tbuckley/cabot-search huggingface dataset:
In situ repurposing of dendritic cells with CRISPR/Cas9-based nanomedicine to induce transplant tolerance
Authors: Yue Zhang, Song Shen, Gui Zhao, Cong-Fei Xu, Hou-Bing Zhang, Ying-Li Luo, Zhi-Ting Cao, Jia Shi, Zhi-Bin Zhao, Zhe-Xiong Lian, Jun Wang
Journal: Biomaterials (2019)
Abstract 15681: Decline of Popliteal Artery Flow-Mediated Dilation (FMD) With Aging and Possible Involvement of Asymmetric Dimethylarginine (ADMA) in Healthy Men
Authors: Akihiro Nakamura, Shoko Kajitani, Masanori Kanazawa, Masateru Kudo, Hideaki Endo, Tohru Takahashi, Eiji Nozaki
Journal: Circulation (2017)

Aim: Using brachial and popliteal artery, we examined 1) whether the differences of flow-mediated vasodilation (FMD) responses between upper and lower extremity arteries are affected by aging and g...
Chronic graft‐versus‐host disease and inhibition of interleukin‐17: proof of concept in humans
Authors: P.‐E. Debureaux, A. Masson, M. Battistella, F. Fontbrune, G. Socié, J.D. Bouaziz, D. Michonneau
Journal: British Journal of Dermatology (2019)

Psoriasiform chronic graft‐versus‐host disease (GvHD) is a rare clinical presentation recently described after allogeneic haematopoietic stem cell transplantation. It is characterized by the combination of clinical and pathological characteristics of psoriasis together with pathological features of chronic GvHD. As described for psoriasis, psoriasiform chronic GvHD is characterized by the infiltration of T helper 17 CD8+ T cells producing both interferon‐γ and interleukin‐17. However, no data are available about the efficacy of interleukin‐17 blockade in the treatment of patients with psoriasiform chronic GvHD. What's already known about this topic? Psoriasiform chronic graft‐versus‐host disease (GvHD) is a rare clinical presentation with a poor durable response to steroids. Animal models and human data suggest that psoriasiform GvHD could be induced through interleukin‐17 production by donor T cells. What does this study add? We describe the first case of a patient with psoriasiform GvHD and persistent improvement on treatment with secukinumab, an anti‐interleukin‐17A antibody.
Cost-Effectiveness of Cabozantinib in the Second-Line Treatment of Advanced Hepatocellular Carcinoma
Authors: Enrique Soto-Perez-de-Celis, Pedro N. Aguiar, Mónica L. Cordón, Yanin Chavarri-Guerra, Gilberto de Lima Lopes
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Treatment options are limited for patients with advanced hepatocellular carcinoma (HCC) that progresses after treatment with sorafenib. Cabozantinib, an oral small molecule inhibitor of multiple tyrosine kinase receptors, recently showed improved overall survival (OS) compared with placebo in sorafenib-pretreated patients with advanced HCC in the CELESTIAL trial. This study assessed the cost-effectiveness of cabozantinib for second-line treatment of patients with advanced HCC from a US healthcare system perspective. Patients and Methods: Cost and utility data were extracted from the CELESTIAL trial and used to determine the cost-effectiveness of cabozantinib compared with placebo plus best supportive care. The main outcome of this study was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY) gained by using cabozantinib compared with placebo plus best supportive care in sorafenib-pretreated HCC. Results: In the base-case analysis using data from the CELESTIAL trial, the incremental QALY and ICER were 0.067 and $1,040,675 for cabozantinib compared with placebo and best supportive care. OS reported in the CELESTIAL trial (hazard ratio, 0.76; 95% CI, 0.63–0.92) had the strongest association with the ICER. In one-way sensitivity analyses, there were no scenarios in which cabozantinib was cost-effective. In a cost-threshold analysis, cabozantinib would have to be priced at least $50 per pill to be cost-effective considering a willingness to pay of $100,000 per QALY. Although the CELESTIAL trial demonstrated that cabozantinib improves OS compared with placebo in patients with HCC that progresses after treatment with sorafenib, our analysis shows that cabozantinib is not a cost-effective therapy in this scenario. Conclusions: At current costs, cabozantinib is not cost-effective for second-line therapy of HCC in the United States.
Reflectance confocal microscopy-guided carbon dioxide laser ablation of low-risk basal cell carcinomas: A prospective study
Authors: Cristian Navarrete-Dechent, Miguel Cordova, Konstantinos Liopyris, Oriol Yélamos, Saud Aleissa, Brian Hibler, Heidy Sierra, Aditi Sahu, Nina Blank, Milind Rajadhyaksha, Anthony Rossi
Journal: Journal of the American Academy of Dermatology (2019)
AB0709 INFLUENCE OF DIETETARY INTAKES ON SPONDYLOARTHRITIS : AN OBSERVATIONAL PROSPECTIVE STUDY
Authors: Kathy Nguyen, Pascale Vergne-Salle, Anne-Catherine Fressinaud-Marie, Philippe Bertin
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Dysbiosis can be found in inflammatory joint diseases and induces alterations of the protective function of the intestinal barrier (1). Yet intestinal inflammation exists in ankylosing spondylitis, which is as much severe as the disease is active (2). Benefits of diets and their influence on the microbiota diversity and inflammation deserve to be studied in spondyloarthritis. <h3>Objectives:</h3> The aim of the study was to investigate the nutritional profil in active spondyloarthritis. <h3>Methods:</h3> An observational prospective monocentric study based in a french rheumatology department based in Limoges was conducted between February and July 2018, demographic and disease data were collected, in addition to the treatments and the food frequency questionnaire. Voluntary patients over 18 years of age with spondyloarthritis defined by aSAS classification were included. Patients with a diagnosis of inflammatory bowel disease or a bariatric surgery history were excluded of the study. The primary outcome was the correlation between omega-3, vitamin C, refined sugars, fibers and ultra-processed food intakes and the disease activity assessed by aSDAS CRP and BASDAI scores. <h3>Results:</h3> Among 140 patients included, there was no statistically significant difference in omega-3, vitamin C, refined sugars, fibers or ultra-processed food intakes between patients with active spondyloarthritis (BASDAI ≥ 4 or aSDAS CRP ≥ 1,3) and very active (ASDAS ≥ 2,1) and patients with unactive disease. The quality of life score and fatigue score were more important in the active and very active disease forms, likewise for the digestive symptoms but there was no link founded in the different nutrients intakes, neither with the associated treatment. <h3>Conclusion:</h3> Althouth our study did not find any nutritional profil in active spondyloarthritis, there was an alteration of quality of life and more digestive symptoms in the active group. Future researches are however required to explore the impact of dietatary intakes on the disease activity of spondyloarthritis. <h3>References</h3> [1] Costello M-E, Robinson PC, Benham H, Brown MA. The intestinal microbiome in human disease and how it relates to arthritis and spondyloarthritis. Best Pract Res Clin Rheumatol. Avr2015;29(2):202-12 [2] Hascelik G, Oz B, Olmez N, Memis a, Yoruk G, Unsal B, et al. Association of macroscopic gut inflammation with disease activity, functional status and quality of life in ankylosing spondylitis. Rheumato int. mai 2009;29(7):755-81) <h3>Disclosure of interests:</h3> None declared
Prediction of Site-Specific Amino Acid Distributions and Limits of Divergent Evolutionary Changes in Protein Sequences
Authors: M. Porto
Journal: Molecular Biology and Evolution (2005)

We derive an analytic expression for site-specific stationary distributions of amino acids from the Structurally Constrained Neutral (SCN) model of protein evolution with conservation of folding stability. The stationary distributions that we obtain have a Boltzmann-like shape, and their effective temperature parameter, measuring the limit of divergent evolutionary changes at a given site, can be predicted from a site-specific topological property, the principal eigenvector of the contact matrix of the native conformation of the protein. These analytic results, obtained without free parameters, are compared with simulations of the SCN model and with the site-specific amino acid distributions obtained from the Protein Data Bank. These results also provide new insights into how the topology of a protein fold influences its designability, i.e. the number of sequences compatible with that fold. The dependence of the effective temperature on the principal eigenvector decreases for longer proteins, a possible consequence of the fact that selection for thermodynamic stability becomes weaker in this case.
Survival analysis of linitis plastica advanced gastric cancer patients receiving S-1 plus cisplatin.
Authors: Yosuke Kumekawa, Keisho Chin, Hiroki Osumi, Mariko Ogura, Masato Ozaka, Mitsukuni Suenaga, Eiji Shinozaki, Satoshi Matsusaka, Takeshi Sano, Nobuyuki Mizunuma
Journal: Journal of Clinical Oncology (2013)

e15105 Background: Linitis plastica gastric cancer (LPGC) has been known to have worse prognosis than non-LPGC. Clinical trial using molecular targeting agent has been ongoing for LPGC. However it remains unknown whether to be better to change the chemotherapy for the patients. S-1 plus cisplatin (SP) is the standard chemotherapy for previously untreated Japanese advanced gastric cancer (AGC). Methods: To clarify the clinical feature and outcome of LPGC treated with chemotherapy, we retrospectively compared the patients with unresectable or metastatic LPGC and non-LPGC who received SP as the first-line chemotherapy in Cancer Institute Hospital of JFCR between 2007 and 2011. Results: In the period there were 687 patients with AGC who received systemic chemotherapy and 223 (LPGC 63 and non- LPGC 160) patients received SP as first-line chemotherapy. LPGC patients were more frequent in female (44.0% vs. 26.9%; P=0.016). LPGC was more likely to have non-measurable disease (39.7% vs. 14.4%; P&lt;0.001), peritoneal metastasis (73% vs. 35.6% P&lt;0.001), and diffuse type histology (diffuse type 85.7% vs. 56.3%, intestinal type 7.9% vs. 27.5%; P&lt;0.001). LPGC was less likely to have liver metastasis (7.9% vs. 27.5%; P&lt;0.001), and no evaluable distant metastasis in computed tomography (81.0% vs. 93.8%; P=0.010). Other clinicopathological characteristics were follows (LPGC patients vs. non-LPGC patients): median age (57 vs. 62 years), disease status (recurrent 11.1% vs. 18.8%), ECOG PS 0 (81.0% vs. 81.9%), number of metastatic sites (1: 52.4% vs. 46.9, 2: 39.7% vs. 46.9%, ³a3: 7.9% vs. 6.2%), lymph node metastasis (63.5% vs. 70.6%), prior gastrectomy (31.7% vs. 35.6%). They were not significantly different. Median overall survival time is 383 days (95% CI 332-564) in LPGC patients and 473 days (95% CI 412-555) in non-LPGC patients (P=0.363). Median time to treatment failure is 229 days (95% CI 155 - 280) in LPGC patients and 189 days (95% CI 156 -219) in non-LPGC patients (P=0.245). Conclusions: Although clinicopathological backgrounds were not identical, it was suggested that the prognosis of the patients treated with SP was not different between advanced or metastatic LPGC and non-LPGC.
The effects of MicroRNA deregulation on pre-RNA processing network in multiple myeloma
Authors: Sophia Adamia, Ivane Abiatari, Samir B. Amin, Mariateresa Fulciniti, Stephane Minvielle, Cheng Li, Philippe Moreau, Herve Avet-Loiseau, Nikhil C. Munshi, Kenneth C. Anderson
Journal: Leukemia (2019)
Widespread B cell perturbations in HIV-1 infection afflict naive and marginal zone B cells
Authors: Thomas Liechti, Claus Kadelka, Dominique L. Braun, Herbert Kuster, Jürg Böni, Melissa Robbiani, Huldrych F. Günthard, Alexandra Trkola
Journal: The Journal of Experimental Medicine (2019)

Perturbations in B cells are a hallmark of HIV-1 infection. This is signified by increased numbers of exhausted CD21neg memory B cells, driven by continuous antigen-specific and bystander activation. Using high-dimensional flow cytometry, we demonstrate that this exhausted phenotype is also prevalent among peripheral antigen-inexperienced naive and marginal zone (MZ) B cells in acute and chronic HIV-1 infection. A substantial fraction of naive and MZ B cells exhibit down-regulated CD21 levels and diminished response to B cell receptor (BCR)–dependent stimulation. Compared with CD21pos subsets, the CD21neg naive and MZ B cells differ in the expression of chemokine receptors and activation markers. Effective antiretroviral treatment normalizes peripheral naive and MZ B cell populations. Our results emphasize a more widely spread impairment of B cells in HIV-1 infection than previously appreciated, including antigen-inexperienced cells. This highlights the importance of monitoring functional capacities of naive B cells in HIV-1 infection, as exhausted CD21neg naive B cells may severely impair induction of novel B cell responses.
PF392 MONOCLONAL GAMMOPATHY AND HYPOGAMMAGLOBULINEMIA AS INDEPENDENT PROGNOSTIC FACTORS IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA: A RETROSPECTIVE MULTICENTRIC EXPERIENCE
Authors: A. Corbingi, I. Innocenti, A. Tomasso, R. Pasquale, A. Visentin, M. Varettoni, F. Autore, F. Morelli, L. Trentin, G. Reda, L. Laurenti
Journal: HemaSphere (2019)

Background: Chronic Lymphocytic Leukemia (CLL) is an indolent B‐cell lymphoproliferative disorder. Several prognostic factors such as IGHV mutation status and chromosomal aberrations as trisomy 12, del11q, del13q or del17p have been detected so far. More recent genetic mutations such as BIRC3, SF3B1, NOTCH1 and TP53 stratifies even further the prognosis and outcome in CLL patients (pts). However all data above reported, because of expensive techniques and experience typical of big laboratories, are not available to all medical centers while data concerning the presence of hypogammaglobulinemia, IgM or IgG monoclonal gammopathy are easily achievable, even though the prevalence and the impact on natural history of CLL pts is controversial and contradictory. Aims: The aim of the study is to evaluate the prevalence and the outcome of monoclonal IgM/CLL, IgG/CLL and hypogammaglobulinemia compared with CLL pts with normal immunoglobulin (Ig) levels. Methods: We collected from four different Italian centers 1359 pts diagnosed with typical CLL from 1987 to 2017 with a baseline assessment of serum Ig, immunofixation, chromosomal aberrations and clinical features; evaluating their impact on time to progression (TTP), time to treatment (TTT) and overall survival (OS). Results: Once assessment was made, pts included in our study who met eligibility criteria were 1359. Median age was similar in all the groups and data gathered from the four centers showed an overlapping rate about prevalence and time‐dependent‐parameters in CLL pts and their related subclasses.The overall prevalence of monoclonal gammopathy is 14% of whom 128 pts (9%) with IgG/CLL, 68 pts (5%) with IgM/CLL. Hypogammaglobulinemia was detected in 172 pts (13%) while 991 pts (73%) had no evidence of paraprotein. Among the groups, serum IgG paraprotein showed a correlation with a poorer and shorter overall survival (OS) and an inferior clinical outcome. Summary/Conclusion: Our study provided data about prevalence and prognosis of monoclonal gammopaty and hypogammaglobulinemia in CLL patients. Serum Ig paraprotein was present in 14% of all CLL pts with a worst outcome in IgG/CLL group. Thus, making of serum Ig, a simple data to obtain, useful to assess CLL prognosis. image
Abstract 40: Interleukin-10 Deficiency Impairs Reparative Properties of Bone Marrow-derived Endothelial Progenitor Cell Exosomes Function in Ischemic Myocardium
Authors: Yujia Yue, Venkata N Garikipati, Yan Tang, Zhongjian Chen, Jibin Zhou, Emily Nickoloff, Chunlin Wang, Cindy Benedict, Erhe Gao, Mohsin Khan, Suresh Verma, Raj Kishore
Journal: Circulation Research (2016)

Endothelial progenitor cell (EPC) based therapy promotes neovascularization in ischemic myocardium. Studies suggest that therapeutic effect of stem cells is largely due to paracrine mechanisms including stem cell-derived exosomes that are emerging as key paracrine mediators of stem cell functions. However, the autologous transplantation of EPCs in patients with systemic inflammation, which is a common symptom in patients with ischemic heart diseases, yield modest results suggesting the compromised cell function and altered exosome performance. We hypothesized that EPCs under inflammatory stress secrete dysfunctional exosomes with altered contents including packaged microRNAs, which eventually compromises exosomes repair ability in ischemic myocardium. Whether modulation of identified targets like specific microRNAs in the cargo of exosomes can rescue and/or enhance their reparative properties of dysfunctional exosomes is not known. We have previously shown in Interleukin-10 (IL-10) KO mice (model mimicking systemic inflammation) that loss of IL-10 impairs EPCs functions via miR-375. After cell expansion, we isolated exosomes from these two groups and compared their functions in terms of cell survival, proliferation, migration and angiogenic capacity in vitro and in vivo . We report that WT-EPC-exosomes (Exo) transplantation in the ischemic myocardium after MI significantly improved post-infarct repair, neovascularization and left ventricle functions. Our in vitro studies revealed that WT-EPC-Exo treatment enhanced endothelial cells proliferation and tube formation and inhibited apoptosis; whereas IL-10 KO-EPC-Exo exhibited opposite effects, suggesting that reparative capacity of WT-EPC-Exo is lost in exosomes derived from IL-10 KO-EPCs. Exosome miRNA profiling revealed a drastically different expression patterns with enrichment of inflammation induced microRNAs including significantly higher expression of miR-375. Interestingly, Knockdown of miR-375 in IL-10-EPCs decreased the expression level of miR-375 in their exosomes and partly rescued their angiogenic dysfunctions. Taken together, our studies suggest that modulation of miR-375 in IL-10 KO-EPC-Exo can rescue its phenotype and promote cardiac repair.
Proposed Key Characteristics of Male Reproductive Toxicants as an Approach for Organizing and Evaluating Mechanistic Evidence in Human Health Hazard Assessments
Authors: Xabier Arzuaga, Martyn T. Smith, Catherine F. Gibbons, Niels E. Skakkebæk, Erin E. Yost, Brandiese E. J. Beverly, Andrew K. Hotchkiss, Russ Hauser, Rodrigo L. Pagani, Steven M. Schrader, Lauren Zeise, Gail S. Prins
Journal: Environmental Health Perspectives (2019)

Background: Assessing chemicals for their potential to cause male reproductive toxicity involves the evaluation of evidence obtained from experimental, epidemiological, and mechanistic studies. Although mechanistic evidence plays an important role in hazard identification and evidence integration, the process of identifying, screening and analyzing mechanistic studies and outcomes is a challenging exercise due to the diversity of research models and methods and the variety of known and proposed pathways for chemical-induced toxicity. Ten key characteristics of carcinogens provide a valuable tool for organizing and assessing chemical-specific data by potential mechanisms for cancer-causing agents. However, such an approach has not yet been developed for noncancer adverse outcomes. Objectives: The objective in this study was to identify a set of key characteristics that are frequently exhibited by exogenous agents that cause male reproductive toxicity and that could be applied for identifying, organizing, and summarizing mechanistic evidence related to this outcome. Discussion: The identification of eight key characteristics of male reproductive toxicants was based on a survey of known male reproductive toxicants and established mechanisms and pathways of toxicity. The eight key characteristics can provide a basis for the systematic, transparent, and objective organization of mechanistic evidence relevant to chemical-induced effects on the male reproductive system. https://doi.org/10.1289/EHP5045
<i>Vital Signs:</i> Trends in Human Rabies Deaths and Exposures — United States, 1938–2018
Authors: Emily G. Pieracci, Christine M. Pearson, Ryan M. Wallace, Jesse D. Blanton, Erin R. Whitehouse, Xiaoyue Ma, Kendra Stauffer, Richard B. Chipman, Victoria Olson
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Each year, rabies causes approximately 59,000 deaths worldwide, including approximately two deaths in the United States. Before 1960, dogs were a common reservoir of rabies in the United States; however, increasingly, species of wildlife (e.g., bats, raccoons) are the main reservoirs. This report characterizes human rabies deaths, summarizes trends in rabies mortality, and highlights current rabies risks in the United States.Rabies trends in the United States during 1938-2018 were analyzed using national rabies surveillance data. Data from the Healthcare Cost and Utilization Project for 2006-2014 were used to estimate the number of postexposure prophylaxis (PEP) visits per 100,000 persons during 2017-2018. The Centers for Medicare & Medicaid Services' average sales price data were used to estimate PEP costs.From 1960 to 2018, a total of 125 human rabies cases were reported in the United States; 36 (28%) were attributed to dog bites during international travel. Among the 89 infections acquired in the United States, 62 (70%) were attributed to bats. In 2018, approximately 55,000 persons sought PEP after contact with a potentially rabid animal.In the United States, wildlife rabies, especially in bats, continues to pose a risk to humans. Travelers also might be exposed to canine rabies in countries where the disease is still present; increased awareness of rabies while traveling abroad is needed. Vaccinating pets, avoiding contact with wildlife, and seeking medical care if one is bitten or scratched by an animal are the most effective ways to prevent rabies. Understanding the need for timely administration of PEP to prevent death is critical.
Marie-Joseph Albert Menagé
Authors: Hélène Apthorp
Journal: BMJ (2019)

Marie-Joseph Albert Menage, known as Albert, was born in Mauritius into an established French-Mauritian family and was the eldest of 13 children. He initially qualified as a sugar chemist, and his ambition was to study medicine, following in the footsteps of other family members. This was made possible by the support of Sir Hubert Seddon. On a visit to Mauritius in 1945 to advise on a polio epidemic, Seddon recommended that the young man he had met should study medicine at …