24 results on '"F. Foss"'
Search Results
2. 831 Proteasome inhibitor functional profiling in CTCL
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S. Xu, J. Lewis, A. King, S. Umlauf, K. Carlson, F. Foss, and M. Girardi
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Cell Biology ,Dermatology ,Molecular Biology ,Biochemistry - Published
- 2022
3. Phase 2 trial of the farnesyltransferase inhibitor tipifarnib for relapsed/refractory peripheral T-cell lymphoma.
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Witzig T, Sokol L, Kim WS, de la Cruz Vicente F, Martín García-Sancho A, Advani R, Roncero Vidal JM, de Oña Navarrete R, Marín-Niebla A, Rodriguez Izquierdo A, Terol MJ, Domingo-Domenech E, Saunders A, Bendris N, Mackey J, Leoni M, and Foss F
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- Humans, Female, Male, Middle Aged, Aged, Adult, Aged, 80 and over, Treatment Outcome, Enzyme Inhibitors therapeutic use, Enzyme Inhibitors adverse effects, Neoplasm Recurrence, Local drug therapy, Antineoplastic Agents therapeutic use, Antineoplastic Agents adverse effects, Lymphoma, T-Cell, Peripheral drug therapy, Lymphoma, T-Cell, Peripheral mortality, Quinolones therapeutic use, Quinolones adverse effects, Farnesyltranstransferase antagonists & inhibitors
- Abstract
Abstract: A phase 2, international, open-label, nonrandomized, single-arm trial was conducted to evaluate the efficacy and safety of tipifarnib, a farnesyltransferase inhibitor, as monotherapy for relapsed/refractory peripheral T-cell lymphoma (PTCL) and to evaluate tumor mutation profile as a biomarker of response. Adults with relapsed/refractory PTCL received tipifarnib 300 mg orally twice daily for 21 days in a 28-day cycle. The primary end point was objective response rate (ORR); secondary end points included ORR, progression-free survival (PFS), duration of response (DOR), and adverse events (AEs) in specific subtypes. Sixty-five patients with PTCL were enrolled: n = 38 angioimmunoblastic T-cell lymphoma (AITL), n = 25 PTCL not otherwise specified, and n = 2 other T-cell lymphomas. The ORR was 39.7% (95% confidence interval [CI], 28.1-52.5) in all patients and 56.3% (95% CI, 39.3-71.8) for AITL. Median PFS was 3.5 months overall (954% CI, 2.1-4.4), and 3.6 months (95% CI, 1.9-8.3) for AITL. Median DOR was 3.7 months (95% CI, 2.0-15.3), and greatest in patients with AITL (7.8 months; 95% CI, 2.0-16.3). The median overall survival was 32.8 months (95% CI, 14.4 to not applicable). Tipifarnib-related hematologic AEs were manageable and included neutropenia (43.1%), thrombocytopenia (36.9%), and anemia (30.8%); other tipifarnib-related AEs included nausea (29.2%) and diarrhea (27.7%). One treatment-related death occurred. Mutations in RhoA, DNMT3A, and IDH2 were seen in 60%, 33%, and 27%, respectively, in the AITL tipifarnib responder group vs 36%, 9%, and 9% in the nonresponder group. Tipifarnib monotherapy demonstrated encouraging clinical activity in heavily pretreated relapsed/refractory PTCL, especially in AITL, with a manageable safety profile. This trial was registered at www.ClinicalTrials.gov as #NCT02464228., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2024
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4. Real World Data on Efficacy and Safety of EPOCH in T-Cell Lymphoma.
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Straining R, Foss F, Schiffer M, Amin K, Agarwal S, Isufi I, Huntington S, Kothari S, Seropian S, Girardi M, and Sethi T
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Background: T-cell lymphomas are a heterogeneous group of lymphoid malignancies with poor outcomes. Frontline multiagent chemotherapy options include CHOP (prednisone, vincristine, cyclophosphamide, and doxorubicin), brentuximab-CHP, CHOEP, and EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin)., Patients and Methods: We report our single institution data for safety and efficacy of EPOCH in 38 patients with aggressive T-cell lymphoma including both peripheral T cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL)., Results: Eighteen patients received EPOCH as first-line and 21 in the relapsed/refractory (R/R) setting. In 36 evaluable patients, the overall response rate (ORR) was 77% (95% CI, 61%-89%) with 19 (53%) patients achieving complete response (CR) (95% CI, 36%-69%). The ORR in first line and R/R settings were 80% (95% CI, 46%-94%) and 75% (95% CI, 52%-90%), respectively. Response rate was similar in African American versus Caucasian patients but was higher in CD30 negative versus positive patients. Most common grade 3/4 adverse events included cytopenias., Conclusions: Overall, EPOCH was well tolerated with high response rates in first line and R/R setting., Competing Interests: Disclosure Dr Francine Foss is on the speakers bureau for Pfizer. No other relevant disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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5. ASTCT and USCLC Clinical Practice Recommendations for Allogeneic Stem Cell Transplant in Mycosis Fungoides and Sézary Syndrome.
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Goyal A, O'Leary D, Dabaja B, Weng WK, Zain J, Cutler C, Guitart J, Kim YH, Geskin LJ, Hoppe RT, Wilson LD, Beaven AW, Horwitz S, Allen PB, Barta SK, Bohjanen K, Brammer JE, Carter JB, Comfere N, DeSimone JA, Dusenbery K, Duvic M, Huen A, Jagadeesh D, Kelsey CR, Khodadoust MS, Lechowicz MJ, Mehta-Shah N, Moskowitz AJ, Olsen EA, Poh C, Pro B, Querfeld C, Sauter C, Sokol L, Sokumbi O, Wilcox RA, Zic JA, Hamadani M, and Foss F
- Abstract
Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). While MF generally follows an indolent course, a subset of patients will experience progressive and/or treatment-refractory disease; Sézary syndrome is an aggressive lymphoma associated with high morbidity and mortality. Although allogeneic hematopoietic cell transplant (allo-HCT) is the only currently available potentially curative treatment modality for MF/SS there is no published guidance on referral criteria, transplant timing orallo-HCT approach. To develop consensus clinical practice recommendations, we performed a Delphi survey of 32 specialists in dermatology (n = 9), transplant hematology/oncology (n = 10), non-transplant hematology/oncology (n = 8), and radiation oncology (n = 5) from across the United States. Consensus required agreement of ≥75% of participants. Sixteen consensus statements were generated on four topics: (1) criteria for referral for consideration for allo-HCT, (2) allo-HCT preparative regimens and procedures (3) disease status at the time of allo-HCT, and (4) multidisciplinary management in the pre- and post-transplant settings. These clinical practice guidelines provide a framework for decision-making regarding allo-HCT for MF/SS and highlight areas for future prospective investigation., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2024
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6. Costs of care during chimeric antigen receptor T-cell therapy in relapsed or refractory B-cell lymphomas.
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Di M, Potnis KC, Long JB, Isufi I, Foss F, Seropian S, Gross CP, and Huntington SF
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- Humans, Male, Middle Aged, Female, Health Care Costs statistics & numerical data, Lymphoma, B-Cell therapy, Lymphoma, B-Cell economics, Aged, Health Expenditures, Receptors, Antigen, T-Cell therapeutic use, Immunotherapy, Adoptive economics, Lymphoma, Large B-Cell, Diffuse therapy, Lymphoma, Large B-Cell, Diffuse economics, Receptors, Chimeric Antigen
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High upfront cost may be a barrier to adopting chimeric antigen receptor T-cell (CAR-T) therapy for relapsed or refractory B-cell lymphoma. Data on the real-world costs are limited. Using the Blue Cross Blue Shield Axis database, we evaluated 271 commercially insured patients who received CAR-T therapy for B-cell lymphoma (median age = 58 years; men = 68%; diffuse large B-cell lymphoma = 87%; inpatient CAR-T therapy = 85%). Our peri-CAR-T period of interest was from 41 days before to 154 days after CAR-T therapy index divided into seven 28-day intervals. Median total costs were $608 100 (interquartile range, IQR = $534 100-$732 800); 8.5% of patients had total costs exceeding $1 million. The median cost of CAR-T therapy products was $402 500, and the median out-of-pocket copayment was $510. Monthly costs were highest during the month of CAR-T therapy administration (median = $521 500), with median costs below $25 000 in all other 28-day intervals. Costs of CAR-T therapy use were substantial, largely driven by product acquisition. Future studies should examine the relationship between costs, access, and financial outcomes., (© The Author(s) 2024. Published by Oxford University Press.)
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- 2024
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7. Generation and optimization of off-the-shelf immunotherapeutics targeting TCR-Vβ2+ T cell malignancy.
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Ren J, Liao X, Lewis JM, Chang J, Qu R, Carlson KR, Foss F, and Girardi M
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- Humans, Jurkat Cells, Immunotherapy, Adoptive, Clone Cells, Receptors, Antigen, T-Cell genetics, Receptors, Chimeric Antigen genetics
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Current treatments for T cell malignancies encounter issues of disease relapse and off-target toxicity. Using T cell receptor (TCR)Vβ2 as a model, here we demonstrate the rapid generation of an off-the-shelf allogeneic chimeric antigen receptor (CAR)-T platform targeting the clone-specific TCR Vβ chain for malignant T cell killing while limiting normal cell destruction. Healthy donor T cells undergo CRISPR-induced TRAC, B2M and CIITA knockout to eliminate T cell-dependent graft-versus-host and host-versus-graft reactivity. Second generation 4-1BB/CD3zeta CAR containing high affinity humanized anti-Vβ scFv is expressed efficiently on donor T cells via both lentivirus and adeno-associated virus transduction with limited detectable pre-existing immunoreactivity. Our optimized CAR-T cells demonstrate specific and persistent killing of Vβ2+ Jurkat cells and Vβ2+ patient derived malignant T cells, in vitro and in vivo, without affecting normal T cells. In parallel, we generate humanized anti-Vβ2 antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC) by Fc-engineering for NK cell ADCC therapy., (© 2024. The Author(s).)
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- 2024
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8. Allogeneic transplantation and cellular therapies in cutaneous T-cell lymphoma.
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Goyal A and Foss F
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- Humans, Transplantation, Homologous, Skin Neoplasms therapy, Skin Neoplasms pathology, Lymphoma, T-Cell, Cutaneous therapy, Lymphoma, T-Cell, Cutaneous etiology, Lymphoma, T-Cell, Cutaneous pathology, Mycosis Fungoides therapy, Mycosis Fungoides pathology, Sezary Syndrome therapy, Sezary Syndrome pathology, Hematopoietic Stem Cell Transplantation methods
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Introduction: Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common types of cutaneous T-cell lymphoma. Although many available treatments offer temporary disease control, allogeneic hematopoietic stem cell transplant (allo-HSCT) is the only curative treatment option for advanced stage MF and SS. CAR T-cell therapy is a promising new avenue for treatment., Areas Covered: In this review, we discuss the evidence supporting the use of allo-HSCT for the treatment of MF/SS, including disease status at the time of transplant, conditioning regimen, total body irradiation (TBI), and donor lymphocyte infusion (DLI). We also address the potential role for CAR T-cell therapy in CTCL., Expert Opinion: Allo-HSCT is an effective treatment for patients with advanced MF and SS. However, significant research is required to determine optimal treatment protocols. Data support the use of reduced-intensity conditioning regimens and suggests that the use of TBI for debulking of skin disease may result in more durable remissions. Donor lymphocyte infusions (DLI) appear to be particularly effective in inducing complete remission in MF/SS patients with relapsed or residual disease. Challenges with CAR-T therapies in T-cell lymphoma include T-cell fratricide due to shared antigens on malignant and nonmalignant T-cells, penetrance into the skin compartment, and CAR-T cell persistence.
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- 2024
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9. Allogeneic stem cell transplant for treatment of mycosis fungoides and Sezary syndrome: a systematic review and meta-analysis.
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Goyal A, O'Leary D, and Foss F
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- Humans, Transplantation, Homologous, Neoplasm Recurrence, Local, Transplantation Conditioning, Recurrence, Retrospective Studies, Sezary Syndrome therapy, Sezary Syndrome pathology, Mycosis Fungoides therapy, Mycosis Fungoides pathology, Hematopoietic Stem Cell Transplantation, Graft vs Host Disease, Skin Neoplasms
- Abstract
Allogeneic hematopoietic stem cell transplant (allo-HSCT) has been noted to be a potential curative treatment in cases of advanced-stage mycosis fungoides (MF) or Sezary syndrome (SS). To assess outcomes of allo-HSCT for MF/SS we performed a systematic review and meta-analysis including 15 manuscripts and 557 patients, published from 2010-2023. Meta-analysis revealed 1-year and 3+year overall survival (OS) of 51% (95% CI 39-64%) and 40% (32-49%). Progression-free survival at 1 year and 3+years were 42% (31-53%) and 33% (25-42%). Non-relapse mortality was 18% (13-23%). Relapse occurred in of 47% (40-53%) with a median time to relapse of 7.9 months (range 1.6-24 months). Rates of acute and chronic graft-versus-host disease (GVHD) were 45% (35-55%) and 40% (33-48%). Reduced-intensity conditioning (RIC) was associated with superior OS compared to myeloablative conditioning (MAC) (58% vs. 30%, p < 0.001). Of patients with relapse after allo-HSCT, 46% treated with donor lymphocyte infusion (DLI) achieved complete remission. These data support use of allo-HSCT for treatment of advanced-stage MF/SS and suggest superiority of RIC over MAC. Rates of GVHD were comparable to allo-HSCT in general. The improved OS for RIC and high rate of CR with DLI underscore the importance of the graft-versus-lymphoma effect in allo-HSCT for MF/SS., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2024
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10. Clinicopathologic Features of Cutaneous T-Cell Lymphomas With Extracutaneous Metastasis: A Case Series.
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Tang H, Matsumoto N, Foss F, Xu M, and Ahmed A
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- Humans, Skin pathology, Bone Marrow pathology, Skin Neoplasms pathology, Mycosis Fungoides pathology, Sezary Syndrome pathology, Lymphoma, Large-Cell, Anaplastic, Lymphoma, T-Cell, Cutaneous pathology
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Background: In advanced stages, Cutaneous T-cell lymphomas (CTCL) can metastasize to extracutaneous regions. CTCL with metastasis exhibits unique clinicopathologic characteristics., Patients and Methods: This study collected 35 cases of primary CTCL with extracutaneous metastasis from a single institution over a period of 20 years. Clinicopathologic features including demographics, CD30 expression, large cell transformation, metastatic sites, T-cell receptor clonality studies and survival data were analyzed., Results: The study identified various CTCL entities including mycosis fungoides (MF), Sezary syndrome (SS), cutaneous anaplastic large cell lymphoma (C-ALCL), and primary cutaneous peripheral T-cell lymphoma, not otherwise specified (pcPTCL-NOS). Limited data showed that metastasis can be independent of large cell transformation and/or CD30 expression. Lymph nodes were the most common site of metastasis, followed by the bone marrow. Oropharyngeal metastasis is likely to accompany visceral organ or brain metastasis (P = .049). MF had a longer interval to metastasis than SS (P = .038). Patients with lymph node only metastasis have better survival than patients with metastasis to other sites (P = .012)., Conclusion: To the best of our knowledge, there are limited studies analyzing the clinicopathologic features of different CTCL entities with metastasis as a single population. This research provides valuable insights into the unique characteristics of metastatic CTCL., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2023
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11. Impact of Memory T Cells on SARS-COV-2 Vaccine Response in Hematopoietic Stem Cell Transplant.
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VanOudenhove J, Liu Y, Nelakanti R, Kim D, Busarello E, Ovalle NT, Qi Z, Mamillapalli P, Siddon A, Bai Z, Axtmayer A, Corso C, Kothari S, Foss F, Isufi I, Tebaldi T, Gowda L, Fan R, Seropian S, and Halene S
- Abstract
During the COVID-19 pandemic, hematopoietic stem cell transplant (HSCT) recipients faced an elevated mortality rate from SARS-CoV-2 infection, ranging between 10-40%. The SARS-CoV-2 mRNA vaccines are important tools in preventing severe disease, yet their efficacy in the post-transplant setting remains unclear, especially in patients subjected to myeloablative chemotherapy and immunosuppression. We evaluated the humoral and adaptive immune responses to the SARS-CoV-2 mRNA vaccination series in 42 HSCT recipients and 5 healthy controls. Peripheral blood mononuclear nuclear cells and serum were prospectively collected before and after each dose of the SARS-CoV-2 vaccine. Post-vaccination responses were assessed by measuring anti-spike IgG and nucleocapsid titers, and antigen specific T cell activity, before and after vaccination. In order to examine mechanisms behind a lack of response, pre-and post-vaccine samples were selected based on humoral and cellular responses for single-cell RNA sequencing with TCR and BCR sequencing. Our observations revealed that while all participants eventually mounted a humoral response, transplant recipients had defects in memory T cell populations that were associated with an absence of T cell response, some of which could be detected pre-vaccination.
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- 2023
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12. FISH Panel for Leukemic Cutaneous T-Cell Lymphoma: Extended Patient Cohort Correlation with Blood Involvement and Clinical Outcomes.
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Avery J, Kim SR, Cheng W, Foss F, and Girardi M
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The genomic basis of cutaneous T-cell lymphoma has been characterized by gene copy number alterations and genomic sequencing, but there are few clinical tests that are being widely used to inform the diagnosis and prognosis of leukemic cutaneous T-cell lymphoma that may arise as a progression from mycosis fungoides or de novo as Sézary syndrome. An 11-gene FISH panel of TP53 , RB1 , DNMT3A , FAS , ZEB1 , ARID1A , ATM , and CDKN2A deletions and MYC , signal transducer and activator of transcription gene ( STAT ) 3/5B , and CARD11 amplifications was previously found to encapsulate >95% of gene copy number variations in leukemic cutaneous T-cell lymphoma. Through a retrospective analysis of patients with leukemic cutaneous T-cell lymphoma seen at the Yale Cancer Center from 2014 to 2020, we gathered the relevant genes as they became available and correlated them to factors with prognostic relevance as a proof of concept to show the potential utility in further developing a limited gene panel for prognosis. In this study, we show that the abnormal FISH results show an association with clinically relevant factors (blood stage, CD4:8 ratio, and percentage blood involvement) and have a nonsignificant statistical trend (>90%) toward correlation with overall survival. In addition, the previous cost-effective panels were signal transducer and activator of transcription ( STAT ) 3/5B , MYC , TP53 , and ARID1A . We now suggest adding RB1 and ZEB1 on the basis of our findings., (© 2023 The Authors.)
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- 2023
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13. Cultivating Integration via Placemaking: an ArcGIS StoryMap and Inventory of Refugee-Centered Farming Organizations in the USA.
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Foss F, Gibbes C, and Skop E
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This paper inventories the number, type, location, and characteristics of refugee resettlement agencies and refugee third sector organizations (RTSOs) in creating opportunities for placemaking and longer-term integration via refugee-centered farming programs in the USA. Using an ArcGIS StoryMap and accompanying database, we map how resettlement organizations engage in farming programs and provide insight into the various actors implementing refugee resettlement and integration policy in the USA, while also highlighting the role of place and placemaking in that process. Findings indicate that there are 40 total organizations involved in 30 states, with 100 farm sites scattered across 48 cities, primarily found in nontraditional sites of resettlement. Using Ager and Strang's ( Journal of Refugee Studies , 21(2):166-191, 2008) integration model as a theoretical starting point, we use a two-cycle content analysis to illustrate that organizations have diverse goals focusing on employment, social connections, health, safety and security, and placemaking. Sponsored activities and community projects concentrate on workforce training and community-supported agriculture. This interactive visualization and analysis of existing programs nationwide allow the organizations involved, policymakers, scholars, and members of the public to explore the locations of programs with pertinent information about each organization. The research also illustrates that refugee-centered farming organizations should continue to emphasize their efforts on placemaking as a beneficial strategy for the longer-term integration of resettled refugees. Additionally, this research contributes to larger debates and theoretical understandings of longer-term integration by extending Ager and Strang's ( Journal of Refugee Studies , 21(2):166-191, 2008) integration model and embedding place and placemaking as underpinning elements in the process., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature B.V. 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)
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- 2023
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14. Correction to: Real-Life Barriers to Diagnosis of Early Mycosis Fungoides: An International Expert Panel Discussion.
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Hodak E, Geskin L, Guenova E, Ortiz-Romero PL, Willemze R, Zheng J, Cowan R, Foss F, Mangas C, and Querfeld C
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- 2023
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15. Real-Life Barriers to Diagnosis of Early Mycosis Fungoides: An International Expert Panel Discussion.
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Hodak E, Geskin L, Guenova E, Ortiz-Romero PL, Willemze R, Zheng J, Cowan R, Foss F, Mangas C, and Querfeld C
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- Humans, Diagnosis, Differential, Skin Neoplasms pathology, Mycosis Fungoides diagnosis
- Abstract
Mycosis fungoides (MF) is a rare, primary cutaneous T-cell lymphoma that is challenging to diagnose due to its heterogeneous clinical presentation and complex histology. The subtlety of the initial clinical appearance of MF can result in diagnostic delays and hesitancy to refer suspected cases to specialist clinics. An unmet need remains for greater awareness and education. Therefore, an international expert panel of dermatologists, oncologists, hematologists, and dermatopathologists convened to discuss and identify barriers to early and accurate MF diagnosis that could guide clinicians toward making a correct diagnosis. Confirmation of MF requires accurate assessment of symptoms and clinical signs, and subsequent correlation with dermatopathological findings. This review summarizes the expert panel's guidance, based on the literature and real-life experience, for dermatologists to help include MF in their list of differential diagnoses, along with simple clinical and histopathologic checklists that may help clinicians to suspect and identify potential MF lesions and reduce diagnostic delays., (© 2022. The Author(s).)
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- 2023
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16. Expansion microscopy of mouse brain organotypic slice cultures to study protein distribution.
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Bissen D, Kracht MK, Foss F, and Acker-Palmer A
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- Animals, Brain diagnostic imaging, Mice, Organ Culture Techniques, Microscopy, Receptors, AMPA metabolism
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Assessing protein distribution with super-resolution in tissue is often complicated and restrictive. Here, we describe a protocol for immunostaining and expansion microscopy imaging of mouse brain organotypic slice cultures. We detail an Imaris analysis workflow to analyze the surface vs intracellular distribution of AMPA receptors at super-resolution during homeostatic plasticity. We have optimized the protocol for brain organotypic slice culture and tested in acute brain slices. This protocol is suitable to study protein distribution under multiple plasticity paradigms. For complete details on the use and execution of this protocol, please refer to Bissen et al. (2021)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2022
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17. Peripheral Blood Involvement at Staging in Patients With Aggressive Peripheral T-Cell Lymphoma.
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Avery J, Chandhok N, Rainey C, Torres R, Huntington S, Isufi I, Seropian S, Xu ML, and Foss F
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- Flow Cytometry, Humans, Prognosis, Retrospective Studies, Lymphoma, T-Cell pathology, Lymphoma, T-Cell, Peripheral pathology
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Introduction: Peripheral T-Cell Lymphomas (PTCL) are a rare subgroup of lymphomas with a poor outcome.Traditional prognostic measures rely heavily on disease stage, and with the advent of targeted treatment, further stratificationcriteria are needed to guide treatment. To date, the impact of blood involvement at diagnosis on outcomes has not been assessed., Materials and Methods: We retrospectively reviewed blood involvement by flow cytometry at diagnosis in 102 consecutivelytreated patients who had flow cytometry data available at diagnosis. Of these, 78 patients with nodal subtypes were identified andstudied in this analysis., Results: Of 78 patients with nodal subtypes of PTCL who had flow data available at the time ofdiagnosis, circulating populations of malignant T cells matching those in the biopsied lymph nodes were found in 21 patients bymultiparameter flow cytometry. A positive flow cytometry was highly correlated with bone marrow involvement. The patientswith a negative flow cytometry had a trend toward a longer median PFS compared to those with a positive flow but there was noimpact on overall survival., Conclusions: Circulating malignant tumor cells can be found in the peripheral blood in a subset ofpatients with aggressive nodal T-cell lymphomas, including peripheral t-cell lymphoma not otherwise specified andangioimmunoblastic T-cell lymphomas, and blood involvement is correlated with bone marrow involvement., (Copyright © 2022. Published by Elsevier Inc.)
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- 2022
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18. Primary cutaneous lymphoma: recommendations for clinical trial design and staging update from the ISCL, USCLC, and EORTC.
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Olsen EA, Whittaker S, Willemze R, Pinter-Brown L, Foss F, Geskin L, Schwartz L, Horwitz S, Guitart J, Zic J, Kim YH, Wood GS, Duvic M, Ai W, Girardi M, Gru A, Guenova E, Hodak E, Hoppe R, Kempf W, Kim E, Lechowicz MJ, Ortiz-Romero P, Papadavid E, Quaglino P, Pittelkow M, Prince HM, Sanches JA, Sugaya M, Vermeer M, Zain J, Knobler R, Stadler R, Bagot M, and Scarisbrick J
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- Clinical Trials as Topic, Humans, Neoplasm Staging, United States, Lymphoma, T-Cell, Cutaneous diagnosis, Lymphoma, T-Cell, Cutaneous pathology, Lymphoma, T-Cell, Cutaneous therapy, Mycosis Fungoides diagnosis, Mycosis Fungoides pathology, Mycosis Fungoides therapy, Sezary Syndrome diagnosis, Sezary Syndrome pathology, Sezary Syndrome therapy, Skin Neoplasms diagnosis, Skin Neoplasms pathology, Skin Neoplasms therapy
- Abstract
The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sézary syndrome, the most common type of PCL, none exist for the other PCLs. In addition, staging of the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous LymphomaConsortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for the Research and Treatment of Cancer (EORTC) now propose updated staging and guidelines for the study design, assessment, endpoints, and response criteria in clinical trials for all the PCLs in alignment with that of the Lugano guidelines. These recommendations provide standardized methodology that should facilitate planning and regulatory approval of new treatments for these lymphomas worldwide, encourage cooperative investigator-initiated trials, and help to assess the comparative efficacy of therapeutic agents tested across sites and studies., (© 2022 by The American Society of Hematology.)
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- 2022
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19. Safety considerations with the current treatments for peripheral T-cell lymphoma.
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Sethi T, Montanari F, and Foss F
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- Humans, Lymphoma, T-Cell etiology, Lymphoma, T-Cell pathology, Lymphoma, T-Cell therapy, Lymphoma, T-Cell, Peripheral complications, Lymphoma, T-Cell, Peripheral drug therapy
- Abstract
Introduction: Peripheral T-Cell Lymphomas (PTCL) constitute a heterogeneous group of aggressive T - and natural killer (NK)-cell disorders and are associated with a poor prognosis. Frontline treatments often consist of anthracycline-based combination chemotherapy with the exception of NK-T cell lymphomas, where such combinations are ineffective due to the presence of P-glycoprotein which leads to multidrug resistance. Infectious and immune mediated side effects might be more pronounced in or unique to T-cell lymphomas due to the selection of agents which target multiple T-cell subtypes and also an immunocompromised state induced by the lymphomas themselves., Areas Covered: This review provides a comprehensive overview of safety considerations of treatment regimens used for peripheral T-cell lymphomas. We cover regimens used in both frontline and relapsed settings including combination chemotherapy, single agent chemotherapies and immunotherapies., Expert Opinion: Treatment of T-cell lymphomas often requires sequencing of several therapies due to lower efficacy of available treatment regimens in curing the disease compared to that seen in B-cell non-Hodgkin lymphomas. In addition, certain complications are more common in T-cell lymphomas due to their unique immunobiology. An understanding of these salient aspects is important for all providers who treat patients with this challenging disease group.
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- 2022
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20. Outcomes of Allogeneic Hematopoietic Cell Transplantation in T Cell Prolymphocytic Leukemia: A Contemporary Analysis from the Center for International Blood and Marrow Transplant Research.
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Murthy HS, Ahn KW, Estrada-Merly N, Alkhateeb HB, Bal S, Kharfan-Dabaja MA, Dholaria B, Foss F, Gowda L, Jagadeesh D, Sauter C, Abid MB, Aljurf M, Awan FT, Bacher U, Badawy SM, Battiwalla M, Bredeson C, Cerny J, Chhabra S, Deol A, Diaz MA, Farhadfar N, Freytes C, Gajewski J, Gandhi MJ, Ganguly S, Grunwald MR, Halter J, Hashmi S, Hildebrandt GC, Inamoto Y, Jimenez-Jimenez AM, Kalaycio M, Kamble R, Krem MM, Lazarus HM, Lazaryan A, Maakaron J, Munshi PN, Munker R, Nazha A, Nishihori T, Oluwole OO, Ortí G, Pan DC, Patel SS, Pawarode A, Rizzieri D, Saba NS, Savani B, Seo S, Ustun C, van der Poel M, Verdonck LF, Wagner JL, Wirk B, Oran B, Nakamura R, Scott B, and Saber W
- Subjects
- Humans, Middle Aged, Transplantation Conditioning adverse effects, Transplantation, Homologous adverse effects, Graft vs Host Disease epidemiology, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Prolymphocytic, T-Cell therapy
- Abstract
T cell prolymphocytic leukemia (T-PLL) is a rare, aggressive malignancy with limited treatment options and poor long-term survival. Previous studies of allogeneic hematopoietic cell transplantation (alloHCT) for T-PLL are limited by small numbers, and descriptions of patient and transplantation characteristics and outcomes after alloHCT are sparse. In this study, we evaluated outcomes of alloHCT in patients with T-PLL and attempted to identify predictors of post-transplantation relapse and survival. We conducted an analysis of data using the Center for International Blood and Marrow Transplant Research database on 266 patients with T-PLL who underwent alloHCT between 2008 and 2018. The 4-year rates of overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM) were 30.0% (95% confidence interval [CI], 23.8% to 36.5%), 25.7% (95% CI, 20% to 32%), 41.9% (95% CI, 35.5% to 48.4%), and 32.4% (95% CI, 26.4% to 38.6%), respectively. In multivariable analyses, 3 variables were associated with inferior OS: receipt of a myeloablative conditioning (MAC) regimen (hazard ratio [HR], 2.18; P < .0001), age >60 years (HR, 1.61; P = .0053), and suboptimal performance status, defined by Karnofsky Performance Status (KPS) <90 (HR, 1.53; P = .0073). Receipt of an MAC regimen also was associated with increased TRM (HR, 3.31; P < .0001), an elevated cumulative incidence of grade II-IV acute graft-versus-host disease (HR, 2.94; P = .0011), and inferior DFS (HR, 1.86; P = .0004). Conditioning intensity was not associated with relapse; however, stable disease/progression was correlated with increased risk of relapse (HR, 2.13; P = .0072). Both in vivo T cell depletion (TCD) as part of conditioning and KPS <90 were associated with worse TRM and inferior DFS. Receipt of total body irradiation had no significant effect on OS, DFS, or TRM. Our data show that reduced-intensity conditioning without in vivo TCD (ie, without antithymocyte globulin or alemtuzumab) before alloHCT was associated with long-term DFS in patients with T-PLL who were age ≤60 years or who had a KPS >90 or chemosensitive disease., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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21. T-Cell Lymphomas, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.
- Author
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Horwitz SM, Ansell S, Ai WZ, Barnes J, Barta SK, Brammer J, Clemens MW, Dogan A, Foss F, Ghione P, Goodman AM, Guitart J, Halwani A, Haverkos BM, Hoppe RT, Jacobsen E, Jagadeesh D, Jones A, Kallam A, Kim YH, Kumar K, Mehta-Shah N, Olsen EA, Rajguru SA, Rozati S, Said J, Shaver A, Shea L, Shinohara MM, Sokol L, Torres-Cabala C, Wilcox R, Wu P, Zain J, Dwyer M, and Sundar H
- Subjects
- Humans, Immunoblastic Lymphadenopathy diagnosis, Immunoblastic Lymphadenopathy pathology, Immunoblastic Lymphadenopathy therapy, Lymphoma, T-Cell diagnosis, Lymphoma, T-Cell therapy, Lymphoma, T-Cell, Peripheral diagnosis, Lymphoma, T-Cell, Peripheral therapy
- Abstract
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoproliferative disorders arising from mature T cells, accounting for about 10% of non-Hodgkin lymphomas. PTCL-not otherwise specified is the most common subtype, followed by angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma, anaplastic lymphoma kinase-negative, and enteropathy-associated T-cell lymphoma. This discussion section focuses on the diagnosis and treatment of PTCLs as outlined in the NCCN Guidelines for T-Cell Lymphomas.
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- 2022
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22. Efficacy and safety of mogamulizumab by patient baseline blood tumour burden: a post hoc analysis of the MAVORIC trial.
- Author
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Cowan RA, Scarisbrick JJ, Zinzani PL, Nicolay JP, Sokol L, Pinter-Brown L, Quaglino P, Iversen L, Dummer R, Musiek A, Foss F, Ito T, Rosen JP, and Medley MC
- Subjects
- Antibodies, Monoclonal, Humanized, Humans, Neoplasm Recurrence, Local, Tumor Burden, Mycosis Fungoides, Skin Neoplasms
- Abstract
Background: Mogamulizumab was compared with vorinostat in the phase 3 MAVORIC trial (NCT01728805) in 372 patients with relapsed/refractory mycosis fungoides (MF) or Sézary syndrome (SS) who had failed ≥1 prior systemic therapy. Mogamulizumab significantly prolonged progression-free survival (PFS), with a superior objective response rate (ORR) vs. vorinostat., Objectives: This post hoc analysis was performed to evaluate the effect of baseline blood tumour burden on patient response to mogamulizumab., Methods: PFS, ORR, time to next treatment (TTNT), skin response (modified Severity-Weighted Assessment Tool [mSWAT]) and safety were assessed in patients stratified by blood classification (B0 [n = 126], B1 [n = 62], or B2 [n = 184], indicating increasing blood involvement)., Results: Investigator-assessed PFS was longer for mogamulizumab versus vorinostat across all blood classes, significantly so for B1 and B2 patients. ORR was higher with mogamulizumab than with vorinostat in all blood classification groups and more markedly so with escalating B class (B0: 15.6% vs. 6.5%, P = 0.0549; B1: 25.8% vs. 6.5%, P = 0.2758; B2: 37.4% vs. 3.2%, P < 0.0001). TTNT was significantly longer for patients treated with mogamulizumab versus vorinostat with B1 (12.63 vs. 3.07 months; HR 0.32 [95% CI 0.16-0.67]; P = 0.0018) and B2 (13.07 vs. 3.53 months; HR 0.30 [95% CI 0.21-0.43]; P < 0.0001) blood involvement. In the mogamulizumab arm, 81 patients (43.5%) had ≥50% change in the mSWAT vs. 41 patients (22.0%) with vorinostat; mSWAT improvements with mogamulizumab occurred most often in B1 and B2 patients. Rapid, sustained reductions were seen in CD4
+ CD26- cell counts and CD4:CD8 ratios in mogamulizumab patients for all B classes. Treatment-emergent adverse events were less frequent overall with mogamulizumab and similar in frequency regardless of B class., Conclusions: This post hoc analysis indicates greater clinical benefit with mogamulizumab vs. vorinostat in patients with MF and SS classified as having B1 and B2 blood involvement., (© 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)- Published
- 2021
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23. How we treat advanced stage cutaneous T-cell lymphoma - mycosis fungoides and Sézary syndrome.
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Sethi TK, Montanari F, Foss F, and Reddy N
- Subjects
- Adrenal Cortex Hormones therapeutic use, Aged, Antibodies, Monoclonal therapeutic use, Antineoplastic Agents therapeutic use, Bexarotene therapeutic use, Biomarkers, Tumor blood, Clinical Trials as Topic, Combined Modality Therapy, Delayed Diagnosis, Diagnosis, Differential, Electrons therapeutic use, Hematopoietic Stem Cell Transplantation, Histone Deacetylase Inhibitors therapeutic use, Humans, Interferon-alpha therapeutic use, Male, Mycosis Fungoides diagnosis, Mycosis Fungoides pathology, Mycosis Fungoides physiopathology, Neoplasm Staging, Neoplastic Stem Cells chemistry, Neoplastic Stem Cells pathology, PUVA Therapy, Photopheresis, Prognosis, Retinoids therapeutic use, Sezary Syndrome diagnosis, Sezary Syndrome pathology, Sezary Syndrome physiopathology, Signal Transduction, Skin Neoplasms diagnosis, Skin Neoplasms pathology, Skin Neoplasms physiopathology, T-Lymphocyte Subsets chemistry, T-Lymphocyte Subsets pathology, Mycosis Fungoides therapy, Sezary Syndrome therapy, Skin Neoplasms therapy
- Abstract
T-cell lymphomas (TCLs) constitute a rare subset of non-Hodgkin lymphomas, with mycosis fungoides/Sézary syndrome (MF/SS) being the most common subtype of cutaneous TCLs (CTCLs). Considered an incurable but treatable disease, MF/SS management presents several challenges including diagnostic delays, debilitating effect on patients' quality of life, need for several lines of therapies, multidisciplinary care and cumulative drug toxicities limiting duration of use. The present review intends to provide an overview of the recent advances in our understanding of the biology of CTCL and how these are being leveraged to provide additional treatment options for management of advanced and recurrent disease. In addition, the discussion of the different modalities of treatment is summarised to further outline the importance of multidisciplinary care and early referral to CTCL centres., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)
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- 2021
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24. Adverse cardiovascular events in patients treated with mogamulizumab.
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Kwan JM, Henry ML, Cook K, Higgins A, Cuomo J, Foss F, and Baldassarre LA
- Abstract
Study Objectives: Mogamulizumab is an important treatment for T-cell leukemia and lymphoma. Adverse cardiovascular events (ACE) after mogamulizumab therapy have not been investigated. The aim of the study is to investigate ACE occurrence after mogamulizumab therapy., Methods: The International World Health Organization database, VigiBase, was analyzed from January 2013 to August 2019 for all adverse events, including ACE, that occurred after mogamulizumab treatment. ACE was defined as: cardiac death, myocardial infarction, heart failure, myocarditis, arrhythmia, vasculitis, thrombosis, palpitations and new hypertension., Results: ACE after mogamulizumab therapy affected 28 out of 650 unique patients (4.3%). Heart failure (42.8%) and ventricular arrhythmias (17.85%) were most common. ACE accounted for 10% of all fatal adverse outcomes, and 25% of all ACE were fatal. Time to fatal outcome was significantly shorter for patients with ACE compared to non-cardiovascular events, with a mean of 7.7 days (SD 6.91) vs 73 days (SD 90.7), p = 0.017, respectively. There was an increased total number of adverse cardiovascular events in patients greater than 65 and in Asian countries., Conclusions: Cardiovascular toxicity with mogamulizumab is a possible early occurring adverse outcome associated with high mortality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)
- Published
- 2021
- Full Text
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