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Purpose To evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) heavily pretreated with anthracycline and taxanes. Methods In this single-arm, phase II study, patients with HER2-negative MBC previously treated with anthracycline and taxanes as second- to fifth chemotherapy received PLD (Duomeisu®, generic doxorubicin hydrochloride liposome) 40 mg/m2 every 4 weeks until disease progression, unacceptable toxicity, or completion of six cycles. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), and safety. Results Of 44 enrolled patients (median age, 53.5 years; range, 34–69), 41 and 36 were evaluable for safety and efficacy, respectively. In total, 59.1% (26/44) of patients had ≥ 3 metastatic sites, 86.4% (38/44) had visceral disease, and 63.6% (28/44) had liver metastases. Median PFS was 3.7 months (95% confidence interval [CI] 3.3–4.1) and median OS was 15.0 months (95% CI 12.1–17.9). ORR, DCR, and CBR were 16.7%, 63.9%, and 36.1%, respectively. The most common adverse events (AEs) were leukopenia (53.7%), fatigue (46.3%), and neutropenia (41.5%), with no grade 4/5 AEs. The most common grade 3 AEs were neutropenia (7.3%) and fatigue (4.9%). Patients experienced palmar-plantar-erythrodysesthesia (24.4%, 2.4% grade 3), stomatitis (19.5%, 7.3% grade 2), and alopecia (7.3%). One patient displayed a left ventricular ejection fraction decline of 11.4% from baseline after five cycles of PLD therapy. Conclusion PLD (Duomeisu®) 40 mg/m2 every 4 weeks was effective and well-tolerated in patients with HER2-negative MBC heavily pretreated with anthracycline and taxanes, revealing a potentially viable treatment option for this population. Trial registration Chinese Clinical Trial Registry: ChiCTR1900022568.

Combining the killing ability of chemotherapy drugs on tumor cells with the inhibiting ability of genetic drugs on tumor cell growth, a dual drug delivery system loaded with therapy drugs and siRNA has gradually received more and more research and extensive attention. In this paper, we designed a DNA nano-assembly based on rolling circle amplification that can co-deliver doxorubicin (Dox) and siRNA simultaneously. In order to fully exploit the potential of the dual loading system in cancer treatment, we selected STAT3 gene as a target and used siRNA to target STAT3 of mRNA and reduce the STAT3 expression in mouse melanoma cell line (B16); meanwhile, Dox as a chemotherapy drug was combined with multivalent aptamers specifically targeting B16 to achieve efficient delivery of siRNA and Dox. The results showed that the synergistic delivery system could achieve high efficiency in targeting and inhibiting proliferation in mouse melanoma cells. In addition, the synergistic effect of the dual delivery system on apoptosis of cancer cells was significantly better than that of single drug delivery systems.

DNA nanotechnology is beginning to yield unique advantages in the area of drug delivery. For the dual-targeting and proliferation suppression of cancer cells, a "willow branch" DNA assembly based on rolling circle amplification (RCA) was built. Three single-stranded DNAs, including antibody modified cDNAs, aptamer cDNAs, and simple cDNAs, were employed in the DNA self-assembly, along with the RCA scaffolds (every 63 bases is a repeat unit). "Willow branch" DNA (WB DNA) assembly successfully linked multiple antibodies and aptamers together to achieve dual targeting of cancer cells. Binding of CD44 antibodies and S2.2 aptamers to receptors on the cell membrane inhibits both pathways, β-catenin signaling and nuclear factor-kappa B-specific transcription activity, through feedback regulation. Results demonstrated that WB DNA assembly could effectively exert multivalency clustering cell-surface receptors, modulating signal pathways and inhibiting proliferation. This study proposes a new approach for cancer dual-target and proliferation inhibition by clustering multivalent receptors.

Objective Population-based epidemiological data on left common iliac vein (LCIV) compression is scarce. This study aimed to investigate the prevalence of LCIV compression in an asymptomatic population and patients with left iliofemoral deep vein thrombosis (IF-DVT). Materials and Methods Nonprobability sampling method was used in this multicenter cross-sectional study. The minimum diameter of LCIV and right common iliac vein minimum were measured. The percentage of LCIV compression (LCIV-CP) was calculated. Compression severity (CS) was classified as mild (CP ≤ 50%), moderate (50% < CP ≤ 70%), and severe (CP > 70%). Results In all, 896 subjects constituted the asymptomatic population and 93 patients constituted the IF-DVT population. In the asymptomatic population, LCIV-CP ranged from 1.1% to 89.9% (mean 44.0%), and people with mild, moderate, and severe CS accounted for 62.3%, 28.2%, and 9.5%, respectively. In the IF-DVT population, the mean LCIV-CP was 71.1% (range 42.2%–95.2%), and patients with severe CS accounted for 75.3%. Gender and age differences in LCIV-CP and CS distribution were observed in the asymptomatic population. Females, the young- and middle-aged group had higher LCIV-CPs. In the population with moderate-severe CS, the middle-aged group accounted for a larger proportion. Middle-aged females comprised the highest percentage of patients with moderate or severe CS. Sex and age affected the LCIV-CP and CS distribution. No gender and age differences were observed in the IF-DVT population. Conclusions LCIV compression is common in population. Middle-aged females are the predominant population with moderate-severe compression. Overlapping of LCIV-CP in the asymptomatic and IF-DVT population is significant and other risk factors should be integrated into the consideration when assessing the risk of IF-DVT secondary to LCIV compression.

Background Potato (Solanum tuberosum L.) continuous cropping causes the decrease of tuber yield, deterioration of quality and soil degradation in the semi-arid area. These negative effects can generally be mitigated by legume rotation and mulching. However, little is known about how can mulching and legume rotation alleviate the above damage through altering soil environment. Methods A field experiment was conducted to investigate changes in soil properties and microbial community in response to legume rotation and mulching under six planting patterns: potato continuous cropping without film mulching (PC), potato continuous cropping with film mulching (PCF), potato–broad bean rotation without film mulching (R1), potato–broad bean rotation with film mulching (R1F), potato–pea rotation without film mulching (R2) and potato–pea rotation with film mulching (R2F). Results Compared with the PC, the R1F and R2F had significantly enhanced the contents of alkaline nitrogen (AN), available phosphorus (AP), available potassium (AK), total carbon (TC) and total nitrogen (TN), but reduced soil pH and electrical conductivity (EC). The Shannon index of fungi in R1F and R2 was significantly higher than other treatments. The dominant bacterial and fungal phyla of each treatment was Proteobacteria and Ascomycota. R1, R1F, R2 and R2F enhanced the relative abundance of metabolic fungi and altered key differential microbial species. Soil EC, AN and AK were major factors influencing the soil bacterial and fungal communities. Conclusion Overall, the study demonstrated that potato-broad bean/pea rotation with mulching can be adopted as the preferred cropping systems to alleviate potato continuous cropping obstacles through enhancing soil fertility and regulating soil microbial communities in the semi-arid of Loess Plateau, China. Graphical Abstract

Background Cadmium (Cd) pollution has brought harm to the growth and development of potato. Glutathione (GSH) is an important antioxidant that may play an active role in the response of a potato to Cd stress. However, how GSH influences the effect of Cd on potatoes is unknown. In this study, we investigated the effects of exogenous GSH on the phenylpropanoid biosynthesis pathway and plant hormone signal transduction pathway in potatoes under Cd stress to explore new ideas for how potatoes respond to Cd stress. We cultured 21-day-old 'Atlantic’ plantlets in Murashige and Skoog (MS) medium supplemented with 500 μmol/L CdCl2 or 500 μmol/L CdCl2 + 400 μmol/L GSH. We then investigated the activities of key enzymes in the phenylpropanoid biosynthesis pathway, hormone levels, and the expression levels of related genes at different time points. Results Analysis showed that 96 h of treatment with glutathione led to an increase in the expression levels of genes encoding phenylalanine ammonia-lyase (PAL), cinnamyl alcohol dehydrogenase (CAD) and peroxidase (POD); an increase in the enzymic activities of PAL, CAD and POD; and an increase in the content of lignin. The content of lignin was positively correlated with the expression levels of several genes (PAL: PG0031457, CAD: PG0005359, POD: PG0011640 and PG0015106). In addition, the levels of Salicylic acid (SA) and Jasmonic acid (JA) increased significantly, the expression levels of the genes encoding transcription factor TGA (PG2023696), pathogenesis-related protein 1 (PR1) (PG0005111), and the transcription inhibitor Aux/IAA (PG0006093) all increased while the expression levels of jasmonate ZIM domain-containing protein (JAZ) (PG0004367), auxin influx carrier (AUX) (PG0006550) and auxin response factor (ARF) (PG0005794) all decreased. We also observed a reduction in the content of IAA. Conclusion Exogenous GSH improved the tolerance of potato, Atlantic cv. to Cd stress by regulating the phenylpropanoid biosynthesis pathway and the plant hormone signal transduction pathway. Graphical Abstract

Background The potato (Solanum tuberosum L.) is an important food crop in the alkaline soil area of northwest China. It is abundant in ascorbic acid (vitamin C), which facilitates iron absorption in the body. The large consumption of potato makes it a good food source of iron absorption for human body. However, iron deficiency in alkaline soil regions reduced chlorophyll synthesis in the leaves, resulting in lower photosynthesis and less sugar supply to the plant's healthy organs, significantly restricted crop development and yield, and inflicted major economic losses. Methods In this study, a 2-year (2020–2021) field trial was designed. Under foliar application of five different iron fertilizers: ferric sulfate [(Fe2(SO4)3], T1; ferrous sulfate (FeSO4·7H2O), T2; citric acid/ferric sulfate (CA/Fe2(SO4)3), T3; citric acid/ferrous sulfate (CA/FeSO4·7H2O), T4; ethylenediamine tetra acetic acid (EDTA-Fe·Na), T5, changes in potato plant photosynthesis were compared to no iron fertilization, CK conditions. The effects of various iron fertilizers on the yield, quality, and iron content of potato tubers, their correlations to chlorophyll levels, and the characteristics of photosynthetic fluorescence were studied. Results The results indicated that spraying iron fertilizers increased the yield, quality and Fe content of the tubers, which might be due to the improvement of the plants’ photosynthetic pigment content, gas exchange parameters and chlorophyll fluorescence. In two consecutive years of cultivation, we found that potato tuber yield and Fe content increased in potatoes treated with five iron fertilizer sprays. Among them, tuber yield increased most significantly by T5 and T3 treatments compared to CK, while Fe content was significantly higher by the T5 treatment than by CK and other treatments. Tuber yield was increased by 33.28% and 18.85% in 2020 and 50.74% and 54.48% in 2021 by T5 and T3 treatments, respectively, compared to CK. Fe content was increased by 112.64% and 54.98% in 2020 and 2021 by T5 treatment, respectively, compared to CK. Conclusions EDTA-Fe·Na and CA/Fe2(SO4)3 excelled over the other iron fertilizers. The findings of this study are instructive for developing cost-effective iron fertilizer management systems to maximize the impact of iron biofortification on human health. Graphical Abstract

Purpose To evaluate GT0918, a 2nd-generation AR antagonist, for its AR down-regulation activity among breast cancer patients. Methods The effect of GT0918 on AR protein expression was evaluated in AR expression breast cancer cells and in breast cancer xenograft model. A 3 + 3 phase I dose-escalation study was launched in Peking University Cancer Hospital. The endpoints included dose finding, safety, pharmacokinetics, and antitumor activity. Results GT0918 was demonstrated to effectively suppress the expression of AR protein and the growth of AR-positive breast cancer tumors in mouse xenograft tumor models. All patients treated with GT0918 were at a QD dose-escalation of five dose levels from 100 to 500 mg. The most common treatment-related AEs of any grade were asthenia, anemia, decreased appetite, increased blood cholesterol, increased blood triglycerides, decreased white blood cell count, and increased low-density lipoprotein. Grade 3 AEs were fatigue (2 of 18, 11.1%), aspartate aminotransferase increase (1 of 18, 5.6%), alanine aminotransferase increase (1 of 18, 5.6%), and neutrophil count decrease (1 of 18, 5.6%). Clinical benefit rate (CBR) in 16 weeks was 23.1% (3/13). Among 7 AR-positive patients, 6 can evaluate efficacy, and 2 completed 23.5- and 25-cycle treatment, respectively (as of 2020/1/20). PK parameters showed a fast absorption profile of GT0918 in the single-dose study. GT0918 and its major metabolite reached steady-state serum concentration levels at day 21 after multiple dosing. Conclusion GT0918 can effectively inhibit AR-positive breast cancer tumor growth. GT0918 was demonstrated well tolerated with a favorable PK profile. The suitable dose of GT0918 was 500 mg QD and may provide clinical benefits for AR-positive mBC.

The first-principles method of density functional theory (DFT) is used to study the structural stability and electrochemical properties of B doped graphene with concentrations of 3.125%, 6.25% and 18.75% respectively, and their lithium storage mechanism and characteristics are further studied. The results show that the doped systems all have negative adsorption energy, indicating that the structures can exist stably, and the adsorption energy of lithium ions on graphene decreases with the increase of B doping concentration. Among them, the B

This study aimed to examine the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and other clinicopathological features in HER2+ MBC patients who received first-line anti-HER2 therapy. A total of 129 patients were assigned to NLR-low and NLR-high groups based on a cutoff value of 3.0 at baseline. Peripheral blood lymphocyte subsets and gene mutations in circulating tumor DNA were analyzed by flow cytometry and Next-generation sequencing, respectively. Survival was evaluated by the Kaplan–Meier method and Cox regression analysis. Of the 129 patients, 77 and 52 were assigned to the NLR-low (≤3) and NLR-high (>3) groups, respectively. Compared with NLR-high patients, the NLR-low patients had significantly longer median progression-free survival (PFS) (11.7 vs. 7.7 months) (p = 0.001, HR = 2.703 95% CI 1.543–4.736 and overall survival (OS) (37.4 vs. 28.7 months) (p = 0.044, HR = 2.254 95% CI 1.024–4.924). Furthermore, this association was independent of metastatic sites or estrogen receptor status. Peripheral blood CD3+ (p = 0.034) and CD4+ (p = 0.010) T cell numbers were significantly higher in the NLR-low group than the NLR-high group. The mutational profile of MBC was generally similar between the two groups. Baseline NLR was a prognostic factor of PFS and OS for patients with HER2+ MBC in the first-line setting. These results may facilitate the selection of patients who will benefit most from anti-HER2 treatment.

The manufacture of large-scale and highly ordered fluorescent assemblies has received more and more scientific attention in recent years. An ingenious and low-cost strategy for constructing large-scale DNA nanoarrays by rolling circle amplification (RCA) and a simplified DNA origami technique is proposed in this study. Thrombins are used to trigger the excitation of the fluorescent groups modified on the aptamer staple strands of nanoladders, which leads to the delicate construction of millimeter large-scale fluorescent nanoarrays, whose fluorescence intensity could be effectively regulated by the concentration of thrombin. The above fluorescent nanoarrays will generate a potential application value in the fields of biosensors, super-resolution imaging, and novel light-emitting devices.

Background: Androgen receptor (AR) blocker has become an increased interest in the treatment of BC, in which about 60-80% patients showed AR positive. However, currently no AR blocker has been approved in mBC. GT0918 is a new chemical entity of AR blocker with possible AR down-regulation. This study is an open-label, single-center, dose escalation phase I trial to assess GT0918 in mBC female patients who have progressed after systemic treatments in China. The primary objectives are to identify the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs). The secondary objectives are to assess pharmacokinetics and pharmacodynamics of GT0918 with single and multiple dosage applications. (CTR20170757) Methods: Patients (pts) with historically confirmed mBC who had progressed after either chemotherapy, hormonal or targeted therapy, or could not tolerate currently standard therapies were eligible. With the starting dose at 100 mg of GT0918, the decision of dose escalation in the 3+3 design was based on the safety and tolerability assessments. GT0918 was administered orally once, followed by a 7-day off-treatment period for single dose PK analysis of drug elimination. Then GT0918 oral administration was resumed once daily for 28 consecutive days and multiple dose PK analysis was assessed at the end of first cycle (28 days). The first 28-days on treatment (cycle 1) was defined as DLT period. Pts manifesting an objective response or stable disease and likely to have clinical benefit from continued treatment were continued on GT0918 thereafter until they experienced one of following events of intolerable toxicities, disease progression or withdrew consent. Results: 18 pts were enrolled and treated with GT0918 since 9/6/2017 as defined in protocol at five dose levels: 100 mg (n = 3), 200 mg (n = 4), 300 mg (n = 4), 400 mg (n = 4) and 500 mg (n = 3) (as to 7/2/2019). All pts progressed more than two lines of therapies with 83.3% (15/18) pts were treated ≥3rd lines. Out of 6 confirmed AR positive pts, two (33.3%) at 300 mg cohort had finished 17 and 19 cycles individually and continue treatment (as 7/2/19). No DLT was observed and MTD has not been reached. GT0918 related adverse events (AEs) were grade 1 or 2 as per CTCAE v4.03, including fatigue, hypertriglyceridemia, anemia, hypercholesterolemia, increased LDL, nausea, loss of appetite, increased ALT, increase of weight loss, constipation and thrombocytopenia. PK profile analysis showed that in the single-dose study, GT0918 showed a fast absorption profile. In the multiple-dose study, the steady-state serum concentration level of GT0918 and its main metabolite were attained at 21 days. Conclusions: Proxalutamide (GT0918) administrated orally once a day is well tolerated in late-stage pts. No DLT has occurred at maximum dose 500 mg. Pts with AR positive biomarker could have better clinical outcomes with GT0918 treatment. GT0918 and its main metabolite exhibited a nonlinear pharmacokinetic profile over the dose range from 100mg to 500 mg. An expanded/phase Ib in AR positive mBC pts has launched in China to evaluate the anti-tumor activity and safety of GT0918. 200 mg and 300 mg were selected for dose expansion. Citation Format: Huiping Li, Ran Ran, Guohong Song, Hanfang Jiang, Ruyan Zhang, Yaxin Liu, Luping Meng, Phoebe Zhang, Ke Chen, Qiaoxia Zhou, Karl Zhou, Youzhi Tong. Evaluation of safety, pharmacokinetics and pharmacodynamics of proxalutamide (GT0918), a potent androgen receptor (AR) blocker, in patients with metastatic breast cancer (mBC): Phase I dose escalation trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-17-05.

Background: Angiogenesis is a key mechanism of tumour growth. Apatinib is an oral tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor 2 (VEGFR-2) and blocks downstream signalling and inhibiting tumour angiogenesis. It was approved in China to treat gastric cancer in October 2014. However, as breast cancer with a chest wall metastasis (CWM) has rich vascular distribution, whether Apatinib is also effective for breast cancer with a chest wall metastasis remains unknown. Therefore, we designed this clinical study to address this question. Method: The trial involved four centres in China from September 2016 to July 2019. It enrolled patients (pts) who were diagnosed of HER2 negative breast cancer with CWM and experienced first line or could not afford standard treatment. The patients were given Apatinib 500mg/day (single or combined with endocrine therapy if hormone receptor positive (HR+)) until progression or side effect not tolerated. Each patient had at least one measurable lesion according to Response Evaluation Criteria in Solid Tumours (RECIST), version 1.1.This study was approved by ethics committee at the Ethics Committee of Beijing Cancer Hospital, and all participants provided written informed consent. The trial was also Register to clinicaltrial.gov ( NCT02878057). Results: 30 pts were enrolled in the study with a median age of 50 (range 35-69) years old. Among the 30 pts, there were 23 ER positive pts (76.7%). 17 pts (56.7%) had more than 2 sites of metastasis, and 5 pts had invasive metastasis (16.6%). 15 pts (50%) were multi pre-treated. The response of 19 pts (63.3%) could be evaluated, and the overall response rate was 57.9% (no CR, 11 cases reached PR, 2 in HR-, 9 in HR+). and the median PFS was 8.6 months (range 0.5-29.5; 95% CI 0.0-18.7). The tumour in chest wall shrunk obviously. Side effects also existed. 15 pts (50%) had hypertension (grade 3: 6.7%); 10 pts (33.3%) had proteinuria (grade 3: 20%); 4 pts (13.3%) had fatigue (grade 3: 3.3%); 3 pts (10%) had bilirubin increase (grade 3: 6.7%). 8 pts discontinued the treatment due to side effects and 3 due to personal reasons. The Apatinib dose was reduced from 500mg to 250mg for most pts 18/30 (60%), and some pts took 500 mg and 250 mg every other day 10/30 (33.3). Conclusion: Apatinib was effective for pts with chest wall metastasis and pts could benefit from longer PFS. However, the side effects should be pay more attention from start on apatinib treatment. Citation Format: Huiping Li, Cuizhi Geng, Guohong Song, Hanfang Jiang, Zhongshen Tong, Junlan Yang, Ran Ran, Ruyan Zhang, Yaxin Liu, Xinyu Gui, Maorong Wei, Lu Xue. Apatinib in the treatment of HER-2 negative advanced breast cancer with chest wall metastasis multicenter phase II clinical study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-40.

Background: Fulvestrant 500mg has been proved better efficacy in breast cancer with hormone receptor positive (HR+),and then become an optional strategy for primary or second line treatment of HR+ positive metastasis breast cancer (MBC). Methods: In this real world study, we retrospectively analyzed the patients with HR+ HER 2 negative MBC who received fulvestrant 500mg treatment at Beijing cancer hospital during January 2015 to December 2018. Clinical benefit rate (CBR), progression free survival (PFS), overall survival (OS) and adverse events were investigated. Results: There were 306 patients enrolled, median age was 48.7(range 20-75) years, median line of fulvestrant was 2.11(range 1-6), 68.3%(209/306) patients were involved with visceral metastasis. The CBR was 68.6%, median PFS was 8.41m (95%CI: 7.079m-9.743m, range 0.89m-80.16m). Among the patients received fulvestrant at the first line, the PFS was 10.55m(95%CI:6.46m-14.64m, range 0.92m-34.3m). The median OS hasn’t been obtained. In subgroup analysis, the patients without liver metastasis(12.49m vs. 4.60m, p4, 12.65m vs. 7.72m vs. 3.98m respectively, p2 lines, 14.06m vs. 7.79m vs. 3.52m respectively, p Conclusions: Fulvestrant was an effective and safe regimen in endocrine therapy for hormone receptor positive HER2 negative MBC. The patients who were in first line treatment, absence of liver metastasis and small tumor burden might be more benefit from fulvestrant. Corresponding authors: Huiping Li, huipingli2012@hotmail.com; Guohong Song, songguohong918@hotmail.com, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Rd, Beijing 100142, China Citation Format: Wen Lei, Huiping Li, Guohong Song, Ruyan Zhang, Ran Ran, Ying Yan. Efficacy observation of 306 patients with fulvestrant 500mg treatment in hormone-receptor positive HER2 negative metastasis breast cancer, a real world study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-11-20.

Background: Fulvestrant 500mg has proved its clinical effectiveness in previous trials as primary or second line treatment of hormone receptor positive, human epidermal receptor 2 negative (HR+/HER2˗) post-menopausal advanced breast cancer. This real-world study aimed to investigate the efficacy and safety of Fulvestrant in HR+/HER2˗ Chinese advanced breast cancer patients. Method: HR+/HER2˗ advanced breast cancer patients who received Fulvestrant 500mg from January 2015 to December 2018 in Beijing Cancer Hospital were enrolled in this retrospective study. Progression free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS) and adverse events (AEs) of Fulvestrant were investigated. Result: In total 303 enrolled patients [median age was 51 years (range: 21-82)], 255 (84.2%) patients were at postmenopausal status at the start of Fulvestrant treatment and 264 patients (87.1%) had advanced breast cancer. The median PFS (95% confidence interval) was 14.1 months (10.1-18.0) for the first-line, 11.2 months (2.2-20.3) for the second-line and 6.7 months (4.8-8.5) for ≥third-line of Fulvestrant. The ORR and CBR were 3.8% and 86.8% for the first-line, 5.5% and 75.4% for the second-line, 1.1% and 61.1% for ≥third-line of Fulvestrant. The multivariate subgroup analyses showed, PFS was significantly longer for the patients with light tumor burden, less palliative chemotherapy before Fulvestrant and long disease-free interval. For patients receiving Fulvestrant after palliative chemotherapy, the median PFS was numerically greater in maintenance treatment group than those who progressed after chemotherapy. Only 5.0% of patients (15/303) experienced adverse events and majority were grade 1-2. The most common adverse event was headache and palpitation, with merely one patient had severe adverse event (pulmonary embolism). Conclusion: Fulvestrant is an effective, safe and well-tolerated treatment regimen in endocrine therapy for HR+/HER2˗ metastatic breast cancer. Light tumor burden, less palliative chemotherapy before Fulvestrant and long disease-free survival (DFS) might be the ideal condition of Fulvestrant treatment. Fulvestrant can be effective for premenopausal patients with drug-induced menopause. Patients of different luminal subtypes can benefit from Fulvestrant. For patients with visceral metastases, presence of liver metastases rather than lung metastases was poor prognostic factor. Fulvestrant may also be considered as a maintenance treatment after first-line palliative chemotherapy.

Background. Due to extended life expectancy and recent improvements in surgical techniques, limb salvage has replaced amputation as the gold standard and is now performed in 90–95% of upper extremity malignancies. However, many of these salvage procedures are associated with significant postsurgical complications. In particular, the clavicula pro humero (CPH) procedure is associated with high rates of nonunion. We present our experience with upper extremity salvage using the free vascularized fibular flap (VFF) after failure or nonunion of the original CPH procedure in the pediatric population. Methods. Five patients under the age of 18 diagnosed with upper extremity sarcoma who underwent tumor resection with immediate CPH reconstruction complicated with nonunion, and subsequent revision with free VFF were included. Data on patient demographics, oncologic characteristics, surgical procedures, intraoperative details, postoperative complications, and time to graft union were recorded. Results. Five patients (average age = 8.4 years; range = 5–10 years at surgery date) underwent secondary limb salvage procedure with free VFF reconstruction following failed CPH reconstruction for proximal humeral osteosarcoma (n = 4) or Ewing sarcoma (n = 1). The mean follow-up was 3.7 years. Complications occurred in five patients (100%), with three patients requiring reoperation (60%). Four patients achieved graft union (average union time = 3.7 months) and successful limb reconstruction. Four patients were alive with no local recurrence of the disease. One patient did not achieve union and was lost to follow-up. Conclusion. Primary bone tumors in the pediatric population require wide surgical resection, and reconstruction often has high complication rates that can warrant further procedures. A free VFF is a viable option for upper extremity salvage after previously failed reconstructions because it provides vascularized tissue to a scarred tissue bed and allows for the replacement or augmentation of large bony defects.

BACKGROUND Preoperative risk assessment is essential in determining which surgical candidates will have the most to gain from an operation. The 5-item modified frailty index (mFI-5) has been validated as an effective way to determine this risk. This study sought to evaluate the performance of the mFI-5 as a predictor of postoperative complications after tissue expander placement. METHODS Patients who underwent placement of a tissue expander were identified using the 2012 to 2018 American College of Surgeons National Surgical Quality Improvement Project database. Univariate and multivariate regression analysis models were used to assess how mFI-5, the components of the mFI-5 (functional status, diabetes, chronic obstructive pulmonary disease, chronic heart failure, and hypertension), and other factors commonly used to risk stratify (age, body mass index [BMI], American Society of Anesthesiologists (ASA) classification, and history of smoking) were associated with complications. RESULTS In 44,728 tissue expander placement cases, the overall complication rate was 10.5% (n = 4674). The mFI-5 score was significantly higher in the group that experienced complications (0.08 vs 0.06, P < 0.001). Compared with the mFI-5 individual components and other common variables used preoperatively to risk stratify patients, univariate analysis demonstrated that mFI-5 had the largest effect size (odds ratio [OR], 5.46; confidence interval [CI], 4.29-6.94; P < 0.001). After controlling for age, BMI, ASA classification, and history of smoking, the mFI-5 still remained the predictor of complications with the largest effect size (OR, 2.25; CI, 1.70-2.97; P < 0.001). In assessing specific complications, the mFI-5 is the independent predictor with the largest significant effect size for surgical dehiscence (OR, 12.76; CI, 5.58-28.18; P < 0.001), surgical site infection (OR, 6.68; CI, 4.53-9.78; P < 0.001), reoperation (OR, 5.23; CI, 3.90-6.99; P < 0.001), and readmission (OR, 4.59; CI, 3.25-6.45; P < 0.001) when compared with age, BMI, ASA class, and/or history of smoking alone. CONCLUSIONS The mFI-5 can be used as an effective preoperative predictor of postoperative complications in patients undergoing tissue expander placement. Not only does it have the largest effect size compared with other historical perioperative risk factors, it is more predictive than each of its individual components.

Understanding the social attributes of urban residents, such as occupations, settlement characteristics etc., has important significance in social research, public policy formulation and business. Most of the current methods for obtaining people’s social attributes by analyzing of social networks cannot reflect the relationship between the occupational characteristics and their daily movements. However, the current methods of using spatio-temporal data analysis are limited by the characteristics of the samples, and focus more on travel patterns and arrival time predictions. Based on coarse-grained CDR (Call Detail Record) data, this paper proposes an approach to infer occupation attribute by analyzing the travel patterns of personnel and incorporating more enhanced information. Finally we uses the CDR data of 6 million people to analyze and extract two types of people: college students in Beijing and urban hummingbirds and the F1 score of our proposed model is more than 0.95.

e13050 Background: This study was to compare the efficacy and safety of different nab-paclitaxel dose schedule in patients with HER-2 negative recurrent/metastatic breast cancer in order to find a more suitable treatment option for Chinese patients. Methods: This is a single-center, open-label, randomized, phase II trial. Eligible female patients with HER-2 negative recurrent/metastatic breast cancer and up to 2 lines of prior chemotherapy regardless of any endocrine therapy were randomly assigned (1:1) to either nab-paclitaxel (125mg/m2 IV days 1, 8, every 21 days, 3-week group) or nab-paclitaxel (125mg/m2 IV days 1, 8, 15, every 28 days, 4-week group) until progressive disease or completion of 6-8 cycles of treatment. After completing 6-8 cycles, if the efficacy evaluation is CR, PR or SD, the investigator can decide whether to carry out maintenance therapy. The primary endpoint is PFS. Secondary endpoints are ORR, OS and safety. Results: Between March 2019 and July 2021, 104 patients with HER-2 negative breast cancer were randomly assigned to treatment (3-week group, n = 51; 4-week group, n = 53). Median follow-up was 16.4 and 15.8 months. In the 3-week and 4-week groups, respectively, 39 (76.5%) and 42 (79.2%) patients had HR positive disease and 37 (72.5%) and 43 (81.1%) patients had visceral metastasis. In two groups, respectively, 30 (58.8%) and 20 (37.7%) patients didn’t receive prior endocrine therapy. 20 (39.2%) and 32 (60.4%) patients had received 1 to 3 lines of prior endocrine therapy. 30 (58.8%) patients of 3-week group and 30 (56.6%) patients of 4-week group were enrolled at first-line chemotherapy, and 13 (25.5%) of 3-week group patients and 16 (30.2%) patients of 4-week group were enrolled at second-line chemotherapy, as third-line chemotherapy there were only 8 (15.7%) in 3-week group and 7 (13.2%) in 4-week group. Among all patients, 33 (64.7%) in the 3-week group and 16 (30.2%) in the 4-week group had received 6-8 cycles according to the regimen of study, and 32 (97.0%) of 3-week group and 15 (93.8%) of 4-week group patients who finished the regimen choose to receive maintenance treatment (endocrine or chemotherapy).In two groups, respectively, median PFS was 9.6 months and 7.5 months (HR 0.905; 95%CI 0.569-1.440) and ORR were 50.0% (23/46) and 46.9% (23/49) in the evaluable population. Median OS was 22.5 months in the 3-week group and has not yet been reached for the 4-week group. According to NCI-CTCAE V5.0, 3-week group vs 4-week group respectively, the grade 3-4 adverse events (≥2 patients) were neutropenia (13.7% vs 34.0%), leukopenia (7.8% vs 17.0%) and peripheral neurotoxicity (0 vs 3.8%). Conclusions: Preliminary results suggest that compared with the 4-week regimen, the 3-week regimen of nab-paclitaxel seems to be more suitable and adaptable for Chinese patients with advanced breast cancer. This study is still in follow-up and updated data will be presented. Clinical trial information: NCT04192331.

The cerebellar posterior vermis generates an estimation of our motion (translation) and orientation (tilt) in space using cues originating from semicircular canals and otolith organs. Theoretical work has laid out the basic computations necessary for this signal transformation, but details on the cellular loci and mechanisms responsible are lacking. Using a multicomponent modeling approach, we show that canal and otolith information are spatially and temporally matched in mouse posterior vermis Purkinje cells and that Purkinje cell responses combine translation and tilt information. Purkinje cell-specific inhibition of protein kinase C decreased and phase-shifted the translation component of Purkinje cell responses, but did not affect the tilt component. Our findings suggest that translation and tilt signals reach Purkinje cells via separate information pathways and that protein kinase C-dependent mechanisms regulate translation information processing in cerebellar cortex output neurons.

Background The role of peripheral blood lymphocyte (pBL) in breast cancer has long been studied. However, the predictive role of pBL in advanced breast cancer (ABC) is poorly understood. Methods A total of 303 patients with ABC were consecutively recruited at our center between January 2015 and September 2019. At baseline, pBL subtypes were detected in all patients with 229 blood samples available for circulating tumor DNA (ctDNA) detection. pBL was analyzed through flow cytometry. ctDNA-based gene mutations were detected using next generation sequencing. The cutoff value of pCTL was estimated by X-tile software. Progression free survival (PFS) was estimated by Kaplan-Meier curve and Cox hazard proportion regression model, with difference detection by log-rank test. Results Median follow-up time of the study was 21.0 months. The median age of diagnosis was 52.0 years. Among the pBL subtypes, only pCTL level was found predictive for PFS in the HER2+ patients whom received anti-HER2 therapy (13.1 vs. 5.6 months, P = 0.001). However, the predictive role of pCTL was not found in HR-positive (P = 0.716) and TNBC (P = 0.202). pCTL high associated with suppressive immune indictors including lower CD4/CD8 ratio (P = 0.004) and high level of Treg cell (P = 0.004). High occurrence of FGFR1 amplification which has been reported as immune suppressor was also found in HER2+ patients with pCTL high (22.2% vs. 4.3%, P = 0.048). Conclusions Higher pCTLs level associated with shorter PFS and FGFR1 mutation in HER2+ ABC patients., Highlights • High pCTL level predicts shorter first-line PFS in HER2+ patients receiving anti-HER2 based regimens. • The predictive role of pCTL level found in HER2+ patients was not applicable in HR+ and TNBC patients. • High level of pCTL was associated with immunosuppressive status and FGFR1 mutations in HER2+ breast cancer patients.

BACKGROUD: Women with unilateral breast cancer are at increased risk for developing contralateral disease. The objective of the single-center retrospective study was to evaluate the incidence of bilateral breast cancer (BBC) and to analyze the clinicopathological characteristics for BBC in China. METHODS: We retrospectively reviewed the electronic medical records of 3924 female patients with breast cancer consecutively treated at the department of Breast Oncology in the Peking University Cancer Hospital between 2006 and 2016. BBC was categorized as synchronous (within 6 months) or metachronous bilateral breast cancer (after 6 months of a first tumor). Patients with BBC were identified according to the criteria described by Chaudary et al. Patients with stage IV first breast cancer, and those who were found to have distant metastases between the first and second primary breast cancer were excluded. Analyses of demographic, clinicopathologic, and treatment characteristics were done between sBBC and mBBC. RESULTS: The incidence of BBC in our population was 3.2% (127 of 3924). Of those, 2.5 % ( 99 of 3924) were metachronous bilateral breast cancer ( mBBC ), and 0.71 % (28 of 3924) were synchronous bilateral breast cancer ( sBBC ). The overall median age of the patients at first diagnosis was 45 years (range, 27-81 years). The age of onset of the first mBBC was significantly younger than that of sBBC ( p = 0.027). In mBBC subgroups, the median time interval between first and second tumors was 68 months (range, 7-342 months), and 80.8% of the second tumor were diagnosed within 10 years of the diagnosis of the first tumor. A positive family history of breast cancer was found in 25% of sBBC and 9.1% of mBBC ( p = 0.025). In ER-negative first tumor of mBBC, 56.1% of the second tumor were ER-positive. Mastectomy was the commonest surgery performed in these patients. CONCLUSIONS: Our results confirmed the necessity of screening contralateral breast at the diagnosis of unilateral breast cancer and following-up for Chinese patients with breast cancer. Citation Format: Li H, Jiang H, Zhang R, Shao B, Yan Y, Ran R, Di L. Bilateral breast cancer in China: A 10-year single-center retrospective 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 P3-10-13.

Objective Triple-negative breast cancer (TNBC) is a heterogeneous disease with poor prognosis. Circulating tumor cells (CTCs) are a promising predictor for breast cancer prognoses but their reliability regarding progression-free survival (PFS) is controversial. We aim to verify their predictive value in TNBC. Methods In present prospective cohort study, we used the Pep@MNPs method to enumerate CTCs in baseline blood samples from 75 patients with TNBC (taken at inclusion in this study) and analyzed correlations between CTC numbers and outcomes and other clinical parameters. Results Median PFS was 6.0 (range: 1.0-25.0) months for the entire cohort, in whom we found no correlations between baseline CTC status and initial tumor stage (P=0.167), tumor grade (P=0.783) or histological type (P=0.084). However, among those getting first-line treatment, baseline CTC status was positively correlated with ratio of peripheral natural killer (NK) cells (P=0.032), presence of lung metastasis (P=0.034) and number of visceral metastatic site (P=0.037). Baseline CTC status was predictive for PFS in first-line TNBC (P=0.033), but not for the cohort as a whole (P=0.118). This prognostic limitation of CTC could be ameliorated by combining CTC and NK cell enumeration (P=0.049). Conclusions Baseline CTC status was predictive of lung metastasis, peripheral NK cell ratio and PFS in TNBC patients undergoing first-line treatment. We have developed a combined CTC-NK enumeration strategy that allows us to predict PFS in TNBC without any preconditions.

Potato dry rot (PDR), caused by Fusarium sulphureum (F. sulphureum) is a serious storage disease and can cause post-harvest rotting and seed piece decay after planting. Physiological and dynamic transcriptome analyses were detected in two PDR-resistant varieties (LS and Atl) to explore the resistant mechanism of potato. The phenylalanine ammonia lyase (PAL) and lignin content rapidly increased after infection at 0.5, 1, 2, 4, 8, 16 days post inoculation (dpi). Meanwhile, the common up-regulated differentially expressed genes (DEGs) were 1025, 1334 and 1394 in LS and Atl at 1, 3, 7 dpi (vs 0 dpi), respectively. STEM (Short Time-series Expression Miner software) and KEGG enrichment analysis revealed that “lignin synthesis-related pathways” and “MAPK signaling pathway-plant” were significantly enriched in the two varieties. The high expressions of PAL, 4CL, CAD and POD genes promoted the synthesis of lignin in the downstream of the pathway, which was filled to the secondary cell wall to increase the resistance to PDR. In addition, FLS2 gene perceived F. sulphureum infection to initiate MAPK cascades signal transduction, and subsequently up-regulated PR1 defensive genes to respond to pathogen attack. These novel findings elucidate the mechanism of dry rot at the transcriptomic level for the first time, and also provide candidate genes for molecular assisted screening and breeding of resistance to PDR.

Aim We aimed to clarify tumor features and prognosis of pregnancy‐associated breast cancer (PABC) among Chinese women. Methods PABC was defined as breast cancer diagnosed during pregnancy or within a year after delivery. Patients with PABC were selected from breast cancer cases of women ≤45 years treated at our institution between December 2012 and December 2017, and one non‐PABC control was matched for stage, age, and year of diagnosis for each case. Results Forty‐one women with PABC were identified (22 diagnosed during pregnancy and 19 within 1 year of delivery). There were significantly more progesterone receptor (PR)‐ and triple‐negative tumors in the PABC (56.1% and 24.4%, respectively) than in the non‐PABC group (31.7% and 4.9%, respectively) (P = .045 and .026, respectively). Human epidermal growth factor receptor 2 positivity was the same in both groups (31.7%). Median disease‐free survival (DFS) was 29.0 months (95% confidence interval [CI], 6.5‐51.5 months) in the PABC and 40.9 months (95% CI, 22.8‐58.8 months) in the non‐PABC group (P = .167). Median overall survival (OS) was 82.8 months in the PABC (95% CI, 39.3‐126.5 months) versus 80.1 months (95% CI, 56.7‐103.6 months) in the non‐PABC group (P = .131). Conclusion Histological features were similar in both groups, except that PR‐ and triple‐negative tumors were more frequent in the PABC group. Survival analyses show similar OS for patients with PABC and non‐PABC. DFS tended to be shorter in the PABC group; however, this difference was not statistically significant., After matching PABC cases with non‐PABC cases for stage and age (±1 year), as well as year of diagnosis secondarily (±1 year),on survival analysis, the median DFS tended to be shorter in women with PABC than in non‐PABC; however, this difference was not statistically significant and the median OS of the two groups were almost the same.

Paclitaxel (T) plus gemcitabine (G) is an active concomitant combination for the treatment of metastatic breast cancer (MBC). However, the efficacy of sequential administration of these two drugs is unclear. This randomized phase II study was conducted to evaluate the efficacy of T and G administered either as a concomitant or as a sequential regimen in patients with MBC.Patients with MBC (n=66) were randomized to either receive 6 cycles of concomitant T and G or 4 cycles of T followed by 4 cycles of G, as first line chemotherapy. With no progression, the arms would switch to maintenance with paclitaxel. Progression free survival (PFS) was defined as the primary endpoint; secondary endpoints were the overall response rate (ORR), overall survival (OS), and toxicity. In total, 33 patients were randomized to the concomitant or sequential arms. Patient characteristics were well balanced. The median number of chemotherapy cycles was 6 for the concomitant arm and 8 for the sequential arm.No significant difference was observed in terms of PFS, ORR, and OS. Only 13 (39.4%) patients progressed in the sequential arm. Although there was no significant difference between the two arms (p=0.056),the sequential arm had a remarkable trend of longer PFS than the concomitant arm. Toxicities were manageable and similar in both arms.The incidence of neutropenia was significantly higher in the concomitant arm (90.9%) than in the sequential arm (60.6%). Grade 3 or 4 neutropenia was not significantly different between the two arms.Concomitant and sequential treatment with paclitaxel and gemcitabine had no significant difference in terms of PFS.

1019 Background: Androgen receptor (AR) is an emerging prognostic marker and therapeutic target in breast cancer. AR is expressed in 60% to 80% of breast cancers. Recent studies have shown the association between AR signaling and tumor carcinogenesis in breast cancer, suggesting AR pathway as a potential target for breast cancer treatment. However, no AR targeting therapies have been approved for treating breast cancer. GT0918 is a new chemical entity of AR antagonist with possible AR down-regulation. We had finished the phase I study and submitted the paper. Here we present a multicenter, open-label phase Ib trial assessing the safety and efficacy of GT0918 in women with AR positive metastatic breast cancer. The primary objective is to evaluate the efficacy of GT0918. The secondary objectives are to assess its safety and to explore the relevant biomarkers. Methods: This is an expansion study of a phase I dose-escalation trial. In this phase Ib study, only patients with AR positive metastatic breast cancer were enrolled. All eligibled patients would take GT0918 orally once a day, of a 28 -day cycle. After 2 cycles’ safety and tolerability assessment, patients could choose to continue their treatment until they experience disease progression, intolerable toxicities, death, or withdrew consent. The primary efficacy endpoints were 8-week disease control rate (DCR) and 16-week DCR. The secondary efficacy endpoint was progression free survival (PFS). Results: In total, 45 patients were enrolled in the study at 200mg (n = 30) and 300mg (n = 15) doses. The most common (≥10%) treatment-related adverse events (AEs) were asthenia (42.2%), aspartate aminotransferase increased (26.7%), blood cholesterol increased(17.8%), alanine aminotransferase increased (17.8%), decreased appetite (17.8%), blood triglycerides increased (13.3%), blood lactate dehydrogenase increased (13.3%), anaemia (13.3%), blood alkaline phosphatase increased (11.1%), gamma-glutamyltransferase increased (11.1%), urinary tract infection (11.1%). Grade 3/4 AEs were reported in 9 patients (20%). No treatment-related deaths occurred. The 8-week and 16-week DCR were both 22.2% (n = 10) (95% CI 10.08%, 34.37%). The median PFS was 1.8 months (95% CI 1.8, 1.9) in all patients. 12 out of 45 (26.7%) were triple negative breast cancer cases. The median PFS was 1.9 months (95% CI 1.7, 9.1), 4 out of 12 patients (33.3%) > 6 months, 2 out of 12 patients (16.7%) > 9 months. Conclusions: GT0918 has been shown to be well tolerated and may provide potential clinical benefits to AR positive metastatic breast cancer patients. This study demonstrated triple negative in AR positive patients had more benefit. Clinical trial information: NCT04103853 .

In recent years, as the development of environment science, new demands are needed for the cultivation of environmental protection talents. The improvement of scientific literacy has become an urgent need in the cultivation of undergraduate students major in environmental science and engineering. A good talent training model can promote the output of environmental protection talents and support the future environmental construction. In this paper, authors introduced the settings and practice of “Environmental Microbiology Practice” (EMP) in Miami College of Henan University. The teaching group of Miami College believed that EMP is the most suitable teaching link to help undergraduates understand the frontiers of the subject and improve scientific research thinking and did a series of reforms on the EMP course around (1) Current microbiological industry practice; (2) Frontier expansion of environmental microbiology; (3) Cultivation of scientific literacy. Combined with the students’ achievements and a questionnaire, the effectiveness of EMP has also been analyzed. By analyzing the practice of EMP in Miami College, this study provided an effective way for the improvement of scientific literacy and quality of undergraduate students. This cultivation idea and method is also of great significance for the cultivation of reserve talents of environmental protection who meet the needs of environmental scientific research and environmental protection in the new era.

Background The impact of pregnancy on clinico-pathological features and prognosis of breast cancer remains controversial.We aimed to evaluate the impact of the association of pregnancy with breast cancer on tumor feature and prognosis- overall survival (OS) and disease free survival (DFS). Methods We defined Pregnancy Associated Breast Cancer (PABC) as breast cancer diagnosed during pregnancy or within a year following delivery. We enrolled PABC patients(pts) treated at our institution between December 2012 and December 2017 , and for each case, one non-PABC control was matched for stage, age, and year of diagnosis. Chis-quare and Fisher’s exact test, the Kaplan-Meier method, and Cox’s regression model were used. Univariate and multivariate analyses were performed to assess the parameters associated with prognosis. Results 41 women with PABC were identified; 22 pts were diagnosed during pregnancy and 19 were diagnosed within one year of postpartum. There were more PR negative and triple negative tumors in the PABC(56.1% and 24.4%) than in the non-PABC(31.7% and 4.9%) (p = 0.045 and 0.026 respectively). The HER2 positivity was the same in the two group, both 31.7%. Median DFS in PABC pts was 29.0 months (95% CI range 6.5-51.5 months ) compared with 40.9 months (95% CI range 22.8–58.8 months) in the non-PABC pts(p = 0.167). Median OS in two groups were similar and even longer in PABC group, 82.8 months in PABC pts range(95% CI 39.3-126.5months) compared with 80.1 months (95% CI range 56.7-103.6months) in the non-PABC pts( p = 0.131). Conclusions The results show histological features were similar in both groups, except that triple-negative tumors were more common in the PABC group. The survival analyses show similar OS for patients diagnosed with PABC compared with non-PABC patients, and DFS tends to be shorter for PABC but no significant difference was observed. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

e24029Background: In estrogen receptor-positive breast cancer patients (pts), more than 30% have primary hormone therapy (HT) resistance while the precise mechanism underlies remain unclear. Our st...

Transverse dunes and linear dunes are simulated numerically in order to make clear the mechanism of the formation of two kinds of typical sand dunes. The numerical method employed in this study can be divided into three parts: (i) Calculation of the air flow above the sand dunes; (ii) Estimation of the sand transfer caused by the flow through the friction; (iii) Determination of the shape of the sand ground. Since the computational area has been changed due to the last step, these procedures are repeated until typical shapes of the sand dunes are formed. One kind of the simulated dunes, which is formed by one wind direction, becomes essentially parallel straight ridges at right angle to the wind direction with only one slip-face on the lee side, which is known as the transverse dunes; The other one, which is formed by two directional wind, becomes essentially parallel straight ridge at the converging direction with two slip-faces on both sides, which is known as linear dunes.

Based on the existing issues and status of urban mass transit (UMT) safety at home and abroad, many key influence factors for UMT safety are proposed in this paper. First, we have analyzed all relevant factors and causations of UMT safety under the human-machine-environmental system. Then, a safety assessment approach based on analytical hierarchy process is proposed in this paper for UMT operating security system. The multi-hierarchy valuation structure is established on the basis of key influence factors for UMT safety. The proposed approach can adjust the balance of safety assessment factors, and provide decision-making advices for the department managers for safety management and safety assessment.

A novel approach to construct accurate and interpretable fuzzy classification system based on hybrid co-evolution algorithm is proposed in this paper. First, the necessary conditions of interpretability are analyzed. Second, the search ability of Michigan-style and Pittsburgh-style genetic algorithm is examined respectively for designing fuzzy classification system. It is clearly demonstrated that each algorithm has its own advantages and disadvantages. We combine these two algorithms into a single hybrid co-evolution algorithm. The hybrid co-evolution algorithm owns three species including the number of fuzzy rules species, the premise structure species and the parameters species. Considering both precision and interpretability, the fitness function is calculated on cooperation of individuals from the three species. The proposed approach is applied to several benchmark problems, and the results show its validity.