tbuckley/cabot-search huggingface dataset:
Dual antiplatelet therapy using cilostazol for secondary prevention in patients with high-risk ischaemic stroke in Japan: a multicentre, open-label, randomised controlled trial
Authors: Kazunori Toyoda, Shinichiro Uchiyama, Takenori Yamaguchi, J Donald Easton, Kazumi Kimura, Haruhiko Hoshino, Nobuyuki Sakai, Yasushi Okada, Kortaro Tanaka, Hideki Origasa, Hiroaki Naritomi, Kiyohiro Houkin, Keiji Yamaguchi, Masanori Isobe, Kazuo Minematsu, Shinya Goto, Tatsuya Isomura, Masayasu Matsumoto, Yasuo Terayama, Hidekazu Tomimoto, Teiji Tominaga, Satoshi Yasuda, Naoko Kumagai
Journal: The Lancet Neurology (2019)
Cadmium-induced reactive oxygen species activates MAPK and mTOR pathways and induces apoptosis of PC12 and SH-SY5Y cells
Authors: Shile Huang, Long Chen
Journal: Cancer Research (2008)

3556  Cadmium (Cd), a highly toxic environmental pollutant, induces neuronal apoptosis. However, the underlying mechanism remains to be defined. Here we show that Cd induced apoptosis of PC12 and SH-SY5Y cells, and concurrently induced generation of reactive oxygen species (ROS) in the cells. Exposure to hydrogen peroxide mimicked the effect of Cd, inducing the cell death in a time- and concentration-dependent manner. Pretreatment of the cells with N-acetyl-L-cysteine (NAC), an antioxidant and ROS scavenger, suppressed Cd-induced ROS elevation, and prevented Cd-induced cell death, suggesting that Cd induced apoptosis is associated with its induction of ROS production. Recently we have demonstrated that activation of MAPK and mTOR network is related to Cd-induced apoptosis of the neuronal cells. Here, we further show that activation of Erk1/2, JNK and p38 MAPK, and mTOR-mediated S6K1 and 4E-BP1 pathways are triggered by Cd-induced ROS. This is supported by the findings that NAC completely blocked the activation. In addition, we also noticed that Z-VAD-FMK, a pan caspase inhibitor, only partially protected against Cd-induced cell death, implying a caspase-dependent and -independent apoptotic mechanisms involved. Taken together, the results reveal that Cd may induce ROS generation and activate MAPK and mTOR pathways, leading to neuronal apoptosis. Our data suggest that antioxidants may be exploited for prevention of Cd-induced Parkinson’s disease, Alzheimer’s disease and other neurodegenerative disorders.
Aldosterone induces trained immunity: the role of fatty acid synthesis
Authors: Charlotte D C C van der Heijden, Samuel T Keating, Laszlo Groh, Leo A B Joosten, Mihai G Netea, Niels P Riksen
Journal: Cardiovascular Research (2019)

Supranormal levels of aldosterone are associated with an increased cardiovascular risk in humans, and with accelerated atherosclerosis in animal models. Atherosclerosis is a low-grade inflammatory disorder, with monocyte-derived macrophages as major drivers of plaque formation. Monocytes can adopt a long-term pro-inflammatory phenotype after brief stimulation with microbial pathogens or endogenous atherogenic lipoproteins via a process termed trained immunity. In this study, we aimed to investigate whether aldosterone can induce trained immunity in primary human monocytes in vitro and explored the underlying mechanism.We exposed human monocytes to aldosterone for 24 h, after which they were rested to differentiate into monocyte-derived macrophages for 5 days, and re-stimulated with toll-like receptor 2 and 4 ligands on day 6. We demonstrated that aldosterone augments pro-inflammatory cytokine production and reactive oxygen species production in monocyte-derived macrophages after re-stimulation, via the mineralocorticoid receptor. Fatty acid synthesis was identified as a crucial pathway necessary for this induction of trained immunity and pharmacological inhibition of this pathway blunted aldosterone-induced trained immunity. At the level of gene regulation, aldosterone promoted enrichment of the transcriptionally permissive H3K4me3 modification at promoters of genes central to the fatty acid synthesis pathway.Aldosterone induces trained immunity in vitro, which is dependent on epigenetically mediated up-regulation of fatty acid synthesis. These data provide mechanistic insight into the contribution of aldosterone to inflammation, atherosclerosis, and cardiovascular disease.
Intraoperative radiotherapy with electronic brachytherapy system in breast cancer patients: Systematic review
Authors: M.B. Vasileva, D. Kostova-Lefterova, S.I. Maslyankov, T.V. Paycheva, A.I. Vlahova, Z.I. Zahariev, V.M. Pavlov, G.T. Todorov, K.G. Angelov, A.A. Konsoulova
Journal: Annals of Oncology (2019)

Background: The long-term effectiveness and cosmetic outcomes after intraoperative radiotherapy (IORT) delivered with Xoft® Axxent® Electronic Brachytherapy (eBx®) System in early breast cancer (EBC) is still under evaluation. This system is available in 11 countries around Europe. We aimed to investigate the experience of the European countries with this system and compare the outcomes with the first results in Bulgaria. Methods: We search the PubMed, Scopus and ScienceDirect for clinical trials published before 2019, investigating the effectiveness of an IORT delivered with Axxent® eBx® system as a single radiation dose (20 Gy) in patients with EBC. Our search strategy included: "breast cancer, IORT, Axxent", "breast cancer, IORT, electronic" and "Axxent, breast". The identified final reports were compared to a prospective case series of 12 patients fulfilling the GEC- ESTRO low risk group criteria and treated at Department of surgery, Alexandrovska University Hospital, Sofia, Bulgaria. Results: We searched through 791 results and found 13 eligible studies (Ivanov (2011); Costa (2015); Dickler (2015); Hanna (2015); Zammit (2016); Chowdhry (2017); Hung-Wen Lai (2017); G. Proulx (2017); Olsen (2018); Osorio (2018); Lozares (2018); Silverstein (2018) and Syed (2018)), with a total of 3319 patients. Only Dickler reports results from 5-years follow up. Five of the studies were conducted in Europe. The first published European results come 4 years after the first results from US. Comparison of the outcomes of European studies with ours is shown on Table.Table130P European studies evaluating the effectiveness of Axxent® eBx® system, single dose, 20GyStudyCountryPatients (N)Median follow up (months)Cosmetic outcomesRecurrence, %CostaPT3018excellent3.3ZammitUK25>12excellent0OsorioES24216goodxLozaresES150xx0SyedUSA / PT117419.5x0.85VasilevaBG1215excellent0 Open table in a new tab Conclusions: The European studies using the Axxent® eBx®system for IORT show excellent cosmetic results, low recurrence rate and convenience for both patients and medical team in terms of duration of treatment. Still, trials with larger number patients and longer follow up time are needed for conclusions on recurrence rates. Legal entity responsible for the study: Mariela Vasileva-Slaveva. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Corrigendum to “Multifunctional calcium phosphate nano-contrast agent for combined nuclear, magnetic and near-infrared in vivo imaging” [Biomater. 34 (2013) 7143–7157]
Authors: Anusha Ashokan, Genekehal S. Gowd, Vijay H. Somasundaram, Arun Bhupathi, Reshmi Peethambaran, A.K.K. Unni, Shanmugasundaram Palaniswamy, Shantikumar V. Nair, Manzoor Koyakutty
Journal: Biomaterials (2019)
Abstract 17540: Get With the Guidelines Heart Failure Risk Score Predicts Mortality in Unselected Cardiac Intensive Care Unit Patients
Authors: Jacob C Jentzer, Courtney Bennett, Brandon Wiley, R. Scott Wright, Gregory W Barsness
Journal: Circulation (2017)

Introduction: The Get With The Guidelines-Heart Failure (GWTG-HF) risk score predicts inpatient mortality in hospitalized patients with acute heart failure. The predictive utility of the GWTG-HF ri...
Complete Metabolic Response Assessed by FDG PET/CT to FOLFIRI-Aflibercept in Second-Line Treatment of Metastatic Colorectal Cancer
Authors: Karim Amrane, Luc Ollivier, Pierre-Yves Salaun, Jean-Philippe Metges, Ronan Abgral
Journal: Clinical Nuclear Medicine (2019)

Abstract FOLFIRI-aflibercept chemotherapy is indicated in second-line treatment of metastatic colorectal cancer (mCRC) after progression under FOLFOX (±bevacizumab). Nevertheless, its proven therapeutic efficacy in clinical trials was based on partial responses. And to date, only 2 cases of complete response assessed by CT were reported in literature. We report a complete metabolic response assessed by FDG PET/CT in a 50-year-old woman with mCRC treated by FOLFIRI-aflibercept. This also confirms that FDG PET/CT is emerging as a useful approach for therapeutic assessment of targeted drugs in mCRC.
Viral, bacterial, and fungal infections of the oral mucosa: Types, incidence, predisposing factors, diagnostic algorithms, and management
Authors: H. M. H. N. Bandara, Lakshman P. Samaranayake
Journal: Periodontology 2000 (2019)

Abstract For millions of years, microbiota residing within us, including those in the oral cavity, coexisted in a harmonious symbiotic fashion that provided a quintessential foundation for human health. It is now clear that disruption of such a healthy relationship leading to microbial dysbiosis causes a wide array of infections, ranging from localized, mild, superficial infections to deep, disseminated life‐threatening diseases. With recent advances in research, diagnostics, and improved surveillance we are witnessing an array of emerging and re‐emerging oral infections and orofacial manifestations of systemic infections. Orofacial infections may cause significant discomfort to the patients and unnecessary economic burden. Thus, the early recognition of such infections is paramount for holistic patient management, and oral clinicians have a critical role in recognizing, diagnosing, managing, and preventing either new or old orofacial infections. This paper aims to provide an update on current understanding of well‐established and emerging viral, bacterial, and fungal infections manifesting in the human oral cavity.
Trifluridine/tipiracil (FTD/TPI) in patients (pts) aged ≥65 years with metastatic gastric/gastroesophageal junction cancer (mGC/mGEJC): Subgroup analysis from TAGS.
Authors: Kohei Shitara, Toshihiko Doi, Hisashi Hosaka, Peter C. Thuss-Patience, Armando Santoro, Paula Jiménez-Fonseca, Federico Longo, Ozgur Ozyilkan, Irfan Cicin, David Park, Mohamedtaki Abdulaziz Tejani, Aziz Zaanan, Domenico Bilancia, Carles Pericay, Mustafa Ozguroglu, MARIA ALSINA, Lukas Makris, Sandra McGuigan, David H. Ilson
Journal: Journal of Clinical Oncology (2019)

4037 Background: 60% of newly diagnosed GC pts are &gt; 65 y of age, a proportion that is increasing. The global phase 3 study TAGS (NCT02500043) demonstrated the efficacy and safety of FTD/TPI in previously treated pts with mGC/mGEJC. Here we report results in the pt subgroup aged ≥65 in TAGS. Methods: Pts with mGC/mGEJC treated with ≥2 prior chemotherapy regimens were randomized (2:1) to receive FTD/TPI (35 mg/m 2 BID on days 1–5 and 8–12 of each 28-day cycle) or placebo, plus best supportive care. A preplanned efficacy/safety analysis was performed in pts aged ≥65 y. Results: Of 507 randomized pts, 228 (45%) were aged ≥65 y (range 65–89). The pt subset aged ≥65 y was similar to the overall population, except for a higher incidence of moderate renal impairment in the elderly subgroup (31% vs 17%). For pts aged ≥65 y, baseline characteristics were generally balanced across the treatment groups, although more pts treated with FTD/TPI than with placebo had ECOG PS 1 (69% vs 59%). FTD/TPI had an efficacy benefit in pts aged ≥65 y, and the FTD/TPI safety profile was similar in this subgroup vs the overall population (table). Treatment-related deaths (one in each treatment group) did not occur in pts aged ≥65 y. No drug-related deaths associated with cardiotoxicity were reported in pts aged ≥65 y. Although dose modifications were used more often in this subgroup, there was no increase in discontinuations vs the overall population. Conclusions: FTD/TPI was safe and effective in pts aged ≥65 y, who had a higher incidence of moderate renal impairment vs the overall population. Clinical trial information: NCT02500043. [Table: see text]
Comment on Feig et al. Pumps or Multiple Daily Injections in Pregnancy Involving Type 1 Diabetes: A Prespecified Analysis of the CONCEPTT Randomized Trial. Diabetes Care 2018;41:2471–2479
Authors: Julia M. Sacha, Wendy S. Lane
Journal: Diabetes Care (2019)

The Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT), reported on by Feig et al. (1), yielded unexpected results, showing that users of multiple daily injections (MDI) experienced decreases in HbA1C, had small but insignificant increases in time spent in target range at 24 weeks’ gestation, and birthed fewer infants with neonatal hypoglycemia and neonatal intensive care unit admissions when compared with pump users. Insulin pump therapy is generally accepted as the optimal way to manage type 1 diabetes (T1D), as it offers greater glycemic control and decreased hypoglycemia when compared with MDI (2). Similar benefits have generally been assumed to hold true for pregnant patients with …
Mental health in elite athletes: International Olympic Committee consensus statement (2019)
Authors: Claudia L Reardon, Brian Hainline, Cindy Miller Aron, David Baron, Antonia L Baum, Abhinav Bindra, Richard Budgett, Niccolo Campriani, João Mauricio Castaldelli-Maia, Alan Currie, Jeffrey Lee Derevensky, Ira D Glick, Paul Gorczynski, Vincent Gouttebarge, Michael A Grandner, Doug Hyun Han, David McDuff, Margo Mountjoy, Aslihan Polat, Rosemary Purcell, Margot Putukian, Simon Rice, Allen Sills, Todd Stull, Leslie Swartz, Li Jing Zhu, Lars Engebretsen
Journal: British Journal of Sports Medicine (2019)

Mental health symptoms and disorders are common among elite athletes, may have sport related manifestations within this population and impair performance. Mental health cannot be separated from physical health, as evidenced by mental health symptoms and disorders increasing the risk of physical injury and delaying subsequent recovery. There are no evidence or consensus based guidelines for diagnosis and management of mental health symptoms and disorders in elite athletes. Diagnosis must differentiate character traits particular to elite athletes from psychosocial maladaptations.Management strategies should address all contributors to mental health symptoms and consider biopsychosocial factors relevant to athletes to maximise benefit and minimise harm. Management must involve both treatment of affected individual athletes and optimising environments in which all elite athletes train and compete. To advance a more standardised, evidence based approach to mental health symptoms and disorders in elite athletes, an International Olympic Committee Consensus Work Group critically evaluated the current state of science and provided recommendations.
Bone Marrow T Cells Are Driven into Exhaustion By Acute Leukemia in Pediatric Patients Based on Protein and Transcriptome Analysis
Authors: Semjon Willier, Paula Rothaemel, Jonas Wilhelm, Dana Stenger, Theresa Kaeuferle, Irene Schmid, Michael H. Albert, Vera Binder, Meino Rohlfs, Sebastian Hollizeck, Christoph Klein, Franziska Blaeschke, Tobias Feuchtinger
Journal: Blood (2018)
A systemic review of information requirements of young women with breast cancer undergoing mastectomy or breast conserving surgery
Authors: T. Mehmood
Journal: Annals of Oncology (2019)

Background: Young women with breast cancer have poorer prognosis, greater lifetime risk of local recurrence, contralateral recurrence, and distant disease, regardless of surgery received. Here we systematically review published evidence relating to the information requirements and preferences of young women diagnosed with early-stage breast cancer offered a choice between mastectomy and breast conservation surgery (BCS). Findings will inform the development of a surgical decision aid for young women. Methods: Eight databases were searched to identify research examining information requirements of young women facing breast oncological surgery treatment decisions. Twelve studies met the inclusion criteria. Data were extracted and summarized in a narrative synthesis. Results: Findings indicate that young women prefer greater and more detailed information regarding treatment side effects, sexuality, and body image. Younger age of diagnosis leads to an increased risk perception of developing a body image and career. Information is required in a continuum throughout the treatment experience and not only at diagnosis when treatment decisions are made. Young women show differing levels of participation preferences. Conclusions: Young women find decision-making challenging when the characteristics of diagnosis provide a surgical choice between mastectomy and breast conservation surgery. Efforts should be made to provide information regarding sexuality, body image, reconstruction, fertility and likelihood of familial predisposition. Further research is needed to identify the specific level and information requirements of this young-onset group. The low number of studies indicates a need to design studies targeting specifically this age group of breast cancer patients. Legal entity responsible for the study: NWGH. Funding: Has not received any funding. Disclosure: The author has declared no conflicts of interest.
Fast, Efficient, and Targeted Liposome Delivery Mediated by DNA Hybridization
Authors: Hongyan Li, Qing Liu, Bart J. Crielaard, Jan W. de Vries, Mark Loznik, Zhuojun Meng, Xintong Yang, Robert Göstl, Andreas Herrmann
Journal: Advanced Healthcare Materials (2019)

Abstract Safety and efficacy, two significant parameters in drug administration, can be improved by site‐specific delivery approaches. Here a fast, efficient, and targeted liposome delivery system steered by a DNA hybridization recognition mechanism is presented. For this purpose, lipid‐terminated DNA is inserted in both liposome and cell membranes by simple mixing of the components. Cellular accumulation of cargo encapsulated in the liposomal core is substantially enhanced when the DNA sequence on the cell is complementary to that on the liposome. Additionally, in mixed cell populations, liposomes discriminate targets by their complementary DNA sequences. Exposure of cells to low temperature and endocytosis inhibitors suggests a caveolae‐dependent endocytosis uptake pathway. Mechanistically, hybridization between DNA strands spatially traps liposomes and cell membranes in close proximity, consequently increases the local liposome concentration, and thereby enhances cellular uptake of liposomes and their payload. This programmable delivery system might contribute to new applications in molecular biology and drug delivery.
Augmentation of HIV-specific T cell function by immediate treatment of hyperacute HIV-1 infection
Authors: Zaza M. Ndhlovu, Samuel W. Kazer, Thandeka Nkosi, Funsho Ogunshola, Daniel M. Muema, Gursev Anmole, Shayda A. Swann, Amber Moodley, Krista Dong, Tarylee Reddy, Mark A. Brockman, Alex K. Shalek, Thumbi Ndung’u, Bruce D. Walker
Journal: Science Translational Medicine (2019)

Sustained viremia after acute HIV infection is associated with profound CD4+ T cell loss and exhaustion of HIV-specific CD8+ T cell responses. To determine the impact of combination antiretroviral therapy (cART) on these processes, we examined the evolution of immune responses in acutely infected individuals initiating treatment before peak viremia. Immediate treatment of Fiebig stages I and II infection led to a rapid decline in viral load and diminished magnitude of HIV-specific (tetramer+) CD8+ T cell responses compared to untreated donors. There was a strong positive correlation between cumulative viral antigen exposure before full cART-induced suppression and immune responses measured by MHC class I tetramers, IFN-γ ELISPOT, and CD8+ T cell activation. HIV-specific CD8+ T responses of early treated individuals were characterized by increased CD127 and BCL-2 expression, greater in vitro IFN-γ secretion, and enhanced differentiation into effector memory (Tem) cells. Transcriptional analysis of tetramer+ CD8+ T cells from treated persons revealed reduced expression of genes associated with activation and apoptosis, with concurrent up-regulation of prosurvival genes including BCL-2, AXL, and SRC Early treatment also resulted in robust HIV-specific CD4+ T cell responses compared to untreated HIV-infected individuals. Our data show that limiting acute viremia results in enhanced functionality of HIV-specific CD4+ and CD8+ T cells, preserving key antiviral properties of these cells.
The Development and Validation of an Electronic Health Record (EHR)-Based Algorithm for Identifying Treatment Failure in Newly Diagnosed Hodgkin Lymphoma (HL) Treated in a US Community Oncology Setting
Authors: Chun R Chao, Lanfang Xu, Nancy Cannizzaro, Angie Mae Rodday, Joseph Feliciano, Anita J Kumar, Andrew M. Evens, Susan K Parsons
Journal: Blood (2018)
Predictive Value of 16α-[18F]-Fluoro-17β-Estradiol PET as a Biomarker of Progestin Therapy Resistance in Patients With Atypical Endometrial Hyperplasia and Low-Grade Endometrial Cancer
Authors: Shizuka Yamada, Hideaki Tsuyoshi, Tetsuya Tsujikawa, Hidehiko Okazawa, Yoshio Yoshida
Journal: Clinical Nuclear Medicine (2019)

Abstract For early-stage endometrial cancer patients who wish to preserve fertility, progestin treatment is effective. However, repeated endometrial curettage to evaluate treatment response may cause infertility. The clinical courses of 3 patients who were treated with fertility-sparing progestin treatment and underwent serial 18 F-FES PET before and after treatment are presented. The SUVmean decreased greatly in patients with pathologically complete response (44.2%, 46.2%), whereas there was only a small change (22.5%) in the patient with pathologically stable disease who finally underwent hysterectomy. 18 F-FES PET can be a noninvasive method to evaluate response to fertility-sparing progestin treatment.
APP (AMBERG-PERFORATION-PROJECT) – DEVELOPMENT AND EVALUATION OF AN INTERDISCIPLINARY, SYSTEMATIC APPROACH FOR ENDOSCOPIC MANAGEMENT OF IATROGENIC PERFORATION IN A GERMAN SECONDARY REFERRAL CENTER
Authors: T Decassian, M Dauer, V Groß
Journal: Endoscopy (2019)

In recent years there has been a shift of paradigm in the management of iatrogenic gastrointestinal perforations from surgical towards primary endoscopic management. In order to establish and evaluate this concept in our own hospital, we developed the Amberg-perforation-Project.