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Article ; Online: Getting to Know Your Patient: Content Analysis of Patients' Answers to a Questionnaire for Promoting Person-Centered Care.

Bergers, Juno Hk / Wessels-Wynia, Hester / Seute, Tatjana / Janssens, Astrid / van Delden, Johannes Jm

2024 Volume 16, Page(s) e48573

Abstract: Background: Person-centered care (PCC) encourages patients to actively participate in health care, thus facilitating care that fits the life of the patient. Therefore, health care professionals (HCPs) need to know the patient. As part of a broad policy ... ...

Abstract	Background: Person-centered care (PCC) encourages patients to actively participate in health care, thus facilitating care that fits the life of the patient. Therefore, health care professionals (HCPs) need to know the patient. As part of a broad policy for improving PCC, a digital questionnaire ("We would like to know you") consisting of 5 questions has previously been developed to help HCPs to get to know the patient with the help of patient and staff involvement. Objective: The purpose of this study was to provide insight into the content and aims of the questionnaire to understand its potential and usability. Methods: We conducted a qualitative, retrospective content analysis of patients' answers using NVivo Pro (QSR International). The questionnaire was used in the outpatient neuro-oncology department of a Dutch academic hospital. Results: Of 374 invited patients, 78 (20.9%) completed the questionnaire. We selected a sample of 42 (54%) of the 78 patients. Patients used a median of 16 (IQR 7-27) words per question, and most answers were easily interpretable. When asked about important activities, social activities, sports, or maintaining a normal life were most frequently mentioned. Patients wrote about fear of the disease, its possible influence on life, or fear of the future in general. Patients wanted HCPs to know about their care and communication preferences or shared personal information. They formulated expectations about effective treatment, communication, and the care process. Conclusions: The questionnaire seems usable because patients provide interpretable answers that take little time to read, which HCPs can use to personalize care. Our study shows the potential of the questionnaire to help deliver PCC.
Language	English
Publishing date	2024-03-04
Publishing country	Canada
Document type	Journal Article
ZDB-ID	2573853-7
ISSN	2152-7202 ; 2152-7202
ISSN (online)	2152-7202
ISSN	2152-7202
DOI	10.2196/48573
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Article ; Online: Epidemiology of adult meningioma: Report from the Dutch Brain Tumour Registry (2000-2019).

Ho, Vincent K Y / Anten, Monique M / Garst, Anniek / Bos, Eelke M / Snijders, Tom J / Eekers, Daniëlle B P / Seute, Tatjana

European journal of neurology

2023 Volume 30, Issue 10, Page(s) 3244–3255

Abstract: Background and purpose: Meningiomas are the most common primary tumours of the central nervous system. This study aimed to provide comprehensive nationwide estimates on the incidence, prevalence and prognostic impact of meningioma diagnosis in the ... ...

Abstract	Background and purpose: Meningiomas are the most common primary tumours of the central nervous system. This study aimed to provide comprehensive nationwide estimates on the incidence, prevalence and prognostic impact of meningioma diagnosis in the Netherlands. Methods: Adult patients diagnosed with meningioma in 2000-2019 were selected from the Dutch Brain Tumour Registry (DBTR), part of the Netherlands Cancer Registry (NCR). Time trends in age-adjusted incidence and prevalence rates were evaluated using the estimated annual percentage change (EAPC). Relative survival rates were calculated using the Pohar Perme estimator. Case completeness of the DBTR/NCR was estimated through record linkage with one of the Dutch neuro-oncology centres. Results: From a total of 23,454 cases of meningioma, 11,306 (48.2%) were histologically confirmed and 12,148 (51.8%) were radiological diagnoses. Over time, the incidence of diagnosis increased from 46.9 per 1,000,000 inhabitants (European Standardized Rate [ESR]) to 107.3 (EAPC 4.7%, p < 0.01), with an increase in the incidence of radiological diagnoses from 14.0 to 70.2 per 1,000,000 ESR (EAPC 9.1%, p < 0.01). The prevalence of meningioma was estimated at 1012/1,000,000 on 1 January 2020, with almost 17,800 individuals having had a diagnosis of meningioma. Relative survival rate at 10 years for grade 1 meningiomas was 91.0% (95% confidence interval [CI] 89.4%-92.3%), 71.3% (95% CI 66.8%-75.2%) for grade 2 meningiomas and 36.4% (95% CI 27.3%-45.6%) for grade 3 meningiomas. Local case completeness was estimated at 97.6% for histologically confirmed meningiomas and 84.5% for radiological diagnoses. Conclusion: With a near-complete registry, meningioma prevalence was estimated at over 1000 per 1,000,000 inhabitants.
MeSH term(s)	Humans ; Adult ; Meningioma/epidemiology ; Meningioma/pathology ; Central Nervous System ; Incidence ; Brain Neoplasms/epidemiology ; Transcription Factors ; Meningeal Neoplasms/epidemiology ; Meningeal Neoplasms/pathology ; Registries
Chemical Substances	Transcription Factors
Language	English
Publishing date	2023-07-21
Publishing country	England
Document type	Journal Article
ZDB-ID	1280785-0
ISSN	1468-1331 ; 1351-5101 ; 1471-0552
ISSN (online)	1468-1331
ISSN	1351-5101 ; 1471-0552
DOI	10.1111/ene.15979
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Article ; Online: STAT5b is a marker of poor prognosis, rather than a therapeutic target in glioblastomas.

Dubois, Nadège / Berendsen, Sharon / Tan, Katherine / Schoysmans, Laurent / Spliet, Wim / Seute, Tatjana / Bours, Vincent / Robe, Pierre A

International journal of oncology

2022 Volume 61, Issue 4

Abstract: The copy number and mRNA expression of STAT5b were assessed in samples from the TCGA repository of glioblastomas (GBM). The activation of this transcription factor was analyzed on tissue microarrays comprising 392 WHO 2016 GBM samples from our clinical ... ...

Abstract	The copy number and mRNA expression of STAT5b were assessed in samples from the TCGA repository of glioblastomas (GBM). The activation of this transcription factor was analyzed on tissue microarrays comprising 392 WHO 2016 GBM samples from our clinical practice. These data were correlated with patient survival using multivariable Cox analysis and, for a subset of 167 tumors, with signs of tumor invasiveness on the MRI. The effects of STAT5b knockdown by siRNA were assessed on the growth, therapeutic resistance, invasion and migration of GBM cell lines U87, U87‑EGFRVIII and LN18 and primary cultures GM2 and GM3. The activation, but not the copy number or the mRNA expression of nuclear transcription factor STAT5b expression correlated inversely with patient survival independently of IDH1R132H status, age, Karnofsky Performance Score, treatment and tumor volume. STAT5b inhibition neither altered the cell proliferation nor reduced the clonogenic proliferative potency of GBM cells, and did not sensitize them to the cytotoxic effect of ionizing radiation and temozolomide
MeSH term(s)	Brain Neoplasms/drug therapy ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioblastoma/drug therapy ; Glioblastoma/genetics ; Glioblastoma/metabolism ; Humans ; Prognosis ; RNA, Messenger ; STAT5 Transcription Factor/genetics ; STAT5 Transcription Factor/metabolism
Chemical Substances	RNA, Messenger ; STAT5 Transcription Factor ; STAT5B protein, human
Language	English
Publishing date	2022-09-07
Publishing country	Greece
Document type	Journal Article
ZDB-ID	1154403-x
ISSN	1791-2423 ; 1019-6439
ISSN (online)	1791-2423
ISSN	1019-6439
DOI	10.3892/ijo.2022.5414
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Article: Pathology-proven extradural ("distant") metastases of gliomas in adults in the Netherlands between 1971 and 2018: a systematic case series.

den Hartog, Sanne J / van der Kolk, Anja / Bruggink, Annette / Seute, Tatjana / Wesseling, Pieter / Wilbers, Joyce

Neuro-oncology practice

2021 Volume 8, Issue 3, Page(s) 317–324

Abstract: Background: Diffuse gliomas are the most frequent primary tumors originating in the central nervous system parenchyma. Although the majority of these tumors are highly malignant, extradural metastases (EDM) are extremely rare. We aimed to perform a ... ...

Abstract	Background: Diffuse gliomas are the most frequent primary tumors originating in the central nervous system parenchyma. Although the majority of these tumors are highly malignant, extradural metastases (EDM) are extremely rare. We aimed to perform a systematic review of patients with pathology-proven EDM of diffuse gliomas in the Netherlands. Methods: From the Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands information on all cases with EDM between 1971 and October 2018 was retrieved. Patients aged < 18 years or with a diagnosis of ependymoma or continuous tumor growth from intradural to extradural were excluded. Demographics, initial tumor diagnosis, treatment characteristics, location of the EDM, and survival data were collected. IDH1 R132H immunohistochemistry was performed on cases in which a paraffin block of the metastatic tumor could be retrieved. Results: Twenty-five patients with diffuse glioma and pathology-proven EDM were identified. Median age at diagnosis of glioma was 46 years (IQR: 35-59); 21 patients (84%) were male. Histopathologic diagnosis was glioblastoma in 17 patients (68%) and lower-grade tumor in eight patients. In 3 out of 12 patients of which a paraffin block could be retrieved immunohistochemistry revealed an Conclusion: EDM of diffuse glioma are rare. They occur most frequently in patients with glioblastoma, however, they can also originate from lower-grade, IDH-mutant gliomas. In daily practice, EDM of diffuse glioma should be considered in patients with tumefactive lesions of the bone or lymph nodes.
Language	English
Publishing date	2021-01-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2768945-1
ISSN	2054-2585 ; 2054-2577
ISSN (online)	2054-2585
ISSN	2054-2577
DOI	10.1093/nop/npab006
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Article: Early Surgery Prolongs Professional Activity in IDH Mutant Low-Grade Glioma Patients: A Policy Change Analysis.

Robe, Pierre A / Rados, Matea / Spliet, Wim G / Hoff, Reinier G / Gosselaar, Peter / Broekman, Marike L D / van Zandvoort, Martine J / Seute, Tatjana / Snijders, Tom J

Frontiers in oncology

2022 Volume 12, Page(s) 851803

Abstract: Background: Until 2015, Dutch guidelines recommended follow-up and biopsy rather than surgery as initial care for suspected low-grade gliomas (LGG). Given evidence that surgery could extend patient survival, our center stopped following this guideline ... ...

Abstract	Background: Until 2015, Dutch guidelines recommended follow-up and biopsy rather than surgery as initial care for suspected low-grade gliomas (LGG). Given evidence that surgery could extend patient survival, our center stopped following this guideline on January 1, 2010 and opted for early maximal safe resection of LGG. The effects of early surgery on the ability of patients to work remains little documented. Methods: A total of 104 patients operated on at our center between January 2000 and April 2013 and diagnosed with the WHO 2016 grade 2 astrocytoma, IDH mutant or oligodendroglioma, IDH mutant and deleted 1p19q were included. The clinical characteristics, survival, and work history of patients operated on before or after January 2010 were obtained from the patients' records and compared. The minimal follow-up was 8 years. Results: As per policy change, the interval between radiological diagnosis and first surgery decreased significantly after 2010. Likewise, before 2010, 25.8% of tumors were initially biopsied, 51.6% were resected under anesthesia, and 22.5% under awake conditions versus 14.3%, 23.8%, and 61.9% after this date ( Conclusion: A policy shift towards early aggressive surgical treatment of IDH mutant LGG is safe and prolongs the patients' ability to work.
Language	English
Publishing date	2022-03-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.851803
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Article: Central Nervous System Progression in Primary Vitreoretinal Lymphoma with Bilateral and Unilateral Involvement: A Systematic Review and Meta-Analysis.

van Rooij, Josephus L M / Tokarska, Klaudia A / Ten Dam-van Loon, Ninette H / Wessels, Peter H / Seute, Tatjana / Minnema, Monique C / Snijders, Tom J

Cancers

2022 Volume 14, Issue 12

Abstract: Background: Primary vitreoretinal lymphoma (PVRL) is either unilateral or bilateral at initial presentation. Progression to a central nervous system (CNS) lymphoma is regularly observed and these patients seem to have an inferior survival. Knowledge of ... ...

Abstract	Background: Primary vitreoretinal lymphoma (PVRL) is either unilateral or bilateral at initial presentation. Progression to a central nervous system (CNS) lymphoma is regularly observed and these patients seem to have an inferior survival. Knowledge of the predictive value of laterality for CNS progression may facilitate risk stratification and the development of more effective treatment strategies, and eventually, improve outcomes. The objective of this analysis is to estimate the risk of CNS progression for patients with bilateral versus unilateral involvement of PVRL. Methods: Systematic literature search for studies on CNS progression in PVRL with bilateral and unilateral involvement according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We assessed the risk of bias and the methodological quality of studies using the Quality in Prognosis Studies (QUIPS) tool. Risk ratios of CNS progression in PVRL with bilateral and unilateral involvement were calculated and combined via a meta-analysis. Results: Twenty-five small-sized (total Conclusions: CNS progression is common in PVRL. From the limited available evidence, there is no significant difference in CNS progression between bilateral and unilateral PVRL.
Language	English
Publishing date	2022-06-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14122967
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Article ; Online: Tumor-related molecular determinants of neurocognitive deficits in patients with diffuse glioma.

van Kessel, Emma / Berendsen, Sharon / Baumfalk, Anniek E / Venugopal, Hema / Krijnen, Eva A / Spliet, Wim G M / van Hecke, Wim / Giuliani, Fabrizio / Seute, Tatjana / van Zandvoort, Martine J E / Snijders, Tom J / Robe, Pierre A

Neuro-oncology

2022 Volume 24, Issue 10, Page(s) 1660–1670

Abstract: Background: Cognitive impairment is a common and debilitating symptom in patients with diffuse glioma, and is the result of multiple factors. We hypothesized that molecular tumor characteristics influence neurocognitive functioning (NCF), and aimed to ... ...

Abstract	Background: Cognitive impairment is a common and debilitating symptom in patients with diffuse glioma, and is the result of multiple factors. We hypothesized that molecular tumor characteristics influence neurocognitive functioning (NCF), and aimed to identify tumor-related markers of NCF in diffuse glioma patients. Methods: We examined the relation between cognitive performance (executive function, memory, and psychomotor speed) and intratumoral expression levels of molecular markers in treatment-naive patients with diffuse glioma. We performed a single-center study in a consecutive cohort, through a two-step design: (1) hypothesis-free differential expression and gene set enrichment analysis to identify candidate oncogenetic markers for cognitive impairment. Nineteen molecular markers of interest were derived from this set of genes, as well as from prior knowledge; (2) correlation of cognitive performance to intratumoral expression levels of these nineteen molecular markers, measured with immunohistochemistry. Results: From 708 included patients with immunohistochemical data, we performed an in-depth analysis of neuropsychological data in 197, and differential expression analysis in 65 patients. After correcting for tumor volume and location, we found significant associations between expression levels of CD3 and IDH-1 and psychomotor speed; between IDH-1, ATRX, NLGN3, BDNF, CK2Beta, EAAT1, GAT-3, SRF, and memory performance; and between IDH-1, P-STAT5b, NLGN3, CK2Beta, and executive functioning. P-STAT5b, CD163, CD3, and Semaphorin-3A were independently associated after further correction for histopathological grade. Conclusion: Molecular characteristics of glioma can be independent determinants of patients' cognitive functioning. This suggests that besides tumor volume, location, and histological grade, variations in glioma biology influence cognitive performance through mechanisms that include perturbation of neuronal communication. These results pave the way towards targeted cognition improving therapies in neuro-oncology.
MeSH term(s)	Biomarkers, Tumor/genetics ; Brain Neoplasms/complications ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Brain-Derived Neurotrophic Factor ; Glioma/complications ; Glioma/genetics ; Glioma/pathology ; Humans ; Neuropsychological Tests ; Semaphorin-3A
Chemical Substances	Biomarkers, Tumor ; Brain-Derived Neurotrophic Factor ; Semaphorin-3A
Language	English
Publishing date	2022-02-11
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/noac036
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Article ; Online: Conventional MRI Criteria to Differentiate Progressive Disease From Treatment-Induced Effects in High-Grade (WHO Grade 3-4) Gliomas.

Flies, Christina M / van Leuken, Karlijn H / Ten Voorde, Marlies / Verhoeff, Joost J C / De Vos, Filip Y F / Seute, Tatjana / Robe, Pierre A / Witkamp, Theodoor D / Hendrikse, Jeroen / Dankbaar, Jan Willem / Snijders, Tom J

Neurology

2022 Volume 99, Issue 1, Page(s) e77–e88

Abstract: Background and objectives: Posttreatment radiologic deterioration of an irradiated high-grade (WHO grade 3-4) glioma (HGG) may be the result of true progressive disease or treatment-induced effects (TIE). Differentiation between these entities is of ... ...

Abstract	Background and objectives: Posttreatment radiologic deterioration of an irradiated high-grade (WHO grade 3-4) glioma (HGG) may be the result of true progressive disease or treatment-induced effects (TIE). Differentiation between these entities is of great importance but remains a diagnostic challenge. This study assesses the diagnostic value of conventional MRI characteristics to differentiate progressive disease from TIE in HGGs. Methods: In this single-center, retrospective, consecutive cohort study, we included adults with a HGG who were treated with (chemo-)radiotherapy and subsequently developed a new or increasing contrast-enhancing lesion on conventional follow-up MRI. TIE and progressive disease were defined radiologically as stable/decreased for ≥6 weeks or Response Assessment in Neuro-Oncology progression and histologically as TIE without viable tumor or progressive disease. Two neuroradiologists assessed 21 preselected MRI characteristics of the progressive lesions. The statistical analysis included logistic regression to develop a full multivariable model, a diagnostic model with model reduction, and a Cohen kappa interrater reliability (IRR) coefficient. Results: A total of 210 patients (median age 61 years, interquartile range 54-68, 189 male) with 284 lesions were included, of whom 141 (50%) had progressive disease. Median time to progressive disease was 2 (0.7-6.1) and to TIE 0.9 (0.7-3.5) months after radiotherapy. After multivariable modeling and model reduction, the following determinants prevailed: radiation dose (odds ratio [OR] 0.68, 95% CI 0.49-0.93), longer time to progression (TTP; OR 3.56, 95% CI 1.84-6.88), marginal enhancement (OR 2.04, 95% CI 1.09-3.83), soap bubble enhancement (OR 2.63, 95% CI 1.39-4.98), and isointense apparent diffusion coefficient (ADC) signal (OR 2.11, 95% CI 1.05-4.24). ORs >1 indicate higher odds of progressive disease. The Hosmer & Lemeshow test showed good calibration ( Discussion: Several characteristics from conventional MRI are significant predictors for the discrimination between progressive disease and TIE. However, IRR was variable. Conventional MRI characteristics from this study should be incorporated into a multimodal diagnostic model with advanced imaging techniques. Classification of evidence: This study provides Class II evidence that in patients with irradiated HGGs, radiation dose, longer TTP, marginal enhancement, soap bubble enhancement, and isointense ADC signal distinguish progressive disease from TIE.
MeSH term(s)	Adult ; Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/radiotherapy ; Cohort Studies ; Diffusion Magnetic Resonance Imaging/methods ; Glioma/diagnostic imaging ; Glioma/therapy ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Reproducibility of Results ; Retrospective Studies ; Soaps ; World Health Organization
Chemical Substances	Soaps
Language	English
Publishing date	2022-04-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000200359
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Article: Complications, compliance, and undertreatment do not explain the relationship between cognition and survival in diffuse glioma patients.

van Kessel, Emma / Krijnen, Eva A / IJpelaar, Suzanne / Huenges Wajer, Irene M C / Ruis, Carla / Seute, Tatjana / De Vos, Filip Y F L / Verhoeff, Joost J C / Robe, Pierre A / van Zandvoort, Martine J E / Snijders, Tom J

Neuro-oncology practice

2022 Volume 9, Issue 4, Page(s) 284–298

Abstract: Background: Cognitive deficits occur in all different grades of glioma. In a recent study, we found these deficits to be independently, and possibly causally, related to survival in diffuse gliomas. In this study, we investigated whether the ... ...

Abstract	Background: Cognitive deficits occur in all different grades of glioma. In a recent study, we found these deficits to be independently, and possibly causally, related to survival in diffuse gliomas. In this study, we investigated whether the relationship between cognition and survival was mediated by three different factors: undertreatment, complications of treatment, and compliance. We hypothesized that patients with cognitive impairment may undergo less intensive treatment, be less compliant, and suffer more from complications, resulting in shortened survival for cognitively impaired patients. Methods: In a retrospective cohort study of patients undergoing awake craniotomy between operative neuropsychological assessments in five cognitive domains. We used Structural Equation Modeling to perform mediation analyses. Mediation analyses are analyses to evaluate whether a variable is a factor Results: In total 254 patients were included, of whom 111 patients were LGG patients and 143 were HGG patients. The most frequently impaired domain was memory (37.8% Conclusions: This suggests that other mechanisms should be involved in the relation between cognition and survival. Hypothetically, cognitive functioning can act as a marker for diffuse infiltration of the tumor or cognitive functioning and survival could be determined by overlapping germline and somatic tumoral molecular-genetic factors.
Language	English
Publishing date	2022-04-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2768945-1
ISSN	2054-2585 ; 2054-2577
ISSN (online)	2054-2585
ISSN	2054-2577
DOI	10.1093/nop/npac027
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Article ; Online: Effects of valproic acid on histone deacetylase inhibition in vitro and in glioblastoma patient samples.

Berendsen, Sharon / Frijlink, Elselien / Kroonen, Jèrôme / Spliet, Wim G M / van Hecke, Wim / Seute, Tatjana / Snijders, Tom J / Robe, Pierre A

Neuro-oncology advances

2019 Volume 1, Issue 1, Page(s) vdz025

Abstract: Background: The antiepileptic drug valproic acid (VPA) inhibits histone deacetylase in glioblastoma cells in vitro, which influences several oncogenic pathways and decreases glioma cell proliferation. The clinical relevance of these observations remains ...

Abstract	Background: The antiepileptic drug valproic acid (VPA) inhibits histone deacetylase in glioblastoma cells in vitro, which influences several oncogenic pathways and decreases glioma cell proliferation. The clinical relevance of these observations remains unclear, as VPA does not seem to affect glioblastoma patient survival. In this study, we analyzed whether the in vitro effects of VPA treatment on histone acetylation are also observed in tumor tissues of glioblastoma patients. Methods: The in vitro effects of VPA treatment on histone acetylation were assessed with immunofluorescence and western blotting. On tissue microarrays and in fresh-frozen glioblastoma tissues we investigated the histone acetylation patterns of patients who were either treated with VPA or did not receive antiepileptic drugs at the time of their surgery. We also performed mRNA expression-based and gene set enrichment analyses on these tissues. Results: VPA increased the expression levels of acetylated histones H3 and H4 in vitro, in agreement with previous reports. In tumor samples obtained from glioblastoma patients, however, VPA treatment affected neither gene (set) expression nor histone acetylation. Conclusions: The in vitro effects of VPA on histone acetylation status in glioblastoma cells could not be confirmed in clinical tumor samples of glioblastoma patients using antiepileptic doses of VPA, which reflects the lack of effect of VPA on the clinical outcome of glioblastoma patients.
Language	English
Publishing date	2019-11-12
Publishing country	England
Document type	Journal Article
ZDB-ID	3009682-0
ISSN	2632-2498 ; 2632-2498
ISSN (online)	2632-2498
ISSN	2632-2498
DOI	10.1093/noajnl/vdz025
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