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Journal articles on the topic 'Innocare'

Author: Grafiati

Published: 29 June 2021

Last updated: 29 July 2025

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1

Zhou, Daobin, Jie Jin, Zheng-zheng Fu, et al. "Efficacy and Safety of Orelabrutinib in Relapsed/Refractory Waldenstrom's Macroglobulinemia Patients." Blood 138, Supplement 1 (2021): 46. http://dx.doi.org/10.1182/blood-2021-149350.

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Abstract Background Waldenstrom's Macroglobulinemia (WM) is a B-cell disorder characterized primarily by bone marrow infiltration with lymphoplasmacytic cells, along with immunoglobulin M (IgM) monoclonal gammopathy. Bruton's tyrosine kinase (BTK) plays a key role in signaling pathways for the survival of WM clone, particular in patients harboring MYD88 L265P mutations. However, due to target selectivity issue, Clinical uses of early BTK inhibitors are still compromised with off-target activities to many other kinases besides BTK. Orelabrutinib is a novel, highly potent small molecule inhibito

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Xu, Wei, Yongping Song, Zengjun Li, et al. "Safety, Tolerability and Efficacy of Orelabrutinib, Once a Day, to Treat Chinese Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Cell Leukemia." Blood 134, Supplement_1 (2019): 4319. http://dx.doi.org/10.1182/blood-2019-123331.

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Bruton's Tyrosine Kinase (BTK) plays a critical role in B-cell receptor (BCR) signaling, which mediates B-cell proliferation, migration, and adhesion. As a therapeutic target, its clinical significance has been well established in multiple subtypes of non-Hodgkin's lymphoma (NHL). Orelabrutinib (ICP-022) is a novel, potent irreversible BTK inhibitor with much improved target selectivity in comparison to Ibrutinib and Acalabrunitib, which leads to improved safety profiles. With a proprietary formulation, Orelabrutinib achieves high bioavailability comparing to other BTK inhibitors. Results of P

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Song, Yuqin, Yongping Song, Lihong Liu, et al. "Safety and Efficacy of Orelabrutinib Monotherapy in Chinese Patients with Relapsed or Refractory Mantle Cell Lymphoma: A Multicenter, Open-Label, Phase II Study." Blood 134, Supplement_1 (2019): 755. http://dx.doi.org/10.1182/blood-2019-126305.

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Mantle cell lymphoma (MCL), a subtype of aggressive B-cell non-Hodgkin lymphoma (NHL), remains challenging with unsatisfied outcomes from standard therapy. The clinical significance of Bruton's Tyrosine Kinase (BTK) inhibitors has been validated in multiple subtypes of NHL. Ibrutinib, the first BTK inhibitor, has been approved by FDA for the treatment of refractory and relapse (r/r) MCL. In spite of encouraging efficacy, clinically often referred adverse events such as diarrhea, bleeding and atrial fibrillation, respectively following ibrutinib treatment. It has been hypothesized that poor tar

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Xu, Wei, Yongping Song, Tingyu Wang, et al. "Updated Results from the Phase II Study of Orelabrutinib Monotherapy in Chinese Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Cell Leukemia." Blood 136, Supplement 1 (2020): 26–27. http://dx.doi.org/10.1182/blood-2020-134531.

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Orelabrutinib (ICP-022) is a novel and highly selective irreversible BTK inhibitor. We previously reported that orelabrutinib had high bioavailability with ~100% BTK occupancy at 24 hours at 150 mg daily dosing regimen and demonstrated excellent safety and efficacy profiles at median follow-up of 8.7 months in a Phase I/II trial of refractory/relapsed (r/r) CLL/SLL (Chronic Lymphocytic Leukemia/Small Cell Leukemia). Here we present an updated analysis of efficacy and safety results from the clinical study of Orelabrutinib in Chinese patients with r/r CLL/SLL following extended treatment. This

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Li, R., X. Zhu, S. Liu, et al. "LB0005 ORELABRUTINIB, AN IRREVERSIBLE INHIBITOR OF BRUTON’S TYROSINE KINASE (BTK), FOR THE TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS (SLE): RESULTS OF A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE IB/IIA DOSE-FINDING STUDY." Annals of the Rheumatic Diseases 81, Suppl 1 (2022): 210.2–210. http://dx.doi.org/10.1136/annrheumdis-2022-eular.5086a.

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BackgroundOrelabrutinib is an oral, highly-selective, irreversible inhibitor of Bruton’s tyrosine kinase (BTK). Orelabrutinib has been approved for the treatment of B cell malignancies in China. Two distinct lupus animal models showed significant efficacy of orelabrutinib in reducing disease activity, which supported the clinical development of orelabrutinib in Systemic Lupus Erythematosus (SLE).ObjectivesThis phase Ib/IIa, randomized, double-blind, placebo-controlled, dose-finding study aimed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), preliminary effic

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Song, Yuqin, Wei Xu, Yongping Song, et al. "Pooled Analysis of Safety Data from Clinical Trials of Orelabrutinib Monotherapy in Hematologic Malignancies." Blood 136, Supplement 1 (2020): 43. http://dx.doi.org/10.1182/blood-2020-140172.

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Background: Bruton tyrosine kinase (BTK) is one of the key kinases implicated in the pathogenesis of multiple B cell malignancies. Orelabrutinib is a novel, highly selective and potent irreversible BTK inhibitor with minimal activities against other kinases (ITK, EGFR, ERBB2, etc.). As thus orelabrutinib may avoid off-target related adverse events and shall have improved safety profiles comparing to other BTK inhibitors. Here we present the safety profile of orelabrutinib analyzed based on data from 5 ongoing clinical studies in B cell malignancies (Table 1). Methods: Safety data of 266 patien

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Song, Yuqin, Yongping Song, Lihong Liu, et al. "Long-Term Safety and Efficacy of Orelabrutinib Monotherapy in Chinese Patients with Relapsed or Refractory Mantle Cell Lymphoma: A Multicenter, Open-Label, Phase II Study." Blood 136, Supplement 1 (2020): 1. http://dx.doi.org/10.1182/blood-2020-141781.

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Background: In spite of years of effort, Mantle Cell Lymphoma (MCL) remains a clinical challenge. The clinical significance of Bruton's Tyrosine Kinase (BTK) inhibitor has been validated with the approvals by FDA for the treatment of multiple subtypes of NHL including refractory and relapse (r/r) MCL. However, some serious adverse events (AEs) due to poor target selectivity (inhibition of EGFR, TEC, BMX and others), such as diarrhea, sever bleeding and atrial fibrillation, remain as challenges in clinic. Orelabrutinib is a novel, potent irreversible BTK inhibitor with high selectivity for BTK.

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8

Xu, Wei, Yongping Song, Tingyu Wang, et al. "Orelabrutinib Monotherapy in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Updated Long Term Results of Phase II Study." Blood 138, Supplement 1 (2021): 2638. http://dx.doi.org/10.1182/blood-2021-146491.

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Abstract Introduction Orelabrutinib is a novel and highly selective irreversible Bruton tyrosine kinase (BTK) inhibitor approved in China for the treatment of patients with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We previously reported that orelabrutinib had high bioavailability with ~100% BTK occupancy at 24 hours at 150 mg daily dosing regimen and had demonstrated excellent safety and efficacy profiles in a phase II trial of R/R CLL/SLL. Here we present the long-term result of this study. Methods This is an open-label, multicenter, phase I

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Eyre, Toby A., Nirav N. Shah, Steven Le Gouill, et al. "BRUIN MCL-321: A Phase 3 Open-Label, Randomized Study of Pirtobrutinib Versus Investigator Choice of BTK Inhibitor in Patients with Previously Treated, BTK Inhibitor Naïve Mantle Cell Lymphoma (Trial in Progress)." Blood 138, Supplement 1 (2021): 2422. http://dx.doi.org/10.1182/blood-2021-145920.

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Abstract Background: Covalent Bruton's Tyrosine Kinase (BTK) inhibitors (BTKi) have transformed the management of relapsed mantle cell lymphoma (MCL), but these treatments are not curative and the majority of patients will require additional treatment. Covalent BTKi share pharmacologic liabilities (e.g. low oral bioavailability, short half-life) that collectively may lead to suboptimal BTK target coverage especially in rapidly proliferating tumors with high BTK protein turnover such as MCL. To address these limitations, pirtobrutinib, a highly selective, non-covalent BTKi that inhibits both wi

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Guo, Ye, Chunwang Yuan, Weimin Ding, et al. "Gunagratinib, a highly selective irreversible FGFR inhibitor, in patients with previously treated locally advanced or metastatic cholangiocarcinoma harboring FGFR pathway alterations: A phase IIa dose-expansion study." Journal of Clinical Oncology 41, no. 4_suppl (2023): 572. http://dx.doi.org/10.1200/jco.2023.41.4_suppl.572.

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572 Background: ICP-192 (gunagratinib), developed by InnoCare Pharma, is a novel pan-FGFR (fibroblast growth factor receptors) inhibitor that potently and selectively inhibits FGFR 1, 2, 3 and 4 activities irreversibly by covalent binding. Here we present data from an ongoing phase IIa dose-expansion study (ICP-CL-00301 NCT03758664) of gunagratinib in patients with cholangiocarcinoma (CCA). Methods: Eligible participants were aged 18-75 years, had locally advanced or metastatic CCA with FGFR2 fusions or rearrangements, and had disease progression after ≥1 prior treatment or intolerant of prior

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Guo, Ye, Chunwang Yuan, Jieer Ying, et al. "Phase I result of ICP-192 (gunagratinib), a highly selective irreversible FGFR inhibitor, in patients with advanced solid tumors harboring FGFR pathway alterations." Journal of Clinical Oncology 39, no. 15_suppl (2021): 4092. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.4092.

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4092 Background: ICP-192 (gunagratinib), developed by InnoCare Pharma, is a novel pan-FGFR (fibroblast growth factor receptors) inhibitor that potently and selectively inhibits FGFR activities irreversibly by covalent binding. Preclinical data showed that gunagratinib overcomes the acquired resistance to the first-generation reversible FGFR inhibitors, e.g., infigratinib. ICP-CL-00301 is a phase I, first-in-human, clinical study which includes a dose escalation followed by dose expansion. The safety and tolerability as well as pharmacokinetics/pharmacodynamics (PK/PD) of gunagratinib were eval

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Grzesik, Benjamin, Tom Baumann, Thomas Walter, et al. "InnoCube—A Wireless Satellite Platform to Demonstrate Innovative Technologies." Aerospace 8, no. 5 (2021): 127. http://dx.doi.org/10.3390/aerospace8050127.

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A new innovative satellite mission, the Innovative CubeSat for Education (InnoCube), is addressed. The goal of the mission is to demonstrate “the wireless satellite”, which replaces the data harness by robust, high-speed, real-time, very short-range radio communications using the SKITH (SKIpTheHarness) technology. This will make InnoCube the first wireless satellite in history. Another technology demonstration is an experimental energy-storing satellite structure that was developed in the previous Wall#E project and might replace conventional battery technology in the future. As a further payl

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Nurhayati, Endang, Venny Indria Ekowati, and Ines Ika Saputri. "Improving Softskills of College Students in PPBSBJ Course With Adaptation of The Innocamp Method." Jurnal Penelitian Humaniora 23, no. 1 (2019): 34–48. http://dx.doi.org/10.21831/hum.v23i1.24465.

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This study was aimed at improving student softskills in solving problems on the development, training, and preservation of language, literature, and Javanese culture in practice in Mata Kuliah Pembinaan Bahasa, Sastra, dan Budaya Jawa (PPBSBJ) course with the adaptation of the innocamp method. It was categorized as quantitative descriptive study. The instruments used were: (1) questionnaire of pretest and posttest, and (2) observation sheet. The qualitative data in this study were obtained by two methods, namely: literature and field studies with interviews and questionnaires. While quantitati

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Li, Yijing, Yang Liu, Joseph McIntosh, et al. "AZD4320 Is a Novel and Potent BCL-2/XL Dual Inhibitor in Targeting Aggressive Mantle Cell Lymphoma." Blood 136, Supplement 1 (2020): 44. http://dx.doi.org/10.1182/blood-2020-140775.

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Introduction: Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin's lymphoma. It is an incurable disease with frequent relapse from chemotherapies, targeted therapies, and cell therapies. Dysregulated expression of BCL-2 family members resulting in enhanced cell survival frequently occurs in many cancer types and often contributes to the development of therapeutic resistance. The BCL-2 inhibitor venetoclax has been shown to be effective in treating refractory/relapsed MCL patients. However, resistance often occurs and one of the underlying mechanisms of this resistance is the in

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Varma, Ashwin, William B. Feldman, Aaron S. Kesselheim, and Edward R. Cliff. "Abstract 929: Characterizing first- & second-generation follow on drugs: Clinical trial & development timelines of Bruton tyrosine kinase (BTK) inhibitors." Cancer Research 84, no. 6_Supplement (2024): 929. http://dx.doi.org/10.1158/1538-7445.am2024-929.

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Abstract Once a promising new cancer therapy emerges, other manufacturers often develop drugs with the same molecular target. Some follow on drugs offer meaningful benefit via improved efficacy or reduced toxicity, but others offer minimal benefit. We hypothesized there are two cohorts of follow on drugs: those developed concurrently before efficacy & safety of the therapy is established (first generation) & those developed as follow ons after that point (second generation). We analyzed BTK inhibitor (BTKi) development to evaluate patterns of concurrent & follow on development. Met

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Villamarín-Bello, Beatriz, Berta Uriel-Latorre, Florentino Fdez-Riverola, María Sande-Meijide, and Daniel Glez-Peña. "Gold Standard Evaluation of an Automatic HAIs Surveillance System." BioMed Research International 2019 (September 23, 2019): 1–10. http://dx.doi.org/10.1155/2019/1049575.

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Hospital-acquired Infections (HAIs) surveillance, defined as the systematic collection of data related to a certain health event, is considered an essential dimension for a prevention HAI program to be effective. In recent years, new automated HAI surveillance methods have emerged with the wide adoption of electronic health records (EHR). Here we present the validation results against the gold standard of HAIs diagnosis of the InNoCBR system deployed in the Ourense University Hospital Complex (Spain). Acting as a totally autonomous system, InNoCBR achieves a HAI sensitivity of 70.83% and a spe

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17

Forni, Pier Massimo. "Forme innocue nel [French left quote]Decameron[French right quote]." MLN 104, no. 1 (1989): 39. http://dx.doi.org/10.2307/2904990.

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18

Jordan, Alexa A., Joseph McIntosh, Yang Liu, et al. "Targeting Antibody Checkpoint Fcgriib Using Monoclonal Antibody BI-1206 to Overcome Therapeutic Resistance in Mantle Cell Lymphoma." Blood 136, Supplement 1 (2020): 35. http://dx.doi.org/10.1182/blood-2020-140849.

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Mantle cell lymphoma (MCL) is a rare but aggressive B-cell non-Hodgkin's lymphoma that represents 6% of all lymphomas in the United States. Recent therapies including anti-CD20 antibody rituximab, BTK inhibitors, and BCL-2 inhibitors alone or in combination have shown great anti-MCL efficacy. However, primary and acquired resistance to one or multiple therapies commonly occurs, resulting in poor clinical outcome. Therefore, resistance to such therapies is currently an unmet clinical challenge in MCL patients. Therapeutic strategies to overcome this resistance holds promise to significantly imp

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Li, Yijing, Yang Liu, Yuxuan Che, et al. "Combination Therapy of Bcl-2/X L dual Inhibitor AZD0466 with Acalabrutinib to Overcome Therapeutic Resistance in Aggressive R/R Mantle Cell Lymphoma." Blood 138, Supplement 1 (2021): 1867. http://dx.doi.org/10.1182/blood-2021-151609.

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Abstract Introduction As a rare form of non-Hodgkin's lymphoma, mantle cell lymphoma (MCL) is an aggressive subtype. This is largely due to frequent relapses after therapies including paradigm shifting therapies BTK inhibitors (BTKi), such as ibrutinib and acalabrutinib, and Bcl-2 inhibitor (Bcl-2i) venetoclax after long-term treatment in the clinic. Dysregulation of Bcl-2 and Bcl-X L, contributes to therapeutic resistance in MCL. AZD0466 is a novel and highly potent Bcl-2/X L dual inhibitor with active moiety AZD4320. Our preliminary data showed AZD4320 is potent in inhibiting cell viability

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Bansal, Radhika, Paschalis Vergidis, Pritish K. Tosh, et al. "Vaccine Titers in Lymphoma Patients Receiving Chimeric Antigen Receptor T Cell Therapy." Blood 138, Supplement 1 (2021): 3857. http://dx.doi.org/10.1182/blood-2021-153500.

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Abstract Background: While CD19 chimeric antigen receptor T cell therapy (CAR-T) therapy does not use myeloablative chemotherapy, patients with aggressive lymphoma treated with CAR-T are immunosuppressed from lymphodepletion chemotherapy, and prolonged B cell aplasia and hypogammaglobulinemia from CAR-T. The impact of CAR-T on immunologic protection from vaccine-preventable diseases (and thus the need to revaccinate) has not been formally studied. We report the vaccine titers of patients treated with CAR-T at Mayo Clinic, Rochester. Methods: We conducted a retrospective chart review of patient

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Liu, Yang, Vivian Changying Jiang, Joseph McIntosh, Alexa A. Jordan, Yijing Li, and Michael Wang. "Overcoming CAR T Resistance with Non-Covalent BTK Inhibitor Loxo-305 in Mantle Cell Lymphoma." Blood 136, Supplement 1 (2020): 10. http://dx.doi.org/10.1182/blood-2020-137645.

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Background: Mantle cell lymphoma (MCL) is a distinctive B-cell non-Hodgkin's lymphoma characterized by poor prognosis. Despite clinical success of the covalent Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, a subset of patients need to discontinue ibrutinib therapy due to treatment related adverse events, which are primarily caused by off-target effects. Furthermore, primary or acquired resistance to ibrutinib continues to emerge and often leads to dismal clinical outcomes. Therefore, exploration of more target-specific BTK inhibitors is crucial to minimize the adverse events and provide

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Liu, Yang, Shuangtao Zhao, Changying Changying Jiang, et al. "Interrogation of Dysregulated Pathways Enables Precision Medicine in Mantle Cell Lymphoma." Blood 136, Supplement 1 (2020): 33. http://dx.doi.org/10.1182/blood-2020-140794.

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Background: Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy that is initially responsive but ultimately relapses after frontline therapy. Although the first-in-class Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has achieved a 68% overall response rate in relapsed/refractory MCL patients, most experience disease progression after ibrutinib treatment. Furthermore, the diverse heterogeneity of molecular alterations in each patient makes improving patient outcome with a uniform regimen extremely challenging. Therefore, identification of effective drug therapies, especially pers

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Fontana, Piero, Urs Boutellier, and Marco Toigo. "Non-invasive haemodynamic assessments using Innocor™ during standard graded exercise tests." European Journal of Applied Physiology 108, no. 3 (2009): 573–80. http://dx.doi.org/10.1007/s00421-009-1252-x.

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Mansano, Josyane, and Elias Marques de Medeiros Neto. "RELEITURA DA TUTELA DE EVIDÊNCIA BASEADA EM PRECEDENTES." REVISTA BRASILEIRA DE DIREITO PROCESSUAL 29, no. 116 (2021): 1–24. http://dx.doi.org/10.52028/rbdpro.v9i116.210703sp.

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The CPC has greatly innocame the systematics of provisional injunction, when it regulates the protection of evidence, in art. 311. The purpose of this study is a rereading of Art. 311, in order to demonstrate the importance of the institute of evidence protection when it is based on precedents. And the challenge would be to apply this institute not only in the precedents based on cases of repetitive thesis and binding summary, but also in the hypotheses provided for in art. 927, of the CPC, and in the provisions of Art. 332 of the CPC. Therefore, what is intended is the expansion of the hypoth

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Radwan, Marwa, Nashwa Helmy, and Mohamed Mousa. "Assessment of Proteomic and Molecular Techniques in Isolation of Listeria Monocytogenes in Minced Meat." Alexandria Journal of Veterinary Sciences 74, no. 2 (2022): 31. http://dx.doi.org/10.5455/ajvs.19829.

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Listeria monocytogenes is one of the emerging pathogens worldwide. The aim of this study was to evaluate and Assess different techniques; Conventional cultural methods; Biochemical identification; Automated Biochemical identification (Vitek 2 compact); Proteomic identification MALDI-TOF MS and Molecular identification (RT- PCR) in Isolation and Identification of Listeria monocytogenes in minced meat retailed in local markets in Alexandria City, Egypt. Prevalence of suspected listeria spp. isolated from examined samples of minced meat by conventional culture method were 65% (65/100), while prev

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Jiang, Vivian Changying, Shaojun Zhang, Junwei Lian, et al. "Single Cell Transcriptomic Evolution and Resistance Mechanisms of BTK and BCL-2 Inhibition in Mantle Cell Lymphoma." Blood 136, Supplement 1 (2020): 33–34. http://dx.doi.org/10.1182/blood-2020-140882.

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Introduction: Mantle cell lymphoma (MCL) is a rare and aggressive subtype of B-cell non-Hodgkin's lymphoma with high risk of relapse after frontline therapies. Ibrutinib and venetoclax are two efficacious therapies for refractory/relapsed MCL patients. However, resistance to these therapies occurs frequently and is an urgent unmet clinical need. To understand the underlying mechanism of how intra- and inter-tumor heterogeneity (ITH) and its immune microenvironment contributes to therapeutic resistance, we performed a state-of-art single cell RNA sequencing on longitudinal samples from ibrutini

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Lian, Junwei, Yu Xue, Alexa A. Jordan, et al. "Targeting Transcription Checkpoint Using a Novel CDK9 Inhibitor in Mantle Cell Lymphoma." Blood 136, Supplement 1 (2020): 28–29. http://dx.doi.org/10.1182/blood-2020-140865.

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Introduction Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma that accounts for 5-8% of all non-Hodgkin lymphomas. Despite the Bruton's tyrosine kinase inhibitor ibrutinib and the BH3 mimetic BCL2 inhibitor venetoclax (ABT-199) have proven to be effective therapeutic strategies for MCL, most patients often experience disease progression after treatment. Thus, developing a novel drug to overcome this aggressive relapsed/refractory malignancy is an urgent need. Cyclin-dependent kinase 9 (CDK9) is a serine/threonine kinase belonging to the CDK family which regulates multiple cellular p

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Bansal, Radhika, Anatilde Gonzalez Guerrico, Henan Zhang, et al. "Peak Absolute Lymphocyte Count Post CAR-T Is Associated with Clinical Response and Survival Outcome in Aggressive Lymphoma." Blood 138, Supplement 1 (2021): 3856. http://dx.doi.org/10.1182/blood-2021-151295.

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Abstract Introduction Chimeric antigen receptor T cell (CAR-T) expansion has been consistently identified as a predictor of clinical response. However, there are no clinically available test to measure CAR-T presence after infusion for the FDA approved CAR-T therapy. We hypothesize that the lymphocyte expansion which can be readily measured as absolute lymphocyte count (ALC) in blood count differential could be a clinically accessible surrogate for CAR-T expansion in patients who receive FDA approved CD19 CAR-T to treat aggressive B-cell non-Hodgkin lymphoma (NHL). We examined the ALC levels i

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Jin, Jingling, Yijing Li, Yang Liu та ін. "Bispecific CD19-CD20 and CD19-CD22 CAR-T Cells with Glycogen Synthase Kinase (GSK)-3β Inhibitor TWS119 Treatment Have Superior Therapeutic Effects on Mantle Cell Lymphoma". Blood 138, Supplement 1 (2021): 1698. http://dx.doi.org/10.1182/blood-2021-150000.

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Abstract Introduction: Chimeric antigen receptor (CAR) - expressing T cells have shown breakthrough clinical successes to hematological malignancies such as diffuse large B cell lymphoma. Intensive development on CAR-T cell therapies are being developed in many common lymphomas. However, the development of CAR-T cell therapies in mantle cell lymphoma (MCL), a rare lymphoma has lagged behind. So far only CD19 CAR-T has been applied to MCL treatment, and MCL frequent relapse from prior CD19 CAR-T therapy with CD19 antigen loss. Bispecific CAR-T cells target two tumor antigens at once could reduc

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Che, Yuxuan, Yang Liu, Lingzhi Li, et al. "Abemaciclib-Based Combinational Therapies to Overcome Therapeutic Resistance in Mantle Cell Lymphoma." Blood 136, Supplement 1 (2020): 33–34. http://dx.doi.org/10.1182/blood-2020-140856.

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Introduction The past decades witnessed dramatic improvement of overall survival rate of mantle cell lymphoma (MCL) patients by constant efforts in developing novel therapeutic strategies that include ibrutinib and venetoclax. Nevertheless, resistance is still a major challenge in refractory/relapsed MCL patients. Chromosomal translocation t(11:14)(q13:q32) of the cyclin D1 (CCND1) gene is the hallmark of MCL, which leads to overexpression of cyclin D1. This overexpression promotes aberrant cell cycle progression by activating CDK4/6. Abemaciclib is a selective CDK4/6 inhibitor used as a clini

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Desai, Sanjal H., Betsy Laplant, William R. Macon, et al. "Lenalidomide/RCHOP (R2CHOP) Produces High Response Rates and Overall Survival in New, Untreated Diffuse Large B Cell Lymphoma Transformed from Follicular Lymphoma- Results from MC078E." Blood 136, Supplement 1 (2020): 47–48. http://dx.doi.org/10.1182/blood-2020-141298.

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Introduction: Transformation of low grade follicular lymphoma (FL) to diffuse large B cell lymphoma (DLBCL) carries a poor prognosis. In retrospective studies, 5-year survival of transformed DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) without autologous stem cell transplant is 40-60%, underscoring need to improve frontline treatment of transformed DLBCL beyond R-CHOP. The overall response rate (ORR) to lenalidomide used as a single agent for relapsed transformed non Hodgkin lymphoma was 45% with 21% complete response (CR) rate and a median d

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Sheth, Shreya S., Dawn M. Maxey, Alice E. Drain, and Jeffrey A. Feinstein. "Validation of the Innocor Device for Noninvasive Measurement of Oxygen Consumption in Children and Adults." Pediatric Cardiology 34, no. 4 (2012): 847–52. http://dx.doi.org/10.1007/s00246-012-0555-6.

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Li, Yijing, Yang Liu, Yuxuan Che, et al. "Dual Targeting Bcl-2 By Venetoclax and Mcl-1 By AZD5991 to Overcome Therapeutic Resistance in Aggressive R/R Mantle Cell Lymphoma." Blood 138, Supplement 1 (2021): 1181. http://dx.doi.org/10.1182/blood-2021-151062.

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Abstract Introduction Mantle cell lymphoma (MCL) is an aggressive subtype of non-Hodgkin's lymphoma. Frequent relapse from prior therapies remains a major medical challenge. BTK inhibitors (BTKi), such as ibrutinib and acalabrutinib, have demonstrated clinical benefit in MCL patients, however, resistance to BTKi is acquired by most MCL patients following initial response in the clinic. Unbalanced pro- and anti-apoptotic proteins have been shown to contribute to therapeutic resistance. Bcl-2 inhibitor venetoclax was approved by FDA to treat chronic lymphocytic leukemia, small lymphocytic lympho

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Jiang, Vivian Changying, Qingsong Cai, Dapeng Hao, et al. "Single Cell Transcriptomic Profiling of Patient-Derived Xenografts of Mantle Cell Lymphoma Reveals a Special Tumor Cell Population: Seed Cells for Disease Dissemination and Progression." Blood 138, Supplement 1 (2021): 1319. http://dx.doi.org/10.1182/blood-2021-149280.

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Abstract Introduction Mantle cell lymphoma (MCL) patients often presents at later stages and progress through its disease course by frequent involvement of multiple dissemination sites including spleen, liver, bone marrow (BM), peripheral blood (PB), and gastrointestinal tract (GI). This devious behavior translates into high degree of clinicopathologic heterogeneity, which may compromise therapies and promote relapse. Therefore, dissecting the cellular and molecular profiling and trafficking is critical in understanding the role of tissue tropism and evolution patterns contributing to its biol

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Khurana, Arushi, Matthew Hathcock, Radhika Bansal, et al. "Response to Bridging Therapy As a Predictor of Outcomes for Chimeric Antigen Receptor Therapy in Large B-Cell Lymphoma." Blood 138, Supplement 1 (2021): 3841. http://dx.doi.org/10.1182/blood-2021-154186.

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Abstract Background: Bridging therapy (BT) was not allowed in the ZUMA-1 pivotal trial for axicabtagene ciloleucel (axi-cel) chimeric antigen receptor T-cell therapy (CAR-T) . Since then, several real-world studies have shown the use of bridging therapy to be associated with worse overall survival, duration of response, and complete remission rates. In addition, patients requiring BT during CAR-T manufacturing have a more aggressive and higher tumor burden of disease, also factors associated with poor outcomes. Therefore, factors that can predict outcomes in this high-risk patient cohort are r

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Liu, Yang, Changying Jiang, Fangfang Yan, et al. "Pirtobrutinib Overcomes Ibrutinib and Venetoclax Resistance in Mantle Cell Lymphoma." Blood 138, Supplement 1 (2021): 1182. http://dx.doi.org/10.1182/blood-2021-151401.

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Abstract Background Mantle cell lymphoma (MCL) is a rare and aggressive B-cell lymphoma characterized by poor prognosis. Although remarkable therapeutic advances have been made by covalent Bruton's tyrosine kinase (BTK) inhibition and CAR T cell therapy, therapeutic resistance inevitably occurs and leads to dismal clinical outcome. Pirtobrutinib (LOXO-305) is a next-generation, highly selective and non-covalent BTK inhibitor. A phase 1/2 BRUIN study showed that pirtobrutinib demonstrated promising efficacy in heavily pretreated MCL patients with or without prior covalent BTK inhibition. Here,

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Che, Yuxuan, Yang Liu, Yijing Li, et al. "Abemaciclib in Combination with Copanlisib to Overcome Therapeutic Resistance in Mantle Cell Lymphoma." Blood 138, Supplement 1 (2021): 2253. http://dx.doi.org/10.1182/blood-2021-150942.

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Abstract Introduction Although novel therapeutic strategies including BTK and Bcl-2 inhibitors have dramatically improved the prognosis of MCL patients, resistance to these treatments is inevitable. We recently reported that the tumor suppressor gene CDKN2A were commonly deleted in ibrutinib-resistant tumors, leading to upregulation of CDK4/6 signaling. Among the other hallmarks are the mTOR/PI3K, Myc and OXPHOS pathways. Therefore, we attempt to exploit combinatory targeting of CDK4/6 and PI3K pathways to overcome therapy resistance using in vitro and PDX models. Methods Ibrutinib or venetocl

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Yao, Yixin, Lingzhi Li, Yuxuan Che, et al. "Targeting the Synthetic Lethality Interaction of MTAP and PRMT5 to Overcome Drug Resistance and Enhance Anti-Cancer Immunity in Mantle Cell Lymphoma." Blood 136, Supplement 1 (2020): 15. http://dx.doi.org/10.1182/blood-2020-138553.

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Background: Complex genetic, epigenetic alterations and metabolic reprogramming are among the hallmarks of mantle cell lymphoma, an aggressive B-cell type of non-Hodgkin's lymphoma. CDKN2A and MTAP are frequently co-deleted in human cancers including MCL. Deletion of MTAP gene results in the accumulation of methylthioadenosine (MTA), a selective inhibitor of protein arginine methyltransferase 5 (PRMT5), signifying a dependence of MTAP deleted tumors on PRMT5. PRMT5 plays an important role in normal cellular processes via epigenetic and post-translational modification of RNA splicing, DNA repai

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Yao, Yixin, Yuxuan Che, Yang Liu, et al. "MCL Cells in Tumor Microenvironment Impair T-Cell Metabolic Fitness and Effector Function." Blood 136, Supplement 1 (2020): 16. http://dx.doi.org/10.1182/blood-2020-139611.

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Background: Mantle cell lymphoma (MCL) is an aggressive, incurable B cell malignancy. Major advances have been achieved with the development of clinically effective targeted agents including BTK and BCL-2 inhibitors. However, patients often relapse after these treatments. The emerging immune therapies combining immune checkpoint blockade and adoptive T-cell transfer are becoming increasingly desirable, but patient responses are heterogeneous, with a significant rate of failure. Tumor microenvironment (TME) plays an important role by inducing immune checkpoint and immune suppressive signaling o

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Jiang, Vivian Changying, Junwei Lian, Shengjian Huang, et al. "Oncogenic MALT1 Promotes Cell Survival and Mediates Ibrutinib Resistance and Ibrutinib-Venetoclax Resistance in Mantle Cell Lymphoma." Blood 136, Supplement 1 (2020): 18. http://dx.doi.org/10.1182/blood-2020-140871.

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Both as monotherapies and in combination, the Bruton's tyrosine kinase inhibitor ibrutinib and the BH3 mimetic BCL2 inhibitor venetoclax have proven to be efficacious and are now widely used treatment options for mantle cell lymphoma (MCL) patients. However, mono- and dual- resistance frequently develops, necessitating investigation into the mechanisms mediating resistance to these therapies. To investigate the mechanism of ibrutinib resistance, we generated two ibrutinib-resistant cells due to marked BTK knockdown via CRISPR/CAS9 from JeKo-1, which is ibrutinib-sensitive and venetoclax-resist

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Jiang, Vivian Changying, Shaojun Zhang, Shuangtao Zhao, et al. "Xeno-MCL: Genomic, Transcriptomic and Pathologic Landscape Associated with Disease Progression, Clonal Evolution and Tissue Tropism in Patient-Derived Xenografts of Mantle Cell Lymphoma." Blood 136, Supplement 1 (2020): 20. http://dx.doi.org/10.1182/blood-2020-140878.

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Mantle cell lymphoma (MCL) is an aggressive subtype of non-Hodgkin lymphoma with poor diagnosis. Frequent relapse to frontline therapies is one of the major medical challenges in MCL. This is likely due to the extremely complex inter- and intra-tumor heterogeneity (ITH) in MCL patients. MCL patients display diverse clinicopathological profiles and tissue dissemination patterns, which can involve both nodal and extra nodal sites, including splenomegaly, hepatomegaly, lymphadenopathy, and involvement of bone marrow (BM), gastrointestinal (GI) tract, peripheral blood (PB), and the central nervous

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Khurana, Arushi, Raphael Mwangi, Stephen M. Ansell, et al. "Estimates and Timing of Therapy Initiation during the First Decade for Patients with Follicular Lymphoma Who Were Observed at Diagnosis." Blood 136, Supplement 1 (2020): 7–8. http://dx.doi.org/10.1182/blood-2020-141011.

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Background: Observation or "wait and watch" (W/W) strategy remains a viable option in the rituximab era for asymptomatic, stage II-IV, low-tumor burden patients with FL grade 1-2, 3A. Studies to date both in pre and post rituximab era have not shown an overall survival benefit from immediate treatment in such low-risk patients.To improve our understanding and to better counsel FL patients on W/W strategy, we sought to estimate the incidence of treatment initiation at landmark time points in our prospectively observed cohort from the Molecular Epidemiology Resource (MER) of the University of Io

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Bayfield, K. J., C. Saunders, E. Alton, and J. C. Davies. "ePS04.3 Comparison of CF and non-CF LCI results using the Exhalyzer D and Innocor™ devices." Journal of Cystic Fibrosis 14 (June 2015): S48. http://dx.doi.org/10.1016/s1569-1993(15)30154-5.

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Nie, Lei, Yang Liu, Yuxuan Che, et al. "Establishment of Patient-Derived Organoid Culture Platform of Mantle Cell Lymphoma." Blood 138, Supplement 1 (2021): 3508. http://dx.doi.org/10.1182/blood-2021-152994.

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Abstract Background Mantle Cell Lymphoma (MCL) is a rare incurable non-Hodgkin's lymphoma despite remarkable recent therapeutic innovations such as CAR T cell therapies. Drug sensitivity and immunotherapy efficacy assays using preclinical tumor models are important in new therapy development. As for preclinical tumor models, in addition to the commonly used mouse model such as patient-derived xenograft (PDX) and genetically engineered mouse models, a 3 rd tumor model, the patient-derived organoid (PDO) in 3D culture model has been established in many types of solid tumors. However, no PDO mode

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Kamel, Serageldin, Li-Wei Chen, Gregory Ravizzini, et al. "Radiomic Phenotypes of High and Low Lesion SUV Components for the Prediction of Refractory Disease in Hodgkin's Lymphoma Patients Treated with ABVD Based Therapy." Blood 138, Supplement 1 (2021): 3996. http://dx.doi.org/10.1182/blood-2021-153517.

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Abstract Background: Hodgkin's lymphoma (HL) is a curable malignancy. However, some patients are refractory to frontline therapy. Early prediction of response to frontline therapy could identify patients who may benefit from more intensive therapy. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has an established role in the management of HL. Radiomic features provide a way of quantifying imaging phenotypes and have shown promising results as predictors of outcomes in different lymphomas. Furthermore, great interest has been focused on the heterogeneit

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Yan, Fangfang, Changying Jiang, Qingsong Cai, et al. "Dynamic Reprogramming and Evolution Associated with Sequential Resistance to Ibrutinib and CAR T Therapy in Mantle Cell Lymphoma." Blood 138, Supplement 1 (2021): 2396. http://dx.doi.org/10.1182/blood-2021-149214.

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Abstract Introduction FDA approval for CD19 chimeric antigen receptor (CAR) T therapy with Brexucabtagene Autoleucel (BA) for relapsed mantle cell lymphoma (MCL) is a milestone advance. However, most patients relapsed after Bruton's tyrosine kinase (BTK) inhibitor ibrutinib therapy and CAR T therapy, making it urgent and essential to uncover the underlying mechanisms that govern resistance to ibrutinib and BA, as well as potential therapeutic targets. Method Two cohorts of primary patient samples were longitudinally collected at pre- and post-ibrutinib therapy (cohort 1, n = 12, samples = 28)

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Jiang, Vivian Changying, Yang Liu, Joseph McIntosh, et al. "Targeting ROR1 Using the Antibody Drug Conjugate Vls-101 in Aggressive Mantle Cell Lymphoma." Blood 136, Supplement 1 (2020): 33. http://dx.doi.org/10.1182/blood-2020-137660.

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ROR1 is a transmembrane receptor with tightly controlled expression during embryonic development. While it is expressed on multiple tumor types it is not expressed in normal adult tissues. ROR1-positive B cell non-Hodgkin's lymphomas (B-NHL) include mantle cell lymphoma (MCL), and diffuse large B cell lymphoma. Given its unique expression pattern, ROR1 represents a tumor-specific therapeutic target with little or no normal tissue toxicity. VLS-101, utilizes the UC-961 anti-ROR1 antibody which is conjugated to monomethyl auristatin E (MMAE) via a cleavable linker. VLS-101/ROR1 complex induce in

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Audil, Hadiyah Y., Paul J. Hampel, Daniel L. Van Dyke, et al. "Impact of Deletion6q23 Identified By FISH in Patients with Chronic Lymphocytic Leukemia." Blood 136, Supplement 1 (2020): 12–13. http://dx.doi.org/10.1182/blood-2020-139068.

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Background: Cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH) are known to differentially impact prognosis in patients with chronic lymphocytic leukemia (CLL). Deletion6q23 (del6q23) has been reported in ~2-3% of CLL patients at diagnosis; however, its prognostic significance remains indeterminate. Methods: We identified previously untreated CLL patients from the Mayo Clinic CLL Database seen between 1/1995 - 2/2020 who had FISH performed. The clinical characteristics, concomitant cytogenetic abnormalities, time to first therapy (TTFT), and overall survival (OS) w

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Bayfield, K., M. McGovern, A. Simpson, et al. "P207 Reliability Of Measurements Using Innocor Breath By Breath Analyser During A Maximal Exercise Test In Cystic Fibrosis Patients." Thorax 69, Suppl 2 (2014): A167—A168. http://dx.doi.org/10.1136/thoraxjnl-2014-206260.336.

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Foo, Lin, Jerome Cornette, Jasmine Tay, and Christoph Lees. "B2. Measurement of cardiac output in a healthy pregnancy cohort: comparison of vicorder and inert gas re-breathing technique (Innocor)." Journal of Maternal-Fetal & Neonatal Medicine 29, sup2 (2016): 7. http://dx.doi.org/10.1080/14767058.2016.1234767.

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