Publications by authors named "Daniel Lai"

137 Publications

To be or not to be: relationship between grandparent status and health and wellbeing.

BMC Geriatr 2021 03 24;21(1):204. Epub 2021 Mar 24.

Department of Applied Social Sciences, The Hong Kong Polytechnic University, 11 Yuk. Choi Road, Hung Hum, Kowloon, Hong Kong.

Background: It is common for older people to become grandparents in later life. However, the impacts of grandparenting on their health and well-being remain ambiguous, especially in Chinese society, where the family is in the core of culture. The current study explored the relationship between grandparenthood and Chinese older people's health and psychological well-being in Hong Kong.

Methods: Cross-sectional data were collected from a sample of 1208 Hong Kong Chinese older people aged 55 and above through a telephone survey conducted in 2019. Participants were grouped into three categories: current grandparents (n = 507), grandparents-to-be (n = 275), and grandparents-not-to-be (n = 426). Multivariate linear regressions were performed to examine the relationship between grandparenting status and health and well-being outcomes, including self-rated physical health, mental health, resilience, and happiness. The potential moderating roles of older adults' demographic characteristics, including age, sex, education, marital status, financial status, were also examined.

Results: Bivariate analyses suggested statistically significant differences between health and well-being across the three groups of participants. Regression models showed that, compared with grandparents-not-to-be, being a current grandparent was associated with a significantly higher happiness level. Being a future grandparent was associated with significantly higher levels of happiness, resilience, and self-rated physical health. Moderating analyses showed that age, marital status, and educational level could moderate the relationship between grandparent status and resilience and self-rated mental health.

Conclusions: The current study offers preliminary insights into the significant relationship between grandparenthood and older adults' health and well-being. It calls for future studies to further explore the mechanisms between grandparenthood and the healthy ageing of different subgroups of older adults.
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http://dx.doi.org/10.1186/s12877-021-02052-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989105PMC
March 2021

The Older, the Happier?: A Cross-Sectional Study on the "Paradox of Aging" in China.

Res Aging 2021 Feb 25:164027521994225. Epub 2021 Feb 25.

Department of Sociology, 8205University of Victoria, British Columbia, Canada.

The "paradox of aging" refers to the phenomenon that even though people's physical health and functions may decline when they enter later adulthood, their happiness does not necessarily. Previous studies have shown that older adults' better emotional regulation skills may contribute to the maintenance of their happiness. This study aims to examine the relationship between age, health, and happiness, and the moderating role of emotional stability. We adopted a nationally representative sample (n = 10,968) from the Chinese General Social Survey (CGSS) and performed weight-adjusted regression models with interaction terms. There is generally an S-shaped age-happiness relationship with significant urban-rural differences. Emotional stability buffers the negative association between health and happiness, and this moderating effect was stronger among older than younger adults, especially in rural China. This study calls for special attention paid to the oldest-old population in rural China and older adults' emotional regulation skills.
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http://dx.doi.org/10.1177/0164027521994225DOI Listing
February 2021

Soft gold nanowire sponge antenna for battery-free wireless pressure sensors.

Nanoscale 2021 Feb;13(7):3957-3966

Department of Chemical Engineering, Monash University Clayton, Victoria 3800, Australia.

The past decade has witnessed growing interest in developing soft wearable pressure sensors with the ultimate goal of transforming today's hospital-centered diagnosis to tomorrow's patient-centered bio-diagnosis. In this context, battery-free wireless antenna-based pressure sensors will be highly advantageous for ubiquitous real-time health monitoring. However, current wireless antennas are largely based on thin films from traditional bulk metallic films or novel nanomaterials with an air-cavity design, which can only be operated in a limited pressure range due to the rigidity of active films and/or inherent cavity dimensions. Herein we report a soft battery-free wireless pressure sensor that is based on a three-dimensional (3D) porous gold nanowire foam-elastomer composite and is fabricated by solution-based conformal electroless plating technology, followed by elastomer encapsulation. We observe a transducer trade-off point for our foam antenna, below which the inductive effect and capacitive effect function together and above which the capacitive effect dominates. When an external pressure is applied, initially the inductance and capacitance increase simultaneously but the capacitance decreases afterwards. This can be transformed into a variable resonant frequency that first decreases linearly and then increases (in the capacitance domination pressure range). Importantly, the linear detection range of the sensor can be tuned simply by adjusting the thickness of the sponge or the rigidity of the elastomer (PDMS). We can achieve a wide pressure range of 0-248 kPa, which is the largest linear detection range reported in the literature (typically from 0 to 30 kPa) to the best of our knowledge. As a proof of concept, we further demonstrated that our gold nanowire foam sensor can be used to weigh people under both static and dynamic conditions.
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http://dx.doi.org/10.1039/d0nr07621jDOI Listing
February 2021

Hopes and Wishes of Clients with Mentally Illness in Hong Kong.

Community Ment Health J 2021 Jan 28. Epub 2021 Jan 28.

International Social Service Hong Kong Branch, 130 Hennessy Rd, Wan Chai, Hong Kong, China.

Recovery is a progressive process involving support to people with mental illness to take control of their life through the enhancement of motivation, self-drive, and responsibility. Drawing on qualitative interviews with 61 patients with mental illness aged between 40 and 75 in the community or residential settings, this study examined the wishes and hopes of clients who were in recovery. Participants described wishes and hopes for autonomy and independence in finances, accommodation, and health; stable housing or accommodation; meaningful occupation or employment; 'giving back' to society by serving others; intimate relationships; and gaining back 'lost time.' Wishes and hopes were motivating factors contributing to physical, mental, and social health over time, motivating clients with mental illness to live happily. To foster recovery, mental health practitioners should consider the identification and fulfilment of wishes and hopes in health and social care programs for this unique client group.
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http://dx.doi.org/10.1007/s10597-021-00779-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841978PMC
January 2021

Adult-type granulosa cell tumor of the ovary: a FOXL2-centric disease.

J Pathol Clin Res 2021 May 11;7(3):243-252. Epub 2021 Jan 11.

Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada.

Adult-type granulosa cell tumors (aGCTs) account for 90% of malignant ovarian sex cord-stromal tumors and 2-5% of all ovarian cancers. These tumors are usually diagnosed at an early stage and are treated with surgery. However, one-third of patients relapse between 4 and 8 years after initial diagnosis, and there are currently no effective treatments other than surgery for these relapsed patients. As the majority of aGCTs (>95%) harbor a somatic mutation in FOXL2 (c.C402G; p.C134W), the aim of this study was to identify genetic mutations besides FOXL2 C402G in aGCTs that could explain the clinical diversity of this disease. Whole-genome sequencing of 10 aGCTs and their matched normal blood was performed to identify somatic mutations. From this analysis, a custom amplicon-based panel was designed to sequence 39 genes of interest in a validation cohort of 83 aGCTs collected internationally. KMT2D inactivating mutations were present in 10 of 93 aGCTs (10.8%), and the frequency of these mutations was similar between primary and recurrent aGCTs. Inactivating mutations, including a splice site mutation in candidate tumor suppressor WNK2 and nonsense mutations in PIK3R1 and NLRC5, were identified at a low frequency in our cohort. Missense mutations were identified in cell cycle-related genes TP53, CDKN2D, and CDK1. From these data, we conclude that aGCTs are comparatively a homogeneous group of tumors that arise from a limited set of genetic events and are characterized by the FOXL2 C402G mutation. Secondary mutations occur in a subset of patients but do not explain the diverse clinical behavior of this disease. As the FOXL2 C402G mutation remains the main driver of this disease, progress in the development of therapeutics for aGCT would likely come from understanding the functional consequences of the FOXL2 C402G mutation.
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http://dx.doi.org/10.1002/cjp2.198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072996PMC
May 2021

Exoskeleton Application to Military Manual Handling Tasks.

Hum Factors 2020 Nov 18:18720820957467. Epub 2020 Nov 18.

5399 Victoria University, Melbourne, Australia.

Objective: The aim of this review was to determine how exoskeletons could assist Australian Defence Force personnel with manual handling tasks.

Background: Musculoskeletal injuries due to manual handling are physically damaging to personnel and financially costly to the Australian Defence Force. Exoskeletons may minimize injury risk by supporting, augmenting, and/or amplifying the user's physical abilities. Exoskeletons are therefore of interest in determining how they could support the unique needs of military manual handling personnel.

Method: Industrial and military exoskeleton studies from 1990 to 2019 were identified in the literature. This included 67 unique exoskeletons, for which Information about their current state of development was tabulated.

Results: Exoskeleton support of manual handling tasks is largely through squat/deadlift (lower limb) systems (64%), with the proposed use case for these being load carrying (42%) and 78% of exoskeletons being active. Human-exoskeleton analysis was the most prevalent form of evaluation (68%) with reported reductions in back muscle activation of 15%-54%.

Conclusion: The high frequency of citations of exoskeletons targeting load carrying reflects the need for devices that can support manual handling workers. Exoskeleton evaluation procedures varied across studies making comparisons difficult. The unique considerations for military applications, such as heavy external loads and load asymmetry, suggest that a significant adaptation to current technology or customized military-specific devices would be required for the introduction of exoskeletons into a military setting.

Application: Exoskeletons in the literature and their potential to be adapted for application to military manual handling tasks are presented.
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http://dx.doi.org/10.1177/0018720820957467DOI Listing
November 2020

A real-time fuzzy logic biofeedback controller for freestyle swimming body posture adjustment.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:4620-4623

Wearable body area networks (BANs) have been widely used in activity measurements for kinematic information collection. This paper presents the design and implementation of a wearable device used as a training tool in freestyle swimming. The device supplies a close-loop control mechanism via a fuzzy logic controller. Swimming posture data is collected quantitatively and audibly fed back to swimmers in real time through bone conductors. Two recreational swimmers were invited to participate in a series of experiments including 7 days of baseline capability test (no feedback), 7 days of feedback training, and 2 days of retention test. It was found that both swimmers could well adapt to the feedback instructions. A maximum of 7.62% of lap time improvement and 29.64% of trunk roll improvement were observed in FB training, and such pattern was maintained after feedback was removed. We conclude that real-time fuzzy logic feedback can be used to improve recreational swimmers performance.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176237DOI Listing
July 2020

Epiclomal: Probabilistic clustering of sparse single-cell DNA methylation data.

PLoS Comput Biol 2020 09 23;16(9):e1008270. Epub 2020 Sep 23.

Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

We present Epiclomal, a probabilistic clustering method arising from a hierarchical mixture model to simultaneously cluster sparse single-cell DNA methylation data and impute missing values. Using synthetic and published single-cell CpG datasets, we show that Epiclomal outperforms non-probabilistic methods and can handle the inherent missing data characteristic that dominates single-cell CpG genome sequences. Using newly generated single-cell 5mCpG sequencing data, we show that Epiclomal discovers sub-clonal methylation patterns in aneuploid tumour genomes, thus defining epiclones that can match or transcend copy number-determined clonal lineages and opening up an important form of clonal analysis in cancer. Epiclomal is written in R and Python and is available at https://github.com/shahcompbio/Epiclomal.
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http://dx.doi.org/10.1371/journal.pcbi.1008270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546467PMC
September 2020

Effectiveness of a peer-based intervention on loneliness and social isolation of older Chinese immigrants in Canada: a randomized controlled trial.

BMC Geriatr 2020 09 21;20(1):356. Epub 2020 Sep 21.

The Calgary Chinese Elderly Citizens' Association, Calgary, Canada.

Background: Social isolation is a key concern for immigrant older adults. We examined the effectiveness of a peer-based intervention in reducing loneliness, social isolation, and improving psychosocial well-being with a sample of aging Chinese immigrants.

Methods: Sixty community-dwelling older Chinese immigrants aged 65 and older were randomly assigned to an intervention group and a control group (n = 30 each) in a randomized control parallel trial design. Intervention group participants received an eight-week peer support intervention. Twenty-four volunteers aged 48 to 76 engaged in two-on-one peer support through home visits and telephone calls to provide emotional support, problem-solving support, and community resource sharing. Social workers who are not blinded to the group assignment measured the changes of both the intervention group and the control group participants in a range of psychosocial outcomes including three primary outcomes (loneliness, social support, barriers to social participation) and five secondary outcomes (depressive symptoms, anxiety, life satisfaction, happiness, and purpose in life).

Results: The 30 intervention group participants showed a statistically significant decrease in loneliness and increase in resilience when compared to the 30 control group participants. They reported fewer barriers to social participation, fewer depressive symptoms, increased life satisfaction, and happiness while no such improvements were observed in the control group.

Conclusions: There is a need to further examine the use of peer-based interventions for both program effectiveness and delivery efficiency. In the era of population aging and increasing immigration, diverse aging adults can be trained to fill volunteer support roles via peer-based intervention approaches.

Trial Registration: ISRCTN, ISRCTN14572069 , Registered 23 December 2019 - Retrospectively registered.
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http://dx.doi.org/10.1186/s12877-020-01756-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507625PMC
September 2020

Single cell transcriptomes of normal endometrial derived organoids uncover novel cell type markers and cryptic differentiation of primary tumours.

J Pathol 2020 10 22;252(2):201-214. Epub 2020 Aug 22.

Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC, Canada.

Endometrial carcinoma, the most common gynaecological cancer, develops from endometrial epithelium which is composed of secretory and ciliated cells. Pathologic classification is unreliable and there is a need for prognostic tools. We used single cell sequencing to study organoid model systems derived from normal endometrial endometrium to discover novel markers specific for endometrial ciliated or secretory cells. A marker of secretory cells (MPST) and several markers of ciliated cells (FAM92B, WDR16, and DYDC2) were validated by immunohistochemistry on organoids and tissue sections. We performed single cell sequencing on endometrial and ovarian tumours and found both secretory-like and ciliated-like tumour cells. We found that ciliated cell markers (DYDC2, CTH, FOXJ1, and p73) and the secretory cell marker MPST were expressed in endometrial tumours and positively correlated with disease-specific and overall survival of endometrial cancer patients. These findings suggest that expression of differentiation markers in tumours correlates with less aggressive disease, as would be expected for tumours that retain differentiation capacity, albeit cryptic in the case of ciliated cells. These markers could be used to improve the risk stratification of endometrial cancer patients, thereby improving their management. We further assessed whether consideration of MPST expression could refine the ProMiSE molecular classification system for endometrial tumours. We found that higher expression levels of MPST could be used to refine stratification of three of the four ProMiSE molecular subgroups, and that any level of MPST expression was able to significantly refine risk stratification of the copy number high subgroup which has the worst prognosis. Taken together, this shows that single cell sequencing of putative cells of origin has the potential to uncover novel biomarkers that could be used to guide management of cancers. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/path.5511DOI Listing
October 2020

Chemogenomic profiling of breast cancer patient-derived xenografts reveals targetable vulnerabilities for difficult-to-treat tumors.

Commun Biol 2020 Jun 16;3(1):310. Epub 2020 Jun 16.

Rosalind & Morris Goodman Cancer Research Centre, McGill University, Montréal, QC, H3A 1A3, Canada.

Subsets of breast tumors present major clinical challenges, including triple-negative, metastatic/recurrent disease and rare histologies. Here, we developed 37 patient-derived xenografts (PDX) from these difficult-to-treat cancers to interrogate their molecular composition and functional biology. Whole-genome and transcriptome sequencing and reverse-phase protein arrays revealed that PDXs conserve the molecular landscape of their corresponding patient tumors. Metastatic potential varied between PDXs, where low-penetrance lung micrometastases were most common, though a subset of models displayed high rates of dissemination in organotropic or diffuse patterns consistent with what was observed clinically. Chemosensitivity profiling was performed in vivo with standard-of-care agents, where multi-drug chemoresistance was retained upon xenotransplantation. Consolidating chemogenomic data identified actionable features in the majority of PDXs, and marked regressions were observed in a subset that was evaluated in vivo. Together, this clinically-annotated PDX library with comprehensive molecular and phenotypic profiling serves as a resource for preclinical studies on difficult-to-treat breast tumors.
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http://dx.doi.org/10.1038/s42003-020-1042-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298048PMC
June 2020

Lower Limb Kinematics Trajectory Prediction Using Long Short-Term Memory Neural Networks.

Front Bioeng Biotechnol 2020 8;8:362. Epub 2020 May 8.

Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia.

This study determined whether the kinematics of lower limb trajectories during walking could be extrapolated using long short-term memory (LSTM) neural networks. It was hypothesised that LSTM auto encoders could reliably forecast multiple time-step trajectories of the lower limb kinematics, specifically linear acceleration (LA) and angular velocity (AV). Using 3D motion capture, lower limb position-time coordinates were sampled (100 Hz) from six male participants (age 22 ± 2 years, height 1.77 ± 0.02 m, body mass 82 ± 4 kg) who walked for 10 min at 5 km/h on a 0% gradient motor-driven treadmill. These data were fed into an LSTM model with a sliding window of four kinematic variables with 25 samples or time steps: LA and AV for thigh and shank. The LSTM was tested to forecast five samples (i.e., time steps) of the four kinematic input variables. To attain generalisation, the model was trained on a dataset of 2,665 strides from five participants and evaluated on a test set of 1 stride from a sixth participant. The LSTM model learned the lower limb kinematic trajectories using the training samples and tested for generalisation across participants. The forecasting horizon suggested higher model reliability in predicting earlier future trajectories. The mean absolute error (MAE) was evaluated on each variable across the single tested stride, and for the five-sample forecast, it obtained 0.047 m/s thigh LA, 0.047 m/s shank LA, 0.028 deg/s thigh AV and 0.024 deg/s shank AV. All predicted trajectories were highly correlated with the measured trajectories, with correlation coefficients greater than 0.98. The motion prediction model may have a wide range of applications, such as mitigating the risk of falls or balance loss and improving the human-machine interface for wearable assistive devices.
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http://dx.doi.org/10.3389/fbioe.2020.00362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227385PMC
May 2020

Sense of Community Mediating Between Age-Friendly Characteristics and Life Satisfaction of Community-Dwelling Older Adults.

Front Psychol 2020 4;11:86. Epub 2020 Mar 4.

Oxford Institute of Population Ageing, University of Oxford, Oxford, United Kingdom.

The growth of age-friendly community initiatives underscores a paradigmatic shift from the individual to the community, addressing dynamic transactions between people and the environment they are living in. The purpose of the present study is to address the gap in existing research by examining the psycho-social effects of the sense of community in mediating between WHO domains of age-friendliness and the life satisfaction of older adults. Data were obtained from 898 participants in Hong Kong. Path analysis was conducted. Two AFC domains, Social Participation as well as Community Support and Health Services, were found to be associated with life satisfaction. Sense of community was found to mediate between these two domains and life satisfaction. The implications of these findings are discussed with reference to developing opportunities in social participation of older adults and enhancing community/health support services in the context of developing sustainability in the community.
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http://dx.doi.org/10.3389/fpsyg.2020.00086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064721PMC
March 2020

TMEM30A loss-of-function mutations drive lymphomagenesis and confer therapeutically exploitable vulnerability in B-cell lymphoma.

Nat Med 2020 04 24;26(4):577-588. Epub 2020 Feb 24.

Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.

Transmembrane protein 30A (TMEM30A) maintains the asymmetric distribution of phosphatidylserine, an integral component of the cell membrane and 'eat-me' signal recognized by macrophages. Integrative genomic and transcriptomic analysis of diffuse large B-cell lymphoma (DLBCL) from the British Columbia population-based registry uncovered recurrent biallelic TMEM30A loss-of-function mutations, which were associated with a favorable outcome and uniquely observed in DLBCL. Using TMEM30A-knockout systems, increased accumulation of chemotherapy drugs was observed in TMEM30A-knockout cell lines and TMEM30A-mutated primary cells, explaining the improved treatment outcome. Furthermore, we found increased tumor-associated macrophages and an enhanced effect of anti-CD47 blockade limiting tumor growth in TMEM30A-knockout models. By contrast, we show that TMEM30A loss-of-function increases B-cell signaling following antigen stimulation-a mechanism conferring selective advantage during B-cell lymphoma development. Our data highlight a multifaceted role for TMEM30A in B-cell lymphomagenesis, and characterize intrinsic and extrinsic vulnerabilities of cancer cells that can be therapeutically exploited.
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http://dx.doi.org/10.1038/s41591-020-0757-zDOI Listing
April 2020

Audiovisual integrative training for augmenting cognitive- motor functions in older adults with mild cognitive impairment.

BMC Geriatr 2020 02 17;20(1):64. Epub 2020 Feb 17.

Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong.

Background: Previous studies indicated that the behavioral performances of older adults could be enhanced by multisensory integration. This pilot study tested the benefits of an audiovisual integrative (AV) training for improving the cognitive and upper limb motor functions in older adults with mild cognitive impairment (MCI).

Methods: Twenty participants, according to their MoCA scores, with ten in each of a MCI (mean age = 63.3 years) and healthy older adult group (mean age = 64.7 years), engaged in AV integrative training. They were recruited from the Institute of Active Ageing at the Hong Kong Polytechnic University. The screening was conducted from February to March 2018 and the training program which consisted of three sessions (2 h each) was conducted from 14-28th May 2018. Their executive function, attention and upper limb functions were measured by the Stroop Test and Purdue Pegboard Test respectively.

Results: The mixed linear model analysis results showed significant Time x Group interaction effects in the time used in the Stroop Test (dots) (p = 0.042) and the Purdue Pegboard scores (non-dominant hand use) (p = 0.025). The MCI group exhibited significantly more improvements in attentional control and non-dominant hand motor functions after the training.

Conclusions: The findings suggest that the AV integrative training has the potential for enhancing the cognitive and motor functions of older adults with MCI. Furthermore, AV integrative training can serve as an alternative non-pharmacological intervention for combating neurodegeneration in older adults.

Trial Registration: This study has been retrospectively registered at the Chinese Clinical Trial Registry which is a World Health Organisation approved registry.

Trial Registration: Current Controlled Trials ChiCTR2000029408, January 29th, 2020.
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http://dx.doi.org/10.1186/s12877-020-1465-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027117PMC
February 2020

Personal care expectations: Photovoices of Chinese ageing adults in Hong Kong.

Health Soc Care Community 2020 05 9;28(3):1071-1081. Epub 2020 Jan 9.

Department of Applied Social Sciences, The Hong Kong Polytechnic University, Hong Kong, China.

The increasing ageing population contributes to growing demands for personal care that fulfils ageing adults' preferences and expectations. This study explored Chinese ageing adults' expected forms and sources of future personal care and the factors influencing care expectations. A qualitative photovoice research method - which integrated photography, interviews and group discussions - was used for data collection between January and April 2016. Through purposive sampling, 36 community-residing participants aged 51-80 years took photographs that captured personal care preferences or expectations within individual, familial and societal contexts. Participants described feelings of worry, uncertainty and unpreparedness for future care needs and arrangements. They preferred practicing self-care for as long as possible and remaining in their homes and communities ("ageing in place") through support from assistive technologies, family members or home-based and community services. Institutional care was regarded as the last resort. The findings reflected discrepancies between ageing adults' care preferences and realities and their ambivalent attitudes towards filial care when switching between roles. Confronted with the increasingly unreliable family care, financial resources and insufficient community services, participants anticipated receiving institutional care that would be less satisfying or that they would dislike. As caregivers, ageing adults displayed strong commitment to filial obligations, whereas when perceiving themselves as care receivers they felt that they could not expect care from their children because of practical considerations. By understanding preferred care forms and sources, actors can devote resources, policies and interventions to support self-care through proactive planning and technological advancement, foster "ageing in place" through family and community care, and improve institutional care to enable ageing with dignity.
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http://dx.doi.org/10.1111/hsc.12940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187378PMC
May 2020

Clonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing.

Cell 2019 Nov;179(5):1207-1221.e22

Department of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada.

Accurate measurement of clonal genotypes, mutational processes, and replication states from individual tumor-cell genomes will facilitate improved understanding of tumor evolution. We have developed DLP+, a scalable single-cell whole-genome sequencing platform implemented using commodity instruments, image-based object recognition, and open source computational methods. Using DLP+, we have generated a resource of 51,926 single-cell genomes and matched cell images from diverse cell types including cell lines, xenografts, and diagnostic samples with limited material. From this resource we have defined variation in mitotic mis-segregation rates across tissue types and genotypes. Analysis of matched genomic and image measurements revealed correlations between cellular morphology and genome ploidy states. Aggregation of cells sharing copy number profiles allowed for calculation of single-nucleotide resolution clonal genotypes and inference of clonal phylogenies and avoided the limitations of bulk deconvolution. Finally, joint analysis over the above features defined clone-specific chromosomal aneuploidy in polyclonal populations.
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http://dx.doi.org/10.1016/j.cell.2019.10.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912164PMC
November 2019

Dissociation of solid tumor tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses.

Genome Biol 2019 10 17;20(1):210. Epub 2019 Oct 17.

Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada.

Background: Single-cell RNA sequencing (scRNA-seq) is a powerful tool for studying complex biological systems, such as tumor heterogeneity and tissue microenvironments. However, the sources of technical and biological variation in primary solid tumor tissues and patient-derived mouse xenografts for scRNA-seq are not well understood.

Results: We use low temperature (6 °C) protease and collagenase (37 °C) to identify the transcriptional signatures associated with tissue dissociation across a diverse scRNA-seq dataset comprising 155,165 cells from patient cancer tissues, patient-derived breast cancer xenografts, and cancer cell lines. We observe substantial variation in standard quality control metrics of cell viability across conditions and tissues. From the contrast between tissue protease dissociation at 37 °C or 6 °C, we observe that collagenase digestion results in a stress response. We derive a core gene set of 512 heat shock and stress response genes, including FOS and JUN, induced by collagenase (37 °C), which are minimized by dissociation with a cold active protease (6 °C). While induction of these genes was highly conserved across all cell types, cell type-specific responses to collagenase digestion were observed in patient tissues.

Conclusions: The method and conditions of tumor dissociation influence cell yield and transcriptome state and are both tissue- and cell-type dependent. Interpretation of stress pathway expression differences in cancer single-cell studies, including components of surface immune recognition such as MHC class I, may be especially confounded. We define a core set of 512 genes that can assist with the identification of such effects in dissociated scRNA-seq experiments.
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http://dx.doi.org/10.1186/s13059-019-1830-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796327PMC
October 2019

Probabilistic cell-type assignment of single-cell RNA-seq for tumor microenvironment profiling.

Nat Methods 2019 10 9;16(10):1007-1015. Epub 2019 Sep 9.

Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.

Single-cell RNA sequencing has enabled the decomposition of complex tissues into functionally distinct cell types. Often, investigators wish to assign cells to cell types through unsupervised clustering followed by manual annotation or via 'mapping' to existing data. However, manual interpretation scales poorly to large datasets, mapping approaches require purified or pre-annotated data and both are prone to batch effects. To overcome these issues, we present CellAssign, a probabilistic model that leverages prior knowledge of cell-type marker genes to annotate single-cell RNA sequencing data into predefined or de novo cell types. CellAssign automates the process of assigning cells in a highly scalable manner across large datasets while controlling for batch and sample effects. We demonstrate the advantages of CellAssign through extensive simulations and analysis of tumor microenvironment composition in high-grade serous ovarian cancer and follicular lymphoma.
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http://dx.doi.org/10.1038/s41592-019-0529-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485597PMC
October 2019

Local Crack-Programmed Gold Nanowire Electronic Skin Tattoos for In-Plane Multisensor Integration.

Adv Mater 2019 Oct 25;31(41):e1903789. Epub 2019 Aug 25.

Department of Chemical Engineering, Monash University, Clayton, Victoria, 3800, Australia.

Sensitive, specific, yet multifunctional tattoo-like electronics are ideal wearable systems for "any time, any where" health monitoring because they can virtually become parts of the human skin, offering a burdenless "unfeelable" wearing experience. A skin-like, multifunctional electronic tattoo made entirely from gold using a standing enokitake-mushroom-like vertically aligned nanowire membrane in conjunction with a programmable local cracking technology is reported. Unlike previous multifunctional systems, only a single material type is needed for the integrated gold circuits involved in interconnects and multiplexed specific sensors, thereby avoiding the use of complex multimaterials interfaces. This is possiblebecause the programmable local cracking technology allows for the arbitrary fine-tuning of the properties of elastic gold conductors from strain-insensitive to highly strain-sensitive simply by adjusting localized crack size, shape, and orientations-a capability impossible to achieve with previous bulk cracking technology. Furthermore, in-plane integration of strain/pressure sensors, anisotropic orientation-specific sensors, strain-insensitive stretchable interconnects, temperature sensors, glucose sensors, and lactate sensors without the need of soldering or gluing are demonstrated. This strategy opens a new general route for the design of next-generation wearable electronic tattoos.
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http://dx.doi.org/10.1002/adma.201903789DOI Listing
October 2019

The Impact of Intergenerational Relationship on Health and Well-Being of Older Chinese Americans.

J Am Geriatr Soc 2019 08;67(S3):S557-S563

Institute for Health, Health Care Policy and Aging Research, Rutgers, The State University of New Jersey, New Brunswick, New Jersey.

Background/objectives: Among older adults, intergenerational support can help to improve well-being. This study examines the correlation between intergenerational relationships and the subjective well-being among older Chinese immigrants in the United States.

Design: Hierarchical multiple regression analyses were applied to test the association between intergenerational relationships and self-rated well-being. The mediating effects of sense of control and the moderation effects of support from friends were also tested.

Sample: A cross-sectional sample of 2717 older Chinese immigrants, aged 60 years and older, with children and grandchildren was drawn from the Population Study of Chinese Elderly.

Measurements: Study measures included four items concerning intergenerational relationships: the Pearlin Mastery Scale, two items on seeking support from friends, and single items measuring self-rated health status and quality of life.

Results: Only the feeling of closeness with children was positively linked with subjective well-being, while coresidence and frequency of talking were not. Support from friends moderated the association with self-rated health status, while sense of control partially mediated the association between feeling of closeness and both self-rated health status and quality of life.

Conclusion: A stronger sense of closeness with children correlates to self-rated health status and quality of life among older Chinese immigrants. The effects of sociocultural changes affecting Chinese American families, and potential implications for older adults' health, could be addressed through strategies to develop emotional closeness with their families and to support sense of control and well-being among older Chinese adults. J Am Geriatr Soc 67:S557-S563, 2019.
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http://dx.doi.org/10.1111/jgs.15893DOI Listing
August 2019

Environmental Factors Associated with Chinese Older Immigrants' Social Engagement.

J Am Geriatr Soc 2019 08;67(S3):S571-S576

Institute for Health, Health Care Policy and Aging Research, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey.

Background/ Objectives: Prior research has shown that social engagement is beneficial to older adults' health and well-being. This study examined the association between environmental factors and social engagement of older Chinese immigrants in the United States.

Sample: A cross-sectional data set of Chinese immigrants in the greater Chicago, IL, area (Population Study of Chinese Elderly; n = 3159), was used in this study.

Design: Multiple regression models were used to test the associations between older adults' engagement in cognitive and social activities and environmental factors, including financial difficulties, social support, neighborhood cohesion, neighborhood disorder, and sense of community.

Measurement: Eight questions measuring participants' engagement in cognitive and social activities, a single-item question measuring financial difficulties, a 12-item social support measurement, an eight-item neighborhood cohesion measurement, and a six-item neighborhood disorder and sense of community scale.

Results: Having fewer financial difficulties and a cohesive neighborhood is related to a higher level of engagement in both cognitive and social activities. More social support from family and friends and a sense of community are associated with higher levels of social activities engagement, but not cognitive activity engagement. Neighborhood cohesion has a stronger association with social engagement than other environmental factors and most individual-level factors. Surprisingly, neighborhood disorder is positively related to social activity engagement, which needs further examination. The associations between environmental factors and social engagement showed no significant difference between healthy and unhealthy older adults.

Conclusion: This study highlights the need for policies and programs to promote an active lifestyle among older immigrants by creating facilitative social and physical environments. J Am Geriatr Soc 67:S571-S576, 2019.
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http://dx.doi.org/10.1111/jgs.15899DOI Listing
August 2019

The experience of growing old in chronic mental health patients.

Aging Ment Health 2020 09 2;24(9):1514-1522. Epub 2019 May 2.

Department of International Relations, The University of Sussex, Sussex, UK.

Research evidence has demonstrated disparities and barriers associated with mental illness, which creates challenges for individuals with mental illness to maintain physical, mental, and social health as they age. The aim of this study was to examine the meaning of aging from the perspective of individuals with mental illness and explore their motivations and challenges to adopting healthy aging lifestyles and practices. Using a qualitative narrative inquiry approach, interviews were conducted with 61 aging patients with mental illness aged 40 and older in community and institutional settings in Hong Kong. Participants discussed the meaning of healthy aging in terms of meaningful occupation and use of time, and independence and autonomy. Motivating factors included a desire to avoid 'burdening' other people, to 'give back' to society, and gain back 'lost time'. These were connected to strategies for healthy aging, including social relationships and activities, spirituality, and healthy lifestyles. Challenges to adopting healthy aging practices included physical health difficulties and medication side effects, lack of purpose and boredom associated with daily routines and use of time, and conflicts and loss affecting family and peer relationships. Social and health services should be tailored to support aging individuals with mental illness and their families, addressing motivations and barriers to adopting healthy lifestyles. Promoting healthy aging practices to enable individuals with mental illness to achieve healthy aging is important for preparing for the aging of this population.
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http://dx.doi.org/10.1080/13607863.2019.1609903DOI Listing
September 2020

clonealign: statistical integration of independent single-cell RNA and DNA sequencing data from human cancers.

Genome Biol 2019 03 12;20(1):54. Epub 2019 Mar 12.

Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.

Measuring gene expression of tumor clones at single-cell resolution links functional consequences to somatic alterations. Without scalable methods to simultaneously assay DNA and RNA from the same single cell, parallel single-cell DNA and RNA measurements from independent cell populations must be mapped for genome-transcriptome association. We present clonealign, which assigns gene expression states to cancer clones using single-cell RNA and DNA sequencing independently sampled from a heterogeneous population. We apply clonealign to triple-negative breast cancer patient-derived xenografts and high-grade serous ovarian cancer cell lines and discover clone-specific dysregulated biological pathways not visible using either sequencing method alone.
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http://dx.doi.org/10.1186/s13059-019-1645-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417140PMC
March 2019

Risk and protective factors associated with domestic abuse among older Chinese in the People's Republic of China.

Arch Gerontol Geriatr 2019 May - Jun;82:120-127. Epub 2019 Feb 11.

Department of Applied Social Sciences, The Hong Kong Polytechnic University of Hong Kong, Hong Kong.

Objectives: To identify risk and protective factors associated with elder abuse among older Chinese with cognitive and physical impairment in the People's Republic of China (PRC).

Methods: 1002 dyads of care recipients and family caregivers were interviewed.

Results: The mutually reported rates were 9.7%, 0.8%, 33.2%, and 39.7% for psychological abuse, physical abuse, financial exploitation, and caregiver neglect respectively. Caregiver burden, care recipient neuropsychiatric symptoms, and cognitive impairments are prominent risk factors, while protective factors associated with multiple abuse subtypes include caregiver's use of emotion-focused and solution-focused coping, perception of familism, and premorbid relationship rewards. Distinct factors were observed for respective forms of abuse. Psychological abuse with family poverty; Caregiver neglect with caregiver's substance use and poor physical health; Financial exploitation with caregiver's neurotic personality, as well as care recipient's younger age, absence of chronic illness, and co-residence between the caregiver and care recipient.

Discussion: Both similar and distinct factors were observed for different forms of abuse, potentially useful for designing prevention and intervention programs.
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http://dx.doi.org/10.1016/j.archger.2019.02.001DOI Listing
February 2020

Molecular and Genetic Characterization of MHC Deficiency Identifies EZH2 as Therapeutic Target for Enhancing Immune Recognition.

Cancer Discov 2019 04 31;9(4):546-563. Epub 2019 Jan 31.

Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.

We performed a genomic, transcriptomic, and immunophenotypic study of 347 patients with diffuse large B-cell lymphoma (DLBCL) to uncover the molecular basis underlying acquired deficiency of MHC expression. Low MHC-II expression defines tumors originating from the centroblast-rich dark zone of the germinal center (GC) that was associated with inferior prognosis. MHC-II-deficient tumors were characterized by somatically acquired gene mutations reducing MHC-II expression and a lower amount of tumor-infiltrating lymphocytes. In particular, we demonstrated a strong enrichment of mutations in both MHC-I- and MHC-II-negative primary lymphomas, and observed reduced MHC expression and T-cell infiltrates in murine lymphoma models expressing mutant . Of clinical relevance, EZH2 inhibitors significantly restored MHC expression in -mutated human DLBCL cell lines. Hence, our findings suggest a tumor progression model of acquired immune escape in GC-derived lymphomas and pave the way for development of complementary therapeutic approaches combining immunotherapy with epigenetic reprogramming. SIGNIFICANCE: We demonstrate how MHC-deficient lymphoid tumors evolve in a cell-of-origin-specific context. Specifically, mutations were identified as a genetic mechanism underlying acquired MHC deficiency. The paradigmatic restoration of MHC expression by EZH2 inhibitors provides the rationale for synergistic therapies combining immunotherapies with epigenetic reprogramming to enhance tumor recognition and elimination...
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http://dx.doi.org/10.1158/2159-8290.CD-18-1090DOI Listing
April 2019

Extraversion personality, perceived health and activity participation among community-dwelling aging adults in Hong Kong.

PLoS One 2018 12;13(12):e0209154. Epub 2018 Dec 12.

School of Humanities and Communication, Guangdong University of Finance and Economics, Guangzhou, China.

Activity participation is essential to the wellbeing of aging adults. Divergent levels of activity participation within aging populations have been explained from diverse perspectives, but the interaction effects of key determinants, such as personality and health, are often ignored. This study examines the effects of extravert personality on aging adults' activity levels by addressing its interaction with perceived physical health and mental health. A sample of 304 adults aged 50 and older was selected using systematic sampling from participants of an institute for promoting active aging at a university in Hong Kong in 2017. Data on socio-demographic characteristics, perceived physical and mental health, extraversion personality traits, and level of activity participation were collected using a telephone survey. Most participants (46.7%) reported moderate activity levels and over a quarter (26.6%) reported high or low activity levels. Multi-nominal logistic regression analyses show that extraversion was associated with an increased likelihood of reporting moderate (OR = 1.85, p = .036) but not high (p > .05) activity levels when adjusted for perceived physical and mental health and socio-demographics, with low activity levels being the constant comparison. Meanwhile, extraversion predicted both moderate (OR = 3.84, p = .014) and high (OR = 5.06, p = .032) activity levels for participants with poor or average perceived mental health. However, the interaction effects of extraversion with perceived physical health or mental health were not significant in predicting either moderate or high activity levels (p > .05). The implications for enhancing activity participation among aging adults are discussed in view of both personality and perceived health status.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209154PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291235PMC
May 2019

Perceived victimization risk, avoidance behavior, and health of community-dwelling older adults in urban China.

Aging Ment Health 2020 01 9;24(1):171-177. Epub 2018 Nov 9.

Department of Applied Social Sciences, The Hong Kong Polytechnic University, Hong Kong, China.

This study examined the associations between perceived crime-specific victimization risk, avoidance behavior, and their relationships with health of older adults. A representative sample of 453 Chinese aged 60 and older from Kunming provided information on their socio-demographic characteristics, perceived crime victimization risk, avoidance behavior, physical and mental health. Avoidance behavior was common among participants, with 61.4% avoiding unsafe areas and 42.2% avoiding social activities. Path analyses showed that perceived risk of vandalism was associated with avoiding participating in social activities, while perceived risk of attack was related to avoiding unsafe areas during the day. Meanwhile, avoiding social activities and perceived risk of vandalism were significant predictors of poor mental health, and avoiding unsafe areas was a salient predictor of poor physical health. Perceived risk of attack had an indirect effect on physical health through avoiding unsafe areas during the day. Study findings highlight the importance of addressing perceived victimization risk in encouraging social participation and mobility among older adults.
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http://dx.doi.org/10.1080/13607863.2018.1523879DOI Listing
January 2020

Cognitive Stimulating Play Intervention for Dementia: A Feasibility Randomized Controlled Trial.

Am J Alzheimers Dis Other Demen 2019 02 28;34(1):63-71. Epub 2018 Oct 28.

4 Factor-Inwentash Faculty of Social Work, University of Toronto, Toronto, Ontario, Canada.

This study investigates the feasibility and the preliminary efficacy of a Cognitive Stimulating Play Intervention on cognitive functions. Thirty older people with early to moderate dementia were recruited from 2 day-care centers, which were randomized into intervention and control groups. The recruitment, attendance, completion rates, and the interview with staff showed that the intervention was feasible. Analysis of covariance results showed that there was a significant difference between groups on memory storage and retrieval functions. The mean memory storage and retrieval functions were 5.92 (95% confidence interval [CI]: 1.83-9.91; P = .006) and 4.12 (95% CI: 0.75-7.50; P = .018) points higher than that for the control group, respectively, which contributed moderate to large effects (partial η = 0.189-0.248). There was no significant difference between groups in global cognition measured using the Montreal Cognitive Assessment and verbal fluency. Practical issues that emerged during implementation were discussed.
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http://dx.doi.org/10.1177/1533317518808036DOI Listing
February 2019