Matthew Daniels - Academia.edu (original) (raw)

Papers by Matthew Daniels

Cardiovascular Research, 2018

If you have not been to the ACC Scientific Sessions, you might not realize this meeting is a lot ... more If you have not been to the ACC Scientific Sessions, you might not realize this meeting is a lot closer to the clinical coalface than it is to basic science. That is not a bad thing, but the reality is that cardiovascular research is slovenly in comparison to the inroads basic science has made in the other major disease of our era, cancer. We are tied down with descriptive disease entities like 'atrial fibrillation' (AF). AF is common, you have a lifetime risk of 1:4 of developing it. 1 Contemporary AF classification describes how long it lasts (paroxysmal, persistent or permanent) rather than what causes it. It's like talking about cancer in terms of the amount of tumour-a Starbuckian classification of Tall, Grande and Venti which oncology abandoned decades ago. AF causes stroke, and death by promoting clot formation in the heart, 1 so there was good news on the clinical horizon that the anti-coagulants (that reduce stroke and death in patients with AF) based on factor Xa inhibition now appear to have an effective antidote 2 that translates into clinical practice based on the interim analyses presented for the Annexa-4 study (

Nature Communications

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–... more Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility.

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BMC research notes, Jan 18, 2018

Cardiomyocytes derived from human-induced pluripotent stem cells are a powerful platform for high... more Cardiomyocytes derived from human-induced pluripotent stem cells are a powerful platform for high-throughput drug screening in vitro. However, current modalities for drug testing, such as electrophysiology and fluorescence imaging have inherent drawbacks. To circumvent these problems, we report the development of a bioluminescent Ca indicator GmNL(Ca), and its application in a customized microscope for high-throughput drug screening. GmNL(Ca) gives a 140% signal change with Ca, and can image drug-induced changes of Ca dynamics in cultured cells. Since bioluminescence requires application of a chemical substrate, which is consumed over ~ 30 min we made a dedicated microscope with automated drug dispensing inside a light-tight box, to control drug addition. To overcome thermal instability of the luminescent substrate, or small molecule, dual climate control enables distinct temperature settings in the drug reservoir and the biological sample. By combining GmNL(Ca) with this adaptation...

Frontiers in cell and developmental biology, 2018

Autosomal dominant optic atrophy (ADOA) is usually caused by mutations in the essential gene, OPA... more Autosomal dominant optic atrophy (ADOA) is usually caused by mutations in the essential gene, OPA1. This encodes a ubiquitous protein involved in mitochondrial dynamics, hence tissue specificity is not understood. Dysregulated mitophagy (mitochondria recycling) is implicated in ADOA, being increased in OPA1 patient fibroblasts. Furthermore, autophagy may be increased in retinal ganglion cells (RGCs) of the OPA1 mouse model. We developed a mouse model for studying mitochondrial dynamics in order to investigate mitophagy in ADOA. We crossed the OPA1 mouse with our RedMIT/GFP-LC3 mouse, harboring red fluorescent mitochondria and green fluorescent autophagosomes. Colocalization between mitochondria and autophagosomes, the hallmark of mitophagy, was quantified in fluorescently labeled organelles in primary cell cultures, using two high throughput imaging methods Imagestream (Amnis) and IN Cell Analyzer 1000 (GE Healthcare Life Sciences). We studied colocalization between mitochondria and...

Nature communications, Dec 14, 2016

Luminescence imaging has gained attention as a promising bio-imaging modality in situations where... more Luminescence imaging has gained attention as a promising bio-imaging modality in situations where fluorescence imaging cannot be applied. However, wider application to multicolour and dynamic imaging is limited by the lack of bright luminescent proteins with emissions across the visible spectrum. Here we report five new spectral variants of the bright luminescent protein, enhanced Nano-lantern (eNL), made by concatenation of the brightest luciferase, NanoLuc, with various colour hues of fluorescent proteins. eNLs allow five-colour live-cell imaging, as well as detection of single protein complexes and even single molecules. We also develop an eNL-based Ca(2+) indicator with a 500% signal change, which can image spontaneous Ca(2+) dynamics in cardiomyocyte and neural cell models. These eNL probes facilitate not only multicolour imaging in living cells but also sensitive imaging of a wide repertoire of proteins, even at very low expression levels.

Heart, 2015

To the Editor We read with great interest the article by Choi et al. 1 In this study, the authors... more To the Editor We read with great interest the article by Choi et al. 1 In this study, the authors evaluated the increment of the extent of late gadolinium enhancement (LGE) in patients with hypertrophic cardiomyopathy (HCM). This study reproduces our previous paper, ‘Progression of myocardial fibrosis assessed with cardiac magnetic resonance in hypertrophic cardiomyopathy’,2 and cited in the current European Society of Cardiology guidelines for HCM. Choi et al found a fast progression of fibrosis in HCM, confirming …

Obstetric Medicine, 2011

Home birth is becoming increasingly popular. Labour in the privacy and comfort of a familiar envi... more Home birth is becoming increasingly popular. Labour in the privacy and comfort of a familiar environment has clear appeal. Home birth is usually as safe for low-risk women with appropriate prenatal care. Yet events during delivery can be unpredictable and may be stressful for unprepared family members. Here we report a case of Tako-tsubo cardiomyopathy, also known as broken-heart syndrome, in a relative attending an impromptu home delivery. Thus, while home delivery is generally safe for the mother we ask: is it safe for everyone involved?

Catheterization and Cardiovascular Interventions, 2013

PloS one, 2017

Identification of drug induced electrical instability of the heart curtails development, and intr... more Identification of drug induced electrical instability of the heart curtails development, and introduction, of potentially proarrhythmic drugs. This problem usually requires complimentary contact based approaches such as patch-clamp electrophysiology combined with field stimulation electrodes to observe and control the cell. This produces data with high signal to noise but requires direct physical contact generally preventing high-throughput, or prolonged, phenotyping of single cells or tissues. Combining genetically encoded optogenetic control and spectrally compatible calcium indicator tools into a single adenoviral vector allows the analogous capability for cell control with simultaneous cellular phenotyping without the need for contact. This combination can be applied to single rodent primary adult cardiomyocytes, and human stem cell derived cardiomyocytes, enabling contactless small molecule evaluation for inhibitors of sodium, potassium and calcium channels suggesting it may be...

Additional file 1. Oligonucleotides used in this study.

Current Treatment Options in Cardiovascular Medicine

Purpose As second and third waves of the COVID-19 pandemic challenge healthcare in North America ... more Purpose As second and third waves of the COVID-19 pandemic challenge healthcare in North America and Europe once again, we analyze the impact of the first wave on routine elective cardiovascular care, and the differential COVID risk emerging within our patient groups and staff. Perspective We describe the need to sustainably resume, and temporarily expand, routine elective cardiac services in the face of resurgent COVID-19. Some, but not all, cardiac patient groups are particularly vulnerable to adverse outcomes following COVID-19 infection. We explore mitigation measures at the institutional level to increase resilience within cardiac services to enable them to operate deep into subsequent waves of COVID infection which place unprecedented demands on intensive care infrastructure. As measures to eradicate the virus appear to have failed in many countries, and vaccine roll-out will take many months we take the view that the threat imposed by endemic COVID-19 alters the way elective ...

Current Treatment Options in Cardiovascular Medicine, 2021

As second and third waves of the COVID-19 pandemic challenge healthcare in North America and Euro... more As second and third waves of the COVID-19 pandemic challenge healthcare in North America and Europe once again, we analyze the impact of the first wave on routine elective cardiovascular care, and the differential COVID risk emerging within our patient groups and staff. We describe the need to sustainably resume, and temporarily expand, routine elective cardiac services in the face of resurgent COVID-19. Some, but not all, cardiac patient groups are particularly vulnerable to adverse outcomes following COVID-19 infection. We explore mitigation measures at the institutional level to increase resilience within cardiac services to enable them to operate deep into subsequent waves of COVID infection which place unprecedented demands on intensive care infrastructure. As measures to eradicate the virus appear to have failed in many countries, and vaccine roll-out will take many months we take the view that the threat imposed by endemic COVID-19 alters the way elective procedural care shou...

Open Heart

AimsIn response to the COVID-19 pandemic, the UK was placed under strict lockdown measures on 23 ... more AimsIn response to the COVID-19 pandemic, the UK was placed under strict lockdown measures on 23 March 2020. The aim of this study was to quantify the effects on physical activity (PA) levels using data from the prospective Triage-HF Plus Evaluation study.MethodsThis study represents a cohort of adult patients with implanted cardiac devices capable of measuring activity by embedded accelerometery via a remote monitoring platform. Activity data were available for the 4 weeks pre-implementation and post implementation of ‘stay at home’ lockdown measures in the form of ‘minutes active per day’ (min/day).ResultsData were analysed for 311 patients (77.2% men, mean age 68.8, frailty 55.9%. 92.2% established heart failure (HF) diagnosis, of these 51.2% New York Heart Association II), with comorbidities representative of a real-world cohort.Post-lockdown, a significant reduction in median PA equating to 20.8 active min/day was seen. The reduction was uniform with a slightly more pronounced ...

Catheterization and Cardiovascular Interventions

Social media allows interventional cardiologists to disseminate and discuss research and clinical... more Social media allows interventional cardiologists to disseminate and discuss research and clinical cases in real-time, to demonstrate and learn innovative techniques, to build professional networks, and to reach out to patients and the general public. Social media provides a democratic platform for all participants to influence the conversation and demonstrate their expertise. This review addresses the use of social media for these purposes in interventional cardiology, as well as respect for patient privacy, how to get started on social media, the creation of high-impact social media content, and the role of traditional journals in the age of social media. In the future, we hope that interventional cardiology fellowship programs will incorporate social media training into their curricula. In addition, professional societies may adapt to the rapid dissemination of data on social media by developing processes to update guidelines more rapidly and more frequently.

Structural Heart

By Failing to Prepare, you are Preparing to Fail - Benjamin Franklin Congenital malformations of ... more By Failing to Prepare, you are Preparing to Fail - Benjamin Franklin Congenital malformations of the pulmonary trunk and valve are a spectrum of conditions (e.g. subvalvar, valvar or supravalvar pu...

Oxford Medical Case Reports

ABSTRACTFamilial hypercholesterolemia (FH) is an autosomal dominant condition that increases the ... more ABSTRACTFamilial hypercholesterolemia (FH) is an autosomal dominant condition that increases the risk of premature cardiovascular disease. Despite advances in treatment, it remains under detected and under treated. As an inherited condition, it poses a risk to the patient and family members. Most cases are due to defective low-density lipoprotein receptor (LDLR) activity. Heterozygous mutations are common (1:250–1:300). Homozygous FH is very rare (2–3 in a million), with higher circulating cholesterol levels and a poorer cardiovascular prognosis. We present the management of a case of homozygous hypercholesterolemia due to homozygous LDLR mutation. The patient subsequently developed severe coronary artery and aortic valve disease despite aggressive lipid-lowering therapy. We review advanced lipid management options that include lipoprotein apheresis, Proprotein Convertase Subtilisin/Kexin type 9 inhibition, and the microsomal triglyceride transfer protein inhibitor lomitapide.

Cardiovascular Diagnosis and Therapy

Computed tomography (CT) plays a key role in the peri-procedural planning of left atrial appendag... more Computed tomography (CT) plays a key role in the peri-procedural planning of left atrial appendage occlusion (LAAO) device placement and post-procedural evaluation. The geometric variability of the interatrial septum, left atrium, and the left atrial appendage morphology can be fully visualized and intuitively appreciated through CT-derived, patient-specific 3D model unique to each individual's anatomy. This review further defines the strengths and limitations of CT peri-procedural imaging in the planning of LAAO.

Current Pharmaceutical Biotechnology

In 1791, Galvani established that electricity activated excitable cells. In the two centuries tha... more In 1791, Galvani established that electricity activated excitable cells. In the two centuries that followed, electrode stimulation of neuronal, skeletal and cardiac muscle became the adjunctive method of choice in experimental, electrophysiological, and clinical arenas. This approach underpins breakthrough technologies like implantable cardiac pacemakers that we currently take for granted. However, the contact dependence, and field stimulation that electrical depolarization delivers brings inherent limitations to the scope and experimental scale that can be achieved. Many of these were not exposed until reliable in vitro stem-cell derived experimental materials, with genotypes of interest, were produced in the numbers needed for multi-well screening platforms (for toxicity or efficacy studies) or the 2D or 3D tissue surrogates required to study propagation of depolarization within multicellular constructs that mimic clinically relevant arrhythmia in the heart or brain. Here the limi...