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Introduction: The immune system mediates important effects on bone metabolism, but little has been done to understand immunotherapy’s role in this interaction. This study aims to describe and identify risk factors for the occurrence and/or exacerbation of vertebral fractures (vertebral fracture progression) during immune checkpoint inhibitors (ICIs). Methods: We conducted an observational, retrospective, monocentric study. We collected data on melanoma and NSCLC patients, treated with first-line ICIs at the Medical Oncology Department ASST Spedali Civili of Brescia, between January 2015 and November 2021, and with a median follow-up of 20.1 (6–36) months. We collected data on patients, diseases, immune-related adverse events, and cortico-steroid therapy initiated on concomitant ICIs. Results: We identified 135 patients, 65 (48.2 %) with locally advanced/metastatic melanoma and 70 (51.8 %) with locally advanced/metastatic non-small cell lung cancer (NSCLC). Twenty-one (15.6 %) patients already had an asymptomatic vertebral fracture at baseline before starting ICIs in monotherapy. A total of ten patients, or 7.4 %, had a vertebra fracture progression defined as a new vertebral fracture or a worsening of a previous fracture. There was a strong relation between the steroid therapy and irAEs with vertebra fracture progression [OR (95 % CI) 8.1 (3.7–17.8) p-value

Abstract Background Since the beginning of the anti-COVID-19 vaccination campaign, it has become evident that vaccinated subjects exhibit considerable inter-individual variability in the response to the vaccine that could be partly explained by host genetic factors. A recent study reported that the immune response elicited by the Oxford-AstraZeneca vaccine in individuals from the United Kingdom was influenced by a specific allele of the human leukocyte antigen gene HLA-DQB1. Methods We carried out a genome-wide association study to investigate the genetic determinants of the antibody response to the Pfizer-BioNTech vaccine in an Italian cohort of 1351 subjects recruited in three centers. Linear regressions between normalized antibody levels and genotypes of more than 7 million variants was performed, using sex, age, centers, days between vaccination boost and serological test, and five principal components as covariates. We also analyzed the association between normalized antibody levels and 204 HLA alleles, with the same covariates as above. Results Our study confirms the involvement of the HLA locus and shows significant associations with variants in HLA-A, HLA-DQA1, and HLA-DQB1 genes. In particular, the HLA-A*03:01 allele is the most significantly associated with serum levels of anti-SARS-CoV-2 antibodies. Other alleles, from both major histocompatibility complex class I and II are significantly associated with antibody levels. Conclusions These results support the hypothesis that HLA genes modulate the response to Pfizer-BioNTech vaccine and highlight the need for genetic studies in diverse populations and for functional studies aimed to elucidate the relationship between HLA-A*03:01 and CD8+ cell response upon Pfizer-BioNTech vaccination.

Abstract Ultrasonic vocalizations (USVs) analysis represents a fundamental tool to study animal communication. It can be used to perform a behavioral investigation of mice for ethological studies and in the field of neuroscience and neuropharmacology. The USVs are usually recorded with a microphone sensitive to ultrasound frequencies and then processed by specific software, which help the operator to identify and characterize different families of calls. Recently, many automated systems have been proposed for automatically performing both the detection and the classification of the USVs. Of course, the USV segmentation represents the crucial step for the general framework, since the quality of the call processing strictly depends on how accurately the call itself has been previously detected. In this paper, we investigate the performance of three supervised deep learning methods for automated USV segmentation: an Auto-Encoder Neural Network (AE), a U-NET Neural Network (UNET) and a Recurrent Neural Network (RNN). The proposed models receive as input the spectrogram associated with the recorded audio track and return as output the regions in which the USV calls have been detected. To evaluate the performance of the models, we have built a dataset by recording several audio tracks and manually segmenting the corresponding USV spectrograms generated with the Avisoft software, producing in this way the ground-truth (GT) used for training. All three proposed architectures demonstrated precision and recall scores exceeding $$90\%$$ 90 % , with UNET and AE achieving values above $$95\%$$ 95 % , surpassing other state-of-the-art methods that were considered for comparison in this study. Additionally, the evaluation was extended to an external dataset, where UNET once again exhibited the highest performance. We suggest that our experimental results may represent a valuable benchmark for future works.

O objetivo deste artigo é discutir os resultados de uma maior participação nas cadeias globais de valor (CGVs) para a redução dos índices de pobreza na América Latina e Caribe (ALC), especialmente tendo em vista o aumento da miséria no contexto pós-pandêmico. A hipótese testada no artigo é a de que quanto maior for a inserção da região da ALC nas cadeias globais de valor, menor será o nível de pobreza. Para testá-la, realiza-se uma análise de regressão linear múltipla com dados sobre a inserção da região em CGVs, oriundos da United Nations Conference on Trade and Development (UNCTAD), bem como com informações de pobreza extraídas do Banco Mundial, tendo por período de análise o intervalo entre 1991 e 2018. Como resultados, observa-se um decréscimo tímido na inserção da ALC em CGVs. Apesar disso, identifica-se uma correlação entre a participação em CGVs e a redução da pobreza, confirmando-se, com ressalvas, a hipótese proposta.

Abstract This paper aims to discuss and demonstrate the non-tariff challenges to Mercosur’s trade integration. Its Common External Tariff (CET) and exceptions will be discussed, as well as the evolution of its non-tariff protectionism framework in the last three decades. This is an unprecedented exploratory exercise on all 5019 non-tariff measures (NTM) notified by Mercosur members to the WTO from 1995 to 2020. As main results, we see that (i) members with fewer exceptions to the CET are the ones that most use NTMs to protect their markets; (ii) the stock of NTMs targeted at members and non-members varies accordingly; (iii) of the 10 countries most targeted by NTMs imposed by Mercosur members, its own members figure in the 3rd, 4th, 7th, and 8th positions; (iv) the bloc lacks deep regulatory harmonization, especially with regard to sanitary and phytosanitary barriers in 11 sectors. Based on these results, two critical policy action plans are suggested to the bloc.

Food residues are a promising resource for obtaining natural pigments, which may replace artificial dyes in the industry. However, their use still presents challenges due to the lack of suitable sources and the low stability of these natural compounds when exposed to environmental variations. In this scenario, the present study aims to identify different food residues (such as peels, stalks, and leaves) as potential candidates for obtaining natural colorants through eco-friendly extractions, identify the colorimetric profile of natural pigments using the RGB color model, and develop alternatives using nanotechnology (e.g., liposomes, micelles, and polymeric nanoparticles) to increase their stability. The results showed that extractive solution and residue concentration influenced the RGB color profile of the pigments. Furthermore, the external leaves of Brassica oleracea L. var. capitata f. rubra, the peels of Cucurbita maxima, Cucurbita maxima x Cucurbita moschata, and Beta vulgaris L. proved to be excellent resources for obtaining natural pigments. Finally, the use of nanotechnology proved to be a viable alternative for increasing the stability of natural colorants over storage time.

We report a multicenter experience of open conversions (OC) for aortic endograft infections (AEI). We retrospectively analyzed all patients who underwent OC for AEI after endovascular aneurysm repair (EVAR), from 1997 to 2021 in 12 Italian centers. The endpoints were as follows: mortality (30-days, in-hospital), major postoperative complications. Follow-up data included: survival, aortic-related complications, infection persistence or reoccurrence. Fifty-eight patients (mean age: 73.8 ± 6.6 years) were included. Median time from EVAR to OC was 14 months (interquartile range 7–45). Thirty-five patients (60.3%) were symptomatic at presentation. Aortic reconstruction was anatomic in 32 patients (55.2%), extra-anatomic in 26 (44.8%). Thirty-day mortality was 31% (18/58). Six additional patients died after 30 days during the same hospitalization (in-hospital mortality: 41.4%). Most common post-operative complications included respiratory failure (38.6%) and renal insufficiency (35.1%). During 28.1 ± 4 months follow-up, 4 aneurysm-related deaths were recorded. Infection re-occurred in 29.4% of the patients. Estimated survival was 50% at 1 year, and 30% at 5 years, and was significantly lower for patients who underwent extra-anatomic reconstructions (37 vs 61% at 1 year, 16 vs 45% at 5 years; log-rank P =.021). OC for AEI is associated with high early mortality. The poor mid-term survival is influenced by aortic complications and infection re-occurrence. [ABSTRACT FROM AUTHOR]

Introduction:Laryngeal web is a rare cause of pediatric stridor and respiratory distress. The clinical presentation is variable and symptoms usually correlate with the severity of the airway obstruction. Case Reports:We describe the cases of three children unexpectedly diagnosed with laryngeal web after a severe episode of bronchiolitis and after thirteen and eleven years, respectively, of persistent symptoms despite asthma medications.Conclusion:Even if it is a rare cause of stridor and respiratory distress, congenital subglottic web could be a life threatening condition and clinicians should always consider it in the differential diagnosis of persistent noisy breathing, even in adolescents and young adults.

IntroductionImmunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.MethodsHere we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation.ResultsWe show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus.DiscussionThese data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20.

Enterococci are commonly found in the environment and humans as a part of the normal microbiota. Among these, Enterococcus faecalis and Enterococcus faecium can convert into opportunistic pathogens, making them a major cause of nosocomial infections. The rapid diffusion of vancomycin-resistant strains and their impact on nosocomial settings is of considerable concern. Approximately one-third of the E. faecium infections in Italy are caused by vancomycin-resistant strains. This study explored the hypothesis that the oral cavity could represent a silent reservoir of virulent enterococci. A sample of 862 oral flora specimens collected from healthy human volunteers in Central Italy was investigated by real-time PCR to detect E. faecalis and E. faecium, as well as the genetic elements that most frequently determine vancomycin resistance. The prevalence of E. faecalis was 19%, a value that was not associated with alcohol consumption, tobacco smoking, or age of the subjects. Less frequently detected, with an overall prevalence of 0.7%, E. faecium was more common among people older than 49 years of age. The genes conferring vancomycin resistance were detected in only one sample. The results indicate that the oral cavity can be considered a reservoir of clinically relevant enterococci; however, our data suggest that healthy individuals rarely carry vancomycin-resistant strains.

The global consumption of vegan foods is experiencing an expressive upward trend, underscoring the critical need for quality control measures based on nutritional and functional considerations. This study aimed to evaluate the functional quality of caviar and salmon analog food inks based on pulses combined with nano ingredients and produced in our laboratory (LNANO). The primary objective of this work was to determine the total antioxidant compounds contained in these samples using a voltammetric technique with a glassy carbon electrode. The samples underwent ethanolic extraction (70%) with 1 h of stirring. The voltammograms were acquired in a phosphate buffer electrolyte, pH 3.0 with Ag/AgCl (KCl 3 mol L−1) as the reference electrode and platinum wire as the auxiliary electrode. The voltammograms revealed prominent anodic current peaks at 0.76–0.78 V, which are attributed to isoflavones. Isoflavones, known secondary metabolites with substantial antioxidant potential commonly found in pulses, were identified. The total isoflavone concentrations obtained ranged from 31.5 to 64.3 mg Eq genistein 100 g−1. The results not only validated the efficacy of the electrochemical sensor for quantifying total antioxidant compounds in the samples but also demonstrated that the concentration of total isoflavones in caviar and salmon analogs fell within the expected limits.

Molecular solar thermal systems, which absorb light, store it, and release it as heat, have been extensively researched, yet many potential candidates remain unexplored. To expand this range, five specifically designed ortho-dianthrylbenzenes were investigated. Anthracene dimers have been underexplored due to issues like photooxidation and varying photodimerization efficiency. The presented systems address these challenges by aryl-linking two anthracene moieties, achieving photodimerization quantum yields ranging from 11.5% to 16% in mesitylene. The impact of donor or acceptor groups on energy storage time (9–37 years), energy storage density (0.14–0.2 MJ kg−1), and solar energy storage efficiency (0.38–0.66%) was evaluated. The experimental results, supported by density functional theory-based modeling, highlight the potential of anthracene-based photoswitches for molecular solar thermal applications and encourage further exploration of similar systems. [ABSTRACT FROM AUTHOR]

Abstract Background Mesenchymal stromal cells (MSCs) are able to migrate and engraft at sites of inflammation, injuries, and tumours, but little is known about their fate after local injection. The purpose of this study is to perform MSC tracking, combining in vivo 7-T magnetic resonance imaging (MRI) and histological assessment, following lung injection in a rat model. Methods Five lungs were injected with ferumoxide-labelled MSCs and five with perfluorocarbon-labelled MSCs and underwent 7-T MRI. MRI acquisitions were recorded immediately (T0), at 24 h (T24) and/or 48 h (T48) after injection. For each rat, labelled cells were assessed in the main organs by MRI. Target organs were harvested under sterile conditions from rats sacrificed 0, 24, or 48 h after injection and fixed for histological analysis via confocal and structured illumination microscopy. Results Ferumoxide-labelled MSCs were not detectable in the lungs, whereas they were not visible in the distant sites. Perfluorocarbon-labelled MSCs were seen in 5/5 injected lungs at T0, in 1/2 at T24, and in 1/3 at T48. The fluorine signal in the liver was seen in 3/5 at T0, in 1/2 at T24, and in 2/3 at T48. Post-mortem histology confirmed the presence of MSCs in the injected lung. Conclusions Ferumoxide-labelled cells were not seen at distant sites; a linear decay of injected perfluorocarbon-labelled MSCs was observed at T0, T24, and T48 in the lung. In more than half of the experiments, perfluorocarbon-labelled MSCs scattering to the liver was observed, with a similar decay over time as observed in the lung.

RESUMO Objetivo Realizar uma revisão sistemática investigando a metacognição no transtorno bipolar (TB). Os objetivos secundários incluem explorar os correlatos clínicos e sociodemográficos da metacognição no TB e como a metacognição varia de acordo com o estado afetivo, estabelecer uma comparação com outros transtornos mentais e investigar se as intervenções metacognitivas no TB são eficazes ou não. Métodos Realizou-se uma revisão sistemática da literatura científica sobre a metacognição em pacientes com TB. Foram buscados estudos clínicos originais sobre o tema nas bases de dados Medline, ISI , PsycINFO e SciELO. Os termos de busca empregados foram: “metacognition” OR “metacognitive” OR “metamemory” AND “bipolar” OR “mania” OR “manic” . Resultados Foram selecionados nove artigos. A metacognição parece estar mais prejudicada no TB do que em controles e menos prejudicada do que na esquizofrenia. Por sua vez, parece não haver diferença entre bipolares e deprimidos unipolares quanto à capacidade metacognitiva. Maior nível educacional e maior duração da doença parecem estar associados a uma melhor capacidade metacognitiva, enquanto a maior gravidade dos sintomas de TB está associada a uma pior metacognição. O treinamento metacognitivo em pacientes com TB é uma perspectiva clínica promissora. Conclusão Os estudos sobre metacognição no TB são escassos, mas a literatura existente indica possíveis fatores clínicos e sociodemográficos associados a pior metacognição no transtorno, sugerindo também que intervenções terapêuticas metacognitivas podem ser clinicamente relevantes para o manejo do TB.

The present study was undertaken with an aim to formulate enteric coated tablets of Tenatoprazole (a novel proton pump inhibitor with an imidazopyridine ring) to improve bioavailability by avoiding degradation. Different core tablets were prepared using approved excipients by direct compression method and evaluated for different parameters like hardness, thickness, friability and disintegration time. Sub-coating was done for optimized formulation (F5) by using HPMC 5 cps with buildup of 3% w/w and finally enteric coating was done by using HPMCP, Eudragit L30 D55 and HPMC Acetate succinate (HPMCAS) with an average weight buildup of 5%, 8% and 10% w/w. all formulations were evaluated for different parameters like hardness, friability, thickness, disintegration time, drug content and dissolution studies and compared with marketed sample. Results indicated that, methacrylic acid polymers exhibited better dissolution rate than cellulose polymers. The optimized formulation was subjected to stability studies as per ICH guidelines for 3 months and was observed that no significant change was observed.

Abstract Here, we demonstrate that introduction of halogen atoms at the tyrosine 10 phenol ring of the DSGYEV sequence derived from the flexible amyloid‐β N‐terminus, promotes its self‐assembly in the solid state. In particular, we report the crystal structures of two halogen‐modified sequences, which we found to be stabilized in the solid state by halogen‐mediated interactions. The structural study is corroborated by Non‐Covalent Interaction (NCI) analysis. Our results prove that selective halogenation of an amino acid enhances the supramolecular organization of otherwise unstructured biologically‐relevant sequences. This method may develop as a general strategy for stabilizing highly polymorphic peptide regions.