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Purpose Breast cancer is increasing around the globe, including Asia. We aimed to examine the survival and risk of contralateral breast cancer (CBC) in Asian breast cancer patients with BRCA mutations. MethodsA total of 128 breast cancer patients with germline BRCA mutations and 4,754 control breast cancer patients were enrolled. Data on clinical pathologic characteristics, survival and CBC were collected from the medical record. The rates of survival and CBC were estimated by Kaplan-Meier method. Results The mean age of onset in BRCA mutation carriers was significantly younger than control patients (BRCA vs. Non-BRCA: 43.9 vs. 53.2 years-old). BRCA mutation carriers had a higher proportion of triple-negative breast cancer (TNBC) (52%) than control patients (12%, pBRCA mutation patients than in control cases (hazard ratio (HR) = 3.95, 95% CI 2.71-5.75); when stratified by genotype, the HRs (95%CI) were 4.84 (3.00-7.82) for BRCA1 and 3.13 (1.78-5.49) for BRCA2 carriers, respectively. Moreover, BRCA1 mutation patients with triple-negative breast cancer (TNBC) as their first breast cancer had the highest risk of CBC (HR = 5.55, 95% CI 3.29-9.34). However, we did not observe any differences in relapse-free survival and overall survival between mutation carriers and control patients. ConclusionOur study suggest that BRCA patients had a significantly higher risk of developing CBC, particularly for BRCA1 mutation carriers with TNBC as the first breast cancer.

Aims and objectives The aims of the study were to (i) estimate the prevalence of frailty among older adults with type 2 diabetes, and (ii) investigate risk factors associated with frailty in the study group. Background The high prevalence of frailty among older adults and its adverse health impacts including higher risks for physical disabilities and a higher mortality rate is quickly evolving to become an important public health issue. Design A cross-sectional design. Methods Data were collected from the Clinical Diabetes Centre of our study group. Frailty was assessed using the Chinese version of the Tilburg frailty indicator. Other questionnaires included Activities of Daily Living, Mini-Mental State Examination, Taiwan Geriatric Depression Scale and Instrumental Activities of Daily Living. Multivariable logistic regression was established to identify factors associated with frailty. The STrengthening the Reporting of OBservational studies in Epidemiology checklist was used preparing the manuscript. Results A total of 248 subjects were recruited in this study, a total of 66 participants had frailty (26.6%). Our results showed that factors including age, number of chronic diseases, cerebrovascular accident, renal diseases, frequency of falling, frequency of hyperglycaemia, Activities of Daily Living, depression, Mini-Mental State Examination, and Instrumental Activities of Daily Living ≧1 task disability were correlated with frailty in older adults with type 2 diabetes. After adjusting for confounding factors, multivariate logistic regression analyses showed a significant increase in the probability of frailty by 1.72-times when comparing type 2 diabetes subjects with depression to those without depression. Conclusion This study revealed that depression is a significant factor associated with the occurrence of frailty among older adults with type 2 diabetes. Relevance to clinical practice Our results provided strong clinical evidence showing depression as an important factor associated with the risk of frailty in older individuals with type 2 diabetes. We recommend early detection via routine screenings for symptoms of depression during diabetes care to achieve early prevention or the delay of frailty and its implicated adverse health consequences.

Purpose: This study reports the MTD, recommended phase 2 dose (RP2D), and preliminary efficacy of alpelisib or buparlisib used in combination with tamoxifen plus goserelin in premenopausal patients with hormone receptor–positive (HR+), HER2-negative (HER2−) advanced breast cancer (ABC). Patients and Methods: This study enrolled premenopausal women with HR+, HER2− ABC. Patients received tamoxifen (20 mg once daily) and goserelin acetate (3.6 mg every 28 days) with either alpelisib (350 mg once daily; n = 16) or buparlisib (100 mg once daily; n = 13) in 28-day cycles until MTD was observed. Results: The criteria for MTD were not met for both alpelisib and buparlisib. The RP2D of alpelisib and buparlisib in combination with tamoxifen and goserelin were 350 mg and 100 mg, respectively. Both combinations met protocol-specified criteria for tolerability. The most common grade 3/4 treatment-emergent adverse events (TEAE) were hypokalemia (12.5%), hyperglycemia (6.3%), and rash (6.3%) for alpelisib and alanine aminotransferase increase (30.8%), aspartate aminotransferase increase (23.1%), and anxiety (15.4%) for buparlisib. TEAEs led to treatment discontinuation in 18.8% and 53.8% of alpelisib- and buparlisib-treated patients, respectively. Progression-free survival was 25.2 months in the alpelisib group and 20.6 months in the buparlisib group. Conclusions: The RP2Ds of alpelisib and buparlisib were 350 mg and 100 mg, respectively. No unexpected safety findings were reported. Although an early-phase study, data suggest that alpelisib plus endocrine therapy may be a potentially efficacious treatment that warrants further evaluation for premenopausal patients with HR+, HER2− ABC. See related commentary by Clark et al., p. 371

Background Coprescription is a potential medical problem for older adults that could induce polypharmacy and subsequent complications. In Taiwan, Chinese herbal medicine (CHM) is popular among the older adults. Investigating the coprescription trends in Western medicine, CHM and dental medicine is important to avoid possible polypharmacy. Methods We analyzed data from the Longitudinal Health Insurance Database 2000 (LHID 2000) in Taiwan. Patients ≥ 60 years old who received coprescription of Western medicine, Chinese herbal medicine and drugs for dental care from 1997 to 2013 were included. The odds ratio (OR) and 95% confidence interval (95% CI) were estimated by a logistic regression model for evaluating the correlation between baseline characteristics and coprescription. Results A total of 233,594 patients were included for the analysis. Most patients receiving coprescriptions live in the northern Taiwan and with a monthly income lower than 20,000 new Taiwan dollars. The trends in older adults using Western medicine alone or CHM alone decreased over time, but the cohort using dental medicine alone had the opposite result. Decreased trends in coprescription with age were noted. The trends in the proportion of coprescription and the number of days of coprescription increased with the calendar year. Increased trends in the proportion of patients with coprescription were also found, except for the cohort of patients who used both Western medicine and CHM. Patients who were female, aged 70-79 years and residents from the outside islands of Taiwan were prone to receive coprescription. Conclusions Coprescription in older patients is not uncommon in Taiwan. Healthcare providers and policymakers should be aware of the complex coprescription pattern in the older adults.

In this study, molecular dynamics (MD) are used to simulate the nanoimprinting behaviors of (001) Ni thin films using 3×3 array cuboid diamond punch. Different pitch of the punches was used to investigate the effect of the interaction among the forming pattern and the quality of the formed holes. Forming force was evaluated including normal and tractional force of the punch during pressing process. The dislocation behavior was also monitoring during the holes forming. The result showed that the pitch of the punch was 2w could get the best forming pattern.

A variety of epigenetic dysregulations are observed in thyroid malignancies. EZH2, the catalytic subunit of polycomb repressive complex 2, is upregulated in advanced thyroid cancers. EZH2 can catalyze trimethylation of histone H3 at lysine 27 (H3K27me3) and contribute to transcriptional silencing of target genes. Here, we investigated the immunohistochemical expression of H3K27me3 in neoplastic and normal thyroid tissues. Normal thyroid epithelial cells typically exhibited nuclear staining of moderate intensity. A similar expression pattern was observed in nodular goiters and follicular adenomas. By contrast, strong H3K27me3 expression was evident in 80% (8/10) lymphocytic thyroiditis, 63% (80/127) papillary thyroid cancer, 41% (7/17) follicular thyroid cancer, and 73% (8/11) poorly differentiated and anaplastic thyroid cancer. In differentiated thyroid cancer, strong H3K27me3 expression was associated with extrathyroidal extension (p

Background The information of Oncotype DX applied in Asian breast cancer patients is limited. A recurrence index for distant recurrence (RI-DR) has been developed for early-stage breast cancer (EBC) from tumor samples in Chinese patients. In this study, we compared the prognostic performance of the Oncotype DX (ODx) recurrence score (RS) with the RI-DR for any recurrence risk type. Materials and methods One hundred thirty-eight (138) patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative EBC who were previously tested with ODx were included for testing with the RI-DR. The cutoff score to partition the low- and high-risk patients was 26 for RS and 36 for RI-DR. The primary endpoint was recurrence-free survival (RFS). Results The concordance between the RI-DR and RS was 83% in N0 patients and 81% in node-positive patients when the RS score cutoff was set at 26. With a median follow-up interval of 36.8 months, the 4-year RFS for the high- and low-risk groups categorized by the RS were 61.9% and 95.0%, respectively (hazard ratio: 10.6, 95.0% confidence interval [CI]: 1.8–62.9). The 4-year RFS in the high- and low-risk groups categorized by the RI-DR were 72.6% and 98.5%, respectively (hazard ratio: 18.9, 95% CI: 1.8–138.8). Conclusion This paper illustrated the performance of RI-DR and ODx RS in breast cancer women in Taiwan. There was high concordance between the RI-DR and RS. The RI-DR is not inferior to the RS in predicting RFS in EBC patients. This study will fill the gap between the current and best practice in Chinese patients., Utilization of Oncotype DX is uncommon in Asia due to lack of clinical data. We compare a clinical-genomic model, developed from Taiwan, to Oncotype 21-gene panel in Chinese patients.

A four-path filter/mixer for surface acoustic wave (SAW)-less frequency division duplex (FDD) radio receivers is proposed, targeting high linearity and compression requirements. A bottom-plate mixing technique improves linearity by reducing the gate-source voltage modulation of the MOSFET switches. Differential bottom-plate mixing allows for switch sharing which halves the effective switch resistance to reduce drain-source voltage modulation. The first four-path switch-RC filter stage with bottom-plate mixing and a shared switch renders 2nd-order voltage-domain RF-bandpass filtering around the LO frequency. Extra out-of-band rejection is implemented combined with $V$ – $I$ conversion and zero-IF frequency down-conversion in the second cross-coupled switch-RC four-path stage, which offers a low-ohmic high-linearity current path for out-of-band interferers. A prototype chip fabricated in a 28-nm CMOS technology achieves an out-of-band IIP3 of +44 dBm, IIP2 of +90 dBm and blocker 1-dB gain-compression point of +13 dBm for a blocker frequency offset of 80 MHz. At this offset frequency, the measured desensitization is only 0.6 dB for a 0-dBm blocker, and 3.5 dB for a 10-dBm blocker at 0.7-GHz LO (i.e., 6- and 9-dB blocker noise figure). The chip consumes 38–96 mW for LO-frequencies of 0.1–2 GHz and occupies an active area of 0.49 mm2.

ContextSpiking is one of the most frequently used scoring techniques in volleyball games, and around 80% of shoulder pain in volleyball players is linked with the spiking movement.ObjectiveTo investigate the differences in glenohumeral joint, scapular, and trunk movements during the spiking motion between volleyball players with and those without shoulder pain.DesignCross-sectional study.SettingUniversity laboratory.Patients or Other ParticipantsTwenty amateur volleyball players with shoulder pain (age = 21.8 ± 1.79 years, with an average of 4.0 ± 0.92 years of volleyball experience and 6.0 ± 3.51 months of shoulder pain) and 20 sex-, age-, and experience-matched control participants.Main Outcome Measure(s)The 3-dimensional kinematics of the shoulder joint, scapula, and trunk during spiking were assessed using an electromagnetic tracking system.ResultsCompared with the control group, individuals with shoulder pain demonstrated less scapular posterior tilt (P = .041) and more glenohumeral horizontal abduction (P = .008) and scapular internal rotation (P = .02) at ball contact when performing the cross-body spike.ConclusionsThe decrease in scapular posterior tilt, along with increased glenohumeral horizontal abduction and scapular internal rotation, was associated with shoulder pain in university volleyball players. These changes should be addressed in the training and treatment of young volleyball players.

BackgroundNumerous prospective studies, predominantly in the Caucasian population, have proven the clinical utility of using multigene expression tests to prevent overtreatment in early-stage breast cancer patients with early-stage disease. In this study, we used an Asian population to validate a clinical-genomic assay (RecurIndex®) for estimating the risk of distant recurrence and relapse in early-stage breast cancer patients. MethodsA total of 298 patients with early-stage breast cancer, luminal-like subtype (85.6%) and HER2-enriched/ triple-negative subtype (14.4%), was enrolled in a retrospective study across five participating medical centers in Taiwan. The inclusion criteria were as follows: women (1) who underwent primary surgery without prior induction treatments, (2) with an early pathologic N stage and (3) who received either mastectomy or breast-conserving surgery. Kaplan Meier method and Cox proportional hazards model were used to, respectively, identify independent prognostic factors and calculate the 5- and 10-year survival rates of patients in the low- and high-risk groups assigned by the diagnostic test. A forest plot was produced to assess hazard ratios and 95% confidence intervals. The primary endpoint was distant recurrence-free survival (DRFS) and the secondary endpoint was relapse-free survival (RFS).ResultsThe 10-year DRFS rate was significantly higher in the good prognosis group than in the poor prognosis group (91.9% [95% CI, 86.1-98.1%] versus 62.9% [95% CI, 49.8-79.4%]). The overall hazard ratio for distant recurrence was 1.031 [95% CI, 1.017 - 1.046] per unit Recurrence index-distant recurrence (RI-DR) score increment. ConclusionsThe present study provides robust evidence of the clinical utility of using the RI-DR score to accurately predict clinical outcomes. RecurIndex® could be used to determine the utility of adjuvant chemotherapy in Asian patients, especially those having hormone-receptor positive tumors, leading to a meaningful reduction in adjuvant chemotherapy recommendations.

Objective: Chinese herbal medicine (CHM) is quite popular in Asia. The purpose of this study is to investigate the benefits of decreasing the risk of cirrhosis in patients with non-alcoholic fatty ...

In recent years, indoor positioning system employing Bluetooth has attracted tremendous attention. However, it is investigated that its received channel information is significantly affected by hardware configuration and wireless environments, especially the received dataset of angle of arrival (AOA), which leads to inaccurate channel estimation and positioning. Further-more, AOA estimation at larger angle direction is severely influenced by the variant wireless environment and signal distortion, which has not been resolve in existing literature. In this paper, we propose an advanced I/Q density-based AOA estimation (IQDAE) to deal with the above-mentioned problem, which consists of two sub-schemes. We firstly employ the designed phase difference (PD) filter to convert I/Q signals to phase information and then select the candidate sets by eliminating outliers. Afterward, we conceive a PD density-based classification algorithm to estimate AOA. The experimental results show that the mean absolute error of proposed IQDAE algorithm is comparably smaller than that from the other schemes, including commercial solutions, especially at larger angles. The results indicate that we can effectively increase the service range for the Bluetooth positioning system by adopting the proposed algorithm.

This study analyzed the body composition of individuals with type 2 diabetes (T2DM). In this retrospective chart review study, body composition was measured through multifrequency bioelectrical impedance analysis (InBody 770). Body composition assessments were conducted in individuals with T2DM, who were aged ≥18 years. The parameters included body mass index (BMI), body fat mass (BFM), fat-free mass (FFM), visceral fat area, percent body fat (PBF), appendicular skeletal muscle mass (ASM), and skeletal muscle index (SMI). One-way ANOVA and independent t-tests were used to calculate differences in body composition distribution by age and sex. A total of 2404 participants were recruited. The prevalence of overall low muscle mass and sarcopenic obesity was 28.0% and 18.7%, respectively, which increased with age. The overall prevalence of obesity when PBF was used was 71.5%, which was higher than that when BMI was applied (32.4%). The normal BMI group exhibited a prevalence of low muscle mass of 55.6% and sarcopenic obesity of 34.8%. For both men and women, bodyweight, BFM, FFM, ASM, and SMI all decreased with age. The prevalence of low muscle mass and sarcopenic obesity was high in older adults and people with normal BMI. Using BMI to assess obesity and determine insufficient muscle mass underestimates the prevalence of obesity and neglects the problems of sarcopenia and high body fat in people with normal BMI.

Background This study was conducted to collect clinical safety, tolerability, and efficacy data with the use of everolimus (EVE) combined with exemestane (EXE) in patients with advanced breast cancer (ABC). Methods The EVEREXES trial initiated in 2012, provided early access to the first dual blockade treatment with EVE + EXE in patients with HR+, HER2 - ABC in Asia and other emerging growth countries. Postmenopausal women with HR+, HER2 - ABC who had documented recurrence or progression, following a nonsteroidal aromatase inhibitor therapy, were treated with EVE (10 mg/day) + EXE (25 mg/day) orally. Results A total of 235 patients received >= 1 dose of study medication. At the end of the study, all patients ceased the treatment. Disease progression (66.0%) was the primary reason of discontinuation. The most common AEs (>= 20%) were stomatitis, decreased appetite, hyperglycemia, rash, aspartate aminotransferase increased, anemia, alanine aminotransferase increased, cough, and fatigue. No new safety concerns were identified in the current study. Median progression-free survival (PFS) in the Asian subset was similar to that of the overall population (9.3 months in both groups). Confirmed overall response rate (ORR) was achieved for 19.6% of the patients. Efficacy of EVE + EXE across subgroups (prior CT, line of treatment, and presence of visceral metastases) was maintained. Conclusion The safety and efficacy results from EVEREXES trial are consistent to data previously reported in BOLERO-2. These results support that EVE + EXE could be a viable treatment option for the postmenopausal women with HR+, HER2 - ABC in Asian region., Novartis Pharma AG, Base, Switzerland; NovartisNovartis, The EVEREXES trial was funded by Novartis Pharma AG, Base, Switzerland. Funding for medical editorial support was also provided by Novartis.

We previously identified that the expression of chitinase-3-like protein 1 (CHI3L1) was upregulated during thyroid cancer progression. Here, we investigated the prognostic significance of CHI3L1 expression in thyroid neoplasms and examined the potential oncogenic roles. CHI3L1 immunochemical staining was performed on tissue microarrays of benign and malignant thyroid tumours. Compared with normal thyroid tissue and benign thyroid lesions that had low or no detectable CHI3L1 expression, CHI3L1 was overexpressed in both differentiated and undifferentiated thyroid cancer. High CHI3L1 expression was associated with extrathyroidal extension, lymph node metastasis, and shorter recurrence-free survival in differentiated thyroid cancer. The biological roles of CHI3L1 were further investigated by gain- and loss-of-function assays. CHI3L1 silencing suppressed clonogenicity, migration, invasion, anoikis resistance, and angiogenesis in thyroid cancer cells, although exogenous CHI3L1 treatment promoted these malignant phenotypes. Cysteine-rich angiogenic inducer 61 (CYR61) was identified as a downstream target of CHI3L1 by RNA-seq analysis. CYR61 silencing or treatment reversed the alterations induced by CHI3L1 modulation. Our results demonstrate that CHI3L1 is overexpressed in thyroid cancer and is associated with an increased risk of disease recurrence. Additionally, CYR61 may participate in CHI3L1-mediated tumour progression. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

This study experimentally investigated the influence of geometrical parameters on improved circulating inclined fluidized beds (ICIFB) for HVAC duct systems. The geometrical parameters include the inclined angle, base height of the regeneration bed, and particle channel height of the adsorbent bed. An optimal ICIFB system was developed based on the experimental results. Compared to the circulating erect fluidized bed system (CEFB) and the circulating inclined fluidized bed system (CIFB), the optimal ICIFB system could increase adsorption/desorption performance by 32.4% and 23.5%, respectively, under the same operating conditions. The optimal ICIFB system had the highest energy factor with up to 0.67 kg/kW h, which was 77.9% and 40.1% higher than the CEFB system and the CIFB system, respectively. The total adsorption was also measured for the optimal ICIFB system working nine hours per day (air volume = 850 cm3/h) under different monthly outside air conditions in Taiwan. The results showed that year-round total adsorption of 729.5 kg, which was 14.1% more than the CIFB system. The ICIFB system can combine with HVAC duct systems set up above the ceiling. Compared to conventional dehumidification systems, it saves space, has better dehumidification performance, and has a lower pressure drop, thus, it is suitable for residential air-conditioning systems.

A mixer-first receiver (RX) with enhanced selectivity and high dynamic range is proposed, targeting to remove surface acoustic-wave-filters in mobile phones and cover all frequency bands up to 6 GHz. Capacitive negative feedback across the baseband (BB) amplifier serves as a blocker bypassing path, while an extra capacitive positive feedback path offers further blocker rejection. This combination of feedback paths synthesizes a complex pole pair at the input of the BB amplifier, which is upconverted to the RF port to obtain steeper RF bandpass filter roll-off and reduced distortion. This paper explains the circuit principle and analyzes RX performance. A prototype chip fabricated in 45-nm partially depleted silicon on insulator (SOI) technology achieves high out-of-band linearity (input-referred third-order intercept point (IIP3) = 39 dBm and input-referred second-order intercept point (IIP2) = 88 dB) combined with sub-3-dB noise figure. Desensitization due to a 0-dBm blocker is only 2.2 dB at 1.4 GHz.

Background To describe an unusual case of traumatic globe luxation with optic chiasmal avulsion and review the existing literature on this rare condition for further discussion of mechanisms, diagnosis, and management. Methods Case report and review of existing case reports and case series identified through literature search. Results A 28-year-old woman, with no previous medical history, had left globe luxation and optic chiasm avulsion after being stabbed directly into the left orbit with the use of the stiletto high heel of a shoe. Automated visual field testing detected a temporal hemianopia in the unaffected eye despite normal central visual acuity. Chiasmal avulsion was demonstrated by MRI. Conclusions This case suggests that perimetry and MRI should always be considered in traumatic globe luxation to localize the site of injury. Temporal hemianopia in the fellow eye indicates a concomitant chiasmal injury.

The thermal performance of a building-integrated earth-air heat exchanger (EAHE) retrofitted with a supplementary water piping system has been analyzed. The EAHE system has no excavation cost by integrating with the building foundation and gets better cooling performance by flowing supplementary water from residential water well to the foundation-integrated water-based EAHE (FIWEAHE) system. The experimental and numerical investigation was conducted to analyze the air conditioning performance of the FIWEAHE system. The simulated bulk temperature and humidity ratio of outlet air were validated with the year-round experimental data. After mixing with the circulating water from the residential water well, the cooling capacity of the FIWEAHE system enhanced from 3.21 kW to 4.84 kW, and its moisture removal rate soared from 1.97 kg/h to 4.24 kg/h during summer operation. The outlet air temperature varying from 24 to 26 °C in summer and 20–21 °C in winter can meet the standard of indoor thermal comfort. The mean COP of the FIWEAHE system during summer and winter operation is calculated as 10.5 and 1.74, respectively. Relation curves among air velocity and energy-efficient design of pipe geometry were developed to be the future design guideline of the FIWEAHE system.

This study experimentally investigates the theoretical performance of the periodic total heat exchanger. The total heat exchanger has a double flow-circuit heat exchange function for periodic positive- and reverse-directional pumping. The operating period parameters are 2 minutes, 3 minutes, 4 minutes, 6 minutes, and 8 minutes. Under the temperature and humidity ratio differences, 10 °C and 4 g kg−1, the operating period of 3 min results in optimal performance of sensible heat effectiveness, latent heat effectiveness, and total heat effectiveness. This study also proposes the lumped system, with dimensionless analysis assumption applied to the whole, and solves it in a one-dimensional model involving the heat and mass transport equations. The dimensionless operating period dominates latent heat effectiveness, while the latent heat effectiveness decreases when the dimensionless operating period increases.

Manuring ground used for crop production is an important agricultural practice. Should antibiotic-resistant enteric bacteria carried in the manure be transferred to crops that are consumed raw, their consumption by humans or animals will represent a route of exposure to antibiotic resistance genes. Treatment of manures prior to land application is a potential management option to reduce the abundance of antibiotic resistance genes entrained with manure application. In this study, dairy manure that was untreated, anaerobically digested, mechanically dewatered or composted was applied to field plots that were then cropped to lettuce, carrots and radishes. The impact of treatment on manure composition, persistence of antibiotic resistance gene targets in soil following application, and distribution of antibiotic resistance genes and bacteria on vegetables at harvest was determined. Composted manure had the lowest abundance of antibiotic resistance gene targets compared to the other manures. There was no significant difference in the persistence characteristics of antibiotic resistance genes following land application of the various manures. Compared to unmanured soil, antibiotic resistance genes were detected more frequently in soil receiving raw or digested manure, whereas they were not in soil receiving composted manure. The present study suggests that vegetables grown in ground receiving raw or digested manure are at risk of contamination with manure-borne antibiotic resistant bacteria, whereas vegetables grown in ground receiving composted manure are less so.

Depression is a common bio-psycho-social problem in hemodialysis (HD) patients. Traditional Chinese medicine has been used for symptom management in patients with depression. Identification of the specific constitution in traditional Chinese medicine is critical for personalized care. However, the association between depression and specific constitution in HD patients is unknown.We conducted a cross-sectional study in all chronic HD patients (HD for more than 3 months) at China Medical University Hospital in Taiwan. The depression symptom severity was determined using the Beck Depression Inventory II (BDI-II). Clinical patterns in Chinese medicine were determined using the Constitution in Chinese Medicine Questionnaire. The association between constitution and depression was analyzed using logistic regression.We recruited 467 chronic hemodialysis patients, including 219 females and 248 males, with a mean age of 63±12years. The mean duration of HD was 5.8 years. The mean score for the BDI-II was 11 (interquartile range 8-14). The major constitution was Yang-deficiency (43.7%) among these chronic HD patients. Qi-deficiency was correlated with a duration of HD of more than 5.8 years (p=0.04). Qi-deficiency [odds ratio (OR): 4.05, 95% confidence interval (CI): 1.69-9.72, p0.01] was also associated with depression in logistic regression with adjustments for confounders, including calcium, phosphorus and hemoglobin levels.Qi-deficiency constitution in Chinese medicine is associated with depression in chronic HD patients. Further studies are needed to determine whether treating Qi-deficiency integrating Chinese medicine treatment can improve patients' depression symptoms.

Metaheuristics have recently been commonly used to solve complex problems in real applications. Some scholars used multiple populations in metaheuristic approaches to shorten the execution time in finding nearly optimal solutions. In this paper, we revisit the properties of sub-population execution for genetic algorithm (GA) and design a level-wise hierarchical sub-population architecture. We also make experiments for comparing the performance of the architecture for unimodal and multimodal functions. The experimental results show that using the hierarchical GA architecture produces a more significant improvement on multimodal functions than on unimodal ones.

Pituitary metastasis is an unusual event of cancer progression and breast cancer is the most common primary neoplasm metastasizing to the pituitary in the female population. Most patients who have developed pituitary metastasis were clinically asymptomatic. However, it is difficult to diagnose pituitary metastases due to the lack of specific symptomatology. We herein describe the presentation of one patient with symptomatic pituitary metastasis resulting from primary breast cancer. Subsequent to surgical intervention and loco-regional radiotherapy, the patient had a favorable outcome.

Importance Prospective assessment of treatments known to benefit patients in global clinical trials in specific racial groups is essential. Objective To compare the efficacy, safety, and tolerability of adding pertuzumab to trastuzumab and docetaxel vs placebo, trastuzumab, and docetaxel in Asian patients with ERBB2-positive early or locally advanced breast cancer. Design, Setting, and Participants This multicenter, double-blind, placebo-controlled phase 3 trial enrolled 329 women with ERBB2-positive early (T2-3, N0-1, M0) or locally advanced breast cancer (T2-3, N2 or N3, M0; T4, any N, M0) and primary tumor larger than 2 cm from March 14, 2016, to March 13, 2017. Analysis of the primary end point was performed on an intention-to-treat basis. Interventions Before surgery, patients received 4 cycles of intravenous pertuzumab (840-mg loading dose and 420-mg maintenance doses), trastuzumab (8-mg/kg loading dose and 6-mg/kg maintenance doses), and docetaxel (75 mg/m2) or intravenous placebo, trastuzumab, and docetaxel every 3 weeks. After surgery, patients received 3 cycles of intravenous fluorouracil, epirubicin, and cyclophosphamide followed by 13 cycles of the same intravenous anti-ERBB2 therapy (pertuzumab and trastuzumab or placebo and trastuzumab) for up to 1 year. Main Outcomes and Measures The primary end point was independent review committee–assessed total pathologic complete response rate. The 2-sided Cochran-Mantel-Haenszel test, stratified by disease category and hormone receptor status, was used to compare rates between treatment groups. Results In total, 329 female patients were randomized (pertuzumab, 219; and placebo, 110; mean [SD] age, 48.8 [9.5] years). In the intention-to-treat population, total pathologic complete response rates were 39.3% (86 of 219) in the pertuzumab group and 21.8% (24 of 110) in the placebo group (difference, 17.5% [95% CI, 6.9%-28.0%];P = .001). Of the most common grade 3 or higher adverse events, there was a higher incidence of neutropenia in the pertuzumab group (83 of 218 [38.1%] vs 36 of 110 [32.7%]). Serious adverse events were reported in 10.1% of patients (22 of 218) in the pertuzumab group and 8.2% of patients (9 of 110) in the placebo group. Conclusions and Relevance Treatment with pertuzumab, trastuzumab, and docetaxel resulted in a statistically significant improvement in the total pathologic complete response rate vs placebo, trastuzumab, and docetaxel for the neoadjuvant treatment of ERBB2-positive early or locally advanced breast cancer in Asian patients. Safety data were in line with the known pertuzumab safety profile and generally comparable between treatment groups. The PEONY trial adds to the totality of data showing the benefit of the pertuzumab regimen. Trial Registration ClinicalTrials.gov identifier:NCT02586025

This study focused on using the released heat from a heat pump as the heat source at 40–50 °C to regenerate a silica gel/polymer composite desiccant wheel and also on using the adsorb heat of the heat pump to dehumidify the processed air by condensing it and creating a high relative humidity condition, which helped to improve the performance of the composite desiccant wheel. The desiccant wheel was placed behind the evaporator to handle the second stage of dehumidification, achieving total dehumidification by 7 g kg −1 . A new composite desiccant made of 80% silica gel, 10% polyacrylic acid and 10% polyacrylic sodium (SG8PS1PA1) was chosen due to its high average adsorption rate and its low average temperature increase of outlet air. Composite desiccants can be made into any shape, so a low-pressure-drop composite desiccant wheel with air flow channels can be designed to reduce the power consumption of the system. Under the same conditions, a composite desiccant in a heat pump system exhibited an energy factor of 2.3 kg kW −1 h −1 , outperforming the silica-gel-based system by 130% and consuming less power than traditional dehumidification systems. Finally, the composite desiccant wheel-heat pump system was installed in a building and underwent long-term testing.

1082 Background: Our previous study ( Clin Cancer Res. 2015;21(8):1851) demonstrated that bevacizumab preconditioning followed by etoposide and cisplatin (BEEP) is a highly effective treatment for breast cancer (BC) patients (pts) with brain metastases (BM) progressing from WBRT. We conducted a randomized phase II study A-PLUS (NCT02185352) to test whether using BEEP as an induction therapy could enhance the efficacy of WBRT and provide systemic control. Methods: BC pts with measurable BM not suitable for surgery/radiosurgery and had not received WBRT were randomized (2:1) to experimental arm: induction BEEP for 3 cycles (~2 months [ms]) followed by WBRT or control arm: upfront WBRT. The BEEP regimen consists of bevacizumab 15 mg/kg on day 1, and etoposide 70 mg/m2/day on days 2-4, cisplatin 70 mg/m2 on day 2, followed by prophylaxis GCSF, every 21 days. After WBRT in both arms, pts received treatment of physician’s choice except BEEP until BM progression. Stratification was based on the Graded Prognostic Assessment score. Primary endpoint was brain-specific progression free survival (BS-PFS) based on RECIST 1.1, with a total of 108 pts, power of 0.8 at the 2-sided α level of 0.2. Results: Of 112 enrolled pts, 74 were in experimental arm and 38 in control arm. Baseline patient characteristics were generally balanced between arms. With median follow up of 28.7 ms, median BS-PFS was 8.1 vs. 6.5 ms ( p= 0.146; HR 0.71 [95% CI 0.44-1.13]), which met the primary endpoint (pre-defined α level of 0.2). Results of preplanned analysis included: 2-month brain-specific objective response rate of BEEP alone vs. WBRT was 41.9% vs. 52.6% ( p= 0.613); 8-month BS-PFS rate was 48.7% vs. 26.3% ( p= 0.027); median PFS was 6.4 vs. 4.7 ms ( p= 0.071; HR 0.67 [95% CI 0.43-1.04]), and extra-BM PFS was 7.9 vs. 5.0 ms ( p= 0.141; HR 0.71 [95% CI 0.46-1.12]). Median overall survival was 15.6 vs. 13.6 ms ( p= 0.855; HR 0.96 [95% CI 0.59-1.55]), with 31.6% of pts in control arm received BEEP regimen treatment after BM progression. The most common all-grade adverse events (AEs) in experimental arm were neutropenia (30.2%), nausea (27.9%), anemia (27.4%), and leukopenia (24.2%). Most AEs were mild to moderate in severity. Two pts discontinued BEEP treatment due to grade 4 nephrotoxicity and grade 3 infection, respectively. Conclusions: BEEP as induction treatment followed by WBRT for BC pts with BM may improve control of both BM and systemic disease. Further validation by a phase III study is necessary. Clinical trial information: NCT02185352 .

3560 Background: Numerous prospective studies, predominantly in Caucasian population, have proven the clinical utility of using multigene expression tests to prevent overtreatment in early breast cancer (EBC) patients. Since racial and ethnic disparities exist in genetic and biological factors that could influence the disease, the primary purpose of this study is to access the clinical utility of RecurIndex, a recurrence risk test, that is based on a genomic profiling derived from Asian women. Methods: A total of 298 patients with EBC, luminal subtype (85.6%), HER2 subtype (7.7%) and triple-negative subtype (6.7%), were enrolled in a retrospective study across Taiwan medical centers. Kaplan Meier and Cox Proportional Hazards model were used to, respectively, identify independent prognostic factors and calculate the survival rates. The prediction model was then tested using the area under the receiver operating characteristic curve (AUC). The primary endpoint was distant recurrence-free survival (DRFS). Results: The 10-year DRFS was significantly higher in the good-prognosis group than the poor-prognosis group (92.0% [95% CI, 86.1-98.2] versus 63.0% [95% CI, 49.9-79.5]) (Table). The overall hazard ratio for distant recurrence was 1.031 (95% CI, 1.017±1.046) per RI score increment. In addition, in a subset of 179 cases (60.1%), the model yielded an 82.3% correct classification rate for predicting DR with a sensitivity of 87.0%, a specificity of 68.6% and negative predictive values of 97.3%. Conclusions: The present study provides robust evidence of the clinical utility of RI-DR to predict clinical outcomes. RecurIndex could be used to determine the utility of chemotherapy in Asian patients, especially in hormone-receptor positive and HER2 negative disease, leading to a meaningful reduction in adjuvant chemotherapy recommendations. [Table: see text]

This study proposes a liquid desiccant dehumidification system combined with shallow geothermal energy. Calcium chloride solution is adopted as a desiccant that is sprayed directly on outdoor air for dehumidification purposes. Shallow geothermal energy is a clean renewable energy that is located beneath the ground surface approximately 3–50 m deep. In this study, the shallow geothermal energy water is utilized as a substitute for chilled water or cooling water. Shallow geothermal energy water, at about 20–22 °C, could precool outdoor air and cool the desiccant solution. Precooling outdoor air before it enters the dehumidifier can remove a sensible cooling load in advance and increase the performance of the dehumidifier. Moreover, the lower temperature solution is beneficial for enhancing sensible, latent, and total heat transfer rates. Based on the calculated results, under the same operating conditions, compared to the condensation system and the traditional liquid desiccant dehumidification system, the proposed system saves 86% and 82%, respectively, on power consumption. Result shows that a liquid desiccant dehumidification system integrated with shallow geothermal energy is an effective approach to enhance dehumidification performance and cooling capacity.

Smartphones play an essential role in our daily life. Connected to the internet, we can easily keep in touch with family and friends, even if far away, while ever more apps serve us in numerous ways. To support all of this, higher data rates are needed for ever more wireless users, leading to a very crowded radio frequency spectrum. To achieve high spectrum efficiency while reducing unwanted interference, high-quality band-pass filters are needed. Piezo-electrical Surface Acoustic Wave (SAW) filters are conventionally used for this purpose, but such filters need a dedicated design for each new band, are relatively bulky and also costly compared to integrated circuit chips. Instead, we would like to integrate the filters as part of the entire wireless transceiver with digital smartphone hardware on CMOS chips. The research described in this thesis targets this goal. It has recently been shown that N-path filters based on passive switched-RC circuits can realize high-quality band-select filters on CMOS chips, where the center frequency of the filter is widely tunable by the switching-frequency. As CMOS downscaling following Moore’s law brings us lower clock-switching power, lower switch on-resistance and more compact metal-to-metal capacitors, N-path filters look promising. This thesis targets SAW-less wireless receiver design, exploiting N-path filters. As SAW-filters are extremely linear and selective, it is very challenging to approximate this performance with CMOS N-path filters. The research in this thesis proposes and explores several techniques for extending the linearity and enhancing the selectivity of N-path switched-RC filters and mixers, and explores their application in CMOS receiver chip designs. First the state-of-the-art in N-path filters and mixer-first receivers is reviewed. The requirements on the main receiver path are examined in case SAW-filters are removed or replaced by wideband circulators. The feasibility of a SAW-less Frequency Division Duplex (FDD) radio receiver is explored, targeting extreme linearity and compression Irequirements. A bottom-plate mixing technique with switch sharing is proposed. It improves linearity by keeping both the gate-source and gate-drain voltage swing of the MOSFET-switches rather constant, while halving the switch resistance to reduce voltage swings. A new N-path switch-RC filter stage with floating capacitors and bottom-plate mixer-switches is proposed to achieve very high linearity and a second-order voltage-domain RF-bandpass filter around the LO frequency. Extra out-of-band (OOB) rejection is implemented combined with V-I conversion and zero-IF frequency down-conversion in a second cross-coupled switch-RC N-path stage. It offers a low-ohmic high-linearity current path for out-of-band interferers. A prototype chip fabricated in a 28 nm CMOS technology achieves an in-band IIP3 of +10 dBm , IIP2 of +42 dBm, out-of-band IIP3 of +44 dBm, IIP2 of +90 dBm and blocker 1-dB gain-compression point of +13 dBm for a blocker frequency offset of 80 MHz. At this offset frequency, the measured desensitization is only 0.6 dB for a 0-dBm blocker, and 3.5 dB for a 10-dBm blocker at 0.7 GHz operating frequency (i.e. 6 and 9 dB blocker noise figure). The chip consumes 38-96 mW for operating frequencies of 0.1-2 GHz and occupies an active area of 0.49 mm2. Next, targeting to cover all frequency bands up to 6 GHz and achieving a noise figure lower than 3 dB, a mixer-first receiver with enhanced selectivity and high dynamic range is proposed. Capacitive negative feedback across the baseband amplifier serves as a blocker bypassing path, while an extra capacitive positive feedback path offers further blocker rejection. This combination of feedback paths synthesizes a complex pole pair at the input of the baseband amplifier, which is up-converted to the RF port to obtain steeper RF-bandpass filter roll-off than the conventional up-converted real pole and reduced distortion. This thesis explains the circuit principle and analyzes receiver performance. A prototype chip fabricated in 45 nm Partially Depleted Silicon on Insulator (PDSOI) technology achieves high linearity (in-band IIP3 of +3 dBm, IIP2 of +56 dBm, out-of-band IIP3 = +39 dBm, IIP2 = +88 dB) combined with sub-3 dB noise figure. Desensitization due to a 0-dBm blocker is only 2.2 dB at 1.4 GHz operating frequency. IIFinally, to demonstrate the performance of the implemented blocker-tolerant receiver chip designs, a test setup with a real mobile phone is built to verify the sensitivity of the receiver chip for different practical blocking scenarios.

The clinical benefit of adding platinum to adjuvant chemotherapy for patients with triple-negative breast cancer (TNBC) has not been well investigated, although it was associated an improved response rate in neoadjuvant setting. We retrospectively analyzed the time to tumor progression (TTP) and overall survival (OS) of patients with resected stage I-III TNBC who were treated with or without cisplatin-containing chemotherapy (CisCT or noCisCT) during 2004 and 2010. Of 129 patients, 25 received CisCT. In univariate analysis, the mean TTP for CisCT and noCisCT was 4.42 and 5.88 years, respectively ( P = .004). The mean OS for CisCT and noCisCT was 6.76 and 9.63 years, respectively ( P = .24). After adjusting for other clinicopathologic factors, only clinical stage II/III disease was independently associated with worse OS. The adjusted hazard ratio for CisCT was 1.48 ( P = .46) and was not statistically significant. In this small retrospective study, adding cisplatin to adjuvant chemotherapy for early TNBC with unknown BRCA mutation status did not benefit OS.

Background Genetic data for traditional Taiwanese (Formosan) agriculture is essential for tracing the origins on the East Asian mainland of the Austronesian language family, whose homeland is generally placed in Taiwan. Three main models for the origins of the Taiwanese Neolithic have been proposed: origins in coastal north China (Shandong); in coastal central China (Yangtze Valley), and in coastal south China. A combination of linguistic and agricultural evidence helps resolve this controversial issue. Results We report on botanically informed linguistic fieldwork of the agricultural vocabulary of Formosan aborigines, which converges with earlier findings in archaeology, genetics and historical linguistics to assign a lesser role for rice than was earlier thought, and a more important one for the millets. We next present the results of an investigation of domestication genes in a collection of traditional rice landraces maintained by the Formosan aborigines over a hundred years ago. The genes controlling awn length, shattering, caryopsis color, plant and panicle shapes contain the same mutated sequences as modern rice varieties everywhere else in the world, arguing against an independent domestication in south China or Taiwan. Early and traditional Formosan agriculture was based on foxtail millet, broomcorn millet and rice. We trace this suite of cereals to northeastern China in the period 6000–5000 BCE and argue, following earlier proposals, that the precursors of the Austronesians, expanded south along the coast from Shandong after c. 5000 BCE to reach northwest Taiwan in the second half of the 4th millennium BCE. This expansion introduced to Taiwan a mixed farming, fishing and intertidal foraging subsistence strategy; domesticated foxtail millet, broomcorn millet and japonica rice; a belief in the sacredness of foxtail millet; ritual ablation of the upper incisors in adolescents of both sexes; domesticated dogs; and a technological package including inter alia houses, nautical technology, and loom weaving. Conclusion We suggest that the pre-Austronesians expanded south along the coast from that region after c. 5000 BCE to reach northwest Taiwan in the second half of the 4th millennium BCE. Electronic supplementary material The online version of this article (10.1186/s12284-018-0247-9) contains supplementary material, which is available to authorized users.

A mixer-first receiver enhanced with capacitive positive feedback is proposed to obtain a steeper filter roll-off and enhanced linearity, while keeping low noise figure. It covers all sub-6GHz cellular bands and achieves a high IIP3 of +39dBm and blocker 1dB gain compression point of +12dBm for a blocker frequency-offset of 80MHz at f LO =2GHz. The NF ranges from 2.4dB at f LO =1GHz to 5.4dB at f LO =6GHz. The chip has been fabricated in Globalfoundries 45nm SOI technology on a high resistivity substrate.

This Metaheuristics are easy to use and usually get good solutions for complex problems. There were many approaches proposed in improving the performance of the metaheuristics. In the past, we proposed a hierarchical execution architecture of GA to shorten the generation number needed to find final solutions. In this paper, we embed different migration mechanisms in the hierarchical sub- population architecture and compare their performance. Experiments are also made for verifying the effectiveness and efficiency of the proposed migration mechanisms. From the experimental results, it is found that the migration mechanism in the hierarchical sub- population architecture could improve solution quality.

Human 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1) plays a vital role in steroidogenesis in breast tumors and may therefore be a suitable target for treatment of breast cancer. This study investigated the role of HSD3B1 in the pathogenesis of breast cancer in clinical and experimental settings. Expression of HSD3B1 in primary tumors of 258 breast cancer patients was evaluated by immunohistochemistry. Screening of breast cancer cell lines indicated that triple-negative MDA-MB-231 cells expressed HSD3B1. The effects from genetic and pharmacologic inhibition of HSD3B1 were assessed in vitro and in vivo. The findings showed that 44% of the 258 breast cancers were HSD3B1-positive. The HSD3B1-positivity was associated with advanced-stage disease (p = 0.009) and reduced recurrence-free survival (p = 0.048) but not with tumor subtype or estrogen receptor status. Silencing of HSD3B1 or treatment with an HSD3B1 inhibitor (trilostane) reduced colony formation in breast cancer cells. Knockdown of HSD3B1 inhibited cell proliferation and migration. Analysis of a murine xenograft tumor model indicated that trilostane significantly slowed tumor growth. Expression of HSD3B1 in breast cancer is negatively associated with prognosis. The study found HSD3B1 to be a potential therapeutic target for breast cancer independent of estrogen receptor status.

LTE-advanced wireless receivers require high-linearity up-front filtering to prevent corruption of the in-band signals by strong out-of-band (OOB) signals and self-interference from the transmitter. SAW duplexer filters are generally used for this purpose, but supporting the plethora of existing and new bands becomes troublesome with separate filters for each band. In this paper we explore the possibility of combining an isolator with on-chip filtering. However, even with 15dB isolation, the on-chip filter needs to deal with up to +10dBm TX leakage and −15dBm OOB blocking, which requires an extremely high IIP3 around +50dBm and IIP2 around +90dBm. Recently inductorless tunable N-path-filter-based receivers achieved >10dBm compression point and good IIP3 of 20 to 30dBm. In order to further improve the receiver linearity to approach the extremely high IIP3 requirement for a SAW-less receiver, a high-linearity N-path bandpass/notch filter topology and receiver architecture are proposed in this paper.

With ever-increasing data in the field of medical imaging, the availability of robust methods for quantitative analysis in large-scale studies is the need of the hour. In recent times, there has been a significant increase in the use of deep learning, in particular of convolutional neural networks (CNNs), in the field of computer vision and image analysis. In contrast to traditional shallow classifiers, deep learning methods need less domain-specific feature engineering. The architecture can automatically learn hierarchies of relevant features from raw data. Despite the many success stories from computer vision, so far there are only rather few studies on deep learning in the field of medical imaging. In this chapter, we will look more closely at a specific application of CNNs, namely segmentation of normal brains from magnetic resonance images (MRI). We will characterize the types of errors from CNN-based segmentation and compare them with the errors from a model-based registration approach. The emphasis of this chapter is on comparing errors made by model-driven and data-driven approaches. In conclusion, we notice that the two methods make complementary errors. The CNN errors can be reduced by including more training data and by finding ways to incorporate the geometric information that registration-based algorithms rely on.

Objective Phyllodes tumors are composed of a benign epithelial component and a cellular spindle cell stroma that form a leaf-like structure. The purpose of this study was to define changes in patient characteristics, histopathologic parameters, and the outcome during two periods: before and after the introduction of core needle biopsy for preoperative diagnosis. Methods Records were reviewed of 170 patients with phyllodes tumors who were managed surgically. Patients treated from 1997 to 2004 (n = 101) were compared with patients treated from 2006 to 2013 (n = 69). Results The analysis of the two treatment periods revealed that the tumor size at diagnosis increased from 4.6 cm during the earlier period to 7.0 cm during the recent period (p

Triple-negative breast cancer (TNBC) is a highly heterogeneous and recurrent subtype of breast cancer that lacks an effective targeted therapy. To identify candidate therapeutic targets, we profiled global gene expression in TNBC and breast tumor-initiating cells with a patient survival dataset. Eight TNBC-related kinases were found to be overexpressed in TNBC cells with stem-like properties. Among them, expression of PKC-α, MET, and CDK6 correlated with poorer survival outcomes. In cases coexpressing two of these three kinases, survival rates were lower than in cases where only one of these kinases was expressed. In functional tests, two-drug combinations targeting these three kinases inhibited TNBC cell proliferation and tumorigenic potential in a cooperative manner. A combination of PKC-α-MET inhibitors also attenuated tumor growth in a cooperative manner in vivo. Our findings define three kinases critical for TNBC growth and offer a preclinical rationale for their candidacy as effective therapeutic targets in treating TNBC. Cancer Res; 74(17); 4822–35. ©2014 AACR.

Previous studies have typically indicated that only one composition factor, such as wick structures or working fluids, affects the thermal resistance or critical heat flux of heat pipes. In this study, the composition factors influencing thermal performance, such as wick structures, working fluids, the modulation fields of working fluids, and combinations of these factors, were thoroughly investigated. The evaluated materials comprised microgrooved, sintered, and wickless heat pipes; magnetic nanofluids exhibiting volumetric fractions (vol.) of 0.16%–3.20%; and deionized water. A strong magnetic field of 200 Oe was applied. The results indicated that combining grooved heat pipes and a 0.80% vol. of magnetic nanofluids or sintered heat pipes and a 0.16% vol. of magnetic nanofluids yielded the optimal promotions: the thermal resistance was reduced by approximately 80% and the critical heat flux was enhanced 2.7-fold compared with general wickless heat pipes filled with deionized water. These findings should serve as a valuable reference when designing heat pipe exchangers for use in air-conditioning systems.

Previous studies have shown that local anesthetics may induce apoptosis in some cell types. In this study, we investigated the apoptotic effects of local anesthetics in human breast tumor cells.Human breast cancer (MCF-7) and mammary epithelial (MCF-10A) cell lines were treated with lidocaine and/or bupivacaine. Cell viability, DNA fragmentation, and annexin V immunofluorescence staining were assessed. The effects on apoptosis-related protein expression were investigated by Western blot analysis. The findings were extended to studies in an in vivo xenograft model.Treatment of breast tumor cells with lidocaine and bupivacaine resulted in inhibition of cell viability via induction of apoptosis. The effects were more prominent in MCF-7 cells than in MCF-10A cells. Treatment with local anesthetics induced caspase 7, 8, 9, and poly ADP-ribose polymerase cleavage. The cleavage of caspase 7 and poly ADP-ribose polymerase induced by local anesthetics were effectively blocked by caspase inhibitors. Furthermore, treatment of MCF-7 xenografts with local anesthetics resulted in higher expression of cleaved caspase 7 and an increase in terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining.Lidocaine and bupivacaine induce apoptosis of breast tumor cells at clinically relevant concentrations. Our results reveal previously unrecognized beneficial actions of local anesthetics and call for further studies to assess the oncologic advantages of their use during breast cancer surgery.

Purpose Cancer cells develop acquired resistance induced by chemotherapeutic drugs. In this study, we investigated the effects of brief treatment with cytotoxic drugs on the phenotype of breast cancer cells. Methods Breast cancer cells MCF7 and BT-474 were briefly treated with paclitaxel or doxorubicin. Clonogenic, migration, and invasion assays were performed on the treated cells. Western blot analysis and RhoA activity assay were also performed. Results Breast cancer cells when briefly treated with paclitaxel or doxorubicin showed reduced clonogenic ability. Doxorubicin, but not paclitaxel, augmented cell migration and invasion. The invasion-promoting effects of doxorubicin were lost when the two drugs were sequentially used in combination. Myosin light chain (MLC) 2 phosphorylation and RhoA activity were upregulated by doxorubicin and downregulated by paclitaxel. Pretreatment with RhoA inhibitors abolished the migration- and invasion-promoting effects of doxorubicin. Conclusion Doxorubicin activates the RhoA/MLC pathway and enhances breast cancer cell migration and invasion. Therefore, this pathway might be explored as a therapeutic target to suppress anthracycline-enhanced tumor progression.

This study applied powder-tracing techniques to mount Cu and W powders on A6061-T6 aluminum sheets to investigate the material flow mechanism of friction stir spot welding (FSSW) using various geometric tools. The experimental results showed that the geometry of the tools plays a crucial role and determines the entrances of material flow during FSSW. It was believed that instantaneous voids were filled up with material flow in all directions for triangular pins, and the voids were located at the pin bottom for cylindrical pins. In accordance with the plastic rule of material flow, the pressure gradient is the necessary condition to cause material flow during FSSW; therefore, the transient constraint space (TCS) is required to generate pressure in this space. Enlargement of the TCS accompanies the evolution of the stir zone (SZ). A generated void causes a steep pressure gradient, which is regarded as the entrance of material flow. A tool with screw threads causes downward driving force, which determines the intermixing behavior between the upper and lower sheets, and also affects the size of the SZs.

In this paper, the new 4-moduli set {22n, 22n+1-1, 2n+1, 2n-1} with 6n-bit DR, which is appropriate for RNS applications. An efficient algorithm for residue-to-binary conver­sion is derived based on New Chinese remainder theorem II (New CRT-II). Next, the converter hardware is also designed to achieve average 36.6% performance saving in terms of the Area× Delay when comparing with the latest converter with 4-moduli set under the same DR require­ment.

Sewage sludge recovered from wastewater treatment plants contains antibiotic residues and is rich in antibiotic resistance genes, selected for and enriched in the digestive tracts of human using antibiotics. The use of sewage sludge as a crop fertilizer constitutes a potential route of human exposure to antibiotic resistance genes through consumption of contaminated crops. Several gene targets associated with antibiotic resistance (catA1, catB3, ereA, ereB, erm(B), str(A), str(B), qnrD, sul1, and mphA), mobile genetic elements (int1, mobA, IncW repA, IncP1 groups -α, -β, -δ, -γ, -ε), and bacterial 16S rRNA (rrnS) were quantified by qPCR from soil and vegetable samples obtained from unamended and sludge-amended plots at an experimental field in London, Ontario. The qPCR data reveals an increase in abundance of gene targets in the soil and vegetables samples, indicating that there is potential for additional crop exposure to antibiotic resistance genes carried within sewage sludge following field application. It is therefore advisable to allow an appropriate delay period before harvesting of vegetables for human consumption.

Liver kinase B1 (LKB1) is a tumor suppressor, and its loss might lead to activation of the mammalian target of rapamycin (mTOR) and tumorigenesis. This study aimed to determine the clinical relevance of LKB1 gene and protein expression in breast cancer patients. LKB1 protein expression was evaluated using immunohistochemistry in tumors from early breast cancer patients in two Taiwanese medical centers. Data on LKB1 gene expression were obtained from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) data set. The correlations between LKB1 expression, clinicopathologic factors, and patient outcome were analyzed. LKB1 expression was significantly associated with estrogen receptor (ER) expression in 2 of the 4 cohorts, but not with other clinicopathologic factors. LKB1 expression was not a predictor for relapse-free survival, overall survival (OS), or breast cancer-specific survival. In a subgroup analysis of the two Taiwanese cohorts, high LKB1 protein expression was predictive of high OS in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients (P = 0.013). Our study results indicate that LKB1 expression is not prognostic in the whole population of breast cancer patients, but it is a potential predictor of OS in the subset of HER2-positive patients

The effects of tool geometry on the microstructure and tensile shear strength of friction stir spot-welded A6061-T6 Al alloy sheets were investigated in the present study. Friction stir spot welding (FSSW) was carried out at a tool speed of 2500 rpm, plunging rate of 1 mm/s, and dwell time of 3 s. Four types of tools with the same shoulder shape and size, but different pin profiles (threaded cylindrical, smooth cylindrical, threaded triangular, and smooth triangular) were used to carry out FSSW. The mechanical and metallurgical properties of the FSSW specimens were characterized to evaluate the performance of the different tools. Experimental results show that the pin profile significantly alters the hook geometry, which in turn affects the tensile shear strength of the friction stir spot welds. The welds made using the conventional thread cylindrical tool have the largest elongation and yield the highest tensile strength (4.78 kN). The welds made using the smooth cylindrical tool have the lowest tensile strength. The welds made using the threaded triangular and smooth triangular tools both have a tensile-shear load of about 4 KN; however, the welds made using the threaded triangular tool have a better elongation than those made using the smooth triangular tool.

Background and Objectives Inflammation has been implicated in the initiation and progression of thyroid cancer. Neutrophil-to-lymphocyte ratio (NLR) is a simple index of systemic inflammatory response, and has been shown to be a prognostic indicator in some types of cancer. The aim of this study was to examine the relationship between NLR and clinicopathological features in patients with differentiated thyroid cancer. Methods Total white blood cell and differential counts of 159 patients with differentiated thyroid cancer were compared to those of 318 age- and sex-matched controls undergoing thyroidectomy for benign thyroid nodules. Clinicopathological variables, stratified by NLR tertiles, were analyzed. Results There was no difference in NLR between patients having benign and malignant thyroid nodules (P = 0.293). Cancer patients in the higher NLR tertile had significantly larger tumor size (P = 0.004). Higher NLR was observed in patients with high American Thyroid Association (ATA) risk of recurrence. Conclusions High preoperative NLR was associated with increased tumor size and high ATA risk of recurrence in patients with differentiated thyroid cancer. J. Surg. Oncol. 2013;107:493–497. © 2012 Wiley Periodicals, Inc.

Epidemiological studies suggest an important link between obesity and thyroid cancer. The adipose tissue-derived polypeptide leptin acting via leptin receptor may modulate cell migration of thyroid cancer cells. Previously we have demonstrated that leptin receptor is overexpressed in papillary thyroid cancer and is associated with tumor aggressiveness. The present study was undertaken to explore the possible regulatory factors which would influence leptin receptor expression in papillary thyroid cancer cells. We found that DNA methyltransferase inhibitor (5-Aza-2'-deoxycytidine) and histone deacetylase inhibitor (trichostatin A) reduced leptin receptor expression. Conversely, insulin upregulated leptin receptor expression in a time- and dose-dependent manner. Hypoxia-mimicking agent (cobalt chloride) had no effect on leptin receptor expression. Taken together, our study provides evidence that epigenetic events and insulin stimulation take part in regulation of leptin receptor expression in papillary thyroid cancer cells.

Obesity is associated with a higher incidence of thyroid cancer. Adiponectin is one of the most abundant adipokines with a pleiotropic role in metabolism and in the development and progression of cancer. It has been shown that circulating adiponectin level is inversely associated with the risk of thyroid cancer. This study aimed to investigate the possible association between the expression of adiponectin receptors (AdipoR1 and AdipoR2) and clinicopathological variables in papillary thyroid cancer. We found that protein levels of AdipoR1 and AdipoR2 were increased in some thyroid cancer specimens compared with adjacent normal thyroid tissues. Thyroid cancer cells expressed AdipoR1 and AdipoR2, which were attenuated by histone deacetylase inhibitors valproic acid and trichostatin A. Adiponectin stimulated AMP-activated protein kinase phosphorylation in thyroid cancer cells. We further determined the expression of AdipoR1 and AdipoR2 by immunohistochemical staining in primary tumor samples and metastatic lymph nodes. AdipoR1 was expressed in 27 % of primary tumors and AdipoR2 in 47 %. Negative expression of both adiponectin receptors was significantly associated with extrathyroidal invasion, multicentricity, and higher TNM stage. There was a trend toward decreased disease-free survival in patients with negative tumor expression of AdipoR1 and AdipoR2 (log-rank P = 0.051). Collectively, overexpression of adiponectin receptors was observed in some tumor tissues of papillary thyroid cancer and was associated with a better prognosis.