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Glioblastomas exhibit vast inter- and intra-tumoral heterogeneity, complicating the development of effective therapeutic strategies. Current in vitro models are limited in preserving the cellular and mutational diversity of parental tumors and require a prolonged generation time. Here, we report methods for generating and biobanking patient-derived glioblastoma organoids (GBOs) that recapitulate the histological features, cellular diversity, gene expression, and mutational profiles of their corresponding parental tumors. GBOs can be generated quickly with high reliability and exhibit rapid, aggressive infiltration when transplanted into adult rodent brains. We further demonstrate the utility of GBOs to test personalized therapies by correlating GBO mutational profiles with responses to specific drugs and by modeling chimeric antigen receptor T cell immunotherapy. Our studies show that GBOs maintain many key features of glioblastomas and can be rapidly deployed to investigate patient-specific treatment strategies. Additionally, our live biobank establishes a rich resource for basic and translational glioblastoma research.
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Técnicas de Cultura de Células/métodos , Glioblastoma/metabolismo , Organoides/crescimento & desenvolvimento , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Bancos de Espécimes Biológicos , Feminino , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Modelos Biológicos , Organoides/metabolismo , Reprodutibilidade dos Testes , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
The recurrent multiwave nature of coronavirus disease 2019 (COVID-19) necessitates updating its symptomatology. We characterize the effect of variants on symptom presentation, identify the symptoms predictive and protective of death, and quantify the effect of vaccination on symptom development. With the COVID-19 cases reported up to August 25, 2022 in Hong Kong, an iterative multitier text-matching algorithm was developed to identify symptoms from free text. Multivariate regression was used to measure associations between variants, symptom development, death, and vaccination status. A least absolute shrinkage and selection operator technique was used to identify a parsimonious set of symptoms jointly associated with death. Overall, 70.9% (54 450/76 762) of cases were symptomatic with 102 symptoms identified. Intrinsically, the wild-type and delta variant caused similar symptoms among unvaccinated symptomatic cases, whereas the wild-type and omicron BA.2 subvariant had heterogeneous patterns, with seven symptoms (fatigue, fever, chest pain, runny nose, sputum production, nausea/vomiting, and sore throat) more frequent in the BA.2 cohort. With ≥2 vaccine doses, BA.2 was more likely than delta to cause fever among symptomatic cases. Fever, blocked nose, pneumonia, and shortness of breath remained jointly predictive of death among unvaccinated symptomatic elderly in the wild-type-to-omicron transition. Number of vaccine doses required for reducing occurrence varied by symptoms. We substantiate that omicron has a different clinical presentation compared to previous variants. Syndromic surveillance can be bettered with reduced reliance on symptom-based case identification, increased weighing on symptoms predictive of death in outcome prediction, individual-based risk assessment in care homes, and incorporating free-text symptom reporting.
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COVID-19 , Vacinas , Idoso , Humanos , SARS-CoV-2/genética , COVID-19/epidemiologia , Hong Kong/epidemiologia , FebreRESUMO
INTRODUCTION: Emerging evidence supports mindfulness as a potential psychotherapy for post-traumatic stress disorder (PTSD). Individuals with subthreshold PTSD experience significant impairment in their daily life and functioning due to PTSD symptoms, despite not meeting the full diagnostic criteria for PTSD in DSM-5. Mindfulness skills, including non-judgmental acceptance, attentional control and openness to experiences may help alleviate PTSD symptoms by targeting characteristics such as intensified memory processing, dysregulated hyperarousal, avoidance, and thought suppression. This trial aims to test the effects of mindfulness-based cognitive therapy (MBCT) when compared to an active control. METHOD AND ANALYSIS: This 1:1 randomised controlled trial will enroll 160 participants with PTSD symptoms in 2 arms (MBCT vs. Seeking Safety), with both interventions consisting of 8 weekly sessions lasting 2 h each week and led by certified instructors. Assessments will be conducted at baseline (T0), post-intervention (T1), and 3 months post-intervention (T2), with the primary outcome being PTSD symptoms measured by the PTSD checklist for DSM-5 (PCL-5) at T1. Secondary outcomes include depression, anxiety, attention, experimental avoidance, rumination, mindfulness, and coping skills. Both intention-to-treat and per-protocol analyses will be performed. Mediation analysis will investigate whether attention, experimental avoidance, and rumination mediate the effect of mindfulness on PTSD symptoms. DISCUSSION: The proposed study will assess the effectiveness of MBCT in improving PTSD symptoms. The findings are anticipated to have implications for various areas of healthcare and contribute to the enhancement of existing intervention guidelines for PTSD. TRIAL REGISTRATION NUMBER: ChiCTR2200061863.
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Atenção Plena , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/terapia , Transtornos de Estresse Pós-Traumáticos/psicologia , Atenção Plena/métodos , Adulto , Terapia Cognitivo-Comportamental/métodos , Feminino , Masculino , China , Pessoa de Meia-Idade , Resultado do Tratamento , População do Leste AsiáticoRESUMO
BACKGROUND: Depression is a global health priority. Maintaining and delaying depressive symptoms in older adults is a key to healthy aging. This study aimed to identify depressive symptom trajectories, predictors and mortality, while also exploring the relationship between air quality and depressive symptoms in older adults in the Hong Kong community over 14 years. METHODS: This study is a longitudinal study in Hong Kong. The target population was community-dwelling older adults over age 65. Depressive symptoms were measured by the Geriatric Depression Scale (GDS-15). Group-based trajectory model was used to identify heterogeneity in longitudinal changes over 14 years and examine the associations between baseline variables and trajectories for different cohort members using multinomial logistic regression. The Kaplan-Meier method was employed to conduct survival analysis and explore the variations in survival probabilities over time among different trajectory group. Linear mixed model was used to explore the relationship between air quality and depressive symptoms. RESULTS: A total of 2828 older adults were included. Three different trajectories of depressive symptoms in older people were identified: relatively stable (15.4%), late increase (67.1%) and increase (17.5%). Female, more number of chronic diseases, poor cognitive function, and poor health-related quality of life (HRQOL) were significantly associated with other less favorable trajectories compared with participants with stable levels of depressive symptoms. The late increase group had a lower mortality rate than the relatively stable and increased groups. Lower baseline ambient air pollutant exposure to NO2 over 14 years was significantly associated with fewer depressive symptoms. CONCLUSIONS: In this study, we found that a late increase in depressive symptoms was the predominant trend in older Chinese people in Hong Kong. Poorer HRQOL was predictive of less favorable trajectories of depressive symptoms. Ambient air pollution was associated with depressive symptoms. This novel observation strengthens the epidemiological evidence of longitudinal changes in depressive symptoms and associations with late-life exposure to air pollution.
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Poluição do Ar , Depressão , População do Leste Asiático , Idoso , Feminino , Humanos , Poluição do Ar/efeitos adversos , Estudos de Coortes , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/psicologia , Hong Kong/epidemiologia , Estudos Longitudinais , Qualidade de Vida , MasculinoRESUMO
BACKGROUND: This study aimed to identify the significant physical, psychological, and social determinants associated with EuroQuol-5D (EQ-5D) among Chinese older people with chronic musculoskeletal pain, and to evaluate how these determinants affected the five dimensions of EQ-5D. METHOD: This is a cross-sectional study. Data were collected through a cohort involving 946 community-dwelling older people aged ≥ 60 with chronic musculoskeletal pain in Hong Kong. Selected independent variables were categorized into physical, psychological, and social domains. Physical variables included age, sex, body mass index (BMI), pain severity score, number of pain regions, the most painful site, and the number of comorbidities. Psychological variables included depression level measured using the 9-question Patient Health Questionnaire (PHQ-9), and anxiety level measured using the Generalized Anxiety Disorder Assessment (GAD-7). Social variables included living, marital, and social welfare recipient's status. The dependent variables comprised the index scores and the five dimensions of the EQ-5D descriptive system. Ordinal least squares (OLS) model and logistic regression model were used for data analysis. RESULTS: The mean age of the participants was 67.1 (SD = 5.1), with 77.6% being female. Higher pain severity scores (beta (ß) coefficient =-0.044, P < 0.001), depression scores (ß=-0.007, P < 0.001) and higher anxiety scores (ß=-0.01, P < 0.001) were associated with lower EQ-5D index scores. Specifically, knee pain (ß=-0.061, P < 0.001) was significantly associated with lower EQ-5D index scores. Participants with higher pain severity and depression scores were more likely to report problems in most EQ-5D dimensions. Participants with anxiety primarily faced challenges related to mood, and those with knee pain were more likely to have problems with mobility and daily activities. CONCLUSION: Among the selected determinants in our study, pain intensity, depression, anxiety, and knee pain were identified as key determinants associated with reduced HRQoL in older Chinese people with chronic musculoskeletal pain. Each of these determinants showed distinct associations with different dimensions of the EQ-5D, potentially informed resource allocation and the development of targeted interventions to improve the overall HRQoL of this specific population.
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Dor Crônica , População do Leste Asiático , Dor Musculoesquelética , Idoso , Feminino , Humanos , Masculino , Dor Crônica/diagnóstico , Dor Crônica/epidemiologia , Estudos Transversais , Nível de Saúde , Dor Musculoesquelética/diagnóstico , Dor Musculoesquelética/epidemiologia , Qualidade de Vida/psicologia , Inquéritos e Questionários , Pessoa de Meia-IdadeRESUMO
Parameter estimation for nonlinear dynamic system models, represented by ordinary differential equations (ODEs), using noisy and sparse data, is a vital task in many fields. We propose a fast and accurate method, manifold-constrained Gaussian process inference (MAGI), for this task. MAGI uses a Gaussian process model over time series data, explicitly conditioned on the manifold constraint that derivatives of the Gaussian process must satisfy the ODE system. By doing so, we completely bypass the need for numerical integration and achieve substantial savings in computational time. MAGI is also suitable for inference with unobserved system components, which often occur in real experiments. MAGI is distinct from existing approaches as we provide a principled statistical construction under a Bayesian framework, which incorporates the ODE system through the manifold constraint. We demonstrate the accuracy and speed of MAGI using realistic examples based on physical experiments.
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BACKGROUND: Virtual reality (VR) in different immersive conditions has been increasingly used as a nonpharmacological method for managing chronic musculoskeletal pain. OBJECTIVE: We aimed to assess the effectiveness of VR-assisted active training versus conventional exercise or physiotherapy in chronic musculoskeletal pain and to analyze the effects of immersive versus nonimmersive VR on pain outcomes. METHODS: This systematic review of randomized control trials (RCTs) searched PubMed, Scopus, and Web of Science databases from inception to June 9, 2024. RCTs comparing adults with chronic musculoskeletal pain receiving VR-assisted training were included. The primary outcome was pain intensity; secondary outcomes included functional disability and kinesiophobia. Available data were pooled in a meta-analysis. Studies were graded using the Cochrane Risk-of-Bias Tool version 2. RESULTS: In total, 28 RCTs including 1114 participants with some concerns for a high risk of bias were identified, and 25 RCTs were included in the meta-analysis. In low back pain, short-term outcomes measured post intervention showed that nonimmersive VR is effective in reducing pain (standardized mean difference [SMD] -1.79, 95% CI -2.72 to -0.87; P<.001), improving disability (SMD -0.44, 95% CI -0.72 to -0.16; P=.002), and kinesiophobia (SMD -2.94, 95% CI -5.20 to -0.68; P=.01). Intermediate-term outcomes measured at 6 months also showed that nonimmersive VR is effective in reducing pain (SMD -8.15, 95% CI -15.29 to -1.01; P=.03), and kinesiophobia (SMD -4.28, 95% CI -8.12 to -0.44; P=.03) compared to conventional active training. For neck pain, immersive VR reduced pain intensity (SMD -0.55, 95% CI -1.02 to -0.08; P=.02) but not disability and kinesiophobia in the short term. No statistical significances were detected for knee pain or other pain regions at all time points. In addition, 2 (8%) studies had a high risk of bias. CONCLUSIONS: Both nonimmersive and immersive VR-assisted active training is effective in reducing back and neck pain symptoms. Our study findings suggest that VR is effective in alleviating chronic musculoskeletal pain. TRIAL REGISTRATION: PROSPERO CRD42022302912; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=302912.
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Dor Crônica , Dor Musculoesquelética , Realidade Virtual , Humanos , Dor Musculoesquelética/terapia , Dor Musculoesquelética/psicologia , Dor Crônica/terapia , Dor Crônica/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia de Exposição à Realidade Virtual/métodos , Adulto , Terapia por Exercício/métodos , Dor Lombar/terapia , Dor Lombar/psicologia , Masculino , FemininoRESUMO
Infectious diseases, including COVID-19, are crucial public health issues and may lead to considerable fear among the general public and stigmatization of, and discrimination against, specific populations. This meta-analysis aimed to estimate the pooled prevalence of stigma in infectious disease epidemics. We systematically searched PubMed, PsycINFO, Embase, MEDLINE, Web of Science, and Cochrane databases since inception to June 08, 2021, and reported the prevalence of stigma towards people with infectious diseases including SARS, H1N1, MERS, Zika, Ebola, and COVID-19. A total of 50 eligible articles were included that contributed 51 estimates of prevalence in 92722 participants. The overall pooled prevalence of stigma across all populations was 34% [95% CI: 28-40%], including enacted stigma (36% [95% CI: 28-44%]) and perceived stigma (31% [95% CI: 22-40%]). The prevalence of stigma in patients, community population, and health care workers, was 38% [95% CI: 12- 65%], 36% [95% CI: 28-45%], and 30% [95% CI: 20-40%], respectively. The prevalence of stigma in participants from low- and middle-income countries was 37% [95% CI: 29-45%], which is higher than that from high-income countries (27% [95% CI: 18-36%]) though this difference was not statistically significant. A similar trend of prevalence of stigma was also observed in individuals with lower education (47% [95% CI: 23-71%]) compared to higher education level (33% [95% CI: 23-4%]). These findings indicate that stigma is a significant public health concern, and effective and comprehensive interventions are needed to counteract the damaging effects of the infodemics during infectious disease epidemics, including COVID-19, and reduce infectious disease-related stigma.
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COVID-19 , Doenças Transmissíveis , Vírus da Influenza A Subtipo H1N1 , Infecção por Zika virus , Zika virus , Humanos , PrevalênciaRESUMO
PURPOSE OF REVIEW: Numerous observations have indicated an increased risk of developing various types of cancers, as well as cancer-related mortality, among patients with diabetes and obesity. The purpose of this review is to outline multiple-cancer screening among these patients through a team-based approach and to present the findings of a pioneering integrated care program designed for patients with obesity with a specific emphasis on cancer prevention. RECENT FINDINGS: A community-based multi-cancer prevention program, which provides all services in one location and utilizes team-based approaches, is reported to be feasible and has the potential to enhance the uptake rate of multiple cancers screening among patients with diabetes and obesity. The team-based approach is a commonly utilized method for managing patients with diabetes, obesity, and cancer, and has been shown to be efficacious. Nevertheless, research on team-based cancer screening programs for patients with diabetes and obesity remains limited. Providing a comprehensive screening for colorectal, prostate, and breast cancer, as well as metabolic syndrome, during a single clinic visit has been proven effective and well-received by participants.
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Diabetes Mellitus , Síndrome Metabólica , Neoplasias , Masculino , Humanos , Neoplasias/complicações , Neoplasias/epidemiologia , Diabetes Mellitus/epidemiologia , Obesidade/complicações , Obesidade/epidemiologiaRESUMO
INTRODUCTION: There is a lack of studies evaluating mindfulness-based interventions for children with attention-deficit hyperactivity disorder (ADHD) compared with an evidence-based control. This randomized controlled trial (RCT) evaluated the effects of mindfulness for youth (MYmind) in improving children's attention, behavior, and parent-related outcomes versus cognitive behavioral therapy (CBT). METHODS: A total of 138 families of children with ADHD aged 8-12 years were recruited from the community with 69 randomized to MYmind and 69 to CBT. Participants were assessed at baseline, immediately after intervention, at 3 months and 6 months. The primary outcome was the attention score of the Sky Search subtest of the Test of Everyday Attention for Children (TEA-Ch). Secondary outcomes were child behavior and parent-related assessments. Linear mixed models were used to assess the efficacy of MYmind compared with CBT. RESULTS: Both MYmind and CBT significantly improved children's attention score at 6 months (MYmind: ß = 1.48, p = 0.013, Cohen's d = 0.32; CBT: ß = 1.46, p = 0.008, d = 0.27). There were significant within-group improvements in most secondary outcomes. No significant difference was shown for both primary or secondary outcomes between the two arms at any time point. CONCLUSIONS: Both MYmind and CBT appeared to improve children's attention and behavior outcomes, although no difference was found between these two interventions. This is the largest RCT so far comparing MYmind and CBT although there was loss of follow-up assessments during the pandemic. Further RCTs adopting a non-inferiority design are needed to validate the results.
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Transtorno do Deficit de Atenção com Hiperatividade , Terapia Cognitivo-Comportamental , Atenção Plena , Comportamento Problema , Criança , Humanos , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Atenção Plena/métodos , Terapia Cognitivo-Comportamental/métodos , Pais/psicologiaRESUMO
BACKGROUND: Hong Kong has a relatively low incidence rate of COVID-19 across the globe. Nevertheless, ethnic minorities in Hong Kong, especially South Asians (SAs) and Southeast Asians (SEAs), face numerous physical, mental, social, economic, cultural and religious challenges during the pandemic. This study explores the experiences of SA and SEA women in a predominantly Chinese metropolitan city. METHODS: Ten SA and SEA women were recruited and face-to-face interviews were conducted. Questions about participants' daily life experience, physical and mental health conditions, economic situation and social interaction amid COVID-19 pandemic were asked to assess the impact of COVID-19. RESULTS: SAs and SEAs have a distinctive family culture, and women experienced significant physical and mental impact of COVID-19 due to their unique gender role in the family. In addition to taking care of their family in Hong Kong, SA and SEA women also had to mentally and financially support family members residing in their home countries. Access to COVID-related information was restricted due to language barrier. Public health measures including social distancing imposed extra burden on ethnic minorities with limited social and religious support. CONCLUSIONS: Even when COVID-19 incidence rate is relatively low in Hong Kong, the pandemic made life even more challenging for SAs and SEAs, which is a community already struggling with language barriers, financial woes, and discrimination. This in turn could have led to greater health inequalities. Government and civil organizations should take the social determinants of health inequalities into account when implementing COVID-19-related public health policies and strategies.
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COVID-19 , Humanos , Feminino , COVID-19/epidemiologia , Pandemias , Hong Kong/epidemiologia , População do Sudeste Asiático , Grupos Minoritários/psicologiaRESUMO
INTRODUCTION: Although social isolation is associated with premature death and somatic and mental diseases, evidence of its long-term effect on sarcopenia is scarce. This study aimed to examine the longitudinal association between social isolation and possible sarcopenia. METHODS: We extracted baseline and 4-year follow-up data from the China Health and Retirement Longitudinal Study and included participants aged 45 years or above. Social isolation was measured by factors including living alone, marital status, frequency of contact with adult children and friends, and participation in social activity. The change in social isolation from baseline to follow-up was classified into stable, progressive, and regressive groups. Possible sarcopenia was detected using the handgrip strength and five-time chair-stand test. Using mixed-effects logistic regression, we studied the effect of baseline isolation and the change in isolation status on possible sarcopenia at a 4-year follow-up. RESULTS: A total of 5,289 participants aged 45-90 years and without possible sarcopenia at baseline were included. After 4 years, possible sarcopenia was detected in 21.7% (1,146/5,289) of the participants. Compared with the low social isolation group, the middle (OR = 1.53, 95% confidence interval [CI] = 1.16-2.04, p = 0.003) and high social isolation groups (OR = 1.65, 95% CI = 1.26-2.18, p < 0.001) were associated with a higher risk of possible sarcopenia. Being not married/cohabiting (OR = 1.58, 95% CI = 1.19-2.10, p = 0.002), lack of contact with children (OR = 1.86, 95% CI = 1.21-2.85, p = 0.004), and lack of social activities (OR = 1.26, 95% CI = 1.04-1.53, p = 0.019) were associated with an increased risk of possible sarcopenia. Compared with the stable social isolation group, the progressive group was associated with a greater risk of possible sarcopenia (OR = 1.51, 95% CI = 1.17-1.95, p = 0.001). CONCLUSIONS: Social isolation is associated with an increased risk of possible sarcopenia. Progressive social isolation further elevates the risk. The most vulnerable groups are middle-aged and older people who live alone, are not socially active, and lack contact with their children.
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Sarcopenia , Humanos , Pessoa de Meia-Idade , Idoso , Sarcopenia/epidemiologia , Sarcopenia/etiologia , Estudos Longitudinais , Força da Mão , Isolamento Social , China/epidemiologiaRESUMO
BACKGROUND: The use of online and mobile internet and social media has been increasing in healthcare service delivery. However, there is limited literature on the acceptance and use of online health services for older adults with multimorbidity who require more medical care and assistance. This study aims to explore the use of social media in older adults with multimorbidity in Hong Kong primary care and to assess the feasibility and usage of online health services in this population, including satisfaction, preference, and problems encountered. METHODS: This is a cross-sectional study among older adults with multimorbidity conducted between November 2020 and March 2021 in a Hong Kong primary care programme. Online and face-to-face services were offered based on the needs of the participants. Demographic characteristics and health conditions were assessed at baseline. Participants using online services were invited to complete a feedback questionnaire. RESULTS: The study included 752 participants, of which 66.1% use social media every day. Participants who declined to use online services were found to be significantly older, live alone, have lower income, have social security assistance, have greater cognitive decline, and be less depressed (p < 0.05). Non-responders to the online questionnaire had fewer years of education and greater cognitive decline (p < 0.05). The median satisfaction with the online services was 8 (interquartile range: 7, 9), and 14.6% of the participants preferred online more than face-to-face services. Lower education levels, fewer internet connection issues, and more self-efficacy on mobile apps were associated with a higher level of online satisfaction after adjustment (p < 0.05). Fewer internet connection issues and more self-efficacy on mobile apps were associated with participants' preference for online services (p < 0.05). CONCLUSIONS: More than half of Hong Kong older adults with multimorbidity in primary care use social media daily. Internet connection issues can be a significant barrier to the usage of online services in this population. Prior use and training can be beneficial to enhance use and satisfaction in older adults.
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COVID-19 , Humanos , Idoso , COVID-19/epidemiologia , COVID-19/terapia , Multimorbidade , Hong Kong/epidemiologia , Estudos Transversais , Serviços de Saúde , Satisfação Pessoal , Atenção Primária à SaúdeRESUMO
BACKGROUND: In addition to high vaccination levels, COVID-19 control requires uptake and continued adherence to personal hygiene and social distancing behaviors. It is unclear whether residents of a city with successive experience in worldwide pandemics such as SARS, would quickly adopt and maintain preventive behaviors. METHODS: A population-based, longitudinal telephone survey was conducted between in first local wave of the COVID-19 pandemic (April 2020) and third local wave (December 2020) (n = 403). The study examined factors associated with personal hygiene and social distancing behavior fatigue, as measured by reduced adherence. RESULTS: Over 9 months, face mask use increased (96.5-100%, p < 0.001). Although habitual hand hygiene remained unchanged (92.0%), blue collar workers and non-working individuals showed higher risk of hand hygiene fatigue. There was a decline (p < 0.05) in avoidance of social gatherings (81.1 to 70.7%), avoidance of public places (52.9-27.5%) and avoidance of international travel (81.9-77.4%) even with rising caseloads. Lowered perception of COVID-19 disease severity was associated with decreased avoidance of social gatherings and public places while lower education was associated with decline in avoidance of social gatherings. CONCLUSION: Even in regions with past pandemic experience, maintaining social distancing behaviors during a protracted pandemic remains a major public health challenge.
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COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Hong Kong/epidemiologia , SARS-CoV-2 , Estudos LongitudinaisRESUMO
BACKGROUND: HIV testing is the cornerstone of strategies for achieving the fast-track target to end the AIDS epidemic by 2030. Self-testing has been proven to be an effective health intervention for men who have sex with men (MSM). While social network-based approaches for distributing HIV self-tests are recommended by the World Health Organization, their implementation consists of multiple steps that need to be properly evaluated. OBJECTIVE: This study aimed to assess the implementation cascade of a social network-based HIV self-test approach for reaching MSM who had never undergone testing in Hong Kong. METHODS: This is a cross-sectional study. Seed MSM participants were recruited through different web-based channels, who in turn invited their peers to participate in this study. A web-based platform was set up to support the recruitment and referral process. Participants could request for an oral fluid or a finger-prick HIV self-test, with or without real-time support, after completing a self-administered questionnaire. Referrals could be made upon uploading the test result and passing the web-based training. Characteristics of participants completing each of these steps and their preferences for the type of HIV self-test were evaluated. RESULTS: A total of 463 MSM were recruited, including 150 seeds. Participants recruited by seeds were less likely to have previously been tested for HIV (odds ratio [OR] 1.80, 95% CI 1.06-3.04, P=.03) and have lower confidence in performing self-tests (OR 0.66, 95% CI 0.45-0.99, P=.045). Almost all (434/442, 98%) MSM who completed the questionnaire requested a self-test, of whom 82% (354/434) had uploaded their test results. Participants requesting support were new to self-testing (OR 3.65, 95% CI 2.10-6.35, P<.001) and less confident in carrying out the self-test correctly (OR 0.35, 95% CI 0.22-0.56, P<.001). More than half (216/354, 61%) of the eligible participants initiated the referral process by attempting the web-based training with a passing rate of 93% (200/216). They were more likely to have sought sex partners (OR 2.20, 95% CI 1.14-4.25, P=.02), especially through location-based networking apps (OR 2.13, 95% CI 1.31-3.49, P=.002). They also gave higher usability scores along the implementation cascade (median 81 vs 75, P=.003). CONCLUSIONS: The social network approach was effective in diffusing HIV self-tests in the MSM community and reaching nontesters. Support and option to choose a preferable type of self-test are essential to address users' individual needs when delivering HIV self-tests. A positive user experience throughout the processes along the implementation cascade is vital to transform a tester into a promoter. TRIAL REGISTRATION: ClinicalTrials.gov NCT04379206; https://clinicaltrials.gov/ct2/show/NCT04379206.
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Infecções por HIV , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , Autoteste , Estudos Transversais , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Teste de HIV , Rede SocialRESUMO
Hypertension (HT) continues to be a leading cause of cardiovascular death and an enormous burden on the healthcare system. Although telemedicine may provide improved blood pressure (BP) monitoring and control, it remains unclear whether it could replace face-to-face consultations in patients with optimal BP control. We hypothesized that an automatic drug refill coupled with a telemedicine system tailored to patients with optimal BP would lead to non-inferior BP control. In this pilot, multicenter, randomized control trial (RCT), participants receiving anti-HT medications were randomly assigned (1:1) to either the telemedicine or usual care group. Patients in the telemedicine group measured and transmitted their home BP readings to the clinic. The medications were refilled without consultation when optimal control (BP < 135/85 mmHg) was confirmed. The primary outcome of this trial was the feasibility of using the telemedicine app. Office and ambulatory BP readings were compared between the two groups at the study endpoint. Acceptability was assessed through interviews with the telemedicine study participants. Overall, 49 participants were recruited in 6 months and retention rate was 98%. Participants from both groups had similar BP control (daytime systolic BP: 128.2 versus 126.9 mmHg [telemedicine vs. usual care], p = 0.41) and no adverse events. Participants in the telemedicine group had fewer general outpatient clinic attendances (0.8 vs. 2, p < 0.001). Interviewees reported that the system was convenient, timesaving, cost saving, and educational. The system could be safely used. However, the results must be verified in an adequately powered RCT. Trial registration: NCT04542564.
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Hipertensão , Telemedicina , Humanos , Projetos Piloto , Estudos de Viabilidade , Hipertensão/tratamento farmacológico , Telemedicina/métodos , Pressão Sanguínea , Atenção Primária à Saúde , Monitorização Ambulatorial da Pressão Arterial/métodosRESUMO
The COVID-19 pandemic has substantially induced worries and affected individual mental health and subjective well-being. Nonetheless, a high level of social capital could potentially protect individuals who suffer from mental health problems and thus promote their subjective well-being, especially under the social distancing policies during the pandemic. To this end, based on a random sample of 1053 Hong Kong adults, structural equation modeling was applied to study the path relationships between the worries of COVID-19, social capital, mental health problems, and subjective well-being. The study found that worries during the pandemic were associated with mental health and subjective well-being, through social capital as a mediator. Moreover, social capital exhibited a stronger influence on mental health and subjective well-being in the economically inactive group than in the economically active group. This study highlights the important role of social capital during the COVID-19 pandemic. While Hong Kong's COVID-19 response has primarily focused on disease prevention, it must be noted that social services and mutual-help activities are also crucial for people to withstand the crisis.
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The SARS-CoV-2 spike (S) protein facilitates viral infection, and has been the focus of many structure determination efforts. Its flexible loop regions are known to be involved in protein binding and may adopt multiple conformations. This article identifies the S protein loops and studies their conformational variability based on the available Protein Data Bank structures. While most loops had essentially one stable conformation, 17 of 44 loop regions were observed to be structurally variable with multiple substantively distinct conformations based on a cluster analysis. Loop modeling methods were then applied to the S protein loop targets, and the prediction accuracies discussed in relation to the characteristics of the conformational clusters identified. Loops with multiple conformations were found to be challenging to model based on a single structural template.
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COVID-19/virologia , SARS-CoV-2/química , Glicoproteína da Espícula de Coronavírus/química , Análise por Conglomerados , Humanos , Modelos Moleculares , Conformação ProteicaRESUMO
BACKGROUND & AIMS: Extracellular vesicles (EVs) play a pivotal role in connecting tumor cells with their local and distant microenvironments. Herein, we aimed to understand the role (on a molecular basis) patient-derived EVs play in modulating cancer stemness and tumorigenesis in the context of hepatocellular carcinoma (HCC). METHODS: EVs from patient sera were isolated, quantified and characterized. The EVs were vigorously tested, both in vitro and in vivo, through various functional assays. Proteomic analysis was performed to identify the functional components of EVs. The presence and level of polymeric immunoglobulin receptor (pIgR) in circulating EVs and tumor and non-tumorous tissues of patients with HCC were determined by ELISA, immunoblotting, immunohistochemistry and quantitative PCR. The functional role and underlying mechanism of EVs with enhanced pIgR expression were elucidated. Blockade of EV-pIgR with neutralizing antibody was performed in nude mice implanted with patient-derived tumor xenografts (PDTXs). RESULTS: Circulating EVs from patients with late-stage HCC (L-HCC) had significantly elevated pIgR expression compared to the EVs released by control individuals. The augmenting effect of L-HCC-EVs on cancer stemness and tumorigenesis was hindered by an anti-pIgR antibody. EVs enriched with pIgR consistently promoted cancer stemness and cancerous phenotypes in recipient cells. Mechanistically, EV-pIgR-induced cancer aggressiveness was abrogated by Akt and ß-catenin inhibitors, confirming that the role of EV-pIgR depends on the activation of the PDK1/Akt/GSK3ß/ß-catenin signaling axis. Furthermore, an anti-pIgR neutralizing antibody attenuated tumor growth in mice implanted with PDTXs. CONCLUSIONS: This study illustrates a previously unknown role of EV-pIgR in regulating cancer stemness and aggressiveness: EV-pIgR activates PDK1/Akt/GSK3ß/ß-catenin signaling cascades. The blockade of the intercellular communication mediated by EV-pIgR in the tumor microenvironment may provide a new therapeutic strategy for patients with cancer. LAY SUMMARY: The World Health Organization estimates that more than 1 million patients will die from liver cancer, mostly hepatocellular carcinoma (HCC), in 2030. Understanding the underlying mechanism by which HCC acquires aggressive attributes is crucial to improving the diagnosis and treatment of patients. Herein, we demonstrated that nanometer-sized extracellular vesicles released by tumors promote cancer stemness and tumorigenesis. Within these oncogenic vesicles, we identified a key component that functions as a potent modulator of cancer aggressiveness. By inhibiting this functional component of EVs using a neutralizing antibody, tumor growth was profoundly attenuated in mice. This hints at a potentially effective therapeutic alternative for patients with cancer.
Assuntos
Carcinoma Hepatocelular , Vesículas Extracelulares , Neoplasias Hepáticas , Receptores de Imunoglobulina Polimérica , Animais , Anticorpos Neutralizantes , Carcinogênese/metabolismo , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Vesículas Extracelulares/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , Neoplasias Hepáticas/genética , Camundongos , Camundongos Nus , Proteômica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Imunoglobulina Polimérica/metabolismo , Microambiente Tumoral , beta Catenina/genéticaRESUMO
Background Radiogenomics of pediatric medulloblastoma (MB) offers an opportunity for MB risk stratification, which may aid therapeutic decision making, family counseling, and selection of patient groups suitable for targeted genetic analysis. Purpose To develop machine learning strategies that identify the four clinically significant MB molecular subgroups. Materials and Methods In this retrospective study, consecutive pediatric patients with newly diagnosed MB at MRI at 12 international pediatric sites between July 1997 and May 2020 were identified. There were 1800 features extracted from T2- and contrast-enhanced T1-weighted preoperative MRI scans. A two-stage sequential classifier was designed-one that first identifies non-wingless (WNT) and non-sonic hedgehog (SHH) MB and then differentiates therapeutically relevant WNT from SHH. Further, a classifier that distinguishes high-risk group 3 from group 4 MB was developed. An independent, binary subgroup analysis was conducted to uncover radiomics features unique to infantile versus childhood SHH subgroups. The best-performing models from six candidate classifiers were selected, and performance was measured on holdout test sets. CIs were obtained by bootstrapping the test sets for 2000 random samples. Model accuracy score was compared with the no-information rate using the Wald test. Results The study cohort comprised 263 patients (mean age ± SD at diagnosis, 87 months ± 60; 166 boys). A two-stage classifier outperformed a single-stage multiclass classifier. The combined, sequential classifier achieved a microaveraged F1 score of 88% and a binary F1 score of 95% specifically for WNT. A group 3 versus group 4 classifier achieved an area under the receiver operating characteristic curve of 98%. Of the Image Biomarker Standardization Initiative features, texture and first-order intensity features were most contributory across the molecular subgroups. Conclusion An MRI-based machine learning decision path allowed identification of the four clinically relevant molecular pediatric medulloblastoma subgroups. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Chaudhary and Bapuraj in this issue.