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Acute myeloid leukemia (AML) is a heterogeneous blood-related neoplasm that predominantly afflicts older adults with a poor prognosis due to their physical condition and the presence of medical accompanying comorbidities, adverse biological disease features, and suitability for induction intensive chemotherapy and allogenic stem cells transplantation. Recent research into the molecular and biological factors contributing to disease development and progression has led to significant advancements in treatment approaches for older patients with AML. This review article discusses the latest biological and therapeutic developments that are transforming the management of AML in older adults.

This paper uses digital approaches to investigate Priene’s (Turkey) archaeological area. The city was built ex novo, after a catastrophic earthquake around 350 BC, on a new site facing the Mediterranean Sea. The city suffered a slow decline following centuries of development and was abandoned after the 12th century. The remains of Priene were discovered in the 17th century, and different excavations and studies have been conducted in the last few centuries. The city’s remains have been studied from various archaeological and historical points of view. It is documented that the city suffered different earthquakes during its existence, as demonstrated by the partial restorations and damage patterns visible within the remains. This contribution offers a methodological and interdisciplinary approach for studying and enhancing archaeological heritage. This paper presents the preliminary results of the first comprehensive digital acquisition of the Aegean city of Priene. The digitization approaches here described focused on digital acquisition and 3D modeling restitution in the form of virtual reconstructions of two monumental buildings: the Doric Stoa near the Temple of Athena Polias and the Theater. The procedure was complementary to the analysis and comprehension of previous numerous studies carried out by British and German institutions, where digital acquisition and restitution techniques have led to the validation of previously obtained results. For the first time, digital models have been used as tools for accessing heterogeneous knowledge, and they have been incorporated into the discourse of archeological studies. Indeed, the interdisciplinary team went beyond archaeological data to attempt to digitally reconstruct monumental complexes and conduct preliminary structural evaluations scientifically.

This article analyzes the processes of compressing hydrogen in the gaseous state, an aspect considered important due to its contribution to the greater diffusion of hydrogen in both the civil and industrial sectors. This article begins by providing a concise overview and comparison of diverse hydrogen-storage methodologies, laying the groundwork with an in-depth analysis of hydrogen’s thermophysical properties. It scrutinizes plausible configurations for hydrogen compression, aiming to strike a delicate balance between energy consumption, derived from the fuel itself, and the requisite number of compression stages. Notably, to render hydrogen storage competitive in terms of volume, pressures of at least 350 bar are deemed essential, albeit at an energy cost amounting to approximately 10% of the fuel’s calorific value. Multi-stage compression emerges as a crucial strategy, not solely for energy efficiency, but also to curtail temperature rises, with an upper limit set at 200 °C. This nuanced approach is underlined by the exploration of compression levels commonly cited in the literature, particularly 350 bar and 700 bar. The study advocates for a three-stage compression system as a pragmatic compromise, capable of achieving high-pressure solutions while keeping compression work below 10 MJ/kg, a threshold indicative of sustainable energy utilization.

During the COVID-19 crisis, organizations had to demonstrate organizational resilience (OR) to continue to carry out their missions. We conducted qualitative research to identify the factors that contributed to the OR of police and penitentiary institutions in French-speaking Switzerland, in terms of their operations and management. The modes of action and crisis responses of these emergency services, regularly confronted with crises and particularly impacted during the pandemic, are worthy of attention. To this end, we synthesized the OR factors that are frequently identified in both theoretical and empirical review articles and identified four theoretical conceptualizations: (a) resilience engineering, (b) ecological resilience (these two are the most widely used), (c) a third way situating resilience at an intermediate stage in a metamodel representing the evolution of organizations from a fragile to antifragile state, and (d) a conceptualization focusing on the temporal dimension of OR. Based on the results of 25 semi-structured interviews with executives from cantonal police forces and prisons, we present what we consider to be the key levers in a three-phase resilience process (upstream, during, and after the shock): anticipatory and proactive organizational culture, information management and communication, liminal leadership practices, social and environmental practices, agility-enhancing governance practices, and learning capabilities. Our results largely confirm that these parameters significantly contributed to the OR of the institutions in question. They also enable us to propose winning configurations of factors that can increase the potential for OR.

Immunotherapy has shown significant improvement in the survival of patients with hepatocellular carcinoma (HCC) compared to TKIs as first-line treatment. Unfortunately, approximately 30% of HCC exhibits intrinsic resistance to ICIs, making new therapeutic combinations urgently needed. The dysregulation of the Notch signaling pathway observed in HCC can affect immune cell response, reducing the efficacy of cancer immunotherapy. Here, we provide an overview of how Notch signaling regulates immune responses and present the therapeutic rationale for combining Notch signaling inhibition with ICIs to improve HCC treatment. Moreover, we propose using exosomes as non-invasive tools to assess Notch signaling activation in hepatic cancer cells, enabling accurate stratification of patients who can benefit from combined strategies.

Myelopoiesis provides for the formation and continued renewal of cells belonging primarily to the innate immune system. It is a highly plastic process that secures the response to external and internal stimuli to face acute and changing needs. Infections and chronic diseases including cancer can modulate it by producing several factors, impacting proliferation and differentiation programs. While the lymphocytic compartment has attracted major attention due to the role of adaptive immunity in anticancer immune response, in recent years, research has found convincing evidence that confirms the importance of innate immunity and the key function played by emergency myelopoiesis. Due to cancer’s ability to manipulate myelopoiesis to its own advantage, the purpose of this review is to outline myelopoiesis processes within the tumor microenvironment and suggest possible therapeutic lines of research to restore the physiological functioning of the host’s immune system, with a special outlook on hepatocellular carcinoma (HCC).

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder resulting from mutations in the NF1 gene. Patients harboring these mutations are predisposed to a spectrum of peripheral nerve sheath tumors (PNSTs) originating from Schwann cells, of which malignant peripheral nerve sheath tumors (MPNSTs) are the deadliest, with limited treatment options. Therefore, an unmet need still exists for more effective therapies directed at these aggressive malignancies. Cold atmospheric plasma (CAP) is a reactive oxygen species (ROS) and reactive nitrogen species (RNS) generating ionized gas that has been proposed to be a potential therapeutic modality for cancer. In this study, we sought to determine the effects of CAP on NF1-associated PNSTs. Utilizing established mouse and human cell lines to interrogate the effects of CAP in both in vitro and in vivo settings, we found that NF1-associated PNSTs were highly sensitive to CAP exposure, resulting in cell death. To our knowledge, this is the first application of CAP to NF1-associated PNSTs and provides a unique opportunity to study the complex biology of NF1-associated tumors.

Purpose: The aim was to analyze the accuracy of digital models and 3D-printed casts from full-arch digital impressions using two intraoral scanners (iTeroTM and PrimescanTM). Materials and methods: A crossover reliability study was designed, scanning children and teenagers with iTeroTM and PrimescanTM. Accuracy was evaluated by measuring intercanine, intermolar, and ipsilateral canine–molar distances intraorally and comparing these measurements with those from plaster casts, digital models obtained with intraoral scanners, and 3D-printed casts. A paired comparison and a general linear model with a one-way repeated measures ANOVA procedure were carried out with a confidence level of 95% (p ≤ 0.05). Results: A total of 51 subjects were analyzed (mean age 12.35 ± 2.57). Statistical differences (p < 0.05) were found in the upper and lower arch regarding accuracy in comparison to intraoral measurements, except for the iTeroTM-printed cast and canine–molar upper right and intercanine lower distances (p > 0.05 for all comparisons). Regarding a comparison between reproduction methods, the plaster cast oversized the intercanine upper distance in comparison with both intraoral scanners’ digital models and the PrimescanTM-printed cast (p = 0.001), but there were no differences in the lower arch (p > 0.05 for all comparisons). Conclusion: Intraoral scanners reproduce tooth structures with similar accuracy to conventional methods.

We present a comprehensive computational study of UV/Vis absorption spectra of significant food colorants, specifically anthocyanins and curcumin tautomers, dissolved in polar protic solvents, namely water and ethanol. The absorption spectra are simulated using two fully polarizable quantum mechanical (QM)/molecular mechanics (MM) models based on the fluctuating charge (FQ) and fluctuating charge and dipoles (FQFμ) force fields. To accurately capture the dynamical aspects of the solvation phenomenon, atomistic approaches are combined with configurational sampling obtained through classical molecular dynamics (MD) simulations. The calculated QM/FQ and QM/FQFμ spectra are then compared with experiments. Our findings demonstrate that a precise reproduction of the UV/Vis spectra of the studied pigments can be achieved by adequately accounting for configurational sampling, polarization effects, and hydrogen bonding interactions.

Conservation, characterization and exploitation of agrobiodiversity are key factors to guarantee food security and face future challenges such as climate changes. These issues are the subject of a series of international agreements, such as the Convention of Biological Diversity, with its Nagoya Protocol, and the International Treaty on Plant Genetic Resources for Food and Agriculture (ITPGRFA) adopted in 2001 and entered into force in 2004. Italy ratified the Treaty in 2004 and instituted a long-lasting program, RGV-FAO, to implement it. CREA is one of the three organizations involved in the RGV-FAO Program, together with the National Research Council (CNR) and Reti Semi Rurali. CREA maintains a total of 40,186 accessions including cereals, vegetables, fruits, forages, industrial crops, forest and woody crops, medicinal and aromatic plants, and their wild relatives. Accessions are conserved using different ex situ conservation systems (seeds, in vivo plants, vegetative organs and in vitro plantlets), and characterized using genetic, morpho-phenological and/or biochemical methods. Herein, we will present the CREA long-lasting program RGV-FAO with some examples of the use of plant genetic resources in breeding programs, including molecular approaches. Some critical issues related to access and benefit sharing in PGRFA, such as the Nagoya Protocol and the Digital Sequence Information, will be discussed, highlighting their potential impact on food security and on the advancement of knowledge.

Antarctica, one of the most extreme environments on Earth, hosts diverse microbial communities. These microbes have evolved and adapted to survive in these hostile conditions, but knowledge on the molecular mechanisms underlying this process remains limited. The Italian Collection of Antarctic Bacteria (Collezione Italiana Batteri Antartici (CIBAN)), managed by the University of Messina, represents a valuable repository of cold-adapted bacterial strains isolated from various Antarctic environments. In this study, we sequenced and analyzed the genomes of 58 marine Gammaproteobacteria strains from the CIBAN collection, which were isolated during Italian expeditions from 1990 to 2005. By employing genome-scale metrics, we taxonomically characterized these strains and assigned them to four distinct genera: Pseudomonas, Pseudoalteromonas, Shewanella, and Psychrobacter. Genome annotation revealed a previously untapped functional potential, including secondary metabolite biosynthetic gene clusters and antibiotic resistance genes. Phylogenomic analyses provided evolutionary insights, while assessment of cold-shock protein presence shed light on adaptation mechanisms. Our study emphasizes the significance of CIBAN as a resource for understanding Antarctic microbial life and its biotechnological potential. The genomic data unveil new horizons for insight into bacterial existence in Antarctica.

Ursodeoxycholic acid (UDCA) and acetoacetate are natural compounds present in the human intestine and blood, respectively. A number of studies highlighted that besides their well-known primary biological roles, both compounds possess the ability to influence a variety of cellular processes involved in the etiology of various diseases. These reasons suggested the potential of acetoacetate–UDCA hybrids as possible therapeutic agents and prompted us to develop a synthetic strategy to selectively derivatize the hydroxyl groups of the bile acid with acetoacetyl moieties. 3α-acetoacetoxy UDCA was obtained (60% isolated yield) via the regioselective transesterification of methyl acetoacetate with UDCA promoted by the Candida antarctica lipase B (CAL-B). 3α,7β-bis-acetoacetoxy UDCA was obtained instead by thermal condensation of methyl acetoacetate and UDCA (80% isolated yield). This bis-adduct was finally converted to the 7β-acetoacetoxy UDCA (82% isolated yield) via CAL-B catalyzed regioselective alcoholysis of the ester group on the 3α position. In order to demonstrate the value of the above new hybrids as UDCA-based scaffolds, 3α-acetoacetoxy UDCA was subjected to multicomponent Biginelli reaction with benzaldehyde and urea to obtain the corresponding 4-phenyl-3,4-dihydropyrimidin-2-(1H)-one derivative in 65% isolated yield.

The two primary classes of opioid substances are morphine and its synthetic derivative, heroin. Opioids can cross the placental barrier, reaching fetal circulation. Therefore, at any gestational age, the fetus is highly exposed to pharmacologically active opioid metabolites and their associated adverse effects. This review aimed to investigate all the studies reported in a timeframe of forty years about prenatal and postnatal outcomes of opioid exposition during pregnancy. Clinical and toxicological aspects, as well as pharmacogenetic and epigenetic research focusing on fetal and infant effects of opioid use during pregnancy together with their medico-legal implications are exposed and discussed.

Osteoarthritis is a common chronic condition in the elderly population and, with falls, represents a major public health problem. Patients with hip or knee osteoarthritis often have poor balance, which is considered an important risk factor for falls. In recent years, there has been increasing research supporting the use of robotic rehabilitation to improve function after total knee and hip replacement. The aim of this study is to investigate the effects of robotic balance rehabilitation on elderly patients who have undergone hip and knee replacement, with the aim of reducing the risk of falls and improving balance and walking, as well as motor function, fatigue, and overall quality of life. Twenty-four elderly patients with knee or hip replacement underwent robotic balance treatment with the Hunova® platform or conventional treatment three times a week for four weeks. Patients underwent an assessment of balance, walking, autonomy, quality of life and fatigue. Patients who underwent rehabilitation with Hunova® showed an improvement in dynamic balance (p = 0.0039) and walking (p = 0.001) and a reduction in both motor (p = 0.001) and cognitive (p = 0.05) fatigue. The study found that specific treatment for balance disorders in these patients could improve balance and reduce the risk of falling.

The aim of this study was to evaluate whether there were significant sex x time interactions in lipoprotein(a) (Lp(a)) and low-density lipoprotein cholesterol (LDL-C) response to treatment with the Proprotein Convertase Subtilisin/Kexin type 9 inhibitor (PCSK9i) Evolocumab, in a real-life clinical setting. For this purpose, we pooled data from 176 outpatients (Men: 93; Women: 83) clinically evaluated at baseline and every six months after starting Evolocumab. Individuals who had been on PCSK9i for less than 30 months and nonadherent patients were excluded from the analysis. Over time, absolute values of Lp(a) plasma concentrations significantly decreased in the entire cohort (p-value < 0.001) and by sex (p-value < 0.001 in men and p-value = 0.002 in and women). However, there were no sex-related significant differences. Absolute plasma concentrations of LDL-C significantly decreased over time in the entire cohort and by sex (p-value < 0.001 always), with greater improvements in men compared to women. The sex x time interaction was statistically significant in LDL-C (all p-values < 0.05), while absolute changes in Lp(a) were not influenced by either sex or time (all p-value > 0.05). Our data partially reinforce the presence of differences in response to treatment to PCSK9i between men and women and are essential to gain a better understanding of the relationship between LDL-C and Lp(a) lowering in response to PCSK9i. Further research will clarify whether these sex-related significant differences translate into a meaningful difference in the long-term risk of ASCVD.

High lipoprotein(a) (Lp(a)) plasma levels are significantly associated with an increased risk of developing atherosclerotic cardiovascular diseases (ASCVD). The aim of this analysis was to estimate the prevalence and characteristics of patients potentially eligible for Lp(a)-lowering therapies in a real-world setting (i.e., patients with ASCVD and Lp(a) levels > 70 mg/dL). For this reason, we pooled data from a large cohort of Italian outpatients (N = 5961; men: 2879, women: 3982) with dyslipidemia. A binary logistic regression analysis was used to determine the significant predictors of ASCVD in the cohort, which were age (Odds Ratio (OR): 1.158, 95% Confidence Interval (CI): 1.114 to 1.203, p < 0.001), low-density lipoprotein cholesterol at entry (OR: 1.989, 95% CI: 1.080 to 1.198, p = 0.020) and Lp(a) (OR: 1.090, 95% CI: 1.074 to 1.107, p < 0.001). In our cohort, almost half of patients with ASCVD (44.7%) may be eligible to be treated with Lp(a)-lowering agents. Interestingly, patients who do not meet the treatment criteria despite high Lp(a) (50–70 mg/dL), respectively, account for 4.7% and 7.3% of those in primary and secondary ASCVD prevention. In conclusion, in our large cohort of outpatients with dyslipidemia, the prevalence of individuals with ASCVD and very high Lp(a) plasma levels is quite high, even with a conservative estimation.

Plasmopara viticola is a destructive oomycete that affects grapevines, causing significant economic losses worldwide. This study highlights how the plant Glechoma hederacea might be at the basis for the development of biofungicides to control P. viticola. The aqueous extract obtained from G. hederacea aerial parts showed strong inhibition activity against P. viticola, comparable to that of copper hydroxide. The bioguided purification of the extract by chromatographic techniques led to the isolation of six pure metabolites, identified as the aromatic compounds carvacrol, caffeic acid and methyl caffeate, the flavonoids cirsimaritin and apigenin and the polyphenolic acid rosmarinic acid by spectroscopic methods. This is the first report about the isolation of methyl caffeate and cirsimaritin from G. hederacea. Caffeic acid and methyl caffeate showed the highest disease severity reduction, while carvacrol, cirsimaritin and apigenin also showed moderate activity against P. viticola. The inhibitory activity of the aqueous extract could suggest synergetic or additive action of caffeic acid and methyl caffeate together with other compounds contained in the extract. This study provides insights into the potential of G. hederacea as an allelopathic tool for developing control methods against P. viticola, revealing the combined action of different metabolites involved in the mechanism of action of the active compounds.

Neurosyphilis is a rare but life-threatening complication of syphilis that can develop even decades after the primary infection and can be unrecognized. Seizures and status epilepticus (SE) may represent the first manifestation in a previously undiagnosed syphilitic patient. We present an exemplification case of a new onset refractory status epilepticus caused by neurosyphilis and we reviewed the existing literature. We selected all studies reporting cases of SE in the context both of patients with a known diagnosis of syphilis and as the first manifestation of neurosyphilis. We identified 50 patients, mostly composed of immunocompetent, middle-aged males. Thirty-nine patients (83%) presented a new onset SE. A history of subtle and rapidly progressive mood and/or cognitive impairment suggesting a limbic encephalitis-like presentation was frequently observed. Focal frontal or temporal SE was reported in 26. Brain MRI frequently showed T2/FLAIR hyperintensities widely involving the medial temporal structures and the frontal lobes. This review should increase the clinician’s awareness of neurosyphilis as a possible etiology of a new onset SE of unknown etiology, especially in the context of a “limbic encephalitis”-like clinical presentation. Prompt recognition and treatment for neurosyphilis partially or completely reverse neurologic sequelae, changing the natural history of the disease.

(1) Background: Innovation and continuous demand in the field of visual enhancing technologies and video streaming have led to the discovery of new systems capable of improving visualization and illumination of the surgical field. The exoscope was brought into neurosurgical routine, and nearly ten years later, modern 3D systems have been introduced and tested, giving encouraging results. (2) Methods: In order to evaluate the surgeon’s confidence with the exoscope and their increasing ability in terms of time spent and quality of the final achievement since their first encounter with the technique, an experimental trial on 18 neurosurgeons from a single Institution was performed to evaluate the learning curve for the use of the VITOM-3D exoscope in neurosurgical practice on a model of brain and dura mater. (3) Results: A significant improvement in the quality of the performance, number of errors made, and reduction in the time was found after the third iteration of the task, by when almost all the participants felt more comfortable and confident. No significant differences between senior neurosurgeons and resident neurosurgeons were reported. (4) Conclusions: Our results show that three iterations are enough to gain confidence with the exoscope from its first use, regardless of previous experience and training with an operating microscope.

A hydride of Yb2Pd2Sn could be synthesized with approximately 2 H atoms per f.u. The hydrogenation leads to a volume expansion while preserving the tetragonal symmetry (P4/mbm). The lattice reaction is strongly anisotropic, and the 5% expansion in c is partly compensated by the 0.5% compression in a. The hydride is paramagnetic at least down to 0.5 K. Yb remains at or very close to the 3+ (4f13) state, as in Yb2Pd2Sn. Specific heat C/T vs. T shows an upturn existing already in Yb2Pd2Sn, but it is much more pronounced in the hydride (1.8 J/mol f.u. K2 for T → 0, i.e., more than twice higher than in its precursor). This is interpreted as lowering the Kondo temperature due to H bonding.

Chronic urticaria (CU) is one of the most common skin disorders worldwide. Among the inducible subgroup of CU, cold urticaria (ColdU) can affect both children and adults and is the only type associated with the risk of anaphylaxis without cofactors. In the scientific literature, data about cold anaphylaxis (ColdA) are poor, especially at pediatric age, and little is known about risk factors associated with the onset of systemic reactions and about the criteria for prescribing adrenaline auto-injectors (AAIs) in these patients. We describe the clinical characteristics and management of a case series of 21 patients with a history of ColdA, and we compare them with the pediatric case reports and case series published so far. On the basis of the scientific literature and of our case series of patients, we suggest that AAI should be prescribed to all high-risk patients: those with urticaria caused by cold-water immersion, oropharyngeal reactions, and with a previous history of systemic symptoms or anaphylaxis.

Frailty is characterized by increased vulnerability, which impairs the ability to cope with stressors and represents a risk factor for the development of disability. Moreover, the population of older adults is continuously increasing. For this reason, frailty and aging represent very important social and health topics. The management of elderly patients, especially when they are hospitalized, is complex and requires the collaboration of multiple professionals and different approaches to intervene in the multi-morbidity that characterizes this population. A significant percentage of hospitalized older patients present several comorbidities that cause prolonged hospital stays. This condition could lead to clinical complications, increased costs of care, and a higher likelihood of in-hospital death. Aging is a concept that encompasses several symptoms and requires a multidisciplinary and specific approach, especially during hospitalization and in acute care settings. The present study aims to evaluate how intensive rehabilitation treatment is accompanied by improvement in some hematological and clinical parameters and could contribute to an evolution in disability among elderly patients. The results of the present research show the crucial role of rehabilitation treatment in the development of disability, independence, and self-sufficiency in a population of older inpatients in a post-acute care setting. Further research should be conducted to identify other biomarkers useful in the management of frail patients.

The term neuroinflammation defines the reactions of astrocytes and microglia to alterations in homeostasis in the diseased central nervous system (CNS), the exacerbation of which contributes to the neurodegenerative effects of Alzheimer’s disease (AD). Local environmental conditions, such as the presence of proinflammatory molecules, mechanical properties of the extracellular matrix (ECM), and local cell–cell interactions, are determinants of glial cell phenotypes. In AD, the load of the cytotoxic/proinflammatory amyloid β (Aβ) peptide is a microenvironmental component increasingly growing in the CNS, imposing time-evolving challenges on resident cells. This study aimed to investigate the temporal and spatial variations of the effects produced by this process on astrocytes and microglia, either directly or by interfering in their interactions. Ex vivo confocal analyses of hippocampal sections from the mouse model TgCRND8 at different ages have shown that overproduction of Aβ peptide induced early and time-persistent disassembly of functional astroglial syncytium and promoted a senile phenotype of reactive microglia, hindering Aβ clearance. In the late stages of the disease, these patterns were altered in the presence of Aβ-plaques, surrounded by typically reactive astrocytes and microglia. Morphofunctional characterization of peri-plaque gliosis revealed a direct contribution of astrocytes in plaque buildup that might result in shielding Aβ-peptide cytotoxicity and, as a side effect, in exacerbating neuroinflammation.

Belted pig breeds have unique, distinguishing phenotypic characteristics. This review summarises the current knowledge on pig breeds displaying a belted coat pattern. Belts of different widths and positions around the animal’s trunk characterise specific pig breeds from all around the world. All the breeds included in the present paper have been searched through the FAO domestic animal diversity information system (DAD-IS), Every country was checked to identify all breeds described as having black or red piebald coat pattern variations. Advances in genomic technologies have made it possible to identify the specific genes and genetic markers associated with the belted phenotype and explore the genetic relationships between different local breeds. Thus, the origin, history, and production traits of these breeds, together with all the genomic information related to the mechanism of skin pigmentation, are discussed. By increasing our understanding of these breeds, we can appreciate the richness of our biological and cultural heritage and work to preserve the biodiversity of the world’s animals.

This paper offers a set of comprehensive guidelines aimed at facilitating the widespread adoption of hydrogen in the industrial hard-to-abate sectors. The authors begin by conducting a detailed analysis of these sectors, providing an overview of their unique characteristics and challenges. This paper delves into specific elements related to hydrogen technologies, shedding light on their potential applications, and discussing feasible implementation strategies. By exploring the strengths and limitations of each technology, this paper offers valuable insights into its suitability for specific applications. Finally, through a specific analysis focused on the steel sector, the authors provide in-depth information on the potential benefits and challenges associated with hydrogen adoption in this context. By emphasizing the steel sector as a focal point, the authors contribute to a more nuanced understanding of hydrogen’s role in decarbonizing industrial processes and inspire further exploration of its applications in other challenging sectors.

Due to its effectiveness, ibuprofen is one of the most popular anti-inflammatory drugs worldwide. However, the poor water solubility of this active ingredient severely limits its spectrum of pharmaceutical formulations (and often results in severe adverse effects due to high administered doses). To overcome these limitations, in this work, we enzymatically synthesized more hydrophilic derivatives of ibuprofen through its covalent attachment to two biobased polyalcohols: erythritol and glycerol. Herein, we report the optimized reaction conditions to produce an IBU–erythritol ester (82% ± 4% of conversion) by using Candida antarctica lipase B (CalB). Furthermore, we also report the enantioselective solventless esterification of (S)-ibuprofen with glycerol (83% ± 5% of conversion), exploiting immobilized Rhizomucor miehei lipase as a biocatalyst. The full NMR characterizations of the prodrug esters were performed via 1H, 13C-NMR, DEPT, COSY, HSQC, and HMBC-NMR. The approach reported in this work can be extended to a large variety of poorly water-soluble active pharmaceutical ingredients (APIs).

The paper presents results from a study on integrative lighting in real middle school classrooms located in a school building in Turin, Italy. The contribution of both daylighting and electric lighting was considered. Besides the existing configuration of electric lighting systems (fluorescent luminaires), a set of six possible retrofitting solutions was considered, all using LED luminaires. The research addressed two main objectives: (i) To verify if the circadian values (melanopic equivalent daylight illuminance m-EDI) in the classrooms could meet the recommended values reported in recent literature, for instance, in the WELL protocol, (ii) to assess the influence on integrative lighting (photopic and melanopic illuminances) played by the electric lighting, as a function of the different lighting systems, and by daylighting, as a function of different room orientations and sky conditions. Results showed that the existing spaces benefit from high daylighting amount, whilst the existing lighting systems provide an insufficient m-EDI. Even when last-generation LED lighting systems were ideally used for retrofitting, no solution was able to meet the three-point WELL recommendation, while two solutions only allowed the one-point recommendation to be met. Some design implications concerned with the results were critically discussed.

Allergic proctocolitis (AP) is a benign condition, frequent in childhood, that is classified as a non-IgE-mediated food allergy. The prevalence is unknown; however, its frequency appears to be increasing, especially in exclusively breastfed infants. Clinical manifestations typically begin in the first few months of life with the appearance of bright red blood (hematochezia), with or without mucus, in the stool of apparently healthy, thriving infants. Most cases of AP are caused by cow’s milk proteins; however, other allergens, such as soy, egg, corn, and wheat, may be potential triggers. Diagnosis is based on the patient’s clinical history and on the resolution of signs and symptoms with the elimination of the suspected food antigen from the diet and their reappearance when the food is reintroduced into the diet. The treatment of AP is based on an elimination diet of the trigger food, with resolution of the symptoms within 72–96 h from the beginning of the diet. The prognosis of AP is good; it is a self-limiting condition, because most children can tolerate the trigger food within one year of life, with an excellent long-term prognosis. The purpose of this review is to provide an update on the current knowledge and recommendations in epidemiological, diagnostic, and therapeutic terms to the pediatricians, allergists, and gastroenterologists who may find themselves managing a patient with AP.

Porcine Reproductive and Respiratory Syndrome (PRRS) caused by the PRRS virus affects farmed pigs worldwide, causing direct and indirect losses. The most severe manifestations of PRRS infection are observed in piglets and pregnant sows. The clinical outcome of the infection depends on the PRRSV strain’s virulence, the pregnancy state of the female, environmental factors, the presence of protective antibodies due to previous infections, and the host’s genetic susceptibility. The latter aspect was investigated in this study, in particular, evaluating the most significant polymorphisms (SNPs) of the CD163 gene in slaughtered pigs reared in Central Italy. Total RNAs were extracted from 377 swine samples and subjected to RT-PCR targeted to the CD163 gene, followed by sequencing analysis. Contextually, the viral RNA was detected by RT-qPCR in order to phenotypically categorize animals into infected and not infected. In particular, 36 haplotypes were found, and their frequencies ranged from 0.13% to 35.15%. There were 62 resulting genotypes, three of which were associated with a putative resistance to the disease. Both the haplotypes and genotypes were inferred by PHASE v.2.1 software. To the best of our knowledge, this type of investigation was conducted for the first time on pig livestock distributed in different regions of Central Italy. Thus, the obtained findings may be considered very important since they add useful information about swine genetic background in relation to PRRS infection, from the perspective of adopting Marker-Assisted Selection (MAS) as a possible and alternative strategy to control this still widespread disease.

Productivity and production quality have become primary goals for the success of companies in all industrial and manufacturing sectors. Performance in terms of productivity is influenced by several factors including machinery efficiency, work environment and safety conditions, production processes organization, and aspects related to workers’ behavior (human factors). In particular, work-related stress is among the human factors that are most impactful and difficult to capture. Thus, optimizing productivity and quality in an effective way requires considering all these factors simultaneously. The proposed system aims to detect workers’ stress and fatigue in real time using wearable sensors and machine learning techniques and also integrate all data regarding the monitoring of production processes and the work environment into a single platform. This allows comprehensive multidimensional data analysis and correlation research, enabling organizations to improve productivity through appropriate work environments and sustainable processes for workers. The on-field trial demonstrated the technical and operational feasibility of the system, its high degree of usability, and the ability to detect stress from ECG signals exploiting a 1D Convolutional Neural Network (accuracy 88.4%, F1-score 0.90).

Ocimum basilicum (sweet basil) is an economically important aromatic herb; in Italy, approximately 1000 ha of “Genovese-type” basil are grown annually in greenhouses and open fields and are subjected to Downy Mildew (DM) disease, caused by Peronospora belbahrii, leading to huge crop losses. Mutation of the Susceptibility (S) gene DMR6 (Downy Mildew Resistant 6) has been proven to confer a broad-spectrum resistance to DM. In this work, an effective Genome Editing (GE) approach mediated by CRISPR/Cas9 in O. basilicum ‘Italiko’, the élite cultivar used to produce “Pesto Genovese D.O.P”, was developed. A highly efficient genetic transformation method mediated by A. tumefaciens has been optimized from cotyledonary nodes, obtaining 82.2% of regenerated shoots, 84.6% of which resulted in Cas9+ plants. Eleven T0 lines presented different type of mutations in ObDMR6; 60% were indel frameshift mutations with knock-out of ObDMR6 of ‘FT Italiko’. Analysis of six T1 transgene-free seedlings revealed that the mutations of T0 plants were inherited and segregated. Based on infection trials conducted on T0 plants, clone 22B showed a very low percentage of disease incidence after 14 days post infection. The aromatic profile of all in vitro edited plants was also reported; all of them showed oxygenated monoterpenes as the major fraction.

Breast implants are widely used for reconstructive and/or cosmetic purposes. Inflammations and infections of breast implants represent important complications in clinical practice. The proper management of complications is necessary: diagnostic imaging plays a key role in detecting sites of inflammation and/or infection. The present review aims to illustrate the radiological findings of these conditions with different imaging techniques, such as mammography (MX), ultrasound (US), magnetic resonance imaging (MRI), and nuclear medicine imaging. A knowledge of these findings is essential for radiologists and nuclear medicine physicians to provide helpful information for the clinical management of these complications.

Electrochemotherapy (ECT) is a standard of care in veterinary and human oncology. The treatment induces a well-characterized local immune response which is not able to induce a systemic response. In this retrospective cohort study, we evaluated the addition of gene electrotransfer (GET) of canine IL-2 peritumorally and IL-12 intramuscularly to enhance the immune response. Thirty canine patients with inoperable oral malignant melanoma were included. Ten patients received ECT+GET as the treatment group, while twenty patients received ECT as the control group. Intravenous bleomycin for the ECT was used in both groups. All patients had compromised lymph nodes which were surgically removed. Plasma levels of interleukins, local response rate, overall survival, and progression-free survival were evaluated. The results show that IL-2 and IL-12 expression peaked around days 7–14 after transfection. Both groups showed similar local response rates and overall survival times. However, progression-free survival resulted significantly better in the ECT+GET group, which is a better indicator than overall survival, as it is not influenced by the criterion used for performing euthanasia. We can conclude that the combination of ECT+GET using IL-2 and IL-12 improves treatment outcomes by slowing down tumoral progression in stage III–IV inoperable canine oral malignant melanoma.

Angioedema (AE) is a vascular reaction of subcutaneous and submucosal tissues that identifies various clinical pictures and often is associated with wheals. AE without wheals (AEwW) is infrequent. The ability to distinguish between AEwW mediated by mast cells and bradykinin-mediated or leukotriene-mediated pathways is often crucial for a correct diagnostic–therapeutic and follow-up approach. AEwW can be hereditary or acquired. Factors typically correlated with hereditary angioedema (HAE) are a recurrence of episodes, familiarity, association with abdominal pain, onset after trauma or invasive procedures, refractoriness to antiallergic therapy, and lack of pruritus. The acquired forms of AE can present a definite cause based on the anamnesis and diagnostic tests. Still, they can also have an undetermined cause (idiopathic AE), distinguished according to the response to antihistamine in histamine-mediated and non-histamine-mediated forms. Usually, in childhood, AE responds to antihistamines. If AEwW is not responsive to commonly used treatments, it is necessary to consider alternative diagnoses, even for pediatric patients. In general, a correct diagnostic classification allows, in most cases, optimal management of the patient with the prescription of appropriate therapy and the planning of an adequate follow-up.

Fetal inflammatory response syndrome (FIRS) represents the fetal inflammatory reaction to intrauterine infection or injury, potentially leading to multiorgan impairment, neonatal mortality, and morbidity. Infections induce FIRS after chorioamnionitis (CA), defined as acute maternal inflammatory response to amniotic fluid infection, acute funisitis and chorionic vasculitis. FIRS involves many molecules, i.e., cytokines and/or chemokines, able to directly or indirectly damage fetal organs. Therefore, due to FIRS being a condition with a complex etiopathogenesis and multiple organ dysfunction, especially brain injury, medical liability is frequently claimed. In medical malpractice, reconstruction of the pathological pathways is paramount. However, in cases of FIRS, ideal medical conduct is hard to delineate, due to uncertainty in diagnosis, treatment, and prognosis of this highly complex condition. This narrative review revises the current knowledge of FIRS caused by infections, maternal and neonatal diagnosis and treatments, the main consequences of the disease and their prognoses, and discusses the medico-legal implications.

Air quality in Europe continues to remain poor in many areas, with regulation limits often exceeded by many countries. The EU Life-IP PREPAIR Project, involving administrations and environmental protection agencies of eight regions and three municipalities in Northern Italy and Slovenia, was designed to support the implementation of the regional air quality plans in the Po Valley, one of the most critical areas in Europe in terms of pollution levels. In this study, four air quality modelling systems, based on three chemical transport models (CHIMERE, FARM and CAMx) were applied over the Po Valley to assess the sensitivity of PM2.5 concentrations to NOx and NH3 emission reductions. These two precursors were reduced (individually and simultaneously) from 25% up to 75% for a total of 10 scenarios, aimed at identifying the most efficient emission reduction strategies and to assess the non-linear response of PM2.5 concentrations to precursor changes. The multi-model analysis shows that reductions across multiple emission sectors are necessary to achieve optimal results. In addition, the analysis of non-linearities revealed that during the cold season, the efficiency of PM2.5 abatement tends to increase by increasing the emission reductions, while during summertime, the same efficiency remains almost constant, or slightly decreases towards higher reduction strengths. Since the concentrations of PM2.5 are greater in winter than in summer, it is reasonable to infer that significant emission reductions should be planned to maximise reduction effectiveness.

Sweet basil (Ocimum basilicum L.; Fam. Lamiaceae) is an annual herbaceous plant with a high economic value used in folk medicine, pharmacology, and food production. In Italy, most of the varieties are used to produce the famous “pesto” sauce; however, almost all of them are susceptible to basil downy mildew (BDM) disease, strongly decreasing the growth of the fresh leaves and the survival of the whole plant. Nowadays, CRISPR/Cas9 technology is recognized to be a prominent way to enhance basil genetic breeding. In this work, we present an optimized protocol for in vitro direct regeneration of an elite cultivar, which is the major limiting factor for the transformation of O. basilicum. Regeneration has been obtained from different explants (leaves, cotyledons, cotyledonary nodes); the highest frequency has been obtained from cotyledonary nodes of seedlings germinated on MS medium containing TDZ. This protocol may be used for biotechnological applications as genome editing techniques to obtain basil-downy-mildew-disease-resistant clones.

Patients with heart transplantation (HT) have an increased risk of COVID-19 disease and the efficacy of vaccines on antibody induction is lower, even after three or four doses. The aim of our study was to assess the efficacy of four doses on infections and their interplay with immunosuppression. We included in this retrospective study all adult HT patients (12/21–11/22) without prior infection receiving a third or fourth dose of mRNA vaccine. The endpoints were infections and the combined incidence of ICU hospitalizations/death after the last dose (6-month survival rate). Among 268 patients, 62 had an infection, and 27.3% received four doses. Following multivariate analysis, three vs. four doses, mycophenolate (MMF) therapy, and HT < 5 years were associated with an increased risk of infection. MMF ≥ 2000 mg/day independently predicted infection, together with the other variables, and was associated with ICU hospitalization/death. Patients on MMF had lower levels of anti-RBD antibodies, and a positive antibody response after the third dose was associated with a lower probability of infection. In HT patients, a fourth dose of vaccine against SARS-CoV-2 reduces the risk of infection at six months. Mycophenolate, particularly at high doses, reduces the clinical effectiveness of the fourth dose and the antibody response to the vaccine.