• International Journal of Stem Cells
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• v.16 no.3
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• pp.293-303
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• 2023

Background and Objectives: The physiological oxygen tension in fetal brains (~3%, physioxia) is beneficial for the maintenance of neural stem cells (NSCs). Sensitivity to oxygen varies between NSCs from different fetal brain regions, with midbrain NSCs showing selective susceptibility. Data on Hif-1𝛼/Notch regulatory interactions as well as our observations that Hif-1𝛼 and oxygen affect midbrain NSCs survival and proliferation prompted our investigations on involvement of Notch signalling in physioxia-dependent midbrain NSCs performance. Methods and Results: Here we found that physioxia (3% O₂) compared to normoxia (21% O₂) increased proliferation, maintained stemness by suppression of spontaneous differentiation and supported cell cycle progression. Microarray and qRT-PCR analyses identified significant changes of Notch related genes in midbrain NSCs after long-term (13 days), but not after short-term physioxia (48 hours). Consistently, inhibition of Notch signalling with DAPT increased, but its stimulation with Dll4 decreased spontaneous differentiation into neurons solely under normoxic but not under physioxic conditions. Conclusions: Notch signalling does not influence the fate decision of midbrain NSCs cultured in vitro in physioxia, where other factors like Hif-1𝛼 might be involved. Our findings on how physioxia effects in midbrain NSCs are transduced by alternative signalling might, at least in part, explain their selective susceptibility to oxygen.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.1
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• pp.100-108
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• 2021

Purpose: Percutaneous endoscopic gastrostomy (PEG) tube placements are commonly performed pediatric endoscopic procedures. Because of underlying disease, these patients are at increased risk for airway-related complications. This study compares patient characteristics and complications following initial PEG insertion with general endotracheal anesthesia (GETA) vs. anesthesia-directed deep sedation with a natural airway (ADDS). Methods: All patients 6 months to 18 years undergoing initial PEG insertion within the endoscopy suite were considered for inclusion in this retrospective cohort study. Selection of GETA vs. ADDS was made by the anesthesia attending after discussion with the gastroenterologist. Results: This study included 168 patients (GETA n=38, ADDS n=130). Cohorts had similar characteristics with respect to sex, race, and weight. Compared to ADDS, GETA patients were younger (1.5 years vs. 2.9 years, p=0.04), had higher rates of severe American Society of Anesthesiologists (ASA) disease severity scores (ASA 4-5) (21% vs. 3%, p<0.001), and higher rates of cardiac comorbidities (39.5% vs. 18.5%, p=0.02). Significant associations were not observed between GETA/ADDS status and airway support, 30-day readmission, fever, or pain medication in unadjusted or adjusted models. GETA patients had significantly increased length of stay (eβ=1.55, 95% confidence interval [CI]=1.11-2.18) after adjusting for ASA class, room time, anesthesia time, fever, and cardiac diagnosis. GETA patients also had increased room time (eβ=1.20, 95% CI=1.08-1.33) and anesthesia time (eβ=1.50, 95% CI=1.30-1.74) in adjusted models. Conclusion: Study results indicate that younger and higher risk patients are more likely to undergo GETA. Children selected for GETA experienced longer room times, anesthesia times, and hospital length of stay.

• The Journal of Advanced Prosthodontics
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• v.15 no.1
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• pp.1-10
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• 2023

PURPOSE. Accuracy of image matching between resting and smiling facial models is affected by the stability of the reference surfaces. This study aimed to investigate the morphometric variations in subdivided facial units during resting, posed and spontaneous smiling. MATERIALS AND METHODS. The posed and spontaneous smiling faces of 33 adults were digitized and registered to the resting faces. The morphological changes of subdivided facial units at the forehead (upper and lower central, upper and lower lateral, and temple), nasal (dorsum, tip, lateral wall, and alar lobules), and chin (central and lateral) regions were assessed by measuring the 3D mesh deviations between the smiling and resting facial models. The one-way analysis of variance, Duncan post hoc tests, and Student's t-test were used to determine the differences among the groups (α = .05). RESULTS. The smallest morphometric changes were observed at the upper and central forehead and nasal dorsum; meanwhile, the largest deviation was found at the nasal alar lobules in both the posed and spontaneous smiles (P < .001). The spontaneous smile generally resulted in larger facial unit changes than the posed smile, and significant difference was observed at the alar lobules, central chin, and lateral chin units (P < .001). CONCLUSION. The upper and central forehead and nasal dorsum are reliable areas for image matching between resting and smiling 3D facial images. The central chin area can be considered an additional reference area for posed smiles; however, special cautions should be taken when selecting this area as references for spontaneous smiles.

• Journal of Gastric Cancer
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• v.19 no.4
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• pp.375-392
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• 2019

Preoperative chemo- and radiotherapeutic strategies followed by surgery are currently a standard approach for treating locally advanced gastric and esophagogastric junction cancer in Western countries. However, in a large number of cases, the tumor is extremely resistant to these treatments and the patients are exposed to unnecessary toxicity and delayed surgical therapy. The current clinical trials evaluating the combination of preoperative systemic therapies with modern targeted and immunotherapeutic agents represent a unique opportunity for identifying predictive biomarkers of response to select patients that would benefit the most from these treatments. However, it is of utmost importance that these potential biomarkers are corroborated by extensive preclinical and translational research. The aim of this review article is to present the most promising biomarkers of response to classic chemotherapeutic, anti-HER2, antiangiogenic, and immunotherapeutic agents that can be potentially useful for personalized preoperative systemic therapies in gastric cancer patients.

• Toxicological Research
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• v.35 no.4
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• pp.319-330
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• 2019

Adverse drug reactions (ADRs) constitute key factors in determining successful medication therapy in clinical situations. Integrative analysis of electronic medical record (EMR) data and use of proper analytical tools are requisite to conduct retrospective surveillance of clinical decisions on medications. Thus, we suggest that electronic medical recording and human genetic databases are considered together in future directions of pharmacovigilance. We analyzed EMR-based ADR studies indexed on PubMed during the period from 2005 to 2017 and retrospectively acquired 1161 (29.6%) articles describing drug-induced adverse reactions (e.g., liver, kidney, nervous system, immune system, and inflammatory responses). Of them, only 102 (8.79%) articles contained useful information to detect or predict ADRs in the context of clinical medication alerts. Since insufficiency of EMR datasets and their improper analyses may provide false warnings on clinical decision, efforts should be made to overcome possible problems on data-mining, analysis, statistics, and standardization. Thus, we address the characteristics and limitations on retrospective EMR database studies in hospital settings. Since gene expression and genetic variations among individuals impact ADRs, pharmacokinetics, and pharmacodynamics, appropriate paths for pharmacovigilance may be optimized using suitable databases available in public domain (e.g., genome-wide association studies (GWAS), non-coding RNAs, microRNAs, proteomics, and genetic variations), novel targets, and biomarkers. These efforts with new validated biomarker analyses would be of help to repurpose clinical and translational research infrastructure and ultimately future personalized therapy considering ADRs.

• IMMUNE NETWORK
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• v.22 no.3
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• pp.22.1-22.25
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• 2022

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2), has spread over the world causing a pandemic which is still ongoing since its emergence in late 2019. A great amount of effort has been devoted to understanding the pathogenesis of COVID-19 with the hope of developing better therapeutic strategies. Transcriptome analysis using technologies such as RNA sequencing became a commonly used approach in study of host immune responses to SARS-CoV-2. Although substantial amount of information can be gathered from transcriptome analysis, different analysis tools used in these studies may lead to conclusions that differ dramatically from each other. Here, we re-analyzed four RNA-sequencing datasets of COVID-19 samples including human bronchoalveolar lavage fluid, nasopharyngeal swabs, lung biopsy and hACE2 transgenic mice using the same standardized method. The results showed that common features of COVID-19 include upregulation of chemokines including CCL2, CXCL1, and CXCL10, inflammatory cytokine IL-1β and alarmin S100A8/S100A9, which are associated with dysregulated innate immunity marked by abundant neutrophil and mast cell accumulation. Downregulation of chemokine receptor genes that are associated with impaired adaptive immunity such as lymphopenia is another common feather of COVID-19 observed. In addition, a few interferon-stimulated genes but no type I IFN genes were identified to be enriched in COVID-19 samples compared to their respective control in these datasets. These features are in line with results from single-cell RNA sequencing studies in the field. Therefore, our re-analysis of the RNA-seq datasets revealed common features of dysregulated immune responses to SARS-CoV-2 and shed light to the pathogenesis of COVID-19.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.27 no.4
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• pp.224-235
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• 2024

Purpose: Biliary atresia (BA) is the leading cause of neonatal cholestasis (25-45%). The primary treatment is hepatic portoenterostomy (Kasai procedure), but only 20-40% provide long-term benefits. This study aimed to develop a predictive model for surgical efficacy by comparing preoperative and early postoperative indicators in infants with different outcomes. Methods: We enrolled 166 infants with BA (93 girls, 73 boys) who underwent the Kasai procedure between September 2002 and December 2021, dividing them into favorable or adverse outcome groups. Over 40 parameters were measured, and the diagnostic significance of the prognostic model was evaluated. Results: Kasai surgery was efficacious in 69 patients (42%) and non-efficacious in 97 (58%). Our model assesses efficacy by day 14 after surgery, improving on the <34 µmol/L direct bilirubin threshold established for 3-6 months after the procedure. Including the Desmet fibrosis score refined the model. Conclusion: Blood cholesterol below 5.41 mmol/L, direct bilirubin below 56.3 µmol/L on postoperative days 14±3, and a low Desmet score indicate a high probability of efficacious Kasai surgery in infants with BA.

• KSBB Journal
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• v.28 no.6
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• pp.339-348
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• 2013

Translational research (TR) as high quality research can accelerate collaboration strongly between biotechnology-based researchers and clinical-research experts for overcoming diseases. TR facilitates basic science translated to clinical efficacy and effectiveness from bench (basic science) to bedside (clinical practice) for the enhancement of human health. Disease-oriented TR programs were defined as unilateral, bilateral and multilateral TR in this patent performance analysis. Patent performance was measured in a R&D project on Health and Medical Technology to enhance the productivity of R&D investment on disease-oriented TR in Health Technology (HT). Patent Map (PM) analysis and Bibliometrics were conducted to collect information for the assessment of research patents of TR programs. Futhermore, PIAS (Patent Information Analysis System) and Thinklear programs were applied for quantitative and qualitative analysis successfully. These indicate that multi-dimensional analysis of patent performance for disease-oriented TR could promote the connection of R&D-IP (Research and Development-Intellectural Property) and R&BD (Research and Business Development) supporting system significantly.

• International Journal of Stem Cells
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• v.16 no.1
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• pp.108-116
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• 2023

γδ T cells are a rare and unique prototype of T cells that share properties with natural killer cells in secondary lymphoid organs. Although many studies have revealed the function and importance of adult-derived γδ T cells in cancer biology and regenerative medicine, the low numbers of these cells hamper their application as therapeutic cell sources in the clinic. To solve this problem, pluripotent stem cell-derived γδ T cells are considered alternative cell sources; however, few studies have reported the generation of human pluripotent stem cell-derived γδ T cells. In the present study, we investigated whether lymphoid lineage γδ T cells were successfully generated from human pluripotent stem cells via hemogenic endothelium under defined culture conditions. Our results revealed that pluripotent stem cells successfully generated γδ T cells with an overall increase in transcriptional activity of lymphoid lineage genes and cytolytic factors, indicating the importance of the optimization of culture conditions in generating lymphoid lineage γδ T cells. We uncovered an initial step in differentiating γδ T cells that could be applied to basic and translational investigations in the field of cancer biology. Based on our result, we will develop an appropriate method to purify γδ T cells with functionality and it helpful for the study of basic mechanism of γδ T cells in pathophysiologic condition as well as clinic application.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2379-2381
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• 2014

It is becoming progressively more understandable that phytochemicals derived from edible plants have shown potential in modelling their interactions with their target proteins. Rapidly accumulating in-vitro and in- vivo evidence indicates that anthocyanins have anticancer activity in rodent models of cancer. More intriguingly, evaluation of bilberry anthocyanins as chemopreventive agents in twenty-five colorectal cancer patients has opened new window of opportunity in translating the findings from laboratory to clinic. Confluence of information suggests that anthocyanins treated cancer cells reveal up-regulation of tumor suppressor genes. There is a successive increase in the research-work in nutrigenomics and evidence has started to shed light on intracellular-signaling cascades as common molecular targets for anthocyanins. In this review we bring to l imelight how anthocyanins induced apoptosis in cancer cells via activation of extrinsic and intrinsic pathways.