The implementation of sentinel lymph node (SLN) biopsy is changing the scenario in the surgical treatment of early-stage cervical cancer and the oncologic safety of replacing bilateral pelvic lymphadenectomy with SLN biopsy is currently under investigation. One of the undisputed values of SLN biopsy is its diagnostic accuracy in detecting low-volume metastases (LVM) via pathologic ultrastaging. In early-stage cervical cancer, the reported incidence of LVM ranges from 4 to 20%. The prognostic impact and the role of adjuvant treatment in patients with LVM is still unclear. Some non-prespecified analyses in prospective studies showed no impact on the oncologic outcomes compared to node-negative disease. However, the heterogeneity of the studies, the differences in the disease stage and the use of adjuvant treatment, and the concomitant pelvic lymphadenectomy (PLND) make any conclusion on this topic hard. Current guidelines suggest considering micrometastasis (MIC) as a node-positive disease, while isolated tumor cells (ITC) as a node-negative disease, with a low level of evidence. This review aims to highlight the unanswered questions about the definition, identification, prognostic and therapeutic role of LVM and underline the present and future challenges we are facing. We hope this review will guide further research, giving robust evidence on LVM and their impact on clinical practice.

Zn2GeO4 is considered a very promising alternative to current luminescent semiconductors. Previous results suggest that its emitted wavelength may depend on different variables, such as particle size and morphology, among others. In this work, we have prepared pure and highly homogeneous Zn2GeO4 nanorods under hydrothermal synthesis conditions with a willemite-like structure. Their luminescent properties have been explored and their band gap estimated, which are distinct to previously reported Zn2GeO4 bulk particles. Therefore, our results identify particle morphology as a crucial factor for maximizing and fine-tuning the luminesce of Zn2GeO4 nano-phosphors.

THz radiation has assumed a great importance thanks to the efforts in the development of technological tools used in this versatile band of the electromagnetic spectrum. Here we propose a reflecting bi-mirror axicon-like device with wavelength-independent long focusing performances in the THz band, by exploiting the high thermo-mechanical deformation of the elastomer polydimethylsiloxane (PDMS). This deformation permits to achieve significant optical path modulations in the THz band and effective focusing. The surface of a PDMS layer is covered with a gold thin film, acting as heater thanks to its absorption for wavelengths below ~500 nm . An invariance property of the Fresnel integral has been exploited to verify experimentally the THz performances of the device with an ordinary visible laser source, finding excellent agreement with the theoretical predictions at 1 and 3 THz. The same property allowed also to verify experimentally that the axicon focus has a longitudinal extension much greater than that one exhibited by a benchmark cylindrical mirror with the same optical power. The axicon is thermo-mechanically stable up to a heating power of 270 mW, although it might be potentially exploited at higher powers with a minor degradation of the optical performances.

It is now well accepted that most chronic diseases have a common feature which is “low-grade” inflammation. Whether inflammation is causal or rather consequent to these diseases is still a matter of debate. A key factor of inflammation is considered to be “oxidative stress”, which is the result of an alteration of redox homeostasis which is critical for the regulation of physiological cell and organ metabolism and proliferation. The term “oxidative stress” is how-ever often used in an inappropriate manner as the primary target of the initial oxidative radical, superoxide ion, is nitric oxide which, being in large excess, acts as a “buffer”, yielding reactive nitrogen species. It is only once the superoxide fluxes exceed the nitric oxide fluxes that true “oxidative stress” occurs. Nitro-oxidative stress is a more appropriate term which takes into account the evolving generation of reactive nitrogen and oxygen species and their effects on cell and organ pathophysiology. The molecular bases of redox homeostasis and nitro-oxidative stress will be presented and discussed using obesity-linked inflammation as a path-ophysiological example.

This paper systematically discusses the application of reinforcement learning in automatic driving system. Reinforcement learning frameworks show significant advantages in optimizing decision making, predictive perception, path planning, and controller design, exceeding the limitations of traditional supervised learning methods. The paper highlights the critical role of components such as scene understanding, positioning, and map making in autonomous driving systems, which provide reliable environmental awareness through deep learning and sensor fusion technologies to support intelligent decision-making in complex urban environments. In addition, the paper discusses innovative approaches to safety reinforcement learning to reduce risk in autonomous driving and ensure that systems adhere strictly to safety constraints while maximizing expected rewards. These findings provide an important theoretical and practical basis for further improving algorithm robustness, managing multi-agent interactions, and integrating ethical considerations in the future.

A healthy 47-year-old woman consulted the Oral Surgery and Implantology Unit of the University Hospitals of Geneva with a request to treat her painful tooth 11 and replace the missing tooth 21. The dental history revealed that the patient had lost teeth 21 and 22 due to advanced caries. On clinical examination, tooth 11 showed an ill-fitting prosthetic crown with overhanging margins, an increased localized probing depth of 8 mm in the disto-vestibular area and sensitivity to percussion. The edentulous site 21 showed horizontal bone atrophy. Radiological examination revealed a well-defined unilocular radiotransparent lesion surrounded by a thin radiolucent border, located at the apex of tooth 11 and measuring 10 x 8 mm. The treatment consisted of extraction of 11, enucleation of the apical lesion, insertion of implants at sites 11 and 21 with simultaneous bone augmentation in a single surgical procedure with aesthetic and functional results at 3-year follow-up without any complications. Our case highlights that immediate implant placement in case of cystic periapical lesion represents a good valid alternative to standard treatment.

We propose the Hamiltonian formalism of Bianchi type 1 cosmological model for perfect fluid. We have considered both the equation of state parameter ω and the cosmological constant Λ as the function of volume V(t) which is defined by the product of three scale factors of the Bianchi type 1 line element. We propose a Lagrangian for the anisotropic Bianchi type-1 model in view of a variable mass moving in a variable potential . We can decompose the anisotropic expansion in terms of expansion and shearing motion by Lagrangian mechanism. We have considered a canonical transformation from expanding scale factor to scalar field ø which helps us to give the proper classical definition of that scalar field in terms of scale factors of the mentioned model. This definition helps us to explain the cosmological inflation. We have used large anisotropy(as in the cases of Bianchi models) and proved that cosmic inflation is not possible in such large anisotropy. Therefore we can conclude that the extent of anisotropy is less in case of our universe. Otherwise the inflation theory which explained the limitations of Big Bang cannot be resolved.Part II is contained with some analysis of the lagrangian ; derived in Part I ; on the quintessence model.

In this paper we will consider the cosmic fluid to be dissipating i.e it has both bulk and shearing viscosity. We propose the Hamiltonian formalism of Bianchi type 1 cosmological model for cosmic fluid which is dissipating i.e it has both shearing and bulk viscosity. We have considered both the equation of state parameter ω and the cosmological constant Λ as the function of volume V(t) which is defined by the product of three scale factors of the Bianchi type 1 line element. We propose a Lagrangian for the anisotropic Bianchi type-1 model in view of a variable mass moving in a variable potential . We can decompose the anisotropic expansion of Bianchi type 1 in terms of expansion and shearing motion by Lagrangian mechanism. We have considered a canonical transformation from expanding scale factor to scalar field ø which helps us to give the proper classical definition of that scalar field in terms of scale factors of the mentioned model. By this transformation we can express the mass to be moving in a scalar potential field. This definition helps us to explain the nature of expansion of universe during cosmological inflation. We have used large anisotropy(as in the cases of Bianchi models) and proved that cosmic inflation is not possible in such large anisotropy. Therefore we can conclude that the extent of anisotropy is less in case of our universe. Otherwise the inflation theory which explained the limitations of Big Bang cannot be resolved. In the case of bulk and shearing viscous fluid we get the solution of damped harmonic oscillator after the cosmological inflation.Part I contains the calculations of bulk viscous fluids and Part II contains the calculations of bulk and shearing viscous fluid.At the end we have also provided the relation of shearing and expansion.Part III will give the approximation of low viscosity to solve the viscous fluid problem.

The overlap of visual items in data visualization techniques is a known problem aggravated by data volume and available visual space issues. Several methods have been applied to mitigate occlusion in data visualizations, such as Random Jitter, Transparency, Layout Reconfiguration, Focus+Context Techniques, etc. This paper aims to present a comparative study to read visual variables values with partial overlap. The study focuses on categorical data representations varying the percentage limits of partial overlap and the number of distinct values for each visual variable: Hue, Lightness, Saturation, Shape, Text, Orientation, and Texture. A computational application generates random scenarios for a unique visual pattern target to perform location tasks. Each scenario presented the visual items in a grid layout with 160 elements (10 x16), each visual variable had from 3 to 5 distinct values encoded, and the partial overlap percentage applied, represented by a gray square in the center o each grid element, were 0% (control), 50%, 60%, and 70%. Similar to the preliminary tests, the tests conducted in this study involved 48 participants organized into four groups, with 126 tasks per participant, and the application captured the response and time for each task performed. The result analysis indicates that the Hue, Lightness, and Shape visual variables are robust to high percentages of occlusion and gradual increase in encoded visual values. The Text visual variable show promising results for accuracy, and resolution time was a bit higher than the last visual variables mentioned. In contrast, the Texture visual variable presented lower accuracy to high levels of occlusion and more different visual encoding values. At last, the Orientation and Saturation visual variables got the highest error and worst perfomance rates during the tests.

Here we studied Bianchi type-III string cosmological models generated by means of a cloud of strings with particles connected to them in the framework of Lyra geometry considering five-dimensional space-time. To obtain the exact solutions of field equations we consider that the shear scalar and the scalar expansion are proportional, σ∞θ which leads to D=cn and secondly we adopt the assumption considering the Reddy String Condition, ρ+λ=0. From the two different cases obtained here, first case leads to the Bianchi type-III string cosmological model in Lyra geometry in five-dimensional space-time and the second case leads to the five-dimensional vacuum universe in general relativity. The Geometrical and physical properties of the model universe are studied comparing with the present day’s observational findings. The model universe obtained here starts with the big bang and as time progresses both particle density ρp and energy density ρ decreases with expansion of our Universe.

A study of Bianchi Type I cosmological model is undertaken in the framework of creation of particles. To accommodate the creation of new particles, the universe is regarded as an Open thermodynamical system. The energy conservation equation is modified with the incorporation of a creation pressure in the energy momentum tensor. Exact solutions of the field equations are obtained (i) for a particular choice of the particle creation function and (ii) by considering the deceleration parameter to be constant. In the first model the behavior of the solution at late times is investigated. The physical aspects of the model have also been discussed. In the case of the second model we have restricted our analysis to the power law behaviour for the average scale factor. This leads to a particular form for the particle creation function. The behavior of the solution is investigated and the physical aspects of the model have also been discussed for the matter dominated era.

Purpose is to o review the pathogenic mechanism for ocular hypertension and glaucoma development after pars plana vitrectomy. Both acute and chronic causes are considered and special attention is paid to the theories and clinical evidence on the risk of developing Open Angle Glaucoma (OAG) after Pars Plana Vitrectomy (PPV). Most existing scientific literature on the issue agree on the role of ascorbate as an oxygen scavenger within the vitreous chamber. Oxygen tension in the vitreous and anterior chamber is maximum inn proximity of the retinal surface and endothelium, respectively and steeply decreases toward the lens; on both sides, and trabeculate. Vitreous removal and, to a lesser extent, liquefaction, greatly reduces oxygen tension gradient in vitreous chamber while cataract extraction has similar effects on anterior chamber oxygen gradients. Oxygen derivatives originated from the cornea and retina are actively reduced by the vitreous gel and/or the crystalline lens. Vitreous removal and cataract extraction reduce drastically this function. Most reported clinical series confirm this hypothesis although protocol difference and follow-up length greatly impact the reliability of results.

Meta-aminobenzoic acid, an important model system in the study of polymorphism and crystallization of active pharmaceutical ingredients, exist in water in both the nonionic (mABA) and zwitterionic (mABA^±) forms. However, the constituent molecules of the polymorph that crystallizes from aqueous solutions are zwitterionic. This study reports atomistic simulations of the events surrounding the early stage of crystal nucleation of meta-aminobenzoic acid from aqueous solutions. Ab initio molecular dynamics was used to simulate the hydration of mABA± and mABA, and to quantify the interaction of these molecules with the surrounding water molecules. Density functional theory calculations were conducted to determine the low-lying energy conformers of meta-aminobenzoic acid dimers and compute the Gibbs free energies in water of nonionic, (mABA)₂, zwitterionic, (mABA^±)₂ and nonionic-zwitterionic, (mABA)(mABA^±), species. Classical molecular dynamics simulations of mixed mABA–mABA^± aqueous solutions were carried out to examine the aggregation of meta-aminobenzoic acid. According to these simulations the selective crystallization of the polymorph which constituent molecules are zwitterionic is driven by the formation of zwitterionic dimers in solution, which are thermodynamically more stable than (mABA)₂ and (mABA)(mABA^±) pairs. This work represents a paradigm of the role of molecular processes during the early stages of crystal nucleation in affecting polymorph selection during crystallization from solution.

Ascorbate; Pars Plana Vitrectomy; Open Angle Glaucoma; Oxidative Stress; Vitreous Me-tabolism 0. How to Use This Template

The ongoing COVID-19 pandemic is shaking the foundations of public health governance all over the world. Researchers are challenged by informing and supporting authorities on acquired knowledge and practical implications. This commentary applies established theories of risk perception research to COVID-19 and reflects on the role of risk perceptions in these unprecedented times. Moreover, it calls for utilizing the knowledge on risk perception to improve health risk communication, build trust and contribute to a collaborating governance.

In this study, the analysis of the changes of SARS-CoV-2 Orf3a protein during pandemic is reported. Orf3a, a conserved protein in the Coronaviruses, is involved in virus replication and release. A software workflow able to carry out a quick, systematic and repeatable screening of the SARS-CoV-2 genome isolates to detect protein mutations, was utilized to scan 70,752 high-quality SARS-CoV-2 genomes available in GISAID databank at the end of August 2020. All ORF3a mutations in the virus genomes were grouped according to the collection date interval and over the entire data set. The considered intervals were start of collection-February, March, April, May, June, July and August 2020. The top five most frequent variants were examined within each collection interval. Overall, seventeen variants have been isolated. Ten of the seventeen mutant sites occur within the transmembrane (TM) domain of ORF3a and are in contact with the central pore or side tunnels. The other variant sites are in different places of the Orf3a structure. Within the entire sample, the five most frequent mutations are V13L, Q57H, Q57H+A99V, G196V and G252V. The same analysis identified 28 sites identically conserved in all the genome isolates. These sites are possibly involved in stabilization of monomer, dimer, tetramerization and interaction with other cellular components. The results here reported can be helpful to understand virus biology and to design new therapeutic strategies.

This publication highlights the effect of mechanochemical treatment in a high-speed thermoki-netic mixer as an alternative for recycling ground tire rubber (GTR). The GTR initially has an 80% gelled fraction and presented up to 50% gel fraction in the most intensive condition (5145 rpm, s2). Processing at the lowest speed (2564 rpm, s1) resulted in greater selectivity concerning the mechanochemical treatment (K~1). In the most intense processing condition (10 min. at s2), more significant degradation was observed via random scission with a reduction of the glass transition temperature, Tg (11ºC), an increase of the soluble polymer fraction, and a more signif-icant reduction in crosslink density. The artificial neural network could describe and correlate the thermal degradation profile and processing conditions with the physicochemical characteris-tics of the GTR. The approach presented here represents an alternative for mechanochemical treatment since it can reduce the crosslink density with selectivity and in short times (1-3 min.).

A Smart Home is characterized by the presence of a huge number of small, low power devices, along with more classical devices. According to the Internet of Things (IoT) paradigm, all of them are expected to be always connected to the Internet in order to provide enhanced services. In this scenario, an attacker can undermine both the network security and the user’s security/privacy. Traditional security measures are not sufficient, because they are too difficult to setup and are either too weak to effectively protect the user or too limiting for the new services effectiveness. The paper suggests to dynamically adapt the security level of the smart home network according to the user perceived risk level what we have called network sentiment analysis. The security level is not fixed, established by a central system (usually by the Internet Service Provider) but can be changed with the users cooperation. The security of the smart home network is improved by a distributed firewalling and Intrusion Detection Systems both to the smart home side as to the Internet Service Provider side. These two parts must cooperate and integrate their actions for reacting dynamically to new and ongoing threats. Moreover, the level of network sentiment detected can be propagate to nearby home networks (e.g. the smart home networks of the apartments inside a building) to increase/decrease their level of security, thus creating a true in-line Intrusion Prevention System (IPS). The paper also presents a test bed for Smart Home to detect and counteract to different attacks against the IoT devices,,Wi-Fi and Ethernet connections .

Bianchi type III string cosmological models (massive and geometric) in presence of magnetic field with vacuum energy density following the techniques used by Letelier (1979) and Stachel (1980) are obtained. We find that the energy conditions (dominant as well as weak) given by Hawking and Ellis (1974) are satisfied for the models. Also the solutions obtained satisfy conservation equation for massive string with magnetic field and vacuum energy density. The models in general, represent anisotropic phase of space-time due to the presence of string. However, the models isotropize at late time and in special case. It has also been shown that the magnetic field is directly linked with the matter. For string dust model, the state finder parameters {r,s} are in excellent agreement with Planck results (Sahni et al. (2003)). The physical and geometrical aspects of the models with special cases are also discussed.

Definitions of bronchopulmonary dysplasia (BPD) or post-prematurity respiratory disease (PPRD) aim to stratify the risk of mortality and morbidity, with an emphasis on long-term respiratory outcomes. There is no univocal classification of BPD, due to its complex multifactorial nature and the substantial heterogeneity of clinical presentation. Currently, there is no definitive cure available for extremely premature very-low-birth-weight infants with BPD, and challenges in finding targeted preventive therapies persist. However, innovative stem cells-based postnatal therapies targeting BPD-free survival are emerging, which are likely to be offered in the first few days of life to higher-risk subpopulations of premature infants. Hence the need for easy-to-use noninvasive tools for a standardized, precise and reliable BPD assessment at a very early stage, to support clinical decision-making and to predict the response to treatment. In this non-systematic review, we present an overview of strategies for monitoring preterm infants with early and evolving BPD-PPRD, and make some remarks on future prospects, with a focus on near-infrared spectroscopy (NIRS).

The feasibility of hydroelectric plants depends on a variety of factors: water resource regime, geo-graphical, geological and environmental context, available technology, construction cost and eco-nomic value of produced energy. Choices about the building or renewal of hydroelectric plants should be based on the forecast of the future trend of these factors at least during the project life of the system. Focusing on the economic value of the produced energy this paper examines its influ-ence on the feasibility of hydroelectric plants. Analysis, referred to Italian case, were based on three different phases: i) the economic sustainability of small-scale hydroelectric plants under a minimum price guaranteed to the hydroelectric operator; ii) the estimate of the incentives to reach the thresholds of "acceptability" and "bankability" of the investment; iii) the analysis of results ob-tained in the previous phases using a model of the evolution of the electricity price in the period 2014-2100.

During the last 150 years, the trout-culture industry focused on enhancing trout populations by stocking, in response to the growing anglers’ demand and the habitat degradation associated to the rapid urbanization and hydropower development. The industrialized north of Italy, home to the Italian Alpine and subalpine trout populations, is the source of most of the revenues of the national trout-culture industry. Its rapid growth and the massive introduction of non-native interfertile trouts eroded the genetic diversity of native lineages, leading to harsh confrontations between scientists, institutions, and sportfishing associations. We review here the state of art of the taxonomy and distribution of the northern Italian native trouts, presenting both scientific results and historical documentation. We think the only native trouts in this region are Salmo marmoratus, widespread in this region, plus small and fragmented populations of S. ghigii, present only in the Southwestern Alps. We strongly recommend the interruption of stocking of domesticated interfertile non-native trouts in this area, and recommend the adoption of Evolutionary Significant Units for salmonid fishery management. We further propose future research directions for a sustainable approach to the conservation and ecosystem management of the fishery resources and inland waters of northern Italy.

In recent years there has been an increasing interest in developing novel materials based on natural biopolymers as a renewable alternative of petroleum-based plastics. The availability of proteins derived from agricultural by-products, along with their favourable properties, has fostered a renewed interest in protein-based materials, promoting research in innovative technologies. In this study we propose the use of rapeseed protein-rich meal as main ingredient for the preparation of novel sustainable materials combining excellent environmental properties such as biodegradability and renewable origin. Application as sustainable products in the present high-tech society needs modification of basic native properties of these natural compounds. The original route proposed in this paper consists in the preparation via compression moulding of flexible biomaterials stabilized by crosslinkers/chain extenders. Investigation of the effects of different denaturing and disulfide bond reducing agents, crosslinkers, and preparation conditions on the material mechanical behaviour demonstrated that the novel materials have appreciable strength and stiffness. The results show the potential of utilizing full meal from vegetable by-products to prepare protein-based materials with granted ecofriendly characteristics and mechanical properties adequate to specific structural applications.

Microfluidic technology has become a powerful tool for several applications in chemistry, physics, biology, and engineering. Benefiting from the advantages of flowing fluids in the laminar regime, droplet-based microfluidics enable the development of various delivery systems based on food-grade emulsions, such as multiple emulsions, microgels, microcapsules, solid lipid micro-particles, and giant liposomes. Besides, by manipulating fluids on a micrometer scale with low-energy demand, it is possible to control the size, shape, and dispersity of droplets generated, which makes microfluidic emulsification an excellent strategy to modulate delivery system properties depending on the entrapped compound type. Thus, this review points out the most current advances in droplet-based microfluidic processes, in which food-grade materials were successfully utilized to develop simple and complex delivery systems. In that context, we sum-marized the principles of droplet-based microfluidics, introducing the most common microde-vices geometries, manufacturing materials, and forces involved in the different droplet generation processes within the microchannels. Subsequently, the encapsulated compound type, classified as lipophilic or hydrophilic functional compounds, was used as a starting point to present current advances in delivery systems based on food-grade emulsions and assembly using microfluidic technologies. Finally, we discuss the limitations and perspectives of scale-up in droplet-based microfluidic approaches, including the challenges that have limited the transition of microfluidic processes from lab-scale to industrial-scale.

In this paper, a robust nonlinear dynamic controller is designed for a wind turbine with a permanent magnet synchronous generator. The wind turbine is subject to variations in all the parameters appearing in its mathematical model. Furthermore, the wind velocity is considered unavailable for direct measurement. This situation is of particular interest in practical applications, where only the nominal parameter values are known, and accurate wind velocity measurement is challenging due to perturbations caused by the turbine itself, even with appropriate sensors. The problem addressed in this work involves tracking the reference angular velocity corresponding to the wind velocity. To achieve accurate tracking, appropriate compensation of the perturbation terms resulting from parameter uncertainties and wind estimation errors is required. To address this problem, an estimator of the wind velocity is utilized, along with high–order sliding mode parameter estimators, to ensure high–performance operation of the turbine.

The Coronavirus Disease 2019 (COVID-19) is a new viral infection caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2). Genomic analyses have revealed that SARS-CoV-2 is related to Pangolin and Bat coronaviruses. In this report, a structural comparison between the Sars-CoV-2 Envelope and Membrane proteins from different human isolates with homologous proteins from closely related viruses is described. The analyses here reported show the high structural similarity of Envelope and Membrane proteins to the counterparts from Pangolin and Bat coronavirus isolates. However, the comparisons have also highlighted structural differences specific of Sars-CoV-2 proteins which may be correlated to the cross-species transmission and/or to the properties of the virus. Structural modelling has been applied to map the variant sites onto the predicted three-dimensional structure of the Envelope and Membrane proteins.

Usually, towed hydrophone arrays are instrumented with a set of compasses. Data from these sensors are utilized while beamforming the acoustic signal for target bearing estimation. However, elements of the hydrophone array mounted in the neighborhood of a compass can affect the Earth’s magnetic field detection. The effects depend upon the kind of elements present in the platform hosting the compass. If the disturbances are constant in time, they can be compensated for by means of a magnetic calibration. This process is commonly known as soft and hard iron compensation. In this paper, a solution is presented to carry out the magnetic calibration of a COTS (Commercial Off The Shelf) digital compass without unattainable sensor motion. This approach is particularly suited in applications where a physical rotation of the platform that hosts the sensor is unfeasible. In our case, the platform consists in an assembled and operational towed hydrophone array. A standard calibration process relies on physical rotation of the platform and thus on the use of the geomagnetic field as a reference during the compensation. As a variation on this approach, we provide to the sensor an artificial reference magnetic field to simulate the unfeasible physical rotation. We obtain this by using a tri-axial Helmholtz coil, which enables programmability of the reference magnetic field and assures the required field uniformity. In our work, the simulated geomagnetic field is characterized in terms of its uncertainty. The analysis indicates that our method and experimental set-up represent a suitably accurate approach for the soft and hard iron compensation of the compasses equipped in the hydrophone array under test.

One of the most rapidly advancing areas of deep learning research aims at creating models that learn to disentangle the latent factors of variation from a data distribution. However, modeling joint probability mass functions is usually prohibitive, which motivates the use of conditional models assuming that some information is given as input. In the domain of numerical cognition, deep learning architectures have successfully demonstrated that approximate numerosity representations can emerge in multi-layer networks that build latent representations of a set of images with a varying number of items. However, existing models have focused on tasks requiring to conditionally estimate numerosity information from a given image. Here we focus on a set of much more challenging tasks, which require to conditionally generate synthetic images containing a given number of items. We show that attention-based architectures operating at the pixel level can learn to produce well-formed images approximately containing a specific number of items, even when the target numerosity was not present in the training distribution.

The building sector accounts for nearly 40% of total primary energy consumption in the U.S. and E.U. and 20% of worldwide delivered energy consumption. Climate projections predict an increase of average annual temperatures between 1.1-5.4°C by 2100. As urbanization is expected to continue increasing at a rapid pace, the energy consumption of buildings is likely to play a pivotal role in the overall energy budget. In this study we used EnergyPlus building energy models to estimate the future energy demands of commercial buildings in Salt Lake County, Utah, USA, using locally-derived climate projections. We found significant variability in the energy demand profiles when simulating the study buildings under different climate scenarios, based on the energy standard the building was designed to meet, with reductions ranging from 10% to 60% in natural gas consumption for heating and increases ranging from 10% to 30% in electricity consumption for cooling. A case study, using projected 2040 building stock, showed a weighted average decrease in heating energy of 25% and an increase of 15% in cooling energy. We also found that building standards between ASHRAE 90.1-2004 and 90.1-2016 play a comparatively smaller role than variation in climate scenarios on the energy demand variability within building types. Our findings underscore the large range of potential future building energy consumption which depend on climatic conditions, as well as building types and standards.

The World Health Organization (WHO) recently added snakebite envenoming to the priority list of Neglected Tropical Diseases (NTD). It is thought that ~75% of mortality following snakebite occurs outside the hospital setting, making the temporal gap between a bite and antivenom administration a major therapeutic challenge. Small molecule therapeutics (SMTs) have been proposed as potential pre-referral treatments for snakebite to help address this gap. Herein, we discuss the characteristics, potential uses and development of SMTs as potential treatments for snakebite envenomation. We focus on SMTs that are secretory phospholipase A2 (sPLA2) inhibitors and metalloprotease (MP) inhibitors.

Much evidence suggests a correlation between degeneration and mitochondrial impairment. Typical cases of degeneration can also be observed in physiological phenomena (aging) as well as in neurological neurodegenerative diseases and cancer. All these pathologies have as a common denominator the dyshomeostasis of mitochondrial bioenergy. Even neurodegenerative diseases show a bioenergetics imbalance in their pathogenesis or progression. Huntington's chorea and Parkinson's disease are both neurodegenerative diseases, but while Huntington's disease is a genetic, and progressive disease with early manifestation and severe penetrance, Parkinson's disease is a pathology with a multifactorial aspect. Indeed, there are different types of Parkinson/Parkinsonism. Many forms are early onset diseases linked to gene mutation, others can appear in young adults and senescent only post-injury, and a final group is idiopathic. Huntington's was defined as a hyperkinetic disorder, while Parkinson's is a hypokinetic disorder; but in the middle, there are a lot of similarities as well as neuronal excitability, the loss of striatal function, psychiatric comorbidity, etc. In the review, we would embrace the theories that both diseases start and develop in light of mitochondrial dysfunction. These dysfunctions act on energy metabolism and reduce the vitality of neurons in many different brain areas.

Acute lymphoblastic leukemia (ALL) is a blood cancer that primarily affects children but also adults. It is due to the malignant proliferation of lymphoid precursor cells that invade the bone marrow and can spread to extramedullary sites. ALL is divided into B cell (85%) and T cell lineages (10 to 15%); rare cases are associated with the natural killer (NK) cell lineage (<1%). To date, the survival rate in children with ALL is excellent while in adults continues to be poor. Despite the therapeutic progress, there are subsets of patients that still have high relapse rates after chemotherapy or hematopoietic stem cell transplantation (HSCT) and an unsatisfactory cure rate. Hence, the identification of more effective and safer therapy choices represents a primary issue. In this review, we will discuss novel therapeutic options including bispecific antibodies, antibody-drug conjugates,chimeric antigen receptor (CAR)-based therapies, and other promising treatments for both pediatric and adult patients.

Neuronal PAS domain protein 2 (NPAS2) is a hemeprotein comprising a basic helix-loop-helix domain (bHLH) and two heme-binding sites, the PAS-A and PAS-B domains. This protein acts as a pyridine nucleotide-dependent and gas-responsive CO-dependent transcription factor and is encoded by a gene whose expression fluctuates with circadian rhythmicity. NPAS2 can heterodimerize with ARNTL in the activating limb of the transcriptional/translational feedback loop operating the circadian clock circuitry. NPAS2 can functionally substitute for the core transcription factor and histone/protein acetylase CLOCK in the molecular clockwork endowing central oscillators in the suprachiasmatic nuclei of hypothalamus as well as in peripheral oscillators in the cell of other body tissues, such as the liver and kidney.

Infections caused by KPC-producing K. pneumoniae continue to pose a significant clinical challenge due to emerging resistance to new antimicrobials. We investigated the association between two drugs whose roles have been repurposed against multidrug-resistant bacteria: fosfomycin and temocillin. Temocillin exhibits unusual stability against KPC enzymes, while fosfomycin acts as a potent “synergizer”. We conducted in vitro antimicrobial activity studies on 100 clinical isolates of KPC-producing K. pneumoniae using a combination of fosfomycin and temocillin. The results demonstrated synergistic activity in 91% of the isolates. Subsequently, we assessed the effect on Galleria mellonella larvae using 5 different KPC-Kp isolates. The addition of fosfomycin to temocillin increased larvae survival from 73 to 97% (+Δ 32%; isolate 1), from 93 to 100% (+Δ 7%; isolate 2), from 63 to 86% (+Δ 36%; isolate 3), from 63 to 90% (+Δ 42%; isolate 4), and from 93 to 97% (+Δ 4%; isolate 10), respectively. Among the temocillin-resistant KPC-producing K. pneumoniae isolates (24 isolates), the addition of fosfomycin reduced temocillin MIC values below the resistance breakpoint in all isolated except one. Temocillin combined with fosfomycin emerges as a promising combination against KPC-producing K. pneumoniae, warranting further clinical evaluation.

The size of TiO2 (either nanometric or micrometric) can significantly affect both its photocatalytic and photoelectrochemical properties, thus altering the photooxidation of organic pollutants in air or water. The purpose of this work is to give an account of the photoelectrochemical and photocatalytic features of some nano- and micro-sized TiO2 commercial powders towards a model reaction, the photooxidation of acetone. Cyclic voltammograms (CV) of TiO2 particulated electrodes under UV illumination experiments were carried out in either saturated O2 or N2 solutions for a direct correlation with the photocatalytic process. In addition, the effect of different reaction conditions on the photocatalytic efficiency under UV light in both aqueous and gaseous phases was also investigated. CV curves with the addition of acetone under UV light showed a negative shift of the photocurrent onset, confirming the efficient transfer of photoproduced reactive oxygen species (ROSs), e.g., hydroxyl radicals, or holes to acetone molecules. The photocatalytic experiments showed that the two nano-sized samples exhibit the best photocatalytic performance. The different photoactivity of the micro-sized samples is probably attributed to their morphological differences, affecting both the amount and distribution of free ROSs involved in the photooxidation reaction.

Protective coatings, in recent years also from nanocomposite formulations, are commonly applied onto architectural stone and stone artefacts, mainly to prevent absorption into the porous stone structure of condensed water and dissolved atmospheric pollutants. While standard protocols are available to assess a coating’s performance, understanding the response of the coating-stone system is a complex task, due to the interplay of various factors determining the overall behaviour. Characterization techniques allowing to correlate the extent and nature of surface modification upon treatment with the most relevant physical properties (i.e water absorption and surface wettability) are thus of great interest. Electrokinetic analysis based on streaming current measurements, thanks to its sensitivity towards even minor changes in the surface chemical composition, may fulfil such requirement. Indeed, by involving the interaction with a testing aqueous electrolyte solution, this technique allows to probe not only the outer surface but also the outermost layer of the pore network, which plays a crucial role in the interaction of the stone with condensed atmospheric water. In this work a correlation was found between the extent of surface modification, as determined by streaming current measurements, surface wettability and capillary water absorption of 6 coating-lithotype combinations (3 lithotypes and 2 nanocomposites).

In this paper we exploit concepts from Information Theory to improve the classical Chvatal’s greedy algorithm for the Set Covering Problem. In particular, we develop a new greedy procedure, called Surprisal-Based Greedy Heuristic (SBH), incorporating the computation of a “surprisal” measure when selecting the solution columns. Computational experiments, performed on instances from the OR-Library, show that SBH yields a 2.5% improvement in terms of the objective function value over the Chvatal’s algorithm while retaining similar execution times, making it suitable for real-time applications. The new heuristic was also compared with Kordalewski’s greedy algorithm, obtaining similar solutions with much lower times on large instances, and Grossmann and Wool’s algorithm for unicost instances, where SBH obtained better solutions.

In recent years, pathoconnectomics emerged as an interesting framework for the investigation and better comprehension of disorders affecting the brain. Research in this field has used so far structural, functional, metabolic and genetic data, but limited attention was addressed to the possible role of vascularization. In the present work the following aspects making it a valuable candidate to pathoconnectomics investigation are discussed: i) The vascular system is by its nature a network, endowed with directionality information on the basis of circulation; ii) The current imaging techniques allow in vivo detection of the vascular system to a good level of detail; iii) The information extracted from this kind of data could interact in a meaningful way with the functional profile of the brain, being the BOLD effect in turn based on blood flow; iv) Further evidence could be found in support of the trophic failure hypothesis; v) Data about vascularization could allow to bring in the pathoconnectomics framework cardiovascular and metabolic disorders. We suggest, therefore, that the evaluation of vascular connectivity (which we propose to name “vesselomics”) could enhance the pathoconnectomics paradigm, and provide new elements towards the understanding of brain pathology.

Much evidence suggests a correlation between degeneration and mitochondrial impairment. Typical cases of degeneration can also be observed in physiological phenomena (aging) as well as in neurological neurodegenerative diseases and cancer. All these pathologies have as a common denominator the dyshomeostasis of mitochondrial bioenergy. Even neurodegenerative diseases show a bioenergetics imbalance in their pathogenesis or progression. Huntington's chorea and Parkinson's disease are both neurodegenerative diseases, but while Huntington's disease is a genetic, and progressive disease with early manifestation and severe penetrance, Parkinson's disease is a pathology with a multifactorial aspect. Indeed, there are different types of Parkinson/Parkinsonism. Many forms are early onset diseases linked to gene mutation, others can appear in young adults and senescent only post-injury, and a final group is idiopathic. Huntington's was defined as a hyperkinetic disorder, while Parkinson's is a hypokinetic disorder; but in the middle, there are a lot of similarities as well as neuronal excitability, the loss of striatal function, psychiatric comorbidity, etc. In the review, we would embrace the theories that both diseases start and develop in light of mitochondrial dysfunction. These dysfunctions act on energy metabolism and reduce the vitality of neurons in many different brain areas.

This work investigates a new nanostructured gas-diffusion-layer (nano-GDL) to improve performance of air-cathode Single-Chamber-Microbial-Fuel-Cells (a-SCMFCs). The new nano-GDLs improves the direct oxygen-reduction-reaction by exploiting the best of nanofibers from electrospinning in terms of high surface ratio to volume and high porosity, and laser-based processing to promote adhesion. Nano-GDLs by electrospinning were fabricated directly collecting two nanofibers mats on the same carbon-based electrode, acting as the substrate. Each layer was designed with a specific function: water resistant, oxygen permeable polyvinylidene-difluoride (PVDF) nanofibers served as a barrier to prevent water-based electrolyte leakage, while an inner layer of cellulose nanofibers was added to promote oxygen diffusion towards the catalytic sites. The maximum current density obtained for a-SCMFCs with the new nano-GDLs is (132.2 ± 10.8) mA m^-2, and it doubles the current density obtained with standard PTFE-based GDL (58.5 ± 2.4 mA m^-2), used as reference material. The energy recovery (EF) factor, i.e. the ratio of the power output to the inner volume of the device, was then used to evaluate the overall performance of a-SCMFCs. a-SCMFCs with nano-GDL provided an EF value of 60.83 mJ m^-3: one order of magnitude higher than the value of 3.92 mJ m^-3 obtained with standard GDL

We report the case of a 61-year-old woman who was referred to the Oral Surgery and Implantology Unit of the University Hospitals of Geneva to take care edentulous sites after dental avulsions of teeth 11 and 21 following traumatic shock due to endotracheal intubation under general anaesthesia. The dental history revealed that the patient had a history of generalized chronic periodontitis that had been treated several years earlier. Treatment consisted, for the first time to our knowledge, of immediate insertion of implants at sites 11 and 21 with simultaneous bone augmentation in a single surgical procedure and immediate restorations.

From the critical premises that underpin the debate between archeology and architecture, evi-dence emerges, namely that the musealization of building or urban remains of the past is even more harmful, for the purposes of its real understanding, than that of any other artefact. In a country, Italy, that has archeological presences more than any other, architecture must contribute to overcoming the consolidated aporia that the Contemporary, understood not only as a period but also and above all as its “forms and functions”, it’s structurally in opposition to the conser-vation of the archeological heritage. What is presented is an attempted exercise for “inhabiting archaeology”, that is, trying to re-grant inclusive usability to a historical fragment, which has lost the elements necessary for its habitability. The set of questions, doubts and steps have been high-lighted more than the final “figure” of the project: an essential form directly connected with the primordial principles of its constitution, for a project that protects and encourages to visit the complex, trying to offer new perspectives, new narratives and new connections that translate into the possibility of being – for those who visit this place – the protagonists of a unique experience made of history, memory and continuous discoveries.

Recently, we have witnessed a booming development of composites and multi-dopant metal oxides to be employed as novel photocatalysts. Yet the practical application of photocatalysis for environmental purposes is still elusive. Concerns about the unknown fate and toxicity of nanoparticles, unsatisfactory performance in real conditions, mass transfer limitations and durability issues have so far discouraged investments in full-scale applications of photocatalysis. Herein, we provide a critical overview of the main challenges that are limiting large-scale application of photocatalysis in air and water/wastewater purification. We then discuss the main approaches reported in the literature to tackle these shortcomings, such as the design of photocatalytic reactors that retain the photocatalyst, the study of degradation of micropollutants in different water matrices, and the development of gas-phase reactors with optimized contact time and irradiation. Furthermore, we provide a critical analysis of research-practice gaps such as treatment of real water and air samples, degradation of pollutants with actual environmental concentrations, photocatalyst deactivation, and cost and environmental life-cycle assessment.

Background and Objectives: Mechanical and biological complications can lead to system fracture or screw loss on dental implants. Narrow and regular platforms have been used without a consensus about the effect of distance the abutment from the prosthetic platform margin. The aim of this study is to evaluate different insertion torques in the deformation of tri-channel platform connections through two- and three-dimensional measurements with micro-CT. Materials and Methods: 164 implants were divided into groups (platform diameter and type): 3.5, 3.75, and 4.3 mm NP (Narrow Platform), and 4.3 mm RP (Regular Platform). Each implant-platform group was then divided into four subgroups (n = 10) with different torques: T45 (45 Ncm), T80 (80 Ncm), T120 (120 Ncm) and T150 (150 Ncm). The implant-abutment-screw assemblies were scanned and the images obtained were analyzed. Results: A significant difference was observed for the linear and volume measures between the different platforms (p &lt;0.01) and the different implant insertion torques (p &lt;0.01). Qualitative analysis suggested higher deformation resistance for the 3.75 NP compared to the 3.5 NP, and RP was more resistant compared to the NP. Conclusions: The 0.25-mm increment in the implant platform did not increase the resistance to the applied insertion torques; the 4.3-mm implant was significantly stronger compared to the 3.5-mm implant and the proposed micro-CT analysis was considered valid for both 2D and 3D analyses of micro gaps, qualitatively and quantitatively.

The focus of the current research indicates a new Bianchi type-V anisotropic, homogeneous astrophysical model with modified theory of f(R, T) gravity and Λ(t), time-dependent cosmological constant. The significant effect of the model is that the field equations solutions find using a time-dependent quadratic deceleration parameter. We observed anisotropy parameter remains constant both in the belated universe and early universe. The deportment of the equation of state (EOS) parameter, pressure, and energy density, cosmological constant and other parameters are also discussed. This cosmological model indicated the possibility of an accelerating universe with negative pressure, such as a universe dominated by dark energy. Om(z) diagnostic test suggested that the universe starts with quintessence nature and ends as a phantom model. Also, energy conditions of this model are represented here to ensure the model is physically reasonable and based on observations.

Electrochemotherapy (ECT) is one of the newest therapeutic strategies employed as medical procedure for skin neoplasms’ treatment, especially for Classic Kaposi’s Sarcoma (CKS). The aim of this study was to demonstrate ECT clinical response and local control of CKS disease. Primary endpoint was to value the worth and efficacy of this local therapy in CKS skin lesions’ treatment. Nineteen CKS patients were enrolled, 14 males and 5 females with median age at diagnosis of 72. Complete response (CR) has been gained in 12 patients after first ECT attempt, meanwhile 3 and 4 out of 19 patients obtained a Partial response (PR), so that they underwent to a second and a third ECT treatment, each other. Clinical response was evaluated during all the time of the follow-up, which ranged between 3 months and 4 years with a median of 18 months. CKS skin lesions control still represents a challenge for surgeons and oncologists. Nevertheless, according to this and other authors’ recent experiences, ECT could be considered the gold standard strategy for early-stage patients, but at the same time it could be considered as a valid option in controlling Kaposi’s Sarcoma locally advanced lesions.

Material and methods. The trial was carried out over two years in Southern Italy. Two grapevine rootstocks, 110R and SO4, were compared to evaluate the water extraction ability from the soil and the effect on the yield and quality of the Cardinal grapevine table cultivar. Therefore, a new approach to plant water consumption based on sap flow was adopted. Results. The earlier and faster water refilling of the xylem in Cardinal onto 110R (C/110R) appears responsible for the earlier evolution of the phenological phases than Cardinal onto SO4 (C/SO4). The maximum length of the principal shoot was reached in Cardinal/110R compared to C/SO4, while a higher number of lateral shoots with lower internode has changed canopy architecture and light distribution in C/SO4. The 110R used more water compared to SO4; it was possible to quantify the real transpired flux of the plant per day: sap flow was 12.3 L.plant-1.d-1 and 11.7 L.plant-1d-1 in C/110R in the first and second year, respectively, while it was 14% lower in alternative graft combination. Conclusions. However, C/SO4 was able to sustain leaf water status and physiological mecha-nisms, although with lesser performance than C/110R, but that did not cause negative effects on production parameters.

This study presents the development of a diglycidyl monomer containing two imine groups that can act as dynamic and reversible bonds. During the curing of the monomer with two different amine hardeners, we confirmed the formation of new imine groups due to the transamination reaction, not reported before, between the imine groups of the diepoxy monomer with the amine groups of the hardener. The effect of this structural change is observed for the first time in the stress relaxation behavior, resulting in the overlapping of two different relaxation modes. The analytical modelling could extract two distinct characteristic relaxation times using a double-element Maxwell model. A second characterization of the stress relaxation process by frequency sweep experiments was performed to corroborate the results obtained, confirming speedy stress relaxation. Acid-catalyzed hydrolysis was performed on the studied materials, demonstrating the complete degradation of the network. We finally confirmed that the synthesized diepoxy compound is suitable for preparing carbon fiber-reinforced composite materials, demonstrating easy fiber impregnation, fast reshaping and especially a total degradation of the polymer matrix that allows the recovery of the carbon fibers in mild conditions. This epoxy-amine system is an excellent candidate for overcoming the traditional limits of thermosets in preparing fiber-reinforced composites.

Severe asthma patients are at increased risk of major exacerbations and they need to be monitored regularly. The COVID-19 pandemic has impressively impacted on the health care resources. The telemedicine approach applied to the follow-up of asthmatic patients has been proved to be effective in monitoring their disease and adherence to the therapy. The aim of our study was to investigate the satisfaction of severe asthma patients, before the activation of a telemedicine management complemented by a standard of care. An ad hoc questionnaire was developed and sent by e-mail to 180 severe asthma patients. Most of subjects (82%) were confident with the idea of doing self-measurements and self-managing their disease; 77% of subjects favoured to carry out virtual visit and telemedicine. 93% of patients considered easy the self-injection therapy. 94% of subjects felt safe and 93% were not worried while self-administering. Only mild adverse events were reported in 22% subjects after self-administration. Our results showed an agreement between what is considered necessary and practicable by healthcare personnel and what is perceived by the severe asthma patients, in terms of treatment and monitoring of the disease with Telehealth. Biologics have a safety profile and can be easily self-administred at home

The aim of this study was to measure the effects on 3D active cervical Range of Motion (ACROM) and perceived pain of a n elastic taping (ET) application in the cervical area. Thirty participants (n: 22M and 8F, age 35.4±4.4 years; body height 173.1±8.4 cm; body mass 73.5±12.8 kg) for the study group (SG) and twenty subjects (n: 11M and 9F, age 32.6±3.9 years; body height 174.9±10.9 cm; body mass 71.2±12.9 kg) for the control group (CG) were recruited. All subjects were symptomatic for neck and cervical pain in baseline condition. Each group performed on ACROM test and the perceived pain on neck basing as Numerical Rating Scale (NRS 0-10, a.u.): at the baseline (T0); after 20' from ET application (T1); after three days of wearing the ET application (T2). Between T0 and T1 an ET was applied on the cervical area of the SG participants. Statistical analysis did not show any significant change in CG in any measurement session for ACROM and neck pain parameters. Conversely, the SG showed significant improvements for ACROM rotation left (T0 64.8 ± 7.7° - T2 76.0 ± 11.1° p &lt; 0.000) and right (T0 66.0 ± 11.9° - T2 74.2 ± 9.6° p &lt; 0.000); lateral inclination left (T0 37.5 ± 6.9° - T2 40.6 ± 10.8° p &lt; 0.000) and right (T0 36.5 ± 7.9° - T2 40.9 ± 5.2° p &lt; 0.000); flexion posterior (T0 47.0 ± 12.9° - T2 55.1 ± 12.3° p &lt; 0.001) and anterior (T0 55.0 ± 3.6° - T2 62.9 ± 12.0° p &lt; 0.006). A significant decrease was measure also in SG for pain NRS between T0 and T2 (T0 7.5 ± 1.0° - T1 5.5 ± 1.4 - T2 1.4 ± 1.5° p &lt; 0.000). In conclusion, the results of this study underline the usefulness of a bilateral and symmetrical ET cervical application in terms to enhance multiplanar ACROM and to reduce subjective self-perceived cervical pain when it is needed. These findings can be applied for managing musculoskeletal health of different kind of individuals.

Radiological imaging is essential for acute patient management in Intensive Care Units (ICUs); however, it introduces the risk of exposure to ionizing radiation. This review synthesizes research on radiation exposure in intensive care unit (ICU) settings, highlighting its rise during the COVID-19 pandemic and repetitive imaging. Our analysis extends to radiation safety thresholds, revealing that some ICU patients exceed annual occupational limits, emphasizing the need to balance diagnostic utility against potential long-term risks, such as cancer. Prospective studies have demonstrated an increase in the median Cumulative Effective Dose (CED) in patients with trauma over time, prompting calls for improved awareness and monitoring. Moreover, innovative dose-reduction strategies and optimized protocols, especially in neuro-ICU units, promise to mitigate these risks. This review highlights the essential but risky role of radiological imaging in critical care. It advocates rigorous radiation management protocols to safeguard patient health, while ensuring the continuity of high-quality medical care.

Mucosal healing (MH) is the main treatment target in ulcerative colitis and Crohn’s disease, and it is defined by a combination of complete endoscopic and histologic remission. Indeed, the complete resolution of mucosal inflammation should be confirmed at histology. Neutrophil infiltration represents the unique histological marker in discriminating the active vs quiescent phase of disease, also including crypt injuries (cryptitis and crypt abscesses), erosions and ulcerations. Basal plasmacytosis do not qualify by itself the remission in inflammatory bowel diseases (IBD), but it represents a diagnostic clue, mostly at onset. Several histological scoring systems have been developed to evaluate therapeutic efficacy, even though they often resulted tricky and subjective. Moreover, these scores listed a heterogeneous group of histological features as parameters. The recently proposed simplified histological score on MH was based on neutrophils and their distribution in the gut mucosa was also considered, aiming to provide a simple, time-sparing and reproducible tool to be applied to the routinary diagnostic practice. The artificial intelligence could be a promising tool both in evaluating and standardizing the histological assessment of disease activity in IBD. Moreover, novel molecules involved in the inflammatory dynamics in the gut could be employed in supporting the diagnostic practice in IBD.

Background: Recently the role of nutraceutical compounds in the prevention of human diseases is rapidly increasing. Here, we aim to evaluate the beneficial effect of dietary supplementation with seven active principles, lycopene, sulphoraphane, silymarin, glutathione, escin, tryptophan, green tea catechins, on human health. Methods: An extensive search of PubMed and Medline database was performed with the following keywords: “silymarin”, “sulforaphane”, “lycopene”, “green tea catechins”, “tryptophan”, “glutathione” and “escin” accompanied by the keywords “supplement”, “supplementation”, “nutraceutics”. All pre-clinical and clinical trials have been considered for this review. Results: One-hundred and eighteen full-text articles were eligible for inclusion in this review. The papers examined presented considerable variability due to the wide heterogeneity of dosages administered, population involved and outcomes pursued. Conclusion: Nutritional supplementation with lycopene, sulphoraphane, silymarin, glutathione, escin, tryptophan and green tea catechins appears to exert a wide range of benefits on human health, ranging from mood and cognition to cardiovascular health, fertility, metabolism, antioxidant and anti-inflammatory capabilities, potential anti-cancer effects. Further studies are required to better define the potential synergic effect, optimal dosage, mechanism of action and tolerability profile of these substances.

LSM4 is an essential yeast gene encoding a component of different LSM complexes involved in the regulation of mRNA splicing, stability and translation. In previous papers we reported that the expression in S. cerevisiae of the K. lactis Lsm4 gene lacking the C-terminal Q/N-rich domain in a Lsm4 null strain S. cerevisiae (Sclsm4D1) restored cell viability. Nevertheless, in this transformed strain we observed some phenotypes which are typical markers of regulated cell death, Reactive Oxygen Species and oxidated RNA accumulation. In this paper we report that a similar truncation operated in the S. cerevisiae LSM4 gene confers to cells the same phenotypes observed with the K.lactis LSM4D1 gene. Up to now there was no evidence on the direct involvement of LSM4 in autophagy. Here we found that the Sclsm4D1 mutant showed defects in the induction of autophagy and it was very sensitive to nitrogen starvation or treatment with low doses of rapamycin, an inducer of autophagy. Moreover, both during nitrogen starvation and ageing, the Sclsm4D1 mutant accumulated cytoplasmic autophagy-related structures, suggesting a role of Lsm4 in Phagophore Assembly Site (PAS) processing and/or vacuolar autophagosome internalization

The aim of the study is to evaluate the predictive factors of response to induction chemotherapy in patients with resectable NSCLC, treated at the unit of Thoracic Surgery of Siena University Hospital with radical surgery. From January 1, 2013 to December 31, 2020, 78 patients were recruited. We analyzed the outcomes in terms of 5-years OS based on the Estimated Regression Rate, N2 downstaging and age; two patients’ subgroups were created by age (Group A: age &lt;66 years-old; Group B: age &gt;66 years-old). No 5-year OS difference was observed based on age, while it was observed in patients with N2 downstaging (p=0.031). Bewtween patients with N2 downstaging, only patients in Group A had a significantly increased 5-year OS (p=0.019), while this was not observed in Group B (p=0-321); the same result was observed with the Estimated Regression Rate &gt; 50% (Group A p=0.005; Group B p=0.391). The percentage of disease regression and the N2 down-staging after induction chemotherapy have great value on the survival, although this advantage seems to be observed mostly in younger patients. A multidisciplinary oncologic discussion of clinical cases could provide support in the careful selection of the ideal patients to undergo neoadjuvant treatment before radical surgery.

Background: Recently the role of nutraceutical compounds in the prevention of human diseases is rapidly increasing. Here, we aim to evaluate the beneficial effect of dietary supplementation with seven active principles, lycopene, sulphoraphane, silymarin, glutathione, escin, tryptophan, green tea catechins, on human health. Methods: An extensive search of PubMed and Medline database was performed with the following keywords: “silymarin”, “sulforaphane”, “lycopene”, “green tea catechins”, “tryptophan”, “glutathione” and “escin” accompanied by the keywords “supplement”, “supplementation”, “nutraceutics”. All pre-clinical and clinical trials have been considered for this review. Results: One-hundred and eighteen full-text articles were eligible for inclusion in this review. The papers examined presented considerable variability due to the wide heterogeneity of dosages administered, population involved and outcomes pursued. Conclusion: Nutritional supplementation with lycopene, sulphoraphane, silymarin, glutathione, escin, tryptophan and green tea catechins appears to exert a wide range of benefits on human health, ranging from mood and cognition to cardiovascular health, fertility, metabolism, antioxidant and anti-inflammatory capabilities, potential anti-cancer effects. Further studies are required to better define the potential synergic effect, optimal dosage, mechanism of action and tolerability profile of these substances.

The electrochemical CO2 reduction reaction can lead to high value-added molecules production while helping decrease anthropogenic CO2 emissions. Copper can reduce CO2 to more than thirty different hydrocarbons and oxygenates, but it lacks the required selectivity. We present a computational investigation of the role of nano-structuring and alloying in Cu-based catalysts on the activity and selectivity of CO2 reduction to one-carbon products: carbon monoxide, formic acid, formaldehyde, methanol, and methane. The adsorption, activation, and conversion of CO2 were computed on monometallic and bimetallic (decorated and core-shell) 55-atom Cu-based clusters. The dopant metals considered were Ag, Cd, Pd, Pt, and Zn, located at different coordination sites. The relative binding strength of the intermediates at different applied potentials were used to identify the optimal catalyst for the selective CO2 conversion to one carbon products. It was discovered that single atom doping with Cd and Zn is optimal for the CO2 to carbon monoxide conversion. The core-shell models with Ag, Pd, and Pt provided higher selectivity for formic acid and formaldehyde. The Cu-Pt and Cu-Pd showed lowest overpotential for methane formation.

The continuous development in the field of industrial automation and electric mobility has led to the need for more efficient electrical machines with high power density. The improvement of electrical machines slot filling factors is one of the measures to satisfy these requirements. In recent years, this topic has aroused greater interest in the industrial sector, since the evolution of the winding technological manufacturing processes allows an economically sustainable realization of ordered winding arrangements, rather than random ones. Moreover, the manufacture of electrical machines windings must be preceded by an accurate design phase in which it is possible to evaluate the maximum slot filling factor obtainable for a given wire shape and for its dimensions. For this purpose, this paper presents an algorithmic approach for the evaluation of maximum slot filling factors in electrical machines under ideal geometric premise. In particular, this algorithm has a greater degree of flexibility with respect to the algorithm approaches found in the literature, since the study has been extended to round, rectangular and hexagonal wire sections. Furthermore, the slot filling factor calculation was carried out both for standard and non-standard slots. The algorithmic approach proposed can be considered as an additional useful tool for the fast design of electrical machine windings.

Winding design methods have been a subject of research for many years of the past century. Many methods have been developed, each one characterized by some advantages and some drawbacks. Nowadays, the star of slots is the most widespread design tool for electrical machine windings. In this context, this paper presents a simple and effective procedure to determine the distribution of the EMF stars and of the winding configuration in all possible typologies of electrical machines equipped with symmetrical windings. Moreover, this procedure can also be easily implemented in a computer program in order to perform automated winding designs for rotating electrical machines. Several examples are provided in order to validate the proposed procedure.

Background/Objectives: Encouraging results reported of Platelet-Rich Plasma (PRP) treatment for knee osteoarthritis (KOA). The present retrospective study reports the efficacy and safety of a high dose of neutrophile and red blood cell-depleted PRP to treat 212 patients with KOA. Methods: 212 consecutive patients diagnosed with Kellgren-Lawrence (KL) grading 1-3 KOA chronic knee pain for at least 1 year were treated with 3 injections at 15-day intervals with a high dose of neutrophil-depleted PRP (4 billion platelets). Clinical outcomes were retrospectively recorded as a percentage of responders at 3,6, and 12-month follow-up, following the OMERACT-OARSI criteria. Pain through VAS score and WOMAC score have also been recorded. Results: 4ml of PRP containing 4X109 platelets were obtained by single spin centrifugation and injected intra-articular into each patient with no pre-activation. The overall responder rate of patients responding to OMERACT-OARSI criteria at 3,6,12 months was 68.9%, 72,7% and 70,6%. There was a significant improvement in VAS and WOMAC scores at 3-, 6- and 12-month follow-up compared to the pre-treatment value (p&lt; 0.01). The lowest VAS score was observed at 6 months overall and in all three-grade KL groups. KL2 groups showed the best results regarding pain reduction and WOMAC score at 6 months (p&lt; 0.01). Conclusions: a high dose of neutrophil-depleted PRP is an effective treatment for KL1-3 KOA. It provides symptomatic relief, can potentially reduce disease progression, and has sustained effects for up to 12 months.

Total bilateral Limbal Stem Cells Deficiency is a pathologic condition of the ocular surface due to the loss of corneal stem cells. Cultivated Oral Mucosa Epithelial Transplantation (COMET) is the only autologous successful treatment for this pathology in clinical application, although non-physiological peripheric corneal vascularization often occurs. Properly characterizing the regenerated ocular surface is needed for a reliable follow-up. So far, the univocal identification of transplanted oral mucosa had been challenging. Previously proposed markers were shown co-expressed by the different ocular surface epithelia in a homeostatic or perturbated environment. In this study, we compared the transcriptome profile of human oral mucosa, limbal and conjunctival cells, identifying PITX2 as a new marker that univocally distinguishes the transplanted oral tissue from the other epithelia. We validated PITX2 at RNA and protein levels to investigate 10-year follow-up cor-neal samples derived from a COMET-treated aniridic patient. Moreover, we found novel angiogenesis-related factors differentially expressed in the three epithelia and instrumental in explaining the neovascularization in COMET-treated patients. These results will support the follow-up analysis of patients transplanted with oral mucosa and provide new tools to understand the regeneration mechanism of the transplanted cornea.

Corundum-rich (up to 55 vol.%) felsic dykes formed by albite, ±K-feldspar, ±hercynite and ±biotite-siderophyllite cut the lower crustal rocks exposed in the Ivrea-Verbano Zone (NW Italy). Zircon is an abundant accessory mineral and its investigation through LA-ICP-(MC)MS has allowed to directly constrain the timing of emplacement, as well as petrology and geochemistry of parental melts. Zircons are characterised by very large concentration in REE, Th, U, Nb and Ta, and negative Eu anomaly. U–Pb analysis points to Norian emplacement ages (223±7 Ma and 224±6 Ma), whereas large positive εHf(t) values (+13 on average) indicate a derivation from depleted to mildly enriched mantle source. The mantle signature and the corundum oversaturation were preserved thanks to limited crustal contamination of the host, HT refractory granulites and mafic intrusives. According to the geochemical data and to the evidence of the development of violent explosions into the conduits, it is proposed that dykes segregated from peraluminous melts produced by exsolution processes affecting volatile-rich differentiates during alkaline magmatism. This work provides robust evidence about the transition of the geochemical affinity of Southern Alps magmatism from orogenic-like to anorogenic during Norian, linked to a regional uprising of the asthenosphere and change of tectonic regime.

Polyvinyl Alcohol (PVA)/ Graphene Quantum Dots (GQDs) polymer nanocomposite films have been prepared, and the relationship between their structural, thermal and nanoscale morphologi-cal properties, and their photoluminescent response, has been investigated. Although according to X-ray Diffraction (XRD), Fourier-Transform Infrared Spectroscopy (FT-IR) and Differential Thermal Analysis (DTA) the incorporation of GQDs does not significantly affect the percentage crystallinity of the PVA matrix, for a range of added GQD concentrations, Atomic Force Micros-copy (AFM) showed the formation of islands with apparent crystalline morphology on the surface of the PVA/GQD films, with GQD presumably acting as a nucleating agent for island growth. The incorporation of GQD also led to the formation of characteristic surface pores with increased stiffness and frictional contrast, according to Ultrasonic Force Microscopy (UFM) and Frictional Force Microscopy (FFM) data. The photoluminescence (PL) spectra of the films were found to de-pend both on the amount of GQD incorporated and on the film morphology. For GQD loads > 1,2wt%, a GQD-related band was observed at ~ 1650 cm-1 in FT-IR, along with an increase in the PL band at lower energy. For a load of ~2wt% GQD, the surface morphology was characterized by extended cluster aggregates with lower stiffness and friction than the surrounding matrix, and the PL signal decreased.

3D meso-scale structures that can reach up to centimeters in overall size but retain micro- or nano-features, proved to be promising in various science fields ranging from micro-mechanical metamaterials to photonics and bio-medical scaffolds. In this work we present synchronization of the linear and galvano scanners for efficient femtosecond 3D optical printing of objects at the meso-scale (from sub-μm to sub-cm spanning five orders of magnitude). In such configuration the linear stages provide stitch-free structuring at nearly limitless (up to tens-of-cm) working area, while galvo-scanners allow to achieve translation velocities in the range of mm/s-cm/s without sacrificing nano-scale positioning accuracy and preserving undistorted shape of the final print. The principle behind this approach is demonstrated, proving its inherent advantages in comparison to separate use of only linear stages or scanners. The printing rate is calculated in terms voxels/s, showcasing the capability to maintain an optimal feature size while increasing throughput. Full capabilities of this approach are demonstrated by fabricating structures that reach millimeters in size but still retain μm-scale features: scaffolds for cell growth, microlenses and photonic crystals. All this is combined into a benchmark structure: a meso-butterfly. Provided results show that synchronization of two scan modes is crucial for the end goal of industrial-scale implementation of this technology and makes the laser printing well aligned with similar approaches in nanofabrication by electron and ion beams.

We describe the development and validation of a HPLC-MS/MS method to assess the pharmacokinetics and tumour distribution of ZST316, an arginine analogue with inhibitory activity towards dimethylarginine dimethylaminohydrolase 1 (DDAH1) and vasculogenic mimicry, and its active metabolite L-257 in a xenograft model of triple negative breast cancer (TNBC). The method proved to be reproducible, precise, and highly accurate for the measurement of both compounds in plasma and tumour tissue following acute and chronic (five days) intraperitoneal administration of ZST316 (30mg/Kg daily) in six-week-old SCID mice inoculated with MDA-MB-231 TNBC cells. ZST316 was detected in tumour tissue and plasma after 1 hour (6.47 and 9.01M, respectively) and 24 hours (0.13 and 0.16M, respectively) following acute administration, without accumulation during chronic treatment. Similarly, the metabolite L-257 was found in tumour tissue and plasma after 1 hour (15.06 and 8.72M, respectively) and 24 hours (0.17 and 0.17M, respectively) following acute administration of ZST316, without accumulation during chronic treatment. The half-live after acute and chronic treatment ranged between 4.4-7.1hrs (plasma) and 4.5-5.0hrs (tumour) for ZST316, and 4.2-5.3hrs (plasma) and 3.6-4.9hrs (tumour) for L-257. The results of our study demonstrate the a) capacity to accurately measure ZST316 and L-257 concentrations in plasma and tumour tissue in mice using the newly developed HPLC-MS/MS method, b) rapid conversion of ZST316 into L-257, c) good intra-tumour penetration of both compounds, and d) lack of accumulation of both ZST316 and L-257 in plasma and tumour tissue during chronic administration. The new HPLC-MS/MS method is useful to investigate the in vivo effects of ZST316 and L-257 on vasculogenic mimicry, tumour mass, and metastatic burden in xenograft models of TNBC.

Background: Reliable HPV testing and genotyping are essential for quality assurance in HPV-based primary screening, disease management and for monitoring the impact of HPV vaccination. The clinical validation of HPV molecular diagnostic assays has significantly contributed to these objectives, however little emphasis has been placed in assuring sample quality. This study aims to assess the accuracy of sample cellularity assessment using C-C Motif Chemokine Receptor 5 (CCR5) gene target as a marker of sample adequacy in molecular diagnostics. Methods: Jurkat cell line samples were counted both using Thoma cell-counting chamber and Fluorescent-Activated Cell Sorting (FACS). Jurkat cell line samples at three different concentrations were subsequently evaluated using the OncoPredict HPV Quality Control (QC) real-time PCR assay, employing CCR5 for molecular cellularity quantification. Results: Cellularity values obtained were comparable across the 3 different methods for all dilutions of the cell line tested. Conclusions: The results obtained from this study show that CCR5 represents a promising molecular marker for the accurate quantification of sample cellularity, confirming its use as a reliable sample adequacy control, thus reducing the risk of “false negative” results.

Background: Peyronie’s disease (PD) represents a challenging urological disease, due to not optimal post-operative surgical outcomes. We aim to evaluate if vacuum erection devices (VED) treatment before pe-nile curvature surgery is able to improve the post-operative surgical outcomes. Methods: All enrolled patients were assigned to the following groups: a) treatment group, VED treatment (3 times per week) starting 3 months before surgery and (3 times per week) one months after surgery and b) control group, VED treatment (3 times per week) one months after surgery. Follow-up urologic visits were scheduled at 3 and 6 months after surgery and the two groups were compared. Results: Thirty-eight patients have been enrolled (median age 67 years, 57-74, IQR), 20 in the treatment group and 18 in the control group. At the follow-up visits, the two groups are different in terms of IIEF-5 (26 vs 24; p=0.02), ‘yes’ to SEP2 and 3 (85% vs 55%; p<0.001, 85% vs 50%; p<0.001, respectively) and PDQ (-16 vs -11; p=0.03). Complete correction of penile curvature was achieved in 36 patients (94.7%). In the treatment group, no hourglass deformity has been reported, while in the control group 1 patient reported a mild hourglass deformity. In the treatment group, we obtained a longer total penile length (median +1.5 cm). The overall satisfaction rate was 98% in the treatment group and 96% in the control group. Conclusions: The VED treatment before penile curvature surgery in patients affected by PD is able to improve the post-operative surgery.

The current invasion of the Mediterranean Sea by the Atlantic blue crab Callinectes sapidus entails the implementation of effective strategies of control and management. In native areas, the species is highly appreciated as a hard- and soft-shell seafood, and hard-shell fisheries are developing in a number of invaded countries. Here, to verify alternative approaches for enhancing the commercial value of the species, we carried out a pilot experiment to test a flow-through system for the production of soft-shell blue crabs. Fifty crabs were collected in the Lesina lagoon (Adriatic Sea, Italy) and inspected for the coloration of the line on the distal edge of the fifth pereiopod. Accordingly, they were grouped into three groups showing no, white, and red lines, symptomatic of the progression of the pre-molt phase, and maintained for 31 days in a flow-through pond system. The overall mortality rate determined during the trial was similar across the three groups and ranged between 10 and 20%, indicating that the flow-through system was effective for rearing the crabs. In addition, the molting rate was 10%, 65%, and 85% for individuals at an early, intermediate, and advanced pre-molt stage, confirming that the line coloration can be used as an effective indicator of the advancement of the molting process. Our study provides a first contribution towards the introduction in the Mediterranean fishery sector of novel procedures and practices for the production of soft-shell blue crabs, which may represent a cost-effective strategy to enhance the capture and commercialization of this invasive species as a high quality and valuable shellfish product.

Climbing plants require an external support to grow vertically and enhance light acquisition. Climbers that find a suitable support have greater performance and fitness than those that remain prostrate. Support search is characterized by oscillatory movements (i.e., circumnutation), in which plants rotate around a central axis during their growth. Numerous studies have elucidated the mechanistic details of circumnutation, but how this phenomenon is controlled remains unclear. Here, we use supervised machine learning algorithms to generate models that learn to discriminate between the presence/absence of a support in the environment. Results indicate that there is a difference in the pattern of circumnutation, depending on the presence of a support, that can be learned and classified rather accurately. We also identify distinctive kinematic features that contribute to the classification tasks. Overall, machine learning approaches appear to be powerful tools for understanding the movement of plants.

Myasthenia gravis (MG) is a disease characterized by typical clinical and immunopathogenic pe-culiarities, which correlate with age and sex/gender. Accordingly, MG patients show thymic al-terations and auto-antibodies productions, that can be the expression of a different pathogenetic mechanism related to age and gender. This determines, in relation to age at and sex/gender, a dif-ferent MG onset, prognosis, and outcome. Therefore, diverse MG forms can be identified, classi-fied, and characterized in relation to their different features, and precisely there are early onset and late-onset forms of MG. It has been hypothesized that the cause of appearance the two diverse forms of MG can be ascribed mainly to the diverse genetic and epigenetic factors. In this narrative review, we will analyze and discuss about the interplay of age- and sex-related factors (i.e. genet-ic and epigenetic factors) related to two different MG forms and how they contribute to their di-verse pathogenesis.

Background: The management of penile cancer patients has some grey zones, one of them being the timing of prophylactic pelvic lymph node dissection. Here, we review the impact of timing of prophylactic inguinal and pelvic lymph node dissection on patients’ outcome. Methods: Relevant databases were searched according to recommendations by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Before the systematic review we present a narrative review on the indications for lymph node dissection and the impact of pathological anatomical considerations on the timing of prophylactic lymph node dissection and patients’ outcome. The primary research questions were disease-free and overall survival rate in patients who underwent early or late lymph node dissection after penile cancer diagnosis. Results: Four clinical trials were included in the systematic review. Conclusions: The survival rate of patients with penile cancer is strictly associated with the timing of prophylactic pelvic lymph node dissection. Even though there are no randomized controlled trials we conclude that there is evidence for a strong recommendation that lymph node dissection should be performed as soon as possible after diagnosis with3 months as a realistic cut-off time between early and late. According to the present evidence base, lymph node dissection should be offered the sooner the better to all patients at high risk of lymph node metastasis.

The Mediterranean diet has among its cornerstones the use of olive oil for its nutraceutical and organoleptic properties. Despite the numerous merits, olive-oil mill wastewater (OMWW), which is generated by the olive-oil extraction process, is one of the most serious environmental pollutants in the Mediterranean countries. The polluting potential of OMWW is due to its high content of tannins, polyphenols, polyalcohols, pectins and lipids. In this experiment, we tested the ability of five microalgae of the Chlorella group (SEC_LI_ChL_1, CL-Sc, CL-Ch, FB and Idr) in lowering the percentage of total phenolic compounds in vegetation water. In order to close the recovery cycle of a fortified citrus olive oils previously developed, we tested the vegetation wa-ter obtained with three different extraction processes (conventional, lemon and orange peels) at three concentrations each (10%, 25% and 50%). Results showed that strains Idr, FB and CL-Sc from the Lake Massaciuccoli can tolerate vegetation water from conventional and lemon peels extraction up to 25%; these strains can also reduce the phenolic compounds within the tests. The results demonstrate that the application of microalgae for OMWW treatment represent an inter-esting opportunity, and an eco-friendly low-cost solution to be developed within the companies as a full-scale approach.

The liver health of Gilthead sea bream and European sea bass fed fishmeal-free diets including various proportions of plant proteins, insect and poultry by-product meals, was investigated through biochemical and histological analyses using a new Liver Index (LI) formula. Four isoproteic (45% DM) and isolipidic (20% DM) diets were compared: a control, plant-based diet (CV) and other three test ones where 40% of a plant protein-rich ingredient mixture was replaced by Hermetia illucens (H40) or poultry by-product (P40) meals alone or in combination (H10P30). The trials lasted 12 and 18 weeks for sea bream and sea bass, respectively. The results so far ob-tained highlighted species-specific differences in the physiological response to dietary changes. In sea bream, the biochemical and histological responses suggest favorable physiological status and liver health, with higher serum cholesterol (CHO) and triglyceride (TAG) levels and moderate hepatocyte lipid accumulation with the H10P30 diet compared to CV (p<0.05). In sea bass, all diets resulted in elevated serum TAG levels and liver lipid accumulation particularly in fish fed the P40 one (p<0.05) which resulted in the highest LI, coupled with higher frequency of severe lipid accumulation, hypertrophy, cord loss, peripheral nuclei displacement and pyknosis. In conclusion sea bream well adapted to the test diets, while sea bass exhibited altered hepatic lipid metabolism leading to incipient liver steatosis, likely due to the high lipid content of the diets including the insect and poultry meals. The LI developed in this study proved to be a reliable tool for assessing the effects of dietary changes on liver health of sea bream and sea bass, consistent with biochemical and histological findings.

Inflammation is an essential protective response against injury or infection. Physiological inflammation eliminates the pathogen, promotes tissue repair and healing. An exaggerated, out of control inflammation, however, can become pathological. Inflammation can generate secondary cell damage, inflame the vessels (endothelitis), activate coagulation processes. Among these pathogenetic factors (cell damage, inflammation, endothelitis, coagulopathies), self-amplification mechanisms can be created, spreading beyond the initial site, up to Multiple Organ Failure (MOF) and host death. If the inflammation does not resolve in a physiological way, the remodeling of the tissues can be maladaptive and lead to the onset of chronic inflammatory degenerative diseases. Diseases such as sepsis, burns, polytrauma, severe forms of influenza or COVID-19, are characterized by a condition of hyperinflammation, associated with a condition of immunosuppression. The initial events triggered by the pathogen (cell damage, interferon response in the case of viruses) ignite the inflammation by activating the inflammasome, the transcription factor NFkB, the release of pro-inflammatory eicosanoids (Prostaglandins, Leukotrienes, Thromboxanes) by neutrophils and macrophages. Hence, the cells of the innate immune system produce pro-inflammatory cytokines. Indeed, the ‘’eicosanoid storm’’ precedes the ‘’cytokine storm’’. Eicosanoids are a group of potent endogenous lipid mediators derived from omega-6 fatty acids Arachidonic Acid (AA). Eicosanoids include a group of molecules with pro-inflammatory (Prostaglandins, Leukotriens) and pro-coagulant (Thromboxanes) action. In addition, Arachidonic Acid (AA) is the source of Lipoxins (LXs). Lipoxins belong to a group of molecules collectively referred to as specialized pro-solving mediators (SPMs) which also include molecules derived from w-3 eicosapentaenoic acid (EPA): Resolvins (ReV-E sieres) and w-3 docohexanoic (DHA): Resolvins D-series (ReV D-series); Protectins (PTs); Maresins (MaRs). SPMs are important for the resolution phase of inflammation to take place properly. Their deficiency could be involved in both acute uncontrolled inflammation and chronic inflammation. The active regulation of the acute inflammatory process, integrating the precursors of Specialized Pro-resolving Mediators (SPMs), such as ⍵-6 and ⍵-3 in balanced ratio, or the SPMs themselves, could be a complementary therapeutic approach useful for taming the "storm of cytokines '' which characterizes exaggerated forms of inflammation. ⍵-3 and ⍵-6 are part of already widely used, readily available, inexpensive and safe supplements. Resolvins have already been included in clinical trials for various other inflammatory diseases (eye diseases, periodontal diseases).

Background: Spinal schwannomas and meningiomas are the most common spinal cord benign tumors in adults and total excision is the goal of the treatment. The traditional surgical approach is performed by total laminectomy, but recently unilateral hemilaminectomy has been recognized as a valuable surgical alternative. We report the clinical results of patients affected by spinal schwannoma and meningioma in whom total laminectomy or unilateral hemilaminectomy were performed. Material and Methods: A retrospective study of patients who underwent resection of spinal meningioma or schwannoma by laminectomy or unilateral hemilaminectomy approaches in our Institute from January 2013 to January 2023 was made. The baseline data of these patients, operative approach and postoperative outcome were compared. Results: The study was performed on 41 patients with mean age of 62.5 ±14.6 years. Our series included 24 (59%) cases of schwannomas and 17 (41%) cases of meningiomas, with a prevalent location in the thoracic spine. The average schwannomas volume was 3,6 ±2,7 cm3, whereas the average meningiomas volume was 1.1 ±0.5 cm3. Total excision was achieved in all cases. Operative time of schwannomas was longer (p=0.001) respect to meningiomas with higher intra-operative blood loss (p=0.000). Total laminectomy approach was performed in 24 out of 41 patients (59%) and unilateral hemilaminectomy approach in 17 out of 41 (41%) patients. Unilateral hemilaminectomy was associated with shorter postoperative bed rest (p=0.003), shorter hospitalization (p=0.028) and lower postoperative pain (p=0.02) respect to total laminectomy. Conclusions: Both spinal schwannomas and spinal meningiomas in various size can be safely and effectively treated with unilateral hemilaminectomy approach. This approach grants more advantages compared with standard total laminectomy, including shorter postoperative bed rest, shorter hospitalization and reduced postoperative pain.

Severe COVID-19 disease is characterised by an exaggerated inflammatory response, called cytokine storm, accompanied by a condition of immune depression. Even sepsis is characterised by an exaggerated inflammatory response, called SIRS (Systemic Inflammatory Response Syndrome), accompanied by a condition of immune depression called CARS (compensatory anti-inflammatory response syndrome). Clinical studies reveal that most sepsis patients who did not die during the hyper inflammatory response (SIRS) subsequently succumbed to the condition of immune depression (CARS). Severe acute pancreatitis begins with local inflammation that induces systemic inflammatory response syndrome (SIRS), accompanied and followed by a compensatory anti-inflammatory response (CARS). In COVID-19 disease, the male response to SARS CoV-2 virus is typically characterised by a robust inflammatory response. Instead, a cell-mediated immune response is dominant in women. This means that the male sex tends to have a more robust hyper inflammatory response than the female one. Furthermore, in women the condition of immune depression is less represented, therefore they are more protected. Sepsis, severe acute pancreatitis and COVID-19 disease evolve between two fundamental aspects: hyper inflammation and immunodepression. The experience gained over years of studies of sepsis and severe acute pancreatitis suggests that therapies should be differentiated according to the evolutionary stage of the disease. The goal is to save the lives of most patients with COVID-19 disease. The identification of critical points, suitable for designing the windows of therapeutic opportunity, may allow the use of therapeutic interventions, in the COVID-19 disease, which are effective (there are no approved drugs yet), safe (without significant side effects), targeted (based on the evolutionary phase of the disease) personalized, (based on sex, co-morbidities, age, etc.) and timely (based on signs, symptoms, laboratory parameters and instrumental investigations).

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early and progresses with age. B cells play a central role in this process, contributing to cytokine production, defective regulatory functions, and abnormal immunoglobulin production, even in the central nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ B cells, are effective for both relapsing-remitting (RR) and progressive-relapsing (PR) MS. While effective against MS symptoms and lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce the immune response to COVID-19 vaccination. By using high-parameter flow cytometry, we examined the antigen-specific (Ag+) immune response six months post-third COVID-19 mRNA-vaccination in MS patients with RR and PR forms on aCD20 therapy. Despite lower Ag+ B cell responses and lower levels of anti-SARS-CoV2, both total and neutralizing antibodies, RR and PR patients developed strong Ag+ T cell responses. We observed similar percentages and numbers of Ag+ CD4+ T cells and high proportion of Ag+ CD8+ T cells, with slight differences in T cell phenotype and functionality, that however suggested the presence of differences in immune responses driven by age and disease severity.

To evaluate whether the extent of cardiac damage in severe aortic stenosis (AS) might be associated with the occurrence of conduction system disorders after TAVI. A total of 153 symptomatic patients with severe AS who had a TAVI were categorized before the procedure according to the extent of cardiac damage: stage 1 (13.5%): no or LV damage; stage 2 (58.8%): left atrial/mitral valve damage, atrial fibrillation (AF); stage 3 (27.7%): low-flow state, pulmonary vasculature/tricuspid valve/RV damage. After TAVI, 34% of patients exhibited LBBB and 10% high-degree atrioventricular block (HD-AVB). No patient in group 1 developed HD-AVD whereas new LBBB was frequent in groups 2 and 3. Twenty-one patients presented with resolutive paroxysmal AF with a higher rate for each group increment (group 1: n=0, 0%; group 2: n=11,15.7%; group 3: n=10, 30.3%) (p = 0.012). Patients in group 3 had the higher rate of permanent pacemaker implantation (PPMI) (group 1: n=1, 6.3%; group 2: n=7,10%; group 3: n=9, 27.3%) (p=0.012). No patient in group 1 died during the hospital stay. In conclusion, cardiac damage staging of AS might help identify patients at higher risk of conduction disorders and PPMI requirement after TAVI.

Securing funding is a critical yet complex task for organizations and individuals. This study presents an innovative chatbot designed to streamline the process using advanced Natural Language Processing (NLP) techniques and, specifically, a Retrieval-Augmented Generation (RAG) pipeline optimized for real-world applications. Our chatbot assists users in identifying suitable public tenders for financial support through natural language queries and a comprehensive public data database. The chatbot operates in a two-stage interaction model, initially providing summarized tender information for exploratory brainstorming, followed by detailed data upon user selection. A custom filtering mechanism ensures that the user interface elements responsible for swapping the interaction stages are consistent with the responses generated by the conversational agent. Human-evaluation tests demonstrated an average accuracy of 90.4% in document retrieval, with an average of 2.11 interactions required to find a specific tender. User satisfaction, rated on a scale of 1 to 5, averaged 3.14 (±1.73), indicating generally positive user experience with room for improvement. This approach addresses challenges of relevance, accuracy, and conversational flow, resulting in a reliable chatbot that simplifies the process of finding funding opportunities.

Alterations in the composition and diversity, metabolism, and products of the microbiome, and of the gut microbiome (GM), have been shown to be closely associated with the onset and progression of many human diseases, including cancer (i.e. hematological neoplasms). Acute lymphoblastic leukemia (ALL) is the most common form of childhood malignancy. Affected cases present typical alterations of GM, followed by inflammation, which contribute to its progression, response to therapy, as well as possible relapses. Recent evidence also reports that GM influences the development and functions of the newborn's hematopoietic system through the process of developmental programming during fetal life, as well as its susceptibility to the onset of onco-hematological pathologies, namely ALL. Furthermore, in children with ALL, GM has been found to vary in composition, variety, and functions during the clinical stages of ALL, and such variation may influence and predict the complications and prognosis of ALL after chemotherapy treatment or stem cell hematopoietic transplant. Here, we suggest some therapeutic strategies, which can be applied at two levels of intervention to recover the microbiome, and consequently prevent/delay ALL or arrest its progression.

To assess the degree to which it has met its commitments under the Paris Agreement, Morocco is called upon to carry out carbon assessments and transparent evaluations. Within the forestry sector, little is known about the role of Morocco’s forests in contributing to carbon uptake. With this aim, we applied for the first time in literature the 3-PG model to Cedrus atlantica ((Endl.) Manetti ex Carrière, 1855), which represents about 131.800 ha of Morocco’s forest area (i.e. Azrou forest). Through the Differential Evolution - Markov Chains (DE-MC) we tested and assessed the sensitivity and calibrated the 3-PG model. This process-based model provided significant results regarding the carbon sequestration capacity. The results showed the following: i- Parameters related to stand properties, canopy structure, and processes, as well as biomass partitioning, are the most important or sensitive for the performance of the model; ii- The DE-MC method optimized the values of the 3-PG parameters which was confirmed by the means of Gelman-Rubin convergence test; iii- According to the predictions of the calibrated 3-PG, the Net Primary Production in the pure Azrou forest varies between 0.32 and 7.88 tC.ha−1.yr−1, it is equal in average to 4.9 tC.ha−1.yr−1, which given the total area corresponds to 7078 tC.yr−1.

In the last decades bioresorbable and biodegradable polymers have gained a very good reputation both in research and in industry thanks to their unique characteristics. They are, indeed, able to ensure high performances and biocompatibility, at the same time avoiding post-healing surgical interventions for devices removal. In the medical device industrial use of such biopolymers, it is widely known that product formulation and manufacturing need to follow specific procedures in order to ensure both proper mechanical properties and desired degradation profile. Moreover, also the sterilization method is crucial and its impact on physical properties is generally underestimated. In this work we focused our attention on the effect of different terminal sterilization methods on two commercially available poly(L-lactide-co-ε-caprolactone) with equivalent chemical composition (70% PLA and 30% PCL) and relatively similar initial molecular weight, but different chains arrangement and crystallinity. Results obtained show that crystallinity plays a key role, helping in preserving the narrow distribution of chains and, as a consequence, defined physical properties. These statements can be used as guidelines for a better choice of the most adequate biodegradable polymers in the production of resorbable medical devices.

Detection of human movement requires lightweight, flexible systems to detect mechanical parameters (like strain and pressure) not interfering with user activity, and that he/she can wear comfortably. In this work we address such multifaceted challenge with the development of smart garments for lower limb motion detection, like a textile kneepad and anklet in which soft sensors and readout electronics are embedded for detecting movement of the specific joint. Stretchable capacitive sensors with a three-electrode configuration are built combining conductive textiles and elastomeric layers, and distributed at knee and ankle. They show an excellent behavior in the ~30% strain range, hence the correlation between their responses and the optically tracked Euler angles is allowed for basic lower limb movements. Bending during knee flexion/extension is detected, and it is discriminated from any external contact by implementing in real time a low computational algorithm. The smart anklet is designed to address joint motion detection in and off the sagittal plane. In this work, ankle dorsi/plantar flexion, adduction/abduction, and rotation are retrieved. Both smart garments show a high accuracy in movement detection, with a RMSE less than 4° in the worst case.

Cestrum parqui L'Herit. (Solanaceae family) is a species of forest shrub, self-incompatible and specialized in pollination, widespread in the subtropical area of the planet and now widely dis-tributed also in the Mediterranean area. The constituents of its leaves have antimicrobial, anti-cancer, insecticidal, antifeedant, and herbicidal properties. The spread of this species represents a valuable source of compounds with high biological value. Research on potential uses, under-standing of the nutritional and functional composition, and applications of C. parqui extracts is important and very promising for its commercial use. To date, there are some reports on the potential applications of C. parqui extracts as selective natural pesticides and for their potential phytotoxic role. Scientific knowledge and the use of extraction techniques for these components are essential for commercial applications. This article summarizes the research and recent studies available on the botany, phytochemistry, functional properties, and commercial applications of C. parqui as a biopesticide.

The rapid evolution of Next Generation Sequencing in clinical settings and the resulting challenge of variants interpretation in the light of constantly updated information, requires robust data management systems and organized approaches to variant reinterpretation. In this paper, we present iVar: a freely available and highly customizable tool provided with a user-friendly web interface. It represents a platform for the unified management of variants identified by different sequencing technologies. iVar accepts, as input, VCF files and text annotation files and elaborates them, optimizing data organization and avoiding redundancies. Updated annotations can be periodically re-uploaded and associated to variants as historicize attributes. Data can be visualized through variant-centered and sample-centered interfaces. A customizable search functionality can be exploited to periodically check if pathogenicity related data of a variant are changed over time. Patient recontacting ensuing from variant reinterpretation is made easier by iVar through the effective identification of all patients present in the database and carrying a specific variant. We tested iVar by uploading 4171 VCF files and 1463 annotation files, obtaining a database of 4166 samples and 22569 unique variants. iVar has proven to be a useful tool with good performances for collecting and managing data from medium-throughput

Understanding the dynamics of Organic Carbon mineralization is fundamental in forecasting biosphere to atmosphere Net Carbon Ecosystem Exchange (NEE). With this perspective, we developed 3D-CMCC-PSM, a new version of the hybrid Process Based Model 3D‐CMCC FEM where also heterotrophic respiration (R_h) is explicitly simulated. The aim was to quantify NEE as a forward problem, by subtracting Ecosystem Respiration (R_eco) to Gross Primary Productivity (GPP). To do so, we developed a simplification of the Soil Carbon dynamics routine proposed in DNDC [1]. The method calculates decomposition as a function of soil moisture, temperature, state of the organic compartments, and relative abundance of microbial pools. Given the pulse dynamics of soil respiration, we introduced modifications in some of the principal constitutive relations involved in phenology and littering sub-routines. We quantified the model structure related uncertainty in NEE, by running our training simulations over 1000 random parameter-sets extracted from parameters distributions expected from literature. 3D-CMCC-PSM predictability was tested on independent time series for 6 Fluxnet sites. The model resulted in daily and monthly estimations highly consistent with the observed time series. It showed lower predictability in Mediterranean ecosystems, suggesting that it may need further improvements in addressing evapotranspiration and water dynamics.

Background: There is a growing interest in TKA components alignment, especially around the kinematic technique, which aims at reestablishing the alignment of the native knee. However, the practical application of this technique has some limitations; (2) Methods: A series of consecutive full weight-bearing lower limbs radiographs performed in our Hospital without signs of osteoarthritis, post-traumatic deformities, and any previous surgical procedure (e.g. any joint replacement , osteotomy, anterior cruciate ligament reconstruction) were included. Several radiological parameters as the bisector line were measured by three members of our orthopedic unit and were then used to assess the inter-observer reliability.; (3) Results: 110 radiographic images belonging to 59 patients (both legs for 51 patients and one leg for 8 patients) were finally included in the present analysis. The bisector of the trochelar groove was perpendicular to the femoral joint line (mean 89.4°).; (4) Conclusions: The main finding of the current study was that the new anatomic landmark investigated, the bisector of the trochlear groove, was perpendicular to the femoral joint line viewed in the AP weight-bearing radiograph of the entire lower limbs of the healthy knee and therefore could potentially simplify the achievement of the kinematic alignment during a TKA procedure.

Background: The validation of laser usage during laparoscopic procedures, notably by Camran Nezhat in the late 1980s, has been significant. Lasers offer precision and depth control in tissue vaporization without bleeding. Surgical intervention remains central in managing endometrio-sis-associated pain and infertility, especially for patients unresponsive to hormonal therapy. Methods: This retrospective cohort study included 200 patients with SPE who underwent laparo-scopic laser vaporization. Surgery was performed using a CO2 laser, and histological confirma-tion of endometriosis was obtained for all cases. Pain scores and SF-36 questionnaire domains were assessed preoperatively and postoperatively. Fertility outcomes were evaluated among pa-tients desiring pregnancy. Results: Significant improvements in pain score and SF-36 questionnaire domains were ob-served postoperatively (p-value

Peritoneal dialysis (PD) is a home-based efficacious modality for replacement of renal function in end-stage kidney failure patients but is still under-prescribed. A major limitation is the durability of the dialytic technique. Continuous exposure of the peritoneum to bioincompatible conventional glucose-based solutions is thought to be the main cause of long-term morpho-functional peritoneal changes eventually resulting in ultrafiltration failure. Poor PD solution biocompatibility is primarily related to the high glucose content, which is not only detrimental to the peritoneal membrane but has many potential metabolic side effects. To improve the clinical outcome and prolong the survival of the treatment, PD-related bioincompatibility urgently needs to be overcome. However, combining dialytic and osmotic efficacy with a satisfactory biocompatible profile proves quite difficult. New approaches targeting the composition of the PD solution include replacement of glucose with other osmotic agents and the addition of cytoprotective or osmo-metabolic compounds. Other strategies include infusion of mesenchymal cells or the administration of orally active agents. In the present article we review the current evidence on efforts to improve the biocompatible and functional performance of PD, focusing on studies performed in vivo (animal models of PD, human subjects on PD).

Smoker’s paradox usually refers to the common observation of a favourable outcome of smoker patients in acute myocardial infarction. The interpretation of this phenomenon is still controversial and not fully explained. We aimed at assessing whether smoking could be associated with mortality in a large cohort of prospectively enrolled patients with ST segment elevation myocardial infarction (STEMI) referred to primary percutaneous coronary intervention (pPCI). From April 2006 to December 2018 a population of 2456 STEMI patients treated with primary PCI were prospectively enrolled in the MATRIX registry. Ischemic time, clinical, demographics, angiographic data and 1-year follow-up were collected. Among 2546 patients admitted with STEMI 1007 (41%) were current smokers. Smokers were 10 years younger and had lower crude in-hospital and 1-year mortality (1.5% vs 6%, p&lt;0.0001 and 5% vs 11%, p&lt;0.0001), shorter ischemic time (203 [147-299] vs 220 [154-334] minutes, p=0.002) and shorter decision time (60 [30-135] vs 70 [36-170] minutes, p=0.0063). After propensity-matching, age, cardiogenic shock and low TIMI score were associated with in-hospital mortality, while smoking habit was still associated with reduced mortality. Smoking was also associated with reduced death rate at 1-year follow-up (HR 0.54, 95% CI [0.37 - 0.78]; p&lt;0.001). Our data show a protective link between smoking status and mortality in patients with STEMI, the so called “smoker’s paradox”. This could be explained not only by the shorter ischemic time and younger age of the smoking population but also by a specific pathogenetic effect of smoking underlying the onset of STEMI and response to therapies.

Introduction Emergency laparotomy is a surgical procedure associated with significantly higher mortality rates compared to elective surgeries. Awake laparotomy under neuraxial anaesthesia has recently emerged as a promising approach in abdominal surgery to improve patient outcomes. This study aims to evaluate the feasibility and potential benefits of using lumbar spinal anaesthesia as the primary anaesthetic technique in emergency laparotomies. Methods We conducted a case series involving 16 patients who underwent emergency laparotomy for bowel ischemia, perforation, or occlusion. Lumbar spinal anaesthesia was employed as the main anaes-thetic technique. We analysed patient demographics, clinical characteristics, intraoperative details, and postoperative outcomes. The primary outcome measures included the adequacy of postoper-ative pain control, the incidence of postoperative complications, and mortality rates. Results Among the 16 patients, adequate postoperative pain control was achieved, with only 2 patients requiring additional analgesia. Postoperative complications, including sepsis, wound dehiscence, and pneumonia, were observed in 7 patients (44%). The observed mortality rate was relatively low at 6% (1 patient). Notably, conversion to general anaesthesia was not necessary in any of the cases, and no early readmissions were reported. Discussion Our findings highlight the feasibility and potential benefits of using neuraxial anaesthesia in emergency laparotomies. The observed low mortality rate and the avoidance of conversion to general anaesthesia suggest that lumbar spinal anaesthesia may be a useful alternative in emer-gency settings. However, the occurrence of postoperative complications in 44% of patients indi-cates the need for cautious patient selection and close monitoring. Further research with larger sample sizes is warranted to fully elucidate the efficacy, safety, and potential impact of this tech-nique on patient outcomes in emergency laparotomies.

CPPU (Forchlorfenuron (1-(2-chloropyridin-4-yl)-3-phenylurea), a synthetic cytokinin, is extensively used to enhance fruit size and quality size in several crops, including kiwifruit. This study examines the effects of three different CPPU application strategies on two different crop loads on the main fruit quality parameters. Our results show that a two application of CPPU significantly increased fruit weight, especially under standard crop load conditions, due to better resource allocation. Fruit firmness improved with 2 and 3-times CPPU applications, likely due to enhanced cell wall development, and was consistently affected by crop load, with higher loads resulting in softer fruits. CPPU applied twice did not significantly influence soluble solids content. This parameter was instead significantly influenced by the crop load, with standard load fruit showing higher sugar accumulation. Fruit dry weight showed similar trends, with CPPU having a more pronounced effect under standard crop loads. Overall, CPPU proved to be a cost-effective strategy to enhance fruit quality, particularly in orchards with standard crop loads, by balancing yield and sugar content.

The years 2021 and 2022 showed that maritime logistics are prone to interruptions. Especially the ports turned out to be bottlenecks with long queues of waiting vessels. This leads to the question of whether this can be (at least partly) mitigated by means of better and more flexible terminal operations. Digital Twins have been in use in production and logistics to increase flexibility in operations and are considered a reasonable fit. They are suitable for real-time data integration to support decision-making. However, the true potential of Digital Twins to enhance terminal operations still needs to be further investigated. A Delphi study is conducted to explore operational pain points, best practices to counter them, and how these best practices can be supported by Digital Twins. A questionnaire with 16 propositions is developed, and a panel of 17 experts is asked for their degrees of confirmation for each. The results indicate that today’s terminal operations are far from ideal and leave space for optimisation. The experts see great potential in analysing past working shifts data to identify reasons for poor terminal performance. Moreover, they agree on the proposed best practices and support the use of aiding IT solutions.

This retrospective observational study describes the results of an ad-hoc designated prevention protocol aimed at containing the spread of the scabies infestation among healthcare workers (HCWs) of a large University Hospital in Italy. The outbreak started on October 2022 and a preventive protocol was set up thanks to a multidisciplinary approach. HCWs at high scabies risk were defined as subjects working in UOs with more than five confirmed cases of scabies, close contacts of a confirmed case of scabies, or HCWs with signs and symptoms of the disease. All cases of at high scabies risk underwent a dermatological examination and the infested HCWs were suspended from work until definitive healing. Mass prophylactic treatment was established for all HCWs working in UOs with more than five confirmed cases of scabies. Until March 2023, out of 183 screening dermatological examinations, 21 (11.5%) were diagnostic for scabies. We obtain a prevalence of scabies of 2.6% (21/800) and a duration of the outbreak of 14.7 weeks. Statistical analysis shows a significant association between scabies and being a nurse and have an allergy to dust mites. We obtained a low prevalence of scabies infection, limiting the duration of the outbreak and the related economic burden.

This study evaluated the effect of pig diet supplementation with an Olea europaea L. extract on the muscle fatty acid composition. Ten commercial hybrid pigs (Large White x (Landrace x Duroc)) were randomly assigned to two experimental treatments and fed either a standard diet (C) or diet with olive leaves extract (OL). For 90 days, the OL group received the olive leaf extract (300 mg/head/day), which mainly comprises oleuropein diglucoside, luteolin-7-glucoside, and verbascoside. The phenolic content, antioxidant activity, bioactive molecules’ characterization, and the fatty acids profile of meat and diet were performed. The results indicated that while the OL supplementation did not significantly alter the overall chemical composition of the meat or the pigs' performance, it did modify the lipid profile of the meat. The OL diet results in a significant reduction in SFA and an increase in oleic acid in meat, which correspondingly elevates the total MUFA content. Dietary treatment reduced the sum of n-6 PUFA in the meat of the OL group, and resulted in a significantly lower n-6/n-3 PUFA ratio. Therefore, these findings suggest that incorporating olive leaf extract into the pig diet enhances the nutritional and functional quality of the meat by improving its fatty acid profile.

Frequent and excessive consumption of alcohol, be it episodic or sustained misuse, ranks among the top causes of mortality globally. This comprehensive analysis seeks to elucidate how alcohol misuse precipitates death, with a particular focus on associated cardiac anomalies. Notably, the phenomenon of "Holiday Heart Syndrome," linked to binge drinking, is recognized for inducing potentially fatal cardiac arrhythmias. Moreover, persistent alcohol consumption is implicated in the development of alcoholic cardiomyopathy, a condition that underlies heart failure and arrhythmic disturbances of the heart. Additionally, individuals undergoing withdrawal from alcohol frequently exhibit disruptions in normal heart rhythm, posing a risk of death. This review further delves into additional alcohol-related mortality factors, including the heightened likelihood of hypertension, cerebrovascular accidents (strokes), and the connection between excessive alcohol use and Takotsubo syndrome.

In the longtime challenge of identifying specific, easily-detectable and reliable biomarkers of Idiopathic Pulmonary Fibrosis (IPF), bronchoalveolar lavage fluid (BALF) proteomics is providing interesting new insights into its pathogenesis. To the best of our knowledge, the present study is the first shotgun proteomic investigation of EVs isolated from BALF of IPF patients. Our main aim was to characterize the proteome of the vesicular component of BALF and to explore its individual impact on the pathogenesis of IPF. To this purpose, ultracentrifugation was chosen as EVs isolation technique and their purification was assessed by TEM, 2DE and LC-MS/MS. Our 2DE data and scatter plots showed considerable differences between the proteome of EVs and that of whole BALF and of its fluid component. Analysis of protein content and protein functions evidenced that EV proteins are predominantly involved in cytoskeleton remodeling, adenosine signaling, adrenergic signaling, C-peptide signaling and lipid metabolism. Our findings may suggest a wider system involvement in the disease pathogenesis and support the importance of pre-fractioning of complex samples, like BALF, in order to let low-abundant proteins-mediated pathways to emerge.

Background: Dimethylfumarate (DMF) is an orally administered fumaric acid esters (FAE) approved for plaque psoriasis. The most represented adverse event for incidence reported in all studies regarding multiple sclerosis and psoriasis treatment was flushing followed by gastrointestinal and lymphopenia (AEs). We report our experience on effective management strategies in patients with dimethylfumarate fushing induced. Methods: The purpose of our study is addressed to propose feasibles strategies able to mitigate adverse events developing in order to improve therapy compliance. We report our real life experience of 20 patients affected by mild to moderate plaque psoriasis in treatement with DMF 10 male and 10 female, with 45,4 years old mean age underwent to a reducing a daily dosage regimen with DMF from 120 mg to 30 mg tablets. Patients experience flushing around 30-45 minutes after assuming the medication.per day. Results: Patients achieving a good adherence and efficacious results in terms of PASI 75 reduction after 16 weeks of treatment. Conclusion: DMF is efficacious and has a favorable benefit–risk profile, thanks to the possibility of implementing posology strategies in order to optimize adherence to the therapy.

Scanning magnetic microscopy is a new tool that has recently been used to map magnetic fields with good spatial resolution and field sensitivity. This technology has great advantages over other instruments; for example, its operation does not require cryogenic technology, which reduces its operational cost and complexity. Here, we describe the construction of a customizing scanning magnetic microscope based on commercial Hall-effect sensors at room temperature that achieves a spatial resolution of 200 µm. Two scanning stages on the x- and y-axes of precision, consisting of two coupled actuators, control the position of the sample, and this microscope can operate inside or outside a magnetic shield. We obtained magnetic field sensitivities better than 521 nT_rms/√Hz between 1 and 10 Hz, which correspond to a magnetic momentum sensitivity of 9.20 × 10^–10 Am². In order to demonstrate the capability of the microscopy, polished thin sections of geological samples, samples containing microparticles and magnetic nanoparticles were measured. For the geological samples, a theoretical model was adapted from the magnetic maps obtained by the equipment. Vector field maps are valuable tools for the magnetic interpretation of samples with a high spatial variability of magnetization. These maps can provide comprehensive information regarding the spatial distribution of magnetic carriers. In addition, this model may be useful for characterizing isolated areas over samples or investigating the spatial magnetization distribution of bulk samples at the micro and millimeter scales. As an auxiliary technique, a magnetic sweep map was created using Raman spectroscopy; this map allowed the verification of different minerals in the samples. This equipment can be useful for many applications that require samples that need to be mapped without a magnetic field at room temperature, including rock magnetism, the nondestructive testing of steel materials and the testing of biological samples. The equipment can not only be used in cutting-edge research but also serve as a teaching tool to introduce undergraduate, master's and Ph.D. students to the measurement methods and processing techniques used in scanning magnetic microscopy.

Abstract Purpose Despite a considerable amount of literature on dual-energy-CT(DECT) iodine uptake of the head and neck, the physiologic iodine uptake of this region has not been defined yet. This study aims to establish reference values for the iodine uptake of healthy organs to facilitate clinical application. Material and Methods: Consecutive venous DECT scans of head and neck were reviewed, and unremarkable exams were included (n=617). 35 region of interest measurements were performed in 16 anatomical regions. Iodine uptake was compared among different organs/tissues and subgroup analysis was performed (male [n=403] vs female [n=214]; young [n=207] vs middle-aged [n=206] vs old [n=204]; normal weight [n=314] vs overweight [n=196] vs obese [n=107]]). Results: Overall mean iodine uptake values ranged between 0.5 and 9.4mg/ml. Women showed higher iodine concentration in the cervical vessels and higher uptake for the parotid gland, masseter muscle, submandibular glands, sublingual glands, palatine tonsils, tongue body, thyroid gland, and the sternocleidomastoid muscle than men (p0.04). With increasing age, intravascular iodine concentrations increased as well as iodine uptake for cerebellum and thyroid gland, while values for tongue and palatine tonsils were lower compared to younger subjects (p0.03). Iodine concentrations for parotid glands and sternocleidomastoid muscles decreased with higher BMI (p0.004), while normal-weighted patients showed higher iodine values inside the jugular veins, other cervical glands, and tonsils versus patients with higher BMI (p0.04). Conclusion: Physiologic iodine uptake values of cervical organs and tissues show gender-, age-, and BMI-related differences, which should be considered in clinical routine of head and neck DECT.