Search

The presence of gas hydrates is well known in the marine realm southwest off Taiwan due to the widespread distribution of bottom simulating reflectors in seismic records. To learn more about gas hydrate systems and their dynamics at passive and active margins, we drilled boreholes with MARUM-MeBo200 seafloor drill rig at areas where geophysical indications for gas hydrates have been detected in the past. Several gas hydrate proxies like negative chloride anomalies in the pore water, cold spots detected by infrared thermal scans on cores, increased resistivity, and lithological parameters clearly showed the presence of hydrates in the drilled sections. However, gas hydrate was not recovered by MeBo most likely because of small crystal sizes which dissociated during recovery from the seafloor. Three holes were drilled at southern summit of Formosa Ridge down to 126 m below seafloor (mbsf) and recovered sediments from which in situ hydrate saturation values were estimated between 1 and 10% at 15–42 mbsf and even higher values of up to 38% below 100 mbsf. The latter are probably related to the sealing effect of carbonate precipitation which occur at 85–95 mbsf directly above the hydrate-enriched layer. Four holes were drilled at Four-Way Closure Ridge where a maximum drilling depth of 143.90 m was reached. Hydrate presence starts in 65 mbsf continuing down-core with a range of 1–29% gas hydrate saturation in fine-grained homogenous clay. An abrupt change to higher gas hydrate saturation values of up to 80% occurs below 109 mbsf where silty and sandy turbidite layers are often intercalated. Such high gas hydrate contents only occur in the sand layers and not in the fine-grained sediments intercalated to the sand deposits.

Stochastic modeling and analysis of international key compar- isons (interlaboratory comparisons) pose several fundamental questions for statistical methodology. A key comparison (KC) is specifically designed to derive the key comparison reference value and to assess conformance of cal- ibrations by participating national metrology laboratories at a few, "key", settings for a particular measurement process. An approach to the statis- tical study of key comparisons data is proposed using a model taken from meta-analysis. This model leads to a class of weighted means estimators for the consensus value and to a method of assessing the uncertainty of the resulting estimates. The need for statistically sound analytic methods for collaborative metrology studies data motivates this paper. Several approaches are known, but at present there is no commonly accepted methodology for statistical analysis of the inter- laboratory studies. The paper begins with a review of the central issues arising in statistical modeling and analysis of international key comparisons data, proceeds to formalize the mathematical structure for these data and then compares sev- eral procedures for calculation of the Key Comparison Reference Value (KCRV) and for the estimation of the uncertainty for this value. Evaluation of KCRV is demanded by the main document on international cooperation for measurement quality assurance, the Mutual Recognition Agreement (MRA) (1999) published by Le Comite International des Poids et Mesures. The MRA is realized through KC which typically involve National Metrology Institutes (NMI) each of which

Chlorfenapyr is a moderately dangerous insecticide widely used in agriculture. The mortality of acute poisoning patients is high, and there is no effective treatment. This paper retrospectively analyzes the clinical data of two cases of compound chlorfenapyr poisoning. The main symptoms of the patients were high fever, sweating, gradual coma, increased creatine kinase and myoglobin, with delayed poisoning symptoms. Despite comprehensive treatment, both patients died eventually. It indicated that chlorfenapyr was highly toxic and had a high mortality. In addition to routine symptomatic treatment for patients with acute poisoning, blood purification treatment should be actively carried out in the early stage.虫螨腈是农业广泛应用的一种中度危险杀虫剂，急性中毒患者死亡率较高，尚无有效治疗手段。本文对2例复配虫螨腈中毒病例临床资料回顾性分析，患者主要表现为高热、出汗、逐渐昏迷、肌酸激酶及肌红蛋白升高，有迟发中毒表现，虽经综合治疗但最终2名患者均死亡。提示虫螨腈毒性强，致死率高。对于急性中毒患者除常规对症治疗外，应早期积极行血液净化治疗。.

Low temperature Carbon Nano-tubes (CNTs) growth technology is developed in this work with the insert of Al (Aluminum) between Ni (Nickel) and Ti (Titanium) as the reactant. The optimized Al thicknesses are also investigated. CNTs growth at the low temperature below 400 °C is the key factor for the back end of line compatible process integration. In this work, we grow the CNTs by thermal chemical vapor deposition process at 350 and 400 °C. The low ratio of peak ID/IG in Raman spectra and scanning electron microscope images proves the CNTs material quality. On the other hand, the high thermal conductivity (k) value of ∼50 W m − 1 K − 1 is also demonstrated. Both high material quality and k value on our low temperature grown CNTs show promising opportunities for the integration of semiconductor three dimensional packages and power-via related applications.

BACKGROUND: Currently there is limited information to guide health professionals regarding the optimal time frame to initiate safe and effective oral feedings to preterm infants. The study aims to revise and validate a streamlined version of the Traditional Chinese-Preterm Oral Feeding Readiness Assessment Scale, the TC-POFRAS®, and evaluate its construct validity in the clinical decisions regarding feeding readiness of preterm infants. METHODS: Eighty-one clinically stable preterm infants were assessed using the TC-POFRAS for oral feeding readiness. Item-total correlation analysis was used to check if any item was inconsistent with the averaged TC-POFRAS scores. Cronbach’s α coefficient was used to evaluate the inter-item consistency. Exploratory factor analysis was used to determine the coherence of variables to reorganize assessment domains. The revised version of TC-POFRAS (TC-POFRAS®) was developed and a new cut-off score based on discriminant accuracy was established. RESULTS: Based on the results from statistical analysis, five items (“lips posture,” “tongue posture,” “biting reflex,” “gag reflex,” and “tongue cupping”) were deleted from the original TC-POFRAS to form the TC-POFRAS®. The TC-POFRAS®’s global accuracy was 92.1%. The cut-off value of 19 was the one that presented the most optimization of sensitivity based on specificity. The TC-POFRAS® was reconstructed into corrected gestational age and five behavioral domains. CONCLUSIONS: The TC-POFRAS® is considered a valid, safe, and accurate objective instrument to assist health professionals to initiate oral feeding of preterm infants.

This study aims to investigate the expression levels and values of autophagy genes light chain 3 (LC3) and autophagy-related 5 (ATG5) in intestinal-type gastric cancer. Ninety samples of normal gastric mucosa, intraepithelial neoplasia, and gastric cancer tissue were used in this study. The messenger ribonucleic acid (mRNA) and protein expression levels of autophagy genes LC3 and ATG5 were detected using quantitative reverse transcription polymerase chain reaction, Western blot, and the immunohistochemistry method. The correlations of the autophagy genes and certain clinical pathological parameters were analyzed. The results showed that LC3 mRNA expression was 43.76 ± 20.31 in the normal group, 111.29 ± 18.65 in the intraepithelial neoplasia group, and 131.78 ± 26.29 in the gastric cancer group, while ATG5 mRNA expression was 4.52 ± 2.37 in the normal group, 7.09 ± 1.88 in the intraepithelial neoplasia group, and 10.25 ± 2.81 in the gastric cancer group. The differences between the groups were statistically significant (P0.05). The protein expression of LC3 in the normal group was 1.05 ± 0.41, 1.53 ± 0.36 in the intraepithelial neoplasia group, and 1.99 ± 0.14 in the gastric cancer group. The protein expression of ATG5 was 0.78 ± 0.24 in the normal group, 1.37 ± 0.39 in the intraepithelial neoplasia group, and 2.04 ± 0.63 in the gastric cancer group. The differences between the groups were statistically significant (P0.05). The positive rate of LC3 protein expression was 33.3% in the normal group and 60% in the intraepithelial neoplasia group, and the difference was statistically significant (χ

Background: Neoadjuvant systemic therapy (NST) is the standard treatment for locally advanced breast cancer. Early studies have demonstrated that the rate of breast conservation was significantly increased and NST is now widely applied to operable breast cancer to increase breast conservation rate and to achieve better cosmetic outcome after breast conservative surgery (BCS). For patients who achieved pathologic complete response (pCR), they were perfect candidate for BCS. However, data from prospectively randomized trials have shown that, with the significantly increase of pCR by adding new drugs in the neoadjuvant regimen, BCS rate does not significantly increased. The purpose of current study is to identify factors that have influence on surgical option in patients that have achieved complete response in the breast after NST. Methods: From January 2009 to July 2016, 1150 patients with breast cancer received NST in our institute. There were 103 patients achieved complete response (CR) in the breast and were included in current analysis. Medical records were reviewed regarding to individual surgeon, pre-NST clinicopathologic characteristics, and post-NST image findings. Risk factors for mastectomy were assessed by univariate and multivariate analyses. Results: Of the 103 patients who achieved CR in the breast, 40 of them (38.8%) received mastectomy. In univariate analysis, physician factor, larger initial tumor size, advanced clinical stages, as well as post-NST image findings including skin change, residual tumor ≥3 cm, short nipple-tumor distance, and residual axillary lymph node(LN) on ultrasound and segmental/diffuse distribution of malignant calcification on mammography were associated with more mastectomy. In multivariate analysis, physician factor (OR=5.192, CI [1.562 – 17.257], p=0.021), residual axillary LN on echography (OR=4.000, CI [1.552 – 10.319], p=0.004), and segmental/diffuse distribution of malignant calcification on mammography (OR=7.500, CI [1.819 – 30.916], p=0.018) were independently related to mastectomy in patients who achieved CR in the breast after NST. Conclusion: Physician factor, residual axillary LN and segmental/diffuse malignant calcifications were risk factors for mastectomy in patients who achieved CR in the breast after NST. In addition to embrace current treatment guidelines of surgical management after NST, our data provide valuable additional information to avoid unnecessary mastectomy. Citation Format: Kou H-W, Shen S-C, Chen S-C. Factors impacting surgical option in patients who achieved complete response in the breast after neoadjuvant systemic therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-13-10.

Background Abemaciclib is a selective CDK4 & 6 inhibitor approved on a continuous dosing schedule for HR+, HER2- advanced breast cancer (ABC) as monotherapy (MONARCH 1) and in combination with endocrine therapy (ET). A previous Phase 1b (NCT01394016) cohort of HR+ ABC patients (pts) demonstrated efficacy of abemaciclib monotherapy (150mg and 200mg Q12H starting dose); given the small sample size and nonrandomized design the impact of the starting dose was unclear. nextMONARCH 1 (NCT02747004) evaluated abemaciclib in 2 monotherapy arms, in a randomized setting. Abemaciclib has been associated with dose-dependent early onset diarrhea that is well managed with antidiarrheal therapy. nextMONARCH 1 also explored the 200mg Q12H abemaciclib dose in combination with prophylactic loperamide to reduce incidence/severity of diarrhea and dose adjustments. A third arm evaluated abemaciclib + tamoxifen as a strategy to overcome endocrine resistance. Methods nextMONARCH 1 is a multicenter, randomized, open-label, Phase 2 study of abemaciclib or abemaciclib + tamoxifen in women with HR+, HER2- ABC who have progressed on or after prior ET and previously received chemotherapy. Pts were stratified by presence of liver metastases and prior use of tamoxifen in the advanced setting. Randomization was 1:1:1 to abemaciclib 150mg Q12H + daily tamoxifen 20mg (Arm A) or abemaciclib 150mg Q12H (Arm B); or abemaciclib 200mg Q12H + prophylactic loperamide (Arm C). Key eligibilities were ≥2 chemotherapy regimens (1-2 administered in metastatic setting), measurable disease and no prior treatment with CDK4 & 6 inhibitors. Primary objective was progression free survival (PFS). Key secondary objectives included objective response rate (ORR), dclinical benefit rate (CBR), and safety. PFS analysis tested superiority of Arm A to C at ∼110 events across the 2 arms assuming a hazard ratio (HR) of 0.667 to achieve ∼80% power. Arm B would be considered non-inferior to Arm C if the observed PFS HR is Results 234 pts were randomized to Arms A (n=78), B (n=79) and C (n=77). 166 PFS events have been observed (A: 57; B: 54; C: 55). Median PFS was 9.1 months in Arm A, 6.5 in Arm B and 7.4 in Arm C (A vs C: HR=.815, 95% CI, .556-1.193, p=.293; B vs C: HR=1.045, 95% CI, .711-1.535 p=.811). Investigator-assessed ORR was 34.6%, 24.1% and 32.5% (confirmed ORR: 25.6%, 19.0%, 28.6%) and CBR was 61.5%, 49.4% and 51.9% in Arms A, B and C, respectively. Prophylactic loperamide reduced the incidence and severity of diarrhea (C: 62.3%, Gr 3: 7.8%) compared to MONARCH 1 (90.2%, Gr 3: 19.7%, Dickler et al. 2017) resulting in similar rates of diarrhea with 150mg abemaciclib without prophylaxis (A: 53.8%, Gr 3: 1.3%; B: 67.1%, Gr 3: 3.8%). The adverse event profile across arms was generally consistent with other breast studies of abemaciclib. Conclusions nextMONARCH 1 confirmed single-agent activity of abemaciclib in heavily pretreated pts with HR+, HER2- ABC. Efficacy of abemaciclib monotherapy at 150mg was similar to 200mg. Combining tamoxifen with abemaciclib did not demonstrate a statistically significant improvement in PFS compared to abemaciclib monotherapy. Addition of prophylactic loperamide to abemaciclib 200mg resulted in diarrhea similar to 150mg without prophylaxis. Citation Format: Hamilton E, Cortes J, Dieras V, Ozyilkan O, Chen S-C, Petrakova K, Manikhas A, Jerusalem G, Hegg R, Lu Y, Bear MM, Johnston EL, Martin M. nextMONARCH 1: Phase 2 study of abemaciclib plus tamoxifen or abemaciclib alone in HR+, HER2- advanced breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD1-11.

Defecation is a complex process and up to 25% of the population suffer from symptoms of defecatory dysfunction. For functional testing, diagnostics, and therapy of anorectal disorders, it is important to know the optimal defecation position. is The aim of this study was to evaluate defecation pressure patterns in side lying, seated and squatting defecation positions in normal subjects using a simulated stool device called Fecobionics.The Fecobionics expulsion parameters were assessed in an interventional study design conducted from May 29 to December 9 2019. Subjects were invited to participate in the study through advertisement at The Chinese University of Hong Kong. The Fecobionics device consisted of a core containing pressure sensors at the front (caudal end) and rear (cranial end) and a polyester-urethane bag spanning most of the core length which also contained sensors. The Fecobionics bag was distended to 50 ml in the rectum of normal subjects (no present and past symptoms of defecatory disorders, no prior abdominal surgery, medication or chronic diseases). Studies were done in side lying (left lateral recumbent position), seated (hip flexed 90°) and squatting position (hip flexed 25°). Pressure endpoints including the rear-front pressure diagram and defecation indices were compared between positions.Twelve subjects (6 females/6 males, mean age 26.3 ± 2.6 [19.0-48.0] years) were included and underwent the planned procedures. The resting anal pressure for side lying and seated positions were 33.1 ± 4.1 cmHThe delay in expelling the Fecobionics device in the lying position was associated with dyssynergic pressure patterns on the device. Quantitative differences were not found between the seated and squatting position. Trial Registration http://www.clinicaltrials.gov Identifier: NCT03317938.

Sepsis-induced acute liver injury (ALI) involves multiple systems in the body. The disease is acute and critical, with various symptoms, including extensive necrosis of liver cells. There is currently no effective treatment to deal with ALI in a timely manner. This study verified the therapeutic effect of Krüppel-like factor 15 (KLF15) on ALI by studying its anti-apoptotic effect on the liver.We induced ALI in mice with lipopolysaccharide (LPS)/D-galactosamine (D-GaIN). Recombinant mouse KLF15 was used to treat mice to examine the protective effects of KLF15 on mouse liver and the effects of apoptosis-related molecules. In addition, we cultured Kupffer cells and determined the anti-inflammatory and anti-apoptotic effects of KLF15 and its mechanism by overexpressing KLF15.Exogenous KLF15 effectively reduced the levels of TIBL, ALT, AST, and inflammatory factors (COX-2, MCP-1, IL-1β, and TNF-α) in mouse serum. The results of HE staining also demonstrate that KLF15 improves the morphology of liver tissue. In addition, the expression of KLF15 in LPS-induced Kupffer cells was significantly reduced and KLF15 increased the viability of Kupffer cells and decreased the level of inflammation in Kupffer cells. In both in vivo and in vitro experiments, KLF15 reduced the level of apoptosis in hepatocytes or Kupffer cells and inhibited the activity of the p38MAPK/ERK1/2 signaling pathway.KLF15 reduces the apoptosis and inflammation levels of liver and Kupffer cells by inhibiting the p38MAPK/ERK1/2 signaling pathway and alleviates LPS/D-GaIN-induced ALI.

Acute lung injury (ALI) is the most common complication of sepsis, with rapid onset and high mortality. There is currently no effective treatment for ALI. Therefore, we looked for a good method of treating ALI by studying the effect and mechanism of Nesfatin-1 on ALI.We used LPS to induce mouse and human alveolar epithelial cell line BEAS-2B to construct an ALI model. Recombinant Nesfatin-1 was administered subcutaneously to mice or used to stimulate BEAS-2B cells. We collected mouse bronchoalveolar lavage fluid and mouse lung tissue to detect changes in inflammatory factors and oxidative stress levels. In addition, we examined the expression changes of HMGB1 to study the mechanism of Nesfatin-1.Exogenous Nesfatin-1 significantly attenuated LPS-induced ALI and reduced inflammation levels and oxidative stress levels in mouse lung tissue. In cell experiments, Nesfatin-1 also reduced inflammation levels and oxidative stress levels in BEAS-2B cells. In addition, Nesfatin-1 reduced the expression of HMGB1 in mouse lung tissues and BEAS-2B cells, and decreased the activity of p38MAPK and NF-κB signaling pathways in the inflammation-related pathway downstream of HMGB1. However, after overexpression of HMGB1, the therapeutic effect of Nesfatin-1 on ALI was attenuated.Nesfatin-1 regulates the expression of HMGB1 in alveolar epithelial cells. By reducing the expression of HMGB1, Nesfatin-1 can reduce the inflammation-related signaling pathway downstream of HMGB1 to reduce the level of inflammation and oxidative stress in alveolar epithelial cells, thereby alleviating ALI.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of hepatocellular carcinoma (HCC) was published in 2018, and covered the diagnosis, management, treatment and follow-up of early, intermediate and advanced disease. At the ESMO Asia Meeting in November 2018 it was decided by both the ESMO and the Taiwan Oncology Society (TOS) to convene a special guidelines meeting immediately after the Taiwan Joint Cancer Conference (TJCC) in May 2019 in Taipei. The aim was to adapt the ESMO 2018 guidelines to take into account both the ethnic and the geographic differences in practice associated with the treatment of HCC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with intermediate and advanced/relapsed HCC representing the oncology societies of Taiwan (TOS), China (CSCO), India (ISMPO) Japan (JSMO), Korea (KSMO), Malaysia (MOS) and Singapore (SSO). The voting was based on scientific evidence, and was independent of the current treatment practices, the drug availability and reimbursement situations in the individual participating Asian countries.

The aim of this study was to detect the expression of long non-coding ribonucleic acid (lncRNA) colorectal neoplasia differentially expressed gene (CRNDE) in the kidney tissues of mice with sepsis-induced acute kidney injury (AKI) and its effect on KI, and to further explore its mechanism.A total of 60 male C57 mice were randomly divided into 3 groups based on a random number table, including the control group (Sham group, n=20), sepsis-related KI group [lipopolysaccharide (LPS) group, n=20] and CRNDE inhibition group [LPS + CRNDE small interfering ribonucleic acid (siRNA) group, n=20]. Mice in LPS and LPS + CRNDE siRNA groups were intraperitoneally injected with 5 mg/kg LPS, while the tail vein was injected with 5 μL CRNDE siRNAs. After 12 h, the expression level of lncRNA CRNDE in kidney tissues of mice in each group was detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). At the same time, 2 mL of orbital blood was collected from each mouse, and the levels of creatinine and blood urea nitrogen were detected. Subsequently, kidney tissue samples were collected from mice in each group. Periodic acid Schiff (PAS) staining was used to assess the injury of renal tubulointerstitium, followed by scoring. Hematoxylin and eosin (HE) staining was applied to detect cell injury in kidney tissues. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was adopted to examine the apoptosis in kidney tissues in mice of each group. Meanwhile, the distribution and expression of p65 in kidney tissues of mice in each group were determined via immunohistochemical staining. Finally, the expression of Toll-like receptor 3 (TLR3)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in kidney tissues of mice in each group was detected using Western blotting.Compared with the Sham group, lncRNA CRNDE level in the kidney of the LPS group was remarkably up-regulated (p0.05). The levels of creatinine and blood urea nitrogen in LPS + CRNDE siRNA group were notably lower than those of the LPS group (p0.05). PAS staining results manifested that renal tubulointerstitial injury in the LPS group was significantly more serious than that of the LPS + CRNDE siRNA group (p0.05). According to HE staining results, serious edema, rupture and necrosis observed in kidney tissue cells of the LPS group. However, after the intervention of CRNDE siRNA, cell edema and necrosis were markedly relieved. In addition, TUNEL staining results indicated that the apoptotic level of kidney tissue cells in the LPS + CRNDE siRNA group was significantly lower than that of the LPS group (p0.05). Subsequent immunofluorescence staining demonstrated that p65 expression in the LPS group increased significantly, which was markedly inhibited by CRNDE siRNA intervention (p0.05). Furthermore, Western blotting displayed that CRNDE siRNA could effectively inhibit the activation of TLR3 and p65 in mouse kidney tissue induced by LPS (p0.05).Inhibition of CRNDE can reduce sepsis-induced KI by blocking the activation of the TLR3/NF-κB pathway. Moreover, CRNDE is expected to become a target for clinical treatment of sepsis-related KI.

Background HannaH (NCT00950300) compared subcutaneous and intravenous trastuzumab (H SC and H IV) as neoadjuvant–adjuvant therapy for HER2-positive breast cancer. The co-primary endpoints of pathological complete response (pCR) and serum trough concentration at predose cycle 8 demonstrated noninferiority between H SC and H IV. Efficacy analyses of event-free survival (EFS) and overall survival (OS) at a median follow-up of 40 months supported this noninferiority. Safety analyses also confirmed the consistency of the safety profile across both arms. In this final follow-up analysis, we report the long-term efficacy and safety outcomes at 5 years of treatment-free follow-up (TFFU; 6 years in total). The correlation between total pCR (tpCR; absence of invasive neoplastic cells in ipsilateral nodes and the breast) and EFS was also explored. Methods Enrolled patients (n=596; pts) were randomized to receive 4 cycles of docetaxel, then 4 cycles of 5-fluorouracil/epirubicin/cyclophosphamide concurrently with 3-weekly fixed-dose 600mg H SC or H IV (loading: 8mg/kg; maintenance: 6mg/kg) in the neoadjuvant setting. Post-surgery, pts received an additional 10 cycles of H SC or H IV in the adjuvant setting to complete 1 year of anti-HER2 therapy. EFS (time from randomization to local, regional, or distant recurrence, contralateral breast cancer, or death) and OS were calculated using the Kaplan-Meier method. Adverse events (AEs) and serious AEs were recorded and graded per standard criteria. Results In total, 297 pts were randomized to the H SC arm and 299 to the H IV arm; 294 and 297 pts were included in the respective efficacy analysis populations. Median duration of follow-up (including TFFU) was 70.8 and 71.4 months in the H SC and H IV arms, respectively. EFS and OS were similar across both study arms (Table 1). Pts who achieved tpCR had longer EFS and OS vs. those who did not (Table 1). Table 1 H SCH IVHazard Ratio (95% CI)6-year EFS, % (95% CI)n=294n=297 Overall65 (59;70)65 (60;71)0.98 (0.74;1.29)tpCR status*tpCRn=102n=90 80 (73;88)83 (75;91) no tpCRn=158n=173 57 (49;65)61 (54;69) 6-year OS, % (95% CI)n=294n=297 Overall84 (79;88)84 (79;88)0.94 (0.61;1.45)* Efficacy per protocol population Cardiac AE incidence was low and consistent across study arms (Table 2). Table 2Pts, n (%)H SC (n=297)H IV (n=298)Any AE290 (98)282 (95)≥ Grade 3 AE158 (53)160 (54)Serious AE65 (22)45 (15)Cardiac AE44 (15)42 (14)LVEF decline (≥10%-points from baseline to Conclusion Long-term efficacy EFS and OS results confirmed the noninferiority of H SC compared with H IV, as demonstrated by pCR and pharmacokinetic endpoints. tpCR was associated with longer EFS and OS. The overall safety profile of H SC was consistent with that of H IV. Citation Format: Jackisch C, Stroyakovskiy D, Pivot X, Ahn J-S, Melichar B, Chen S-C, Meyenberg C, Al-Sakaff N, Heinzmann D, Hegg R. Efficacy and safety of subcutaneous or intravenous trastuzumab in patients with HER2-positive early breast cancer after 5 years' treatment-free follow-up: Final analysis from the phase III, open-label, randomized HannaH study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD3-11.

This letter reports a new method using boron plasma doping and nanosecond laser annealing for further improvement of contact engineering. Up to 8% device performance improvement is demonstrated by using this technique in a conventional FinFET architecture. The key value of this letter relies on the plasma doping of fin vertical sidewalls and the super-activation of dopants, without any volume consumption between the epitaxial source and the drain. Furthermore, the TCAD simulation result points out that combining this method with the wrap-around contact structure can double the boost of transistor performance. We believe that this will bring us a new milestone in ultra-low contact resistance.

In recent years, as a result of the significant development of information and communications technology, people have been paying much attention to automated guided vehicles (AGVs). In the ongoing global coronavirus disease 2019 (COVID-19) pandemic, hospital services have been seriously impacted. In the severe medical situation in hospitals, there is a serious shortage of human resources. This paper presents a novel automated guided vehicle (AGV) for guidance and service. The AGV is comprised of a microcontroller unit (MCU), a power unit, a human sensing unit, a collision warning unit, and a path sensing unit. The motion speed of the AGV and the distance between the AGV and the person being guided are determined by the MCU, the power unit, sensors, and an algorithm. The collision warning unit comprises three ultrasonic sensors and an infrared sensor in the front of the AGV in order to avoid obstacles. The trajectory results of the planned and actual paths are in good agreement. The AGV provides safe and effective guidance for people moving towards their destination. The AGV achieves excellent guidance results and shows great potential for guidance applications in hospitals.

Background For breast cancer (BC) patients with brain metastases (BM) who are not suitable for surgery/radiosurgery, whole brain radiotherapy (WBRT) remained the only standard treatment. Recently, we have demonstrated that bevacizumab preconditioning followed by etoposide and cisplatin (BEEP) is a highly effective treatment for BM of BC progressing from WBRT (Clin Cancer Res. 2015;21(8):1851). The CNS objective response rate is 77.1% according to volumetric criteria, and 60% according to RECIST 1.1. It has been demonstrated that enlarged brain tumor size is a predictor of WBRT failure. We hypothesized that, for BC with BM, induction BEEP treatment could decrease the size of brain metastases and thereby enhance effectiveness of WBRT. Methods This is a Phase II, randomized, open-labelled study (NCT02185352). Key inclusion criteria: BC with measurable brain metastatic tumor who had not received WBRT and not suitable for surgery or radiosurgery; KPS ≥30%. Key exclusion criteria: patients who had leptomeningeal metastases; history of disease progression during prior cisplatin treatment. In the experimental arm, patients will be treated by induction BEEP for three cycles followed by WBRT. In the control arm, patients will receive upfront WBRT for brain metastases. The BEEP regimen consist of bevacizumab (15 mg/kg) on Day 1 and, with a 1 day window period, followed by etoposide (70 mg/m2/day, Day 2 to Day 4) and cisplatin (70 mg/m2, Day 2), in a 21-day cycle. Stratification is based on the Graded Prognostic Assessment (GPA) score. Primary endpoint: brain-specific progression free survival (PFS) according to RECIST 1.1; key secondary endpoint: the 2-month brain-specific objective response rate (BS-ORR) of BEEP alone and WBRT alone. Other secondary endpoints include overall survival, extra-CNS tumor PFS, safety, time-to-improvement of neurological function,brain-specific PFS according to volumetric criteria, and BS-ORR. Approximately 126 patients will be 2:1 randomized. Multi-center recruitment is ongoing. To our knowledge this is the first randomized trial investigating a targeted therapy plus chemotherapy as induction regimen followed by WBRT as first line treatment for BC with BM. Citation Format: Lu Y-S, Tseng L-M, Yu J-C, Rau K-M, Chao T-Y, Chen S-C, Chiu C-F, Chang Y-C, Chen TW-W, Lin C-H, Chang D-Y, Chao T-C, Huang S-M, Huang C-S, Cheng A-L. Randomized phase II study of induction bevacizumab, etoposide and cisplatin followed by whole brain radiotherapy (WBRT) versus WBRT alone in breast cancer with untreated brain metastases (A-PLUS) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-04-03.

Background: TH3RESA was a Phase III randomized study to evaluate the efficacy and safety of trastuzumab emtansine (T-DM1) compared to treatment of physician's choice (TPC) in patients with HER2+ MBC who have progression after at least two regimens of HER2-directed therapy. Population pharmacokinetic (PK) and exposure-response (E-R) analyses were performed to characterize T-DM1 PK as well as E-R relationship for key efficacy and safety endpoints in the population. Methods: Post-hoc analysis based on historical T-DM1 population PK models was performed to assess whether PK is consistent with historical data. E-R analyses with OS and PFS were conducted using Cox proportional hazard (CPH) models with exposure metrics (model-predicted Cycle 1 Cmin and AUCss) included in the model. Logistic regression models were used for binary endpoints of overall response rate (ORR) and key safety endpoints with exposure metrics included as continuous variable only. To supplement the E-R analysis for OS and PFS, case matching analyses were conducted to compare OS and PFS in the lowest exposure quartile (Q1) vs. higher exposure quartiles (Q2-4) to their corresponding matched control. Results: Historical T-DM1 population PK model well described T-DM1 PK in TH3RESA study. In CPH analyses with OS and PFS, hazard ratios (HR) of both efficacy endpoints consistently decreased with increasing T-DM1 exposure. The E-R relationship is supported by case matching analyses, where T-DM1 treated patients were stratified by model-predicted Cycle 1 Cmin. HRs of OS and PFS for patients at Q2−4 versus their matched TPC patients (HR (95%CI): 0.58 (0.44, 0.78) for OS; 0.47 (0.36, 0.62) for PFS) were numerically smaller than that of T-DM1 treated patients at Q1 versus their corresponding matched TPC patients (HR (95%CI): 0.96 (0.63, 1.47) for OS; 0.92 (0.64, 1.32) for PFS). For ORR, an E-R trend was also noted. On the other hand, no E-R relationship was identified with key safety endpoints. HR for Quartile of Cmin Before and After Adjusting for Risk Factors QuartileUnadjusted HR (95% CI)Adjusted HR (95% CI)OSQ11.14 (0.832, 1.55)0.886 (0.64, 1.23) Q20.828 (0.6, 1.14)0.685 (0.493, 0.952) Q30.532 (0.374, 0.757)0.559 (0.391, 0.798) Q40.352 (0.238, 0.521)0.405 (0.272, 0.603)PFSQ10.852 (0.63, 1.15)0.831 (0.614, 1.12) Q20.635 (0.463, 0.872)0.619 (0.451, 0.85) Q30.428 (0.3, 0.609)0.442 (0.31, 0.632) Q40.237 (0.158, 0.357)0.258 (0.171, 0.389) HR for Quartile of AUCss Before and After Adjusting for Risk Factors QuartileUnadjusted HR (95% CI)Adjusted HR (95% CI)OSQ11.07 (0.782, 1.47)0.774 (0.555, 1.08) Q20.651 (0.464, 0.912)0.567 (0.402, 0.801) Q30.662 (0.472, 0.929)0.736 (0.523, 1.04) Q40.406 (0.280, 0.588)0.458 (0.315, 0.667)PFSQ10.69 (0.505, 0.941)0.657 (0.481, 0.897) Q20.66 (0.479, 0.908)0.681 (0.494, 0.940) Q30.524 (0.377, 0.730)0.545 (0.390, 0.760) Q40.235 (0.155, 0.355)0.253 (0.167, 0.383) Conclusion: T-DM1 PK in TH3RESA patient population is similar to historical data. Although an E-R relationship was observed for efficacy, the results need to be interpreted with caution given the potential confounding association between risk factor and PK. No E-R relationship was observed for the safety endpoints examined. Citation Format: Chen S-C, Polhamus D, Riggs M, French J, Wang X, Smitt M, Hoersch S, Strasak A, Chernyukhin N, Quartino A, Jin J, Girish S, Li C. Population pharmacokinetics (PK) and exposure-response (E-R) analysis of trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer (MBC) who have received at least two prior regimens of HER2-directed therapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-26.

To elucidate whether microRNA-7b-5p (miRNA-7b-5p) could inhibit adipose differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs) through regulating IRS2, thereby alleviating the progression of osteoporosis.Expression levels of miRNA-7b-5p and IRS2 in hMSCs at different stages of adipogenic differentiation and osteogenic differentiation were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. After transfection of miRNA-7b-5p mimic or pcDNA-IRS2 in hMSCs, lipid droplet formation in cells was observed by oil red O staining. Expressions of C/EBPα and PPARγ were detected by qRT-PCR and Western blot. The potential target gene of miRNA-7b-5p was predicted by bioinformatics and verified by dual-luciferase reporter gene assay. Finally, expressions of IRS2 in hMSCs transfected with miRNA-7b-5p-NC, miRNA-7b-5p mimic or co-transfected with miRNA-7b-5p mimic and pcDNA-IRS2 were examined.Expressions of miRNA-7b-5p and IRS2 gradually decreased with the prolongation of adipogenic differentiation, but increased during osteogenic differentiation of hMSCs. Transfection of miRNA-7b-5p mimic reduced oil red O staining after adipogenic differentiation and downregulated mRNA and protein levels of C/EBPα and PPARγ. Transfection of pcDNA-IRS2 increased oil red O staining after osteogenic differentiation and upregulated mRNA and protein levels of C/EBPα and PPARγ. Dual-luciferase reporter gene results showed that miRNA-7b-5p could bind to IRS2. Overexpression of IRS2 reversed the downregulated mRNA and protein levels of adipogenic-related genes C/EBPα and PPARγ due to the overexpression of miRNA-7b-5p.MiRNA-7b-5p inhibits the adipogenic differentiation of hMSCs through IRS2, thus alleviating the development of osteoporosis.