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The ever-growing knowledge regarding NSCLC molecular biology has brought innovative therapies into clinical practice; however, the treatment situation in the non-metastatic setting is rapidly evolving. Indeed, immunotherapy-based perioperative treatments are currently considered the standard of care for patients with resectable NSCLC in the absence of EGFR mutations or ALK gene rearrangements. Recently, data have been presented on the use of tyrosine kinase inhibitors (TKIs) in the adjuvant and locally advanced setting for patients with NSCLC harboring such driver gene alterations. The aim of the current work is to review the available evidence on the use of targeted treatments in the non-metastatic setting, together with a summary of the ongoing trials designed for actionable gene alterations other than EGFR and ALK. To date, 3-year adjuvant osimertinib treatment has been demonstrated to improve DFS and OS and to reduce CNS recurrence in resected EGFR-mutated NSCLC in stage IB–IIIA (TNM 7th edition). The use of osimertinib after chemo-radiation in stage III unresectable EGFR-mutated NSCLC showed the relevant PFS improvement. In the ALK-positive setting, 2-year alectinib treatment was shown to clearly improve DFS compared to adjuvant standard chemotherapy in resected NSCLC with stage IB (≥4 cm)–IIIA (TNM 7th edition). Several trials are ongoing to establish the optimal adjuvant TKI treatment duration, as well as neoadjuvant TKI strategies in EGFR- and ALK-positive disease, and (neo)adjuvant targeted treatments in patients with actionable gene alterations other than EGFR or ALK. In conclusion, our review depicts how the current treatment scenario is expected to rapidly change in the context of non-metastatic NSCLC with actionable gene alterations, hence appropriate molecular testing from the early stages has become crucial to establish the most adequate approaches both in the perioperative and the locally advanced disease.

Background: A significant number of young individuals are readmitted one or more times shortly after their first episode of psychosis. Readmission may represent a marker of psychopathological vulnerability. Our primary aim was to evaluate the impact of clinical and socio-demographic variables on readmission at 12-month follow-up. Secondly, our goal was to determine whether the use of Long-Acting Injection (LAI) antipsychotics provides notable benefits compared to oral medications in preventing subsequent readmissions. Subjects and methods: 80 patients hospitalised for the first time with a diagnosis of psychotic disorder (ICD-10 criteria) were retrospectively assessed through clinical records. The mean age was 21.7 years. Patients were predominantly male (n = 62, 77.5%), and 55 subjects had at least 8 years of education. 50% of the sample was “NEET” (not in education, employment, or training). Results: 35 patients (43.8%) were discharged with a LAI antipsychotic, while 45 (56.2%) recieved oral antipsychotic therapy. Substance use (p = 0.04) and oral antipsychotics at discharge (p = 0.003) were significantly associated with readmission at 1 year. We did not find any significant predictors of being discharged with LAI therapy. Conclusion: Our findings underlined the importance of identifying patients at risk of readmission in order to prevent future rehospitalization and promote appropriate prevention strategies. LAIs should be considered as a first-choice treatment for patients hospitalised for FEP since they proved to be effective in preventing relapse.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has had a global impact and resulted in millions of deaths worldwide. The course of the Janus kinase signaling transducers and activators (JAK-STAT) pathway is an important molecular pathway that is involved in the cellular response to various cytokines and growth factors promoting an inflammatory response. The overactivation of the JAK-STAT signaling pathway in coronavirus disease 2019 (COVID-19) and its effect on acute respiratory distress syndrome (ARDS)-induced inflammatory processes was observed in various clinical articles that focused on JAK-STAT regulation regarding angiotensin converting enzyme 2 (ACE2) expression and cytokine storm release. Down-regulation of the JAK-STAT signaling pathway through inhibitors decreases the inflammatory response by decreasing cytokine storm release. However, the increased regulation of JAK-STAT in severe COVID-19 patients caused cytokines such as interferon alpha (IFN-α) to promote the phosphorylation of STATs. This response indicated an imbalance with JAK-STAT regulation and its inability to induce the transcription of interferon stimulated response elements. Furthermore, an increase in ACE2 regulation was noted to also increase JAK-STAT signaling, yet the down-regulation of JAK-STAT signaling can result in the overexpression of ACE2 by binding to SARS-CoV-2 and increasing STAT1 expression. Data suggest that inflammatory cytokines enhance the activation of ACE2 in endothelial cells via JAK-STAT pathway. Increasing the regulation of the JAK-STAT signaling pathway enhances the release of cytokines such as tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ), further expressing ACE2. The expression of ACE2 regulates STAT1 and STAT2 expression, leading to the up-regulation of the inflammasomal complexes in hyper-inflammatory responses from the JAK-STAT pathway. Through the review of various clinical reports, the effect of the JAK-STAT signaling pathway on ARDS-induced inflammatory response was observed and correlated with the expression of ACE2 and cytokine storm release in severe COVID-19 cases.

Models are a core element in performing local estimation of the climate change input. In this work, a novel approach to perform a fast downscaling of global temperature anomalies on a regional level is presented. The approach is based on a set of data-driven models linking global temperature anomalies and regional and global emissions to regional temperature anomalies. In particular, due to the limited number of available data, a linear autoregressive structure with exogenous input (ARX) has been considered. To demonstrate their relevance to the existing literature and context, the proposed ARX models have been employed to evaluate the impact of temperature anomalies on rice production in a socially, economically, and climatologically fragile area like Southeast Asia. The results show a significant impact on this region, with estimations strongly in accordance with information presented in the literature from different sources and scientific fields. The work represents a first step towards the development of a fast, data-driven, holistic approach to the climate change impact evaluation problem. The proposed ARX data-driven models reveal a novel and feasible way to downscale global temperature anomalies to regional levels, showing their importance in comprehending global temperature anomalies, emissions, and regional climatic conditions.

In breast cancer volumetric-modulated arc therapy (VMAT) planning, the rotation of the gantry around the target implies a greater dose spreading to the whole heart, compared to tangential-field standard treatment. A consecutive cohort of 121 breast cancer patients treated with the VMAT technique was investigated. The correlation of breast volume, heart volume and lung volume with mean heart dose (mHD) and mean and maximum LAD dose (mLAD dose, MLAD dose) was tested, and a subsequent a linear regression analysis was carried out. VMAT treatment plans from 56 left breast cancer and 65 right breast cancer patients were analyzed. For right-sided patients, breast volume was significantly correlated with mHD, mLAD and MLAD dose, while for left-sided patients, breast volume was significantly correlated with mHD and mLAD, while heart volume and lung volume were correlated with mHD, mLAD and MLAD dose. Breast volume was the only predictor of increased heart and LAD dose (p ≤ 0.001) for right-sided patients. In left-sided patients, heart and lung were also predictors of increased mHD (p = 0.005, p ≤ 0.001) and mean LAD dose (p = 0.009, p ≤ 0.001). In this study, we observed an increase in heart and LAD doses in larger-breasted patients treated with VMAT planning. In right-sided patients, breast volume was shown to be the only predictor of increased heart dose and LAD dose.

Down syndrome (DS) is one of the most common chromosomal disorders. In addition to this variety of dysmorphic features. DS is also associated with a wide range of diseases and related comorbidities affecting different organs and systems. These comorbidities, together with societal and environmental influences, have a negative impact on physical activity in people with DS. Low levels of physical activity and energy expenditure have been identified as crucial players in worsening the acquisition of motor skills and executive functions. Executive functions are critical for the many skills (creativity, flexibility, self-control, and discipline) impacting our quality of life and make it possible to control impulses, mentally play with ideas, and stay focused. We proposed a broad overview of the available literature regarding motor skills and executive functions in pediatric patients with DS to understand the specific challenges for tailoring physical activity interventions. Motor skill interventions are effective in improving motor competence and performance on cognitive, emotional, and physical aspects in children with DS. Interventions based on executive functions in DS subjects are effective to contrast the cognitive decline and improve the everyday use of executive functions in youth and adults. Targeted interventions are mandatory for maximizing the benefits of physical activity, minimizing potential risks, and ultimately improving the overall health outcomes and quality of life for individuals with DS.

Atherosclerosis is a pathological condition characterized by the inflammation of arterial vessels, leading to serious cardiovascular outcomes such as myocardial infarction, stroke, and death [...]

A new fossil gray whale genus and species, Glaucobalaena inopinata, is established based on craniomandibular remains from the Pliocene Sabbie d’Asti Formation, Piedmont, northwestern Italy. The holotype (MGPT-PU 19512) consists of two cranial fragments corresponding to the posterolateral corners of the skull, including both partial periotics, and in the posterior portion of the right mandibular ramus preserving the condyle and angular process. The new taxon is characterized by gray whale (eschrichtiid) synapomorphies in the posterior portion of the mandible (dorsally raised mandibular condyle with articular surface faced dorsoposteriorly, well-developed and robust angular process of the mandible) and in the earbone (massive transverse elongation of the pars cochlearis, indistinct flange of the ventrolateral tuberosity, and triangular and short anterior process of the periotic). A CT scan of the cranial fragments allowed us to reconstruct tridimensional renderings of the periotic, revealing the dorsal morphology of this bone. A phylogenetic analysis confirmed the inclusion of Glaucobalaena inopinata within Eschrichtiidae (the family to whom gray whales are included) and showed that it is monophyletic with Gricetoides aurorae; our phylogenetic results show that Eschrichtioides gastaldii is the sister group of the genus Eschrichtius. Our work lends further support to the idea that Eschrichtiidae is a separate family of baleen whales, characterized by specialized ecomorphological characters evident in both skull and mandibular architecture.

Glaucoma is chronic optic neuropathy whose pathogenesis has been associated with the altered metabolism of Trabecular Meshwork Cells, which is a cell type involved in the synthesis and remodeling of the trabecular meshwork, the main drainage pathway of the aqueous humor. Starting from previous findings supporting altered ubiquitin signaling, in this study, we investigated the ubiquitin-mediated turnover of myocilin (MYOC/TIGR gene), which is a glycoprotein with a recognized role in glaucoma pathogenesis, in a human Trabecular Meshwork strain cultivated in vitro in the presence of dexamethasone. This is a validated experimental model of steroid-induced glaucoma, and myocilin upregulation by glucocorticoids is a phenotypic marker of Trabecular Meshwork strains. Western blotting and native-gel electrophoresis first uncovered that, in the presence of dexamethasone, myocilin turnover by proteasome particles was slower than in the absence of the drug. Thereafter, co-immunoprecipitation, RT-PCR and gene-silencing studies identified STUB1/CHIP as a candidate E3-ligase of myocilin. In this regard, dexamethasone treatment was found to downregulate STUB1/CHIP levels by likely promoting its proteasome-mediated turnover. Hence, to strengthen the working hypothesis about global alterations of ubiquitin-signaling, the first profiling of TMCs ubiquitylome, in the presence and absence of dexamethasone, was here undertaken by diGLY proteomics. Application of this workflow effectively highlighted a robust dysregulation of key pathways (e.g., phospholipid signaling, β-catenin, cell cycle regulation) in dexamethasone-treated Trabecular Meshwork Cells, providing an ubiquitin-centered perspective around the effect of glucocorticoids on metabolism and glaucoma pathogenesis.

On 4 November 2021, during the rising phase of solar cycle 25, an intense geomagnetic storm (Kp = 8−) occurred. The effects of this storm on the outer magnetospheric region up to the ionospheric heights have already been examined in previous investigations. This work is focused on the analysis of the solar wind conditions before and during the geomagnetic storm, the high-latitude electrodynamics conditions, estimated through empirical models, and the response of the atmosphere in both hemispheres, based on parameters from the ECMWF ERA5 atmospheric reanalysis dataset. Our investigations are also supported by counter-test analysis and Monte Carlo tests. We find, for both hemispheres, a significant correspondence, within 1–2 days, between high-latitude electrodynamics variations and changes in the temperature, specific humidity, and meridional and zonal winds, in both the troposphere and stratosphere. The results indicate that, in the complex solar wind–atmosphere relationship, a significant role might be played by the intensification of the polar cap potential. We also study the reciprocal relation between the ionospheric Joule heating, calculated from a model, and two adiabatic invariants used in the analysis of solar wind turbulence.

Per- and polyfluoroalkyl substances (PFASs) have been under intense investigation by the scientific community due to their persistence in the environment and potentially hazardous effects on living organisms. In order to tackle the presence of these compounds in water, to date, the research has been strongly focused on the evaluation of the effectiveness of different types of technologies. Considering the extreme complexity of the matter of PFASs and our relatively low knowledge in this topic, the following question arises: is the “chemical only” approach that is followed for evaluating the effectiveness of technologies for PFAS removal from water reliable enough? In this work, some limitations of the present approach are discussed, highlighting the reasons why it cannot be considered a reliable tool to correctly estimate the effectiveness of technology when referring to emerging compounds such as PFASs. Bioassays can play a key role in moving towards an integrated bio-chemical evaluation (chemical analysis and ecotoxicological evaluation), which is strongly encouraged. This represents the only way to completely characterize a water matrix and fully evaluate the impact of technologies when dealing with micropollutants in water, such as PFASs. Future research should focus on defining an optimal battery of bioassays that specifically fit to best represent changes in water quality in terms of short- and long-term impacts on living organisms.

Background: Actionable driver mutations account for 40–50% of NSCLC cases, and their identification clearly affects treatment choices and outcomes. Conversely, non-actionable mutations are genetic alterations that do not currently have established treatment implications. Among co-occurring alterations, the identification of concurrent actionable genomic alterations is a rare event, potentially impacting prognosis and treatment outcomes. Methods: We retrospectively evaluated the prevalence and patterns of concurrent driver genomic alterations in a large series of NSCLCs to investigate their association with clinicopathological characteristics, to assess the prognosis of patients whose tumor harbors concurrent alterations in the genes of interest and to explore their potential therapeutic implications. Results: Co-occurring driver alterations were identified in 26 out of 1520 patients with at least one gene alteration (1.7%). Within these cases, the incidence of concurrent actionable gene alterations was 39% (0.7% of the overall cohort). Among compound actionable gene mutations, EGFR was the most frequently involved gene (70%). The most frequent association was EGFR mutations with ROS1 rearrangement. Front-line targeted treatments were the preferred approach in patients with compound actionable mutations, with dismal median PFS observed (6 months). Conclusions: Advances in genomic profiling technologies are facilitating the identification of concurrent mutations. In patients with concurrent actionable gene alterations, integrated molecular and clinical data should be used to guide treatment decisions, always considering rebiopsy at the moment of disease progression.

In orthopedics, X-rays and computed tomography (CT) scans play pivotal roles in diagnosing and treating bone pathologies. Machine bulkiness and the emission of ionizing radiation remain the main problems associated with these techniques. The accessibility and low risks related to ultrasound handling make it a popular 2D imaging method. Indeed, 3D ultrasound assembles 2D slices into a 3D volume. This study aimed to implement a probe-tracking method for 6 DoF 3D ultrasound. The proposed method involves a dodecahedron with ArUco markers attached, enabling computer vision tracking of the ultrasound probe’s position and orientation. The algorithm focuses on the data acquisition phase but covers the basic reconstruction required for data generation and analysis. In the best case, the analysis revealed an average error norm of 2.858 mm with a standard deviation norm of 5.534 mm compared to an infrared optical tracking system used as a reference. This study demonstrates the feasibility of performing volumetric imaging without ionizing radiation or bulky systems. This marker-based approach shows promise for enhancing orthopedic imaging, providing a more accessible imaging modality for helping clinicians to diagnose pathologies regarding complex joints, such as the shoulder, replacing standard infrared tracking systems known to suffer from marker occlusion problems.

The use of agroforestry biomass provides several advantages, both from an environmental point of view, in terms of the mitigation of global warming, and in terms of a circular economy for agricultural or agroforestry companies that reuse pruning residues as a source of energy. However, even if the use of energy pellets resulting from the pruning residues of various agroforestry species has excellent potential for the valorization of agricultural by-products, the physicochemical characteristics of these pellets have been scarcely studied by the scientific community. In this context, this study aims to assess the valorization potential of various lignocellulosic material residues produced during agroforestry activities. The objectives of the study include evaluating the chemical and physical characteristics of pellets produced with different mixtures of agroforestry biomass (olive, citrus, black locust, poplar, paulownia, etc.) in order to determine the optimal pellet blend from an energy and physicochemical perspective. The results of this study demonstrate that this comprehensive analysis provides valuable information on the optimization of biomass mixtures for better energy valorization, addressing both compositional and combustion-related challenges. In fact, it is observed that the addition of citrus and olive biomass to the various mixtures increases their energy potential. Furthermore, all of the pellets analyzed are found to possess an adequate and useful durability index (PDI) for their handling during storage and transport operations. This study demonstrates that olive and citrus pruning residues can be used to improve biomasses that have poor suitability in energetic, physical, and chemical terms. Further studies could be useful to understand which specific interaction mechanisms have an influence on emissions in order to optimize mixtures using different biomass sources for sustainable energy production.

Third-generation tyrosine kinase inhibitors are the first-line gold standard in treating advanced non-small-cell lung cancer bearing common EGFR mutations, but data documenting clinical efficacy in uncommon mutations are currently limited. In this paper, we describe the case of a patient bearing uncommon compound EGFR mutations in exon 20, who experienced a near-complete response to third-line Osimertinib, with metabolic complete response of pulmonary, nodal and ostheolytic lesions. This radiological assessment corresponded to an ECOG PS improvement (from three to one) and a substantial clinical benefit for the patients. Out of two mutations, S768I was associated with poor response to third-generation TKI and V774M had unknown clinical significance, highlighting the complexity of the correct management of these kinds of mutations. We reviewed the literature to document the up-to-date preclinical and clinical data concerning third-generation tyrosine kinase inhibitors for the treatment of patients bearing uncommon EGFR mutations.

Background/Objectives: To investigate macular vascular biomarkers for the detection of primary open-angle glaucoma (POAG). Methods: A total of 56 POAG patients and 94 non-glaucomatous controls underwent optical coherence tomography angiography (OCTA) assessment of macular vessel density (VD) in the superficial (SCP), and deep (DCP) capillary plexus, foveal avascular zone (FAZ) area, perimeter, VD, choriocapillaris and outer retina flow area. POAG patients were classified for severity based on the Glaucoma Staging System 2 of Brusini. ANCOVA comparisons adjusted for age, sex, race, hypertension, diabetes, and areas under the receiver operating characteristic curves (AUCs) for POAG/control differentiation were compared using the DeLong method. Results: Global, hemispheric, and quadrant SCP VD was significantly lower in POAG patients in the whole image, parafovea, and perifovea (p < 0.001). No significant differences were found between POAG and controls for DCP VD, FAZ parameters, and the retinal and choriocapillaris flow area (p > 0.05). SCP VD in the whole image and perifovea were significantly lower in POAG patients in stage 2 than stage 0 (p < 0.001). The AUCs of SCP VD in the whole image (0.86) and perifovea (0.84) were significantly higher than the AUCs of all DCP VD (p < 0.05), FAZ parameters (p < 0.001), and retinal (p < 0.001) and choriocapillaris flow areas (p < 0.05). Whole image SCP VD was similar to the AUC of the global retinal nerve fiber layer (RNFL) (AUC = 0.89, p = 0.53) and ganglion cell complex (GCC) thickness (AUC = 0.83, p = 0.42). Conclusions: SCP VD is lower with increasing functional damage in POAG patients. The AUC for SCP VD was similar to RNFL and GCC using clinical diagnosis as the reference standard.

Various next-generation ALK TKIs are available as first-line options for ALK-positive NSCLC, with alectinib and lorlatinib being commonly preferred. However, no direct comparison between them has been conducted, making it impossible to pick a winner. We performed an analytic, ‘non-comparative’ assessment of the two phase 3 pivotal clinical trials showing superiority of alectinib (ALEX) and lorlatinib (CROWN) in comparison to crizotinib. Overall, the two studies were very similar in the study design and patient characteristics, with the exception of the selection and evaluation of brain metastases. PFS hazard ratios numerically favored lorlatinib, both according to the investigator and to BICR. Notably, the 3-year PFS rate was numerically higher with lorlatinib (64%) than with alectinib (46.4%). Despite similar response rates and overall intracranial response, the rate of complete intracranial response was higher with lorlatinib, with a cumulative incidence risk of CNS disease progression at 12 months of 9.4% with alectinib and 2.8% with lorlatinib. The peculiar toxicities of lorlatinib were related to lipidic profile alterations, peripheral oedema and cognitive effects, with no impact on cardiovascular risk nor impairment in quality of life versus crizotinib. Furthermore, the rate of permanent treatment discontinuation due to adverse events was numerically higher with alectinib (26%) than with lorlatinib (7%). In conclusion, despite the immature OS data for both drugs, the efficacy of lorlatinib appears higher than alectinib while maintaining a manageable toxicity profile.

Black soldier fly larvae (BSFL) can convert various organic substrates into high added-value biomass. In addition, the residue can be used as a soil conditioner. Several studies have been conducted on a laboratory scale that may not represent what happens on a prototype scale. Using fruit and vegetable waste as a basic substrate, mixing them with agro-industry by-products (called co-substrates), the Hermes project set up a process on medium (2 kg) and large (10 kg) scales with two different feeding regimes (1.25 g/BSFL and 2 g/BSFL). At the mature stage, larval biomass was separated from frass (the by-product of the larval rearing). The production of larval proteins and fats and the use of frass as soil conditioning were evaluated. The lowest feeding regime (1.25 g/BSFL) provided the best waste valorization. The shift towards higher production scales is not completely linear. The addition of co-substrates to fruit and vegetable waste, as they are provided by the large-scale retail trade, can help to standardize a process as part of an insect farm. The frass recovered from the residue of rearing (on the diet or on the agrifood leftovers) was composted and used in field to grow a processing tomato variety. The addition of composted frass assured a slightly lower yield than synthetic fertilizer but there was no statistically significant difference (p > 0.10). This suggests that partial replacement of synthetic fertilizer with composted frass has potential. Overall, the work demonstrated that, using a multidisciplinary approach, the interest and the value in building a supply chain based on bioconversion mediated by Hermetia illucens can be emphasized.

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma accounting for 15% of lung cancers with dismal survival outcomes. Minimal changes in therapy and prognosis have occurred in SCLC for the past four decades. Recent progress in the treatment of extensive-stage disease (ES-SCLC) has been marked by incorporating immune checkpoint inhibitors (ICIs) into platinum-based chemotherapy, leading to modest improvements. Moreover, few second-line-and-beyond treatment options are currently available. The main limitation for the molecular study of SCLC has been the scarcity of samples, because only very early diseases are treated with surgery and biopsies are not performed when the disease progresses. Despite all these difficulties, in recent years we have come to understand that SCLC is not a homogeneous disease. At the molecular level, in addition to the universal loss of retinoblastoma (RB) and TP53 genes, a recent large molecular study has identified other mutations that could serve as targets for therapy development or patient selection. In recent years, there has also been the identification of new genetic subtypes which have shown us how intertumor heterogeneity exists. Moreover, SCLC can also develop intratumoral heterogeneity linked mainly to the concept of cellular plasticity, mostly due to the development of resistance to therapies. The aim of this review is to quickly present the current standard of care of ES-SCLC, to focus on the molecular landscapes and subtypes of SCLC, subsequently present the most promising therapeutic strategies under investigation, and finally recap the future directions of ongoing clinical trials for this aggressive disease which still remains a challenge.

Gut-dysbiosis-induced lipopolysaccharides (LPS) translocation into systemic circulation has been suggested to be implicated in nonalcoholic fatty liver disease (NAFLD) pathogenesis. This study aimed to assess if oleuropein (OLE), a component of extra virgin olive oil, lowers high-fat-diet (HFD)-induced endotoxemia and, eventually, liver steatosis. An immunohistochemistry analysis of the intestine and liver was performed in (i) control mice (CTR; n = 15), (ii) high-fat-diet fed (HFD) mice (HFD; n = 16), and (iii) HFD mice treated with 6 µg/day of OLE for 30 days (HFD + OLE, n = 13). The HFD mice developed significant liver steatosis compared to the controls, an effect that was significantly reduced in the HFD + OLE-treated mice. The amount of hepatocyte LPS localization and the number of TLR4+ macrophages were higher in the HFD mice in the than controls and were lowered in the HFD + OLE-treated mice. The number of CD42b+ platelets was increased in the liver sinusoids of the HFD mice compared to the controls and decreased in the HFD + OLE-treated mice. Compared to the controls, the HFD-treated mice showed a high percentage of intestine PAS+ goblet cells, an increased length of intestinal crypts, LPS localization and TLR4+ expression, and occludin downregulation, an effect counteracted in the HFD + OLE-treated mice. The HFD-fed animals displayed increased systemic levels of LPS and zonulin, but they were reduced in the HFD + OLE-treated animals. It can be seen that OLE administration improves liver steatosis and inflammation in association with decreased LPS translocation into the systemic circulation, hepatocyte localization of LPS and TLR4 downregulation in HFD-induced mouse model of NAFLD.

Mast cells (MCs) are tissue-resident immune cells distributed in all tissues and strategically located close to blood and lymphatic vessels and nerves. Thanks to the expression of a wide array of receptors, MCs act as tissue sentinels, able to detect the presence of bacteria and parasites and to respond to different environmental stimuli. MCs originate from bone marrow (BM) progenitors that enter the circulation and mature in peripheral organs under the influence of microenvironment factors, thus differentiating into heterogeneous tissue-specific subsets. Even though MC activation has been traditionally linked to IgE-mediated allergic reactions, a role for these cells in other pathological conditions including tumor progression has recently emerged. However, several aspects of MC biology remain to be clarified. The advent of single-cell RNA sequencing platforms has provided the opportunity to understand MCs’ origin and differentiation as well as their phenotype and functions within different tissues, including the gut. This review recapitulates how single-cell transcriptomic studies provided insight into MC development as well as into the functional role of intestinal MC subsets in health and disease.

Fibrosis is a pathological condition consisting of a delayed deposition and remodeling of the extracellular matrix (ECM) by fibroblasts. This deregulation is mostly triggered by a chronic stimulus mediated by pro-inflammatory cytokines, such as TNF-α and IL-1, which activate fibroblasts. Due to their anti-inflammatory and immunosuppressive potential, dental pulp stem cells (DPSCs) could affect fibrotic processes. This study aims to clarify if DPSCs can affect fibroblast activation and modulate collagen deposition. We set up a transwell co-culture system, where DPSCs were seeded above the monolayer of fibroblasts and stimulated with LPS or a combination of TNF-α and IL-1β and quantified a set of genes involved in inflammasome activation or ECM deposition. Cytokines-stimulated co-cultured fibroblasts, compared to unstimulated ones, showed a significant increase in the expression of IL-1β, IL-6, NAIP, AIM2, CASP1, FN1, and TGF-β genes. At the protein level, IL-1β and IL-6 release as well as FN1 were increased in stimulated, co-cultured fibroblasts. Moreover, we found a significant increase of MMP-9 production, suggesting a role of DPSCs in ECM remodeling. Our data seem to suggest a crosstalk between cultured fibroblasts and DPSCs, which seems to modulate genes involved in inflammasome activation, ECM deposition, wound healing, and fibrosis.

Mining wastewater (MWW) can contain mercury in high concentrations. In this study, four autochthonous aquatic plant species (Eichhornia Crassipes—EC, Marsilea Quadrifolia—MQ, Ludwigia Helminthorrhiza—LH, and Lemna Minor—LM) were identified and tested for phytoaccumulation of total mercury (THg). To better study the accumulation phenomenon and macrophyte responses, this work has been divided into three phases, and pilot-scale reactors have been used to simulate real conditions. The results highlighted that, in case of 15 µgTHg,fed, the bioconcentration factor (BCF) was significantly higher in EC (19.04) and LH (18.41) with respect to MQ and LM (almost six times and two times higher, respectively). EC granted the best results in terms of THg accumulation (50.90%) and lower evapotranspiration of THg phenomenon with respect to LH. A significant decrease of the BCF (from 23.45 to 21.98) and an increase of the TF (from 0.23 up to 0.73) after 42 d highlighted that a breaking-time in terms of THg accumulation was reached due to the deterioration of the roots. In terms of the kinetics of THg removal by bioaccumulation, an HLT of 69.31 d was found, which is more than the breaking-time of the EC system, proving that a periodic replacement of exhausted macrophytes is required to obtain a higher percentage of THg removal.

This article aims to describe Vertical Edgeless Preparation (VEP), a full-crown vertical preparation technique initially introduced by the Porta Mascarella Group in the 1980s. The method is defined as “periodontally driven” because its main indication is teeth with a loss of periodontal attachment, and it aims to obtain healthier periodontal tissues. This work describes the step-by-step procedure for performing this prosthetic technique and its indications, contraindications, impression phases, temporary crown management, and its biological concept of periodontal dominance.

Many technologies for the treatment of arsenic-containing drinking water are available, but most of them are more effective on arsenic oxidized forms. Therefore, the pre-oxidation of As3+ is necessary. The electrochemical processes represent a very promising method due to the simultaneous oxidation of compounds using electrochemical conditions and the reactive radicals produced. In this work, As3+ oxidation was experimentally studied at a pilot scale using an electrochemical oxidation cell (voltage: 10 V; current: 1.7 A). The effect of the initial arsenite concentration, pH, and conductivity of drinking water on the oxidation of As3+ into As5+ was investigated. The results showed that the initial As3+ concentration strongly directly influences the oxidation process. Increasing the initial arsenite concentration from 500 to 5000 µg L−1, the pseudo-first order kinetic constant (k) strongly decreased from 0.521 to 0.038 min−1, and after 10 min, only 21.3% of As3+ was oxidized (vs. 99.9% in the case of As3+ equal to 500 µg L−1). Slightly alkaline conditions (pH = 8) favored the electrochemical oxidation into As5+, while the process was partially inhibited in the presence of a more alkaline or acidic pH. The increase in conductivity up to 2000 µS cm−1 enhanced the kinetic of the oxidation, despite remaining on the same order of magnitude as in the case of conductivity equal to 700 µS cm−1. After 10 min, 99.9 and 95% of As3+ was oxidized, respectively. It is the opinion of the authors that the influence of other operational factors, such as voltage and current density, and the impact of the high concentration of other pollutants should be deeply studied in order to optimize the process, especially in the case of an application at full scale. However, these results provide helpful indications to future research having highlighted the influence of initial As3+ concentration, pH, and conductivity on the electrochemical oxidation of arsenic.

Rhabdomyosarcoma (RMS) is an aggressive form of cancer that accounts for half of all pediatric soft tissue sarcomas. Little progress has been made in improving survival outcomes over the past three decades. Mouse models of rhabdomyosarcoma are a critical component of translational research aimed at understanding tumor biology and developing new, improved therapies. Though several models exist, many common mutations found in human rhabdomyosarcoma tumors remain unmodeled and understudied. This study describes a new model of embryonal rhabdomyosarcoma driven by the loss of Nf1 and Ink4a/Arf, two mutations commonly found in patient tumors. We find that this new model is histologically similar to other previously-published rhabdomyosarcoma models, although it substantially differs in the time required for tumor onset and in tumor growth kinetics. We also observe unique sex-dependent phenotypes in both primary and newly-developed orthotopic syngeneic allograft tumors that are not present in previous models. Using in vitro and in vivo studies, we examined the response to vincristine, a component of the standard-of-care chemotherapy for RMS. The findings from this study provide valuable insight into a new mouse model of rhabdomyosarcoma that addresses an ongoing need for patient-relevant animal models to further translational research.

Background: Cortisol levels, oxidative stress, and lower cerebral performance seem to be closely related. This study aimed to evaluate the question of whether exam stress affected oxidative stress and endothelial function parameters in the salivary samples of students. Methods: A total of 114 healthy students were recruited. All students were subjected to a 21-item DASS questionnaire to assess perceived stress. Cortisol levels, biomarkers of oxidative stress, and endothelial function were evaluated at T0, during the semester, and T1, in the morning before the exam, in saliva samples. In vitro, HUVECs were stimulated with cortisol, and oxidative stress and endothelial function parameters were evaluated. Results: At T1, cortisol levels were significantly increased compared with the levels during the semester. Moreover, exam results correlated inversely with the DASS score at T1. In addition, NOX2, H2O2 and endothelin-1 significantly increased, while NO bioavailability decreased. In vitro, HUVECs treatment with human cortisol determined the increase of oxidative stress and the decrease of endothelial function, in association with impaired eNOS phosphorylation. Conclusion: NOX2-mediated oxidative stress is a mechanism that could mediate cortisol-induced transient endothelial dysfunction during academic examination. Therefore, strategies to monitor or modulate oxidative stress could help students to reduce the impact of examination-related stress.

The measurement of the ground forces on a real structure or mechanism in operation can be time-consuming and expensive, particularly when production cannot be halted to install sensors. In cases in which disassembling the parts of the system to accommodate sensor installation is neither feasible nor desirable, observing the structure or mechanism in operation and quickly deducing its force trends would facilitate monitoring activities in industrial processes. This opportunity is gradually becoming a reality thanks to the coupling of artificial intelligence (AI) with design techniques such as the finite element and multi-body methods. Properly trained inferential models could make it possible to study the dynamic behavior of real systems and mechanisms in operation simply by observing them in real time through a camera, and they could become valuable tools for investigation during the operation of machinery and devices without the use of additional sensors, which are difficult to use and install. In this paper, the idea presented is developed and applied to a simple mechanism for which the reaction forces during operating conditions are to be determined. This paper explores the implementation of an innovative vision-based virtual sensor that, through data-driven training, is able to emulate traditional sensing solutions for the estimation of reaction forces. The virtual sensor and relative inferential model is validated in a scenario as close to the real world as possible, taking into account interfering inputs that add to the measurement uncertainty, as in a real-world measurement scenario. The results indicate that the proposed model has great robustness and accuracy, as evidenced by the low RMSE values in predicting the reaction forces. This demonstrates the model’s effectiveness in reproducing real-world scenarios, highlighting its potential in the real-time estimation of ground reaction forces in industrial settings. The success of this vision-based virtual sensor model opens new avenues for more robust, accurate, and cost-effective solutions for force estimation, addressing the challenges of uncertainty and the limitations of physical sensor deployment.

Currently, the recovery of resources from urban wastewater (WW) represents a priority. On this topic, the potential recovery of cellulose for its subsequent reuse in different sectors is gaining interest. In this work, a large-size conventional wastewater treatment plant (WWTP) was selected as a case study. A preliminary mechanical treatment was used, with the aim of separating, quantifying, and characterizing cellulose in WW. The results suggest that the per-capita production of dry primary cellulosic sludge (D-PCS) is equal to 1.46 ± 0.13 kgD-PCS PE−1 y−1, with an average calorific value of 21.04 MJ kg−1DM. Cellulosic fibres have an average length of >100 µm and a thickness of 2–5 µm. The D-PCS was subsequently treated via medium-temperature pyrolysis; a total of 29.5% of the initial D-PCS was converted into pyrolyzed primary cellulosic sludge (P-PCS) and only 26% into pyrolytic gas. More than 44.5% of the dried cellulose can be converted into pyrolytic oil. Moreover, three different scenarios of recovery have been considered, and the impact of cellulose separation in terms of COD fluxes entering the WWTP and potential energy recovery has been studied. The results suggested that, in this case study, the potential separation of the primary cellulosic sludge from the influent water flux would have no significant impact on COD load entering the biological treatments and biogas production in the anaerobic digestion of the secondary sludge.

The need to use renewable sources and matrices with energy potential is widely recognized. The development of innovative technologies aimed at the improvement of energy conversion processes and reducing environmental impacts is currently receiving increasing attention from the scientific community and policymakers. The presence of sugars in airborne particle materials is attributed to biomass combustion. For this reason, these compounds are considered markers of biomass burning. The purpose of this work was to evaluate the emissions produced by agroforestry biomass burning (citrus pruning) by simultaneously sampling both stack emissions and atmospheric particulates in the area around a biomass boiler to understand the real contribution of biomass burning to atmospheric pollution. The combustion tests were carried out by comparing the processes with and without particulate abatement system to see how biomass combustion’s contribution to particulate emission can be controlled and reduced. During the tests, the focus was on particulate matter (PM) speciation in terms of sugar marker identification and determination. This study aims to increase knowledge to better understand the contribution of biomass plants to air pollution and differentiate it from the contributions of other sources, such as vehicular traffic or domestic heating.

Dental implants are regularly employed in tooth replacement, the good clinical outcome of which is strictly correlated to the choice of an appropriate implant biomaterial. Titanium-based implants are considered the gold standard for rehabilitation of edentulous spaces. However, the insurgence of allergic reactions, cellular sensitization and low integration with dental and gingival tissues lead to poor osseointegration, affecting the implant stability in the bone and favoring infections and inflammatory processes in the peri-implant space. These failures pave the way to develop and improve new biocompatible implant materials. CERID dental implants are made of a titanium core embedded in a zirconium dioxide ceramic layer, ensuring absence of corrosion, a higher biological compatibility and a better bone deposition compared to titanium ones. We investigated hDPSCs’ biological behavior, i.e., cell adhesion, proliferation, morphology and osteogenic potential, when seeded on both CERID and titanium implants, before and after cleansing with two different procedures. SEM and AFM analysis of the surfaces showed that while CERID disks were not significantly affected by the cleansing system, titanium ones exhibited well-visible modifications after brush treatment, altering cell morphology. The proliferation rate of DPSCs was increased for titanium, while it remained unaltered for CERID. Both materials hold an intrinsic potential to promote osteogenic commitment of neuro-ectomesenchymal stromal cells. Interestingly, the CERID surface mitigated the immune response by inducing an upregulation of anti-inflammatory cytokine IL-10 on activated PBMCs when a pro-inflammatory microenvironment was established. Our in vitro results pave the way to further investigations aiming to corroborate the potential of CERID implants as suitable biomaterials for dental implant applications.

In recent years, the application of machine learning for virtual sensing has revolutionized the monitoring and management of information. In particular, electrochemical sensors generate large amounts of data, allowing the application of complex machine learning/AI models able to (1) reproduce the measured data and (2) predict and manage faults in the measuring sensor. In this work, data-driven models based on an autoregressive model and an artificial neural network have been identified and used to (i) evaluate sensor redundancy and (ii) predict and manage faults in the context of electrochemical sensors for the measurement of ethanol. The approach shows encouraging results in terms of both performance and sensitivity analyses, allowing for the reconstruction of the values measured by two sensors in a series of six sensors with different dopant levels and to reproduce their values after a fault.

Background: From a young age, children learn different motor skills known as fundamental motor skills. The acquisition of these skills is crucial for the future development of context-tailored actions that could improve adherence to physical activity (PA) practice. Motor competence and function deficits have been associated with pediatric obesity. We reviewed the literature data regarding motor competence in pediatrics and impaired motor performance in children and adolescents with obesity. Methods: We assessed the abstracts of the available literature (n = 110) and reviewed the full texts of potentially relevant articles (n = 65) that were analyzed to provide a critical discussion. Results: Children and adolescents with obesity show impaired motor performance, executive functions, postural control, and motor coordination. Children’s age represents a crucial point in the development of motor skills. Early interventions are crucial to preventing declines in motor proficiency and impacting children’s PA and overall fitness levels. Conclusions: To involve children, the PA protocol must be fun and tailored in consideration of several aspects, such as clinical picture, level of physical fitness, and motor skills. A supervised adapted exercise program is useful to personalized PA programs from an early pediatric age.

The management of unowned cats is an emerging problem, with public institutions and citizens’ concerns regarding their care and arrangement. Little is known regarding the outcome of traumatic orthopedic injuries in these patients. Indeed, complete functional recovery (CFR) should be the goal of treatment for return to their original location or adoption. The aim was to identify clinical factors influencing CFR in traumatized unowned cats with orthopedic lesions. This category of cats referred by the veterinary public service over three years was enrolled. Various clinical variables were retrospectively collected from the medical records and evaluated by nominal logistic analysis. Forty-eight unowned cats were enrolled, with a median estimated age of 24 (1–180) months and a body weight of 3 (0.7–5) kg. Thirty-four (71%) patients reached CFR. Estimated age, body weight, time from trauma to therapeutic intervention, spine involvement, presence of comorbidities, hospitalization time, and the radiographic score results were significantly associated with CFR. A longer time to therapeutic intervention seemed to be associated with a better outcome. Probably, cats severely traumatized did not live long enough to be evaluated and treated. Lighter cats experienced more severe consequences following blunt trauma. Younger and lighter cats bore a higher risk of panleukopenia-related death.

Background: For selected women diagnosed with breast cancer (BC), partial reconstructive techniques involve displacement or replacement procedures to improve cosmesis without compromising oncological safety. This study aims to evaluate the surgical outcomes of the round block (RB) compared with the subaxillary flap (SF) technique for patients with upper outer tumor. Patients and Methods: Thirty-three patients treated with oncoplastic conserving surgery (15 RB and 18 SF) were enrolled in this retrospective study. After carrying out a comparison of baseline characteristics, all cases were recruited for postoperative evaluation of oncological and cosmetic parameters. Moreover, we investigated several scoring combinations to check whether they could discriminate surgeon and patient satisfaction according to different functional results. Results: Median age (p < 0.05), average tumor size (p > 0.05), estimated resection volume (p > 0.05), and nodal involvement (p > 0.05) were slightly higher in the SF group. A greater frequency of DCIS (p < 0.05) in the RB series correlated with reintervention for positive margins (p > 0.001). At a mean follow-up of 19 months, no locoregional recurrences were recorded and early and late complications were comparable (p > 0.05). The overall satisfaction with cosmesis was characterized by similar proportions of good results (p > 0.05), with some details more related to each procedure. Conclusion: The proposed techniques represent effective solutions for reshaping that follows upper outer wide excision, achieving comparable complication rates, low reinterventions, and good aesthetic results in relation to technical and social functioning evaluations. However, it is crucial to establish a careful patient selection in order to manage correct surgical planning while predicting any potential sequelae or complication.

Mitral valve prolapse (MVP) is a common valvular disease, affecting 2–3% of the adult human population and is a degenerative condition. A total of 5–10% of the afflicted will develop severe mitral regurgitation, cardiac dysfunction, congestive heart failure, and sudden cardiac death. Naturally occurring myxomatous MVP in dogs closely resembles MVP in humans structurally, and functional consequences are similar. In both species, valvular interstitial cells (VICs) in affected valves exhibit phenotype consistent with activated myofibroblasts with increased alpha-smooth muscle actin (αSMA) expression. Using VICs collected from normal and MVP-affected valves of dogs, we analyzed the miRNA expression profile of the cells and their associated small extracellular vesicles (sEV) using RNA sequencing to understand the role of non-coding RNAs and sEV in MVP pathogenesis. miR-145 was shown to be upregulated in both the affected VICs and sEV, and overexpression of miR-145 by mimic transfection in quiescent VIC recapitulates the activated myofibroblastic phenotype. Concurrently, KLF4 expression was noted to be suppressed by miR-145, confirming the miR-145—KLF4—αSMA axis. Targeting this axis may serve as a potential therapy in controlling pathologic abnormalities found in MVP valves.

Alterations in microvasculature represent some of the earliest pathological processes across a wide variety of human diseases. In many organs, however, inaccessibility and difficulty in directly imaging tissues prevent the assessment of microvascular changes, thereby significantly limiting their translation into improved patient care. The eye provides a unique solution by allowing for the non-invasive and direct visualization and quantification of many aspects of the human microvasculature, including biomarkers for structure, function, hemodynamics, and metabolism. Optical coherence tomography angiography (OCTA) studies have specifically identified reduced capillary densities at the level of the retina in several eye diseases including glaucoma. This narrative review examines the published data related to OCTA-assessed microvasculature biomarkers and major systemic cardiovascular disease. While loss of capillaries is being established in various ocular disease, pilot data suggest that changes in the retinal microvasculature, especially within the macula, may also reflect small vessel damage occurring in other organs resulting from cardiovascular disease. Current evidence suggests retinal microvascular biomarkers as potential indicators of major systemic cardiovascular diseases, including systemic arterial hypertension, atherosclerotic disease, and congestive heart failure.

Genetic testing is crucial in inherited arrhythmogenic channelopathies; however, the clinical interpretation of genetic variants remains challenging. Incomplete penetrance, oligogenic, polygenic or multifactorial forms of channelopathies further complicate variant interpretation. We identified the KCNQ1/p.D446E variant in 2/63 patients with long QT syndrome, 30-fold more frequent than in public databases. We thus characterized the biophysical phenotypes of wildtype and mutant IKs co-expressing these alleles with the β-subunit minK in HEK293 cells. KCNQ1 p.446E homozygosity significantly shifted IKs voltage dependence to hyperpolarizing potentials in basal conditions (gain of function) but failed to shift voltage dependence to hyperpolarizing potentials (loss of function) in the presence of 8Br-cAMP, a protein kinase A activator. Basal IKs activation kinetics did not differ among genotypes, but in response to 8Br-cAMP, IKs 446 E/E (homozygous) activation kinetics were slower at the most positive potentials. Protein modeling predicted a slower transition of the 446E Kv7.1 tetrameric channel to the stabilized open state. In conclusion, biophysical and modelling evidence shows that the KCNQ1 p.D446E variant has complex functional consequences including both gain and loss of function, suggesting a contribution to the pathogenesis of arrhythmogenic phenotypes as a functional risk allele.

Background and Objectives: Stenotrophomonas maltophilia is a ubiquitous, aerobic, Gram-negative bacillus causing increasing concern in patients affected by haematological malignancies. Materials and Methods: We report a case series from two centres in Northern Italy to describe the characteristics, outcome and microbiological response of S. maltophilia infections in patients with haematological malignancies and/or allogenic hematopoietic stem cell transplantation (aHSCT). Results: Ten patients were included. The median age was 67 years, and seven patients (70%) were males. The median Charlson Comorbidity Index was 6 (IQR: 4–8). The most frequent haematological comorbidities were acute myeloid leukaemia (AML; n = 3; 30%) and non-Hodgkin’s lymphoma (n = 3; 30%). Three (30%) patients underwent aHSCT before infection, all for AML. All the patients had undergone a recent antibiotics course and had an indwelling central venous catheter before infection. The main clinical presentations were nosocomial pneumonia, with (2; 20%) or without (4; 40%) secondary bloodstream infection and CRBSI (3; 30%). Four patients were treated with cefiderocol in monotherapy or combinations therapy with cotrimoxazole. The rest of the patients were treated with cotrimoxazole or levofloxacin in monotherapy. Conclusions: Despite a high rate of clinical improvement (90%) after starting antimicrobial therapy, we faced high 30-day mortality (30%) and in-hospital mortality (50%) rates in a highly comorbid population.

Collecting urban solid waste (USW) is a critical and essential phase for proper waste management and valorization. To date, many data are available for large cities, but few studies have focused on low-density areas, such as mountainous regions. Considering this lack in the literature, this study aimed to compare two separate waste collection systems in two mountainous valleys in terms of effectiveness and GHG emissions. In the first scenario, a mixed collection system (door-to-door + centers) was used, while in the other, waste was separately collected by a full door-to-door system. The results suggested that the full door-to-door system achieved better performance than the mixed collection system (door-to-door + centers), with a fraction of separate waste collection compared to the unit equals (0.84 ± 0.01 vs. 0.79 ± 0.02). Moreover, the full door-to-door system represented the best option for collecting separate waste in mountainous areas in terms of GHG emissions, with 11.21 kgCO2, eq twaste−1 emitted vs. 15.62 kgCO2, eq twaste−1 in the case of the mixed system. Despite utilities emitting a higher amount of GHGs in the door-to-door scenario (4.66 kgCO2, eq inh−1 y−1), they were fully compensated for by the low GHG emissions from citizens in the mixed scenario (1.77 kgCO2, eq inh−1 y−1 vs. 6.65 kgCO2, eq inh−1 y−1). Given the low amount of data on this topic, this work could be considered as a pioneer study of waste management in mountainous areas by comparing the results of two systems regarding effectiveness and GHG emissions. The outcomes of this study could be helpful for waste utilities, institutional agencies, and local communities and also serve as a tool for decision-making in the case of comparing the different options for USW collection systems.

The purpose of this study was to investigate how lateralization shoulder angle (LSA) and distalization shoulder angle (DSA) are related to clinical and kinematic outcomes after reverse total shoulder arthroplasty. Thirty-three patients were evaluated at least six months postoperatively. The Single Assessment Numeric Evaluation (SANE), Constant Murley Score (CMS), Simple Shoulder Test (SST), and Visual Analogue Scale (VAS) were used. Shoulder kinematics was evaluated with a stereophotogrammetric system. LSA and DSA inter-rater reliability was analysed through the interclass correlation coefficient (ICC). Stepwise forward linear regression analysis was conducted between LSA and DSA with clinical scales and kinematic measures, between which a correlation analysis was conducted. The inter-rater reliability for LSA (mean ICC = 0.93) and DSA (mean ICC = 0.97) results were good to excellent. Greater LSA values were associated with higher peaks of internal rotation (p = 0.012, R2 = 0.188) and range of motion (ROM) (p = 0.037, R2 = 0.133). SANE (p = 0.009), CMS (p = 0.031), and SST (0.026) were positively correlated to external rotation, while VAS (p = 0.020) was negatively related. Abduction peaks were positively related to CMS (p = 0.011) and SANE (p = 0.037), as well as abduction ROM (SANE, p = 0.031; CMS, p = 0.014).

Phospholipase C Zeta 1 (PLCZ1) is considered a major sperm-borne oocyte activation factor. After gamete fusion, PLCZ1 triggers calcium oscillations in the oocyte, resulting in oocyte activation. In assisted fertilization, oocyte activation failure is a major cause of low fertility. Most cases of oocyte activation failures in humans related to male infertility are associated with gene mutations and/or altered PLCZ1. Consequently, PLCZ1 evaluation could be an effective diagnostic marker and predictor of sperm fertilizing potential for in vivo and in vitro embryo production. The characterization of PLCZ1 has been principally investigated in men and mice, with less known about the PLCZ1 impact on assisted reproduction in other species, such as cattle and horses. In horses, sperm PLCZ1 varies among stallions, and sperm populations with high PLCZ1 are associated with cleavage after intracytoplasmic sperm injection (ICSI). In contrast, bull sperm is less able to initiate calcium oscillations and undergo nuclear remodeling, resulting in poor cleavage after ICSI. Advantageously, injections of PLCZ1 are able to rescue oocyte failure in mouse oocytes after ICSI, promoting full development and birth. However, further research is needed to optimize PLCZ1 diagnostic tests for consistent association with fertility and to determine whether PLCZ1 as an oocyte-activating treatment is a physiological, efficient, and safe method for improving assisted fertilization in cattle and horses.

The introduction of immunotherapy revolutionized the treatment landscape in metastatic melanoma. Despite the impressive results associated with immune checkpoint inhibitors (ICIs), only a portion of patients obtain a response to this treatment. In this scenario, the research of predictive factors is fundamental to identify patients who may have a response and to exclude patients with a low possibility to respond. These factors can be host-associated, immune system activation-related, and tumor-related. Patient-related factors can vary from data obtained by medical history (performance status, age, sex, body mass index, concomitant medications, and comorbidities) to analysis of the gut microbiome from fecal samples. Tumor-related factors can reflect tumor burden (metastatic sites, lactate dehydrogenase, C-reactive protein, and circulating tumor DNA) or can derive from the analysis of tumor samples (driver mutations, tumor-infiltrating lymphocytes, and myeloid cells). Biomarkers evaluating the immune system activation, such as IFN-gamma gene expression profile and analysis of circulating immune cell subsets, have emerged in recent years as significantly correlated with response to ICIs. In this manuscript, we critically reviewed the most updated literature data on the landscape of predictive factors in metastatic melanoma treated with ICIs. We focus on the principal limits and potentiality of different methods, shedding light on the more promising biomarkers.

Conservation Agriculture (CA) and the System of Rice Intensification (SRI) are both agroecologically-oriented production systems that support more productive, sustainable, and resource-conserving farming, with synergies arising from their respective assemblages of reinforcing agronomic methods. This review article examines the compatibility between CA and SRI, considering examples of their being utilized in complementary ways. The application of CA principles enhances the growth, yield, and performance of the crops grown under the cropping system as well as the health and resilience of the whole ecosystem. SRI practices create more favorable conditions for the development of crop plants below- and above-ground, including conditions that can be enhanced by CA management. SRI practices such as reduced plant density m−2 can elicit a better phenotypic expression of the genetic potentials of crops grown with CA. For these two agronomic systems to converge at the field level, some of their respective practices for plant, soil, water, and nutrient management need to be modified or aligned. One such adaptation is to practice SRI in CA systems on permanent, no-till, mulch-covered raised beds, with rainfall or irrigation water in the furrows between the beds furnishing and controlling water and providing weed suppression and improved nutrient recycling. SRI rice cropping can benefit from the CA practices of no-tillage, mulch soil cover, and diversified cropping, both in paddies and on raised beds. Several examples have shown that this convergence of cropping systems is feasible for smallholding farmers as well as for larger-scale producers and also that SRI practices within a CA system are amenable to considerable mechanization. Further research and experimentation are needed to identify and assess appropriate practices for capitalizing upon their synergies.

Few studies have evaluated the effectiveness of shoulder rehabilitation in virtual environments. The objective of this study was to investigate the performance of a custom virtual reality application (VR app) with a stereophotogrammetric system considered the gold standard. A custom VR app was designed considering the recommended rehabilitation exercises following arthroscopic rotator cuff repair. Following the setting of the play space, the user’s arm length, and height, five healthy volunteers performed four levels of rehabilitative exercises. Results for the first and second rounds of flexion and abduction displayed low total mean absolute error values and low numbers of unmet conditions. In internal and external rotation, the number of times conditions were not met was slightly higher; this was attributed to a lack of isolated shoulder movement. Data is promising, and volunteers were able to reach goal conditions more often than not. Despite positive results, more literature comparing VR applications with gold-standard clinical parameters is necessary. Nevertheless, results contribute to a body of literature that continues to encourage the application of VR to shoulder rehabilitation programs.

Only 20% of children worldwide reach the suggested physical activity (PA) levels, and the COVID-19 restrictions seemed to have worsened this situation. In addition, physical fitness (PF) is a crucial marker of health and combined with PA could predict future health status. The aim of this study was to compare reported PA and PF levels in a sample of Italian adolescents. We administered the International PA Questionnaire and International Fitness Enjoyment Scale to 208 adolescents aged 16.0 ± 1.5 (N = 166 females, 16 ± 2.0 years) recruited from a high school in the province of Milan (Italy). The majority of the subjects were “Minimally active” but reported adequate PF levels. In particular, subjects who reported a “Very good” PF perception, had a lower PA level. The misperception of reported PA and PF from our sample could reduce the future PA level in adolescents and lead to a negative spiral of disengagement in PA. These findings should lead to more attention on and improvements to PA promotion in the adolescent population after the restrictions caused by the COVID-19 pandemic.

HSCT from an unrelated HLA-mismatched donor (MMUD) is one of the alternatives where an HLA-matched donor is not found. The aim of this study was to compare GvHD prophylaxis with anti-thymocyte globulin (ATG) vs. post-transplant cyclophosphamide (PT-Cy). Thirty-nine adult patients were uniformly treated with rabbit ATG-Cy-A-MTX and peripheral blood stem cell (PBSC) and 40 adult patients with PT-Cy-MMF-tacrolimus and PBSC. This retrospective study was registered at ClinicalTrials.gov NCT04598789. Three-year overall survival was 42% vs. 64% for ATG and PT-Cy (p < 0.0005), three-year treatment-related mortality (TRM) was 36% vs. 8% (p = 0.0033) and the three-year relapse incidence (RI) was 15% vs. 28% (p = NS), respectively. The incidences of day-100 GvHD graded II–IV and III–IV were 39% vs. 7% (p = 0.0006) and 11% vs. 0% (p = 0.04), respectively, whereas the three-year cGvHD incidences were 48% vs. 13% (p = 0.0005), respectively. We were able to show how PT-Cy can reduce the incidence of GvHDs and TRM in adults, but relapse remains an issue.

Gut barrier disruption can lead to enhanced intestinal permeability, which allows endotoxins, pathogens, and other proinflammatory substances to move through the intestinal barrier into circulation. Intense exercise over a prolonged period increases intestinal permeability, which can be further worsened by the increased production of reactive oxygen species (ROS) and pro-inflammatory cytokines. The aim of this study was to assess the degree of intestinal permeability in elite football players and to exploit the effect of cocoa polyphenols on intestinal permeability induced by intensive physical exercise. Biomarkers of intestinal permeability, such as circulating levels of zonulin, a modulator of tight junctions, occludin, a tight junction protein, and LPS translocation, were evaluated in 24 elite football players and 23 amateur athletes. Moreover, 24 elite football players were randomly assigned to either a dark chocolate (>85% cocoa) intake (n = 12) or a control group (n = 12) for 30 days in a randomized controlled trial. Biochemical analyses were performed at baseline and after 30 days of chocolate intake. Compared to amateur athletes, elite football players showed increased intestinal permeability as indicated by higher levels of zonulin, occludin, and LPS. After 30 days of dark chocolate intake, decreased intestinal permeability was found in elite athletes consuming dark chocolate. In the control group, no changes were observed. In vitro, polyphenol extracts significantly improved intestinal damage in the human intestinal mucosa cell line Caco-2. These results indicate that chronic supplementation with dark chocolate as a rich source of polyphenols positively modulates exercise-induced intestinal damage in elite football athletes.

Alfvén waves play an important role in the stability, heating, and transport of magnetized plasmas. They are found to be ubiquitous in solar winds (SW), which mainly propagate outward from the Sun, especially in high-speed streams that originate from coronal holes. When high-speed streams impinge on the Earth’s magnetosphere, the impact of Alfvénic fluctuations can cause magnetic reconnections between the intermittent southward Interplanetary Magnetic Field (IMF) and the geomagnetic field, resulting in energy injection from the SW into the Earth’s magnetosphere. In this work, we tested a rotation procedure from the Heliocentric Earth Ecliptic (HEE) to the Mean ElectroMagnetic Fields Aligned (MEMFA) reference frame. This is achieved by means of the Empirical Mode Decomposition (EMD) method for both the SW velocity and IMF at 1 AU. Our aim is to check the reliability of the method and its limitations in identifying Alfvénic fluctuations through the spectral analysis of time series in the MEMFA coordinate system. With this procedure, we studied the fluctuations in the main-field-aligned direction and those in the orthogonal plane to the main field. To highlight the peculiarities of each case of study and be able to better identify Alfvén waves when applying this procedure to real data, we reproduced the magnetic and velocity fields of a typical corotating high-speed stream. We tested the procedure in several cases by varying the amplitude of Alfvén waves and noise. We performed the spectral analysis of the Mean Field Aligned (MFA) component of both the magnetic and velocity fields to define the power related to the two main directions: the one aligned to the ambient magnetic field and the one orthogonal to it. The efficiency of the procedure and the results’ reliability are supported by Monte Carlo (MC) tests. The method is also applied to a real case that is represented by a selected corotating SW stream that occurred during August 2008, which fell in the solar minimum of solar cycle 23. The results are also compared with those obtained by using Elsässer variables to analyze the Alfvénicity of fluctuations via the normalized cross helicity and the normalized residual energy.

Monitoring shoulder kinematics, including the scapular segment, is of great relevance in the orthopaedic field. Among wearable systems, magneto-inertial measurement units (M-IMUs) represent a valid alternative for applications in unstructured environments. The aim of this systematic literature review is to report and describe the existing methods to estimate 3D scapular movements through wearable systems integrating M-IMUs. A comprehensive search of PubMed, IEEE Xplore, and Web of Science was performed, and results were included up to May 2023. A total of 14 articles was included. The results showed high heterogeneity among studies regarding calibration procedures, tasks executed, and the population. Two different techniques were described, i.e., with the x-axis aligned with the cranial edge of the scapular spine or positioned on the flat surface of the acromion with the x-axis perpendicular to the scapular spine. Sensor placement affected the scapular motion and, also, the kinematic output. Further studies should be conducted to establish a universal protocol that reduces the variability among studies. Establishing a protocol that can be carried out without difficulty or pain by patients with shoulder musculoskeletal disorders could be of great clinical relevance for patients and clinicians to monitor 3D scapular kinematics in unstructured settings or during common clinical practice.