Analysis of the Functionality of the Feed Chain in Olive Pitting, Slicing and Stuffing Machines by IoT, Computer Vision and Neural Network Diagnosis

Olive pitting, slicing and stuffing machines (DRR in Spanish) are characterized by the fact that their optimal functioning is based on appropriate adjustments. Traditional systems are not completely reliable because their minimum error rate is 1–2%, which can result in fruit loss, since the pitting process is not infallible, and food safety issues can arise. Such minimum errors are impossible to remove through mechanical adjustments. In order to achieve this objective, an innovative solution must be provided in order to remove errors at operating speed rates over 2500 olives/min. This work analyzes the appropriate placement of olives in the pockets of the feed chain by using the following items: (1) An IoT System to control the DRR machine and the data analysis. (2) A computer vision system with an external shot camera and a LED lighting system, which takes a picture of every pocket passing in front of the camera. (3) A chip with a neural network for classification that, once trained, classifies between four possible pocket cases: empty, normal, incorrectly de-stoned olives at any angles (also known as a “boat”), and an anomalous case (foreign elements such as leafs, small branches or stones, two olives or small parts of olives in the same pocket). The main objective of this paper is to illustrate how with the use of a system based on IoT and a physical chip (NeuroMem CM1K, General Vision Inc.) with neural networks for sorting purposes, it is possible to optimize the functionality of this type of machine by remotely analyzing the data obtained. The use of classifying hardware allows it to work at the nominal operating speed for these machines. This would be limited if other classifying techniques based on software were used

Digenic inheritance in cystinuria mouse model

Cystinuria is an aminoaciduria caused by mutations in the genes that encode the two subunits of the amino acid transport system b0,+, responsible for the renal reabsorption of cystine and dibasic amino acids. The clinical symptoms of cystinuria relate to nephrolithiasis, due to the precipitation of cystine in urine. Mutations in SLC3A1, which codes for the heavy subunit rBAT, cause cystinuria type A, whereas mutations in SLC7A9, which encodes the light subunit b0,+AT, cause cystinuria type B. By crossing Slc3a1-/- with Slc7a9-/- mice we generated a type AB cystinuria mouse model to test digenic inheritance of cystinuria. The 9 genotypes obtained have been analyzed at early (2- and 5-months) and late stage (8-months) of the disease. Monitoring the lithiasic phenotype by X-ray, urine amino acid content analysis and protein expression studies have shown that double heterozygous mice (Slc7a9+/-Slc3a1+/-) present lower expression of system b0,+ and higher hyperexcretion of cystine than single heterozygotes (Slc7a9+/-Slc3a1+/+ and Slc7a9+/+Slc3a1+/-) and give rise to lithiasis in 4% of the mice, demonstrating that cystinuria has a digenic inheritance in this mouse model. Moreover in this study it has been demonstrated a genotype/phenotype correlation in type AB cystinuria mouse model providing new insights for further molecular and genetic studies of cystinuria patients

Circadian rhythms in the efficacy of intravenous alteplase in patients with acute ischemic stroke and middle cerebral artery occlusion

Peer ReviewedPostprint (author's final draft

Análisis en tiempo real del funcionamiento de la cadena de alimentación de las máquinas deshuesadoras de aceitunas mediante diagnosis por visión artificial y redes neuronales

Las máquinas deshuesadoras de aceitunas se caracterizan porque su funcionamiento óptimo está vinculado a un buen ajuste: Selección de un plato de alimentación adecuado a la variedad de aceituna y su calibre, de las características geométricas de la cadena de alimentación, etc. El primero de estos elementos fija la entrada óptima de aceitunas en la cadena de alimentación impidiendo que queden cangilones vacíos o se llenen con más de una aceituna. El segundo elemento fija la correcta posición de la aceituna para ser deshuesada, evitando que esta sea deshuesada por un eje que no sea el principal. El trabajo propuesto analiza en tiempo real la correcta ubicación de las aceitunas en los cangilones de la cadena de alimentación, para ello se utiliza: 1.-Un sistema de visión artificial con disparo externo capaz de extraer una foto de cada cangilón que pase frente a una cámara. 2.-Una red neuronal clasificadora basada en un chip físico, de manera que adecuadamente entrenada, permita clasificar el cangilón en cuatro posibles estados: vacío, normal, con aceituna mal posicionada en “barco” y caso anómalo (dos aceitunas en un mismo cangilón, aceituna rota o aceituna mal posicionada no en barco). El trabajo muestra el uso de dos chips físicos con redes neuronales para la clasificación: a) Intel Curie b) NeuroMem CM1. El uso de los chips físicos Intel Curie y sobretodo Neuromem CM1K por su mayor capacidad y escalabilidad, ha sido satisfactorio y por tanto se comprueba un gran potencial para la clasificación. Se ha comprobado que la velocidad de transmisión de la información por puerto serie es suficiente para las velocidades habituales de las máquinas deshuesadoras, en torno a 1.800 aceitunas/min. Para poder realizar las pruebas se ha desarrollado una interfaz mediante la aplicación QT en lenguaje C++ que permite poder configurar de manera sencilla las imágenes a procesar y las condiciones de contorno para la detección de los fallos indicados

Impact of coadministration of proton-pump inhibitors and palbociclib in hormone receptor-positive/HER2-negative advanced breast cancer

Background: The capsule formulation of CDK4/6 inhibitor palbociclib has reduced solubility at gastric pH > 4.5 and may have decreased activity when used with proton-pump inhibitors (PPI). Herein, we report the effect of PPI on palbociclib capsule activity and safety in the PARSIFAL study. Methods: First -line endocrine-sensitive, hormone receptor-positive (HR +)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) patients received palbociclib capsules plus fulvestrant or letrozole. The primary endpoint was progression-free survival (PFS). This post-hoc analysis compared PPI use. Patients were PPI-na & iuml;ve (N-PPI) if not on PPI during the study, and either early (E-PPI) or long-term PPI (LT-PPI) if on PPI at study entry or for at least >= 2/3 of treatment, respectively. PPI groups were not mutually exclusive. Results: Among 486 patients, 66.9 % were N-PPI, 13.2 % E-PPI, 18.7 % LT-PPI, and 11.5 % of the PPI users were defined as neither. Median PFS (mPFS) was 29.6 months in the study population, 28.7 months in N-PPI, 23.0 months in E-PPI (Hazard Ratio [HR] 1.5; 95%Confidence Interval [CI] 1.1 -2.2; p = 0.024), and 23.0 months in LT-PPI (HR 1.4; 95%CI 1.0 -1.9; p = 0.035). By landmark analysis, PPI use was associated with poorer mPFS at 3 and 12 months. Grade >= 3 hematological adverse events occurred in 71.7 % of N-PPI, 57.8 % of E-PPI (p = 0.021), and 54.9 % of LT-PPI (p = 0.003). Dose reductions and dosing delays due to hematological toxicity occurred in 70.8 % of N-PPI, 56.3 % of E-PPI (p = 0.018), and 52.7 % of LT-PPI (p = 0.002). Conclusions: PPI use may reduce palbociclib capsule toxicity, dose modifications, and clinical activity in HR +/ HER2- ABC

Lymphangioleiomyomatosis: Searching for potential biomarkers

Biomarkers; Lymphangioleiomyomatosis; MetalloproteinasesBiomarcadores; Linfangioleiomiomatosis; MetaloproteinasasBiomarcadors; Limfangioleiomiomatosi; MetaloproteinasesBackground: Vascular endothelial growth factor-D (VEGF-D) is the most commonly used biomarker for diagnosing lymphangioleiomyomatosis (LAM). However, lung biopsy is often necessary as well; therefore, defining new biomarkers for LAM is crucial. The aim of this study was to describe the diagnostic accuracy of a variety of biomarkers. Methods: We assessed 13 analytes in serum related to extracellular matrix remodeling, lymphatic involvement and angiogenesis in a cohort of patients with LAM, comparing them with patients with other cystic lung diseases (OCLD) and healthy women. A scoring method based on the cut-point of each VEGF-D and metalloproteinase-2 (MMP-2) was used to evaluate the diagnostic performance of the marker combination. Results: A total of 97 subjects were recruited: 59 (61%) LAM patients, 18 (19%) OCLD patients, and 20 (20%) healthy female controls. MMP-2 was the only extracellular matrix remodeling biomarker able to differentiate LAM patients from OCLD and healthy patients. Serum MMP-2 was higher in LAM patients [median 578 (465–832) ng/ml] than in patients with OCLD and healthy controls [medians 360 (314–546) and 427 (365–513) ng/ml, respectively (p < 0.0001)]. The area under ROC curve (AUC) of MMP-2 was 0.785 and that of VEGF-D 0.815 (p = 0.6214). The sensitivity/specificity profiles of each biomarker (54/92% for MMP-2, 59/95% for VEGF-D) yielded a composite score (−6.36 + 0.0059 × VEGF-D + 0.0069 × MMP-2) with higher accuracy than each component alone (AUC 0.88 and sensitivity/specificity 79/87%). Conclusion: Combining MMP-2 and VEGF-D may increase diagnostic accuracy for LAM.This project was supported by the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), grant number: PI 638/2018. The funders have no role in study design, data and analysis collection, decision to publish, or preparation of the manuscript

Palbociclib Rechallenge for Hormone Receptor–Positive/HER-Negative Advanced Breast Cancer: Findings from the Phase II BioPER Trial

Purpose: To assess the efficacy and exploratory biomarkers of continuing palbociclib plus endocrine therapy (ET) beyond pro-gression on prior palbociclib-based regimen in patients with hor-mone receptor-positive/HER2-negative (HR+/HER2-) advanced breast cancer (ABC).Patients and Methods: The multicenter, open-label, phase II BioPER trial included women who had experienced a progressive disease (PD) after having achieved clinical benefit on the immedi-ately prior palbociclib plus ET regimen. Palbociclib (125 mg, 100 mg, or 75 mg daily orally for 3 weeks and 1 week off as per prior palbociclib-based regimen) plus ET of physician's choice were administered in 4-week cycles until PD or unacceptable toxicity. Coprimary endpoints were clinical benefit rate (CBR) and percent-age of tumors with baseline loss of retinoblastoma (Rb) protein expression. Additional endpoints included safety and biomarker analysis.Results: Among 33 patients enrolled, CBR was 34.4% [95% confidence interval (CI), 18.6-53.2; P < 0.001] and 13.0% of tumors (95% CI, 5.2-27.5) showed loss of Rb protein expression, meeting both coprimary endpoints. Median progression-free survival was 2.6 months (95% CI, 1.8-6.7). No new safety signals were reported. A signature that included baseline mediators of therapeutic resistance to palbociclib and ET (low Rb score, high cyclin E1 score, ESR1 mutation) was independently associated with shorter median progression-free survival (HR, 22.0; 95% CI, 1.71-282.9; P = 0.018). Conclusions: Maintaining palbociclib after progression on prior palbociclib-based regimen seems to be a reasonable, investigational approach for selected patients. A composite biomarker signature predicts a subset of patients who may not derive a greater benefit from palbociclib rechallenge, warranting further validation in larger randomized controlled trials

Safety and efficacy of ribociclib plus letrozole in patients with HR+, HER2– advanced breast cancer: Results from the Spanish sub-population of the phase 3b CompLEEment-1 trial

Background: Breast cancer is the most common malignancy and the second leading cause of cancer-related mortality in Spanish women. Ribociclib in combination with endocrine therapy (ET) has shown superiority in prolonging survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) vs. ET alone.Methods: CompLEEment-1 is a single-arm, open-label phase 3b trial evaluating ribociclib plus letrozole in a broad population of patients with HR+, HER2- ABC. The primary endpoints were safety and tolerability. Here we report data for Spanish patients enrolled in CompLEEment-1.Results: A total of 526 patients were evaluated (median follow-up: 26.97 months). Baseline characteristics showed a diverse population with a median age of 54 years. At study entry, 56.5% of patients had visceral metastases and 8.7% had received prior chemotherapy for advanced disease. Rates of all-grade and Grade >= 3 adverse events (AEs) were 99.0% and 76.2%, respectively; 21.3% of patients experienced a serious AE, and 15.8% of AEs led to treatment discontinuation. AEs of special interest of neutropenia, increased alanine aminotransferase, increased aspartate aminotransferase and QTcF prolongation occurred in 77.8%, 14.8%, 11.4% and 4.0% of patients, respectively. Patients aged >70 years experienced increased rates of all-grade and Grade >= 3 neutropenia and anemia. Efficacy results were consistent with the global study.Conclusions: Results from Spanish patients enrolled in CompLEEment-1 are consistent with global data showing efficacy and a manageable safety profile for ribociclib plus letrozole treatment in patients with HR+, HER2-ABC, including populations of interest (NCT02941926).Trial registration: ClinicalTrials.gov NCT0294192

The antioxidant l-Ergothioneine prevents cystine lithiasis in the Slc7a9-/- mouse model of cystinuria

The high recurrence rate of cystine lithiasis observed in cystinuria patients highlights the need for new therapeutic options to address this chronic disease. There is growing evidence of an antioxidant defect in cystinuria, which has led to test antioxidant molecules as new therapeutic approaches. In this study, the antioxidant l-Ergothioneine was evaluated, at two different doses, as a preventive and long-term treatment for cystinuria in the Slc7a9-/- mouse model. l-Ergothioneine treatments decreased the rate of stone formation by more than 60% and delayed its onset in those mice that still developed calculi. Although there were no differences in metabolic parameters or urinary cystine concentration between control and treated mice, cystine solubility was increased by 50% in the urines of treated mice. We also demonstrate that l-Ergothioneine needs to be internalized by its transporter OCTN1 (Slc22a4) to be effective, as when administrated to the double mutant Slc7a9-/-Slc22a4-/- mouse model, no effect on the lithiasis phenotype was observed. In kidneys, we detected a decrease in GSH levels and an impairment of maximal mitochondrial respiratory capacity in cystinuric mice that l-Ergothioneine treatment was able to restore. Thus, l-Ergothioneine administration prevented cystine lithiasis in the Slc7a9-/- mouse model by increasing urinary cystine solubility and recovered renal GSH metabolism and mitochondrial function. These results support the need for clinical trials to test l-Ergothioneine as a new treatment for cystinuria.This work has been funded by the Instituto de Salud Carlos III through the projects PI16/00267-R-FEDER and PI20/00200 to VN (Co-funded by European Regional Development Fund. ERDF, a way to build Europe), and by La Marató de TV3 through the project 202025-30 to VN and 202025-32 to FVP. Generalitat de Catalunya Grant SGR2017-191 to VN. We also thank CERCA Programme/Generalitat de Catalunya for institutional support.Peer reviewe

Clinical and Histopathological Amelioration of Experimental Autoimmune Encephalomyelitis by AAV Vectors Expressing a Soluble Interleukin-23 Receptor

The role of the T helper (Th)17 pathway has been clearly demonstrated in the onset and progression of autoimmune diseases, where interleukin (IL)-23 is a key molecule in maintaining the response mediated by Th17 cells. As a consequence, recent strategies based on blocking the interaction between IL-23 and its receptor (IL-23R), for example the anti-p19 antibody tildrakizumab, have been developed to regulate the Th17 pathway from the initial stages of the disease. Here, a soluble (s)IL-23R cDNA was cloned in expression plasmids and viral vectors. The clinical efficacy of sIL-23R was evaluated in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis mice intravenously injected with a single dose of adeno-associated virus AAV8- sIL-23R vectors. Cytokine secretion was determined by multiplexassay, while histopathological analysis of the central nervous system was performed to study demyelination, inflammatory infiltration, and microglia and astroglia activation. We observed that administration of adeno-associated vector 8 encoding sIL-23R was associated with a significant disease improvement,including delay in the onset of the clinical signs; slower progress of the disease;interference with IL-23- mediated signal transducer and activator of transcription response by inhibiting of signal transducer and activator of transcription 3 phosphorylation; reduced demyelination and infiltration in the central nervous system; and lower astrocyte and microglia activation. Our results suggest that the use of vectors carrying sIL-23R to block the IL-23/IL-23R interaction may be a new therapeutic strategy for the treatment of multiple sclerosis.The online version of this article (doi:10.1007/s13311-017-0545-8) contains supplementary material, which is available to authorized users