Landgraf B., Kollaritsch H., Wiedermann G., Wernsdorfer W.H. https://doi.org/10.1093/nar/gkw405 (2016). Tamoxifen is an estrogen receptor (ER) ligand with widespread use in clinical and basic research settings. Due to the extensive list of side effects that may occur with tamoxifen, discuss your risk for any side effects with your healthcare provider before you start treatment. If you have questions about side effects, call your doctor. Xu Wang, Ph.D., staff scientist in the Wong laboratory and lead author of the study, observed that mice treated with tamoxifen gained resistance to light-induced eye injuries. The remaining extract was suspended in 1mL of dichloromethane, transferred to a Liquid chromatographymass spectrometry (LCMS) vial, evaporated under a nitrogen stream and resuspended in 50% methanol for LCMS analysis. (D) Survival curve of mice following TAM treatment PO or IP with different concentrations. This can increase the risk of becoming seriously ill if you get Covid-19, although being fully vaccinated is the best protection against serious illness due to Covid-19. Please enable it to take advantage of the complete set of features! These lines are mainly used for lineage tracing, taking advantage of permanent induction of the reporter even after TAM delivery is discontinued. https://doi.org/10.1002/dvg.20569 (2009). Drug Metab. Immunol. Concerning ER type, many studies have utilized Cre/ERT2, which has a modified human ER ligand binding domain, whereas the Cre/Esr1 used here has a modified mouse ER ligand binding domain. Article 2022 Aug 5;14(15):3811. doi: 10.3390/cancers14153811. We'd love to keep in touch about news, events and how you can get involved. The TAM inducible Cre/loxP system is widely used for genetic manipulation in vivo to control transgene expression and track individual cells or cell lineages3,27. Light injury, induced by exposing mice to short-duration, high-intensity light, normally leads to degeneration of photoreceptors. Tell all of your health care providers and lab workers that you take this medicine (tamoxifen tablets). These optimal conditions constitute a compromise between increased induction of YFP in immune cells and minimal toxicity in vivo. If you have any questions about this medicine (tamoxifen tablets), please talk with the doctor, pharmacist, or other health care provider. If you are of childbearing age, use a birth control method that does not use hormones (like a condom, diaphragms with spermicide, or plain IUDs) if sexually active to prevent pregnancy. If you are not sure when to start taking this Clipboard, Search History, and several other advanced features are temporarily unavailable. For subsequent experiments with 3mg and 6mg doses, TAM was purchased from ApexBio (B5965). 37, 943953. sharing sensitive information, make sure youre on a federal Comparison of TAM concentration between different tissues regardless the dose and delivery route of TAM (A; n=21/group), and when given IP versus PO 3mg and 6mg dose from pooled tissues (B; n=21/group). designed and performed experiments, interpreted data and wrote the manuscript. 4. Overall, induction of YFP was higher when giving mice 2.4mg TAM compared to 1.2mg (either IP or PO). Dispos 19, 3643 (1991). Clipboard, Search History, and several other advanced features are temporarily unavailable. Provided by the Springer Nature SharedIt content-sharing initiative. J. Clin. https://doi.org/10.1002/immu.200310005 (2003). Saito, K. et al. Powers, J. L. et al. J. Appl. If you think there has been an overdose, call your poison control center or get medical care right away. Blood 97, 324326. Animals were euthanized and necropsied either 7 or 28days post initiation of treatment. Immunobiology. This system is used to address the function of specific genes3,9,10,11, including those relating to immune cells. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Optimization of TAM delivery and dosing depends largely on the target site or tissue and concentration of the drug. Eur. Kim, H., Kim, M., Im, S. K. & Fang, S. Mouse Cre-LoxP system: General principles to determine tissue-specific roles of target genes. 4A,B). Call your doctor right away if you have signs of a blood clot like chest pain or pressure, coughing up blood, shortness of breath; swelling, warmth, numbness, change of color, or pain in a leg or arm; or trouble speaking or swallowing. If you are not sure what kind of birth control to use talk to your doctor. Signs of an allergic reaction, like rash; Signs of high calcium levels like weakness, confusion, feeling tired. November 2012 in Augsburg. Ther. Bmc Dev. World Malaria Report 2020: 20 Years of Global Progress & Challenges. WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Biol. www.sciencedaily.com/releases/2017/03/170313103052.htm (accessed March 1, 2023). anemia. Mice were treated with 5 injections every other day (over 10days). PubMed Central you are at risk for blood clots. Before (A) %YFP+cells induced by 4-OHT in gated immune cell populations (all from 72h time point, except those underlined, from 48h). The site is secure. 5F). ScienceDaily, 13 March 2017. Moderate and high amounts of tamoxifen in MHC-MerCreMer mice induce a DNA damage response, leading to heart failure and death. Exp. 3C,D were compared using MannWhitney test. In such a ubiquitous system, whether all cells express Cre/ER to the same level and induce loxP recombination to the same extent remains unclear. Besser wre es aber, erst gar nicht in Versuchung zu geraten, sich illegal Dopingmittel zu beschaffen. https://doi.org/10.1182/blood.V97.1.324 (2001). Mice were maintained in a temperature-controlled environment (2026C), fed irradiated chow (Purina Lab Diet 5053, PMI, St Louis, MO) and given unrestricted access to acidified water. Tissue samples were lysed with 2mL ACK buffer and filtered through a 70m cell strainer. It may lower the chance of getting cancer in For unclear reasons, induction of Cre/YFP was nearly double in thymocytes compared to peripheral T cells, and was particularly high in double positive (DP) cells (nearly 25%). Please enable it to take advantage of the complete set of features! The inherent toxicity of different types of oil should be comparatively assessed in future studies to minimize these adverse effects. AMD is a leading cause of vision loss among people age 50 and older. Vitorino M, Alpuim Costa D, Vicente R, Calea T, Santos C. Cancers (Basel). Uterine cancer (endometrial cancer and uterine sarcoma), Pulmonary embolism (blood clot in the lung). PubMed Central Swallow whole with some water or other drink. https://doi.org/10.1124/jpet.110.178301 (2011). The reporter is not expressed under physiologic conditions, but TAM-induced excision of the loxP-flanked STOP cassette upstream enables its transcription12. Find out more about vaccinations after lymph node removal. But in the tamoxifen-treated mice, the team unexpectedly observed little to no photoreceptor degeneration. 244, 305318. Google Scholar. Tamoxifen also reduced levels of inflammatory cytokines -- signaling molecules that trigger inflammation -- produced by the microglia. Ihr Arzt . J. Pharmacol. This site needs JavaScript to work properly. 6. Data are presented as meanSEM. Frequencies of YFP+cells from various lymphoid tissues (LNs, spleen, peripheral blood and bone marrow) were quantified on gated T/B lymphocytes (Suppl. Call your doctor or get medical However, there may be confounding effects of TAM on mice due to the delivery vehicle, which should be addressed in future studies. Genesis 50, 908913. Tell all of your health care providers that you take this medicine (tamoxifen tablets). Mixed model ANOVA test with repetitive measures was carried out to identify significant differences when testing different concentrations and delivery methods. Wir liefern in der Schweiz und nach Liechtenstein. Yes, tamoxifen has been reported as causing cataracts and may increase the need for cataract surgery. 26. Less well known are the effects of tamoxifen on immune function, which we discuss here. Its common to have lymph nodes under the arm removed as part of surgery for breast cancer. To hear from us, please sign up below. Moreover, the effect of TAM was long lasting, and Cre induction continued to increase 34weeks after discontinuing TAM administration. 530, 343363. 3B(cf)), which is consistent with the hepatic lipidosis24,25. Interestingly, there was a parallel increase in expression of the YFP reporter, revealing that Cre activity increases most dramatically within the first week after initiating treatment, and then steadily rises at a slower rate despite discontinuation of TAM dosing. Does hormone therapy affect the immune system? TAM was cleared from all tissues measured 28days after initiation of TAM administration, with all concentrations measuring less than 0.2ng/mL (data no shown). (C) Fraction of weight lost in mice following TAM treatment for 5 consecutive days, either IP or PO (n=10/group). eCollection 2022. Treating mice with high dose of TAM increases YFP induction among CD45+cells but also results in liver injury. According to our observations, these side effects appeared reversible upon efficient elimination of TAM in serum and tissues and resulted in normalization of tissue pathology up to 4weeks after initiation of treatment. If you get pregnant while taking tamoxifen citrate tablets, stop taking them right away and contact your doctor. CAS Mice were treated for a period of 5days either IP or by oral gavage (PO) with 0.1mL (3mg) or 0.2mL (6mg). Article Frequency of YFP expressing cells (%) in (A) B cells (B220+CD3), (B) T cells (B220CD3+), (C) CD4+T cells (B220CD3+CD4+CD8), (D) CD8+T cells (B220CD3+CD4CD8+), (E) single positive CD4+/CD8+, double positive (DP) and double negative (DN) thymocytes, (F) CD11b+CD11cmacrophages, (G) CD11bCD11c+, (H) CD11c+MHCII+and (I) CD11c+CD11b+dendritic cell populations, (J) CD11b+Gr-1and (K) CD11b+Gr-1+cells. Protoc. First, because the mice used were either homozygous or heterozygous for the YFP reporter transgene (YFP+/+and YFP+/, respectively), we needed to ensure that the activity of the CAG promoter driving YFP expression was not confounded by the number of transgene copies. If you have questions, Information Fig. PubMed Statistical analyses were performed on Prism 8, version 8.1.0. https://doi.org/10.1007/s12033-014-9738-0 (2014). pharmacist if you have questions about the best way to throw out drugs. Keep all drugs out of the reach of children and pets. 3D). Do not share your drugs with others and do not take anyone else's drugs. Within the tissue samples, concentration of TAM measured on day 7 post-treatment did not differ among liver, spleen, thymus and LN tissues when not differentiated by dose or administration route (Fig. Cre-dependent DNA recombination activates a STING-dependent innate immune response. Information Fig. These include: Infections can . Hyg. PZ: Dennoch ist der Nutzen, ein deutlich reduziertes Brustkrebs-Risiko, ja auch nicht von der Hand zu weisen. 1995 May 17;87(10):746-50. doi: 10.1093/jnci/87.10.746. 2. Last updated on Apr 29, 2022. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Yes, hair loss and hair thinning (alopecia) can occur with tamoxifen. It is in a class known as a selective estrogen receptor modulator (SERM) and is used to treat hormone receptor-positive breast cancer. 2022 Dec 17;11(12):1554. doi: 10.3390/pathogens11121554. reduce the risk of a new cancer developing in the other breast by about 50%. 2D). Our in vitro data showed that, in conditions where 4-OHT is non-limiting, there remains an inherent limitation for immune cells, particularly T cells, to induce Cre-mediated recombination. PubMed Central Throw away unused or expired drugs. 5.Who is more at risk from Covid-19? Leukocytosis (presence of circulating leukocytes above normal range)was found in PO treated animals but only with 6mg (Fig. PMC We noted a significant increase in the frequency of YFP positive CD45+cells when treating mice with 2.4mg TAM, reaching 40% by day 30 under the best conditions (Fig. These findings led to a presumptive diagnosis of hepatic lipidosis in the livers of animals treated with all doses of TAM necropsied 7days after initiation of treatment24. 5B). First, tamoxifen may be useful in the treatment of immune-mediated disorders, particularly of those arising from aberrant T-helper 1 cell activity, including allograft rejection, Crohn's disease, and Th1-mediated autoimmune conditions such as diabetes mellitus, scleroderma, and multiple sclerosis. Distinct populations of immune cells are targeted depending on the tissue-specific Cre-transgenic mouse. If you are using tamoxifen to lower your risk of getting breast cancer (for example, women with Ductal Carcinoma in Situ (DCIS) and women at high risk for breast cancer), discuss your risk for any side effects with your healthcare provider before you start treatment. Genesis 51, 725733. Subscribe to Drugs.com newsletters for the latest medication news, new drug approvals, alerts and updates. Tell your healthcare provider about all of your medicines, including prescription, over-the-counter, vitamins and herbal products. Hormone-receptor positive (HR+) breast cancer (BC) (including the luminal A and the luminal B subtypes) is the most common type of tumor in women diagnosed with early-stage BC (EBC). This site needs JavaScript to work properly. Read it again each time this medicine (tamoxifen tablets) is We provided non-specific stimulation for T cells and B cells to improve viability. Our breast care nurses and highly trained staff on our free and confidential Helpline are here for you. Rossant, J. Krebs Ist Eine Erfahrung Auf Die Ich Lieber Verzichtet Htte Ein Tagebuch In Bildern By Miriam Engelberg gesundheitsmagazin fr krebserkrankungen. Common side effects of Soltamox include hot flashes, weight loss, abnormal or absence of menstrual periods, vaginal discharge, vaginal bleeding, lightheadedness, dizziness, headache, vomiting, nausea . You must check Parasitol. The study, recently reported in the Journal of Neuroscience, suggests tamoxifen might work for the treatment of age-related macular degeneration (AMD) and retinitis pigmentosa (RP), blinding diseases that lack good treatment options. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. Disclaimer. The specificity of conditional gene targeting: A case for Cre reporters. See Suppl. Cole, L. K., Jacobs, R. L. & Vance, D. E. Tamoxifen induces triacylglycerol accumulation in the mouse liver by activation of fatty acid synthesis. 2A). *p0.05, **p0.01, ***p0.001. Functional analysis of various promoters in lentiviral vectors at different stages of in vitro differentiation of mouse embryonic stem cells. Registered Office: Fifth Floor, Ibex House, 42-47 Minories, London EC3N 1DY. de Boer, J. et al. Genesis 26, 99109. 10, 2262. https://doi.org/10.1038/s41467-019-10239-4 (2019). Plasmodium berghei ANKA; immune system; malaria; oestrogens; tamoxifen. The easiest way to lookup drug information, identify pills, check interactions and set up your own personal medication records. The https:// ensures that you are connecting to the 269271, 2015. https://doi.org/10.1101/pdb.prot077966 (2015). Epub 2011 Mar 29. Cre/ER recombinases remain unexpressed until activated by the TAM metabolite, which provides external and time-specific control of Cre activity. YFP expression in B cells was comparable across different tissues (~30%) (Fig. Commun. Trop. 5A), however the highest concentration of TAM was detected in animals dosed with 6mg IP regardless of the source of the tissue (Fig. CAS Mixed model ANOVA test with repetitive measures was performed to identify significant differences following 3mg TAM treatment PO (A,B). https://doi.org/10.1007/s11248-009-9342-4 (2010). To determine the degree of liver damage and the effect on inflammation, we measured levels of ALT and white blood cell (WBC) count. Information Fig. Symptoms typically appear during childhood and slowly progress over many years, often causing blindness. Information Fig. The methods lower limit of quantitation was 0.1ng/mL. Med. Unable to load your collection due to an error, Unable to load your delegates due to an error. Mature mice metabolize TAM to 4-OHT rapidly, producing comparable serum levels of the two compounds7,8. Tamoxifen, a selective oestrogen receptor modulator used in breast cancer treatment due to its antagonistic effect on oestrogen receptors and , is also studied because of its potential therapeutic use for several parasitic diseases. Nucleic Acids Res. In clinical studies 5.2% of women taking tamoxifen reported alopecia compared to 4.4% of women taking a placebo (an inactive pill). Samples were acquired on FACSCantoII and Fortessa from Becton Dickinson (BD), followed by data analysis using FlowJo software (version 10; BD). Additionally, IP delivery of the drug at 6mg resulted in increased tissue TAM concentration compared to PO (Fig. Available for Android and iOS devices. MannWhitney test was used for unpaired sample comparisons. Does having lymph nodes removed affect your immune system? Pharmacol. 2019 Nov 27;18(1):378. doi: 10.1186/s12936-019-3012-7. ***p0.001, ****p0.0001. 1A). 1106 million cells were stained in 100 L volume of FACS buffer with the following anti-mouse monoclonal antibodies: CD45 (APC-Cy7, clone 30-F11), CD3 (PE-Cy7, clone 145-2C11), CD45R/B220 (AF700, clone RA3-6B2), CD4 (PE, clone GK1.5), CD8 (BV510, clone 53-6.7), CD11c (PE, clone N418), CD11b (Pacific Blue, clone M1/70), MHC-II (AF700, clone M5/114.15.2), biotinylated Gr-1 (Ly-6G/Ly-6C) (clone RB6-8C5, detected by streptavidin (APC)), anti-mouse CD16/32 FcR block (clone93), propidium iodide. We review the growing body of evidence which demonstrates immunomodulatory effects of tamoxifen, including in vitro and in vivo studies as well as observations made in breast cancer patients treated with tamoxifen. For the first experiment, 1.2mg and 2.4mg TAM was prepared from powder (Sigma, T5648) dissolved in 100% ethanol (biology grade) (ThermoFisher Scientific BP2818100) at 100mg/mL. Lab. The government recommends everyone follow the same actions to reduce the risk of catching Covid-19 or passing it on to others. Splenocytes from CAG-Cre/Esr1 mice were subjected to density gradient isolation (Lymphoprep; StemCell Technologies, # 07801; per manufacturers instructions) and treatment with ACK buffer. However, not all cancer treatments affect the immune system. Liquidliquid extraction was utilized to isolate TAM by mixing 50L of either mouse serum or tissue homogenate combined with the internal standard (TAM Day 5) with 3mL of a 3-to-2 hexane/dichloromethane mixture. Keep all drugs in a safe place. "Breast cancer drug dampens immune response, protecting light-sensing cells of the eye." https://doi.org/10.1093/nar/26.6.1427 (1998). Thank you for visiting nature.com. Aguilar-Castro J, Cervantes-Candelas LA, Buenda-Gonzlez FO, Fernndez-Rivera O, Nolasco-Prez TJ, Lpez-Padilla MS, Chavira-Ramrez DR, Cervantes-Sandoval A, Legorreta-Herrera M. Front Cell Infect Microbiol. H.C. performed experiments and interpreted data. You may report side effects to the FDA at 1-800-332-1088. These results identify the toxic effects of higher doses of TAM administered, particularly when given IP. Toxicol. In past studies, TAM dosage has been altered based on animal age, target tissue, and other factors21. 33, 68. Wang ML, Cao YM, Luo EJ, Zhang Y, Guo YJ. One such factor is the activity of the CAG promoter driving Cre expression. Call your doctor for medical advice about side effects. Sakaguchi, M. et al. you are taking medicines to thin your blood, like warfarin, (also called Coumadin). Information Table S1A). Concentration of TAM measured in tissues. Hepatology 52, 12581265. 2021 Mar 26;12:643851. doi: 10.3389/fendo.2021.643851. PLoS ONE 8, e54009. & Gounari, F. Generation of CD4CreER(T2) transgenic mice to study development of peripheral CD4-T-cells. "Translation to the clinic can happen reasonably rapidly because tamoxifen, as an FDA-approved drug, already has a well-characterized safety profile," he explained. However . Some cancer treatments, such as chemotherapy, affect the immune system making it harder for the body to fight infections. If you are allergic to this medicine (tamoxifen tablets); any part of this medicine (tamoxifen tablets); or any other drugs, foods, or substances. World Health Organization; Geneva, Switzerland: 2020. Comparison of tissue TAM concentration between IP injection and PO when give TAM with high dose6mg (E) and low dose3mg (F) (n=45/group). MannWhitney test was used for unpaired sample comparisons. NCI CPTC Antibody Characterization Program. S3). Additionally, we investigated the effect of TAM on the clinical picture of the mice including clinical pathology and histopathological changes. Anim. PubMedGoogle Scholar. Bersell, K. et al. Follow all instructions closely. Bethesda, MD 20894, Web Policies Specifically, Tat-regulated expression of the CAG promoter resulted in efficient reporter expression throughout T cell development in the thymus, especially in immature and developing T cells37. 1B, 2AC, 3A, 4A,B). Das dazu notwendige Handwerkszeug, nmlich grndliche . PubMed Solvent B was increased linearly to 95% over 7min and maintained through 7.5min with a total run time of 8min. Biol. 337, 710717. Pathogens. See this image and copyright information in PMC. 2022 Sep 27;12:968325. doi: 10.3389/fcimb.2022.968325. A low white blood count means youre more at risk of infection. the other breast after one has cancer. 4C,D). The two doses had different effects on morbidity and mortality. 56, 779785 (2017). 17-Estradiol Is Involved in the Sexual Dimorphism of the Immune Response to Malaria. Article Information Fig. https://doi.org/10.1007/978-1-4939-7095-7_19 (2017). Get emergency medical help right away if you have signs of an allergic reaction such as: rash, hives, itching; trouble breathing, swallowing, or talking; tightness in the chest or throat; wheezing; swelling of your face, lips, mouth tongue, or throat or anywhere on your body; red, swollen, blistered, or peeling skin with or without fever. Data show the meanSEM (from 2 mice). It is not intended to provide medical or other professional advice. 53, 171178. Data are presented as meanSEM. Second, given that cellular T-helper 1 immunity is targeted against cancer cells, the tamoxifen-induced shift away from cellular immunity represents a significant step in fostering a cancerogenic environment. Do not take 2 doses at the same time or extra doses. Accessibility PubMed Sakhi et al Trop J Pharm Res, September 2021; 20(9): 1949 Tropical Journal of Pharmaceutical Research September 2021; 20 (9): 1949-1959 ISSN: 1596-5996 (print); 1596-9827 (electronic) 2022 May 30;13:902855. doi: 10.3389/fmicb.2022.902855. R.J.C. The ubiquitous inducible CAG-Cre/Esr1 system in conjunction with the Cre-inducible YFP reporter provides a useful model to perform longitudinal analyses using whole blood to optimize TAM dosage and route of administration. Immun. Be sure to have regular breast exams. Selection of which promoters to use is based on Cre expression in specific cells and tissues19. your ability to move around is limited for most of your waking hours. Genesis 32, 818 (2002). Having trastuzumab (Herceptin) could mean youre more at risk of getting coronavirus or becoming very ill if you get it. Article 15, 16301639. Do not take tamoxifen if you are allergic to it or any inactive ingredients found in the medicine. There was no mortality or substantial morbidity noted in these mice, and frequencies of YFP+cells in another cohort of mice reached significance at day 21 and day 32, with maximal induction of~40% (Fig. Written By:Sayer Ji, Founder Cancer's Origin, Prevention, Treatment, and Lifesaving Patient Empowerment and Resilience Strategies. Zovirax kan ogs tages oftere, hvis du er p hj risiko for at udvikle herpes virus, tager visse lgemidler ssom steroider, eller har en historie af viral syndrom, herunder herpes simplex udbrud. Curr. Here, we assessed dosage and delivery of TAM for activation of Cre in immune cell subsets assessed longitudinally and spatially using transgenic mice with ubiquitously expressed Cre/ER and the Cre-inducible fluorescent reporter YFP. Furthermore, expression of Cyp2d in immune cells and lymphoid tissues is negligible relative to expression in liver (Suppl. Samples were washed with complete medium and resuspended 5mL of medium for counting. We analyzed the level of YFP expression from YFP+/+and YFP+/ mice separately, in peripheral blood during longitudinal analysis, in total splenocytes, and in different spleen populations at endpoint (Suppl. Protoc. Generic name: Tamoxifen Tablets [ta-MOKS-i-fen] If it is close to the time for your next dose, skip the missed dose and go back to your normal time. Front Microbiol. Coping with worry. Last updated 24 June 2022. *p0.05, ***p0.001, ****p0.0001. Animals treated with TAM, regardless of the dose and route of delivery, experienced marked weight loss following 5days of treatment, which correlated with TAM serum concentrations following treatment (Suppl. This study was supported by internal funds. 105, 1113. The most common tamoxifen side effects may include: If you have rust or brown-colored vaginal discharge or vaginal bleeding, contact your doctor right away. Animal experiments were carried out at the Columbia Center for Translation Immunology, under a protocol reviewed and approved by Columbias Institutional Animal Care and Use Committee (IACUC). Tamoxifen works by blocking the action of estrogen, a female hormone. Your doctor will tell you how often to have these. Taking hormone therapy, including tamoxifen, letrozole, anastrozole, exemestane and goserelin, does not affect your immune system. Nebenwirkungen bei mehr als jeder zehnten behandelten Frau sind belkeit, Hautausschlag, Flssigkeitsansammlung im Gewebe, Scheidenausfluss und -blutungen, Zyklusvernderungen und menopausale Symptome wie Hitzewallungen und Erschpfung. Barnestein R, Galland L, Kalfeist L, Ghiringhelli F, Ladoire S, Limagne E. Oncoimmunology. 2020 Oct;143:110091. doi: 10.1016/j.mehy.2020.110091. 129X1-Gt(ROSA)26Sor
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