Plasmonic Au@Ag Core-Shell Nanoisland Film for Photothermal Inactivation and Surface-Enhanced Raman Scattering Detection of Bacteria.

Plasmonic metal nanomaterials have been extensively investigated for their utilizations in biomedical sensing and treatment. In this study, plasmonic Au@Ag core-shell nanoisland films (Au@AgNIFs) were successfully grown onto a glass substrate using a seed-mediated growth procedure. The nanostructure of the Au@AgNIFs was confirmed through scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and atomic force microscopy (AFM). The UV-Vis spectra of the Au@AgNIFs exhibited a broad absorption in the visible range from 300 to 800 nm because of the surface plasmon absorption. Under simulated sunlight exposure, the temperature of optimal Au@AgNIF was increased to be 66.9 °C to meet the requirement for photothermal bacterial eradication. Furthermore, the Au@AgNIFs demonstrated a consistent photothermal effect during the cyclic on/off exposure to light. For photothermal therapy, the Au@AgNIFs revealed superior efficiency in the photothermal eradication of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). With their unique nanoisland nanostructure, the Au@AgNIFs exhibited excellent growth efficiency of bacteria in comparison with that of the bare glass substrate. The Au@AgNIFs were also validated as a surface-enhanced Raman scattering (SERS) substrate to amplify the Raman signals of E. coli and S. aureus. By integrating photothermal therapy and SERS detection, the Au@AgNIFs were revealed to be a potential platform for bacterial theranostics.

Using alert dwell time to filter universal clinical alerts: A machine learning approach.

BACKGROUND: Alerts in computerized physician order entry (CPOE) systems can improve patient safety. However, alerts in rule-based systems cannot be customized based on individual patient or user characteristics. This limitation can lead to the presentation of irrelevant alerts and subsequent alert fatigue. OBJECTIVE: We used machine learning approaches with alert dwell time to filter out irrelevant alerts for physicians based on contextual factors. METHODS: We utilized five machine learning algorithms and a total of 1,120 features grouped into six categories: alert, demographic, environment, diagnosis, prescription, and laboratory results. The output of the models was the alert dwell time within a specified time window to determine the optimal range by the sensitivity analysis. RESULTS: We used 813,026 records (19 categories) from the hospital's outpatient clinic data from 2020 to 2021. The sensitivity analysis showed that a time window with a range of 0.3-4.0 s had the best performance, with an area under the receiver operating characteristic (AUROC) curve of 0.73 and an area under the precision-recall curve (AUPRC) of 0.97. The model built with alert and demographic feature groups showed the best performance, with an AUROC of 0.73. The most significant individual feature groups were alert and demographic, with AUROCs of 0.66 and 0.62, respectively. CONCLUSION: Our study found that alerts and user and patient demographic features are more crucial than clinical features when constructing universal context-aware alerts. Using alert dwell time in combination with a time window is an effective way to determine the trigger status of an alert. The findings of this study can provide useful insights for researchers working on specific and universal context-aware alerts.

Effectiveness of Stereotactic Ablative Radiotherapy for Systemic Therapy Respondents with Inoperable Pulmonary Oligometastases and Oligoprogression.

Stereotactic ablative radiotherapy (SABR) may improve survival in patients with inoperable pulmonary oligometastases. However, the impact of pulmonary oligometastatic status after systemic therapy on SABR outcomes remains unclear. Hence, we investigated the outcomes of SABR in 45 patients with 77 lung tumors and the prognostic value of pulmonary oligoprogression. Eligibility criteria were pulmonary oligometastases (defined as ≤5 metastatic lung tumors), controlled extrapulmonary disease (EPD) after front-line systemic therapy, SABR as primary local treatment for inoperable pulmonary metastases, and consecutive imaging follow-up. Oligometastatic lung tumor was classified into controlled or oligoprogressive status. Overall survival (OS), in-field progression-free survival (IFPFS), out-field progression-free survival (OFPFS), and prognostic variables were evaluated. With 21.8 months median follow-up, the median OS, IFPFS, and OFPFS were 28.3, not reached, and 6.5 months, respectively. Two-year OS, IFPFS, and OFPFS rates were 56.0%, 74.2%, and 17.3%, respectively. Oligoprogressive status (p = 0.003), disease-free interval < 24 months (p = 0.041), and biologically effective dose (BED10) < 100 Gy (p = 0.006) were independently associated with inferior OS. BED10 ≥ 100 Gy (p = 0.029) was independently correlated with longer IFPFS. Oligoprogressive status (p = 0.017) and EPD (p = 0.019) were significantly associated with inferior OFPFS. Grade ≥ 2 radiation pneumonitis occurred in four (8.9%) patients. Conclusively, SABR with BED10 ≥ 100 Gy could provide substantial in-field tumor control and longer OS for systemic therapy respondents with inoperable pulmonary oligometastases. Oligoprogressive lung tumors exhibited a higher risk of out-field treatment failure and shorter OS. Hence, systemic therapy should be tailored for patients with oligoprogression to reduce the risk of out-field treatment failure. However, in the absence of effective systemic therapy, SABR is a reasonable alternative to reduce resistant tumor burden.

Investigating nurses' acceptance of patients' bring your own device implementation in a clinical setting: A pilot study.

Objective: The popularity of the â€‹"bring your own device (BYOD)" â€‹concept has grown in recent years, and its application has extended to the healthcare field. This study was aimed at examining nurses' acceptance of a BYOD-supported system after a 9-month implementation period. Methods: We used the technology acceptance model to develop and validate a structured questionnaire as a research tool. All nurses (n â€‹= â€‹18) responsible for the BYOD-supported wards during the study period were included in our study. A 5-point Likert scale was used to assess the degree of disagreement and agreement. Statistical analysis was performed in SPSS version 24.0. Results: The questionnaire was determined to be reliable and well constructed, on the basis of the item-level content validity index and Cronbach α values above 0.95 and 0.87, respectively. The mean constant values for all items were above 3.95, thus suggesting that nurses had a positive attitude toward the BYOD-supported system, driven by the characteristics of the tasks involved. Conclusions: We successfully developed a BYOD-supported system. Our study results suggested that nursing staff satisfaction with BYOD-supported systems could be effectively increased by providing practical functionalities and reducing clinical burden. Hospitals could benefit from the insights generated by this study when implementing similar systems.

MicroRNA-196a-5p targeting LRP1B modulates phenotype of thyroid carcinoma cells.

INTRODUCTION: Thyroid cancer (TC) is a common endocrine malignancy, comprising nearly one-third of all head and neck malignancies worldwide. MicroRNAs (miRNAs) have been implicated in the malignant progression of multiple cancers; however, their contribution to thyroid diseases has not been fully explored. MATERIAL AND METHODS: This study aimed to illustrate the regulatory mechanism of microRNA-196a-5p in TC progression and to investigate whether microRNA-196a-5p affects progression of TC cells by targeting low-density lipoprotein receptor-associated protein 1B (LRP1B). MicroRNA-196a-5p and LRP1B expression status in TC cells and normal human thyroid cells was detected by quantative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. Dual-luciferase reporter assay, cell counting kit-8 (CCK-8) assay, scratch healing assay, and Transwell assay were also performed. RESULTS: The results showed that microRNA-196a-5p expression was up-regulated and LRP1B expression was down regulated in TC cells. In addition, the upregulation of microRNA-196a-5p facilitated progression of TC cells. Silencing microRNA-196a-5p led to the opposite results. Dual-luciferase reporter assay offered evidence for microRNA-196a-5p targeting LRP1B in TC. MicroRNA-196a-5p could target LRP1B to facilitate proliferation, invasion, and migration of TC cells. CONCLUSION: Overall, this study revealed that microRNA-196a-5p may be a cancer-promoting microRNA that plays an important role in TC progression.

Benzyl isothiocyanate attenuates activation of the NLRP3 inflammasome in Kupffer cells and improves diet-induced steatohepatitis.

The NLRP3 inflammasome plays an important role in the pathogenesis of numerous inflammation-related diseases. Benzyl isothiocyanate (BITC) is rich in cruciferous vegetables and possesses potent antioxidant, anti-inflammatory, anti-cancer, and anti-obesogenic properties. In this study, we investigated the role of the NLRP3 inflammasome in the protection by BITC against steatohepatitis and insulin resistance. A mouse model of high-fat/cholesterol/cholic acid diet (HFCCD)-induced steatohepatitis, LPS/nigericin-stimulated primary Kupffer cells, and IL-1ß treated primary hepatocytes were used. BITC attenuated LPS/nigericin-induced activation of the NLRP3 inflammasome by enhancing protein kinase A-dependent NLRP3 ubiquitination, which increased the degradation of NLRP3 and reduced IL-1ß secretion in Kupffer cells. In hepatocytes, BITC pretreatment reversed the IL-1ß-induced decrease in the phosphorylation of IR, AKT, and GSK3ß in response to insulin. After 12 weeks of HFCCD feeding, increases in blood alanine aminotransferase (ALT) and glucose levels were ameliorated by BITC. Hepatic IL-1ß production, macrophage infiltration, and collagen expression induced by HFCCD were also mitigated by BITC. BITC suppresses activation of the NLRP3 inflammasome in Kupffer cells by enhancing the PKA-dependent ubiquitination of NLRP3, which leads to suppression of IL-1ß production and subsequently ameliorates hepatic inflammation and insulin resistance.

Hypomethylation-mediated overexpression of ITGA2 stimulates cell invasion and migration of thyroid carcinoma.

OBJECTIVE: To study the molecular mechanism of DNA methylation-mediated ITGA2 overexpression in thyroid carcinoma (TC). METHODS: First, 450K methylation data and mRNA expression profiles in TCGA-THCA dataset were downloaded from TCGA database. ITGA2 was identified as a methylation-driven gene by using R package "MethylMix". Afterwards, qRT-PCR, western blot and flow cytometry assay were performed to measure ITGA2 expression in TC cells. Methylation-specific PCR was utilized to measure promoter region methylation of ITGA2 in TC cells. Transwell and wound healing assays were carried out to assess cell invasive and migratory properties. RESULTS: Compared with normal cells, TC cells presented significantly increased ITGA2 expression. In addition, ITGA2 expression was controlled by DNA methylation. Hypomethylation of CpG island resulted in an increased ITGA2 expression. Hence, methylation and expression levels of ITGA2 were inversely associated. Moreover, overexpression of ITGA2 and promoter region hypomethylation facilitated cell invasive and migratory abilities in TC. CONCLUSION: These findings authenticated that promoter region hypomethylation of ITGA2 fostered ITGA2 expression as well as TC cell invasion and migration.

Luminal pressure gradient and risk of arteriovenous fistula nonmaturation.

While arteriovenous fistula (AVF) nonmaturation is a major issue of hemodialysis care, an effective treatment to improve AVF maturation remains lacking. AVF introduces pulsatile arterial blood flow into its venous limb and produces high luminal pressure gradient, which may have adverse effect on vascular remodeling. As such, the aim of the present study is to investigate effect of luminal pressure gradient on AVF nonmaturation. This single-center, prospective observational study includes patients receiving autologous AVF creation. Participants received early postoperative ultrasound 5-7 days after surgery to collect parameters including diameters, flow rates, and volume at inflow and outflow sites. Luminal pressure gradient was estimated by using modified Bernoulli equation. The outcome was spontaneous AVF maturation within 8 weeks after surgery without intervention. Thirty patients were included, of which the mean age was 66.9 years and 70% were male. At the end of study, 13 (43.3%) patients had spontaneous AVF maturation. All demographic and laboratory characteristics were similar between patients with mature and nonmature AVF. Regarding ultrasonographic parameters, nonmature AVF showed significantly higher inflow/outflow diameter ratio, inflow velocity, and luminal pressure gradient. While these 3 parameters were significantly correlated, multivariate logistic regression showed their significant association with AVF nonmaturation. Receiver operating characteristic curve exhibited their high predictive value for AVF nonmaturation. Our findings showed that higher inflow/outflow ratio, inflow velocity, and AVF luminal pressure gradient in early postoperative ultrasound predicted risk of AVF nonmaturation. Reducing inflow/outflow diameter ratio or inflow rate may be an approach to improve AVF maturation. The predictive value of this early assessment might have impact on the clinical practice of AVF care.

Retrospective Analysis for Dose Reduction to Organs at Risk with New Personalized Breast Holder (PERSBRA) in Left Breast IMRT.

This study evaluated dose differences in normal organs at risk, such as the lungs, heart, left anterior descending artery (LAD), right coronary artery, left ventricle, and right breast under personalized breast holder (PERSBRA), when using intensity-modulated radiation therapy (IMRT). This study evaluated the radiation protection offered by PERSBRA in left breast cancer radiation therapy. Here, we retrospectively collected data from 24 patients with left breast cancer who underwent breast-conserving surgery as well as IMRT radiotherapy. We compared the dose differences in target coverage and organs at risk with and without PERSBRA. For target coverage, tumor prescribed dose 95% coverage, conformity index, and homogeneity index were evaluated. For organs at risk, we compared the mean heart dose, mean left ventricle dose, LAD maximum and mean dose, mean left lung receiving 20 Gy, 10 Gy, and 5 Gy of left lung volume, maximum and mean coronary artery of the right, maximum of right breast, and mean dose. Good target coverage was achieved with and without PERSBRA. When PERSBRA was used with IMRT, the mean dose of the heart decreased by 42%, the maximum dose of LAD decreased by 26.4%, and the mean dose of LAD decreased by 47.0%. The mean dose of the left ventricle decreased by 54.1%, the volume (V20) of the left lung that received 20 Gy decreased by 22.8%, the volume (V10) of the left lung that received 10 Gy decreased by 19.8%, the volume (V5) of the left lung that received 5 Gy decreased by 15.7%, and the mean dose of the left lung decreased by 23.3%. Using PERSBRA with IMRT greatly decreases the dose to organs at risk (left lung, heart, left ventricle, and LAD). This study found that PERSBRA with IMRT can achieve results similar to deep inspiration breath-hold radiotherapy (DIBH) in terms of reducing the heart radiation dose and the risk of developing heart disease in patients with left breast cancer who cannot undergo DIBH.

Alerts in Clinical Decision Support Systems (CDSS): A Bibliometric Review and Content Analysis.

A clinical decision support system (CDSS) informs or generates medical recommendations for healthcare practitioners. An alert is the most common way for a CDSS to interact with practitioners. Research about alerts in CDSS has proliferated over the past ten years. The research trend is ongoing with new emerging terms and focus. Bibliometric analysis is ideal for researchers to understand the research trend and future directions. Influential articles, institutes, countries, authors, and commonly used keywords were analyzed to grasp a comprehensive view on our topic, alerts in CDSS. Articles published between 2011 and 2021 were extracted from the Web of Science database. There were 728 articles included for bibliometric analysis, among which 24 papers were selected for content analysis. Our analysis shows that the research direction has shifted from patient safety to system utility, implying the importance of alert usability to be clinically impactful. Finally, we conclude with future research directions such as the optimization of alert mechanisms and comprehensiveness to enhance alert appropriateness and to reduce alert fatigue.

MicroRNA-873-5p suppresses cell malignant behaviors of thyroid cancer via targeting CXCL5 and regulating P53 pathway.

We aimed to examine the roles of microRNA-873-5p and CXCL5 in thyroid cancer (TC) cells. qRT-PCR was adopted to measure the expression levels of CXCL5 mRNA and microRNA-873-5p in TC cells, and western blot was adopted to evaluate the CXCL5 protein expression level. Bioinformatics analysis was done to predict the upstream gene of CXCL5. Dual-luciferase assay was applied to validate the binding relationship of CXCL5 and the upstream regulatory gene. Cell experiments were done to detect the effects of microRNA-873-5p targeting CXCL5 on malignant progression of cancer cells. Western blot was adopted to demonstrate the phosphorylation level of P53 pathway related-proteins. CXCL5 was upregulated in TC cells and tissues. The results of in vitro assays displayed that CXCL5 downregulation dramatically suppressed the malignant behaviors of TC cells. MicroRNA-873-5p suppressed CXCL5 expression, but the suppressive effect of microRNA-873-5p on TC cells was abolished through CXCL5 overexpression. Additionally, microRNA-873-5p could mediate p53 pathway and thereby inhibit the malignant behaviors of TC cells through targeting CXCL5. In summary, we proved that microRNA-873-5p repressed the malignant behaviors of TC cells through targeting CXCL5 and P53 pathway, indicating that microRNA-873-5p can be a biomarker for TC.

MiR-221-3p Facilitates Thyroid Cancer Cell Proliferation and Inhibit Apoptosis by Targeting FOXP2 Through Hedgehog Pathway.

Thyroid cancer (TC) is most often found in the endocrine system, the incidence of which has been on a continuous increase in recent years. For a better treatment of it, it becomes a pressing matter to further delve into the mechanism of TC onset and progression. FOXP2 is lowly expressed in diverse cancer, which has a deep connection with malignant progression of tumors. However, in TC, studies about this gene are exceedingly limited. In this study, FOXP2 was discovered to be lowly expressed in TC tissues based on the analysis of TCGA database. This finding was further confirmed by the qRT-PCR that FOXP2 was lowly expressed in TC cell lines. The results of a series of cell function assays demonstrated that overexpressed FOXP2 could hamper TC cell proliferation and stemness, facilitate apoptosis, and arrest the cell cycle. For a deep exploration of its mechanism, we mined its upstream factor miR-221-3p with the aid of starBase and mirDIP databases. The dual-luciferase reporter assay was employed to verify the binding relationship between miR-221-3p and FOXP2. Besides, we also discovered the HEDGEHOG pathway existing downstream of FOXP2 by gene set enrichment analysis. Based on these findings, we also performed a rescue experiment, the result of which indicated that the overexpression of FOXP2 was able to reverse the effects of overexpressed miR-221-3p in several cell activities including proliferation, sphere-formation, apoptosis, and cell cycle. Besides, it could also have an impact on the expression of HEDGEHOG pathway-related proteins influenced by overexpressed miR-221-3p. Our study provided the new insights into the mechanism by which miR-221-3p functions in the development of TC.

Voice-based control system for smart hospital wards: a pilot study of patient acceptance.

BACKGROUND: The smart hospital's concept of using the Internet of Things (IoT) to reduce human resources demand has become more popular in the aging society. OBJECTIVE: To implement the voice smart care (VSC) system in hospital wards and explore patient acceptance via the Technology Acceptance Model (TAM). METHODS: A structured questionnaire based on TAM was developed and validated as a research tool. Only the patients hospitalized in the VSC wards and who used it for more than two days were invited to fill the questionnaire. Statistical variables were analyzed using SPSS version 24.0. A total of 30 valid questionnaires were finally obtained after excluding two incomplete questionnaires. Cronbach's α values for all study constructs were above 0.84. RESULT: We observed that perceived ease of use on perceived usefulness, perceived usefulness on user satisfaction and attitude toward using, and attitude toward using on behavioral intention to use had statistical significance (p < .01), respectively. CONCLUSION: We have successfully developed the VSC system in a Taiwanese academic medical center. Our study indicated that perceived usefulness was a crucial factor, which means the system function should precisely meet the patients' demands. Additionally, a clever system design is important since perceived ease of use positively affects perceived usefulness. The insight generated from this study could be beneficial to hospitals when implementing similar systems to their wards.

Inhibition of ß-catenin signaling attenuates arteriovenous fistula thickening in mice by suppressing myofibroblasts.

BACKGROUND: Arteriovenous fistula (AVF) is the most important vascular access for hemodialysis; however, preventive treatment to maintain the patency of AVFs has not been developed. In endothelium, ß-catenin functions in both the intercellular adherens complex and signaling pathways that induce the transition of endothelial cells to myofibroblasts in response to mechanical stimuli. We hypothesize that mechanical disturbances in the AVF activate ß-catenin signaling leading to the transition of endothelial cells to myofibroblasts, which cause AVF thickening. The present study aimed to test this hypothesis. METHODS: Chronic kidney disease in mice was induced by a 0.2% adenine diet. AVFs were created by aortocaval puncture. Human umbilical vein endothelial cells (HUVECs) were used in the cell experiments. A pressure-culture system was used to simulate mechanical disturbances of the AVF. RESULTS: Co-expression of CD31 and smooth muscle alpha-actin (αSMA), loss of cell-cell adhesions, and the expression of the myofibroblast marker, integrin subunit ß6 (ITGB6), indicated transition to myofibroblasts in mouse AVF. Nuclear translocation of ß-catenin, decreased axin2, and increased c-myc expression were also observed in the AVF, indicating activated ß-catenin signaling. To confirm that ß-catenin signaling contributes to AVF lesions, ß-catenin signaling was inhibited with pyrvinium pamoate; ß-catenin inhibition significantly attenuated AVF thickening and decreased myofibroblasts. In HUVECs, barometric pressure-induced nuclear localization of ß-catenin and increased expression of the myofibroblast markers, αSMA and ITGB6. These changes were attenuated via pretreatment with ß-catenin inhibition. CONCLUSIONS: The results of this study indicate that mechanical disturbance in AVF activates ß-catenin signaling to induce the transition of endothelial cells to myofibroblasts. This signaling cascade can be targeted to maintain AVF patency.

Constructing a thyroid cancer prognostic risk model based on CD8+ T cell associated genes.

Thyroid cancer (TC) is a common and curable endocrine tumor occurring in the head and neck characterized by a low mortality rate compared to other malignancies. In this study, the immune microenvironment of TC was investigated to identify biomarkers. The mRNA and clinical data available in this study were accessed from The Cancer Genome Atlas-Thyroid Cancer (TCGA-THCA) dataset. Differences in immune infiltration levels of TC and normal samples were assessed by CIBERSORT. Thyroid cancer samples were classified into high- and low-abundance groups according to the median abundance of immune cell infiltration, and CD8+ T cells were notably correlated with the survival status. Differential expression analysis was conducted on CD8+ T cells to obtain immune-related differentially expressed genes (DEGs). Subsequently, a prognostic risk model was established through Cox regression analysis. According to the median risk score, samples in the training set and validation set were assigned to high- and low-risk groups. The survival and ROC curves demonstrated that the model possesses favorable prognostic prediction ability. Furthermore, the results of gene set enrichment analysis (GSEA) indicated differences between the high- and low-risk groups in terms of ECM receptor interaction and transforming growth factor ß (TGF-ß) signaling pathways. The tumor microenvironment of TC samples was evaluated by ESTIMATE, which showed that stromal scores were higher in the high-risk group. Finally, simple-sample GSEA (ssGSEA) was performed on TC samples. The results indicated a higher infiltration level of NK cells in the low-risk group, as well as a lower level in the high-risk group. In terms of immune function-related gene sets, genes related to APC co-inhibition, cytolytic activity, HLA and T cell co-inhibition were observed to present higher expression levels in the low-risk group. In general, this study built a 6-gene prognostic risk assessment model based on CD8+ T cells through bioinformatics analysis, which is expected to be a reference for clinicians to judge the prognosis of TC patients.

Construction and Evaluation of a Tumor Mutation Burden-Related Prognostic Signature for Thyroid Carcinoma.

Thyroid carcinoma is a type of prevalent cancer. Its prognostic evaluation depends on clinicopathological features. However, such conventional methods are deficient. Based on mRNA, single nucleotide variants (SNV), and clinical information of thyroid carcinoma from The Cancer Genome Atlas (TCGA) database, this study statistically analyzed mutational signature of patients with this disease. Missense mutation and SNV are the most common variant classification and variant type, respectively. Next, tumor mutation burden (TMB) of sample was calculated. Survival status of high/low TMB groups was analyzed, as well as the relationship between TMB and clinicopathological features. Results revealed that patients with high TMB had poor survival status, and TMB was related to several clinicopathological features. Through analysis on DEGs in high/low TMB groups, 381 DEGs were obtained. They were found to be mainly enriched in muscle tissue development through enrichment analysis. Then, through Cox regression analysis, a 5-gene prognostic signature was established, which was then evaluated through survival curves and receiver operation characteristic (ROC) curves. The result showed that the signature was able to effectively predict patient's prognosis and to serve as an independent prognostic risk factor. Finally, through Gene Set Enrichment Analysis (GSEA) on high/low-risk groups, DEGs were found to be mainly enriched in signaling pathways related to DNA repair. Overall, based on the TCGA-THCA dataset, we constructed a 5-gene prognostic signature through a trail of bioinformatics analysis.

MiR-222-3p promotes the proliferation, migration and invasion of papillary thyroid carcinoma cells through targeting SLC4A4.

OBJECTIVE: An increasing number of studies indicate that miR-222-3p is upregulated in various cancers and can regulate tumor progression. This study aimed to explore the regulatory mechanism of miR-222-3p in papillary thyroid carcinoma (PTC). METHODS: TCGA database was used to dig differentially expressed miRNAs and mRNAs in PTC tissue. Relevant references were searched to determine target miRNA. StarBase, TargetScan and miRDB were applied to predict mRNAs that had binding sites with the target miRNA. Then, the mRNAs were intersected with differentially downregulated mRNAs in TCGA to determine the target mRNA. qRT-PCR was exerted to evaluate gene expression of miR-222-3p and SLC4A4 in PTC. Western blot was performed out to evaluate the protein expression of SLC4A4 in PTC cells. CCK-8, wound healing assay and cell invasion assay were undertaken to observe the proliferative, migratory, and invasive abilities of PTC cells. Dual-luciferase assay was employed to test the binding relationship between miR-222-3p and SLC4A4. RESULTS: MiR-222-3p was highly expressed in PTC while SLC4A4 was lowly expressed. Moreover, miR-222-3p was able to promote the proliferation, invasion, and migration of PTC cells. SLC4A4 was able to reverse these promotive effects of miR-222-3p. CONCLUSION: MiR-222-3p can promote the proliferation, migration and invasion of PTC cells through targeting SLC4A4. MiR-222-3p is expected to be a molecular therapeutic target for PTC patients.

Parathyroid Hormone Induces Transition of Myofibroblasts in Arteriovenous Fistula and Increases Maturation Failure.

CONTEXT: Arteriovenous fistula (AVF) maturation failure remains a clinical dilemma, and its pathobiology is largely unclear. Secondary hyperparathyroidism is a complication of chronic renal failure that is associated with cardiovascular disease. While parathyroid hormone (PTH) has a prosclerotic effect on vascular smooth muscle cells (VSMCs), its role in AVF maturation failure remained unknown. OBJECTIVE: This work aimed to investigate the association between plasma PTH and AVF maturation. METHODS: Patients receiving AVF creation were enrolled retrospectively. A mouse model of secondary hyperparathyroidism and aortocaval AVF was used to investigate the effect of PTH on an AVF lesion. A cell model of VSMCs treated with PTH in a pressurized culture system was used to disclose the signaling pathway underlying the effect of PTH on an AVF lesion. RESULTS: In patients receiving AVF creation, higher PTH was associated with an increased risk for maturation failure. In a mouse model, vascular wall thickness and myofibroblasts of AVF significantly increased with higher PTH. When the same mice were treated with cinacalcet, AVF lesions were attenuated by suppression of PTH. A cell model showed that PTH increased the marker of myofibroblasts, integrin ß6 subunit (ITGB6), via the phosphorylated protein kinase B pathway. Finally, in the same model of mice AVF, higher PTH also increased the expression of ITGB6 in the smooth muscle layer of AVF, suggesting the transition to myofibroblast. CONCLUSION: Overall, our results suggest that higher PTH increased the risk of AVF maturation failure through increasing the transition of VSMCs to myofibroblasts. Lowering PTH may be a strategy to enhance AVF maturation.

Renal protective effect of sacubitril/valsartan in patients with heart failure.

Sacubitril/valsartan is a combined neprilysin inhibitor/angiotensin II receptor blocker designed for treatment of heart failure (HF). Nonetheless, its renal protective effect remained an issue of debate. This retrospective cohort study investigated the renal protective effect of sacubitril/valsartan in HF patients. HF patients on sacubitril/valsartan or valsartan for > 30 days were matched for gender, age, estimated glomerular filtration rate (eGFR), and left ventricular ejection fraction (LVEF) to be enrolled into analysis. The follow-up period was 18 months. The outcomes included end eGFR, renal function decline defined as 20% reduction of eGFR, mortality, and HF-related hospitalization. Each group had 137 patients after matching. The mean age was 72.7 years and 65.7% were male. Mean eGFR was 70.9 mL/min/1.73 m2 and LVEF was 54.0% at baseline. Overall, the eGFR of sacubitril/valsartan groups was significantly higher than valsartan group at the end (P < 0.01). Subgroup analysis showed that the difference in eGFR was significant in subgroups with LVEF ≥ 40% or eGFR ≥ 60 mL/min/1.73 m2. Multivariate Cox regression model showed that sacubitril/valsartan group had significantly reduced risk for renal function decline (hazard ratio: 0.5, 95% confidence interval: 0.3-0.9). Kaplan-Meier curve showed no difference in the risk for cardiovascular mortality, all-cause mortality or HF-related hospitalization. We showed renal protective effect of neprilysin inhibition in HF patients and specified that subgroups with LVEF ≥ 40% or eGFR ≥ 60 mL/min/1.73 m2 were sensitive to this effect, suggesting an optimal subgroup of this treatment.

A novel method to retrieve alerts from a homegrown Computerized Physician Order Entry (CPOE) system of an academic medical center: Comprehensive alert characteristic analysis.

BACKGROUND: The collection and analysis of alert logs are necessary for hospital administrators to understand the types and distribution of alert categories within the organization and reduce alert fatigue. However, this is not readily available in most homegrown Computerized Physician Order Entry (CPOE) systems. OBJECTIVE: To present a novel method that can collect alert information from a homegrown CPOE system (at an academic medical center in Taiwan) and conduct a comprehensive analysis of the number of alerts triggered and alert characteristics. METHODS: An alert log collector was developed using the Golang programming language and was implemented to collect all triggered interruptive alerts from a homegrown CPOE system of a 726-bed academic medical center from November 2017 to June 2018. Two physicians categorized the alerts from the log collector as either clinical or non-clinical (administrative). RESULTS: Overall, 1,625,341 interruptive alerts were collected and classified into 1,474 different categories based on message content. The sum of the top 20, 50, and 100 categories of most frequently triggered alerts accounted for approximately 80, 90 and 97 percent of the total triggered alerts, respectively. Among alerts from the 100 most frequently triggered categories, 1,266,818 (80.2%) were administrative and 312,593 (19.8%) were clinical alerts. CONCLUSION: We have successfully developed an alert log collector that can serve as an extended function to retrieve alerts from a homegrown CPOE system. The insight generated from the present study could also potentially bring value to hospital system designers and hospital administrators when redesigning their CPOE system.