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  1. Article ; Online: Including non-dietary sources into an exposure assessment of the European Food Safety Authority: The challenge of multi-sector chemicals such as Bisphenol A.

    von Goetz, N / Pirow, R / Hart, A / Bradley, E / Poças, F / Arcella, D / Lillegard, I T L / Simoneau, C / van Engelen, J / Husoy, T / Theobald, A / Leclercq, C

    Regulatory toxicology and pharmacology : RTP

    2017  Volume 85, Page(s) 70–78

    Abstract: In the most recent risk assessment for Bisphenol A for the first time a multi-route aggregate exposure assessment was conducted by the European Food Safety Authority. This assessment includes exposure via dietary sources, and also contributions of the ... ...

    Abstract In the most recent risk assessment for Bisphenol A for the first time a multi-route aggregate exposure assessment was conducted by the European Food Safety Authority. This assessment includes exposure via dietary sources, and also contributions of the most important non-dietary sources. Both average and high aggregate exposure were calculated by source-to-dose modeling (forward calculation) for different age groups and compared with estimates based on urinary biomonitoring data (backward calculation). The aggregate exposure estimates obtained by forward and backward modeling are in the same order of magnitude, with forward modeling yielding higher estimates associated with larger uncertainty. Yet, only forward modeling can indicate the relative contribution of different sources. Dietary exposure, especially via canned food, appears to be the most important exposure source and, based on the central aggregate exposure estimates, contributes around 90% to internal exposure to total (conjugated plus unconjugated) BPA. Dermal exposure via thermal paper and to a lesser extent via cosmetic products may contribute around 10% for some age groups. The uncertainty around these estimates is considerable, but since after dermal absorption a first-pass metabolism of BPA by conjugation is lacking, dermal sources may be of equal or even higher toxicological relevance than dietary sources.
    MeSH term(s) Adolescent ; Adult ; Aged ; Benzhydryl Compounds ; Child ; Child, Preschool ; Diet ; Environmental Exposure/analysis ; Environmental Pollutants ; Europe ; Female ; Food Contamination ; Government Agencies ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Models, Theoretical ; Paper ; Phenols ; Skin Absorption ; Young Adult
    Chemical Substances Benzhydryl Compounds ; Environmental Pollutants ; Phenols ; bisphenol A (MLT3645I99)
    Language English
    Publishing date 2017-04
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 604672-1
    ISSN 1096-0295 ; 0273-2300
    ISSN (online) 1096-0295
    ISSN 0273-2300
    DOI 10.1016/j.yrtph.2017.02.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Including non-dietary sources into an exposure assessment of the European Food Safety Authority

    von Goetz, N. / Pirow, Ralph / Hart, A. / Bradley, E. / Poças, F. / Arcella, D. / Lillegard, I. T. L. / Simoneau, C. / van Engelen, J. / Husoy, T. / Theobald, A. / Leclercq, C.

    The challenge of multi-sector chemicals such as Bisphenol A

    2017  

    Keywords ddc:610
    Language English
    Publishing country de
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Including non-dietary sources into an exposure assessment of the European Food Safety Authority

    von Goetz, N. / Pirow, Ralph / Hart, A. / Bradley, E. / Poças, F. / Arcella, D. / Lillegard, I. T. L. / Simoneau, C. / van Engelen, J. / Husoy, T. / Theobald, A. / Leclercq, C.

    The challenge of multi-sector chemicals such as Bisphenol A

    2017  

    Keywords Text ; ddc:610
    Language English
    Publishing country de
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Toward a Contemporary Definition of Health.

    Bradley, Kent L / Goetz, Thomas / Viswanathan, Sheila

    Military medicine

    2018  Volume 183, Issue suppl_3, Page(s) 204–207

    Abstract: Aristotle saw that the striving of humanity was toward being well - a physical, mental and spiritual state where life flourished. A contemporary definition of health recognizes that disease and disability can and often do co-exist with wellness. In this ... ...

    Abstract Aristotle saw that the striving of humanity was toward being well - a physical, mental and spiritual state where life flourished. A contemporary definition of health recognizes that disease and disability can and often do co-exist with wellness. In this new conception, health is transformed from a state that requires the absence of disease to a state where the central theme is the fullness of life. Health becomes not a static state of being, but a dynamic quality of living where body, mind, and spirit are fully employed to make the most of each day.
    MeSH term(s) Concept Formation ; Health/trends ; Humans ; Spirituality
    Language English
    Publishing date 2018-11-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 391061-1
    ISSN 1930-613X ; 0026-4075
    ISSN (online) 1930-613X
    ISSN 0026-4075
    DOI 10.1093/milmed/usy213
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Alternating 17β-Estradiol and Aromatase Inhibitor Therapies Is Efficacious in Postmenopausal Women with Advanced Endocrine-Resistant ER+ Breast Cancer.

    Schwartz, Gary N / Kaufman, Peter A / Giridhar, Karthik V / Marotti, Jonathan D / Chamberlin, Mary D / Arrick, Bradley A / Makari-Judson, Grace / Goetz, Matthew P / Soucy, Shannon M / Kolling, Fred / Demidenko, Eugene / Miller, Todd W

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2023  Volume 29, Issue 15, Page(s) 2767–2773

    Abstract: Purpose: Strategies to implement estrogen therapy for advanced estrogen receptor-positive (ER+) breast cancer are underdeveloped. Preclinical data suggest that cycling treatment with 17β-estradiol followed by estrogen deprivation can control tumor ... ...

    Abstract Purpose: Strategies to implement estrogen therapy for advanced estrogen receptor-positive (ER+) breast cancer are underdeveloped. Preclinical data suggest that cycling treatment with 17β-estradiol followed by estrogen deprivation can control tumor growth long-term.
    Patients and methods: Postmenopausal women with advanced ER+/HER2- breast cancer with recurrence or progression on ≥ 1 antiestrogen or aromatase inhibitor (AI)-based therapy were eligible. Patients received 17β-estradiol (2 mg orally, three times a day) for 8 weeks followed by AI (physician's choice) for 16 weeks, alternating treatments on an 8-week/16-week schedule until disease progression. Patients then optionally received continuous single-agent treatment until a second instance of disease progression. Endpoints included 24-week clinical benefit and objective response per RECIST, and tumor genetic alterations.
    Results: Of 19 evaluable patients, clinical benefit rate was 42.1% [95% confidence interval (CI), 23.1%-63.9%] and objective response rate (ORR) was 15.8% (95% CI, 5.7%-37.9%). One patient experienced a grade 3 adverse event related to 17β-estradiol. Among patients who received continuous single-agent treatment until a second instance of disease progression, clinical benefit was observed in 5 of 12 (41.7%) cases. Tumor ER (ESR1) mutations were found by whole-exome profiling in 4 of 7 (57.1%) versus 2 of 9 (22.2%) patients who did versus did not experience clinical benefit from alternating 17β-estradiol/AI therapy. The only two patients to experience objective responses to initial 17β-estradiol had tumor ESR1 mutations.
    Conclusions: Alternating 17β-estradiol/AI therapy may be a promising treatment for endocrine-refractory ER+ breast cancer, including following progression on CDK4/6 inhibitors or everolimus. Further study is warranted to determine whether the antitumor activity of 17β-estradiol differs according to ESR1 mutation status.
    MeSH term(s) Humans ; Female ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Aromatase Inhibitors/adverse effects ; Postmenopause ; Antineoplastic Agents, Hormonal/therapeutic use ; Antineoplastic Agents, Hormonal/pharmacology ; Estradiol ; Estrogens ; Disease Progression
    Chemical Substances Aromatase Inhibitors ; Antineoplastic Agents, Hormonal ; Estradiol (4TI98Z838E) ; Estrogens
    Language English
    Publishing date 2023-06-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-23-0112
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: An electron paramagnetic resonance study of the affinity of nitrite for methemoglobin.

    Goetz, Bradley I / Shields, Howard W / Basu, Swati / Wang, Pamela / King, S Bruce / Hogg, Neil / Gladwin, Mark T / Kim-Shapiro, Daniel B

    Nitric oxide : biology and chemistry

    2009  Volume 22, Issue 2, Page(s) 149–154

    Abstract: Recent data suggests that reactions of nitrite with ferric hemoglobin are potentially important in heme-protein dependent NO signaling. Our group and others are evaluating the role of reductive nitrosylation reactions in the generation of N(2)O(3) as a ... ...

    Abstract Recent data suggests that reactions of nitrite with ferric hemoglobin are potentially important in heme-protein dependent NO signaling. Our group and others are evaluating the role of reductive nitrosylation reactions in the generation of N(2)O(3) as a signaling molecule. The latter reaction is hypothesized to involve reactions on NO, nitrite and methemoglobin to form N(2)O(3) in an anhydrase reaction. Of potential importance to these reactions is the affinity of methemoglobin for nitrite and the reactivity of nitrite-bound methemoglobin with nitric oxide. In this paper, we review work related to the electronic structure of nitrite-bound methemoglobin and its dissociation constant. We present new data using electron paramagnetic resonance spectroscopy which confirm that methemoglobin has a much higher affinity for nitrite, under certain conditions, than reported in classical observations. Interestingly the affinity is greatest at lower pH and low nitrite:methemoglobin ratios. These data suggest additional interesting chemistry in the reaction of nitrite with ferric and ferrous heme species. Moreover, this reaction could serve as a paradigm for ferric heme reactions with nitrite.
    MeSH term(s) Electron Spin Resonance Spectroscopy ; Methemoglobin/chemistry ; Methemoglobin/metabolism ; Nitrites/chemistry ; Nitrites/metabolism
    Chemical Substances Nitrites ; Methemoglobin (9008-37-1)
    Language English
    Publishing date 2009-11-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1362794-6
    ISSN 1089-8611 ; 1089-8603
    ISSN (online) 1089-8611
    ISSN 1089-8603
    DOI 10.1016/j.niox.2009.10.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: PTEN activation contributes to neuronal and synaptic engulfment by microglia in tauopathy.

    Benetatos, Joseph / Bennett, Rachel E / Evans, Harrison T / Ellis, Sevannah A / Hyman, Bradley T / Bodea, Liviu-Gabriel / Götz, Jürgen

    Acta neuropathologica

    2020  Volume 140, Issue 1, Page(s) 7–24

    Abstract: Phosphatase and tensin homolog (PTEN) regulates synaptic density in development; however, whether PTEN also regulates synapse loss in a neurodegenerative disorder such as frontotemporal lobar degeneration with Tau deposition (FTLD-Tau) has not been ... ...

    Abstract Phosphatase and tensin homolog (PTEN) regulates synaptic density in development; however, whether PTEN also regulates synapse loss in a neurodegenerative disorder such as frontotemporal lobar degeneration with Tau deposition (FTLD-Tau) has not been explored. Here, we found that pathological Tau promotes early activation of PTEN, which precedes apoptotic caspase-3 cleavage in the rTg4510 mouse model of FTLD-Tau. We further demonstrate increased synaptic and neuronal exposure of the apoptotic signal phosphatidylserine that tags neuronal structures for microglial uptake, thereby linking PTEN activation to synaptic and neuronal structure elimination. By applying pharmacological inhibition of PTEN's protein phosphatase activity, we observed that microglial uptake can be decreased in Tau transgenic mice. Finally, we reveal a dichotomous relationship between PTEN activation and age in FTLD-Tau patients and healthy controls. Together, our findings suggest that in tauopathy, PTEN has a role in the synaptotoxicity of pathological Tau and promotes microglial removal of affected neuronal structures.
    MeSH term(s) Aged ; Aged, 80 and over ; Animals ; Female ; Humans ; Male ; Mice ; Microglia/metabolism ; Middle Aged ; Neurons/pathology ; PTEN Phosphohydrolase/metabolism ; Synapses/pathology ; Tauopathies/metabolism ; Tauopathies/pathology
    Chemical Substances PTEN Phosphohydrolase (EC 3.1.3.67)
    Language English
    Publishing date 2020-03-31
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1079-0
    ISSN 1432-0533 ; 0001-6322
    ISSN (online) 1432-0533
    ISSN 0001-6322
    DOI 10.1007/s00401-020-02151-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Book ; Online: On Leakage in Machine Learning Pipelines

    Sasse, Leonard / Nicolaisen-Sobesky, Eliana / Dukart, Juergen / Eickhoff, Simon B. / Götz, Michael / Hamdan, Sami / Komeyer, Vera / Kulkarni, Abhijit / Lahnakoski, Juha / Love, Bradley C. / Raimondo, Federico / Patil, Kaustubh R.

    2023  

    Abstract: Machine learning (ML) provides powerful tools for predictive modeling. ML's popularity stems from the promise of sample-level prediction with applications across a variety of fields from physics and marketing to healthcare. However, if not properly ... ...

    Abstract Machine learning (ML) provides powerful tools for predictive modeling. ML's popularity stems from the promise of sample-level prediction with applications across a variety of fields from physics and marketing to healthcare. However, if not properly implemented and evaluated, ML pipelines may contain leakage typically resulting in overoptimistic performance estimates and failure to generalize to new data. This can have severe negative financial and societal implications. Our aim is to expand understanding associated with causes leading to leakage when designing, implementing, and evaluating ML pipelines. Illustrated by concrete examples, we provide a comprehensive overview and discussion of various types of leakage that may arise in ML pipelines.

    Comment: first draft
    Keywords Computer Science - Machine Learning ; Computer Science - Artificial Intelligence
    Publishing date 2023-11-07
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Large-scale migration into Britain during the Middle to Late Bronze Age.

    Patterson, Nick / Isakov, Michael / Booth, Thomas / Büster, Lindsey / Fischer, Claire-Elise / Olalde, Iñigo / Ringbauer, Harald / Akbari, Ali / Cheronet, Olivia / Bleasdale, Madeleine / Adamski, Nicole / Altena, Eveline / Bernardos, Rebecca / Brace, Selina / Broomandkhoshbacht, Nasreen / Callan, Kimberly / Candilio, Francesca / Culleton, Brendan / Curtis, Elizabeth /
    Demetz, Lea / Carlson, Kellie Sara Duffett / Edwards, Ceiridwen J / Fernandes, Daniel M / Foody, M George B / Freilich, Suzanne / Goodchild, Helen / Kearns, Aisling / Lawson, Ann Marie / Lazaridis, Iosif / Mah, Matthew / Mallick, Swapan / Mandl, Kirsten / Micco, Adam / Michel, Megan / Morante, Guillermo Bravo / Oppenheimer, Jonas / Özdoğan, Kadir Toykan / Qiu, Lijun / Schattke, Constanze / Stewardson, Kristin / Workman, J Noah / Zalzala, Fatma / Zhang, Zhao / Agustí, Bibiana / Allen, Tim / Almássy, Katalin / Amkreutz, Luc / Ash, Abigail / Baillif-Ducros, Christèle / Barclay, Alistair / Bartosiewicz, László / Baxter, Katherine / Bernert, Zsolt / Blažek, Jan / Bodružić, Mario / Boissinot, Philippe / Bonsall, Clive / Bradley, Pippa / Brittain, Marcus / Brookes, Alison / Brown, Fraser / Brown, Lisa / Brunning, Richard / Budd, Chelsea / Burmaz, Josip / Canet, Sylvain / Carnicero-Cáceres, Silvia / Čaušević-Bully, Morana / Chamberlain, Andrew / Chauvin, Sébastien / Clough, Sharon / Čondić, Natalija / Coppa, Alfredo / Craig, Oliver / Črešnar, Matija / Cummings, Vicki / Czifra, Szabolcs / Danielisová, Alžběta / Daniels, Robin / Davies, Alex / de Jersey, Philip / Deacon, Jody / Deminger, Csilla / Ditchfield, Peter W / Dizdar, Marko / Dobeš, Miroslav / Dobisíková, Miluše / Domboróczki, László / Drinkall, Gail / Đukić, Ana / Ernée, Michal / Evans, Christopher / Evans, Jane / Fernández-Götz, Manuel / Filipović, Slavica / Fitzpatrick, Andrew / Fokkens, Harry / Fowler, Chris / Fox, Allison / Gallina, Zsolt / Gamble, Michelle / González Morales, Manuel R / González-Rabanal, Borja / Green, Adrian / Gyenesei, Katalin / Habermehl, Diederick / Hajdu, Tamás / Hamilton, Derek / Harris, James / Hayden, Chris / Hendriks, Joep / Hernu, Bénédicte / Hey, Gill / Horňák, Milan / Ilon, Gábor / Istvánovits, Eszter / Jones, Andy M / Kavur, Martina Blečić / Kazek, Kevin / Kenyon, Robert A / Khreisheh, Amal / Kiss, Viktória / Kleijne, Jos / Knight, Mark / Kootker, Lisette M / Kovács, Péter F / Kozubová, Anita / Kulcsár, Gabriella / Kulcsár, Valéria / Le Pennec, Christophe / Legge, Michael / Leivers, Matt / Loe, Louise / López-Costas, Olalla / Lord, Tom / Los, Dženi / Lyall, James / Marín-Arroyo, Ana B / Mason, Philip / Matošević, Damir / Maxted, Andy / McIntyre, Lauren / McKinley, Jacqueline / McSweeney, Kathleen / Meijlink, Bernard / Mende, Balázs G / Menđušić, Marko / Metlička, Milan / Meyer, Sophie / Mihovilić, Kristina / Milasinovic, Lidija / Minnitt, Steve / Moore, Joanna / Morley, Geoff / Mullan, Graham / Musilová, Margaréta / Neil, Benjamin / Nicholls, Rebecca / Novak, Mario / Pala, Maria / Papworth, Martin / Paresys, Cécile / Patten, Ricky / Perkić, Domagoj / Pesti, Krisztina / Petit, Alba / Petriščáková, Katarína / Pichon, Coline / Pickard, Catriona / Pilling, Zoltán / Price, T Douglas / Radović, Siniša / Redfern, Rebecca / Resutík, Branislav / Rhodes, Daniel T / Richards, Martin B / Roberts, Amy / Roefstra, Jean / Sankot, Pavel / Šefčáková, Alena / Sheridan, Alison / Skae, Sabine / Šmolíková, Miroslava / Somogyi, Krisztina / Somogyvári, Ágnes / Stephens, Mark / Szabó, Géza / Szécsényi-Nagy, Anna / Szeniczey, Tamás / Tabor, Jonathan / Tankó, Károly / Maria, Clenis Tavarez / Terry, Rachel / Teržan, Biba / Teschler-Nicola, Maria / Torres-Martínez, Jesús F / Trapp, Julien / Turle, Ross / Ujvári, Ferenc / van der Heiden, Menno / Veleminsky, Petr / Veselka, Barbara / Vytlačil, Zdeněk / Waddington, Clive / Ware, Paula / Wilkinson, Paul / Wilson, Linda / Wiseman, Rob / Young, Eilidh / Zaninović, Joško / Žitňan, Andrej / Lalueza-Fox, Carles / de Knijff, Peter / Barnes, Ian / Halkon, Peter / Thomas, Mark G / Kennett, Douglas J / Cunliffe, Barry / Lillie, Malcolm / Rohland, Nadin / Pinhasi, Ron / Armit, Ian / Reich, David

    Nature

    2021  Volume 601, Issue 7894, Page(s) 588–594

    Abstract: Present-day people from England and Wales have more ancestry derived from early European farmers (EEF) than did people of the Early Bronze ... ...

    Abstract Present-day people from England and Wales have more ancestry derived from early European farmers (EEF) than did people of the Early Bronze Age
    MeSH term(s) Archaeology ; Europe ; Farmers ; France ; Genome, Human/genetics ; Human Migration/history ; Humans ; Infant ; United Kingdom
    Language English
    Publishing date 2021-12-22
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-021-04287-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Author Correction: PANDORA-seq expands the repertoire of regulatory small RNAs by overcoming RNA modifications.

    Shi, Junchao / Zhang, Yunfang / Tan, Dongmei / Zhang, Xudong / Yan, Menghong / Zhang, Ying / Franklin, Reuben / Shahbazi, Marta / Mackinlay, Kirsty / Liu, Shichao / Kuhle, Bernhard / James, Emma R / Zhang, Liwen / Qu, Yongcun / Zhai, Qiwei / Zhao, Wenxin / Zhao, Linlin / Zhou, Changcheng / Gu, Weifeng /
    Murn, Jernej / Guo, Jingtao / Carrell, Douglas T / Wang, Yinsheng / Chen, Xuemei / Cairns, Bradley R / Yang, Xiang-Lei / Schimmel, Paul / Zernicka-Goetz, Magdalena / Cheloufi, Sihem / Zhou, Tong / Chen, Qi

    Nature cell biology

    2021  Volume 23, Issue 6, Page(s) 676

    Abstract: A Correction to this paper has been published: https://doi.org/10.1038/s41556-021-00687-w. ...

    Abstract A Correction to this paper has been published: https://doi.org/10.1038/s41556-021-00687-w.
    Language English
    Publishing date 2021-05-03
    Publishing country England
    Document type Published Erratum
    ZDB-ID 1474722-4
    ISSN 1476-4679 ; 1465-7392
    ISSN (online) 1476-4679
    ISSN 1465-7392
    DOI 10.1038/s41556-021-00687-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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