LIVIVO - Search results -

Search results

Result 1 - 10 of total 37

Search options

Article ; Online: Proteasome-Associated Syndromes: Updates on Genetics, Clinical Manifestations, Pathogenesis, and Treatment.

Zhang, Jiahui / Tao, Panfeng / Deuitch, Natalie T / Yu, Xiaomin / Askentijevich, Ivona / Zhou, Qing

2024 Volume 44, Issue 4, Page(s) 88

Abstract: The ubiquitin-proteasome system (UPS) has a critical role in post-translational protein modification that is essential for the maintenance of all cellular functions, including immune responses. The proteasome complex is ubiquitously expressed and is ... ...

Abstract	The ubiquitin-proteasome system (UPS) has a critical role in post-translational protein modification that is essential for the maintenance of all cellular functions, including immune responses. The proteasome complex is ubiquitously expressed and is responsible for degradation of short-lived structurally abnormal, misfolded and not-needed proteins that are targeted for degradation via ubiquitin conjugation. Over the last 14 years, an increasing number of human diseases have been linked to pathogenic variants in proteasome subunits and UPS regulators. Defects of the proteasome complex or its chaperons - which have a regulatory role in the assembly of the proteasome - disrupt protein clearance and cellular homeostasis, leading to immune dysregulation, severe inflammation, and neurodevelopmental disorders in humans. Proteasome-associated diseases have complex inheritance, including monogenic, digenic and oligogenic disorders and can be dominantly or recessively inherited. In this review, we summarize the current known genetic causes of proteasomal disease, and discuss the molecular pathogenesis of these conditions based on the function and cellular expression of mutated proteins in the proteasome complex.
MeSH term(s)	Humans ; Proteasome Endopeptidase Complex/genetics ; Proteasome Endopeptidase Complex/metabolism ; Syndrome ; Ubiquitin/metabolism
Chemical Substances	Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Ubiquitin
Language	English
Publishing date	2024-04-05
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	779361-3
ISSN	1573-2592 ; 0271-9142
ISSN (online)	1573-2592
ISSN	0271-9142
DOI	10.1007/s10875-024-01692-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1640: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: A framework to identify ethical concerns with ML-guided care workflows: a case study of mortality prediction to guide advance care planning.

Cagliero, Diana / Deuitch, Natalie / Shah, Nigam / Feudtner, Chris / Char, Danton

Journal of the American Medical Informatics Association : JAMIA

2023 Volume 30, Issue 5, Page(s) 819–827

Abstract: Objective: Identifying ethical concerns with ML applications to healthcare (ML-HCA) before problems arise is now a stated goal of ML design oversight groups and regulatory agencies. Lack of accepted standard methodology for ethical analysis, however, ... ...

Abstract	Objective: Identifying ethical concerns with ML applications to healthcare (ML-HCA) before problems arise is now a stated goal of ML design oversight groups and regulatory agencies. Lack of accepted standard methodology for ethical analysis, however, presents challenges. In this case study, we evaluate use of a stakeholder "values-collision" approach to identify consequential ethical challenges associated with an ML-HCA for advanced care planning (ACP). Identification of ethical challenges could guide revision and improvement of the ML-HCA. Materials and methods: We conducted semistructured interviews of the designers, clinician-users, affiliated administrators, and patients, and inductive qualitative analysis of transcribed interviews using modified grounded theory. Results: Seventeen stakeholders were interviewed. Five "values-collisions"-where stakeholders disagreed about decisions with ethical implications-were identified: (1) end-of-life workflow and how model output is introduced; (2) which stakeholders receive predictions; (3) benefit-harm trade-offs; (4) whether the ML design team has a fiduciary relationship to patients and clinicians; and, (5) how and if to protect early deployment research from external pressures, like news scrutiny, before research is completed. Discussion: From these findings, the ML design team prioritized: (1) alternative workflow implementation strategies; (2) clarification that prediction was only evaluated for ACP need, not other mortality-related ends; and (3) shielding research from scrutiny until endpoint driven studies were completed. Conclusion: In this case study, our ethical analysis of this ML-HCA for ACP was able to identify multiple sites of intrastakeholder disagreement that mark areas of ethical and value tension. These findings provided a useful initial ethical screening.
MeSH term(s)	Humans ; Workflow ; Advance Care Planning ; Ethnicity ; Qualitative Research
Language	English
Publishing date	2023-02-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1205156-1
ISSN	1527-974X ; 1067-5027
ISSN (online)	1527-974X
ISSN	1067-5027
DOI	10.1093/jamia/ocad022
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4128: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 312: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: The Perceived Influence of Neurofibromatosis Type 1(NF1) on the Parents' Relationship.

Wiener, Lori / Bedoya, Sima Zadeh / Goyal, Archita / Gordon, Mallorie / Deuitch, Natalie / Widemann, Brigitte

Children (Basel, Switzerland)

2023 Volume 10, Issue 3

Abstract: Neurofibromatosis type 1 (NF1) is a genetic condition affecting 1 in 3000 individuals. Having a child with a chronic illness can introduce both practical and emotional challenges to a parental relationship. This cross-sectional study was administered to ... ...

Abstract	Neurofibromatosis type 1 (NF1) is a genetic condition affecting 1 in 3000 individuals. Having a child with a chronic illness can introduce both practical and emotional challenges to a parental relationship. This cross-sectional study was administered to 50 parents of children with NF1, diagnosed between the ages of 1-24. Each participant was provided a 50-item self-report survey to complete during an inpatient or outpatient visit. The survey gathered information on the participants' views of the spouse/partner relationship, coping mechanisms, and elements that supported emotional connections. While the majority of parental relationships were reported to remain strong, the mean relationship quality was perceived to have decreased compared to prior to the child's diagnosis. Compassionate and open communication, shared perspective, having time alone with their partner outside of medical situations, and dyadic coping were identified as strategies that could strengthen the relationship. The identified stressors to the parental relationship during the NF1 illness trajectory can inform interventions and help guide development of a couple's intervention. The National Cancer Institute, NIH Institutional Review Board approved this study (12-C-0206).
Language	English
Publishing date	2023-02-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2732685-8
ISSN	2227-9067
ISSN	2227-9067
DOI	10.3390/children10030448
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Revisiting TNF Receptor-Associated Periodic Syndrome (TRAPS): Current Perspectives.

Cudrici, Cornelia / Deuitch, Natalie / Aksentijevich, Ivona

International journal of molecular sciences

2020 Volume 21, Issue 9

Abstract: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory syndrome characterized by prolonged and recurrent episodes of fever, abdominal and/or chest pain, arthralgia, myalgia, and erythematous rash. ... ...

Abstract	Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory syndrome characterized by prolonged and recurrent episodes of fever, abdominal and/or chest pain, arthralgia, myalgia, and erythematous rash. TRAPS is associated with heterozygous variants in the
MeSH term(s)	Biomarkers ; Disease Management ; Disease Susceptibility ; Fever/diagnosis ; Fever/etiology ; Fever/metabolism ; Fever/therapy ; Genetic Predisposition to Disease ; Genetic Variation ; Hereditary Autoinflammatory Diseases/diagnosis ; Hereditary Autoinflammatory Diseases/etiology ; Hereditary Autoinflammatory Diseases/metabolism ; Hereditary Autoinflammatory Diseases/therapy ; Humans ; Molecular Diagnostic Techniques ; Molecular Targeted Therapy ; Phenotype ; Receptors, Tumor Necrosis Factor, Type I/genetics ; Receptors, Tumor Necrosis Factor, Type I/metabolism
Chemical Substances	Biomarkers ; Receptors, Tumor Necrosis Factor, Type I
Language	English
Publishing date	2020-05-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21093263
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: TNF-Blockade for Primary Stroke Prevention in Adenosine Deaminase 2 Deficiency: A Case Series.

Soldatos, Ariane / Toro, Camilo / Hoffmann, Patrycja / Romeo, Tina / Deuitch, Natalie / Brofferio, Alessandra / Aksentijevich, Ivona / Kastner, Daniel L / Ombrello, Amanda K

Neurology(R) neuroimmunology & neuroinflammation

2023 Volume 10, Issue 3

Abstract: Objectives: Adenosine deaminase 2 deficiency (DADA2) is a genetic, neurologic, and systemic vasculitis syndrome, which can lead to recurrent strokes, typically lacunar. In the cohort of now 60 patients followed up at the NIH Clinical Center (NIH CC), no ...

Abstract	Objectives: Adenosine deaminase 2 deficiency (DADA2) is a genetic, neurologic, and systemic vasculitis syndrome, which can lead to recurrent strokes, typically lacunar. In the cohort of now 60 patients followed up at the NIH Clinical Center (NIH CC), no patient has had a stroke since starting tumor necrosis factor (TNF) blockade. We present a family with multiple affected children to highlight the importance of TNF blockade not just as secondary stroke prevention but also as primary stroke prevention in genetically affected but clinically asymptomatic patients. Methods: A proband with recurrent cryptogenic strokes was referred for evaluation at the NIH CC. The parents and 3 clinically asymptomatic siblings were also evaluated. Results: The proband was diagnosed with DADA2 based on biochemical testing; her antiplatelet therapies were discontinued, and she was started on TNF blockade for secondary stroke prevention. Her 3 asymptomatic siblings were subsequently tested and 2 were found to be biochemically affected. One of them elected to start TNF blockade for primary stroke prevention and the other sibling declined this approach and experienced a stroke. A second genetic sequence variant was subsequently identified in the Discussion: This family illustrates the importance of testing for DADA2 in young patients with cryptogenic stroke, given the hemorrhagic risks with antiplatelet drugs in these patients and effectiveness of TNF blockade as secondary stroke prevention. In addition, this family highlights the importance of screening all siblings of affected patients because they may be presymptomatic, and we advocate starting TNF blockade for primary stroke prevention in those who are found to be genetically or biochemically affected.
MeSH term(s)	Humans ; Child ; Female ; Adenosine Deaminase/genetics ; Intercellular Signaling Peptides and Proteins ; Stroke/prevention & control ; Tumor Necrosis Factor-alpha
Chemical Substances	Adenosine Deaminase (EC 3.5.4.4) ; Intercellular Signaling Peptides and Proteins ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2023-03-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2767740-0
ISSN	2332-7812 ; 2332-7812
ISSN (online)	2332-7812
ISSN	2332-7812
DOI	10.1212/NXI.0000000000200073
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Translating genomic testing results for pediatric critical care: Opportunities for genetic counselors.

Deuitch, Natalie / Soo-Jin Lee, Sandra / Char, Danton

Journal of genetic counseling

2019 Volume 29, Issue 1, Page(s) 78–87

Abstract: Genomic sequencing (GS), such as whole genome and exome sequencing, is rapidly being integrated into pediatric critical care settings. Results are being used to make high impact decisions including declarations of futility, withdrawal of care, and ... ...

Abstract	Genomic sequencing (GS), such as whole genome and exome sequencing, is rapidly being integrated into pediatric critical care settings. Results are being used to make high impact decisions including declarations of futility, withdrawal of care, and rationing of scarce resources. In this qualitative study, we conducted interviews with clinicians involved in the care of critically ill children with congenital heart disease (CHD) to investigate their views on implementation of GS into clinical practice. Interviews were transcribed and inductively analyzed for major themes using grounded theory and thematic analysis. Three major themes emerged surrounding the use of genomic information in the high-stakes, time pressured decision making that characterizes clinical care of critically ill children with CHD: (a) that clinicians felt they did not have sufficient training to accurately assess genetic results despite pressure to incorporate results into clinical decisions; (b), that they desire knowledge support from genetic specialists, such as genetic counselors, who both understand the critical care context and are available within the time constraints of critical care clinical pressures; and (c), that clinicians feel a pressing need for increased genetics education to be able to safely and appropriately incorporate GS results into clinical decisions Our data suggest that genetics specialists may need a stronger presence in the pediatric critical care setting.
MeSH term(s)	Child ; Counselors ; Critical Care ; Female ; Genetic Counseling ; Genetic Testing ; Grounded Theory ; Humans ; Male ; Pediatrics ; Qualitative Research ; Whole Exome Sequencing
Language	English
Publishing date	2019-11-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1117799-8
ISSN	1573-3599 ; 1059-7700
ISSN (online)	1573-3599
ISSN	1059-7700
DOI	10.1002/jgc4.1182
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 4263: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Novel ADA2 Compound Heterozygous Mutations Resulting in Deficiency of Adenosine Deaminase 2 in a Pair of Siblings.

Guo, Li / Wang, Jun / Yang, Xinghui / Zheng, Rongjun / Deuitch, Natalie / Tao, Panfeng / Zhou, Qing

Journal of clinical immunology

2021 Volume 41, Issue 4, Page(s) 837–842

MeSH term(s)	Adenosine Deaminase/chemistry ; Adenosine Deaminase/deficiency ; Biomarkers ; Child ; DNA Mutational Analysis ; Genetic Association Studies/methods ; Genetic Predisposition to Disease ; Heterozygote ; Humans ; Intercellular Signaling Peptides and Proteins/chemistry ; Intercellular Signaling Peptides and Proteins/deficiency ; Magnetic Resonance Imaging ; Male ; Mutation ; Pedigree ; Phenotype ; Siblings ; Structure-Activity Relationship ; Tomography, X-Ray Computed
Chemical Substances	Biomarkers ; Intercellular Signaling Peptides and Proteins ; ADA2 protein, human (EC 3.5.4.4) ; Adenosine Deaminase (EC 3.5.4.4)
Language	English
Publishing date	2021-01-30
Publishing country	Netherlands
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	779361-3
ISSN	1573-2592 ; 0271-9142
ISSN (online)	1573-2592
ISSN	0271-9142
DOI	10.1007/s10875-021-00981-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1640: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Revisiting TNF Receptor-Associated Periodic Syndrome (TRAPS)

Cornelia Cudrici / Natalie Deuitch / Ivona Aksentijevich

International Journal of Molecular Sciences, Vol 21, Iss 3263, p

Current Perspectives

2020 Volume 3263

Abstract	Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory syndrome characterized by prolonged and recurrent episodes of fever, abdominal and/or chest pain, arthralgia, myalgia, and erythematous rash. TRAPS is associated with heterozygous variants in the TNFRSF1A gene, which encodes the TNFR1 (tumor necrosis factor receptor 1) receptor. Disease-causing variants are found exclusively in the extracellular domain of TNFR1 and affect receptor structure and binding to the TNF ligand. The precise mechanism of the disease is still unclear, but it is thought that intracellular accumulation of misfolded mutant protein leads to endoplasmic reticulum stress and enhanced inflammatory responses through constitutive activation of various immune pathways. Other possible mechanisms contributing to the disease pathogenesis include defective receptor shedding, TNF-induced cell death, production of reactive oxygen species, and autophagy impairment. Patients’ leucocytes are hyperresponsive to stimulation and produce elevated levels of proinflammatory cytokines. Systemic autoimmune (AA) amyloidosis is an important cause of morbidity and mortality in TRAPS. Over the last two decades, new therapies have changed the progression and outcome of the disease. In this review, we summarize clinical data from 209 patients with validated pathogenic variants reported in the literature and discuss TRAPS diagnosis, pathogenesis, and treatment options.
Keywords	tumor necrosis factor receptor-associated periodic syndrome (TRAPS) ; TNFR1 ; AA amyloidosis ; autoinflammatory disorders ; misfolding disease ; TNF inhibitors ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Parental Attitudes Toward Clinical Genomic Sequencing in Children With Critical Cardiac Disease.

Gal, Dana B / Deuitch, Natalie / Lee, Sandra Soo Jin / Simon, Rosalie Tang / Char, Danton S

Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

2021 Volume 22, Issue 8, Page(s) e419–e426

Abstract: Objectives: Through improving diagnostics and prognostics genomic sequencing promises to significantly impact clinical decisions for children with critical cardiac disease. Little is known about how families of children with critical cardiac disease ... ...

Abstract	Objectives: Through improving diagnostics and prognostics genomic sequencing promises to significantly impact clinical decisions for children with critical cardiac disease. Little is known about how families of children with critical cardiac disease perceive the impact of genomic sequencing on clinical care choices. Design: Qualitative interview study. Setting: A high-volume, tertiary pediatric heart center. Subjects: Families of children with critical cardiac disease. Interventions: None. Measurements and main results: Thematic analysis of interview response content. Thirty-five families were interviewed. Three themes emerged: 1) benefits versus challenges of having genomic sequencing results, and 2) fears of clinical applications of genomic sequencing, and 3) nonclinical fears related to genomic sequencing. Participants struggled with perceived uses of genomic sequencing-derived knowledge. They described comfort in foreknowledge of their child's likely disease course but articulated significant apprehension around participating in care decisions with limited knowledge of genomic sequencing, genomic sequencing uses to inform clinical resource rationing decisions, and genomic sequencing uses by third parties impacting financial pressures families experience caring for a child with critical cardiac disease. Conclusions: Families' perceptions of genomic sequencing uses in critical cardiac disease appear to strain their overall trust in the health system. Erosion of trust is concerning because the potential of genomic sequencing in critical cardiac disease will be unrealized if families are unwilling to undergo genomic sequencing, let alone to participate in the ongoing research needed to link genomic sequencing variants to clinical outcomes. Our findings may have implications for genomic sequencing use in children with other critical, high-acuity diseases.
MeSH term(s)	Attitude ; Child ; Family ; Genomics ; Heart Diseases/diagnosis ; Heart Diseases/genetics ; Humans ; Parents ; Qualitative Research
Language	English
Publishing date	2021-02-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2052349-X
ISSN	1947-3893 ; 1529-7535
ISSN (online)	1947-3893
ISSN	1529-7535
DOI	10.1097/PCC.0000000000002669
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5600: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 472: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Genomic Landscape of Patients with Germline

Yu, Kai / Deuitch, Natalie / Merguerian, Matthew / Cunningham, Lea / Davis, Joie / Bresciani, Erica / Diemer, Jamie / Andrews, Elizabeth / Young, Alice / Donovan, Frank / Sood, Raman / Craft, Kathleen / Chong, Shawn / Chandrasekharappa, Settara / Mullikin, Jim / Liu, Paul P

bioRxiv : the preprint server for biology

2023

Abstract: Germline : Key points: Comprehensive genomic profile of patients with FPDMM with ... ...

Abstract	Germline Key points: Comprehensive genomic profile of patients with FPDMM with germline
Language	English
Publishing date	2023-01-17
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.01.17.524290
Database	MEDical Literature Analysis and Retrieval System OnLINE

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Inter-library loan at ZB MED