Ich verkaufe Wein, ich gebe keine Geschenke!" Preliminary results of the interim analysis suggest that overall survival may also be improved, but the data are not sufficiently mature to assess this end point with precision. Included in this category were patients with stage III disease with visible residual tumor after primary debulking surgery, inoperable stage III disease, or any stage IV disease, as well as those who had received neoadjuvant chemotherapy. 22. Niraparib also prolonged the time without progression or death in the patients who had a complete response after chemotherapy (16.4 months vs. 9.5 months; hazard ratio, 0.60). Der alte Mann sagt: " Warum schreist du? As of the data cutoff on May 17, 2019, a total of 246 patients were still receiving treatment with niraparib or placebo (Figure 1). U okviru kompanije nalaze se: proizvodno preduzeće Moravka i lanac maloprodajnih marketa Zlatan Trag.. Stalno smo u potazi za dinamičnim, vrednim, kreativnim, odgovornim i … Übersetzung Lektion 23 . A sans serif typeface with 48 styles, available from Adobe Fonts for sync and web use. In the PRIMA trial, we found that patients with newly diagnosed advanced ovarian cancer who received niraparib after having a response to first-line platinum-based chemotherapy had significantly longer progression-free survival than those who received placebo in the overall population. † According to the Eastern Cooperative Oncology Group (ECOG) performance-status evaluation, a score of 0 indicates that the patient is fully active and able to carry on all predisease performance without restriction, and a score of 1 indicates that the patient is restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. The efficacy of niraparib in patients with newly diagnosed advanced ovarian cancer after a response to firs… At the time of the trial design, consideration of the reported median duration of progression-free survival for patients with ovarian cancer with a BRCA mutation who received placebo led to an estimated median duration of progression-free survival of 21 months in the patients with homologous-recombination deficiency and 14 months in the overall population for the sample-size estimation. Patients who had undetermined status with regard to homologous recombination were included in the subgroup with homologous-recombination proficiency. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. Within the population with homologous-recombination deficiency, the median duration of progression-free survival was 22.1 months in the niraparib group and 10.9 months in the placebo group (hazard ratio, 0.40; 95% CI, 0.27 to 0.62) in the subgroup with BRCA mutations and 19.6 months and 8.2 months, respectively (hazard ratio, 0.50; 95% CI, 0.31 to 0.83), in the subgroup without BRCA mutations. Start studying Vokabeln Prima Nova Lektion 1. Prima (dříve Prima Family, Premiéra TV) je česká komerční televizní stanice.Licenci na vysílání získala v roce 1992, k zahájení vysílání došlo 20. června 1993 pod názvem Premiéra TV v Praze a jejím okolí. On the Eastern Cooperative Oncology Group (ECOG) performance-status evaluation, a score of 0 indicates that the patient is fully active and able to carry on all predisease performance without restriction, and a score of 1 indicates that the patient is restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. The frequency of adverse events was greater in the niraparib group than in the placebo group, which was consistent with the class effects of PARP inhibitors. The primary efficacy analysis was performed after disease progression or death had occurred in 154 patients with homologous-recombination deficiency and in 386 patients in the overall population. Translated As of today, the G-lyrics are finally published! (Details regarding the clinical sites are provided in Table S1 in the Supplementary Appendix.) Lektion 7 - Eine Toga für Publius. Die Nacht war dunkel. Safety and dose modification for patients receiving niraparib. Low-grade nausea and fatigue were common in the two groups. Übersetzung und Lösungen von Buch und Arbeitsheft ), and MITO and the Department of Obstetrics and Gynecology, San Raffaele Scientific Institute (G.M.) G. Es ist eine schöne Reise. Overall survival was a key secondary end point. Ann Oncol 2017;28:Suppl 5:mdx372.032-mdx372.032. Learn vocabulary, terms, and more with flashcards, games, and other study tools. Results of this trial confirm the hypothesis that treatment with niraparib provides a longer duration of progression-free survival than placebo in the overall population. ), NSGO and Rigshospitalet–Copenhagen University Hospital, Copenhagen (M.R.M. Du nimmst Wein, aber du bezahlst kein Geld. BRCA1/2 mutations associated with progression-free survival in ovarian cancer patients in the AGO-OVAR 16 study. We found that among patients with newly diagnosed advanced ovarian cancer, those who received daily oral therapy with the PARP inhibitor niraparib after a response to platinum-based chemotherapy had a significantly longer duration of progression-free survival than those who received placebo. Harter P, Johnson T, Berton-Rigaud D, et al. Dr. González-Martín reports receiving consulting fees, lecture fees, and travel support from AstraZeneca and Pharma Mar, grant support, consulting fees, lecture fees, and travel support from Tesaro and Roche Holding, consulting fees from Clovis Oncology, Merck, Genmab, ImmunoGen, and Oncoinvent; Dr. Pothuri, receiving advisory board fees from Tesaro; Dr. Vergote, receiving consulting fees, paid to his institution, from Advaxis, Eisai, MSD Belgium, F. Hoffmann–La Roche, Millennium Pharmaceuticals, Oncoinvent, and Sotio, consulting fees, paid to his institution, and travel support from Roche, Genmab, Pharma Mar, Clovis Oncology, AstraZeneca, Tesaro, and Immunogen, grant support, paid to his institution, from Amgen, Stichting tegen Kanker, and Roche, participating in contracted research for Oncoinvent and Genmab, and travel support from Takeda Oncology; Dr. Christensen, receiving advisory board fees from Tesaro; Dr. Graybill, receiving advisory board fees, consulting fees, and lecutre fees from Tesaro; Dr. Mirza, receiving advisory board fees and fees for serving on the board of directors from Karyopharm Therapeutics, fees for serving on the board of directors from Sera Prognostics, lecture fees from Roche, Oncology Venture, and Zailab, grant support, lecture fees, and advisory board fees from AstraZeneca and Clovis Oncology, grant support and advisory board fees from Pfizer, grant support, advisory board fees, and lecture fees from Tesaro, lecture fees and advisory board fees from Genmab, advisory board fees from Biocad, Sotio, Geneos Therapeutics, Merck, and Seattle Genetics, and grant support from Boehringer Ingleheim; Dr. Lorusso, receiving advisory board fees from AstraZeneca, Clovis Oncology, Genmab, Immunogen, and Amgen, grant support, paid to her institution, and consulting fees from Pharma Mar, and grant support, paid to her institution, and advisory board fees from Merck; Dr. Freyer, receiving honoraria and consulting fees from Tesaro, Clovis Oncology, Bristol-Myers Squibb, Merck, Novartis, Eli Lilly, and Biogaran, grant support, honoraria, consulting fees, and travel support from AstraZeneca and Roche Holding, honoraria, consulting fees, and travel support from Pfizer, and grant support, honoraria, and consulting fees from Mylan; Dr. Redondo, receiving grant support and advisory fees from Pharma Mar and Roche, advisory fees from AstraZeneca and Tesaro, and grant support from Eisai; Dr. Moore, receiving grant support from Angle and consulting fees from Fujirebio Diagnostics; Dr. O’Cearbhaill, receiving advisory board fees from Clovis, Tesaro, and GlaxoSmithKline; Dr. Backes, receiving advisory board fees from Tesaro and Agenus, grant support and advisory board fees from Clovis, Merck, and Eisai, grant support from ImmunoGen, and lecture fees from CEC Oncology; Dr. Barretina-Ginesta, receiving lecture fees, advisory board fees, and travel support from Tesaro, AstraZeneca, and Roche, advisory board fees from Clovis Oncology, and lecture fees and travel support from Pharma Mar and Merck; Dr. Shahin, receiving grant support, lecture fees, consulting fees, and advisory board fees from Tesaro, advisory board fees and lecture fees from Merck and AstraZeneca, grant support, lecture fees, and serving as the principal investigator of a trial for Clovis Oncology, and consulting fees and lecture fees from Pacira Pharmaceuticals; Dr. Mangili, receiving consulting fees from AstraZeneca, consulting fees, lecture fees, and travel support from Tesaro, and travel support from Roche Holding; Drs. Five patients who did not receive either niraparib or placebo after randomization were excluded from the safety analysis. Prepare to become a physician, build your knowledge, lead a health care organization, and advance your career with NEJM Group information and services. Validation of the EORTC QLQ-C30 quality of life questionnaire through combined qualitative and quantitative assessment of patient-observer agreement. 2. However, the use of bevacizumab is limited because of safety concerns, and data are lacking on its use in the growing number of patients who receive neoadjuvant chemotherapy.2,3 Olaparib, an inhibitor of poly(adenosine diphosphate [ADP]–ribose) (PARP), has been associated with longer progression-free survival than placebo among patients with BRCA-mutated tumors, which includes approximately 15 to 20% of the patients with ovarian cancer, after a response to first-line platinum-based chemotherapy.4 Therefore, most patients with advanced ovarian cancer do not have an effective treatment option to substantially reduce the risk of death or progressive disease after first-line chemotherapy.5,6. Ann Oncol 2018;29:1784-1792. In the initial protocol, all the patients started at a fixed dose of 300 mg once daily. Adobe Fonts is the easiest way to bring great type into your workflow, wherever you are. Ich hab auch bereits hier auf der Seite nach geschaut aber alle Links die ich fand waren veraltet. Start studying Prima Nova, Lektion 5. Homologous recombination deficiency (HRD) score predicts response to platinum-containing neoadjuvant chemotherapy in patients with triple-negative breast cancer. Qual Life Res 2011;20:1727-1736. Gynecol Oncol 2019;154:255-258. All the patients had high-grade serous or endometrioid tumors that were classified as stage III or IV, according to the criteria of the International Federation of Gynecology and Obstetrics. Übersicht aller Apps. 19. Mechanistic rationale for inhibition of poly(ADP-ribose) polymerase in ETS gene fusion-positive prostate cancer. One case of myelodysplastic syndrome was identified in a patient in the niraparib group. Home. Brenner JC, Ateeq B, Li Y, et al. Among the two thirds of patients in the PRIMA trial who received neoadjuvant chemotherapy, the receipt of niraparib was associated with a 41% lower relative risk of disease progression or death than placebo. ); Israeli Society of Gynecologic Oncology and Department of Gynecology and Gynecologic Oncology, Hillel Yaffe Medical Center, Technion Israel Institute of Technology, Haifa, Israel (I.B. Further details and eligibility criteria are provided in the Supplementary Appendix. Of the 733 patients who had undergone randomization, 373 (50.9%) had tumors with homologous-recombination deficiency on myChoice testing; among these patients, 223 had tumors with BRCA mutations, and 150 had tumors without BRCA mutations (Fig. G Lektion 30 | Die Tragödie der Antigone. Latein Lösungen Lektion 5 z Text: Hallo ich brauchvom buch primaA lektion 5 z text ich kann sie nicht : cursus lektion 20 blauer kasten klein aber, prima nova textband lektion 27 seite 136 text G, latein prima t26, prima a lektion 27 g text. — all in Pennsylvania; GOG and the Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee (W.H.B. Patients receiving placebo were not allowed to cross over to receive niraparib treatment during the trial. Characteristics of the Patients at Baseline. Randomization was performed in a double-blind manner with the use of an interactive Web-response system, with stratification according to clinical response after first-line platinum-based chemotherapy (complete or partial response), receipt of neoadjuvant chemotherapy (yes or no), and status regarding tumor homologous recombination (deficient vs. proficient or not determined). Praćenjem tržišta i osluškivanjem potreba kupaca, Prima Nova prati nove, atraktivne i savremene promene. Safety was assessed through the monitoring of adverse events, laboratory testing, measurement of vital signs, and physical examination. There was a higher frequency of myelosuppression and low-grade nausea in the niraparib group than in the placebo group. In this population, the interim overall survival analysis showed an estimated probability of survival at 24 months of 81% in the niraparib group and 59% in the placebo group (hazard ratio, 0.51; 95% CI, 0.27 to 0.97). The primary end point was progression-free survival in patients who had tumors with homologous-recombination deficiency and in those in the overall population, as determined on hierarchical testing. The most common adverse events of grade 3 or higher were anemia (in 31.0% of the patients), thrombocytopenia (in 28.7%), and neutropenia (in 12.8%). Other secondary end points were the time until the first subsequent therapy, progression-free survival 2 (defined as time from randomization to progression while the patient was receiving a subsequent anticancer therapy), pharmacokinetic analyses, and patient-reported outcomes (scores on the FOSI, EQ-5D-5L, and EORTC-QLQ-C30/OV28 instruments). Eligible patients were at least 18 years of age and had newly diagnosed, histologically confirmed advanced cancer of the ovary, peritoneum, or fallopian tube (collectively defined as ovarian cancer). prima.nova. Homologous-recombination deficiency was defined as the presence of a BRCA deleterious mutation, a score of at least 42 on the myChoice test,9-11 or both. Latein Lösungen Lektion 5 z Text: ... prima Lektion 23 g text, triumph des paullus, latein prima Seite 92 Nummer b ... cursus lektion 20 blauer kasten klein aber, prima nova textband lektion 27 seite 136 text G, latein prima t26, prima a lektion 27 g text, prima band 1 kap 17 z text . At the 24-month interim analysis, the rate of overall survival was 84% in the niraparib group and 77% in the placebo group (hazard ratio, 0.70; 95% CI, 0.44 to 1.11). The demographic and clinical characteristics of the patients at baseline were balanced in the two trial groups (Table 1). NEW! Lesen und Schreiben bereitet diesen Freude. Niraparib extends treatment beyond chemotherapy and provides a sustained progression-free survival benefit for those at risk for early relapse, including the one third of patients who had a partial response to platinum-based chemotherapy (8.3 months vs. 5.6 months with placebo; hazard ratio, 0.60). ), and GOG and the Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College (R.E.O. In the overall population, the corresponding progression-free survival was 13.8 months and 8.2 months (hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). Myelosuppressive adverse events were the main reason for discontinuation but were infrequent (4.3% for thrombocytopenia in the niraparib group) (Table S8). T. Auf hoher See. This article was published on September 28, 2019, and last updated on November 14, 2019, at NEJM.org. A prespecified interim analysis for overall survival was conducted at the time of the primary analysis of progression-free survival. This video is unavailable. Lektionen 1-21: Amazon.es: Utz, Clement, Kammerer, Andrea: Libros en idiomas extranjeros No new safety signals were identified for niraparib. ); the Division of Gynecologic Oncology, Ohio State University, Columbus (F.B. Ovary: Globocan 2018. Die … Use of homologous recombination deficiency (HRD) score to enrich for niraparib sensitive high grade ovarian tumors. The efficacy of niraparib in patients with newly diagnosed advanced ovarian cancer after a response to first-line platinum-based chemotherapy is unknown. Groenvold M, Klee MC, Sprangers MAG, Aaronson NK. The most trusted, influential source of new medical knowledge and clinical best practices in the world. Lyon, France: International Agency for Research on Cancer, 2018 (https://gco.iarc.fr/today/data/factsheets/cancers/25-Ovary-fact-sheet.pdf). Niraparib is an oral, highly selective PARP1 and PARP2 inhibitor that has been approved as maintenance therapy in patients with recurrent ovarian cancer who have had a response to platinum-based chemotherapy. Ovarian cancer is a leading cause of death from gynecologic cancers in women worldwide.1 The standard treatment for newly diagnosed advanced epithelial ovarian cancer is surgical cytoreduction and systemic platinum–taxane combination chemotherapy. 10. Sun, Malinowska, Li, and Gupta, being employed by Tesaro; and Dr. Monk, receiving honoraria and lecture fees from Tesaro. 23. Quizlet flashcards, activities and games help you improve your grades. * Percentages may not total 100 because of rounding. Watch Queue Queue HRD denotes homologous-recombination deficiency, and ULN upper limit of the normal range. Die Pferde eilen durch den Zirkus … No other potential conflict of interest relevant to this article was reported. The clinical benefit of niraparib in the overall population was not driven only by the subgroup of patients with BRCA mutations. Among the most common grade 3 or higher adverse events in the niraparib group were anemia (in 31.0% of the patients), thrombocytopenia (in 28.7%), and neutropenia (in 12.8%). 8 personas están hablando de esto. S1). Before enrollment, all the patients had received six to nine cycles of first-line platinum-based chemotherapy, which had resulted in a complete or partial response, according to investigator assessment. Explore Proxima Nova designed by Mark Simonson at Adobe Fonts. Quintus sagt: " Ich lache! J Clin Oncol 2015;33:5532-5532. abstract. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer, Niraparib is an oral, highly selective PARP1 and PARP2 inhibitor that has been approved as maintenance therapy in patients with recurrent ovarian cancer who have had a response to platinum-based chemotherapy. The objective assessment of progressive disease was determined by central radiologic and clinical review in a blinded manner, according to RECIST (Response Evaluation Criteria in Solid Tumors), version 1.1.14 Clinical progression was reviewed if an increased CA125 level was accompanied by histologic proof or clinical symptoms, as specified in the protocol. Joint ENGOT and GOG Foundation requirements for trials with industry partners. † The most common adverse events were reported in at least 20% of the patients in the niraparib group and are listed in descending order of frequency. We determined that the enrollment of at least 620 patients (including 310 patients who had tumors with homologous-recombination deficiency) would provide a power of more than 90% to detect a significant difference in progression-free survival between niraparib and placebo at a one-sided type I error of 0.025.19,20 These criteria corresponded to a hazard ratio for disease progression or death of 0.50 in the group with homologous-recombination deficiency and 0.65 in the overall population of all the patients who had undergone randomization. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. The vertical shading indicates the 95% confidence interval for the overall population. In the population with homologous-recombination deficiency, the interim analysis showed an estimated probability of 24-month survival of 91% in the niraparib group and 85% in the placebo group (hazard ratio, 0.61; 95% CI, 0.27 to 1.39). Indications for treatment interruptions and dose reductions were defined in the protocol. Prima Nova d.o.o. prisutna je na tržištu od 2006. godine sa centrom u Leskovcu, u Tekstilnoj 97. 7. Gynecol Oncol 2017;146:58-63. Cancer Genome Atlas Research Network. Vergote I, Coleman RL, Pignata S, et al. Among the patients in this category, the median progression-free survival was significantly longer in the niraparib group than in the placebo group (21.9 months vs. 10.4 months; hazard ratio for disease progression or death, 0.43; 95% confidence interval [CI], 0.31 to 0.59; P<0.001). Cancer Cell 2011;19:664-678. Ich frage dich: Glaubst du, dass Gespenster existieren? New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). (Ab Lektion 22 bitte) Also ein Link oder Fotos aus einem alten Lateinheft ist mir relativ egal. Niraparib has shown efficacy both in patients who have tumors with. Nach dem Tod des Ödipus stritten sich Eteokles und Polyneikes über die Herrschaft der Stadt. Among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received niraparib had significantly longer progression-free survival than those who received placebo, regardless of the presence or absence of homologous-recombination deficiency. Currently, the most common treatment strategy with these patients is active surveillance. The trial was designed by the sponsor, GlaxoSmithKline, in collaboration with the European Network for Gynecological Oncological Trial (ENGOT) groups and the cooperative group leadership of GOG Partners (a component of the Gynecologic Oncology Group Foundation), according to the ENGOT model C.12 The sponsor was responsible for overseeing the collection, analysis, and interpretation of the data. Delayed Second Dose versus Standard Regimen for Covid-19 Vaccination, Serum Neutralizing Activity Elicited by mRNA-1273 Vaccine — Preliminary Report, Case 5-2021: A 68-Year-Old Man with Delirium and Renal Insufficiency, Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults, Avacopan for the Treatment of ANCA-Associated Vasculitis, https://gco.iarc.fr/today/data/factsheets/cancers/25-Ovary-fact-sheet.pdf, https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf, for the PRIMA/ENGOT-OV26/GOG-3012 Investigators. Mathews CA, Moore KN, Colombo N, et al. In the PRIMA trial, the primary end point was progression-free survival in patients who had tumors with homologous-recombination deficiency and in those in the overall population, as determined on hierarchical testing. ); Multicenter Italian Trials in Ovarian Cancer and Gynecologic Malignancies (MITO) and Fondazione IRCCS National Cancer Institute of Milan (D.L. The use of olaparib as a first-line treatment is limited to patients with BRCA mutations, as it was assessed in the SOLO1 trial.4 Notable differences exist between the SOLO1 and PRIMA populations. Concise summaries and expert physician commentary that busy clinicians need to enhance patient care. 5 talking about this. Test scores (which range from 1 to 100, with higher scores indicating a greater number of genomic abnormalities) represent a continuum on the basis of loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions. The median relative dose intensity (the proportion of administered doses relative to planned doses) was 63% for niraparib and 99% for placebo. National Comprehensive Cancer Network, 2019 (https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf). Subgroup analysis of the data from SOLO1 showed that in the patients with residual disease after debulking surgery, the treatment effect of olaparib (progression-free survival of 29.4 months with olaparib vs. 11.3 months with placebo; hazard ratio, 0.44; 95% CI, 0.25 to 0.77) was similar to that of niraparib in patients with BRCA mutations and residual disease in PRIMA (22.1 months with niraparib vs. 10.9 months with placebo; hazard ratio, 0.40; 95% CI, 0.27 to 0.62).23. Safety improved with the implementation of the individualized dosing regimen (Tables S10 and S11). abstract. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. Hier findest du die G-Text Lösungen. One patient in the niraparib group received the diagnosis of myelodysplastic syndrome in the context of bowel perforation, sepsis, and progressive disease. Du bist ein Dieb! In this randomized, double-blind, phase 3 trial, we randomly assigned patients with newly diagnosed advanced ovarian cancer in a 2:1 ratio to receive niraparib or placebo once daily after a response to platinum-based chemotherapy. Case Records of the Massachusetts General Hospital, Telemedicine and Medical Licensure — Potential Paths for Reform, No Cure without Care — Soothing Science Skepticism. 18. ); GOG and the Division of Gynecologic Oncology, University of Pennsylvania, Philadelphia (A.F.H. T . Progression-free Survival in the Two Primary Populations. Historically, clinical activity with PARP inhibitors has been associated with the presence of BRCA mutations, with most studies conducted in this selected patient population. This treatment effect occurred without a decrement in quality of life, as assessed by patient-reported outcomes. Apps für IOS und Android. The primary objective of the PRIMA (PRIMA/ENGOT-OV26/GOG-3012) trial was to test the efficacy and safety of niraparib maintenance therapy after a response to platinum-based chemotherapy in patients with newly diagnosed advanced ovarian cancer at high risk for relapse. Ich allerdings werde immer wieder durch erstaunliche Geschichten bewegt und erschreckt. Complementary mechanisms of action for niraparib, including PARP-regulated gene transcription, ribosome biogenesis, and immune activation, may explain this clinical observation.21,22 These analyses suggest that treatment with niraparib after first-line platinum-based chemotherapy extends benefit to all patients. Melissa zeigt die Kleider des Senators/der Senatoren. Prima Nova d.o.o. Ab heute sind endlich die G-Texte veröffentlicht! Melissa zeigt die Kleider der Herrin/der Herrinnen. In 1928, FIGC had decided a reform of the league structure of Italian football. 1. — all in Canada; Groupe d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens and Service d’Oncologie Médicale, Centre Hospitalier Lyon-Sud, Lyon, France (G.F.); Arbeitsgemeinschaft Gynäkologische Onkologie and the Department of Gynecology and Obstetrics, Klinikum der Stadt Ludwigshafen, Ludwigshafen, Germany (K.B. Of the 733 patients who underwent randomization, 373 (50.9%) had tumors with homologous-recombination deficiency. The median duration of progression-free survival in patients with homologous-recombination deficiency was 21.9 months with niraparib and 10.4 months with placebo (hazard ratio for disease progression or death, 0.43; 95% confidence interval [CI], 0.31 to 0.59; P<0.001) (Figure 2A).
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