Molecular pathology quality control in Southeast Asia: Results of a multiregional quality assurance study from MASTER KEY Asia.

Tissue specimen quality assurance is a major issue of precision medicine for rare cancers. However, the laboratory standards and quality of pathological specimens prepared in Asian hospitals remain unknown. To understand the methods in Southeast Asian oncology hospitals and to clarify how pre-analytics affect the quality of formalin-fixed paraffin-embedded (FFPE) specimens, a questionnaire surveying pre-analytical procedures (Part I) was administered, quality assessment of immunohistochemistry (IHC) staining and DNA/RNA extracted from the representative FFPE specimens from each hospital (Part II) was conducted, and the quality of DNA/RNA extracted from FFPE of rare-cancer patients for genomic sequencing (Part III) was examined. Quality measurements for DNA/RNA included ΔΔCt, DV200, and cDNA yield. Six major cancer hospitals from Malaysia, Philippines, and Vietnam participated. One hospital showed unacceptable quality for the DNA/RNA assessment, but improved by revising laboratory procedures. Only 57% (n = 73) of the 128 rare-cancer patients' specimens met both DNA and RNA quality criteria for next-generation sequencing. Median DV200 was 80.7% and 64.3% for qualified and failed RNA, respectively. Median ΔΔCt was 1.25 for qualified and 4.89 for failed DNA. Longer storage period was significantly associated with poor DNA (fail to qualify ratio = 1579:321 days, p < 0.001) and RNA (fail to qualify ratio = 1070:280 days, p < 0.001). After improvement of pre-analytical factors, the qualification rate increased for hospitals A and E from 41.5% to 70.5% and 62.5% to 86%, respectively. This is the first report to elucidate the pre-analytical laboratory procedures of main Southeast Asian oncology hospitals. An external quality assessment program may improve factors associated with tumor FFPE specimen quality.

Visibility Graph Analysis of Reservoir-Triggered Seismicity: The Case of Song Tranh 2 Hydropower, Vietnam.

In this study, the visibility graph analysis of seismicity triggered by Song Tranh 2 hydropower (Vietnam) is performed. The relationship between the seismic (the Gutenberg-Richter b-value) and topological (the k-M slope) parameters of seismicity is analysed. Our findings indicate that the relationship between the Gutenberg-Richter b-value and the k-M slope of the investigated seismicity is in agreement with that characterising the tectonic seismicity. The results obtained from analysing the reservoir-triggered seismicity of Song Tranh 2 area could contribute to better characterisation of the relationship between the seismological and topological parameters of seismicity, strengthening the universal character of the relationship between the b-value and the k-M slope.

Cobalt/Lewis Acid Catalysis for Hydrocarbofunctionalization of Alkynes via Cooperative C-H Activation.

A catalytic system comprising a cobalt-diphosphine complex and a Lewis acid (LA) such as AlMe3 has been found to promote hydrocarbofunctionalization reactions of alkynes with Lewis basic and electron-deficient substrates such as formamides, pyridones, pyridines and related azines, imidazo[1,2-a]pyridines, and azole derivatives through site-selective C-H activation. Compared with known Ni/LA catalytic systems for analogous transformations, the present catalytic systems not only feature convenient setup using inexpensive and bench-stable precatalyst and ligand such as Co(acac)3 and 1,3-bis(diphenylphosphino)propane (dppp) but also display distinct site-selectivity toward C-H activation of pyridone and pyridine derivatives. In particular, a completely C4-selective alkenylation of pyridine has been achieved for the first time. Meanwhile, the present catalytic system proved to promote exclusively C5-selective alkenylation of imidazo[1,2-a]pyridine derivatives. Mechanistic studies including DFT calculations on the Co/Al-catalyzed addition of formamide to alkyne have suggested that the reaction involves cleavage of the carbamoyl C-H bond as the rate-limiting step, which proceeds through a ligand-to-ligand hydrogen transfer (LLHT) mechanism leading to an alkenyl(carbamoyl)cobalt intermediate.

A 28-year observational study of urinary cadmium and ß2 -microglobulin concentrations in inhabitants in cadmium-polluted areas in Japan.

The biological half-life of cadmium (Cd) is as long as 10-30 years. Exposure to this element induces renal tubular dysfunction, which is considered irreversible. ß2 -microglobulin (ß2 -MG) is a low-molecular-weight protein, and urinary ß2 -MG is one of the most useful and critical indicators for the early detection of renal tubular dysfunction. However, very little research has been published concerning the long-term observation of Cd-induced adverse health effects. As such, this follow-up study was conducted for 28 years to clarify the relationship between the concentration of Cd and ß2 -MG in the urine of 28 inhabitants (14 male and 14 female) living in the Kakehashi River basin, Ishikawa prefecture (Japan), previously one of the most highly Cd-polluted regions in this country. All subjects were over 60 years old in 2014 and participated in all six health examinations conducted over 28 years (1986-2014). Urine was collected at the appropriate time and kept frozen to analyze urinary Cd and ß2 -MG concentrations. The urinary Cd concentration was found to decrease by nearly half between 1986 and 2008 in both male and female subjects, whereas it increased significantly from 2008 to 2014 in males. In contrast, urinary ß2 -MG concentrations tended to increase over the 28-year study period in both sexes. Urinary Cd and ß2 -MG concentrations in females were significantly higher than those in males in this Cd-polluted region. Age is more strongly associated with urinary ß2 -MG concentration than recent Cd body burden. Copyright © 2016 John Wiley & Sons, Ltd.

Biosorption and biodegradation of a sulfur dye in high-strength dyeing wastewater by Acidithiobacillus thiooxidans.

The ability of the bacterial strain Acidithiobacillus thiooxidans to remove sulfur blue 15 (SB15) dye from water samples was examined. This bacterium could not only oxidize sulfur compounds to sulfuric acid but also promote the attachment of the cells to the surface of sulfidic particles, therefore serving as an efficient biosorbent. The biosorption isotherms were better described by the Langmuir equation than by the Freundlich or Dubinin-Radushkevich equation. Also, the biosorption process followed the pseudo-second-order kinetics. At pH 8.3 and SB15 concentrations up to 2000 mg L(-1) in the biomass/mineral salt solution, the dye removal and decolorization were 87.5% and 91.4%, respectively, following the biosorption process. Biodegradation was proposed as a subsequent process for the remaining dye (250-350 mg L(-1)). A central composite design was used to analyze independent variables in the response surface methodology study. Under the optimal conditions (i.e., initial dye concentration of 300 mg L(-1), initial biomass concentration of 1.0 g L(-1), initial pH of 11.7, and yeast extract dose of 60 mg L(-1)), up to 50% of SB15 was removed after 4 days of biodegradation.

Painting blood vessels and atherosclerotic plaques with an adhesive drug depot.

The treatment of diseased vasculature remains challenging, in part because of the difficulty in implanting drug-eluting devices without subjecting vessels to damaging mechanical forces. Implanting materials using adhesive forces could overcome this challenge, but materials have previously not been shown to durably adhere to intact endothelium under blood flow. Marine mussels secrete strong underwater adhesives that have been mimicked in synthetic systems. Here we develop a drug-eluting bioadhesive gel that can be locally and durably glued onto the inside surface of blood vessels. In a mouse model of atherosclerosis, inflamed plaques treated with steroid-eluting adhesive gels had reduced macrophage content and developed protective fibrous caps covering the plaque core. Treatment also lowered plasma cytokine levels and biomarkers of inflammation in the plaque. The drug-eluting devices developed here provide a general strategy for implanting therapeutics in the vasculature using adhesive forces and could potentially be used to stabilize rupture-prone plaques.

Families in transition (FIT) study protocol: feasibility, acceptability and preliminary effects of a group-based parent training in parents of youth in psychiatric residential treatment.

INTRODUCTION: Although adolescents make treatment gains in psychiatric residential treatment (RT), they experience significant difficulty adapting to the community and often do not sustain treatment gains long term. Their parents are often not provided with the necessary support or behaviour management skillset to bridge the gap between RT and home. Parent training, a gold standard behaviour management strategy, may be beneficial for parents of these youth and web-based parent training programmes may engage this difficult-to-reach population. This study focuses on a hybrid parent training programme that combines Parenting Wisely (PW), a web-based parent training with facilitated discussion groups (Parenting Wisely for Residential Treatment (PWRT)). This study aims to: (1) establish the feasibility and acceptability of PWRT, (2) evaluate whether PWRT engages target mechanisms (parental self-efficacy, parenting behaviours, social support, family function) and (3) determine the effects of PWRT on adolescent outcomes (internalising and externalising behaviours, placement restrictiveness). METHODS AND ANALYSIS: In this randomised control trial, parents (n=60) will be randomly assigned to PWRT or treatment as usual. Each week for 6 weeks, parents in the PWRT condition will complete two PW modules (20 min each) and attend one discussion group via Zoom (90 min). Adolescents (n=60) will not receive intervention; however, we will evaluate the feasibility of adolescent data collection for future studies. Data from parents and adolescents will be collected at baseline, post intervention (6 weeks post baseline) and 6 months post baseline to allow for a robust understanding of the longer-term effects of PWRT on treatment gain maintenance. ETHICS AND DISSEMINATION: The study has been approved by The Ohio State University Institutional Review Board (protocol number 2022B0315). The outcomes of the study will be shared through presentations at both local and national conferences, publications in peer-reviewed journals and disseminated to the families and organisations that helped to facilitate the project. TRIAL REGISTRATION NUMBER: NCT05764369 (V.1, December 2022).

Community-engaged Research Disruption: The Impact of the COVID-19 Pandemic on Research With Communities.

BACKGROUND: The pandemic has had dire consequences on community-engaged research. OBJECTIVES: We describe research challenges imposed by the pandemic on our breast and cervical cancer intervention study with Southeast Asian immigrant women, and strategies used to maintain study continuity. METHODS: The pandemic's impact on the research team, recruitment and retention of participants, study design, and strategies executed to these issues are described. RESULTS: Strategies employed to address research challenges include implementing coronavirus disease 2019 protocols for conducting community research; recruiting participants online, outside of the planned community locations, and through social media; and enhancing the study design by using respondent-driven sampling. In addition to educating communities about early cancer detection, we also provided information and resources about coronavirus disease 2019, including transmission mitigation, testing, and vaccination. CONCLUSIONS: Continuing to engage the communities in our study is critical to our long-term goal of eliminating cancer screening disparities in Southeast Asian immigrant communities.

Mapping for Engagement: Setting up a Community Based Participatory Research Project to Reach Underserved Communities at Risk for Hepatitis C in Ho Chi Minh City, Vietnam.

BACKGROUND: Approximately 1. 07 million people in Vietnam are infected with hepatitis C virus (HCV). To address this epidemic, the South East Asian Research Collaborative in Hepatitis (SEARCH) launched a 600-patient cohort study and two clinical trials, both investigating shortened treatment strategies for chronic HCV infection with direct-acting antiviral drugs. We conducted ethnographic research with a subset of trial participants and found that the majority were aware of HCV infection and its implications and were motivated to seek treatment. However, people who inject drugs (PWID), and other groups at risk for HCV were under-represented, although injecting drug use is associated with high rates of HCV. MATERIAL AND METHODS: We designed a community-based participatory research (CBPR) study to engage in dialogues surrounding HCV and other community-prioritized health issues with underserved groups at risk for HCV in Ho Chi Minh City. The project consists of three phases: situation analysis, CBPR implementation, and dissemination. In this paper, we describe the results of the first phase (i.e., the situation analysis) in which we conducted desk research and organized stakeholder mapping meetings with representatives from local non-government and community-based organizations where we used participatory research methods to identify and analyze key stakeholders working with underserved populations. RESULTS: Twenty six institutions or groups working with the key underserved populations were identified. Insights about the challenges and dynamics of underserved communities were also gathered. Two working groups made up of representatives from the NGO and CBO level were formed. DISCUSSION: Using the information provided by local key stakeholders to shape the project has helped us to build solid relationships, give the groups a sense of ownership from the early stages, and made the project more context specific. These steps are not only important preliminary steps for participatory studies but also for other research that takes place within the communities.

Virtual organelle self-coding for fluorescence imaging via adversarial learning.

SIGNIFICANCE: Our study introduces an application of deep learning to virtually generate fluorescence images to reduce the burdens of cost and time from considerable effort in sample preparation related to chemical fixation and staining. AIM: The objective of our work was to determine how successfully deep learning methods perform on fluorescence prediction that depends on structural and/or a functional relationship between input labels and output labels. APPROACH: We present a virtual-fluorescence-staining method based on deep neural networks (VirFluoNet) to transform co-registered images of cells into subcellular compartment-specific molecular fluorescence labels in the same field-of-view. An algorithm based on conditional generative adversarial networks was developed and trained on microscopy datasets from breast-cancer and bone-osteosarcoma cell lines: MDA-MB-231 and U2OS, respectively. Several established performance metrics-the mean absolute error (MAE), peak-signal-to-noise ratio (PSNR), and structural-similarity-index (SSIM)-as well as a novel performance metric, the tolerance level, were measured and compared for the same algorithm and input data. RESULTS: For the MDA-MB-231 cells, F-actin signal performed the fluorescent antibody staining of vinculin prediction better than phase-contrast as an input. For the U2OS cells, satisfactory metrics of performance were archieved in comparison with ground truth. MAE is <0.005, 0.017, 0.012; PSNR is >40 / 34 / 33 dB; and SSIM is >0.925 / 0.926 / 0.925 for 4',6-diamidino-2-phenylindole/hoechst, endoplasmic reticulum, and mitochondria prediction, respectively, from channels of nucleoli and cytoplasmic RNA, Golgi plasma membrane, and F-actin. CONCLUSIONS: These findings contribute to the understanding of the utility and limitations of deep learning image-regression to predict fluorescence microscopy datasets of biological cells. We infer that predicted image labels must have either a structural and/or a functional relationship to input labels. Furthermore, the approach introduced here holds promise for modeling the internal spatial relationships between organelles and biomolecules within living cells, leading to detection and quantification of alterations from a standard training dataset.

Burnout Study of Clinical Nurses in Vietnam: Development of Job Burnout Model Based on Leiter and Maslach's Theory.

PURPOSE: This study aimed to create a Vietnamese version of both the Maslach Burnout Inventory-General Survey (MBI-GS) and Areas of Worklife Scale (AWS) to assess the burnout state of Vietnamese clinical nurses and to develop a causal model of burnout of clinical nurses. METHODS: We conducted a descriptive design using a cross-sectional survey. The questionnaire was hand divided directly by nursing departments to 500 clinical nurses in three hospitals. Vietnamese MBI-GS and AWS were then examined for reliability and validity. We used the revised exhaustion +1 burnout classification to access burnout state. We performed path analysis to develop a Vietnamese causal model based on the original model by Leiter and Maslach's theory. RESULTS: We found that both scales were reliable and valid for assessing burnout. Among nurse participants, the percentage of severe burnout was 0.7% and burnout was 15.8%, and 17.2% of nurses were exhausted. The best predictor of burnout was "on-duty work schedule" that clinical nurses have to work for 24 hours. In the causal model, we also found similarity and difference pathways in comparison with the original model. CONCLUSION: Vietnamese MBI-GS and AWS were applicable to research on occupational stress. Nearly one-fifth of Vietnamese clinical nurses were working in burnout state. The causal model suggested a range of factors resulting in burnout, and it is necessary to consider the specific solution to prevent burnout problem.

HER2 Status and Its Heterogeneity in Gastric Carcinoma of Vietnamese Patient.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is related to the pathogenesis and poor outcome of numerous types of carcinomas, including gastric carcinoma. Gastric cancer patients with HER2 positivity have become potential candidates for targeted therapy with trastuzumab. METHODS: We investigated 208 gastric cancer specimens using immunohistochemistry (IHC), fluorescence in situ hybridization and dual in situ hybridization (ISH). We also investigated the concordance between IHC and ISH. The correlation between HER2 status and various clinicopathological findings was also investigated. RESULTS: In total, 15.9% (33/208) and 24.5% (51/208) of gastric cancers showed HER2 gene amplification and protein overexpression, respectively. A high level of concordance between ISH and IHC analyses (91.3%, κ = 0.76) was found. A significant correlation between HER2 status and intestinal-type (p < .05) and differentiated carcinomas (p < .05) was also noted. The HER2 heterogeneity was high in gastric cancers; we found 68.8% phenotypic heterogeneity and 57.6% genotypic heterogeneity. Heterogeneity in HER2 protein expression and gene amplification showed a close association with diffuse histologic type and IHC 2+. CONCLUSIONS: HER2 protein overexpression and gene amplification were detected in 24.5% and 15.9% of gastric cancer specimens, respectively. Intestinal-type showed a higher level of HER2 protein overexpression and gene amplification than diffuse type. HER2 status also showed a significant relationship with well- and moderately-differentiated carcinomas. The ratio of phenotypic and genotypic heterogeneity of HER2 was high in gastric carcinomas and was associated with HER2 IHC 2+ and diffuse histologic type.

Having a lot of a good thing: multiple important group memberships as a source of self-esteem.

Membership in important social groups can promote a positive identity. We propose and test an identity resource model in which personal self-esteem is boosted by membership in additional important social groups. Belonging to multiple important group memberships predicts personal self-esteem in children (Study 1a), older adults (Study 1b), and former residents of a homeless shelter (Study 1c). Study 2 shows that the effects of multiple important group memberships on personal self-esteem are not reducible to number of interpersonal ties. Studies 3a and 3b provide longitudinal evidence that multiple important group memberships predict personal self-esteem over time. Studies 4 and 5 show that collective self-esteem mediates this effect, suggesting that membership in multiple important groups boosts personal self-esteem because people take pride in, and derive meaning from, important group memberships. Discussion focuses on when and why important group memberships act as a social resource that fuels personal self-esteem.

Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug.

Immuno-isolation of islets has the potential to enable the replacement of pancreatic function in diabetic patients. However, host response to the encapsulated islets frequently leads to fibrotic overgrowth with subsequent impairment of the transplanted grafts. Here, we identified and incorporated anti-inflammatory agents into islet-containing microcapsules to address this challenge. In vivo subcutaneous screening of 16 small molecule anti-inflammatory drugs was performed to identify promising compounds that could minimize the formation of fibrotic cell layers. Using parallel non-invasive fluorescent and bioluminescent imaging, we identified dexamethasone and curcumin as the most effective drugs in inhibiting the activities of inflammatory proteases and reactive oxygen species in the host response to subcutaneously injected biomaterials. Next, we demonstrated that co-encapsulating curcumin with pancreatic rat islets in alginate microcapsules reduced fibrotic overgrowth and improved glycemic control in a mouse model of chemically-induced type I diabetes. These results showed that localized administration of anti-inflammatory drug can improve the longevity of encapsulated islets and may facilitate the translation of this technology toward a long-term cure for type I diabetes.