tbuckley/cabot-search huggingface dataset:
Diet Alters Entero-Mammary Signaling to Regulate the Breast Microbiome and Tumorigenesis
Authors: David R. Soto-Pantoja, Mohamed Gaber, Alana A. Arnone, Steven M. Bronson, Nildris Cruz-Diaz, Adam S. Wilson, Kenysha Y.J. Clear, Manuel U. Ramirez, Gregory L. Kucera, Edward A. Levine, Sophie A. Lelièvre, Lesley Chaboub, Akiko Chiba, Hariom Yadav, Pierre-Alexandre Vidi, Katherine L. Cook
Journal: Cancer Research (2021)

Abstract Obesity and poor diet often go hand-in-hand, altering metabolic signaling and thereby impacting breast cancer risk and outcomes. We have recently demonstrated that dietary patterns modulate mammary microbiota populations. An important and largely open question is whether the microbiome of the gut and mammary gland mediates the dietary effects on breast cancer. To address this, we performed fecal transplants between mice on control or high-fat diets (HFD) and recorded mammary tumor outcomes in a chemical carcinogenesis model. HFD induced protumorigenic effects, which could be mimicked in animals fed a control diet by transplanting HFD-derived microbiota. Fecal transplants altered both the gut and mammary tumor microbiota populations, suggesting a link between the gut and breast microbiomes. HFD increased serum levels of bacterial lipopolysaccharide (LPS), and control diet–derived fecal transplant reduced LPS bioavailability in HFD-fed animals. In vitro models of the normal breast epithelium showed that LPS disrupts tight junctions (TJ) and compromises epithelial permeability. In mice, HFD or fecal transplant from animals on HFD reduced expression of TJ-associated genes in the gut and mammary gland. Furthermore, infecting breast cancer cells with an HFD-derived microbiome increased proliferation, implicating tumor-associated bacteria in cancer signaling. In a double-blind placebo-controlled clinical trial of patients with breast cancer administered fish oil supplements before primary tumor resection, dietary intervention modulated the microbiota in tumors and normal breast tissue. This study demonstrates a link between the gut and breast that mediates the effect of diet on cancer. Significance: This study demonstrates that diet shifts the microbiome in the gut and the breast tumor microenvironment to affect tumorigenesis, and oral dietary interventions can modulate the tumor microbiota in patients with breast cancer.
AB0097 DIAGNOSTIC ACCURACY OF SERUM MARKERS IN LARGE VESSEL VASCULITIS AND CORRELATION WITH PET IMAGING
Authors: R. Bilici Salman, H. Satiş, A. Avanoglu Guler, H. Karadeniz, H. Küçük, S. Haznedaroglu, A. Tufan, B. Goker, U. O. Akdemir, L. O. Atay, H. Paşaoğlu, M. A. Ozturk
Journal: Annals of the Rheumatic Diseases (2021)

Background: The onset of symptoms in large-vessel vasculitis (LVV) tends to be subacute, which often leads to a delay in diagnosis, during which time vascular disease may start and progress to become symptomatic. PET/CT has been recognised since the 2003s as a promising tool in evaluating of LVV. There is no gold standard diagnostic laboratory tests for this patient group, novel markers for active LVV is needed. Objectives: to investigate the association between vascular inflammation, as detected by PET imaging and interleukin-6 (IL-6), pentraxin3 (PTX3), and B-cell-activating-factor (BAFF) in subjects with LVV. Methods: The study included 67 patients patients with newly diagnosed GCA (n= 27) or TA (n=9) and healthy control (n= 31) who had been referred to the Rheumatology Unit at Gazi University, between December 2017 and August 2020. PET images obtained from an 29 patients (22 with GCA and 7 with TA) who had not received any corticosteroid treatment prior to PET imaging and blood sampling. IL-6, PTX3, and BAFF levels were determined quantitatively by enzyme-linked immunosorbent assay (ELISA) kits. Results: 36 patients with LVV (20 females,16 males; age 64,5±16,6) and 31 HC (14 females,17 males; age37,1±9,6) were analysed. Serum levels of IL-6,PTX3, BAFF, ESR and CRP are increased in patients with newly diagnosed LVV compared with those in control subjects. In a ROC analysis, serum IL-6 provided excellent discrimination of newly diagnosed LVV patients from HC, as indicated by AUCs&gt;0.90. Serum BAFF also accurately distinguished newly diagnosed LVV patients from HC with AUCs&gt;0.80. Serum PTX3 did not provide an AUC&gt;0.80. In this study, we correlate vascular inflammation, as detected by PET imaging in newly diagnosed LVV patients, with the ESR, CRP. PTX3, IL-6 and BAFF. As a result, none of these markers has been associated with vascular inflammation as measured using PET. Conclusion: In conclusion, our study shows that serum levels of PTX3, IL-6 and BAFF are increased in most LVV patients. The diagnostic value of BAFF and IL-6, both separately and in combination, should be further evaluated in larger cohorts of LVV patients, as well as in patients with infections or other inflammatory conditions. However, none of these markers has been associated with vascular inflammation as measured using PET. Disclosure of Interests: None declared
Polyclonal expansion of TCR Vβ 21.3 <sup>+</sup> CD4 <sup>+</sup> and CD8 <sup>+</sup> T cells is a hallmark of multisystem inflammatory syndrome in children
Authors: Marion Moreews, Kenz Le Gouge, Samira Khaldi-Plassart, Rémi Pescarmona, Anne-Laure Mathieu, Christophe Malcus, Sophia Djebali, Alicia Bellomo, Olivier Dauwalder, Magali Perret, Marine Villard, Emilie Chopin, Isabelle Rouvet, Francois Vandenesch, Céline Dupieux, Robin Pouyau, Sonia Teyssedre, Margaux Guerder, Tiphaine Louazon, Anne Moulin-Zinsch, Marie Duperril, Hugues Patural, Lisa Giovannini-Chami, Aurélie Portefaix, Behrouz Kassai, Fabienne Venet, Guillaume Monneret, Christine Lombard, Hugues Flodrops, Jean-Marie De Guillebon, Fanny Bajolle, Valérie Launay, Paul Bastard, Shen-Ying Zhang, Valérie Dubois, Olivier Thaunat, Jean-Christophe Richard, Mehdi Mezidi, Omran Allatif, Kahina Saker, Marlène Dreux, Laurent Abel, Jean-Laurent Casanova, Jacqueline Marvel, Sophie Trouillet-Assant, David Klatzmann, Thierry Walzer, Encarnita Mariotti-Ferrandiz, Etienne Javouhey, Alexandre Belot
Journal: Science Immunology (2021)

MIS-C is characterized by a polyclonal activation of Vβ21.3 + CD4 + and CD8 + T cells that poorly respond to SARS-CoV-2 antigens.
HIV in the age of COVID-19
Authors: Talha Burki
Journal: The Lancet Infectious Diseases (2021)

resilienthiv programmesafricancountries havemaintainedviral suppressionduring HIV in the age of COVID-19As the world marks the 40th anniversary of the HIV/AIDS epidemic, we ask what impact the COVID-19 pandemic is having on HIV programmes around the world.Talha Burki reports.
AB0383 OCULAR MANIFESTATIONS DURING GIANT CELL ARTERITIS
Authors: A. Mzabi, N. Adaily, L. Ines, I. Ben Hassine, J. Anoun, M. Karmani, F. Ben Fredj, C. Laouani
Journal: Annals of the Rheumatic Diseases (2021)

Background: Horton’s disease (HD) or giant cell arteritis (GCA) is a segmental and plurifocal giant cell inflammatory panarteritis, predominant in large and medium sized vessels. Ocular damage during giant cell arteritis is frequent and is considered the most serious damage, possibly causing blindness in 15% of cases in recent series (1). Objectives: Describe the different ophthalmological manifestations during GCA. Methods: This is a retrospective monocentric descriptive study of 19 files of subjects diagnosed with HD, hospitalized in the internal medicine department of de Sousse between January 2000 and December 2020. Results: The average age of patients at diagnosis was 70 years, with extremes of 53 and 92 years. There were 14 females (71.4%) and 5 males (28.6%). Ophthalmologic manifestations were present in 13 patients (71%), 6 of whom were female. Decreased visual acuity was reported in 8 cases (58.33%) with biolateral blindness in one case, visual blur in 9 cases (75%), eye pain in two cases. Ophthalmological examination was normal in 8 cases (42%). A decrease in visual acuity was objective in 4 cases (21%). One case of nodular episcleritis was noted. The fundus showed anterior ischemic optic neuropathy in 2 cases (10.5%) and left optic atrophy in another case. A visual field was performed in 2 cases showing associated retrobulbar optic neuritis. Therapeutically, Methylprednisolone boli were prescribed in patients with anterior ischemic optic neuropathy, followed by oral corticosteroid therapy at a dose of 1mg/kg/day. A dose of 0.7 mg/kg/day of prednisone was prescribed in the other cases. Blindness was irreversible. Conclusion: The most common eye diseases in HD are acute anterior ischemic optic neuritis, retinal artery occlusion and posterior ischemic optic neuropathy. Episcleritis is a rare ophthalmologic manifestation of this vasculitis (2). More exceptionally, Horton’s disease may cause NORB by affecting the vessels that supply the optic nerve (&lt; 5% of cases)(3,4). In our series of studies, acute anterior ischemic optic neuritis was less observed than in the literature. This is probably due to the reduced number of patients. References: [1]M.Khedher. I.Rachdi. Z.Aydi. F.Daoud. B.Ben Dhaou. F.Boussema. Eye damage during Horton’s disease: about 42 cases. La Revue de Médecine Interne 2017; 38:115. [2]Rim Klii. Wafa Chebbi. Nodular episcleritis: an unusual inaugural manifestation of Horton’s disease. Pan Afr Med J 2015; 21: 20. [3]M.EssouriI.RachdiF.DaoudZ.AydiH.ZoubeidiB.Ben Dhaou et al. Retrobulbar Optic Neuropathy in Internal Medicine. La Revue de Médecine Interne 2018; 39: 132. [4]M A González-Gay, C García-Porrúa, J Llorca, A H Hajeer, F Brañas, A Dababneh et al. Visual manifestations of giant cell arteritis. Trends and clinical spectrum in 161 patients. Medicine (Baltimore) 2000;79(5):283-92. Disclosure of Interests: None declared
Radiotherapy is associated with a deletion signature that contributes to poor outcomes in patients with cancer
Authors: Emre Kocakavuk, Kevin J. Anderson, Frederick S. Varn, Kevin C. Johnson, Samirkumar B. Amin, Erik. P. Sulman, Martijn P. Lolkema, Floris P. Barthel, Roel G. W. Verhaak
Journal: Nature Genetics (2021)
Transmural cystoscopy with an ultra-slim basket for migrated stent removal after endosonography-guided hepatic cyst drainage
Authors: Saburo Matsubara, Takayuki Tanaka, Keito Nakagawa, Kentaro Suda, Takeshi Otsuka, Masashi Oka, Sumiko Nagoshi
Journal: Endoscopy (2021)

A 55-year-old woman with a huge hepatic cyst was admitted because of abdominal pain, fever, and jaundice. Computed tomography suggested cyst infection and cholestasis due to obstructed bile ducts ([Fig. 1]). Because surgical or percutaneous interventions were refused, endoscopic ultrasound (EUS)-guided drainage with double-guidewire technique [1] was attempted via the stomach. However, the gastric end of a 7-Fr double-pigtail plastic stent was misplaced in the peritoneal cavity. Although a fully covered metal stent was deployed over another guidewire to catch the double-pigtail plastic stent in the cyst, the hepatic end of the fully covered metal stent was misplaced in the peritoneal cavity again ([Fig. 2]). Following additional EUS-guided drainage with an external tube from the duodenal bulb, a standard endoscope was inserted into the peritoneal cavity through the fully covered metal stent, but the double-pigtail plastic stent could not be found ([Fig. 3]).
Minimal residual disease assessment by multiparameter flow cytometry in transplant-eligible myeloma in the EMN02/HOVON 95 MM trial
Authors: Stefania Oliva, Davine Hofste op Bruinink, Lucie Rihova, Mattia D’Agostino, Lucia Pantani, Andrea Capra, Bronno van der Holt, Rossella Troia, Maria Teresa Petrucci, Tania Villanova, Pavla Vsianska, Romana Jugooa, Claudia Brandt-Hagens, Milena Gilestro, Massimo Offidani, Rossella Ribolla, Monica Galli, Roman Hajek, Francesca Gay, Michele Cavo, Paola Omedé, Vincent H. J. van der Velden, Mario Boccadoro, Pieter Sonneveld
Journal: Blood Cancer Journal (2021)

Minimal residual disease (MRD) by multiparameter flow cytometry (MFC) is the most effective tool to define a deep response in multiple myeloma (MM). We conducted an MRD correlative study of the EMN02/HO95 MM phase III trial in newly diagnosed MM patients achieving a suspected complete response before maintenance and every 6 months during maintenance. Patients received high-dose melphalan (HDM) versus bortezomib-melphalan-prednisone (VMP) intensification, followed by bortezomib-lenalidomide-dexamethasone (VRd) versus no consolidation, and lenalidomide maintenance. Bone marrow (BM) samples were processed in three European laboratories, applying EuroFlow-based MFC protocols (eight colors, two tubes) with 10-4-10-5 sensitivity. At enrollment in the MRD correlative study, 76% (244/321) of patients were MRD-negative. In the intention-to-treat analysis, after a median follow-up of 75 months, 5-year progression-free survival was 66% in MRD-negative versus 31% in MRD-positive patients (HR 0.39; p < 0.001), 5-year overall survival was 86% versus 69%, respectively (HR 0.41; p < 0.001). MRD negativity was associated with reduced risk of progression or death in all subgroups, including ISS-III (HR 0.37) and high-risk fluorescence in situ hybridization (FISH) patients (HR 0.38;). In the 1-year maintenance MRD population, 42% of MRD-positive patients at pre-maintenance became MRD-negative after lenalidomide exposure. In conclusion, MRD by MFC is a strong prognostic factor. Lenalidomide maintenance further improved MRD-negativity rate.
AB0731 CERVICAL SPINE INVOLVEMENT IN PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS
Authors: S. Bouden, N. Ben Chekaya, A. Ben Tekaya, O. Saidane, R. Tekaya, I. Mahmoud, L. Abdelmoula
Journal: Annals of the Rheumatic Diseases (2021)

Background: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. In contrast to adult rheumatoid arthritis, where numerous studies have shown a high prevalence of involvement of the cervical spine, few studies have been published examining this entity in JIA. Objectives: We aimed to analyze clinical and radiological findings of cervical spine involvement in patients with JIA. Methods: A retrospective study including 35 patients was conducted between 2010 and 2019. The patients enrolled met the ILAR criteria for the diagnosis of JIA. Clinical, biological, and radiological data were collected. Patients had a radiological evaluation that included cervical spine x-rays in antero-posterior, lateral and lateral views with flexion. Results: Thirty-five patients were enrolled. The mean age of the disease onset was 9 years [3-15]. The mean age of the patients at the time of the study was 37.8 years [17-69]. The mean duration of the disease was 27 years [2-56]. These patients were assigned to discrete JIA categories: rheumatoid factor positive polyarthritis (43.5%), rheumatoid factor negative polyarthritis (21.7%), enthesitis-related arthritis (17.4%), oligoarthritis (13%) and psoriatic arthritis (4.4%). Sixteen patients (45%) reported neck pain. Cervical spine involvement occurred on average 7 years [0-13] after the JIA onset. Cervical spine radiographs showed anterior atlantoaxial subluxation (&gt; 5mm) in 8 patients. Magnetic-resonance imagining was performed in 9 patients that had abnormal neurological examination showing a pannus formation of C1-C2 junction (3 cases), a basilar invagination (4 cases) and erosions of the odontoid process (2 cases). A cervical collar has been used for immobilization in patients with significant cervical spine damage. A C1-C2 arthrodesis was proposed to 4 patients. Conclusion: These findings suggest that the presence of cervical involvement in JIA patients is frequent. Radiologic assessment of cervical spine should be systematically performed for early detection and to prevent its complications. Disclosure of Interests: None declared
Insights into Mechanism of A<i>β</i><sub>42</sub> Fibril Growth on Surface of Graphene Oxides: Oxidative Degree Matters
Authors: Huan He, Juan Xu, Chen‐Qiao Li, Tian Gao, Peng Jiang, Feng‐Lei Jiang, Yi Liu
Journal: Advanced Healthcare Materials (2021)

Abstract The filamentous β ‐amyloid deposition has been regarded as the hallmark pathology of Alzheimer's disease (AD). Nanomaterials such as graphene oxides (GOs) have achieved significant progress in the therapy of AD, but the molecular pathway of the growth propagation remains challenging to investigate, especially on the surfaces of materials. The thermodynamics and kinetics of fibril elongation on GO surfaces with different oxidative degrees have been investigated by a combination of in vitro experiments and simulations. ThT kinetics, calorimetric measurements, and TEM observations suggest that low oxidative GO‐10 promotes the fibril elongation, while both high oxidative GO‐20 and GO‐40 inhibit the fibril elongation. Computational results reveal that the apparent regulation behaviors of GOs on filament growth depend on the balance between the promoting effect by templating the incoming of monomers and the retarding effect by capturing the monomer during docking and locking phases through hydrogen bonding. This work will promote the understanding of the interplay between biomolecules and materials, thus providing new thoughts for the rational design of novel materials for amyloidosis therapy.
Biomimetic Scaffolds with a Mineral Gradient and Funnel‐Shaped Channels for Spatially Controllable Osteogenesis
Authors: Jichuan Qiu, Jaewan Ahn, Dong Qin, Stavros Thomopoulos, Younan Xia
Journal: Advanced Healthcare Materials (2021)

Abstract A facile method is described herein for generating a mineral gradient in a biodegradable polymer scaffold. The gradient is achieved by swelling a composite film made of polycaprolactone (PCL) and hydroxyapatite (HAp) nanoparticles with a PCL solution. During the swelling process, the solvent and PCL polymer chains diffuse into the composite film, generating a gradient in HAp density at their interface. The thickness of the mineral gradient can be tuned by varying the extent of swelling to match the length scale of the natural tendon‐to‐bone attachment (20−60 µm). When patterned with an array of funnel‐shaped channels, the mineral gradient presents stem cells with spatial gradations in both biochemical cues (e.g., osteoinductivity and conductivity associated with the HAp nanoparticles) and mechanical cues (e.g., substrate stiffness) to stimulate their differentiation into a graded distribution of cell phenotypes. This new class of biomimetic scaffolds holds great promise for facilitating the regeneration of the injured tendon‐to‐bone attachment by stimulating the formation of a functionally graded interface.
POS0362 INVESTIGATING THE ANKYLOSING SPONDYLITIS-ASSOCIATED REGULATORY SNPS AT THE RUNX3 LOCUS WITH A FUNCTIONAL GENOMICS APPROACH
Authors: M. Vecellio, P. B. Wordsworth, C. J. Cohen
Journal: Annals of the Rheumatic Diseases (2021)

Background: Of the &gt;100 genetic associations with ankylosing spondylitis (AS), RUNX3 transcription factor (TF) involved in diverse immunological processes, is robustly (10 −15 ) associated. 1 The biggest challenge is to understand the mechanism behind this association. We demonstrated the association between AS and the single nucleotide polymorphism (SNP) rs4648889 located in a 2kb regulatory locus upstream of the RUNX3 promoter can be explained by allele-specific effects on TF recruitment that alter gene expression, specifically in CD8+ T-cells. 2 We recently dissected the full plethora of TFs affected by rs4648889 AS-associated allele showing the NuRD complex and IRF5 differentially bound and having a crucial role in CD8+ T-cells function 3 . Nevertheless, other post-GWAS approaches are needed to elucidate the function of RUNX3 AS-associated SNPs (i.e. the lead SNP rs6600247 ). Objectives: The purpose of this work is to define the functional effect of rs6622047 in CD8+ T-cells and monocytes. In specific, we expect to define the impact of AS-associated allele to TF binding and to evaluate chromosome looping between rs6600247 and the RUNX3 promoter. Methods: The epigenetic landscape of SNP rs6600247 was defined using Roadmap database. In vitro functional studies were performed to characterize the effects of this SNP on TFs binding. Chromosome conformation capture (3C) provided critical functional evidence for looping among AS-associated SNPs and the RUNX3 promoter. Results: (1) In silico data revealed a c-MYC ChIP-seq peak in GM12878 lymphoblastoid cells overlapping rs6600247 ; (2) Mobility shift assays (EMSAs) and WB-EMSAs showed reduced DNA/protein binding in the presence of the AS-risk allele in CD14+ monocytes. C-MYC binding-site is disrupted and binding abolished in the presence of the AS-risk allele; (3) 3C experiments indicate low interaction frequency between SNP rs6600247 and RUNX3 promoter. Conclusion: The enhancer upstream the RUNX3 gene has a plausible functional role in AS, probably by regulating gene transcription and DNA looping. These observations are critically important in defining dysregulated pathways and potential therapeutic drug targets. References: [1]IGAS et al. Nat Genet . 2013 Jul;45(7):730-8. [2]Vecellio M. et al, Ann Rheum Dis. 2016 Aug;75(8):1534-40. [3]Vecellio et al Arthritis Rheumatol 2020. doi: 10.1002/art.41628. Acknowledgements: We thank Professor Julian Knight for his constructive advices and comments to the present work. Disclosure of Interests: None declared
Natural History of Patients With Ischemia and No Obstructive Coronary Artery Disease
Authors: Harmony R. Reynolds, Michael H. Picard, John A. Spertus, Jesus Peteiro, Jose Luis Lopez Sendon, Roxy Senior, Mohammad C. El-Hajjar, Jelena Celutkiene, Michael D. Shapiro, Patricia A. Pellikka, Dennis F. Kunichoff, Rebecca Anthopolos, Khaled Alfakih, Khaled Abdul-Nour, Michel Khouri, Leonid Bershtein, Mark De Belder, Kian Keong Poh, John F. Beltrame, James K. Min, Jerome L. Fleg, Yi Li, David J. Maron, Judith S. Hochman
Journal: Circulation (2021)

Ischemia with no obstructive coronary artery disease (INOCA) is common and has an adverse prognosis. We set out to describe the natural history of symptoms and ischemia in INOCA.CIAO-ISCHEMIA (Changes in Ischemia and Angina over One Year in ISCHEMIA Trial Screen Failures With INOCA) was an international cohort study conducted from 2014 to 2019 involving angina assessments (Seattle Angina Questionnaire) and stress echocardiograms 1 year apart. This was an ancillary study that included patients with a history of angina who were not randomly assigned in the ISCHEMIA trial. Stress-induced wall motion abnormalities were determined by an echocardiographic core laboratory blinded to symptoms, coronary artery disease status, and test timing. Medical therapy was at the discretion of treating physicians. The primary outcome was the correlation between the changes in the Seattle Angina Questionnaire angina frequency score and changes in echocardiographic ischemia. We also analyzed predictors of 1-year changes in both angina and ischemia, and we compared CIAO participants with ISCHEMIA participants with obstructive coronary artery disease who had stress echocardiography before enrollment, as CIAO participants did.INOCA participants in CIAO were more often female (66% of 208 versus 26% of 865 ISCHEMIA participants with obstructive coronary artery disease, P<0.001), but the magnitude of ischemia was similar (median 4 ischemic segments [interquartile range, 3-5] both groups). Ischemia and angina were not significantly correlated at enrollment in CIAO (P=0.46) or ISCHEMIA stress echocardiography participants (P=0.35). At 1 year, the stress echocardiogram was normal in half of CIAO participants, and 23% had moderate or severe ischemia (≥3 ischemic segments). Angina improved in 43% and worsened in 14%. Change in ischemia over 1 year was not significantly correlated with change in angina (ρ=0.029).Improvement in ischemia and angina were common in INOCA but not correlated. Our INOCA cohort had a degree of inducible wall motion abnormalities similar to concurrently enrolled ISCHEMIA participants with obstructive coronary artery disease. Our results highlight the complex nature of INOCA pathophysiology and the multifactorial nature of angina. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02347215.