tbuckley/cabot-search huggingface dataset:
Natural killer cells and type II interferon in Ro/SSA and La/SSB autoantibody-exposed newborns at risk of congenital heart block
Authors: Margarita Ivanchenko, Gudny Ella Thorlacius, Malin Hedlund, Vijole Ottosson, Lauro Meneghel, Sophia Björkander, Amina Ossoinak, Joanna Tingström, Katarina Bremme, Eva Sverremark-Ekström, Kristina Gemzell-Danielsson, Sven-Erik Sonesson, Karine Chemin, Marie Wahren-Herlenius
Journal: Annals of the Rheumatic Diseases (2020)

Objective Congenital heart block (CHB) with immune cell infiltration develops in the fetus after exposure to maternal Ro/La autoantibodies. CHB-related serology has been extensively studied, but reports on immune-cell profiles of anti-Ro/La-exposed neonates are lacking. In the current study, we characterised circulating immune-cell populations in anti-Ro/La+mothers and newborns, and explored potential downstream effects of skewed neonatal cell populations. Methods In total, blood from mothers (n=43) and neonates (n=66) was sampled at birth from anti-Ro/La+ (n=36) and control (n=30) pregnancies with or without rheumatic disease and CHB. Flow cytometry, microarrays and ELISA were used for characterising cells and plasma. Results Similar to non-pregnant systemic lupus erythematosus and Sjögren-patients, anti-Ro/La+mothers had altered B-cell subset frequencies, relative T-cell lymphopenia and lower natural killer (NK)-cell frequencies. Surprisingly, their anti-Ro/La exposed neonates presented higher frequencies of CD56 dim CD16 hi NK cells (p&lt;0.01), but no other cell frequency differences compared with controls. Type I and II interferon (IFN) gene-signatures were revealed in neonates of anti-Ro/La+ pregnancy, and exposure of fetal cardiomyocytes to type I IFN induced upregulation of several NK-cell chemoattractants and activating ligands. Intracellular flow cytometry revealed IFNγ production by NK cells, CD8 + and CD4 + T cells in anti-Ro/La exposed neonates. IFNγ was also detectable in their plasma. Conclusion Our study demonstrates an increased frequency of NK cells in anti-Ro/La exposed neonates, footprints of type I and II IFN and an upregulation of ligands activating NK cells in fetal cardiac cells after type I IFN exposure. These novel observations demonstrate innate immune activation in neonates of anti-Ro/La+pregnancy, which could contribute to the risk of CHB.
Senescence of Alveolar Type 2 Cells Drives Progressive Pulmonary Fibrosis
Authors: Changfu Yao, Xiangrong Guan, Gianni Carraro, Tanyalak Parimon, Xue Liu, Guanling Huang, Apoorva Mulay, Harmik J. Soukiasian, Gregory David, Stephen S. Weigt, John A. Belperio, Peter Chen, Dianhua Jiang, Paul W. Noble, Barry R. Stripp
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Idiopathic pulmonary fibrosis (IPF) is an insidious and fatal interstitial lung disease associated with declining pulmonary function. Accelerated aging, loss of epithelial progenitor cell function and/or numbers, and cellular senescence are implicated in the pathogenies of IPF. Objectives: We sought to investigate the role of alveolar type 2 (AT2) cellular senescence in initiation and/or progression of pulmonary fibrosis and therapeutic potential of targeting senescence-related pathways and senescent cells. Methods: Epithelial cells of 9 control donor proximal and distal lung tissues and 11 IPF fibrotic lung tissues were profiled by single-cell RNA sequencing to assesses the contribution of epithelial cells to the senescent cell fraction for IPF. A novel mouse model of conditional AT2 cell senescence was generated to study the role of cellular senescence in pulmonary fibrosis. Measurements and Main Results: We show that AT2 cells isolated from IPF lung tissue exhibit characteristic transcriptomic features of cellular senescence. We used conditional loss of Sin3a in adult mouse AT2 cells to initiate a program of p53-dependent cellular senescence, AT2 cell depletion, and spontaneous, progressive pulmonary fibrosis. We establish that senescence rather than loss of AT2 cells promotes progressive fibrosis and show that either genetic or pharmacologic interventions targeting p53 activation or senescence block fibrogenesis. Conclusions: Senescence of AT2 cells is sufficient to drive progressive pulmonary fibrosis. Early attenuation of senescence-related pathways and elimination of senescent cells are promising therapeutic approaches to prevent pulmonary fibrosis.
Manipulation of immune‒vascular crosstalk: new strategies towards cancer treatment
Authors: Yang Zhao, Xiangrong Yu, Jia Li
Journal: Acta Pharmaceutica Sinica B (2020)

Tumor vasculature is characterized by aberrant structure and function, resulting in immune suppressive profiles of tumor microenvironment through limiting immune cell infiltration into tumors, endogenous immune surveillance and immune cell function. Vascular normalization as a novel therapeutic strategy tends to prune some of the immature blood vessels and fortify the structure and function of the remaining vessels, thus improving immune stimulation and the efficacy of immunotherapy. Interestingly, the presence of "immune‒vascular crosstalk" enables the formation of a positive feedback loop between vascular normalization and immune reprogramming, providing the possibility to develop new cancer therapeutic strategies. The applications of nanomedicine in vascular-targeting therapy in cancer have gained increasing attention due to its specific physical and chemical properties. Here, we reviewed the recent advances of effective routes, especially nanomedicine, for normalizing tumor vasculature. We also summarized the development of enhancing nanoparticle-based anticancer drug delivery via the employment of transcytosis and mimicking immune cell extravasation. This review explores the potential to optimize nanomedicine-based therapeutic strategies as an alternative option for cancer treatment.
Global maps of travel time to healthcare facilities
Authors: D. J. Weiss, A. Nelson, C. A. Vargas-Ruiz, K. Gligorić, S. Bavadekar, E. Gabrilovich, A. Bertozzi-Villa, J. Rozier, H. S. Gibson, T. Shekel, C. Kamath, A. Lieber, K. Schulman, Y. Shao, V. Qarkaxhija, A. K. Nandi, S. H. Keddie, S. Rumisha, P. Amratia, R. Arambepola, E. G. Chestnutt, J. J. Millar, T. L. Symons, E. Cameron, K. E. Battle, S. Bhatt, P. W. Gething
Journal: Nature Medicine (2020)
An integrated multi-omics approach identifies epigenetic alterations associated with Alzheimer’s disease
Authors: Raffaella Nativio, Yemin Lan, Greg Donahue, Simone Sidoli, Amit Berson, Ananth R. Srinivasan, Oksana Shcherbakova, Alexandre Amlie-Wolf, Ji Nie, Xiaolong Cui, Chuan He, Li-San Wang, Benjamin A. Garcia, John Q. Trojanowski, Nancy M. Bonini, Shelley L. Berger
Journal: Nature Genetics (2020)
A Comparison of the Efficacy and Safety of Entecavir Versus Lamivudine Through 240 Weeks of Treatment in Korean Patients with HBeAg-negative Chronic Hepatitis B
Authors: Kwan Sik Lee, Young-Oh Kweon, Soon Ho Um, Byung-Ho Kim, Young Suk Lim, Seung Woon Paik, Jeong Heo, Heon Ju Lee, Dong Joon Kim, Tae Hun Kim, Young Sok Lee, Kwan Soo Byun, Dae-Ghon Kim, Myung Seok Lee, Cyril Llamoso, Kyungha Yu, Dong Jin Suh
Journal: Hepatology (2018)
TiNivo: safety and efficacy of tivozanib-nivolumab combination therapy in patients with metastatic renal cell carcinoma
Authors: L. Albiges, P. Barthélémy, M. Gross-Goupil, S. Negrier, M.N. Needle, B. Escudier
Journal: Annals of Oncology (2020)

Treatment with tivozanib, a highly selective and potent vascular endothelial growth factor receptor tyrosine kinase inhibitor, has demonstrated single-agent efficacy in advanced renal cell carcinoma (RCC) along with minimal off-target toxicities and a favorable adverse event (AE) profile. We report final results from TiNivo, a phase Ib/II study of tivozanib combined with nivolumab.In phase Ib, patients with metastatic RCC received tivozanib 1.0 mg once daily (QD) for 21 days followed by 7 days off treatment (n = 3) or tivozanib 1.5 mg QD (n = 3) plus nivolumab 240 mg every 2 weeks. The maximum tolerated dose was determined to be tivozanib 1.5 mg, and 22 additional patients were enrolled at the maximum tolerated dose for phase II. Primary end points included safety and tolerability, with secondary end points of objective response rate, disease control rate, and progression-free survival.In total, 25 patients were treated with tivozanib 1.5 mg QD [12 (48%) treatment-naïve; 13 (52%) previously treated]. Treatment-related grade 3/4 AEs were reported in 20 patients (80%); 4 patients (17%) experienced AEs that led to dose reduction, and 8 (32%) discontinued due to AEs. The objective response rate was 56% (including one complete response) and disease control rate was 96%, with a median time to best response of 7.9 weeks. Twenty patients (80%) had tumor shrinkage. With a median follow-up of 19.0 months (range, 12.6-22.8), median progression-free survival was 18.9 months (95% confidence interval 16.4-not reached) in all patients and was similar in treatment-naïve and previously treated patients.Tivozanib plus nivolumab combination therapy showed a generally tolerable AE profile and promising antitumor efficacy. These results support further development of tivozanib combined with nivolumab as a treatment option in patients with treatment-naïve or previously treated metastatic RCC.NCT03136627.
Mitigating increased variability of multiple breath washout indices due to tidal breathing
Authors: Sylvia Verbanck, Daniel Schuermans, Manuel Paiva, Paul D. Robinson, Eef Vanderhelst
Journal: European Respiratory Journal (2020)

<b>By studying tidal volume dependence of diagnostic multiple breath washout (MBW) indices, it can be determined how breathing patterns can be modulated to obtain less variable MBW outcomes and shorten MBW test duration in the clinical routine</b>https://bit.ly/32GxRWj
TREML4 receptor regulates inflammation and innate immune cell death during polymicrobial sepsis
Authors: Christina Nedeva, Joseph Menassa, Mubing Duan, Chuanxin Liu, Marcel Doerflinger, Andrew J. Kueh, Marco J. Herold, Pamali Fonseka, Thanh Kha Phan, Pierre Faou, Harinda Rajapaksha, Weisan Chen, Mark D. Hulett, Hamsa Puthalakath
Journal: Nature Immunology (2020)
Re: Alison Birtle, Mark Johnson, John Chester, et al. Adjuvant Chemotherapy in Upper Tract Urothelial Carcinoma (the POUT Trial): A Phase 3, Open-label, Randomised Controlled Trial. Lancet 2020;395:1268–77
Authors: Nirmish Singla, Vitaly Margulis
Journal: European Urology (2020)
Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis
Authors: Kristian Reich, Kenji Kabashima, Ketty Peris, Jonathan I. Silverberg, Lawrence F. Eichenfield, Thomas Bieber, Aleksandra Kaszuba, Jill Kolodsick, Fan E. Yang, Margaret Gamalo, Dennis R. Brinker, Amy M. DeLozier, Jonathan M. Janes, Fabio P. Nunes, Jacob P. Thyssen, Eric L. Simpson
Journal: JAMA Dermatology (2020)

Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced disease severity in moderate to severe atopic dermatitis (AD) in 2 phase 3 monotherapy studies.
Prevalence of COVID-19 Infection in Hemodialysis Patients Detected Using Serologic Screening
Authors: Diana Rodríguez-Espinosa, José Jesús Broseta, Elena Cuadrado, Francisco Maduell
Journal: Journal of the American Society of Nephrology (2020)

The communication by Clarke et al.1 published this past July reports a high prevalence of serologically detected coronavirus disease 2019 (COVID-19) infection among patients of two London hemodialysis units. A universal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening program, with detection of IgG and IgM against the virus and bimonthly RT-PCR test, was also performed in the two units affiliated to our center, Hospital Clínic of Barcelona. Interestingly, some remarkable differences between our findings and the ones published in this journal are worth noting. Even though there is a much higher overall prevalence in the city of London than here in Barcelona (14.5%, and 7% respectively),1,2 the prevalence in the studied population of patients on in-center hemodialysis is strikingly higher (36.2%, 129 of 356). In contrast, our in-center hemodialysis prevalence was much closer to that of the general population (9.2%, 13 of 141). The infection precaution measures adopted by the London cohort on the basis of the National Institute for Health and Care Excellence guidelines seem similar to ours.3,4 However, there are some significant differences. First, every patient, nurse, and cleaning staff member, regardless of COVID-19 status, has always been required to wear a mask during the totality of the hemodialysis session. Second, our screening system adds the bimonthly RT-PCR test, with which we have diagnosed two asymptomatic patients and thus, provided proper isolation for their hemodialysis sessions. Finally, a SARS-CoV-2 RT-PCR–positive patient could only be deisolated after two consecutively negative results at least 2 weeks after the initial diagnosis. Although epidemiologic disparities are expected between countries, it is important to inform of different experiences, such as those exposed in this letter. These deisolation, detection, and physical barrier preventive measures were stricter than those applied in London. Thus, they may have reduced the viral exposure of such a high-risk population and at least in part, may explain the difference in prevalence seen between both cohorts. Disclosures F. Maduell reports being on speakers bureaus for Amgen, Baxter, Braun, Fresenius Medical Care, Metronic, and Nipro. All remaining authors have nothing to disclose. Funding None.
Abstract 15718: Diagnostic Utility of Cardiac Troponin T Levels in Patients With Infiltrative Cardiomyopathy
Authors: Seiji Takashio, Yasuhiro Izumiya, Kyoko Hirakawa, Kyohei Marume, Masahiro Yamamoto, Mitsuharu Ueda, Taro Yamashita, Hatsue Ishibashi-Ueda, Satoshi Yasuda, Yukio Ando, Toshihisa Anzai, Kenichi Tsujita
Journal: Circulation (2017)

Introduction: Cardiac amyloidosis and Fabry disease are major infiltrative cardiomyopathy and an important differential diagnosis in patients with myocardial hypertrophy. Recently, novel and diseas...
Erratum to: Continuous renal replacement therapy versus intermittent hemodialysis in intensive care patients: impact on mortality and renal recovery
Authors: Anne-Sophie Truche, Michael Darmon, Sébastien Bailly, Christophe Clec’h, Claire Dupuis, Benoit Misset, Elie Azoulay, Carole Schwebel, Lila Bouadma, Hatem Kallel, Christophe Adrie, Anne-Sylvie Dumenil, Laurent Argaud, Guillaume Marcotte, Samir Jamali, Philippe Zaoui, Virginie Laurent, Dany Goldgran-Toledano, Romain Sonneville, Bertrand Souweine, Jean-Francois Timsit
Journal: Intensive Care Medicine (2016)
Calcium silicate bioactive ceramics induce osteogenesis through oncostatin M
Authors: Panyu Zhou, Demeng Xia, Zhexin Ni, Tianle Ou, Yang Wang, Hongyue Zhang, Lixia Mao, Kaili Lin, Shuogui Xu, Jiaqiang Liu
Journal: Bioactive Materials (2020)

Immune reactions are a key factor in determining the destiny of bone substitute materials after implantation. Macrophages, the most vital factor in the immune response affecting implants, are critical in bone formation, as well as bone biomaterial-mediated bone repair. Therefore, it is critical to design materials with osteoimmunomodulatory properties to reduce host-to-material inflammatory responses by inducing macrophage polarization. Our previous study showed that calcium silicate (CS) bioceramics could significantly promote osteogenesis. Herein, we further investigated the effects of CS on the behavior of macrophages and how macrophages regulated osteogenesis. Under CS extract stimulation, the macrophage phenotype was converted to the M2 extreme. Stimulation by a macrophage-conditioned medium that was pretreated by CS extracts resulted in a significant enhancement of osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), indicating the important role of macrophage polarization in biomaterial-induced osteogenesis. Mechanistically, oncostatin M (OSM) in the macrophage-conditioned medium promoted osteogenic differentiation of BMSCs through the ERK1/2 and JAK3 pathways. This in vivo study further demonstrated that CS bioceramics could stimulate osteogenesis better than β-TCP implants by accelerating new bone formation at defective sites in the femur. These findings improve our understanding of immune modulation of CS bioactive ceramics and facilitate strategies to improve the in vitro osteogenesis capability of bone substitute materials.
Prognostic Value of Prerevascularization Fractional Flow Reserve Mediated by the Postrevascularization Level
Authors: Rikuta Hamaya, Murray A. Mittleman, Masahiro Hoshino, Yoshihisa Kanaji, Tadashi Murai, Joo Myung Lee, Ki Hong Choi, Jun-Jie Zhang, Fei Ye, Xiaobo Li, Zhen Ge, Shao-Liang Chen, Tsunekazu Kakuta
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The prognostic value of pre–percutaneous coronary intervention (PCI) fractional flow reserve (FFR) may be associated with the post-PCI FFR and their interaction. To correctly interpret the prognostic value of pre-PCI FFR, it is essential to understand to what extent the association of pre-PCI FFR with clinical outcomes is explained by post-PCI FFR. <h3>Objective</h3> To investigate the extent to which post-PCI FFR mediates the association of pre-PCI FFR with vessel-related outcomes using an international, multicenter collaboration registry. <h3>Design, Setting, and Participants</h3> This cohort study used pooled patient data from 4 international FFR registries. A total of 1488 patients with pre-PCI FFR of 0.80 or less who underwent elective PCI were included. Data collection was conducted from November 2011 to August 2019, and analysis was conducted from September 2019 to July 2020. <h3>Main Outcomes and Measures</h3> The primary outcome was target vessel failure (TVF) during 2 years of follow-up. The extent to which post-PCI FFR of less than 0.90 mediated the association of pre-PCI FFR less than 0.75 (vs pre-PCI FFR of 0.75 or greater) with TVF was evaluated using a mediation analysis in a counterfactual framework. <h3>Results</h3> Among 1488 patients, the mean (SD) age was 63.5 (9.9) years and 1161 patients (78.0%) were men. The median (interquartile range) pre-PCI and post-PCI FFR were 0.71 (0.62-0.76) and 0.88 (0.83-0.92), respectively. The direct association of low pre-PCI FFR (ie, &lt;0.75) with TVF was significant (odds ratio, 1.81; 95% CI, 1.03-3.17;<i>P</i> = .04), while the mediation by post-PCI FFR level of less than 0.90 was not (indirect association: odds ratio, 1.03; 95% CI, 0.98-1.09;<i>P</i> = .24). In sensitivity analyses using several pre-PCI cutoffs, the mediations by post-PCI FFR were consistently weak. <h3>Conclusions and Relevance</h3> In this study, the association of pre-PCI FFR with TVF was not significantly mediated by post-PCI FFR. Poor prognosis due to progressed atherosclerosis, represented as low FFR, may not be reversed by successful PCI that increases FFR. Therefore, the prognostic value of pre-PCI FFR may mainly reflect the global atherosclerotic burden, not the extent of the modifiable epicardial stenosis.
Effect on women in a general practice in Devon ..
Authors: C. J Seamark
Journal: BMJ (1995)

Scare over oral contraceptivesEffect on behaviour ofwomen attending a family planning clinic EDrTOR,-The Department of Health's recent press release concerning the safety of some third generation contraceptive pills has important consequences for women using oral contraception.I To document their views and any change in behaviour of women taking the contraceptive pill after this warning, a survey was carried out at a large family planning clinic.After the announcement a telephone helpline was established at the clinic.This took 2348 calls on the first seven days, and the number of attendances rose from an expected 700 to 2029 in that week.One week later a piloted questionnaire
Establishment of a High‐risk MDS/AML Cell Line YCU‐AML1 and its Xenograft Model Harboring t(3;3) and Monosomy 7
Authors: Hiroyoshi Kunimoto, Yumi Fukuchi, Koichi Murakami, Junji Ikeda, Hiroshi Teranaka, Ikuma Kato, Takuya Miyazaki, Makiko Enaka, Takayuki Mitsuhashi, Etsuko Yamazaki, Kaori Kameyama, Mitsuru Murata, Shinichiro Okamoto, Hideaki Nakajima
Journal: HemaSphere (2020)

Acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) with both inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and monosomy 7 defines an extremely aggressive myeloid cancer whose molecular pathogenesis and optimal therapeutic strategy still remain unclear. We established a new MDS/AML cell line, YCU-AML1, and its patient-derived xenograft (PDX) model from a high-risk MDS patient who later transformed into AML harboring both t(3;3)(q21;q26.2) and monosomy 7. YCU-AML1 cells propagated in co-culture system with stromal cells in granulocyte macrophage colony-stimulating factor (GM-CSF)-dependent manner. CD34+ bone marrow cells derived from our PDX model showed high EVI1 and low GATA2 expression. Moreover, mutational profile of our MDS/AML model was consistent with recently published mutational spectrum of myeloid malignancies with inv(3)/t(3;3). These data suggest that YCU-AML1 cells and its MDS/AML model strongly mimics a high-risk human myeloid cancer with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and monosomy 7 in terms of both clinical phenotype and molecular basis. We believe our model can be used as a feasible tool to further explore molecular pathogenesis and novel treatment strategy of high-risk MDS/AML with t(3;3)(q21;q26.2) and monosomy 7.