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  1. Article ; Online: Disability-related inequalities in health and well-being are mediated by barriers to participation faced by people with disability. A causal mediation analysis.

    Aitken, Zoe / Bishop, Glenda M / Disney, George / Emerson, Eric / Kavanagh, Anne M

    Social science & medicine (1982)

    2022  Volume 315, Page(s) 115500

    Abstract: Large inequalities in health and well-being exist between people with and without disability, in part due to poor socio-economic circumstances, and potentially also related to societal factors including issues associated with accessibility and ... ...

    Abstract Large inequalities in health and well-being exist between people with and without disability, in part due to poor socio-economic circumstances, and potentially also related to societal factors including issues associated with accessibility and participation. To better understand the contribution of societal factors, we used a unique longitudinal survey of disability in Great Britain to quantify the extent to which barriers to participation contribute to poorer health and well-being. We used data from 2354 individuals who participated in three waves of the Life Opportunities Survey between 2009 and 2014 and compared five health and well-being outcomes (self-rated health, anxiousness, life satisfaction, life worth, happiness) between adults who acquired an impairment and those who remained disability-free. Causal mediation analysis was conducted to quantify how much of the effect of disability acquisition on each outcome was explained by barriers to participation in employment, economic life, transport, community, leisure and civic activities, social contact, and accessibility. People who recently acquired a disability had poorer health and well-being compared to people with no disability. Barriers to participation explained 15% of inequalities in self-rated health, 28% for anxiousness, 32% for life satisfaction, 37% for life worth, and 70% for happiness. A substantial proportion of the inequalities in health and well-being experienced by people with recently acquired disability were socially produced, driven by barriers to participation in different life domains. Furthermore, there was evidence that barriers to participation mediated the effect of well-being measured to a greater extent than the more clinically aligned measures, self-reported health and anxiousness. These findings highlight modifiable factors amenable to public health interventions that could lead to substantial improvements in health and well-being for people with disability.
    MeSH term(s) Adult ; Humans ; Mediation Analysis ; Disabled Persons ; Employment ; Surveys and Questionnaires ; Leisure Activities ; Social Participation
    Language English
    Publishing date 2022-11-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 4766-1
    ISSN 1873-5347 ; 0037-7856 ; 0277-9536
    ISSN (online) 1873-5347
    ISSN 0037-7856 ; 0277-9536
    DOI 10.1016/j.socscimed.2022.115500
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Precise Targeted Cleavage of a r(CUG) Repeat Expansion in Cells by Using a Small-Molecule-Deglycobleomycin Conjugate.

    Angelbello, Alicia J / DeFeo, Mary E / Glinkerman, Christopher M / Boger, Dale L / Disney, Matthew D

    ACS chemical biology

    2020  Volume 15, Issue 4, Page(s) 849–855

    Abstract: RNA repeat expansions cause more than 30 neurological and neuromuscular diseases with no known cures. Since repeat expansions operate via diverse pathomechanisms, one potential therapeutic strategy is to rid them from disease-affected cells, using ... ...

    Abstract RNA repeat expansions cause more than 30 neurological and neuromuscular diseases with no known cures. Since repeat expansions operate via diverse pathomechanisms, one potential therapeutic strategy is to rid them from disease-affected cells, using bifunctional small molecules that cleave the aberrant RNA. Such an approach has been previously implemented for the RNA repeat that causes myotonic dystrophy type 1 [DM1, r(CUG)
    MeSH term(s) Animals ; Bleomycin/analogs & derivatives ; Bleomycin/chemistry ; Bleomycin/pharmacology ; Cell Line ; DNA/chemistry ; DNA Cleavage/drug effects ; DNA Damage/drug effects ; DNA-Binding Proteins/genetics ; Mice ; RNA-Binding Proteins/genetics ; Trinucleotide Repeat Expansion/drug effects
    Chemical Substances DNA-Binding Proteins ; Mbnl1 protein, mouse ; RNA-Binding Proteins ; cugamycin ; Bleomycin (11056-06-7) ; deglycobleomycin (78314-57-5) ; DNA (9007-49-2)
    Language English
    Publishing date 2020-03-18
    Publishing country United States
    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.
    ISSN 1554-8937
    ISSN (online) 1554-8937
    DOI 10.1021/acschembio.0c00036
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Genesis of improved quality in imaging through a national Australian echocardiography registry.

    Eccleston, David / Scalia, Gregory / Kearney, Leighton / Cross, David / Cehic, Daniel / Disney, Patrick / Xu, Xiao-Fang / Cain, Peter / Srivastava, Piyush M

    Open heart

    2022  Volume 9, Issue 1

    Abstract: ... E/e', LA area, rhythm, RVSP) by time and state using de-identified data. Key performance outcomes ... variability fell for both EF and E/e' (p<0.002).: Conclusions: This large-scale collaboration provides ...

    Abstract Background: Despite rapid technological advances and growth, quality in imaging has not received the focus seen elsewhere in cardiovascular medicine, resulting in significant gaps between guidelines and practice. Contemporary echocardiography practice requires comprehensive real-time data collection to allow dynamic auditing and benchmarking of key performance indices. The American College of Cardiology (ACC) proposed additional data standardisation, structured reporting identifying key data elements and imaging registries. In the absence of an Australian echocardiography registry, we developed a national clinical quality registry (GenesisCare Cardiovascular Outcomes Echo Registry). We hypothesised that measurement and local reporting of data would improve compliance of echo studies with quality guidelines and hence their clinical value.
    Methods and results: We prospectively collected data on 4 099 281 echocardiographic studies entered directly into a central electronic database from 63 laboratories across four Australian states between 2010 and 2021. Real-time auditing of key data elements and introduction of quality improvement pathways were performed to maximise completeness and uniformity of data acquisition and reporting. We compared completeness of key data element acquisition (AV peak velocity, left ventricular ejection fraction, E/e', LA area, rhythm, RVSP) by time and state using de-identified data. Key performance outcomes benchmarked against the aggregated study cohort and international standards were reported to individual sites to drive quality improvement. Between 2010 and 2014 there were significant improvements in data completeness (72.0%+/-26.8% vs 86.8%+/-13.5%, p=0.02), which were maintained to 2020. In addition, interstate variability fell for both EF and E/e' (p<0.002).
    Conclusions: This large-scale collaboration provides a platform for the development of major quality improvement initiatives in echocardiography. Introduction of local quality assurance programmes via a unified national data set significantly improved the completeness of reporting of key echo quality measures. This in turn significantly improved the quality of, and reduced the interstate variability of, echo data. Developing a centralised database allowed rapid adoption nationally of local quality improvements.
    MeSH term(s) Australia ; Echocardiography ; Humans ; Registries ; Stroke Volume ; United States ; Ventricular Function, Left
    Language English
    Publishing date 2022-05-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2747269-3
    ISSN 2053-3624
    ISSN 2053-3624
    DOI 10.1136/openhrt-2021-001797
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Reprogramming of Protein-Targeted Small-Molecule Medicines to RNA by Ribonuclease Recruitment.

    Zhang, Peiyuan / Liu, Xiaohui / Abegg, Daniel / Tanaka, Toru / Tong, Yuquan / Benhamou, Raphael I / Baisden, Jared / Crynen, Gogce / Meyer, Samantha M / Cameron, Michael D / Chatterjee, Arnab K / Adibekian, Alexander / Childs-Disney, Jessica L / Disney, Matthew D

    Journal of the American Chemical Society

    2021  Volume 143, Issue 33, Page(s) 13044–13055

    Abstract: ... improve selectivity even across different biomolecules, i.e., protein versus RNA. ...

    Abstract Reprogramming known medicines for a novel target with activity and selectivity over the canonical target is challenging. By studying the binding interactions between RNA folds and known small-molecule medicines and mining the resultant dataset across human RNAs, we identified that Dovitinib, a receptor tyrosine kinase (RTK) inhibitor, binds the precursor to microRNA-21 (pre-miR-21). Dovitinib was rationally reprogrammed for pre-miR-21 by using it as an RNA recognition element in a chimeric compound that also recruits RNase L to induce the RNA's catalytic degradation. By enhancing the inherent RNA-targeting activity and decreasing potency against canonical RTK protein targets in cells, the chimera shifted selectivity for pre-miR-21 by 2500-fold, alleviating disease progression in mouse models of triple-negative breast cancer and Alport Syndrome, both caused by miR-21 overexpression. Thus, targeted degradation can dramatically improve selectivity even across different biomolecules, i.e., protein versus RNA.
    MeSH term(s) Benzimidazoles/chemistry ; Benzimidazoles/pharmacology ; Humans ; MicroRNAs/antagonists & inhibitors ; MicroRNAs/metabolism ; Molecular Structure ; Nephritis, Hereditary/drug therapy ; Nephritis, Hereditary/metabolism ; Protein Kinase Inhibitors/chemistry ; Protein Kinase Inhibitors/pharmacology ; Quinolones/chemistry ; Quinolones/pharmacology ; Receptor Protein-Tyrosine Kinases/antagonists & inhibitors ; Receptor Protein-Tyrosine Kinases/metabolism ; Ribonucleases/antagonists & inhibitors ; Ribonucleases/metabolism ; Small Molecule Libraries/chemistry ; Small Molecule Libraries/pharmacology ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/metabolism
    Chemical Substances 4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one ; Benzimidazoles ; MIRN21 microRNA, human ; MicroRNAs ; Protein Kinase Inhibitors ; Quinolones ; Small Molecule Libraries ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; Ribonucleases (EC 3.1.-)
    Language English
    Publishing date 2021-08-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3155-0
    ISSN 1520-5126 ; 0002-7863
    ISSN (online) 1520-5126
    ISSN 0002-7863
    DOI 10.1021/jacs.1c02248
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: First record of Scuttle fly, Megaselia (M) scalaris (Loew) (Diptera

    Laleh Ebrahimi / R. Henry L. Disney / Alireza Haghshenas / Ebrahim Gilasian / Masood Amir-Maafi / Shahram Shahrokhi Khaneghah

    Egyptian Journal of Biological Pest Control, Vol 33, Iss 1, Pp 1-

    Phoridae) as a parasitoid of Sunn pest, Eurygaster integriceps Puton (Hemiptera: Scutelleridae) from Iran

    2023  Volume 4

    Abstract: ... body. This study is a new record of M. scalaris as a parasitoid of E. intergriceps in Iran. ... role in decreasing the population’s level in overwintering sites. In the present study, adults of E ... for fixing and identification. Assessment of dissected adult E. integriceps under a stereomicroscope revealed ...

    Abstract Abstract The Scuttle fly, Eurygaster integriceps Puton (Hemiptera: Scutelleridae) is a key pest of wheat and barley. The pest is univoltine and migrates from wheat fields following harvest to high elevations; then, the following spring it moves back to the fields. Natural enemies may have an important role in decreasing the population’s level in overwintering sites. In the present study, adults of E. integriceps were collected from overwintering sites in Isfahan province, Iran, in October 2022 and transferred to the laboratory. One week after sampling, dead adults were isolated and divided into three groups: one group was dissected under a stereomicroscope, and parasitoid larvae were extracted from the cadavers; the second one was incubated in Petri dishes sealed with parafilm, individually for four weeks, and emerged pupae were collected; and the third group was incubated in the closed boxes, and emerged flies were collected for fixing and identification. Assessment of dissected adult E. integriceps under a stereomicroscope revealed that the insect was parasitized with Megaselia scalaris (Loew) (Diptera: Phoridae) larvae. Per adult, up to 13 larvae were found inside E. integriceps. The last instar larvae were pupated outside the E. integriceps body. This study is a new record of M. scalaris as a parasitoid of E. intergriceps in Iran.
    Keywords Sunn pest ; Eurygaster integriceps ; Megaselia scalaris parasitoid ; Overwintering site ; Agriculture ; S
    Subject code 590
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher SpringerOpen
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Whole-Brain Mapping of Direct Inputs to Dopamine D1 and D2 Receptor-Expressing Medium Spiny Neurons in the Posterior Dorsomedial Striatum.

    Lu, Jiayi / Cheng, Yifeng / Xie, Xueyi / Woodson, Kayla / Bonifacio, Jordan / Disney, Emily / Barbee, Britton / Wang, Xuehua / Zaidi, Mariam / Wang, Jun

    eNeuro

    2021  Volume 8, Issue 1

    Abstract: The posterior dorsomedial striatum (pDMS) is mainly composed of medium spiny neurons (MSNs) expressing either dopamine D1 receptors (D1Rs) or D2Rs. Activation of these two MSN types produces opposing effects on addictive behaviors. However, it remains ... ...

    Abstract The posterior dorsomedial striatum (pDMS) is mainly composed of medium spiny neurons (MSNs) expressing either dopamine D1 receptors (D1Rs) or D2Rs. Activation of these two MSN types produces opposing effects on addictive behaviors. However, it remains unclear whether pDMS D1-MSNs or D2-MSNs receive afferent inputs from different brain regions or whether the extrastriatal afferents express distinct dopamine receptors. To assess whether these afferents also contained D1Rs or D2Rs, we generated double transgenic mice, in which D1R-expressing and D2R-expressing neurons were fluorescently labeled. We used rabies virus-mediated retrograde tracing in these mice to perform whole-brain mapping of direct inputs to D1-MSNs or D2-MSNs in the pDMS. We found that D1-MSNs preferentially received inputs from the secondary motor, secondary visual, and cingulate cortices, whereas D2-MSNs received inputs from the primary motor and primary sensory cortices, and the thalamus. We also discovered that the bed nucleus of the stria terminalis (BNST) and the central nucleus of the amygdala (CeA) contained abundant D2R-expressing, but few D1R-expressing, neurons in a triple transgenic mouse model. Remarkably, although limited D1R or D2R expression was observed in extrastriatal neurons that projected to D1-MSNs or D2-MSNs, we found that cortical structures preferentially contained D1R-expressing neurons that projected to D1-MSNs or D2-MSNs, while the thalamus, substantia nigra pars compacta (SNc), and BNST had more D2R-expressing cells that projected to D2-MSNs. Taken together, these findings provide a foundation for future understanding of the pDMS circuit and its role in action selection and reward-based behaviors.
    MeSH term(s) Animals ; Brain/metabolism ; Brain Mapping ; Corpus Striatum/metabolism ; Dopamine ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neurons/metabolism ; Receptors, Dopamine D1/genetics ; Receptors, Dopamine D1/metabolism ; Receptors, Dopamine D2/genetics ; Receptors, Dopamine D2/metabolism
    Chemical Substances Receptors, Dopamine D1 ; Receptors, Dopamine D2 ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2021-01-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2800598-3
    ISSN 2373-2822 ; 2373-2822
    ISSN (online) 2373-2822
    ISSN 2373-2822
    DOI 10.1523/ENEURO.0348-20.2020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: A Multicenter Study of Patient Acceptability of the IBD Disk Tool and Patient-Reported Disabilities.

    Sharma, Neel / Savelkoul, Edo / Disney, Benjamin / Shah, Ashit / De Silva, Shanika / Pattni, Sanjeev / Iacucci, Marietta / Cooney, Rachel / Ghosh, Subrata

    Digestive diseases and sciences

    2021  Volume 67, Issue 2, Page(s) 457–462

    Abstract: Background: IBD, both Crohn's disease and ulcerative colitis, is associated with significant functional disability. Gastrointestinal symptoms alone are not the sole purpose of the interaction between patients and providers. In order to ascertain ... ...

    Abstract Background: IBD, both Crohn's disease and ulcerative colitis, is associated with significant functional disability. Gastrointestinal symptoms alone are not the sole purpose of the interaction between patients and providers. In order to ascertain patients' disabilities, we utilized the recently developed IBD Disk to help determine their functional concerns and initiate relevant conversation. We aimed to ascertain patient acceptability and their major disabilities.
    Patients and methods: In this multicenter study, IBD patients at their outpatient visit were given the paper version of the IBD Disk. Patients were asked to score their level of disability for each item of the IBD Disk. The completed scores were then shared with their healthcare provider to act as a focus of discussion during the consultation. Patients and clinicians were also asked to provide informal qualitative feedback as to the benefits of the IBD Disk and areas for improvement.
    Results: A total of 377 (female 60%) patients completed the questionnaires over the study period. Patient acceptability scored on a 0-10 Likert scale was excellent. All patients scored all domains of disability. Sleep, energy, and joint pain were the highest scoring domains of the IBD Disk, scoring higher than digestive symptoms. Clinicians and patients agreed that the IBD Disk allowed for ease of communication about disability symptoms and relevance to their day-to-day functioning.
    Conclusion: The IBD Disk is a novel easy-to-use tool to assess the functional disability of patients. We next plan to utilize it in the form of an electronic app internationally and in relation to treatment commencement and escalation.
    MeSH term(s) Abdominal Pain/physiopathology ; Adult ; Arthralgia/physiopathology ; Attitude of Health Personnel ; Fatigue/physiopathology ; Feasibility Studies ; Female ; Gastroenterologists ; Humans ; Inflammatory Bowel Diseases/physiopathology ; Male ; Middle Aged ; Patient Acceptance of Health Care ; Patient Reported Outcome Measures ; Qualitative Research ; Sleep Wake Disorders/physiopathology ; Surveys and Questionnaires
    Language English
    Publishing date 2021-03-15
    Publishing country United States
    Document type Journal Article ; Multicenter Study
    ZDB-ID 304250-9
    ISSN 1573-2568 ; 0163-2116
    ISSN (online) 1573-2568
    ISSN 0163-2116
    DOI 10.1007/s10620-021-06893-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Violence and Mental Health: Does Disability Make a Difference?

    Rachele, Jerome N / Disney, George / Milner, Allison / Emerson, Eric / Krnjacki, Lauren / Kavanagh, Anne M

    Epidemiology (Cambridge, Mass.)

    2019  Volume 31, Issue 1, Page(s) e6–e7

    MeSH term(s) Disabled Persons/psychology ; Humans ; Mental Disorders/epidemiology ; Violence/psychology
    Language English
    Publishing date 2019-11-05
    Publishing country United States
    Document type Letter
    ZDB-ID 1053263-8
    ISSN 1531-5487 ; 1044-3983
    ISSN (online) 1531-5487
    ISSN 1044-3983
    DOI 10.1097/EDE.0000000000001119
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Programming inactive RNA-binding small molecules into bioactive degraders.

    Tong, Yuquan / Lee, Yeongju / Liu, Xiaohui / Childs-Disney, Jessica L / Suresh, Blessy M / Benhamou, Raphael I / Yang, Chunying / Li, Weimin / Costales, Matthew G / Haniff, Hafeez S / Sievers, Sonja / Abegg, Daniel / Wegner, Tristan / Paulisch, Tiffany O / Lekah, Elizabeth / Grefe, Maison / Crynen, Gogce / Van Meter, Montina / Wang, Tenghui /
    Gibaut, Quentin M R / Cleveland, John L / Adibekian, Alexander / Glorius, Frank / Waldmann, Herbert / Disney, Matthew D

    Nature

    2023  Volume 618, Issue 7963, Page(s) 169–179

    Abstract: Target occupancy is often insufficient to elicit biological activity, particularly for RNA, compounded by the longstanding challenges surrounding the molecular recognition of RNA structures by small molecules. Here we studied molecular recognition ... ...

    Abstract Target occupancy is often insufficient to elicit biological activity, particularly for RNA, compounded by the longstanding challenges surrounding the molecular recognition of RNA structures by small molecules. Here we studied molecular recognition patterns between a natural-product-inspired small-molecule collection and three-dimensionally folded RNA structures. Mapping these interaction landscapes across the human transcriptome defined structure-activity relationships. Although RNA-binding compounds that bind to functional sites were expected to elicit a biological response, most identified interactions were predicted to be biologically inert as they bind elsewhere. We reasoned that, for such cases, an alternative strategy to modulate RNA biology is to cleave the target through a ribonuclease-targeting chimera, where an RNA-binding molecule is appended to a heterocycle that binds to and locally activates RNase L
    MeSH term(s) Humans ; Genes, jun/genetics ; Genes, myc/genetics ; MicroRNAs/antagonists & inhibitors ; MicroRNAs/chemistry ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Nucleic Acid Conformation ; RNA, Messenger/antagonists & inhibitors ; RNA, Messenger/chemistry ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Structure-Activity Relationship ; Substrate Specificity ; Endoribonucleases/chemistry ; Endoribonucleases/metabolism ; Transcriptome
    Chemical Substances 2-5A-dependent ribonuclease (EC 3.1.26.-) ; MicroRNAs ; MIRN155 microRNA, human ; RNA, Messenger ; Endoribonucleases (EC 3.1.-)
    Language English
    Publishing date 2023-05-24
    Publishing country England
    Document type Journal Article
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-023-06091-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Models of Intermediate Care Organization and Staffing at an Academic Medical Center: Considerations of an Inpatient Planning Committee.

    Hager, David N / Dezube, Rebecca / Disney, Sarah M / Flanagan, Eleni / Huang, Shanshan / Kakadiya, Kinjal / Langlotz, Ronald / Lautzenheiser, Matthew B / Street, Lara / Michalek, Andrew / Biddison, Lee D / Desai, Sanjay V / Herzke, Carrie A

    Journal of intensive care medicine

    2022  Volume 37, Issue 10, Page(s) 1288–1295

    Abstract: Rationale: ...

    Abstract Rationale:
    MeSH term(s) Academic Medical Centers ; Humans ; Inpatients ; Nursing Staff, Hospital ; Personnel Staffing and Scheduling ; Workforce
    Language English
    Publishing date 2022-01-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 632828-3
    ISSN 1525-1489 ; 0885-0666
    ISSN (online) 1525-1489
    ISSN 0885-0666
    DOI 10.1177/08850666211062151
    Database MEDical Literature Analysis and Retrieval System OnLINE

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