tbuckley/cabot-search huggingface dataset:
Intracellular codelivery of anti-inflammatory drug and anti-miR 155 to treat inflammatory disease
Authors: Chao Teng, Chenshi Lin, Feifei Huang, Xuyang Xing, Shenyu Chen, Ling Ye, Helena S. Azevedo, Chenjie Xu, Zhengfeng Wu, Zhongjian Chen, Wei He
Journal: Acta Pharmaceutica Sinica B (2020)

Atherosclerosis (AS) is a lipid-driven chronic inflammatory disease occurring at the arterial subendothelial space. Macrophages play a critical role in the initiation and development of AS. Herein, targeted codelivery of anti-miR 155 and anti-inflammatory baicalein is exploited to polarize macrophages toward M2 phenotype, inhibit inflammation and treat AS. The codelivery system consists of a carrier-free strategy (drug-delivering-drug, DDD), fabricated by loading anti-miR155 on baicalein nanocrystals, named as baicalein nanorods (BNRs), followed by sialic acid coating to target macrophages. The codelivery system, with a diameter of 150 nm, enables efficient intracellular delivery of anti-miR155 and polarizes M1 to M2, while markedly lowers the level of inflammatory factors in vitro and in vivo. In particular, intracellular fate assay reveals that the codelivery system allows for sustained drug release over time after internalization. Moreover, due to prolonged blood circulation and improved accumulation at the AS plaque, the codelivery system significantly alleviates AS in animal model by increasing the artery lumen diameter, reducing blood pressure, promoting M2 polarization, inhibiting secretion of inflammatory factors and decreasing blood lipids. Taken together, the codelivery could potentially be used to treat vascular inflammation.
Abstract 17113: The Comparison of Usefulness of Bioresorbable Polymer-Everolimus Eluting Stent (EES) With Platinum Chromium-EES and EES in Patients With The End-Stage Chronic Kidney Disease Including Hemodialysis
Authors: Takao Sato, Katsuharu Hatada, Shouhei Kishi, Kouichi Fuse, Satoshi Fujita, Yoshio Ikeda, Hitoshi Kitazawa, Minoru Takahashi, Yoshifusa Aizawa, Taku Matsubara, Masaaki Okabe
Journal: Circulation (2017)

Introduction: The outcomes of the first-generation drug-eluting stent (DES) were disappointing in patients with chronic kidney disease (CKD), especially hemodialysis (HD). Currently, new-generation...
Mass spectrometry imaging-based metabolomics to visualize the spatially resolved reprogramming of carnitine metabolism in breast cancer
Authors: Chenglong Sun, Fukai Wang, Yang Zhang, Jinqian Yu, Xiao Wang
Journal: Theranostics (2020)

New insights into tumor-associated metabolic reprogramming have provided novel vulnerabilities that can be targeted for cancer therapy.Here, we propose a mass spectrometry imaging (MSI)-based metabolomic strategy to visualize the spatially resolved reprogramming of carnitine metabolism in heterogeneous breast cancer.Methods: A wide carnitine coverage MSI method was developed to investigate the spatial alternations of carnitines in cancer tissues of xenograft mouse models and human samples.Spatial expression of key metabolic enzymes that are closely associated with the altered carnitines was examined in adjacent cancer tissue sections.Results: A total of 17 carnitines, including L-carnitine, 6 short-chain acylcarnitines, 3 middle-chain acylcarnitines, and 7 long-chain acylcarnitines were imaged.L-carnitine and short-chain acylcarnitines are significantly reprogrammed in breast cancer.A classification model based on the carnitine profiles of 170 cancer samples and 128 normal samples enables an accurate identification of breast cancer.CPT 1A, CPT 2, and CRAT, which are extensively involved in carnitine system-mediated fatty acid β-oxidation pathway were also found to be abnormally expressed in breast cancer.Remarkably, the expressions of CPT 2 and CRAT were found for the first time to be altered in breast cancer.Conclusion: These data not only expand our understanding of the complex tumor metabolic reprogramming, but also provide the first evidence that carnitine metabolism is reprogrammed at both the metabolite and enzyme levels in breast cancer.
A myoferlin gain‐of‐function variant associates with a new type of hereditary angioedema
Authors: Anastasia Ariano, Maria D'Apolito, Maria Bova, Francesco Bellanti, Stefania Loffredo, Giovanna D'Andrea, Mariano Intrieri, Angelica Petraroli, Angela Bruna Maffione, Giuseppe Spadaro, Rosa Santacroce, Maurizio Margaglione
Journal: Allergy (2020)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Nutritional Requirements for Sustaining Health and Performance During Exposure to Extreme Environments
Authors: Stefan M. Pasiakos
Journal: Annual Review of Nutrition (2020)

Dietary guidelines are formulated to meet minimum nutrient requirements, which prevent deficiencies and maintain health, growth, development, and function. These guidelines can be inadequate and contribute to disrupted homeostasis, lean body mass loss, and deteriorated performance in individuals who are working long, arduous hours with limited access to food in environmentally challenging locations. Environmental extremes can elicit physiological adjustments that alone alter nutrition requirements by upregulating energy expenditure, altering substrate metabolism, and accelerating body water and muscle protein loss. The mechanisms by which the environment, including high-altitude, heat, and cold exposure, alters nutrition requirements have been studied extensively. This contemporary review discusses physiological adjustments to environmental extremes, particularly when those adjustments alter dietary requirements.
AB0272 Switching from Etanercept original to Etanercept biosimilar. EXPERIENCE IN A TERTIARY HOSPITAL.
Authors: V. Aldasoro, J. Mendizabal, S. Perez Garcia, G. Sada Urmeneta, J. Restrepo Vélez, N. Del Val del Amo, I. Paniagua Zudaire, R. Gutiérrez Polo, L. Horcada, L. Garrido Courel, C. Fito-Manteca
Journal: Annals of the Rheumatic Diseases (2020)

Background: With the arrival of biosimilar drugs and savings policies to make the health system sustainable, hospital managers have chosen to make changes from original molecules to biosimilar drugs. Objectives: This work aims to reflect what happens when making these switchings. Methods: We reviewed 235 patients who started Etanercept original in Rheumatology at Navarra Hospital Complex and Henares University Hospital and their switch to Etanercept biosimilar with a follow-up of 6 months. Results: The switch was performed in 174 patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), ankylosing spondylitis (AS), juvenile idiopathic arthritis, SAPHO and spondyloarthritis. 9.8% discontinued treatment: 6 RA (8.1%), 5 PsA (9.8 %) and 6 AS (20.7%); all of them in the injection presentation. 12 patient stopped treatment due to ineffecacy, 2 due to reaction at the injection site, 2 due to diarrhea and 1 due to headache. Among 88.2% of patients who returned to Etanercept original, 28.6% did not achieve good response and had to change of treatment. The median time from Etanercept original beginning until the moment of switching was 54 (40-87) months. Conclusion: In our series, approximately 10% of switching patients failed after a 6-month of follow-up; when trying to return to Etanercept original 28.6% did not achieve response. The median persistence time in the original molecule and the percentage of failures observed in AS could be two conditions to consider before switching. A longer-term follow-up and a greater number of patients are necessary to ratify these data. Table 1 DISEASE STOPPED CAUSE BACK TO Etanercept original CONTINUE Etanercept original TIME UNTIL SWITCH (meses) AS Reaction at the injection site Yes Yes 28 AS Headache Yes Yes 54 AS Ineffecacy Yes Yes 126 RA Ineffecacy Yes No 25 AS Diarrhea Yes Yes 87 RA Ineffecacy Yes Yes 37 PsA Ineffecacy No No 43 RA Ineffecacy Yes Yes 54 PsA Ineffecacy Yes No 93 PsA Ineffecacy No No 132 PsA Ineffecacy Yes Yes 62 RA Ineffecacy Yes Yes 142 RA Reaction at the injection site Yes Yes 51 RA Ineffecacy Yes No 56 PsA Ineffecacy Yes No 40 AS Ineffecacy Yes Yes 26 AS Diarrhea Yes Yes 48 Disclosure of Interests: Vicente Aldasoro Speakers bureau: Roche, Abbvie, MSD, UCB, Pfizer, Menarini, Grunenthal, Gebro, Novartis, Janssen, Javier Mendizabal: None declared, Sara Perez Garcia: None declared, Guillen Sada Urmeneta: None declared, Juliana Restrepo Vélez: None declared, Natividad del Val del Amo: None declared, Inmaculada Paniagua Zudaire: None declared, Ricardo Gutiérrez Polo: None declared, Loreto Horcada: None declared, Laura Garrido Courel: None declared, C. Fito-Manteca: None declared
Efficacy and Moderators of Internet-Based Interventions in Adults with Subthreshold Depression: An Individual Participant Data Meta-Analysis of Randomized Controlled Trials
Authors: Jo Annika Reins, Claudia Buntrock, Johannes Zimmermann, Simon Grund, Mathias Harrer, Dirk Lehr, Harald Baumeister, Kiona Weisel, Matthias Domhardt, Kotaro Imamura, Norito Kawakami, Viola Spek, Stephanie Nobis, Frank Snoek, Pim Cuijpers, Jan Philipp Klein, Steffen Moritz, David Daniel Ebert
Journal: Psychotherapy and Psychosomatics (2020)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Evidence on effects of Internet-based interventions to treat subthreshold depression (sD) and prevent the onset of major depression (MDD) is inconsistent. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; We conducted an individual participant data meta-analysis to determine differences between intervention and control groups (IG, CG) in depressive symptom severity (DSS), treatment response, close to symptom-free status, symptom deterioration and MDD onset as well as moderators of intervention outcomes. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Randomized controlled trials were identified through systematic searches via PubMed, PsycINFO, Embase and Cochrane Library. Multilevel regression analyses were used to examine efficacy and moderators. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Seven trials (2,186 participants) were included. The IG was superior in DSS at all measurement points (posttreatment: 6–12 weeks; Hedges’ g = 0.39 [95% CI: 0.25–0.53]; follow-up 1: 3–6 months; g = 0.30 [95% CI: 0.15–0.45]; follow-up 2: 12 months, g = 0.27 [95% CI: 0.07–0.47], compared with the CG. Significantly more participants in the IG than in the CG reached response and close to symptom-free status at all measurement points. A significant difference in symptom deterioration between the groups was found at the posttreatment assessment and follow-up 2. Incidence rates for MDD onset within 12 months were lower in the IG (19%) than in the CG (26%). Higher initial DSS and older age were identified as moderators of intervention effect on DSS. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Our findings provide evidence for Internet-based interventions to be a suitable low-threshold intervention to treat individuals with sD and to reduce the incidence of MDD. This might be particularly true for older people with a substantial symptom burden.
Effects of Inorganic Arsenic on Human Prostate Stem-Progenitor Cell Transformation, Autophagic Flux Blockade, and NRF2 Pathway Activation
Authors: Lishi Xie, Wen-Yang Hu, Dan-Ping Hu, Guangbin Shi, Ye Li, Jianfu Yang, Gail S. Prins
Journal: Environmental Health Perspectives (2020)

Inorganic arsenic (iAs) is an environmental toxicant associated with an increased risk of prostate cancer in chronically exposed populations worldwide. However, the biological mechanisms underlying iAs-induced prostate carcinogenesis remain unclear. We studied how iAs affects normal human prostate stem-progenitor cells (PrSPCs) and drives transformation and interrogated the molecular mechanisms involved. PrSPCs were enriched by spheroid culture from normal human primary or immortalized prostate epithelial cells, and their differentiation capability was evaluated by organoid culture. Microarray analysis was conducted to identify iAs-dysregulated genes, and lentiviral infection was used for stable manipulation of identified genes. Soft agar colony growth assays were applied to examine iAs-induced transformation. For in vivo study, PrSPCs mixed with rat urogenital sinus mesenchyme were grafted under the renal capsule of nude mice to generate prostatelike tissues, and mice were exposed to 5 ppm (∼65μM) iAs in drinking water for 3 months. Low-dose iAs (1μM) disturbed PrSPC homeostasis in vitro, leading to increased self-renewal and suppressed differentiation. Transcriptomic analysis indicated that iAs activated oncogenic pathways in PrSPCs, including the KEAP1-NRF2 pathway. Further, iAs-exposed proliferative progenitor cells exhibited NRF2 pathway activation that was sustained in their progeny cells. Knockdown of NRF2 inhibited spheroid formation by driving PrSPC differentiation, whereas its activation enhanced spheroid growth. Importantly, iAs-induced transformation was suppressed by NRF2 knockdown. Mechanistically, iAs suppressed Vacuolar ATPase subunit VMA5 expression, impairing lysosome acidification and inhibiting autophagic protein degradation including p62, which further activated NRF2. In vivo, chronic iAs exposure activated NRF2 in both epithelial and stroma cells of chimeric human prostate grafts and induced premalignant events. Low-dose iAs increased self-renewal and decreased differentiation of human PrSPCs by activating the p62-NRF2 axis, resulting in epithelial cell transformation. NRF2 is activated by iAs through specific autophagic flux blockade in progenitor cells, which may have potential therapeutic implications. https://doi.org/10.1289/EHP6471.
AB0436 CHANGES OF LYMPHOCYTE SUBSETS AND CLINICAL INDEXES IN PERIPHERAL BLOOD OF PATIENTS WITH ANTI-PHOSPHOLIPID SYNDROME
Authors: W. Niu, H. Y. Wen
Journal: Annals of the Rheumatic Diseases (2020)

Background: Anti-phospholipid Syndrome (APS) is a non-inflammatory autoimmune disease, which can be divided into primary and secondary. Changes in lymphocyte numbers in APS are caused by disruption of the immune balance. Objectives: The levels of lymphocyte subsets in peripheral blood of patients with anti-phospholipid syndrome were observed and their clinical indexes were analyzed. Methods: 53 patients with anti-phospholipid syndrome (APS) were collected as the case group and divided into two groups of A, B according to whether primary and 50 health examiners as the healthy control group. The levels of peripheral lymphocyte subsets and laboratory data [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelets (PLT)]levels in the three groups were analyzed. The measurement data is not subject to normal distribution using the Median-Quartile method for statistical description; multiple sample comparisons using the Kruskal-Wallis H test; p &lt;0.05 as the difference is statistically significant. Results: (1) The rates of thrombosis and adverse pregnancy in the two case groups were significantly increased. In the two case groups, the ESR and CRP were higher than those in the healthy control group, and the CRP in group A was higher. (2) Compared with the healthy control group, the levels of CD8 + T, CD4 + T/CD8 + T in case A group were increased,while the levels of total T,CD4 + T, CD8 + T,CD4 + T/CD8 + T,Th2 and Treg cells were decreased. However,there was no significant difference in Th17 cells level and Th17/Treg ratio compared with the healthy control group. Conclusion: APS patients were more prone to have thrombosis, adverse pregnancy and thrombocytopenia. The changes of lymphocyte subsets were seen in peripheral blood, and the primary and secondary had different directions and different degrees of manifestation.However, whether the secondary factors can aggravate the clinical indicators of APS is still unclear. References: [1]Simonin Laurent,Pasquier Elisabeth,Leroyer Christophe et al. Lymphocyte Disturbances in Primary Antiphospholipid Syndrome and Application to Venous Thromboembolism Follow-Up.[J].Clin Rev Allergy Immunol, 2017, 53: 14-27.doi:10.1007/s12016-016-8568-1. Disclosure of Interests: None declared
An uninvited commentary on “Comparison of surgical outcomes between video-assisted anal fistula treatment and fistulotomy plus seton for complex anal fistula: A propensity score matching analysis - Retrospective cohort study” [Int. J. Surg. 75 (2020) 99–100]
Authors: Joyce Tau Shin Lim, Fu Chuen Kon
Journal: International Journal of Surgery (2020)
Redeployment of dermatologists during COVID-19: Implementation of a large-scale, centralized results management infrastructure
Authors: Nina A. Ran, Sara S. Samimi, Junqian Zhang, Krisda H. Chaiyachati, Colleen P. Mallozzi, C. William Hanson, John T. Howell, Susan C. Day, Nicholas K. Mollanazar
Journal: Journal of the American Academy of Dermatology (2020)
An unexpected cause of iron deficiency
Authors: Thomas Edward Conley, Timothy Andrews, Arvind Arumainathan, Paul O'Toole, Philip J Smith, Sreedhar Subramanian
Journal: Gut (2020)

A 70-year-old man presented with progressive weight loss and intermittent lower abdominal pain. Bowel habit was unchanged, there was no overt blood loss and there were no constitutional symptoms. His medical history included vascular Parkinson’s, hypertension, osteoarthritis, type 2 diabetes mellitus and colonic polyps. His medications included pantoprazole and clopidogrel.

On physical examination, his abdominal and digital rectal examinations were unremarkable. Laboratory tests revealed normocytic (mean cell volume 84.1 fL) hypoferritinaemia (15 μg/L) with low haemoglobin (123 g/L). Coeliac serology, other haematinics and immunoglobulin profile were normal. Urinalysis excluded haematuria.

Gastroscopy and duodenal biopsies were normal and urease test was negative for Helicobacter pylori . CT colonography identified a 22 mm proximal sigmoid lesion with a depressed centre concerning for extension beyond the …
SAT0547 RADIOGRAPHIC IMAGING IN ASSESSMENT OF FLUOROSCOPIC GUIDED INJECTION OF RHEUMATOID ATLANTOAXIAL JOINT INFLAMMATION
Authors: D. Fouad, S. Rashad, M. Ghaly, M. Hassanien
Journal: Annals of the Rheumatic Diseases (2020)

Background: Rheumatoid spondylitis is a feature of long-lasting Rheumatoid arthritis (RA) that is presented by neck pain, headache and sleep disturbance. Atlantoaxial joint (AAJ) is the commonest cervical spine joint that affected in patients with RA. When it is involved, it can be associated with dangerous complications. Magnetic Resonance Imaging (MRI) can be used for assessing the disease activity, the amount of cartilage destruction, associated cervical myelopathy and differentiating synovial fluid from inflammatory pannus (Taniguchi D, et al., 2008). Objectives: This study aimed to evaluate the efficacy of intra-articular steroid injection of inflamed AAJ in RA patients, regarding neck pain, headache and sleep quality using pre and post-interventions MRI. Methods: A prospective case control study. Patients with inflamed AAJ were recruited. Group 1 (AAJ group, n = 30), received intraarticular AAJ steroid injection, guided by fluoroscopy and Group 2 (control group, n = 30), received systemic steroids. Both groups were assessed with: Visual Analogue scale (VAS) for nocturnal neck pain and headache. Pittsburgh sleep quality index (PSQI) was used for sleep disturbance. Pre and post contrasts enhanced MRI interventions were done for both groups during the period of follow up (three months). Results: Nocturnal neck pain, headache and sleep disturbance have significantly decreased, during follow up visits (3 months), in AAJ group in comparison to the control group. The Pre-intervention nocturnal pain score was 60.3 ±17.1 in AAJ group &amp; 58.5 ±17.9 in control group. Pain has significantly decreased after 2weeks in AAJ group with continuous improvement till 3 months’ post-intervention 6.9 ±4.65 &amp; 51.26 ±10.54 respectively. The pre-intervention headache was 22.68 ±16.74 in AAJ group &amp; 45.17 ±15.83 in control group decreased to 7.54 ±5.23 &amp; 48.52 ±11.98 respectively post intervention. The percentage of patients who had sleep disturbance at baseline was 66.7% &amp; 73.3% in AAJ and control groups respectively which has significantly decreased to 6.7% &amp; 43.3% after 3 months. Regarding MRI, AAJ group had a statistical significant decrease in the percentage of patients with MRI synovial enhancement, inflammatory pannus, fibrosis and bone marrow edema in comparison to control group 3 months post intervention. All post-procedural side effects resolved within thmonth without further medical intervention, and no long-term sequelae were identified Conclusion: Fluoroscopic guided intra-articular steroid injection of inflamed atlantoaxial joints is considered a beneficial therapeutic option in rheumatoid arthritis patients regarding clinical and radiological assessments. References: [1]Taniguchi D, Tokunaga D, Hase H, et al. Evaluation of lateral instability of AAJ in RA using dynamic open-mouth view radiographs . Clin Rheumatol. 2008 Jul. 27(7):851-7. Disclosure of Interests: None declared
Abstract 13272: MiR-200c-5p Regulates Epithelial-to-Mesenchymal Transition in Epicardial Mesothelial Cells by Targeting Epicardial Follistatin-Related Protein 1
Authors: Elena Pontemezzo, Eleonora Foglio, Enza Vernucci, Marco D’agostino, Alessandra Magenta, Astanina Elena, Federico Bussolino, Matteo Russo, Federica Limana
Journal: Circulation (2019)

Background: Recent findings suggest that epithelial to mesenchymal transition (EMT), a key step during heart development, is involved in cardiac tissue repair following myocardial infarction (MI). ...