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Simple Summary: Around 15% of sporadic colorectal cancers exhibit microsatellite instability. This unique tumor population appears to be poorly responsive to conventional chemotherapy and, conversely, reveals excellent results with immunotherapy. Our data, as demonstrated by propensity score-matched and win ratio analyses, show that there are no substantial differences between unstable and stable tumors in early colorectal cancers treated with surgery alone. On the contrary, stable tumors did much better than unstable tumors in the advanced stages of colorectal cancer undergoing conventional adjuvant treatment. Determination of the status of the DNA mismatch repair system is crucial in high-risk colorectal cancers to optimize treatment. A deficient DNA mismatch repair (MMR) system is identified in a non-negligible part of sporadic colorectal cancers (CRCs), and its prognostic value remains controversial. High tumor mutational burden, along with a poor response to conventional chemotherapy and excellent results from immunotherapy, are the main features of this subset. The aim of this study was to evaluate the predictive value of DNA MMR system status for its best treatment. Four hundred and three CRC patients, operated on from 2014 to 2021 and not treated with immunotherapy, entered this study. Immunohistochemistry and polymerase chain reaction, as appropriate, were used to unequivocally group specimens into microsatellite stable (MSS) and instable (MSI) tumors. The win-ratio approach was utilized to compare composite outcomes. MSI tumors accounted for 12.9% of all series. The right tumor location represented the most important factor related to MSI. The status of the DNA MMR system did not appear to correlate with outcome in early-stage CRCs not requiring adjuvant treatment; in advanced stages undergoing conventional chemotherapy, MSI tumors showed significantly poorer overall and disease-free survival rates and the highest win ratio instead. The determination of DNA MMR status is crucial to recommending correct management. There is clear evidence that instable CRCs needing adjuvant therapy should undergo appropriate treatments. [ABSTRACT FROM AUTHOR]

The organized large-scale retail sector has been gradually establishing itself around the world, and has increased activities exponentially in the pandemic period. This modern sales system uses Data Mining technologies processing precious information to increase profit. In this direction, the extreme gradient boosting (XGBoost) algorithm was applied in an industrial project as a supervised learning algorithm to predict product sales including promotion condition and a multiparametric analysis. The implemented XGBoost model was trained and tested by the use of the Augmented Data (AD) technique in the event that the available data are not sufficient to achieve the desired accuracy, as for many practical cases of artificial intelligence data processing, where a large dataset is not available. The prediction was applied to a grid of segmented customers by allowing personalized services according to their purchasing behavior. The AD technique conferred a good accuracy if compared with results adopting the initial dataset with few records. An improvement of the prediction error, such as the Root Mean Square Error (RMSE) and Mean Square Error (MSE), which decreases by about an order of magnitude, was achieved. The AD technique formulated for large-scale retail sector also represents a good way to calibrate the training model.

Background and purpose: pericoronary fat over-inflammation might lead to the development and destabilization of coronary plaque in patients with pre-diabetes (PDM). Notably, pericoronary fat could over-express the sodium-glucose cotransporter 2 (SGLT2) and leptin, along with decreased sirtuin 6 (SIRT6) expression in PDM vs. normoglycemic (NG) patients undergoing coronary artery bypass grafting (CABG) for acute myocardial infarction (AMI). However, in the current study, we evaluated inflammatory markers, SGLT2, SIRT6, and leptin levels in pericoronary fat and, subsequently, 12-month prognosis comparing PDM to NG subjected to CABG for AMI. In addition, we evaluated in PDM patients the effects of metformin therapy on SIRT6 expression, leptin, and SGLT2 levels, and assessed its beneficial effect on nitrotyrosine and inflammatory cytokine levels. Methods: we studied AMI patients referred for CABG, divided into PDM and NG-patients. PDM patients were divided into never-metformin users and metformin users. Finally, we evaluated major adverse cardiac events (MACE) at a 12-month follow-up. Results: the MACE was 9.1% in all PDM and 3% in NG patients (p < 0.05). Metformin users presented a significantly lower MACE rate in PDM than never-metformin users (p < 0.05). PDM showed higher inflammatory cytokines, 3-nitrotyrosine levels, SGLT2, and leptin content, and decreased SIRT6 protein levels in pericoronary fat compared to NG-patients (p < 0.05). PDM never-metformin-users showed higher SGLT2 and leptin levels in pericoronary fat than current-metformin-users (p < 0.05). Conclusions: metformin therapy might ameliorate cardiovascular outcomes by reducing inflammatory parameters, SGLT2, and leptin levels, and finally improving SIRT6 levels in AMI-PDM patients treated with CABG.

The characterization of a quarry site which is suitable for railway ballast aggregate production represents a big challenge for the mining industry. The knowledge of structural discontinuities within local geological materials is fundamental to guide mining operations, optimize investments, and guarantee quarry security. This research work presents an innovative methodology for the subsurface investigation of a quarry excavation area down to a depth of about 50 m in Falconara Albanese, Calabria, Italy. The proposed methodological approach incorporates photogrammetry, drone technology, and GPR data acquisition and processing. Photogrammetry represents the first step for obtaining a 3D topographical model reconstruction of the whole quarry, helping to detail the acquisition approach and properly plan the subsequent drone survey. In particular, two 120 MHz antennas have been mounted on the drone and two profiles have been acquired above and across the quarry. Results show the presence of fractured material and demonstrate the applicability of the method for identification of areas that are more suitable for railway ballast production. The presented method is therefore capable of detecting subsurficial fractures at a quarry site by means of a relatively fast and cost-effective procedure. Results are achieved within the framework of an industry project.

Summary: Rehabilitation is considered the most effective treatment for promoting the recovery of motor deficits after stroke. One of the most challenging experimental goals is to unambiguously link brain rewiring to motor improvement prompted by rehabilitative therapy. Previous work showed that robotic training combined with transient inactivation of the contralesional cortex promotes a generalized recovery in a mouse model of stroke. Here, we use advanced optical imaging and manipulation tools to study cortical remodeling induced by this rehabilitation paradigm. We show that the stabilization of peri-infarct synaptic contacts accompanies increased vascular density induced by angiogenesis. Furthermore, temporal and spatial features of cortical activation recover toward pre-stroke conditions through the progressive formation of a new motor representation in the peri-infarct area. In the same animals, we observe reinforcement of inter-hemispheric connectivity. Our results provide evidence that combined rehabilitation promotes the restoration of structural and functional features distinctive of healthy neuronal networks. : Robotic training combined with transient contralesional inactivation was recently shown to promote a generalized recovery after stroke. Here, Allegra Mascaro et al. investigate how this rehabilitation paradigm affects neuronal and vascular plasticity of the mouse cortex. Synaptic stabilization is associated with angiogenesis and recovery of a segregated motor representation. Keywords: robotic rehabilitation, pharmacological therapy, two-photon microscopy, in vivo, cerebral cortex, spine plasticity, photothrombosis, optogenetics, calcium imaging, angiogenesis

Coating fruits with shellac after storage improves fruit appearance. Moreover, it could preserve better their intrinsic quality and prevent physiological disorders such as superficial scald. During two years the influence of the coating with shellac and of the related treatment process was investigated on apple cv. Red Delicious and Fuji at the Research Centre Laimburg taking into account the difference in quality, before the coating, after storage either in CA-ULO, CA-ULO with SmartFresh or in dynamic CA by means of chlorophyll fluorescence (DCA-CF). On treated Red Delicious a trend for lower water-loss and scald and for higher firmness was observed after shelf-life. On treated Fuji we could demonstrate that the thermal shock involved in the coating process induced lenticel breakdown, and not the coating itself.

Human epidermal growth factor receptor 2 (HER2) is a transmembrane growth factor receptor with tyrosine kinase activity regulating cell growth and survival. HER2 amplification is responsible for protein overexpression with a negative impact on prognosis, but HER2-overexpressing patients could be treated with anti-HER2 therapy. In gastric cancer HER2 overexpression is observed in approximately 22% of patients, but prognostic significance in this context is not clear. In colon adenocarcinoma, HER2 gene amplification is reported in a wide range from 0% to 83%. The wide range of reported series could be essentially attributable to a difference in scoring systems for HER2 protein expression. The use of testing score, although measuring the same protein, is different from gastric cancer to colorectal cancer. Herein the different scoring models are reported.

Toll-like receptors (TLRs) are key receptors through which infectious and non-infectious challenges act with consequent activation of the inflammatory cascade that plays a critical function in various acute and chronic diseases, behaving as amplification and chronicization factors of the inflammatory response. Previous studies have shown that synthetic analogues of lipid A based on glucosamine with few chains of unsaturated and saturated fatty acids, bind MD-2 and inhibit TLR4 receptors. These synthetic compounds showed antagonistic activity against TLR4 activation in vitro by LPS, but little or no activity in vivo. This study aimed to show the potential use of N-palmitoyl-D-glucosamine (PGA), a bacterial molecule with structural similarity to the lipid A component of LPS, which could be useful for preventing LPS-induced tissue damage or even peripheral neuropathies. Molecular docking and molecular dynamics simulations showed that PGA stably binds MD-2 with a MD-2/(PGA)3 stoichiometry. Treatment with PGA resulted in the following effects: (i) it prevented the NF-kB activation in LPS stimulated RAW264.7 cells; (ii) it decreased LPS-induced keratitis and corneal pro-inflammatory cytokines, whilst increasing anti-inflammatory cytokines; (iii) it normalized LPS-induced miR-20a-5p and miR-106a-5p upregulation and increased miR-27a-3p levels in the inflamed corneas; (iv) it decreased allodynia in peripheral neuropathy induced by oxaliplatin or formalin, but not following spared nerve injury of the sciatic nerve (SNI); (v) it prevented the formalin- or oxaliplatin-induced myelino-axonal degeneration of sciatic nerve. SIGNIFICANCE STATEMENT We report that PGA acts as a TLR4 antagonist and this may be the basis of its potent anti-inflammatory activity. Being unique because of its potency and stability, as compared to other similar congeners, PGA can represent a tool for the optimization of new TLR4 modulating drugs directed against the cytokine storm and the chronization of inflammation.

Amyloidosis is a systemic disease characterized by the accumulation of insoluble aggregates in various organs, leading to parenchymal damage. When these amyloid fibrils are deposited in the extracellular matrix of the cardiac structures, the condition is referred to as cardiac amyloidosis (CA). The extent of organ involvement determines the degree of cardiac impairment, which can significantly impact prognosis. The two most implicated proteins in CA are transthyretin and misfolded monoclonal immunoglobulin light chains. These proteins give rise to two distinct clinical forms of CA: transthyretin amyloidosis (ATTR-CA) and light-chain amyloidosis (AL-CA). ATTR-CA is further classified into two subtypes: ATTRm-CA, which occurs at a younger age and is caused by hereditary misfolded mutated proteins, and ATTRwt-CA, which is an acquired wild-type form more commonly observed in older adults, referred to as senile amyloidosis. While AL-CA was considered the most prevalent form for many years, recent autopsy studies have revealed an increase in cases of ATTRwt-CA. This narrative review aims to describe the clinical and imaging features of CA, with a particular focus on cardiac complications and mortality associated with the AL form. Early identification and differentiation of CA from other disorders are crucial, given the higher risk and severity of cardiac involvement in AL-CA. Furthermore, emphasis is placed on the potential utility of cardiovascular magnetic resonance imaging in detecting early cases of CA. [ABSTRACT FROM AUTHOR]

In the last two decades, reports of canine heartworm (HW) infection have increased even in non-endemic areas, with a large variability in prevalence data due to the diagnostic strategy employed. This study evaluated the relative performance of two microtiter plate ELISA methods for the detection of HW antigen in determining the occurrence of Dirofilaria immitis in a dog population previously tested by the modified Knott’s test and SNAP 4Dx Plus test. The prevalence of this infection in the sheltered dog population (n = 363) from a high-risk area for HW infection was 44.4% according to the modified Knott’s test and 58.1% according to a point-of-care antigen ELISA. All serum samples were then evaluated by a microtiter plate ELISA test performed with and without immune complex dissociation (ICD). The prevalence increased from 56.5% to 79.6% following ICD, indicating a high proportion of samples with immune complexing. Comparing these results to that of the modified Knott’s test, the samples negative for microfilariae (mfs) and those positive only for D. repens mfs demonstrated the greatest increase in the proportion of positive results for D. immitis by ELISA following ICD. While the ICD method is not recommended for routine screening, it may be a valuable secondary strategy for identifying HW infections in dogs.

Una creciente desafección hacia la publicidad tradicional y la exigencia de autenticidad en la comunicación han llevado a los consumidores a privilegiar, en el último decenio, formas de publicidad más acompasadas con los intereses de su público de referencia y a integrarlas como piezas más informativas que promocionales al convertir el contenido de la marca en parte de su narración. Sobre estas bases, se ha investigado el documental como formato del contenido de marca a fin de analizar sus características narrativas como estrategia de comunicación publicitaria. La hipótesis de partida es que, más allá de los elementos narrativos objetivos e racionales, propios de la retórica del logos aristotélico, se construye un discurso emotivo (pathos) con el que se intenta comunicar al público la imagen de una marca (ethos) socialmente comprometida con su público. Así, la marca se propone como una autoridad en el ámbito de los intereses de sus consumidores potenciales, quienes se identificarán más fácilmente con ella.

Focal cortical stroke often leads to persistent motor deficits, prompting the need for more effective interventions. The efficacy of rehabilitation can be increased by ‘plasticity-stimulating’ treatments that enhance experience-dependent modifications in spared areas. Transcallosal pathways represent a promising therapeutic target, but their role in post-stroke recovery remains controversial. Here, we demonstrate that the contralesional cortex exerts an enhanced interhemispheric inhibition over the perilesional tissue after focal cortical stroke in mouse forelimb motor cortex. Accordingly, we designed a rehabilitation protocol combining intensive, repeatable exercises on a robotic platform with reversible inactivation of the contralesional cortex. This treatment promoted recovery in general motor tests and in manual dexterity with remarkable restoration of pre-lesion movement patterns, evaluated by kinematic analysis. Recovery was accompanied by a reduction of transcallosal inhibition and ‘plasticity brakes’ over the perilesional tissue. Our data support the use of combinatorial clinical therapies exploiting robotic devices and modulation of interhemispheric connectivity.