Established in 1913, the foundation used the Rockefeller family wealth to ostensibly promote "public health" by funding mass vaccination campaigns and the founding of public health authorities around the world. Importantly, our results suggest that the effects of AKT inhibition on metabolism are uncoupled from its effect on MM survival, as overexpression of the full length (40 kDa) antiapoptotic protein MCL-1 prevented AKT inhibitorinduced cell death but did not rescue glycolysis or OXPHOS activity. Multiple myeloma (MM) is a malignancy characterized by the clonal expansion of plasma cells in the bone marrow. In 1913 JDR established the Rockefeller Foundation to "promote the well-being of mankind throughout the world." In keeping with this broad commitment, the foundation has given important global assistance to public health, medical education, improved food production, scientific advancement, social research, and the arts. Similar to other cancer types, MM cells predominantly fulfill their energetic demands via glycolysis,2,3 a phenomenon known as the Warburg effect.4 In agreement, it was shown that the glycolysis rate-limiting enzyme, hexokinase II (HK2), is highly expressed in MM and is associated with poor prognosis.2,5,6. Bar graphs (right panels) depict basal respiration values, and means SEM are shown (one-way ANOVA, with Bonferroni multiple comparison test, P< .0001, P< .001, P< .01, P< .05; ns= not significant. Original data are available on request from the corresponding author, Jeroen E. J. Guikema (j.e.guikema@amsterdamumc.nl). Bair, Deirdre, "Jung - A Biography" London: Time-Warner Books UK, 2004, This page was last edited on 28 April 2023, at 05:29. American spin-off organizations associated with these Rockefeller-supported programs include the American Eugenics Society (synonymous with Rockefeller's Population Council) and the Human Genome Project). This implies that most glucose is converted into lactate and cannot be used for the TCA cycle, suggesting that other carbon sources fuel OXPHOS in MM. She was quoted as saying, "I married King Tutankhamen when I was only sixteen years old. American Cancer Society - Wikipedia Glycolysis, TCA cycle, and OXPHOS gene sets significantly depleted in MK2206-treated control clones in comparison with FOXO-deficient and untreated clones (Figure3B, supplemental Figure3A-C). CTRL, control; ES, enrichment score; FDR, false discovery rate; KEGG, Kyoto Encyclopedia of Genes and Genomes; KO, knockout; NES, normalized enrichment score. She says Lavender reminds her regularly to get screened, noting that colorectal cancer disproportionately affects the Black community. [2] Together, Harold and Edith were the parents of five children, three of whom survived to adulthood: A famous story about McCormick involves an evening in 1901 during a party. The R2 genomics analysis and visualization platform (http://r2.amc.nl) was used for k-means clustering based on the GEP data and survival analysis using the Kaplan-Meier method. doi: https://doi.org/10.1182/bloodadvances.2022007383. The American Cancer Society suggests that people with average risk for colorectal cancer should get screened starting at age 45. Cell numbers and specific cell death were determined by 7-aminoactinomycin D staining (BioLegend, San Diego, CA) and calculated as published previously.18 Experimental details for the glucose uptake assay are provided in the supplemental Materials and Methods. However, when glucose is present, glycolysis remains the major source of ATP production for HMCLs, as is evident from their limited glycolytic reserve. This document may not be reprinted without the express written permission of Northwest Arkansas Newspapers LLC. However, our results suggest that acetyl-CoA is not limiting for OXPHOS in MM cells because an increased acetyl-CoA formation caused by DCA treatment did not boost basal mitochondrial respiration. Also, tours of the MammoVan, UAMS' mobile mammography unit, will be offered. Laurance received many honors for his efforts on behalf of the environment and cancer research and treatment. Mary Rockefeller, the wife of New York State Governor Nelson Rockefeller, sews the first of the new union labels onto a garment, January 15, 1959. How Rockefeller founded modern medicine and killed natural cures Indict World Economic Forum on Twitter: "https://youtube.com/watch?v John Rockefeller: How he took control over Modern Medicine In agreement, the phosphorylation of FOXO1 (Thr24) and FOXO3 (Thr32), which mark their inactivation, followed a similar pattern (Figure1F). Rockefeller was allegedly instrumental in financially supporting the American Society for the Control of Cancer (the predecessor of the American Cancer Society) founded in 1913 by a small group of doctors and laypeople. Classification of patients with MM according to several metabolism-associated gene sets revealed that the FOXO-dependent repression of these genes confers a favorable prognosis. John Rockefeller and modern medicine: Abraham Flexner was born in 1866 in Louisville, Kentucky. The Cancer Within Modern Medicine Part 1 & 2 | SGT Report SAID RICHES HURT CHILDREN Harold F. McCormick, Ex-Husband, Has Received $30,000 a Year Since Divorce. Her mother would play piano and they would all sing. For the glycolysis pathway, red, blue, and yellow symbols indicate >1.5-fold (FOXO-dependent) decrease in gene expression in LME-1, MM1.S, and XG-3, respectively. Lavender's experience would be positive as well. John D. Rockefeller is also the son of the founder of the pharmaceutical industry in the US. ; Her Leadership of Chicago Society Unchallenged to the End", "Fowler McCormick Dies at 74; ExChairman of Harvester", "MRS. MAX OSER DIES ON COAST; Granddaughter of the Late John D. Rockefeller, Sister of Fowfer McCormick ", "MRS. OSER GOES TO MOTHER; Rides in Twentieth Century to Bedside of Mrs. McCormick", "The Aryan Christ: The Secret Life of Carl Jung - ResearchGate", "A Quirky Visionary: Edith Rockefeller McCormick Reigned as Queen of Chicago's Elite", "MRS. H.F. M'CORMICK BACK AFTER 8 YEARS; Rockefeller's Daughter Denies Planning Divorce Action Against International Harvester Head. The American Society for the Control of Cancer (the forerunner of the American Cancer Society) was established with the aid of John D. Rockefeller, and the first X-ray machine was put into use. Within days of Harold's remarriage, Edith announced plans to marry Edward Krenn, a 28 year old Austrian architect. No striking differences in the extracellular acidification rates (ECARs) or basal oxygen consumption rates (OCRs) were observed, indicating similar basal glycolysis and OXPHOS activity (Figure1A, supplemental Figure1A). (A) Seahorse XF real-time metabolic profiling of HMCLs (red symbols) and BCLs (blue, green, yellow, and light blue symbols), CpG-activated PBMNCs and purified human peripheral blood B cells (pink symbols). For several years, he ran a college prep school in his home town of Louisville. A year later, she and her husband established the John McCormick Institution of Infectious Diseases in Chicago, a source of funding for the researchers who later isolated the bacterium responsible for the disease. Lavender was 42 when she was diagnosed. April 30, 2023 at 7:30 a.m. Betsy Lavender at the Winthrop Rockefeller Cancer Institute at UAMS. Although novel treatment strategies have improved the prognosis and outcome of MM, most patients eventually relapse and become refractory to further treatment.1 Cancer cells are characterized by metabolic alterations, which are driven by oncogenes. They would also make fudge and cookies to deliver to the neighbors, and they regularly visited nursing homes where her family and another local family would entertain the residents. Upon graduation from high school, Lavender headed to the University of Arkansas at Fayetteville where she studied advertising and public relations. On Saturday, Betsy Lavender will lead a team in the "Be a Part of the Cure Walk" hosted by the University of Arkansas for Medical Sciences' Winthrop P. Rockefeller Cancer Institute in Little Rock. Stasz, Clarice. And the fact that she's willing to scream it from the mountaintops makes me love her even more.". Second, these LE gene sets were used to partition patients with MM into 2 groups using k-means clustering, representing high or low expression of LE FOXOrepressed genes from glycolysis-, the TCA cycle or OXPHOS-associated gene sets. Meanwhile, Harold married Ganna Walska, a Polish opera singer in August 1922, becoming her fourth husband. Last year, the walk raised about $250,000. That's for another blog post but here is a quote from John D. Rockefeller that summarizes his vision for . For the LE TCA and LE OXPHOS high groups (n= 178 and n= 170, respectively), the 5.5-year survival rate was 57% vs for the LE TCA and LE OXPHOS low groups, it was 71% (n= 598 and n= 606, respectively) (Figure5A). Cell lines, cell culture conditions, and details on reagents are provided in the supplemental Materials and Methods. Sterling Drug, Inc., the largest holding company in the Rockefeller Drug Empire and its 68 subsidiaries, showed profits in 1961 of $23,463,719 after taxes, on net assets of $43,108,106 - a 54% profit. As for cancer, oh yeah, the American Cancer Society was founded by none other than Rockefeller in 1913. SHE TESTIFIES IN COURT He Is Absent and Makes No Defense, Although Represented by Counsel. These effects appear to be cell/tissue contextspecific because several studies report the opposite, showing that FOXO expression is actually required for glucose metabolism and the TCA cycle in neural and intestinal stem cells.50,51 In agreement with our data, it was shown that FOXO3a antagonized MYC and repressed genes involved in the mitochondrial respiration in colon cancer cells52 and in glycolysis in melanoma cells.53. John D. Rockefeller (1839-1937), founder of the Standard Oil Company, became one of the world's wealthiest men and a major philanthropist. 1 Cancer cells are characterized by metabolic alterations, which are driven by oncogenes. She would continue her practice after her return to America, attracting many socialite patients from around the United States. They lived on the Arkansas side, which she calls the "good side" of Texarkana. To continue their mission today, Shah says the RF must "directly confront climate change". All flow cytometry data were obtained using a FACSCanto or LSR Fortessa (BD Biosciences, Franklin Lakes, NJ) and analyzed using FlowJo software (FlowJo, Ashland, OR). After a business trip in September 2012, however, she knew something was wrong. A heterogeneous response to 2-DG (half maximal effective concentrations [EC50s] ranging from 0.9 mM to >100 mM) was observed, which did not differ significantly between the BCL subtypes, although it is noteworthy that MM1.S (an HMCL) and Namalwa (a BLCL) showed a marked resistance (EC50 >100 mM) (Figure1B & supplemental Figure1B). "I remembered that I loved everything at UAMS then," she says. Financials & Governance. This result is surprising because it was previously shown that a shorter (36 kDa) MCL-1 isoform is required for normal mitochondrial bioenergetics in mouse embryonic fibroblasts.54 However, it is unlikely that the overexpression of the shorter MCL-1 isoform would rescue mitochondrial respiration because we found many OXPHOS-associated genes decreased in a FOXO-dependent fashion upon AKT inhibition. Edith Rockefeller McCormick - Wikipedia American Cancer Society - 1913 . However, this resulted in reduced proliferation and cell death in several HMCLs, suggesting that the ATP generated from mitochondrial respiration is not sufficient to meet the metabolic demands of MM cells. This indicates that in HMCLs and BLCLs, the glycolytic function is at its maximum and suggests that MM and BL are particularly reliant on glycolysis for proliferation and survival and have limited capacity to utilize glycolysis in response to increased energetic demands. She called her parents to say she wanted to come home to Texarkana to see a doctor. "Betsy Lavender has been such a tireless warrior and powerful voice about the importance of early detection for colon cancer," Couric says. As one of the wealthiest and most influential families in North America in the last 200 years, headed up by patriarch John D. Rockefeller I (pictured), the Rockefellers played an integral role in . HOPE AGAINST HOPE | WORD AND PRAYER | 27-04-2023 - Facebook (A) Kaplan-Meier univariate analysis for the OS of k-means clusteringdefined groups of patients with MM (776 patients in total). She also helped local candidates campaign, putting up yard signs and other tasks. The oxidation of galactose to pyruvate by glycolysis yields no netATP, forcing cells to rely on mitochondrial respiration for ATPgeneration, which is characterized by an increased OCR (Figure1D).30,31 Galactose caused a significant decrease in the ECAR/OCR ratio in all HMCLs tested, indicating that HMCLs can switch to OXPHOS when forced to do so (Figure1E). (B) Basal glycolysis in HMCLs and MMPCs (n= 2 patients) treated with 2.5 M MK2206 (blue bars) for 20 hours or untreated (red bars). New York: St. Martin's Press, 1995. performed analyses on clinical data and gene expression datasets; R.H.H. The first International Congress in Human Genetics to convene after WWII was held in Copenhagen in 1956. After dinner, where they met Clinton and his wife, Hillary, they got back on the charter bus and headed home. By the turn on the 20th century, he controlled 90% of all oil refineries in the U.S. through his oil company, Standard Oil, which was later on broken up to become Chevron, Exxon, Mobil etc. "It was the change and not knowing what was going to happen dealing with what was thrown at you and making the best way out of it.". FDR, ES, NES, and P-value are shown in the plots. She then traveled to Denver to work with media logistics for the Democratic National Convention. In 1912, they hired prominent architect Charles A. Platt to build a mansion on their large country estate, located directly on Lake Michigan in Lake Forest, Illinois, which they named Villa Turicum, and which had extensive architecturally landscaped gardens. Sheila Yount Special to the Democrat-Gazette Black Americans are about 20% more likely to get colorectal cancer and about 40% more likely to die from it than other ethnic groups. GEP data were obtained using samples from patients with MM who were at baseline and were undergoing total therapy 2 (TT2) or TT3 protocols.22 The clinical course for the patients showing high expression of these FOXO-repressed metabolic genes was characterized by a highly inferior OS (P< .0001). A local paper noted, of the first fair, that "One feature of the exhibit will be a collection of newspaper and magazine clippings, from various countries during the last 200 years emphasizing the storm of protest which greeted every suggestion for a freer social status for women. She is especially interested in raising awareness. Senator Herbert Lehman looks over her right shoulder, while Governor Rockefeller stands over her left shoulder. [7], In 1913, she travelled to Zurich to be treated for depression by Carl Gustav Jung, and contributed generously to the Zrich Psychological Society. To test this, the effects of the hexokinase inhibitor 2-deoxy-D-glucose (2-DG) on the survival of BCLs were determined. Whereas in patients with smoldering MM, only the LE OXPHOS gene set was significantly enriched (supplemental Figure4A-C). We passed out Clinton buttons and stickers." When evidence began to emerge that petroleum based medicine was causing cancer, Rockefeller founded the American Cancer Society, through which he suppressed that information. CI, confidence interval; B2M, beta2-microglobulin; Hb, hemoglobin; HR, hazard ratio; ISS, International Staging System; LDH, lactate dehydrogenase. She and Harold, along with other wealthy patrons, founded the Grand Opera Company, the first in Chicago, in 1909. It will be her second year to participate in the walk, and she hopes to raise even more money than she did last year, when her team took top fundraising honors in the individuals category. [10] In 1919 McCormick donated land she had received from her father as a wedding gift to the Forest Preserve of Cook County, to be developed as a zoological garden, later to become Chicago's Brookfield Zoo. It's sad to know how brainwashed breast cancer awareness is about chemotherapy, radiation, and surgery. The increased reliance of cancer cells on glycolysis is often associated with decreased mitochondrial respiration, suggesting that aerobic glycolysis occurs at the expense of oxidative phosphorylation (OXPHOS).4 However, many tumors exhibit increased glycolysis and OXPHOS.7-9. According to the American Cancer Society, screening can often find colorectal cancer early, before it has spread, making it easier to treat. "I think attitude probably was most important to me," she says, adding that it is important never to give up and "to make the best of everything. Rockefeller Foundation's new focus on climate change signals the next In accordance, despite their high rate of glycolysis, it was shown that MM cells also use OXPHOS because a combined treatment with the mitochondrial respiratory complex I inhibitor, metformin, and the glucose uptake inhibitor, ritonavir, synergized to induce death in MM cells.10 The rewiring of metabolic pathways and the flexibility to utilize different substrates are closely linked to recurrent genetic aberrations that characterize MM.11 In addition to fulfilling increased energy demands, several reports described changes in metabolism that lead to drug resistance in refractory MM.11,12 However, the key molecular factors that determine dynamic metabolic changes in MM cells have not been studied in detail. From this we conclude that AKT-mediated negative regulation of FOXO licenses the expression of glycolysis- and TCA-associated genes in MM but not in premalignant plasma cell disorders, most likely reflecting higher energetic demands due to the increased proliferation of MM cells. Expression of FOXO-repressed metabolic genes predicts poor survival in patients with MM. (C) Seahorse XF mitochondrial stress test profiles of CTRL clones (left panels, n= 2), and FOXO KO clones (middle panels, n= 2) treated for 20 hours with 2.5 M MK2206 (blue lines) or left untreated (red lines). G protein-coupled receptors (GPCRs) modulate diverse cellular signaling pathways and are important drug targets. From hectic politics to the unexpected peril of colorectal cancer, Lavender just laces up her shoes and deals with whatever life throws at her. Moreover, we show that the FOXO-dependent repression of metabolic genes predicts superior overall survival (OS) in a large cohort of patients with MM. (A) Immunoblot analysis of HK2 and PKM2 in LME-1, MM1.S, and LP-1 HMCLs treated overnight with 2.5 M MK2206 AKT inhibitor or left untreated. Bioorthogonal Tethering Enhances Drug Fragment Affinity for G Protein When evidence began to emerge that petroleum based medicine was causing cancer, Rockefeller founded the American Cancer Society, through which he suppressed that information. During the race for ASG president, Lavender says, her friend's opponent had more money and used it to make professional yard signs. Its global headquarters is located in the American Cancer Society Center in Atlanta, Georgia. In that respect, (combinatorial) targeting of signaling pathways that regulate metabolic plasticity may be a preferred approach, placing the AKT kinase in the limelight again, where the prevention of feedback regulation and/or activation of salvage pathways will be key for a successful therapeutic modality. The gene set enrichment analysis (GSEA) software (http://www.broad.mit.edu/gsea)26 and the Molecular Signature Database were used for GSEAs and leading edge (LE) analyses. David Dubinsky, the president of the ILGWU, stands to his left, holding a pair of scissors. The authors thank Berend Hooibrink (flow cytometry core facility, Amsterdam University Medical Centers) for excellent flow cytometry assistance. Still, she thrived in the unpredictable, always-on lifestyle. Longtime friends are not surprised at Lavender's dedication to colorectal cancer awareness and prevention. Margaret Higgins Sanger (born Margaret Louise Higgins; September 14, 1879 - September 6, 1966), also known as Margaret Sanger Slee, was an American birth control activist, sex educator, writer, and nurse.Sanger popularized the term "birth control", opened the first birth control clinic in the United States, and established organizations that evolved into the Planned Parenthood Federation of . Lavender had early-onset colorectal cancer. Interestingly, the spare respiratory capacity and the maximum respiration increased in the majority of the HMCLs (5 out of 6) (Figure1D). (A) Univariate analysis of subgroups (n= 776 patients; alternative numbers of patients indicated in case values/data were missing) for OS. On her first trip to Iowa in September 2007, she thought she would only be there a few days and packed accordingly. As for cancer, the American Cancer Society was founded by Rockefeller himself in 1913. "I'm most grateful to have grown up in my family and in Texarkana," Lavender says. EDITH ROCKEFELLER TO GET $8,419,032", "J.D. During aerobic glycolysis, glucose is converted to pyruvate and subsequently to acetyl-CoA to fuel the TCA cycle and OXPHOS. In agreement, the glycolytic rate of primary MM cells was lower than that of HMCLs, perhaps explained by the low invitro proliferative capacity of primary cells. (D) Fold change of ECAR, basal respiration, maximum respiration, and spare respiratory capacity (OCR) from a Seahorse XF mitochondrial stress test in HMCLs treated with DCA (25 mM for 20 hours) or cultured for 4 days in a galactose-containing medium (11.1 mM, no glucose). (A) GSEA in MMPCs from newly diagnosed patients with MM (n= 75) vs bone marrow plasma cells obtained from healthy donors (n= 15) showing that the shared FOXOrepressed gene set is enriched in MMPCs, indicating lower FOXO activity in these cells. Edith Rockefeller McCormick (August 31, 1872 August 25, 1932) was an American socialite, daughter of Standard Oil co-founder John D. Rockefeller. AKT inhibition suppresses glycolysis and OXPHOS in MM cells. Nov. 5, 2018. After radiation, chemotherapy and surgery at UAMS, Lavender spent time recuperating in Texarkana at her family home. John D. Rockefeller's American Cancer Society Never Meant to 'CURE' Cancer "I felt comfortable.". The American Cancer Society (ACS) is a nationwide voluntary health organization dedicated to eliminating cancer.Established in 1913, the society is organized into six geographical regions of both medical and lay volunteers operating in more than 250 Regional offices throughout the United States. "We had gone to almost every state by the time I graduated high school," she says, adding that after high school she and her mother and sister traveled even more. What the super-rich really did during World War II - MSN by They would go to the beach, to the Smoky Mountains, to Disney World, Cape Canaveral and more. Moreover, the FOXO-dependent repression of glycolysis- and TCA-associated genes correlates with a favorable prognosis in a large cohort of patients with MM. The 5.5-year survival rate was 54% in the LE glycolysis high group (n= 137) vs 71% in the LE glycolysis low group (n= 639). OCR values from the Seahorse XF mitochondrial stress test are depicted, and means SEM are shown (t-test, n= 5-6 measurements).ttest,P< .05; MMPC, primary MM plasma cells. Participants can choose to do a 1K or 5K route (both are wheelchair and stroller accessible). (D) Schematic representation of the glycolysis metabolic pathway and the TCA cycle. To determine the functional metabolic features of HMCLs in comparison with other mature malignant B-cell lines (BCLs), normal activated human peripheral blood mononuclear cells (PBMNCs), and activated purified B cells, glycolysis and mitochondrial stress tests were performed. Upon graduation, he moved his family to Texarkana, where he joined a local law firm. It was rumored that when this was whispered to her at the dinner table, she proceeded to merely nod her head and allowed the party to continue without incident. "Sometimes, I think it was better than any drug they could have given me," she says. Her friend won. This suggests that AKT is the pivotal kinase that crucially regulates both glycolysis and mitochondrial respiration in MM. To further assess metabolic adaptability, HMCLs were cultured for 4 days in a medium in which glucose was replaced with galactose. "[16] She followed up in Time magazine by stating "My interest in reincarnation is of many years' standing. How John D. Rockefeller Influenced Modern Medicine This notion, in combination with our finding that MM cells display limited metabolic adaptability suggests that the FOXO-dependent regulation of metabolic features may represent an attractive therapeutic Achilles heel. Part 2: How healthcare became the system it is today: Post Flexner Despite the known role of AKT in modulating cellular metabolism, little is known about the downstream factors of AKT that control the metabolic adaptability of MM cells. To continue their mission today, Shah says the RF must "directly confront climate change." Experimental details are provided in the supplemental Materials and Methods. MM cells show restricted glycolytic reserve and heterogeneous metabolic flexibility. To exclude the possibility that a perturbed AKT signaling indirectly affected mitochondrial respiration because of its effect on glycolysis, the OCR was determined in LME-1 and MM1.S, with either glucose, pyruvate, or glutamine present in the Seahorse medium as a single carbon source. [20][21] She and two of her children, John and Editha, are buried in Graceland Cemetery in Chicago. To continue their mission today, Shah says the RF must "directly confront climate change". ); and the Translational Research Institute (TRI) and grant KL2 TR003108 through the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) (T.C.A.). "So during Colon Cancer Month [March], I'm a beast about promoting screenings. Mean values for basal glycolysis andnormalized glycolytic reserve (percentage of basal glycolysis) based on ECAR and mean values for basal respiration and normalized spare respiratory capacity(percentage of basal respiration) based on OCR are depicted (one-way ANOVA with Bonferroni multiple comparisons test; HMCLs vs BCLs, n= 5 measurements. 01 May 2023 02:14:13 . John D. Rockefeller, Sr. Rockefeller Archive Center. "She is literally living proof that screening saves lives. In the multivariate stepwise Cox regression analysis, the LE TCA (high)defined high-risk status remained an adverse variable that predicted inferior OS, along with age (>65 years), increased LDH levels (190 U/L), GEP70 score,33 GEP-derived delTP53,34 and gain of chromosome 1q (Figure6B). We raise nearly all of our money through private individual donations, which helps to . She's had this special experience there, and she loves to share it with everyone.". Patient material was obtained according to the ethical standards of our institutional medical ethical committee, as well as in agreement with the 1975 declaration of Helsinki, as revised in1983. MM cells are characterized by the high expression of lactate dehydrogenase,35-37 which catalyzes the conversion of pyruvate into lactate instead of into acetyl-CoA. They later moved to Chicago. "Having that many people there, it was just incredible.". ROCKEFELLER JR. GREETS DYING SISTER; Mrs. Edith McCormick Has Relapse in the Night, but Soon Rallies", "MRS. McCORMICK'S ESTATE; Once Estimated at $40,000,000 -- Great Losses Since Crash of 1929", Edith Rockefeller McCormick Trust records, https://en.wikipedia.org/w/index.php?title=Edith_Rockefeller_McCormick&oldid=1152097548, John Rockefeller McCormick (18971901), who died young from.
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