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Background: Although the necessity and benefits of having the open and public discussion about suicide have been recognized, youths’ opinions regarding such discussion remain unknown. Aims: To explore youths’ attitudes toward open suicide discussion, particularly concerning their preference of discussion contexts and impacts of Internet use. Method: This exploratory sequential mixed-methods study targeted Hong Kong youths aged 15 to 19. A total of six focus groups and 12 individual interviews were held ( N = 40). Topics included adolescents’ views of open suicide discussion, concerns, perceived benefits, and preferred contexts. The questionnaire survey ( N = 1,676) was conducted subsequently to investigate the prevalence of youths’ perspectives on public discussion of suicide and relationships with discussion contexts, use of social media platforms, and motivations of online expression. Results: Qualitative findings revealed three types of attitudes toward open suicide discussion: reluctance, support, and indifference. Major barriers included cultural norms, topic sensitivity, privacy concerns, contagion effect, fear of embarrassment, and unpleasant experiences in school programs. Results of quantitative analyses showed that reluctance was the dominant attitude among adolescents, and taboo was the top concern. Variations in youths’ attitudes were related to gender, school academic banding, and suicide-related experiences. Notably, adolescents who had been exposed to suicide messages in contexts of peer networks and online platforms were more likely to endorse open suicide discussion. In addition, an increased likelihood of engaging in public suicide discussion was associated with the use of Instagram, WhatsApp, and Snapchat, and the motive of ‘expressing emotions and opinions’ online. Conclusions: Our results indicated a prevalent rejection among adolescents toward open suicide discussion, suggesting the issue of stigma, the need for tailored programs, the value of appropriate contexts, and the impact of Internet use. These findings may facilitate the development of school-based suicide prevention initiatives and the efficacy of online services for suicide-related communication.

Oncomine analysis shows IRAK1 overexpression in cancers of breast, bladder, brain, colon, lung and ovary

Suppl Materials, Figure Legends 1-7 and Tables showing clinico-pathological correlation of endogenous IRAK1, the effect of IRAK1 alternations on tumorigenicity as well as pathway analysis of HCC cells with or without IRAK1 suppressed

Supplementary Fig. 1. Transcriptional upregulation of Cav1 expression by HIF-1α in HCC cells under hypoxia. Supplementary Fig. 2. Cav1 expression is regulated by HIF1α and is HIF2 independent. Supplementary Fig. 3. Hypoxia promotes HCC cell motility and invasiveness in vitro. Supplementary Fig. 4. Hypoxia promotes HCC metastasis in animal model. Supplementary Fig. 5. Validation of S100P expression in Cav1 knockdown stable clones. Supplementary Fig. 6. Restoration of S100P expression in Cav1 stable knockdown clones. Supplementary Fig. 7. Analysis of sh-8001/S100P cells using orthotopic liver implantation subjected to hepatic artery ligation (HAL). Supplementary Fig. 8. Expression of S100P in stable knockdown clones. Supplementary Table 1. Deregulation of genes determined by microarray profiles of paired non-target control (sh-Ctl) and Cavl knockdown cells (sh-8001) with fold change greater than 2.

Frequent relapse and drug resistance in patients with hepatocellular carcinoma (HCC) can be attributed to the existence of tumor-initiating cells (TIC) within the tumor bulk. Therefore, targeting liver TICs may improve the prognosis of these patients. From transcriptome sequencing of 16 pairs of clinical HCC samples, we report that interleukin-1 receptor-associated kinase 1 (IRAK1) in the TLR/IRAK pathway is significantly upregulated in HCC. IRAK1 overexpression in HCC was further confirmed at the mRNA and protein levels and correlated with advanced tumor stages and poor patient survival. Interestingly, IRAK4, an upstream regulator of IRAK1, was also consistently upregulated. IRAK1 regulated liver TIC properties, including self-renewal, tumorigenicity, and liver TIC marker expression. IRAK1 inhibition sensitized HCC cells to doxorubicin and sorafenib treatment in vitro via suppression of the apoptotic cascade. Pharmacological inhibition of IRAK1 with a specific IRAK1/4 kinase inhibitor consistently suppressed liver TIC populations. We identified aldo-keto reductase family 1 member 10 (AKR1B10) as a novel downstream target of IRAK1, which was found to be overexpressed in HCC and significantly correlated with IRAK1 expression. Knockdown of AKR1B10 negated IRAK1-induced TIC functions via modulation of the AP-1 complex. Inhibition of IRAK1/4 inhibitor in combination with sorafenib synergistically suppressed tumor growth in an HCC xenograft model. In conclusion, targeting the IRAK4/IRAK1/AP-1/AKR1B10 signaling pathway may be a potential therapeutic strategy against HCC.Significance: IRAK4/IRAK1/AP-1/AKR1B10 signaling pathway regulates cancer stemness and drug resistance and may be a novel therapeutic target in HCC. Cancer Res; 78(9); 2332–42. ©2018 AACR.

Stanniocalcin 1 (STC1), a secreted protein, is upregulated in human cancers including hepatocellular carcinoma (HCC). While most HCCs develop from chronic liver disease, which involves progressive parenchymal injury and fibrosis, the role of STC1 in this preneoplastic stage remains poorly understood. In this study we investigated the clinical relevance and functional significance of secreted STC1 in liver fibrosis. To this end, the STC1 level was determined in the serum samples of chronic hepatitis B patients and correlated with the degree of liver fibrosis. Diagnostic performance of STC1 was analysed by area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value, and negative predictive value. The results were compared with other well-characterised serum biomarkers for liver fibrosis: Aspartate transaminase to Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4). The functional role of STC1 was interrogated by in vitro experiments using cell line models. Expression of fibrogenic markers was quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Our results showed that the serum STC1 level in chronic hepatitis B patients was positively correlated with the degree of liver fibrosis and showed a stepwise increase in accordance with the severity of fibrosis. The AUROCs for detecting significant fibrosis (9.0 kPa) and cirrhosis (12.0 kPa) was 0.911 and 0.880, respectively. STC1 demonstrated a superior specificity and positive predictive value when compared to APRI and FIB-4. Consistent with this, STC1 was elevated in the liver tissues and sera of CCl

This study investigates the effect of political orientation on public trust in Hong Kong’s courts. In measuring institutional legitimacy, the prior literature, predominantly written in the US context, largely focuses on the police force and demographic factors. Building on previous studies of the role of procedural fairness in determining the degree of institutional trust, this article contributes to a strand of developing literature which highlights how political ideology may color one’s views of legal authorities. Based on a 2020 survey on public trust in Hong Kong’s courts, this article presents a sobering portrayal of a hitherto “most trustworthy institution” in Hong Kong’s deeply polarized and rapidly changing political environment.

BackgroundLittle is known about the effects of physical exercise on sleep-dependent consolidation of procedural memory in individuals with schizophrenia. We conducted a randomized controlled trial (RCT) to assess the effectiveness of physical exercise in improving this cognitive function in schizophrenia.MethodsA three-arm parallel open-labeled RCT took place in a university hospital. Participants were randomized and allocated into either the high-intensity-interval-training group (HIIT), aerobic-endurance exercise group (AE), or psychoeducation group for 12 weeks, with three sessions per week. Seventy-nine individuals with schizophrenia spectrum disorder were contacted and screened for their eligibility. A total of 51 were successfully recruited in the study. The primary outcome was sleep-dependent procedural memory consolidation performance as measured by the finger-tapping motor sequence task (MST). Assessments were conducted during baseline and follow-up on week 12.ResultsThe MST performance scored significantly higher in the HIIT (n = 17) compared to the psychoeducation group (n = 18) after the week 12 intervention (p < 0.001). The performance differences between the AE (n = 16) and the psychoeducation (p = 0.057), and between the AE and the HIIT (p = 0.999) were not significant. Yet, both HIIT (p < 0.0001) and AE (p < 0.05) showed significant within-group post-intervention improvement.ConclusionsOur results show that HIIT and AE were effective at reverting the defective sleep-dependent procedural memory consolidation in individuals with schizophrenia. Moreover, HIIT had a more distinctive effect compared to the control group. These findings suggest that HIIT may be a more effective treatment to improve sleep-dependent memory functions in individuals with schizophrenia than AE alone.

Background/aim The aim of this study was to describe the clinicopathological features of hepatocellular carcinoma (HCC) diagnosed at 40 years of age or below. Materials and methods Expression of CK19, Glypican-3 and β-catenin was assessed in clinical samples by immunohistochemistry (IHC). IHC expression was correlated with clinicopathological parameters. Hotspot mutations in TP53 gene were analyzed by sequencing. Results Thirty-six cases were included with a male to female ratio of 3:1. Eighty percent of cases were associated with chronic hepatitis B infection. CK19 and GPC3 were expressed in 61% and 56% of cases, respectively. Only one case demonstrated β-catenin over-expression. TP53 hotspot mutation was identified in 4 cases. Number of tumor nodules, vascular invasion, and preoperative serum AFP level were associated with prognosis. Conclusion A higher CK19 expression rate was observed in our young-onset HCC cohort, whereas β-catenin pathway activation and TP53 gene mutation events were less frequent. Conventional clinicopathological parameters remain predictors of survival.

Relapse prevention is an important goal in the clinical management of psychosis. Cognitive deficits/deterioration can provide useful insights for monitoring relapse in psychosis patients.This was a prospective, naturalistic 1-year follow-up study involving 110 psychosis patients with full clinical remission. Relapse, defined as the recurrence of psychotic symptoms, was monitored monthly along with digital tracking of verbal and visual working memory using a mobile app developed for this study. Cognitive deterioration was defined as worsening performance over 2 months prior to relapse or study termination, whichever was earlier. Other clinical, cognitive, functioning, and psychosocial variables were also collected.At 1 year, 18 (16.36%) patients relapsed, of which 6 (33.33%) required hospitalization. Relapse was predicted by verbal working memory deterioration 2 months prior to relapse (p = 0.029), worse medication adherence (p = 0.018), and less resilience (p = 0.014).Verbal working memory deterioration is a novel early sign of relapse. It is a clearly defined, objectively measurable, and reproducible marker that can help clinicians and healthcare workers identify patients at risk of relapse and make decisions about maintenance therapy. Moreover, digital monitoring is a viable tool in the management of relapse.

Liver cirrhosis represents an advanced stage of chronic liver disease and is associated with significant morbidity, mortality, and risk of cancer development. While sex disparity of liver diseases has been observed, understanding at a genetic level awaits more thorough investigation. In this study, we performed a sex-specific analysis of the microRNA (miR) profiles in hepatitis B virus (HBV)-associated cirrhosis by small RNA-sequencing using clinical tissue samples. Potential associated signaling pathways, downstream gene targets, and upstream regulators were highlighted by computational prediction analyses based on the differentially expressed miRs (DEmiRs). From our results, deregulation of miRs in cirrhosis showed a marked difference between males and females by the degree and pattern. Sixty-five (64 up-regulated, 1 down-regulated) and 12 (6 up-regulated, 6 down-regulated) DEmiRs were found in males and females, respectively, when compared with their respective control group. A number of DEmiRs were only observed in one sex but not the other. In addition, 26 DEmiRs were identified between cirrhosis female and cirrhosis male groups. Fatty acid biosynthesis pathway, extracellular matrix-receptor interaction, p53 signaling, Hippo signaling, tumor necrosis factor signaling, the forkhead box O signaling, as well as gene targets ribosomal protein S27 like, methyl CpG binding protein 2, and estrogen receptor 1, may contribute to the pathogenesis and biological behavior of cirrhosis in a sex-specific manner. Analysis of the Cancer Genome Atlas data set suggested a role of sex-specific DEmiRs in multistep hepatocarcinogenesis. Conclusion: Our findings illustrate that miR profiles in HBV-associated cirrhosis are distinct between the males and females and suggest a potential role of sex-specific biomarkers and molecular mechanisms in disease development and progression.

ObjectiveWe examined the serological, virological (in serum and liver) and histological profiles in chronic hepatitis B virus (HBV) patients during and after completion of multiple dose (MD) ARC-520.DesignThe present phase 1b study was a multidose, open-label extension cohort of patients that had received single dose ARC-520 in our previous study. Eight patients received 4–9 4 weekly doses of MD ARC-520 and entecavir. Liver biopsies were performed in six patients. Intrahepatic and serum HBV DNA, HBV RNA and viral antigens were measured.ResultsAll patients had 28.9–30.4 months of follow-up after the last MD. All three hepatitis B e antigen (HBeAg)-positive patients had profound reductions in hepatitis B surface antigen (HBsAg), HBeAg, hepatitis B core-related antigen and HBV RNA with two undergoing HBeAg seroconversion. One further achieved HBsAg seroconversion (anti-HBs level of 25.1 IU/L) and the remaining two had HBsAg reductions of −1.7 and −3.5 log IU/mL >30 months after MD. Among the five HBeAg-negative patients, four had modest HBsAg reduction >29 months after completion of MD and one achieved HBsAg seroconversion (anti-HBs level of 152.5 IU/L) and was negative for liver HBsAg staining. Entecavir was successfully stopped in this patient 12 months after HBsAg seroconversion. Temporally related alanine aminotransferase elevations preceded by HBsAg reductions were observed in three patients suggesting immune activation. HBcAg staining was negative in all six biopsied patients. Two patients with <10% HBsAg positive staining of hepatocytes had correspondingly low serum HBsAg levels of 1.5 and 11.5 IU/mL.ConclusionsMD ARC-520 therapy achieved sustained and profound reductions of viral antigens and HBV RNA. HBsAg seroclearance was achievable.Trial registration numberNCT02065336.

Introduction: Hepatocellular carcinoma (HCC) is the sixth most frequently diagnosed cancer and the third leading cause of cancer deaths. Liver fibrosis (LF) is a progressive disease and cirrhosis, the advanced stage of LF, is per se a risk factor for HCC. Moreover, LF persists after the development of HCC. Stanniocalcin 1 (STC1), as a serum biomarker of both HCC and LF as we previously reported, was found to be secreted from HCC cells and hepatic stellate cells (HSCs). STC1 promoted cell migration and invasion of HCC and activation of HSCs, suggesting that STC1 could be an actionable target of both diseases. As a secretory protein, STC1 could potentially be targeted by an antibody approach. Objectives: This study aims to investigate the therapeutic values of targeting secretory STC1 in HCC and LF models using antibody approach, including in the interplay between HSCs and HCC cells. Methods: Human anti-STC1 antibody was harvested and purified from a hybridoma cell line of a designed epitope. In vitro transwell migration and invasion assays were performed on human HCC cell lines. Co-culture assays were set up with HCC cells cultured in conditioned medium (CM) collected from LX2, a human HSC cell line. Expression of fibrogenic markers were measured by western blotting, qPCR and ELISA. Results: Enforcement of STC1, either by viral transfection of STC1-overexpressing vector or by the treatment of recombinant STC1 protein, increased the migration and invasion of HCC cells. The effects were abrogated by the co-treatment of anti-STC1 antibody. The enhanced migratory and invasive abilities of HCC cells induced by activated HSC CM were abolished by anti-STC1 antibody. In addition, anti-STC1 antibody suppressed the secretion of type I collagen (COL1) and the intracellular expression of fibrogenic markers alpha-smooth muscle actin (ɑSMA) and TIMP metallopeptidase inhibitor 1 (TIMP1) in TGFβ1-activated HSCs. Conclusion: Anti-STC1 antibody displays therapeutic effects on HCC in vitro. It is also shown to suppress the expression of fibrogenic markers in activated HSCs. Anti-STC1 antibody is a potential therapeutic strategy for both HCC and LF. Citation Format: Alfred Long-Hin Suen, Kristy Kwan-Shuen Chan, Regina Cheuk-Lam Lo. Anti-Stanniocalcin 1 antibody as a potential therapeutic strategy for liver fibrosis and hepatocellular carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3982.

Aim Sex differences are well documented in schizophrenia, but have been much less studied in at-risk mental state (ARMS) for psychosis. We aimed to examine sex differences in symptomatology, cognition, social and role functioning in individuals with ARMS, with specific focus on clarifying relationships between sex, negative symptoms and functioning. Methods One hundred and seventy-seven Chinese participants aged 15-40 years with ARMS were recruited from a specialized early intervention service in Hong Kong. ARMS status was verified by Comprehensive Assessment of At-Risk Mental State. Assessments encompassing symptom profiles, a brief battery of cognitive tests and social and role functioning were conducted. Brief Negative Symptom Scale was adapted to measure negative symptoms at the level of five core domains. Results Males with ARMS exhibited significantly poorer social functioning and more severe asociality of negative symptoms than female counterparts. Mediation analysis revealed that sex difference in social functioning became statistically insignificant when asocality was included in the model, indicating that asociality mediated the relationship between sex and social functioning. No sex differences were observed in other core domains of negative symptoms, other symptom dimensions, cognitive measures and role functioning. Conclusions This study suggests that sex differences in ARMS may be less pronounced that those observed in established psychotic disorders. Our findings of differential pattern of asociality between sexes and its mediating role on sex difference in social functioning underscore the importance in investigating negative symptoms at a separable domain-level. Further research is required to identify sex-specific predictors of longitudinal outcomes in at-risk populations.

Background Psychotic disorders are associated with a high rate of relapse. In addition to medication non-adherence, some psychosocial factors have been found to be predictive of relapse (e.g., poor premorbid adjustment, high expressed emotion and substance misuse). Impairments in cognitive functions including general memory functioning, set shifting, attention, processing speed and working memory have also been indicative of a subsequent psychotic episode. As clinical appointments do not always allow for timely or accurate detection of these early warning signs, the ReMind app is developed to explore potential relapse predictors and enhance the process of relapse monitoring. Aim The ReMind app aims (1) to assess whether verbal or visual working memory predicts psychotic relapse in 1 year and (2) to determine whether social factors such as stressful life events, level of expressed emotion and medication adherence also predict relapse in 1 year. Methods This is a one-year prospective follow-up study involving 176 remitted patients diagnosed with schizophrenia or non-affective psychoses. Monthly relapse predictor assessments will be conducted via ReMind throughout the one-year study duration. These assessments include neurocognitive tasks and psychosocial questionnaires. Results Recruitment began in August 2017 and is still ongoing. Preliminary user feedback suggested an overall positive experience with the app. Conclusion The ReMind app presents a step forward to the identification and sensitive detection of reliable psychosis relapse predictors. With its anticipated success, it may offer an alternative means of monitoring relapse for the Chinese-speaking population in the future.

Despite widespread interest in social media use, little is known about the heterogeneity of underlying motivations for online engagement among at-risk adolescents. This study adopted a mixed-methods approach to evaluate the motives of online expression among Hong Kong youths aged 15-19, as well as their relationships to online help-seeking willingness and suicide risks. In total, 6 focus groups and 12 individual interviews were conducted (

Background Social networking sites (SNSs) have gained popularity in recent years for help seeking and self-distress expression among adolescents. Although online suicidal expression is believed to have major benefits, various concerns have also been raised, particularly around privacy issues. Understanding youths’ help-seeking behavior on SNSs is critical for effective suicide prevention; however, most research neglects the impacts of the private SNS context. Objective This study aims to examine youths’ private SNS use via the new Instagram feature, Close Friends, and its association with both online and offline help-seeking willingness as well as youths’ suicidality. Methods This study employed an exploratory sequential mixed methods approach with a combination of explorative qualitative interviews and a systematic quantitative survey, targeting youth aged 15-19 years in Hong Kong. The motivations for utilizing Close Friends and concerns regarding online expression were addressed in the focus group and individual interviews (n=40). A cross-sectional survey (n=1676) was conducted subsequently with eligible secondary school students to examine the prevalence of Close Friends usage, their online and offline help-seeking willingness, and suicide-related experiences. Results A total of 3 primary motives for using Close Friends were identified during interviews, including (1) interaction and help seeking, (2) release of negative emotions, and (3) ventilation and self-expression. Most participants also highlighted the privacy concerns associated with public online communication and the importance of contacting close friends for emotional support. Survey results showed that use of Close Friends was quite prevalent among adolescents (1163/1646, 70.66%), with around 46% (754/1646, 45.81%) of respondents being frequent users. Differences by gender and school academic banding were also revealed. Regarding help-seeking intentions, youths were generally positive about seeking help from peers and friends offline (1010/1266, 79.78%) yet negative about seeking assistance from online friends or professionals with whom they had not yet developed a real-world connection (173/1266, 13.67%). Most notably, frequencies of Close Friends usage were differentially associated with online and offline help-seeking willingness and youths’ suicidality. Compared with nonusers, those who had ever used the feature were more likely to seek offline support (adjusted odds ratios [AORs] 1.82-2.36), whereas heavy use of Close Friends was associated with increased odds of online help-seeking willingness (AOR 1.76, 95% CI 1.06-2.93) and a higher risk of suicidality (AOR 1.53, 95% CI 1.01-2.31). Conclusions The popularity of Close Friends reflects the increasing need for private online expression among youth. This study demonstrates the importance of Close Friends for self-expression and private conversation and inadequacy of peer support for suicidal adolescents. Further research is needed to identify the causal relationship between Close Friends usage and help-seeking willingness to guide the advancement of suicide prevention strategies. Researchers and social media platforms may cooperate to co-design a risk monitoring system tailored to the private SNS context, assisting professionals in identifying youth at risk of suicide.

We study the determinants of aviation CO2 emissions by designing an econometric model applied to a panel data set covering all flights departing from Lombardy, Italy over the 1997–2011 period. We consider two dimensions of CO2 emissions: total and per available seat kilometer. The latter is a measure of emission efficiency. We focus on different categories of determinants: technical progress; aircraft and network carrier management; policy/business decisions that may not be oriented to limiting CO2, but may indirectly affect it by offsetting projected outcomes of policies adopted to reduce emissions (e.g., the EU Emission Trading Scheme (ETS) or the ICAO Carbon Offsetting and Reduction Scheme for International Aviation); and others. We find that although aircraft size increases total emissions, it reduces emissions per available seat kilometers (ASK), while the route distance increases total emissions and decreases emissions per ASK, implying that CO2 is less of a problem for long-haul connections. Technical progress decreases CO2 emissions per ASK with an estimated elasticity equal to −0.06%. Last, liberalization in the EU market has generated the development of low-cost carriers, which in turn have lowered CO2 emission per ASK, that is, liberalization in Europe has brought the collateral effect of reducing the CO2 externality per passenger.

Aim Psychiatric comorbidity frequently occurs with at-risk mental state (ARMS) for psychosis. Its relationships with psychopathology, cognition and functioning, however, remain to be further clarified. We aimed to examine prevalence and correlates of psychiatric comorbidity, and its associations with psychosocial functioning and subjective quality-of-life (QoL) in a representative sample of Chinese ARMS individuals. Methods One hundred ten help-seeking participants aged 15 to 40 years with ARMS were recruited from a specialized early psychosis service in Hong Kong. ARMS status was verified by comprehensive assessment of at-risk mental state (CAARMS). Comorbid Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition non-psychotic psychiatric disorders at baseline were ascertained using diagnostic interview and medical record review. Assessments encompassing symptom profiles, psychosocial functioning, subjective QoL and a brief cognitive battery were conducted. Results Forty-nine (44.5%) ARMS participants were diagnosed as having comorbid non-psychotic psychiatric disorders at baseline, primarily depressive and anxiety disorders. Binary multiple logistic regression analysis revealed that female gender, more severe depressive symptoms, higher suicidality and poorer global cognitive functioning were independently associated with comorbid diagnosis status. ARMS participants with psychiatric comorbidity displayed significantly more limited extended social networks and poorer subjective QoL than those without psychiatric comorbidity. Conclusion Comorbid disorders were frequently observed in Chinese ARMS individuals, and were linked to poorer cognition and higher suicide risk. Our findings underscore a potential critical role of psychiatric comorbidity in determining social functioning and subjective QoL in at-risk individuals. Further longitudinal research is required to clarify trajectories of comorbid disorder status and its prospective impact on clinical and functional outcomes in ARMS populations.

This empirical study shows age makes a difference in how people evaluate Hong Kong’s legal and political institutions amid the former British colony’s chronic democratic deficit and rising political discontent since its return to Chinese rule in 1997. Using data from a 2015 survey of 3525 local residents conducted 6 months after the end of the ‘Umbrella Movement’ – a pro-democracy protest lasting 79 days, it reveals a glaring gap between older and younger people in their evaluations of Hong Kong’s electoral system and human rights, and more importantly, the latter’s rising localist sentiment. If perceived illegitimacy of a regime discourages legal compliance, these findings do not bode well for Hong Kong’s long-term governance. The largely youth-led protests that erupted in the summer of 2019 against a now-withdrawn bill that would have allowed extradition to Mainland China, which plunged the city into its worst political crisis since 1997, are ominous signs.

Most studies highlighted the association between psychological distress and socioeconomic status (SES). There were weaker explanations for distress found in the middle classes, especially in Asian countries. We conducted a questionnaire survey with 1626 adult Chinese primary-care attenders from 13 private and 6 public clinics in different districts of Hong Kong. Their demographic background and distress level measured by GHQ-12 were analysed. We found that respondents with younger age, better education, and lower income were more likely to be distressed. In a multiple logistic regression model, age and income, but not education, were significant predictors for distress. Highest rates of distress were found among the unemployed (45.5%) and the students (37.1%), followed by service workers and shop sales workers (33.0%), associate professionals (32.0%), and clerks (29.2%). Craftworkers (9.1%), plant and machine operators (11.5%), and retired people (12.8%) were least likely to be distressed, followed by professionals (21.0%). Apart from SES, the findings suggest that young age, academic and job stressors, and low self-esteem are significant factors for distress. These factors may be intensified in a Chinese context by peer comparison resulting in a state of relative deprivation.

The underpinnings of language deviations in psychotic symptoms (eg, formal thought disorder, delusions) remain unclear. We examined whether the semantic networks underlying word associations are useful predictors of clinical outcomes in psychosis. Fifty-one patients with schizophrenia and other psychotic disorders and 51 matched healthy controls generated words in a Cantonese continued word association task. Patterns of word associations were examined using semantic similarity metrics derived from word embeddings (fastText) and the structure of individual semantic networks. A longitudinal design—baseline and 6 months later—enabled investigation of the relationship of changes in semantic associations in patients who were in an acute psychotic state at baseline compared to clinical stabilization 6 months later. The semantic similarity measure increased over time in patients, while it remained stable in controls. Moreover, the change in semantic similarity over time correlated with the changes in patients’ formal thought disorder symptoms. There were differences in individual semantic networks between the groups at both time points. Patients had less structured networks on average, as evidenced by a smaller network diameter and clustering coefficient, and smaller average shortest path lengths. The identification of several state-like semantic measures that change over time with patients’ mental states allows for nuanced comparison with clinical measures. Semantic measures are complex. Semantic similarity was a state-like measure that changed over time with mental state in psychotic disorders, whereas individual semantic network parameters were trait-like and stable over time.

Background & Aims: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer (PLC) associated with a poor prognosis. Given the challenges in its identification and its clinical implications, biomarkers are critically needed. We aimed to investigate the diagnostic and prognostic value of the immunohistochemical expression of Nestin, a progenitor cell marker, in a large multicentric series of PLCs.Methods: We collected 461 cHCC-CCA samples from 32 different clinical centers. Control cases included 368 hepatocellular carcinomas (HCCs) and 221 intrahepatic cholangiocarcinomas (iCCAs). Nestin immunohistochemistry was performed on whole tumor sections. Diagnostic and prognostic performances of Nestin expression were determined using receiver-operating characteristic curves and Cox regression modeling.Results: Nestin was able to distinguish cHCC-CCA from HCC with AUCs of 0.85 and 0.86 on surgical and biopsy samples, respectively. Performance was lower for the distinction of cHCC-CCA from iCCA (AUCs of 0.59 and 0.60). Nestin, however, showed a high prognostic value, allowing identification of the subset of cHCC-CCA (“Nestin High”, >30% neoplastic cells with positive staining) associated with the worst clinical outcome (shorter disease-free and overall survival) after surgical resection and liver transplantation, as well as when assessment was performed on biopsies.Conclusion: We show in different clinical settings that Nestin has diagnostic value and that it is a useful biomarker to identify the subset of cHCC-CCA associated with the worst clinical outcome. Nestin immunohistochemistry may be used to refine risk stratification and improve treatment allocation for patients with this highly aggressive malignancy. Lay summary: There are different types of primary liver cancers (i.e. cancers that originate in the liver). Accurately identifying a specific subtype of primary liver cancer (and determining its associated prognosis) is important as it can have a major impact on treatment allocation. Herein, we show that a protein called Nestin could be used to refine risk stratification and improve treatment allocation for patients with combined hepatocellular carcinoma, a rare but highly aggressive subtype of primary liver cancer.

The liver is the commonest site of cancer metastasis. In this study, we asked whether the immune tumor microenvironment in liver metastases was governed by the β-catenin activation status of the tumor. To this end, we analyzed CD8 and FoxP3 immunohistochemical expression against β-catenin expression status of the tumor in a cohort of 52 liver samples with metastatic carcinoma. The results showed that colorectal primary constituted the largest proportion of metastatic carcinoma showing β-catenin overexpression. Intra-tumoral CD8 count was lower and FoxP3 count was higher when compared with the non-tumoral liver parenchyma. β-catenin overexpression was associated with a lower CD8 count in the tumor region (p = 0.003). In summary, our findings are in support of an altered immune tumor microenvironment vs. the non-tumor liver tissues in the metastatic site. Suppression of CD8 count was associated with activated Wnt/β-catenin signaling in the metastatic tumor.

Achieving functional recovery in patients with psychosis is a challenge in clinical practice. Investigating the complex interplay between cognition, symptoms, insight and functional outcome in first episode psychosis will be crucial to understanding the factors leading to better functioning.In this 12-month prospective follow-up study, we investigated how cognition, clinical symptoms, and insight into illness affected overall functioning in 160 patients with first episode psychosis recruited from the Early Assessment Service for Young People with Psychosis (EASY) in Hong Kong from July 1, 2014 to June 30, 2016. Cognition was assessed at baseline while symptoms, insight, and functioning were assessed at 12-month follow-up. Structural equation modelling was used to examine the direct and indirect relationships between functioning and other latent constructs.Symptoms (negative symptoms and general psychopathology) and insight were shown to be significant mediators between cognition and functioning. The significant direct relationship between cognition and functioning (β = 0.387; p 0.001) became insignificant (β = 0.079; p = 0.578) after including symptoms and insight in the model. Symptoms and insight were significantly associated with cognition (symptoms, β = -0.469; p 0.001; insight, β = -0.372; p 0.001) and predicted functioning (symptoms, β = -0.558; p 0.001; insight, β = -0.264; p 0.01).Symptoms and insight mediated the effects of cognition on functioning. Interventions for improving functioning in patients with first episode psychosis should target not only cognition but also symptoms and insight.

BackgroundHealth professionals including psychiatrists were reported to have stigmatising opinions on psychiatric patients. Their views may be affected by clinical, social and cultural factors.ObjectiveThis study explored the views of Chinese psychiatrists on stigmatisation of psychiatric patients.MethodsFocus group discussions with psychiatrists were conducted in Hong Kong. Their views towards stigmatisation of psychiatric patients and strategies to reduce stigmatisation were discussed.FindingsThe psychiatrists perceived the clinical needs to classify the patients according to the diagnoses and they did not see it as stigmatisation. They believed that some mental illnesses are characterised with violence or deviance, and were not completely curable. Instead of trying to eliminate stigma, they managed in ways that took social expectations into consideration. They might offer a relative vague diagnostic label to save the ‘face’ of the patients and secure greater acceptance for the illness from the public. They tended to accept family members to make decisions on behalf of the patients. Reconciling public interest and patients’ autonomy, they encouraged stable psychotic patients to live in the community but agreed to institutionalise those patients with violent behaviours.ConclusionWhile the psychiatrists argued that the diagnosis was not a form of stigma, they were sensitive enough and framed responses to patients in ways to minimise stigma. They tended to believe that stigma was inevitable given the nature of some psychotic disorders. Disguising the stigma appeared to be the common approach to deal with stigma in a Chinese context.Clinical ImplicationsThe psychiatrists, especially those practicing in a Chinese context, may consider a wider perspective of community mental health rehabilitation which is not limited to social stability but also social life.

The benefits of physical activity for successful aging are well established. Few interventions however, target older Asian Americans who may have distinct needs for cultural and linguistic tailoring. The heterogeneity among Asian Americans underscores the need to elucidate specific physical activity preferences by ethnic subgroup. To better understand older Chinese Americans’ perceptions about physical activity, we conducted a community-engaged, mixed methods study with 60 participants. Through survey and focus groups, four emerging themes characterized perceptions of physical activity: (a) physical activities benefit the body and mind, (b) traditional Chinese culture influences perceptions and preferences for physical activity, (c) physical activity presents opportunities for social engagement, and (d) physical activity facilitates family harmony. Design recommendations includes encouraging mind–body approaches, incorporating culturally specific practices, highlighting opportunities for social engagement, and emphasizing the potential for improved harmony.

Very few data are available to demonstrate the economic benefit of early paliperidone palmitate once-monthly long-acting injectable (PP1M) treatment in patients with schizophrenia or schizoaffective disorder.This study has retrospectively compared the healthcare utilization and associated costs of pre- and post-PPIM treatment in 413 patients with schizophrenia or schizoaffective disorder recruited from three major public hospitals providing psychiatric services in Hong Kong. Patients were categorized into early treatment (≤3 years since diagnosis) and chronic (3 years) groups, and also whether they were receiving polypharmacy (POP).It was found that patients who were started on early therapy with no POP had the most favourable outcomes. Overall results of the entire cohort, including both early and late treatments, indicate that there was a slight increase in annual in-patient days (IP) per patient and outpatient visit (OP) by 3.18 and 1.87, respectively, and a decrease in emergency room visit (ER) of 0.9 (p 0.05). For non-polypharmacy (NP) patients receiving early PP1M therapy, there was a significant decrease in IP and ER of 21.56 (p 0.05) and 1.15 (p 0.05), respectively, but an increase in OP of 1.88 (p 0.05). For patients with POP, there was an all-across increase in IP and all-across decrease in OP and ER. In monetary terms, a NP patient receiving early therapy may have an overall saving of HKD40,878 (USD5,241, 1USD = 7.8HKD) per year compared to HKD6,224 (USD798) in patients where therapy was given after 3 years. For patients with POP, there was an all-across increase in overall spending despite reductions in OP and ER.From the 413 patients studied, potential annual savings is higher by early administration of PPIM in patients with NP. Analysis using multivariate linear regression based on generalized estimating equations and sensitivity analysis using a linear mixed model supported the findings.

Recovery-oriented practice has been advocated in mental health services in Hong Kong since 2009. Well-being has become an important area of focus for mental health services. Positive Psychotherapy for Psychosis (PPP) is a well-being-focused intervention for use in psychosis, with preliminary evidence from a randomized controlled trial in the United Kingdom of impact on well-being and symptomatology. The aim of this study was to test the effectiveness of PPP on the well-being of people with psychosis in Hong Kong. The study was a randomized controlled trial with two-arm parallel groups. Both groups received treatments as usual, and in addition the intervention group received a 13-session intervention based on a Cantonese Chinese translation of the PPP manual. Intention-to-treat analysis was used. The trial was registered (ANZCTR: ACTRN12620000464965). A total of 154 participants (78 intervention, 76 control) were recruited. As compared to control group, intervention group participants showed significant changes over time on the primary outcome of well-being assessed using the Chinese Short Warwick-Edinburgh Mental Well-being Scale (p = 0.001) and on secondary outcomes of hope (Agency subscale: p = 0.029) and self-efficacy (p = 0.001). Positive Psychotherapy for Psychosis was found to be an effective treatment in improving the well-being and other mental health outcomes for people with psychosis. It can be recommended for use in mental health services to promote recovery.

Recent research on second‐generation long‐acting injectable antipsychotics (LAI SGAs) has proven its effectiveness in minimizing medication nonadherence problem and reducing relapses. Administered by medical professionals, making quick detection of nonadherence possible, long‐acting injectable antipsychotics (LAIs) facilitate immediate intervention and recovery process, and thus are favored by psychiatrists. Despite a higher initial cost with LAIs, the subsequent schizophrenia‐related health costs for hospitalizations and outpatients are greatly reduced. With reference to guidelines published by psychiatric associations around the globe, this article looks at scenarios in Hong Kong on the management of severe mentally ill patients with regard to the use of a host of psychosocial interventions as well as LAI SGAs as a preferable treatment. In particular, it examines the benefits of using LAI SGAs for Hong Kong patients who demonstrated high nonadherence treatment rates due to their social environment. It assesses the rationale behind the early usages of LAI SGAs, which help to provide better recovery outcomes for patients.

Hepatocellular carcinoma (HCC) is a biologically aggressive cancer. Targeted therapy is in need to tackle challenges in the treatment perspective. A growing body of evidence suggests a promising role of pharmacological inhibition of PIM (proviral integration site for Moloney murine leukaemia virus) kinase in some human haematological and solid cancers. Yet to date, the potential application of PIM inhibitors in HCC is still largely unexplored. In the present study we investigated the pre-clinical efficacy of PIM inhibition as a therapeutic approach in HCC. Effects of PIM inhibitors on cell proliferation, migration, invasion, chemosensitivity, and self-renewal were examined in vitro. The effects of PIM inhibitors on tumour growth and chemoresistance in vivo were studied using xenograft mouse models. Potential downstream molecular mechanisms were elucidated by RNA sequencing (RNA-seq) of tumour tissues harvested from animal models. Our findings demonstrate that PIM inhibitors SGI-1776 and PIM447 reduced HCC proliferation, metastatic potential, and self-renewal in vitro. Results from in vivo experiments supported the role of PIM inhibition in suppressing of tumour growth and increasing chemosensitivity of HCC toward cisplatin and doxorubicin, the two commonly used chemotherapeutic agents in trans-arterial chemoembolisation (TACE) for HCC. RNA-seq analysis revealed downregulation of the MAPK/ERK pathway upon PIM inhibition in HCC cells. In addition, LOXL2 and ICAM1 were identified as potential downstream effectors. Taken together, PIM inhibitors demonstrated remarkable anti-tumourigenic effects in HCC in vitro and in vivo. PIM kinase inhibition is a potential approach to be exploited in formulating adjuvant therapy for HCC patients of different disease stages. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The Convention on the Rights of the Child emphasizes that the education of the child should be directed to the development of respect for human rights and fundamental freedoms. However, though Hong Kong is a one of the States Parties to the Convention on the Rights of the Child, the government does not put much emphasis on promoting Convention on the Rights of the Child. Children’s rights education is not compulsory in schools or in teacher training institutions in Hong Kong. It is detrimental if teachers do not possess adequate knowledge and positive attitudes towards children’s rights as they hold a crucial role in educating children about their rights and nurturing rights-respecting students. Through modifying Rogers and Wrightsman’s Children’s Rights Attitudes Scale, the present research examined pre-service teachers’ attitudes towards children’s self-determination rights, nurturance rights, and the conflict between self-determination and nurturance rights, and also their knowledge of children’s rights, in order to uncover the areas of improvements.

BackgroundWhile qualitative studies suggested that continuity of care by primary care physicians (PCPs) facilitated consultations for psychological problems, there was limited quantitative evidence. This survey compared management of psychological distress between patients with and without a regular PCP.MethodsA questionnaire survey was conducted with 1626 adult primary care attenders from 13 private and 6 public clinics in Hong Kong. Management of psychological distress between respondents with a regular PCP and those without were compared. Effects of demographic factors were adjusted for by multivariable logistic regression.ResultsAmong the 1626 respondents, 650 (40.0%) reported that they had ever experienced psychological distress. Of the 650 respondents experienced distress, 307 (47.2%) had a regular PCP. A significantly higher proportion of patients with a regular PCP than those without reported: (i) their PCPs sometimes/often asked about psychological problems [37.7 versus 20.1%, adjusted OR = 2.241]; (ii) they sometimes/often mentioned their psychological problems to PCPs [45.2 versus 24.9%, adjusted OR = 2.503]; and (iii) their distress had been treated by PCPs [22.1 versus 13.4%, adjusted OR = 1.702].ConclusionPatients with a regular PCP have around double odds of receiving mental health care. Continuity of care by PCPs should be emphasized in mental health care delivery.

Frequent relapse and drug resistance in patients with hepatocellular carcinoma (HCC) can be attributed to the existence of tumor-initiating cells (TIC) within the tumor bulk. Therefore, targeting liver TICs may improve the prognosis of these patients. From transcriptome sequencing of 16 pairs of clinical HCC samples, we report that interleukin-1 receptor-associated kinase 1 (IRAK1) in the TLR/IRAK pathway is significantly upregulated in HCC. IRAK1 overexpression in HCC was further confirmed at the mRNA and protein levels and correlated with advanced tumor stages and poor patient survival. Interestingly, IRAK4, an upstream regulator of IRAK1, was also consistently upregulated. IRAK1 regulated liver TIC properties, including self-renewal, tumorigenicity, and liver TIC marker expression. IRAK1 inhibition sensitized HCC cells to doxorubicin and sorafenib treatment in vitro via suppression of the apoptotic cascade. Pharmacological inhibition of IRAK1 with a specific IRAK1/4 kinase inhibitor consistently suppressed liver TIC populations. We identified aldo-keto reductase family 1 member 10 (AKR1B10) as a novel downstream target of IRAK1, which was found to be overexpressed in HCC and significantly correlated with IRAK1 expression. Knockdown of AKR1B10 negated IRAK1-induced TIC functions via modulation of the AP-1 complex. Inhibition of IRAK1/4 inhibitor in combination with sorafenib synergistically suppressed tumor growth in an HCC xenograft model. In conclusion, targeting the IRAK4/IRAK1/AP-1/AKR1B10 signaling pathway may be a potential therapeutic strategy against HCC. Significance: IRAK4/IRAK1/AP-1/AKR1B10 signaling pathway regulates cancer stemness and drug resistance and may be a novel therapeutic target in HCC. Cancer Res; 78(9); 2332–42. ©2018 AACR.

The hepatic repair complex in the setting of cirrhosis has received increasing attention, as it implies the regression of cirrhosis, which was traditionally taken to be an irreversible state. In this brief review, the patterns of fibrosis, the existing staging systems for chronic liver disease and the histopathological features of cirrhosis regression are discussed. (Clin Mol Hepatol 2017;23:302-307)