Comparing Visual-Only and Visual-Palpation Post-Mortem Lung Scoring Systems in Slaughtering Pigs

Respiratory diseases continue to pose significant challenges in pig production, and the assessment of lung lesions at the abattoir can provide valuable data for epidemiological investigations and disease surveillance. The evaluation of lung lesions at slaughter is a relatively simple, fast, and straightforward process but variations arising from different abattoirs, observers, and scoring methods can introduce uncertainty; moreover, the presence of multiple scoring systems complicates the comparisons of different studies, and currently, there are limited studies that compare these systems among each other. The objective of this study was to compare validated, simplified, and standardized schemes for assessing surface-related lung lesions in slaughtered pigs and analyze their reliability under field conditions. This study was conducted in a high-throughput abattoir in Italy, where two different scoring methods (Madec and Blaha) were benchmarked using 637 plucks. Statistical analysis revealed a good agreement between the two methods when severe or medium lesions were observed; however, their ability to accurately identify healthy lungs and minor injuries diverged significantly. These findings demonstrate that the Blaha method is more suitable for routine surveillance of swine respiratory diseases, whereas the Madec method can give more detailed and reliable results for the respiratory and welfare status of the animals at the farm level

A Spatially Resolved Dark- versus Light-Zone Microenvironment Signature Subdivides Germinal Center-Related Aggressive B Cell Lymphomas

We applied digital spatial profiling for 87 immune and stromal genes to lymph node germinal center (GC) dark- and light-zone (DZ/LZ) regions of interest to obtain a differential signature of these two distinct microenvironments. The spatially resolved 53-genes signature, comprising key genes of the DZmutational machinery and LZ immune and mesenchymal milieu, was applied to the transcriptomes of 543 GC-related diffuse large B cell lymphomas and double-hit ( DH) lymphomas. According to the DZ/LZ signature, the GC-related lymphomas were sub-classified into two clusters. The subgroups differed in the distribution of DH cases and survival, with most DH displaying a distinct DZ-like profile. The clustering analysis was also performed using a 25-genes signature composed of genes positively enriched in the non-B, stromal sub-compartments, for the first time achieving DZ/LZ discrimination based on stromal/immune features. The report offers new insight into the GC microenvironment, hinting at a DZ microenvironment of origin in DH lymphomas

Germinal center dysregulation by histone methyltransferase EZH2 promotes lymphomagenesis

Protection against deadly pathogens requires the production of high-affinity antibodies by B cells, which are generated in germinal centers (GCs). Alteration of the GC developmental program is common in many B cell malignancies. Identification of regulators of the GC response is crucial to develop targeted therapies for GC B cell dysfunctions, including lymphomas. The histone H3 lysine 27 methyltransferase enhancer of zeste homolog 2 (EZH2) is highly expressed in GC B cells and is often constitutively activated in GC-derived non-Hodgkin lymphomas (NHLs). The function of EZH2 in GC B cells remains largely unknown. Herein, we show that Ezh2 inactivation in mouse GC B cells caused profound impairment of GC responses, memory B cell formation, and humoral immunity. EZH2 protected GC B cells against activation-induced cytidine deaminase (AID) mutagenesis, facilitated cell cycle progression, and silenced plasma cell determinant and tumor suppressor B-lymphocyte–induced maturation protein 1 (BLIMP1). EZH2 inhibition in NHL cells induced BLIMP1, which impaired tumor growth. In conclusion, EZH2 sustains AID function and prevents terminal differentiation of GC B cells, which allows antibody diversification and affinity maturation. Dysregulation of the GC reaction by constitutively active EZH2 facilitates lymphomagenesis and identifies EZH2 as a possible therapeutic target in NHL and other GC-derived B cell diseases.Published versio

Upregulation of mGlu2 receptors via NF-kB p65 acetylation is involved in the proneurogenic and antidepressant effects of acetyl-L-carnitine

Acetyl-L-carnitine (ALC) is a naturally occurring molecule with an important role in cellular bioenergetics and as donor of acetyl groups to proteins, including NF-kappa B p65. In humans, exogenously administered ALC has been shown to be effective in mood disturbances, with a good tolerability profile. No current information is available on the antidepressant effect of ALC in animal models of depression and on the putative mechanism involved in such effect. Here we report that ALC is a proneurogenic molecule, whose effect on neuronal differentiation of adult hippocampal neural progenitors is independent of its neuroprotective activity. The in vitro proneurogenic effects of ALC appear to be mediated by activation of the NF-kappa B pathway, and in particular by p65 acetylation, and subsequent NF-kappa B-mediated upregulation of metabotropic glutamate receptor 2 (mGlu2) expression. When tested in vivo, chronic ALC treatment could revert depressive-like behavior caused by unpredictable chronic mild stress, a rodent model of depression with high face validity and predictivity, and its behavioral effect correlated with upregulated expression of mGlu2 receptor in hippocampi of stressed mice. Moreover, chronic, but not acute or subchronic, drug treatment significantly increased adult born neurons in hippocampi of stressed and unstressed mice. We now propose that this mechanism could be potentially involved in the antidepressant effect of ALC in humans. These results are potentially relevant from a clinical perspective, as for its high tolerability profile ALC may be ideally employed in patient subpopulations who are sensitive to the side effects associated with classical antidepressant

Video of task design and experimental conditions

Here you can find a video showing our immersive virtual scenario reproducing the collaborative workstation with the cobot UR10e. The video shows the five experimental tasks conducted by our participants. More specifically, a pick-and-place task was executed via button-based and action-based controls, and under both single- and dual-task conditions reflecting various levels of task demans. Furthermore, an arithmetic task was also executed to have a baseline of the cogntiive capacities of our participants. The dual-task was created by adding the arithmetic task to the pick-and-place task, which were to be performed concurrently. For the arithmetic task, a series of numbers ranging between 1 and 10 were randomly ptesented in text format. The participants were asked to sum these numbers and report the arithmetic result in a virtual keyboard by using the VR controller. In the pick-and-place task, participants were asked to pick the bolt from the workstation and place it into the box. In the button-based control condition, they only used the VR controller buttons, thus not involving any physical action. In the action-based control condition, instead, they could physically reach the cobot effector and drag it to the desired position, thus interacting more naturally with the digital replica of the cobot

The virtualization of human–robot interactions: a user-centric workload assessment

Interest in the virtualization of human-robot interactions is increasing, yet the impact that collaborating with either virtual or physical robots has on the human operator's mental state is still insufficiently studied. In the present work, we aimed to fill this gap by conducting a systematic assessment of a human-robot collaborative framework from a user-centric perspective. Mental workload was measured in participants working in synergistic co-operation with a physical and a virtual collaborative robot (cobot) under different levels of task demands. Performance and implicit and explicit workload were assessed as a function of pupil size variation and self-reporting questionnaires. In the face of a similar self-reported mental demand when maneuvering the virtual or physical cobot, operators showed shorter operation times and lower implicit workload when interacting with the virtual cobot compared to its physical counterpart. Furthermore, the benefits of collaborating with a virtual cobot most vividly manifested when the user had to position the robotic arm with higher precision. These results shed light on the feasibility and importance of relying on multidimensional assessments in real-life work settings, including implicit workload predictors such as pupillometric measures. From a broader perspective, our findings suggest that virtual simulations have the potential to bring significant advantages for both the user's mental well-being and industrial production, particularly for highly complex and demanding tasks

Novel cycloAmpRGD-Sunitinib Dual Conjugates as Potent Targeted Anti-angiogenic Tools

In recent years, targeted therapies that selectively address receptors and pathways involved in tumor genesis and progression have attracted growing interest. Some integrin subfamilies (e.g. αVβ3, αVβ5 and α5β1) have shown to be involved, even by close cooperation with other cell receptors (e.g. vascular endothelial growth factor receptors, VEGFRs) in tumor angiogenesis, which plays crucial role in tumor development and dissemination. Recent studies clearly demonstrated a complex in vivo regulation of tumor angiogenesis events; in particular, the αVβ3 integrin receptor is physically and functionally correlated with the VEGFR2 receptor within endothelial cells (ECs), suggesting that dual specific agents capable of inhibiting them would have a great anti-angiogenesis potential. Our research group has recently introduced a new class of cyclic semipeptide ligands, cycloAmpRGD, containing the Arg-Gly-Asp (RGD) sequence and 4-aminoproline scaffolds. These ligands demonstrated to efficiently and selectively bind to the αVβ3 integrin and their binding capability is preserved even in the presence of covalently conjugated “bulky loads” (cytotoxic and chelating agents). Here we report the synthesis, characterization and biological evaluation of a series of dual conjugates of type I, wherein the ligand cycloAmpRGD is covalently associated to a Sunitinib-derived moiety, a clinically approved anti-angiogenic multikinase inhibitor. The binding competence of these candidates toward the αVβ3 integrin in EC lines, their kinase inhibitory activity toward VEGFR2, and their ability to block endothelial cell capillary formation in vitro are described, in comparison with the single agents and related combinations. Encouraging results point to the notion that the covalent conjugation of cycloAmpRGD and Sunitinib may be of high therapeutic potential for tumor angiogenesis inhibition