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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.

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.

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.

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 p p p 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.

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.

MicroRNAs (miRNA) have been implicated in HCV infection. The present study analyzed the effects of let-7g on HCV infection in vitro, in clinical tissue and serum samples. Here, we show that the expression of let-7g in serum and liver tissue is significantly higher in patients with sustained virologic response (SVR). We show that interferon (IFN)/ribavirin (RBV) induces let-7g expression through p38/AP-1 signaling. Overexpression of let-7g reduced HCV gene or core protein level and inhibited the HCV viral load. The let-7g and IFN/RBV have additively inhibitory effect on HCV replication. These data implicate let-7g as a new therapeutic drug to additively cooperate with IFN/RBV to repress HCV replication. Key messages: let-7g expression is increased in serum and liver tissue of patients with SVR. Interferon/ribavirin induces let-7g expression through p38/AP-1 signaling. Overexpression of let-7g can repress HCV replication. Let-7g additively cooperates with interferon/ribavirin to repress HCV replication. Lin28B silencing can reverse let-7g expression and repress HCV replication.

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. 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. 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. These findings reveal the functional Phe31Ile polymorphism tagSNP of AURKA may be a strong susceptibility gene in ABC-related oral cancer occurrence. The results of this betel-related oral cancer study provide the evidence of environment–gene interaction for early prediction and molecular diagnosis.

Microdrills are fundamental cutting tools used in mechanical microdrilling. The web thickness of a microdrill is an important design parameter in balancing drill rigidity and chip removal ability. Conventional destructive method for measuring the web thickness is currently adopted by some microdrill manufactures. The conventional method must be carried out manually by experienced inspectors and thus lacks sufficient efficiency and accuracy. To improve the drawbacks of the conventional method, a vision-aided automation system for performing the destructive web thickness measurement is introduced in this paper. Based on the integration of motion and logic control, machine vision, and image processing techniques, an automated measuring process is then established. Experiments to measure the web thickness of microdrill samples were conducted to test the feasibility and effectiveness of the presented automation system and automated measuring process. The experimental results showed that the presented vision-aided automation system, in combination with the automated measuring process, could be an efficient and precise manner for replacing the conventional manual procedure in performing the destructive web thickness measurement of certain microdrills.

This study investigated whether a thin renal cortex or any morphological kidney measurements can be predictors of post percutaneous nephrostomy (PCN) renal function, thereby lessening the need for the procedure.All patients underwent unilateral PCN that were performed under sonographic and fluoroscopic guidance. Kidney morphological measurements were subsequently taken to measure residual renal function; a thin renal cortex was defined from a computed tomography (CT) showing a cortical thickness10 mm. Urine output was recorded daily, with patients divided into anuric and nonanuric groups.Morphological measurements of residual renal function, such as renal length (p=0.004), renal width (p=0.004), renal thickness (p=0.008), and renal size (p=0.004) were significantly higher in nonanuric than anuric patients. Urine output increased by 85.47 ml/day for every millimetre increase in renal width (p=0.026) and 65.31 ml/day for every millimetre increase in renal thickness (p=0.024). Simple linear regression analyses showed that cancer patients had a significantly lower urine output (358.73 ml/day; p=0.046) than those without cancer.This study showed that urine output and other clinical data can provide an index to evaluate residual renal function before deciding to perform PCN procedures.

To investigate whether the addition of nitroglycerine to transcatheter arterial (chemo)embolization (TAE/TACE) can increase the delivery and effectiveness of TAE/TACE in patients with hepatocellular carcinoma (HCC) by dual-energy CT.HCC patients (BCLC stage A or B) were randomized to (n = 51) or not to (n = 50) receive nitroglycerine and an emulsion of Lipiodol with or without doxorubicin, followed by embolization with Gelfoam pledgets. Dual-energy CT was performed pre- and 1 to 3 months post-embolization to assess changes in tumour diameter and Lipiodol levels in tumours.Median tumour diameter decreased from baseline in both groups with and without nitroglycerine (7.11 % vs. 12.5 %, respectively), and was statistically significant in the group receiving nitroglycerine (P = 0.023). There was no difference between the two groups in disease response (P = 0.237). The concentration and percentage of Lipiodol retained in tumours were significantly greater in patients treated with nitroglycerine compared to those without (median concentration 15.05 mg/mL vs. 4.40 mg/mL, respectively, P 0.001; median percentage 82.01 % vs. 36.75 %, respectively, P 0.001).Nitroglycerine increased delivery of the Lipiodol emulsion via TAE/TACE to HCC tumours with significant tumour reduction. Dual-energy CT can accurately quantify the amount of Lipiodol deposited in tumours.• Nitroglycerine improves delivery of tumour-targeted therapy via enhanced permeability and retention. • In hepatocellular carcinoma, nitroglycerine added to TAE/TACE showed greater tumour reduction. • Dual-energy CT can reliably quantify the amount of Lipiodol in TAE/TACE.

Background A genome-wide association study uncovered Chitinase 3 like 1 (CHI3L1) as a candidate gene for asthma susceptibility. CHI3L1, which encodes the YKL-40 protein, is associated with asthma in Western European and American populations and with atopy in a Korean population. However, asthma-associated polymorphisms remain unknown for a Taiwanese population. Methods We enrolled 628 adult asthmatic patients and 1:1 age-sex matched community-based controls in southern Taiwan and performed a combined effect sizes analysis to test if CHI3L1 polymorphisms were related to genetic risks for asthma in the Asian population. Ten tagSNP polymorphisms for the CHI3L1 gene were selected from the HapMap database and genotyped using a TaqMan allelic discrimination assay. Results Adjusted odds ratios of the CHI3L1 rs1538372 CC genotype (aOR = 1.97, 95% CI: 1.23–3.14) and the rs10399931 GG genotype (aOR = 1.77, 95% CI: 1.13–2.77) were significantly associated with asthma in the Taiwanese populations. Predictive values of forced expiratory volume in the first second of the forced vital capacity (12.37%, P = 0.03) and of forced vital capacity (12.10%, P = 0.036) decreased in conjunction with an increase in YKL-40 levels among CHI3L1 rs1538372 CC carriers; these values were 16.1% (P = 0.004) and 14.5% (P = 0.011), respectively, among CHI3L1 rs10399931 GG carriers. Furthermore, steroid use by asthma patients did not affect serum YKL-40 levels, but both polymorphisms had significant effects on YKL-40 levels in asthma patients who used steroids. Conclusions Our findings suggest that the CHI3L1 polymorphisms rs1538372 and rs10399931 can be used as genetic markers for predicting asthma risk in the Taiwanese population.