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Article ; Online: Adolescents and young adults (AYA) with cancer: the clinical course of COVID-19 infections.

Wolfson, Julie A / Davis, Elizabeth S / Saha, Aniket / Martinez, Isaac / McCall, David / Kothari, Prachi / Brackett, Julienne / Dickens, David S / Kahn, Alissa R / Schwalm, Carla / Sharma, Archana / Richman, Joshua / Cuglievan, Branko / Bhatia, Smita / Dai, Chen / Levine, Jennifer M / Johnston, Emily E

Journal of the National Cancer Institute

2024

Abstract: Adolescents and Young Adults (AYAs: 15-39 y) with cancer face unique vulnerabilities, yet remain under-represented on clinical trials, including adult registries of COVID-19 in cancer (AYAs: 8-12%). Thus, we leveraged the Pediatric Oncology COVID-19 Case ...

Abstract	Adolescents and Young Adults (AYAs: 15-39 y) with cancer face unique vulnerabilities, yet remain under-represented on clinical trials, including adult registries of COVID-19 in cancer (AYAs: 8-12%). Thus, we leveraged the Pediatric Oncology COVID-19 Case Report (POCC) to examine the clinical course of COVID-19 among AYAs with cancer. POCC collects de-identified clinical and sociodemographic data regarding 0-39yo with cancer (AYAs = 37%) and COVID-19 from >100 institutions. Between 04/01/2020-11/28/2023, 191 older AYAs [22-39y] and 640 younger AYAs [15-21y] were captured. Older AYAs were less often hospitalized (p < .001), admitted to the intensive care unit (ICU, p = .02), and/or required respiratory support (p = .057). In multivariable analyses, older AYAs faced 80% lower odds of ICU admission but 2.3-times greater odds of changes to cancer-directed therapy. Unvaccinated patients had 5.4-times higher odds of ICU admission. Among AYAs with cancer, the COVID-19 course varies by age. These findings can inform pediatric/adult oncology teams surrounding COVID-19 management and prevention.
Language	English
Publishing date	2024-04-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2992-0
ISSN	1460-2105 ; 0027-8874 ; 0198-0157
ISSN (online)	1460-2105
ISSN	0027-8874 ; 0198-0157
DOI	10.1093/jnci/djae085
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Article: A novel human fetal lung-derived alveolar organoid model reveals mechanisms of surfactant protein C maturation relevant to interstitial lung disease.

Lim, Kyungtae / Rutherford, Eimear N / Sun, Dawei / Van den Boomen, Dick J H / Edgar, James R / Bang, Jae Hak / Matesic, Lydia E / Lee, Joo-Hyeon / Lehner, Paul J / Marciniak, Stefan J / Rawlins, Emma L / Dickens, Jennifer A

bioRxiv : the preprint server for biology

2023

Abstract: Alveolar type 2 (AT2) cells maintain lung health by acting as stem cells and producing pulmonary ... ...

Abstract	Alveolar type 2 (AT2) cells maintain lung health by acting as stem cells and producing pulmonary surfactant
Language	English
Publishing date	2023-09-04
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.08.30.555522
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Article ; Online: Novel insights into surfactant protein C trafficking revealed through the study of a pathogenic mutant.

Dickens, Jennifer A / Rutherford, Eimear N / Abreu, Susana / Chambers, Joseph E / Ellis, Matthew O / van Schadewijk, Annemarie / Hiemstra, Pieter S / Marciniak, Stefan J

The European respiratory journal

2022 Volume 59, Issue 1

Abstract: Background: Alveolar epithelial cell dysfunction plays an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), but remains incompletely understood. Some monogenic forms of pulmonary fibrosis are associated with expression of mutant ...

Abstract	Background: Alveolar epithelial cell dysfunction plays an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), but remains incompletely understood. Some monogenic forms of pulmonary fibrosis are associated with expression of mutant surfactant protein C (SFTPC). The commonest pathogenic mutant, I73T, mislocalises to the alveolar epithelial cell plasma membrane and displays a toxic gain of function. Because the mechanisms explaining the link between this mutant and IPF are incompletely understood, we sought to interrogate SFTPC trafficking in health and disease to understand the functional significance of SFTPC-I73T relocalisation. Methods: We performed mechanistic analysis of SFTPC trafficking in a cell model that reproduces the Results: We show that wild-type SFTPC takes an unexpected indirect trafficking route Conclusion: These data show for the first time that all SFTPC transits the cell surface during normal trafficking, and the I73T mutation accumulates at the cell surface through both retarded trafficking and active recycling. This understanding of normal SFTPC trafficking and how the I73T mutant disturbs it provides novel insight into SFTPC biology in health and disease, and in the contribution of the SFTPC mutant to IPF development.
MeSH term(s)	Alveolar Epithelial Cells ; Humans ; Idiopathic Pulmonary Fibrosis/genetics ; Mutation ; Pulmonary Surfactant-Associated Protein C/genetics ; Pulmonary Surfactant-Associated Protein C/metabolism ; Surface-Active Agents
Chemical Substances	Pulmonary Surfactant-Associated Protein C ; SFTPC protein, human ; Surface-Active Agents
Language	English
Publishing date	2022-01-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639359-7
ISSN	1399-3003 ; 0903-1936
ISSN (online)	1399-3003
ISSN	0903-1936
DOI	10.1183/13993003.00267-2021
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Zs.A 2322: 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 292: Show issues

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Article ; Online: Measuring the effects of α

Chambers, Joseph E / Dickens, Jennifer A / Marciniak, Stefan J

Biology of the cell

2018 Volume 110, Issue 11, Page(s) 249–255

Abstract: An important function of the endoplasmic reticulum (ER) is to serve as a site of secretory protein folding. When the accumulation of misfolded proteins threatens to disturb luminal homoeostasis, the cell is said to experience ER stress. By contrast, the ... ...

Abstract	An important function of the endoplasmic reticulum (ER) is to serve as a site of secretory protein folding. When the accumulation of misfolded proteins threatens to disturb luminal homoeostasis, the cell is said to experience ER stress. By contrast, the accumulation of well-folded proteins inside the ER leads to a distinct form of strain called ER overload. The serpins comprise a large family of proteins whose folding has been studied in great detail. Some mutant serpins misfold to cause ER stress, whereas others fold but then polymerise to cause ER overload. We discuss recent advances in the use of dynamic fluorescence imaging to study these phenomena. We also discuss a new technique that we recently published, rotor-based organelle viscosity imaging (ROVI), which promises to shed more light on the biophysical features of ER stress and ER overload.
MeSH term(s)	Animals ; Biophysical Phenomena ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum/ultrastructure ; Humans ; Inclusion Bodies/metabolism ; Polymerization ; Viscosity ; alpha 1-Antitrypsin/metabolism
Chemical Substances	alpha 1-Antitrypsin
Language	English
Publishing date	2018-09-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	245745-3
ISSN	1768-322X ; 0399-0311 ; 0248-4900
ISSN (online)	1768-322X
ISSN	0399-0311 ; 0248-4900
DOI	10.1111/boc.201800023
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Zs.A 758: Show issues

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Article ; Online: Brief Report: A Novel Sodium/Iodide Symporter Mutation, S356F, Causing Congenital Hypothyroidism.

Durgia, Harsh / Nicholas, Adeline K / Schoenmakers, Erik / Dickens, Jennifer A / Halanaik, Dhanapathi / Sahoo, Jayaprakash / Kamalanathan, Sadishkumar / Schoenmakers, Nadia

Thyroid : official journal of the American Thyroid Association

2021 Volume 32, Issue 2, Page(s) 215–218

Abstract: The sodium-iodide symporter (NIS, SLC5A5) is expressed at the basolateral membrane of the thyroid follicular cell, and facilitates the thyroidal iodide uptake required for thyroid hormone biosynthesis. Biallelic loss-of-function mutations in NIS are a ... ...

Abstract	The sodium-iodide symporter (NIS, SLC5A5) is expressed at the basolateral membrane of the thyroid follicular cell, and facilitates the thyroidal iodide uptake required for thyroid hormone biosynthesis. Biallelic loss-of-function mutations in NIS are a rare cause of dyshormonogenic congenital hypothyroidism. Affected individuals typically exhibit a normally sited, often goitrous thyroid gland, with absent uptake of radioiodine in the thyroid and other NIS-expressing tissues. We report a novel homozygous NIS mutation (c.1067 C>T, p.S356F) in four siblings from a consanguineous Indian kindred, presenting with significant hypothyroidism. Functional characterization of the mutant protein demonstrated impaired plasma membrane localization and cellular iodide transport.
MeSH term(s)	Congenital Hypothyroidism/genetics ; Female ; Humans ; India ; Infant, Newborn ; Mutation/genetics ; Symporters/genetics
Chemical Substances	Symporters ; sodium-iodide symporter (4XE5NDT4K1)
Language	English
Publishing date	2021-12-16
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1086044-7
ISSN	1557-9077 ; 1050-7256
ISSN (online)	1557-9077
ISSN	1050-7256
DOI	10.1089/thy.2021.0478
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Zs.A 3307: 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 106: Show issues

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Article ; Online: WD Repeat Domain 1 (WDR1) Deficiency Presenting as a Cause of Infantile Inflammatory Bowel Disease.

Millstead, Jenna / Kamat, Aarti / Duffner, Ulrich / Abdel-Mageed, Aly / Freswick, Peter / Dickens, David / Stumph, Jennifer / Prokop, Jeremy W / Hartog, Nicholas L

Journal of pediatric gastroenterology and nutrition

2021 Volume 71, Issue 4, Page(s) e113–e117

Abstract: Infantile and very early onset inflammatory bowel disease (VEOIBD) are a rare phenomenon wherein patients develop intestinal inflammation with typical IBD symptoms before ages 2 and 6, respectively. In recent years, there has been an increasing number of ...

Abstract	Infantile and very early onset inflammatory bowel disease (VEOIBD) are a rare phenomenon wherein patients develop intestinal inflammation with typical IBD symptoms before ages 2 and 6, respectively. In recent years, there has been an increasing number of monogenetic immunological disorders identified that lead a child to develop VEOIBD. We present a case of an infant boy who presented with hematochezia and thrombocytopenia in the first week of life and developed IBD by the age of 1 month. Additional clues to his diagnosis included lymphopenia and nuclear herniation observed in his neutrophils. Compound heterozygous damaging variants were identified in WD Repeat Domain 1 (WDR1) by whole-exome sequencing (WES) and represents a novel cause of VEOIBD. Our patient's IBD and immunologic phenotype was successfully treated by hematopoietic stem cell transplant (HSCT).
MeSH term(s)	Colitis ; Humans ; Infant ; Inflammatory Bowel Diseases/complications ; Inflammatory Bowel Diseases/diagnosis ; Inflammatory Bowel Diseases/genetics ; Male ; Microfilament Proteins/deficiency ; Phenotype ; WD40 Repeats ; Whole Exome Sequencing
Chemical Substances	Microfilament Proteins ; WDR1 protein, human
Language	English
Publishing date	2021-02-02
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	603201-1
ISSN	1536-4801 ; 0277-2116
ISSN (online)	1536-4801
ISSN	0277-2116
DOI	10.1097/MPG.0000000000002826
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Zs.A 1728: Show issues

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Article ; Online: Pulmonary endoplasmic reticulum stress-scars, smoke, and suffocation.

Dickens, Jennifer A / Malzer, Elke / Chambers, Joseph E / Marciniak, Stefan J

The FEBS journal

2018 Volume 286, Issue 2, Page(s) 322–341

Abstract: Protein misfolding within the endoplasmic reticulum (ER stress) can be a cause or consequence of pulmonary disease. Mutation of proteins restricted to the alveolar type II pneumocyte can lead to inherited forms of pulmonary fibrosis, but even sporadic ... ...

Abstract	Protein misfolding within the endoplasmic reticulum (ER stress) can be a cause or consequence of pulmonary disease. Mutation of proteins restricted to the alveolar type II pneumocyte can lead to inherited forms of pulmonary fibrosis, but even sporadic cases of pulmonary fibrosis appear to be strongly associated with activation of the unfolded protein response and/or the integrated stress response. Inhalation of smoke can impair protein folding and may be an important cause of pulmonary ER stress. Similarly, tissue hypoxia can lead to impaired protein homeostasis (proteostasis). But the mechanisms linking smoke and hypoxia to ER stress are only partially understood. In this review, we will examine the role of ER stress in the pathogenesis of lung disease by focusing on fibrosis, smoke, and hypoxia.
MeSH term(s)	Animals ; Asphyxia/physiopathology ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum/pathology ; Endoplasmic Reticulum Stress ; Humans ; Hypoxia/physiopathology ; Protein Folding ; Pulmonary Fibrosis/physiopathology ; Smoking/physiopathology ; Unfolded Protein Response
Language	English
Publishing date	2018-01-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.14381
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Zs.A 260: Show issues

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Article ; Online: Characteristics of Health Care Settings Where Adolescents and Young Adults Receive Care for ALL.

Wolfson, Julie A / Grimes, Allison C / Nuno, Michelle / Kerber, Charlotte L / Ramakrishnan, Subhash / Beauchemin, Melissa / Dickens, David / Levine, Jennifer M / Roth, Michael E / Scialla, Michele / Woods, Wendy / Vargas, Sarah / Boayue, Koh B / Chang, George J / Stock, Wendy / Hershman, Dawn / Curran, Emily / Advani, Anjali / O'Dwyer, Kristen /

Luger, Selina / Liu, Jane Jijun / Freyer, David R / Sung, Lillian / Parsons, Susan K

JCO oncology practice

2024 Volume 20, Issue 4, Page(s) 491–502

Abstract: Purpose: Individuals diagnosed with cancer between 15 and 39 years (adolescent and young adult [AYA]) face unique vulnerability. Detail is lacking about care delivery for these patients, especially those with ALL. We address these knowledge gaps by ... ...

Abstract	Purpose: Individuals diagnosed with cancer between 15 and 39 years (adolescent and young adult [AYA]) face unique vulnerability. Detail is lacking about care delivery for these patients, especially those with ALL. We address these knowledge gaps by describing AYA ALL care delivery details at National Cancer Institute Community Oncology Research Program (NCORP) (sub)affiliates by model of care. Methods: Participating institutions treated at least one AYA with ALL from 2012 to 2016. Study-specific criteria were used to determine the number of unique clinical facilities (CFs) per NCORP and their model of care (adult/internal medicine [IM], pediatric, mixed [both]). Surveys completed by NCORPs for each CF by model of care captured size, resources, services, and communication. Results: Among 84 participating CFs (adult/IM, n=47; pediatric, n=15; mixed, n=24), 34% treated 5-10 AYAs with ALL annually; adult/IM CFs more often treated <5 (adult/IM, 60%; pediatric, 40%; mixed, 29%). Referral decisions were commonly driven by an age/diagnosis combination (58%), with frequent ALL-specific age minimums (87%) or maximums (80%). Medical, navigational, and social work services were similar across models while psychology was available at more pediatric CFs (pediatric, 80%; adult/IM, 40%; mixed, 46%-54%). More pediatric or mixed CFs reported oncologists interacting with pediatric/adult counterparts via tumor boards (pediatric, 93%; adult/IM, 26%; mixed, 96%) or initiating contact (pediatric, 100%; adult/IM, 77%; mixed 96%); more pediatric CFs reported an affiliated counterpart (pediatric, 53%; adult, 19%). Most CFs reported no AYA-specific resources (79%) or meetings (83%-98%). Conclusion: System-level aspects of AYA ALL care delivery have not been examined previously. At NCORPs, these characteristics differ by models of care. Additional work is ongoing to investigate the impact of these facility-level factors on guideline-concordant care in this population. Together, these findings can inform a system-level intervention for diverse practice settings.
MeSH term(s)	Humans ; Adolescent ; Young Adult ; Child ; Neoplasms/epidemiology ; Neoplasms/therapy ; Neoplasms/diagnosis ; Delivery of Health Care ; Oncologists ; Surveys and Questionnaires
Language	English
Publishing date	2024-01-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	3028198-2
ISSN	2688-1535 ; 2688-1527
ISSN (online)	2688-1535
ISSN	2688-1527
DOI	10.1200/OP.23.00328
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Zs.A 7198: Show issues

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Article ; Online: CC-16 as a biomarker in chronic obstructive pulmonary disease.

Dickens, Jennifer A / Lomas, David A

COPD

2012 Volume 9, Issue 5, Page(s) 574–575

MeSH term(s)	Biomarkers ; Humans ; Pulmonary Disease, Chronic Obstructive/metabolism ; Pulmonary Disease, Chronic Obstructive/physiopathology ; Uteroglobin/metabolism ; Uteroglobin/physiology
Chemical Substances	Biomarkers ; SCGB1A1 protein, human ; Uteroglobin (9060-09-7)
Language	English
Publishing date	2012-10-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2171107-0
ISSN	1541-2563 ; 1541-2555
ISSN (online)	1541-2563
ISSN	1541-2555
DOI	10.3109/15412555.2012.718926
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Zs.A 5990: Show issues

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Article ; Online: Evaluation of the Association Between Congenital Cytomegalovirus Infection and Pediatric Acute Lymphoblastic Leukemia.

Geris, Jennifer M / Schleiss, Mark R / Hooten, Anthony J / Langer, Erica / Hernandez-Alvarado, Nelmary / Roesler, Michelle A / Sample, Jeannette / Williams, Lindsay A / Dickens, David S / Mody, Rajen J / Ravindranath, Yaddanapudi / Gowans, Kate L / Pridgeon, Matthew G / Spector, Logan G / Nelson, Heather H

JAMA network open

2023 Volume 6, Issue 1, Page(s) e2250219

Abstract: Importance: Acute lymphoblastic leukemia (ALL) is the most common form of pediatric cancer, and a leading cause of death in children. Understanding the causes of pediatric ALL is necessary to enable early detection and prevention; congenital ... ...

Abstract	Importance: Acute lymphoblastic leukemia (ALL) is the most common form of pediatric cancer, and a leading cause of death in children. Understanding the causes of pediatric ALL is necessary to enable early detection and prevention; congenital cytomegalovirus (cCMV) has recently been identified as a potential moderate-to-strong factor associated with risk for ALL. Objective: To compare the prevalence of cCMV infection between ALL cases and matched controls. Design, setting, and participants: In this population-based case-control study of ALL cases and matched controls, cases consisted of children aged 0 to 14 years between 1987 and 2014 with an ALL diagnosis identified through the Michigan Cancer Surveillance Program and born in Michigan on or after October 1, 1987. Cancer-free controls were identified by the Michigan BioTrust for Health and matched on age, sex, and mother's race and ethnicity. Data were analyzed from November to May 2022. Exposures: cCMV infection measured by quantitative polymerase chain reaction in newborn dried blood spots. Main outcomes and measures: ALL diagnosed in children aged 0 to 14 years. Results: A total of 1189 ALL cases and 4756 matched controls were included in the study. Bloodspots were collected from participants at birth, and 3425 (57.6%) participants were male. cCMV was detected in 6 ALL cases (0.5%) and 21 controls (0.4%). There was no difference in the odds of cCMV infection comparing ALL cases with controls (odds ratio, 1.30; 95% CI, 0.52-3.24). Immunophenotype was available for 536 cases (45.1%) and cytogenetic data for 127 (27%). When stratified by subtype characteristics, hyperdiploid ALL (74 cases) was associated with 6.26 times greater odds of cCMV infection compared with unmatched controls (95% CI, 1.44-27.19). Conclusions and relevance: In this case-control study of cCMV and pediatric ALL, cCMV was associated with increased risk of hyperdiploid ALL. These findings encourage continued research.
MeSH term(s)	Infant, Newborn ; Child ; Humans ; Male ; Female ; Case-Control Studies ; Cytomegalovirus Infections/epidemiology ; Cytomegalovirus Infections/complications ; Prevalence ; Michigan ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology
Language	English
Publishing date	2023-01-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2574-3805
ISSN (online)	2574-3805
DOI	10.1001/jamanetworkopen.2022.50219
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