tbuckley/cabot-search huggingface dataset:
Junctional Adhesion Molecule 2 Intensifies T Lymphopoiesis of Hematopoietic Stem Cells By Facilitating Notch/Delta Signaling
Authors: Visnja Radulovic, Mark Van Der Garde, Valgardur Sigurdsson, Alya Zriwil, Svetlana Soboleva, Ewa Sitnicka Quinn, Shin Kaneko, Kenichi Miharada
Journal: Blood (2017)
Abstract 14119: Decellularized Arterial Extracellular Matrix-Based Hydrogel Supports 3D Bioprinting of the Media Layer of Small-Caliber Blood Vessels
Authors: Gabriel R Liguori, Viktor Sinkunas, Tácia T Liguori, Emerson G Moretto, Prashant K Sharma, Martin C Harmsen, Luiz Felipe P Moreira
Journal: Circulation (2019)

Introduction: Tissue-engineered vascular grafts represent a promising alternative for the replacement of small-caliber blood vessels (SCBV). Recently, 3D bioprinting emerged as a new tissue-enginee...
Response to: ‘Risk of systemic lupus erythematosus in patients with idiopathic thrombocytopenic purpura: population-based cohort study’ by Goulielmos and Zervou
Authors: Fang Xiao Zhu, Jing-Yang Huang, James Cheng-Chung Wei
Journal: Annals of the Rheumatic Diseases (2020)

We thank Goulielmos et a l1 for their interests on our article entitled ‘Risk of systemic lupus erythematosus (SLE) in patients with idiopathic thrombocytopenic purpura (ITP): a population-based cohort study’.2

Goulielmos et al raised possible mechanism and explanation about the link of ITP and SLE. We appreciated their review and comments on sensitised platelets, shared genetic background and similar molecular signatures of these two diseases. We also agree that these genetic …
SP0146 Czech self-help society of as patients and its activities
Authors: MO Konrad
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> The totalitarian system in former communist countries limited the activities of people and lead to their passive role in society. The individuality of people was suppressed and a paternalistic approach to patients lead to certain dehumanisation of public health care. The velvet revolution in the Czech Republic in the year 1989 changed not only the political and economical system, but also brought new possibilities in health care. Among many other things it lead to emergence of patient self-help societies. The initiative came from both rheumatologists and enthusiastic patients. One of these societies was ankylosing spondylitis (AS) self-help society – Club of AS Sufferers, founded in the year 1990. One of the main goals of the Club was patient education. An information newsletter has been published regularly bringing articles on all aspects of AS. Later, an audio-cassette with home exercise was released and a guidebook for patients was published and circulated among members. After an enthusiastic beginning was more and more apparent that the goals of the Club would be more difficult to achieve than expected. There is some inertia in the people’s attitudes to life and it is difficult to bring new models of behaviour into reality: the responsibility of every individual for his or her life including health matters and active role in disease management. These problems are a burden for foundation of vast number of self-help groups at district level. The prosperity of modern society is based on very effective economic system, which makes great demands on people. Some rheumatic diseases, like AS, are chronic and begin at young age. Mainly for these patients it is difficult to face all problems imposed from both the disease and life, especially employment. The negative perception of society can be difficult problem to overcome, misconceptions sometimes held by employers can bring problems in a job. The public awareness of rheumatic diseases is rather poor, the opinions, like arthritis is a disease of old age, still prevail. To change the situation it will be necessary to inform the society about these problems. We feel that this will be one of our new goals in the future, but this goal is beyond the possibilities of an individual self-help society like Club of AS Sufferes. The solution may be in a national and, possibly, international cooperation among all organisations of rheumatologists, health professionals and patients. Only such a partnership can initiate a campaign for solving these problems. The European Manifesto or the Bone and Joint Decade 2000–2010 can be a good starting point for, probably long term, effort to improve the quality of life for people with rheumatic diseases.
In patients with CKD having CT with contrast media, no prehydration and prehydration did not differ for AKI
Authors: Neesh Pannu
Journal: Annals of Internal Medicine (2020)

Source Citation Timal RJ, Kooiman J, Sijpkens YWJ, et al. Effect of no prehydration vs sodium bicarbonate prehydration prior to contrast-enhanced computed tomography in the prevention of postcontrast acute kidney injury in adults with chronic kidney disease: the Kompas randomized clinical trial. JAMA Intern Med. 2020;180:533-41. 32065601
DNA methylation maintains the CLDN1-EPHB6-SLUG axis to enhance chemotherapeutic efficacy and inhibit lung cancer progression
Authors: Jia-En Wu, Yi-Ying Wu, Chia-Hao Tung, Yao-Tsung Tsai, Hsuan-Yu Chen, Yuh-Ling Chen, Tse-Ming Hong
Journal: Theranostics (2020)

The loss of cancer-cell junctions and escape from the primary-tumor microenvironment are hallmarks of metastasis. A tight-junction protein, Claudin 1 (CLDN1), is a metastasis suppressor in lung adenocarcinoma. However, as a metastasis suppressor, the underlying molecular mechanisms of CLDN1 has not been well studied. Methods: The signaling pathway regulated by CLDN1 was analyzed by Metacore software and validated by immunoblots. The effect of the CLDN1-EPHB6-ERK-SLUG axis on the formation of cancer stem-like cells, drug resistance and metastasis were evaluated by sphere assay, aldefluor assay, flow cytometry, migration assay, cytotoxicity, soft agar assay, immunoprecipitation assay and xenograft experiments. Furthermore, the methylation-specific PCR, pyrosequencing assay, chromatin immunoprecipitation and reporter assay were used to study the epigenetic and RUNX3-mediated CLDN1 transcription. Finally, the molecular signatures of RUNX3/CLDN1/SLUG were used to evaluate the correlation with overall survival by using gene expression omnibus (GEO) data. Results: We demonstrated that CLDN1 repressed cancer progression via a feedback loop of the CLDN1-EPHB6-ERK1/2-SLUG axis, which repressed metastasis, drug resistance, and cancer stemness, indicating that CLDN1 acts as a metastasis suppressor. CLDN1 upregulated the cellular level of EPHB6 and enhanced its activation, resulting in suppression of ERK1/2 signaling. Interestingly, DNA hypermethylation of the CLDN1 promoter abrogated SLUG-mediated suppression of CLDN1 in low-metastatic cancer cells. In contrast, the histone deacetylase inhibitor trichostatin A or vorinostat facilitated CLDN1 expression in high-metastatic cancer cells and thus increased the efficacy of chemotherapy. Combined treatment with cisplatin and trichostatin A or vorinostat had a synergistic effect on cancer-cell death. Conclusions: This study revealed that DNA methylation maintains CLDN1 expression and then represses lung cancer progression via the CLDN1-EPHB6-ERK1/2-SLUG axis. Because CLDN1 enhances the efficacy of chemotherapy, CLDN1 is not only a prognostic marker but a predictive marker for lung adenocarcinoma patients who are good candidates for chemotherapy. Forced CLDN1 expression in low CLDN1-expressing lung adenocarcinoma will increase the chemotherapy response, providing a novel therapeutic strategy.
Ramucirumab combined with FOLFOX as front-line therapy for advanced esophageal, gastroesophageal junction, or gastric adenocarcinoma: a randomized, double-blind, multicenter Phase II trial
Authors: H.H. Yoon, J.C. Bendell, F.S. Braiteh, I. Firdaus, P.A. Philip, A.L. Cohn, N. Lewis, D.M. Anderson, E. Arrowsmith, J.D. Schwartz, L. Gao, Y. Hsu, Y. Xu, D. Ferry, S.R. Alberts, Z.A. Wainberg
Journal: Annals of Oncology (2019)
OP0060 Mice deficient in leptin (ob/ob) or in leptin receptor (db/db) have a milder form of antigen-induced arthritis
Authors: N Busso, A So, V Péclat, C Gabay
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Leptin, the product of the ob gene, is synthesised exclusively by adipocytes to regulate the body weight in a central manner through its interaction with the long isoform of leptin receptor, Ob-Rb. However, Ob-Rb is also expressed in lymphoid tissues and leptin has been shown to regulate the cell-mediated immunity. <h3>Objectives</h3> To examine the role of leptin <i>in vivo</i> by analysing the phenotype of mice deficient in leptin (ob/ob) or in Ob-Rb (db/db) during antigen-induced arthritis (AIA). <h3>Methods</h3> Arthritis was induced by an intraarticular injection of methylated bovine serum albumin (mBSA) in the knees of previously immunised ob/ob, db/db, control littermates and wild-type mice, all in C57BL/6 background. The severity of arthritis was determined by 99m Technetium (99m Tc) uptake. In addition, the degree of articular inflammation was also determined after sacrifice by histology scoring. Levels of circulating immunoglobulins and antibodies against mBSA were measured by ELISA. The responses of isolated lymph node cells to mBSA were also examined. <h3>Results</h3> Joint inflammation, as measured by 99m Tc uptake, was significantly reduced in ob/ob mice as compared with control littermates and wild-type mice (on day 1 of arthritis: p &lt; 0.002 and p &lt; 0.001, respectively; on day 3: p &lt; 0.03 and p &lt; 0.02, respectively). In addition, histology studies showed that ob/ob mice had markedly less synovial inflammation than lean controls (p &lt; 0.04). In contrast, there was no difference in proteoglycan content within the articular cartilage as assessed by Safranin-O staining. The <i>in vivo</i> production of antibodies against mBSA was significantly decreased in ob/ob mice as compared with controls (p &lt; 0.03). Circulating levels of total and anti-mBSA IgG1, IgG2a, and IgG2b were significantly lower in ob/ob mice than in controls, whereas levels of IgM were not different. <i>In vitro</i> lymph node cell proliferation in response to mBSA was significantly reduced in ob/ob mice as compared with controls. In addition, production of interferon-gamma by cultured lymph node cells was significantly lower in ob/ob than in control mice, whereas opposite results were observed for IL-10. Experiments performed in db/db mice confirmed the findings in leptin-deficient mice. <h3>Conclusion</h3> Leptin appears to regulate both the cellular and humoral components of the immune response against mBSA and to contribute to the mechanisms of joint inflammation in AIA. In addition, these results demonstrate that the effects of leptin on the immune system are mediated through its interaction with Ob-Rb.
Nanomedicine therapies modulating Macrophage Dysfunction: a potential strategy to attenuate Cytokine Storms in severe infections
Authors: Jingping Liu, Meihua Wan, Christopher J. Lyon, Tony Y. Hu
Journal: Theranostics (2020)

Cytokine storms, defined by the dysregulated and excessive production of multiple pro-inflammatory cytokines, are closely associated with the pathology and mortality of several infectious diseases, including coronavirus disease 2019 (COVID-19). Effective therapies are urgently needed to block the development of cytokine storms to improve patient outcomes, but approaches that target individual cytokines may have limited effect due to the number of cytokines involved in this process. Dysfunctional macrophages appear to play an essential role in cytokine storm development, and therapeutic interventions that target these cells may be a more feasible approach than targeting specific cytokines. Nanomedicine-based therapeutics that target macrophages have recently been shown to reduce cytokine production in animal models of diseases that are associated with excessive proinflammatory responses. In this mini-review, we summarize important studies and discuss how macrophage-targeted nanomedicines can be employed to attenuate cytokine storms and their associated pathological effects to improve outcomes in patients with severe infections or other conditions associated with excessive pro-inflammatory responses. We also discuss engineering approaches that can improve nanocarriers targeting efficiency to macrophages, and key issues should be considered before initiating such studies.
Locoregional Management of Early-Stage Breast Cancer
Authors: Benjamin O. Anderson, Janice A. Lyons
Journal: Journal of the National Comprehensive Cancer Network (2020)

Locoregional management of early-stage breast cancer has been trending toward less-extensive axillary resections, based on increasing evidence showing that patients with 1 or 2 positive sentinel nodes and/or micrometastases can safely be managed with sentinel node biopsy alone, thereby avoiding complete axillary lymph node dissection (cALND) in the significant majority of patients. Because of the 15% to 20% lymphedema risk associated with cALND, increasing efforts are being made to avoid the procedure when evidence suggests that more limited procedures are safe, as reflected by acceptable locoregional recurrence rates. Axillary radiotherapy (RT) has been shown to be an effective alternative to ALND for patients fitting criteria from the pivotal AMAROS trial: patients with T1/T2 disease and are clinically node-negative, who undergo either breast-conserving therapy or mastectomy. Considerations for RT begin with the question of nodal involvement, with treatment planned accordingly. With more neoadjuvant therapy being used, there are nuances in locoregional management that clinicians must now appreciate, both in terms of ALND and axillary RT.
A Qualitative Analysis of Career Advice Given to Women Leaders in an Academic Medical Center
Authors: Gianrico Farrugia, Christina K. Zorn, Amy W. Williams, Kate K. Ledger
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Women in academic medicine continue to face systemic obstacles on their paths to leadership. In addition to improving recruitment and advancement opportunities, academic medical centers must facilitate a cultural shift that ensures sustained leadership pathways for women. <h3>Objective</h3> To better understand, from the perspective of women leaders, the workplace and cultural changes that need to take place in academic medicine to increase inclusivity and gender equity. <h3>Design, Setting, and Participants</h3> This qualitative study of 40 women physicians and administrators with senior leadership roles at Mayo Clinic, a nonprofit academic medical center and research institution with campuses in Arizona, Florida, and Minnesota, examined participants' responses to a question regarding their paths to leadership. Replies were submitted between November and December 2018. <h3>Main Outcomes and Measures</h3> Women were asked to describe career advice (positive or negative) they had received that was the hardest to accept but, in retrospect, turned out to be valuable. <h3>Results</h3> Of 40 participants, 25 (63%) were physicians and 15 (37%) were administrators at Mayo Clinic; 27 (68%) had achieved the role of chair or the administrative equivalent. Career experience ranged from 6 to 40 years. Of the 40 women leaders queried, 38 (95%) provided written responses, which were separated into the 4 following categories: leadership styles are perceived as having gendered qualities, attaining leadership skills involves a strategic learning process, collisions between personal life and the workplace should not deter individuals from pursuing leadership roles, and leadership pathways for women involved hurdles. These categories represented a roadmap illuminating perceptions about the academic medical workplace. <h3>Conclusions and Relevance</h3> These findings link generalizable principles to help to drive new strategies for gender parity. Shifting the culture of academic medicine begins with fully understanding impediments to women's advancement. The advice women leaders recounted offered a roadmap as well as a glimpse of the extra effort required for women to succeed amid some of the system's limitations and obstacles. A more complete understanding of gender biases may help to shape future programs to expand inclusivity and establish sustained leadership paths for women.
The Movember Prostate Cancer Landscape Analysis: an assessment of unmet research needs
Authors: Michelle M. Kouspou, Jenna E. Fong, Nadine Brew, Sarah T. F. Hsiao, Seanna L. Davidson, Peter L. Choyke, Tony Crispino, Suneil Jain, Guido W. Jenster, Beatrice S. Knudsen, Jeremy L. Millar, Nicole Mittmann, Charles J. Ryan, Bertrand Tombal, Mark Buzza
Journal: Nature Reviews Urology (2020)

Prostate cancer is a heterogeneous cancer with widely varying levels of morbidity and mortality. Approaches to prostate cancer screening, diagnosis, surveillance, treatment and management differ around the world. To identify the highest priority research needs across the prostate cancer biomedical research domain, Movember conducted a landscape analysis with the aim of maximizing the effect of future research investment through global collaborative efforts and partnerships. A global Landscape Analysis Committee (LAC) was established to act as an independent group of experts across urology, medical oncology, radiation oncology, radiology, pathology, translational research, health economics and patient advocacy. Men with prostate cancer and thought leaders from a variety of disciplines provided a range of key insights through a range of interviews. Insights were prioritized against predetermined criteria to understand the areas of greatest unmet need. From these efforts, 17 research needs in prostate cancer were agreed on and prioritized, and 3 received the maximum prioritization score by the LAC: first, to establish more sensitive and specific tests to improve disease screening and diagnosis; second, to develop indicators to better stratify low-risk prostate cancer for determining which men should go on active surveillance; and third, to integrate companion diagnostics into randomized clinical trials to enable prediction of treatment response. On the basis of the findings from the landscape analysis, Movember will now have an increased focus on addressing the specific research needs that have been identified, with particular investment in research efforts that reduce disease progression and lead to improved therapies for advanced prostate cancer.
Fumarate modulates phospholipase A2 receptor autoimmunity-induced podocyte injury in membranous nephropathy
Authors: Hyung Ah Jo, Jin Seong Hyeon, Seung Hee Yang, Youngae Jung, Hunjoo Ha, Chang Wook Jeong, Cheol Kwak, Yaerim Kim, Hajeong Lee, Jung Pyo Lee, Kwon Wook Joo, Chun Soo Lim, Yon Su Kim, Geum-Sook Hwang, Dong Ki Kim
Journal: Kidney International (2020)
FRI0003 ELEVATED HISTONE H4 IN NEUTROPHIL EXTRACELLULAR TRAPS PROMOTES MACROPHAGE ACTIVATION IN BEHÇET’S DISEASE
Authors: L. LI, X. Yu, J. Liu, H. Chen, W. Zheng
Journal: Annals of the Rheumatic Diseases (2020)

Background: Neutrophil-released neutrophil extracellular traps (NETs) are upregulated and promote autoinflammation and thrombosis in Behçet’s disease (BD), a multi-system inflammatory disease with unknown etiology 1,2 . However, whether NETs promote macrophage activation in BD remains unclear. Objectives: To investigate the potential role of NETs in promoting aberrant macrophage activation in BD. Methods: We quantified NETs by measuring dsDNA using ELISA and immunofluorescence. Macrophages were stimulated with BD- and healthy controls (HC)-derived NETs, and IL-8 and TNF-α production were measured by ELISA. NETs-stimulated macrophages were incubated with naive CD4 + T cells, and Th1 cell differentiation was examined on day 7 by flow cytometry. Histones H1, H2A, H2B, H3, H4, S100A8 and neutrophil elastase in NETs were analyzed by western blot. Macrophages were stimulated with anti-Histone 4 antibody-treated NETs, and IL-8 production was measured by ELISA. Results: Circulating NETs (2336±534 ng/ml vs. 1472±549 ng/ml, P =0.0008) and neutrophil-derived NETs (909.2±485.2 ng/ml vs. 582.4±199.2 ng/ml, P =0.0108) were significantly higher in BD patients compared with those in HC. BD NETs stimulated macrophages to produce a higher level of IL-8 (17±4 ng/ml vs. 13±4 ng/ml, P =0.0474) and TNF-α (166±61 pg/ml vs. 102±48 pg/ml, P =0.0132) than HC NETs. Moreover, BD NETs promoted macrophages to facilitate Th1 differentiation than HC NETs (33±10% vs. 24±7%, P =0.0398). Western blot analysis revealed more Histone H4 (289076 (144365, 544038) IOD values vs. 42121 (6958, 129625) IOD values, P =0.0286), but not Histones H1, H2A, H2B, H3, S100A8 or neutrophil elastase in BD NETs compared to HC NETs. Importantly, neutralizing Histone H4 abrogated the BD NETs-stimulated IL-8 overproduction by macrophages (9.99±2.07 ng/ml vs. 13.95±2.91 ng/ml, P =0.021). Conclusion: BD NETs promoted macrophages activation, which might be mediated by a higher level of Histone H4. References: [1]Safi R., Kallas R., Bardawil T., et al. Neutrophils contribute to vasculitis by increased release of neutrophil extracellular traps in Behçet’s disease. J. Dermatol. Sci. 2018;92:143–150. [2]Le Joncour a, Martos r, Loyau s, et al. Critical role of neutrophil extracellular traps (NETs) in patients with Behcet’s disease. Ann Rheum Dis 2019;78:1274–1282. Disclosure of Interests: None declared
Hepatitis Delta Virus Acts as an Immunogenic Adjuvant in Hepatitis B Virus-Infected Hepatocytes
Authors: Christine Y.L. Tham, Janine Kah, Anthony T. Tan, Tassilo Volz, Adeline Chia, Katja Giersch, Yvonne Ladiges, Alessandro Loglio, Marta Borghi, Camille Sureau, Pietro Lampertico, Marc Lütgehetmann, Maura Dandri, Antonio Bertoletti
Journal: Cell Reports Medicine (2020)

Hepatitis delta virus (HDV) requires hepatitis B virus (HBV) to complete its infection cycle and causes severe hepatitis, with limited therapeutic options. To determine the prospect of T cell therapy in HBV/HDV co-infection, we study the impact of HDV on viral antigen processing and presentation. Using in vitro models of HBV/HDV co-infection, we demonstrate that HDV boosts HBV epitope presentation, both in HBV/HDV co-infected and neighboring mono-HBV-infected cells through the upregulation of the antigen processing pathway mediated by IFN-β/λ. Liver biopsies of HBV/HDV patients confirm this upregulation. We then validate in vitro and in a HBV/HDV preclinical mouse model that HDV infection increases the anti-HBV efficacy of T cells with engineered T cell receptors. Thus, by unveiling the effect of HDV on HBV antigen presentation, we provide a framework to better understand HBV/HDV immune pathology, and advocate the utilization of engineered HBV-specific T cells as a potential treatment for HBV/HDV co-infection.