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  1. Article ; Online: As time goes by: Treatment challenges in elderly people with multiple sclerosis.

    Gelibter, Stefano / Saraceno, Lorenzo / Pirro, Fiammetta / Susani, Emanuela Laura / Protti, Alessandra

    Journal of neuroimmunology

    2024  Volume 391, Page(s) 578368

    Abstract: A demographic shift in multiple sclerosis (MS) is leading to an increased number of elderly people with MS (pwMS) and a rise in late-onset MS (LOMS) cases. This shift adds complexity to the treatment management of these patients, due to enhanced ... ...

    Abstract A demographic shift in multiple sclerosis (MS) is leading to an increased number of elderly people with MS (pwMS) and a rise in late-onset MS (LOMS) cases. This shift adds complexity to the treatment management of these patients, due to enhanced treatment-associated risks and the possible interplay between immunosenescence and disease-modifying therapies (DMTs). In the present paper, we performed a systematic review of the current evidence concerning the relationship between aging and treatment management in elderly pwMS. Our literature search identified 35 original studies relevant to this topic. The gathered evidence consistently indicates a diminished efficacy of DMTs in older pwMS, particularly in preventing disability accrual. Against this background, high-efficacy therapies (HETs) appear to show less benefit over moderate-low-efficacy DMTs in older patients. These data mainly derive from observational retrospective studies or meta-analyses conducted on randomized clinical trials (RCTs). RCTs, however, exclude pwMS older than 55 years, limiting our ability to acquire robust evidence regarding this patient group. Regarding treatment discontinuation in elderly pwMS with stable disease, the available data, which mainly focuses on older injectable DMTs, suggests that their suspension appears to be relatively safe in terms of disease activity. Nevertheless, the first RCT specifically targeting treatment discontinuation recently failed to demonstrate the non-inferiority of treatment discontinuation over continuation, in terms of MRI activity. On the other hand, the evidence on the impact of discontinuation on disease progression is more conflicting and less robust. Furthermore, there is an important lack of studies concerning sequestering DMTs and virtually no data on the discontinuation of anti-CD20 monoclonal antibodies. De-escalation strategy is gaining attention as a de-risking approach alternative to complete treatment discontinuation. It may be defined as the decision to shift from HETs to less potent DMTs in elderly pwMS who have a stable disease. This strategy could reduce treatment-related risks, while minimizing the risk of disease activity and progression potentially associated with treatment discontinuation. This approach, however, remains unexplored due to a lack of studies. Given these findings, the present scenario underlines the urgent need for more comprehensive and robust studies to develop optimized, data-driven treatment strategies for elderly pwMS and LOMS, addressing the unique challenges of MS treatment and aging.
    Language English
    Publishing date 2024-05-14
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 8335-5
    ISSN 1872-8421 ; 0165-5728
    ISSN (online) 1872-8421
    ISSN 0165-5728
    DOI 10.1016/j.jneuroim.2024.578368
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Coming to Terms with a Conundrum: A Case of Primary Progressive Apraxia of Speech due to Corticobasal Degeneration?

    Karantzoulis, Aristotelis / Susani, Emanuela / Ferrarese, Carlo / Appollonio, Ildebrando / Tremolizzo, Lucio

    Case reports in neurology

    2021  Volume 13, Issue 2, Page(s) 483–489

    Abstract: Primary progressive apraxia of speech (PPAOS) is a progressive disorder impairing the motor speech act leaving linguistic function unattained. Although apraxia of speech frequently co-occurs with other neurodegenerative conditions, PPAOS defines a ... ...

    Abstract Primary progressive apraxia of speech (PPAOS) is a progressive disorder impairing the motor speech act leaving linguistic function unattained. Although apraxia of speech frequently co-occurs with other neurodegenerative conditions, PPAOS defines a clinical syndrome where apraxia of speech is the sole or prominent symptom for much of the disease's natural history. Mounting evidence is beginning to fully define this disease as the epiphenomenon of 4-repeat (4R) tau pathology although other pathologic signatures have been reported. Indeed, PPAOS patients generally present a parkinsonian syndrome late into their natural history mostly qualifying for either corticobasal syndrome (CBS) or progressive supranuclear palsy (PSP). This is starting to be reflected in diagnostic criteria for PSP, namely, in the PSP speech and language (SL) subcategory; however, this inclusion is not reflected for CBS. Here, we present a single case of a patient with PPAOS and her clinical follow-up lasting 6 years, from the time she sought our attention to her death which occurred 8 years into the disease. PPAOS was the only and prominent symptom for most of the illness with extrapyramidal signs overtly presenting in the last months of its course. Clinical evaluation, imaging, genetic, and cerebrospinal fluid biomarkers all pointed toward an underlying CBD pathology, albeit the eventual anatomopathological confirmation was not performed. Had her clinical course been more suggestive of PSP, she would have qualified for criteria as PSP-SL. Our case therefore suggests the hypothetic need to discuss the broadening of the existing CBS criteria to encompass isolated PPAOS.
    Language English
    Publishing date 2021-07-20
    Publishing country Switzerland
    Document type Case Reports
    ZDB-ID 2505302-4
    ISSN 1662-680X
    ISSN 1662-680X
    DOI 10.1159/000517367
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Tixagevimab and cilgavimab use in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder during anti-CD20 treatment: A single-center experience.

    Gelibter, Stefano / Pirro, Fiammetta / Saraceno, Lorenzo / Susani, Emanuela / Moioli, Maria Cristina / Puoti, Massimo / Agostoni, Elio Clemente / Protti, Alessandra

    Journal of neuroimmunology

    2023  Volume 383, Page(s) 578199

    Abstract: Background: B-cell-depleting treatments, such as ocrelizumab and rituximab (anti-CD20), reduce humoral response to SARS-CoV-2 in people with Multiple Sclerosis (pwMS) and Neuromyelitis Optica Spectrum Disorder (NMOSD) and are associated with an ... ...

    Abstract Background: B-cell-depleting treatments, such as ocrelizumab and rituximab (anti-CD20), reduce humoral response to SARS-CoV-2 in people with Multiple Sclerosis (pwMS) and Neuromyelitis Optica Spectrum Disorder (NMOSD) and are associated with an increased risk of a more severe course of COVID-19 disease. The combination of tixagevimab and cilgavimab was authorized for COVID-19 prevention in immunocompromised subjects at high risk of severe COVID-19 disease, including patients treated with anti-CD20. Few real-world studies are available regarding the use of tixagevimab/cilgavimab in pwMS/NMOSD. In the present study, we describe the use of tixagevimab/cilgavimab for SARS-CoV-2 pre-exposure prophylaxis in a cohort of pwMS and NMOSD, treated with ocrelizumab and rituximab respectively.
    Methods: 26 subjects were treated with tixagevimab/cilgavimab, while we used 18 patients as the control group. We collected clinical data at baseline in all patients and during scheduled follow up evaluations. SARS-CoV-2 serological status pre- and post-tixagevimab/cilgavimab treatment was available for 10 patients.
    Results: We observed no adverse events following tixagevimab/cilgavimab treatment. Post-tixagevimab/cilgavimab anti-Spike-1-RBD IgG were significantly higher when compared to baseline values. No difference was found when comparing the percentage of COVID-19 infections between groups. All patients infected with SARS-CoV-2 had mild disease which did not require hospitalization. In patients treated with tixagevimab/cilgavimab, the rate of infection among patients exposed to SARS-CoV-2 was lower, without reaching statistical significance. We observed a significantly longer negativization time in the treated group.
    Conclusions: Our results are not consistent with what was observed in the registration trial and some more recent studies. We did not observe a difference in COVID-19 incidence nor in disease severity in MS and NMOSD between treated and untreated patients. Our different results may be partially explained by the change in SARS-CoV-2 variants epidemiology (i.e. reduced efficacy of tixagevimab and cilgavimab against the currently dominant variants) as well as different patient selection included in the trial and different dose of tixagevimab/cilgavimab used in other studies. The present report provides a real-life experience with tixagevimab/cilgavimab in pwMS and NMOSD treated with anti-CD20, with findings that are in line with the current SARS-CoV-2 epidemiology and the recent evidence regarding SARS-CoV-2 variants. Our results warrant further research to best treat patients in the present and future pandemic scenario.
    MeSH term(s) Humans ; SARS-CoV-2 ; Rituximab/therapeutic use ; Multiple Sclerosis/drug therapy ; Neuromyelitis Optica/drug therapy ; COVID-19
    Chemical Substances tixagevimab ; cilgavimab (1KUR4BN70F) ; Rituximab (4F4X42SYQ6)
    Language English
    Publishing date 2023-09-13
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 8335-5
    ISSN 1872-8421 ; 0165-5728
    ISSN (online) 1872-8421
    ISSN 0165-5728
    DOI 10.1016/j.jneuroim.2023.578199
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: SARS-CoV-2 infection after alemtuzumab in a multiple sclerosis patient: milder disease symptoms in comparison with coinfected relatives: a case report and review of the literature.

    Saraceno, Lorenzo / Susani, Emanuela Laura / Marazzi, Maria Raffaella / Moioli, Maria Cristina / Agostoni, Elio Clemente / Protti, Alessandra

    Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

    2021  Volume 42, Issue 12, Page(s) 4881–4884

    Abstract: Literature data reporting SARS-CoV-2 infection in multiple sclerosis (MS) patients recently treated with immunodepleting agents as cladribine and alemtuzumab are very limited. The relationship between iatrogenic immunodeficiency and risk related to SARS- ... ...

    Abstract Literature data reporting SARS-CoV-2 infection in multiple sclerosis (MS) patients recently treated with immunodepleting agents as cladribine and alemtuzumab are very limited. The relationship between iatrogenic immunodeficiency and risk related to SARS-CoV-2 infection and its severe complications is still not clear. Cautiously, the start of immunosuppressant drugs as alemtuzumab and cladribine during the current COVID-19 pandemic is not recommended unless treatment benefits significantly outweigh potential risks. We report the case of a 30-year-old female MS patient infected by SARS-CoV-2 virus 4 months after alemtuzumab II cycle, while she was still leukopenic and lymphopenic. She had no complications and also presented milder COVID-related signs and symptoms as compared to her coinfected relatives (father, mother and her partner). Anti-S1 and S2 SARS-CoV-2 antibodies, tested 1 month and a half after the infection, resulted positive. We review all cases reported in literature of SARS-CoV-2 infection in MS patients treated with alemtuzumab. None of them had complications or severe disease.
    MeSH term(s) Adult ; Alemtuzumab/adverse effects ; COVID-19 ; Female ; Humans ; Multiple Sclerosis/complications ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis/epidemiology ; Pandemics ; SARS-CoV-2
    Chemical Substances Alemtuzumab (3A189DH42V)
    Language English
    Publishing date 2021-08-24
    Publishing country Italy
    Document type Case Reports ; Journal Article ; Review
    ZDB-ID 2016546-8
    ISSN 1590-3478 ; 1590-1874
    ISSN (online) 1590-3478
    ISSN 1590-1874
    DOI 10.1007/s10072-021-05567-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: First report of PSEN2 mutation presenting as posterior cortical atrophy.

    Tremolizzo, Lucio / Susani, Emanuela / Mapelli, Cristina / Isella, Valeria / Bertola, Francesca / Ferrarese, Carlo / Appollonio, Ildebrando

    Alzheimer disease and associated disorders

    2015  Volume 29, Issue 3, Page(s) 249–251

    MeSH term(s) Alzheimer Disease/diagnosis ; Alzheimer Disease/genetics ; Atrophy/genetics ; Genetic Predisposition to Disease ; Genetic Testing/methods ; Humans ; Male ; Middle Aged ; Mutation/genetics ; Neurodegenerative Diseases/genetics ; Neurodegenerative Diseases/pathology ; Pedigree ; Presenilin-2/genetics
    Chemical Substances PSEN2 protein, human ; Presenilin-2
    Language English
    Publishing date 2015-07
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 1002700-2
    ISSN 1546-4156 ; 0893-0341
    ISSN (online) 1546-4156
    ISSN 0893-0341
    DOI 10.1097/WAD.0000000000000052
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Primitive reflexes in amyotrophic lateral sclerosis: prevalence and correlates.

    Tremolizzo, Lucio / Susani, Emanuela / Lunetta, Christian / Corbo, Massimo / Ferrarese, Carlo / Appollonio, Ildebrando

    Journal of neurology

    2014  Volume 261, Issue 6, Page(s) 1196–1202

    Abstract: Identifying frontal impairment in ALS is an important goal albeit disease-dedicated tools are still scarce. For this reason, we decided to consider primitive reflexes (PRs), variably regarded as correlates of frontal release and/or of upper motor neuron ( ...

    Abstract Identifying frontal impairment in ALS is an important goal albeit disease-dedicated tools are still scarce. For this reason, we decided to consider primitive reflexes (PRs), variably regarded as correlates of frontal release and/or of upper motor neuron (UMN) impairment, often in the setting of dementias. Specifically, the aims of this work consisted in assessing the exact prevalence of the combination of seven PRs in ALS, trying to clarify their role as putative proxies of cognitive impairment or of UMN dysfunction. In this cross-sectional study, 50 consecutive ALS outpatients were evaluated for the presence of: palmomental (PM), corneomandibular (CM), glabella tap (MY), rooting, sucking, snout, and grasping reflexes. Cognitive screening was performed by the Frontal Assessment Battery (FAB) and the Weigl's Sorting test (WST); UMN dysfunction was concomitantly evaluated. PM, CM and MY were more frequently detected (62, 52, and 44 % of the ALS sample, respectively), while the other reflexes were under-represented. Patients displaying three or more PRs had significantly lower FAB and WST scores. On the other hand, UMN dysfunction was only moderately associated to PRs. In conclusion, PRs' assessment is a promising complementary tool for screening cognitive impairment in ALS; however, further work will be necessary to establish its added value with respect to already existing ALS-dedicated screening tools for cognition.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Amyotrophic Lateral Sclerosis/epidemiology ; Amyotrophic Lateral Sclerosis/physiopathology ; Analysis of Variance ; Cognition Disorders/etiology ; Female ; Frontal Lobe/physiopathology ; Hand Strength/physiology ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; Prevalence ; Reflex/physiology ; Statistics as Topic ; Sucking Behavior/physiology
    Language English
    Publishing date 2014-04-13
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 187050-6
    ISSN 1432-1459 ; 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
    ISSN (online) 1432-1459
    ISSN 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
    DOI 10.1007/s00415-014-7342-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Muscle ultrasonography for detecting fasciculations in frontotemporal dementia.

    Tremolizzo, Lucio / Susani, Emanuela / Aliprandi, Angelo / Salmaggi, Andrea / Ferrarese, Carlo / Appollonio, Ildebrando

    Amyotrophic lateral sclerosis & frontotemporal degeneration

    2014  Volume 15, Issue 7-8, Page(s) 546–550

    Abstract: Ultrasound detection of muscle fasciculations was recently proposed for assessing lower motor neuron (LMN) dysfunction in ALS patients. Given the continuum between ALS and frontotemporal degeneration (FTD), the aim of the present study was to evaluate ... ...

    Abstract Ultrasound detection of muscle fasciculations was recently proposed for assessing lower motor neuron (LMN) dysfunction in ALS patients. Given the continuum between ALS and frontotemporal degeneration (FTD), the aim of the present study was to evaluate muscle ultrasound (MUS) in FTD both for feasibility and prevalence of fasciculations. Twenty-two FTD patients were examined (five muscles bilaterally: biceps brachii, first dorsalis interosseous, T10 paraspinalis, vastus lateralis, tibialis anterior) with a 7-MHz linear array transducer and a fasciculation score (FS) computed. Twenty-two matched cognitively-intact control subjects and six ALS patients were also included. Results showed that MUS was feasible, reliable and well tolerated in all subjects. Two FTD/MND patients displayed very high FS values, similar to those in ALS patients. The remaining 20 FTD patients displayed a mean FS value significantly higher than the control group with six patients (30%) having FS values out of the range of controls. Disease progression rate correlated with the FS. In conclusion, MUS can be easily applied to FTD patients and represents a non-invasive technique for defining LMN involvement in these patients. LMN dysfunction is a frequent condition in FTD and might identify a subset of patients with a different clinical course.
    MeSH term(s) Aged ; Amyotrophic Lateral Sclerosis/complications ; Fasciculation/diagnostic imaging ; Fasciculation/etiology ; Female ; Frontotemporal Dementia/complications ; Humans ; Male ; Middle Aged ; Muscle, Skeletal/diagnostic imaging ; Muscle, Skeletal/physiopathology ; Statistics, Nonparametric ; Ultrasonography, Doppler
    Language English
    Publishing date 2014-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2705049-X
    ISSN 2167-9223 ; 2167-8421
    ISSN (online) 2167-9223
    ISSN 2167-8421
    DOI 10.3109/21678421.2014.913636
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Positive signs of functional weakness.

    Tremolizzo, Lucio / Susani, Emanuela / Riva, Michele Augusto / Cesana, Giancarlo / Ferrarese, Carlo / Appollonio, Ildebrando

    Journal of the neurological sciences

    2014  Volume 340, Issue 1-2, Page(s) 13–18

    Abstract: Functional (conversion) neurological symptoms represent as one of the most common situations faced by neurologists in their everyday practice. Among them, acute or subacute functional weakness may mimic very prevalent conditions such as stroke or ... ...

    Abstract Functional (conversion) neurological symptoms represent as one of the most common situations faced by neurologists in their everyday practice. Among them, acute or subacute functional weakness may mimic very prevalent conditions such as stroke or traumatic injury. Hence, accurate and reliable positive signs of functional weakness are valuable for obtaining timely diagnosis and treatment, making it possible to avoid unnecessary or invasive tests and procedures up to thrombolysis. We therefore present here a brief overview of the positive neurological signs of functional weakness available, both in the lower and in the upper limbs, moving from a historical perspective to their relevance in current clinical practice.
    MeSH term(s) Animals ; Humans ; Muscle Weakness ; Nervous System Diseases/complications ; Nervous System Diseases/diagnosis ; Nervous System Diseases/therapy ; Practice Guidelines as Topic ; Somatoform Disorders/complications ; Somatoform Disorders/diagnosis ; Somatoform Disorders/therapy
    Language English
    Publishing date 2014-05-15
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 80160-4
    ISSN 1878-5883 ; 0022-510X ; 0374-8642
    ISSN (online) 1878-5883
    ISSN 0022-510X ; 0374-8642
    DOI 10.1016/j.jns.2014.03.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Behavioural But Not Cognitive Impairment Is a Determinant of Caregiver Burden in Amyotrophic Lateral Sclerosis.

    Tremolizzo, Lucio / Pellegrini, Andrea / Susani, Emanuela / Lunetta, Christian / Woolley, Susan C / Ferrarese, Carlo / Appollonio, Ildebrando

    European neurology

    2016  Volume 75, Issue 3-4, Page(s) 191–194

    Abstract: Background: Caregivers of patients affected by amyotrophic lateral sclerosis (ALS) are involved with great determination in the treatment process since the earliest stages of the disease with an increasing burden to be of help to the ailing persons.: ... ...

    Abstract Background: Caregivers of patients affected by amyotrophic lateral sclerosis (ALS) are involved with great determination in the treatment process since the earliest stages of the disease with an increasing burden to be of help to the ailing persons.
    Aim: To test separately the impact of ALS patients' cognitive and behavioural impairments on caregiver burden and mood status in 84 outpatient/main caregiver couples.
    Design: Patients were tested with the ALS-Cognitive Behavioural Screen (ALSCBS-ci and -bi), Frontal Assessment Battery, Weigl's Sorting Test, Mini-Mental State Examination, Beck's Depression Inventory (BDI). Analogously, caregivers completed the BDI and Caregiver Burden Inventory (CBI).
    Results: CBI correlated with ALSCBS-bi, besides ALSFRS-R, disease progression index and caregiver BDI. Caregiver BDI also correlated with ALSCBS-bi scores. No correlations were found with cognitive tests. The correlation between CBI and the ALSCBS-bi score was specifically sustained by the social burden sub-domain of CBI.
    Conclusions: As previously reported using other tools, behavioural impairment is a determinant of burden and mood in ALS caregivers. Conversely, cognitive impairment fails to emerge as a major target when aiming at easing the increasing burden or improving mood in ALS caregivers.
    MeSH term(s) Adult ; Affect ; Aged ; Amyotrophic Lateral Sclerosis/complications ; Amyotrophic Lateral Sclerosis/psychology ; Attention Deficit and Disruptive Behavior Disorders/etiology ; Attention Deficit and Disruptive Behavior Disorders/psychology ; Caregivers/psychology ; Cognition Disorders/etiology ; Cognition Disorders/psychology ; Cost of Illness ; Female ; Humans ; Male ; Middle Aged ; Psychiatric Status Rating Scales ; Quality of Life/psychology
    Language English
    Publishing date 2016
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 209426-5
    ISSN 1421-9913 ; 0014-3022
    ISSN (online) 1421-9913
    ISSN 0014-3022
    DOI 10.1159/000445110
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Diaphragm ultrasonography in the management of patients with amyotrophic lateral sclerosis.

    Aliberti, Stefano / Messinesi, Grazia / Gramegna, Andrea / Tremolizzo, Lucio / Susani, Emanuela / Pesci, Alberto

    Amyotrophic lateral sclerosis & frontotemporal degeneration

    2013  Volume 14, Issue 2, Page(s) 154–156

    MeSH term(s) Aged ; Amyotrophic Lateral Sclerosis/complications ; Amyotrophic Lateral Sclerosis/diagnostic imaging ; Diaphragm/diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Reproducibility of Results ; Respiratory Function Tests/methods ; Respiratory Insufficiency/diagnostic imaging ; Respiratory Insufficiency/etiology ; Sensitivity and Specificity ; Ultrasonography
    Language English
    Publishing date 2013-03
    Publishing country England
    Document type Letter
    ZDB-ID 2705049-X
    ISSN 2167-9223 ; 2167-8421
    ISSN (online) 2167-9223
    ISSN 2167-8421
    DOI 10.3109/21678421.2012.762931
    Database MEDical Literature Analysis and Retrieval System OnLINE

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