Search

Purpose Despite curative resection, the 5-year survival for patients with resectable pancreatic cancer is less than 20%. Recurrence occurs both locally and at distant sites and effective multimodality adjuvant treatment is needed.Materials and Methods Patients with curatively resected stage IB-IIB pancreatic adenocarcinoma were eligible. Treatment consisted of chemotherapy with gemcitabine 1,000 mg/m2 on days 1 and 8 and cisplatin 60 mg/m2 on day 1 every 3 weeks for two cycles, followed by chemoradiotherapy (50.4 Gy/28 fx) with weekly gemcitabine (300 mg/m2/wk), and then gemcitabine 1,000 mg/m2 on days 1 and 8 every 3 weeks for four cycles. The primary endpoint was 1-year disease-free survival rate. The secondary endpoints were disease-free survival, overall survival, and safety.Results Seventy-four patients were enrolled. One-year disease-free survival rate was 57.9%. Median disease-free and overall survival were 15.0 months (95% confidence interval [CI], 11.6 to 18.4) and 33.0 months (95% CI, 21.8 to 44.2), respectively. At the median follow-up of 32 months, 57 patients (77.0%) had recurrence including 11 patients whose recurrence was during the adjuvant treatment. Most of the recurrences were systemic (52 patients). Stage at the time of diagnosis (70.0% in IIA, 51.2% in IIB, p=0.006) were significantly related with 1-year disease-free survival rate. Toxicities were generally tolerable, with 53 events of grade 3 or 4 hematologic toxicity and four patients with febrile neutropenia.Conclusion Adjuvant gemcitabine and cisplatin chemotherapy followed by chemoradiotherapy with gemcitabine and maintenance gemcitabine showed efficacy and good tolerability in curatively resected pancreatic cancer.

Background/aim We aimed to investigate the role of radiogenomic and deep learning approaches in predicting the KRAS mutation status of a tumor using radiotherapy planning computed tomography (CT) images in patients with locally advanced rectal cancer. Patients and methods After surgical resection, 30 (27.3%) of 110 patients were found to carry a KRAS mutation. For the radiogenomic model, a total of 378 texture features were extracted from the boost clinical target volume (CTV) in the radiotherapy planning CT images. For the deep learning model, we constructed a simple deep learning network that received a three-dimensional input from the CTV. Results The predictive ability of the radiogenomic score model revealed an AUC of 0.73 for KRAS mutation, whereas the deep learning model demonstrated worse performance, with an AUC of 0.63. Conclusion The radiogenomic score model was a more feasible approach to predict KRAS status than the deep learning model.

Highlights • Gastrointestinal symptoms including diarrhea and constipation are common in patients with gynecologic cancer receiving pelvic chemoradiotherapy. • There was an increase of serum IL-6 levels in patients with ≥grade 2 diarrhea during pelvic chemoradiotherapy. • Serum IL-1β and TNFα levels did not change during pelvic chemoradiotherapy. • Radiotherapy-related and clinical factors affect the development of chemoradiotherapy-induced diarrhea., Purpose We investigated whether serum cytokines including Interleukin (IL)-1β, IL-6 and tumor necrosis factor alpha (TNFα) are increased during pelvic chemoradiotherapy (CRT) in patients with gynecologic malignancies, and sought to identify prognostic factors for the development of diarrhea during pelvic CRT. Materials and methods Patients with cervical or endometrial cancer receiving postoperative pelvic CRT were eligible for this prospective study. Patients were evaluated weekly during CRT for symptoms, including diarrhea and constipation. Serum cytokine levels were measured using immunoassays 1 week before CRT, and at week 3 and 5–6 during CRT. Radiotherapy-related parameters such as mean dose, minimum dose, and maximum dose to the small bowel were also analyzed. Multivariate logistic regression analysis was used to assess factors associated with development of enteritis symptoms. Results Twenty-six patients were enrolled, all of whom were eligible for symptom and dosimetric parameter evaluation; 24 were eligible for cytokine level measurement. Cytokine levels did not differ between patients with and without diarrhea before CRT. IL-6 levels increased during CRT, and were significantly higher in patients with diarrhea ≥grade 2 than in those with grade 0–1 at week 5–6 (6.771 ± 2.657 pg/mL vs. 3.396 ± 0.499 pg/mL, p = 0.046). Serum IL-1β and TNFα levels did not change during CRT. Diarrhea before CRT and the maximum dose to the small bowel were independent prognostic factors for CRT-induced diarrhea in the multivariate analysis. Conclusions There was an increase of serum IL-6 levels in patients with ≥grade 2 diarrhea during pelvic CRT. Serum IL-1β and TNFα levels did not change during CRT. Radiotherapy-related and clinical factors affect the development of diarrhea during pelvic CRT.

Summary Background Laparoscopic surgery has been widely used for rectal cancer; however, its long-term outcomes remain controversial. This study aimed to assess the long-term oncological safety of laparoscopic surgery for rectal cancer using 10-year follow-up data of the Comparison of Open versus laparoscopic surgery for mid or low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) trial. Methods The COREAN trial is a, open-label, non-inferiority, randomised controlled trial. Eligible participants were aged 18–80 years, had cT3N0–2M0 middle or low rectal cancer with lesions located within 9 cm of the anal verge, and had been treated with preoperative chemoradiotherapy. Patients were randomly assigned (1:1) to open or laparoscopic surgery with a computer-generated random allocation sequence with a random permuted block design. Neither patients nor clinicians were masked to treatment assignment. Open or laparoscopic total mesorectal excision was done 6–8 weeks after the administration of preoperative concurrent chemoradiotherapy (fluoropyrimidines alone, doublet therapy, or triplet therapy) at a dose of 50·5 Gy over 5·5 weeks. Postoperative adjuvant chemotherapy was administered for 4 months. The primary endpoint of 3-year disease-free survival was published previously. Here, we report 10-year overall survival, disease-free survival, and local recurrence. Analyses were done in the modified intention-to-treat population of all participants who were randomly assigned and provided follow-up data. This study is registered with ClinicalTrials.gov, NCT00470951. Findings Of the 340 patients enrolled in the COREAN trial between April 4, 2006, and Aug 26, 2009 (170 patients in each group), two patients in the laparoscopic surgery group moved abroad and were lost to follow-up, so were not included in this 10-year analysis. The median duration of follow-up was 143 months (IQR 122–156). No differences were observed in 10-year overall survival (74·1% [95% CI 66·8–80·0] in the open surgery group vs 76·8% [69·6–82·5] in the laparoscopic surgery group; p=0·44), 10-year disease-free survival (59·3% [51·1–66·5] vs 64·3% [56·0–71·5]; p=0·20), or 10-year local recurrence (8·9% [5·2–15·0] vs 3·4% [1·4–7·9]; p=0·050) between the open surgery and laparoscopic surgery groups at 10 years after surgery. The stratified hazard ratios, adjusted for ypT and ypN classification and tumour regression grade, for open surgery versus laparoscopic surgery were 0·94 (95% CI 0·63–1·43) for overall survival, 1·05 (0·74–1·49) for disease-free survival, and 2·22 (0·78–6·34) for local recurrence. Interpretation The 10-year follow-up of the COREAN trial confirms the long-term oncological safety of laparoscopic surgery in patients with rectal cancer treated with preoperative chemoradiotherapy. Similar to open surgery, laparoscopic surgery does not compromise long-term survival outcomes in rectal cancer when performed by well trained surgeons. Funding National Cancer Center, Goyang, South Korea.

Purpose In radiotherapy for head and neck cancer, it is crucial to define the appropriate treatment volume to determine treatment outcome and toxicity. We examined the feasibility of omitting elective high retropharyngeal lymph node (RPLN) irradiation in patients with oropharyngeal cancer. Materials and Methods We performed a retrospective review of 189 patients with oropharyngeal squamous cell carcinoma who were treated with definitive or postoperative radiation therapy between 2009 and 2016. Of them, 144 (76.2%) underwent ipsilateral RPLN irradiation up to the superior border of the C1 vertebral body, while the other 45 (23.8%) were irradiated up to the transverse process of the C1 vertebra. High RPLN-treated and spared group were propensity matched based on key clinical variables. Results During the follow-up period, only three patients (one in the high RPLN-treated group and two in the high RPLN-spared group) developed RPLN recurrence. There were no significant between-group differences in 5-year locoregional failure-free survival (82.8% vs. 90.6%; p = 0.14), distant metastasis-free survival (93.1% vs. 93.3%; p = 0.98) and RPLN failure-free survival (99.3% vs. 95.0%; p = 0.09). In the matched groups, high RPLN-spared patients received a lower mean ipsilateral parotid gland dose (mean, 20.8 Gy vs. 29.9 Gy; p < 0.001) and had a lower incidence of chronic xerostomia (grade 0, 43.5% vs. 13.0%; p = 0.023) at 1 year after radiotherapy compared with high RPLN-treated patients. Conclusion Omission of ipsilateral high RPLN irradiation seems safe, and reduces the incidence of chronic xerostomia in patients with oropharyngeal squamous cell carcinoma.

Background/aim To develop a nomogram for predicting the pathological tumor response to preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer based on pre-treatment magnetic resonance imaging (MRI) and blood test characteristics. Patients and methods This retrospective study included 514 patients who underwent MRI and received preoperative CRT followed by surgical resection. Pathological tumor response was assessed as good [Dworak tumor regression grade (TRG) 3 or 4] or poor (TRG 0-2). A nomogram for good response was developed using stepwise logistic regression analysis. Results A nomogram based on longitudinal tumor diameter, extramural tumor invasion depth, carcinoembryonic antigen and hemoglobin levels, age, and interval between CRT and surgery gave an area under the receiver operating characteristic curve for a good response of 0.721 (95%CI=0.676-0.768). Conclusion Our nomogram based on pre-treatment clinical characteristics can predict the tumor response to CRT, which may help identify patients who can benefit most from CRT.

Background/aim This study aimed to analyze the correlation between microsatellite instability (MSI) and inflammatory markers during neoadjuvant CRT in rectal cancer and its influence on prognosis. Patients and methods A total of 549 patients with locally advanced rectal cancer underwent neoadjuvant CRT. Complete blood counts before CRT, and 4-8 weeks after CRT were used to measure neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Results MSI was significantly associated with elevated NLR and PLR after CRT as well as with a change in NLR and PLR during CRT. Neither inflammatory markers nor MSI significantly related to survival. However, in patients with MSI, an increase in NLR and PLR before CRT was significantly correlated with poor overall survival and disease-free survival. Conclusion There is correlation between inflammatory markers and MSI during CRT and it influences prognosis. Therefore, inflammatory markers might have a role in assessing the microenvironment related to MSI and the immunologic response in rectal cancer.

// Jae-Sung Kim 1 , 2 , Daeun Lee 1 , Donggyu Kim 1 , Seok-Jun Mun 1 , 2 , Euni Cho 1 , 2 , Wooic Son 1 and Chul-Su Yang 1 , 2 1 Department of Molecular and Life Science, Hanyang University, Ansan 15588, S. Korea 2 Department of Bionano Technology, Hanyang University, Seoul 04673, S. Korea Correspondence to: Chul-Su Yang, email: chulsuyang@hanyang.ac.kr Keywords: Toxoplasma gondii GRA8 peptide; mitochondria; tumor-targeting; metabolism Received: October 17, 2019 Accepted: December 19, 2019 Published: January 07, 2020 ABSTRACT Targeted tumor and efficient, specific biological drug delivery in vivo has been one of the main challenges in protein-based cancer-targeted therapies. Mitochondria are potential therapeutic targets for various anti-cancer drugs. We have previously reported that protein kinase Cα-mediated phosphorylation of Toxoplasma gondii GRA8 is required for mitochondrial trafficking and regulating the interaction of the C-terminal of GRA8 with ATP5A1/SIRT3 in mitochondria. Furthermore, SIRT3 facilitates ATP5A1 deacetylation, mitochondrial activation, and subsequent antiseptic activity in vivo . Herein we developed a recombinant acidity-triggered rational membrane (ATRAM)-conjugated multifunctional GRA8 peptide (rATRAM-G8-M/AS) comprising ATRAM as the cancer-targeting cell-penetrating peptide, and essential/minimal residues for mitochondrial targeting or ATP5A1/SIRT3 binding. This peptide construct showed considerably improved potency about cancer cell death via mitochondria activity and biogenesis compared with rGRA8 alone in HCT116 human carcinoma cells, reaching an IC 50 value of up to 200-fold lower in vitro and 500-fold lower in vivo . Notably, rATRAM-G8-M/AS treatment showed significant therapeutic effects in a mouse xenograft model through mitochondrial metabolic resuscitation, and it produced negligible immunogenicity and immune responses in vivo . Thus, these results demonstrate that rATRAM-G8-M/AS represents a useful therapeutic strategy against tumors, particularly colon cancer. This strategy represents an urgently needed paradigm shift for therapeutic intervention.

Although replacing biomass, (e.g., wood chips and pellets), with thinning wood and herbaceous biomass is eco-friendly and economically advantageous, their direct utilization in plant boilers is associated with ash-related challenges, including slagging and fouling. The aim of this study is to determine the effects of ash removal treatment (ashless biomass (ALB)) in the context of solid fuel power plant boilers. Ash was removed via neutralization of metal ions and carboxylic acids contained in the biomass ash. The ash removal rate of K, Na, Cl was indicated by assessing the total biomass before and after ash removal treatment, via XRF analysis. Co-combustion with sub-bituminous coal and ALB-treated biomass was analyzed using a drop tube furnace and revealed that NOx and SOx values converged converge toward an approximate 10 ppm error, whereas the Unburned Carbon (UBC) data did not exhibit a specific trend. Factors associated with slagging and fouling, (capture efficiency (CE), and energy based growth rate (GRE)) were calculated. All biomass samples without pretreatment exhibited V-shaped variation. Conversely, for ashless biomass (ALB) samples, CE and GRE gradually decreased. Thus, the ALB technique may minimize slagging and fouling in a boiler, thus, reducing internal corrosion associated with ash deposition and enhancing the economic operation of boilers.

Background The purpose of this study was to analyze the treatment efficacy and safety of stereotactic ablative body radiotherapy (SABR) boost for cervical cancer patients not amenable to brachytherapy. Methods A retrospective review of the medical records from single institution of 25 eligible patients was performed. The patients underwent pelvic radiotherapy (RT) in 25 or 28 fractions with a median dose of 45 Gy (range 44–50.4 Gy). SABR boost was delivered after pelvic RT, with a median dose of 25 Gy (range 20–33 Gy), and a median fraction number of 5 (range 4–6). 21 patients with a follow-up period of more than one year were included in the toxicity analysis, and hematuria and hematochezia that occurred later than 3 months after the RT were graded. Results The median follow-up period after radiotherapy was 2.85 years (range 0.33–6.60). The 3-year local control, locoregional control, disease-free survival, and overall survival rates were 80.9%, 75.8%, 40.9%, and 77.1%, respectively. 5 patients experienced grade 3 toxicity (3 genitourinary, 3 gastrointestinal), and no grade 4–5 toxicity was reported. Univariate analysis showed that cumulative D2cc in equivalent dose in 2 Gy fractions (EQD2) of rectum was marginally predictive for any grade of hematochezia (P = 0.051). Cumulative D2cc EQD2 of bladder was not predictive for hematuria. In the receiver operating characteristic (ROC) curve analysis, the optimal threshold of cumulative rectal D2cc EQD2 was 81.2 Gy for any grade of hematochezia. Conclusion SABR boost for cervical cancer was effective and tolerable. Although it cannot substitute brachytherapy, it can be a treatment option when brachytherapy is not possible.

This paper describes a fully integrated 8-channel front-end module (FEM) single chip IC fabricated with 45-nm RFSOI CMOS process technology for 5G mm-Wave application supporting n257/258/261 triple bands. Its silicon area is 4.29mm × 2.76mm which is comprised of high efficiency Doherty topology power amplifier, low noise amplifier, T/Rx switch, MIPI interface controller and so on. To address module assembly area limitation on the mm-wave antenna PCB, an ultra-thin Embedded Die Substrate (EDS) package is adopted and realizes virtually Zero-space integrate the FEM die in the middle of PCB. The average output power of the Tx is 17dBm with 22% PAE at 5.9% EVM and Rx NF is 3.4dB at the 27GHz.

Purpose: This nationwide multi-institutional study analyzed the patterns of care and outcomes of external beam radiotherapy (EBRT) in localized prostate cancer patients. We compared various risk classification tools and assessed the need for refinements in current radiotherapy (RT) schemes. Methods and Materials: We included non-metastatic prostate cancer patients treated with primary EBRT from 2001 to 2015 in this study. Data of 1573 patients from 17 institutions were analyzed and re-grouped using a risk stratification tool with the highest predictive power for biochemical failure-free survival (BCFFS). We evaluated BCFFS, overall survival (OS), and toxicity rates. Results: With a median follow-up of 75 months, 5- and 10-year BCFFS rates were 82% and 60%, and 5- and 10-year OS rates were 95% and 83%, respectively. NCCN risk classification revealed the highest predictive power (AUC = 0.556, 95% CI 0.524–0.588, p &lt, 0.001). Gleason score, iPSA &lt, 12 ng/mL, intensity-modulated RT (IMRT), and ≥179 Gy1.5 (EQD2, 77 Gy) were independently significant for BCFFS (all p &lt, 0.05). IMRT and ≥179 Gy1.5 were significant factors in the high-risk group, whereas ≥170 Gy1.5 (EQD2, 72 Gy) was significant in the intermediate-risk group and no significant impact of dose was observed in the low-risk group. Both BCFFS and OS improved significantly when ≥179 Gy1.5 was delivered using IMRT and hypofractionation in the high-risk group without increasing toxicities. Conclusions: With NCCN risk classification, dose escalation with modern high-precision techniques might increase survivals in the high-risk group, but not in the low-risk group, although mature results of prospective studies are awaited.

The purpose of this study is to investigate the possibility of interchanging patients on beam-matched linear accelerators (linacs), by evaluating the dosimetric variation and the dose delivery accuracy of volumetric modulated arc therapy (VMAT). Two VitalBeam linacs installed recently in our center were included in this study. For dosimetric data comparison, beam data, such as percentage depth doses (PDDs), beam profiles, output factors, multi-leaf collimator (MLC) leaf transmission factors, and the dosimetric leaf gap (DLG), for 6-MV and 10-MV beams were measured on both linacs. Sixty patients (20 head and neck, 20 lung, and 20 prostate cancers) were selected to evaluate the dosimetric parameters and the delivery accuracy of the VMAT plans created for various treatment sites. All the VMAT plans were generated using the Eclipse treatment planning system (TPS) with the same optimizer algorithm. The dose differences between two beam-matched linacs for planning target volumes (PTVs) and organs at risk (OARs) were recorded and analyzed. Patient-specific dosimetric quality assurance (DQA) using the Electronic Portal Image Device (EPID) were performed, and the measured planar doses were compared with those calculated by using the TPS though absolute dose gamma evaluation using 2%/2 mm and 2%/3 mm criteria. The differences in all dosimetric beam data between the two beam-matched linacs were all within 1% for the 6-MV and the 10-MV beams. For all 60 cases of three treatment sites, no notable differences were observed in the dosimetric comparison and the DVH variation between the beam-matched linacs. The average differences in dosimetric parameters of PTV and OARs were all within 1%. Furthermore, all passing rates of measured doses on the beam-matched linacs were higher than 93% and 97% for the 2%/2 mm and the 2%/3 mm criteria, respectively. Our overall dosimetric variation in beam data and VMAT plans remains within the tolerance of clinical acceptability. Pretreatment verification results were also clinically acceptable, showing good agreement with the calculated doses. Therefore, this study demonstrated the possibility of swapping patients in a VMAT plan without any modification and re-planning between two beam-matched linacs.

Estradiol is a key factor for tumorigenesis and prognosis of hormone receptor-positive breast cancer. Adipocytes are one source of estradiol in patients with breast cancer. Recent studies have shown that phosphorylated ribosomal protein S6 kinase-1 plays a critical role in adipogenesis. Therefore, estrogen depletion therapy might have beneficial effects in phosphorylated ribosomal protein S6 kinase-1-positive breast cancer. This study was conducted to evaluate the value of phosphorylated ribosomal protein S6 kinase-1 as a marker for gonadotropin-releasing hormone agonist treatment, a form of estrogen depletion therapy, for premenopausal patients with HR-positive, human epidermal growth factor receptor 2-negative breast cancer. We reviewed the medical records of 296 premenopausal patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative primary invasive breast cancer treated between 2008 and 2015. Phosphorylated ribosomal protein S6 kinase-1 positivity was defined by immunohistochemical staining scores of 1+, 2+ and 3+, whereas a score of 0 was considered negative. Phosphorylated ribosomal protein S6 kinase-1-positive tumors were found in 74.0% of the patients. In the phosphorylated ribosomal protein S6 kinase-1-positive group, disease-free survival of patients treated with a gonadotropin-releasing hormone agonist was significantly longer than that of patients treated without a gonadotropin-releasing hormone agonist (mean 106.7 months vs mean 91.1 months, P = 0.018). Phosphorylated ribosomal protein S6 kinase-1 is a potential biomarker for predicting the efficacy of gonadotropin-releasing hormone agonist therapy in premenopausal patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer.

PURPOSE We evaluated failure pattern and treatment outcomes of observational approach on regional lymph node (LN) in cutaneous melanoma of extremities and sought to find clinico-pathologic factors related to LN metastases. Material and Methods We retrospectively reviewed 73 patients with cutaneous melanoma of extremities between 2005 and 2016. If preoperative 18-F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) findings were non-specific for regional LNs, surgical resection of primary tumors with adequate margins was performed without sentinel lymph node biopsy (SLNB) and/or complete lymph node dissection (CLND), irrespective of tumor thickness or size. In patients with suspicious or positive findings on PET/CT or CT, SLNB followed by CLND or CLND was performed at the discretion of the surgeon. We defined LN dissection (LND) as SLNB and/or CLND. RESULTS With a median follow-up of 38 months (range, 6 to 138 months), the dominant pattern of failure was regional failure (17 of total 23 events, 74%) in the observation group (n = 56). Pathologic LN metastases were significant factor for poor regional failure-free survival (hazard ration [HR] = 3.21; 95% confidence interval [CI], 1.03-10.33; p = 0.044) and overall survival (HR = 3.62; 95% CI, 1.02-12.94; p = 0.047) in multivariate analysis. In subgroup analysis for cN0 patients according to the preoperative PET/CT findings, LND group showed the better trend of LRFFS (log rank test, p = 0.192) and RFFS (p = 0.310), although which is not statistically significant. CONCLUSION Observational approach on regional LNs on the basis of the PET/CT in patients with cutaneous melanoma of extremities showed the dominant regional failure pattern compared to upfront LND approach. To reveal regional lymph node status, SLND for cN0 patients may of importance in managing cutaneous melanoma patients.

Background To develop and compare delta-radiomics signatures from 2- (2D) and 3-dimensional (3D) features that predict treatment outcomes following preoperative chemoradiotherapy (CCRT) and surgery for locally advanced rectal cancer. Methods In total, 101 patients (training cohort, n = 67; validation cohort, n = 34) with locally advanced rectal adenocarcinoma between 2008 and 2015 were included. We extracted 55 features from T2-weighted magnetic resonance imaging (MRI) scans. Delta-radiomics feature was defined as the difference in radiomics feature before and after CCRT. Signatures were developed to predict local recurrence (LR), distant metastasis (DM), and disease-free survival (DFS) from 2D and 3D features. The least absolute shrinkage and selection operator regression was used to select features and build signatures. The delta-radiomics signatures and clinical factors were integrated into Cox regression analysis to determine if the signatures were independent prognostic factors. Results The radiomics signatures for LR, DM, and DFS were developed and validated using both 2D and 3D features. Outcomes were significantly different in the low- and high-risk patients dichotomized by optimal cutoff in both the training and validation cohorts. In multivariate analysis, the signatures were independent prognostic factors even when considering the clinical parameters. There were no significant differences in C-index from 2D vs. 3D signatures. Conclusions This is the first study to develop delta-radiomics signatures for rectal cancer. The signatures successfully predicted the outcomes and were independent prognostic factors. External validation is warranted to ensure their performance. Electronic supplementary material The online version of this article (10.1186/s13014-019-1246-8) contains supplementary material, which is available to authorized users.

The purpose of this study is to evaluate the performance of a “stealth chamber” as a novel reference detector for measuring the commissioning beam data for a wedge field. The stealth chamber is a transmission ionization chamber intended to be used as a reference chamber for relative dosimetry. The percentage depth doses (PDDs) and the dose profiles of 6-, 8-, and 10-MV photon beams of four wedge filters were measured using the stealth and the CC13 chambers as reference detectors. The PDD and the profile measurements were performed under various field sizes ranging from 4 × 4 cm2 to 20 × 20 cm2. For the evaluate of the performance of the stealth chamber in fields with a physical wedge, all measurement data obtained using the stealth chamber as a reference detector were compared with those measured using two CC13 chambers as both field and reference detectors. For the PDDs, the differences in dosimetric parameters such as the depth of maximum dose (dmax) and the PDD at 10 cm (D10) and 5 cm (D5) were analyzed for both reference detectors. In addition, the root-mean-square error (RMSE) was calculated to measure the agreement of the profiles at dmax and a 10 cm depth. The percentage differences in D10 and D5 between both detectors were less than 1% for all energies and fields with four wedges. Furthermore, the RMSEs of the profiles at dmax and 10-cm depth in both chambers were within 1% for all energies and fields except for the 60° wedge angle. This study found that the use of a stealth chamber to measure the commissioning beam data for a wedge field is feasible, although a relatively large difference in the PDD was observed in the build-up region. However, we recommend careful verification of the PDDs and dose profiles for large field size and wedge angle before clinical use.

The graphic DRAM standard GDDR6 is developed to overcome the limitation of previous standards GDDR5/5X for achieving high-speed operation. This paper introduces 16-Gb GDDR6 DRAM with a per-bit trainable single-ended decision feedback equalizer (DFE), a reference impedance (ZQ)-coded transmitter, and a phase-locked loop (PLL)-less clocking to overcome I/O speed limitation by the DRAM process. Furthermore, this paper optimizes clock- and power-domain crossings and adopts split-die architecture to improve signal integrity (SI). This GDDR6 operates 16 Gb/s/pin with 1.15 V and achieves 18 Gb/s/pin with 1.35 V in the DRAM process.

Objectives Sinus augmentation is frequently used to maintain implant stability when there is severe alveolar bone loss. The aim of this study was to determine the thicknesses and histologic features of the sinus lateral wall and Schneiderian membrane in embalmed cadavers. Design This study included 35 hemimaxillae from 25 cadavers (19 males and 6 females with a mean age at death of 59 years). Specimens obtained from the first premolar to the second molar were embedded in paraffin, stained with hematoxylin-eosin, and observed under a light microscope. The thicknesses of the lateral wall and Schneiderian membrane were measured according to tooth site and measurement level, and their histologic features were evaluated. Results The mean thicknesses of the lateral wall were 2.22, 2.17, 2.64, and 2.64 mm at the first premolar, second premolar, first molar, and second molar, respectively, and 2.79, 2.24, and 2.12 mm at 0, 2, and 8 mm from the sinus floor. The mean thickness of the Schneiderian membrane did not differ significantly between at the sinus floor (0.41 mm) and 2 mm above the floor (0.38 mm). The lateral wall consisted of the outer cortical plate, trabecular bone in the center, and the inner cortical plate near the Schneiderian membrane, being the inner cortical plate the more porous. Conclusions These histomorphometric results for the sinus lateral wall and Schneiderian membrane are expected to provide relevant information for use in sinus augmentation procedures.

The cutting edge of Industry 4.0 has driven everything to be converted to disruptive innovation and digitalized. This digital revolution is imprinted by modern and advanced technology that takes advantage of Big Data and Artificial Intelligence (AI) to nurture from automatic learning systems, smart city, smart energy, smart factory to the edge computing technology, and so on. To harness an appealing, noteworthy, and leading development in smart manufacturing industry, the modern industrial sciences and technologies such as Big Data, Artificial Intelligence, Internet of things, and Edge Computing have to be integrated cooperatively. Accordingly, a suggestion on the integration is presented in this paper. This proposed paper describes the design and implementation of big data platform for intelligence industrial internet of things sensor monitoring system and conveys a prediction of any upcoming errors beforehand. The architecture design is based on edge computing and artificial intelligence. To extend more precisely, industrial internet of things sensor here is about the condition monitoring sensor data — vibration, temperature, related humidity, and barometric pressure inside facility manufacturing factory.

Many groups are working to improve the results of clinical allogeneic islet transplantation in a primate model. However, few studies have focused on the optimal islet dose for achieving normal glycemia without exogenous insulin after transplantation in primate models or on the relationship between rejection and islet amyloid polypeptide (IAPP) expression. We evaluated the dose (10,000, 20,000, and > 25,000 islet equivalents (IEQ)/kg) needed to achieve normal glycemia without exogenous insulin after transplantation using eleven cynomolgus monkeys, and we analyzed the characteristics exhibited in the islets after transplantation. 10,000 IEQ/kg (N = 2) failed to control blood glucose level, despite injection with the highest dose of exogenous insulin, and 20,000 IEQ/kg group (N = 5) achieved unstable control, with a high insulin requirement. However, 25,000 IEQ/kg (N = 4) achieved normal glycemia without exogenous insulin and maintained it for more than 60 days. Immunohistochemistry results from staining islets found in liver biopsies indicated that as the number of transplanted islets decreased, the amount of IAPP accumulation within the islets increased, which accelerated CD3+ T cell infiltration. In conclusion, the optimal transplantation dose for achieving a normal glycemia without exogenous insulin in our cynomolgus monkey model was > 25,000 IEQ/kg, and the accumulation of IAPP early after transplantation, which depends on the transplanted islet dose, can be considered one factor in rejection.

Purpose: The aim of this study was to develop a dosimetric verification system (DVS) using a solid phantom for patient-specific quality assurance (QA) of high-dose-rate brachytherapy (HDR-BT).Methods: The proposed DVS consists of three parts: dose measurement, dose calculation, and analysis. All the dose measurements were performed using EBT3 film and a solid phantom. The solid phantom made of acrylonitrile butadiene styrene (ABS, density = 1.04 g/cm3) was used to measure the dose distribution. To improve the accuracy of dose calculation by using the solid phantom, a conversion factor [CF(r)] according to the radial distance between the water and the solid phantom material was determined by Monte Carlo simulations. In addition, an independent dose calculation program (IDCP) was developed by applying the obtained CF(r). To validate the DVS, dosimetric verification was performed using gamma analysis with 3% dose difference and 3 mm distance-to-agreement criterion for three simulated cases: single dwell position, elliptical dose distribution, and concave elliptical dose distribution. In addition, the possibility of applying the DVS in the high-dose range (up to 15 Gy) was evaluated.Results: The CF(r) between the ABS and water phantom was 0.88 at 0.5 cm. The factor gradually increased with increasing radial distance and converged to 1.08 at 6.0 cm. The point doses 1 cm below the source were 400 cGy in the treatment planning system (TPS), 373.73 cGy in IDCP, and 370.48 cGy in film measurement. The gamma passing rates of dose distributions obtained from TPS and IDCP compared with the dose distribution measured by the film for the simulated cases were 99.41 and 100% for the single dwell position, 96.80 and 100% for the elliptical dose distribution, 88.91 and 99.70% for the concave elliptical dose distribution, respectively. For the high-dose range, the gamma passing rates in the dose distributions between the DVS and measurements were above 98% and higher than those between TPS and measurements.Conclusion: The proposed DVS is applicable for dosimetric verification of HDR-BT, as confirmed through simulated cases for various doses.

Introduction To develop an image-based deep learning model for predicting pathological response in rectal cancer using post-chemoradiotherapy magnetic resonance (MR) imaging. Materials and methods A total of 466 patients with locally advanced rectal cancer who received preoperative chemoradiotherapy followed by surgical resection were collected from single center, among whom 113 (24.3%) were allocated to the holdout testing set. Complete response (pCR) was defined as Dworak tumor regression grade (TRG) 4, while good response (GR) was defined as TRG 3 or 4. Based on post-chemoradiotherapy T2-weighted axial MR images, two deep learning models were developed to predict pCR and GR, respectively. The prediction performance of the deep learning models was evaluated in the testing set and was compared to that of a senior radiologist and a radiation oncologist. Results The deep learning model showed an area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 0.76, 0.30, 0.96, 0.67, 0.87, and 85.0% for predicting pCR and 0.72, 0.54, 0.81, 0.60, 0.77, and 71.7% for predicting GR, respectively. The deep learning model had a superior predictive performance than the observers. Fair agreement between the ground truth and the model was shown for pCR prediction (kappa = 0.34) and GR prediction (kappa = 0.36). Conclusions The post-chemoradiotherapy T2-weighted axial MR image-based deep learning model showed acceptable performance in predicting pCR or GR in patients with rectal cancer, compared with human observers.

Summary: Background: The long-term effects of radical resection on quality of life may influence the treatment selection. The objective of this study was to determine whether abdominoperineal resection has a better effect on the quality of life than sphincter preservation surgery at 3 years after surgery Methods: This prospective, cohort study included patients who underwent radical resection for low rectal cancer. The primary outcomes were European Organisation for Research and Treatment of Cancer QLQ-C30 and CR38 quality of life scores 3 years after surgery, which were compared with linear generalised estimating equations, after adjustment for baseline values, a time effect, and an interaction effect between time and treatment. The secondary outcomes included sexual-urinary functions and oncological outcomes. The study was registered with ClinicalTrials.gov (NCT01461525). Findings: Between December 2011 and August 2016, 342 patients were enrolled: 268 (78•4%) underwent sphincter preservation surgery and 74 (21•6%) underwent abdominoperineal resection. The global quality of life scores did not differ between sphincter preservation surgery and abdominoperineal resection groups (adjusted mean difference, 4•2 points on a 100-point scale; 95% confidence interval [CI], −1•3 to 9•7, p = 0•1316). Abdominoperineal resection was associated with a worse body image (9•8 points; 95% CI, 2•9 to 16•6, p = 0•0052), micturition symptoms (−8•0 points; 95% CI, -14•1 to −1•8, p = 0•0108), male sexual problems (−19•9 points; 95% CI, -33•1 to -6•7, p = 0•0032), less confidence in getting and maintaining an erection in males (0•5 points on a 5-point scale; 95% CI, 0•1 to 0•8, p = 0•0155), and worse urinary symptoms (−5•4 points on a 35-point scale; 95% CI, −8•0 to −2•7, p

Purpose This study proposes a cascaded network model for generating high-resolution doses (i.e., a 1 mm grid) from low-resolution doses (i.e., ≥3 mm grids) with reduced computation time. Methods Using the anisotropic analytical algorithm with three grid sizes (1, 3, and 5 mm) and the Acuros XB algorithm with two grid sizes (1 and 3 mm), dose distributions were calculated for volumetric modulated arc therapy plans for 73 prostate cancer patients. Our cascaded network model consisted of a hierarchically densely connected U-net (HD U-net) and a residual dense network (RDN), which were trained separately following a two-dimensional slice-by-slice procedure. The first network (HD U-net) predicted the downsampled high-resolution dose (generated through bicubic downsampling of the baseline high-resolution dose) using the low-resolution dose; subsequently, the second network (RDN) predicted the high-resolution dose from the output of the first network. Further, the predicted high-resolution dose was converted to its absolute value. We quantified the network performance using the spatial/dosimetric parameters (dice similarity coefficient, mean dose, maximum dose, minimum dose, homogeneity index, conformity index, and V95%, V70%, V50%, and V30%) for the low-resolution and predicted high-resolution doses relative to the baseline high-resolution dose. Gamma analysis (between the baseline dose and the low-resolution dose/predicted high-resolution dose) was performed with a 2%/2 mm criterion and 10% threshold. Results The average computation time to predict a high-resolution axial dose plane was 0.05) between the baseline and predicted doses were observed. The gamma passing rates for the predicted high-resolution does were higher than those for the low-resolution doses. Conclusion The proposed model accurately predicted high-resolution doses for the same dose calculation algorithm. Our model uses only dose data as the input without additional data, which provides advantages of convenience to user over other dose super-resolution methods.

The purpose of this study was to determine the palatal bone and soft tissue thicknesses using a miniscrew-supported maxillary skeletal expander (MSE) in Class III malocclusion. The thicknesses of the palatal bone and soft tissue were measured in cone-beam computed tomography images obtained from 58 patients. All 20 points were crossing points between five levels, which were defined at 3 mm intervals relative to the line connecting the central fossae of the first molar (Level 0), and 2 mm and 4 mm lateral to the anteroposterior reference line (AP line). The palatal bone was significantly thicker in males than females in the anterior palate up to Level 0, while there was no significant sex-related difference in the posterior palate. There was a tendency for the thickness to decrease in the posterior direction, except in females at 2 mm lateral to the AP line. The palatal soft tissue was significantly thicker in males than females in all positions. At 2 mm lateral to the AP line, the palatal soft tissue thickness decreased in the posterior direction. A 4 mm lateral to the AP line, it initially decreased in the posterior direction, and then increasing again at Level − 6 (6 mm posterior of Level 0). As the lateral distance from the AP line increased, the palatal bone thickness decreased while the palatal soft tissue thickness increased. These findings provide quantitative data on the palatal bone and soft tissue thicknesses for the miniscrew-supported MSE in the posterior palate.

Purpose In passive scattering proton beam therapy, scattered protons from the snout and aperture increase the superficial dose, however, treatment planning systems (TPSs) based on analytic algorithms (such as proton convolution superposition) are often inaccurate in this aspect. This additional dose can cause permanent alopecia or severe radiation dermatitis. This study aimed to evaluate the effect of bolus on the superficial radiation dose in passive scattering proton beam therapy. Methods We drew a clinical target volume (CTV) and a scalp‐p (phantom), and created plans using a TPS for a solid water phantom with and without bolus. We calculated the dose distribution in the established plans independently with Monte Carlo (MC) simulation and measured the actual dose distribution with an array of ion chambers and radiochromic films. To assess the clinical impact of bolus on scalp dose, we conducted independent dose verification using MC simulation in a clinical case. Results In the solid water phantom without bolus, the calculated scalp‐p volume receiving 190 cGy was 20% with TPS but 80% with MC simulation when the CTV received 200 cGy. With 2 cm bolus, this decreased from 80% to 10% in MC simulation. With the measurements, average superficial dose to the scalp‐p was reduced by 5.2% when 2 cm bolus was applied. In the clinical case, the scalp‐c (clinical) volume receiving 3000 cGy decreased from 74% to 63% when 2 cm bolus was applied. Conclusion This study revealed that bolus can reduce radiation dose at the superficial body area and alleviate toxicity in passive scattering proton beam therapy.

Background/aim A noninvasive method for predicting a patient's response to neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer would be useful because this would help determine the subsequent treatment strategy. Two types of noninvasive biomarkers have previously been studied, based on radiomics and based on blood test parameters. We hypothesized that a combination of both types would provide a better predictive power, and this has not previously been investigated. Patients and methods Data from 135 patients with locally advanced rectal cancer who underwent nCRT were retrospectively allocated into training and validation cohorts in a 2:1 ratio. Sixty-five radiomics features were extracted from tumors segmented on T2-weighted magnetic resonance images. An elastic net was applied to generate four models for discerning the patients with good responses to nCRT based on radiomics features (model R), blood biomarkers (model B), both (model RB), and a linear combination of models R and B (model R+B). Results Among 65 radiomics features, 17 were selected as robust features for model development. The AUC values of model R, model B, model RB, and model R+B achieved 0.751, 0.627, 0.785, and 0.711 in the training cohort (n=90), and 0.705, 0.603, 0.679, and 0.705 in validation cohort (n=45), respectively. In the entire cohort, models RB and R+B demonstrated a significantly better performance than model B but not R. There was no correlation between the scores of models R and B (p=0.76). Radiomics features had a greater influence than blood biomarkers on models RB and R+B. Conclusion A non-redundancy between radiomics features and blood-based biomarkers was observed. Furthermore, radiomics features are more valuable in terms of predicting response to nCRT. The importance of combining non-invasive biomarkers in future investigations is highlighted.

Background: The long-term effects of radical resection on quality of life may influence the treatment selection. The objective of this study was to compare the quality of life after sphincter preservation surgery or abdominoperineal resection for low rectal cancer. Methods: This prospective, cohort study included patients who underwent radical resection for low rectal cancer. The primary outcomes were EORTC QLQ-C30 and CR38 quality-of-life scores 3 years after surgery, which were compared with linear generalised estimating equations, after adjustment for baseline values, a time effect, and an interaction effect between time and treatment. The secondary outcomes included sexual-urinary functions and oncological outcomes. Findings: Between December 2011 and August 2016, 342 patients were enrolled: 268 (78·4%) underwent sphincter preservation surgery and 74 (21·6%) underwent abdominoperineal resection. After 3 years, abdominoperineal resection was associated with a worse body image (adjusted mean difference, 9·8 points on a 100-point scale; 95% CI, 2·9 to 16·6, p=0·0052), micturition symptoms (-8·0 points; 95% CI, -14·1 to -1·8, p=0·0108), male sexual problems (-19·9 points; 95% CI, -33·1 to -6·7, p=0·0032), less confidence in getting and maintaining an erection in males (0·5 points on a 5-point scale; 95% CI, 0·1 to 0·8, p=0·0155), and worse urinary symptoms (-5·4 points on a 35-point scale; 95% CI, -8·0 to -2·7, p

In the era of precision medicine, the prediction of ovarian function recovery from chemotherapy-induced amenorrhoea using feasible biological markers may be helpful to optimise the treatment strategy for young patients with hormone receptor-positive breast cancer. The purpose of this study was to investigate the accuracy of post-chemotherapy biological markers for predicting the recovery of ovarian function in breast cancer patients of the ASTRRA trial, with chemotherapy-induced amenorrhoea. Using data of 82 participants from a single institution in the ASTRRA trial, the post-chemotherapy serum levels of the anti-Müllerian hormone (AMH), oestradiol, inhibin B and other clinical factors associated with chemotherapy-induced amenorrhoea were evaluated. Recovery of ovarian function was defined by the resumption of menstruation manifested by vaginal bleeding. Fifty-two patients regained menstruation within 55 months after enrolment. In univariate analysis, P = 0.009), oestradiol ≥37 pg/mL (P = 0.003) or AMH ≥800 pg/mL (P = 0.026) were associated with recovery of menstruation. On multivariate analysis, oestradiol (hazard ratio: 3.171, 95% CI: 1.306–7.699, P = 0.011) and AMH (hazard ratio: 2.853, 95% CI: 1.011–8.046, P = 0.048) remained as significant independent predictors for resumption of menstruation. The diagnostic accuracy of age, oestradiol and AMH in predicting the resumption of menstruation was 38.3, 23.3 and 86.7%, respectively. In conclusion, post-chemotherapy AMH level might be a relatively accurate predictor of the recovery of ovarian function, presented by resumption of menstruation in breast cancer patients with chemotherapy-induced amenorrhoea.

Ischemia/reperfusion (I/R) injury inevitably occurs during liver resection and transplantation. Elderly patients poorly recover from these surgeries. This reduced reparative capacity with aging is causatively associated with decreased mitochondrial function after reperfusion. Mitochondrial autophagy (mitophagy) is a vital cellular process that timely clears abnormal and dysfunctional mitochondria. Impaired or insufficient autophagy can contribute to hepatocyte death after I/R. This review describes our current understanding of I/R injury and highlights new mechanistic correlation between sirtuin 1 (SIRT1), mitofusin 2 (MFN2), and autophagy in the pathogenesis of age-dependent hypersensitivity to reperfusion injury. The deacetylation of MFN2 by SIRT1 plays a pivotal role in the recovery from reperfusion injury by modulating the onset of autophagy. Targeting the SIRT1-MFN2 axis could be a new therapeutic target to reduce I/R injury in aged livers. Keywords: Hepatocytes, Autophagy, Mitochondrial autophagy (mitophagy), Aging, Ischemia/reperfusion (I/R), Sirtuin 1-mitofusin 2 (SIRT1-MFN2) axis

Although evidence has emerged to suggest that YAP overexpression is a crucial factor for tumor progression and resistance to targeted drugs in multiple cancers, the miRNA-mediated YAP regulation is still unclear. Here we show that the novel miR-550a-3-5p acts as a tumor suppressor and reverses BRAF inhibitor resistance through the direct targeting of YAP. Our data showed that the miR-550a-3-5p suppressed cell proliferation, metastasis, and tumor sphere formation through the direct inhibition of YAP and its oncogenic pathway in various cancer cell types. In addition, we showed that the YAP signature was associated with poor survival of colon cancer and identified an inverse correlation between miR-550a-3-5p and YAP in colon cancer tissues. Interestingly, this inverse correlation was regulated in a density-dependent manner. Furthermore, high levels of miR-550a-3-5p were associated with a good prognosis of esophageal cancer, which was suggestive of the clinical relevance of miR-550a-3-5p-mediated YAP regulation in multiple cancers. Importantly, we demonstrated that miR-550a-3-5p treatment sensitized vemurafenib-resistant colon and melanoma cells through YAP inhibition with reduced AKT activity. Moreover, the tumor-suppressive activity of miR-550a-3-5p and its sensitization effect for vemurafenib resistance were also observed in tumor xenograft models. Collectively, our data suggest that miR-550a-3-5p acts as a tumor suppressor through the targeting of oncogenic YAP and may be a new therapeutic tool for YAP-mediated BRAF inhibitor resistance in BRAF-mutant cancer cells.

Purpose To investigate interobserver variation in target volume delineations for prostate cancer salvage radiotherapy using planning computed tomography (CT) versus combined planning CT and magnetic resonance imaging (MRI). Materials and methods Ten radiation oncologists independently delineated a target volume on the planning CT scans of five cases with different pathological status after radical prostatectomy. Two weeks later, this was repeated with the addition of planning MRI. The volumes obtained with CT only and combined CT and MRI were compared, and the effect of the addition of planning MRI on interobserver variability was assessed. Results There were large differences in clinical target volume (CTV) delineated by each observer, regardless of the addition of planning MRI (9.44-139.27 cm3 in CT only and 7.77-122.83 cm3 in CT plus MRI) and no significant differences in the mean and standard deviation of CTV. However, there were decreases in mean volume and standard deviation as a result of using the planning MRI. Conclusion This study showed substantial interobserver variation in target volume delineation for salvage radiotherapy. The combination of planning MRI with CT tended to decrease the target volume and the variation.

Background We hypothesized that hippocampal-sparing radiotherapy via volumetric modulated arc therapy (VMAT) could preserve the neurocognitive function (NCF) of patients with primary brain tumors treated with radiotherapy. Methods We reviewed data from patients with primary brain tumors who underwent hippocampal-sparing brain radiotherapy via VMAT between February 2014 and December 2015. The optimization criteria for the contralateral hippocampus was a maximum dose (Dmax) of less than 17 Gy. For NCF evaluations, the Seoul Verbal Learning Test for total recall, delayed recall, and recognition (SVLT-TR, DR, and Recognition) was performed at baseline and at seven months after radiotherapy. Results A total of 26 patients underwent NCF testing seven months after radiotherapy. Their median age was 49.5 years (range 26–77 years), and 14 (53.8%) had grade III/IV tumors. The median Dmax to the contralateral hippocampus was 16.4 Gy (range 3.5-63.4). The median mean dose to the contralateral hippocampus, expressed as equivalent to a 2-Gy dose (EQD2/2), was 7.4 Gy2 (0.7–13.1). The mean relative changes in SVLT-TR, SVLT-DR, and SVLT-Recognition at seven months compared to the baseline were − 7.7% (95% confidence interval [CI], − 19.6% to 4.2%), − 9.2% (95% CI, − 25.4% to 7.0%), and − 3.4% (− 12.7% to 5.8%), respectively. Two patients (7.7%) showed deteriorated NCF in the SVLT-TR and SVLT-DR, and three (11.5%) in the SVLT-Recognition. The mean dose of the left hippocampus and bilateral hippocampi were significantly higher in patients showing deterioration of the SVLT-TR and SVLT-Recognition than in those without deterioration. Conclusions The contralateral hippocampus could be effectively spared in patients with primary brain tumor via VMAT to preserve the verbal memory function. Further investigation is needed to identify those patients who will most benefit from hippocampal-sparing radiotherapy of the primary brain tumor. Electronic supplementary material The online version of this article (10.1186/s13014-018-0975-4) contains supplementary material, which is available to authorized users.

We describe an triboelectric nanogenerator embedded with multilayers consisted of PDMS:electron trapping layer (ETL):PDMS (E-TENG) with oxygen vacancies, producing more localized states in the energy gap, that can accumulate much more transferred electrons by triboelectrification at ETL, thereby enhancing surface charge density of E-TENG. We suggest a working mechanism of an E-TENG with band diagram including electron/charge flows by investigating electrical, chemical and physical properties and suggest the optimal characteristics of ETL depending on the degree of oxygen vacancies, rich, medium and poor, for high performance of E-TENG. Furthermore, we propose the main factors such as localized states of ETL and difference conduction band between polymer and ETL with band diagram as a band well structure, presented space for electrons/charges accumulation, for high surface charge density of E-TENG. As a results, maximum output performance of E-TENG with rich oxygen vacancies of ETL (E-TENG-R) is 618.7 V, 40.4 μA and 22.8 nC/cm2, more than three-fold enhancement compare to pristine TENG. Finally, to effectively generate electrical energy, we apply E-TENG-R to kinematic system as a hand handled gear-cam system, 36 times enhancement of working frequency, with ground structure (EHGS) which produces the maximum 200 V and 100 μA. We charged 110 μF until 5.2 V for 25 s using EHGS and achieved operation of wireless humidity sensor system.

Supplemental Digital Content is available in the text., Background. Perfusate lactate clearance (LC) is considered one of the useful indicators of liver viability assessment during normothermic machine perfusion (NMP); however, the applicable scope and potential mechanisms of LC remain poorly defined in the setting of liver donation after circulatory death. Methods. The ex situ NMP of end-ischemic human livers was performed using the OrganOx Metra device. We further studied the extracellular signal-regulated kinases (phospho-extracellular signal-regulated kinase1/2 [pERK1/2]) pathway and several clinical parameters of these livers with successful LC (sLC, n = 5) compared with non-sLC (nLC, n = 5) in the perfusate (

BackgroundBR101801 is an inhibitor of PI3K γ/δ and DNA-PK. It has received clinical approval from the U.S. FDA as an anticancer drug candidate, and phase 1a/1b is ongoing in the U.S. and South Korea. According to the prior studies PI3K γ/δ inhibition exhibits anticancer immune effects by changing the tumor microenvironment [1]. In addition, ionizing radiation (IR) activates the immune response by causing the destroyed cells to act as antigens [2]. Therefore, the combination of BR101801 and IR can induce cancer cell death and amplify anticancer immune effects. This study aims to demonstrate efficacy of the BR101801 as a potent cancer immunotherapy.MethodsThe enzymatic potency of PI3K isotype and DNA-PK was analyzed by Eurofins. The effects of BR101801 on cell viability were evaluated in 4T1 (breast cancer) and CT-26 (colon cancer) cells for 72 h using WST-8 assay. For in vivo studies, the tumor (4T1 or CT-26)-bearing syngeneic mice were treated with BR101801. To evaluate the synergistic effect, CT-26 tumor-bearing syngeneic mice were treated with vehicle, BR101801, IR (2 Gy or 7.5 Gy), and BR101801 + IR. Immune cells from the spleen or tumor were quantified by flow cytometry.ResultsIn vitro selectivity and target potency of BR101801 on different PI3K isotypes and DNA-PK were studied in a cell-free system. The biochemical IC50 values of BR101801 for PI3K -γ, -δ, and DNA-PK were 15 nM, 2 nM, and 6 nM, respectively. In vitro 50% of maximal inhibition of cell proliferation (GI50) in 4T1 and CT26 cell lines were both above 10 μM. In 4T1 and CT-26 syngeneic models, BR101801 showed the highest tumor inhibitor efficacy (Figure 1). In particular, regulatory T cells (Tregs) & Myeloid derived suppressor cells (MDSC) were decreased and CD8+ T cells were increased in the spleens isolated from the tumor-bearing mice. Compared with other PI3K inhibitors, BR101801 had the highest efficacy, confirming that it changes the immune microenvironment. Moreover, BR101801 was synergistic in combination with 2 Gy or 7.5 Gy of IR in the syngeneic model. Notably, Tregs & Macrophage2 were decreased and CD8+ T cells were increased in the tumor tissue, confirming that the anticancer efficacy.Abstract 600 Figure 1Synergistic effect with ionizing radiation In VivoThe combination of BR101801 and ionising radiation showed synergistic effects in the CT-26 Syngeneic model. BR101801 increases anti-cancer immune cells, CD8 + T cells, and decreases immune suppressor cells Tregs and macrophages through a combination of radiation, resulting in immuno-cancer effects.ConclusionsBR101801 demonstrated an anticancer immune effect by changing the tumor microenvironment and showed synergistic effects with radiation combination therapy. We will confirm the anticancer immunity effect in ongoing clinical trials.ReferencesOkkenhaug K, Graupera M, Vanhaesebroeck B. Targeting PI3K in Cancer: Impact on Tumor Cells, Their Protective Stroma, Angiogenesis, and Immunotherapy. Cancer Discov. 2016; 10: 1090–1105.McKelvey K, Hudson A, Back M, Eade T, Diakos C. Radiation, inflammation and the immune response in cancer. Mammalian Genome. 2018;9:843–865Ethics ApprovalThe protocol and any amendment(s) or procedures involving the care and use of animals in this study were reviewed and approved by the Institutional animal Car and Use Committee (IACUC) of BoRyung Pharm. prior to conduct.[Approval number:BR18130]

Although it has been proposed that the beneficial effect of HER2-targeted therapy in HER2-negative breast cancer is associated with the molecular subtype conversion, the underlying mechanism and the clinical biomarkers are unclear. Our study showed that breast cancer stem cells (BCSCs) mediated HER2 subtype conversion and radioresistance in HER2-negative breast cancer cells and evaluated serum HER2 as a clinical biomarker for HER2 subtype conversion. We found that the CD44+/CD24-/low BCSCs from HER2-negative breast cancer MCF7 cells overexpressed HER2 and EGFR and showed the radioresistant phenotype. In addition, we showed that trastuzumab treatment sensitized the radioresistant phenotype of the CD44+/CD24-/low cells with decreased levels of HER2 and EGFR, which suggested that HER2-targeted therapy in HER2-negative breast cancer could be useful for targeting BCSCs that overexpress HER2/EGFR. Importantly, our clinical data showed that serial serum HER2 measurement synchronously reflected the disease relapse and the change in tumor burden in some patients who were initially diagnosed as HER2-negative breast cancer, which indicated that serum HER2 could be a clinical biomarker for the evaluation of HER2 subtype conversion in patients with recurrent HER2-negative breast cancer. Therefore, our data have provided in vitro and in vivo evidence for the molecular subtype conversion of HER2-negative breast cancer.

Introduction The optimal salvage treatment strategies for lymph node-positive (LNP) patients after radical surgery have not been clearly defined in prostate cancer with biochemical recurrence or persistence of elevated prostate-specific antigen (PSA). In this study, we compared the clinical outcomes of two different salvage treatments, androgen deprivation therapy (ADT) alone versus ADT with radiotherapy (RT). We also investigated prognostic factors that could support the use of ADT with RT in LNP prostate cancer. Materials and methods We retrospectively reviewed 94 LNP prostate cancer patients who underwent radical prostatectomy (RP) followed by salvage treatment between 2004 and 2018. Salvage treatments involved either ADT alone or ADT with RT according to the clinical judgment of the physician. We analyzed clinicopathological and treatment factors related to 2nd biochemical failure (2nd BCF), clinical progression (CP), and progression-free survival (PFS). The cumulative failure after salvage treatment was defined as including both 2nd BCF and CP. Results The median duration of follow-up was 55 months (interquartile range, 35–97 months). Thirty-seven (39.4%) patients were treated with ADT alone, and 57 patients (60.6%) were treated with a combination of ADT with RT. During follow-up period, the incidence of failure after salvage treatment in the ADT alone group and the combined treatment group was 89.2% and 45.6%, respectively (HR, 22.4; 95% CI 5.43–92.1; P < 0.001). The combination of ADT with RT was associated with better 2nd BCF and PFS than ADT alone (P = 0.007 and P = 0.015, respectively). In multivariate analyses, number of positive LN ≥ 2 and PSA nadir ≥ 0.005 ng/ml after RP were associated with poor 2nd BCF, CP, and PFS after salvage treatment. Salvage by combined ADT plus RT showed better 2nd BCF and PFS than ADT alone. Specifically, patients with number of positive LN ≥ 2 or PSA nadir ≥ 0.005 ng/ml after RP showed better 2nd BCF (P = 0.004) or PFS (P = 0.011) when treated with ADT plus RT rather than ADT alone. Conclusions In patients with LNP prostate cancer, salvage ADT plus RT improved 2nd BCF and PFS compared to ADT alone. In particular, when the patients had more than two positive lymph nodes or PSA nadir ≥ 0.005 ng/ml after RP, ADT with RT seems to be a more beneficial salvage treatment resulting in better 2nd BCF and PFS.

To ensure agricultural sustainability and desirable environmental outcomes, stakeholders need systems-based model-driven decision support tools. The objective of this study was to develop a global scale web-based geospatial crop modeling application called Food, Agriculture, and Resource Management system (FARMs), to simplify the application of the crop simulation model —Decision Support System for Agrotechnology Transfer (DSSAT) without requiring users to create input weather, climate, and soil files. FARMs was built based on open source Geographic Information System (GIS) technologies and DSSAT to allow for adaptive management through its ability to perform in-season yield predictions for alfalfa and maize, currently. Validation of FARMs against variety trial data in California was acceptable between measured and simulated yields for alfalfa. The work done in this study showed how a complex model like DSSAT can be translated into a useable web-based decision support tool for near-real-time simulation with the help of open-source GIS technologies.

Ischemia/reperfusion (I/R) injury unavoidably occurs during hepatic resection and transplantation. Aged livers poorly tolerate I/R during surgical treatment. Although livers have a powerful endogenous inhibitor of calpains, calpastatin (CAST), I/R activates calpains, leading to impaired autophagy, mitochondrial dysfunction, and hepatocyte death. It is unknown how I/R in aged livers affects CAST. Human and mouse liver biopsies at different ages were collected during in vivo I/R. Hepatocytes were isolated from 3-month- (young) and 26-month-old (aged) mice, and challenged with short in vitro simulated I/R. Cell death, protein expression, autophagy, and mitochondrial permeability transition (MPT) between the two age groups were compared. Adenoviral vector was used to overexpress CAST. Significant cell death was observed only in reperfused aged hepatocytes. Before the commencement of ischemia, CAST expression in aged human and mouse livers and mouse hepatocytes was markedly greater than that in young counterparts. However, reperfusion substantially decreased CAST in aged human and mouse livers. In hepatocytes, reperfusion rapidly depleted aged cells of CAST, cleaved autophagy-related protein 5 (ATG5), and induced defective autophagy and MPT onset, all of which were blocked by CAST overexpression. Furthermore, mitochondrial morphology was shifted toward an elongated shape with CAST overexpression. In conclusion, CAST in aged livers is intrinsically short-lived and lost after short I/R. CAST depletion contributes to age-dependent liver injury after I/R.

Hepatic steatosis prevails each year. Autophagy is integral in mitochondrial quality control and lipid homeostasis in the liver. No pharmacological strategies are currently available to reduce hepatic steatosis, but exercise has been known to improve clinical outcomes of chronic liver disease, parti