An Insight Into the Experiences of Malaysian Patients With Advanced Cancer and Their Preferences in End-of-Life Care: A Qualitative Study.

BACKGROUND: Preferences of patients with advanced cancer are well studied in Western countries but less so in Asian communities where end-of-life discussions can be seen as taboo. This may lead to patients receiving care that is incongruent with their wishes as their disease progress. It is important for healthcare providers to have a better understanding of patients' experiences and preferences especially in a multicultural country like Malaysia with its diverse beliefs and values to facilitate better planning for future medical care. OBJECTIVES: To explore the experiences and preferences of Malaysian patients with advanced cancer. DESIGN: Qualitative study of semi-structured interviews with thematic analysis. SETTING/SUBJECTS: Purposive sampling of 19 patients with Stage 4 cancer recruited from inpatient and outpatient settings in National Cancer Institute Malaysia. RESULTS: Three major themes emerged in the exploration of patients' experiences and care preferences in facing advanced cancer namely: 1) Dealing with poor prognosis 2) Spirituality as a source of strength and 3) Enablers of advance care planning. CONCLUSION: This study highlighted the preference for healthcare providers to be culturally sensitive during end-of-life care discussion and the need for improved spiritual care for Malaysian patients with advanced cancer. Further studies exploring the role of spiritual and cultural factors in advance care planning among Malaysians would be helpful in guiding these efforts.

The effects of online peer-facilitated learning and distributed pair programming on students' learning.

The COVID-19 pandemic has forced universities and schools around the world to adopt online learning. Teachers may wonder if their students can attain satisfactory learning performance in an online learning environment without teachers' on-the-spot attention. In order to develop students' skills in programming, promote their enjoyment of learning and intention to learn to program, the researchers integrated two innovative teaching approaches, using online peer-facilitated learning and distributed pair programming, and investigated the effects of these on students' online learning performance. This study conducted an experiment that included 128 undergraduates from four class sections of Department of Finance. Thus, the experimental design in this research was a 2 (Peer-facilitated learning vs. non-peer-facilitated learning) × 2 (Distributed pair programming vs. non-distributed pair programming) factorial pretest/post-test design. The participants in this research mainly consisted of four classes of students from a non-computer or information department who took a compulsory course on programming design.' Both quantitative and qualitative data were collected in this study. According to the results, the peer-facilitated learning group exhibited significantly better development of programming skills, enjoyment of learning, and intention to learn, than the non-peer-facilitated learning group. However, expected effects of enhancing the learning of the students in this study who received the distributed pair programming were not found. The design of online pedagogy can be a reference for online educators. The implications of applying online peer-facilitated learning and distributed pair programming to support students' learning and the design of online programming courses are discussed.

Perceived unmet needs of an age-friendly environment: A qualitative exploration of older adults' perspectives in a Malaysian city.

This exploratory qualitative study investigates older adults' unmet needs in the age-friendly city of Ipoh, Malaysia. Seventeen participants were interviewed, including ten older adults residing in Ipoh City for at least six months, four carers, and three professional key informants. Interviews were conducted using semi-structured questions based on the WHO Age-Friendly Cities Framework. A 5P framework for active ageing based on the ecological ageing model was adapted for data analysis. The 5P framework consists of domains of person (micro), process (meso), place (macro), policymaking (macro), and prime, which allows for the dissection of older adults' unmet needs in planning for multilevel approaches, which were employed for analysis. Person: the personal needs requiring improvement included digital divide disparity, inadequate family support, and restricted sports activities attributed to physical limitations. Process: There were fewer social activities and a lack of low-cost and easily accessible venues for seniors. Economic challenges include expensive private healthcare services, variation in the quality of care in older residential care facilities, and limited savings for retirement. Place issues include unequal distribution of exercise equipment, public open spaces, the need for more conducive parking for seniors, and a place for social activities. Difficulties assessing public transportation, digitalized services, and unaffordable e-hailing services are common among seniors. Housing issues for seniors include a lack of barrier-free housing design and unaffordable housing. Policymaking: Insufficient private sector commitment to improving services to older adults, lack of policy governance on the quality of nursing homes, and insufficient multidisciplinary governance collaboration. Prime: Health promotion for preventing age-related illness is required to preserve health in old age, and full-time family caregivers' psychological well-being is often overlooked.

The Histone Deacetylases Hst1 and Rpd3 Integrate De Novo NAD+ Metabolism with Phosphate Sensing in Saccharomyces cerevisiae.

Nicotinamide adenine dinucleotide (NAD+) is a critical cofactor essential for various cellular processes. Abnormalities in NAD+ metabolism have also been associated with a number of metabolic disorders. The regulation and interconnection of NAD+ metabolic pathways are not yet completely understood. By employing an NAD+ intermediate-specific genetic system established in the model organism S. cerevisiae, we show that histone deacetylases (HDACs) Hst1 and Rpd3 link the regulation of the de novo NAD+ metabolism-mediating BNA genes with certain aspects of the phosphate (Pi)-sensing PHO pathway. Our genetic and gene expression studies suggest that the Bas1-Pho2 and Pho2-Pho4 transcription activator complexes play a role in this co-regulation. Our results suggest a model in which competition for Pho2 usage between the BNA-activating Bas1-Pho2 complex and the PHO-activating Pho2-Pho4 complex helps balance de novo activity with PHO activity in response to NAD+ or phosphate depletion. Interestingly, both the Bas1-Pho2 and Pho2-Pho4 complexes appear to also regulate the expression of the salvage-mediating PNC1 gene negatively. These results suggest a mechanism for the inverse regulation between the NAD+ salvage pathways and the de novo pathway observed in our genetic models. Our findings help provide a molecular basis for the complex interplay of two different aspects of cellular metabolism.

Efficacy analysis of virtual reality-based training for activities of daily living and functional task training in stroke patients: A single-subject study.

INTRODUCTION: Virtual reality (VR)-based training for functions such as cognition, upper extremities, balancing, and activities of daily living (ADL) has been used on stroke patients, and its efficacy has been reported. However, no comparison has been made between the efficacy of VR-based training for daily activities that exactly reproduces ADL and functional training. Therefore, this study sought to analyze the difference in independency enhancement of VR-based training for daily activities compared to cognitive and motor functional training. PATIENT CONCERNS AND DIAGNOSIS: This study was conducted on 4 patients who have been diagnosed with stroke and are currently receiving rehabilitation therapy in G hospital located in the city of Gwangju, using A-B-A'-B' design from single-subject experimental designs. INTERVENTIONS: Intervention was performed in 2 ways: application of VR-based training for daily activities after the application of cognitive and motor function training; and application of cognitive and motor function training after the application of VR-based training for daily activities. The Assessment of Motor and Process Skills, Computer Cognitive Screening Assessment System, Box and Block Test, and Grip and Pinch Strength Test were used to measure the changes in the performance of daily activities, cognitive function, and upper extremities function. OUTCOMES: The results confirmed that the performance of daily activities, cognitive function, and upper extremities function was improved after the application of VR-based intervention. In addition, the efficacy of independency enhancement was maximized by the early approach of training for daily activities at the time of VR-based intervention in stroke patients. CONCLUSIONS: VR-based intervention of training for daily activities and functional training can be considered to benefit the improvement of the performance of daily activities, cognitive function, and upper extremities function in stroke patients. In addition, although functional training was also effective in enhancing independency and functional improvement in stroke patients, an early approach to training for ADL based on tasks with objectives was deemed to be more effective.

Integrating online meta-cognitive learning strategy and team regulation to develop students' programming skills, academic motivation, and refusal self-efficacy of Internet use in a cloud classroom.

With the development of technology and demand for online courses, there have been considerable quantities of online, blended, or flipped courses designed and provided. However, in the technology-enhanced learning environments, which are also full of social networking websites, shopping websites, and free online games, it is challenging to focus students' attention and help them achieve satisfactory learning performance. In addition, the instruction of programming courses constantly challenges both teachers and students, particularly in online learning environments. To overcome and solve these problems and to facilitate students' learning, the researchers in this study integrated two teaching approaches, using meta-cognitive learning strategy (MCLS) and team regulation (TR), to develop students' regular learning habits and further contribute to their programming skills, academic motivation, and refusal self-efficacy of Internet use, in a cloud classroom. In this research, a quasi-experiment was conducted to investigate the effects of MCLS and TR adopting the experimental design of a 2 (MCLS vs. non-MCLS) × 2 (TR vs. non-TR) factorial pre-test/post-test. In this research, the participants consisted of four classes of university students from non-information or computer departments enrolled in programming design, a required course. The experimental groups comprised three of the classes, labelled as G1, G2, and G3. G1 concurrently received both the online MCLS and TR intervention, while G2 only received the online MCLS intervention, and G3 only received the online TR intervention. Serving as the control group, the fourth class (G4) received traditional teaching. This study investigated the effects of MCLS, TR, and their combination, on improving students' programming skills, academic motivation, and refusal self-efficacy of Internet use in an online computing course. According to the results, students who received online TR significantly enhanced their programming design skills and their refusal self-efficacy of Internet use a cloud classroom. However, the expected effects of MCLS on developing students' programming skills, academic motivation, and refusal self-efficacy of Internet use were not found in this study. The teaching strategy of integrating MCLS and TR in an online programming course in this study can serve as a reference for educators when conducting online, blended, or flipped courses during the COVID-19 pandemic.

Deep brain stimulation rectifies the noisy cortex and irresponsive subthalamus to improve parkinsonian locomotor activities.

The success of deep brain stimulation (DBS) therapy indicates that Parkinson's disease is a brain rhythm disorder. However, the manifestations of the erroneous rhythms corrected by DBS remain to be established. We found that augmentation of α rhythms and α coherence between the motor cortex (MC) and the subthalamic nucleus (STN) is characteristically prokinetic and is decreased in parkinsonian rats. In multi-unit recordings, movement is normally associated with increased changes in spatiotemporal activities rather than overall spike rates in MC. In parkinsonian rats, MC shows higher spike rates at rest but less spatiotemporal activity changes upon movement, and STN burst discharges are more prevalent, longer lasting, and less responsive to MC inputs. DBS at STN rectifies the foregoing pathological MC-STN oscillations and consequently locomotor deficits, yet overstimulation may cause behavioral restlessness. These results indicate that delicate electrophysiological considerations at both cortical and subcortical levels should be exercised for optimal DBS therapy.

The genesis and functional consequences of cortico-subthalamic beta augmentation and excessive subthalamic burst discharges after dopaminergic deprivation.

The cardinal electrophysiological signs in Parkinson's disease (PD) include augmented beta oscillations in the motor cortex-subthalamic nucleus (MC-STN) axis and excessive burst discharges in STN. We have shown that excessive STN burst discharges have a direct causal relation with the locomotor deficits in PD. To investigate the correlation between the two cardinal signs, we characterized the courses of development of the electrophysiological abnormalities in the hemiparkinsonian rat model. The loss of dopaminergic neurons develops fast, and is histologically completed within 4-7 days of the lesion. The increase in STN burst discharges is limited to the lesioned side, and follows a very similar course. In contrast, beta augmentation has a bilateral presentation, and requires 14-21 days for full development. Behaviorally, the gross locomotor deficits in open field test and limb akinesia in stepping test match the foregoing fast and slow time courses, respectively. A further look into the spike entrainment shows that the oscillations in local field potential (LFP) of the MC effectively entrain the multi-unit (MU) spikes of MC, STN and entopeduncular nucleus (EPN), a rat homolog of human globus pallidus interna (GPi), whereas the LFP of STN or EPN (GPi) cannot entrain the spikes in MC. We conclude that excessive STN burst discharges are a direct consequence, whereas beta augmentation is probably a secondary or adaptive changes in the cortico-subcortical re-entrant loops, to dopaminergic deprivation. Beta augmentation is therefore not so consistently present as excessive STN burst discharges, but could signal more delicate derangements at the level of cortical programming in PD.

Characterization of T-Circles and Their Formation Reveal Similarities to Agrobacterium T-DNA Integration Patterns.

Agrobacterium transfers T-DNA to plants where it may integrate into the genome. Non-homologous end-joining (NHEJ) has been invoked as the mechanism of T-DNA integration, but the role of various NHEJ proteins remains controversial. Genetic evidence for the role of NHEJ in T-DNA integration has yielded conflicting results. We propose to investigate the formation of T-circles as a proxy for understanding T-DNA integration. T-circles are circular double-strand T-DNA molecules, joined at their left (LB) and right (RB) border regions, formed in plants. We characterized LB-RB junction regions from hundreds of T-circles formed in Nicotiana benthamiana or Arabidopsis thaliana. These junctions resembled T-DNA/plant DNA junctions found in integrated T-DNA: Among complex T-circles composed of multiple T-DNA molecules, RB-RB/LB-LB junctions predominated over RB-LB junctions; deletions at the LB were more frequent and extensive than those at the RB; microhomology was frequently used at junction sites; and filler DNA, from the plant genome or various Agrobacterium replicons, was often present between the borders. Ku80 was not required for efficient T-circle formation, and a VirD2 ω mutation affected T-circle formation and T-DNA integration similarly. We suggest that investigating the formation of T-circles may serve as a surrogate for understanding T-DNA integration.

The challenges in managing the growth of indigenous children in Perak State, Malaysia: A qualitative study.

Indigenous peoples in Peninsular Malaysia, known as Orang Asli, have been associated with the problem of malnutrition. Approximately 40% of their children are underweight. Indigenous peoples' distinct social, cultural, and economic traits, which differ from those of the dominant communities in which they live, may pose significant challenges for health care providers (HCPs) in addressing the malnutrition issue. This study explores challenges encountered by HCPs, with at least six months of experience in monitoring the growth parameters of Orang Asli children residing in Perak State in Peninsular Malaysia. A cross-sectional study was conducted between December 2020 and June 2021, involving three focus group discussions and three in-depth interviews. Thematic analysis was used. A total of 19 participants (6 nurses, 5 nursing managers, 4 medical officers, 2 nutritionists, a family medicine specialist, and a paediatrician) took part in this study. The challenges were summarized into four themes: (I) accessibility to nutrition, (II) accessibility to healthcare services, (II) skills of HCPs, and (IV) challenges of implementing nutrition programs. The inability of the Orang Asli children to access nutritious food was due to poverty, different perceptions of life priorities, and the practice of food taboos among the communities. Inadequate infrastructure and transportation discourage parents from bringing their children to healthcare facilities. The belief in and preference for traditional healing, the practice of semi-nomadic lifestyles, and fear of HCPs and their timid nature were factors that prevented Orang Asli children from accessing healthcare services. HCPs need to equip themselves with cross-cultural communication and interaction skills and adapt their skills to environmental challenges to overcome unexpected encounters in mobile clinics. The non-exposed food items, the risk of food basket sharing with other family members, and community feeding programs' coordination were the challenges to be addressed when implementing nutrition programmes for Orang Asli children. The challenges of HCPs are multifactorial and require a multifaceted approach. There is a need for joint efforts of stakeholders, from communities and non-governmental organisations (NGOs) to the health authorities, to address the challenges of HCPs.

Social responsibility perspective in public response to the COVID-19 pandemic: a grounded theory approach.

BACKGROUND: Combating viral outbreaks extends beyond biomedical and clinical approaches; thus, public health prevention measures are equally important. Public engagement in preventive efforts can be viewed as the social responsibility of individuals in controlling an infectious disease and are subjected to change due to human behaviour. Understanding individuals' perception of social responsibility is crucial and is not yet explored extensively in the academic literature. We adopted the grounded theory method to develop an explanatory substantive theory to illustrate the process of how individual responded to the outbreak from a social responsibility perspective. METHODS: In-depth interviews were conducted among 23 Malaysians either through telephone or face-to-face depending on the participant's preference. Both purposive and theoretical sampling were used. Participants were invited to share their understanding, perceptions and activities during the COVID-19 pandemic. They were further probed about their perceptions on complying with the public health interventions imposed by the authorities. The interviews were audio-recorded and transcribed verbatim. Data was analysed via open coding, focus coding and theoretical coding, facilitated by memoing, sketching and modelling. RESULTS: Study findings showed that, social responsibility is perceived within its role, the perceived societal role responsibility. In a particular context, an individual assumed only one of the many expected social roles with their perceived circle of responsibility. Individuals negotiated their actions from this perspective, after considering the perceived risk during the outbreak. The four types of behaviour depicted in the matrix diagram facilitate the understanding of the abstract concept of negotiation in the human decision-making process, and provide the spectrum of different behaviour in relation to public response to the COVID-19 pandemic. CONCLUSIONS: Our study adopted the grounded theory approach to develop a theoretical model that illustrates how individual response to COVID-19 preventive measures is determined by the negotiation between perceived societal role responsibility and perceived infection risk. This substantive theoretical model is abstract, thus has relevance for adoption within similar context of an outbreak.

Appointment structure in Malaysian healthcare system during the COVID-19 pandemic: The public perspective.

INTRODUCTION: Evidence shows physical distancing of one metre or more is important to reduce person-to-person SARS-CoV-2 transmission. This puts the Malaysian public healthcare system to a test when overcrowding has always been an issue. A new clinical appointment structure was proposed in the Malaysian public healthcare system amidst the pandemic to reduce the transmission risk. We aim to explore the general public's view on the proposed clinic appointment structure. METHODS: A cross-sectional anonymous web-based survey was conducted between 10th September 2020 and 30th November 2020. The survey was open to Malaysian aged 18 years and older via various social media platforms. The questionnaire consists of sociodemographic, experience of utilising healthcare facilities, and views on clinic appointment structure. RESULTS: A total of 1,144 complete responses were received. The mean age was 41.4 ± 12.4 years and more than half of the respondents had a preference for public healthcare. Among them, 77.1% reported to have a clinical appointment scheduled in the past. Less than a quarter experienced off-office hour appointments, mostly given by private healthcare. 70.2% answered they would arrive earlier if they were given a specific appointment slot at a public healthcare facility, as parking availability was the utmost concern. Majority hold positive views for after office hour clinical appointments, with 68.9% and 63.2% agreed for weekend and weekday evening appointment, respectively. The top reason of agreement was working commitment during office hours, while family commitment and personal resting time were the main reasons for disagreeing with off-office hour appointments. CONCLUSION: We found that majority of our respondents chose to come early instead of arriving on time which disrupts the staggered appointment system and causes over crowdedness. Our findings also show that the majority of our respondents accept off-office hour appointments. This positive response suggests that off-office hour appointments may have a high uptake amongst the public and thus be a possible solution to distribute the patient load. Therefore, this information may help policy makers to initiate future plans to resolve congestions within public health care facilities which in turn eases physical distancing during the pandemic.

An electrophysiological perspective on Parkinson's disease: symptomatic pathogenesis and therapeutic approaches.

Parkinson's disease (PD), or paralysis agitans, is a common neurodegenerative disease characterized by dopaminergic deprivation in the basal ganglia because of neuronal loss in the substantia nigra pars compacta. Clinically, PD apparently involves both hypokinetic (e.g. akinetic rigidity) and hyperkinetic (e.g. tremor/propulsion) symptoms. The symptomatic pathogenesis, however, has remained elusive. The recent success of deep brain stimulation (DBS) therapy applied to the subthalamic nucleus (STN) or the globus pallidus pars internus indicates that there are essential electrophysiological abnormalities in PD. Consistently, dopamine-deprived STN shows excessive burst discharges. This proves to be a central pathophysiological element causally linked to the locomotor deficits in PD, as maneuvers (such as DBS of different polarities) decreasing and increasing STN burst discharges would decrease and increase the locomotor deficits, respectively. STN bursts are not so autonomous but show a "relay" feature, requiring glutamatergic synaptic inputs from the motor cortex (MC) to develop. In PD, there is an increase in overall MC activities and the corticosubthalamic input is enhanced and contributory to excessive burst discharges in STN. The increase in MC activities may be relevant to the enhanced beta power in local field potentials (LFP) as well as the deranged motor programming at the cortical level in PD. Moreover, MC could not only drive erroneous STN bursts, but also be driven by STN discharges at specific LFP frequencies (~ 4 to 6 Hz) to produce coherent tremulous muscle contractions. In essence, PD may be viewed as a disorder with deranged rhythms in the cortico-subcortical re-entrant loops, manifestly including STN, the major component of the oscillating core, and MC, the origin of the final common descending motor pathways. The configurations of the deranged rhythms may play a determinant role in the symptomatic pathogenesis of PD, and provide insight into the mechanism underlying normal motor control. Therapeutic brain stimulation for PD and relevant disorders should be adaptively exercised with in-depth pathophysiological considerations for each individual patient, and aim at a final normalization of cortical discharge patterns for the best ameliorating effect on the locomotor and even non-motor symptoms.

Addressing Gaps for Health Systems Strengthening: A Public Perspective on Health Systems' Response towards COVID-19.

Strengthening the health systems through gaps identification is necessary to ensure sustainable improvements especially in facing a debilitating outbreak such as COVID-19. This study aims to explore public perspective on health systems' response towards COVID-19, and to identify gaps for health systems strengthening by leveraging on WHO health systems' building blocks. A qualitative study was conducted using open-ended questions survey among public followed by in-depth interviews with key informants. Opinions on Malaysia's health systems response towards COVID-19 were gathered. Data were exported to NVIVO version 12 and analysed using content analysis approach. The study identified various issues on health systems' response towards COVID-19, which were then mapped into health systems' building blocks. The study showed the gaps were embedded among complex interactions between the health systems building blocks. The leadership and governance building block had cross-cutting effects, and all building blocks influenced service deliveries. Understanding the complexities in fostering whole-systems strengthening through a holistic measure in facing an outbreak was paramount. Applying systems thinking in addressing gaps could help addressing the complexity at a macro level, including consideration of how an action implicates other building blocks and approaching the governance effort in a more adaptive manner to develop resilient systems.

Perception of the Movement Control Order during the COVID-19 Pandemic: A Qualitative Study in Malaysia.

Malaysia implemented its first Movement Control Order (MCO) during the early phase of the COVID-19 pandemic to slow the transmission of the virus. This study aimed to explore the public perception of the MCO implementation and people's experiences during this period. The study employed qualitative explorative in-depth interviews conducted with 23 Malaysian adults from various demographic backgrounds. Thematic analysis was performed using NVivo 12. Three main themes were identified: a period of information surge, heterogeneous emotional response, and attempts to adapt. During the MCO, the participants obtained information from multiple platforms. They suggested the need for clear and repeated instructions to avoid confusion and misinformation. They also acknowledged the importance of the MCO in breaking the chain of transmission and safeguarding high-risk groups; however, they also expressed that stricter enforcement from the authorities was warranted. The changes in the participants' work-life routines, lack of physical interaction, and uncertainty about their health and the economy due to the MCO negatively impacted their psychological states. Despite these challenges, the participants attempted to adapt to life under the MCO in different ways. The findings imply that during a crisis, the public tends to seek clear and reliable information, experience emotional turmoil, and adapt to changes. The MCO implementation can be improved through an effective communication strategy and efforts to battle misinformation.

Agrobacterium VirE2 Protein Modulates Plant Gene Expression and Mediates Transformation From Its Location Outside the Nucleus.

Agrobacterium effector protein VirE2 is important for plant transformation. VirE2 likely coats transferred DNA (T-DNA) in the plant cell and protects it from degradation. VirE2 localizes to the plant cytoplasm and interacts with several host proteins. Plant-expressed VirE2 can complement a virE2 mutant Agrobacterium strain to support transformation. We investigated whether VirE2 could facilitate transformation from a nuclear location by affixing to it a strong nuclear localization signal (NLS) sequence. Only cytoplasmic-, but not nuclear-localized, VirE2 could stimulate transformation. To investigate the ways VirE2 supports transformation, we generated transgenic Arabidopsis plants containing a virE2 gene under the control of an inducible promoter and performed RNA-seq and proteomic analyses before and after induction. Some differentially expressed plant genes were previously known to facilitate transformation. Knockout mutant lines of some other VirE2 differentially expressed genes showed altered transformation phenotypes. Levels of some proteins known to be important for transformation increased in response to VirE2 induction, but prior to or without induction of their corresponding mRNAs. Overexpression of some other genes whose proteins increased after VirE2 induction resulted in increased transformation susceptibility. We conclude that cytoplasmically localized VirE2 modulates both plant RNA and protein levels to facilitate transformation.

Adipogenesis in triple-negative breast cancer is associated with unfavorable tumor immune microenvironment and with worse survival.

Cancer-associated adipocytes are known to cause inflammation; however, the role of adipogenesis, the formation of adipocytes, in breast cancer is unclear. We hypothesized that intra-tumoral adipogenesis reflects a different cancer biology than abundance of intra-tumoral adipocytes. The Molecular Signatures Database Hallmark adipogenesis gene set of gene set variant analysis was used to quantify adipogenesis. Total of 5,098 breast cancer patients in multiple cohorts (training; GSE96058 (n = 3273), validation; TCGA (n = 1069), treatment response; GSE25066 (n = 508) and GSE20194 (n = 248)) were analyzed. Adipogenesis did not correlate with abundance of adipocytes. Adipogenesis was significantly lower in triple negative breast cancer (TNBC). Elevated adipogenesis was significantly associated with worse survival in TNBC, but not in the other subtypes. High adipogenesis TNBC was significantly associated with low homologous recombination deficiency, but not with mutation load. High adipogenesis TNBC enriched metabolism-related gene sets, but neither of cell proliferation- nor inflammation-related gene sets, which were enriched to adipocytes. High adipogenesis TNBC was infiltrated with low CD8+ T cells and high M2 macrophages. Although adipogenesis was not associated with neoadjuvant chemotherapy response, high adipogenesis TNBC was significantly associated with low expression of PD-L1 and PD-L2 genes, and immune checkpoint molecules index. In conclusion, adipogenesis in TNBC was associated with cancer metabolism and unfavorable tumor immune microenvironment, which is different from abundance of adipocytes.

Enhanced Primary Health Care Intervention: Perceived Sustainability and Challenges Among Implementers.

PURPOSE: This study aimed to assess and explore perceived sustainability and challenges of the intervention among Health Care Providers (HCPs) who were involved. METHODS: The study applied mixed-method embedded design to analyze both quantitative and qualitative data. Quantitative approach was used to evaluate sustainability perception from 20 intervention clinics via self-reported assessment form whereas qualitative data were obtained through in-depth interview (IDI) and focus group discussions (FGDs) 14 health care professionals participated in IDI session and were either care coordinators, liaison officers (LOs)/clinic managers, or medical officers-in-charge for the clinic's intervention. Nine FGDs conducted comprised 58 HCPs from various categories. RESULTS: HCPs from all the 20 clinics involved responded to each listed Enhanced Primary Healthcare (EnPHC) intervention components as being implemented but the perceived sustainability of these implementation varies between them. Quantitative feedback showed sustainable interventions included risk stratification, non-communicable disease (NCD) screening form, referral within clinics and hospitals, family health team (FHT), MTAC services and mechanisms and medical adherence status. Qualitative feedback highlighted implementation of each intervention components comes with its challenges, and most of it are related to inadequate resources and facilities in clinic. HCPs made initiatives to adapt based on clinical setting to implement the interventions at best level possible, whereby this seems to be one of the core values for sustainability. CONCLUSION: Overall perceptions among HCPs on sustainability of EnPHC interventions are highly influenced by current experiences with existing resources. Components perceived to have inadequate resources are seen as a challenge to sustain. It's crucial for stakeholders to understand implications affecting implementation process if concerns raised are not addressed and allocation of needed resources to ensure overall successfulness and long term sustainability.

Resilience buffers the effects of sleep problems on the trajectory of suicidal ideation from adolescence through young adulthood.

OBJECTIVES: To examine both the between-person and within-person effects of sleep problems on the trajectory of suicidal ideation from ages 14 to 22 and investigate whether resilience moderates the effects. Age and sex differences were explored in the main and interaction effects of sleep problems and resilience on suicidal ideation. METHODS: The study sample included 2491 adolescents (1260 males and 1231 females) who participated in a prospective study spanning 2009 through 2016 in northern Taiwan. Sex-stratified multilevel models were used to examine the between-person and within-person effects of sleep problems and the moderating effects of resilience on the trajectory of suicidal ideation in males and females. RESULTS: Across adolescents, higher levels of sleep problems contributed to an elevated risk of suicidal ideation for both sexes. Within individuals, a higher risk of suicidal ideation was observed when an adolescent's sleep problems exceeded their typical levels. The within-person effects of sleep problems were further determined to vary by age in males, with the effects gradually decreasing throughout late adolescence but increasing again in young adulthood. The buffering effects of resilience were only observed in females. The relationships between the within-person effects of sleep problems and suicidal ideation were only significant in female adolescents with low levels of resilience. CONCLUSIONS: Our findings extend the research by demonstrating both the between-person and within-person association between sleep problems and suicidal ideation. We further revealed age and sex differences in the within-person effects of sleep problems and the buffering effects of resilience. Prevention and intervention programs that target sleep problems could be tailored based on individuals' age, sex, and levels of resilience to prevent suicidal ideation.