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Supplementary Information - PDF file 145K, Supplementary Material and Methods; Supplementary Figure Legend S1 (Proliferation of tumor-specific CD4 T cells by matured DC pulsed with autologous tumor lysate.); Supplementary Figure Legend S2 (In breast tumors TEM and CD11c+ are distinct cell subsets.); Supplementary Tables S1 (Clinical and pathological features of tumors and patients (n=40)); Supplementary Tables S2 (CD11c+ DC and TEM from breast tumors were exposed to autologous CFSE-labeled T cells and their proliferation assessed five days later by flow cytometry.); Supplementary References

Supplementary figures - PDF file 1536K, Figure S1. Proliferation of tumor-specific CD4 T cells by matured DC pulsed with autologous tumor lysate; Figure S2. In breast tumors TEM and CD11c+ are distinct cell subsets

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.

El sistema presupuestario público se inscribe como uno de los pilares del proceso de las finanzas públicas. Se ocupa de organizar la gestión pública y vincular las responsabilidades del Estado en el cumplimiento de sus funciones y en la realización de los planes y programas proyectados. El presupuesto público es el límite de gastos que una entidad puede realizar durante un año, de acuerdo a los ingresos que espera recibir, y debe ser la expresión financiera de los programas y proyectos que ejecutará para alcanzar los objetivos del plan de gobierno. Permite estimar los recursos que se obtendrán y distribuirlos de acuerdo a las prioridades de gobierno, entre las distintas instituciones. En consecuencia, es el principal instrumento de política pública, a través del cual se concretan los objetivos de gobierno y se identifican a las entidades responsables, siendo asimismo un mecanismo redistributivo de la riqueza. El resultado esperado de este proceso es un presupuesto público idóneo como instrumento de gestión y de información de las políticas públicas previstas para el corto y mediano plazo y el grado de efectividad y eficiencia en su cumplimiento. Considerando el carácter federal de nuestro país, las políticas fiscales vinculadas con las jurisdicciones provinciales y municipales, y sus implicancias financieras, deben estar articuladas razonable y adecuadamente con sus propias realidades económicas y sociales, de modo de obtener un panorama multidimensional de la situación de los gobiernos sub-nacionales en el marco de las políticas públicas nacionales, definidas en el presupuesto nacional. Los presupuestos tienen impactos muy concretos en la vida de las personas y el ejercicio efectivo de sus derechos. Los más directos se vinculan con la forma en que se gastan los recursos públicos y las prioridades a las que se asignan los fondos. Pero también existen efectos indirectos como los impactos que un presupuesto tiene en cuestiones como el empleo o la inflación. Fil: Ameriso, Claudia C. Universidad Nacional de Rosario; Argentina

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.

Las finanzas públicas constituyen la rama del conocimiento que se ocupa del funcionamiento económico del Estado. Por lo tanto, su importancia crece en la medida en que el sector público se vuelve más relevante para la actividad económica. En una economía con un Estado poco desarrollado, las finanzas públicas tendrán un papel poco significativo. En cambio, en una economía con un sector público importante, en términos cuantitativos y cualitativos, éstas juegan un rol decisivo. La tributación es un componente esencial de las políticas públicas, siendo los impuestos la fuente fundamental del financiamiento de los programas de gasto público. Si están adecuadamente diseñados, los sistemas impositivos pueden mejorar la gobernanza, la transparencia y la rendición de cuentas. La presión tributaria es un indicador que hace referencia al “peso” que ejerce el Estado sobre una economía al detraer recursos privados de manera coercitiva para el financiamiento de sus actividades. El monitoreo de cerca de la gestión pública, colabora con el uso adecuado de los recursos públicos e induce un mejor desempeño del Estado, por ello el trabajo aborda la evolución de este indicador a nivel nacional, en el contexto de algunos países americanos para derivar, en particular, en la presión fiscal provincial, focalizando en la provincia de Santa Fe, lo que nos permite concluir que la presión impositiva real en Santa Fe es baja en relación con la de otras provincias argentinas, encontrándose en la décima posición dentro de las 13 provincias que cuentan con información disponible. Fil: Ameriso, Claudia C. Universidad Nacional de Rosario; Argentina Fil: Treboux, Javier. Universidad Nacional de Rosario; Argentina

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.

Invasive lobular carcinoma (ILC) is the most frequent special histological subtype of breast cancer, typically characterized by loss of E‐cadherin. It has clinical features distinct from other estrogen receptor‐positive (ER+) breast cancers but the molecular mechanisms underlying its characteristic biology are poorly understood because we lack experimental models to study them. Here, we recapitulate the human disease, including its metastatic pattern, by grafting ILC‐derived breast cancer cell lines, SUM‐44 PE and MDA‐MB‐134‐VI cells, into the mouse milk ducts. Using patient‐derived intraductal xenografts from lobular and non‐lobular ER+ HER2− tumors to compare global gene expression, we identify extracellular matrix modulation as a lobular carcinoma cell‐intrinsic trait. Analysis of TCGA patient datasets shows matrisome signature is enriched in lobular carcinomas with overexpression of elastin, collagens, and the collagen modifying enzyme LOXL1. Treatment with the pan LOX inhibitor BAPN and silencing of LOXL1 expression decrease tumor growth, invasion, and metastasis by disrupting ECM structure resulting in decreased ER signaling. We conclude that LOXL1 inhibition is a promising therapeutic strategy for ILC., Intraductal xenografts of invasive lobular carcinoma (ILC) cells faithfully model this breast cancer subtype, and reveal tumor cell intrinsic ECM remodeling as a critical feature of disease progression that can be exploited therapeutically by targeting LOXL1.

National audience; L'objectif de ce projet de recherche est d'étudier la relation entre la qualité du matériau bois de construction des ruches et les conditions de vie internes des abeilles, envisagée comme source de solutions à certains stress actuels (parasitisme par Varroa destructor, sécheresses) auxquelles les colonies en voie de disparition doivent faire face. Notre méthode de travail consiste à s'appuyer sur des savoirs techniques locaux récoltés au moyen d'enquêtes anthropologiques de terrain pour construire les questions de recherche et bâtir les protocoles expérimentaux. Les hypothèses en cours de test concernent l'influence : des extractibles du bois de châtaignier sur le comportement de Varroa destructor ; du matériau de la ruche (bois, polystyrène) sur le climat hygrothermique interne. Afin d'étudier la dynamique d'évolution de la population du varroa, un outil de comptage automatisé basé sur l'apprentissage supervisé est en cours de développement en collaboration avec une entreprise spécialisée dans la reconnaissance d'images

International audience

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.

Ce mémoire s’intéresse aux Massive Open Online Courses (MOOC) dans le milieu culturel. À travers une étude de cas sur le MOOC Les Origines de l’Homme entre Orange et le Musée de l’Homme, l’hybridité de ce nouveau dispositif pédagogique est mise en perspective. Entre outil de communication et outil pédagogique, le MOOC apparaît non seulement être une innovation pour l’enseignement mais également un outil communicationnel au service de son marché : l’éducation.Cette approche a pour objectif de traiter plusieurs questions relatives au MOOC notamment économiques et sociales, tout en détaillant ses spécificités et ses invariants. Le prisme culturel permet, entre autres, d’observer l’adaptabilité de ces cours en ligne à l’environnement des institutions. Selon les institutions, les cours peuvent ainsi se moduler, dans leur forme et leur contenu. À travers le MOOC, les institutions peuvent donc véhiculée une image. Une analyse sémiologique des vidéos, des newsletters et du site du MOOC Les Origines de l’Homme met ainsi en exergue la retranscription des caractéristiques des musées scientifiques sur ce nouvel outil numérique.