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  1. AU="Arnal, Magdalena"
  2. AU="Holsinger, H"
  3. AU="Herrera-Viedma, Enrique"
  4. AU=Nordbeck Peter
  5. AU="Thomson, Rachael"
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  1. Article: Whole-Blood Gene Expression Profiles Associated with Mortality in Community-Acquired Pneumonia.

    Viasus, Diego / Simonetti, Antonella F / Nonell, Lara / Vidal, Oscar / Meije, Yolanda / Ortega, Lucía / Arnal, Magdalena / Bódalo-Torruella, Marta / Sierra, Montserrat / Rombauts, Alexander / Abelenda-Alonso, Gabriela / Blanchart, Gemma / Gudiol, Carlota / Carratalà, Jordi

    Biomedicines

    2023  Volume 11, Issue 2

    Abstract: 1) Background: Information regarding gene expression profiles and the prognosis of community-acquired pneumonia (CAP) is scarce. We aimed to examine the differences in the gene expression profiles in peripheral blood at hospital admission between ... ...

    Abstract (1) Background: Information regarding gene expression profiles and the prognosis of community-acquired pneumonia (CAP) is scarce. We aimed to examine the differences in the gene expression profiles in peripheral blood at hospital admission between patients with CAP who died during hospitalization and those who survived. (2) Methods: This is a multicenter study of nonimmunosuppressed adult patients who required hospitalization for CAP. Whole blood samples were obtained within 24 h of admission for genome-expression-profile analysis. Gene expression profiling identified both differentially expressed genes and enriched gene sets. (3) Results: A total of 198 samples from adult patients who required hospitalization for CAP were processed, of which 13 were from patients who died. Comparison of gene expression between patients who died and those who survived yielded 49 differentially expressed genes, 36 of which were upregulated and 13 downregulated. Gene set enrichment analysis (GSEA) identified four positively enriched gene sets in survivors, mainly associated with the interferon-alpha response, apoptosis, and sex hormone pathways. Similarly, GSEA identified seven positively enriched gene sets, associated with the oxidative stress, endoplasmic reticulum stress, oxidative phosphorylation, and angiogenesis pathways, in the patients who died. Protein-protein-interaction-network analysis identified
    Language English
    Publishing date 2023-02-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines11020429
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Comorbidity between Alzheimer's disease and major depression: a behavioural and transcriptomic characterization study in mice.

    Martín-Sánchez, Ana / Piñero, Janet / Nonell, Lara / Arnal, Magdalena / Ribe, Elena M / Nevado-Holgado, Alejo / Lovestone, Simon / Sanz, Ferran / Furlong, Laura I / Valverde, Olga

    Alzheimer's research & therapy

    2021  Volume 13, Issue 1, Page(s) 73

    Abstract: Background: Major depression (MD) is the most prevalent psychiatric disease in the population and is considered a prodromal stage of the Alzheimer's disease (AD). Despite both diseases having a robust genetic component, the common transcriptomic ... ...

    Abstract Background: Major depression (MD) is the most prevalent psychiatric disease in the population and is considered a prodromal stage of the Alzheimer's disease (AD). Despite both diseases having a robust genetic component, the common transcriptomic signature remains unknown.
    Methods: We investigated the cognitive and emotional behavioural responses in 3- and 6-month-old APP/PSEN1-Tg mice, before β-amyloid plaques were detected. We studied the genetic and pathway deregulation in the prefrontal cortex, striatum, hippocampus and amygdala of mice at both ages, using transcriptomic and functional data analysis.
    Results: We found that depressive-like and anxiety-like behaviours, as well as memory impairments, are already present at 3-month-old APP/PSEN1-Tg mutant mice together with the deregulation of several genes, such as Ciart, Grin3b, Nr1d1 and Mc4r, and other genes including components of the circadian rhythms, electron transport chain and neurotransmission in all brain areas. Extending these results to human data performing GSEA analysis using DisGeNET database, it provides translational support for common deregulated gene sets related to MD and AD.
    Conclusions: The present study sheds light on the shared genetic bases between MD and AD, based on a comprehensive characterization from the behavioural to transcriptomic level. These findings suggest that late MD could be an early manifestation of AD.
    MeSH term(s) Alzheimer Disease/epidemiology ; Alzheimer Disease/genetics ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor/genetics ; Animals ; Comorbidity ; Depression ; Depressive Disorder, Major/epidemiology ; Depressive Disorder, Major/genetics ; Disease Models, Animal ; Mice ; Mice, Transgenic ; Transcriptome
    Chemical Substances Amyloid beta-Peptides ; Amyloid beta-Protein Precursor
    Language English
    Publishing date 2021-04-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2506521-X
    ISSN 1758-9193 ; 1758-9193
    ISSN (online) 1758-9193
    ISSN 1758-9193
    DOI 10.1186/s13195-021-00810-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Reduced expansion of CD94/NKG2C

    Puiggros, Anna / Blanco, Gonzalo / Muntasell, Aura / Rodríguez-Rivera, María / Nonell, Lara / Altadill, Mireia / Puigdecanet, Eulàlia / Arnal, Magdalena / Calvo, Xavier / Gimeno, Eva / Abella, Eugènia / Abrisqueta, Pau / Bosch, Francesc / Yélamos, José / Ferrer, Ana / López-Botet, Miguel / Espinet, Blanca

    International journal of laboratory hematology

    2021  Volume 43, Issue 5, Page(s) 1032–1040

    Abstract: Introduction: Dysregulated NK cell-mediated immune responses contribute to tumor evasion in chronic lymphocytic leukemia (CLL), although the NK cell compartment in CLL-like monoclonal B-cell lymphocytosis (MBL) is poorly understood. In healthy ... ...

    Abstract Introduction: Dysregulated NK cell-mediated immune responses contribute to tumor evasion in chronic lymphocytic leukemia (CLL), although the NK cell compartment in CLL-like monoclonal B-cell lymphocytosis (MBL) is poorly understood. In healthy individuals, human cytomegalovirus (HCMV) induces the expansion of NK cells expressing high levels of CD94/NKG2C NK cell receptor (NKR) specific for HLA-E.
    Methods: We analyzed the expression of NKG2A, NKG2C, ILT2, KIR, CD161, and CD57 in 24 MBL and 37 CLL. NKG2C was genotyped in these patients and in 81 additional MBL/CLL, while NKG2C gene expression was assessed in 26 cases. In 8 CLL patients with increased lymphocytosis (≥20 × 10
    Results: NKR distribution did not significantly differ between MBL and CLL patients, although they exhibited reduced NKG2C
    Conclusion: Reduced percentages of CD94/NKG2C
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; B-Lymphocytes/pathology ; Cohort Studies ; Cytomegalovirus/isolation & purification ; Cytomegalovirus Infections/complications ; Cytomegalovirus Infections/genetics ; Cytomegalovirus Infections/pathology ; Female ; Gene Deletion ; Humans ; Killer Cells, Natural/pathology ; Leukemia, Lymphocytic, Chronic, B-Cell/complications ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Lymphocytosis/complications ; Lymphocytosis/genetics ; Lymphocytosis/pathology ; Male ; Middle Aged ; NK Cell Lectin-Like Receptor Subfamily C/analysis ; NK Cell Lectin-Like Receptor Subfamily C/genetics ; NK Cell Lectin-Like Receptor Subfamily D/analysis
    Chemical Substances KLRC2 protein, human ; KLRD1 protein, human ; NK Cell Lectin-Like Receptor Subfamily C ; NK Cell Lectin-Like Receptor Subfamily D
    Language English
    Publishing date 2021-02-22
    Publishing country England
    Document type Journal Article
    ZDB-ID 2268590-X
    ISSN 1751-553X ; 1751-5521 ; 0141-9854
    ISSN (online) 1751-553X
    ISSN 1751-5521 ; 0141-9854
    DOI 10.1111/ijlh.13494
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Chronic lymphocytic leukemia-like monoclonal B-cell lymphocytosis exhibits an increased inflammatory signature that is reduced in early-stage chronic lymphocytic leukemia.

    Blanco, Gonzalo / Puiggros, Anna / Sherry, Barbara / Nonell, Lara / Calvo, Xavier / Puigdecanet, Eulàlia / Chiu, Pui Yan / Kieso, Yasmine / Ferrer, Gerardo / Palacios, Florencia / Arnal, Magdalena / Rodríguez-Rivera, María / Gimeno, Eva / Abella, Eugènia / Rai, Kanti R / Abrisqueta, Pau / Bosch, Francesc / Calon, Alexandre / Ferrer, Ana /
    Chiorazzi, Nicholas / Espinet, Blanca

    Experimental hematology

    2021  Volume 95, Page(s) 68–80

    Abstract: Several studies in chronic lymphocytic leukemia (CLL) patients have reported impaired immune cell functions, which contribute to tumor evasion and disease progression. However, studies on CLL-like monoclonal B-cell lymphocytosis (MBL) are scarce. In the ... ...

    Abstract Several studies in chronic lymphocytic leukemia (CLL) patients have reported impaired immune cell functions, which contribute to tumor evasion and disease progression. However, studies on CLL-like monoclonal B-cell lymphocytosis (MBL) are scarce. In the study described here, we characterized the immune environment in 62 individuals with clinical MBL, 56 patients with early-stage CLL, and 31 healthy controls. Gene expression arrays and quantitative reverse transcription polymerase chain reaction were performed on RNA from CD4
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; B-Lymphocytes/metabolism ; B-Lymphocytes/pathology ; Cell Survival ; Clone Cells/metabolism ; Clone Cells/pathology ; Cytokines/blood ; Disease Progression ; Female ; Gene Expression Profiling ; Humans ; Immunoglobulin Heavy Chains/genetics ; Immunoglobulin Variable Region/genetics ; Inflammation/blood ; Inflammation/immunology ; Inflammation/pathology ; Leukemia, Lymphocytic, Chronic, B-Cell/blood ; Leukemia, Lymphocytic, Chronic, B-Cell/immunology ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Lymphocyte Subsets/immunology ; Male ; Middle Aged ; Monocytes/cytology ; Monocytes/immunology ; Monocytes/metabolism ; Paraproteinemias/blood ; Paraproteinemias/immunology ; Paraproteinemias/pathology ; RNA, Neoplasm/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Tissue Array Analysis ; Tumor Escape
    Chemical Substances Cytokines ; Immunoglobulin Heavy Chains ; Immunoglobulin Variable Region ; RNA, Neoplasm
    Language English
    Publishing date 2021-01-07
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 185107-x
    ISSN 1873-2399 ; 0531-5573 ; 0301-472X
    ISSN (online) 1873-2399
    ISSN 0531-5573 ; 0301-472X
    DOI 10.1016/j.exphem.2020.12.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: NGS-based liquid biopsy profiling identifies mechanisms of resistance to ALK inhibitors: a step toward personalized NSCLC treatment.

    Sánchez-Herrero, Estela / Serna-Blasco, Roberto / Ivanchuk, Vadym / García-Campelo, Rosario / Dómine Gómez, Manuel / Sánchez, José M / Massutí, Bartomeu / Reguart, Noemi / Camps, Carlos / Sanz-Moreno, Sandra / Calabuig-Fariñas, Silvia / Jantus-Lewintre, Eloísa / Arnal, Magdalena / Fernández-Orth, Dietmar / Calvo, Virginia / González-Rumayor, Víctor / Provencio, Mariano / Romero, Atocha

    Molecular oncology

    2021  Volume 15, Issue 9, Page(s) 2363–2376

    Abstract: Despite impressive and durable responses, nonsmall cell lung cancer (NSCLC) patients treated with anaplastic lymphoma kinase (ALK) inhibitors (ALK-Is) ultimately progress due to development of resistance. Here, we have evaluated the clinical utility of ... ...

    Abstract Despite impressive and durable responses, nonsmall cell lung cancer (NSCLC) patients treated with anaplastic lymphoma kinase (ALK) inhibitors (ALK-Is) ultimately progress due to development of resistance. Here, we have evaluated the clinical utility of circulating tumor DNA (ctDNA) profiling by next-generation sequencing (NGS) upon disease progression. We collected 26 plasma and two cerebrospinal fluid samples from 24 advanced ALK-positive NSCLC patients at disease progression to an ALK-I. These samples were analyzed by NGS and digital PCR. A tool to retrieve variants at the ALK locus was developed (VALK tool). We identified at least one resistance mutation in the ALK locus in ten (38.5%) plasma samples; the G1269A and G1202R mutations were the most prevalent among patients progressing to first- and second-generation ALK-Is, respectively. Overall, 61 somatic mutations were detected in 14 genes: TP53, ALK, PIK3CA, SMAD4, MAP2K1 (MEK1), FGFR2, FGFR3, BRAF, EGFR, IDH2, MYC, MET, CCND3, and CCND1. Specifically, a deletion in exon 19 in EGFR, a non-V600 BRAF mutation (G466V), and the F129L mutation in MAP2K1 were identified in four patients who showed no objective survival benefit from ALK-Is. Potential ALK-I-resistance mutations were also found in PIK3CA and IDH2. Finally, a c-MYC gain, along with a loss of CCND1 and FGFR3, was detected in a patient progressing on a first-line treatment with crizotinib. We conclude that NGS analysis of liquid biopsies upon disease progression identified different putative ALK-I-resistance mutations in most cases and could be a valuable approach for therapy decision making.
    MeSH term(s) Anaplastic Lymphoma Kinase/drug effects ; Antineoplastic Agents/therapeutic use ; Carcinoma, Non-Small-Cell Lung/blood ; Carcinoma, Non-Small-Cell Lung/cerebrospinal fluid ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Circulating Tumor DNA/blood ; Drug Resistance, Neoplasm/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Lung Neoplasms/blood ; Lung Neoplasms/cerebrospinal fluid ; Lung Neoplasms/drug therapy ; Mutation ; Precision Medicine ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use
    Chemical Substances Antineoplastic Agents ; Circulating Tumor DNA ; Protein Kinase Inhibitors ; Anaplastic Lymphoma Kinase (EC 2.7.10.1)
    Language English
    Publishing date 2021-06-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2415106-3
    ISSN 1878-0261 ; 1574-7891
    ISSN (online) 1878-0261
    ISSN 1574-7891
    DOI 10.1002/1878-0261.13033
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Expression profiling of microRNAs in human bone tissue from postmenopausal women.

    De-Ugarte, Laura / Serra-Vinardell, Jenny / Nonell, Lara / Balcells, Susana / Arnal, Magdalena / Nogues, Xavier / Mellibovsky, Leonardo / Grinberg, Daniel / Diez-Perez, Adolfo / Garcia-Giralt, Natalia

    Human cell

    2018  Volume 31, Issue 1, Page(s) 33–41

    Abstract: Bone tissue is composed of several cell types, which express their own microRNAs (miRNAs) that will play a role in cell function. The set of total miRNAs expressed in all cell types configures the specific signature of the bone tissue in one ... ...

    Abstract Bone tissue is composed of several cell types, which express their own microRNAs (miRNAs) that will play a role in cell function. The set of total miRNAs expressed in all cell types configures the specific signature of the bone tissue in one physiological condition. The aim of this study was to explore the miRNA expression profile of bone tissue from postmenopausal women. Tissue was obtained from trabecular bone and was analyzed in fresh conditions (n = 6). Primary osteoblasts were also obtained from trabecular bone (n = 4) and human osteoclasts were obtained from monocyte precursors after in vitro differentiation (n = 5). MicroRNA expression profiling was obtained for each sample by microarray and a global miRNA analysis was performed combining the data acquired in all the microarray experiments. From the 641 miRNAs detected in bone tissue samples, 346 (54%) were present in osteoblasts and/or osteoclasts. The other 46% were not identified in any of the bone cells analyzed. Intersection of osteoblast and osteoclast arrays identified 101 miRNAs shared by both cell types, which accounts for 30-40% of miRNAs detected in these cells. In osteoblasts, 266 miRNAs were detected, of which 243 (91%) were also present in the total bone array, representing 38% of all bone miRNAs. In osteoclasts, 340 miRNAs were detected, of which 196 (58%) were also present in the bone tissue array, representing 31% of all miRNAs detected in total bone. These analyses provide an overview of miRNAs expressed in bone tissue, broadening our knowledge in the microRNA field.
    MeSH term(s) Aged ; Aged, 80 and over ; Bone and Bones/cytology ; Bone and Bones/metabolism ; Cells, Cultured ; Female ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; MicroRNAs/physiology ; Osteoblasts/metabolism ; Osteoclasts/metabolism ; Postmenopause/genetics ; Postmenopause/metabolism ; Transcriptome/genetics
    Chemical Substances MicroRNAs
    Language English
    Publishing date 2018-01
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 1149134-6
    ISSN 1749-0774 ; 0914-7470
    ISSN (online) 1749-0774
    ISSN 0914-7470
    DOI 10.1007/s13577-017-0181-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Epigenetic footprint enables molecular risk stratification of hepatoblastoma with clinical implications.

    Carrillo-Reixach, Juan / Torrens, Laura / Simon-Coma, Marina / Royo, Laura / Domingo-Sàbat, Montserrat / Abril-Fornaguera, Jordi / Akers, Nicholas / Sala, Margarita / Ragull, Sonia / Arnal, Magdalena / Villalmanzo, Núria / Cairo, Stefano / Villanueva, Alberto / Kappler, Roland / Garrido, Marta / Guerra, Laura / Sábado, Constantino / Guillén, Gabriela / Mallo, Mar /
    Piñeyro, David / Vázquez-Vitali, María / Kuchuk, Olga / Mateos, María Elena / Ramírez, Gema / Santamaría, Manuel López / Mozo, Yasmina / Soriano, Aroa / Grotzer, Michael / Branchereau, Sophie / de Andoin, Nagore García / López-Ibor, Blanca / López-Almaraz, Ricardo / Salinas, José Antonio / Torres, Bárbara / Hernández, Francisco / Uriz, José Javier / Fabre, Monique / Blanco, Julià / Paris, Claudia / Bajčiová, Viera / Laureys, Geneviève / Masnou, Helena / Clos, Ariadna / Belendez, Cristina / Guettier, Catherine / Sumoy, Lauro / Planas, Ramón / Jordà, Mireia / Nonell, Lara / Czauderna, Piotr / Morland, Bruce / Sia, Daniela / Losic, Bojan / Buendia, Marie Annick / Sarrias, Maria Rosa / Llovet, Josep M / Armengol, Carolina

    Journal of hepatology

    2020  Volume 73, Issue 2, Page(s) 328–341

    Abstract: Background & aims: Hepatoblastoma (HB) is a rare disease. Nevertheless, it is the predominant pediatric liver cancer, with limited therapeutic options for patients with aggressive tumors. Herein, we aimed to uncover the mechanisms of HB pathobiology and ...

    Abstract Background & aims: Hepatoblastoma (HB) is a rare disease. Nevertheless, it is the predominant pediatric liver cancer, with limited therapeutic options for patients with aggressive tumors. Herein, we aimed to uncover the mechanisms of HB pathobiology and to identify new biomarkers and therapeutic targets in a move towards precision medicine for patients with advanced HB.
    Methods: We performed a comprehensive genomic, transcriptomic and epigenomic characterization of 159 clinically annotated samples from 113 patients with HB, using high-throughput technologies.
    Results: We discovered a widespread epigenetic footprint of HB that includes hyperediting of the tumor suppressor BLCAP concomitant with a genome-wide dysregulation of RNA editing and the overexpression of mainly non-coding genes of the oncogenic 14q32 DLK1-DIO3 locus. By unsupervised analysis, we identified 2 epigenomic clusters (Epi-CA, Epi-CB) with distinct degrees of DNA hypomethylation and CpG island hypermethylation that are associated with the C1/C2/C2B transcriptomic subtypes. Based on these findings, we defined the first molecular risk stratification of HB (MRS-HB), which encompasses 3 main prognostic categories and improves the current clinical risk stratification approach. The MRS-3 category (28%), defined by strong 14q32 locus expression and Epi-CB methylation features, was characterized by CTNNB1 and NFE2L2 mutations, a progenitor-like phenotype and clinical aggressiveness. Finally, we identified choline kinase alpha as a promising therapeutic target for intermediate and high-risk HBs, as its inhibition in HB cell lines and patient-derived xenografts strongly abrogated tumor growth.
    Conclusions: These findings provide a detailed insight into the molecular features of HB and could be used to improve current clinical stratification approaches and to develop treatments for patients with HB.
    Lay summary: Hepatoblastoma is a rare childhood liver cancer that has been understudied. We have used cutting-edge technologies to expand our molecular knowledge of this cancer. Our biological findings can be used to improve clinical management and pave the way for the development of novel therapies for this cancer.
    MeSH term(s) Biomarkers, Tumor/analysis ; Calcium-Binding Proteins/genetics ; Choline Kinase/antagonists & inhibitors ; Choline Kinase/metabolism ; DNA Methylation ; Drug Discovery/methods ; Epigenesis, Genetic ; Female ; Gene Expression Profiling ; Hepatoblastoma/genetics ; Hepatoblastoma/metabolism ; Hepatoblastoma/mortality ; Hepatoblastoma/pathology ; High-Throughput Screening Assays ; Humans ; Infant ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; Liver Neoplasms/mortality ; Liver Neoplasms/pathology ; Male ; Membrane Proteins/genetics ; Neoplasm Proteins/genetics ; Prognosis ; Risk Assessment/methods ; beta Catenin/genetics
    Chemical Substances BLCAP protein, human ; Biomarkers, Tumor ; CTNNB1 protein, human ; Calcium-Binding Proteins ; DLK1 protein, human ; Membrane Proteins ; Neoplasm Proteins ; beta Catenin ; CHKA protein, human (EC 2.7.1.32) ; Choline Kinase (EC 2.7.1.32)
    Language English
    Publishing date 2020-03-30
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 605953-3
    ISSN 1600-0641 ; 0168-8278
    ISSN (online) 1600-0641
    ISSN 0168-8278
    DOI 10.1016/j.jhep.2020.03.025
    Database MEDical Literature Analysis and Retrieval System OnLINE

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