Hepatocellular Carcinoma Incidence in Alcohol-Associated Cirrhosis: Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Alcohol is one of the leading causes of hepatocellular carcinoma (HCC). However, pooled estimates of HCC incidence in alcohol-associated cirrhosis have not been evaluated systematically. We performed a pooled analysis of time-to-event data to provide robust estimates for the incidence of HCC in alcohol-associated cirrhosis. METHODS: Medline, Embase, Cochrane Central Register, Scopus, and Web of Science were searched from inception to August 2021. Individual patient data were reconstructed from published Kaplan-Meier curves, and a pooled analysis of cumulative HCC incidence was performed using a random-effects model. RESULTS: We screened 5022 articles and included 18 studies (148,333 patients). In the pooled analysis, the cumulative incidence of HCC in alcohol-associated cirrhosis at 1, 5, and 10 years among studies that accounted for the competing risk of death without HCC was 1%, 3%, and 9%, respectively. A secondary analysis by traditional meta-analysis determined that the HCC incidence rate was higher in cohorts enrolled in a HCC surveillance program (18.6 vs 4.8 per 1000 person-years; P = .001) vs those who were not enrolled in a surveillance program. Meta-regression showed that diabetes, smoking, variceal bleeding, and hepatic decompensation were associated with a higher risk of HCC. CONCLUSIONS: Our analysis determined that the 5- and 10- year cumulative risk of HCC in alcohol-associated cirrhosis was 3% and 9%, respectively, with a higher incidence in cohorts that were enrolled in a HCC surveillance program. These data should be validated further in large prospective studies, and may have important implications for HCC screening and surveillance among patients with alcohol-associated cirrhosis.

A Class Effect Network Meta-analysis of Lipid Modulation in Non-alcoholic Steatohepatitis for Dyslipidemia.

Background and Aims: Pharmaceutical therapy for NASH is associated with lipid modulation, but the consensus on drug treatment is limited and lacks comparative analysis of effectiveness. A network meta-analysis was conducted to compare NASH drug classes in lipid modulation. Methods: Online databases were searched for randomized controlled trails (RCTs) evaluating NASH treatments in biopsy-proven NASH patients. Treatments were classified into four groups: (1) inflammation, (2) energy, (3) bile acids, and (4) fibrosis based on the mechanism of action. A Bayesian network analysis was conducted with outcome measured by mean difference (MD) with credible intervals (Crl) and surface under the cumulative ranking curve (SUCRA). Results: Forty-four RCTs were included in the analysis. Bile acid modulating treatments (MD: 0.05, Crl: 0.03-0.07) were the best treatment for improvement in high-density lipid (HDL) cholesterol, followed by treatments modulating energy (MD: 0.03, Crl: 0.02-0.04) and fibrosis (MD: 0.01, Crl: -0.12 to 0.14) compared with placebo. The top three treatments for reduction in triglycerides were treatments modulating energy (MD: -0.46, Crl: -0.49 to -0.43), bile acids (MD: -0.22, Crl: -0.35 to -0.09), and inflammation (MD: -0.08, Crl: -0.13 to -0.03) compared with placebo. SUCRA found treatment modulating fibrosis (MD: -1.27, Crl: -1.76 to -0.79) was the best treatment for reduction in low-density lipid (LDL) cholesterol followed by treatment modulating inflammation (MD: -1.03, Crl: -1.09 to -0.97) and energy (MD: -0.37, Crl: -0.39 to -0.34) compared with placebo, but LDL cholesterol was worsened by treatments modulating bile acids. Conclusions: Network analysis comparing the class effects of dyslipidemia modulation in NASH found that treatment targets can include optimization of atherogenic dyslipidemia. Future studies are required to evaluate the cardiovascular outcomes.

Comparable Outcomes in Early Hepatocellular Carcinomas Treated with Trans-Arterial Chemoembolization and Radiofrequency Ablation.

The guidelines recommend radiofrequency ablation (RFA) for early hepatocellular carcinomas that are less than 3 cm and trans-arterial chemoembolization (TACE) for intermediate-stage tumors. Real-world patient and tumor factors commonly limit strict adherence to the guidelines. We aimed to compare the clinical outcomes for TACE and RFA in early HCC. All consecutive patients from 2010 to 2014 that were treated with locoregional therapy at our institution were enrolled. The decision for TACE or RFA was based on tumor location, stage and technical accessibility for ablation. A subgroup analysis was performed for patients with tumors less than 3 cm. A total of 168 patients underwent TACE while 56 patients underwent RFA. Patients treated with TACE and RFA had 1- and 5-year survival rates of 84.7% and 39.8% versus 91.5% and 51.5%, respectively (p = 0.28). In tumors less than 3 cm, there was no significant difference in overall survival (p = 0.69), time to progression (p = 0.55), or number of treatment sessions required (p = 0.12). Radiofrequency ablation had a significantly higher chance of a complete response (p = 0.004). In conclusion, TACE may be selectively considered for early-stage hepatocellular carcinoma in patients unsuitable for other modalities.

Bending stiffness characterization of Bacillus subtilis' flagellar filament.

The filament of a bacterial flagellum is a tube-like organelle made of a single protein-flagellin-and assembled into multiple polymorphic forms. The filament can be further discretized into four subunit domains (D0, D1, D2, and D3) along the radial direction. However, it remains unclear which subunit domain plays an important role in regulating the rigidity of the filament. In this article, we address how the absence of two outer subunit domains (D2 and D3) affects the bending stiffness of the bacterium B. subtilis' flagellar filament. We first shear off flagellar filaments from the cell body, anchor one of its ends to the wall of a microfluidic channel, and correlate the elongation of the filament with the driving background flow. A numerical model is then applied to determine the bending stiffness of the filament. We find that the bending stiffness does not change drastically when the filament transforms from normal to hyperextended forms, which is estimated to be 2-3 pN⋅µm2. Furthermore, B. subtilis' flagellar filament has similar bending stiffness to Salmonella's, although the radius of the former is almost half of that of the latter, suggesting that the rigidity comes from the inner D0 and D1 subunit domains.

Correction: Antibody-coated microstructures for selective isolation of immune cells in blood.

Correction for 'Antibody-coated microstructures for selective isolation of immune cells in blood' by Jiyu Li et al., Lab Chip, 2020, 20, 1072-1082, DOI: 10.1039/D0LC00078G.

Employment of young people with mental health conditions: making it work.

PURPOSE: The current study was undertaken to understand and describe the meaning of work as well as the barriers and facilitators perceived by young people with mental health conditions for gaining and maintaining employment. MATERIALS AND METHODS: Employing a purposive and maximum variation sampling, 30 young people were recruited and interviewed. The respondents were Singapore residents with a mean age of 26.8 years (SD = 4.5, range 20-34 years); the majority were males (56.7%), of Chinese ethnicity (63.3%), and employed (73.3%), at the time of the interview. Verbatim transcripts were analysed using inductive thematic analysis. RESULTS: Three global themes emerged from the analyses of the narratives, which included (i) the meaning of employment, (ii) barriers to employment comprising individual, interpersonal and systemic difficulties and challenges participants faced while seeking and sustaining employment and (iii) facilitators of employment that consisted of individual and interpersonal factors that had helped the young persons to gain and maintain employment. CONCLUSIONS: Stigma and discrimination emerged as one of the most frequently mentioned employment barriers. These barriers are not insurmountable and can be overcome both through legislation as well as through the training and support of young people with mental health conditions.IMPLICATIONS FOR REHABILITATIONEmployment offers several benefits to people with mental health conditions, including improvement in economic status, self-efficacy, and empowerment.Stigma is a significant barrier to employment for young people with mental health conditions; remaining optimistic about career prospects and getting support from peers is vital to employment success.Disclosure of the mental health condition at the place of work is beneficial to the person's own recovery and helpful to others; however, young people must be empowered to choose when and what they want to disclose and under what circumstances.Families help young people with mental health conditions in achieving their employment goals by offering emotional and instrumental support, as well as motivating them to accomplish more.

Bacteria and cancer cell pearl chain under dielectrophoresis.

In this work, we aim to observe and study the physics of bacteria and cancer cells pearl chain formation under dielectrophoresis (DEP). Experimentally, we visualized the formation of Bacillus subtilis bacterial pearl chain and human breast cancer cell (MCF-7) chain under positive and negative dielectrophoretic force, respectively. Through a simple simulation with creeping flow, AC/DC electric fields, and particle tracing modules in COMSOL, we examined the mechanism by which bacteria self-organize into a pearl chain across the gap between two electrodes via DEP. Our simulation results reveal that the region of greatest positive DEP force shifts from the electrode edge to the leading edge of the pearl chain, thus guiding the trajectories of free-flowing particles toward the leading edge via positive DEP. Our findings additionally highlight the mechanism why the free-flowing particles are more likely to join the existing pearl chain rather than starting a new pearl chain. This phenomenon is primarily due to the increase in magnitude of electric field gradient, and hence DEP force exerted, with the shortening gap between the pearl chain leading edge and the adjacent electrode. The findings shed light on the observed behavior of preferential pearl chain formation across electrode gaps.

Roles, Facilitators and Challenges of Employment Support Specialists Assisting Young People with Mental Health Conditions.

Purpose The present study aimed to understand the roles, effective strategies and facilitators, and challenges of employment support specialists (ESS) in assisting young people with mental health conditions (MHCs) gain and sustain employment in Singapore. Methods An interpretative qualitative design using an inductive approach was adopted for this study. Using a semi-structured interview guide, in-depth interviews were conducted with twenty ESS employed with mental health service providers or other community-based centers. Verbatim transcripts of the interviews were thematically analyzed using inductive methods. ESS were broadly classified as "any professionals providing employment-related support to people with MHCs". Results Majority of the ESS were employed at a tertiary psychiatric institute. Participants included vocational and occupational specialists, case managers and other clinical professionals. Three key themes emerged from the data: (i) descriptions of roles undertaken by the ESS depicting a wide range of services and requisite skillsets; (ii) facilitators that benefit young people with MHCs' in terms of job placement, for example, ESS' attitudes and attributes, and their clients' disposition; and (iii) challenges that deter effective job placements, such as factors pertaining to the ESS themselves, their clients, and clients' employers. Under this theme, ESS also proposed ways to improve employment opportunities of people with MHCs. Conclusions This study provided insight into a range of tasks performed and challenges faced by ESS in Singapore while assisting their clients. There is a need to address ESS' challenges and expectations in order to enhance their efficiency and aid reintegration of young people with MHCs into the workforce and the society.

Caregivers' hopes, expectations and concerns surrounding the employment and future of young people with mental health conditions.

OBJECTIVE: Informal caregivers are often placed in a better position to understand and advocate for the vocational needs of young persons with mental health conditions. However, their opinions are largely ignored in the planning of vocational outcomes. This qualitative study had two broad aims: to explore (1) the perceptions of caregivers of young adults with mental health conditions on issues of paid employment and (2) their views and expectations of employment support services. METHODS: A total of 30 semi-structured interviews were conducted. Caregivers were 45 years old on average, the majority were women (73%) and were of Chinese ethnicity (53%). Most participants (60%) were parents of the young persons with psychotic disorders (57%), or affective and mood disorders, such as depression or anxiety disorders (43%). RESULTS: Thematic analyses of data revealed three superordinate themes: (1) caregiving roles, (2) caregivers' expectations and hopes, and (3) barriers to employmentof young persons with mental health conditions. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Caregivers strongly believed that employment support services should prioritise and advocate for recovery while securing employment. Local mental health employment support services should incorporate the views and expectations of caregivers of young persons with mental health conditions to foster better coordination between stakeholders, and enhance support for successful employment, reintegration into the community, and ultimately recovery for these individuals.

Antibody-coated microstructures for selective isolation of immune cells in blood.

Cell isolation from blood is an important process for diagnosing immune diseases. There are still demands for a user-friendly approach to achieve high cell extraction efficiency and purity of a target immune cell subtype for more promising diagnosis and monitoring. For selective immune cell isolation, we developed a microstructured device, which consists of antibody-coated micropillars and micro-sieve arrays, for isolating a target immune cell subtype from bovine blood samples. The focusing micropillars can guide immune cells flowing to the subsequent micro-sieves based on deterministic lateral shifts of the cells. The arrangement of these microstructures is characterized and configured for the maximal cell capture rate. Surface modification with a selected antibody offers selective cell capture in the micro-sieves based on the antigen-antibody reaction. We prepare a cell mixture of human CD14-expressing leukemia cells (THP-1) and epithelial cells (MDA-MB-231) in diluted blood to characterize the cell isolation operation, with a selective cell isolation yield of >80%, cell purity of ∼100% and cell viability of >93%. Together, this microstructured device strategy can achieve high-yield selective isolation of immune cells from blood samples and support downstream genetic and biochemical cell analyses, contributing to the medical diagnosis of a broad range of immune diseases.

Effectiveness of near-peer simulation for managing the acutely deteriorating patient among residents of an internal medicine junior residency programme.

INTRODUCTION: Near-peer teaching is gaining popularity as a teaching modality, as it improves the learner's understanding, is targeted at an appropriate level and promotes familiarisation. This study was initiated to evaluate the effectiveness of incorporating near-peer instruction into simulation-based training within a junior residency programme. METHODS: 42 first-year residents from an internal medicine junior residency programme were recruited. Participants underwent a simulation-based training programme conducted over five weeks. Each week involved either an emergency or acute clinical scenario. A structured questionnaire was administered prior to and after the course to compare participants' perceived knowledge, experience and confidence in managing the clinical scenarios. RESULTS: In our study, 83% of participants agreed/strongly agreed that the scenarios were realistic. There were improvements in perceived knowledge, experience and confidence after the course. The greatest improvement was seen for experience (post-simulation: median 7.00 [interquartile range (IQR) 6.00‒8.00] vs. pre-simulation: median 5.00 [IQR 3.00-6.25]). 65% of participants were keen to help with future training. CONCLUSION: Near-peer simulation training was found to be a viable and valuable method of instruction for first-year residents for increasing experience, instilling confidence and improving perceived knowledge. Integration of such programmes within medical education curricula shows good promise of continuity, with many first-year residents inspired to organise subsequent sessions.

Psychometric properties of the World Health Organization WHOQOL-BREF Quality of Life assessment in Singapore.

PURPOSE: This study validated the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire with 3400 respondents living in Singapore. METHODS: The ethnic composition was 76.1% Chinese, 12.3% Malay, 9.6% Indian, and 2% Others. The sample included adults with disabilities (28.9%), adults recovering from mental health issues (14%), and adults from the general population (57.1%). Questionnaires about health-related conditions, the effects of disability on everyday functioning (WHODAS 2.0), the WHOQOL-BREF, and add-on modules of QOL of people with disabilities (WHOQOL-DIS) and QOL of elders (WHOQOL-OLD) were administrated. RESULTS: Confirmatory factor analysis supported a construct of QOL made of four domains, revealing good construct validity. The four domains predicted overall QOL and health satisfaction. Good internal consistency was evidenced by high alpha coefficients for the physical (.79), psychological (.82), social relationships (.81), and environment (.83) domains. Convergent validity was shown by moderate correlations between the different questionnaires measuring QOL (WHOQOL-BREF, WHOQOL-DIS, and WHOQOL-OLD), and discriminant validity by a lower correlation between the WHOQOL-BREF and disability. Convergent and divergent validity were also indicated by higher correlations between similar constructs across the different measures, and lower correlations between dissimilar constructs across measures, respectively. Concurrent validity was supported by showing that individuals with chronic medical conditions had lower QOL than individuals without chronic medical conditions. CONCLUSIONS: The results showed that the WHOQOL-BREF has sound psychometric properties and can be used to measure QOL in Singapore.

Claudins and gastric carcinogenesis.

Gastric carcinoma arises from aberrant growth of normal gastric mucosa. There is increasing evidence that claudins (CLDNs) may play a critical role in the significant steps of gastric tumorigenesis, from metaplasia to metastasis. The CLDN family which consists of at least 27 member proteins is known to mediate selective permeability in cellular tight junctions. It is now established that CLDNs are differentially altered in gastric cancer and CLDN proteins are believed to play different roles in the growth and progression of gastric cancer.

Dual-window dual-bandwidth spectroscopic optical coherence tomography metric for qualitative scatterer size differentiation in tissues.

This study investigates the autocorrelation bandwidths of dual-window (DW) optical coherence tomography (OCT) k-space scattering profile of different-sized microspheres and their correlation to scatterer size. A dual-bandwidth spectroscopic metric defined as the ratio of the 10% to 90% autocorrelation bandwidths is found to change monotonically with microsphere size and gives the best contrast enhancement for scatterer size differentiation in the resulting spectroscopic image. A simulation model supports the experimental results and revealed a tradeoff between the smallest detectable scatterer size and the maximum scatterer size in the linear range of the dual-window dual-bandwidth (DWDB) metric, which depends on the choice of the light source optical bandwidth. Spectroscopic OCT (SOCT) images of microspheres and tonsil tissue samples based on the proposed DWDB metric showed clear differentiation between different-sized scatterers as compared to those derived from conventional short-time Fourier transform metrics. The DWDB metric significantly improves the contrast in SOCT imaging and can aid the visualization and identification of dissimilar scatterer size in a sample. Potential applications include the early detection of cell nuclear changes in tissue carcinogenesis, the monitoring of healing tendons, and cell proliferation in tissue scaffolds.