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Article ; Online: A Dual-Enzyme Amplification Loop for the Sensitive Biosensing of Endopeptidases.

Zhou, Chuanwen / Li, Xiaomin / Tang, Sze Wing / Liu, Chunxi / Lam, Michael H W / Lam, Yun Wah

ACS omega

2023 Volume 8, Issue 28, Page(s) 25592–25600

Abstract: ... by a colorimetric horseradish peroxidase-tetramethylbenzidine (HRP-TMB-H ...

Abstract	A rapid and sensitive approach for the detection of endopeptidases via a new analyte-triggered mutual emancipation of linker-immobilized enzymes (AMELIE) mechanism has been developed and demonstrated using a matrix metallopeptidase, a collagenase, as the model endopeptidase analyte. AMELIE involves an autocatalytic loop created by a pair of selected enzymes immobilized on solid substrates via linkers with specific sites that can be proteolyzed by one another. These bound enzymes are spatially separated so that they cannot act upon their corresponding substrates until the introduction of the target endopeptidase analyte that can also cleave one of the linkers. This triggers the self-sustained loop of enzymatic activities to emancipate all the immobilized enzymes. In this proof of concept, signal transduction was achieved by a colorimetric horseradish peroxidase-tetramethylbenzidine (HRP-TMB-H
Language	English
Publishing date	2023-07-07
Publishing country	United States
Document type	Journal Article
ISSN	2470-1343
ISSN (online)	2470-1343
DOI	10.1021/acsomega.3c03533
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Article: Potential Effects of an Exoskeleton-Assisted Overground Walking Program for Individuals With Spinal Cord Injury Who Uses a Wheelchair on Imaging and Serum Markers of Bone Strength: Pre-Post Study.

Bass, Alec / Morin, Suzanne N / Guidea, Michael / Lam, Jacqueline T A T / Karelis, Antony D / Aubertin-Leheudre, Mylène / Gagnon, Dany H

JMIR rehabilitation and assistive technologies

2024 Volume 11, Page(s) e53084

Abstract: Background: As many as 60% of individuals use a wheelchair long term after a spinal cord injury (SCI). This mode of locomotion leads to chronic decline in lower-extremity weight-bearing activities and contributes to the development of severe sublesional ...

Abstract	Background: As many as 60% of individuals use a wheelchair long term after a spinal cord injury (SCI). This mode of locomotion leads to chronic decline in lower-extremity weight-bearing activities and contributes to the development of severe sublesional osteoporosis and high rates of fragility fracture. Overground exoskeleton-assisted walking programs provide a novel opportunity to increase lower-extremity weight bearing, with the potential to improve bone health. Objective: The aim of the study is to measure the potential effects of an exoskeleton-assisted walking program on lower-extremity bone strength and bone remodeling biomarkers in individuals with chronic (≥18 months) SCI who use a wheelchair. Methods: In total, 10 participants completed a 16-week exoskeleton-assisted walking program (34 individualized 1-hour sessions, progressing from 1 to 3 per week). Bone mineral density and bone strength markers (dual-energy x-ray absorptiometry: total body, left arm, leg, total hip, and femoral neck and peripheral quantitative computed tomography: 25% of left femur and 66% of left tibia) as well as bone remodeling biomarkers (formation=osteocalcin and resorption=C-telopeptide) were measured before and after intervention and compared using nonparametric tests. Changes were considered significant and meaningful if the following criteria were met: P<0.1, effect size ≥0.5, and relative variation >5%. Results: Significant and meaningful increases were observed at the femur (femoral neck bone mineral content, bone strength index, and stress-strain index) and tibia (cortical cross-sectional area and polar moment of inertia) after the intervention (all P<.10). We also noted a decrease in estimated femoral cortical thickness. However, no changes in bone remodeling biomarkers were found. Conclusions: These initial results suggest promising improvements in bone strength markers after a 16-week exoskeleton-assisted walking program in individuals with chronic SCI. Additional research with larger sample sizes, longer interventions (possibly of greater loading intensity), and combined modalities (eg, pharmacotherapy or functional electrical stimulation) are warranted to strengthen current evidence. Trial registration: ClinicalTrials.gov NCT03989752; https://clinicaltrials.gov/ct2/show/NCT03989752. International registered report identifier (irrid): RR2-10.2196/19251.
Language	English
Publishing date	2024-01-01
Publishing country	Canada
Document type	Journal Article
ZDB-ID	2798120-4
ISSN	2369-2529
ISSN	2369-2529
DOI	10.2196/53084
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Article ; Online: Highly reproducible rat arterial injury model of neointimal hyperplasia.

Tan, Richard P / Hung, Jui Chien / Chan, Alex H P / Grant, Angus J / Moore, Matthew J / Lam, Yuen Ting / Michael, Praveesuda / Wise, Steven G

PloS one

2023 Volume 18, Issue 8, Page(s) e0290342

Abstract: Models of arterial injury in rodents have been invaluable to our current understanding of vessel restenosis and play a continuing role in the development of endovascular interventions for cardiovascular disease. Mechanical distention of the vessel wall ... ...

Abstract	Models of arterial injury in rodents have been invaluable to our current understanding of vessel restenosis and play a continuing role in the development of endovascular interventions for cardiovascular disease. Mechanical distention of the vessel wall and denudation of the vessel endothelium are the two major modes of vessel injury observed in most clinical pathologies and are critical to the reproducible modelling of progressive neointimal hyperplasia. The current models which have dominated this research area are the mouse wire carotid or femoral injury and the rat carotid balloon injury. While these elicit simultaneous distension of the vessel wall and denudation of the luminal endothelium, each model carries limitations that need to be addressed using a complementary injury model. Wire injuries in mice are highly technical and procedurally challenging due to small vessel diameters, while rat balloon injuries require permanent blood vessel ligation and disruption of native blood flow. Complementary models of vascular injury with reproducibility, convenience, and increased physiological relevance to the pathophysiology of endovascular injury would allow for improved studies of neointimal hyperplasia in both basic and translational research. In this study, we developed a new surgical model that elicits vessel distention and endothelial denudation injury using sequential steps using microforceps and a standard needle catheter inserted via arteriotomy into a rat common carotid artery, without requiring permanent ligation of branching arteries. After 2 weeks post-injury this model elicits highly reproducible neointimal hyperplasia and rates of re-endothelialisation similar to current wire and balloon injury models. Furthermore, evaluation of the smooth muscle cell phenotype profile, inflammatory response and extracellular matrix within the developing neointima, showed that our model replicated the vessel remodelling outcomes critical to restenosis and those becoming increasingly focused upon in the development of new anti-restenosis therapies.
MeSH term(s)	Rats ; Mice ; Animals ; Vascular System Injuries/etiology ; Hyperplasia ; Neointima ; Reproducibility of Results ; Carotid Artery, Common ; Constriction, Pathologic
Language	English
Publishing date	2023-08-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0290342
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Article ; Online: Thalamic circuits for independent control of prefrontal signal and noise.

Mukherjee, Arghya / Lam, Norman H / Wimmer, Ralf D / Halassa, Michael M

Nature

2021 Volume 600, Issue 7887, Page(s) 100–104

Abstract: Interactions between the mediodorsal thalamus and the prefrontal cortex are critical for cognition. Studies in humans indicate that these interactions may resolve uncertainty in decision- ... ...

Abstract	Interactions between the mediodorsal thalamus and the prefrontal cortex are critical for cognition. Studies in humans indicate that these interactions may resolve uncertainty in decision-making
MeSH term(s)	Animals ; Decision Making ; Female ; Humans ; Interneurons/physiology ; Male ; Mediodorsal Thalamic Nucleus/cytology ; Mediodorsal Thalamic Nucleus/physiology ; Mice ; Neural Pathways ; Prefrontal Cortex/cytology ; Prefrontal Cortex/physiology ; Receptors, Dopamine/metabolism ; Receptors, Kainic Acid/metabolism ; Thalamus/cytology ; Thalamus/physiology ; Uncertainty
Chemical Substances	Receptors, Dopamine ; Receptors, Kainic Acid
Language	English
Publishing date	2021-10-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-021-04056-3
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Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Zs.MO 244: Show issues

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Article ; Online: Stable Ventricular Fibrillation: A Paradigm Rather Than Septal Shift?

Bracy, Connor L / Kobres, Pei-Ying / Hockstein, Michael J / Rao, Sriram D / Gupta, Richa / Lam, Phillip H / Sheikh, Farooq H / Hockstein, Maxwell A

ASAIO journal (American Society for Artificial Internal Organs : 1992)

2023 Volume 69, Issue 9, Page(s) 835–840

Abstract: Awake patients in ventricular fibrillation is a phenomenon limited to patients who are mechanically supported. We describe a cohort of patients supported by left ventricular assist devices (LVADs) presenting to the emergency department (ED) at a high- ... ...

Abstract	Awake patients in ventricular fibrillation is a phenomenon limited to patients who are mechanically supported. We describe a cohort of patients supported by left ventricular assist devices (LVADs) presenting to the emergency department (ED) at a high-volume LVAD center while in awake ventricular fibrillation (VF)/ventricular tachycardia (VT). Among 175 patients reviewed, a total of 19 LVAD patients presented to the ED in awake VF/VT between December 2015 and July 2021. On ED presentation, patients maintained a median mean arterial blood pressure (MAP) of 70 mm Hg with a mean LVAD flow of 3.77 L/minute. ED management included cardioversion in the majority of cases: 58% were defibrillated once, 21% were defibrillated multiple times, 68% received amiodarone, and 21% received lidocaine. Inpatient management included defibrillation, ablation, and antiarrhythmic initiation in 37%, 11%, and 84% of cases, respectively. In total, five patients (26%) died with one death attributed to recurrent VT. Our findings support the short-term tolerability of sustained ventricular arrhythmias in LVAD patients, as evidenced by the maintained MAPs and mental status. Clinical teams, however, should be aware of the potential harbinger for in-hospital mortality heralded by an awake VF/VT presentation.
MeSH term(s)	Humans ; Ventricular Fibrillation/etiology ; Ventricular Fibrillation/therapy ; Arrhythmias, Cardiac ; Tachycardia, Ventricular ; Amiodarone ; Lidocaine
Chemical Substances	Amiodarone (N3RQ532IUT) ; Lidocaine (98PI200987)
Language	English
Publishing date	2023-08-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	759982-1
ISSN	1538-943X ; 0162-1432 ; 1058-2916
ISSN (online)	1538-943X
ISSN	0162-1432 ; 1058-2916
DOI	10.1097/MAT.0000000000001984
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Uk I Zs.199: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.B 2435: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Effects of spatially-varying substrate anchoring on instabilities and dewetting of thin nematic liquid crystal films.

Lam, Michael-Angelo Y-H / Kondic, Lou / Cummings, Linda J

Soft matter

2020 Volume 16, Issue 44, Page(s) 10187–10197

Abstract: Partially wetting nematic liquid crystal (NLC) films on substrates are unstable to dewetting-type instabilities due to destabilizing solid/NLC interaction forces. These instabilities are modified by the nematic nature of the films, which influences the ... ...

Abstract	Partially wetting nematic liquid crystal (NLC) films on substrates are unstable to dewetting-type instabilities due to destabilizing solid/NLC interaction forces. These instabilities are modified by the nematic nature of the films, which influences the effective solid/NLC interaction. In this work, we focus on the influence of imposed substrate anchoring on the instability development. The analysis is carried out within a long-wave formulation based on the Leslie-Ericksen description of NLC films. Linear stability analysis of the resulting equations shows that some features of the instability, such as emerging wavelengths, may not be influenced by the imposed substrate anchoring. Going further into the nonlinear regime, considered via large-scale GPU-based simulations, shows however that nonlinear effects may play an important role, in particular in the case of strong substrate anchoring anisotropy. Our simulations show that instability of the film develops in two stages: the first stage involves formation of ridges that are perpendicular to the local anchoring direction; and the second involves breakup of these ridges and formation of drops, whose final distribution is influenced by the anisotropy imposed by the substrate. Finally, we show that imposing more complex substrate anisotropy patterns allows us to reach basic understanding of the influence of substrate-imposed defects in director orientation on the instability evolution.
Language	English
Publishing date	2020-10-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2191476-X
ISSN	1744-6848 ; 1744-683X
ISSN (online)	1744-6848
ISSN	1744-683X
DOI	10.1039/d0sm01416h
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Structural basis for ATG9A recruitment to the ULK1 complex in mitophagy initiation.

Ren, Xuefeng / Nguyen, Thanh N / Lam, Wai Kit / Buffalo, Cosmo Z / Lazarou, Michael / Yokom, Adam L / Hurley, James H

Science advances

2023 Volume 9, Issue 7, Page(s) eadg2997

Abstract: The assembly of the autophagy initiation machinery nucleates autophagosome biogenesis, including in the PINK1- and Parkin-dependent mitophagy pathway implicated in Parkinson's disease. The structural interaction between the sole transmembrane autophagy ... ...

Abstract	The assembly of the autophagy initiation machinery nucleates autophagosome biogenesis, including in the PINK1- and Parkin-dependent mitophagy pathway implicated in Parkinson's disease. The structural interaction between the sole transmembrane autophagy protein, autophagy-related protein 9A (ATG9A), and components of the Unc-51-like autophagy activating kinase (ULK1) complex is one of the major missing links needed to complete a structural map of autophagy initiation. We determined the 2.4-Å x-ray crystallographic structure of the ternary structure of ATG9A carboxyl-terminal tail bound to the ATG13:ATG101 Hop1/Rev7/Mad2 (HORMA) dimer, which is part of the ULK1 complex. We term the interacting portion of the extreme carboxyl-terminal part of the ATG9A tail the "HORMA dimer-interacting region" (HDIR). This structure shows that the HDIR binds to the HORMA domain of ATG101 by β sheet complementation such that the ATG9A tail resides in a deep cleft at the ATG13:ATG101 interface. Disruption of this complex in cells impairs damage-induced PINK1/Parkin mitophagy mediated by the cargo receptor NDP52.
MeSH term(s)	Mitophagy ; Autophagy-Related Proteins/genetics ; Membrane Proteins ; Ubiquitin-Protein Ligases/genetics ; Protein Kinases/genetics
Chemical Substances	Autophagy-Related Proteins ; Membrane Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Protein Kinases (EC 2.7.-)
Language	English
Publishing date	2023-02-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adg2997
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Article ; Online: A Deep Learning Framework for Image-Based Screening of Kawasaki Disease.

Lam, Jonathan Y / Kanegaye, John T / Xu, Ellen / Gardiner, Michael A / Burns, Jane C / Nemati, Shamim / Tremoulet, Adriana H

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: Kawasaki disease (KD) is a leading cause of acquired heart disease in children and is characterized by the presence of a combination of five clinical signs assessed during the physical examination. Timely treatment of intravenous immunoglobin is needed ... ...

Abstract	Kawasaki disease (KD) is a leading cause of acquired heart disease in children and is characterized by the presence of a combination of five clinical signs assessed during the physical examination. Timely treatment of intravenous immunoglobin is needed to prevent coronary artery aneurysm formation, but KD is usually diagnosed when pediatric patients are evaluated by a clinician in the emergency department days after onset. One or more of the five clinical signs usually manifests in pediatric patients prior to ED admission, presenting an opportunity for earlier intervention if families receive guidance to seek medical care as soon as clinical signs are observed along with a fever for at least five days. We present a deep learning framework for a novel screening tool to calculate the relative risk of KD by analyzing images of the five clinical signs. The framework consists of convolutional neural networks to separately calculate the risk for each clinical sign, and a new algorithm to determine what clinical sign is in an image. We achieved a mean accuracy of 90% during 10-fold cross-validation and 88% during external validation for the new algorithm. These results demonstrate the algorithms in the proposed screening tool can be utilized by families to determine if their child should be evaluated by a clinician based on the number of clinical signs consistent with KD.Clinical Relevance- This screening framework has the potential for earlier clinical evaluation and detection of KD to reduce the risk of coronary artery complications.
MeSH term(s)	Child ; Humans ; Mucocutaneous Lymph Node Syndrome/diagnosis ; Mucocutaneous Lymph Node Syndrome/diagnostic imaging ; Deep Learning ; Fever ; Coronary Vessels
Language	English
Publishing date	2023-12-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2694-0604
ISSN (online)	2694-0604
DOI	10.1109/EMBC40787.2023.10340801
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Article ; Online: Correction: An overview of internal medicine point-of-care ultrasound rotations in Canada.

Gaudreau-Simard, Mathilde / Wiskar, Katie / Kilabuk, Elaine / Walsh, Michael H / Sattin, Michael / Wong, Jonathan / Burhani, Zain / Arishenkof, Shane / Yu, Jefrey / Lam, Ada W / Ma, Irene W Y

The ultrasound journal

2022 Volume 14, Issue 1, Page(s) 38

Language	English
Publishing date	2022-09-14
Publishing country	Italy
Document type	Published Erratum
ZDB-ID	2965029-X
ISSN	2524-8987 ; 2036-3176
ISSN (online)	2524-8987
ISSN	2036-3176
DOI	10.1186/s13089-022-00288-0
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Book ; Online: LSTM-based Deep Neural Network With A Focus on Sentence Representation for Sequential Sentence Classification in Medical Scientific Abstracts

Lam, Phat / Pham, Lam / Nguyen, Tin / Tang, Hieu / Michael, Seidl / Schindler, Alexander

2024

Abstract: The Sequential Sentence Classification task within the domain of medical abstracts, termed as SSC, involves the categorization of sentences into pre-defined headings based on their roles in conveying critical information in the abstract. In the SSC task, ...

Abstract	The Sequential Sentence Classification task within the domain of medical abstracts, termed as SSC, involves the categorization of sentences into pre-defined headings based on their roles in conveying critical information in the abstract. In the SSC task, sentences are often sequentially related to each other. For this reason, the role of sentence embedding is crucial for capturing both the semantic information between words in the sentence and the contextual relationship of sentences within the abstract to provide a comprehensive representation for better classification. In this paper, we present a hierarchical deep learning model for the SSC task. First, we propose a LSTM-based network with multiple feature branches to create well-presented sentence embeddings at the sentence level. To perform the sequence of sentences, a convolutional-recurrent neural network (C-RNN) at the abstract level and a multi-layer perception network (MLP) at the segment level are developed that further enhance the model performance. Additionally, an ablation study is also conducted to evaluate the contribution of individual component in the entire network to the model performance at different levels. Our proposed system is very competitive to the state-of-the-art systems and further improve F1 scores of the baseline by 1.0%, 2.8%, and 2.6% on the benchmark datasets PudMed 200K RCT, PudMed 20K RCT and NICTA-PIBOSO, respectively. Comment: 5 pages, 2 figures
Keywords	Computer Science - Computation and Language
Subject code	006
Publishing date	2024-01-28
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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