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Background: Post-transplant cyclophosphamide (PTCY) is widely used as graft versus host disease (GvHD) prophylaxis in allogeneic hematopoietic stem cell transplant (HSCT) recipients, with reported clinical benefits in patients who underwent transplant from a matched unrelated donor (MUD). However, real-life data on clinical efficacy and safety of PTCY in haploidentical and MUD transplantations are still poor. Methods: In our real-life retrospective observational study, we included a total of 40 consecutive adult patients who underwent haploidentical or MUD HSCT for various hematological malignancies and who received PTCY (n = 24) or ATG (n = 16) as GvHD prophylaxis at Hematology Units from hospitals of Salerno and Avellino, Italy, and clinical outcomes were compared. Results: We showed protective effects of PTCY against disease relapse with the relapse rate after transplantation of 16% versus 50% in the ATG arm (p = 0.02). All-cause mortality was lower (36% vs. 75%; p = 0.02) and the 2-year overall survival was slightly superior in patients administered PTCY (61% vs. 42%; p = 0.26). Conclusions: We support the use of PTCY, even in a real-life setting; however, the optimization of this protocol should be further investigated to better balance relapse prevention and GvHD prophylaxis.

Despite advancements in technologies such as time-lapse microscopy and artificial intelligence, the gold standard for embryo selection still relies on standard morphological assessment. Several studies have investigated the correlation between blastocyst characteristics (expansion status, inner cell mass, and trophectoderm) and clinical outcomes, reaching contradictory results. In consideration of these ambiguities in the literature, we performed a retrospective study of 1546 untested first-vitrified–warmed single day 5/6 blastocyst transfers. The purpose of our study is to evaluate three scenarios: (i) independent association between each morphological characteristic (expansion status, inner cell mass, and trophectoderm) and live birth; (ii) comparison between blastocysts with inner cell mass grade A and trophectoderm grade B and blastocysts with inner cell mass grade B and trophectoderm grade A; and (iii) comparison between poor-quality day 5 and top-quality day 6 blastocysts. After adjusting for principal confounders, we report that trophectoderm is more predictive of live births than inner cell mass and expansion status. We observed a trend in favor of top-quality day 6 blastocysts over poor-quality day 5 blastocysts. Moreover, on the same day of development and expansion status, blastocyst BA should be preferable to blastocyst AB.

The High-Energy Particle Detector (HEPD-02) is one of the scientific payloads of the China Seismo-Electromagnetic Satellite (CSES-02). The HEPD-02’s main purpose is to characterize the particle environment in the Earth’s vicinity, identifying sudden changes in the fluxes and correlating them with solar and terrestrial phenomena. Additionally, HEPD-02 also has capabilities in detecting Gamma-Ray Bursts. At the core of HEPD-02, a tower of scintillation counters made of plastic and LYSO crystals is able to recognize electrons in the range between 3 and 100 MeV, protons and nuclei between 30 and 200 MeV/n. Plastic scintillators covering the calorimeter on five sides allow to reject particles entering from the top and not completely absorbed within its volume. In this work, the design of the HEPD-02 is reviewed in comparison to its predecessor, HEPD-01, highlighting the innovations of the new design. The design of each scintillation counter type has been fully validated through a campaign of prototype realization, testing, and characterization. The production of the scintillation counters, including the PMT selection process, is also discussed. Finally, the performance of the counters is compared with simulations, showing an agreement of within 20% with the expected performance, thereby meeting expectations.

Migration plays a crucial role in shaping destination countries’ social and economic landscapes, including in Ecuador. This study aims to explore the benefits and challenges of migration by analyzing the perceptions of Ecuadorians who have directly or indirectly encountered its effects. Using a mixed-methods approach, we surveyed 1048 Ecuadorians and conducted 27 in-depth interviews to capture various viewpoints. The findings reveal a complex perspective: 47% of respondents view migration positively, emphasizing economic opportunities and cultural enrichment, while 53% express concerns about issues such as employment mismatches and barriers to social integration. These insights highlight the need for further research, e.g., to explore tailored policy solutions and deepen the understanding of migration’s multifaceted impact on Ecuador’s society and economy. The results highlight the need to investigate how media perceptions of migration influence the attitudes and decisions of migrants and host communities to design more balanced and realistic information campaigns for informed decision-making.

The conservation of the main protease in viral genomes, combined with the absence of a homologous protease in humans, makes this enzyme family an ideal target for developing broad-spectrum antiviral drugs with minimized host toxicity. GC-376, a peptidomimetic 3CL protease inhibitor, has shown significant efficacy against coronaviruses. Recently, a GC-376-based PROTAC was developed to target and induce the proteasome-mediated degradation of the dimeric SARS-CoV-2 3CLPro protein. Extending this approach, the current study investigates the application of the GC-376 PROTAC to the 3CPro protease of enteroviruses, specifically characterizing its interaction with CVB3 3CPro through X-ray crystallography, NMR (Nuclear Magnetic Resonance) and biochemical techniques. The crystal structure of CVB3 3CPro bound to the GC-376 PROTAC precursor was obtained at 1.9 Å resolution. The crystallographic data show that there are some changes between the binding of CVB3 3CPro and SARS-CoV-2 3CLPro, but the overall similarity is strong (RMSD on C-alpha 0.3 Å). The most notable variation is the orientation of the benzyloxycarbonyl group of GC-376 with the S4 subsite of the proteases. NMR backbone assignment of CVB3 3CPro bound and unbound to the GC-376 PROTAC precursor (80% and 97%, respectively) was obtained. This information complemented the investigation, by NMR, of the interaction of CVB3 3CPro with the GC-376 PROTAC, and its precursor allows us to define that the GC-376 PROTAC binds to CVB3 3CPro in a mode very similar to that of the precursor. The NMR relaxation data indicate that a quench of dynamics of a large part of the protein backbone involving the substrate-binding site and surrounding regions occurs upon GC-376 PROTAC precursor binding. This suggests that the substrate cavity, by sampling different backbone conformations in the absence of the substrate, is able to select the suitable one necessary to covalently bind the substrate, this being the latter reaction, which is the fundamental step required to functionally activate the enzymatic reaction. The inhibition activity assay showed inhibition potency in the micromolar range for GC-376 PROTAC and its precursor. Overall, we can conclude that the GC-376 PROTAC fits well within the binding sites of both proteases, demonstrating its potential as a broad-spectrum antiviral agent.

Introduction and objectives: Aortic valve replacement surgery (SAVR) remains a recommended indication, though its pre-surgical stratification is an ongoing challenge. Despite the widespread use of scores like the STS and EuroSCORE II, they have a number of limitations, while often neglecting structural parameters like left ventricular hypertrophy or left atrium volume. This study aimed to evaluate whether a new adaptation of the Généreux classification in the preoperative risk stratification of severe aortic stenosis (AS) is associated with the primary outcome, and to compare it with the original classification versus the traditional scores in short- and long-term follow-up. Methods: We conducted a retrospective, single-center study involving patients with confirmed severe AS who underwent SAVR. The new stratification categorized patients into three stages. Cox regression analyses were conducted to identify factors associated with mortality, with survival analysis performed using Kaplan–Meier curves. A p-value < 0.05 was considered statistically significant. Results: A total of 508 patients were included. Stage 3 patients had a lower median age (67 years). The median EuroSCORE II and STS scores were 2.75 and 2.62%, respectively (p ≤ 0.001). Over a median follow-up of 81 months, 56 deaths occurred (11%). Kaplan–Meier curve analysis revealed significant differences in all-cause mortality among the three groups (HR 4.073, log-rank p ≤ 0.001). Multivariable analysis identified the three preoperative stages (HR 3.22, [95% CI 1.44–7.20], p = 0.004) and mean transaortic gradient (HR 0.96, [95% CI 0.92–0.99], p = 0.021) as independent variables of mortality. The original Généreux scale AUC was higher (AUC: 0.760, 95% CI: 0.692–0.829) compared to the modified Généreux scale (AUC: 0.758, 95% CI: 0.687–0.829). However, no statistical differences were found between the different scales. Conclusions: Preoperative three-stage classification and low transaortic gradient are factors associated with increased all-cause mortality in patients undergoing SAVR. The proposed staging system performed better in the mortality analysis than EuroSCORE II and STS and was similar to the original classification.

Launched on 22 November 2013, Swarm is the fourth in a series of pioneering Earth Explorer missions and also the European Space Agency’s (ESA’s) first constellation to advance our understanding of the Earth’s magnetic field and the near-Earth electromagnetic environment. Swarm provides an ideal platform in the topside ionosphere for observing ultra-low-frequency (ULF) waves, as well as equatorial spread-F (ESF) events or plasma bubbles, and, thus, offers an excellent opportunity for space weather studies. For this purpose, a specialized time–frequency analysis (TFA) toolbox has been developed for deriving continuous pulsations (Pc), namely Pc1 (0.2–5 Hz) and Pc3 (22–100 mHz), as well as ionospheric plasma irregularity distribution maps. In this methodological paper, we focus on the ULF pulsation and ESF activity observed by Swarm satellites during a time interval centered around the occurrence of the 24 August 2016 Central Italy M6 earthquake. Due to the Swarm orbit’s proximity to the earthquake epicenter, i.e., a few hours before the earthquake occurred, data from the mission may offer a variety of interesting observations around the time of the earthquake event. These observations could be associated with the occurrence of this geophysical event. Most notably, we observed an electron density perturbation occurring 6 h prior to the earthquake. This perturbation was detected when the satellites were flying above Italy.

Background: Pulmonary hypertension (PH) often complicates mitral stenosis (MS). The prognostic impact of pulmonary vascular resistance (PVR) in MS patients remains unclear. Previous study has demonstrated the prognostic impact of right atrial pressure (RAP) in patients with primary PH. We aim to determine the prognostic impact of PVR and RAP in patients with rheumatic MS undergoing percutaneous mitral balloon valvuloplasty (PMBV). Methods: A total of 58 patients with symptomatic severe rheumatic MS who underwent PMBV between 2016 and 2020 were included. Patients were divided into two groups: PVR ≤ 2WU (N = 26) and PVR > 2WU (N = 32). The composite endpoint included death, reintervention or persistent NYHA functional class III-IV during follow-up. Results: The median age was 50 (42–60) years, with 82.8% being female. Median pulmonary artery systolic pressure (PASP) was 42 (35–50.5) mmHg. Patients with PVR ≤ 2WU had lower PASP on both echocardiogram and catheterization. The PMBV success rate was 75.9%. Multivariate analysis, adjusted for PVR, showed RAP as the only independent predictor of the composite endpoint (HR:1.507, 95% CI:1.015–2.237, p = 0.042). The optimal RAP cutoff was 9.5 mmHg (HR:3.481, 95% CI:1.041–11.641; p = 0.043). Conclusions: RAP was an independent predictor of adverse outcomes in patients with rheumatic MS undergoing PMBV, while PVR did not show prognostic significance. These findings suggest that the prognostic value of PVR may be lower than expected.

This report describes the experience in implementing the FAIR principles for the GoTriple Discovery Platform for Social Sciences and Humanities (SSH). It shows how adherence to FAIR should be considered as a continuous process throughout the entire lifespan of any information management system, including GoTriple, rather than a static goal with decisions only made at the design time. This report presents an introduction highlighting the importance of the FAIR principles, indicating how they can be assessed in data management systems. Then, the GoTriple case is presented, with a general overview of this discovery platform before describing some of the implemented practices in support of FAIR. The Discussion Section shows, on the one hand, some virtuous reuse of GoTriple data, together with one major pitfall in the platform’s FAIR implementation. In this sense, this report serves as a case study that can offer insights and actionable advice for those implementing information systems aligned, from the very outset, with the FAIR principles.

Background: Psoriasis is a chronic skin disorder affecting 2–3% of the global population, and is associated with several comorbidities, including psychiatric disorders. This study aimed to identify factors influencing anxiety, depression, and quality of life (QoL) in patients with psoriasis. Methods: This observational study included 112 patients diagnosed with psoriasis. Dermatological and psychiatric assessments were conducted using Psodisk, the Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D), Symptom Checklist-90-Revised (SCL-90-R), and 36-Item Short Form Health Survey (SF-36). Descriptive statistics, correlation analyses, and multivariate regression models were employed. Results: The sample was predominantly middle-aged males (mean age 48.91 years). Females (p < 0.001), patients with arthritis (p < 0.05), and those with a sedentary lifestyle (p < 0.05) showed higher anxiety and depression scores. Psodisk subscales significantly correlated with psychiatric symptoms and QoL measures (p < 0.001). Pain (B: 0.63, p < 0.05; B: −2.03, p < 0.01) and sleep disturbances (B: 0.68, p < 0.01; B: 0.60, p < 0.01; B: −1.46, p < 0.01; B: −1.57, p < 0.05; B: 3.91, p < 0.05) emerged as major predictors of poor mental health and reduced QoL. Conclusions. The study underscores the complex relationship between psoriasis, psychiatric comorbidities, and QoL. Key factors exacerbating anxiety and depression include female gender, arthritis, and sedentary lifestyle. Comprehensive management of psoriasis should address both dermatological and psychological aspects, with a focus on pain relief and improving sleep quality to enhance overall patient well-being.

Earthquake prediction is the holy grail of seismology and one of humanity’s greatest dreams. The Earth’s magnetic field appears to be one of the best possible precursors of earthquakes, although the topic is controversial. Recent advancements have made it possible to observe magnetic fields from satellites with great accuracy. We utilize magnetic measurements from Swarm satellites to explore the potential identification of anomalous magnetic signals preceding earthquakes. Focusing on 1077 major earthquakes that occurred in 2014–2023 in the Alpine–Himalayan belt, we apply an automatic algorithm to data recorded 10 days before each earthquake. This analysis reveals clear pre-earthquake anomalies in the magnetic field components. Notably, a robust correlation is established between the duration of these anomalies and the earthquake magnitude, indicating that as the earthquake magnitude increases, so does the duration of the anomaly. Here we show that this method has a great ability to make predictions (high accuracy 79%, precision 88%, F1-score and hit rate 84%), thus becoming the basis for an Operational Earthquake Prediction System (OEPS).

On 6 February 2023, Turkey experienced its most powerful earthquake in over 80 years, with a moment magnitude (Mw) of 7.7. This was then followed by a second earthquake of Mw 7.6 just nine hours later. According to the lithosphere–atmosphere–ionosphere coupling (LAIC) models, such a significant seismic activity is expected to cause anomalies across various observables, from the Earth’s surface to the ionosphere. This multidisciplinary study investigates the preparatory phase of these two major earthquakes by identifying potential precursors across the lithosphere, atmosphere, and ionosphere. Our comprehensive analysis successfully identified and collected various anomalies, revealing that their cumulative occurrence follows an accelerating trend, either exponential or power-law. Most anomalies appeared to progress from the lithosphere upward through the atmosphere to the ionosphere, suggesting a sequential chain of processes across these geospheres. Notably, some anomalies deviated from this overall trend, manifesting as oscillating variations. We propose that these anomalies support a two-way coupling model preceding major earthquakes, highlighting the potential role of fluid chemistry in facilitating these processes.

Mediterranean hurricanes, also known as medicanes, can cause significant damage to coastal communities. Consequently, they have been the subject of intense study in recent decades. Geographic Information Systems (GISs) and Web-GIS applications are essential for processing and analyzing geographic data from various sources, particularly in the field of spatial planning. Due to their ability to integrate heterogeneous information, these tools can provide experts with a comprehensive overview of relevant geospatial data. Here, we present ARCHIMEDE, a relational geodatabase connected to an open-source Web-GIS platform focused on Mediterranean hurricanes that contains data from recent research on these extreme weather phenomena. These datasets comprise climatic and oceanographic data obtained from remote sensing techniques as well as seismic and geomorphological data obtained from field observations. Consequently, this Web-GIS platform can enhance our understanding of Mediterranean cyclones by relating the physical properties of these natural phenomena with their impacts on coastal regions. ARCHIMEDE is an innovative tool for the dissemination of geographic information to stakeholders, researchers, and decision-makers, offering valuable support for the development of robust coastal management strategies aimed at mitigating the challenges posed by Mediterranean hurricanes.

In recent years, the interest in transcranial magnetic stimulation (TMS) has surged, necessitating deeper understanding, development, and use of low-frequency (LF) numerical dosimetry for TMS studies. While various ad hoc dosimetric models exist, commercial software tools like SimNIBS v4.0 and Sim4Life v7.2.4 are preferred for their user-friendliness and versatility. SimNIBS utilizes unstructured tetrahedral mesh models, while Sim4Life employs voxel-based models on a structured grid, both evaluating induced electric fields using the finite element method (FEM) with different numerical solvers. Past studies primarily focused on uniform exposures and voxelized models, lacking realism. Our study compares these LF solvers across simplified and realistic anatomical models to assess their accuracy in evaluating induced electric fields. We examined three scenarios: a single-shell sphere, a sphere with an orthogonal slab, and a MRI-derived head model. The comparison revealed small discrepancies in induced electric fields, mainly in regions of low field intensity. Overall, the differences were contained (below 2% for spherical models and below 12% for the head model), showcasing the potential of computational tools in advancing exposure assessment required for TMS protocols in different bio-medical applications.

This paper presents an analysis of anomalies detected during the preparatory phase of the 9 November 2022 ML = 5.7 earthquake, occurring approximately 30 km off the coast of the Marche region in the Adriatic Sea (Italy). It was the largest earthquake in Italy in the last 5 years. According to lithosphere–atmosphere–ionosphere coupling (LAIC) models, such earthquake could induce anomalies in various observable variables, from the Earth’s surface to the ionosphere. Therefore, a multiparametric and multilayer approach based on ground and satellite data collected in each geolayer was adopted. This included the revised accelerated moment release method, the identification of anomalies in atmospheric parameters, such as Skin Temperature and Outgoing Longwave Radiation, and ionospheric signals, such as Es and F2 layer parameters from ionosonde measurements, magnetic field from Swarm satellites, and energetic electron precipitations from NOAA satellites. Several anomalies were detected in the days preceding the earthquake, revealing that their cumulative occurrence follows an exponential trend from the ground, progressing towards the upper atmosphere and the ionosphere. This progression of anomalies through different geolayers cannot simply be attributed to chance and is likely associated with the preparation phase of this earthquake, supporting the LAIC approach.

We evaluated the effect of compression leggings with micromassage in association with physical activity on women with lipedema, not previously treated and without recent changes in body weight. The treatment resulted in an improvement in all subjective parameters, in spontaneous and evoked pain, in the volume of the limbs, in the absence of significant changes in body weight, and regardless of the duration of use, age, years of illness, the clinical stage, and body mass index (BMI). Evoked pain did not improve in areas affected by untreated lipedema; foot circumferences did not increase. We found a significant reduction in the thickness of subcutaneous adipose tissue (SAT) and skin evaluated in multiple points of the lower limb. Micromassage compression leggings are proposed as an integral part of conservative treatment. A method is proposed for the clinical evaluation of evoked pain, called the Progressive Pain Check (PPC), which allows for the calculation of a numerical score called the Ricolfi–Patton Score (RPS) and for the ultrasound evaluation of tissues. The method is simple and repeatable and allows for completion of the clinical evaluation of the patient at diagnosis and for an evaluation of the effects of various treatments, even applied to just one side of the body.

Background: We assessed the current practice concerning the axillary management of breast cancer (BC) patients undergoing upfront surgery among radiation oncologists (ROs) practising in Italy. Methods: An online survey via SurveyMonkey (including 21 questions) was distributed amongst ROs in Italy through personal contacts and the Italian Association for Radiotherapy and Clinical Oncology (AIRO) network from August to September 2022. We particularly focused on the emerging omission of axillary lymph node dissection (ALND) in the presence of 1–2 sentinel node-positive patients and the consequent change in the role of regional nodal irradiation (RNI). Results: A total of 101/195 (51% response rate) Italian Radiotherapy Cancer Care Centres answered the survey. With respect to patients with 1–2 sentinel node-positive, the relative proportion of respondents that offer patients ALND a) always, b) only in selected cases, and c) never was 37.6%, 60.4%, and 2.0%, respectively, with no significant geographical (North vs. Centre–South Italy; p = 0.92) or institutional (Academic vs. non-Academic; p = 0.49) differences. Radiation therapy indications varied widely in patients who did not undergo ALND. Among these, about a third of the respondents (17/56, 30.4%) stated that RNI was constantly performed. On the other hand, half of the respondents offered RNI in selected cases, stating that an unfavourable biologic tumour profile and extracapsular nodal extension were considered drivers of their decision. Conclusions: Results of the present survey show the variability of axillary management offered in clinical practice for BC patients undergoing conserving surgery upfront in Italy. Analysis of these attitudes may trigger the modification of some clinical approaches through multidisciplinary collaboration and create the background for future clinical investigations.

Prostate cancer (PC) is the most common type of tumor in men. In the early stage of the disease, it is sensitive to androgen deprivation therapy. In patients with metastatic castration-sensitive prostate cancer (mHSPC), chemotherapy and second-generation androgen receptor therapy have led to increased survival. However, despite advances in the management of mHSPC, castration resistance is unavoidable and many patients develop metastatic castration-resistant disease (mCRPC). In the past few decades, immunotherapy has dramatically changed the oncology landscape and has increased the survival rate of many types of cancer. However, immunotherapy in prostate cancer has not yet given the revolutionary results it has in other types of tumors. Research into new treatments is very important for patients with mCRPC because of its poor prognosis. In this review, we focus on the reasons for the apparent intrinsic resistance of prostate cancer to immunotherapy, the possibilities for overcoming this resistance, and the clinical evidence and new therapeutic perspectives regarding immunotherapy in prostate cancer with a look toward the future.

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.

The coupling processes among the lithosphere, atmosphere, and ionosphere (LAI) during the earthquake preparation phase are still an open scientific debate. Comprehensive LAI coupling effects around the 2022 Ms6.8 Luding earthquake in China are investigated with a multi-parameter and multi-layer approach, including the b-value, revised accelerated moment release, Earth resistivity, ELF magnetic field emissions, atmospheric electric field, surface temperature, foF2 from ionosonde, GNSS TEC, Ne and magnetic field from CSES and Swarm satellites, and energetic electrons from CSES and NOAA satellites. It is found that the anomalies start from the lithospheric parameters as Earth resistivity and b-values 1–2 years before to reflect the local stress loading in the seismic region, then the ionospheric and atmospheric disturbances occur and accelerate −50 days before and −15 days before, and finally the electrons precipitate a few days before. The simultaneous perturbations in LAI illustrate the thermodynamic coupling channel, such as on 24 August, −12 days before. Meanwhile, the abundant developed ionospheric anomalies without atmospheric disturbances demonstrate the electromagnetic coupling way from the lithosphere to the ionosphere directly. Finally, the results demonstrate a two-way model of LAIC: one way is characterized by a slow chain of processes, of thermodynamic nature, starting from the ground and proceeding to the above atmosphere and ionosphere, showing an exponential trend in the cumulative number of anomalies; the second way is characterized by oscillating electromagnetic coupling between the lithosphere and ionosphere, showing intermittent fluctuations in the corresponding cumulative number of anomalies.

Different factors, not limited to the lung, influence the progression of ILDs. A “treatable trait” strategy was recently proposed for ILD patients as a precision model of care to improve outcomes. However, no data have been published so far on the prevalence of TTs in ILD. A prospective, observational, cohort study was conducted within the ILD Program at the IRCCS Humanitas Research Hospital (Milan, Italy) between November 2021 and November 2023. TTs were selected according to recent literature and assigned during multidisciplinary discussion (MDD) to one of the following categories: pulmonary, etiological, comorbidities, and lifestyle. Patients were further divided into four groups according to their post-MDD diagnosis: idiopathic ILD, sarcoidosis, connective tissue disease–ILD, and other ILD. The primary study outcome was the prevalence of each TT in the study population. A total of 116 patients with ILD [63.9% male; median (IQR) age: 69 (54–78) years] were included in the study. All the TTs identified in the literature were found in our cohort, except for intractable chronic cough. We also recognized differences in TTs across the ILD groups, with less TTs in patients with sarcoidosis. This analysis provides the first ancillary characterization of TTs in ILD patients in a real setting to date.

Background: Up to 34% of patients with schizophrenia are resistant to several treatment trials. Lack of continuous and adequate treatment is associated with relapse, rehospitalization, a lower effect of antipsychotic therapy, and higher risk of side effects. Long-acting injectables antipsychotics (LAI APs) enhance compliance and improve clinical outcomes and quality of life in patients with schizophrenia, and thus it may be advisable to administer two LAI APs at the same time in cases of treatment-resistant schizophrenia. The purpose of this review is to summarize the available literature regarding the combined use of two LAI APs in patients with schizophrenia or other psychotic spectrum disorders. Methods: An extensive literature search for relevant articles regarding any combination of two long-acting injectable antipsychotics has been performed from inception up to 9 February 2024, on PubMed, Scopus and APA PsycInfo, according to the PRISMA statement. Only studies reporting combination of two LAI APs and its clinical outcome in patients with schizophrenia and related disorders were selected. Results: After the selection process, nine case reports, four case series and two observational retrospective studies were included in the final analysis. All patients treated with dual LAI APs reported a good response, and no new or unexpected adverse effects due to the combination of two LAIs were reported. Different drug combinations were used, and the most frequent association resulted in aripiprazole monohydrate + paliperidone palmitate once monthly (32 times). Conclusions: Our review highlights that the treatment regimen with two concurrent LAI APs is already widely used in clinical practice and is recognized as providing a promising, effective, and relatively safe therapeutic strategy for treating the schizophrenia spectrum disorders.

Aims: To evaluate whether antibodies specific for the vaccinia virus (VV) are still detectable after at least 45 years from immunization. To confirm that VV-specific antibodies are endowed with the capacity to neutralize Mpox virus (MPXV) in vitro. To test a possible role of polyclonal non-specific activation in the maintenance of immunologic memory. Methods: Sera were collected from the following groups: smallpox-vaccinated individuals with or without latent tuberculosis infection (LTBI), unvaccinated donors, and convalescent individuals after MPXV infection. Supernatant of VV- or MPXV-infected Vero cells were inactivated and used as antigens in ELISA or in Western blot (WB) analyses. An MPXV plaque reduction neutralization test (PRNT) was optimized and performed on study samples. VV- and PPD-specific memory T cells were measured by flow cytometry. Results: None of the smallpox unvaccinated donors tested positive in ELISA or WB analysis and their sera were unable to neutralize MPXV in vitro. Sera from all the individuals convalescing from an MPXV infection tested positive for anti-VV or MPXV IgG with high titers and showed MPXV in vitro neutralization capacity. Sera from most of the vaccinated individuals showed IgG anti-VV and anti-MPXV at high titers. WB analyses showed that positive sera from vaccinated or convalescent individuals recognized both VV and MPXV antigens. Higher VV-specific IgG titer and specific T cells were observed in LTBI individuals. Conclusions: ELISA and WB performed using supernatant of VV- or MPXV-infected cells are suitable to identify individuals vaccinated against smallpox at more than 45 years from immunization and individuals convalescing from a recent MPXV infection. ELISA and WB results show a good correlation with PRNT. Data confirm that a smallpox vaccination induces a long-lasting memory in terms of specific IgG and that antibodies raised against VV may neutralize MPXV in vitro. Finally, higher titers of VV-specific antibodies and higher frequency of VV-specific memory T cells in LTBI individuals suggest a role of polyclonal non-specific activation in the maintenance of immunologic memory.

Intravascular large B-cell Lymphoma (IVLBCL) is a rare subtype of extranodal non-Hodgkin’s lymphoma that is challenging to diagnose and has a poor prognosis. Here, we describe two patients newly diagnosed with IVLBCL at our institution: an African man with hemophagocytic-syndrome-associated IVLBCL and an Italian woman with a cutaneous variant of IVLBCL. They presented with very different clinical manifestations. Both cases were diagnosed in a timely manner, successfully treated, and achieved long-lasting remissions.

Objectives: The first aim of this study was to assess the predictive power of Tend interval (Te) and non-invasive hemodynamic markers, based on bioimpedance in decompensated chronic heart failure (CHF). The second one was to verify the possible differences in repolarization and hemodynamic data between CHF patients grouped by level of left ventricular ejection fraction (LVEF). Finally, we wanted to check if repolarization and hemodynamic data changed with clinical improvement or worsening in CHF patients. Methods: Two hundred and forty-three decompensated CHF patients were studied by 5 min ECG recordings to determine the mean and standard deviation (TeSD) of Te (first study). In a subgroup of 129 patients (second study), non-invasive hemodynamic and repolarization data were recorded for further evaluation. Results: Total in-hospital and cardiovascular mortality rates were respectively 19 and 9%. Te was higher in the deceased than in surviving subjects (Te: 120 ± 28 vs. 100 ± 25 ms) and multivariable logistic regression analysis reported that Te was related to an increase of total (χ2: 35.45, odds ratio: 1.03, 95% confidence limit: 1.02–1.05, p < 0.001) and cardiovascular mortality (χ2: 32.58, odds ratio: 1.04, 95% confidence limit: 1.02–1.06, p < 0.001). Subjects with heart failure with reduced ejection fraction (HFrEF) reported higher levels of repolarization and lower non-invasive systolic hemodynamic data in comparison to those with preserved ejection fraction (HFpEF). In the subgroup, patients with the NT-proBNP reduction after therapy showed a lower rate of Te, heart rate, blood pressures, contractility index, and left ventricular ejection time in comparison with the patients without NT-proBNP reduction. Conclusion: Electrical signals from ECG and bioimpedance were capable of monitoring the patients with advanced decompensated CHF. These simple, inexpensive, non-invasive, easily repeatable, and transmissible markers could represent a tool to remotely monitor and to intercept the possible worsening of these patients early by machine learning and artificial intelligence tools.

A new passivity-based voltage tracker for islanded Direct Current (DC) microgrids is presented in this paper. The proposed design develops a new sufficient condition for passivity-based state feedback with proportional and integral control using the attracting ellipsoid method. In this paper, we consider the time behavior of the extended vector, which completely describes the principle properties of the closed-loop system such as the boundedness of the trajectories within some ellipsoid and the dependence of its “size” on the feedback gains. The next step, which we are realizing in this paper, is the minimization of the attractive ellipsoid by selecting the “best” admissible feedback parameters. Here, it is important to note that the applied feedback is of PD-type (proportional differential) on the system state and I-type (integral) on the output. This is a new construction of the suggested feedback which gives several advantages for a designer. The suggested control is decentralized and uses only the local states; it is cost-effective and avoids the time delays in the communication networks which are needed if centralized control is used. The suggested control is carried out in the bilinear matrix inequality (BMI) framework. Extensive simulation is performed on a test system composed of renewable energy sources, under plug and play (PnP) operations, and uncertainties in distribution lines and loads. The performance of the proposed decentralized voltage controller is compared with that of a voltage tracker present in the literature. The comparison shows the improvements introduced by the proposed control ensure the stability of the dc bus voltage and a quick response under different scenarios of operating conditions.

Chickpea (Cicer arietinum L.) seed proteins show a lot of functional properties leading this legume to be an interesting component for the development of protein-enriched foods. However, both the in-depth proteomic investigation and structural characterization of chickpea seed proteins are still lacking. In this paper a detailed characterization of chickpea seed protein fraction by means of SDS-PAGE, in-gel protein digestion, high-resolution mass spectrometry, and database searching is reported. Through this approach, twenty SDS gel bands were cut and analyzed. While the majority of the bands and the identified peptides were related to vicilin and legumin storage proteins, metabolic functional proteins were also detected. Legumins, as expected, were revealed at 45–65 kDa, as whole subunits with the α- and β-chains linked together by a disulphide bond, but also at lower mass ranges (α- and β-chains migrating alone). Similarly, but not expected, the vicilins were also spread along the mass region between 65 and 23 kDa, with some of them being identified in several bands. An MS structural characterization allowed to determine that, although chickpea vicilins were always described as proteins lacking cysteine residues, they contain this amino acid residue. Moreover, similar to legumins, these storage proteins are firstly synthesized as pre-propolypeptides (Mr 50–80 kDa) that may undergo proteolytic steps that not only cut the signal peptides but also produce different subunits with lower molecular masses. Overall, about 360 different proteins specific of the Cicer arietinum L. species were identified and characterized, a result that, up to the current date, represents the most detailed description of the seed proteome of this legume.

On 4 March 2021, a devastating M8.1 earthquake struck the Kermadec Islands of New Zealand. Given the tremendous energy released during the event, we sought to investigate the event’s potential impact on the ionosphere and the inner Van Allen Belt using data from the high-energy electron detectors on board the NOAA-18 satellite. The survey was also extended to the strongest shallow M6.5+ earthquakes occurring between 150° and 190° in longitude, and between −5° and −35° in latitude over the previous ten years. In nearly all cases, evident electron fluxes entering the loss cone were observed. To explore the possibility of a connection between ionospheric signals and tectonic events in this intensely active region, we analyzed electron losses from the inner Van Allen Belt, taking into account latitude, longitude, day/night times, and proximity to the South Atlantic Anomaly. Compared to previous studies, here only the most significant loss phenomena persistent in the ionosphere were considered. Particular interest was reserved for the intense electron loss events that had a duration spanning from a few to several minutes and occurred several hours before and after strong seismic events. Thereafter, time series of electron counting rates and strong Southern Pacific earthquakes were transformed into binary series, and the series multiplication was investigated. The results suggest four peaks of association, including a first couple between electron perturbations detected for ascending semi-orbits and seismic events and a second one between electron perturbations detected in the southern ionosphere and seismic events. They both anticipated the occurrence of earthquakes, occurring around 4 h before them. Other couples were observed between electron perturbations detected for descending semi-orbits and seismic events and between electron perturbations detected in the northern ionosphere and seismic events. They both occurred around 3 h after the occurrence of earthquakes. The case of perturbations anticipating seismic events has the intriguing properties of sustaining the hypothesis that a physical interaction occurred around 6 h before seismic events as in the West Pacific case. A physical model of electrons detected far several thousands of km from the earthquake epicenters was also presented. However, a simulation of random seismic events suggested that the null hypothesis cannot be fully rejected for these associations, prompting many more analyses and case studies.

The chemical composition of food plays a crucial role in determining its characteristics and properties [...]

Down Syndrome (DS) is the most common chromosomal abnormality compatible with life. The life of patients suffering from DS can be strongly impacted by Recurrent Respiratory tract Infections (RRIs), leading to an increased rate of hospitalisation, a higher need for intensive care and fatality. With a literature review, we summarise here the main etiological factors for RRI in this category of patients, particularly focusing on airway malformations such as tracheomalacia, tracheal bronchus and bronchomalacia, comorbidities associated with the syndrome, like congenital heart diseases, dysphagia, gastroesophageal reflux, musculoskeletal involvement and obesity, and immunologic impairments, involving both innate and adaptive immunity. For these patients, a multidisciplinary approach is imperative as well as some preventive strategies, in particular vaccinations in accordance with their national schedule for immunization.

Magnetic resonance elastography (MRE) is an imaging technique that combines low-frequency mechanical vibrations with magnetic resonance imaging to create visual maps and quantify liver parenchyma stiffness. As in recent years, diffuse liver diseases have become highly prevalent worldwide and could lead to a chronic condition with different stages of fibrosis. There is a strong necessity for a non-invasive, highly accurate, and standardised quantitative assessment to evaluate and manage patients with different stages of fibrosis from diagnosis to follow-up, as the actual reference standard for the diagnosis and staging of liver fibrosis is biopsy, an invasive method with possible peri-procedural complications and sampling errors. MRE could quantitatively evaluate liver stiffness, as it is a rapid and repeatable method with high specificity and sensitivity. MRE is based on the propagation of mechanical shear waves through the liver tissue that are directly proportional to the organ’s stiffness, expressed in kilopascals (kPa). To obtain a valid assessment of the real hepatic stiffness values, it is mandatory to obtain a high-quality examination. To understand the pearls and pitfalls of MRE, in this review, we describe our experience after one year of performing MRE from indications and patient preparation to acquisition, quality control, and image analysis.

Human-dog interaction is the working tool through which the therapeutic, educational and recreational goals of dog-assisted interventions (DAIs) are achieved. A better understanding of the characteristics of this interaction could improve the effectiveness of DAIs. This scoping review addresses the question: how has the human-dog connection been measured in the context of DAIs? After searching the Web of Science and Scopus platforms, only peer-reviewed, primary research studies reporting measures of therapy dog-human interaction, relationship and bond were included. A total of 70 included articles provided information on what was measured (interaction, relationship or bond) and how, as well as the general context (DAIs or experimental situations with therapy dogs). While the majority of the articles identified use behavioural analysis methods to analyse the interaction between the participant/recipient and the therapy dog during DAIs, it was possible to identify some more structured tools that assess the participant/recipient’s interaction, relationship or bond with the therapy dog, as well as tools that consider the animal’s perspective or focus on the dog-handler dyad, indicating growing areas of research. The tools and methods identified can be used by both practitioners and researchers to further explore aspects of human-dog interaction in the field of DAIs.

The brain consists of an interconnected network of neurons tightly packed in the extracellular matrix (ECM) to form complex and heterogeneous composite tissue. According to recent biomimicry approaches that consider biological features as active components of biomaterials, designing a highly reproducible microenvironment for brain cells can represent a key tool for tissue repair and regeneration. Indeed, this is crucial to support cell growth, mitigate inflammation phenomena and provide adequate structural properties needed to support the damaged tissue, corroborating the activity of the vascular network and ultimately the functionality of neurons. In this context, electro-fluid dynamic techniques (EFDTs), i.e., electrospinning, electrospraying and related techniques, offer the opportunity to engineer a wide variety of composite substrates by integrating fibers, particles, and hydrogels at different scales—from several hundred microns down to tens of nanometers—for the generation of countless patterns of physical and biochemical cues suitable for influencing the in vitro response of coexistent brain cell populations mediated by the surrounding microenvironment. In this review, an overview of the different technological approaches—based on EFDTs—for engineering fibrous and/or particle-loaded composite substrates will be proposed. The second section of this review will primarily focus on describing current and future approaches to the use of composites for brain applications, ranging from therapeutic to diagnostic/theranostic use and from repair to regeneration, with the ultimate goal of providing insightful information to guide future research efforts toward the development of more efficient and reliable solutions.

Soil degradation is a global problem and refers to the reduction or loss of the biological and economic productive capacity of the soil resource. In Europe, the countries most affected by soil degradation are undoubtedly those of the Mediterranean basin. Among these, Italy shows clear signs of degradation, with different characteristics, especially in the southern regions, where climatic and meteorological conditions strongly contribute to it. Apulia, the Tavoliere plain in particular, is a fragile and very sensitive ecosystem due to its intrinsic characteristics and the level of anthropic exploitation. Agricultural production pays the highest price, as increasing desertification due to climate change and the loss of agricultural land severely limit the extent of land available to produce food for an ever-growing population. Plant growth-promoting bacteria (PGPB) could be a low-cost and long-term solution to restore soil fertility, as they provide a wide range of benefits in agriculture, including increasing crop productivity, improving soil nutrient levels and inhibiting the growth of pathogens. This review shows how PGPB can be used to improve the quality of soils, their impact on agriculture, their tolerance to abiotic stresses (drought, salinity, heavy metals and organic pollutants) and their feasibility. The use of PGPB could be promoted as a green technology to be applied in marginal areas of Apulia to increase soil fertility, reduce pollution and mitigate the impacts of abiotic stresses and climate change. This is supported by a series of studies showing that the growth of plants inoculated with PGPB is superior to that of non-inoculated plants.

The objective of this investigation was to evaluate Salmonella and Yersinia enterocolitica prevalence in wild boars hunted in Sardinia and further characterize the isolates and analyse antimicrobial resistance (AMR) patterns. In order to assess slaughtering hygiene, an evaluation of carcasses microbial contamination was also carried out. Between 2020 and 2022, samples were collected from 66 wild boars hunted during two hunting seasons from the area of two provinces in northern and central Sardinia (Italy). Samples collected included colon content samples, mesenteric lymph nodes samples and carcass surface samples. Salmonella and Y. enterocolitica detection was conducted on each sample; also, on carcass surface samples, total aerobic mesophilic count and Enterobacteriaceae count were evaluated. On Salmonella and Y. enterocolitica isolates, antimicrobial susceptibility was tested and whole genome sequencing was applied. Salmonella was identified in the colon content samples of 3/66 (4.5%) wild boars; isolates were S. enterica subs. salamae, S. ser. elomrane and S. enterica subs. enterica. Y. enterocolitica was detected from 20/66 (30.3%) wild boars: in 18/66 (27.3%) colon contents, in 3/66 (4.5%) mesenteric lymph nodes and in 3/49 (6.1%) carcass surface samples. In all, 24 Y. enterocolitica isolates were analysed and 20 different sequence types were detected, with the most common being ST860. Regarding AMR, no resistance was detected in Salmonella isolates, while expected resistance towards β-lactams (blaA gene) and streptogramin (vatF gene) was observed in Y. enterocolitica isolates (91.7% and 4.2%, respectively). The low presence of AMR is probably due to the low anthropic impact in the wild areas. Regarding the surface contamination of carcasses, values (mean ± standard deviation log10 CFU/cm2) were 2.46 ± 0.97 for ACC and 1.07 ± 1.18 for Enterobacteriaceae. The results of our study confirm that wild boars can serve as reservoirs and spreaders of Salmonella and Y. enterocolitica; the finding of Y. enterocolitica presence on carcass surface highlights how meat may become superficially contaminated, especially considering that contamination is linked to the conditions related to the hunting, handling and processing of game animals.

Alicyclobacillus acidoterrestris causes spoilage in fruit juices. This research investigated the effects of organic acids on the growth of two strains of A. acidoterrestris at different pH values and temperatures over 2, 7 and 14 days. The results show different impacts of weak acids on A. acidoterrestris’s growth and survival. Ascorbic and malic acids have the highest antimicrobial activity; also, pH played a crucial role. Moreover, the results suggest a possible activity of acids on outgrowing spores rather than on spores. Understanding the organic acids interactions with A. acidoterrestris is crucial for implementing strategies to ensure quality and reduce spoilage incidents.

Fibroblast growth factor 21 (FGF-21), previously recognized as a marker of liver damage and a potential drug target in non-alcoholic fatty liver disease (NAFLD), has unclear implications in hepatitis C virus (HCV) infections. This study aimed to investigate the relationship between FGF-21 levels and liver health in patients with HCV undergoing direct-acting antiviral (DAA) treatment. Forty-five patients were assessed for liver stiffness, blood chemistry, and other relevant metrics before and after achieving sustained viral response (SVR), defined as the absence of detectable HCV-RNA after 24 weeks of treatment. Post-treatment, all patients showed a decrease in liver stiffness and improved liver enzyme levels (AST and ALT), alongside an increase in FGF-21 levels. Interestingly, the increase in FGF-21 correlated negatively with liver stiffness but showed no correlation with hepatic steatosis. The observed elevation in FGF-21 levels at SVR following DAA therapy for chronic HCV infection can be attributed to the restoration of hepatic function, including its synthetic capabilities. Specifically, the mitigation of liver fibrosis post-HCV eradication is expected to lead to improvements in liver function, such as enhanced albumin and FGF-21 production. This improvement in synthetic function likely drives the increase in FGF-21 levels, rather than changes in liver fat content. We suggest a potential role of FGF-21 as a marker of fibrosis and hepatic cytotoxicity and as a drug target beyond NAFLD, to be confirmed by additional studies.

Wheat-based products are largely consumed by children worldwide. Deoxynivalenol (DON) is known for its acute and chronic toxicity and is the most common contaminant of cereal grains. Since no legal limits are set for DON in wheat-based products and specific foods intended for children over 3 years on the market, a high risk of overexposure to this contaminant may emerge. The main objective of the study, conducted in 2018–2019, was to produce a wheat flour intended for children over three years, characterized by a high level of safety in terms of DON content, to be used to produce wheat-derived products. The dedicated flour was produced by adopting tailored procedures like the selection of wheat suppliers, the predetermination of the safe contamination of DON in the final products, and the evaluation of the transfer rate from the wheat flour to derived products (bread, breadsticks, biscuits, plumcake, and focaccia). The results showed that the daily exposure of children was considered to be safe, in a range between 7% (biscuits) and 67% (bread) of DON tolerable daily intake (TDI) and that only by producing a flour characterized by DON levels much lower than those in force, can “safe” products be marketed.

SARS-CoV-2 is inactivated in aerosol (its primary mode of transmission) by means of radiated microwaves at frequencies that have been experimentally determined. Such frequencies are best predicted by the mathematical model suggested by Taylor, Margueritat and Saviot. The alignment between such mathematical prediction and the outcomes of our experiments serves to reinforce the efficacy of the radiated microwave technology and its promise in mitigating the transmission of SARS-CoV-2 in its naturally airborne state.

The composition and physicochemical characteristics of short-aged Pecorino Sardo PDO (Protected Designation of Origin) cheese makes it permissive to Listeria monocytogenes growth. The PDO product specification stipulates that this cheese is produced with whole sheep’s milk inoculated with cultures from the area of origin. Therefore, the use of bioprotective cultures for the inhibition of pathogens in PDO cheeses is allowed only if autochthonous microorganisms are used. Furthermore, bioprotective cultures are generally used on the cheese surface to prevent the outgrowth of L. monocytogenes, the application of which can be time-consuming and require specialist technical knowledge. In this study, we examine the direct addition of bioprotective cultures to the cheese vat and compare the activity of a commercial bioprotective culture (Lactiplantibacillus plantarum) and an autochthonous lactic acid bacterium with bioprotective properties (Lactobacillus delbruekii sups. sunkii), for the inhibition of L. monocytogenes in Pecorino Sardo PDO cheese. Three types of Pecorino Sardo PDO cheese were made with bioprotective cultures added directly to the cheese milk along with the starter inoculum: PSA, with the commercial bioprotective culture; PSB, with the autochthonous bioprotective culture; and a CTRL cheese with no bioprotective culture. A challenge test was performed on each of these cheeses by artificially contaminating the cheese surface with L. monocytogenes (2 Log10 CFU/g). Three batches of each cheese type were analyzed to enumerate mesophilic and thermophilic lactic acid bacteria and to investigate the growth potential of L. monocytogenes during manufacturing, at the end of ripening, at the end of shelf-life, and after 180 days from cheese production. Both bioprotective cultures tested in this study showed inhibitory action against the pathogen with 0.3–1.8 Log10 CFU/g (colony-forming unit per gram) reduction levels. The autochthonous organism, L. sunkii, was as effective as the commercially supplied culture, and the addition of the bioprotective cultures to the cheese-making procedure offered protection against L. monocytogenes. The direct addition of bioprotective cultures to the making procedure of Pecorino Sardo PDO cheese is a potentially innovative strategy to improve the safety of this product.

Testis stimulation with follicle-stimulating hormone (FSH) is one of the empirical treatments proposed for male idiopathic infertility, although reliable markers to predict its efficacy are still lacking. This study aimed to identify parameters able to predict FSH efficacy in terms of pregnancy achievement. A real-world study was conducted, enrolling idiopathic infertile men treated with FSH 150IU three times weekly. Patients were treated until pregnancy achievement or for a maximum of two years and two visits were considered: V0 (baseline) and V1 (end of FSH treatment). Primary endpoints were the V1-V0 percentage change in sperm concentration, total sperm count, and total motile sperm number. In total, 48 pregnancies were recorded (27.7%) among 173 men (age 37.9 ± 6.2 years). All three endpoints increased after FSH administration, and only the V1-V0 percentage of sperm concentration significantly predicted pregnancy (p = 0.007). A V1-V0 sperm concentration of 30.8% predicted pregnancy, and the sperm concentration V1-V0 percentage (Y) required to obtain a pregnancy was predicted according to its baseline values (x): Y = 9.8433x2 − 203.67x + 958.29. A higher number of pregnancies was reached in men with baseline sperm concentration below 7.3 million/mL. Thus, the percentage of sperm concentration increasing after FSH administration could predict the treatment efficacy in terms of pregnancy. At the dosage used, the efficacy was significantly higher in patients with a starting sperm concentration < 7.3 mill/mL. Mathematical analyses identified a function able to predict the sperm concentration increase required to obtain a pregnancy in relation to the baseline sperm number.