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Article ; Online: Correction to: Molecular pathological classification of colorectal cancer-an update.

Dunne, Philip D / Arends, Mark J

Virchows Archiv : an international journal of pathology

2024 Volume 484, Issue 2, Page(s) 287

Language	English
Publishing date	2024-02-28
Publishing country	Germany
Document type	Published Erratum
ZDB-ID	1184867-4
ISSN	1432-2307 ; 0945-6317
ISSN (online)	1432-2307
ISSN	0945-6317
DOI	10.1007/s00428-024-03773-0
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Article ; Online: Molecular pathological classification of colorectal cancer-an update.

Dunne, Philip D / Arends, Mark J

Virchows Archiv : an international journal of pathology

2024 Volume 484, Issue 2, Page(s) 273–285

Abstract: ... for development of transcriptional classifiers and risk stratification methods, taking into account the marked ...

Abstract	Colorectal cancer (CRC) has a broad range of molecular alterations with two major mechanisms of genomic instability (chromosomal instability and microsatellite instability) and has been subclassified into 4 consensus molecular subtypes (CMS) based on bulk RNA sequence data. Here, we update the molecular pathological classification of CRC with an overview of more recent bulk and single-cell RNA data analysis for development of transcriptional classifiers and risk stratification methods, taking into account the marked inter-tumoural and intra-tumoural heterogeneity of CRC. The importance of the stromal and immune components or tumour microenvironment (TME) to prognosis has emerged from these analyses. Attempts to remove the contribution of the tumour microenvironment and reveal neoplastic-specific transcriptional traits involved identification of the CRC intrinsic subtypes (CRIS). The use of immunohistochemistry and digital pathology to implement classification systems are evolving fields. Conventional adenoma versus serrated polyp pathway transcriptomic analysis and characterisation of canonical LGR5+ crypt base columnar stem cell versus ANXA1+ regenerative stem cell phenotypes emerged as key properties for improved understanding of transcriptional signals involved in molecular subclassification of colorectal cancers. Recently, classification by three pathway-derived subtypes (PDS1-3) has been developed, revealing a continuum of intrinsic biology associated with biological, stem cell, histopathological, and clinical attributes.
MeSH term(s)	Humans ; Colorectal Neoplasms/pathology ; Gene Expression Profiling/methods ; Transcriptome ; Tumor Microenvironment
Language	English
Publishing date	2024-02-06
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1184867-4
ISSN	1432-2307 ; 0945-6317
ISSN (online)	1432-2307
ISSN	0945-6317
DOI	10.1007/s00428-024-03746-3
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Article ; Online: Exemplifying practice-based research: the influence of age on myopia progression.

Berkow, David / Dunne, Mark / Logan, Nicola S / Anderson, Stephen J

Clinical & experimental optometry

2024 , Page(s) 1–5

Abstract: Clinical relevance: The electronic storage of patient records and modern-day search engines present private practitioners with a unique opportunity to extract valuable data for investigative research purposes. However, practitioners seldom harness this ... ...

Abstract	Clinical relevance: The electronic storage of patient records and modern-day search engines present private practitioners with a unique opportunity to extract valuable data for investigative research purposes. However, practitioners seldom harness this resource and consequently a vast repository of clinical data remains largely unexplored. Background: This study, based on real-world data from an optometric practice, stands as an example of how clinicians can actively contribute to research. In doing so it underscores the role played by age in determining the rate of natural myopia progression. Methods: A retrospective data analysis of the refractive status, age and optical correction type of participants, was conducted over six years. Forty-four participants were recruited (25 contact lens and 19 spectacle wearers), with a presenting age varying from 5 to 20 years (median, 11 years). Non-cycloplegic, monocular foveal refractions were completed using a ShinNippon open-field autorefractor, corroborated with subjective refraction. The mean spherical equivalent refractive error was calculated for the participants' initial visit (baseline measure) and for a six-year follow-up visit (progression measure), with myopia progression defined as the difference between these measures. Statistical analyses were computed using Decision Tree Analysis, with a significance level set at 95%. Results: The participant age at first visit exerted a significant influence on natural myopia progression over the assessment period (F 1,42 = 17.11, Conclusions: Utilizing the advantage of small real-world data samples, the benefit of research by private practitioners was demonstrated, providing evidence that the age at which a child first presents for an eye examination is highly influential in determining their rate of myopia progression.
Language	English
Publishing date	2024-02-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	639275-1
ISSN	1444-0938 ; 0816-4622
ISSN (online)	1444-0938
ISSN	0816-4622
DOI	10.1080/08164622.2024.2309219
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Article: Somatostatin receptors in congenital hyperinsulinism: Biology to bedside.

van Albada, Mirjam E / Mohnike, Klaus / Dunne, Mark J / Banerjee, Indi / Betz, Stephen F

Frontiers in endocrinology

2022 Volume 13, Page(s) 921357

Abstract: Congenital hyperinsulinism (CHI), although a rare disease, is an important cause of severe hypoglycemia in early infancy and childhood, causing preventable morbidity and mortality. Prompt diagnosis and appropriate treatment is necessary to prevent ... ...

Abstract	Congenital hyperinsulinism (CHI), although a rare disease, is an important cause of severe hypoglycemia in early infancy and childhood, causing preventable morbidity and mortality. Prompt diagnosis and appropriate treatment is necessary to prevent hypoglycaemia mediated brain damage. At present, the medical treatment of CHI is limited to diazoxide as first line and synthetic somatostatin receptor ligands (SRLs) as second line options; therefore understanding somatostatin biology and treatment perspectives is important. Under healthy conditions, somatostatin secreted from pancreatic islet δ-cells reduces insulin release through somatostatin receptor induced cAMP-mediated downregulation and paracrine inhibition of β- cells. Several SRLs with extended duration of action are now commercially available and are being used off-label in CHI patients. Efficacy remains variable with the present generation of SRLs, with treatment effect often being compromised by loss of initial response and adverse effects such as bowel ischaemia and hepatobiliary dysfunction. In this review we have addressed the biology of the somatostatin system contexualised to CHI. We have discussed the clinical use, limitations, and complications of somatostatin agonists and new and emerging therapies for CHI.
MeSH term(s)	Biology ; Child ; Congenital Hyperinsulinism/complications ; Congenital Hyperinsulinism/drug therapy ; Diazoxide/therapeutic use ; Humans ; Insulin/therapeutic use ; Ligands ; Receptors, Somatostatin/therapeutic use ; Somatostatin/therapeutic use
Chemical Substances	Insulin ; Ligands ; Receptors, Somatostatin ; Somatostatin (51110-01-1) ; Diazoxide (O5CB12L4FN)
Language	English
Publishing date	2022-09-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2022.921357
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Article: HYPO-CHEAT's aggregated weekly visualisations of risk reduce real world hypoglycaemia.

Worth, Chris / Nutter, Paul W / Dunne, Mark J / Salomon-Estebanez, Maria / Banerjee, Indraneel / Harper, Simon

Digital health

2022 Volume 8, Page(s) 20552076221129712

Abstract: Background: Children with congenital hyperinsulinism (CHI) are at constant risk of hypoglycaemia with the attendant risk of brain injury. Current hypoglycaemia prevention methods centre on the prediction of a continuous glucose variable using machine ... ...

Abstract	Background: Children with congenital hyperinsulinism (CHI) are at constant risk of hypoglycaemia with the attendant risk of brain injury. Current hypoglycaemia prevention methods centre on the prediction of a continuous glucose variable using machine learning (ML) processing of continuous glucose monitoring (CGM). This approach ignores repetitive and predictable behavioural factors and is dependent upon ongoing CGM. Thus, there has been very limited success in reducing real-world hypoglycaemia with a ML approach in any condition. Objectives: We describe the development of HYPO-CHEAT ( Methods: HYPO-CHEAT aggregates individual CGM data to identify weekly hypoglycaemia patterns. These are visualised via a hypoglycaemia heatmap along with actionable interpretations and targets. The algorithm is iterative and reacts to anticipated changing patterns of hypoglycaemia. HYPO-CHEAT was compared with Dexcom Clarity's pattern identification and Facebook Prophet's forecasting algorithm using data from 10 children with CHI using CGM for 12 weeks. HYPO-CHEAT's efficacy was assessed via change in time below range (TBR). Results: HYPO-CHEAT identified hypoglycaemia patterns in all patients. Dexcom Clarity identified no patterns. Predictions from Facebook Prophet were inconsistent and difficult to interpret. Importantly, the patterns identified by HYPO-CHEAT matched the lived experience of all patients, generating new and actionable understanding of the cause of hypos. This facilitated patients to significantly reduce their time in hypoglycaemia from 7.1% to 5.4% even when real-time CGM data was removed. Conclusions: HYPO-CHEAT's personalised hypoglycaemia heatmaps reduced total and targeted TBR even when CGM was reblinded. HYPO-CHEAT offers a highly effective and immediately available personalised approach to prevent hypoglycaemia and empower patients to self-care.
Language	English
Publishing date	2022-10-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2819396-9
ISSN	2055-2076
ISSN	2055-2076
DOI	10.1177/20552076221129712
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Article: The behaviour change behind a successful pilot of hypoglycaemia reduction with HYPO-CHEAT.

Worth, Chris / Nutter, Paul W / Salomon-Estebanez, Maria / Auckburally, Sameera / Dunne, Mark J / Banerjee, Indraneel / Harper, Simon

Digital health

2023 Volume 9, Page(s) 20552076231192011

Abstract: Background: Children with hypoglycaemia disorders, such as congenital hyperinsulinism (CHI), are at constant risk of hypoglycaemia (low blood sugars) with the attendant risk of brain injury. Current approaches to hypoglycaemia detection and prevention ... ...

Abstract	Background: Children with hypoglycaemia disorders, such as congenital hyperinsulinism (CHI), are at constant risk of hypoglycaemia (low blood sugars) with the attendant risk of brain injury. Current approaches to hypoglycaemia detection and prevention vary from fingerprick glucose testing to the provision of continuous glucose monitoring (CGM) to machine learning (ML) driven glucose forecasting. Recent trends for ML have had limited success in preventing free-living hypoglycaemia, due to a focus on increasingly accurate glucose forecasts and a failure to acknowledge the human in the loop and the essential step of changing behaviour. The wealth of evidence from the fields of behaviour change and persuasive technology (PT) allows for the creation of a theory-informed and technologically considered approach. Objectives: We aimed to create a PT that would overcome the identified barriers to hypoglycaemia prevention for those with CHI to focus on proactive prevention rather than commonly used reactive approaches. Methods: We used the behaviour change technique taxonomy and persuasive systems design models to create HYPO-CHEAT (HYpoglycaemia-Prevention-thrOugh-Cgm-HEatmap-Assisted-Technology): a novel approach that presents aggregated CGM data in simple visualisations. The resultant ease of data interpretation is intended to facilitate behaviour change and subsequently reduce hypoglycaemia. Results: HYPO-CHEAT was piloted in 10 patients with CHI over 12 weeks and successfully identified weekly patterns of hypoglycaemia. These patterns consistently correlated with identifiable behaviours and were translated into both a change in proximal fingerprick behaviour and ultimately, a significant reduction in aggregated hypoglycaemia from 7.1% to 5.4% with four out of five patients showing clinically meaningful reductions in hypoglycaemia. Conclusions: We have provided pilot data of a new approach to hypoglycaemia prevention that focuses on proactive prevention and behaviour change. This approach is personalised for individual patients with CHI and is a first step in changing our approach to hypoglycaemia prevention in this group.
Language	English
Publishing date	2023-08-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2819396-9
ISSN	2055-2076
ISSN	2055-2076
DOI	10.1177/20552076231192011
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Article ; Online: SWI/SNF chromatin remodeling complex in pancreatic ductal adenocarcinoma: Clinicopathologic and immunohistochemical study.

Chen, Irene Y / Ettel, Mark G / Bell, Phoenix D / Huber, Aaron R / Findeis-Hosey, Jennifer J / Wang, Wenjia / Hezel, Aram F / Dunne, Richard F / Drage, Michael G / Agostini-Vulaj, Diana

Human pathology

2024 Volume 144, Page(s) 40–45

Abstract: The SWItch/Sucrose Non-Fermentable (SWI/SNF) complex is a multimeric protein involved in transcription regulation and DNA damage repair. SWI/SNF complex abnormalities are observed in approximately 14-34 % of pancreatic ductal adenocarcinomas (PDACs). ... ...

Abstract	The SWItch/Sucrose Non-Fermentable (SWI/SNF) complex is a multimeric protein involved in transcription regulation and DNA damage repair. SWI/SNF complex abnormalities are observed in approximately 14-34 % of pancreatic ductal adenocarcinomas (PDACs). Herein, we evaluated the immunohistochemical expression of a subset of the SWI/SNF complex proteins (ARID1A, SMARCA4/BRG1, SMARCA2/BRM, and SMARCB1/INI1) within our PDAC tissue microarray to determine whether SWI/SNF loss is associated with any clinicopathologic features or patient survival in PDAC. In our cohort, 13 of 353 (3.7 %) PDACs showed deficient SWI/SNF complex expression, which included 11 (3.1 %) with ARID1A loss, 1 (0.3 %) with SMARCA4/BRG1 loss, and 1 (0.3 %) with SMARCA2/BRM loss. All cases were SMARCB1/INI1 proficient. The SWI/SNF-deficient PDACs were more frequently identified in older patients with a mean age of 71.6 years (SD = 7.78) compared to the SWI/SNF-proficient PDACs which occurred at a mean age of 65.2 years (SD = 10.95) (P = 0.013). The SWI/SNF-deficient PDACs were associated with higher histologic grade, compared to the SWI/SNF-proficient PDACs (P = 0.029). No other significant clinicopathologic differences were noted between SWI/SNF-deficient and SWI/SNF-proficient PDACs. On follow-up, no significant differences were seen for overall survival and progression-free survival between SWI/SNF-deficient and SWI/SNF-proficient PDACs (both with P > 0.05). In summary, SWI/SNF-deficient PDACs most frequently demonstrate ARID1A loss. SWI/SNF-deficient PDACs are associated with older age and higher histologic grade. No other significant associations among other clinicopathologic parameters were seen in SWI/SNF-deficient PDACs including survival.
MeSH term(s)	Humans ; Aged ; Chromatin Assembly and Disassembly ; Pancreatic Neoplasms/genetics ; Carcinoma, Pancreatic Ductal/genetics ; DNA Helicases ; Nuclear Proteins ; Transcription Factors
Chemical Substances	SMARCA4 protein, human (EC 3.6.1.-) ; DNA Helicases (EC 3.6.4.-) ; Nuclear Proteins ; Transcription Factors
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	207657-3
ISSN	1532-8392 ; 0046-8177
ISSN (online)	1532-8392
ISSN	0046-8177
DOI	10.1016/j.humpath.2024.01.013
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Article: Can the Academic and Experiential Study of Flourishing Improve Flourishing in College Students? A Multi-University Study.

Hirshberg, Matthew J / Colaianne, Blake A / Greenberg, Mark T / Inkelas, Karen Kurotsuchi / Davidson, Richard J / Germano, David / Dunne, John D / Roeser, Robert W

Mindfulness

2022 Volume 13, Issue 9, Page(s) 2243–2256

Abstract: Objectives: Significant concerns have been raised about the "mental health crisis" on college campuses, with attention turning to what colleges can do beyond counseling services to address students' mental health and well-being. We examined whether ... ...

Abstract	Objectives: Significant concerns have been raised about the "mental health crisis" on college campuses, with attention turning to what colleges can do beyond counseling services to address students' mental health and well-being. We examined whether primarily first-year (89.1%) undergraduate students ( Methods: In a two-wave, multi-site, propensity-score matched controlled trial (ASHF Results: ASHF participants reported significantly improved mental health (i.e., reduced depression) and flourishing, improvements on multiple attention and social-emotional skills (e.g., attention function, self-compassion), and increases in prosocial attitudes (empathic concern, shared humanity; Cohen's Conclusions: This research provides initial evidence that the ASHF course may be a promising curricular approach to reduce and potentially prevent poor mental health while promoting flourishing in college students. Continued research is needed to confirm these conclusions.
Language	English
Publishing date	2022-07-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2543424-X
ISSN	1868-8535 ; 1868-8527
ISSN (online)	1868-8535
ISSN	1868-8527
DOI	10.1007/s12671-022-01952-1
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Article: An Improved Model of Moderate Sleep Apnoea for Investigating Its Effect as a Comorbidity on Neurodegenerative Disease.

Roberts, Reno / Wall, Mark J / Braren, Ingke / Dhillon, Karendeep / Evans, Amy / Dunne, Jack / Nyakupinda, Simbarashe / Huckstepp, Robert T R

Frontiers in aging neuroscience

2022 Volume 14, Page(s) 861344

Abstract: Sleep apnoea is a highly prevalent disease that often goes undetected and is associated with poor clinical prognosis, especially as it exacerbates many different disease states. However, most animal models of sleep apnoea (e.g., intermittent hypoxia) ... ...

Abstract	Sleep apnoea is a highly prevalent disease that often goes undetected and is associated with poor clinical prognosis, especially as it exacerbates many different disease states. However, most animal models of sleep apnoea (e.g., intermittent hypoxia) have recently been dispelled as physiologically unrealistic and are often unduly severe. Owing to a lack of appropriate models, little is known about the causative link between sleep apnoea and its comorbidities. To overcome these problems, we have created a more realistic animal model of moderate sleep apnoea by reducing the excitability of the respiratory network. This has been achieved through controlled genetically mediated lesions of the preBötzinger complex (preBötC), the inspiratory oscillator. This novel model shows increases in sleep disordered breathing with alterations in breathing during wakefulness (decreased frequency and increased tidal volume) as observed clinically. The increase in dyspnoeic episodes leads to reduction in REM sleep, with all lost active sleep being spent in the awake state. The increase in hypoxic and hypercapnic insults induces both systemic and neural inflammation. Alterations in neurophysiology, an inhibition of hippocampal long-term potentiation (LTP), is reflected in deficits in both long- and short-term spatial memory. This improved model of moderate sleep apnoea may be the key to understanding why this disorder has such far-reaching and often fatal effects on end-organ function.
Language	English
Publishing date	2022-06-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2022.861344
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Article ; Online: Evaluation of antibody-based single cell type imaging techniques coupled to multiplexed imaging of N-glycans and collagen peptides by matrix-assisted laser desorption/ionization mass spectrometry imaging.

Dunne, Jaclyn / Griner, Jake / Romeo, Martin / Macdonald, Jade / Krieg, Carsten / Lim, Mark / Yagnik, Gargey / Rothschild, Kenneth J / Drake, Richard R / Mehta, Anand S / Angel, Peggi M

Analytical and bioanalytical chemistry

2023 Volume 415, Issue 28, Page(s) 7011–7024

Abstract: The integration of matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) with single cell spatial omics methods allows for a comprehensive investigation of single cell spatial information and matrisomal N-glycan and ... ...

Abstract	The integration of matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) with single cell spatial omics methods allows for a comprehensive investigation of single cell spatial information and matrisomal N-glycan and extracellular matrix protein imaging. Here, the performance of the antibody-directed single cell workflows coupled with MALDI-MSI are evaluated. Miralys™ photocleavable mass-tagged antibody probes (MALDI-IHC, AmberGen, Inc.), GeoMx DSP® (NanoString, Inc.), and Imaging Mass Cytometry (IMC, Standard BioTools Inc.) were used in series with MALDI-MSI of N-glycans and extracellular matrix peptides on formalin-fixed paraffin-embedded tissues. Single cell omics protocols were performed before and after MALDI-MSI. The data suggests that for each modality combination, there is an optimal order for performing both techniques on the same tissue section. An overall conclusion is that MALDI-MSI studies may be completed on the same tissue section as used for antibody-directed single cell modalities. This work increases access to combined cellular and extracellular information within the tissue microenvironment to enhance research on the pathological origins of disease.
MeSH term(s)	Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; Antibodies ; Polysaccharides/analysis ; Peptides/analysis ; Collagen ; Lasers
Chemical Substances	Antibodies ; Polysaccharides ; Peptides ; Collagen (9007-34-5)
Language	English
Publishing date	2023-10-16
Publishing country	Germany
Document type	Journal Article
ZDB-ID	201093-8
ISSN	1618-2650 ; 0016-1152 ; 0372-7920
ISSN (online)	1618-2650
ISSN	0016-1152 ; 0372-7920
DOI	10.1007/s00216-023-04983-2
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