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Article ; Online: Navigating the paradox: Exploring resident experiences of vulnerability.

Nichol, Heather / Turnnidge, Jennifer / Dalgarno, Nancy / Trier, Jessica

2024

Abstract: Introduction: Learning and growth in postgraduate medical education (PGME) often require vulnerability, defined as a state of openness to uncertainty, risk, and emotional exposure. However, vulnerability can threaten a resident's credibility and ... ...

Abstract	Introduction: Learning and growth in postgraduate medical education (PGME) often require vulnerability, defined as a state of openness to uncertainty, risk, and emotional exposure. However, vulnerability can threaten a resident's credibility and professional identity. Despite this tension, studies examining vulnerability in PGME are limited. As such, this study aims to explore residents' experiences of vulnerability, including the factors that influence vulnerability in PGME. Methods: Using a constructivist grounded theory approach, individual semi-structured interviews were conducted with 15 residents from 10 different specialities. Interview transcripts were coded and analysed iteratively. Themes were identified and relationships among themes were examined to develop a theory describing vulnerability in PGME. Results: Residents characterised vulnerability as a paradox represented by two overarching themes. 'Experiencing the tensions of vulnerability' explores the polarities between being a fallible, authentic learner and an infallible, competent professional. 'Navigating the vulnerability paradox' outlines the factors influencing the experience of vulnerability and its associated outcomes at the intrapersonal, interpersonal, and systems levels. Residents described needing to have the bandwidth to face the risks and emotional labour of vulnerability. Opportunities to build connections with social agents, including clinical teachers and peers, facilitated vulnerability. The sociocultural context shaped both the experience and outcomes of vulnerability as residents faced the symbolic mask of professionalism. Conclusion: Residents experience vulnerability as a paradox shaped by intrapersonal, interpersonal, and systems level factors. These findings capture the nuance and complexity of vulnerability in PGME and offer insight into creating supportive learning environments that leverage the benefits of vulnerability while acknowledging its risks. There is a need to translate this understanding into systems-based change to create supportive PGME environments, which value and celebrate vulnerability.
Language	English
Publishing date	2024-05-17
Publishing country	England
Document type	Journal Article
ZDB-ID	195274-2
ISSN	1365-2923 ; 0308-0110
ISSN (online)	1365-2923
ISSN	0308-0110
DOI	10.1111/medu.15426
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Article ; Online: Correction: MNK1/NODAL Signaling Promotes Invasive Progression of Breast Ductal Carcinoma In Situ.

Guo, Qianyu / Li, Vivian Z / Nichol, Jessica N / Huang, Fan / Yang, William / Preston, Samuel E J / Talat, Zahra / Lefrère, Hanne / Yu, Henry / Zhang, Guihua / Basik, Mark / Gonçalves, Christophe / Zhan, Yao / Plourde, Dany / Su, Jie / Torres, Jose / Marques, Maud / Habyan, Sara Al / Bijian, Krikor /

Amant, Frédéric / Wichter, Michael / Behbod, Fariba / McCaffrey, Luke / Alaoui-Jamali, Moulay / Giannakopoulos, Nadia V / Brackstone, Muriel / Postovit, Lynne-Marie / Del Rincón, Sonia V / Miller, William H

Cancer research

2024 Volume 84, Issue 8, Page(s) 1373

Language	English
Publishing date	2024-04-15
Publishing country	United States
Document type	Journal Article ; Published Erratum
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-24-0461
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Article ; Online: Triple A therapy: the molecular underpinnings of the unique sensitivity of leukemic promyelocytes to anthracyclines, all-trans-retinoic acid and arsenic trioxide.

Nichol, Jessica N / Garnier, Nicolas / Miller, Wilson H

Best practice & research. Clinical haematology

2014 Volume 27, Issue 1, Page(s) 19–31

Abstract: If looking for a mnemonic to remember the relevant facts about acute promyelocytic leukemia (APL), one just has to remember that APL is a disease of A's. It is acute and it is highly sensitive to treatment with anthracyclines, all-trans-retinoic acid (RA) ...

Abstract	If looking for a mnemonic to remember the relevant facts about acute promyelocytic leukemia (APL), one just has to remember that APL is a disease of A's. It is acute and it is highly sensitive to treatment with anthracyclines, all-trans-retinoic acid (RA) and arsenic trioxide (ATO). The presence of fusions involving the retinoic acid receptor alpha (RARA) is without question the central player driving APL and dictating the response of this disease to these therapeutic agents. However, beyond this knowledge, the molecular mechanisms that contribute to the complicated pathogenesis and the response to treatment of APL are not completely defined. As more is understood about this hematological malignancy, there are more opportunities to refine and improve treatment based on this knowledge. In this review article, we discuss the response of APL to these "A" therapies.
MeSH term(s)	Anthracyclines/pharmacology ; Anthracyclines/therapeutic use ; Antibiotics, Antineoplastic/pharmacology ; Antibiotics, Antineoplastic/therapeutic use ; Arsenicals/pharmacology ; Arsenicals/therapeutic use ; Cell Differentiation/drug effects ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Gene Expression Regulation, Leukemic ; Granulocyte Precursor Cells/drug effects ; Humans ; Leukemia, Promyelocytic, Acute/drug therapy ; Molecular Targeted Therapy ; Neoplasm Proteins/drug effects ; Neoplasm Proteins/genetics ; Neoplasm Proteins/physiology ; Oncogene Proteins, Fusion/drug effects ; Oncogene Proteins, Fusion/genetics ; Oncogene Proteins, Fusion/physiology ; Oxides/pharmacology ; Oxides/therapeutic use ; Topoisomerase II Inhibitors/pharmacology ; Topoisomerase II Inhibitors/therapeutic use ; Transcription, Genetic/genetics ; Tretinoin/pharmacology ; Tretinoin/therapeutic use
Chemical Substances	Anthracyclines ; Antibiotics, Antineoplastic ; Arsenicals ; Neoplasm Proteins ; Oncogene Proteins, Fusion ; Oxides ; Topoisomerase II Inhibitors ; promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein ; Tretinoin (5688UTC01R) ; arsenic trioxide (S7V92P67HO)
Language	English
Publishing date	2014-03
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2048027-1
ISSN	1532-1924 ; 1521-6926
ISSN (online)	1532-1924
ISSN	1521-6926
DOI	10.1016/j.beha.2014.04.009
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Article: Seizure Prophylaxis Following Moderate to Severe Traumatic Brain Injury: Retrospective Investigation of Clinical Practice and the Impact of Clinical Guidelines.

Nichol, Heather / Boyd, John / Trier, Jessica

Cureus

2020 Volume 12, Issue 4, Page(s) e7709

Abstract: ... were eligible for this study (n = 96). Medical records including patient age, sex, Glasgow Coma Scale ...

Abstract	Background Post-traumatic seizure (PTS) is a major complication of traumatic brain injury (TBI). However, there has been controversy in the literature regarding whether anticonvulsants should be used prophylactically to prevent it, and there is significant variability in practice. The objective of this study is to describe seizure prophylaxis practices after moderate to severe TBI and to determine whether the use of seizure prophylaxis increased following the recommendations of the Quebec Institut National d'Excellence en Santé et Services Sociaux and the Ontario Neurotrauma Foundation (INESSS-ONF) guidelines. This study will also compare the characteristics of patients who receive the recommended prophylaxis and those who do not. Methods All adult patients admitted to a level-1 trauma centre for moderate to severe TBI were eligible for this study (n = 96). Medical records including patient age, sex, Glasgow Coma Scale (GCS) score, mechanism of injury, and occurrence of PTS were reviewed in a retrospective manner regarding the administration of recommended seizure prophylaxis. Results The proportion of patients receiving the recommended seizure prophylaxis was 8%. There was no significant increase after the release of the INESSS-ONF guidelines (p: 0.38). There were no significant differences in demographics, injury characteristics, or rates of early PTS between patients receiving the recommended prophylaxis and those not receiving it (p: >0.05). Conclusion The results indicate that the use of the recommended seizure prophylaxis after moderate to severe TBI is low and that the release of the INESSS-ONF guidelines did not increase its use. Patient and injury factors do not appear to influence the use of seizure prophylaxis. These results highlight variability in seizure prophylaxis practices and the importance of understanding local practice patterns. Implementation strategies should be identified to increase adherence to the recommendations and improve patient care.
Language	English
Publishing date	2020-04-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.7709
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Article ; Online: MNK1 signaling induces an ANGPTL4-mediated gene signature to drive melanoma progression.

Yang, William / Khoury, Elie / Guo, Qianyu / Prabhu, Sathyen A / Emond, Audrey / Huang, Fan / Gonçalves, Christophe / Zhan, Yao / Plourde, Dany / Nichol, Jessica N / Dahabieh, Michael S / Miller, Wilson H / Del Rincón, Sonia Victoria

Oncogene

2020 Volume 39, Issue 18, Page(s) 3650–3665

Abstract: ... The ... ...

Abstract	The BRAF
MeSH term(s)	Angiopoietin-Like Protein 4/genetics ; Animals ; Cell Line, Tumor ; Disease Progression ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Knockout Techniques ; Heterografts ; Humans ; Intracellular Signaling Peptides and Proteins/antagonists & inhibitors ; Intracellular Signaling Peptides and Proteins/genetics ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Lung Neoplasms/secondary ; Melanoma/drug therapy ; Melanoma/genetics ; Melanoma/pathology ; Mice ; Mutation/genetics ; Neoplasm Invasiveness/genetics ; Neoplasm Invasiveness/pathology ; Protein Kinase Inhibitors/pharmacology ; Protein Serine-Threonine Kinases/antagonists & inhibitors ; Protein Serine-Threonine Kinases/genetics ; Proto-Oncogene Proteins B-raf/genetics ; Signal Transduction/drug effects ; Skin Neoplasms/drug therapy ; Skin Neoplasms/genetics ; Skin Neoplasms/pathology ; Transcriptome/genetics ; Melanoma, Cutaneous Malignant
Chemical Substances	ANGPTL4 protein, human ; Angiopoietin-Like Protein 4 ; Intracellular Signaling Peptides and Proteins ; Protein Kinase Inhibitors ; MKNK1 protein, human (EC 2.7.1.-) ; BRAF protein, human (EC 2.7.11.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1)
Language	English
Publishing date	2020-03-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/s41388-020-1240-5
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Article ; Online: NPM and BRG1 Mediate Transcriptional Resistance to Retinoic Acid in Acute Promyelocytic Leukemia.

Nichol, Jessica N / Galbraith, Matthew D / Kleinman, Claudia L / Espinosa, Joaquín M / Miller, Wilson H

Cell reports

2016 Volume 14, Issue 12, Page(s) 2938–2949

Abstract: Perturbation in the transcriptional control of genes driving differentiation is an established paradigm whereby oncogenic fusion proteins promote leukemia. From a retinoic acid (RA)-sensitive acute promyelocytic leukemia (APL) cell line, we derived an RA- ...

Abstract	Perturbation in the transcriptional control of genes driving differentiation is an established paradigm whereby oncogenic fusion proteins promote leukemia. From a retinoic acid (RA)-sensitive acute promyelocytic leukemia (APL) cell line, we derived an RA-resistant clone characterized by a block in transcription initiation, despite maintaining wild-type PML/RARA expression. We uncovered an aberrant interaction among PML/RARA, nucleophosmin (NPM), and topoisomerase II beta (TOP2B). Surprisingly, RA stimulation in these cells results in enhanced chromatin association of the nucleosome remodeler BRG1. Inhibition of NPM or TOP2B abrogated BRG1 recruitment. Furthermore, NPM inhibition and targeting BRG1 restored differentiation when combined with RA. Here, we demonstrate a role for NPM and BRG1 in obstructing RA differentiation and implicate chromatin remodeling in mediating therapeutic resistance in malignancies. NPM mutations are the most common genetic change in patients with acute leukemia (AML); therefore, our model may be applicable to other more common leukemias driven by NPM.
MeSH term(s)	CCAAT-Enhancer-Binding Protein-beta/genetics ; CCAAT-Enhancer-Binding Protein-beta/metabolism ; Cell Differentiation/drug effects ; Cell Line, Tumor ; Chromatin Assembly and Disassembly/drug effects ; Chromatin Immunoprecipitation ; DNA Helicases/antagonists & inhibitors ; DNA Helicases/genetics ; DNA Helicases/metabolism ; DNA Topoisomerases, Type II/metabolism ; DNA-Binding Proteins/metabolism ; Drug Resistance, Neoplasm/drug effects ; Humans ; Leukemia, Promyelocytic, Acute/metabolism ; Leukemia, Promyelocytic, Acute/pathology ; Nuclear Proteins/antagonists & inhibitors ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Poly-ADP-Ribose Binding Proteins ; Promoter Regions, Genetic ; Promyelocytic Leukemia Protein/genetics ; Promyelocytic Leukemia Protein/metabolism ; RNA Interference ; RNA, Small Interfering/metabolism ; Real-Time Polymerase Chain Reaction ; Retinoic Acid Receptor alpha/genetics ; Retinoic Acid Receptor alpha/metabolism ; Transcription Factors/antagonists & inhibitors ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcriptional Activation/drug effects ; Tretinoin/toxicity
Chemical Substances	CCAAT-Enhancer-Binding Protein-beta ; CEBPB protein, human ; DNA-Binding Proteins ; Nuclear Proteins ; Poly-ADP-Ribose Binding Proteins ; Promyelocytic Leukemia Protein ; RARA protein, human ; RNA, Small Interfering ; Retinoic Acid Receptor alpha ; Transcription Factors ; nucleophosmin (117896-08-9) ; PML protein, human (143220-95-5) ; Tretinoin (5688UTC01R) ; SMARCA4 protein, human (EC 3.6.1.-) ; DNA Helicases (EC 3.6.4.-) ; DNA Topoisomerases, Type II (EC 5.99.1.3) ; TOP2B protein, human (EC 5.99.1.3)
Language	English
Publishing date	2016-03-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2016.02.074
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Article ; Online: Expanding PML's functional repertoire through post-translational mechanisms.

Nichol, Jessica N / Petruccelli, Luca A / Miller, Wilson H

Frontiers in bioscience (Landmark edition)

2009 Volume 14, Issue 6, Page(s) 2293–2306

Abstract: Post-translational modifications, such as acetylation and ubiquitination, can greatly expand the functionality of a particular protein. The promyelocytic leukemia (PML) protein is a functionally promiscuous protein with proposed roles in many cellular ... ...

Abstract	Post-translational modifications, such as acetylation and ubiquitination, can greatly expand the functionality of a particular protein. The promyelocytic leukemia (PML) protein is a functionally promiscuous protein with proposed roles in many cellular processes. Its cellular headquarters are the macromolecular structures termed PML nuclear bodies. Post-translational modification of PML is emerging as a defining feature of this protein that regulates its physiological consequences. This review will highlight the expansion of our knowledge about the post-translational modifications of PML.
MeSH term(s)	Humans ; Nuclear Proteins/metabolism ; Nuclear Proteins/physiology ; Phosphorylation ; Promyelocytic Leukemia Protein ; Protein Processing, Post-Translational ; Receptors, Retinoic Acid/metabolism ; Retinoic Acid Receptor alpha ; Small Ubiquitin-Related Modifier Proteins/metabolism ; Transcription Factors/metabolism ; Transcription Factors/physiology ; Tumor Suppressor Proteins/metabolism ; Tumor Suppressor Proteins/physiology
Chemical Substances	Nuclear Proteins ; Promyelocytic Leukemia Protein ; RARA protein, human ; Receptors, Retinoic Acid ; Retinoic Acid Receptor alpha ; Small Ubiquitin-Related Modifier Proteins ; Transcription Factors ; Tumor Suppressor Proteins ; PML protein, human (143220-95-5)
Language	English
Publishing date	2009-01-01
Publishing country	Singapore
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2704569-9
ISSN	2768-6698 ; 1093-9946
ISSN (online)	2768-6698
ISSN	1093-9946
DOI	10.2741/3380
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Article ; Online: NPM and BRG1 Mediate Transcriptional Resistance to Retinoic Acid in Acute Promyelocytic Leukemia

Jessica N. Nichol / Matthew D. Galbraith / Claudia L. Kleinman / Joaquín M. Espinosa / Wilson H. Miller Jr.

Cell Reports, Vol 14, Iss 12, Pp 2938-

2016 Volume 2949

Abstract	Perturbation in the transcriptional control of genes driving differentiation is an established paradigm whereby oncogenic fusion proteins promote leukemia. From a retinoic acid (RA)-sensitive acute promyelocytic leukemia (APL) cell line, we derived an RA-resistant clone characterized by a block in transcription initiation, despite maintaining wild-type PML/RARA expression. We uncovered an aberrant interaction among PML/RARA, nucleophosmin (NPM), and topoisomerase II beta (TOP2B). Surprisingly, RA stimulation in these cells results in enhanced chromatin association of the nucleosome remodeler BRG1. Inhibition of NPM or TOP2B abrogated BRG1 recruitment. Furthermore, NPM inhibition and targeting BRG1 restored differentiation when combined with RA. Here, we demonstrate a role for NPM and BRG1 in obstructing RA differentiation and implicate chromatin remodeling in mediating therapeutic resistance in malignancies. NPM mutations are the most common genetic change in patients with acute leukemia (AML); therefore, our model may be applicable to other more common leukemias driven by NPM.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2016-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article: Composition and Biogeography of Planktonic Pro- and Eukaryotic Communities in the Atlantic Ocean: Primer Choice Matters.

Milke, Felix / Sanchez-Garcia, Selene / Dlugosch, Leon / McNichol, Jesse / Fuhrman, Jed / Simon, Meinhard / Wagner-Döbler, Irene

Frontiers in microbiology

2022 Volume 13, Page(s) 895875

Abstract: ... from 52°S to 47°N using universal V4-V5 primers and compared the results with those obtained previously ...

Abstract	Basin-scale biogeographic observations of marine pelagic pro- and eukaryotic communities are necessary to understand forces driving community composition and for providing a baseline to monitor global change. Deep sequencing of rRNA genes provides community composition at high resolution; yet, it is unclear how the choice of primers affects biogeographic patterns. Here, we re-amplified 16S rRNA genes from DNA sampled during R/V Polarstern Cruise ANT28-5 over a latitudinal transect across the Atlantic Ocean from 52°S to 47°N using universal V4-V5 primers and compared the results with those obtained previously with V5-V6 bacteria-specific primers. For validation of our results, we inferred community composition based on 16S rRNA genes of metagenomes from the same stations and single amplified genomes (SAGs) from the Global Ocean Reference Genome (GORG) database. We found that the universal V4-V5 primers retrieved SAR11 clades with similar relative proportions as those found in the GORG database while the V5-V6 primers recovered strongly diverging clade abundances. We confirmed an inverse bell-shaped distance-decay relationship and a latitudinal diversity gradient that did not decline linearly with absolute latitude in the Atlantic Ocean. Patterns were modified by sampling depth, sequencing depth, choice of primers, and abundance filtering. Especially richness patterns were not robust to methodological change. This study offers a detailed picture of the Atlantic Ocean microbiome using a universal set of PCR primers that allow for the conjunction of biogeographical patterns among organisms from different domains of life.
Language	English
Publishing date	2022-06-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2022.895875
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Article ; Online: Erratum for Gebo et al., "Early antibody treatment, inflammation, and risk of post-COVID conditions".

Gebo, Kelly A / Heath, Sonya L / Fukuta, Yuriko / Zhu, Xianming / Baksh, Sheriza / Abraham, Allison G / Habtehyimer, Feben / Shade, David / Ruff, Jessica / Ram, Malathi / Laeyendecker, Oliver / Fernandez, Reinaldo E / Patel, Eshan U / Baker, Owen R / Shoham, Shmuel / Cachay, Edward R / Currier, Judith S / Gerber, Jonathan M / Meisenberg, Barry /

mBio

2023 Volume 15, Issue 1, Page(s) e0297923

Language	English
Publishing date	2023-12-14
Publishing country	United States
Document type	Journal Article ; Published Erratum
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.02979-23
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