Anti-EphA2 Antibodies with Distinct In Vitro Properties Have Equal In Vivo Efficacy in Pancreatic Cancer

The EphA2 receptor tyrosine kinase is overexpressed in a variety of human epithelial cancers and is a determinant of malignant cellular behavior in pancreatic adenocarcinoma cells. Moreover, it is expressed in tumor endothelium and its activation promotes angiogenesis. To better clarify the therapeutic potential of monoclonal antibodies (mAbs) directed to the EphA2 receptor, we generated a large number of mAbs by differential screening of phage-Ab libraries by oligonucleotide microarray technology and implemented a strategy for the rapid identification of antibodies with the desired properties. We selected two high-affinity and highly specific EphA2 monoclonal antibodies with different in vitro properties on the human pancreatic tumor cell line MiaPaCa2. One is a potent EphA2-agonistic antibody, IgG25, that promotes receptor endocytosis and subsequent degradation, and the second is a ligand antagonist, IgG28, that blocks the binding to ephrin A1 and is cross-reactive with the mouse EphA2 receptor. We measured the effect of antibody treatment on the growth of MiaPaCa2 cells orthotopically transplanted in nude mice. Both IgG25 and IgG28 had strong antitumor and antimetastatic efficacy. In vivo treatment with IgG25 determined the reduction of the EphA2 protein levels in the tumor and the phosphorylation of FAK on Tyr576 while administration of IgG28 caused a decrease in tumor vascularization as measured by immunohistochemical analysis of CD31 in tumor sections. These data show that in a pancreatic cancer model comparable therapeutic efficacy is obtained either by promoting receptor degradation or by blocking receptor activation

Entanglement-enhanced probing of a delicate material system

Quantum metrology uses entanglement and other quantum effects to improve the sensitivity of demanding measurements. Probing of delicate systems demands high sensitivity from limited probe energy and has motivated the field's key benchmark-the standard quantum limit. Here we report the first entanglement-enhanced measurement of a delicate material system. We non-destructively probe an atomic spin ensemble by means of near-resonant Faraday rotation, a measurement that is limited by probe-induced scattering in quantum-memory and spin-squeezing applications. We use narrowband, atom-resonant NOON states to beat the standard quantum limit of sensitivity by more than five standard deviations, both on a per-photon and per-damage basis. This demonstrates quantum enhancement with fully realistic loss and noise, including variable-loss effects. The experiment opens the way to ultra-gentle probing of single atoms, single molecules, quantum gases and living cells.Comment: 7 pages, 8 figures; Nature Photonics, advance online publication, 16 December 201

Traian and the Danubian Provinces. The political, economic and religious life in the Danubian Provinces: Proceedings of the 4th International Conference on the Roman Danubian Provinces, Zagreb, 15th - 17th November 2017.

The “Department of Archaeology“ of the Faculty of Humanities and Social Sciences of the University of Zagreb gladly hosted the 4th International Conference on the Roman Danubian Provinces in 2017. The Conference was organized with the support of the Faculty of Humanities and Social Sciences of the University of Zagreb, the Croatian Archaeological Society, and the Croatian Science Foundation through the project 6505 Between the Danube and the Mediterranean. Exploring the role of Roman military in the mobility of people and goods in Croatia during the Roman Era. Since it was organized in Zagreb, the Conference remained in Pannonia, not far from Siscia, the capital of Pannonia Savia, and in the territory of the Res publica Andautoniensium. The main topic of the Conference was Traian and the Roman Danubian Provinces or, more specifically, the political, economic and religious life in the Danubian Provinces.(from the Foreword)The “Department of Archaeology“ of the Faculty of Humanities and Social Sciences of the University of Zagreb gladly hosted the 4th International Conference on the Roman Danubian Provinces in 2017. The Conference was organized with the support of the Faculty of Humanities and Social Sciences of the University of Zagreb, the Croatian Archaeological Society, and the Croatian Science Foundation through the project 6505 Between the Danube and the Mediterranean. Exploring the role of Roman military in the mobility of people and goods in Croatia during the Roman Era. Since it was organized in Zagreb, the Conference remained in Pannonia, not far from Siscia, the capital of Pannonia Savia, and in the territory of the Res publica Andautoniensium. The main topic of the Conference was Traian and the Roman Danubian Provinces or, more specifically, the political, economic and religious life in the Danubian Provinces.(from the Foreword

Traian and the Danubian Provinces. The political, economic and religious life in the Danubian Provinces: Proceedings of the 4th International Conference on the Roman Danubian Provinces, Zagreb, 15th - 17th November 2017.

The “Department of Archaeology“ of the Faculty of Humanities and Social Sciences of the University of Zagreb gladly hosted the 4th International Conference on the Roman Danubian Provinces in 2017. The Conference was organized with the support of the Faculty of Humanities and Social Sciences of the University of Zagreb, the Croatian Archaeological Society, and the Croatian Science Foundation through the project 6505 Between the Danube and the Mediterranean. Exploring the role of Roman military in the mobility of people and goods in Croatia during the Roman Era. Since it was organized in Zagreb, the Conference remained in Pannonia, not far from Siscia, the capital of Pannonia Savia, and in the territory of the Res publica Andautoniensium. The main topic of the Conference was Traian and the Roman Danubian Provinces or, more specifically, the political, economic and religious life in the Danubian Provinces.(from the Foreword)The “Department of Archaeology“ of the Faculty of Humanities and Social Sciences of the University of Zagreb gladly hosted the 4th International Conference on the Roman Danubian Provinces in 2017. The Conference was organized with the support of the Faculty of Humanities and Social Sciences of the University of Zagreb, the Croatian Archaeological Society, and the Croatian Science Foundation through the project 6505 Between the Danube and the Mediterranean. Exploring the role of Roman military in the mobility of people and goods in Croatia during the Roman Era. Since it was organized in Zagreb, the Conference remained in Pannonia, not far from Siscia, the capital of Pannonia Savia, and in the territory of the Res publica Andautoniensium. The main topic of the Conference was Traian and the Roman Danubian Provinces or, more specifically, the political, economic and religious life in the Danubian Provinces.(from the Foreword

Analisi della voce attraverso le Reti Neurali: applicazione di software nello screening delle disfonie.

Background. La disfonia è un sintomo di alterazione qualitativa e/o quantitativa dell’emissione vocale che accompagna una modificazione strutturale o funzionale di uno o più organi coinvolti nella produzione della voce. Per alcune categorie di lavoratori, l’argomento relativo ai disturbi professionali derivanti da uno scorretto utilizzo della voce non è ancora stato definito pienamente in termini di screening e prevenzione. Lo scopo del nostro studio è quello di fornire file relativi alla valutazione della voce da analizzare tramite i Deep Learning, algoritmi di apprendimento automatico ispirati alle reti neurali biologiche con promettenti applicazioni nell’ambito di varie specialità mediche. L’obiettivo è quello di proporre uno strumento di screening di primo livello della voce in grado di indirizzare i soggetti disfonici dal foniatra o dal logopedista. Sarà poi loro compito eseguire su tali pazienti un’analisi completa della voce, al fine di stabilire la causa della disfonia ed impostare un’adeguata terapia. Materiali e Metodi. Sono stati utilizzati 828 file audio raccolti tra Gennaio 2013 e Luglio 2019 e convertiti in spettrogrammi. Ciascuno spettrogramma è stato catalogato secondo una nuova classificazione da noi ideata per poter essere poi analizzato dalle reti neurali. Risultati e conclusione. La nostra classificazione ha fornito risultati altamente accurati sia in termini di sensibilità che di specificità rispetto al gold standard per la diagnosi di disfonia rappresentato dalla laringostroboscopia. Inoltre, la successiva analisi degli spettrogrammi con le reti neurali ha permesso di ottenere risultati promettenti, raggiungendo percentuali di riconoscimento dei soggetti sani e patologici nel 94% dei casi

Optimization of Mixing Conditions for Improving Lactobacillus Paracasei Cba L74 S Growth During Lactic Fermentation of Cooked Navy Beans and Functional Characterization of the Fermented Products

Lactic acid fermentation of legume-based matrices has been gaining an increasing interest in recent years to produce pro- and post-biotic functional foods at high protein content. The optimization of the main process conditions is necessary to improve bacterial growth, microbial metabolic activity, thus the consequent functional properties of the resulting fermented products. A preliminary study of feasibility about the potential of using a leguminous substrate as growth medium for Lactobacillus paracasei CBA L74 was already conducted in previous experimentations. In this work, the effect of improving mixing conditions of a cooked navy bean suspension during the lactic acid fermentation process was investigated and some chemical and physical properties of the resulting fermented products were studied to verify their potential application as functional ingredients in food formulations. The mixing system was optimized by designing an impeller that guarantees a more homogeneous distribution of nutrients and avoids concentration gradients that could inhibit the microorganism proliferation. Bacterial growth, lactic acid production, sugar, and starch consumption were compared with those obtained during previous experimentations carried out with a different impeller. The major availability of nutrients in the fermenting medium reached with the customized impeller allowed a faster achievement of the maximum microbial load (1×109 CFU/mL after 14 h of process) and a lower doubling time of 1.53 h. Furthermore, fermentation led to a reduction in water absorption, oil binding, and foam capacity of the fermented bean powders. Total phenolic and flavonoid content and their antioxidant capacity were not influenced by the fermentation process itself but favored by the previous thermal treatment of sterilization

Prediction of respiratory distress severity and bronchopulmonary dysplasia by lung ultrasounds and transthoracic electrical bioimpedance

This study aims to evaluate whether the assessment of a lung ultrasound score (LUS) by lung ultrasonography and of thoracic fluid contents (TFC) by electrical cardiometry may predict RDS severity and the development of bronchopulmonary dysplasia (BPD) in preterm infants with respiratory distress (RDS). Infants <= 34 weeks' gestation admitted with RDS to two neonatal intensive care units were prospectively enrolled in this observational study. A simultaneous evaluation of LUS and TFC was performed during the first 72 h. The predictivity of LUS and TFC towards mechanical ventilation (MV) need after 24 h and BPD development was evaluated using receiver operating characteristic analysis. Sixty-four infants were included. The area under the curve (AUC) for the prediction of MV need was 0.851 (95%CI, 0.776-0.925, p < 0.001) for LUS and 0.793 (95%CI, 0.724-0.862, p < 0.001) for TFC, while an AUC of 0.876 (95%CI, 0.807-0.946, p < 0.001) was obtained for combined LUS and TFC evaluation. LUS and TFC AUC for BPD prediction were 0.769 (95%CI, 0.697-0.842, p < 0.001) and 0.836 (95%CI, 0.778-0.894, p < 0.001), respectively, whereas their combined assessment yielded an AUC of 0.867 (95%CI, 0.814-0.919, p < 0.001). LUS >= 11 and TFC >= 40 were identified as cut-off values for MV need prediction, whereas LUS >= 9 and TFC >= 41.4 best predicted BPD development. Conclusion: A combined evaluation of LUS and TFC by lung ultrasonography and EC during the first 72 h may represent a useful predictive tool towards short- and medium-term pulmonary outcomes in preterm infants with RDS

Olfactory Dysfunction, Headache, and Mental Clouding in Adults with Long-COVID-19: What Is the Link between Cognition and Olfaction? A Cross-Sectional Study

Smell alteration and cognitive impairment are common features of the Long-COVID Syndrome. Mental clouding, often described as brain fog, might affect smell by altering recollection of odors or through a share mechanism of neuroinflammation. We investigated mental clouding, headache, and cognitive function in adult patients with persistent COVID-19 olfactory dysfunction. This multi-center cross-sectional study enrolled 152 adults with self-reported olfactory dysfunction from 3 tertiary centers specialized in COVID-19 olfactory disorders. Inclusion criteria were smell alterations after COVID-19 persisting over 6 months from infection, age >18 and < 65. Exclusion criteria included smell alterations, headache, or memory problems prior to COVID-19 infection. The patients were evaluated by olfactometry, nasal endoscopy, headache scale, cognitive assessment, Mini Mental State Examination (MMSE), and self-reported measures. Smell dysfunction was stratified and classified based on olfactory deficit severity and presence of olfactory distortion (parosmia, cacosmia). Data on smell disorder, mental clouding, MMSE, and headache were analyzed to assess correlations. Among the 152 patients studied, 50 (32.8%) presented with anosmia, 25 (16.4%) with hyposmia, 10 (6.6%) with parosmia/cacosmia, and 58 patients (38.2%) with a combination of hyposmia and parosmia; seven (4.6%) patients suffered from headache exclusively, and two (1.4%) had headache and mental clouding as their primary symptom. Headache was reported by 76 (50%) patients, and mental clouding by 71 (46.7%). The patients reporting headache, mental clouding, or both, had significantly increased risk of suffering from anosmia and/or hyposmia when compared with their counterparts without these neurological symptoms. No patients had reduced MMSE scores. In our cohort of adult patients with post-COVID-19, smell alterations persisting over 6 months, cognitive impairment and headache were associated with more severe olfactory loss, consistent with neuroinflammatory mechanisms mediating a variety of Long-COVID symptoms