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Abstract We investigated the relationship between the degree of alveolarization and ultrasound-assessed lung aeration in a validated preterm rabbit model of experimental bronchopulmonary dysplasia (BPD). Lung ultrasound findings were heterogeneously abnormal and consisted of zones with interstitial, interstitial-alveolar or consolidated patterns. The median radial alveolar count was 10.1 [8.4–11.5], 7.8 [6.1–9] and 7.3 [1.8–10.1] in rabbits with interstitial, interstitial-alveolar or consolidated ultrasound pattern, respectively (overall p = 0.036). Alveolar count and lung ultrasound score were significantly correlated (ρ = − 0.044 (95%CI: − 1; − 0.143), p = 0.009; τ-b = − 0.362 (95%CI: − 0.6; − 0.1), p = 0.017).

Open-cell ceramic foams are widely used as filters for the purification of molten metals due to their high permeability and high efficiency for capturing non-metallic inclusions. With the consideration of manufacture and filtration behaviour, most filters are produced by replica methods. The intrinsic multiscale porous structure requires the ceramic foams to have sufficient strength. As a consequence, different processing approaches, material compositions and characterizations are investigated. Meanwhile, to further enhance the filtration performance, the functionalization of ceramic foam filters is often conducted with surface coating. This review summarizes the processing and characteristics of ceramic foam filters (CFFs), the nature and formation of non-metallic inclusions (NMIs), the filtration mechanism and applications of CFFs. The characterization of mechanical and filtration performance, as well as the corresponding strengthening and functionalization methods are also presented.

IntroductionIn recent years, the increasing presence of refugees and asylum seekers displaced from their country of origin, determined significant social, economic, humanitarian and public health implications in host countries, including Italy. These populations are exposed to several potential stressful experiences which make them vulnerable to psychological distress. In fact, the majority of studies addressing the topic found a higher prevalence of mental disorders, especially post-traumatic stress disorder and major depressive disorder, in refugees and asylum seekers with respect to the general population. However, heterogeneous prevalence rates have been reported among studies, due to methodological factor as well as to the impact of a variety of risk factors related to stressful experiences lived in the country of origin, during the migration journey and in the host country.ObjectivesThe aim of the present study was to assess the prevalence of the main psychiatric diagnoses in a large group of adult refugees and asylum seekers (N=303) in the reception centers of two provinces of the Campania region, as well as to investigate the impact of potential risk factors on the occurrence of psychiatric disorders.MethodsThe diagnosis of psychiatric disorders and the identification of subjects at high risk to develop psychosis were carried out by means of structured diagnostic interviews. The following variables were explored as potential risk/protective factors to the occurrence of psychiatric disorders: socio-demographic variables, migration status (refugees/asylum seekers) and characteristics of the reception center,assessed by means of an ad hoc questionnaire; cognitive indices assessed by using standardized neuropsychological tests; traumatic experiences and level of political terror in the country of origin, assessed by means of reliable and valid self-report questionnaires.ResultsAt least one mental disorder was found in 29.7% of the sample. Most prevalent diagnoses were depressive disorders, anxiety disorders and PTSD. Women showed, with respect to men, a higher prevalence of anxiety disorders, higher trauma levels, and came from more at-risk countries. Higher trauma levels, better cognitive abilities and unemployment and refugee status were associated to the presence of a current psychiatric disorder in the whole sample.ConclusionsOur findings showed a higher prevalence of depressive disorders and PTSD in the sample of refugees and asylum seekers with respect to the general population and highlighted the role of potential risk factors whose identification may guide the implementation of preventive strategies and early treatments in these people.

Introduction: Plasmodium vivax is the most widely distributed species of malaria in the world. In Brazil, this parasite is responsible for around 90% of cases. Infections caused by P. vivax can generate a variety of symptoms, such as fever, chills, headache, nausea, vomiting and anemia. The immune response directly influences the individual's clinical evolution. The TREM-1 receptor is an important molecule that acts by recognizing the pathogen and amplifying inflammation. Polymorphisms in the gene encoding this protein have been linked to the severity of malaria. Objective: We investigated the association between the SNP rs2234246 (C>T) in the TREM-1 gene and the development of nausea and vomiting in individuals infected with P. vivax in an area of the Brazilian Amazon. Methodology: We analyzed 76 patients with a microscopic and molecular diagnosis of P. vivax and 114 controls from the municipality of Oiapoque in Amapá state, Brazil, on the border with French Guiana. The clinical signs of the individuals were assessed by a nurse. Genomic DNA was extracted from blood samples and the SNP rs2234246 was genotyped by qPCR. The occurrence of nausea and vomiting symptoms was adjusted for the SNP using Logistic Regression. Variables such as: occurrence of anemia, gender, age, length of residence in the study area, number of previous episodes of malaria and period of the last malaria were inserted as adjustment variables for the logistic regression. All analysis was carried out with a 5% significance level. Results: Among the 76 patients, 44.7% reported experiencing nausea and vomiting. As for SNP rs2234246 genotyping, CC = 15, CT = 42 and TT = 19. In the association between the SNP and symptoms, it was observed that infected individuals with the TT mutant genotype for the TREM-1 rs2234246 C>T SNP were 90% less likely (OR = 0.1; 95% CI = 0.0 - 0.6; p = 0.013) to develop nausea and vomiting than wild-type CC individuals. The reduced risk of developing these symptoms may provide relevant insight into the human parasite-host relationship in the population studied, which may suggest a possible protective role for the homozygous mutant allele (TT). Case highlighting characteristics malaria vivax infection, necessitating close clinical and laboratory correlation. Conclusion: Our results aim to help the global public develop a comprehensive understanding of malaria in Brazilian-French Guiana, thereby contributing to malaria control and elimination. Keywords: Immunological Factors, Malaria, Polymorphism, Genetic, Signs and Symptoms. Conflicts of interest: There was no conflicts of interest. Ethics and financing: Declarations of interest: None.

BackgroundERAS is an evidence-based multimodal perioperative protocol focused on stress reduction and promoting a return to function. The aim of this work is to perform a cost-consequence analysis for the implementation of ERAS in major lung resection by means of minimally invasive surgery (VATS) from the public health service perspective, evaluating resource consumption and clinical outcomes with respect to a control group of past patients, which did not adopt an ERAS protocol.MethodsOutcome differences (re-intervention rates, major and minor intraoperative and postoperative complications, readmissions, and mortality) as well as the costs of preoperative, operative, and postoperative care were estimated. The sample consisted of 64 consecutive patients enrolled in the ERAS programme between April 2021 and August 2022, compared to a control group (historical cohort) comprising 31 patients treated from April 2020 to December 2020, prior to the implementation of the ERAS programme. The study sample comprises patients who fulfil the established ERAS protocol inclusion criteria, including general criteria (acceptance of the protocol, proximity of residence, absence of contraindications to physiotherapy and early mobilisation), surgical criteria (anatomical lung resection up to lobectomy, absence of extensive resection, good possibility of conducting the operation in VATS) and anaesthesiologic criteria (ASA ≤2). Costs were quantified using the national health system perspective.ResultsThe average length-of-stay was at least one day shorter in the ERAS group [

Oncolytic virotherapy represents an innovative and promising approach for the treatment of cancer, including multiple myeloma (MM), a currently incurable plasma cell (PC) neoplasm. Despite the advances that new therapies, particularly immunotherapy, have been made, relapses still occur in MM patients, highlighting the medical need for new treatment options. Oncolytic viruses (OVs) preferentially infect and destroy cancer cells, exerting a direct and/or indirect cytopathic effect, combined with a modulation of the tumor microenvironment leading to an activation of the immune system. Both naturally occurring and genetically modified viruses have demonstrated significant preclinical effects against MM cells. Currently, the OVs genetically modified measles virus strains, reovirus, and vesicular stomatitis virus are employed in clinical trials for MM. Nevertheless, significant challenges remain, including the efficiency of the virus delivery to the tumor, overcoming antiviral immune responses, and the specificity of the virus for MM cells. Different strategies are being explored to optimize OV therapy, including combining it with standard treatments and targeted therapies to enhance efficacy. This review will provide a comprehensive analysis of the mechanism of action of the different OVs, and preclinical and clinical evidence, focusing on the role of oncolytic virotherapy as a new possible immunotherapeutic approach also in combination with the current therapeutic armamentarium and underlying the future directions in the context of MM treatments.

Quanto la storia del notariato può servire per affrontare lo studio del documento notarile o viceversa quanto lo studio del documento può servire allo studio del notariato? Il tema è stato ampiamente studiato sia dagli storici del diritto sia dagli specialisti delle tante discipline coinvolte nell’approfondimento della materia delle carte e dei lor redattori (storia del ceto, storia del documento, paleografia e scrittura, diplomatica) con ricerche ora di carattere generale ora mirate all’analisi di particolari aree ora con riguardo a specifici spazi temporali. Nonostante la frammentarietà della documentazione, si è così fatto luce sia sulla storia delle carte e del notariato, sia su innumerevoli varianti dovute alle diversità sociali e organizzative di singoli ambienti in determinati periodi. Per quanto concerne l’alto medioevo, ritengo che qualche ulteriore indicazione possa essere desunta dalla sequenza cronologica degli editti longobardi e delle leggi del regno italico. Questi testi, oltre, a prescrivere le regole per il compimento di specifici atti giuridici e per la redazione delle relative carte, ne indicavano i responsabili della corretta applicazione. L’esame di tali norme ci aiuta anche a comprendere quali preoccupazioni movessero, nei singoli momenti storici, i legislatori e quale fosse il loro intento: innanzitutto, garantire la corrispondenza alla legge e l’effettività delle carte ed evitare il più possibile l’insorgere di controversie tra le parti coinvolte e prevenire controversie giudiziarie o facilitarne la soluzione. Il riconoscimento, avvenuto soltanto nel XII secolo, della fides di coloro che scrivevano le carte in quanto titolari di quello che noi definiamo come un ufficio pubblico fu l’esito non scontato e forse non previsto di un cammino lentissimo nel quale fu prevalente il tentativo dei legislatori di contrastare comportamenti perversi o ripensamenti comunque contrari agli impegni assunti di coloro che volevano negare o aggirare l’efficacia di quelle scritture, talora da loro stessi commissionate. È da questa prospettiva che si potrebbe, dunque, prendere avvio per analizzare il ‘doppio binario’ dei legislatori e i presupposti normativi di un secolare percorso attraverso l’ideazione e la standardizzazione dei requisiti sia di alcuni atti giuridici, sia dell’attività di coloro che ne scrivevano le carte. Da storico del diritto ho scelto, per così dire, di ricominciare da capo per ripercorrere in prospettiva cronologica la successione delle leggi dei regni longobardo e italico mettendo in connessione le prescrizioni relative ai requisiti di carte concernenti specifici atti giuridici con la disciplina dell’attività di coloro che erano incaricati di scriverle. Proprio nel riflettere sulla sequenza di tali disposizioni e della loro ratio, è possibile tracciare un itinerario tra questioni e contesti per individuare la ricorrenza di specifici campi di tensione tra i governanti, i redattori dei documenti e i loro ‘clienti’, originati, secondo i legislatori, da uno dei maggiori problemi del diritto vivente ossia da una generalizzata assenza di quella che noi chiamiamo buona fede.

Purpose: Hyperglycemia is a major risk factor for early lesions of diabetic retinal disease (DRD). Updating the DRD staging system to incorporate relevant basic and cellular mechanisms pertinent to DRD is necessary to better address early disease, disease progression, the use of therapeutic interventions, and treatment effectiveness. Design: We sought to review preclinical and clinical evidence on basic and cellular mechanisms potentially pertinent to DRD that might eventually be relevant to update the DRD staging system. Participants: Not applicable. Methods: The Basic and Cellular Mechanisms Working Group (BCM-WG) of the Mary Tyler Moore Vision Initiative carefully and extensively reviewed available preclinical and clinical evidence through multiple iterations and classified these. Main Outcome Measures: Classification was made into evidence grids, level of supporting evidence, and anticipated future relevance to DRD. Results: A total of 40 identified targets based on pathophysiology and other parameters for DRD were grouped into concepts or evaluated as specific candidates. VEGFA, peroxisome proliferator-activated receptor-alpha related pathways, plasma kallikrein, and angiopoietin 2 had strong agreement as promising for use as biomarkers in diagnostic, monitoring, predictive, prognostic, and pharmacodynamic responses as well as for susceptibility/risk biomarkers that could underlie new assessments and eventually be considered within an updated DRD staging system or treatment, based on the evidence and need for research that would fit within a 2-year timeline. The BCM-WG found there was strong reason also to pursue the following important concepts regarding scientific research of DRD acknowledging their regulation by hyperglycemia: inflammatory/cytokines, oxidative signaling, vasoprotection, neuroprotection, mitophagy, and nutrients/microbiome. Conclusion: Promising targets that might eventually be considered within an updated DRD staging system or treatment were identified. Although the BCM-WG recognizes that at this stage little can be incorporated into a new DRD staging system, numerous potential targets and important concepts deserve continued support and research, as they may eventually serve as biomarkers and/or therapeutic targets with measurable benefits to patients with diabetes. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Abstract This work presents a maturity model for assessing catalogues of semantic artefacts, one of the keystones that permit semantic interoperability of systems. We defined the dimensions and related features to include in the maturity model by analysing the current literature and existing catalogues of semantic artefacts provided by experts. In addition, we assessed 26 different catalogues to demonstrate the effectiveness of the maturity model, which includes 12 different dimensions (Metadata, Openness, Quality, Availability, Statistics, PID, Governance, Community, Sustainability, Technology, Transparency, and Assessment) and 43 related features (or sub-criteria) associated with these dimensions. Such a maturity model is one of the first attempts to provide recommendations for governance and processes for preserving and maintaining semantic artefacts and helps assess/address interoperability challenges.

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.

In this work, refractory components based on alumina were produced by binder jetting using a large-scale 3D printer. The formulation contained several particle fractions up to a grain size of 3 mm, equal to the printer resolution. The binder system contained fine dead burnt magnesia, milled citric acid and reactive alumina, which were added to the aggregate mixture to create the powder bed. Deionized water was deposited from the printer's nozzles and triggered the binding reaction between the magnesia and citric acid. After 24 h, the printed samples were removed from the powder bed, dried and sintered at 1600 °C for 5 h. Reactive alumina contributed to the in situ creation of magnesium aluminate spinel at high temperature. The samples were characterized in terms of Young's modulus of elasticity, bending and compressive strength in 2 directions (parallel and perpendicular to the printing direction). The broken parts were used to investigate physical properties such as the open porosity and bulk density. The microstructure was studied by means of computed tomography. Finally, powder samples were used to determine the phase composition at different stages of production by means of XRD.

A reconstrução histórica dos debates nas doutrinas de direito internacional do século XIX enquanto ciência “nova” que se debruça sobre a própria essência desse ramo do direito na tentativa de fornecer novos paradigmas para o entendimento dos seus sujeitos, das relações entre eles, e das suas fontes, transcendendo aos seculares postulados até então em vigor, é o objetivo desse artigo. Para tanto, a análise ao longo do texto tenta responder três questões, ou seja: porque no século XIX, na Europa e nos Estados Unidos, se manifesta a exigência de legitimar com base científica “as” regras universais nas relações entre os estados e entre os estados e os “povos” como vinculantes e superiores ao direito convencional e positivo? Em que sentido foi entendida a expressão “ciência do direito internacional” e qual foi a função atribuída a tal ciência? Existia um background cultural e científico que condicionou as características e os elementos das várias tentativas de construção científica?

Abstract DNA damage resistance is a major barrier to effective DNA-damaging therapy in multiple myeloma (MM). To discover mechanisms through which MM cells overcome DNA damage, we investigate how MM cells become resistant to antisense oligonucleotide (ASO) therapy targeting Interleukin enhancer binding factor 2 (ILF2), a DNA damage regulator that is overexpressed in 70% of MM patients whose disease has progressed after standard therapies have failed. Here, we show that MM cells undergo adaptive metabolic rewiring to restore energy balance and promote survival in response to DNA damage activation. Using a CRISPR/Cas9 screening strategy, we identify the mitochondrial DNA repair protein DNA2, whose loss of function suppresses MM cells’ ability to overcome ILF2 ASO−induced DNA damage, as being essential to counteracting oxidative DNA damage. Our study reveals a mechanism of vulnerability of MM cells that have an increased demand for mitochondrial metabolism upon DNA damage activation.

The revolutionary technologies behind Industry 4.0 have opened a new era for manufacturing: connected and autonomous machines, collaborative robotics, and monitoring techniques are spreading to increase productivity and sustainability. From the workers’ perspective, they bring new safety threats but also opportunities to solve old ones, while concerns about workers’ privacy arise due to the increase of data sensed and transferred from the shop floor. This paper presents the results of a research project addressing the prediction of dangerous conditions through workplace monitoring with privacy guarantees. This work is driven by a realistic approach starting from the fact that it is entirely centered on a real 14-meter production line equipped with an extensive array of top-tier devices, including robotic arms, autonomous mobile robots, a reconfigurable moving belt, a multi-camera system, and a highly efficient data transport and computation infrastructure. This project shows safety and privacy achievements over six representative use cases such as man-on-the-ground, environmental events (e.g., fire incidents), workers’ errors that can lead to potential accidents, compliance of Personal Protective Equipment (PPE), and gatherings restrictions. The benefits of this study extend to stakeholders such as manufacturers and workers offering safety systems that can be deployed in industrial settings while addressing privacy concerns and providing compliance with regulations. The industrial laboratory at the heart of this study represents with realism a dynamic and interconnected Industry 4.0 and 5.0 environment.

The need for faster and more accessible alternatives to laboratory microscopy is driving many innovations throughout the image and data acquisition chain in the biomedical field. Benchtop microscopes are bulky, lack communications capabilities, and require trained personnel for analysis. New technologies, such as compact 3D-printed devices integrated with the Internet of Things (IoT) for data sharing and cloud computing, as well as automated image processing using deep learning algorithms, can address these limitations and enhance the conventional imaging workflow. This review reports on recent advancements in microscope miniaturization, with a focus on emerging technologies such as photoacoustic microscopy and more established approaches like smartphone-based microscopy. The potential applications of IoT in microscopy are examined in detail. Furthermore, this review discusses the evolution of image processing in microscopy, transitioning from traditional to deep learning methods that facilitate image enhancement and data interpretation. Despite numerous advancements in the field, there is a noticeable lack of studies that holistically address the entire microscopy acquisition chain. This review aims to highlight the potential of IoT and artificial intelligence (AI) in combination with portable microscopy, emphasizing the importance of a comprehensive approach to the microscopy acquisition chain, from portability to image analysis.

Pyelo-hepatic abscess is a rare complication of upper urinary tract infections (UTIs). We describe a case of polymicrobial pyelo-hepatic abscess in an immunocompetent patient. A 71-year-old male patient with a double-J stent for right ureteral lithiasis was admitted in our Infectious Diseases Department for a pyelo-hepatic abscess. Despite a targeted antibiotic therapy against an extended spectrum betalactamase-negative Escherichia coli, the patient did not improve. Further examinations revealed a possible polymicrobial aetiology, including Candida spp. and E. coli resistant to piperacillin/tazobactam but sensitive to third-generation cephalosporins. To date, a paucity of articles regarding pyelo-hepatic abscess exist, consisting mostly of case reports. Urinary stones and a ureteral stent indwelling time exceeding 90 days are known risk factors for upper UTIs and for bacterial dissemination in contiguous organs. Pyelo-hepatic abscesses usually involve Gram-negative bacilli, but they can be polymicrobial, including fungi. As a range of factors could limit the efficacy of antibiotics inside an encapsulated lesion and might contribute to the selection of resistant species during treatment, clinicians should be aware of this complication and try to prevent this event by acting on the main modifiable risk factor.

Osteochondral lesions may be due to trauma or congenital conditions. In both cases, therapy is limited because of the difficulty of tissue repair. Tissue engineering is a promising approach that relies on designed scaffolds with variable mechanical attributes to favor cell attachment and differentiation. Human adipose-derived stem cells (hASCs) are a very promising cell source in regenerative medicine with osteochondrogenic potential. Based on the assumption that stiffness influences cell commitment, we investigated three different scaffolds: a semisynthetic animal-derived GelMA hydrogel, a combined scaffold made of rigid PEGDA coated with a thin GelMA layer and a decellularized plant-based scaffold. We investigated the role of different biomechanical stimulations in the scaffold-induced osteochondral differentiation of hASCs. We demonstrated that all scaffolds support cell viability and spontaneous osteochondral differentiation without any exogenous factors. In particular, we observed mainly osteogenic commitment in higher stiffness microenvironments, as in the plant-based one, whereas in a dense and softer matrix, such as in GelMA hydrogel or GelMA-coated-PEGDA scaffold, chondrogenesis prevailed. We can induce a specific cell commitment by combining hASCs and scaffolds with particular mechanical attributes. However, in vivo studies are needed to fully elucidate the regenerative process and to eventually suggest it as a potential approach for regenerative medicine.