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  1. Article ; Online: Risikofaktoren für die Entstehung und den Verlauf der Schizophrenie.

    Löhrs, Lisa / Hasan, Alkomiet

    Fortschritte der Neurologie-Psychiatrie

    2019  Volume 87, Issue 2, Page(s) 133–143

    Abstract: Schizophrenia is a severe psychiatric disorder with lifetime prevalence about 1 %. Usually, the disorder starts during the adolescence, however it is estimated that around 30 % of first-onsets are beyond the age of 40. The incidence of males is a little ... ...

    Title translation Risk factors for the development of schizophrenia.
    Abstract Schizophrenia is a severe psychiatric disorder with lifetime prevalence about 1 %. Usually, the disorder starts during the adolescence, however it is estimated that around 30 % of first-onsets are beyond the age of 40. The incidence of males is a little bit higher in the adolescence, while from the age of 40 the incidence in females is higher. In this context, the pathogenesis and development of schizophrenia is a complex model of gene-environment interactions and is not, like it was postulated in the earlier "One-Hit" or "Two-Hit" models caused by exclusively one or two single events. The risk to develop schizophrenia is composed of a biological predisposition with multi-genetic risk factors and changes in the neurotransmitter system, immunological influence factors and psychosocial risk factors. Genetic risk factors, perinatal risk factors and complications during birth could increase the probability of the disease. Besides these early risk factors traumatic events during childhood and especially risk factors like cannabis abuse that occur during adolescence which is a sensitive phase in the brain development could influence onset, development and relapse risk of the disease. If timing and sum of the single risk factors interact, they can cause the disturbance of neuronal regeneration and lead to schizophrenia, but the whole interaction of this multifactorial process is still not fully understood.
    MeSH term(s) Adolescent ; Adult ; Child ; Female ; Gene-Environment Interaction ; Humans ; Incidence ; Infant, Newborn ; Male ; Marijuana Abuse/complications ; Pregnancy ; Risk Factors ; Schizophrenia/epidemiology ; Schizophrenia/etiology ; Schizophrenia/genetics
    Language German
    Publishing date 2019-02-25
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 625328-3
    ISSN 1439-3522 ; 0720-4299
    ISSN (online) 1439-3522
    ISSN 0720-4299
    DOI 10.1055/a-0836-7839
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Risikofaktoren für die Entstehung und den Verlauf der Schizophrenie

    Löhrs, Lisa / Hasan, Alkomiet

    Fortschritte der Neurologie · Psychiatrie

    2019  Volume 87, Issue 02, Page(s) 133–143

    Abstract: Gemäß dem derzeitigen Wissen entsteht eine Schizophrenie multifaktoriell – und zwar durch kumulative Wirkung einzelner, für sich unterschwelliger Risikofaktoren. Diese Faktoren (u. a. genetische, psychosoziale, umweltbedingte, prä- und peripartale) ... ...

    Abstract Gemäß dem derzeitigen Wissen entsteht eine Schizophrenie multifaktoriell – und zwar durch kumulative Wirkung einzelner, für sich unterschwelliger Risikofaktoren. Diese Faktoren (u. a. genetische, psychosoziale, umweltbedingte, prä- und peripartale) ziehen strukturelle Gehirnveränderungen und Veränderungen einzelner Neurotransmittersysteme nach sich, die schließlich zum Vollbild der Schizophrenie führen.
    Keywords multifactorial disorder ; gene-environment interaction ; timing and sum of risk factors
    Language German
    Publishing date 2019-02-01
    Publisher © Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 625328-3
    ISSN 1439-3522 ; 0720-4299
    ISSN (online) 1439-3522
    ISSN 0720-4299
    DOI 10.1055/a-0836-7839
    Database Thieme publisher's database

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  3. Article: Risikofaktoren für die Entstehung und den Verlauf der Schizophrenie

    Löhrs, Lisa / Hasan, Alkomiet

    Fortschritte der Neurologie, Psychiatrie

    2019  Volume 87, Issue 2, Page(s) 133–146

    Abstract: Es wird ein Überblick über den aktuellen Erkenntnisstand zu Risikofaktoren für die Entstehung und den Verlauf der Schizophrenie gegeben. Dabei wird auf folgende Aspekte eingegangen: (1) multifaktorielle Genese, (2) Epidemiologie, (3) Ätiologie, (4) ... ...

    Title translation Risk factors for the development and course of schizophrenia
    Abstract Es wird ein Überblick über den aktuellen Erkenntnisstand zu Risikofaktoren für die Entstehung und den Verlauf der Schizophrenie gegeben. Dabei wird auf folgende Aspekte eingegangen: (1) multifaktorielle Genese, (2) Epidemiologie, (3) Ätiologie, (4) Risikofaktoren für die Entstehung einer Schizophrenie, (5) Heritabilität und Geneti, (6) prä- und perinatale Risiken, (7) Geburt und Geburtstraumata, (8) Traumaerfahrungen, (9) psychosoziale Risikofaktoren, (10) Cannabisgebrauch.
    Keywords Cannabis ; Disease Course ; Etiology ; Genetics ; Genetik ; Kannabis ; Krankheitsverlauf ; Psychosocial Factors ; Psychosoziale Faktoren ; Risikofaktoren ; Risk Factors ; Schizophrenia ; Schizophrenie ; Trauma ; Ätiologie
    Language German
    Document type Article
    ZDB-ID 625328-3
    ISSN 1439-3522 ; 0720-4299
    ISSN (online) 1439-3522
    ISSN 0720-4299
    DOI 10.1055/a-0836-7839
    Database PSYNDEX

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  4. Article: Risikofaktoren für die Entstehung und den Verlauf der Schizophrenie

    Löhrs, Lisa / Hasan, Alkomiet

    PSYCH up2date

    2018  Volume 12, Issue 06, Page(s) 467–481

    Keywords Schizophrenie ; Entstehung ; Risikofaktoren ; Gen-Umwelt-Interaktion
    Language German
    Publishing date 2018-10-29
    Publisher Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 2683337-2
    ISSN 2194-8909 ; 2194-8895
    ISSN (online) 2194-8909
    ISSN 2194-8895
    DOI 10.1055/a-0566-6338
    Database Thieme publisher's database

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  5. Article: Risikofaktoren für die Entstehung und den Verlauf der Schizophrenie

    Löhrs, Lisa / Hasan, Alkomiet

    PSYCH up2date

    2018  Volume 12, Issue 6, Page(s) 467–481

    Abstract: Es wird ein Überblick zu Risikofaktoren für die Entstehung und den Verlauf der Schizophrenie gegeben. Nachdem auf die mulktifaktorielle, stufenweise Pathogenese, Epidemiologie und Ätiologie eingegangen wurde, werden Heritabilität und Genetik, prä- und ... ...

    Title translation Risk factors for the development and course of schizophrenia
    Abstract Es wird ein Überblick zu Risikofaktoren für die Entstehung und den Verlauf der Schizophrenie gegeben. Nachdem auf die mulktifaktorielle, stufenweise Pathogenese, Epidemiologie und Ätiologie eingegangen wurde, werden Heritabilität und Genetik, prä- und perinatale Risiken, Geburt und Geburtstrauma, Traumaerfahrungen, psychosoziale Risikofaktoren und Cannabisgebrauch besprochen. Dabei wird festgehalten, dass grundsätzlich keiner der beschriebenen Risikofaktoren allein zur Entwicklung einer Schizophrenie führt, sondern die Summe und der Zeitpunkt des Auftretens sind ausschlaggebend.
    Keywords Birth Trauma ; Cannabis ; Epidemiologie ; Epidemiology ; Erblichkeit ; Etiology ; Geburtstrauma ; Gene ; Genes ; Heritability ; Kannabis ; Psychosocial Factors ; Psychosoziale Faktoren ; Risikofaktoren ; Risk Factors ; Schizophrenia ; Schizophrenie ; Ätiologie
    Language German
    Document type Article
    ZDB-ID 2683337-2
    ISSN 2194-8909 ; 2194-8895
    ISSN (online) 2194-8909
    ISSN 2194-8895
    DOI 10.1055/a-0566-6338
    Database PSYNDEX

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  6. Article ; Online: Blood-brain barrier dysfunction and folate and vitamin B12 levels in first-episode schizophrenia-spectrum psychosis: a retrospective chart review.

    Campana, Mattia / Löhrs, Lisa / Strauß, Johanna / Münz, Susanne / Oviedo-Salcedo, Tatiana / Fernando, Piyumi / Maurus, Isabel / Raabe, Florian / Moussiopoulou, Joanna / Eichhorn, Peter / Falkai, Peter / Hasan, Alkomiet / Wagner, Elias

    European archives of psychiatry and clinical neuroscience

    2023  Volume 273, Issue 8, Page(s) 1693–1701

    Abstract: Vitamin deficiency syndromes and blood-brain barrier (BBB) dysfunction are frequent phenomena in psychiatric conditions. We analysed the largest available first-episode schizophrenia-spectrum psychosis (FEP) cohort to date regarding routine cerebrospinal ...

    Abstract Vitamin deficiency syndromes and blood-brain barrier (BBB) dysfunction are frequent phenomena in psychiatric conditions. We analysed the largest available first-episode schizophrenia-spectrum psychosis (FEP) cohort to date regarding routine cerebrospinal fluid (CSF) and blood parameters to investigate the association between vitamin deficiencies (vitamin B12 and folate) and BBB impairments in FEP. We report a retrospective analysis of clinical data from all inpatients that were admitted to our tertiary care hospital with an ICD-10 diagnosis of a first-episode F2x (schizophrenia-spectrum) between January 1, 2008 and August 1, 2018 and underwent a lumbar puncture, blood-based vitamin status diagnostics and neuroimaging within the clinical routine. 222 FEP patients were included in our analyses. We report an increased CSF/serum albumin quotient (Qalb) as a sign of BBB dysfunction in 17.1% (38/222) of patients. White matter lesions (WML) were present in 29.3% of patients (62/212). 17.6% of patients (39/222) showed either decreased vitamin B12 levels or decreased folate levels. No statistically significant association was found between vitamin deficiencies and altered Qalb. This retrospective analysis contributes to the discussion on the impact of vitamin deficiency syndromes in FEP. Although decreased vitamin B12 or folate levels were found in approximately 17% of our cohort, we found no evidence for significant associations between BBB dysfunction and vitamin deficiencies. To strengthen the evidence regarding the clinical implications of vitamin deficiencies in FEP, prospective studies with standardized measurements of vitamin levels together with follow-up measurements and assessment of symptom severity in addition to CSF diagnostics are needed.
    MeSH term(s) Humans ; Folic Acid ; Schizophrenia/complications ; Schizophrenia/diagnostic imaging ; Retrospective Studies ; Blood-Brain Barrier ; Prospective Studies ; Vitamin B 12 ; Vitamins ; Psychotic Disorders/diagnostic imaging ; Avitaminosis
    Chemical Substances Folic Acid (935E97BOY8) ; Vitamin B 12 (P6YC3EG204) ; Vitamins
    Language English
    Publishing date 2023-03-04
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1045583-8
    ISSN 1433-8491 ; 0175-758X ; 0940-1334
    ISSN (online) 1433-8491
    ISSN 0175-758X ; 0940-1334
    DOI 10.1007/s00406-023-01572-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Clozapine augmentation strategies - a systematic meta-review of available evidence. Treatment options for clozapine resistance.

    Wagner, Elias / Löhrs, Lisa / Siskind, Dan / Honer, William G / Falkai, Peter / Hasan, Alkomiet

    Journal of psychopharmacology (Oxford, England)

    2019  Volume 33, Issue 4, Page(s) 423–435

    Abstract: Background: Treatment options for clozapine resistance are diverse whereas, in contrast, the evidence for augmentation or combination strategies is sparse.: Aims: We aimed to extract levels of evidence from available data and extrapolate ... ...

    Abstract Background: Treatment options for clozapine resistance are diverse whereas, in contrast, the evidence for augmentation or combination strategies is sparse.
    Aims: We aimed to extract levels of evidence from available data and extrapolate recommendations for clinical practice.
    Methods: We conducted a systematic literature search in the PubMed/MEDLINE database and in the Cochrane database. Included meta-analyses were assessed using Scottish Intercollegiate Guidelines Network criteria, with symptom improvement as the endpoint, in order to develop a recommendation grade for each clinical strategy identified.
    Results: Our search identified 21 meta-analyses of clozapine combination or augmentation strategies. No strategies met Grade A criteria. Strategies meeting Grade B included combinations with first- or second-generation antipsychotics, augmentation with electroconvulsive therapy for persistent positive symptoms, and combination with certain antidepressants (fluoxetine, duloxetine, citalopram) for persistent negative symptoms. Augmentation strategies with mood-stabilisers, anticonvulsants, glutamatergics, repetitive transcranial magnetic stimulation, transcranial direct current stimulation or cognitive behavioural therapy met Grades C-D criteria only.
    Conclusion: More high-quality clinical trials are needed to evaluate the efficacy of add-on treatments for symptom improvement in patients with clozapine resistance. Applying definitions of clozapine resistance would improve the reporting of future clinical trials. Augmentation with second-generation antipsychotics and first-generation antipsychotics can be beneficial, but the supporting evidence is from low-quality studies. Electroconvulsive therapy may be effective for clozapine-resistant positive symptoms.
    MeSH term(s) Clozapine/therapeutic use ; Combined Modality Therapy ; Drug Resistance ; Drug Therapy, Combination ; Humans ; Meta-Analysis as Topic
    Chemical Substances Clozapine (J60AR2IKIC)
    Language English
    Publishing date 2019-01-30
    Publishing country United States
    Document type Journal Article ; Systematic Review
    ZDB-ID 639313-5
    ISSN 1461-7285 ; 0269-8811
    ISSN (online) 1461-7285
    ISSN 0269-8811
    DOI 10.1177/0269881118822171
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Evaluation of evidence grades in psychiatry and psychotherapy guidelines.

    Löhrs, Lisa / Handrack, Mirjam / Kopp, Ina / Jessen, Frank / Wagner, Elias / Falkai, Peter / Röh, Astrid / Strube, Wolfgang / Hasan, Alkomiet

    BMC psychiatry

    2020  Volume 20, Issue 1, Page(s) 503

    Abstract: Background: Information regarding the distribution of evidence grades in psychiatry and psychotherapy guidelines is lacking. Based on the German evidence- and consensus- based (S3) psychiatry and psychotherapy and the Scottish Intercollegiate Guidelines ...

    Abstract Background: Information regarding the distribution of evidence grades in psychiatry and psychotherapy guidelines is lacking. Based on the German evidence- and consensus- based (S3) psychiatry and psychotherapy and the Scottish Intercollegiate Guidelines Network (SIGN) treatment guidelines, we aimed to specify how guideline recommendations are composed and to what extent recommendations are evidence-based.
    Methods: Data was collected from all published evidence- and consensus-based S3-classified psychiatry and psychotherapy guidelines. As control conditions, data from German neurology S3-classified guidelines as well as data from recent SIGN guidelines of mental health were extracted. Two investigators reviewed the selected guidelines independently, extracted and analysed the numbers and levels of recommendations.
    Results: On average, 45.1% of all recommendations are not based on strong scientific evidence in German guidelines of psychiatry and psychotherapy. A related pattern can be confirmed for SIGN guidelines, where the mean average of recommendations with lacking evidence is 33.9%. By contrast, in the German guidelines of neurology the average of such recommendations is 16.5%. A total of 24.5% of all recommendations in the guidelines of psychiatry and psychotherapy are classified as level A recommendations, compared to 31.6% in the field of neurology and 31.1% in the SIGN guidelines. Related patterns were observed for B and 0 level recommendations.
    Conclusion: Guidelines should be practical tools to simplify the decision-making process based on scientific evidence. Up to 45% of all recommendations in the investigated guidelines of psychiatry and psychotherapy are not based on strong scientific evidence. The reasons for this high number remain unclear. Possibly, only a limited number of studies answer clinically relevant questions. Our findings thereby question whether guidelines should include non-evidence-based recommendations to be methodologically stringent and whether specific processes to develop expert-opinion statements must be implemented.
    MeSH term(s) Germany ; Humans ; Neurology ; Psychiatry ; Psychotherapy
    Language English
    Publishing date 2020-10-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1471-244X
    ISSN (online) 1471-244X
    DOI 10.1186/s12888-020-02897-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Association of symptom severity and cerebrospinal fluid alterations in recent onset psychosis in schizophrenia-spectrum disorders - An individual patient data meta-analysis.

    Campana, Mattia / Yakimov, Vladislav / Moussiopoulou, Joanna / Maurus, Isabel / Löhrs, Lisa / Raabe, Florian / Jäger, Iris / Mortazavi, Matin / Benros, Michael E / Jeppesen, Rose / Meyer Zu Hörste, Gerd / Heming, Michael / Giné-Servén, Eloi / Labad, Javier / Boix, Ester / Lennox, Belinda / Yeeles, Ksenija / Steiner, Johann / Meyer-Lotz, Gabriela /
    Dobrowolny, Henrik / Malchow, Berend / Hansen, Niels / Falkai, Peter / Siafis, Spyridon / Leucht, Stefan / Halstead, Sean / Warren, Nicola / Siskind, Dan / Strube, Wolfgang / Hasan, Alkomiet / Wagner, Elias

    Brain, behavior, and immunity

    2024  Volume 119, Page(s) 353–362

    Abstract: Neuroinflammation and blood-cerebrospinal fluid barrier (BCB) disruption could be key elements in schizophrenia-spectrum disorderś(SSDs) etiology and symptom modulation. We present the largest two-stage individual patient data (IPD) meta-analysis, ... ...

    Abstract Neuroinflammation and blood-cerebrospinal fluid barrier (BCB) disruption could be key elements in schizophrenia-spectrum disorderś(SSDs) etiology and symptom modulation. We present the largest two-stage individual patient data (IPD) meta-analysis, investigating the association of BCB disruption and cerebrospinal fluid (CSF) alterations with symptom severity in first-episode psychosis (FEP) and recent onset psychotic disorder (ROP) individuals, with a focus on sex-related differences. Data was collected from PubMed and EMBASE databases. FEP, ROP and high-risk syndromes for psychosis IPD were included if routine basic CSF-diagnostics were reported. Risk of bias of the included studies was evaluated. Random-effects meta-analyses and mixed-effects linear regression models were employed to assess the impact of BCB alterations on symptom severity. Published (6 studies) and unpublished IPD from n = 531 individuals was included in the analyses. CSF was altered in 38.8 % of individuals. No significant differences in symptom severity were found between individuals with and without CSF alterations (SMD = -0.17, 95 %CI -0.55-0.22, p = 0.341). However, males with elevated CSF/serum albumin ratios or any CSF alteration had significantly higher positive symptom scores than those without alterations (SMD = 0.34, 95 %CI 0.05-0.64, p = 0.037 and SMD = 0.29, 95 %CI 0.17-0.41p = 0.005, respectively). Mixed-effects and simple regression models showed no association (p > 0.1) between CSF parameters and symptomatic outcomes. No interaction between sex and CSF parameters was found (p > 0.1). BCB disruption appears highly prevalent in early psychosis and could be involved in positive symptomś severity in males, indicating potential difficult-to-treat states. This work highlights the need for considering BCB breakdownand sex-related differences in SSDs clinical trials and treatment strategies.
    Language English
    Publishing date 2024-04-10
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 639219-2
    ISSN 1090-2139 ; 0889-1591
    ISSN (online) 1090-2139
    ISSN 0889-1591
    DOI 10.1016/j.bbi.2024.04.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Association of differential miRNA expression with hepatic vs. peritoneal metastatic spread in colorectal cancer.

    Heublein, Sabine / Albertsmeier, Markus / Pfeifer, David / Loehrs, Lisa / Bazhin, Alexandr V / Kirchner, Thomas / Werner, Jens / Neumann, Jens / Angele, Martin Kurt

    BMC cancer

    2018  Volume 18, Issue 1, Page(s) 201

    Abstract: Background: Though peritoneal carcinomatosis reflects a late stage of colorectal cancer (CRC), only few patients present with synchronous or metachronous liver metastases alongside their peritoneal carcinomatosis. It is hypothesized that this phenomenon ...

    Abstract Background: Though peritoneal carcinomatosis reflects a late stage of colorectal cancer (CRC), only few patients present with synchronous or metachronous liver metastases alongside their peritoneal carcinomatosis. It is hypothesized that this phenomenon may be causally linked to molecular characteristics of the primary CRC. This study used miRNA profiling of primary CRC tissue either metastasized to the liver, to the peritoneum or not metastasized at all thus to identify miRNAs potentially associated with defining the site of metastatic spread in CRC.
    Methods: Tissue of the primary tumor stemming from CRC patients diagnosed for either liver metastasis (LM; n = 10) or peritoneal carcinomatosis (PER; n = 10) was analyzed in this study. Advanced CRC cases without metastasis (M0; n = 3) were also included thus to select on those miRNAs most potentially associated with determining metastatic spread in general. miRNA profiling of 754 different miRNAs was performed in each group. MiRNAs being either differentially expressed comparing PER and LM or even triple differentially expressed (PER vs. LM vs. M0) were identified. Differentially expressed miRNAs were further validated by in silico and functional analysis.
    Results: Comparative analysis identified 41 miRNAs to be differentially expressed comparing primary tumors metastasized to the liver as opposed to those spread to the peritoneum. A set of 31 miRNAs was significantly induced in primary tumors that spread to the peritoneum (PER), while the remaining 10 miRNAs were found to be repressed. Out of these 41 miRNAs a number of 25 miRNAs was triple-differentially expressed (i.e. differentially expressed comparing LM vs. PER vs. M0). The latter underwent in silico analysis. Finally, we demonstrated that miR-31 down-regulated c-MET in DLD-1 colon cancer cells.
    Conclusions: This study demonstrates that CRC primary tumors spread to the peritoneum vs. metastasized to the liver display significantly different miRNA profiles. Larger patient cohorts will be needed to validate whether determination of e.g. miR-31 may aid to predict the course of disease and whether this may help to create individualized follow up or treatment protocols. To determine whether certain miRNAs may be involved in regulating the metastatic potential of CRC, functional studies will be essential.
    MeSH term(s) Biomarkers, Tumor ; Cell Line, Tumor ; Cohort Studies ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Liver Neoplasms/secondary ; Male ; MicroRNAs/genetics ; Neoplasm Staging ; Peritoneal Neoplasms/secondary
    Chemical Substances Biomarkers, Tumor ; MicroRNAs
    Language English
    Publishing date 2018-02-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2041352-X
    ISSN 1471-2407 ; 1471-2407
    ISSN (online) 1471-2407
    ISSN 1471-2407
    DOI 10.1186/s12885-018-4043-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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