maccioni, Bei Gao, Sophie Leclercq, Boris Pirlot, Yves Horsmans, Philippe De Timary, Isabelle Leclercq, Derrick Fouts, Bernd Schnabl, Peter Stärkel
Journal: Gut Microbes (2020)

Background Animal data suggest a role of the gut-liver axis in progression of alcoholic liver disease (ALD), but human data are scarce especially for early disease stages.Methods We included patients with alcohol use disorder (AUD) who follow a rehabilitation program and matched healthy controls. We determined intestinal epithelial and vascular permeability (IP) (using urinary excretion of 51Cr-EDTA, fecal albumin content, and immunohistochemistry in distal duodenal biopsies), epithelial damage (histology, serum iFABP, and intestinal gene expression), and microbial translocation (Gram – and Gram + serum markers by ELISA). Duodenal mucosa-associated microbiota and fecal microbiota were analyzed by 16 S rRNA sequencing. ALD was staged by Fibroscan® (liver stiffness, controlled attenuation parameter) in combination with serum AST, ALT, and CK18-M65.Results Only a subset of AUD patients had increased 51Cr-EDTA and fecal albumin together with disrupted tight junctions and vasculature expression of plasmalemma Vesicle-Associated Protein-1. The so-defined increased intestinal permeability was not related to changes of the duodenal microbiota or alterations of the intestinal epithelium but associated with compositional changes of the fecal microbiota. Leaky gut alone did not explain increased microbial translocation in AUD patients. By contrast, duodenal dysbiosis with a dominance shift toward specific potential pathogenic bacteria genera (Streptococcus, Shuttleworthia, Rothia), increased IP and elevated markers of microbial translocation characterized AUD patients with progressive ALD (steato-hepatitis, steato-fibrosis).Conclusion Progressive ALD already at early disease stages is associated with duodenal mucosa-associated dysbiosis and elevated microbial translocation. Surprisingly, such modifications were not linked with increased IP. Rather, increased IP appears related to fecal microbiota dysbiosis.
Association Between High-Deductible Health Plans and Disparities in Access to Care Among Cancer Survivors
Authors: Megan B. Cole, Jacqueline E. Ellison, Amal N. Trivedi
Journal: JAMA Network Open (2020)

This cross-sectional study uses data from the 2013-2018 National Health Interview Survey to examine the association between enrollment in a high-deductible health plan and access to care among cancer survivors differentiated by race/ethnicity.
Interaction with CD68 and Regulation of GAS6 Expression by Endosialin in Fibroblasts Drives Recruitment and Polarization of Macrophages in Hepatocellular Carcinoma
Authors: Fa Yang, Yan Wei, Donghui Han, Yu Li, Shengjia Shi, Dian Jiao, Jieheng Wu, Qiang Zhang, Changhong Shi, Lijun Yang, Wei Song, Jingliang Zhang, Yueheng Han, Rui Zhang, An-Gang Yang, Dimiter S. Dimitrov, Aizhi Zhao, Weijun Qin, Weihong Wen
Journal: Cancer Research (2020)

Fibroblasts and macrophages play key roles in the development of hepatocellular carcinoma (HCC). However, cross-talk between these two kinds of cells has not been well studied. Endosialin (CD248/TEM1) is a transmembrane glycoprotein that is expressed in certain cancer cells, tumor stromal cells, and pericytes. In this study, we found that endosialin is mainly expressed in cancer-associated fibroblasts (CAF) in HCC and its expression inversely correlates with patient prognosis. Endosialin interacted with CD68 to recruit macrophages and regulated expression of GAS6 in CAFs to mediate M2 polarization of macrophages. The fully human antibody IgG78 bound glycosylated endosialin and induced its internalization in CAFs, thus weakening the cross-talk between CAFs and macrophages. In subcutaneous and orthotopic xenograft models of HCC in nude mice, treatment with IgG78 significantly inhibited tumor growth. These results indicate that endosialin-positive CAFs promote HCC progression and highlight IgG78 as a promising therapeutic candidate for HCC treatment. SIGNIFICANCE: These findings highlight CAF-expressed endosialin as a primary regulator of macrophage recruitment and polarization and demonstrate endosialin inhibition as a potential treatment strategy for HCC. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/18/3892/F1.large.jpg.
IL15 Stimulation with TIGIT Blockade Reverses CD155-mediated NK-Cell Dysfunction in Melanoma
Authors: Joe-Marc Chauvin, Mignane Ka, Ornella Pagliano, Carmine Menna, Quanquan Ding, Richelle DeBlasio, Cindy Sanders, Jiajie Hou, Xian-Yang Li, Soldano Ferrone, Diwakar Davar, John M. Kirkwood, Robert J. Johnston, Alan J. Korman, Mark J. Smyth, Hassane M. Zarour
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Natural killer (NK) cells play a critical role in tumor immunosurveillance. Multiple activating and inhibitory receptors (IR) regulate NK-cell–mediated tumor control. The IR T-cell immunoglobulin and ITIM domain (TIGIT) and its counter-receptor CD226 exert opposite effects on NK-cell–mediated tumor reactivity. Experimental Design: We evaluated the frequency, phenotype, and functions of NK cells freshly isolated from healthy donors and patients with melanoma with multiparameter flow cytometry. We assessed TIGIT and CD226 cell surface expression and internalization upon binding to CD155. We evaluated the role of IL15 and TIGIT blockade in increasing NK-cell–mediated cytotoxicity in vitro and in two mouse models. Results: NK cells are present at low frequencies in metastatic melanoma, are dysfunctional, and downregulate both TIGIT and CD226 expression. As compared with TIGIT− NK cells, TIGIT+ NK cells exhibit higher cytotoxic capacity and maturation, but paradoxically lower cytotoxicity against CD155+ MHC class I–deficient melanoma cells. Membrane bound CD155 triggers CD226 internalization and degradation, resulting in decreased NK-cell–mediated tumor reactivity. IL15 increases TIGIT and CD226 gene expression by tumor-infiltrating NK cells (TiNKs) and, together with TIGIT blockade, increases NK-cell–mediated melanoma cytotoxicity in vitro and decreases tumor metastasis in two mouse melanoma models. Specific deletion of TIGIT on transferred NK cells enhances the antimetastatic activity of IL15, while CD226 blockade decreases the effects of IL15 and TIGIT blockade. Conclusions: Our findings support the development of novel combinatorial immunotherapy with IL15 and TIGIT blockade to promote NK-cell–mediated destruction of MHC class I–deficient melanoma, which are refractory to CD8+ T-cell–mediated immunity. See related commentary by Pietra et al., p. 5274
Remote ischaemic preconditioning ameliorates anthracycline-induced cardiotoxicity and preserves mitochondrial integrity
Authors: Carlos Galán-Arriola, Rocio Villena-Gutiérrez, María I Higuero-Verdejo, Iván A Díaz-Rengifo, Gonzalo Pizarro, Gonzalo J López, Antonio de Molina-Iracheta, Claudia Pérez-Martínez, Rodrigo D García, David González-Calle, Manuel Lobo, Pedro L Sánchez, Eduardo Oliver, Raúl Córdoba, Valentin Fuster, Javier Sánchez-González, Borja Ibanez
Journal: Cardiovascular Research (2020)

Abstract Aims Anthracycline-induced cardiotoxicity (AIC) is a serious adverse effect among cancer patients. A central mechanism of AIC is irreversible mitochondrial damage. Despite major efforts, there are currently no effective therapies able to prevent AIC. Methods and results Forty Large-White pigs were included. In Study 1, 20 pigs were randomized 1:1 to remote ischaemic preconditioning (RIPC, 3 cycles of 5 min leg ischaemia followed by 5 min reperfusion) or no pretreatment. RIPC was performed immediately before each intracoronary doxorubicin injections (0.45 mg/kg) given at Weeks 0, 2, 4, 6, and 8. A group of 10 pigs with no exposure to doxorubicin served as healthy controls. Pigs underwent serial cardiac magnetic resonance (CMR) exams at baseline and at Weeks 6, 8, 12, and 16, being sacrifice after that. In Study 2, 10 new pigs received 3 doxorubicin injections (with/out preceding RIPC) and were sacrificed at week 6. In Study 1, left ventricular ejection fraction (LVEF) depression was blunted animals receiving RIPC before doxorubicin (RIPC-Doxo), which had a significantly higher LVEF at Week 16 than doxorubicin treated pigs that received no pretreatment (Untreated-Doxo) (41.5 ± 9.1% vs. 32.5 ± 8.7%, P = 0.04). It was mainly due to conserved regional contractile function. In Study 2, transmission electron microscopy (TEM) at Week 6 showed fragmented mitochondria with severe morphological abnormalities in Untreated-Doxo pigs, together with upregulation of fission and autophagy proteins. At the end of the 16-week Study 1 protocol, TEM revealed overt mitochondrial fragmentation with structural fragmentation in Untreated-Doxo pigs, whereas interstitial fibrosis was less severe in RIPC+Doxo pigs. Conclusion In a translatable large-animal model of AIC, RIPC applied immediately before each doxorubicin injection resulted in preserved cardiac contractility with significantly higher long-term LVEF and less cardiac fibrosis. RIPC prevented mitochondrial fragmentation and dysregulated autophagy from AIC early stages. RIPC is a promising intervention for testing in clinical trials in AIC.
Peptidase PepP is a novel virulence factor of <i>Campylobacter jejuni</i> contributing to murine campylobacteriosis
Authors: Markus M. Heimesaat, Anna-Maria Schmidt, Soraya Mousavi, Ulrike Escher, Nicole Tegtmeyer, Silja Wessler, Gabriele Gadermaier, Peter Briza, Dirk Hofreuter, Stefan Bereswill, Steffen Backert
Journal: Gut Microbes (2020)

Mechanisms of host–pathogen interactions resulting in immunopathological responses upon human Campylobacter jejuni infection are not completely understood, but the recent availability of murine infection models mimicking key features of campylobacteriosis helps solving this dilemma. During a screen for proteases expressed by C. jejuni, we identified a peptidase of the M24 family as a potential novel virulence factor, which was named PepP. The gene is strongly conserved in various Campylobacter species. A constructed deletion mutant ΔpepP of C. jejuni strain 81–176 grew as efficiently compared to isogenic wild-type (WT) or pepP complemented bacteria. To shed light on the potential role of this protease in mediating immunopathological responses in the mammalian host, we perorally challenged microbiota-depleted IL-10−/- mice with these strains. All strains stably colonized the murine gastrointestinal tract with comparably high loads. Remarkably, pepP deficiency was associated with less severe induced malaise, with less distinct apoptotic and innate immune cell responses, but also with more pronounced proliferative/regenerative epithelial cell responses in the large intestine at d6post-infection. Furthermore, pro-inflammatory mediators were lower in the colon, ileum, and mesenteric lymph nodes of mice that had been challenged with the ΔpepP mutant compared to the WT or pepP complemented strains. This also held true for extra-intestinal organs including liver, kidneys, and lungs, and, strikingly, to systemic compartments. Taken together, protease PepP is a novel virulence determinant involved in mediating campylobacteriosis. The finding that apoptosis in the colon is significantly diminished in mice infected with the pepP mutant highlights the epithelial layer as the first and main target of PepP in the intestine.
Calcium-sensing receptor autoantibody-mediated hypoparathyroidism associated with immune checkpoint inhibitor therapy: diagnosis and long-term follow-up
Authors: Ramona Dadu, Theresa E Rodgers, Van A Trinh, Elizabeth Helen Kemp, Trisha D Cubb, Sapna Patel, Julie M Simon, Elizabeth M Burton, Hussein Tawbi
Journal: Journal for ImmunoTherapy of Cancer (2020)

Immune checkpoint inhibitors (ICIs) have produced significant survival benefit across many tumor types. However, immune-related adverse events are common including autoimmune responses against different endocrine organs. Here, a case of ICI-mediated hypoparathyroidism focusing on long-term follow-up and insights into its etiology is presented.A 73-year-old man developed severe symptomatic hypocalcemia after the initiation of ipilimumab and nivolumab for the treatment of metastatic melanoma. Hypoparathyroidism was diagnosed with undetectable intact parathyroid hormone (PTH). Immunoprecipitation assays, ELISAs, and cell-based functional assays were used to test the patient for antibodies against the calcium-sensing receptor (CaSR). NACHT leucine-rich repeat protein 5 (NALP5) and cytokine antibodies were measured in radioligand binding assays and ELISAs, respectively.The patient's symptoms improved with aggressive calcium and vitamin D supplementation. At 3 years and 3 months since the diagnosis of hypoparathyroidism, PTH was still inappropriately low at 7.6 pg/mL, and attempted discontinuation of calcium and calcitriol resulted in recurrent symptomatic hypocalcemia. Analysis for an autoimmune etiology of the patient's hypoparathyroidism indicated that CaSR antibodies were negative before treatment and detected at multiple time points afterwards, and corresponded to the patient's clinical course of hypoparathyroidism. CaSR antibodies purified from the patient's serum activated the human CaSR. The patient was seronegative for NALP5 and cytokine antibodies, indicating that their hypoparathyroidism was not a manifestation of autoimmune polyendocrine syndrome type 1.The etiology of hypocalcemia is likely autoimmune hypoparathyroidism caused by the development of CaSR-activating antibodies that might prevent PTH release from the parathyroid.
The effects of climate change on respiratory allergy and asthma induced by pollen and mold allergens
Authors: Gennaro D’Amato, Herberto Jose Chong‐Neto, Olga Patricia Monge Ortega, Carolina Vitale, Ignacio Ansotegui, Nelson Rosario, Tari Haahtela, Carmen Galan, Ruby Pawankar, Margarita Murrieta‐Aguttes, Lorenzo Cecchi, Christian Bergmann, Erminia Ridolo, German Ramon, Sandra Gonzalez Diaz, Maria D’Amato, Isabella Annesi‐Maesano
Journal: Allergy (2020)

The impact of climate change on the environment, biosphere, and biodiversity has become more evident in the recent years. Human activities have increased atmospheric concentrations of carbon dioxide (CO2 ) and other greenhouse gases. Change in climate and the correlated global warming affects the quantity, intensity, and frequency of precipitation type as well as the frequency of extreme events such as heat waves, droughts, thunderstorms, floods, and hurricanes. Respiratory health can be particularly affected by climate change, which contributes to the development of allergic respiratory diseases and asthma. Pollen and mold allergens are able to trigger the release of pro-inflammatory and immunomodulatory mediators that accelerate the onset the IgE-mediated sensitization and of allergy. Allergy to pollen and pollen season at its beginning, in duration and intensity are altered by climate change. Studies showed that plants exhibit enhanced photosynthesis and reproductive effects and produce more pollen as a response to high atmospheric levels of carbon dioxide (CO2 ). Mold proliferation is increased by floods and rainy storms are responsible for severe asthma. Pollen and mold allergy is generally used to evaluate the interrelation between air pollution and allergic respiratory diseases, such as rhinitis and asthma. Thunderstorms during pollen seasons can cause exacerbation of respiratory allergy and asthma in patients with hay fever. A similar phenomenon is observed for molds. Measures to reduce greenhouse gas emissions can have positive health benefits.