Controlling the confounding effect of metabolic gene expression to identify actual metabolite targets in microsatellite instability cancers.

BACKGROUND: The metabolome is the best representation of cancer phenotypes. Gene expression can be considered a confounding covariate affecting metabolite levels. Data integration across metabolomics and genomics to establish the biological relevance of cancer metabolism is challenging. This study aimed to eliminate the confounding effect of metabolic gene expression to reflect actual metabolite levels in microsatellite instability (MSI) cancers. METHODS: In this study, we propose a new strategy using covariate-adjusted tensor classification in high dimensions (CATCH) models to integrate metabolite and metabolic gene expression data to classify MSI and microsatellite stability (MSS) cancers. We used datasets from the Cancer Cell Line Encyclopedia (CCLE) phase II project and treated metabolomic data as tensor predictors and data on gene expression of metabolic enzymes as confounding covariates. RESULTS: The CATCH model performed well, with high accuracy (0.82), sensitivity (0.66), specificity (0.88), precision (0.65), and F1 score (0.65). Seven metabolite features adjusted for metabolic gene expression, namely, 3-phosphoglycerate, 6-phosphogluconate, cholesterol ester, lysophosphatidylethanolamine (LPE), phosphatidylcholine, reduced glutathione, and sarcosine, were found in MSI cancers. Only one metabolite, Hippurate, was present in MSS cancers. The gene expression of phosphofructokinase 1 (PFKP), which is involved in the glycolytic pathway, was related to 3-phosphoglycerate. ALDH4A1 and GPT2 were associated with sarcosine. LPE was associated with the expression of CHPT1, which is involved in lipid metabolism. The glycolysis, nucleotide, glutamate, and lipid metabolic pathways were enriched in MSI cancers. CONCLUSIONS: We propose an effective CATCH model for predicting MSI cancer status. By controlling the confounding effect of metabolic gene expression, we identified cancer metabolic biomarkers and therapeutic targets. In addition, we provided the possible biology and genetics of MSI cancer metabolism.

A non-genetic engineering platform for rapidly generating and expanding cancer-specific armed T cells.

BACKGROUND: Cancer-specific adoptive T cell therapy has achieved successful milestones in multiple clinical treatments. However, the commercial production of cancer-specific T cells is often hampered by laborious cell culture procedures, the concern of retrovirus-based gene transfection, or insufficient T cell purity. METHODS: In this study, we developed a non-genetic engineering technology for rapidly manufacturing a large amount of cancer-specific T cells by utilizing a unique anti-cancer/anti-CD3 bispecific antibody (BsAb) to directly culture human peripheral blood mononuclear cells (PBMCs). The anti-CD3 moiety of the BsAb bound to the T cell surface and stimulated the differentiation and proliferation of T cells in PBMCs. The anti-cancer moiety of the BsAb provided these BsAb-armed T cells with the cancer-targeting ability, which transformed the naïve T cells into cancer-specific BsAb-armed T cells. RESULTS: With this technology, a large amount of cancer-specific BsAb-armed T cells can be rapidly generated with a purity of over 90% in 7 days. These BsAb-armed T cells efficiently accumulated at the tumor site both in vitro and in vivo. Cytotoxins (perforin and granzyme) and cytokines (TNF-α and IFN-γ) were dramatically released from the BsAb-armed T cells after engaging cancer cells, resulting in a remarkable anti-cancer efficacy. Notably, the BsAb-armed T cells did not cause obvious cytokine release syndrome or tissue toxicity in SCID mice bearing human tumors. CONCLUSIONS: Collectively, the BsAb-armed T cell technology represents a simple, time-saving, and highly safe method to generate highly pure cancer-specific effector T cells, thereby providing an affordable T cell immunotherapy to patients.

Do teaching staff trust stakeholders and tools in learning analytics? A mixed methods study.

Learning analytics (LA) has gained increasing attention for its potential to improve different educational aspects (e.g., students' performance and teaching practice). The existing literature identified some factors that are associated with the adoption of LA in higher education, such as stakeholder engagement and transparency in data use. The broad literature on information systems also emphasizes the importance of trust as a critical predictor of technology adoption. However, the extent to which trust plays a role in the adoption of LA in higher education has not been examined in detail in previous research. To fill this literature gap, we conducted a mixed method (survey and interviews) study aimed to explore how much teaching staff trust LA stakeholders (e.g., higher education institutions or third-parties) and LA technology, as well as the trust factors that could hinder or enable adoption of LA. The findings show that the teaching staff had a high level of trust in the competence of higher education institutions and the usefulness of LA; however, the teaching staff had a low level of trust in third parties that are involved in LA (e.g., external technology vendors) in terms of handling privacy and ethics-related issues. They also had a low level of trust in data accuracy due to issues such as outdated data and lack of data governance. The findings have strategic implications for institutional leaders and third parties in the adoption of LA by providing recommendations to increase trust, such as, improving data accuracy, developing policies for data sharing and ownership, enhancing the consent-seeking process, and establishing data governance guidelines. Therefore, this study contributes to the literature on the adoption of LA in HEIs by integrating trust factors.

Untangling connections between challenges in the adoption of learning analytics in higher education.

Potential benefits of learning analytics (LA) for improving students' performance, predicting students' success, and enhancing teaching and learning practice have increasingly been recognized in higher education. However, the adoption of LA in higher education institutions (HEIs) to date remains sporadic and predominantly small in scale due to several socio-technical challenges. To better understand why HEIs struggle to scale LA adoption, it is needed to untangle adoption challenges and their related factors. This paper presents the findings of a study that sought to investigate the associations of adoption factors with challenges HEIs face in the adoption of LA and how these associations are compared among HEIs at different scopes of adoption. The study was based on a series of semi-structured interviews with senior managers in HEIs. The interview data were thematically analysed to identify the main challenges in LA adoption. The connections between challenges and other factors related to LA adoption were analysed using epistemic network analysis (ENA). From senior managers' viewpoints, ethical issues of informed consent and resistance culture had the strongest links with challenges of learning analytic adoption in HEI; this was especially true for those institutions that had not adopted LA or who were in the initial phase of adoption (i.e., preparing for or partially implementing LA). By contrast, among HEIs that had fully adopted LA, the main challenges were found to be associated with centralized leadership, gaps in the analytic capabilities, external stakeholders, and evaluations of technology. Based on the results, we discuss implications for LA strategy that can be useful for institutions at various stages of LA adoption, from early stages of interest to the full adoption phase.

Automated Stanford classification of aortic dissection using a 2-step hierarchical neural network at computed tomography angiography.

OBJECTIVES: This study aimed to evaluate the feasibility of automatic Stanford classification of classic aortic dissection (AD) using a 2-step hierarchical neural network. METHODS: Between 2015 and 2019, 130 arterial phase series (57 type A, 43 type B, and 30 negative cases) in aortic CTA were collected for the training and validation. A 2-step hierarchical model was built including the first step detecting AD and the second step predicting the probability (0-1) of Stanford types. The model's performance was evaluated with an off-line prospective test in 2020. The sensitivity and specificity for Stanford type A, type B, and no AD (Sens A, B, N and Spec A, B, N, respectively) and Cohen's kappa were reported. RESULTS: Of 298 cases (22 with type A, 29 with type B, and 247 without AD) in the off-line prospective test, the Sens A, Sens B, and Sens N were 95.45% (95% confidence interval [CI], 77.16-99.88%), 79.31% (95% CI, 60.28-92.01%), and 93.52% (95% CI, 89.69-96.25%), respectively. The Spec A, Spec B, and Spec N were 98.55% (95% CI, 96.33-99.60%), 94.05% (95% CI, 90.52-96.56%), and 94.12% (95% CI, 83.76-98.77%), respectively. The classification rate achieved 92.28% (95% CI, 88.64-95.04%). The Cohen's kappa was 0.766 (95% CI, 0.68-0.85; p < 0.001). CONCLUSIONS: Stanford classification of classic AD can be determined by a 2-step hierarchical neural network with high sensitivity and specificity of type A and high specificity in type B and no AD. KEY POINTS: • The Stanford classification for aortic dissection is widely adopted and divides it into Stanford type A and type B based on the ascending thoracic aorta dissected or not. • The 2-step hierarchical neural network for Stanford classification of classic aortic dissection achieved high sensitivity (95.45%) and specificity (98.55%) of type A and high specificity in type B and no aortic dissection (94.05% and 94.12%, respectively) in 298 test cases. • The 2-step hierarchical neural network demonstrated moderate agreement (Cohen's kappa: 0.766, p < 0.001) with cardiovascular radiologists in detection and Stanford classification of classic aortic dissection in 298 test cases.

Effects of backhand stroke styles on bone mineral content and density in postmenopausal recreational tennis players: a cross-sectional pilot investigation.

BACKGROUND: One-handed backhand (OB) and two-handed backhand (TB) styles are commonly used in tennis, but only TB generates loadings on the non-dominant arm and a greater extension torque on the rear leg, leading to a greater axial torque involving rotation of the hip and trunk. The current study investigated whether those effects can further affect bone area (BA), bone mineral content (BMC) and density (BMD) in postmenopausal recreational tennis players. METHODS: BA, BMC and BMD of the lumbar spine, hip and distal radius were assessed using dual-energy X-ray absorptiometry in TB, OB, and swimmers' group as a control (SG) (all participants self-reported for at least 5 years of exercise history, n = 14 per group). Muscular strength was assessed with a hand dynamometer. Among these three groups, the BA, BMC and BMD of distal radius and muscle strength were assessed using one-way ANOVA, and those of the lumbar region and the hip joint were tested by one-way ANCOVA. RESULTS: TB showed higher BMC and BMD for both lumbar spine and femoral neck than SG (all, p < 0.05). Both OB and TB showed greater BMD inter-trochanter than SG (both, p < 0.05). OB demonstrated greater inter-arm differences in the distal radius, which involved 1/3 distal for BMC and mid-distal radius for BMD compared to the TB and SG (all, p < 0.05). In addition, greater inter-arm asymmetry of grip strength was found in OB compared to TB and SG (both, p < 0.05). CONCLUSION: For postmenopausal women, performing two-handed backhand strokes, leads to higher BMC and BMD in the non-dominant arm, the lumbar region, and hips, indicating potential benefit to maintain bone health and strength. Whether this result leads to reducing the risk of osteoporosis needs to be investigated in further research.

Role of hepatitis D virus in persistent alanine aminotransferase abnormality among chronic hepatitis B patients treated with nucleotide/nucleoside analogues.

BACKGROUND: The biochemical response is a crucial indicator of prognosis in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues (NAs). The impact of hepatitis D virus (HDV) infection on alanine aminotransferase normalization is elusive. METHODS: The longitudinal study recruited 1185 CHB patients who received NAs. These patients were tested for anti-HDV antibody and HDV RNA at the initiation of anti-hepatitis B virus (HBV) therapy and annually for patients who were HDV-seropositive. ALT levels were examined at the first and second year of anti-HBV therapy. ALT abnormality was defined as ALT levels above 40 IU/mL in both male and female, and the risk factors associated with ALT abnormality were analysed. RESULTS: Rates of seropositivity for anti-HDV and HDV RNA were 2.0% and 0.8% among 1185 NA-treated CHB patients, respectively. The strongest factor associated with ALT abnormality (>40 IU/mL) after first year treatment with NAs was HDV RNA seropositivity at year 1 (odds ratio [OR]/95% confidence interval [CI]: 31.44/3.49-283.56, P = 0.002), followed by liver cirrhosis (2.18/1.51-3.15, P < 0.001), detectable HBV DNA at year 1 (OR/CI: 1.99/1.36-2.92, P < 0.001), diabetes (OR/CI: 1.75/1.10-2.78, P = 0.02), body mass index (BMI) (OR/CI: 1.13/1.09-1.18, P < 0.001) and age (OR/CI: 0.97/0.96-0.98, P < 0.001). Among patients who were seronegative for HBV DNA at year 1, the strongest factor associated with ALT abnormality was HDV RNA seropositivity at year 1 (OR/CI: 30.00/3.28-274.05, P = 0.003), followed by liver cirrhosis (OR/CI: 1.83/1.21-2.75, P = 0.004), BMI (OR/CI: 1.16/1.11-1.21, P < 0.001) and age (OR/CI: 0.97/0.96-0.99, P < 0.001). Similarly, the impact of HDV RNA seropositivity on ALT abnormality was noted in patients without detectable HBV DNA but not in those with hepatitis B viremia at treatment year 2 (OR/CI: 10.16/1.33-77.74, P = 0.03). CONCLUSION: HDV infection played an important role in ALT abnormality in CHB patients receiving 1-year and 2-year NAs. The impact was particularly noted in patients who had successfully suppressed HBV DNA.

Tris DBA ameliorates IgA nephropathy by blunting the activating signal of NLRP3 inflammasome through SIRT1- and SIRT3-mediated autophagy induction.

Tris (dibenzylideneacetone) dipalladium (Tris DBA), a small-molecule palladium complex, can inhibit cell growth and proliferation in pancreatic cancer, lymphocytic leukaemia and multiple myeloma. Given that this compound is particularly active against B-cell malignancies, we have been suggested that it can alleviate immune complexes (ICs)-mediated conditions, especially IgA nephropathy (IgAN). The therapeutic effects of Tris DBA on glomerular cell proliferation and renal inflammation and mechanism of action were examined in a mouse model of IgAN. Treatment of IgAN mice with Tris DBA resulted in markedly improved renal function, albuminuria and renal pathology, including glomerular cell proliferation, neutrophil infiltration, sclerosis and periglomerular inflammation in the renal interstitium, together with (Clin J Am Soc Nephrol. 2011, 6, 1301-1307) reduced mitochondrial ROS generation; (Am J Physiol-Renal Physiol. 2011. 301, F1218-F1230) differentially regulated autophagy and NLRP3 inflammasome; (Clin J Am Soc Nephrol. 2012, 7, 427-436) inhibited phosphorylation of JNK, ERK and p38 MAPK signalling pathways, and priming signal of the NLRP3 inflammasome; and (Free Radic Biol Med. 2013, 61, 285-297) blunted NLRP3 inflammasome activation through SIRT1- and SIRT3-mediated autophagy induction, in renal tissues or cultured macrophages. In conclusion, Tris DBA effectively ameliorated the mouse IgAN model and targeted signalling pathways downstream of ICs-mediated interaction, which is a novel immunomodulatory strategy. Further development of Tris DBA as a therapeutic candidate for IgAN is warranted.

Hepatitis B-related outcomes following direct-acting antiviral therapy in Taiwanese patients with chronic HBV/HCV co-infection.

BACKGROUND & AIMS: The outcome of HBV infection, including the dynamics of HBsAg and HBV virological reactivation, among patients coinfected with HCV receiving direct-acting antivirals (DAAs) remains unclear. Thus, we aimed to analyze HBV-related outcomes in these patients. METHODS: Serial HBsAg and HBV DNA levels were measured in 79 HBV/HCV-coinfected patients receiving DAAs (13 receiving anti-HBV nucleot(s)ide analog [NUC] therapy simultaneously). The endpoints included HBsAg dynamics and seroclearance, HBV reactivation (HBV DNA >1 log increase or >100 IU/ml if undetectable at baseline) and HBV-related clinical reactivation. RESULTS: HBsAg levels declined from a median of 73.3 IU/ml at baseline to 16.2 IU/ml at the end-of-DAA treatment and increased to 94.1 IU/ml at 12 months post-treatment. During a mean 11.1-months of follow-up, 8 (10.1%) patients experienced HBsAg seroclearance and 30 (38.0%) HBV reactivation (12-month cumulative incidence, 10.3% and 40.4%, respectively). Patients with pre-treatment HBsAg ≤10 IU/ml had a significantly higher rate of HBsAg seroclearance (hazard ratio [HR] 8.52; 95% CI 1.048-69.312) and lower risk of HBV reactivation than those with pre-treatment HBsAg >10 IU/ml (HR 2.88; 95% CI 1.057-7.844) in multivariate analyses. Six patients (4 cirrhotics) not receiving NUC therapy experienced HBV-related clinical reactivation; 3 of the 4 cirrhotics developed liver failure and 2 died despite immediate NUC therapy. Compared to untreated HBV-monoinfected patients, HBV/HCV-coinfected patients without NUC prophylaxis had a similar rate of HBsAg seroclearance, but a significantly higher risk of HBV reactivation following DAA therapy (HR 6.59; 95% CI 2.488-17.432). CONCLUSIONS: DAA-treated HBV/HCV-coinfected patients had significantly higher rates of HBV seroclearance, particularly among those with low pre-treatment HBsAg titer, but were at higher risk of HBV reactivation, particularly among those with higher pre-treatment HBsAg titer. Prophylactic anti-HBV therapy is essential for cirrhotic patients, irrespective of baseline HBV DNA levels. LAY SUMMARY: We studied outcomes relating to hepatitis B virus (HBV) in patients coinfected with both hepatitis B and C. Patients receiving direct-acting antiviral treatment for hepatitis C were more likely to experience seroclearance (or functional cure of HBV), but were also more likely to experience HBV reactivation, which can lead to hepatitis, liver failure and death. In coinfected cirrhotic patients being treated for HCV, prophylactic treatment for HBV is mandatory.

Serial serologic changes of hepatitis D virus in chronic hepatitis B patients receiving nucleos(t)ides analogues therapy.

BACKGROUND AND AIM: The serial serologic changes of hepatitis D virus (HDV) infection among chronic hepatitis B virus (HBV) infected patients who received oral nucleotide/nucleoside analogues are elusive. METHODS: Serum anti-HDV and HDV RNA among chronic hepatitis B (CHB) patients were tested at the time of initiating anti-HBV therapy and subsequently during the follow-up period. RESULTS: The seropositive rate of anti-HDV and HDV RNA among 2850 CHB patients, was 2.7% and 0.9%, respectively. Factors associated with anti-HDV seropositivity were platelet counts (odds ratio [OR]/95% confidence intervals [CI]: 0.995/0.992-0.999; P = 0.006), HBV DNA levels (OR/CI: 0.81/0.70-0.94; P = 0.005), and hepatitis B e-antigen (HBeAg) seropositivity (OR/CI: 0.22/0.05-0.95; P = 0.04). The only factor associated with HDV RNA positivity among anti-HDV seropositive patients was age (OR/CI: 0.95/0.90-1.00; P = 0.03). The spontaneous clearance rate of serum anti-HDV antibody was 3.0 per 100 person-years with a median follow-up period of 3.5 years (range 2-12 years), whereas the seroclearance rate of HDV RNA was 4.3 per 100 person-years among anti-HDV seropositive patients after a median follow-up period of 6.0 years (range 2-11 years). A baseline anti-HDV titer < 0.5 cut-off index was the only factor predictive of anti-HDV seroclearance (hazard ratio [HR]/CI: 30.11/3.73-242.85; P = 0.001). CONCLUSIONS: HDV infection was not common among patients treated for HBV in Taiwan. Seroclearance of anti-HDV and HDV RNA did occur over time, albeit the chance is rare.

Application of an Artificial Intelligence Trilogy to Accelerate Processing of Suspected Patients With SARS-CoV-2 at a Smart Quarantine Station: Observational Study.

BACKGROUND: As the COVID-19 epidemic increases in severity, the burden of quarantine stations outside emergency departments (EDs) at hospitals is increasing daily. To address the high screening workload at quarantine stations, all staff members with medical licenses are required to work shifts in these stations. Therefore, it is necessary to simplify the workflow and decision-making process for physicians and surgeons from all subspecialties. OBJECTIVE: The aim of this paper is to demonstrate how the National Cheng Kung University Hospital artificial intelligence (AI) trilogy of diversion to a smart quarantine station, AI-assisted image interpretation, and a built-in clinical decision-making algorithm improves medical care and reduces quarantine processing times. METHODS: This observational study on the emerging COVID-19 pandemic included 643 patients. An "AI trilogy" of diversion to a smart quarantine station, AI-assisted image interpretation, and a built-in clinical decision-making algorithm on a tablet computer was applied to shorten the quarantine survey process and reduce processing time during the COVID-19 pandemic. RESULTS: The use of the AI trilogy facilitated the processing of suspected cases of COVID-19 with or without symptoms; also, travel, occupation, contact, and clustering histories were obtained with the tablet computer device. A separate AI-mode function that could quickly recognize pulmonary infiltrates on chest x-rays was merged into the smart clinical assisting system (SCAS), and this model was subsequently trained with COVID-19 pneumonia cases from the GitHub open source data set. The detection rates for posteroanterior and anteroposterior chest x-rays were 55/59 (93%) and 5/11 (45%), respectively. The SCAS algorithm was continuously adjusted based on updates to the Taiwan Centers for Disease Control public safety guidelines for faster clinical decision making. Our ex vivo study demonstrated the efficiency of disinfecting the tablet computer surface by wiping it twice with 75% alcohol sanitizer. To further analyze the impact of the AI application in the quarantine station, we subdivided the station group into groups with or without AI. Compared with the conventional ED (n=281), the survey time at the quarantine station (n=1520) was significantly shortened; the median survey time at the ED was 153 minutes (95% CI 108.5-205.0), vs 35 minutes at the quarantine station (95% CI 24-56; P<.001). Furthermore, the use of the AI application in the quarantine station reduced the survey time in the quarantine station; the median survey time without AI was 101 minutes (95% CI 40-153), vs 34 minutes (95% CI 24-53) with AI in the quarantine station (P<.001). CONCLUSIONS: The AI trilogy improved our medical care workflow by shortening the quarantine survey process and reducing the processing time, which is especially important during an emerging infectious disease epidemic.

Higher NAFLD fibrosis score is associated with impaired eGFR.

BACKGROUND/PURPOSE: Chronic kidney disease (CKD) has become a worldwide health problem, leading to high morbidity and mortality, and non-alcoholic fatty liver disease (NAFLD) is considered a risk factor for CKD. The aim of this study was to explore the relationship between NAFLD fibrosis score (NFS) and the estimated glomerular filtration rate (eGFR), and identify possible risk factors related to the NFS among Taiwanese subjects. METHODS: Subjects were enrolled from the database of the Department of Preventive Medicine of Kaohsiung Municipal Hsiao-Kang Hospital. The eGFR was calculated according to the Taiwanese Modification of Diet in Renal Disease (TMDRD) equation, and the NFS was employed to evaluate the fibrotic level. RESULTS: In total, 11,376 subjects were enrolled in this study, with a mean age of 52.0 ± 6.81 years, including 4529 (39.8%) males. A fasting sugar level ≥100 mg/dL (OR = 1.70, 95% CI = 1.52-1.87) and an abnormal waist circumference (OR = 1.81, 95% CI = 1.65-1.99) were significant factors associated with NFS (p < 0.05). Trends of a decreasing TMDRD score and an increasing NFS with increasing age were noted (p < 0.05). The NFS was significantly negatively correlated with the TMDRD score (standard coefficients: -0.067, p < 0.001). CONCLUSION: A higher NFS is associated with an impaired eGFR in Taiwanese subjects. Controlling risk factors, especially fasting sugar level and waist circumference, may be useful in preventing NFS deterioration, which is negatively correlated with the eGFR.

Clusters of Circulating let-7 Family Tumor Suppressors Are Associated with Clinical Characteristics of Chronic Hepatitis C.

Hepatitis C virus (HCV) infections can cause permanent liver-related diseases, including hepatocellular carcinoma (HCC). Low mortality and incidence of HCC have been observed in patients with chronic hepatitis C undergoing direct-acting antiviral therapy. Tumor suppressive let-7 family members are down-regulated in HCC. The present study, therefore, aimed to investigate whether expression levels for the full spectrum of let-7 family members (let-7a, 7b, 7c, 7d, 7e, 7f, 7g, 7i, and miR-98) in the circulatory system are useful as surveillance biomarkers for liver-related diseases to monitor treatment efficacy during HCV infection. To this end, we measured the levels of mature circulating let-7 family members using quantitative reverse transcription-PCR in 236 patients with HCV infection, and 147 age- and sex-matched controls. Using hierarchical cluster analysis and principal component analysis, three clusters were obtained after measuring expression levels of let-7 family members in the patients and controls. Cluster 1 included let-7a/d/e/g, Cluster 2 comprised let-7b and let-7i, and Cluster 3 comprised let-7c/f/miR-98. Let-7b/c/g represented the three clusters and showed the best survival response to liver cancer when analyzed with respect to patient data. Therefore, considering the circulating levels of let7 b/c/g as representatives of the let-7 family may facilitate effective monitoring of liver-related disease.

Five-year outcome of conventional and drug-eluting transcatheter arterial chemoembolization in patients with hepatocellular carcinoma.

BACKGROUND: Currently, no standard of care or therapies have been established for patients with advanced HCC. We evaluated the efficacy and safety of conventional transarterial chemoembolization using gelatin sponges or microspheres plus lipiodol-doxorubicin (cTACE) and TACE with doxorubicin-loaded drug eluting beads (DEB-TACE). METHODS: This retrospective study included 273 patients who received cTACE (n = 201) or DEB-TACE. Tumor response, survival, and adverse events were evaluated over a 5-year follow-up period. RESULTS: During 5-year follow-up, a greater percentage of patients treated with cTACE died than those treated with DEB-TACE (76.1% vs. 66.7%) (P = 0.045). At the last evaluation, all surviving patients had disease progression and no differences were seen between treatment groups. However, the time to disease progression differed between groups; median time to disease progression was 11.0 months for cTACE and 16.0 months for DEB-TACE (P = 0.019). The median survival time was 37 months in both treatment groups. No significant differences were observed between cTACE and DEB-TACE therapies in subgroups of patients with BCLC stage A or stage B + C either in survival time or time to disease progression (P values > 0.05). No significant differences were observed in survival status or disease progression between cTACE and DEB-TACE in patient subgroups with either tumor number > 5 or with the sum of the diameter of largest five HCC tumors being > 7 cm. CONCLUSIONS: DEB-TACE demonstrates greater long-term benefits than cTACE in treating treatment-naïve patients with HCC. Results of this long-term study support the use of DEB-TACE in treating HCC.

Identification of treatment-experienced hepatitis C patients with poor cost-effectiveness of pegylated interferon plus ribavirin from a real-world cohort.

BACKGROUND/PURPOSE: Pegylated interferon (PegIFN) plus ribavirin (RBV) combination therapy has been the standard of care since 2002. Although a better viral response has been achieved among chronic hepatitis C (CHC) patients in Taiwan, approximately 25% of hepatitis C virus (HCV) genotype 1 (G1) patients and 15% of G2 patients failed to achieve a sustained virological response (SVR) at the first therapy. The actual cost-effectiveness of the retreatment remains elusive. The present study conducted a real-world cost-effectiveness analysis of a large cohort among different pre-specified subgroups of treatment-experienced CHC patients. METHODS: A total of 117 patients with CHC who failed to achieve SVR at the first IFN-based therapy and received a second IFN-based therapy were enrolled. The inpatient and outpatient costs were acquired from National Health Insurance Research Database of Taiwan. The related medical care costs per treatment and per SVR were calculated. RESULTS: We demonstrated that the average cost per SVR achieved was $13,722 in treatment-experienced CHC patients. Especially, patients with HCV G1 infection, baseline viral loads > 400,000 IU/mL, advanced hepatic fibrosis, not achieving a rapid viral response at week 4 or complete early viral response at week 12, had poorer cost-effectiveness for PegIFN/RBV retherapy, ranging from around $15,520 to as high as $72,546 per SVR achieved. CONCLUSION: In the current study, we explored the real-world cost-effectiveness data of PegIFN/RBV for different subgroups of treatment-experienced HCV patients. These findings provide information for policy-makers for making decisions on treatment strategies of costly direct-acting antiviral agents for retreating CHC patients.

Protective effects of elafin against adult asthma.

BACKGROUND: Elafin inhibits serine proteases, such as human neutrophil elastase and proteinase 3, to prevent excessive damage during inflammation. However, the relationship between elafin and asthma is still unclear. Microarray technology was used to evaluate smoking- and asthma-related biomarkers in a discovery-driven manner. We identified candidate genes, e.g., proteinase inhibitor 3 (PI3), related to asthma and smoking from gene expression microarray data sets and evaluated their potential as biomarkers for asthma. METHODS: We used human genome microarray data sets from smoking- and asthma-related gene expression data sets and performed real-time quantitative polymerase chain reaction to measure and validate differences in gene expression. We also recruited adult patients with asthma and age- and sex-matched control patients who were administered a structured questionnaire and evaluated for lung function and plasma elafin levels, which are encoded by the PI3 gene. RESULTS: Six significantly altered candidate genes, PI3, protein kinase C iota, phosphoserine phosphatase, IQ motif-containing GTPase activating protein 1, interleukin 13 receptor α 1, and signal transducing adaptor molecule SH3 domain and ITAM motif 2, were identified from comparisons across the four asthma- and four smoking-related data sets included in this study. An in vitro study of human airway epithelial cells (A549) and a human monocytic cell line (THP-1) demonstrated that PI3 messenger RNA levels were significantly altered by nicotine exposure. Elafin concentration was significantly higher in control patients than in patients with asthma (p < 0.001). The plasma elafin concentration in the highest quartile (≥12.69 ng/mL) was inversely associated with asthma (adjusted odds ratio 0.122 [95% confidence interval, 0.053-0.278]) compared with the lowest quartile (<5.82 ng/mL) after adjusting for age, sex, smoking status, waist-to-hip ratio, percentage predicted forced expiratory volume in 1 second, cockroaches in the home, incense burning, and family history. CONCLUSION: Our study revealed that high elafin levels identified in smoking- and asthma-related microarray data sets and an epidemiologic study significantly reduced the risk of asthma. Further studies of elafin as a potential therapy for asthma are warranted.

AURKA Phe31Ile polymorphism interacted with use of alcohol, betel quid, and cigarettes at multiplicative risk of oral cancer occurrence.

OBJECTIVES: The expression levels of two DNA repair genes (CHAF1A and CHAF1B) and a chromosome segregation gene (AURKA) were susceptible to arecoline exposure, a major alkaloid of areca nut. We hypothesize that genetic variants of these genes might also be implicated in the risk of oral cancer and could be modified by substance use of betel quid or alcohol and cigarettes. MATERIAL AND METHODS: A case-control study, which included 507 patients with oral cancer and 717 matched controls, was performed in order to evaluate the cancer susceptibility by the tagging single-nucleotide polymorphisms (tagSNPs) in AURKA, CHAF1A, and CHAF1B using a genotyping assay and gene-environment interaction analysis. RESULTS: The Phe31Ile polymorphism (rs2273535, T91A) of AURKA was significantly associated with an increased risk of oral cancer (odds ratio (OR) = 2.1, 95% confidence interval (CI) 1.2-3.5). The gene dosage of the 91A allele also showed a significant trend in risk of oral cancer (P = 0.008). Furthermore, we found the AURKA 91AA homozygote was modifiable by substance use of alcohol, betel quid, and cigarettes (ABC), leading to increased risk of oral cancer in an additive or a multiplicative model (combined effect indexes = 1.2-4.0 and 1.5-2.2, respectively). However, no association was observed between the genetic variants of CHAF1A or CHAF1B and oral cancer risk in the study. CONCLUSION: These findings reveal the functional Phe31Ile polymorphism tagSNP of AURKA may be a strong susceptibility gene in ABC-related oral cancer occurrence. CLINICAL RELEVANCE: The results of this betel-related oral cancer study provide the evidence of environment-gene interaction for early prediction and molecular diagnosis.

Shielding during x-ray examination of pediatric female patients with developmental dysplasia of the hip.

Patients with developmental dysplasia of the hip (DDH) generally undergo multiple x-ray examinations of both hip joints. During these examinations, the gonads are completely exposed to radiation, unless shielded. Although many types and sizes of gonad shields exist, they often do not provide adequate protection because of size and placement issues; additionally, these shields are frequently omitted for female patients. Our aim was to assess gonad protection during x-ray examination that is provided by gonad shields designed for individual female patients with DDH.We retrospectively retrieved data from the Picture Archiving and Communication System database; pelvic plain x-ray films from 766 females, 18 years old or younger, were included in our analysis. Based on x-ray measurements of the anterior superior iliac spine, we developed a system of gonad shield design that depended on the distance between anterior superior iliac spine markers. We custom-made shields and then examined shielding rates and shielding accuracy before and after these new shields became available. Standard (general-purpose) shields were used before our custom design project was implemented. The shielding rate and shielding accuracy were, respectively, 14.5% and 8.4% before the project was implemented and 72.7% and 32.2% after it was implemented. A shield that is more anatomically correct and available in several different sizes may increase the likelihood of gonad protection during pelvic x-ray examinations.

A computed tomography radiomics-based model for predicting osteoporosis after breast cancer treatment.

Many treatments against breast cancer decrease the level of estrogen in blood, resulting in bone loss, osteoporosis and fragility fractures in breast cancer patients. This retrospective study aimed to evaluate a novel opportunistic screening for cancer treatment-induced bone loss (CTIBL) in breast cancer patients using CT radiomics. Between 2011 and 2021, a total of 412 female breast cancer patients who received treatment and were followed up in our institution, had post-treatment dual-energy X-ray absorptiometry (DXA) examination of the lumbar vertebrae and had post-treatment chest CT scan that encompassed the L1 vertebra, were included in this study. Results indicated that the T-score of L1 vertebra had a strongly positive correlation with the average T-score of L1-L4 vertebrae derived from DXA (r = 0.91, p < 0.05). On multivariable analysis, four clinical variables (age, body weight, menopause status, aromatase inhibitor exposure duration) and three radiomic features extracted from the region of interest of L1 vertebra (original_firstorder_RootMeanSquared, wavelet.HH_glcm_InverseVariance, and wavelet.LL_glcm_MCC) were selected for building predictive models of L1 T-score and bone health. The predictive model combining clinical and radiomic features showed the greatest adjusted R2 value (0.557), sensitivity (83.6%), specificity (74.2%) and total accuracy (79.4%) compared to models that relied solely on clinical data, radiomic features, or Hounsfield units. In conclusion, the clinical-radiomic predictive model may be used as an opportunistic screening tool for early identification of breast cancer survivors at high risk of CTIBL based on non-contrast CT images of the L1 vertebra, thereby facilitating early intervention for osteoporosis.