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  1. Article: Preparing for Death While Investing in Life: A Narrative Inquiry and Case Report of Home-Based Paediatric Palliative, End-of-Life, and After-Death Care.

    Noyes, Michelle / Delaney, Angela / Lang, Meagan / Maybury, Mellissa / Moloney, Susan / Bradford, Natalie

    Children (Basel, Switzerland)

    2023  Volume 10, Issue 11

    Abstract: Paediatric palliative care is pivotal for addressing the complex needs of children with incurable diseases and their families. While home-based care offers a familiar and supportive environment, delivering comprehensive services in this context is ... ...

    Abstract Paediatric palliative care is pivotal for addressing the complex needs of children with incurable diseases and their families. While home-based care offers a familiar and supportive environment, delivering comprehensive services in this context is challenging. The existing literature on home-based palliative care lacks detailed guidance for its organization and implementation. This qualitative narrative inquiry explores the organization and provision of home-based paediatric palliative care. Data were collected from healthcare practitioners using conversations, storytelling, and reflective journaling. Schwind's Narrative Reflective Process was applied to synthesize the data, resulting in an in-depth case description. The narrative approach illuminates the complexities of home-based paediatric palliative, end-of-life, and after-death care. Key findings encompass the importance of early-care coordination, interprofessional collaboration, effective symptom management, emotional and psychosocial support, and comprehensive end-of-life planning. Through the case study of the child patient, the challenges and strategies for providing holistic, family-centred care within the home environment are described. Practical insights gained from this report can inform the development and improvement of home-based palliative care programs, benefiting researchers, practitioners, and policymakers seeking to optimize care for children and families in similar contexts.
    Language English
    Publishing date 2023-11-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2732685-8
    ISSN 2227-9067
    ISSN 2227-9067
    DOI 10.3390/children10111777
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Efficient detection and monitoring of pediatric brain malignancies with liquid biopsy based on patient-specific somatic mutation screening.

    Kojic, Marija / Maybury, Mellissa K / Waddell, Nicola / Koufariotis, Lambros T / Addala, Venkateswar / Millar, Amanda / Wood, Scott / Pearson, John V / Hansford, Jordan R / Hassall, Tim / Wainwright, Brandon J

    Neuro-oncology

    2023  Volume 25, Issue 8, Page(s) 1507–1517

    Abstract: Background: Brain cancer is the leading cause of cancer-related death in children. Early detection and serial monitoring are essential for better therapeutic outcomes. Liquid biopsy has recently emerged as a promising approach for detecting these tumors ...

    Abstract Background: Brain cancer is the leading cause of cancer-related death in children. Early detection and serial monitoring are essential for better therapeutic outcomes. Liquid biopsy has recently emerged as a promising approach for detecting these tumors by screening body fluids for the presence of circulating tumor DNA (ctDNA). Here we tested the limits of liquid biopsy using patient-specific somatic mutations to detect and monitor primary and metastatic pediatric brain cancer.
    Methods: Somatic mutations were identified in 3 ependymoma, 1 embryonal tumor with multilayered rosettes, 1 central nervous system neuroblastoma, and 7 medulloblastoma patients. The mutations were used as liquid biomarkers for serial assessment of cerebrospinal fluid (CSF) samples using a droplet digital PCR (ddPCR) system. The findings were correlated to the imaging data and clinical assessment to evaluate the utility of the approach for clinical translation.
    Results: We developed personalized somatic mutation ddPCR assays which we show are highly specific, sensitive, and efficient in detection and monitoring of ctDNA, with a positive correlation between presence of ctDNA, disease course, and clinical outcomes in the majority of patients.
    Conclusions: We demonstrate the feasibility and clinical utility of personalized mutation-based liquid biopsy for the surveillance of brain cancer in children. However, even with this specific and sensitive approach, we identified some potential false negative analyses. Overall, our results indicate that changes in ctDNA profiles over time demonstrate the great potential of our specific approach for predicting tumor progression, burden, and response to treatment.
    MeSH term(s) Humans ; Child ; Biomarkers, Tumor/genetics ; Brain Neoplasms/diagnosis ; Brain Neoplasms/genetics ; Liquid Biopsy/methods ; Circulating Tumor DNA/genetics ; Mutation
    Chemical Substances Biomarkers, Tumor ; Circulating Tumor DNA
    Language English
    Publishing date 2023-02-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2028601-6
    ISSN 1523-5866 ; 1522-8517
    ISSN (online) 1523-5866
    ISSN 1522-8517
    DOI 10.1093/neuonc/noad032
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5307: Show issues Location:
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  3. Article ; Online: Circular RNAs drive oncogenic chromosomal translocations within the MLL recombinome in leukemia.

    Conn, Vanessa M / Gabryelska, Marta / Toubia, John / Kirk, Kirsty / Gantley, Laura / Powell, Jason A / Cildir, Gökhan / Marri, Shashikanth / Liu, Ryan / Stringer, Brett W / Townley, Scott / Webb, Stuart T / Lin, He / Samaraweera, Saumya E / Bailey, Sheree / Moore, Andrew S / Maybury, Mellissa / Liu, Dawei / Colella, Alex D /
    Chataway, Timothy / Wallington-Gates, Craig T / Walters, Lucie / Sibbons, Jane / Selth, Luke A / Tergaonkar, Vinay / D'Andrea, Richard J / Pitson, Stuart M / Goodall, Gregory J / Conn, Simon J

    Cancer cell

    2023  Volume 41, Issue 7, Page(s) 1309–1326.e10

    Abstract: The first step of oncogenesis is the acquisition of a repertoire of genetic mutations to initiate and sustain the malignancy. An important example of this initiation phase in acute leukemias is the formation of a potent oncogene by chromosomal ... ...

    Abstract The first step of oncogenesis is the acquisition of a repertoire of genetic mutations to initiate and sustain the malignancy. An important example of this initiation phase in acute leukemias is the formation of a potent oncogene by chromosomal translocations between the mixed lineage leukemia (MLL) gene and one of 100 translocation partners, known as the MLL recombinome. Here, we show that circular RNAs (circRNAs)-a family of covalently closed, alternatively spliced RNA molecules-are enriched within the MLL recombinome and can bind DNA, forming circRNA:DNA hybrids (circR loops) at their cognate loci. These circR loops promote transcriptional pausing, proteasome inhibition, chromatin re-organization, and DNA breakage. Importantly, overexpressing circRNAs in mouse leukemia xenograft models results in co-localization of genomic loci, de novo generation of clinically relevant chromosomal translocations mimicking the MLL recombinome, and hastening of disease onset. Our findings provide fundamental insight into the acquisition of chromosomal translocations by endogenous RNA carcinogens in leukemia.
    MeSH term(s) Animals ; Mice ; Humans ; Translocation, Genetic ; RNA, Circular/genetics ; Myeloid-Lymphoid Leukemia Protein/genetics ; Myeloid-Lymphoid Leukemia Protein/metabolism ; Leukemia/genetics ; Leukemia/pathology ; DNA ; Oncogene Proteins, Fusion/genetics
    Chemical Substances RNA, Circular ; Myeloid-Lymphoid Leukemia Protein (149025-06-9) ; DNA (9007-49-2) ; Oncogene Proteins, Fusion
    Language English
    Publishing date 2023-06-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2078448-X
    ISSN 1878-3686 ; 1535-6108
    ISSN (online) 1878-3686
    ISSN 1535-6108
    DOI 10.1016/j.ccell.2023.05.002
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5650: Show issues Location:
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    Zs.MG 104: Show issues

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  4. Article: Preventing recurrence in Sonic Hedgehog Subgroup Medulloblastoma using the OLIG2 inhibitor CT-179.

    Li, Yuchen / Lim, Chaemin / Dismuke, Taylor / Malawsky, Daniel S / Oasa, Sho / Bruce, Zara C / Offenhäuser, Carolin / Baumgartner, Ulrich / D'Souza, Rochelle C J / Edwards, Stacey L / French, Juliet D / Ock, Lucy S H / Nair, Sneha / Sivakumaran, Haran / Harris, Lachlan / Tikunov, Andrey P / Hwang, Duhyeong / Del Mar Alicea Pauneto, Coral / Maybury, Mellissa /
    Hassall, Timothy / Wainwright, Brandon / Kesari, Santosh / Stein, Gregory / Piper, Michael / Johns, Terrance G / Sokolsky-Papkov, Marina / Terenius, Lars / Vukojević, Vladana / Gershon, Timothy R / Day, Bryan W

    Research square

    2023  

    Abstract: Recurrence is the primary life-threatening complication for medulloblastoma (MB). In Sonic Hedgehog (SHH)-subgroup MB, OLIG2-expressing tumor stem cells drive recurrence. We investigated the anti-tumor potential of the small-molecule OLIG2 inhibitor CT- ... ...

    Abstract Recurrence is the primary life-threatening complication for medulloblastoma (MB). In Sonic Hedgehog (SHH)-subgroup MB, OLIG2-expressing tumor stem cells drive recurrence. We investigated the anti-tumor potential of the small-molecule OLIG2 inhibitor CT-179, using SHH-MB patient-derived organoids, patient-derived xenograft (PDX) tumors and mice genetically-engineered to develop SHH-MB. CT-179 disrupted OLIG2 dimerization, DNA binding and phosphorylation and altered tumor cell cycle kinetics
    Language English
    Publishing date 2023-06-09
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-2949436/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Biologic and clinical features of childhood gamma delta T-ALL: identification of STAG2/LMO2 γδ T-ALL as an extremely high risk leukemia in the very young.

    Kimura, Shunsuke / Polonen, Petri / Montefiori, Lindsey / Park, Chun Shik / Iacobucci, Ilaria / Yeoh, Allen Ej / Attarbaschi, Andishe / Moore, Andrew S / Brown, Anthony / Manabe, Atsushi / Buldini, Barbara / Freeman, Burgess B / Chen, Chelsey / Cheng, Cheng / Kean Hui, Chiew / Li, Chi-Kong / Pui, Ching-Hon / Qu, Chunxu / Tomizawa, Daisuke /
    Teachey, David T / Varotto, Elena / Paietta, Elisabeth M / Arnold, Elizabeth D / Locatelli, Franco / Escherich, Gabriele / Elisa Muhle, Hannah / Marquart, Hanne Vibeke / de Groot-Kruseman, Hester A / Rowe, Jacob M / Stary, Jan / Trka, Jan / Choi, John Kim / Meijerink, Jules P P / Yang, Jun J / Takita, Junko / Pawinska-Wasikowska, Katarzyna / Roberts, Kathryn G / Han, Katie / Caldwell, Kenneth J / Schmiegelow, Kjeld / Crews, Kristine R / Eguchi, Mariko / Schrappe, Martin / Zimmerman, Martin / Takagi, Masatoshi / Maybury, Mellissa / Svaton, Michael / Reiterova, Michaela / Kicinski, Michal / Prater, Mollie S / Kato, Motohiro / Reyes, Noemi / Spinelli, Orietta / Thomas, Paul / Mazilier, Pauline / Gao, Qingsong / Masetti, Riccardo / Kotecha, Rishi S / Pieters, Rob / Elitzur, Sarah / Luger, Selina M / Mitchell, Sharnise / Pruett-Miller, Shondra M / Shen, Shuhong / Jeha, Sima / Köhrer, Stefan / Kornblau, Steven M / Skoczeń, Szymon / Miyamura, Takako / Vincent, Tiffaney L / Imamura, Toshihiko / Conter, Valentino / Tang, Yanjing / Liu, Yen-Chun / Chang, Yunchao / Gu, Zhaohui / Cheng, Zhongshan / Yinmei, Zhou / Inaba, Hiroto / Mullighan, Charles G

    medRxiv : the preprint server for health sciences

    2023  

    Abstract: Purpose: Gamma delta T-cell receptor-positive acute lymphoblastic leukemia (γδ T-ALL) is a high-risk but poorly characterized disease.: Methods: We studied clinical features of 200 pediatric γδ T-ALL, and compared the prognosis of 93 cases to 1,067 ... ...

    Abstract Purpose: Gamma delta T-cell receptor-positive acute lymphoblastic leukemia (γδ T-ALL) is a high-risk but poorly characterized disease.
    Methods: We studied clinical features of 200 pediatric γδ T-ALL, and compared the prognosis of 93 cases to 1,067 protocol-matched non-γδ T-ALL. Genomic features were defined by transcriptome and genome sequencing. Experimental modeling was used to examine the mechanistic impacts of genomic alterations. Therapeutic vulnerabilities were identified by high throughput drug screening of cell lines and xenografts.
    Results: γδ T-ALL in children under three was extremely high-risk with 5-year event-free survival (33% v. 70% [age 3-<10] and 73% [age ≥10],
    Conclusion: γδ T-ALL in children under the age of three is extremely high-risk and enriched for
    Support: The authors are supported by the American and Lebanese Syrian Associated Charities of St Jude Children's Research Hospital, NCI grants R35 CA197695, P50 CA021765 (C.G.M.), the Henry Schueler 41&9 Foundation (C.G.M.), and a St. Baldrick's Foundation Robert J. Arceci Innovation Award (C.G.M.), Gabriella Miller Kids First X01HD100702 (D.T.T and C.G.M.) and R03CA256550 (D.T.T. and C.G.M.), F32 5F32CA254140 (L.M.), and a Garwood Postdoctoral Fellowship of the Hematological Malignancies Program of the St Jude Children's Research Hospital Comprehensive Cancer Center (S.K.). This project was supported by the National Cancer Institute of the National Institutes of Health under the following award numbers: U10CA180820, UG1CA189859, U24CA114766, U10CA180899, U10CA180866 and U24CA196173.
    Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funding agencies were not directly involved in the design of the study, gathering, analysis and interpretation of the data, writing of the manuscript, or decision to submit the manuscript for publication.
    Language English
    Publishing date 2023-11-08
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.11.06.23298028
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  6. Article ; Online: Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes.

    Clarke, Matthew / Mackay, Alan / Ismer, Britta / Pickles, Jessica C / Tatevossian, Ruth G / Newman, Scott / Bale, Tejus A / Stoler, Iris / Izquierdo, Elisa / Temelso, Sara / Carvalho, Diana M / Molinari, Valeria / Burford, Anna / Howell, Louise / Virasami, Alex / Fairchild, Amy R / Avery, Aimee / Chalker, Jane / Kristiansen, Mark /
    Haupfear, Kelly / Dalton, James D / Orisme, Wilda / Wen, Ji / Hubank, Michael / Kurian, Kathreena M / Rowe, Catherine / Maybury, Mellissa / Crosier, Stephen / Knipstein, Jeffrey / Schüller, Ulrich / Kordes, Uwe / Kram, David E / Snuderl, Matija / Bridges, Leslie / Martin, Andrew J / Doey, Lawrence J / Al-Sarraj, Safa / Chandler, Christopher / Zebian, Bassel / Cairns, Claire / Natrajan, Rachael / Boult, Jessica K R / Robinson, Simon P / Sill, Martin / Dunkel, Ira J / Gilheeney, Stephen W / Rosenblum, Marc K / Hughes, Debbie / Proszek, Paula Z / Macdonald, Tobey J / Preusser, Matthias / Haberler, Christine / Slavc, Irene / Packer, Roger / Ng, Ho-Keung / Caspi, Shani / Popović, Mara / Faganel Kotnik, Barbara / Wood, Matthew D / Baird, Lissa / Davare, Monika Ashok / Solomon, David A / Olsen, Thale Kristin / Brandal, Petter / Farrell, Michael / Cryan, Jane B / Capra, Michael / Karremann, Michael / Schittenhelm, Jens / Schuhmann, Martin U / Ebinger, Martin / Dinjens, Winand N M / Kerl, Kornelius / Hettmer, Simone / Pietsch, Torsten / Andreiuolo, Felipe / Driever, Pablo Hernáiz / Korshunov, Andrey / Hiddingh, Lotte / Worst, Barbara C / Sturm, Dominik / Zuckermann, Marc / Witt, Olaf / Bloom, Tabitha / Mitchell, Clare / Miele, Evelina / Colafati, Giovanna Stefania / Diomedi-Camassei, Francesca / Bailey, Simon / Moore, Andrew S / Hassall, Timothy E G / Lowis, Stephen P / Tsoli, Maria / Cowley, Mark J / Ziegler, David S / Karajannis, Matthias A / Aquilina, Kristian / Hargrave, Darren R / Carceller, Fernando / Marshall, Lynley V / von Deimling, Andreas / Kramm, Christof M / Pfister, Stefan M / Sahm, Felix / Baker, Suzanne J / Mastronuzzi, Angela / Carai, Andrea / Vinci, Maria / Capper, David / Popov, Sergey / Ellison, David W / Jacques, Thomas S / Jones, David T W / Jones, Chris

    Cancer discovery

    2020  Volume 10, Issue 7, Page(s) 942–963

    Abstract: Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried ... ...

    Abstract Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, genome, or exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an "intrinsic" spectrum of disease specific to the infant population. These included those with targetable MAPK alterations, and a large proportion of remaining cases harboring gene fusions targeting
    MeSH term(s) Gene Fusion/genetics ; Glioma/genetics ; Humans ; Infant ; Neoplasm Grading ; Prognosis ; Treatment Outcome
    Language English
    Publishing date 2020-04-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2625242-9
    ISSN 2159-8290 ; 2159-8274
    ISSN (online) 2159-8290
    ISSN 2159-8274
    DOI 10.1158/2159-8290.CD-19-1030
    Database MEDical Literature Analysis and Retrieval System OnLINE

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