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Background Increasing data support the role of BCSCs in recurrence and resistance to chemotherapy. However, detecting these cells specifically and targeting them therapeutically remain challenging. We set to identify miRNAs involved in chemoresistance of BCSCs in vitro and the results were assessed in the sera of healthy donors and breast cancer patients treated with neoadjuvant chemotherapy (NAC). Methods In vitro experiments were conducted in the MCF7 cell line grown as mammospheres (MS) in order to enrich a BCSC phenotype. After treatment with 5FU or Paclitaxel (Pac), microRNA profile of chemoresistant cells was analyzed by microarray. The results were compared to miRNAs found in immortalized non-tumorigenic MCF10A cells in order to exclude miRNAs related to normal stem cells. A signature of 6 miRNAs was identified. miR-363-3p, appearing the most relevant, was chosen for further assessment. By RT-qPCR, miR363-3p levels were 20- and 100-fold higher in ALDH+ sorted cells compared to ALDH- MCF7 and MDA-MB-231 cells, respectively. Moreover, overexpression of miR363-3p in MCF7 cells correlated with an increased number of ALDH+ cells and 1.5 more MS formed. In contrast, downregulation of miR363-3p levels induced a decrease in MS size and 2-fold reduction in number. Consistently, miR-363-3p downregulation decreased tumor growth and metastasis of MCF7 cells in an intraductal human-in-mice transplantation model. miRNA was quantified by RT-qPCR in tissue and sera collected prospectively from 40 breast cancer patients before and after NAC (anthracycline-taxane) and also from 25 healthy donors. Results Fifty percent of the patients had luminal A and B tumors (n=20), 32,5% (n=13) had triple negative breast cancer (TNBC), and 17.5% (n=7) had HER2 positive BC. Excluding one patient, who refused the surgical resection, 40% achieved pathological complete response (pCR). Six patients presented disease recurrence. In patients’ tumor before and after NAC, a higher level of miR363-3p was observed compared with benign tissue. In sera of the BC patients, miR363-3p levels were significantly higher than that of healthy donors. After NAC, the levels of miR363-3p remained high among patients who relapsed, whereas they were equivalent to the healthy donors in patients who remained in remission. No correlation between Ki-67, grade 1 or 2 and miR363-3p levels was observed. However, in grade 3 BC, low level of miR363-3p before and after NAC was correlated with pCR and remission. The level of miR363-3p correlated with remission and pCR in patients with TNBC and HER2 BC. Conclusions Assessment in the sera of patients and healthy donors confirms our previous data supporting the role of miR363-3p as predictive factor of resistance to neoadjuvant chemotherapy and disease recurrence. Further investigations are warranted to confirm the role of miR363-3p as a biomarker and potential therapeutic target. Citation Format: Stephanie Renaud, Athina Stravodimou, Maryse Fiche, Ioannis Xenarios, Scabia Valentina, Valerian Dormoy, Marie Galmiche, Cathrin Brisken, Jean-Francois Delaloye, Assia Treboux, Jean-Yves Meuwly, Nicolas Mermod, Khalil Zaman. miR363-3p mediates maintenance of breast cancer stem cells (BCSCs) and predicts resistance to neoadjuvant chemotherapy and disease recurrence [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 P6-10-22.

BackgroundThe aim of the study was to identify risk factors for positive surgical margins in breast-conserving surgery for breast cancer and to evaluate the influence of surgical experience in obtaining complete resection.MethodsAll lumpectomies for invasive breast carcinoma and ductal carcinoma in situ (DCIS) between April 2008 and March 2010 were selected from the database of a single institution. Re-excision rates for positive margins as well as patient and histopathologic tumor characteristics were analyzed. Surgical experience was staged by pairs made of Resident plus Specialist or Consultant. Two periods were defined. During period A, the majority of operations were performed by Residents under supervision of Specialist or Consultant. During period B, only palpable tumors were operated by Residents.ResultsThe global re-excision rate was 27% (50 of 183 patients). The presence of DCIS increased the risk for positive margins: 60% (nine of 15 patients) in the case of sole DCIS compared to 26% (41 of 160 patients) for invasive cancer (p = 0.005) and 35% (42 of 120 patients) in the case of peritumoral DCIS compared to 11% (seven of 62 patients) in the case of sole invasive cancer (p = 0.001). Re-excision rate decreased from 36% (23 of 64 patients) during period A to 23% (27 of 119 patients) during period B (p = 0.055). There was no significant difference between the surgical pairs.ConclusionIn our study, DCIS was the only risk factor for positive surgical margins. Breast-conserving surgery for non-palpable tumors should be performed by Specialists, however, palpable tumors can be safely operated by Residents under supervision.

It is widely accepted that deep neural networks are very efficient for object detection in images. They reach their limit when multiple long line instances have to be detected in very high resolution images. In this paper, we present an original methodology for the recognition of vine lines in high resolution aerial images. The process consists in combining a neural network with a subclassifier. We first compare a traditional U-Net architecture with a U-Net architecture designed for precision agriculture. We then highlight the significant improvement in vine line detection when a DTE is added after the customized U-Net. This methodology addresses the complex task of dissociating vine lines from other agricultural objects. The trained model is not sensitive to the orientation of the lines. Therefore, our experiments have improved the precision by around 15% compared to our improved neural network.

This paper presents the performances of machine learning algorithms on aerial images object detection for high precision agriculture. The dataset used focuses on geotagged pictures of vineyards. We demonstrate that advanced machine learning methodologies like Decision Tree Ensemble, outperform state-of-the-art image recognition algorithms generally used within the agriculture field. The innovative approach described here improve object detection and obtain an accuracy of 94.27% which is an increase of more than 4% compared to the state-of-the-art. Finally, methodology and possible developments for high precision agriculture is discussed in this study.

Estrogen receptor α positive (ER+) or “luminal” breast cancers were notoriously difficult to establish as patient-derived xenografts (PDXs). We and others recently demonstrated that the microenvironment is critical for ER+ tumor cells; by grafting them into milk ducts >90% take rates are achieved and many features of the human disease are recapitulated. This intra-ductal (ID) approach holds promise for personalized medicine, yet human and murine stroma are organized differently and this and other species specificities may limit the value of this model. Here, we analyzed 21 ER+ ID-PDXs histopathologically. We find that ID-PDXs vary in extent and define four histopathological patterns: flat, lobular,in situ, and invasive, which occur in pure and combined forms. The ID-PDXs replicate earlier stages of tumor development than their clinical counterparts. Micrometastases are already detected when lesions appearin situ. Tumor extent, histopathological patterns, and metastatic load correlate with biological properties of their tumors of origin. Our findings add evidence to the validity of the intraductal model forin vivostudies of ER+ breast cancer and raise the intriguing possibility that tumor cell dissemination may occur earlier than currently thought.Conflict of interest statement:The authors declare no conflict of interest.

Estrogen receptor α‐positive (ER‐positive) or ‘luminal’ breast cancers were notoriously difficult to establish as patient‐derived xenografts (PDXs). We and others recently demonstrated that the microenvironment is critical for ER‐positive tumor cells; when grafted as single cells into milk ducts of NOD Scid gamma females, >90% of ER‐positive tumors can be established as xenografts and recapitulate many features of the human disease in vivo. This intraductal approach holds promise for personalized medicine, yet human and murine stroma are organized differently and this and other species specificities may limit the value of this model. Here, we analyzed 21 ER‐positive intraductal PDXs histopathologically. We found that intraductal PDXs vary in extent and define four histopathological patterns: flat, lobular, in situ and invasive, which occur in pure and combined forms. The intraductal PDXs replicate earlier stages of tumor development than their clinical counterparts. Micrometastases are already detected when lesions appear in situ. Tumor extent, histopathological patterns and micrometastatic load correlate with biological properties of their tumors of origin. Our findings add evidence to the validity of the intraductal model for in vivo studies of ER‐positive breast cancer and raise the intriguing possibility that tumor cell dissemination may occur earlier than currently thought. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

This paper presents the impact of machine learning in precision agriculture. State-of-the-art image recognition is applied to a dataset composed of high precision aerial pictures of vineyards. The study presents a comparison of an innovative machine learning methodology compared to a baseline used classically on vineyard and agricultural objects. The baseline uses color analysis and can discriminate interesting objects with an accuracy of (89.6%). The machine learning, an innovative approach for this type of use case, demonstrates that the results can be improved to obtain 94.27% of accuracy. Machine Learning used to enrich and improve the detection of precise agricultural objects is also discussed in this study and opens new perspectives for the future of high precision agriculture.

This paper presents a study of the efficiency of machine learning algorithms applied on an image recognition task. The dataset is composed of aerial GeoTIFF images of 5 different vineyards taken with a drone. It presents the application of two different classification algorithms with an efficiency comparison over a small dataset. A Neural Network algorithm for classification through the TensorFlow platform will be explained first, and a Decision Tree Ensemble algorithm for classification through a machine learning platform will be explained second. This work shows that the accuracy of the Decision Tree Ensemble algorithm (94.27%) outperforms the accuracy of the Deep Learning algorithm (91.22%). This result is based on the final detection accuracy as well as on the computation time.

Summary Background We previously reported the 5-year results of the phase 3 IBCSG 23-01 trial comparing disease-free survival in patients with breast cancer with one or more micrometastatic (≤2 mm) sentinel nodes randomly assigned to either axillary dissection or no axillary dissection. The results showed no difference in disease-free survival between the groups and showed non-inferiority of no axillary dissection relative to axillary dissection. The current analysis presents the results of the study after a median follow-up of 9·7 years (IQR 7·8–12·7). Methods In this multicentre, randomised, controlled, open-label, non-inferiority, phase 3 trial, participants were recruited from 27 hospitals and cancer centres in nine countries. Eligible women could be of any age with clinical, mammographic, ultrasonographic, or pathological diagnosis of breast cancer with largest lesion diameter of 5 cm or smaller, and one or more metastatic sentinel nodes, all of which were 2 mm or smaller and with no extracapsular extension. Patients were randomly assigned (1:1) before surgery (mastectomy or breast-conserving surgery) to no axillary dissection or axillary dissection using permuted blocks generated by a web-based congruence algorithm, with stratification by centre and menopausal status. The protocol-specified primary endpoint was disease-free survival, analysed in the intention-to-treat population (as randomly assigned). Safety was assessed in all randomly assigned patients who received their allocated treatment (as treated). We did a one-sided test for non-inferiority of no axillary dissection by comparing the observed hazard ratios (HRs) for disease-free survival with a margin of 1·25. This 10-year follow-up analysis was not prespecified in the trial's protocol and thus was not adjusted for multiple, sequential testing. This trial is registered with ClinicalTrials.gov, number NCT00072293. Findings Between April 1, 2001, and Feb 8, 2010, 6681 patients were screened and 934 randomly assigned to no axillary dissection (n=469) or axillary dissection (n=465). Three patients were ineligible and were excluded from the trial after randomisation. Disease-free survival at 10 years was 76·8% (95% CI 72·5–81·0) in the no axillary dissection group, compared with 74·9% (70·5–79·3) in the axillary dissection group (HR 0·85, 95% CI 0·65–1·11; log-rank p=0·24; p=0·0024 for non-inferiority). Long-term surgical complications included lymphoedema of any grade in 16 (4%) of 453 patients in the no axillary dissection group and 60 (13%) of 447 in the axillary dissection group, sensory neuropathy of any grade in 57 (13%) in the no axillary dissection group versus 85 (19%) in the axillary dissection group, and motor neuropathy of any grade (14 [3%] in the no axillary dissection group vs 40 [9%] in the axillary dissection group). One serious adverse event (postoperative infection and inflamed axilla requiring hospital admission) was attributed to axillary dissection; the event resolved without sequelae. Interpretation The findings of the IBCSG 23-01 trial after a median follow-up of 9·7 years (IQR 7·8–12·7) corroborate those obtained at 5 years and are consistent with those of the 10-year follow-up analysis of the Z0011 trial. Together, these findings support the current practice of not doing an axillary dissection when the tumour burden in the sentinel nodes is minimal or moderate in patients with early breast cancer. Funding International Breast Cancer Study Group.

Most of today's commercial companies heavily rely on social media and community management tools to interact with their clients and analyze their online behaviour. Nonetheless, these tools still lack evolved data mining and visualization features to tailor the analysis in order to support useful marketing decisions. We present an original methodology that aims at formalizing the marketing need of the company and develop a tool that can support it. The methodology is derived from the Cross-Industry Standard Process for Data Mining (CRISP-DM) and includes additional steps dedicated to the design and development of visualizations of mined data. We followed the methodology in two use cases with Swiss companies. First, we developed a prototype that aims at understanding the needs of tourists based on Flickr and Instagram data. In that use case, we extend the existing literature by enriching hashtags analysis methods with a semantic network based on Linked Data. Second, we analyzed internal customer data of an online discount retailer to help them define guerilla marketing measures. We report on the challenges of integrating Facebook data in the process. Informal feedback from domain experts confirms the strong potential of such advanced analytic features based on social data to inform marketing decisions.

We study ballistic conductance in a three-terminal carbon nanotube system and show that conductance between two of the terminals can be controlled via the third terminal. The conductance is modulated by tuning the energy spectrum of the third terminal. Such a system may provide the core of a nanotransistor. We show more generally that the quasi one-dimensional nature of nanotubes can persist in branched topologies and that insights gained in analyzing one-dimensional systems can therefore be applied in analyzing networks of nanotubes.

Within a socialization paradigm, a model was developed and tested to examine social network influences on adolescent sexual behavior and contraceptive use. It was hypothesized that the social network influences of parents and peers would affect the contraceptive knowledge and premarital sexual attitudes of adolescents. In turn, knowledge and attitudes were expected to influence sexual behavior and contraceptive use. The sample comprised 161 male and 200 female high school students. Results from the LISREL analyses indicated that the model was a good fit to the data and that the model differed significantly between males and females and between virgins and nonvirgins. Approximately 50% of the variance was explainedfor virgin and nonvirgin females, and for virgin males. Parents were more influential for males, whereas friends were more important for females. The transition to nonvirginity seems to produce a greater change in the social environment offemales than of males.

During an eight week period in spring 2005, 10 cases of listeriosis were reported in a small area of northwest Switzerland (150,000 inhabitants). Eight cases were in older immunocompromised patients who became ill with bacteraemia (three deaths), and two cases were in pregnant women who had septic abortion. All cases were due to a serotype 1/2a isolate with one of two pulsovars found by PFGE. Patient interviews quickly revealed that a locally made and distributed soft cheese (known as 'tomme') was the food source responsible for the outbreak. Samples of this cheese, and of butter made in the same factory, revealed Listeria monocytogenes sv 1/2a of the same pulsovar in amounts of 1000-10 000 and 10-100 cfu/g, respectively. The prompt suspension of production, the market recall of the product, and a public alert terminated the outbreak. However, two cases of febrile gastroenteritis due to the same strains were reported within 10 days of product recall. The restricted distribution area of the contaminated cheese and the collaboration of local physicians, medical microbiologists and food health services all contributed to a rapid and successful investigation. This small outbreak of listeriosis reinforces the need for a laboratory-based surveillance system with rapid typing, as well as collaboration between physicians and microbiologists.

Bone marrow-derived endothelial progenitor cells (EPCs) infiltrate into sites of neovascularization in adult tissues and mature into functional blood endothelial cells (BECs) during a process called vasculogenesis. Human marrow-derived EPCs have recently been reported to display a mixed myeloid and lymphatic endothelial cell (LEC) phenotype during inflammation-induced angiogenesis; however, their role in cancer remains poorly understood. We report the in vitro differentiation of human cord blood CD133(+)CD34(+) progenitors into podoplanin(+) cells expressing both myeloid markers (CD11b, CD14) and the canonical LEC markers vascular endothelium growth factor receptor 3 (VEGFR-3), lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), and prospero homeobox 1 (PROX-1). These podoplanin(+) cells displayed sprouting behavior comparable to that of LECs in vitro and a dual hemangiogenic and lymphangiogenic activity in vivo in an endothelial cell sprouting assay and corneal vascularization assay, respectively. Furthermore, these cells expressed vascular endothelium growth factor (VEGF) family members A, -C, and -D. Thus, bone-marrow derived EPCs stimulate hemangiogenesis and lymphangiogenesis through their ability to differentiate into LECs and to produce angiogenic factors. Importantly, plasma from patients with breast cancer induced differentiation of CD34(+) cord blood progenitors into hemangiogenic and lymphangiogenic CD11b(+) myeloid cells, whereas plasma from healthy women did not have this effect. Consistent with these findings, circulating CD11b(+) cells from breast cancer patients, but not from healthy women, displayed a similar dual angiogenic activity. Taken together, our results show that marrow-derived EPCs become hemangiogenic and lymphangiogenic upon exposure to cancer plasma. These newly identified functions of bone-marrow derived EPCs are expected to influence the diagnosis and treatment of breast cancer.

Using three different samples of couples (clinic, nondistressed community, and engaged), we found that 15 minutes was sufficient to witness enough behavior to make reliable (i.e., internally consistent) estimations of most Rapid Marital Interaction Coding System (Heyman & Vivian, 1993) code frequencies. Ten minutes is sufficient for many codes of interest. The ease in which “how much time is necessary” calculations can be made should entice behavioral investigators from a variety of content areas to publish such figures. By empirically investigating a factor that in most fields becomes reified through convention, investigators can conduct observational research that is both maximally efficient and maximally scientifically defensible.

e19599 Background: Infertility secondary to adjuvant chemotherapy is a major problem in young women with breast cancer. We developed a multidisciplinary-multicenter network, the “RRCF”, aiming to o...