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  1. Article ; Online: Provider- and System-Level Barriers and Facilitators to Colonoscopy and Multi-Target Stool DNA for Colorectal Cancer Screening in Rural/Remote Alaska Native Communities.

    Redwood, Diana / Toffolon, Melissa / Flanagan, Christie / Kisiel, John / Kaur, Judith Salmon / Jeffries, Lauren / Zenku, Manusake / Lent, Jennifer / Bachtold, Joseph

    International journal of environmental research and public health

    2023  Volume 20, Issue 22

    Abstract: The Alaska Tribal Health System is working to increase colorectal cancer (CRC) screening among Alaska Native people, who experience the highest CRC rates in the world. This study examined CRC screening provider- and system-level barriers and facilitators ...

    Abstract The Alaska Tribal Health System is working to increase colorectal cancer (CRC) screening among Alaska Native people, who experience the highest CRC rates in the world. This study examined CRC screening provider- and system-level barriers and facilitators from the perspective of healthcare providers serving Alaska Native people in rural/remote communities. A total of 28 provider (physicians, advanced practice, and Community Health Aides/Practitioners) interviews were held from 1 February to 30 November 2021. Colonoscopy provider-level barrier themes included time, competing priorities, and staffing, while system-level barriers included travel costs, weather, and the COVID-19 pandemic. Multi-target stool DNA (mt-sDNA) barrier themes included test viability and unfamiliarity, and previous stool tests experiences. For both tests, limited medical record reminders was a major barrier. Facilitator themes for both tests included community outreach, cultural competency and patient navigation, and clinic/system improvements. In-depth interviews with tribal health providers showed that adding mt-sDNA testing may help address system-level colonoscopy barriers such as waitlists and travel costs, but other barriers remain. Further research is needed into patient barriers and facilitators, as well as the effectiveness of integrating mt-sDNA into a geographically dispersed tribal health system to reduce cancer disparities and build equity in CRC prevention among Alaska Native people.
    MeSH term(s) Humans ; Pandemics ; Early Detection of Cancer ; DNA ; Colorectal Neoplasms/epidemiology ; Colonoscopy ; Mass Screening
    Chemical Substances DNA (9007-49-2)
    Language English
    Publishing date 2023-11-07
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2175195-X
    ISSN 1660-4601 ; 1661-7827
    ISSN (online) 1660-4601
    ISSN 1661-7827
    DOI 10.3390/ijerph20227030
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  2. Article ; Online: When lungs and weights tell different stories.

    Godse, Sanjiv / Brumer, Eliaz / Kizilirmak, Tuba Kockar / Canapari, Craig / Silva, Cicero / Morotti, Raffaella / Jiang, Yong-Hui / Jeffries, Lauren / Chen, Laura / Panacherry, Sherin

    Pediatric pulmonology

    2024  Volume 59, Issue 4, Page(s) 1047–1059

    MeSH term(s) Humans ; Lung/diagnostic imaging
    Language English
    Publishing date 2024-02-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 632784-9
    ISSN 1099-0496 ; 8755-6863
    ISSN (online) 1099-0496
    ISSN 8755-6863
    DOI 10.1002/ppul.26832
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  3. Article ; Online: A novel variant in

    AbuBakr, Fatima / Jeffries, Lauren / Ji, Weizhen / McGrath, James M / Lakhani, Saquib A

    Cold Spring Harbor molecular case studies

    2020  Volume 6, Issue 3

    Abstract: The transforming growth factor-β-activated kinase 1 (TAK1) encoded by mitogen-activated protein kinase kinase kinase ... ...

    Abstract The transforming growth factor-β-activated kinase 1 (TAK1) encoded by mitogen-activated protein kinase kinase kinase 7
    MeSH term(s) Abnormalities, Multiple/diagnosis ; Abnormalities, Multiple/genetics ; Biomarkers ; Facies ; Genetic Association Studies ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; MAP Kinase Kinase Kinases/genetics ; Male ; Mutation ; Phenotype ; Radiography ; Syndrome
    Chemical Substances Biomarkers ; MAP Kinase Kinase Kinases (EC 2.7.11.25) ; MAP kinase kinase kinase 7 (EC 2.7.11.25)
    Language English
    Publishing date 2020-06-12
    Publishing country United States
    Document type Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2835759-0
    ISSN 2373-2873 ; 2373-2873
    ISSN (online) 2373-2873
    ISSN 2373-2873
    DOI 10.1101/mcs.a005207
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  4. Article: Functional testing for variant prioritization in a family with long QT syndrome

    Najari Beidokhti, Maliheh / Bertalovitz, Alexander C. / Ji, Weizhen / McCormack, Jorge / Jeffries, Lauren / Sempou, Emily / Khokha, Mustafa K. / McDonald, Thomas V. / Lakhani, Saquib A.

    Molecular genetics and genomics. 2021 July, v. 296, no. 4

    2021  

    Abstract: Next-generation sequencing platforms are being increasingly applied in clinical genetic settings for evaluation of families with suspected heritable disease. These platforms potentially improve the diagnostic yield beyond that of disease-specific ... ...

    Abstract Next-generation sequencing platforms are being increasingly applied in clinical genetic settings for evaluation of families with suspected heritable disease. These platforms potentially improve the diagnostic yield beyond that of disease-specific targeted gene panels, but also increase the number of rare or novel genetic variants that may confound precise diagnostics. Here, we describe a functional testing approach used to interpret the results of whole exome sequencing (WES) in a family presenting with syncope and sudden death. One individual had a prolonged QT interval on electrocardiogram (ECG) and carried a diagnosis of long QT syndrome (LQTS), but a second individual did not meet criteria for LQTS. Filtering WES results for uncommon variants with arrhythmia association identified four for further analyses. In silico analyses indicated that two of these variants, KCNH2 p.(Cys555Arg) and KCNQ1 p.(Arg293Cys), were likely to be causal in this family’s LQTS. We subsequently performed functional characterization of these variants in a heterologous expression system. The expression of KCNQ1-Arg293Cys did not show a deleterious phenotype but KCNH2-Cys555Arg demonstrated a loss-of-function phenotype that was partially dominant. Our stepwise approach identified a precise genetic etiology in this family, which resulted in the establishment of a LQTS diagnosis in the second individual as well as an additional asymptomatic family member, enabling personalized clinical management. Given its ability to aid in the diagnosis, the application of functional characterization should be considered as a value adjunct to in silico analyses of WES.
    Keywords arrhythmia ; computer simulation ; death ; diagnostic techniques ; electrocardiography ; etiology ; genes ; genomics ; heterologous gene expression ; loss-of-function mutation ; phenotype ; prioritization ; syncope
    Language English
    Dates of publication 2021-07
    Size p. 823-836.
    Publishing place Springer Berlin Heidelberg
    Document type Article
    ISSN 1617-4615
    DOI 10.1007/s00438-021-01780-3
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  5. Article ; Online: TBX5

    Azab, Bilal / Aburizeg, Dunia / Ji, Weizhen / Jeffries, Lauren / Isbeih, Nooredeen Jamal / Al-Akily, Amal Saleh / Mohammad, Hashim / Osba, Yousef Abu / Shahin, Mohammad A / Dardas, Zain / Hatmal, Ma'mon M / Al-Ammouri, Iyad / Lakhani, Saquib

    Molecular medicine reports

    2022  Volume 25, Issue 6

    Abstract: Variants in T‑box transcription factor 5 ( ...

    Abstract Variants in T‑box transcription factor 5 (
    MeSH term(s) Abnormalities, Multiple ; Female ; Heart Defects, Congenital/diagnosis ; Heart Defects, Congenital/genetics ; Heart Defects, Congenital/pathology ; Heart Septal Defects, Atrial/diagnosis ; Heart Septal Defects, Atrial/genetics ; Humans ; Lower Extremity Deformities, Congenital ; Phenotype ; Scimitar Syndrome/genetics ; T-Box Domain Proteins/genetics ; Upper Extremity Deformities, Congenital
    Chemical Substances T-Box Domain Proteins ; T-box transcription factor 5
    Language English
    Publishing date 2022-05-06
    Publishing country Greece
    Document type Journal Article
    ZDB-ID 2469505-1
    ISSN 1791-3004 ; 1791-2997
    ISSN (online) 1791-3004
    ISSN 1791-2997
    DOI 10.3892/mmr.2022.12726
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: DYNC1H1-related disorders: A description of four new unrelated patients and a comprehensive review of previously reported variants.

    Amabile, Sonia / Jeffries, Lauren / McGrath, James M / Ji, Weizhen / Spencer-Manzon, Michele / Zhang, Hui / Lakhani, Saquib A

    American journal of medical genetics. Part A

    2020  Volume 182, Issue 9, Page(s) 2049–2057

    Abstract: Heterozygous variants in the DYNC1H1 gene have been associated chiefly with intellectual disability (ID), malformations in cortical development (MCD), spinal muscular atrophy (SMA), and Charcot-Marie-Tooth axonal type 20 (CMT), with fewer reports ... ...

    Abstract Heterozygous variants in the DYNC1H1 gene have been associated chiefly with intellectual disability (ID), malformations in cortical development (MCD), spinal muscular atrophy (SMA), and Charcot-Marie-Tooth axonal type 20 (CMT), with fewer reports describing other intersecting phenotypes. To better characterize the variable syndromes associated with DYNC1H1, we undertook a detailed analysis of reported patients in the medical literature through June 30, 2019. In sum we identified 200 patients from 143 families harboring 103 different DYNC1H1 variants, and added reports for four unrelated patients identified at our center, three with novel variants. The most common features associated with DYNC1H1 were neuromuscular (NM) disease (largely associated with variants in the stem domain), ID with MCD (largely associated with variants in the motor domain), or a combination of these phenotypes. Despite these trends, exceptions are noted throughout. Overall, DYNC1H1 is associated with variable neurodevelopmental and/or neuromuscular phenotypes that overlap. To avoid confusion DYNC1H1 disorders may be best categorized at this time by more general descriptions rather than phenotype-specific nomenclature such as SMA or CMT. We therefore propose the terms: DYNC1H1-related NM disorder, DYNC1H1-related CNS disorder, and DYNC1H1-related combined disorder. Our single center's experience may be evidence that disease-causing variants in this gene are more prevalent than currently recognized.
    MeSH term(s) Adolescent ; Charcot-Marie-Tooth Disease/genetics ; Charcot-Marie-Tooth Disease/pathology ; Child ; Child, Preschool ; Cytoplasmic Dyneins/genetics ; Female ; Genetic Predisposition to Disease ; Heterozygote ; Humans ; Infant ; Male ; Malformations of Cortical Development/genetics ; Malformations of Cortical Development/pathology ; Muscular Atrophy, Spinal/genetics ; Muscular Atrophy, Spinal/pathology ; Mutation, Missense/genetics ; Phenotype
    Chemical Substances DYNC1H1 protein, human ; Cytoplasmic Dyneins (EC 3.6.4.2)
    Language English
    Publishing date 2020-07-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2108614-X
    ISSN 1552-4833 ; 0148-7299 ; 1552-4825
    ISSN (online) 1552-4833
    ISSN 0148-7299 ; 1552-4825
    DOI 10.1002/ajmg.a.61729
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    Zs.A 1376/A: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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  7. Article ; Online: The latest FADS: Functional analysis of GLDN patient variants and classification of GLDN-associated AMC as a type of viable fetal akinesia deformation sequence.

    Mis, Emily K / Al-Ali, Samir / Ji, Weizhen / Spencer-Manzon, Michele / Konstantino, Monica / Khokha, Mustafa K / Jeffries, Lauren / Lakhani, Saquib A

    American journal of medical genetics. Part A

    2020  Volume 182, Issue 10, Page(s) 2291–2296

    Abstract: Recessive variants in the GLDN gene, which encodes the gliomedin protein and is involved in nervous system development, have recently been associated with Arthrogryposis Multiplex Congenita (AMC), a heterogenous condition characterized by congenital ... ...

    Abstract Recessive variants in the GLDN gene, which encodes the gliomedin protein and is involved in nervous system development, have recently been associated with Arthrogryposis Multiplex Congenita (AMC), a heterogenous condition characterized by congenital contractures of more than one joint. Two cohorts of patients with GLDN-associated AMC have previously been described, evolving the understanding of the condition from lethal to survivable with the provision of significant neonatal support. Here, we describe one additional patient currently living with the syndrome, having one novel variant, p.Leu365Phe, for which we provide functional data supporting its pathogenicity. We additionally provide experimental data for four other previously reported variants lacking functional evidence, including p.Arg393Lys, the second variant present in our patient. We discuss unique and defining clinical features, adding calcium-related findings which appear to be recurrent in the GLDN cohort. Finally, we compare all previously reported patients and draw new conclusions about scope of illness, with emphasis on the finding of pulmonary hypoplasia, suggesting that AMC secondary to GLDN variants may be best fitted under the umbrella of fetal akinesia deformation sequence (FADS).
    MeSH term(s) Arthrogryposis/genetics ; Arthrogryposis/pathology ; Child, Preschool ; Female ; Genetic Predisposition to Disease ; Humans ; Membrane Proteins/genetics ; Mutation ; Nerve Tissue Proteins/genetics ; Pedigree
    Chemical Substances GLDN protein, human ; Membrane Proteins ; Nerve Tissue Proteins
    Language English
    Publishing date 2020-08-19
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 2108614-X
    ISSN 1552-4833 ; 0148-7299 ; 1552-4825
    ISSN (online) 1552-4833
    ISSN 0148-7299 ; 1552-4825
    DOI 10.1002/ajmg.a.61783
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    In stock of ZB MED Cologne/Königswinter

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    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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  8. Article ; Online: Functional testing for variant prioritization in a family with long QT syndrome.

    Najari Beidokhti, Maliheh / Bertalovitz, Alexander C / Ji, Weizhen / McCormack, Jorge / Jeffries, Lauren / Sempou, Emily / Khokha, Mustafa K / McDonald, Thomas V / Lakhani, Saquib A

    Molecular genetics and genomics : MGG

    2021  Volume 296, Issue 4, Page(s) 823–836

    Abstract: Next-generation sequencing platforms are being increasingly applied in clinical genetic settings for evaluation of families with suspected heritable disease. These platforms potentially improve the diagnostic yield beyond that of disease-specific ... ...

    Abstract Next-generation sequencing platforms are being increasingly applied in clinical genetic settings for evaluation of families with suspected heritable disease. These platforms potentially improve the diagnostic yield beyond that of disease-specific targeted gene panels, but also increase the number of rare or novel genetic variants that may confound precise diagnostics. Here, we describe a functional testing approach used to interpret the results of whole exome sequencing (WES) in a family presenting with syncope and sudden death. One individual had a prolonged QT interval on electrocardiogram (ECG) and carried a diagnosis of long QT syndrome (LQTS), but a second individual did not meet criteria for LQTS. Filtering WES results for uncommon variants with arrhythmia association identified four for further analyses. In silico analyses indicated that two of these variants, KCNH2 p.(Cys555Arg) and KCNQ1 p.(Arg293Cys), were likely to be causal in this family's LQTS. We subsequently performed functional characterization of these variants in a heterologous expression system. The expression of KCNQ1-Arg293Cys did not show a deleterious phenotype but KCNH2-Cys555Arg demonstrated a loss-of-function phenotype that was partially dominant. Our stepwise approach identified a precise genetic etiology in this family, which resulted in the establishment of a LQTS diagnosis in the second individual as well as an additional asymptomatic family member, enabling personalized clinical management. Given its ability to aid in the diagnosis, the application of functional characterization should be considered as a value adjunct to in silico analyses of WES.
    MeSH term(s) AMP-Activated Protein Kinases/genetics ; Amino Acid Substitution/genetics ; DNA Mutational Analysis/methods ; ERG1 Potassium Channel/genetics ; Electrocardiography ; Family ; Female ; Genetic Testing/methods ; HEK293 Cells ; Heart Function Tests/methods ; Humans ; KCNQ1 Potassium Channel/genetics ; Long QT Syndrome/genetics ; Long QT Syndrome/physiopathology ; Middle Aged ; Mutation ; Pedigree ; Phenotype ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Protein-Serine-Threonine Kinases/genetics ; Whole Exome Sequencing
    Chemical Substances ERG1 Potassium Channel ; KCNH2 protein, human ; KCNQ1 Potassium Channel ; KCNQ1 protein, human ; PRKAG2 protein, human (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; TNNI3K protein, human (EC 2.7.11.1) ; AMP-Activated Protein Kinases (EC 2.7.11.31)
    Language English
    Publishing date 2021-04-19
    Publishing country Germany
    Document type Case Reports ; Journal Article
    ZDB-ID 2044817-X
    ISSN 1617-4623 ; 1617-4615
    ISSN (online) 1617-4623
    ISSN 1617-4615
    DOI 10.1007/s00438-021-01780-3
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    Zs.A 1198: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  9. Article ; Online: Identification of a novel

    Criscione, June / Ji, Weizhen / Jeffries, Lauren / McGrath, James M / Soloway, Scott / Pusztai, Lajos / Lakhani, Saquib

    Cold Spring Harbor molecular case studies

    2019  Volume 5, Issue 6

    Abstract: Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide. Most cases are multifactorial in etiology, but some are associated with variants in the myocilin gene, ...

    Abstract Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide. Most cases are multifactorial in etiology, but some are associated with variants in the myocilin gene,
    MeSH term(s) Adult ; Amino Acid Sequence/genetics ; Cytoskeletal Proteins/genetics ; Cytoskeletal Proteins/metabolism ; Exons/genetics ; Extracellular Matrix Proteins/genetics ; Eye Proteins/genetics ; Eye Proteins/metabolism ; Family ; Female ; Genetic Testing/methods ; Glaucoma, Open-Angle/genetics ; Glaucoma, Open-Angle/metabolism ; Glycoproteins/genetics ; Glycoproteins/metabolism ; Hispanic Americans/genetics ; Humans ; Intraocular Pressure/genetics ; Male ; Middle Aged ; Mutation/genetics ; Pedigree ; Phenotype ; Young Adult
    Chemical Substances Cytoskeletal Proteins ; Extracellular Matrix Proteins ; Eye Proteins ; Glycoproteins ; olfactomedin ; trabecular meshwork-induced glucocorticoid response protein
    Language English
    Publishing date 2019-12-13
    Publishing country United States
    Document type Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2835759-0
    ISSN 2373-2873 ; 2373-2873
    ISSN (online) 2373-2873
    ISSN 2373-2873
    DOI 10.1101/mcs.a004374
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Siblings with lethal primary pulmonary hypoplasia and compound heterozygous variants in the

    Kiraly-Borri, Catherine / Jevon, Gareth / Ji, Weizhen / Jeffries, Lauren / Ricciardi, Jamie-Lee / Konstantino, Monica / Ackerman, Kate G / Lakhani, Saquib A

    Cold Spring Harbor molecular case studies

    2019  Volume 5, Issue 3

    Abstract: Variants in the mitochondrial alanyl-tRNA synthetase 2 ... ...

    Abstract Variants in the mitochondrial alanyl-tRNA synthetase 2 gene
    MeSH term(s) Abnormalities, Multiple/diagnostic imaging ; Abnormalities, Multiple/genetics ; Abnormalities, Multiple/pathology ; Alanine-tRNA Ligase/genetics ; Amino Acid Substitution ; Fatal Outcome ; Frameshift Mutation ; Genes, Recessive ; Heterozygote ; Humans ; Infant, Newborn ; Leukoencephalopathies/diagnosis ; Leukoencephalopathies/genetics ; Leukoencephalopathies/pathology ; Lung/abnormalities ; Lung/diagnostic imaging ; Lung/pathology ; Lung Diseases/diagnostic imaging ; Lung Diseases/genetics ; Lung Diseases/pathology ; Mitochondria/genetics ; Mitochondria/pathology ; Pedigree ; Phenotype ; Siblings ; Whole Exome Sequencing
    Chemical Substances AARS2 protein, human (EC 6.1.1.7) ; Alanine-tRNA Ligase (EC 6.1.1.7)
    Language English
    Publishing date 2019-06-03
    Publishing country United States
    Document type Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2835759-0
    ISSN 2373-2873 ; 2373-2873
    ISSN (online) 2373-2873
    ISSN 2373-2873
    DOI 10.1101/mcs.a003699
    Database MEDical Literature Analysis and Retrieval System OnLINE

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