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Article ; Online: Discovery of a Potent and Specific M. tuberculosis Leucyl-tRNA Synthetase Inhibitor: (S)-3-(Aminomethyl)-4-chloro-7-(2-hydroxyethoxy)benzo[c][1,2]oxaborol-1(3H)-ol (GSK656).

2017 Volume 60, Issue 19, Page(s) 8011–8026

Abstract: There is an urgent need to develop new and safer antitubercular agents that possess a novel mode of action. We synthesized and evaluated a novel series of 3-aminomethyl 4-halogen benzoxaboroles as Mycobacterium tuberculosis (Mtb) leucyl-tRNA synthetase ( ... ...

Abstract	There is an urgent need to develop new and safer antitubercular agents that possess a novel mode of action. We synthesized and evaluated a novel series of 3-aminomethyl 4-halogen benzoxaboroles as Mycobacterium tuberculosis (Mtb) leucyl-tRNA synthetase (LeuRS) inhibitors. A number of Mtb LeuRS inhibitors were identified that demonstrated good antitubercular activity with high selectivity over human mitochondrial and cytoplasmic LeuRS. Further evaluation of these Mtb LeuRS inhibitors by in vivo pharmacokinetics (PK) and murine tuberculosis (TB) efficacy models led to the discovery of GSK3036656 (abbreviated as GSK656). This molecule shows potent inhibition of Mtb LeuRS (IC
MeSH term(s)	Animals ; Antitubercular Agents/chemical synthesis ; Antitubercular Agents/pharmacokinetics ; Antitubercular Agents/pharmacology ; Boron Compounds/chemical synthesis ; Boron Compounds/pharmacokinetics ; Boron Compounds/pharmacology ; Drug Discovery ; Enzyme Inhibitors/chemical synthesis ; Enzyme Inhibitors/pharmacokinetics ; Enzyme Inhibitors/pharmacology ; Female ; Heterocyclic Compounds, 2-Ring/chemical synthesis ; Heterocyclic Compounds, 2-Ring/pharmacology ; Humans ; Leucine-tRNA Ligase/antagonists & inhibitors ; Mice ; Mice, Inbred C57BL ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/enzymology ; Structure-Activity Relationship ; Substrate Specificity
Chemical Substances	Antitubercular Agents ; Boron Compounds ; Enzyme Inhibitors ; GSK656 ; Heterocyclic Compounds, 2-Ring ; Leucine-tRNA Ligase (EC 6.1.1.4)
Language	English
Publishing date	2017-09-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.7b00631
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Zs.B 151: 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: Combined balance and brisk walking training to improve motor and non-motor symptoms in people with Parkinson disease: abridged secondary publication.

Mak, K Y M / Cheung, T H R / Ho, S L

Hong Kong medical journal = Xianggang yi xue za zhi

2024 Volume 30 Suppl 1, Issue 1, Page(s) 16–17

MeSH term(s)	Humans ; Parkinson Disease/complications ; Walking ; Exercise Therapy ; Postural Balance
Language	English
Publishing date	2024-02-28
Publishing country	China
Document type	Journal Article
ZDB-ID	1239255-8
ISSN	1024-2708
ISSN	1024-2708
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Zs.A 4347: Show issues

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Article ; Online: The role of visual imagery in story reading: Evidence from aphantasia.

Speed, Laura J / Eekhof, Lynn S / Mak, Marloes

Consciousness and cognition

2024 Volume 118, Page(s) 103645

Abstract: Aphantasia is a condition in which people are unable to experience visual imagery. Since visual imagery is thought to be key to language processing, we hypothesized the experience of a story would differ between individuals with aphantasia and controls. ... ...

Abstract	Aphantasia is a condition in which people are unable to experience visual imagery. Since visual imagery is thought to be key to language processing, we hypothesized the experience of a story would differ between individuals with aphantasia and controls. Forty-seven individuals with aphantasia were compared to fifty-one matched controls on their experience of reading a short story and their general reading habits. Aphantasics were less likely to be engaged with, interested in, and absorbed in the story, and experienced reduced emotional engagement with and sympathy for the story characters, compared to controls. Yet, aphantasics and controls did not differ in how much they liked or appreciated the story, and in general, the reading habits of the two groups also did not differ. Results have implications for embodied theories of language, suggesting visual imagery may influence how a story is experienced, but it is not the only route to story enjoyment.
MeSH term(s)	Humans ; Imagination ; Imagery, Psychotherapy/methods ; Language ; Pleasure ; Happiness
Language	English
Publishing date	2024-01-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	1106647-7
ISSN	1090-2376 ; 1053-8100
ISSN (online)	1090-2376
ISSN	1053-8100
DOI	10.1016/j.concog.2024.103645
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Zs.A 3692: Show issues

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Article ; Online: Associations between interconnectedness, compassion, and participation in collective action for people with mental illness: A random-intercept cross-lagged panel modeling approach.

Yu, Ben C L / Mak, Winnie W S / Fu, Amanda C M

The American journal of orthopsychiatry

2024

Abstract: The present study aims to prospectively investigate the relationships between interconnectedness, compassion, and participation in private and public forms of collective action for people with mental illness. Public form refers to collective action at ... ...

Abstract	The present study aims to prospectively investigate the relationships between interconnectedness, compassion, and participation in private and public forms of collective action for people with mental illness. Public form refers to collective action at the macrolevel such as large-scale protests and demonstrations going on in the communities. Private form refers to collective action happening at the microlevel that targets promoting awareness of social inequalities and positive changes among personal social circles, such as calling out microaggressions or correcting others' stigmatizing language. Eligible responses from 501 participants were collected at baseline, with 345 and 318 participants retained at 6-month and 12-month follow-up assessments, respectively. Random-intercept cross-lagged panel models were conducted to investigate the mediating role of compassion in the relationships between interconnectedness and participation in private and public forms of collective action. Interconnectedness was consistently associated with a higher frequency of participation in private form, but not public form, of collective action at subsequent time points. Contrary to the hypothesis, results showed the nonsignificant mediating effect of compassion between interconnectedness and participation in both forms of collective action. The present study highlights the potential of interconnectedness in promoting a private form of collective action for the rights of people with mental illness. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Language	English
Publishing date	2024-04-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	280031-7
ISSN	1939-0025 ; 0002-9432
ISSN (online)	1939-0025
ISSN	0002-9432
DOI	10.1037/ort0000744
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Ui I Zs.228: Show issues

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Article ; Online: Unraveling attrition and retention: A qualitative study with rehabilitation professionals.

Mak, Susanne / Thomas, Aliki / Razack, Saleem / Root, Kelly / Hunt, Matthew

Work (Reading, Mass.)

2024

Abstract: ... physical therapy (PT), and speech-language pathology (S-LP), attrition and retention issues amplify this situation ... of attrition and retention with OTs, PTs and S-LPs who stayed in, or left their profession.: Methods ... study. We used purposeful sampling (maximum variation approach) to recruit OTs, PTs, and S-LPs ...

Abstract	Background: Health human resources are scarce worldwide. In occupational therapy (OT), physical therapy (PT), and speech-language pathology (S-LP), attrition and retention issues amplify this situation and contribute to the precarity of health systems. Objective: To investigate the phenomena of attrition and retention with OTs, PTs and S-LPs who stayed in, or left their profession. Methods: Cultural-historical activity theory provided the theoretical scaffolding for this interpretive description study. We used purposeful sampling (maximum variation approach) to recruit OTs, PTs, and S-LPs from Quebec, Canada. Individual interviews were conducted with 51 OTs, PTs, and S-LPs from Quebec, Canada, in English or French (2019-2020). Inductive and deductive approaches, and constant comparative techniques were used for data analysis. Results: Six themes were developed: 1) characteristics of work that made it meaningful; 2) aspects of work that practitioners appreciate; 3) factors of daily work that weigh on a practitioner; 4) factors that contribute to managing work; 5) relationships with different stakeholders that shape daily work; and 6) perceptions of the profession. Meaningfulness was tied to participants' sense that their values were reflected in their work. Factors outside work shaped participants' work experiences. Recurrent negative experiences led some to leave their profession. Conclusion: Findings underscore a critical need to address contributing factors to attrition and retention which are essential to ensuring the availability of OTs, PTs and SLPs for present and future rehabilitation needs.
Language	English
Publishing date	2024-04-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1394194-x
ISSN	1875-9270 ; 1051-9815
ISSN (online)	1875-9270
ISSN	1051-9815
DOI	10.3233/WOR-230531
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Zs.A 4810: Show issues

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Article ; Online: Dynamic characteristics of parent-adolescent closeness: Predicting adolescent emotion dysregulation.

Chiang, Shou-Chun / Bai, Sunhye / Mak, Hio Wa / Fosco, Gregory M

Family process

2024

Abstract: ... 12 months later. The sample included 144 adolescents (M = 14.62, SD = 0.83) who participated ...

Abstract	Emotion dysregulation is linked to adolescent psychological problems. However, little is known about how lability in daily closeness of parent-adolescent dyads affects the development of emotion dysregulation. This study examined how closeness lability with parents was associated with emotion dysregulation 12 months later. The sample included 144 adolescents (M = 14.62, SD = 0.83) who participated in a baseline assessment, 21-day daily diaries, and a 12-month follow-up assessment. Parents and adolescents both reported adolescent emotion dysregulation at baseline and follow-up assessments, while adolescents reported daily parent-adolescent closeness. Results indicate that lability in father-adolescent closeness was associated with increased emotion dysregulation at 12 months reported by adolescents. However, lability in mother-adolescent closeness was not associated with adolescent emotion dysregulation. Moreover, when baseline father-adolescent closeness was high, greater lability in father-adolescent closeness was associated with decreased emotion dysregulation. Findings indicate that daily fluctuations in father-adolescent closeness are a key family characteristic that links to long-term adolescent emotion dysregulation.
Language	English
Publishing date	2024-02-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	212740-4
ISSN	1545-5300 ; 0014-7370
ISSN (online)	1545-5300
ISSN	0014-7370
DOI	10.1111/famp.12978
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Zs.A 560: Show issues

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Article ; Online: Examining the role of attention focus walking training on conscious motor processing during rehabilitation by older adults at risk of falling: A randomized controlled trial.

Mak, Toby C T / Ng, Shamay S M / Leung, Melody C Y / Wong, Thomson W L

Archives of gerontology and geriatrics

2024 Volume 121, Page(s) 105352

Abstract: This study examined the impact of walking training with different attention focus instructions on real-time conscious motor processing and fall-related rehabilitation outcomes in older adults at risk of falling. A total of 102 community-dwelling older ... ...

Abstract	This study examined the impact of walking training with different attention focus instructions on real-time conscious motor processing and fall-related rehabilitation outcomes in older adults at risk of falling. A total of 102 community-dwelling older adults (mean age = 75.2 years, SD = 6.8 years) were randomly assigned to three groups: no attention focus walking group (NAFWG), external attention focus walking group (EAFWG), or internal attention focus walking group (IAFWG). All groups underwent 12 training sessions. Assessments were conducted at baseline, post-training, and six months later, measuring real-time conscious motor processing, functional balance and gait, balance ability, functional mobility, walking ability, trait conscious motor processing propensity, fear of falling, and recurrent falls. The EAFWG showed significant reduction on real-time conscious motor processing immediately after training (p = 0.015). No changes were observed for the IAFWG and NAFWG. All groups showed significant improvements in functional balance and gait (p < 0.001) and balance ability (p < 0.001) post-training. Implementing external focus instructions during walking training could be a feasible and beneficial strategy for reducing real-time conscious motor processing, which may improve walking performance and prevent falls in older adults. Further research is needed to examine the sustained benefits of these interventions and determine optimal training dosage for older adults with different risks of falling in fall prevention.
MeSH term(s)	Aged ; Humans ; Attention ; Fear ; Gait ; Postural Balance ; Walking ; Aged, 80 and over
Language	English
Publishing date	2024-01-28
Publishing country	Netherlands
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	603162-6
ISSN	1872-6976 ; 0167-4943
ISSN (online)	1872-6976
ISSN	0167-4943
DOI	10.1016/j.archger.2024.105352
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Zs.A 1729: Show issues

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Article: Integrating Demographics and Imaging Features for Various Stages of Dementia Classification: Feed Forward Neural Network Multi-Class Approach.

Cheung, Eva Y W / Wu, Ricky W K / Chu, Ellie S M / Mak, Henry K F

Biomedicines

2024 Volume 12, Issue 4

Abstract: Background: MRI magnetization-prepared rapid acquisition (MPRAGE) is an easily available imaging modality for dementia diagnosis. Previous studies suggested that volumetric analysis plays a crucial role in various stages of dementia classification. In ... ...

Abstract	Background: MRI magnetization-prepared rapid acquisition (MPRAGE) is an easily available imaging modality for dementia diagnosis. Previous studies suggested that volumetric analysis plays a crucial role in various stages of dementia classification. In this study, volumetry, radiomics and demographics were integrated as inputs to develop an artificial intelligence model for various stages, including Alzheimer's disease (AD), mild cognitive decline (MCI) and cognitive normal (CN) dementia classifications. Method: The Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset was separated into training and testing groups, and the Open Access Series of Imaging Studies (OASIS) dataset was used as the second testing group. The MRI MPRAGE image was reoriented via statistical parametric mapping (SPM12). Freesurfer was employed for brain segmentation, and 45 regional brain volumes were retrieved. The 3D Slicer software was employed for 107 radiomics feature extractions from within the whole brain. Data on patient demographics were collected from the datasets. The feed-forward neural network (FFNN) and the other most common artificial intelligence algorithms, including support vector machine (SVM), ensemble classifier (EC) and decision tree (DT), were used to build the models using various features. Results: The integration of brain regional volumes, radiomics and patient demographics attained the highest overall accuracy at 76.57% and 73.14% in ADNI and OASIS testing, respectively. The subclass accuracies in MCI, AD and CN were 78.29%, 89.71% and 85.14%, respectively, in ADNI testing, as well as 74.86%, 88% and 83.43% in OASIS testing. Balanced sensitivity and specificity were obtained for all subclass classifications in MCI, AD and CN. Conclusion: The FFNN yielded good overall accuracy for MCI, AD and CN categorization, with balanced subclass accuracy, sensitivity and specificity. The proposed FFNN model is simple, and it may support the triage of patients for further confirmation of the diagnosis.
Language	English
Publishing date	2024-04-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines12040896
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Article ; Online: Going beyond Mindfulness: How Concentration and Tranquility Commonly Co-Arising with Mindfulness Account for Mental Health.

Chan, Ryan M K / Mak, Winnie W S / Yu, Ben C L

International journal of environmental research and public health

2023 Volume 20, Issue 8

Abstract: Concentration and tranquility usually co-arise with mindfulness during mindfulness practice and in daily life and may potentially contribute to mental health; however, they have rarely been studied in empirical research. The present study aimed to ... ...

Abstract	Concentration and tranquility usually co-arise with mindfulness during mindfulness practice and in daily life and may potentially contribute to mental health; however, they have rarely been studied in empirical research. The present study aimed to examine the relationship of concentration and tranquility with mindfulness and indicators of mental health. With no existing self-report measure assessing concentration and tranquility, the Concentration Scale and Tranquility Scale were first developed and validated. Items were developed based on the extant literature, rated by a group of experts, and selected according to their ratings. Exploratory factor analyses (EFA;
MeSH term(s)	Adult ; Humans ; Mental Health ; Mindfulness ; Stress, Psychological/psychology ; Attention ; Self Report
Language	English
Publishing date	2023-04-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph20085470
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Article ; Online: Chemical carcinogens: implications for cancer treatment.

Liu, Shaofeng / Saunders, Mary / Mak, Tak W

The Journal of clinical investigation

2023 Volume 133, Issue 20

Abstract: ... tumor microenvironment (TME) due to reduced M-CSF expression. Intriguingly, the so-called carcinogen-induced tumor ...

Abstract	Carcinogen exposure has been associated with enhanced cancer immunogenicity that is often attributed to neoantigen generation. However, the broader, neoantigen-independent impact of carcinogens on immune responses to cancer cells remains underexplored. In this issue of the JCI, Huang et al. uncover a mechanism wherein carcinogen-treated cancer cells exhibit an inability to establish an immunosuppressive tumor microenvironment (TME) due to reduced M-CSF expression. Intriguingly, the so-called carcinogen-induced tumor-associated macrophages (TAMs) within this TME exhibited anti-tumor properties instead of the conventional immunosuppressive phenotype. This phenomenon extended to human lung cancers, as evidenced by TAM reprogramming in smokers versus nonsmokers. This study substantially advances our understanding of carcinogen-mediated effects on cancer immunogenicity, potentially redirecting approaches to cancer immunotherapy.
MeSH term(s)	Humans ; Carcinogens/toxicity ; Immunotherapy ; Immunosuppressive Agents ; Lung Neoplasms/therapy ; Phenotype ; Tumor Microenvironment ; Neoplasms/therapy
Chemical Substances	Carcinogens ; Immunosuppressive Agents
Language	English
Publishing date	2023-10-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI174319
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