tbuckley/cabot-search huggingface dataset:
European Respiratory Society guidelines for the management of adult bronchiectasis
Authors: Eva Polverino, Pieter C. Goeminne, Melissa J. McDonnell, Stefano Aliberti, Sara E. Marshall, Michael R. Loebinger, Marlene Murris, Rafael Cantón, Antoni Torres, Katerina Dimakou, Anthony De Soyza, Adam T. Hill, Charles S. Haworth, Montserrat Vendrell, Felix C. Ringshausen, Dragan Subotic, Robert Wilson, Jordi Vilaró, Bjorn Stallberg, Tobias Welte, Gernot Rohde, Francesco Blasi, Stuart Elborn, Marta Almagro, Alan Timothy, Thomas Ruddy, Thomy Tonia, David Rigau, James D. Chalmers
Journal: European Respiratory Journal (2017)

Bronchiectasis in adults is a chronic disorder associated with poor quality of life and frequent exacerbations in many patients. There have been no previous international guidelines.The European Respiratory Society guidelines for the management of adult bronchiectasis describe the appropriate investigation and treatment strategies determined by a systematic review of the literature.A multidisciplinary group representing respiratory medicine, microbiology, physiotherapy, thoracic surgery, primary care, methodology and patients considered the most relevant clinical questions (for both clinicians and patients) related to management of bronchiectasis. Nine key clinical questions were generated and a systematic review was conducted to identify published systematic reviews, randomised clinical trials and observational studies that answered these questions. We used the GRADE approach to define the quality of the evidence and the level of recommendations. The resulting guideline addresses the investigation of underlying causes of bronchiectasis, treatment of exacerbations, pathogen eradication, long term antibiotic treatment, anti-inflammatories, mucoactive drugs, bronchodilators, surgical treatment and respiratory physiotherapy.These recommendations can be used to benchmark quality of care for people with bronchiectasis across Europe and to improve outcomes.
腫瘍造影に対する診断薬キャリアーとしてのポリ(エチレングリコール)誘導体の実現可能性
Authors: Kanazaki Kengo, Sano Kohei, Makino Akira, Yamauchi Fumio, Takahashi Atsushi, Homma Tsutomu, Ono Masahiro, Saji Hideo
Journal: Journal of Controlled Release (2016)
Using Project Echo Telementoring to Improve Sickle Cell Disease Care in the Midwest
Authors: Lisa Marie Shook, Christina Bennett Farrell, Karen A. Kalinyak, Stephen C Nelson, Brandon M. Hardesty, Angeli Rampersad, Kay Linn Saving, Wanda Witten-Shurney, Julie Panepinto, Trisha Calabrese, Lori E. Crosby, Russell E. Ware
Journal: Blood (2016)
Abundant expression of somatic transposon-derived piRNAs throughout Tribolium castaneum embryogenesis
Authors: Maria Ninova, Sam Griffiths-Jones, Matthew Ronshaugen
Journal: Genome biology (2017)

Piwi-interacting RNAs (piRNAs) are a class of short (~26–31-nucleotide) non-protein-coding RNAs expressed in the metazoan germline. The piRNA pathway in arthropods is best understood in the ovary of Drosophila melanogaster, where it acts to silence active transposable elements (TEs). Maternal loading of piRNAs in oocytes is further required for the inheritance of piRNA-mediated transposon defence. However, our understanding of the diversity, evolution and function of the piRNA complement beyond drosophilids is limited. The red flour beetle, Tribolium castaneum, is an emerging model organism separated from Drosophila by ~ 350 million years of evolution that displays a number of features ancestral to arthropods, including short germ embryogenesis. Here, we characterize the maternally deposited and zygotically expressed small RNA and mRNA complements throughout T. castaneum embryogenesis. We find that beetle oocytes and embryos of all stages are abundant in heterogeneous ~ 28-nucleotide RNAs. These small RNAs originate from discrete genomic loci enriched in TE sequences and display the molecular signatures of transposon-derived piRNAs. In addition to the maternally loaded primary piRNAs, Tribolium embryos produce secondary piRNAs by the cleavage of zygotically activated TE transcripts via the ping-pong mechanism. The two Tribolium piRNA pathway effector proteins, Tc-Piwi/Aub and Tc-Ago3, are also expressed throughout the soma of early embryos. Our results show that the piRNA pathway in Tribolium is not restricted to the germline, but also operates in the embryo and may act to antagonize zygotically activated transposons. Taken together, these data highlight a functional divergence of the piRNA pathway between insects.
Fixing medicine by driving down demand and increasing collaboration
Authors: Hugh van’t Hoff
Journal: BMJ (2017)

Godlee asks whether we are ready for “collaborative health.”1 We are already doing this in Gloucestershire. With funding from clinical commissioning groups and Public Health England, Facts4Life is delivering a programme to schools (we have reached our target of half the schools in Gloucestershire) that enables children to explore illness and health, where one stops and the other starts, and the grey area between the two—difficult areas like family illness, dementia, …
Effect of Topical Fluorouracil Cream on Photodamage
Authors: Kaveri Korgavkar, Kachiu C. Lee, Martin A. Weinstock
Journal: JAMA Dermatology (2017)

Photoaging, which is premature skin aging caused by long-term UV exposure, is of aesthetic concern to many patients. To investigate the effect of topical fluorouracil, 5%, cream on photoaging using validated photonumeric scales. The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized clinical trial of 932 US veterans with a recent history of 2 or more keratinocyte carcinomas performed from September 30, 2011, through June 30, 2014, to assess the chemopreventive effects of a standard course of topical fluorouracil. Photographs were taken at baseline and at numerous time points for up to 4 years. In our secondary analysis, 2 independent dermatologists graded these photographs using 4 validated photonumeric scales. A total of 3042 photographs from 281 participants randomized to apply topical fluorouracil or placebo were evaluated at baseline, 6 months, 12 months, and 18 months using 4 photonumeric scales (Griffiths scale, Allergan forehead lines scale, melomental folds scale, and crow's feet scale). Data analysis was performed from November 1, 2016, to January 1, 2017. Participants were randomized to apply topical fluorouracil, 5%, cream or a vehicle control cream to the face and ears twice daily for 2 to 4 weeks for a total of 28 to 56 doses. Effect of a standard course of fluorouracil on the extent of photodamage as measured using 4 photonumeric scales. The study population was predominantly male (274 [97.5%]) and white (281 [100%]), with a mean (SD) age of 71.5 (0.57) years. No statistically significant changes were found in photodamage between baseline and 6 months (Griffiths scale: χ2 = 0.01, P = .93; Allergan forehead lines scale: χ2 = 0.18, P = .67; melomental fold scale: χ2 = 0.03, P = .87; crow's feet scale: χ2 = 2.41, P = .12), 12 months (Griffiths scale: χ2 = 1.39, P = .24; Allergan forehead lines scale: χ2 = 0.64, P = .43; melomental fold scale: χ2 = 0.12, P = .73; crow's feet scale: χ2 = 1.07, P = .30), and 18 months (Griffiths scale: χ2 = 3.11, P = .08; Allergan forehead lines scale: χ2 = 0.89, P = .34; melomental fold scale: χ2 = 1.64, P = .20; crow's feet scale: χ2 = 0.46, P = .50). This study did not demonstrate improvement in photoaging with a standard course of topical fluorouracil, 5%, cream, a finding that may be attributable to a true lack of effect in photodamage or limitations of the photonumeric scales in capturing the effect. The development of photonumeric scales that include manifestations of photoaging other than rhytids, such as lentigines, hyperpigmentation, and telangiectasias, should be considered. clinicaltrials.gov Identifier: NCT00847912.
肝癌の同所性マウスモデルにおける腫瘍増殖を抑制するドキソルビシン負荷ガラクトシル化ポリ(ethyleneglycol)-リトコール酸の併用療法【Powered by NICT】
Authors: Singh Bijay, Jang Yoonjeong, Maharjan Sushila, Kim Hyeon-Jeong, Lee Ah Young, Kim Sanghwa, Gankhuyag Nomundelger, Yang Myeon-Sik, Choi Yun-Jaie, Cho Myung-Haing, Cho Chong-Su
Journal: Biomaterials (2017)
足関節上腕血圧比が高い患者における特徴及び転帰;IMPACT‐ABIレジストリから
Authors: Shimizu Kunihiko, Miura Takashi, Abe Naoyuki, Nishimura Hitoshi, Hashizume Naoto, Oguchi Yasutaka, Minamisawa Masatoshi, Yoshie Koji, Mochidome Tomoaki, Shoin Wataru, Ebisawa Souichiro
Journal: Circulation (2016)
Legionella pneumophila Modulates Mitochondrial Dynamics to Trigger Metabolic Repurposing of Infected Macrophages
Authors: Pedro Escoll, Ok-Ryul Song, Flávia Viana, Bernhard Steiner, Thibault Lagache, Jean-Christophe Olivo-Marin, Francis Impens, Priscille Brodin, Hubert Hilbi, Carmen Buchrieser
Journal: Cell Host & Microbe (2017)
Therapeutic endoscopy-related GI bleeding and thromboembolic events in patients using warfarin or direct oral anticoagulants: results from a large nationwide database analysis
Authors: Naoyoshi Nagata, Hideo Yasunaga, Hiroki Matsui, Kiyohide Fushimi, Kazuhiro Watanabe, Junichi Akiyama, Naomi Uemura, Ryota Niikura
Journal: Gut (2017)

To compare the risks of postendoscopy outcomes associated with warfarin with direct oral anticoagulants (DOACs), taking into account heparin bridging and various types of endoscopic procedures.Using the Japanese Diagnosis Procedure Combination database, we identified 16 977 patients who underwent 13 types of high-risk endoscopic procedures and took preoperative warfarin or DOACs from 2014 to 2015. One-to-one propensity score matching was performed to compare postendoscopy GI bleeding and thromboembolism between the warfarin and DOAC groups.In the propensity score-matched analysis involving 5046 pairs, the warfarin group had a significantly higher proportion of GI bleeding than the DOAC group (12.0% vs 9.9%; p=0.002). No significant difference was observed in thromboembolism (5.4% vs 4.7%) or in-hospital mortality (5.4% vs 4.7%). The risks of GI bleeding and thromboembolism were greater in patients treated with warfarin plus heparin bridging or DOACs plus bridging than in patients treated with DOACs alone. Compared with percutaneous endoscopic gastrostomy, patients who underwent endoscopic submucosal dissection, endoscopic mucosal resection and haemostatic procedures including endoscopic variceal ligation or endoscopic injection sclerotherapy were at the highest risk of GI bleeding among the 13 types of endoscopic procedures, whereas those who underwent lower polypectomy endoscopic sphincterotomy or endoscopic ultrasound-guided fine needle aspiration were at moderate risk.The risk of postendoscopy GI bleeding was higher in warfarin than DOAC users. Heparin bridging was associated with an increased risk of bleeding and did not prevent thromboembolism. The bleeding risk varied by the type of endoscopic procedure.
Salvage Chemoimmunotherapy With Inotuzumab Ozogamicin Combined With Mini–Hyper-CVD for Patients With Relapsed or Refractory Philadelphia Chromosome–Negative Acute Lymphoblastic Leukemia
Authors: Elias Jabbour, Farhad Ravandi, Partow Kebriaei, Xuelin Huang, Nicholas J. Short, Deborah Thomas, Koji Sasaki, Michael Rytting, Nitin Jain, Marina Konopleva, Guillermo Garcia-Manero, Richard Champlin, David Marin, Tapan Kadia, Jorge Cortes, Zeev Estrov, Koichi Takahashi, Yogin Patel, Maria R. Khouri, Jovitta Jacob, Rebecca Garris, Susan O’Brien, Hagop Kantarjian
Journal: JAMA Oncology (2017)

The outcome of patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) is poor. Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to calicheamicin, has single-agent activity in R/R ALL.To evaluate the efficacy and safety of inotuzumab ozogamicin plus low-intensity chemotherapy in patients with R/R ALL.A single-arm, phase 2 study of adults with R/R B-cell ALL conducted at The University of Texas MD Anderson Cancer Center, Houston.The chemotherapy used was lower intensity than hyper-CVAD (cyclophosphamide, vincristine, doxorubicin [trade name, Adriamycin; Pfizer], and dexamethasone) and is referred to as mini-hyper-CVD (mini-HCVD: cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, and cytarabine at 0.5 g/m2 × 4 doses). Inotuzumab was given on day 3 of the first 4 courses at 1.8 to 1.3 mg/m2 for cycle 1 followed by 1.3 to 1.0 mg/m2 for subsequent cycles.The primary end points were the overall response rate and overall survival (OS). Secondary end points included safety, relapse-free survival (RFS), the rate of allogeneic stem cell transplantation (ASCT), and the minimal residual disease (MRD) negativity rate.Fifty-nine patients (30 women and 29 men) with a median age of 35 years (range, 18-87 years) were treated. Overall, 46 patients (78%) responded, 35 of them (59%) achieving complete response. The overall MRD negativity rate among responders was 82%. Twenty-six patients (44%) received ASCT. Grade 3 to 4 toxic effects included prolonged thrombocytopenia (81%; n = 48), infections (73%; n = 43), and hyperbilirubinemia (14%; n = 8). Veno-occlusive disease (VOD) occurred in 9 patients (15%). With a median follow-up of 24 months, the median RFS and OS were 8 and 11 months, respectively. The 1-year RFS and OS rates were 40% and 46%, respectively. The 1-year OS rates for patients treated in salvage 1, salvage 2, and salvage 3 or beyond were 57%, 26%, and 39%, respectively (P = .03).The combination of inotuzumab with low-intensity mini-HCVD chemotherapy shows encouraging results in R/R ALL. The risk of VOD should be considered carefully in patients with previous liver damage and among transplant candidates.clinicaltrials.gov Identifier: NCT01371630.
Whole genome sequencing of ESBL-producing Escherichia coli isolated from patients, farm waste and canals in Thailand
Authors: Chakkaphan Runcharoen, Kathy E. Raven, Sandra Reuter, Teemu Kallonen, Suporn Paksanont, Jeeranan Thammachote, Suthatip Anun, Beth Blane, Julian Parkhill, Sharon J. Peacock, Narisara Chantratita
Journal: Genome Medicine (2017)

Tackling multidrug-resistant Escherichia coli requires evidence from One Health studies that capture numerous potential reservoirs in circumscribed geographic areas. We conducted a survey of extended β-lactamase (ESBL)-producing E. coli isolated from patients, canals and livestock wastewater in eastern Thailand between 2014 and 2015, and analyzed isolates using whole genome sequencing. The bacterial collection of 149 isolates consisted of 84 isolates from a single hospital and 65 from the hospital sewer, canals and farm wastewater within a 20 km radius. E. coli ST131 predominated the clinical collection (28.6%), but was uncommon in the environment. Genome-based comparison of E. coli from infected patients and their immediate environment indicated low genetic similarity overall between the two, although three clinical–environmental isolate pairs differed by ≤ 5 single nucleotide polymorphisms. Thai E. coli isolates were dispersed throughout a phylogenetic tree containing a global E. coli collection. All Thai ESBL-positive E. coli isolates were multidrug resistant, including high rates of resistance to tobramycin (77.2%), gentamicin (77.2%), ciprofloxacin (67.8%) and trimethoprim (68.5%). ESBL was encoded by six different CTX-M elements and SHV-12. Three isolates from clinical samples (n = 2) or a hospital sewer (n = 1) were resistant to the carbapenem drugs (encoded by NDM-1, NDM-5 or GES-5), and three isolates (clinical (n = 1) and canal water (n = 2)) were resistant to colistin (encoded by mcr-1); no isolates were resistant to both carbapenems and colistin. Tackling ESBL-producing E. coli in this setting will be challenging based on widespread distribution, but the low prevalence of resistance to carbapenems and colistin suggests that efforts are now required to prevent these from becoming ubiquitous.
Abstract 230: Specific Mitochondrial Adaptation In Chronic Hypoxic Hearts Results In An Improved Intrinsic Energetic Homeostasis
Authors: Veronique Deschodt-Arsac, Guillaume Calmettes, Laurent Arsac, Bernard Muller, Pierre Dos Santos, Meleze Hocini, Pierre Jais, Michel Haissaguerre, Philippe Diolez
Journal: Circulation Research (2013)

Hypoxic states of the cardiovascular system are often associated with severe cardiac diseases. In spite of impairments in contractile activity, mitochondrial content, cell energy status and calcium transients, we recently demonstrated an improved energy homeostasis in chronic hypoxic hearts explained by a higher mitochondrial sensitivity to ATP/PCr changes, based on combined 31P-NMR spectroscopy and the analytical framework of metabolic control analysis. In the present study, we describe the role of calcium in co-variations in cellular energy status (PCr, ATP) and cardiac work (RPP), in perfused hearts from mice adapted for three weeks to a simulated altitude of 5500 m in a barochamber. Under basal conditions, lower cardiac work and PCr concentration confirmed energetic impairments in chronic hypoxic hearts. At high calcium concentration, cardiac work increased by 40% both in control and hypoxic hearts while a smaller PCr drop in hypoxic hearts, indicating an improved energy homeostasis and higher mitochondrial sensitivity to PCr changes. Stimulating calcium transients by adrenaline and thereby parallel activation of supply and demand components increased cardiac work twice as much only in control hearts (RPP +100%) without any significant PCr variation. The blunted effect of adrenaline in hypoxic hearts is likely the consequence of attenuated ß1-adrenergic receptors stimulation. Inhibition of mitochondrial calcium uniporter by ruthenium red which abolished the mitochondrial-mediated adrenergic regulation was not effective in chronic hearts in contrast of control. We conclude that although chronic hypoxic hearts failed to use calcium transients to optimize their inotropic response to a specific adrenergic stimulation, they present specific adaptation of the energetic homeostasis based on improved energy supply sensitivity. Interestingly this better regulation of the energetic system is not explained by a direct effect of calcium on mitochondria but rather by an optimized metabolic feedback.
New outbreak of legionnaires' disease in the United Kingdom
Authors: C. Joseph
Journal: BMJ (2002)

<h3>Abstract</h3> <h3>INTRODUCTION</h3> The <i>Apolipoprotein E</i> (<i>APOE</i>) ε4 allele is the strongest genetic risk factor for Alzheimer’s disease (AD), while the ε2 allele confers protection. Previous studies report differential DNA methylation of <i>APOE</i> between ε4 and ε2 carriers but associations with epigenome-wide methylation are unknown. <h3>METHODS</h3> The EPIC array was used to identify methylation differences between AD-free <i>APOE</i> ε4 (n=2469) and ε2 (n=1108) carriers using epigenome-wide association analysis and differentially methylated region (DMR) approaches. Results were explored using pathway and meQTL analyses. <h3>RESULTS</h3> Differentially methylated positions were identified in <i>APOE</i>, surrounding genes and genes outside of this locus (<i>DHCR24, LDLR</i> and <i>ABCG1</i>). DMRs were identified in <i>SREBF2, LDLR</i> and <i>SQLE</i>. Pathway and meQTL analyses implicated lipid-related processes; however, blood cholesterol levels could not fully account for the associations. <h3>DISCUSSION</h3> <i>APOE</i> ε4 vs. ε2 carrier status is associated with epigenome-wide methylation differences in cis and trans in genes involved in lipid homeostasis.
Impact of adjuvant endocrine therapy related toxicities on treatment cessation in elderly breast cancer.
Authors: Muhammad Iqbal, Sukesh Manthri, Kathy Robinson, Robert S. Mocharnuk, Meghna R. Desai
Journal: Journal of Clinical Oncology (2017)

e21528 Background: According to American Cancer Society estimates, 252,710 new cases of invasive breast cancer will be diagnosed in women in the U.S. in 2017. Elderly breast cancer patients tend to be undertreated due to age, potential toxicities of adjuvant therapies and intrinsic ageist biases. The purpose of this study was to investigate the incidence of adjuvant endocrine therapy related side effects and their impact on discontinuation of therapy in geriatric breast cancer population. Methods: Data were collected by retrospective medical record review at our institution among breast cancer patients diagnosed after age 65. Adjuvant endocrine therapy included tamoxifen, letrozole, anstrozole and fulvestrant. Grade 3 and 4 toxicities were analyzed by Fisher’s exact test to determine an association with therapy discontinuation. Binary logistic regression was used to assess whether a specific toxic effect could predict for early therapy termination. Treatment termination was defined as inability to complete the proposed duration of endocrine therapy. Results: Out of 269 eligible cases, 221 (82.15%) patients were offered endocrine therapy based on their tumor’s ER and PR receptor status. A total of 216 (97.73%) patients received endocrine therapy while 5 (2.26%) declined treatment. Frequencies of osteopenia (n = 22, 10.2%), osteoporosis (n = 18, 8.3%), arthralgia (n = 35, 16.2%), hot flashes (n = 49, 22.7%), vaginal dryness (n = 3, 1.4%), weight gain (n = 7, 3.2%), fluid retention (n = 4, 1.9%), mood swings (n = 3, 1.4%), deep venous thrombosis (DVT, n = 3, 1.4%), pulmonary embolism (PE, n = 3, 1.4%) and stroke (n = 2, 0.9%) were reported by patients who received endocrine therapy. Among the 44 patients who terminated endocrine therapy early, 38.6% listed arthralgia as the chief cause (OR = 5.37, 95%CI:2.33-12.39, p = 0.0001). We detected no significant correlation between endocrine therapy cessation and other side effects. Conclusions: Arthralgia and hot flashes were the most common side effects observed in elderly breast cancer patients receiving adjunct endocrine therapy. We found that the elderly patients tend to discontinue treatment more often if they develop endocrine therapy related arthralgia.
miR-146a modulates autoreactive Th17 cell differentiation and regulates organ-specific autoimmunity
Authors: Bo Li, Xi Wang, In Young Choi, Yu-Chen Wang, Siyuan Liu, Alexander T. Pham, Heesung Moon, Drake J. Smith, Dinesh S. Rao, Mark P. Boldin, Lili Yang
Journal: Journal of Clinical Investigation (2017)

Autoreactive CD4 T cells that differentiate into pathogenic Th17 cells can trigger autoimmune diseases. Therefore, investigating the regulatory network that modulates Th17 differentiation may yield important therapeutic insights. miR-146a has emerged as a critical modulator of immune reactions, but its role in regulating autoreactive Th17 cells and organ-specific autoimmunity remains largely unknown. Here, we have reported that miR-146a-deficient mice developed more severe experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS). We bred miR-146a-deficient mice with 2D2 T cell receptor-Tg mice to generate 2D2 CD4 T cells that are deficient in miR-146a and specific for myelin oligodendrocyte glycoprotein (MOG), an autoantigen in the EAE model. miR-146a-deficient 2D2 T cells induced more severe EAE and were more prone to differentiate into Th17 cells. Microarray analysis revealed enhancements in IL-6- and IL-21-induced Th17 differentiation pathways in these T cells. Further study showed that miR-146a inhibited the production of autocrine IL-6 and IL-21 in 2D2 T cells, which in turn reduced their Th17 differentiation. Thus, our study identifies miR-146a as an important molecular brake that blocks the autocrine IL-6- and IL-21-induced Th17 differentiation pathways in autoreactive CD4 T cells, highlighting its potential as a therapeutic target for treating autoimmune diseases.