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Article ; Online: Mediating Metabolism: Inhibition of Malic Enzyme 1 (ME1) Restores Endothelial Bioenergetics and Adenosine Signaling in Pulmonary Hypertension.

Rao, Rashmi J / Chan, Stephen Y

2024 Volume 149, Issue 17, Page(s) 1372–1374

MeSH term(s)	Adenosine/metabolism ; Signal Transduction/drug effects ; Humans ; Energy Metabolism/drug effects ; Animals ; Hypertension, Pulmonary/metabolism ; Hypertension, Pulmonary/drug therapy ; Malate Dehydrogenase/metabolism ; Malate Dehydrogenase/antagonists & inhibitors ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/drug effects ; Endothelial Cells/metabolism ; Endothelial Cells/drug effects
Chemical Substances	Adenosine (K72T3FS567) ; Malate Dehydrogenase (EC 1.1.1.37)
Language	English
Publishing date	2024-04-22
Publishing country	United States
Document type	Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Journal Article ; Editorial ; Comment
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/CIRCULATIONAHA.124.068738
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Article ; Online: Broad-scale impacts of coastal mega-infrastructure project on obligatory inshore delphinids: A cautionary tale from Hong Kong.

Chan, Stephen C Y / Karczmarski, Leszek

The Science of the total environment

2024 Volume 920, Page(s) 169753

Abstract: Inshore marine habitats experience considerable anthropogenic pressure, as this is where many adverse effects of human activities concentrate. In the rapidly-changing seascape of the Anthropocene, Hong Kong waters at the heart of world's fastest ... ...

Abstract	Inshore marine habitats experience considerable anthropogenic pressure, as this is where many adverse effects of human activities concentrate. In the rapidly-changing seascape of the Anthropocene, Hong Kong waters at the heart of world's fastest developing coastal region can serve as a preview-window into coastal seas of the future, with ever-growing anthropogenic footprint. Here, we quantify how large-scale coastal infrastructure projects can affect obligatory inshore cetaceans, bringing about population-level consequences that may compromise their long-term demographic viability. As a case in point, we look at the construction of world's longest sea crossing system and broad-scale demographic, social and spatial responses it has caused in a shallow-water delphinid, the Indo-Pacific humpback dolphin (Sousa chinensis). Soon after the infrastructure project began, dolphins markedly altered their home range near construction sites such that these waters no longer functioned as dolphin core areas despite the apparent presence of prey, indicating that anthropogenic impacts outweighed foraging benefits. The contraction of key habitats has in turn led individuals to interact over spatially more constricted area, reshaping their group dynamics and social network. Although there was no apparent decline in dolphin numbers that could be detected with mark-recapture estimates, adult survival rates decreased drastically from 0.960 to 0.904, the lowest estimate for these animals anywhere across the region to date, notably below the previously estimated demographic threshold of their long-term persistence (0.955). It is apparent that during an advanced stage of this coastal infrastructure project, dolphins were under a major anthropogenic pressure that, if sustained, could be detrimental to their long-term persistence as a viable demographic unit. As effective conservation of species and habitats depends on informed management decisions, this study offers a valuable lesson in environmental risk assessment, underscoring the implications of human-induced rapid environmental change on obligatory inshore delphinids-sentinels of coastal habitats that are increasingly degraded in fast-changing coastal seas.
MeSH term(s)	Animals ; Humans ; Hong Kong ; Dolphins ; Cetacea ; Population Dynamics ; Homing Behavior ; Ecosystem
Language	English
Publishing date	2024-01-03
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	121506-1
ISSN	1879-1026 ; 0048-9697
ISSN (online)	1879-1026
ISSN	0048-9697
DOI	10.1016/j.scitotenv.2023.169753
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Article ; Online: Innovations in RNA therapy for hemophilia.

Ragni, Margaret V / Chan, Stephen Y

Blood

2023 Volume 142, Issue 19, Page(s) 1613–1621

Abstract: Given the shortcomings of current factor-, nonfactor-, and adeno-associated virus gene-based therapies, the recent advent of RNA-based therapeutics for hemophilia is changing the fundamental approach to hemophilia management. From small interfering RNA ... ...

Abstract	Given the shortcomings of current factor-, nonfactor-, and adeno-associated virus gene-based therapies, the recent advent of RNA-based therapeutics for hemophilia is changing the fundamental approach to hemophilia management. From small interfering RNA therapeutics that knockdown clot regulators antithrombin, protein S, and heparin cofactor II, to CRISPR/Cas9 gene editing that may personalize treatment, improved technologies have the potential to reduce bleeds and factor use and avoid inhibitor formation. These novel agents, some in preclinical studies and others in early phase trials, have the potential to simplify treatment and improve hemostasis and quality of life. Furthermore, because these therapies arise from manipulation of the coagulation cascade and thrombin generation and its regulation, they will enhance our understanding of hemostasis and thrombosis and ultimately lead to better therapies for children and adults with inherited bleeding disorders. What does the future hold? With the development of novel preclinical technologies at the bench, there will be fewer joint bleeds, debilitating joint disease, orthopedic surgery, and improved physical and mental health, which were not previously possible. In this review, we identify current limitations of treatment and progress in the development of novel RNA therapeutics, including messenger RNA nanoparticle delivery and gene editing for the treatment of hemophilia.
MeSH term(s)	Child ; Humans ; Hemophilia A/therapy ; Hemophilia A/drug therapy ; Hemorrhage/drug therapy ; Hemostasis ; Quality of Life ; RNA, Small Interfering/therapeutic use ; Adult
Chemical Substances	RNA, Small Interfering
Language	English
Publishing date	2023-07-26
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2022018661
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Article ; Online: miR-roring Changes in Blood: miR-210 Reflects Hypoxic Disease Dynamics in Obstructive Sleep Apnea.

Kirillova, Anna / Chan, Stephen Y

American journal of respiratory and critical care medicine

2022 Volume 207, Issue 3, Page(s) 240–242

MeSH term(s)	Humans ; Sleep Apnea, Obstructive/genetics ; Sleep Apnea, Obstructive/physiopathology ; Hypoxia/genetics ; Hypoxia/physiopathology ; Vascular Diseases ; MicroRNAs/genetics
Chemical Substances	MicroRNAs ; MIRN210 microRNA, human
Language	English
Publishing date	2022-10-05
Publishing country	United States
Document type	Editorial ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202209-1709ED
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Article: Pulmonary Arterial Hypertension: Emerging Principles of Precision Medicine across Basic Science to Clinical Practice.

Kelly, Neil J / Chan, Stephen Y

Reviews in cardiovascular medicine

2022 Volume 23, Issue 11

Abstract: Pulmonary arterial hypertension (PAH) is an enigmatic and deadly vascular disease with no known cure. Recent years have seen rapid advances in our understanding of the molecular underpinnings of PAH, with an expanding knowledge of the molecular, cellular, ...

Abstract	Pulmonary arterial hypertension (PAH) is an enigmatic and deadly vascular disease with no known cure. Recent years have seen rapid advances in our understanding of the molecular underpinnings of PAH, with an expanding knowledge of the molecular, cellular, and systems-level drivers of disease that are being translated into novel therapeutic modalities. Simultaneous advances in clinical technology have led to a growing list of tools with potential application to diagnosis and phenotyping. Guided by fundamental biology, these developments hold the potential to usher in a new era of personalized medicine in PAH with broad implications for patient management and great promise for improved outcomes.
Language	English
Publishing date	2022-11-09
Publishing country	Singapore
Document type	Journal Article
ZDB-ID	2108910-3
ISSN	1530-6550
ISSN	1530-6550
DOI	10.31083/j.rcm2311378
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Article ; Online: Endothelial Senescence: A New Age in Pulmonary Hypertension.

Culley, Miranda K / Chan, Stephen Y

Circulation research

2022 Volume 130, Issue 6, Page(s) 928–941

Abstract: Pulmonary hypertension is an enigmatic, deleterious disease driven by multiple heterogeneous causes with a burgeoning proportion of older patients with complex, chronic comorbidities without adequate treatment options. The underlying endothelial ... ...

Abstract	Pulmonary hypertension is an enigmatic, deleterious disease driven by multiple heterogeneous causes with a burgeoning proportion of older patients with complex, chronic comorbidities without adequate treatment options. The underlying endothelial pathophenotypes that direct vasoconstriction and panvascular remodeling remain both controversial and incompletely defined. This review discusses emerging concepts centered on endothelial senescence in pulmonary vascular disease. This principle proposes a more heterogeneous, dynamic pulmonary endothelium in disease; it provides a potentially unifying feature of endothelial dysfunction in pulmonary hypertension irrespective of cause; and it supports a clinically relevant link between aging and pulmonary hypertension like other chronic illnesses. Thus, taking cues from studies on aging and age-related diseases, we present possible opportunities and barriers to diagnostic and therapeutic targeting of senescence in pulmonary hypertension.
MeSH term(s)	Cellular Senescence ; Endothelium, Vascular ; Humans ; Hypertension, Pulmonary/genetics ; Lung ; Vasoconstriction
Language	English
Publishing date	2022-03-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.121.319815
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Article ; Online: A dUTY to Protect: Addressing "Y" We See Sex Differences in Pulmonary Hypertension.

Rao, Rashmi / Chan, Stephen Y

American journal of respiratory and critical care medicine

2021 Volume 206, Issue 2, Page(s) 137–139

MeSH term(s)	Chemokines ; Female ; Genes, Y-Linked ; Humans ; Hypertension, Pulmonary/prevention & control ; Male ; Minor Histocompatibility Antigens ; Nuclear Proteins ; Sex Characteristics
Chemical Substances	Chemokines ; Minor Histocompatibility Antigens ; Nuclear Proteins ; UTY protein, human
Language	English
Publishing date	2021-12-02
Publishing country	United States
Document type	Editorial ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202204-0653ED
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Article ; Online: Prediction of Incident Depression in Middle-Aged and Older Adults using Digital Gait Biomarkers Extracted from Large-Scale Wrist Sensor Data.

Chan, Lloyd L Y / Brodie, Matthew A / Lord, Stephen R

Journal of the American Medical Directors Association

2023 Volume 24, Issue 8, Page(s) 1106–1113.e11

Abstract: Objectives: To determine if digital gait biomarkers captured by a wrist-worn device can predict the incidence of depressive episodes in middle-age and older people.: Design: Longitudinal cohort study.: Setting and participants: A total of 72,359 ... ...

Abstract	Objectives: To determine if digital gait biomarkers captured by a wrist-worn device can predict the incidence of depressive episodes in middle-age and older people. Design: Longitudinal cohort study. Setting and participants: A total of 72,359 participants recruited in the United Kingdom. Methods: Participants were assessed at baseline on gait quantity, speed, intensity, quality, walk length distribution, and walk-related arm movement proportions using wrist-worn accelerometers for up to 7 days. Univariable and multivariable Cox proportional-hazard regression models were used to analyze the associations between these parameters and diagnosed incident depressive episodes for up to 9 years. Results: A total of 1332 participants (1.8%) had incident depressive episodes over a mean of 7.4 ± 1.1 years. All gait variables, except some walk-related arm movement proportions, were significantly associated with the incidence of depressive episodes (P < .05). After adjusting for sociodemographic, lifestyle, and comorbidity covariates; daily running duration, steps per day, and step regularity were identified as independent and significant predictors (P < .001). These associations held consistent in subgroup analysis of older people and individuals with serious medical conditions. Conclusions and implications: The study findings indicate digital gait quality and quantity biomarkers derived from wrist-worn sensors are important predictors of incident depression in middle-aged and older people. These gait biomarkers may facilitate screening programs for at-risk individuals and the early implementation of preventive measures.
MeSH term(s)	Middle Aged ; Humans ; Aged ; Longitudinal Studies ; Depression/diagnosis ; Depression/epidemiology ; Wrist ; Gait ; Walking ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-05-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2171030-2
ISSN	1538-9375 ; 1525-8610
ISSN (online)	1538-9375
ISSN	1525-8610
DOI	10.1016/j.jamda.2023.04.008
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Article ; Online: Author Correction: Development and large-scale validation of the Watch Walk wrist-worn digital gait biomarkers.

Chan, Lloyd L Y / Choi, Tiffany C M / Lord, Stephen R / Brodie, Matthew A

Scientific reports

2023 Volume 13, Issue 1, Page(s) 1155

Language	English
Publishing date	2023-01-20
Publishing country	England
Document type	Published Erratum
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-28191-1
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Article ; Online: Is Maximal or Usual Walking Speed from Large Scale Wrist Sensor Data Better at Predicting Dementia, Depression and Death?

Chan, Lloyd L Y / Lord, Stephen R / Brodie, Matthew A

Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference

2023 Volume 2023, Page(s) 1–4

Abstract: Older people are at increased risk of many adverse health outcomes, including dementia and depression, that burden the global health system. This paper presents algorithms for the large-scale assessment of daily walking speeds. We hypothesize that (i) ... ...

Abstract	Older people are at increased risk of many adverse health outcomes, including dementia and depression, that burden the global health system. This paper presents algorithms for the large-scale assessment of daily walking speeds. We hypothesize that (i) data from wrist-worn sensors can be used to assess walking speed accurately; and that (ii) maximal daily walking speed is a better predictor of health outcomes than usual daily walking speed. First, algorithms were developed and tested using data from 101 participants aged 19 to 91 (47 ± 18) years. Participants wore an AX3 accelerometer (Axivity, UK) on their dominant wrist while undertaking daily life activities with electronic walkway data used for ground truth. Subsequently, prediction models for dementia, depression and death were developed using the data of 47,406 participants (≥ 60 years) from the UK Biobank study. Daily walking speeds were derived from 7-day AX3 data with time-to-events using electronic health records. The accuracy of derived walking speeds was assessed using root mean square error (RMSE). Time-to-events were modelled using Cox regression with inverse hazard ratios reported for univariable models and Harrell's concordance for multivariable models. Derived walking speeds had an RMSE of between 3% and 4% depending on arm position. We found that for simple models, maximal walking speed was significantly better than usual walking speed at predicting time to dementia (1.62 vs 1.34), depression (1.29 vs 1.17) and death (1.56 vs 1.27). However, the addition of known risk factors in subsequent multivariable models reduced the apparent benefit of using maximal as opposed to usual daily walking speed as the gait parameter. In summary, walking speed was accurately measured with a wrist-worn device, and maximal daily waking speed may be better than usual daily walking speed at predicting some adverse health outcomes.Clinical Relevance- This study demonstrated the validity of using a simple and unobtrusive wrist-worn sensor to remotely assess daily walking speed. As a single, modifiable and easily understood measure, maximal walking speed was shown to be better than usual walking speed at predicting time-to-dementia, depression and death. Therefore, the inclusion of maximal daily walking speed into screening programs and clinical interventions presents a promising area for further research.
MeSH term(s)	Humans ; Aged ; Walking Speed ; Walking ; Wrist ; Depression/diagnosis ; Dementia/diagnosis
Language	English
Publishing date	2023-12-11
Publishing country	United States
Document type	Journal Article
ISSN	2694-0604
ISSN (online)	2694-0604
DOI	10.1109/EMBC40787.2023.10340255
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