tbuckley/cabot-search huggingface dataset:
Transthyretin-Binding Activity of Complex Mixtures Representing the Composition of Thyroid-Hormone Disrupting Contaminants in House Dust and Human Serum
Authors: Timo Hamers, Andreas Kortenkamp, Martin Scholze, Douwe Molenaar, Peter H. Cenijn, Jana M. Weiss
Journal: Environmental Health Perspectives (2020)

Background: House dust contains many organic contaminants that can compete with the thyroid hormone (TH) thyroxine (T4) for binding to transthyretin (TTR). How these contaminants work together at levels found in humans and how displacement from TTR in vitro relates to in&nbsp;vivo T4-TTR binding is unknown. Objectives: Our aims were to determine the TTR-binding potency for contaminant mixtures as found in house dust, maternal serum, and infant serum; to study whether the TTR-binding potency of the mixtures follows the principle of concentration addition; and to extrapolate the in vitro TTR-binding potency to in&nbsp;vivo inhibition levels of T4-TTR binding in maternal and infant serum. Methods: Twenty-five contaminants were tested for their in vitro capacity to compete for TTR-binding with a fluorescent FITC-T4 probe. Three mixtures were reconstituted proportionally to median concentrations for these chemicals in house dust, maternal serum, or infant serum from Nordic countries. Measured concentration–response curves were compared with concentration–response curves predicted by concentration addition. For each reconstituted serum mixture, its inhibitor–TTR dissociation constant (Ki) was used to estimate inhibition levels of T4-TTR binding in human blood. Results: The TTR-binding potency of the mixtures was well predicted by concentration addition. The ∼20% inhibition in FITC-T4 binding observed for the mixtures reflecting median concentrations in maternal and infant serum was extrapolated to 1.3% inhibition of T4-TTR binding in maternal and 1.5% in infant blood. For nontested mixtures reflecting high-end serum concentrations, these estimates were 6.2% and 4.9%, respectively. Discussion: The relatively low estimated inhibition levels at median exposure levels may explain why no relationship between exposure to TTR-binding compounds and circulating T4 levels in humans has been reported, so far. We hypothesize, however, that 1.3% inhibition of T4-TTR binding may ultimately be decisive for reaching a status of maternal hypothyroidism or hypothyroxinemia associated with impaired neurodevelopment in children. https://doi.org/10.1289/EHP5911
41P Circulating Tumor Cells (CTCs) and Metronomic Oral Vinorelbine (OV) in Advanced Breast Cancer (ABC) Patients (PTS): Exploratory Prospective Analysis
Authors: G. Aurilio, E. Munzone, E. Botteri, S. Pedroli, M.T. Sandri, L. Adamoli, L. Zorzino, A. Sciandivasci, A. Esposito, F. Nolè
Journal: Annals of Oncology (2012)
Abstract 10668: Alirocumab Reduces Total Hospitalizations and Increases Days Alive and Out of Hospital in the ODYSSEY OUTCOMES Trial
Authors: Michael Szarek, Philippe G Steg, Dina DiCenso, Deepak L Bhatt, Vera A Bittner, Andrzej Budaj, Rafael Diaz, Shaun G Goodman, Nina Gotcheva, J Wouter Jukema, Robert Pordy, Matthew T Roe, Timothée Sourdille, Harvey D White, Denis Xavier, Andreas M Zeiher, Gregory G Schwartz
Journal: Circulation (2019)

Introduction: In the ODYSSEY OUTCOMES trial, compared with placebo, alirocumab reduced the first occurrence of the primary composite endpoint as well as total nonfatal cardiovascular events and all...
Exploiting TCR Recognition of Shared Hotspot Oncogene-encoded Neoantigens
Authors: Irene Olivera, Iñaki Etxeberria, Elixabet Bolaños, María Gato-Cañas, Ignacio Melero
Journal: Clinical Cancer Research (2020)

T-cell recognizable p53 hotspot mutations offer opportunities for immunotherapy and immune monitoring. Recognition of p53 mutations by peripheral blood CD8 and CD4 T lymphocytes has been revealed.See related article by Malekzadeh et al., p. 1267.
Clinical Research Subject Selection during Public Health Disasters: Reconceptualizing Fairness in a Global Ethical Context
Authors: Michael O. S. Afolabi, Stephen O. Sodeke, Ikeolu O. Afolabi
Journal: The American Journal of Bioethics (2020)

The principle of fair subject selection (pFSS) is an integral ingredient that characterizes contemporary clinical research vis-a-vis ethical validation. However, it may be fraught with conflicting ...
Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020
Authors: Julien Riou, Christian L. Althaus
Journal: Eurosurveillance (2020)

Since December 2019, China has been experiencing a large outbreak of a novel coronavirus (2019-nCoV) which can cause respiratory disease and severe pneumonia. We estimated the basic reproduction number R 0 of 2019-nCoV to be around 2.2 (90% high density interval: 1.4–3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and pandemic influenza, indicating a risk of global spread.
Acute Liver Failure (ALF) in Pregnancy: How Much Is Pregnancy Related?
Authors: Lisa C. Casey, Robert J. Fontana, Ariel Aday, David B. Nelson, Jody A. Rule, Michelle Gottfried, Minh Tran, William M. Lee
Journal: Hepatology (2020)

Acute liver failure (ALF), characterized by sudden onset of coagulopathy (international normalized ratio [INR] ≥ 1.5) and encephalopathy, may occur during pregnancy either as a pregnancy-associated etiology or an unrelated and coincidental liver injury. The U.S. Acute Liver Failure Study Group, comprised of 33 tertiary care liver centers, has enrolled consecutive patients with ALF or acute liver injury (ALI; INR ≥ 2.0 with no encephalopathy), over two decades.
Prophylaxis and management of graft versus host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation
Authors: Olaf Penack, Monia Marchetti, Tapani Ruutu, Mahmoud Aljurf, Andrea Bacigalupo, Francesca Bonifazi, Fabio Ciceri, Jan Cornelissen, Ram Malladi, Rafael F Duarte, Sebastian Giebel, Hildegard Greinix, Ernst Holler, Anita Lawitschka, Stephan Mielke, Mohamad Mohty, Mutlu Arat, Arnon Nagler, Jakob Passweg, Hélène Schoemans, Gerard Socié, Carlos Solano, Radovan Vrhovac, Robert Zeiser, Nicolaus Kröger, Grzegorz W Basak
Journal: The Lancet Haematology (2020)
Electrical versus pharmacological cardioversion for emergency department patients with acute atrial fibrillation (RAFF2): a partial factorial randomised trial
Authors: Ian G Stiell, Marco L A Sivilotti, Monica Taljaard, David Birnie, Alain Vadeboncoeur, Corinne M Hohl, Andrew D McRae, Brian H Rowe, Robert J Brison, Venkatesh Thiruganasambandamoorthy, Laurent Macle, Bjug Borgundvaag, Judy Morris, Eric Mercier, Catherine M Clement, Jennifer Brinkhurst, Connor Sheehan, Erica Brown, Marie-Joe Nemnom, George A Wells, Jeffrey J Perry
Journal: The Lancet (2020)
Curriculum vitae: Andrew Rowland
Authors: Xiaoye Wang, April Karlinsky, Merryn Constable, Samantha Gregory, Timothy Welsh, Michael Xiaoye
Journal: BMJ (2017)

Social cues, such as eye gaze and pointing fingers, can increase the prioritisation of specific locations for cognitive processing.A previous study using a manual reaching task showed that, although both gaze and pointing cues altered target prioritisation (reaction times [RTs]), only pointing cues affected action execution (trajectory deviations).These differential effects of gaze and pointing cues on action execution could be because the gaze cue was conveyed through a disembodied head; hence, the model lacked the potential for a body part (i.e., hands) to interact with the target.In the present study, the image of a male gaze model, whose gaze direction coincided with two potential target locations, was centrally presented.The model either had his arms and hands extended underneath the potential target locations, indicating the potential to act on the targets (Experiment 1), or had his arms crossed in front of his chest, indicating the absence of potential to act (Experiment 2).Participants reached to a target that followed a nonpredictive gaze cue at one of three stimulus onset asynchronies.RTs and reach trajectories of the movements to cued and uncued targets were analysed.RTs showed a facilitation effect for both experiments, whereas trajectory analysis revealed facilitatory and inhibitory effects, but only in Experiment 1 when the model could potentially act on the targets.The results of this study suggested that when the gaze model had the potential to interact with the cued target location, the model's gaze affected not only target prioritisation but also movement execution.
NOVEL OPTICAL PROTEOMICS MOLECULARLY PROFILES BREAST CANCER PATIENTS LEADING TO INDIVIDUALISED PROGNOSIS AND TAILORED TREATMENT
Authors: M. T. Kelleher, G. Patel, E. Ofo, Frederic Festy, Cheryl Gillett, Ton Coolen, Sarah Pinder, Boris Vojnovic, Tony Ng, Paul Ellis
Journal: Annals of Oncology (2009)
Offline: 2019-nCoV outbreak—early lessons
Authors: Richard Horton
Journal: The Lancet (2020)

It is still too early, and available information is still too incomplete, to be certain about many aspects of the 2019 novel coronavirus (2019-nCoV) outbreak in China. However, important elements of the management of this global health emergency—and it is an emergency of major international concern—are becoming clearer. As the outbreak accelerates, there are early lessons to be learned. The transmissibility of 2019-nCoV—or at least its geographical distribution—seems to be higher and broader than initially expected.
Transcriptomic Traces of Adult Human Liver Progenitor Cells
Authors: Simone N.T. Kurial, Holger Willenbring
Journal: Hepatology (2020)

Kurial, Simone N.T. B.Sc.; Willenbring, Holger M.D., Ph.D.Editor(s): Corey, Kathleen E.; Malhi, Harmeet Author Information
Sensitizing Triple Negative Breast Cancer to Tamoxifen Chemotherapy via a Redox-Responsive Vorinostat-containing Polymeric Prodrug Nanocarrier
Authors: Weina Ma, Jingjing Sun, Jieni Xu, Zhangyi Luo, Dingwei Diao, Ziqian Zhang, Patrick J. Oberly, Margaret Beth Minnigh, Wen Xie, Samuel M Poloyac, Yi Huang, Song Li
Journal: Theranostics (2020)

There is an urgent and unmet need to develop effective therapies for triple negative breast cancers (TNBCs) which are much more aggressive and have poor prognosis due to lack of receptor targets for Her2-targeted and endocrine therapy.In this study we systematically evaluated the effect of Vorinostat (SAHA, a pan-HDAC inhibitor) in reactivating the expression of functional estrogen receptor α (ERα) and synergizing with tamoxifen (TAM, a selective estrogen-receptor modulator) in antitumor activity.In addition, a SAHA prodrug-based dual functional nanocarrier was developed for codelivery of SAHA and TAM for effective combination therapy.Methods: A SAHA-containing polymeric nanocarrier, POEG-co-PVDSAHA was developed via reversible addition-fragmentation transfer (RAFT) polymerization with SAHA incorporated into the polymer through a redox-responsive disulfide linkage.The effect of both free SAHA and POEG-co-PVDSAHA on reactivating the expression of functional ERα was investigated in several human and murine TNBC cell lines via examining the mRNA and protein expression of ERα target genes.The cytotoxicity of free SAHA and TAM combination and TAM-loaded POEG-co-PVDSAHA micelles was examined via MTT assay.The in vivo antitumor activity of TAM-loaded POEG-co-PVDSAHA was investigated in a murine breast cancer model (4T1.2).Results: Both free SAHA and POEG-co-PVDSAHA were effective in inducing the reexpression of functional estrogen receptor α (ERα), which may have helped to sensitize TNBCs to TAM.More importantly, POEG-co-PVDSAHA self-assembled to form small-sized micellar carrier that is effective in formulating and codelivery of TAM.TAM-loaded POEG-co-PVDSAHA micelles exhibited enhanced and synergistic cytotoxicity against TNBC cell lines compared with free SAHA, free TAM and TAM loaded into a pharmacologically inert control carrier (POEG-co-PVMA).In addition, codelivery of TAM via POEG-co-PVDSAHA micelles led to significantly improved antitumor efficacy in 4T1.2 tumor model compared with other groups such as combination of free SAHA and TAM and TAM-loaded POEG-co-PVMA micelles.Conclusion: Our prodrug-based co-delivery system may provide an effective and simple strategy to re-sensitize TNBCs to TAM-based hormone therapy.
Treat the Symptom, Not the Cause? Pitolisant for Sleepiness in Obstructive Sleep Apnea
Authors: Lynn Marie Trotti
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

signaling may also regulate other cellular functions, including phagocytosis (15, 16).In future studies, it will be important to define which IGF-1-dependent cellular functions are modified by rhIGF-1 treatment.Because most preterm infants who develop BPD have been exposed to more than one inciting "injury," it would be useful to evaluate the efficacy of rhIGF-1 in "multihit" preclinical models of BPD (e.g., antenatal endotoxin followed by postnatal hyperoxia).Finally, because IGF-1 is a potent mitogen (17), longer-term preclinical and human studies are needed to examine its efficacy and safety in neonatal therapy.Nevertheless, the promising findings by Seedorf and colleagues lay the groundwork for future work evaluating rhIGF-1/BP3 as a possible therapeutic strategy for BPD.Of note, a phase 2 RCT (ClinicalTrials.govIdentifier: NCT03253263) evaluating the efficacy of rhIGF-1/BP-3 administration in preterm infants to prevent chronic lung disease through 12 months of corrected age (secondary outcome: BPD at 36 wk) is currently underway.Data from this trial should provide muchneeded evidence regarding the usefulness of rhIGF-1/BP3 as a novel therapy to prevent and/or treat prematurity-associated lung disease.
Tailored regimens for combined hormonal contraceptives
Authors: Zachary Nash, Annette Thwaites, Melanie Davies
Journal: BMJ (2020)

### What you need to know

Despite the advent of newer, more effective, longer acting methods of contraception, combined hormonal contraception (CHC) remains the most popular form of contraception in Europe and North America.1 CHC methods contain both oestrogen and progestogen and prevent pregnancy primarily through suppression of the hypothalamic-pituitary-ovarian axis to achieve anovulation. Oral CHC (“the pill”) is by far the most widely used form of CHC, with 151 million users worldwide.1 Alternative routes of administration are the patch or ring.

Traditionally, CHC has been prescribed as 21 days of hormone treatment (21 pills, or three 7 day patches, or one ring for three weeks) followed by seven days of no treatment or placebo—a hormone-free interval. Although designed to achieve a monthly withdrawal bleed, mimicking a physiological cycle, there is no evidence that a monthly bleed—or indeed any bleed—is required for safety. A number of studies report no evidence of endometrial thickening or histological abnormalities with continuous CHC use.2

In its 2019 guideline, the Faculty of Sexual and Reproductive Health (FSRH) supports the use of “tailored regimens,” highlighting that there is no health benefit from the seven day hormone-free interval and that a shorter interval or fewer intervals may increase contraceptive efficacy.3 Women should be advised, however, that using tailored CHC regimens is currently outside the manufacturer’s licence.

Tailored regimens allow extension of …
Follow-up blood cultures are associated with improved outcome of patients with gram-negative bloodstream infections: retrospective observational cohort study
Authors: M. Giannella, R. Pascale, L. Pancaldi, C. Monari, S. Ianniruberto, P. Malosso, L. Bussini, M. Bartoletti, S. Tedeschi, S. Ambretti, R. Lewis, P. Viale
Journal: Clinical Microbiology and Infection (2020)
Menopausal Estrogen-Alone Therapy and Health Outcomes in Women With and Without Bilateral Oophorectomy
Authors: Philip Sarrel
Journal: Annals of Internal Medicine (2020)

Letters4 February 2020Menopausal Estrogen-Alone Therapy and Health Outcomes in Women With and Without Bilateral OophorectomyPhilip Sarrel, MDPhilip Sarrel, MDYale University School of Medicine, Woodbridge, Connecticut (P.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0679 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read Manson and colleagues' article (1) with interest. Estrogen therapy that is started after hysterectomy and before age 60 years has been shown to have major health benefits compared with placebo. Reports from the Women's Health Initiative have consistently shown a reduced incidence of disease, including breast cancer, in women who receive this therapy. In 2011, the Women's Health Initiative also reported a mortality reduction among women aged 50 to 59 years receiving estrogen therapy. Manson and colleagues' article indicates that reduced mortality associated with estrogen therapy is limited to women who had ovaries removed at ...Reference1. Manson JE, Aragaki AK, Bassuk SS, et al; WHI Investigators. Menopausal estrogen-alone therapy and health outcomes in women with and without bilateral oophorectomy. A randomized trial. Ann Intern Med. 2019;171:406-14. [PMID: 31499528]. doi:10.7326/M19-0274 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Yale University School of Medicine, Woodbridge, Connecticut (P.S.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L19-0679. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoMenopausal Estrogen-Alone Therapy and Health Outcomes in Women With and Without Bilateral Oophorectomy JoAnn E. Manson , Aaron K. Aragaki , Shari S. Bassuk , Rowan T. Chlebowski , Garnet L. Anderson , Jacques E. Rossouw , Barbara V. Howard , Cynthia A. Thomson , Marcia L. Stefanick , Andrew M. Kaunitz , Carolyn J. Crandall , Charles B. Eaton , Victor W. Henderson , Simin Liu , Juhua Luo , Thomas Rohan , Aladdin H. Shadyab , Gretchen Wells , Jean Wactawski-Wende , Ross L. Prentice , and Menopausal Estrogen-Alone Therapy and Health Outcomes in Women With and Without Bilateral Oophorectomy JoAnn E. Manson and Shari S. Bassuk Metrics Cited byPerils of prolonged ovarian suppression and hypoestrogenism in the treatment of breast cancer: Is the risk of treatment worse than the risk of recurrence? 4 February 2020Volume 172, Issue 3Page: 227KeywordsDisclosureEstrogensHealth care providersHysterectomyMenopauseMortalityObstetrics and gynecologyOophorectomyOvariesSurgery ePublished: 4 February 2020 Issue Published: 4 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Cooperation therapy between anti-growth by photodynamic-AIEgens and anti-metastasis by small molecule inhibitors in ovarian cancer
Authors: Jun Dai, Min Xu, Quan Wang, Juliang Yang, Jinjin Zhang, Pengfei Cui, Wenwen Wang, Xiaoding Lou, Fan Xia, Shixuan Wang
Journal: Theranostics (2020)

Metastasis is one of the main causes of death and treatment failure in ovarian cancer. Some small molecule inhibitors can effectively inhibit the metastasis of primary tumors. However, they do not kill the primary tumor cells, which may lead to continuous proliferation. Herein, we have prepared a multifunctional nanoparticles named TPD@TB/KBU2046, which consisted of three functional moieties: (1) KBU2046 (small molecule inhibitor) that can inhibit the metastasis of the primary tumors, (2) TB (photodynamic-AIEgens) that may suppress the growth of the primary tumors, and (3) TPD, which contains TMTP1 (a targeting peptide, which specifically binds to highly metastatic tumor cells) that can enhance the TB/KBU2046 dosage in the tumor site. Methods: The TPD@TB/KBU2046 was prepared by nano-precipitation method. We linked the targeting peptide (TMTP1) to the nanoparticles via amidation reaction. TPD@TB/KBU2046 nanoparticles were characterized for encapsulation efficiency, particle size, absorption spectra, emission spectra and ROS production. The combinational efficacy in image-guided anti-metastasis and photodynamic therapy of TPD@TB/KBU2046 was explored both in vitro and in vivo. Results: The TPD@TB/KBU2046 showed an average hydrodynamic size of approximately 50 nm with good stability. In vitro, TPD@TB/KBU2046 not only inhibited the metastasis of the tumors, but also suppressed the growth of the tumors under AIEgens-mediated photodynamic therapy. In vivo, we confirmed that TPD@TB/KBU2046 has the therapeutic effects of anti-tumor growth and anti-metastasis through subcutaneous and orthotopic ovarian tumor models. Conclusion: Our findings provided an effective strategy to compensate for the congenital defects of some small molecule inhibitors and thus enhanced the therapeutic efficacy of ovarian cancer.
Prolonged Wireless pH Monitoring in Patients With Persistent Reflux Symptoms Despite Proton Pump Inhibitor Therapy
Authors: Stephen Hasak, Rena Yadlapati, Osama Altayar, Rami Sweis, Emily Tucker, Kevin Knowles, Mark Fox, John Pandolfino, C. Prakash Gyawali
Journal: Clinical Gastroenterology and Hepatology (2020)
Racial and ethnic differences in risk of second primary cancers among breast cancer survivors.
Authors: Gregory Sampang Calip, Ernest Law, Eric P. Winer, Naomi Ko
Journal: Journal of Clinical Oncology (2015)

e12592 Background: Disparities exist in breast cancer outcomes between specific racial/ethnic groups in the United States. Reasons for these disparities are multifactorial and include genetic differences, later stage at presentation, access to care and socioeconomic factors. While many aspects of disparities in breast cancer are well defined, less has been documented on racial/ethnic differences in subsequent risk of second primary cancers. The purpose of this study is to evaluate the risk of second primary cancers among different racial/ethnic groups of women diagnosed with a first primary invasive breast cancer. Methods: Retrospective cohort of 134,868 Non-Hispanic White, 17,484 Black, 18,034 Hispanic and 19,802 Asian/Pacific Islander women with stages I-III breast cancer in twelve Surveillance, Epidemiology and End Results Program registries between 2001-2010. Relative risks (RR), 95% confidence intervals (CI), and absolute excess risks were calculated using standardized incidence ratios comparing incidence of second primary cancers in women in the cohort to cancer incidence rates in the general population. RRs and excess risks were estimated for specific cancer sites by racial/ethnic groups and stratified by index breast cancer-related factors. Results: All women were at increased risks of second primary breast cancer and acute myeloid leukemia (AML), with a higher risk among more advanced stage index breast cancer. Black and Asian/Pacific Islander women also had higher relative risk and excess risk of AML that remained elevated among early-stage (I) index breast cancer cases. Conclusions: Women with a history of invasive breast cancer have increased risk of second primary cancers, most notable for second primary breast cancer and AML. These risks for secondary cancers differ by race/ethnicity. Further studies on the possible genetic and biobehavioral mechanisms underlying these differences are warranted. Strategies for breast cancer adjuvant treatment and survivorship care may need to be further individualized with consideration given to race/ethnicity.
Deep learning for prediction of colorectal cancer outcome: a discovery and validation study
Authors: Ole-Johan Skrede, Sepp De Raedt, Andreas Kleppe, Tarjei S Hveem, Knut Liestøl, John Maddison, Hanne A Askautrud, Manohar Pradhan, John Arne Nesheim, Fritz Albregtsen, Inger Nina Farstad, Enric Domingo, David N Church, Arild Nesbakken, Neil A Shepherd, Ian Tomlinson, Rachel Kerr, Marco Novelli, David J Kerr, Håvard E Danielsen
Journal: The Lancet (2020)