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Background: Pediatric CKD is associated with a high risk of cardiovascular disease (CVD). Early detection of subclinical CVD in childhood CKD can be achieved through various cardiovascular (CV) assessments, including carotid intima–media thickness (cIMT), ambulatory blood pressure monitoring (ABPM), and arterial stiffness indices. Lactoferrin (LF), a key functional glycoprotein found in breast milk, has been linked to several diseases and has potential as a biomarker. Methods: In our study of 102 children with CKD stages G1–G4, we explored the relationship between LF and CV risk markers. Results: We found that LF concentration was not related to the severity or underlying causes of childhood CKD, but was positively correlated with overweight/obesity. Lower LF levels were correlated with increased cIMT and elevated arterial stiffness indices. Notably, abnormalities in ABPM profiles were observed in up to 60% of the children with CKD, with low LF levels linked to nighttime hypertension, nocturnal non-dipping, and ABPM abnormalities. Conclusions: In conclusion, LF shows promise as a biomarker for detecting subclinical CVD in children with CKD. Its potential utility in early detection could be instrumental in guiding timely interventions and improving long-term CV outcomes, although further research is needed to clarify the underlying mechanisms.

Electric cell–substrate impedance sensing has been used to measure transepithelial and transendothelial impedances of cultured cell layers and extract cell parameters such as junctional resistance, cell–substrate separation, and membrane capacitance. Previously, a three-path cell–electrode model comprising two transcellular pathways and one paracellular pathway was developed for the impedance analysis of MDCK cells. By ignoring the resistances of the lateral intercellular spaces, we develop a simplified three-path model for the impedance analysis of epithelial cells and solve the model equations in a closed form. The calculated impedance values obtained from this simplified cell–electrode model at frequencies ranging from 31.25 Hz to 100 kHz agree well with the experimental data obtained from MDCK and OVCA429 cells. We also describe how the change in each model-fitting parameter influences the electrical impedance spectra of MDCK cell layers. By assuming that the junctional resistance is much smaller than the specific impedance through the lateral cell membrane, the simplified three-path model reduces to a two-path model, which can be used for the impedance analysis of endothelial cells and other disk-shaped cells with low junctional resistances. The measured impedance spectra of HUVEC and HaCaT cell monolayers nearly coincide with the impedance data calculated from the two-path model.

Abstract Background Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample. Methods Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001. Results The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger. Conclusion UVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.

The production of melons (Cucumis melo L.) in greenhouses relies on pollination. Extreme temperature and insufficient light reduce not only flower visitation by pollinators but also pollen viability, resulting in inefficient pollination. In this study, we investigated the effects of forchlorfenuron [(N-(2-chloro-4-pyridyl)-N′-phenylurea (CPPU)] on the fruit setting and growth of oriental melons (C. melo L. var. makuwa Makino). The primary objective was to devise a new strategy for the management of oriental melons. Treatment with 5 mg·L−1 CPPU a day before flowering (T1), on the day of flowering (T2), and a day after flowering (T3) increased the fruit setting rate (by 20.1% to 30%) in melons subjected to artificial pollination (AP) or no pollination (NP) compared with the rate in those subjected to only artificial pollination without CPPU (CK). CPPU treatment induced unfertilized seeds; in addition, a tendency toward parthenocarpy was noted. The highest fruit setting rate (∼95%) was noted in plants subjected to the following treatments: AP+T1 and NP+T3. The rates of abnormal fruit formation decreased from 45.2% of CK group to 9.4% in plants subjected to AP+T1 and to 19.4% in those subjected to NP+T3. Elevated exogenous concentrations of CPPU markedly increased fruit weight. Plants subjected to NP+10 mg·L−1 CPPU bore the heaviest fruits (541.0 g), which were heavier than those borne by plants subjected to AP+10 mg·L−1 CPPU. CPPU treatment reduced the fruit cavity ratio in a concentration-dependent manner from 47.3% to 33.6% and increased the pulp thickness from 1.5 to 2.5 cm. Notably, supplementary CPPU treatment exerted no significant effects on fruit traits. Regarding taste, inconsistent results were obtained for sugar accumulation. Although the content of cucurbitacin B increased immediately after the initial CPPU treatment, it markedly decreased after 15 days of CPPU treatment. Therefore, mature melons did not have a bitter taste.

Children suffering from chronic kidney disease (CKD) have a high risk of cardiovascular disease (CVD). The early detection and diagnosis of subclinical CVD in pediatric CKD can reduce mortality later in life. Plasma factor 4 (PF4) is a chemokine released by activated platelets. We examined whether or not PF4 in the plasma and urine, its kidney function normalized ratio, and fractional excretion have differential associations with CVD risk markers in 139 youths aged 3 to 18 years old with CKD stages G1–G4. Significant negative correlations were observed between plasma PF4 and cardiovascular surrogate markers, such as the left ventricular mass index (LVMI), carotid intima–media thickness (cIMT), and pulse wave velocity (PWV). The plasma PF4/creatinine (Cr) ratio was lower in CKD children with a high daytime BP and 24 h BP, high BP load, and nocturnal non-dipping status. After adjusting for confounders, the plasma PF4 and plasma PF4/Cr ratio still independently predicted an abnormal ABPM profile. In addition, both the plasma PF4 and plasma PF4/Cr ratio presented a negative correlation with the L-arginine and asymmetric dimethylarginine ratio. These findings provide convincing evidence supporting the link between PF4 and CVD markers in pediatric CKD. Our study highlights the importance of further research to assess the performance of PF4-related biomarkers in predicting CVD events and CKD progression in children with CKD.

Abstract Breast‐conserving surgery (BCS) is the predominant treatment approach for initial breast cancer. However, due to a lack of effective methods evaluating BCS margins, local recurrence caused by positive margins remains an issue. Accordingly, radiation therapy (RT) is a common modality in patients with advanced breast cancer. However, while RT also protects normal tissue and enhances tumor bed doses to improve therapeutic effects, current radiosensitizers cannot meet these urgent clinical needs. To address this, a novel self‐assembled multifunctional nanoprobe (NP) gadolinium (Gd)–diethylenetriaminepentaacetic acid–human serum albumin (HSA)@indocyanine green–Bevacizumab (NPs‐Bev) is synthesized to improve the efficacy of fluorescence‐image‐guided BCS and RT. Fluorescence image guidance of the second near infrared NP improves complete resection in tumor‐bearing mice and accurately discriminates between benign and malignant mammary tissue in transgenic mice. Moreover, targeting tumors with NPs induces more reactive oxygen species under X‐ray radiation therapy, which not only increases RT sensitivity, but also reduces tumor progression in mice. Interestingly, self‐assembled NPs‐Bev using HSA, the magnetic resonance contrast agent and Bevacizumab‐targeting vascular growth factor A, which are clinically safe reagents, are safe in vitro and in vivo. Therefore, the novel self‐assembled NPs provide a solid precision therapy platform to treat breast cancer.

The cabbage cultivar ‘K-Y cross’ is the most important vegetable crop in Taiwan, but it is not easy to produce through the whole year because of the hot summer. For year-round supply, the different postharvest methods such as precooling and modified atmosphere packaging (MAP) were applied to extend the storage period. The respiration rate and ethylene production were measured in a wide range of temperatures from 1 to 30 °C, and the end of precooling temperature was recommended to be around 7 °C (3/4 precooling times). Vacuum precooling (VC) took cabbages only 30 min to decrease from around 27 °C to 7 °C, which was 19 times faster than room precooling (RC). After 3/4 precooling times, temperature distribution from surface to central parts of cabbages was shown to be more uniform by VC than that by RC. After VC, the MAP was applied to maintain the quality traits of cabbages. The passive MAP could decrease the weight loss, yellowing, and physiological disorders and maintain around 2% O2 and 4% CO2 in the 0.03 mm LDPE bags at 1 °C after 12-week storage. Therefore, the quality of cabbages could be maintained over 3 months by combing VC and passive MAP.

Cardiomegaly is an asymptomatic disease. Symptoms, such as palpitations, chest tightness, and shortness of breath, may be the early indications of cardiac hypertrophy, which can be divided into cardiac hypertrophy and ventricular enlargement. Their causes and treatment strategies are different. The early detection of cardiomegaly can help to make decisions for administering drugs and surgical treatments. In addition, with regard to problems in manual inspection, such as time consuming and the need for human interpretations and experiences, an assistive tool is required to automatically develop and identify normal heart or enlarged hearts. Therefore, this study proposes the combination of 2D (two dimensional) and 1D (one dimensional) convolutional neural network based classifier for rapid cardiomegaly screening in clinical applications based on chest X-ray (CXR) examinations in frontal posteroanterior view. The 2D and 1D convolutional processes and multilayer connected classification network are used to enhance the original CXR image and to remove unwanted noises to increase accuracy in feature extraction and pattern recognition tasks. The training dataset and testing dataset are collected from the National Institutes of Health CXR image database, which is used to train the classifier and validate the performance of the classifier in a K-fold cross-validation manner. Experimental results indicate the potential performance for rapid cardiomegaly screening with regard to recall (%), precision (%), accuracy (%), and F1 score.

Asparagus is a potential greenhouse crop, and its production is considerably affected by temperature and light, especially in the summer season. This study investigated the effects of the application of near-infrared (NIR)-reflective diffusion coating on a simple plastic greenhouse on microclimatic conditions, plant response, spear yield, and quality of the asparagus plant in central Taiwan. The results showed that NIR-reflective diffusion coating reduced the mean air temperature inside the greenhouse by 0.3 to 0.9 °C and leaf temperature by 2.3, 2.4, and 2.4 °C at a canopy height of 50, 100, and 50 cm, respectively. Although the accumulated daily light integral (DLI) transmitted in the coated greenhouse exhibited an 18.9% reduction compared with a 16.8% reduction in the noncoated greenhouse, a more uniform spatial light distribution was noted. Therefore, photosynthesis improved in the middle and bottom canopy, and plants could maintain a higher transpiration rate, thus resulting in atmospheric cooling. The average spear yield increased by 31.4% in summer and by 10.1% during the following harvest with a lower crude fiber (CF) content and higher Ca as well as Mg contents. In addition, the number of newly emerged shoots increased by 48.8% after the removal of the mother stalk under coating. NIR-reflective diffusion coating can be used as an energy-saving method for enhancing cooling and improving light use efficiency, thus increasing asparagus production in a greenhouse in summer.

Abstract Valvular heart diseases or chronic valvular dysfunctions are widely treated by percutaneous pulmonary valve implantation (PPVI) in cases requiring prosthetic pulmonary valve implantation and replacement. Commercial pulmonary valve stents (CPVS), sucas Epic™ valved stents or mechanical heart valves, are available to improve narrowed pulmonary valves or address problems of blood flow regurgitation in the right ventricle to pulmonary artery conduit. However, these commercial valve stents have limited availability of different sizes and diameters. Currently, the customized handmade trileaflet‐valved conduit (HTVC) is a novel surgical strategy being used in young adults and children. The HTVC can be designed witdifferent optimal parameters and can be reconstructed as expanded polytetrafluoroethylene (ePTFE)‐valved conduits for PPVI clinical applications. To verify the availability and durability of the HTVC, we validated its hemodynamic and functional performances using a mock circulation system in an in vitro study. At different heart rates and blood flows, we used the forward stroke flow (systolic period) and regurgitation flow (diastolic period) to calculate the pulmonary regurgitation fraction (RF) and ejection efficiency (EE) to evaluate the HTVC performances. We also observed its dynamic behaviours using an endoscopic camera in a pulsatile experimental setting. In addition, we used a Duffing–Holmes‐based chaotic synchronization system to track the trajectories of pulmonary artery pressure waveforms of the HTVC and CPVS, whiccan synchronously obtain the dynamic self‐synchronization errors for quantifying the HTVC's performance. Througin vitro laboratory experiments, the comprehensive dynamic errors were found to be positively correlated witthe RFs and EEs. The experimental results indicate that the results obtained by the HTVC are promising, including a decrease in the RF and an increase in the EE, as compared witCPVSs. Therefore, the dynamic errors can be used to obtain rapid quantitative indications of the performance quality of HTVCs under different hemodynamic conditions for RV‐PA reconstruction.

This study examines several issues concerning the acquisition of evidential markers in Chinese with Taiwan Mandarin-speaking children, including evidential type, acquisition order, and age effect. A production task (i.e., picture-description task) and a comprehension task (i.e., multiple-choice task) were completed by forty children who were divided into two age groups, 3-year-olds and 5-year-olds. Twenty adult native speakers of Taiwan Mandarin were recruited as controls. The results showed that direct evidential markers were comprehended and produced prior to indirect. For the order of acquisition, the child participants found visual markers and non-visual markers equally easy, while they understood reported markers better than inferring markers. Finally, age was identified as a crucial factor in children’s acquisition of Chinese evidential markers. The 3-year-olds had some success with the use of direct evidential markers, but they still had difficulties with indirect evidential markers. The 5-year-olds significantly outperformed the 3-year-olds but they did not reach an adult-like level.

Abstract Background Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p

Abstract Gut microbiota is very important for energy metabolism and regulation, which in turn affect the health and physiological functions of the host, and provide energy required for exercise. Supplementation with probiotics may be one of the ways to change the gut microbiota. In recent years, many studies have shown that probiotic supplementation can effectively improve sports performance. In this study, we screened Lactobacillus plantarum (PL-02), a probiotic of human-origin, from the intestines of 2008 Olympic women's 48 kg weightlifting gold medalist and explored the role of PL-02 in improved exercise endurance performance, reduced fatigue biochemical parameters, and changes in body composition. Male Institute of Cancer Research (ICR) mice were assigned to 0, 2.05 × 109, 4.10 × 109 and 1.03 × 1010 CFU/kg/day groups and were fed by oral gavage once daily for 4 weeks. The results showed that 4 weeks of PL-02 supplementation could significantly increase muscle mass, muscle strength and endurance performance, and hepatic and muscular glycogen storage. Furthermore, PL-02 could significantly decrease lactate, blood urea nitrogen (BUN), ammonia, and creatine kinase (CK) levels after exercise (p

Abstract Notch receptors (Notch1–4) play critical roles in tumorigenesis and metastasis of malignant tumors, including breast cancer. Although abnormal Notch activation is related to various tumors, the importance of single receptors and their mechanism of activation in distinct breast cancer subtypes are still unclear. Previous studies by our group demonstrated that Notch3 may inhibit the emergence and progression of breast cancer. PTEN is a potent tumor suppressor, and its loss of function is sufficient to promote the occurrence and progression of tumors. Intriguingly, numerous studies have revealed that Notch1 is involved in the regulation of PTEN through its binding to CBF-1, a Notch transcription factor, and the PTEN promoter. In this study, we found that Notch3 and PTEN levels correlated with the luminal phenotype in breast cancer cell lines. Furthermore, we demonstrated that Notch3 transactivated PTEN by binding CSL-binding elements in the PTEN promoter and, at least in part, inhibiting the PTEN downstream AKT-mTOR pathway. Notably, Notch3 knockdown downregulated PTEN and promoted cell proliferation and tumorigenesis. In contrast, overexpression of the Notch3 intracellular domain upregulated PTEN and inhibited cell proliferation and tumorigenesis in vitro and in vivo. Moreover, inhibition or overexpression of PTEN partially reversed the promotion or inhibition of cell proliferation induced by Notch3 alterations. In general, Notch3 expression positively correlated with elevated expression of PTEN, ER, lower Ki-67 index, and incidence of involved node status and predicted better recurrence-free survival in breast cancer patients. Therefore, our findings demonstrate that Notch3 inhibits breast cancer proliferation and suppresses tumorigenesis by transactivating PTEN expression.

Background: In the latest rankings, breast cancer ranks first in incidence and fifth in mortality among female malignancies worldwide. Early diagnosis and treatment can improve the prognosis and prolong the survival of breast cancer (BC) patients. The NIMA-related kinase (NEK), a group of serine/threonine kinase, is a large and conserved gene family that includes NEK1–NEK11. The NEK plays a pivotal role in the cell cycle and microtubule formation. However, an integrative analysis of the effect and prognosis value of NEK family members on BC patients is still lacking.Methods: In this study, the expression profiles of NEK family members in BC and its subgroups were analyzed using UALCAN, GEPIA2, and Human Protein Atlas datasets. The prognostic values of NEK family members in BC were evaluated using the Kaplan–Meier plotter. Co-expression profiles and genetic alterations of NEK family members were analyzed using the cBioPortal database. The function and pathway enrichment analysis of the NEK family were performed using the WebGestalt database. The correlation analysis of the NEK family and immune cell infiltration in BC was conducted using the TIMER 2.0 database.Results: In this study, we compared and analyzed the prognosis values of the NEKs. We found that NEK9 was highly expressed in normal breast tissues than BC, and NEK2, NEK6, and NEK11 were significantly highly expressed in BC than adjacent normal tissues. Interestingly, the expression levels of NEK2, NEK6, and NEK10 were not only remarkably correlated with the tumor stage but also with the molecular subtype. Through multilevel research, we found that high expression levels of NEK1, NEK3, NEK8, NEK9, NEK10, and NEK11 suggested a better prognosis value in BC, while high expression levels of NEK2 and NEK6 suggested a poor prognosis value in BC.Conclusion: Our studies show the prognosis values of the NEKs in BC. Thus, we suggest that NEKs may be regarded as novel biomarkers for predicting potential prognosis values and potential therapeutic targets of BC patients.

BackgroundNaja atra bites cause wound necrosis, secondary infection, and necrotizing soft tissue infection (NSTI) requiring repetitive surgeries. Little information is known about the predictors for surgery after these bites.Materials and methodsWe retrospectively evaluated 161 patients envenomed by N. atra, 80 of whom underwent surgery because of wound necrosis and infection. We compared the patients' variables between surgical and non-surgical groups. To construct a surgical risk score, we converted the regression coefficients of the significant factors in the multivariate logistic regression into integers. We also examined the deep tissue cultures and pathological findings of the debrided tissue.ResultsA lower limb as the bite site, a ≥3 swelling grade, bullae or blister formation, gastrointestinal (GI) effects, and fever were significantly associated with surgery in the multivariate logistic regression analysis. The surgical risk scores for these variables were 1, 1, 2, 1, and 2, respectively. At a ≥3-point cutoff value, the model has 71.8% sensitivity and 88.5% specificity for predicting surgery, with an area under the receiver operating characteristic curve of 0.88. The histopathological examinations of the debrided tissues supported the diagnosis of snakebite-induced NSTI. Twelve bacterial species were isolated during the initial surgery and eleven during subsequent surgeries.Discussion and conclusionsFrom the clinical perspective, swelling, bullae or blister formation, GI effects, and fever appeared quickly after the bite and before surgery. The predictive value of these factors for surgery was acceptable, with a ≥3-point risk score. The common laboratory parameters did not always predict the outcomes of N. atra bites without proper wound examination. Our study supported the diagnosis of NSTI and demonstrated the changes in bacteriology during the surgeries, which can have therapeutic implications for N. atra bites.

Grafting is one of the main techniques used in intensive tomato cultivation to address abnormal weather, diseases, insect pests, and continuous cropping problems. In recent years, due to agricultural labor constraints, the industry has needed to make use of more machinery. In this study, a clamping and cutting arrangement device for Solanaceae scion and stock seedlings was developed; it included a UR5 robotic arm to realize the automatic clamping and cutting of multiple seedlings, to facilitate the mechanized grafting of seedlings. The clamping success rate of eggplant and tomato seedlings using this device was 99%. When working with four seedlings in a single operation, the oblique-cutting success rates for eggplant and tomato seedlings were 97.76% and 94.55%, respectively. Moreover, 404 eggplant seedlings and 384 tomato seedlings could be worked with in 1 h. After the splicing and grafting process had been completed, the survival rate of the grafted seedlings was 85%. The simple device structure could be used by the industry to assist operators in clipping and cutting seedlings, reduce the complexity of grafting operations, shorten training times, address the problem of labor constraints in Taiwan’s agricultural industry, and improve product quality and efficiency.

Cardiovascular disease (CVD) is an evolving process that begins in the early stages of chronic kidney disease (CKD) in children. Several surrogate markers, such as ambulatory blood pressure monitoring (ABPM), left ventricular (LV) mass, and arterial stiffness assessment, allow for the early detection of subclinical CVD in pediatric CKD. Four groups of plasma samples (n = 3/group) from congenital anomalies of the kidney and urinary tract (CAKUT), as well as non-CAKUT patients with or without BP abnormalities, were studied to screen differentially expressed proteins using isobaric tags for relative and absolute protein quantification (iTRAQ)-based proteomics. As a result, 20 differentially expressed proteins associated with hypertension in children with CKD were discovered. Among them, apolipoprotein C-II (apoC-II) was found to have the highest abundance among the CKD patients with hypertension. As such, we hypothesized that apoC-II and apolipoprotein C-III (apoC-III) levels were related to BP abnormalities and CVD in children suffering from mild-to-moderate CKD. We examined their associations with surrogate markers of CV risk in 88 pediatric patients with CKD stages G1–G4. Children with CKD stages G2–G4 had a higher plasma apoC-II level than G1 patients (6.35 vs. 5.05 mg/dl, p < 0.05). We observed that ABPM abnormalities, LV mass, and arterial stiffness parameters were greater in CKD children who had stages G2–G4 than in those who had stage G1 (all p < 0.05). Plasma levels of apoC-II and apoC-III were positively correlated with total cholesterol, triglyceride, and low-density lipoprotein (LDL) (all p < 0.001). In multivariate linear regression analyses, apoC-II was correlated with a high LV mass index and an abnormal ABPM profile, and apoC-III was correlated with 24-h hypertension (r = 0.303, p = 0.003) and asleep hypertension (r = 0.379, p < 0.001). Early evaluations of apoC-II and apoC-III, ABPM, and surrogate markers of CV risk will aid in early preventative interventions to reduce the risk of CV in youths suffering from CKD.

PurposeThe basic helix-loop-helix transcription factor (bHLH) transcription factor Twist1 plays a key role in embryonic development and tumorigenesis. p53 is a frequently mutated tumor suppressor in cancer. Both proteins play a key and significant role in breast cancer tumorigenesis. However, the regulatory mechanism and clinical significance of their co-expression in this disease remain unclear. The purpose of this study was to analyze the expression patterns of p53 and Twist1 and determine their association with patient prognosis in breast cancer. We also investigated whether their co-expression could be a potential marker for predicting patient prognosis in this disease.MethodsTwist1 and mutant p53 expression in 408 breast cancer patient samples were evaluated by immunohistochemistry. Kaplan-Meier Plotter was used to analyze the correlation between co-expression of Twist1 and wild-type or mutant p53 and prognosis for recurrence-free survival (RFS) and overall survival (OS). Univariate analysis, multivariate analysis, and nomograms were used to explore the independent prognostic factors in disease-free survival (DFS) and OS in this cohort.ResultsOf the 408 patients enrolled, 237 (58%) had high mutant p53 expression. Two-hundred twenty patients (53.9%) stained positive for Twist1, and 188 cases were Twist1-negative. Furthermore, patients that co-expressed Twist1 and mutant p53 (T+P+) had significantly advanced-stage breast cancer [stage III, 61/89 T+P+ (68.5%) vs. 28/89 T-P- (31.5%); stage II, 63/104 T+P+ (60.6%)vs. 41/104 T-P- (39.4%)]. Co-expression was negatively related to early clinical stage (i.e., stages 0 and I; P = 0.039). T+P+ breast cancer patients also had worse DFS (95% CI = 1.217–7.499, P = 0.017) and OS (95% CI = 1.009–9.272, P = 0.048). Elevated Twist1 and mutant p53 expression predicted shorter RFS in basal-like patients. Univariate and multivariate analysis identified three variables (i.e., lymph node involvement, larger tumor, and T+P+) as independent prognostic factors for DFS. Lymph node involvement and T+P+ were also independent factors for OS in this cohort. The total risk scores and nomograms were reliable for predicting DFS and OS in breast cancer patients.ConclusionsOur results revealed that co-expression of mutant p53 and Twist1 was associated with advanced clinical stage, triple negative breast cancer (TNBC) subtype, distant metastasis, and shorter DFS and OS in breast cancer patients. Furthermore, lymph nodes status and co-expression of Twist1 and mutant p53 were classified as independent factors for DFS and OS in this cohort. Co-evaluation of mutant p53 and Twist1 might be an appropriate tool for predicting breast cancer patient outcome.

Abstract Background Acanthus ilicifolius var. xiamenensis (Acanthaceae) is an old world mangrove species and has long been used as a folk remedy for treating various ailments in traditional medicine. The nature source of A. ilicifolius var. xiamenensis is now in short supply because of the urban development and habitat destruction. To better utilize this resource, biodiversity and bioactivity of endophytic fungi isolated from A. ilicifolius var. xiamenensis were investigated. Results A total of 168 fungal isolates were cultured from leaves and stems of the mangrove plant collected in January (winter) and July (summer) 2014 at Kinmen County, Taiwan. Spent culture extract of 28 isolates were found to have bioactivities against one of the following pathogenic microorganisms: the bacteria Bacillus subtilis, Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) and the fungi Candida albicans and Cryptococcus neoformans. These positive extracts were mostly active against the Gram-positive bacteria and C. albicans. Corynespora cassiicola NTOU4889 and Xylaria sp. NTOU4900 inhibited growth of all 3 test bacteria whereas Phellinus noxius NTOU4917 inhibited both test fungi. A further anti-inflammatory study of culture extracts of these 28 isolates revealed that extracts with a high iNOS inhibition caused a low viability of cells, and those with a low iNOS inhibition had a high cell viability. Three extracts showed low cytotoxicity (i.e. > 100% cell viability) and high iNOS inhibition (

Functional tremors are clear symptoms of neurodegenerative diseases; as such, they indicate the progression of Parkinson's disease (PD). Digitized handwritten pattern analysis of Archimedes' spirals, words, and sentences can help evaluate movement discords in the upper limbs. It offers a simple, comfortable, and repeatable method of examination for clinical applications and at-home monitoring usages. Upper limb tremors can be found in PD, essential tremor (ET), and cerebellar disorders. This paper proposes a quantitative method to scale the variations of functional tremors. The deviation (in cm) and the accumulation angle (in rad) of the feature pattern in polar expression were extracted to scale the variability at different tremor levels. Then, the proposed intelligent classifier, which is used as a perceptual color representation-based classifier (PCRC) and comprises a radial Bayesian network and a color relation analysis method, was employed to screen PD or ET with perceptual color representation. An assistant tool can integrate a smart mobile device (iPad/smartphone) and PCRC into the decision support system for individualized functions to evaluate the progression of the tremor level. The proposed decision support system was validated using data collected from 50 subjects. With fivefold cross-validation, average true positive, average true negative, and hit rates of 92.02%, 88.17% and 90.44%, respectively, were obtained to quantify the performance of the proposed classifier for identifying normal controls and PD or ET.

Pleural effusion is the pathologic accumulation of body fluids around the unilateral or bilateral lungs that is primarily caused by heart disease. A chest radiograph is a rapid examination technique used to provide a preliminary diagnosis of lung and heart diseases. Computer-aided diagnosis with the digitalized image is an automated approach that addresses the drawbacks of manual inspection. In this study, two corner detectors along with a two-dimensional convolution process are used to enhance the chest X-ray image for an accurate extrapolation of the bilateral lung cavities. Based on bounding box pixel analysis, the pixel ratios of the lung anatomy between normal and abnormal conditions can be estimated to identify the pleural effusion size. Next, a smart drainage monitoring system is developed to improve the current functions of the traditional drainage tool and confirm the drainage safety, including (a) drainage volume and required time detection, (b) unplanned removal warning, and (c) physiological status monitoring. The experimental result will be used to determine the feasibility of the proposed effusion volume estimation algorithm and the efficiency of the smart drainage monitoring prototyping tool. The proposed smart drainage monitoring system and the computer-aided method with digitalized images can be further applied in real clinical practice in the intensive care unit.

Cardiovascular disease (CVD) is the main cause of mortality among chronic kidney disease (CKD) patients, both in adults and in children. Hypertension is one of the risk factors of CVD. For early detection of subclinical CVD in pediatric CKD, 24 h ambulatory blood pressure monitoring (ABPM), cardiosonography, and arterial stiffness assessment were evaluated. CAKUT (congenital anomalies of the kidney and urinary tract) are the main etiologies of pediatric CKD. Previously, by a proteomic approach, we identified complement factor H (CFH) and related proteins differentially expressed between children with CAKUT and non-CAKUT CKD. In this study, we aimed to evaluate whether CFH, CFH-related protein-2 (CFHR2), and CFH-related protein-3 (CFHR3) were related to CVD risk in children with CKD. This study included 102 subjects aged 6 to 18 years old. The non-CAKUT group had higher plasma CFHR3 levels than the CAKUT group (p = 0.046). CFHR3 was negatively correlated with LV mass (p = 0.009). CFHR2 was higher in children with CKD with 24 h hypertension in the ABPM profile (p < 0.05). In addition, children with non-CAKUT CKD with day-time hypertension (p = 0.036) and increased BP load (p = 0.018) displayed a lower plasma CFHR3 level. Our results highlight that CFH and related proteins play a role for CVD in children with CKD. Early assessment of CFH, CFHR2, and CFHR3 may have clinical utility in discriminating CV risk in children with CKD with different etiologies.

Pulmonary valve diseases in children and adults include different degrees of stenosis, regurgitation, or congenital defects. Valve repair or replacement surgery is used to treat valvular dysfunction and to improve regurgitations flow for pulmonary valve pathologies. Handmade trileaflet valve designs with different ranges of diameters have been used for pulmonary valved conduit reconstruction among children or adult patients with available conditions. In this paper, we propose a multiple regression model as a cascadecorrelation-network-based estimator to determine optimal trileaflet parameters, including width, length, and upper/lower curved structures, for trileaflet valve reconstruction. The diameter of the main pulmonary artery is determined via computed tomography pulmonary angiography, and a trileaflet valve template is rapidly sketched. The actual valve is constructed using an expanded polytetrafluoroethylene material. Using an experimental pulmonary circulation loop system, design parameters and valve efficacy can be validated by the Taguchi method through calculation of signal-to-noise ratios. Experimental results indicate that in contrast to commercial valve stents, the handmade trileaflet valve exhibits good performance and is a valuable option in treatment of severe pulmonary regurgitation.

Dialysis vascular accesses are critical for patients receiving hemodialysis treatment. However, dialysis access stenosis and further dysfunction are engendered by thrombosis or outflow (venous anastomosis site) stenosis and the progression of inflow (arterial anastomosis site) stenosis. Thus, any narrowed access causes vibrations, turbulent flow, and murmur sounds around stenosis sites. Auscultation and frequency-based techniques are employed to detect these sounds, and frequency components are also validated on the basis of the degree of stenosis (DOS). In this paper, a biophysical experimental model employing an in vitro arteriovenous graft model was established to produce various acoustic signals associated with single stenosis and multiple stenoses. By analyzing various combinations of stenoses, this paper selected suitable features of the frequency and power spectra using the Burg autoregressive method. A multiple regression model applying a higher number of explanatory variables and response variables, as a generalized regression neural network, was employed to identify DOS levels at inflow and outflow sites. The experimental results indicated that the proposed screening model provided a higher average hit rate of >90%, average true-positive rate of >90%, and true-negative rate of 100% in single and multiple stenosis screening, compared with the multiple linear regression model.

Cardiac arrhythmias reveal multiple morphologies in time-domain waveforms. Abnormal beats reflect the origin and the conduction path of the ectopic heart activation pulses, including supraventricular, junctional, and ventricular arrhythmias and conduction abnormalities. This paper proposes a method for automated screening of cardiac arrhythmias using the discrete fractional-order integration (DFOI) and the meta-learning-based intelligent classifier. The DFOI process with the specific fractional order is used to extract the QRS features with the finite computations. It can deal with the irregular time-varying signals. The meta-learning-based intelligent classifier is used to identify the abnormal classes, consisting of a primary multilayer network and several agent networks. Since abnormal QRS complexes are multi-waveforms such as ventricular premature contraction, the classifier needs to retrain with new training patterns for meeting new condition in clinical applications. Thus, this model possesses the learning-to-optimization capability for retraining generalized regression neural network using the particle swarm optimization algorithm. Using incremental new training patterns, each inducer is used to track the past learning experiences through several agent networks. This pattern scheme can gradually enhance the accuracy by refining the optimal parameters of each sub-estimator for pattern recognition. Using the arrhythmia database of the Massachusetts Institute of Technology-Beth Israel Hospital (MIT-BIH) database, the proposed intelligent classifier demonstrated greater efficiency and promising results in average accuracy, positive predictivity, and true negative rate for recognizing electrocardiography signals.

Percutaneous pulmonary valve implantation is an improved technique that is used to treat narrowed pulmonary valves or leaky pulmonary valves in patients with congenital heart disease. This technique represents a promising strategy to reduce surgical risk and operation. In clinical cases, commercial valve stents are sometimes not available for children or special subjects due to restrictions in stent size. Hence, the handmade pulmonary valved conduit provides a strategy to design stents with customized size for valve replacement. In this paper, we propose a meta-learning-based intelligent model to train an estimator (including two sub-estimators) to determine optimal trileaflet parameters for customized trileaflet valve reconstruction. This estimation model overcomes the problem of empirical parameter determination. The meta-learning model possesses learning-to-optimization capability for training generalized regression neural network by particle swarm optimization algorithm. Through incremental training patterns, this scheme can gradually enhance optimization to provide refined parameters for customized designs that can be applicable to individuals of all age groups. The customized handmade pulmonary valved conduit was validated by assessing the regurgitation fraction and the heart pump efficiency using an experimental cardiopulmonary circulation loop system.

Biogenic microvesicles (MVs) play a pivotal role in intercellular signal communication, thus initiating critical biological responses such as the proliferation of cancer cells, gene and protein transport, and chemo-drug resistance. In addition, they have been recognized as having great potential in drug delivery applications. However, the productivity of biologically produced MVs is not sufficient for clinical applications. In this study, synthetic poly(lactic-co-glycolic acid) (PLGA) MVs were prepared via a double emulsion method. The PLGA MVs had a biogenic MV-mimic vesicular structure with a hydrophilic core/surface and hydrophobic interior of the shell, showing great potential for drug delivery. We successfully embedded hydrophobic iron carbonyl (IC), a carbon monoxide (CO) donor, in the PLGA shell region, enabling the delivery of IC in an aqueous solution. Because of the intrinsic properties of PLGA, it was susceptible to temperature, and the MVs could easily collapse in a warm environment, leading to the decomposition of IC into CO. The in vitro result indicated that the cell viability of A549 lung carcinoma cells significantly decreased to 14% after treatment with IC-loaded PLGA MVs for 24 h, suggesting that these synthetic PLGA MVs constitute an excellent drug delivery platform.

Long-term repeating traumatic puncture is required for dialysis therapy, which results in frequent thrombosis and graduate vascular access stenosis, such as inflow or outflow stenosis and coexistence of both. An arteriovenous graft has a higher patency rate than an arteriovenous fistula. This study intends to use the dual-channel auscultation-based non-invasive method to screen inflow and outflow stenoses. Frequency analysis is used to decompose phonoangiography (PAG) signals to frequency features using the different data length of acoustic data. Burg autoregressive method is employed to extract the key frequency parameters from sufficient spectral data, including characteristic frequencies and distinct peaks of power spectral densities (PSDs). In big data processing, PSDs and the degree of stenosis (DOS) have been validated to show a positive correlation with sufficient big spectral data. An intelligent machine learning model, bidirectional hetero-associative memory network (BHAMN), is carried out to identify the level of DOS at the inflow site, the mid-site, or the outflow site of a vascular access. The experimental results will indicate that the proposed intelligent machine learning model has higher hit rates.

Dialysis vascular accesses are critical for dialysis therapy, but they frequently suffer from stenotic complications. Higher patency rates and thrombosis rates are a concern to nephrology nurses and patients. These complications are complex events, including inflow stenosis, outflow stenosis, and coexistence of both. Therefore, a biophysical experimental model is employed to mimic the various combinations of stenoses and dialysis circulation circuits on a virtual adult hand. Considering the suggested signal preprocessing specifications, auscultation method and frequency analysis technique are used to extract the key frequency components from sufficient big spectral data. Key frequency components, depending on the degree of stenosis (DOS) (positive correlation), are validated using multiple regression models with multiple explanatory variables and response variables. A new machine learning method, radial-based colour relation analysis, is employed to identify the level of DOS at the inflow and outflow sites. In contrast to the multiple linear regression and traditional machine learning method, the experimental results indicated that the proposed screening model had higher accuracy (hit rate), true-positive rate, and true-negative rate in clinical indication.

Maintaining adequate dry weight and fluid volume balance is an important issue for dialysis patients. Malnutrition and sodium intake are the primary factors that cause fluid volume imbalance and changes in body weights. Inadequate dry weight control results in higher levels of blood pressures and is related to various complications, such as volume overload, hypertension, congestive symptoms, and cardiovascular diseases. Moreover, inadequate fluid removal provokes hypotension during dialysis treatment. Thus, we propose an early warning tool based on fuzzy color reason analysis in predialysis healthcare for hypervolemia screening. The anthropometric method is a rapid, non-invasive, and simple technique for estimating the total body water. In this study, Watson standard formula is employed to estimate cross-sectional standard of total body water with the patient characteristics, including gender, age, height, and weight. In contrast to the experienced anthropometric formulas, Watson formula has less than 2% of margin errors and provides a criterion as a reference manner to estimate the total body water in patient’s normal dry weight. In addition, inadequate dry weight and total body water controls will lead to higher blood pressures. The systolic blood pressure is also an indicator to evaluate pre-hypertension of 120–139 mmHg and hypertension of greater than or equal to 140 mmHg. Therefore, the levels of two indicators, total body water and systolic blood pressure, are parameterized with fuzzy membership grades to describe the normal and the specific ranges of undervolemia and hypervolemia. A color reason analysis utilizes a hue–saturation–value color model to design a color perceptual manner for separating normal condition from hypervolemia or undervolemia. Normalized hue angle and saturation value provide a promising visual representation with color codes to realize the patients’ diagnosis. Dialysis patients with hypertension demonstrated that the proposed model can be used in clinical applications. In addition, a healthcare chair is carried out to measure blood pressure and weight in predialysis. The proposed assistant tool integrates an electronic pressure monitor and an electronic weight monitor, and fuzzy color reason analysis is also intended to be established in an intelligent vehicle via a WiFi wireless local area network for cloud computing.

Overexpression of Twist, a highly conserved basic helix-loop-helix transcription factor, is associated with epithelial-mesenchymal transition (EMT) and predicts poor prognosis in various kinds of cancers, including breast cancer. In order to further clarify Twist's role in breast cancer, we detected Twist expression in breast cancer tissues by immunohistochemistry. Twist expression was observed in 54% (220/408) of breast cancer patients and was positively associated with tumor size, Ki67, VEGF-C and HER2 expression. Conversely, Twist was negatively associated with estrogen receptor (ER), progesterone receptor (PgR) and E-cadherin expression. Patients with Twist expression had a poorer prognosis for 30-month disease free survival (DFS) (82.9%) than patients with negative Twist (92.3%). Overexpression of Twist led to dramatic changes in cellular morphology, proliferation, migratory/invasive capability, and expression of EMT-related biomarkers in breast cancer cells. Moreover, we show that Twist serves as a driver of tumorigenesis, as well as an inducer of EMT, at least in part, through activation of the Akt and extracellular signal-regulated protein kinase (ERK) pathways which are critical for Twist-mediated EMT. Our results demonstrate that Twist expression is an important prognostic factor in breast cancer patients.

Effective human factors and usability engineering assessment in the initial phase of medical device design can eliminate or reduce the likelihood of injury incidents caused by users' inability to correctly perceive and operate the device because of poor user interface designs. Currently, relevant authorities worldwide are attaching greater importance to the management of documents required for reviews before medical device becomes commercially available. Therefore, this study analyzed the existing medical device management system to clarify the principles associated with medical device human factors and usability engineering assessment currently employed in Taiwan. Relevant international standards are referenced to clarify the principles of medical device design and development to reduce user risks. Moreover, the inquiries and management of human factors and usability engineering studies and the reviews and requirements for production commercialization in the United States, the European Union, Japan, South Korea, China, and various international organizations were compared to provide a comprehensive outline of management principles in human factors and usability engineering for future medical device. Accordingly, a globally standardized review system can be established to accelerate the product development and upgrade of the medical device industry in Taiwan, thereby reinforcing its international competitiveness. [ABSTRACT FROM AUTHOR]