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  1. Article ; Online: Current Understanding of the Neurobiology of Agitation

    Christopher W.T. Miller / Vedrana Hodzic / Eric Weintraub

    Western Journal of Emergency Medicine, Vol 21, Iss

    2020  Volume 4

    Abstract: Introduction: Managing agitation in the clinical setting is a challenge that many practitioners face regularly. Our evolving understanding of the etiological factors involved in aggressive acts has better informed our interventions through pharmacologic ... ...

    Abstract Introduction: Managing agitation in the clinical setting is a challenge that many practitioners face regularly. Our evolving understanding of the etiological factors involved in aggressive acts has better informed our interventions through pharmacologic and behavioral strategies. This paper reviews the literature on the neurobiological underpinnings of aggressive behaviors, linking psychopathology with proposed mechanisms of action of psychiatric medications shown to be effective in mitigating agitation. Methods: We performed a review of the extant literature using PubMed as a primary database. Investigation focused on neurobiology of agitation and its relation to the current evidence base for particular interventions. Results: There are well-established pathways that can lead to increased autonomic response and the potential for violence. Psychopathology and substance-induced perceptual distortions may lead to magnification and overestimation of environmental threat, heightening the potential for aggression. Additional challenges have arisen with the advent of several novel drugs of abuse, many of which lead to atypical clinical presentations and which can elude standard drug screens. Our interventions still lean on the evidence base found in Project BETA (Best Practices in Evaluation and Treatment of Agitation). Although not a new drug and not included in the Project BETA guidelines, ketamine and its use are also discussed, given its unique pharmacology and potential benefits when other protocoled interventions have failed. Conclusion: Aggression can occur due to manifold reasons in the clinical setting. Having an informed understanding of the possible determinants of agitation can help with more tailored responses to individual patients, limiting the unnecessary use of medications or of interventions that could be deemed forceful.
    Keywords Medicine ; R ; Medical emergencies. Critical care. Intensive care. First aid ; RC86-88.9
    Subject code 610
    Language English
    Publishing date 2020-07-01T00:00:00Z
    Publisher eScholarship Publishing, University of California
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: A Systematic Approach to Developing Virtual Patient Vignettes for Pediatric Health Equity Research.

    Mulchan, Siddika S / Miller, Megan / Theriault, Christopher B / Zempsky, William T / Hirsh, Adam

    Health equity

    2022  Volume 6, Issue 1, Page(s) 862–872

    Abstract: Objective: The aim of this study was to describe a systematic approach to developing virtual patient (VP) vignettes for health equity research in pediatric pain care.: Methods: VPs were initially developed to depict the body posture and movements of ... ...

    Abstract Objective: The aim of this study was to describe a systematic approach to developing virtual patient (VP) vignettes for health equity research in pediatric pain care.
    Methods: VPs were initially developed to depict the body posture and movements of actual children experiencing pain. Researchers and clinicians with expertise in pediatric pain worked closely with a professional animator to portray empirically supported pain expression in four, full-motion, virtual male characters of two races (i.e., White and Black). Through an iterative process, VPs were refined to (1) appear realistic in a clinical setting and (2) display archetypal pain behavior and expression during a 1-min video clip without sound. Text vignettes were developed with consultation from experts in pain care and presented alongside VPs to assess clinical decision-making. VP vignettes were piloted in a sample of pediatric providers (
    Results: Informed by the literature and expertise of stakeholders, several revisions were made to improve VPs' facial grimacing and realism before piloting. VPs appeared to accurately capture important aspects of pain expression and behavior common among pediatric patients with pain disorders. Additional refinements to the text vignettes were made based on provider feedback to improve clarity and clinical relevance.
    Conclusions: This article presents a working framework to facilitate a systematic approach to developing VP vignettes. This framework is a first step toward advancing health equity research by isolating psychosocial and interpersonal factors affecting provider behavior and decision-making. Future research is needed to validate the use of VP vignettes for assessing provider behavior contributing to health inequities for youth with pain disorders.
    Language English
    Publishing date 2022-11-22
    Publishing country United States
    Document type Journal Article
    ISSN 2473-1242
    ISSN (online) 2473-1242
    DOI 10.1089/heq.2022.0108
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: T regulatory cells: an overview and intervention techniques to modulate allergy outcome.

    Nandakumar, Subhadra / Miller, Christopher Wt / Kumaraguru, Uday

    Clinical and molecular allergy : CMA

    2009  Volume 7, Page(s) 5

    Abstract: Dysregulated immune response results in inflammatory symptoms in the respiratory mucosa leading to asthma and allergy in susceptible individuals. The T helper type 2 (Th2) subsets are primarily involved in this disease process. Nevertheless, there is ... ...

    Abstract Dysregulated immune response results in inflammatory symptoms in the respiratory mucosa leading to asthma and allergy in susceptible individuals. The T helper type 2 (Th2) subsets are primarily involved in this disease process. Nevertheless, there is growing evidence in support of T cells with regulatory potential that operates in non-allergic individuals. These regulatory T cells occur naturally are called natural T regulatory cells (nTregs) and express the transcription factor Foxp3. They are selected in the thymus and move to the periphery. The CD4 Th cells in the periphery can be induced to become regulatory T cells and hence called induced or adaptive T regulatory cells. These cells can make IL-10 or TGF-b or both, by which they attain most of their suppressive activity. This review gives an overview of the regulatory T cells, their role in allergic diseases and explores possible interventionist approaches to manipulate Tregs for achieving therapeutic goals.
    Language English
    Publishing date 2009-03-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 2126317-6
    ISSN 1476-7961 ; 1476-7961
    ISSN (online) 1476-7961
    ISSN 1476-7961
    DOI 10.1186/1476-7961-7-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: T regulatory cells

    Kumaraguru Uday / Miller Christopher WT / Nandakumar Subhadra

    Clinical and Molecular Allergy, Vol 7, Iss 1, p

    an overview and intervention techniques to modulate allergy outcome

    2009  Volume 5

    Abstract: Abstract Dysregulated immune response results in inflammatory symptoms in the respiratory mucosa leading to asthma and allergy in susceptible individuals. The T helper type 2 (Th2) subsets are primarily involved in this disease process. Nevertheless, ... ...

    Abstract Abstract Dysregulated immune response results in inflammatory symptoms in the respiratory mucosa leading to asthma and allergy in susceptible individuals. The T helper type 2 (Th2) subsets are primarily involved in this disease process. Nevertheless, there is growing evidence in support of T cells with regulatory potential that operates in non-allergic individuals. These regulatory T cells occur naturally are called natural T regulatory cells (nTregs) and express the transcription factor Foxp3. They are selected in the thymus and move to the periphery. The CD4 Th cells in the periphery can be induced to become regulatory T cells and hence called induced or adaptive T regulatory cells. These cells can make IL-10 or TGF-b or both, by which they attain most of their suppressive activity. This review gives an overview of the regulatory T cells, their role in allergic diseases and explores possible interventionist approaches to manipulate Tregs for achieving therapeutic goals.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Allergy and Immunology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 610
    Language English
    Publishing date 2009-03-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Multiple sclerosis presenting as acute acquired comitant esotropia in a pediatric patient.

    Armenti, Stephen T / Miller, Jason M L / Gomez-Hassan, Diana / Gappy, Christopher / Cornblath, Wayne T

    Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus

    2020  Volume 25, Issue 1, Page(s) 45–47

    Abstract: Acute acquired comitant esotropia (AACE) is a rare form of esotropia in the older pediatric population. Although the workup for pediatric AACE varies, patients often do not undergo lab testing and imaging, because the overwhelming majority of cases are ... ...

    Abstract Acute acquired comitant esotropia (AACE) is a rare form of esotropia in the older pediatric population. Although the workup for pediatric AACE varies, patients often do not undergo lab testing and imaging, because the overwhelming majority of cases are idiopathic. We describe AACE as the presenting manifestation of multiple sclerosis in a pediatric patient. His only other finding was a horizontal jerk nystagmus isolated to end gaze. Magnetic resonance imaging revealed extensive demyelinating lesions, with a small thalamic lesion possibly accounting for his esotropia. Our case underscores the need for extensive diagnostic workup for any ophthalmic or neurologic findings or symptoms accompanying AACE.
    MeSH term(s) Acute Disease ; Child ; Esotropia/diagnosis ; Esotropia/etiology ; Humans ; Magnetic Resonance Imaging ; Multiple Sclerosis/complications ; Multiple Sclerosis/diagnosis ; Retrospective Studies
    Language English
    Publishing date 2020-11-02
    Publishing country United States
    Document type Case Reports ; Research Support, Non-U.S. Gov't
    ZDB-ID 1412476-2
    ISSN 1528-3933 ; 1091-8531
    ISSN (online) 1528-3933
    ISSN 1091-8531
    DOI 10.1016/j.jaapos.2020.08.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Severe asthma and the omalizumab option

    Johnston Chambless / Krishnaswamy Narayanaswamy / Miller Christopher WT / Krishnaswamy Guha

    Clinical and Molecular Allergy, Vol 6, Iss 1, p

    2008  Volume 4

    Abstract: Abstract Atopic diseases and asthma are increasing at a remarkable rate on a global scale. It is now well recognized that asthma is a chronic inflammatory disease of the airways. The inflammatory process in many patients is driven by an immunoglobulin E ( ...

    Abstract Abstract Atopic diseases and asthma are increasing at a remarkable rate on a global scale. It is now well recognized that asthma is a chronic inflammatory disease of the airways. The inflammatory process in many patients is driven by an immunoglobulin E (IgE)-dependent process. Mast cell activation and release of mediators, in response to allergen and IgE, results in a cascade response, culminating in B lymphocyte, T lymphocyte, eosinophil, fibroblast, smooth muscle cell and endothelial activation. This complex cellular interaction, release of cytokines, chemokines and growth factors and inflammatory remodeling of the airways leads to chronic asthma. A subset of patients develops severe airway disease which can be extremely morbid and even fatal. While many treatments are available for asthma, it is still a chronic and incurable disease, characterized by exacerbation, hospitalizations and associated adverse effects of medications. Omalizumab is a new option for chronic asthma that acts by binding to and inhibiting the effects of IgE, thereby interfering with one aspect of the asthma cascade reviewed earlier. This is a humanized monoclonal antibody against IgE that has been shown to have many beneficial effects in asthma. Use of omalizumab may be influenced by the cost of the medication and some reported adverse effects including the rare possibility of anaphylaxis. When used in selected cases and carefully, omalizumab provides a very important tool in disease management. It has been shown to have additional effects in urticaria, angioedema, latex allergy and food allergy, but the data is limited and the indications far from clear. In addition to decreasing exacerbations, it has a steroid sparing role and hence may decrease adverse effects in some patients on high-dose glucocorticoids. Studies have shown improvement in quality of life measures in asthma following the administration of omalizumab, but the effects on pulmonary function are surprisingly small, suggesting a disconnect between pulmonary function, exacerbations and quality of life. Anaphylaxis may occur rarely with this agent and appropriate precautions have been recommended by the Food and Drug Administration (FDA). As currently practiced and as suggested by the new asthma guidelines, this biological agent is indicated in moderate or severe persistent allergic asthma (steps 5 and 6).
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Allergy and Immunology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 610
    Language English
    Publishing date 2008-05-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Severe asthma and the omalizumab option.

    Miller, Christopher Wt / Krishnaswamy, Narayanaswamy / Johnston, Chambless / Krishnaswamy, Guha

    Clinical and molecular allergy : CMA

    2008  Volume 6, Page(s) 4

    Abstract: Atopic diseases and asthma are increasing at a remarkable rate on a global scale. It is now well recognized that asthma is a chronic inflammatory disease of the airways. The inflammatory process in many patients is driven by an immunoglobulin E (IgE)- ... ...

    Abstract Atopic diseases and asthma are increasing at a remarkable rate on a global scale. It is now well recognized that asthma is a chronic inflammatory disease of the airways. The inflammatory process in many patients is driven by an immunoglobulin E (IgE)-dependent process. Mast cell activation and release of mediators, in response to allergen and IgE, results in a cascade response, culminating in B lymphocyte, T lymphocyte, eosinophil, fibroblast, smooth muscle cell and endothelial activation. This complex cellular interaction, release of cytokines, chemokines and growth factors and inflammatory remodeling of the airways leads to chronic asthma. A subset of patients develops severe airway disease which can be extremely morbid and even fatal. While many treatments are available for asthma, it is still a chronic and incurable disease, characterized by exacerbation, hospitalizations and associated adverse effects of medications. Omalizumab is a new option for chronic asthma that acts by binding to and inhibiting the effects of IgE, thereby interfering with one aspect of the asthma cascade reviewed earlier. This is a humanized monoclonal antibody against IgE that has been shown to have many beneficial effects in asthma. Use of omalizumab may be influenced by the cost of the medication and some reported adverse effects including the rare possibility of anaphylaxis. When used in selected cases and carefully, omalizumab provides a very important tool in disease management. It has been shown to have additional effects in urticaria, angioedema, latex allergy and food allergy, but the data is limited and the indications far from clear. In addition to decreasing exacerbations, it has a steroid sparing role and hence may decrease adverse effects in some patients on high-dose glucocorticoids. Studies have shown improvement in quality of life measures in asthma following the administration of omalizumab, but the effects on pulmonary function are surprisingly small, suggesting a disconnect between pulmonary function, exacerbations and quality of life. Anaphylaxis may occur rarely with this agent and appropriate precautions have been recommended by the Food and Drug Administration (FDA). As currently practiced and as suggested by the new asthma guidelines, this biological agent is indicated in moderate or severe persistent allergic asthma (steps 5 and 6).
    Language English
    Publishing date 2008-05-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 2126317-6
    ISSN 1476-7961 ; 1476-7961
    ISSN (online) 1476-7961
    ISSN 1476-7961
    DOI 10.1186/1476-7961-6-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: A small-molecule TrkB ligand improves dendritic spine phenotypes and atypical behaviors in female Rett syndrome mice.

    Medeiros, Destynie / Ayala-Baylon, Karen / Egido-Betancourt, Hailey / Miller, Eric / Chapleau, Christopher A / Robinson, Holly A / Phillips, Mary L / Yang, Tao / Longo, Frank / Li, Wei / Pozzo-Miller, Lucas

    bioRxiv : the preprint server for biology

    2023  

    Abstract: ... density in CA1 pyramidal neurons in slice cultures from male wildtype (WT) mice, where typical BDNF levels ... heterozygous (HET) mice, we treated 4-6-month-old female MeCP2-GFP WT and HET mice with peripheral injections ... comparable to that in WT controls, while MeCP2-GFP-expressing neurons showed larger spines, similar ...

    Abstract Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in methyl-CpG-binding protein-2 (MECP2), encoding a transcriptional regulator of many genes, including brain-derived neurotrophic factor (Bdnf). BDNF mRNA and protein levels are lower in RTT autopsy brains and in multiple brain regions of Mecp2-deficient mice, and experimentally increasing BDNF levels improve atypical phenotypes in Mecp2 mutant mice. Due to the low blood-brain barrier permeability of BDNF itself, we tested the effects of a brain penetrant, small molecule ligand of its TrkB receptors. Applied in vitro, LM22A-4 increased dendritic spine density in pyramidal neurons in cultured hippocampal slices from postnatal day (P) 7 male Mecp2 knockout (KO) mice as much as recombinant BDNF, and both effects were prevented by the TrkB receptor inhibitors K-252a and ANA-12. Consistent with its partial agonist activity, LM22A-4 did not affect spine density in CA1 pyramidal neurons in slice cultures from male wildtype (WT) mice, where typical BDNF levels outcompete its binding to TrkB. To identify neurons of known genotypes in the "mosaic" brain of female Mecp2 heterozygous (HET) mice, we treated 4-6-month-old female MeCP2-GFP WT and HET mice with peripheral injections of LM22A-4 for 4 weeks. Surprisingly, mutant neurons lacking MeCP2-GFP showed dendritic spine volumes comparable to that in WT controls, while MeCP2-GFP-expressing neurons showed larger spines, similar to the phenotype we described in symptomatic male Mecp2 KO mice where all neurons lack MeCP2. Consistent with this non-cell-autonomous mechanism, a 4-week systemic treatment with LM22A-4 had an effect only in MeCP2-GFP-expressing neurons in female Mecp2 HET mice, bringing dendritic spine volumes down to WT control levels, and without affecting spines of MeCP2-GFP-lacking neurons. At the behavioral level, we found that female Mecp2 HET mice engaged in aggressive behaviors significantly more than WT controls, which were reduced to WT levels by a 4-week systemic treatment with LM22A-4. Altogether, these data revealed differences in dendritic spine size and altered behaviors in Mecp2 HET mice, while providing support to the potential usefulness of BDNF-related therapeutic approaches such as the partial TrkB agonist LM22A-4.
    Language English
    Publishing date 2023-11-17
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.11.09.566435
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Antimicrobial implications of vitamin D.

    Youssef, Dima A / Miller, Christopher Wt / El-Abbassi, Adel M / Cutchins, Della C / Cutchins, Coleman / Grant, William B / Peiris, Alan N

    Dermato-endocrinology

    2011  Volume 3, Issue 4, Page(s) 220–229

    Abstract: Evidence exists that vitamin D has a potential antimicrobial activity and its deficiency has deleterious effects on general well-being and longevity. Vitamin D may reduce the risk of infection through multiple mechanisms. Vitamin D boosts innate immunity ...

    Abstract Evidence exists that vitamin D has a potential antimicrobial activity and its deficiency has deleterious effects on general well-being and longevity. Vitamin D may reduce the risk of infection through multiple mechanisms. Vitamin D boosts innate immunity by modulating production of anti-microbial peptides (AMPs) and cytokine response. Vitamin D and its analogues via these mechanisms are playing an increasing role in the management of atopic dermatitis, psoriasis, vitiligo, acne and rosacea. Vitamin D may reduce susceptibility to infection in patients with atopic dermatitis and the ability to regulate local immune and inflammatory responses offers exciting potential for understanding and treating chronic inflammatory dermatitides. Moreover, B and T cell activation as well as boosting the activity of monocytes and macrophages also contribute to a potent systemic anti-microbial effect. The direct invasion by pathogenic organisms may be minimized at sites such as the respiratory tract by enhancing clearance of invading organisms. A vitamin D replete state appears to benefit most infections, with the possible noteworthy exception of Leishmaniasis. Antibiotics remain an expensive option and misuse of these agents results in significant antibiotic resistance and contributes to escalating health care costs. Vitamin D constitutes an inexpensive prophylactic option and possibly therapeutic product either by itself or as a synergistic agent to traditional antimicrobial agents. This review outlines the specific antimicrobial properties of vitamin D in combating a wide range of organisms. We discuss the possible mechanisms by which vitamin D may have a therapeutic role in managing a variety of infections.
    Language English
    Publishing date 2011-10-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2540047-2
    ISSN 1938-1980 ; 1938-1980
    ISSN (online) 1938-1980
    ISSN 1938-1980
    DOI 10.4161/derm.3.4.15027
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Prenatal ozone exposure programs a sexually dimorphic susceptibility to high-fat diet in adolescent Long Evans rats.

    Stewart, Erica J / Dye, Janice A / Schladweiler, Mette C / Phillips, Pamela M / McDaniel, Katherine L / Richards, Judy H / Grindstaff, Rachel D / Padgett, William T / Moore, Makala L / Hill, Donna / Gordon, Christopher J / Kodavanti, Urmila P / Miller, Colette N

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology

    2022  Volume 36, Issue 12, Page(s) e22664

    Abstract: Altered fetal growth, which can occur due to environmental stressors during pregnancy, may program a susceptibility to metabolic disease. Gestational exposure to the air pollutant ozone is associated with fetal growth restriction in humans and rodents. ... ...

    Abstract Altered fetal growth, which can occur due to environmental stressors during pregnancy, may program a susceptibility to metabolic disease. Gestational exposure to the air pollutant ozone is associated with fetal growth restriction in humans and rodents. However, the impact of this early life ozone exposure on offspring metabolic risk has not yet been investigated. In this study, fetal growth restriction was induced by maternal inhalation of 0.8 ppm ozone on gestation days 5 and 6 (4 hr/day) in Long Evans rats. To uncover any metabolic inflexibility, or an impaired ability to respond to a high-fat diet (HFD), a subset of peri-adolescent male and female offspring from filtered air or ozone exposed dams were fed HFD (45% kcal from fat) for 3 days. By 6 weeks of age, male and female offspring from ozone-exposed dams were heavier than offspring from air controls. Furthermore, offspring from ozone-exposed dams had greater daily caloric consumption and reduced metabolic rate when fed HFD. In addition to energy imbalance, HFD-fed male offspring from ozone-exposed dams had dyslipidemia and increased adiposity, which was not evident in females. HFD consumption in males resulted in the activation of the protective 5'AMP-activated protein kinase (AMPKα) and sirtuin 1 (SIRT1) pathways in the liver, regardless of maternal exposure. Unlike males, ozone-exposed female offspring failed to activate these pathways, retaining hepatic triglycerides following HFD consumption that resulted in increased inflammatory gene expression and reduced insulin signaling genes. Taken together, maternal ozone exposure in early pregnancy programs impaired metabolic flexibility in offspring, which may increase susceptibility to obesity in males and hepatic dysfunction in females.
    MeSH term(s) Pregnancy ; Animals ; Rats ; Humans ; Male ; Female ; Adolescent ; Diet, High-Fat/adverse effects ; Rats, Long-Evans ; Ozone/toxicity ; Fetal Growth Retardation ; Obesity/metabolism ; Vitamins
    Chemical Substances Ozone (66H7ZZK23N) ; Vitamins
    Language English
    Publishing date 2022-11-27
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.202201514R
    Database MEDical Literature Analysis and Retrieval System OnLINE

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