Amyloids result from the aggregation of several unrelated proteins, due to either specific mutations or promoting intra- or extra-cellular conditions. Structurally, they are rich in intermolecular β-sheets and are the causative agents of several diseases, both neurodegenerative and systemic. It is believed that the most toxic species are small aggregates, referred to as oligomers, rather than the final fibrillar assemblies. Their mechanisms of toxicity are mostly mediated by aberrant interactions with the cell membranes, with resulting derangement of membrane-related functions. Much effort is being put in the search for natural antiamyloid agents, and/or in the development of synthetic molecules. Actually, it is well documented that the prevention of amyloid aggregation results in several cytoprotective effects. Here, we portray the state of the art in the field. Several natural compounds are effective antiamyloid agents, notably tetracyclines and polyphenols. They are generally non-specific, as documented by their partially overlapping mechanisms, and the capability to interfere with the aggregation of several unrelated proteins. Among rationally designed molecules, we mention the prominent examples of β-breakers peptides, whole antibodies and fragments thereof, and the special case of drugs contrasting transthyretin aggregation. In this framework, we stress the pivotal role of the computational approaches. When combined with biophysical methods, in several cases they have helped clarify in detail the protein/drug modes of interaction, which make it plausible that more effective drugs will be developed in the future.

According to the French Agency for Food, Environmental and Occupational Health & Safety, electromagnetic hypersensitivity affects more than 3 million people in France, and headaches are a very frequent cause of complaint in electrohypersensitive patients, to the point of dominating the clinical picture. These headaches share characteristics with migraine pathology, and clinical improvement with anti-migraine therapy has led us to consider that the headache in the electrohypersensitive patient may be a variant of the migraine disease mediated by the TRPA1 receptor, which if confirmed, would offer effective therapeutic possibilities to relieve the electrohypersensitive patient.

Tadalafil is a selective phosphodiesterase type-5 (PDE5) inhibitor that is approved for the treatment of men with erectile dysfunction (ED) and/or benign prostate hyperplasia (BPH) associated symptoms. Besides its classical actions on PDE5 within the genitourinary tract, where the specific enzyme expression is maximal, it may exert different systemic effects. This is mainly due to the pleiotropic distribution of PDE5 enzyme throughout human (and animal) body, where it can exert protective effects in different clinical conditions. Recently, it has been demonstrated that tadalafil may display novel actions on androgen receptor (AR) expression and activity, cytochrome P19a1 (Cyp19a1) and estrogen receptor β (ERβ) expression in different in vitro systems, such as adipose, bone and prostate cancer cells where it can act as a selective modulator of steroid hormone production. This may determine novel potential mechanism(s) of control in pathophysiologic pathways. In this review we summarize basic research and translational results applicable to the use of tadalafil in the treatment of different clinical conditions.

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. The changes in the correct visual acuity and the reduction in geographic atrophy progression were evaluated. Several new drugs have shown some promising results, including those targeting the complement cascade and agents called neuroprotective. The action potential of the two groups of drugs is to block the complement cascade model for immunomodulating agents, and prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. To the best of knowledge, and after extensive studies on the matter, there are still many investigations to be carried out on dry AMD in collaboration between researchers. They will have to identify truly effective molecules, understand the practical potential of pluripotent stem cells, and refine gene therapies. Only in-depth clinical trials will be able to allow the most appropriate and personalized treatments for each dry AMD patient.

The work consisted in identifying possible effects from heavy metals (HMs) pollution due to waste disposal activities in three potentially polluted sites located in Basilicata (Italy), where a release of pollutants with values over the thresholds allowed by the Italian legislation was detected. The potential variations in the physiological efficiency of vegetation have been analyzed through the multitemporal processing of satellite images. In detail, Landsat 5 Thematic Mapper (TM) and Landsat 8 Operational Land Imager (OLI) images were used to calculate the Normalized Difference Vegetation Index (NDVI) trend over the years. Then, the multitemporal trends were analyzed using the median of Theil-Sen, a non-parametric estimator particularly suitable for the treatment of remote sensing data, being able to minimize the outlier effects due to exogenous factors. Finally, the subsequent application of the Mann-Kendall test on the trends identified by Theil-Sen slope allowed the evaluation of trends significance and, therefore, the areas characterized by the effects of contamination on vegetation. The application of the procedure to the three survey sites led to the exclusion of the presence of significant effects of HMs contamination on the vegetation surrounding the sites during the years of waste disposal activities.

Sexual Issues played a significant role in Judaism’s engagement with its Greco-Roman world. This paper will examine that engagement in the Hellenistic Greco-Roman era to the end of the first century CE. In part sexual issues were a key element of demarcation between Jews and the wider community, alongside such matters as circumcision, food laws, sabbath keeping and idolatry. Jewish writers, such as Philo of Alexandria, make much of the alleged sexual profligacy of their Gentile contemporaries, not least in association with wild drunken parties, same-sex relations and pederasty. Jews, including the emerging Christian movement, claimed the moral high ground. In part, however, matters of sexuality were also areas where intercultural influence is evident, such as in the shift in Jewish tradition from polygyny to monogyny, but also in the way Jewish and Christian writers adapted the suspicion and sometimes rejection of passions characteristic of some popular philosophies of their day, seeing them as allies in their moral crusade.

According to the Water Framework Directive, the Ecological Flow (Eflow) is assumed to be the minimum water discharge required to achieve and maintain the environmental objectives of “good quality status” in a natural water body. It is highly recognized that, the hydrological regime of natural flow plays a primary and crucial role influencing the physical conditions of habitats, which in turn determines the biotic composition and sustainability of aquatic ecosystems. Furthermore, the simple assumption to supply a minimum instream during dry periods is not enough any longer in order to protect the river environment. The recent hydro-ecological understanding states that all flow components might be considered as operational targets for water management, starting from base flows (including low flows) to high and flood regimes in terms of magnitude, frequency, duration, timing and rate of change. Several codes have been developed and applied on different case studies in order to define common tools to be implemented for the Eflow assessment. The study proposes the application of the Indicators of Hydrologic Alteration methodology (IHA by TNC) coupled to the valuation of the Index of Hydrological Regime Alteration (IARI by ISPRA) as an operative tool to define the ecological flow in each monitoring cross section to support the sustainable water resources management and planning. The case study of Agri River, in Basilicata (Southern Italy) is presented. The analyses have been carried out on monthly discharge data derived applying the HEC-Hydrological Modelling System at the basin scale using the daily rain data measurements obtained by the regional rainfall gauge stations and calibrated through the observed inlet water discharge registered at the Lago del Pertusillo reservoir station.

In the last two decades, the discovery of various pathways involved in renal cell carcinoma (RCC) have led to the development of biologically-driven targeted therapies. Hypoxia inducible factors (HIFs), angiogenic growth factors, von Hippel-Lindau (VHL) gene mutations and oncogenic miRNAs play essential roles in the pathogenesis and drug resistance of clear cell renal cell carcinoma. These insights have led to the development of VEGF inhibitors, mTOR inhibitors and immunotherapeutic agents which have significantly improved outcomes of patients with advanced RCC. HIF inhibitors will be a valuable asset in the growing therapeutic armamentarium of RCC. Various histone deacetylase (HDAC)inhibitors, including selenium and agents such as PT2385 and PT2977, are being explored in various clinical trials as potential HIF inhibitors to ameliorate the outcomes of RCC patients. In this article, we will review the current treatment options and highlight the potential role of selenium in the modulation of drug resistance biomarkers expressed in ccRCC tumors.

This work is aimed at the development of innovative, easy and cheap methods for the stabilization, inertization and valorisation of the organic fraction of municipal solid waste (OFMSW). For the first time, two original processes for transforming the organic waste into an inert, odorless and sanitized material were here proposed. The first one, called dual step, starts with grinding of the OFMSW, by means of an industrial shredder. After being finely ground, the organic waste was exposed to a sterilization process by means of UV/ozone radiations or thermal treatment (stabilization phase) in order to obtain a complete removal of the OFMSW’s bacterial activity. By means of several microbiological analyses, the best sterilization method was chosen. The incorporation in a thermosetting matrix was, then, carried out through mixing the sterilized and finely ground organic waste into a water soluble urea formaldehyde (UF) based resin, with a formaldehyde content less than 1% wt, followed by a thermal treatment for UF-resin crosslinking (inertization phase). An alternative cheaper and easier process, called one step, was also proposed and investigated, by combining the sterilization with the curing thermal process (at higher temperature) of the thermosetting matrix. The preliminary experimental results reported in this paper suggest that both the proposed methods could be considered suitable for the production of high valorized innovative OFMSW-derived panels or bricks, that could find application in several fields, such as building or constructions materials. Finally a brief description of the prototype machinery is reported properly designed for implementing OFMSW stabilization and valorisation processes developed in this research work.

In this paper the application of the solid-state cooling based on barocaloric effect in the cold food supply chain is investigated. Barocaloric solid-state technology is applied to the final chain links of the cold food supply chain, regarding the steps of retail and domestic conservation. In this context a barocaloric cooler with regard to food needing to be kept at 5°C (273 K), in order to operate with a promising cooling technology that result energy efficient and environmentally friendly. The categories of food interested in the investigation are meets and fresh food products like soft cheese, yogurt, milk. The energy performances of the barocaloric system have been carried out and compared with a commercial vapor compression refrigerator of a similar size, both operating with R600a under the same working conditions. Basing on the following consideration one can conclude that barocaloric cooling is a favourable technology to be employed in the last link chains of the cold food supply chain if the system operates in ABR cycle at frequencies between 1.25 and 1.50 Hz with a regenerator made of acetoxy silicone rubber as solid-state refrigerant and 50%EG-50%water mixture as heat transfer fluid flowing at the optimal velocity of 0.15 m s-1 that guarantees an appropriate trade-off between the temperature span, the cooling power and the coefficient of performances. Under these conditions the barocaloric system overperforms the domestic vapor compression cooler operating with R600a.

Several studies have demonstrated that the p75NTR low-affinity receptor of Nerve Growth Factor (NGF), is produced in abnormally large amounts in several human cancer types. However, the role of p75NTR varies substantially depending on cell context, so that a dual role of this receptor protein in tumor cell survival and invasion, as well as cell death, has been supported in recent studies. Herein we explored for the first time the expression of p75NTR in human specimens (nr=40) from testicular germ cell tumors (TGCTs), mostly seminomas. Nuclear overexpression of p75NTR was detected by immunohistochemistry in tumor tissue as compared to normal tissue, whereas neither NGF nor its high-affinity TrkA receptor was detected. An increased nuclear staining of phospho-JNK, belonging to the p75NTR signaling pathway, and its pro-apoptotic target gene, p53, was concomitantly observed. Interestingly, our analysis revealed that decreased expression frequency of p75NTR, p-JNK, and p53 was related to staging progression, thus suggesting that p75NTR may represent a specific marker of differentiation in TGCTs.

Calcium sulphate (CS) is currently used as a bioabsorbable, completely synthetic and sterile material in the management of infected tissues and dead spaces (DS) mainly resulting from surgical procedures. Residual DS in the postoperative, may create an environment where hematomas fill up and bacteria can proliferate, leading to a high incidence of postoperative infections. Considering the available reviews in the literature, CS has been mainly studied in orthopedic surgery mostly giving brilliant results and low complication rates. Nowadays, orthopedists avail it in the form of pearls both as a bone void filler and as an “off-label” delivery agent for antibiotics in arthroplasty, chronic osteomyelitis and open fractures, paving the way of its application in many other contexts given its natural dis-position to biodegradation. In the last years, CS beads have been gaining ground in the general, vascular and endocrinological surgical specialties. Despite its clear potential and the increasing number of scientific evidences on the safety and effectiveness of CS application in the prophylaxis and treatment of infections, there are not many studies reporting on its application in fields other than orthopedics, with a substantial paucity in plastic and reconstructive surgery literature. This is some-how surprising, since reconstructive surgery often deals with complex wounds secondary to bone and soft tissue exposure, suture dehiscence, trauma, and surgical site infections. As far as we know this is the first updated systematic review assessing the state of the art, indications and new perspectives on the application of CS beads in plastic and reconstructive surgery.

Nanocrystalline silicon oxide (nc-SiOx:H) is a multipurpose material with its varied application in solar cells as a transparent front contact, intermediate reflector, back reflector layer and even tunnel layer for passivating contacts, owing to easy tailoring of its optical properties. In this work, we systematically investigate the influence of gas mixture (SiH4, CO2, PH3 and H2), RF power and process pressure on the optical, structural and passivation properties of thin n-type nc-SiOx:H films prepared in an industrial, high throughput, plasma-enhanced chemical vapor deposition (PECVD) reactor. We provide a detailed description of the n-type nc-SiOx:H material develop-ment using various characterization techniques (SEM, EDX, Raman spectroscopy, and spectro-scopic ellipsometry) with a focus on the relationship between the material properties and the pas-sivation they provide to n-type c-Si wafers characterized by their effective carrier lifetime (τeff). Further, we also outline the parameters to be kept in mind while developing different n-type nc-SiOx:H layers for different solar cell applications. We report a tunable optical gap (1.8 – 2.3 eV) for our n-type nc-SiOx:H films as well as excellent passivation properties with τeff up to 3.5 ms (iVoc ~ 715 mV) before annealing. Oxygen content plays an important role in determining the crystallinity and hence passivation quality of the deposited nanocrystalline silicon oxide films.

Sars-CoV-2 outbreak represents a public health emergency, affecting different regions of the world. Lung is the organ more damaged due to the high presence of Sars-CoV-2 binding receptor ACE2 on epithelial alveolar cells. Severity of infection vary from absence of symptomatology to be more severe, characterized by acute respiratory distress syndrome (ARDS), multiorgan failure and sepsis requiring treatment in Intensive Care Unit (ICU).It is not still clear why in a small percentage of patients immune system is not able to efficiently suppress viral replication. It has been documented as predictive factors for severity and susceptibility affections of cardiovascular system such as heart failure (HF), coronary heart disease (CHD) and risk factors for atherosclerotic progression, hypertension and diabetes among others.Atherosclerotic progression, as chronic inflammation process, is characterized by immune system dysregulation leading to pro-inflammatory pattern, including (Interleukin 6) IL-6, Tumor Necrosis Factor α (TNF-α) and IL-1β raise. Reviewing immune system and inflammation profiles in atherosclerosis and laboratory results report in severe Sars-CoV-2 infection we have supposed a pathogenetic correlation. Atherosclerosis may be a pathogenetic ideal substrate to high viral replication ability leading to adverse outcomes, how reported in patients with cardiovascular factors. Moreover, level of atherosclerotic progression may impact on a different degree of severe infection and in a vicious circle feeding itself Sars-CoV-2 may exacerbate atherosclerotic progression due to excessive and aberrant plasmatic concentration of cytokines.

We propose a new statistical analysis of the Acoustic Emissions (AE) produced in a series of triaxial deformation experiments leading to fractures and failure of two different rocks, namely, Darley Dale Sandstone (DDS) and AG Granite (AG). By means of q-statistical formalism, we are able to characterize the pre-failure processes in both types of rocks. In particular, we study AE inter-event time and AE inter-event distance distributions. Both of them can be reproduced with q-exponential curves, showing universal features which are observed here for the first time and could be important in order to understand more in detail rock fractures dynamics.

FeIFeI Fe2(S2C3H6)(CO)6(µ-CO) (1a-CO) and its FeIFeII cationic species (2a+-CO) are the simplest model of the CO-inhibited [FeFe] hydrogenase active site, which is known to undergo CO photolysis within a temperature- dependent process whose products and mechanism are still a matter of debate. Using Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TDDFT) computations, the ground state and low-lying excited state potential energy surfaces (PESs) of 1a-CO and 2a+-CO have been explored aimed at elucidating the dynamics of the CO photolysis yielding Fe2(S2C3H6)(CO)6 (1a) and Fe2(S2C3H6)(CO)6+ (2a+), two simple models of the catalytic site of the enzyme. Two main results came out from these investigations. First, a-CO and 2a+-CO are both bound with respect to any CO dissociation with lowest free energy barriers around 10 kcal mol-1, suggesting that at least 2a+-CO might be synthetized. Second, focusing on the cationic form, we found at least two clear excited state channels along the PESs of 2a+-CO that are unbound with respect to equatorial CO dissociation.

Puberty identifies the transition from childhood to adulthood. It normally lasts from 3 to 5 years and begins from 9 years in males and 8 years in females, although with differences related to familiarity and geographical origin. Precocious puberty is the onset of signs of pubertal development before age 8 in girls and before age 9 in boys, it has an incidence of 1/5000–1/10.000 with an F:M ratio ranging from 3:1 to 20:1. Based on the mechanism that triggers puberty, precocious puberty can be classified as central, also known as gonadotropin-dependent precocious puberty or true precocious puberty, and peripheral, also known as gonadotropin-independent precocious puberty or precocious pseudopuberty. Thus, the main aim of this narrative report is to describe the standard clinical management and therapy of precocious puberty according to the experience and expertise of pediatricians and pediatric endocrinologists at Policlinico Umberto I, Sapienza University of Rome, Italy. In the suspicion of early sexual maturation, it is important to collect information regarding the age of onset, the speed of maturation of secondary sexual characteristics, exposure to exogenous sex steroids and the presence of neurological symptoms. The objective examination, in addition to the evaluation of secondary sexual characteristics, must also include the evaluation of auxological parameters. Initial laboratory investigations should include serum gonadotropin levels (LH and FSH) and serum levels of the sex steroids. Brain MRI should be performed as indicated by the 2009 Consensus Statement in all boys regardless of chronological age and in all girls with onset of pubertal signs before 6 years of age. The gold standard in the treatment of central precocious puberty is represented by GnRH analogs, whereas as far as peripheral forms are concerned, the triggering cause must be identified and treated. At the moment there are no reliable data establishing the criteria for discontinuation of GnRH analogs therapy. However, numerous pieces of evidence suggest that the therapy should be suspended at the physiological age at which puberty occurs.

Recent studies have shown that the mechanical properties of bioinspired periodic composite materials can be strongly influenced by finite deformation effects, leading to highly nonlinear static and dynamic behaviors at multiple length scales. For instance, in porous periodic nacre-like microstructures, microscopic and macroscopic instabilities may occur for a given uniaxial loading process and, as a consequence, wave attenuation properties may evolve as a function of the microstructural evolution, giving it the designation of metamaterials. The numerical outcomes provide new opportunities to design bioinspired soft composite metamaterials characterized by high deformability and enhanced elastic wave attenuation capabilities given by the insertion of voids and lead cores.

Increasingly, conservation genetics pinpoint the use of biological matrices collected without stressing wildlife. Cervid’s antlers seem to fit with this need. We verified the amplification success rate from DNA obtained from red deer antlers collected in the State Nature Reserve of Bosco della Mesola, Northern Italy and its use for conservation purposes. Here occurs the only native red deer population of peninsular Italy, recently recognized as a distinct subspecies (Cervus elaphus italicus). Four antlers stored at room temperature for four years and four samples highly degraded by environmental conditions were analyzed using a multimarker approach. We utilized a simple, inexpensive method to extract DNA from drilled antlers powder. This study confirms that weathered antlers can be a suitable source of DNA also in Mediterranean climate characterized by strong seasonal fluctuations, and not only in dry climates. Our results pointed out that only burr drilling yielded good quality amplifiable DNA. Antlers can be used in particular for molecular genetic studies on rare or threatened species of cervids as providing an efficient and cost-effective non-invasive sampling.

The assessment of seismic risk in urban areas with high seismicity is certainly one of the most important problems that territorial managers have to face. A reliable evaluation of this risk is the basis for the design of both specific seismic improvement interventions and emergency management plans. Unappropriate seismic risk assessments may provide misleading results and induce bad decisions with relevant economic and social impact.The seismic risk in urban areas is mainly linked to three factors, namely, “hazard”, “exposure” and “vulnerability”. Hazard measures the potential of an earthquake to produce harm; exposure evaluates the amount of population exposed to harm; vulnerability represents the proneness of considered buildings to suffer damages in case of an earthquake. Estimates of such factors may not always coincide with the perceived risk of the resident population. The propensity to implement structural seismic improvement interventions aimed at reducing the vulnerability of buildings depends significantly on the perceived risk.This paper investigates on the difference between objective and perceived risk and highlights some critical issues. The aim of this study is to calibrate opportune policies, which allow addressing the most appropriate seismic risk mitigation options with reference to current levels of perceived risk. We propose the introduction of a Seismic Policy Prevention index (SPPi). This methodology is applied to a case-study focused on a densely populated district of the city of Catania (Italy).

Seismic vulnerability assessment in urban areas would in principle require the detailed modeling of each single building and the implementation of complex numerical calculations. This procedure is clearly difficult to apply at urban scale where many buildings have to be considered and therefore it is essential to have simplified, but at the same time reliable, approaches to vulnerability assessment. Among the proposed strategies, one of the most interesting concerns the application of machine learning algorithms, able to classify buildings according to their vulnerability on the basis of training procedures applied to existing datasets. In this paper machine learning algorithms will be applied to a dataset which collects and catalogs the structural characteristics of a large number of buildings and reports the damage observed in L’Aquila territory during the intense seismic activity occurred in 2009. A combination of a trained neural network and a random forest algorithm allows to identify an opportune “a-posteriori” vulnerability score, deduced from the observed damage, which is compared to an “a-priori” vulnerability one, evaluated taking into account characteristic indexes for building’s typologies. By means of this comparison an inverse approach to seismic vulnerability assessment, which can be extended to different urban centers, is proposed.

Optic neuritis (ON) is the most common cause of vision loss in young adults. It manifests as acute or subacute vision loss, often accompanied by retrobulbar discomfort or pain on eye movements. Typical ON is associated with Multiple Sclerosis and is generally mild and steroid-responsive, whereas atypical forms are characterized by unusual features, such as optic disc edema, poor treatment response and bilateral involvement, and are often associated with autoantibodies against aquaporin-4 (AQP4) and Myelin Oligodendrocyte Glycoprotein (MOG). However, in rare cases AQP4 and MOG antibodies will come back negative, plunging the clinician in a diagnostic conundrum. Seronegative ON warrants a broad differential diagnosis, including autoantibody-associated, granulomatous, and systemic disorders. These rare forms need to be identified promptly, as their management and prognosis is greatly different. The scope of this review is to describe possible, rarer etiologies of ON when AQP4 and MOG antibodies are negative and discuss their diagnosis and treatment.

Brushless Synchronous Machines (BSM) are replacing conventional synchronous machines with static excitation in generation facilities due to the absence of sparking and lower maintenance. However, this excitation system makes challenging measuring electric parameters in the rotor. This fact highly difficult the detection of ground faults, which are the most common type of electrical fault in electric machines. In this paper, a ground fault detection method for BSM is proposed. It is based on an inductive AC/DC rotating current sensor installed in the shaft. In case of a ground fault in the rotating parts of the BSM, a fault current will flow through the rotor’s sensor, inducing voltage in its stator. Analyzing the frequency components of the induced voltage the detection of a ground fault in the rotating elements is possible. The ground faults detection method proposed covers the whole rotor and discern between DC and AC sides. To corroborate the detection method, experimental tests have been performed using a prototype of this sensor connected to laboratory synchronous machines achieving satisfactory results.

(1) Background: Grapes and their associated by-products (as grape pomace, GP) stand out for their polyphenol content, which makes them a source of bioactive compounds with antioxidant capacity. The aim of this research was to determine if the inclusion of 50 g/kg of GP in the diet of hens could enrich egg with antioxidants and to study its effect on internal and external egg quality parameters. (2) Methods: A trial was conducted with two genetic lines of hens, which were fed either a control diet or a diet containing 50 g/kg of GP. Performance, internal and external egg quality, and egg yolk content of vitamins E and A, and gallic acid were determined; (3) Results: In eggs laid by hens fed GP diet, Haugh units and yolk colour score were enhanced, and eggshell became thinner, but without affecting the breaking strength. No dietary effect was observed on vitamin contents in yolk. Higher gallic acid content was observed in yolk of eggs laid by hens fed the GP diet, suggesting that some dietary phenolic compounds could be transferred to the eggs. Hen genetics influenced egg weight, albumen Haugh units, shell thickness and α- and γ-tocopherol concentration in yolks; (4) Conclusions: Dietary inclusion of GP improved the internal quality of eggs, enriching yolks with a phenolic compound, but reduced shell thickness.

The aim of this paper is to establish a valid procedure for better understanding all the phenomena associated with the high-speed machining of Glass Fibre Reinforced Plastic (GFRP) composites. Both rectangular and circular specimens were machined at high speeds (up to 50 m/min) in order to understand what occurred for all values of fiber orientation angles during machining operations. An innovative testing methodology was proposed and studied to investigate the phenomenon of burr formation and thus understand how to avoid it during machining operations. To this end, the forces arising during the machining process and the roughness of the resulting surface, were carefully studied and correlated with the cutting angle. Additionally, the cutting surface and chip morphology formed during cutting tests were examined using a high-speed camera. Close correlations are found between the variations of the cutting forces' signals and the trends of the roughness and the morphology of the machined surface.

The increasing availability of longitudinal data (repeated numerical observations of same units at different times) requires the development of flexible techniques to automatically detect common errors in such data. Besides obvious and easily identifiable cases, such as missing or out-of-range data, large longitudinal dataset often present problems not easily traceable by the techniques used for generic datasets. In particular, elusive and baffling problems are i) inversion of one or more values from one unit to another; ii) anomalous jumps in the series of values, iii) errors in the timing of the values due to a recalculation operated by the data providers to compensate previous errors. This work proposes a statistical-mathematical approach based on a system of indicators that is able to capture the complexity of the described problems by working at the formal level, regardless of the specific meaning of the data. The proposed approach identifies suspect erroneous data and is applicable in a variety of contexts. We implement this approach in a relevant database of European Higher Education institutions (ETER) by analyzing Total academic staff, that is one of the most important variables, used in empirical analysis as proxy of size and also considered by policy makers at European level.

Head and neck squamous cell carcinoma (HNSCC) arise from the mucosal epithelium in the oral cavity, pharynx, sino-nasal region, and larynx. Laryngeal squamous cell carcinoma (LSCC) represents one-third of all head and neck cancers. Dysregulated RNA-related pathways define an important molecular signature in this aggressive carcinoma. The Survival Motor Neuron (SMN) protein regulates fundamental aspects of the RNA metabolism but, curiously, its role in cancer is virtually unknown. For the first time, here we focus on SMN in cancer context. We conducted a pilot study in a total of 20 patients with LSCC where SMN was found overexpressed at both the protein and transcript levels. By a cellular model of human laryngeal carcinoma, we demonstrated that SMN impacts cancer-relevant behaviors and perturbs key players of cell migration, invasion, and adhesion. Furthermore, in LSCC we showed a physical interaction between SMN and the epidermal growth factor receptor (EGFR), whose overexpression is an important feature in these tumours. This study candidates SMN as novel therapeutic target in LSSC, and likely in the whole spectrum of HNSCC. Overall, we provide the first analysis of SMN in human cancer.

The ongoing COVID-19 pandemic dictated new priorities in biomedicine research. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is a single-stranded positive-sense RNA virus. In this pilot study, we optimized our padlock assay to visualize genomic/subgenomic regions using formalin-fixed paraffin-embedded placental samples obtained from a confirmed case of COVID-19. SARS-CoV-2 RNA was localized in trophoblastic cells. We also checked the presence of the virion by immunolocalization of its glycoprotein spike. In addition, we imaged mitochondria of placental villi keeping in mind that the mitochondrion has been suggested as a potential residence of the SARS-CoV-2 genome. Indeed, we observed a substantial overlapping of SARS-CoV-2 RNA and mitochondria in trophoblastic cells. This intriguing linkage correlated with an aberrant mitochondrial network. Overall, to our knowledge, this is the first study that provides the evidence of a co-localization of the SARS-CoV-2 genome and mitochondria in SARS-CoV-2 infected tissue. These findings also support the notion that SARS-CoV-2 infection could reprogram mitochondrial activity in highly specialized maternal/fetal interface.

Over the last few years, Earth Observation (EO) data has shifted towards increased use to produce official statistics, particularly in the agriculture sector. National statistics offices worldwide, including in Asia and the Pacific, are expanding their use of EO data to produce agricultural statistics such as crop classification, yield estimation, irrigation mapping, and crop loss estimation. The advances in image classification, such as pixel-based and phenology-based classifications, and machine learning create new opportunities for researchers to analyze EO data applied to agriculture statistics. However, it requires the ground truth (GT) data because classification result mainly depends on the quality of GT. Therefore, in this study, we introduced a random sampling approach to design and collect GT data using EO imagery and ancillary data. As a result of data collection, GT data improve the algorithms and validates classification results. Nevertheless, despite the importance of GT data, they are rarely disseminated as a data product in themselves. Thus, this results in an untapped opportunity to share GT data as a global public good, and improved use of survey and census data as a source of GT data.

Outdoor exercise is beneficial for psychophysical well-being. Limited studies have compared outdoor and virtual reality (VR) indoor physical activities, especially in coastal settings. Therefore, this study aimed to assess the impact of outdoor coastal walking and indoor walking in a VR simulation with a similar environment on physiological and psychological variables in healthy adults. Twenty-six subjects (14M and 12F; age 25.2 ± 2.5 years) voluntarily participated in this crossover randomized controlled and counterbalanced study and were allocated under three conditions: VR indoor walking (INVR), outdoor walking (OUT) and standard indoor walking (IN). IN and INVR conditions were performed on a treadmill (speed 4.5 Km/h) and the OUT was per-formed on a seaside pedestrian road. The same outdoor environment was displayed in the visor during the INVR. Heart rate (HRmean/max), Physical Activity Enjoyment (PACES-It) and State of Mindfulness for Physical Activity (SMS-PA) were assessed at the end of each condition. The OUT condition showed significantly greater PACES-It scores and HRmean than IN and INVR (p<0.001) and greater SMS-PA scores and HRmax than IN (p<0.01 and p<0.05, respectively). No significant dif-ferences were found between OUT and INVR regarding HRmax and SMS-PA scores (p>0.05). Findings suggest that physical activity in an immersive technology may lead to physiological loads comparable to the outdoor environment. OUT is more enjoyable than IN and INVR but exhibits a mindfulness response comparable to INVR. Therefore, INVR could be an alternative to OUT for those who cannot engage in outdoor activities for various reasons.

Dynamic analyses and seismic assessments of multi-storey buildings at urban level require large-scale simulations and computational procedures based on simplified but accurate numerical models. At this aim the present paper propos-es an equivalent non-uniform beam-like model, suitable for the dynamic analysis of buildings with asymmetric plan and non-uniform vertical distribution of mass and stiffness. The equations of motion of this beam-like model, which pre-sents only shear and torsional deformability, are derived through the application of Hamilton’s principle. The linear dy-namic behaviour is evaluated by discretizing the continuous non-uniform model according to a Rayleigh-Ritz approach based on a suitable number of modal shapes of the uniform shear-torsional beam. In spite of its simplicity, the model is able to reproduce the dynamic behaviour of low- and mid-rise buildings with a significant reduction of the computa-tional burden with respect to that required by more general models. The efficacy of the proposed approach has been tested, by means of comparisons with linear FEM simulations, on three multi-storey buildings characterized by different irregularities. The satisfactory agreement, in terms of natural frequencies, modes of vibration and seismic response, proves the capability of the proposed approach to reproduce the dynamic response of complex spatial multi storey frames.

In this paper we present experimental results concerning Acoustic Emission (AE) recorded during cyclic compression tests on two different kinds of brittle building materials, namely concrete and basalt. The AE inter-event times were investigated through a non-extensive statistical mechanics analysis which shows that their decumulative probability distributions follow q-exponential laws. The entropic index q and the relaxation parameter q  1=Tq, obtained by fitting the experimental data, exhibit systematic changes during the various stages of the failure process, namely (q; Tq) linearly align. The Tq = 0 point corresponds to the macroscopic breakdown of the material. The slope, including its sign, of the linear alignment appears to depend on the chemical and mechanical properties of the sample. These results provide an insight on the warning signs of the incipient failure of building materials and could therefore be used in monitoring the health of existing structures such as buildings and bridges.

Innovative tissue engineering biomimetic hydrogels based on hydrophilic polymers have been investigated for their physical and mechanical properties. 5% to 25% by volume loading PHEMA-nanosilica glassy hybrid samples were equilibrated at 37°C in aqueous physiological isotonic and hypotonic saline solutions (0.15 and 0.05 M NaCl) simulating two limiting possible compositions of physiological extracellular fluids. The glassy and hydrated hybrid materials were characterized both for dynamo-mechanical properties and equilibrium absorptions in the two physiological-like aqueous solutions. Mechanical and the morphological modifications occurring in the samples have been described. The 5% volume nanosilica loading hybrid nanocomposite composition showed mechanical characteristics in the dry and hydrated states that were comparable to those of cortical bone and articular cartilage, respectively, and then chosen for further sorption kinetics characterization. Sorption and swelling kinetics were monitored up to equilibrium. Changes in water activities and osmotic pressures in the water-hybrid systems equilibrated at the two limiting solute molarities of the physiological solutions have been related to the observed anomalous sorption modes using the Flory-Huggins interaction parameter approach. The bulk modulus of the dry and glassy PHEMA-5% nanosilica hybrid at 37°C has been observed to be comparable with the values of the osmotic pressures generated from the sorption of isotonic and hypotonic solutions. The anomalous sorption modes and swelling rates are coherent with the difference between osmotic swelling pressures and hybrid glassy nano-composite bulk modulus: the lower the differences the higher the swelling rate and equilibrium solution uptakes. Bone tissue engineering benefits of use of tuneable biomimetic scaffold biomaterials that can be “designed” to act as biocompatible and biomechanically active hybrid interfaces are discussed.

This article addresses the problem of formation control of a quadrotor and one (or more) marine vehicles operating at the surface of the water with the end goal of encircling the boundary of a chemical spill, enabling such vehicles to carry and release chemical dispersants used during ocean cleanup missions to break-up oil molecules. Firstly, the mathematical models of the Medusa class of marine robots and quadrotor aircrafts are introduced, followed by the design of single vehicle motion controllers that allow these vehicles to follow a parameterized path individually using Lyapunov based techniques. At a second stage, a distributed controller using event triggered communications is introduced, enabling the vehicles to perform cooperative path following missions according to a pre-defined geometric formation. In the next step, a real time path planning algorithm is developed that makes use of a camera sensor, installed on-board the quadrotor. This sensor enables the detection in the image of which pixels encode parts of a chemical spill boundary and use them to generate and update in real time a set of smooth B-spline based paths for all the vehicles to follow cooperatively. The performance of the complete system is evaluated by resorting to 3-D simulation software, making it possible to simulate visually a chemical spill. Results from real water trials are also provided for parts of the system, where two Medusa vehicles are required to perform a static lawn-mowing path following mission cooperatively at the surface of the water.

Cryonotothenioidea is the main group of fishes that thrive in the extremely cold Antarctic environment, thanks to the acquisition of peculiar morphological, physiological and molecular adaptations. We have previously disclosed that IgM, the main immunoglobulin isotype in teleosts, display typical cold-adapted features. Recently, we have analyzed the gene encoding the heavy chain constant region (CH) of the IgT isotype from the Antarctic teleost Trematomus bernacchii (family Nototheniidae), characterized by the near-complete deletion of the CH2 domain. Here, we aimed to track the loss of the CH2 domain along notothenioid phylogeny and to identify its ancestral origins. To this end, we obtained the IgT gene sequences from several species belonging to the Antarctic families Nototheniidae, Bathydraconidae and Artedidraconidae. All species display a CH2 remnant of variable size, encoded by a short Cτ2 exon, which retains functional splicing sites and therefore is included in the mature transcript. We also considered representative species from the three non-Antarctic families: Eleginopsioidea (Eleginops maclovinus), Pseudaphritioidea (Pseudaphritis urvillii) and Bovichtidae (Bovichtus diacanthus and Cottoperca gobio). Even though only E. maclovinus, the sister taxa of Cryonotothenioidea, shared the partial loss of Cτ2, the other non-Antarctic notothenioid species displayed early molecular signatures of this event. These results shed light on the evolutionary path that underlies the origins of this remarkable gene structural modification.

Introduction: Drug interactions (DDIs) represent an important clinical problem particularly in elderly patients due to polytherapy, comorbidity and physiological change in pharmacodynamic and pharmacokinetic pathways. In this study we investigated the association between drugs prescribed during hospital or clinical room discharge and the development of DDIs with drugs daily used from each patient. Methods: we performed an observational, retrospective, multicenter study on medical records of outpatients referred to general practitioners. Drug interactions (DDIs) were measured using the drug interactions probability scale. Collected data were analyzed using the Statistical Package for the Social Sciences. Results: During the study we evaluated 1,622 medical records. We recorded the development of DDIs in 10.3% of patients, of those 11.6% induced the hospitalization. Logistic regression showed an association between DDIs and sex and number of drugs used (P = 0.023). Conclusion: this real-life study shows that DDIs are common in elderly patients and physicians must take more attention after hospital discharge revaluating the treatment in order to reduce the risk of DDIs and hospitalization.

Predictive numerical models in the study of ground-borne vibrations generated by railway sys-tems have traditionally relied on the segmented approach of subsystems. In this approach, loads are individually applied, and the cumulative effect of rolling stock is obtained through superposi-tion. While this method serves to mitigate computational costs, it may not fully capture the com-plex interactions involved in ground-borne vibrations. Recent advancements in computational and software tools have enabled the development of more sophisticated vibrational pollution models. These advanced models encompass the entire dynamic system, from the rolling stock to the terrain, allowing for continuous simulations with a defined time step. Furthermore, the incorporation of computational contact tools between various ele-ments not only ensures temporal accuracy but also extends the analysis to the frequency domain. This paper explores the evolution of predictive numerical models in the context of ground-borne vibrations generated by trains on ballasted tracks. It highlights the shift from segmented models to continuous simulations, demonstrating the progressive advancement towards more comprehen-sive and accurate representations of railway-induced and generated vibrations in the track sur-roundings as an additional way of evaluate sustainability of infrastructures. In particular, this development of a numerical model from its inception aimed to expand upon ex-isting emission - prediction models by enriching the data with frequency-domain information. This approach has been driven by the aspiration to bridge the gap between numerical predictions and measured signals, striving for a higher level of accuracy in our obtained results. This model can predict the impact of a high-speed rail (HSR) vehicle passing on its own track. It possesses sufficient information in both the time and frequency domains to precisely characterize vibrations. This initiative marks a pivotal advancement, enabling us to more effectively capture the intricacies of ground-borne vibrations and their impact on the surrounding environment due to a deeper comprehension of the occurrences in the frequency domain, there's a heightened ca-pability to accurately characterize vibrations.

The global malaria community has picked up the theme of malaria elimination in greater than 90 % of the world’s population in the next decade. The recent reports of P. vivax in all sub-Saharan Africa, including Duffy negative individuals, threaten the efforts to achieve elimination. This is not only in view of strategies that are tailored only to P. falciparum elimination, but also due to currently revealed biological characteristics of P. vivax concerning the relapse patterns of hypnozoites and conservation of a large biomass at cryptic sites in the bone marrow and spleen. A typical scenario has been observed in Botswana from the period between 2008 to 2018, which palpably projects how P. vivax could endanger efforts at malaria elimination where the two parasites co-exist. The need for the global malaria community, NMPs, funding agencies and relevant stakeholders to engage in a forum to discuss and recommend clear pathways for sub-Saharan Africa regarding malaria elimination including P. vivax, is warranted.

The Musa textilis var. Abuab has high fiber quality (FQ) but has low resistance against abaca bunchy top virus (AbBTV); the Musa balbisiana var. Pacol, has low FQ but high resistance against AbBTV. Their backcrosses (BC2 and BC3) possess both desirable traits. Analysis using RNA-seq showed that the regulatory divergence of Abuab and Pacol is largely explained by cis differences with 27.4% and 22.3% if we are to assess it using BC2 and BC3, respectively. Cis differences between the two genotypes are significantly reduced from BC2 to BC3 due to changes in genomic constitution. Trans, on the other hand, is robust to changes in allelic composition. All these are attributed to the loss of heterozygosity in the BC3 relative to BC2. Further analysis showed that both backcrosses exhibited genome-wide preferential expression of Pacol- over Abuab-specific alleles, despite the wider genetic presence of the latter in the hybrids. The ratio of the two genotype-specific expressed transcripts and the ratio of their corresponding genetic make-up are significantly disproportionate, a phenomenon which we refer here as “genome–transcriptome incongruence”. We also observed preferential expression switching in which several genes prefer Abuab- (or Pacol-) specific allele in the BC2 but switched to Pacol- (or Abuab-) specific allele in the BC3 genome.

Idiopathic acute pancreatitis (IAP) presents a diagnostic challenge and refers to cases where the cause of acute pancreatitis remains uncertain despite a comprehensive diagnostic evalua-tion. Endoscopic ultrasound (EUS) has emerged as a valuable tool in the diagnostic workup of IAP. This review explores the pivotal role of EUS in detecting the actual cause of IAP, as-sessing its accuracy, timing, safety, and future technological improvement. Following PRISMA guidelines, 60 pertinent studies were selected and analysed. EUS emerges as a cru-cial diagnostic tool, particularly when conventional imaging fails. It can offer intricate visu-alization of the pancreas, biliary system, and adjacent structures. High accuracy of EUS is evident in detecting the actual causes of IAP such as microlithiasis, small bile duct stones, pancreas divisum, and small pancreatic tumors. Optimal timing for EUS is post-resolution of the acute phase of the disease. EUS, when conducted by experienced endoscopists, it boasts minimal safety concerns, and is crucial to prevent complications. EUS-guided interventions, including fine-needle aspiration, collection drainage, and biopsies, aid in cytological analy-sis. With high diagnostic accuracy, safety, and therapeutic potential, EUS is able to improve patient outcomes when managing IAP. Further refinement of EUS techniques and cost-effectiveness assessment of EUS-guided approaches need to be explored in multicenter prospective studies. This review underscores EUS as a transformative tool in unraveling IAP's enigma and advancing diagnostic and therapeutic strategies.

The fresh bulbs of Stenomesson miniatum, a plant belonging to Amaryllidaceae family with a poorly investigated phytochemical profile, were traditionally employed by Andean healers to treat tumors and abscesses. The aims of this study were to characterize the alkaloid extract from the bulbs of S. miniatum and test its cytotoxic and antibacterial potential. The alkaloid extract was characterized by dereplication using various techniques (CPC, NMR, UPLC-HRMS) and referring to in-home or online databases for spectroscopic data matching. Cytotoxic activities were evaluated on A431 human epidermoid carcinoma cells through a metabolic assay, and on Jurkat human acute T-leukemia cells through a cell-impermeant fluorescent nuclear probe. Antibacterial assays were carried out against Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes by using a standardized microdilution broth method 96-well plate. Eleven known Amaryllidaceae alkaloids were identified together with another compound determined as being an extraction artefact. The alkaloid extract showed good cytotoxic activity against both the tumor cell lines, reaching an IC50 of 3.3 µg/mL against A431 cells and of 10.9 µg/mL against Jurkat cells. The analysis of the fractions allowed the activity to be attributed to the presence of pretazettine and haemathamine. Conversely, no antibacterial activities were recorded for any of the samples.

In this work, the analytical Lagrange-Kirchhoff model for the deformation for a taiko plate silicon is proposed. Under the conditions of validity of the linear theory of thin plates, the model is in agreement with the experimental data.

Ensuring access to water, sanitation, and hygiene (WASH) facilities, coupled with behavior change education in schools, is fundamental for fostering a conducive learning environment and promoting principles of inclusion, dignity, and equality. This study focuses on 12 primary schools in Anápolis, Brazil, encompassing 4,394 students and 248 teachers. WASH assessments were conducted through a questionnaire, observation of water and sanitation facilities and structures, and microbiological analysis. Over the period 2018 to 2020, the proportion of schools with safely managed drinking water surged from 42% to 92%. However, sanitation conditions in the schools were categorized as a basic level, with hygiene services rated as limited in 92% of the schools due to the absence of soap. While this study reveals that Anápolis schools generally align with WASH guidelines for basic/advanced drinking water services, there is a crucial need for enhancements in both hardware and software facilities to address sanitation and hygiene challenges.

Supramolecular structures are of great interest due to their applicability in various scientific and industrial fields. These fields of scientific action include promising applications i biomedical areas, in sensing, and in conductive and electrical phases. The sensible definition of supramolecular molecules is being set by investigators, who, because of the different sensitivities of their methods and observational timescales, may have different views as to what constitute these supramolecular structures. Besides, diverse polymers can be found to offer unique avenues for multifunctional systems with properties in medicine industrial applications. Aspects of this review provide different conceptual strategies to address molecular design, properties, and potential applications of self-assembly materials and the use of metal coordination as a feasible and useful strategy for constructing complex supramolecular structures. In this order of appreciations and ideas order, it is that this review report involves classic topics such as hydrogels that range from their relationship with drug delivery systems, to metallo-supramolecular materials, through applications in ophthalmic systems, in applications that require adhesiveness and electrically conductive hydrogels. This review also addresses systems that are largely based on hydrogel chemistry and the enormous opportunities to design very specific structures for applications that demand enormous specificity.

The detection of subtle changes in the pituitary dimensions has relevant implications since this gland is crucial for the endocrine system. In cats, few studies established the cut-offs values of the pituitary gland’s dimensions, but using small and inhomogeneous samples. The aims of this study were: to determine by computed tomography (CT) the pituitary linear dimensions and the pituitary-to-brain (P:B) ratio in a sample of domestic short-haired (DSH) cats; to assess the effects of sex, age and weight on pituitary dimensions; to evaluate the inter- and intra-observer agreement for such measurements. Exclusion criteria were: clinical, laboratory or CT alterations of pituitary gland or brain diseases, fractures of the neurocranium, or diabetes mellitus. Pituitary dimensions and brain area were assessed by two different observers using multiplanar reconstructions and automated segmentation tools. Fifty-one cats were included in the final sample. The intraclass correlation coefficient for intra- and inter-observer reliability showed good/excellent and moderate/good reliability, respectively. No differences between sexes were detected, and negligible correlations were found with age and weight. Findings from the current study provided normal reference values for pituitary height (1.88 – 4.01 mm) and P:B ratio (0.25 – 0.49), useful for assessing abnormally enlarged pituitary gland in DSH cats.

The SARS-CoV-2 polybasic furin cleavage site is still a missing link. Remarkably, the two arginine residues of this protease recognition site are encoded by the CGG codon, which is rare in Betacoronavirus. However, the arginine pair is common at viral furin cleavage sites, but are not CGG-CGG encoded. The question is: Is this genetic footprint unique to the SARS-CoV-2? To address the issue, using Perl scripts, here I dissect in detail the NCBI Virus database in order to report the arginine dimers of the Betacoronavirus proteins. The main result reveals that a group of Middle East respiratory syndrome-related coronavirus (MERS-CoV) (isolates: camel/Nigeria/NVx/2016, host: Camelus dromedarius) also have the CGG-CGG arginine pair in the spike protein polybasic furin cleavage region. In addition, CGG-CGG encoded arginine pairs were found in the orf1ab polyprotein from HKU9 and HKU14 Betacoronavirus, as well as, in the nucleocapsid phosphoprotein from few SARS-CoV-2 isolates. To quantify the probability of finding the arginine CGG-CGG codon pair in Betacoronavirus, the likelihood ratio (LR) and a Markov model were defined. In conclusion, it is highly unlikely to find this genetic marker in betacoronaviruses wildlife, but they are there. Collectively, results shed light on recombination as origin of the virus CGG-CGG arginine pair in the S1/S2 cleavage site.

The incremental sheet forming represents a relatively recent technology that guarantees high customization, thanks to the layered manufacturing principle typical of rapid prototyping, and cost-effectiveness, because it does not require dedicated equipment. Research has initially shown that this process is effective in metal materials capable of withstanding plastic deformation but, in recent years, the interest in this technique has been increasing for the manufacture of complex polymer sheet components as an alternative to the conventional technologies, based on heating-shaping-cooling manufacturing routes. Conversely, incremental formed polymer sheets can suffer from some peculiar defects, for example twisting. To reduce the risk of this phenomenon and the occurrence of failures, a viable way is to choose toolpath strategies that make the tool/sheet contact conditions less severe, and this represents the main goal of the present research. Polycarbonate sheets were worked by incremental forming; in detail, cone frusta with a fixed wall angle were manufactured with a reference and a stair toolpath strategy, and both the forming forces and the twist angle were monitored. The analysis of the results highlighted that a stair toolpath involving an alternation of diagonal up and vertical down steps represents a useful strategy to mitigate the forming forces and, with them, the occurrence of the twisting phenomenon in incremental formed thermoplastic sheets.

Boron Neutron Capture Therapy (BNCT) is a promising binary disease-targeted therapy, as neutrons preferentially kill cells labeled with boron (¹⁰B), which makes it a precision medicine treatment modality that provides a therapeutic effect exclusively on patient-specific tumor spread. Contrary to what is usual in radiotherapy, BNCT proposes cell-tailored treatment planning rather than to the tumor mass. The success of BNCT depends mainly on the sufficient spatial biodistribution of ¹⁰B located around or within neoplastic cells to produce a high-dose gradient between the tumor and healthy tissue. However, it is not yet possible to precisely determine the concentration of ¹⁰B in a specific tissue in real-time using noninvasive methods. Critical issues remain to be resolved if BNCT is to become a valuable, minimally invasive, and efficient treatment. Moreover, functional imaging technologies such as PET can be applied to determine biological information that can be used for the combined-modality radiotherapy protocol for each specific patient. Anyway, not only imaging methods but also proteomics and gene expression methods will facilitate BNCT becoming a modality of personalized medicine. This work provides an overview of the fundamental principles, recent advances, and future directions of BNCT as cell-targeted cancer therapy for personalized radiation treatment.

Eysenhardtia platycarpa (Fabaceae) is a medicinal plant used in México and it lacks biotechnological studies for its use. The aim of this work was to establish a cell suspension cultures (CSC) of E. platycarpa, determine the phytochemical profile, and evaluate its antifungal activity. Friable callus and CSC were established with 2 mg/L 1-naphthaleneacetic acid plus 0.1 mg/L kinetin. The highest total phenolics of CSC was 15.6 mg GAE/g dry weight and the total flavonoids content ranged from 56.2 to 104.1 µg QE/g dry weight. CG‒MS analysis showed that the dichloromethane extracts of CSC, sapwood and heartwood have a high amount of hexadecanoic acid (22.3 ‒ 35.3 %) and steroids (13.5 ‒ 14.7%). Heartwood and sapwood defatted hexane extracts have the highest amount of stigmasterol (≈ 23.4%) and β-sitosterol (≈ 43%), and leaf extracts presented β-amyrin (16.3%). Methanolic leaves extracts showed mostly sugars and some polyols, mainly D-pinitol (74.3%). Dichloromethane and fatty hexane extracts of CSC exhibited the percentages inhibition higher for Sclerotium cepivorum with 71.5 and 62.0%, respectively. The maximum inhibition for Rhizoctonia solani was with fatty hexane extracts of the sapwood (51.4%). Our study suggest that CSC extracts could be used as a possible complementary alternative to synthetic fungicides.

Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer characterized by two etiologies: the first one, observed in most cases, is attributed to Merkel cell polyomavirus (MCPyV), a DNA tumor virus, while the second one is due to ultraviolet (UV) radiation exposure. Currently, there are limited diagnostic, prognostic, and therapeutic biomarkers available for MCC. MicroRNAs (miRNAs) are small RNA molecules that do not code for proteins but regulate various cellular processes, including cell cycle progression, proliferation, differentiation, and apoptosis. The dysregulation of miRNAs has been associated with a wide range of cancers since they can act as either tumor suppressors or oncogenes. This paper aims to collect, summarize and re-organize the recent discoveries concerning miRNAs, whose dysregulation in the pathogenesis and progression of MCC is slowly emerging. Furthermore, the potential clinical applications of miRNAs as diagnostic biomarkers, possible differentiation between MCPyV-related and unrelated MCC, predictors of response to therapy and prognostics are also discussed. From this review, it emerges that miRNAs may have, in the near future, the potential to become clinically significant in improving the diagnostic accuracy, prognostic evaluation, and therapeutic options of MCCs. Finally, the new perspectives on the poorly explored field of artificial intelligence in MCC are provided.

All living organisms require some metal ions for their energy production as well as metabolic and biosynthetic processes. Within cells, metal ions are involved in the formation of adducts interact with metabolites and macromolecules (proteins and nucleic acids). The proteins that require binding to one or more metal ions to be able to carry out their physiological function are called metalloproteins. About one third of all protein structures in the Protein Data Bank involve metalloproteins. Over the past few years there has been a tremendous progress in the number of computational tools and techniques making use of 3D structural information to support the investigation of metalloproteins. This trend has been boosted also by the successful applications of neural networks and deep learning approaches in molecular and structural biology at large. In this review, we discuss recent advances in the development and availability of resources dealing with metalloproteins from a structure-based perspective. We start by addressing tools for the prediction of metal-binding sites (MBSs) using structural information on apo-proteins. Then, we provide an overview of methods for and lessons learned from the structural comparison of MBSs in a fold-independent manner. We then move to describing databases of metalloprotein/MBS structures. Finally, we summarize recent DL applications enhancing the functional interpretation of metalloprotein structures.

This work analyzes the visibility and scientific impact of publications related to agricultural value chains. The incidence of bibliometric indicators allows for the interpretation of bibliographic information generated worldwide. Objective: The objective of this research is to analyze the published literature and bibliometric indicators on agricultural value chains. The Web of Science database was used to extract value chains data. The study analyzed articles published between 2010 and 2020. The keywords used are "agricultural value chains'' and articles from journals or studies related to the subject were selected for bibliometric analysis and methodological review. In the search for the keyword, a total of 4208 results were extracted, of which 1,669 records were considered for analysis. The bibliometric analysis of the data reveals that Wageningen University (55) has the highest number of publications, followed by Chinese Acad Sci (26). The author Klerkx L (9) has the highest number of records, followed by Hellin J (7). With respect to the countries with the greatest contributions on the subject are: the People's Republic of China, Germany, Italy, France and the United States. The study contributes to the analysis of bibliometrics and provides a methodological review of published journal articles on agricultural value chains. This bibliographic study presents the history of research development in agricultural value chains.

The teaching of the lunge technique in fencing is critical in the developmental age. The relations of anthropometrics with kinematics of lunge was studied only in adult fencers, and no study exist in young considering the different level of experience. Our aims were to assess, in young fencers, which factors, between the anthropometric and the kinematics, were mostly connected with lunge performance (speed and excursion) in different genders and expertise levels. Fifteen young fencers participated in this study. Lunge kinematics, anthropometric characteristics and force expressed in vertical jump tests were collected. Maximal lunge velocity resulted mainly correlated with the posterior knee’s extension ((r=0.56, p=0.031). The lunge distance and mean hip velocity were mostly correlated with fencers’ height (r=0.85, p=0.000 and r=0.76, p=0.001) and FFM (r=0.8, p=0.000 and r=0.73, p=0.002). Experts and non-experts show significant differences in fat free mass, area of upper arm, and of thighs (Effect Size = 1,27 – 1,33, p= 0,021-0,035). From our results it emerges that, in this age range, the analysed aspects of lunge performance are mainly correlated with participant’s anthropometry. Moreover, it is already possible in this age span, to find technical differences linked to the experience.

Background: Limited research has explored sex-specific differences in death predictors of HF pa-tients with ischemic (iCMP) and nonischemic (niCMP) cardiomyopathy. This study assessed sex differences in niCMP and iCMP prognosis. Methods: We studied 7,487 patients with HF between February 2017 and September 2020. Clini-cal features and echocardiographic findings were collected. We used Kaplan-Meier, Cox propor-tional hazards models, and score chi-square of Cox regression to determine death predictors in women and men. Results: mean age was 64.3±14.2 years, with 4,417 (59%) males. Women with iCMP and niCMP exhibited significantly higher mean age, higher mean left ventricular ejection fraction, and smaller left ventricular diastolic diameter than men. Over 2.26 years of follow-up, 325 (14.7%) women and 420 (15.7%) men, and 211 women (24.5%) and 519 men (29.8%) died in niCMP (p=NS) and iCMP (p=0.004), respectively. Cumulative incidence of death was higher in men with iCMP (log-rank p<0.0001) but similar in niCMP. Cox regression showed chronic kidney disease, dia-betes, stroke, atrial fibrillation, age, and myocardial infarction, as main predictors of death for iCMP in women and men. Conclusion: Women exhibited a better prognosis than men in iCMP, but similar for niCMP. Nevertheless, sex was not an independent predictor of death for both CMP.

This research investigates the effects of torsional moments on the mechanical behavior of thin-walled open-ended vertical pile foundations subjected to lateral wind loads. The warping and torsion effect generated over the piles due to the resultant lateral load impact outside the shear center is analyzed in-field tests. Complementarily, a two-dimensional finite element model based on the simple bending stress-strain state as well as a three-dimensional finite element model considering torsional effects were implemented and their results analyzed. Finally, a comparative analysis between the in-field lateral loading tests and the finite element model approaches was established and correlations between the errors and the parameters of influence were highlighted. From the results, it has been ascertained that the slender thin-walled open-ended pile foundations are particularly sensitive to small load deviations from their center of gravity, this leads to the fact that the slenderer and the more eccentricity of the load, the more it affects the torsion and warping of the pile. Calculation methodologies usually consider a simple in-plane bending behavior which conducts to errors between 44 and 58% of the experimental results.

Neuroscience has overwhelmingly and understandably focused on the synaptic modality of signal transmission. There is evidence, however, that from an evolutionary perspective, non-synaptic transmission (NST) preceded synaptic signaling. Moreover, in modern nervous systems, NST coexists and extensively interacts with synaptic transmission modifying neuronal dynamics. In fact, NST remains widespread in complex animals, especially within the interoceptive system where the dearth of insulating barriers such as myelin sheaths and the blood-brain barrier enhances the communication between neural and non-neural tissues mediated by NST. We suggest that this physiological arrangement makes a fundamental contribution to interoception¾the process of sensing visceral states¾which is an essential underpinning of the capacity to feel and the foundation of affective processing.

The effects of morphine (MOR) and dexmedetomidine (DEX) on the MAC of isoflurane were measured in rats chronically treated with the synthetic cannabinoid WIN 55,212-2 (WIN55). Methods: The MAC of isoflurane was determined in 32 male rats from expiratory samples at the time of tail clamping. The effects of morphine (MAC(ISO+MOR)) and dexmedetomidine (MAC(ISO+DEX)) on the MAC of isoflurane in untreated rats and rats treated for 21 days with WIN 55,212-2 (MAC(ISO+WIN55+MOR)) and (MAC(ISO+WIN55+DEX)) were measured. Prior to the administration of morphine and dexmedetomidine, the MAC of the isoflurane was measured in both untreated rats (MAC(ISO)) and those treated with WIN 55,212-2 (MAC(ISO+WIN55)). Results: The minimum alveolar concentration was measured as 1.32 ± 0.06 in the MAC(ISO) group and 1.69 ± 0.09 in the MAC(ISO+WIN55) group. The MAC of the MAC(ISO+MOR) group was 0.97 ± 0.02 (26% less than the control group, MAC(ISO)). MAC was measured as 1.55 ± 0.08 in the MAC(ISO+WIN55+MOR) group (8% less than the MAC(ISO+WIN55) group), 0.68 ± 0.10 in the MAC(ISO+DEX) group (48% less than the control group, MAC(ISO)), and 0.67 ± 0.08 in the MAC(ISO+WIN55+DEX) group (60% less than the MAC(ISO+WIN55) group). Conclusions: The administration of WIN 55,212-2 for 21 days increases the MAC of isoflurane in rats. The sparing effect on isoflurane of morphine decreases in rats chronically treated with the synthetic cannabinoid, WIN 55,212-2. Dexmedetomidine increases its sparing effect on the minimum alveolar concentration of isoflurane in rats chronically treated with WIN 55,212-2.

This study investigated whether export performance is correlated with innovation. We explicitly considered five types of innovation: a) process innovation; b) product innovation; c) process and product innovation; d) product innovation new to the firm; and e) product innovation new to the market. We en-larged the findings of R&D-export and R&D-investment relations using a vast sample of cross-European firms. We considered innovation as endogenous and determined by R&D through a process characterized by the role of the regional technological environment. Our analysis enabled us to propose an integrated model incorporating R&D, innovation and export, in a framework of simultaneous equations which consider their mutual correlations. To the best of our knowledge, this work is the first in recent years to empirically compute the relation between R&D and tangible investment at the micro level. Econometric results showed that product and process innovation are positively linked to the export intensity of European manufacturing firms. The results also showed complementarity effects between the two kinds of innovation. The av-erage effect on export intensity from carrying out process innovation is larger than that found for product innovation, except in cases where the product is new to the market. When both types of innovation have been carried out, a larger effect results than that found for product or process innovation alone. Furthermore, the average marginal effect on export intensity from innovations of any kind among those studied here is highly positive and significant.

This paper analyses the COVID-19 crisis and its management, under the Austrian Economics. The attention is focused in the States’ coercive intervention, to evaluate the positive or negative effects of pandemic, according to the Principles of Political Economy and the theory of capital and economic cycles. The paper examines the specific case of massive intervention by governments and, especially, central banks in monetary and financial markets to deal with the pandemic by seeking to lessen its effects. Also, it is offered a critical analysis on simultaneous government policies involving taxes and an increase in public spending which are presented as the panacea and universal remedy for the evils that afflict the society, instead of promoting the transit to Wellbeing Economics. To conclude the review, there is a proposal of paradigm review, in the way to offer a sustainable model.

Cancer survival continues to improve in high-income countries, partly explained by advances in screening and treatment. Previous studies have mainly examined the relationship between individual dietary components and cancer prognosis in tumours with good therapeutic response (breast, colon and prostate cancers). The aim of this review was to assess qualitatively (and quantitatively where appropriate) the associations of dietary patterns and cancer prognosis from published prospective cohort studies, as well as the effect of diet interventions by means of randomized controlled trials (RCT). A systematic search was conducted in PubMed, and a total of 35 prospective cohort studies and 14 RCT published between 2011 and 2021 were selected. Better overall diet quality was associated with improved survival among breast and colorectal cancer survivors; adherence to the Mediterranean diet was associated to lower risk of mortality in colorectal and prostate cancer survivors. A meta-analysis using a random-effects model showed that higher versus lower diet quality was associated with a 23% reduction in overall mortality in breast cancer survivors. There was evidence that dietary interventions, generally combined with physical activity, improved overall quality of life, though most studies were in breast cancer survivors. Further cohort and intervention studies in other cancers are needed to make more specific recommendations.

Postprandial glucose levels between 4 and 7.9 hours (PPG4–7.9h) correlate with mortality from various diseases including hypertension, diabetes, cardiovascular disease, and cancer. This study aimed to assess if predicted PPG4–7.9h could diagnose diabetes. Two groups of participants were involved: Group 1 (4420 participants) had actual PPG4–7.9h, while Group 2 (8422 participants) lacked this measure but had all the diabetes diagnostic measures. Group 1 underwent multiple linear regression to predict PPG4–7.9h using 30 predictors, achieving accuracy within 11.1 mg/dL in 80% of the participants. Group 2 had PPG4–7.9h predicted using this model. Receiver operating characteristic curve analysis showed that predicted PPG4–7.9h could diagnose diabetes with an accuracy of 87.3% in Group 2, with a sensitivity of 75.1% and specificity of 84.1% at the optimal cutoff of 102.5 mg/dL. Simulation on 10,000 random samples from Group 2 revealed that 175 participants may be needed to investigate PPG4–7.9h as a diabetes diagnostic marker with a power of at least 80%. In conclusion, predicted PPG4–7.9h appears to be a promising diagnostic indicator for diabetes. Future studies seeking to ascertain its definitive diagnostic value might require a minimum sample size of 175 participants.

Microplastics and nanoplastics (MP/NPs) have been found everywhere they have been searched. On the top of Everest, in the Mariana Trench, on the clouds e recently, microplastics have been discovered in the human placenta, meconium and babies’ feces. In this review we explain what the consequences of the presence of these pollutants in fetuses and newborns are, with particular attention to human breastfeeding. Finally, we outline the possible political and social solutions to the problem of plastic overproduction that characterizes the modern world.

An extension of the Stoney formula for the case of a back side metallized 8” silicon taiko wafer has been developed, in the elastic regime, within the frame of the theory of elasticity. A good correlation between the calculated warpage, determined by the stress released by a given back side metallization (BSM), and the corresponding experimental warpages of the same thick metal layers deposited on an 8” silicon taiko wafer provides evidences of the correctness of the developed theory. This development suggests the possibility to extend this approach to the case of 8” taiko wafers based on a wide band gap semiconductor such as silicon carbide (SiC).

The SARS-CoV-2 high infectivity is due to the functional polybasic furin cleavage site in the S protein. How it was acquired is unknown. There are two challenges to face: (i) an evolutionary model, to fit the origin of the coronavirus; and (ii) a molecular mechanism for the site acquisition. Here we show genomic fingerprints which are specific of Pangolin-CoVs, Bat-SARS-like (CoVZC45, CoVZXC21), bat RatG13 and human SARS-CoV-2 coronaviruses. This, along with phylogenetic analysis, we found that these species have the same evolutionary origin in the bat, including a genetic recombination of S gene between Pangolin-CoV (2017) and RatG13 ancestors. However, this does not explain why SARS-CoV-2 is the only of them with the furin site, which consists in four amino acid (PRRA) motif. The Arginine doublet is encoded by CGGCGG codons. Surprisingly, none of the Arginine doublet of other furin site of viral proteins from several type of viruses, are encoded by the CGGCGG codons. This makes it difficult to consider a virus recombination as mechanism for the PRRA acquisition. The origin of SARS-CoV-2, is the origin of the recognition cleavage site. The bat coronavirus RaTG13 appears to be the closest relative of the SARS-CoV-2, but was isolated in 2013. So, new RatG13 samples would provide insights into the acquisition of the polybasic motif.

Blockchain technology has emerged as a necessity for the decentralization of payment methods and transactions, but it has brought with it many properties of distributed systems that have made it a crucial technology for overcoming some of society's challenges, especially in the context of decentralizing services, transparency of information, availability, and security. Its architecture and communication methods, although possessing some complex nuances to understand, particularly for the lay audience in the field of distributed systems, protocols, and computer networks. In this article, we will explore some topics of distributed systems related to blockchain technology.

Objective: The goal of this study was to analyse the attitudes and perceptions of emergency and mental health nurses through the validation of the SM-GIBED scale in specialised care in Spain on alcoholics and other drug-dependent patients. Design and Setting: This cross-sectional study was developed using the Spanish hospital version of the Seaman-Mannello scale to denominate the SM-GIBED scale. Participants: 170 Emergency and Mental Health Nursing from five Spanish Hospitals. Intervention: Self-administered questionnaire to analiyse the perceptions and attitudes about the drug addict and the alcoholic. Primary and Secondary Outcome Measures: A descriptive and inferential analysis of the study variables was carried out. A psychometric analysis was performed to validate the scale. Results: A total of 170 questionnaires were collected from 257 healthcare workers. Overall, 99.1% of the participants had contact with drug-dependent patients during their professional experience. Nearly 75% had difficulties in treating them. The psychometric analysis of the SM-GIBED scale in the Spanish context obtained values of KMO = 0.655 and Bartlett's test p < 0.000. Cronbach's alpha of 0.738 was obtained from the reliability analysis. A reliability analysis of each of the SM-GIBED questions found no case with an alpha lower than 0.71. In conclusion, positive aspects include an ingratiating attitude and subject-to-subject communication when nurses self-define as empathic and non-paternalistic. Among the negative aspects, there is a lack of communication skills and assertiveness with these patients. This highlights a certain degree of resignation and dissatisfaction when working with drug addicts.

Background: to assess the benefit of a deep inspiration breath hold (DIBH) over standard irradiation technique, and eventually to identify anatomical and/or treatment preplanning characteristics correlated with LAD dose. Methods: We retrospectively identified patients with left-sided breast cancer who underwent whole breast radiotherapy in DIBH. All patients had both plans in DIBH and free-breathing (FB). Receiving operating characteristics (ROC analysis) were performed to define the cut-off point of parameters to predict LAD maximum dose >10 Gy and LAD mean dose > 4 Gy. Areas under the curve (AUCs) were calculated for all variables. Post-test probability has been calculated to evaluate advantage for parameters combination. Results: One hundred ninety-seven patients were identified. LAD dose was significantly reduced in DIBH plans with maximum and mean dose reduced by 31.7% (mean value 3.5 Gy vs 4.8 Gy, p=<0.001) and 28.1% (mean value 8.2 Gy vs 12.8 Gy, p=<0.001) in DIBH plans compared to FB plans. The strongest predictor of LAD maximum dose > 10 Gy and a LAD mean dose > 4 Gy was the minimum distance of LAD from tangent open fields. Other parameters were lung volume and heart volume for LAD Dmax > 10 Gy and lung volume, heart volume and breast separation for LAD Dmean > 4 Gy. Conclusion: The dosimetric benefit of DIBH is valid for all patients and DIBH should be preferred for all left sided patients.

Isokinetic testing of the knee joint is the “gold standard” in strength assessment in sport especially in soccer, where it is part of pre-season screening to establish norms in case of injuries. There are many devices on the market that make it difficult to use of normative data. Isokinetics literature in females’ soccer players is scarce in comparison to males. Furthermore, evaluation protocols strongly differ from each other, using different ranges of speeds, movement patterns and output data. Thus, it is difficult for the researcher and the clinician to choose a correct protocol for isokinetic evaluation in female soccer players. The indexes of isokinetic performance that are widely accepted are the hamstring/quadriceps (H/Q) ratio and dominant/non-dominant (D/ND) ratio as reference. In this review are highlighted some common features of isokinetic testing in female soccer players of different levels of qualification. From this study, it emerges that, for a reliable test, 3 reps at the speed of 60°/sec in knee flexion/extension is preferable due to the high reliability and that an optimal H/Q ratio in healthy female soccer players of different level of qualification and age is 50%, while the interlimb differences (D/ND) should be below 10%.

There is an increasing pressure by community and customers forcing companies to insert environmental concerns in their practices. To help companies initiatives, the green bonds market was incepted. Our research question is how to select bonds in a growing billion-dollar market. This paper presents a multi-criteria decision analysis (MCDA) model to enable investors identify opportunities based not only in opinions, but grounded on objective facts. Analytic Hierarchy Process (AHP) and Complex Proportional Assessment (COPRAS) are two MCDA methods applied in this paper. Top-fifteen green bonds ranked by specialized media were assessed with the proposed MCDA model. Criteria included the Environmental Performance Index (EPI) proposed by Yale University, and common financial indicators as assets, risks (β), and dividends. The new AHP–COPRAS rank is compared with another published by specialized media.

Ever since pharmacy has become a profession, pharmacist's role has been continuously subjected to changes due to specific influences from historical, socio-economic, political, and scientific context. Nowadays the classic perception of pharmaceutical profession in Community Pharmacy is facing worldwide extinction due to many factors. Modern services, such as online, mail-order, and telephone-order pharmacies are increasingly gaining ground thanks to their ability to facilitate customer demand. However, at the same time, they are endangering “face-to-face” contact, affecting the building of customer loyalty based on direct “human” interaction, and consequently reducing pharmacists to mere commercial figures. Communication is in fact emphasized as the essential element to build a solid and appropriate interpersonal relationship with the client, to make the consultancy process effective, and to strengthen pharmacist's professionalism in community pharmacy. The aim of this work is to analyze pharmacist’s role in modern society by pinpointing the factors affecting pharmacy profession practice. Specific purpose will be improving both the academic training of future professionals and their capacity to approach public relations through a deepened study and practice of behavioral, communication, educational, and sociological methodologies and techniques that would allow the development of more effective communication skills useful for providing an efficient consultancy service.

Lipid mesophases are being intensively studied as potential candidates for drug-delivery purposes. Extensive experimental characterization has unveiled a wide palette of release features depending on the nature of the host lipids and of the guest molecule, as well as on the environmental conditions. However, only few simulation works have addressed the matter, which hampers a solid rationalization of the richness of outcomes observed in experiments. Particularly, to date there are no theoretical works addressing the impact of hydropathy on the transport of a molecule within lipid mesophases, despite the significant fraction of hydrophobic molecules among currently-available drugs. Similarly, the high heterogeneity of water mobility in the nanoscopic channels within lipid mesophases has also been neglected. To fill this gap, we introduce here a minimal model to account for these features in a lamellar geometry, and systematically study the role played by hydropathy and water-mobility heterogeneity by Brownian-dynamics simulations. We unveil a fine interplay between the presence of free-energy barriers, the affinity of the drug for the lipids, and the reduced mobility of water in determining the net molecular transport. More in general, our work is an instance of how multiscale simulations can be fruitfully employed to assist experiments in release systems based on lipid mesophases.

Introduction: Osteosarcomas of the jaw (OSJ) are rare tumors with a different behavior from osteosarcomas of other bones. This study aims to analyze the clinical, pathological, and therapeutic characteristics of this type of sarcoma. Methods: a retrospective observational study of cases diagnosed with OSJ registered at the “La Paz” University Hospital (Madrid). Results: Eight cases with a diagnosis of OSJ were obtained in a study period of 22 years (2000-2022). The mean age was 41 years. The distribution was 1:1 between the maxilla and mandible. Painful inflammation was the most frequent clinical manifestation. Conventional osteoblastic osteosarcoma was the most common. Survival at 5 years was 50%, while at 10 years, it decreased to 25%. Conclusions: OSJ differs from conventional osteosarcomas of long tubular bones. Surgery continues to be the mainstay of treatment; more studies are needed in which more standardized protocols can be proposed for adjuvant therapeutic management.

Many species of the Asteraceae family are used in traditional Mexican medicine for possessing healing properties. Ageratina pichinchensis (Asteraceae) is a plant used for the treatment of gastric ulcers, deep wounds and for its antifungal effects. The aim of this study was to establish a cell suspension culture of A. pichinchensis, quantify the anti-inflammatory constituents 2,3-dihydrobenzofuran and 3-epilupeol, to evaluate the anti-inflammatory potential of its extracts and perform a phytochemical analysis. Cell suspension cultures were established in MS culture medium supplemented with 30 g L-1 sucrose and 1.0 g L-1 α-naphthaleneacetic acid (NAA) plus 0.1 mg L-1 6-furfurylaminopurine (KIN). The ethyl acetate extracts of cell suspension cultures analyzed by GC revealed that the maximum production of compounds The anti-inflammatory activity of these extracts exhibited significant inhibition of NO production. Furthermore, the phytochemical study of EtOAc and MeOH extracts of the biomass on day 20 led to the identification of 17 known compounds. The structures of compounds were assigned by analysis of 1D and 2D NMR data and the remainder by GC-MS. This is the first report of the production of the (-)-Artemesinol, (-)-Artemesinol glucoside, Encecalin and 3,5-diprenyl-acetophenone compounds by a cell suspension cultures of A. pichinchensis.

The province of Jaén (Andalusia, Spain), despite being declared the European territory with the largest number of defensive constructions (castles, fortifications, etc.), has few conservation plans, with many remains included on the Red List of Spanish Heritage ly-ing abandoned. This poses a challenge for landscape conservation and the optimal use of the province’s tourism potential. In this paper we present the early implementation of an ongoing methodological approach designed to alleviate this situation. It takes advantage of data from the Sentinel 2A and 2B satellites, HBIM, RPAS, GIS and fieldwork that will be applied across five archaeological case studies. It has been tested for the first time in the village of Magaña. Three main objectives and phases of this methodological approach have been designed: 1. Preparation of an Environmental Risk Chart with which to answer such ques-tions as “How have climate change, anthropic alterations and environmental characteris-tics affected the state of conservation of certain heritage sites?” 2. Preparation of HBIM models to foster monitorisation and conservation policies for the main archaeological remains and improving their protection based on digital and technological tools. 3. Building a Smart Tourism App for mobile devices aimed at promoting smart tourism by digitalising and virtualising tourist itineraries and archaeological remains. Finally, public administrations will be apprised of the need to implement a conservation policy for cultural assets and their surroundings in a simple, quick and cost-effective man-ner.

The province of Jaén (Andalusia, Spain), despite being declared the European territory with the largest number of defensive constructions (castles and fortifications), has few conservation plans, with many remains included on the Red List of Spanish Heritage lying abandoned. This presents a problem for the conservation of the landscape and the optimal use of the province’s tourism potential. Through the study case of Magaña hamlet two actions are proposed to alleviate this situation: The creation of an archaeological and environmental risk chart with which to answer such questions as “How have climate change, anthropic alterations and environmental charac-teristics affected the state of conservation of certain heritage sites?” and to put forward proposals for improving their protection using as a basis digital and technological tools, such as remote sensing (SAR), taking advantage of data from the Sentinel 2A and 2B satellites, HBIM, RPAS and GIS. To foster the promotion of smart tourism by digitalising and virtualising tourist routes and archaeological remains by building a Smart Tourism App for mobile devices. Finally, public administrations will be apprised of the need to implement a conservation policy for cultural as-sets and their surroundings in a simple, quick and cost-effective manner.

The construction industry, a vital sector of the global economy, is projected to grow significantly over the next 15 years. Despite its importance, this industry struggles with inefficiency, high costs, prolonged timelines, and substantial ecological impacts. These challenges have led governments to advocate for Building Information Modeling (BIM) to enhance Efficiency and sustainability through comprehensive digital representations of physical and functional characteristics. The effective integration of BIM technology hinges on the active participation of industry providers, raising the question of how these providers can positively contribute to improving BIM dimen-sions. This study investigates the potential of coopetition networks within the Portuguese Orna-mental Stone industries (OS-PT) to address this challenge. Coopetition networks, which blend competition and cooperation, foster collaborative networks among companies to enhance their re-sponse to digital supply chains. The research employs an Experimental Pilot Network facilitated by an Industrial Internet of Things (IIoT) artefact to assess the benefits of coopetition networks. The findings demonstrate that transitioning from current practices (CB.P) to coopetition network practices (CN.P) significantly improves operational Efficiency, labour productivity, and sustaina-bility. Specifically, the transition resulted in a 15.6% increase in on-time delivery performance, a 27.38% improvement in labour productivity, and a 21.8% reduction in CO₂ emissions per part produced. These improvements align with Sustainable Development Goals (SDGs) 8, 9, 11, and 13, highlighting the strategic value of coopetition in driving innovation and sustainability in the construction industry. Future research should explore the scalability of these findings across different sectors and further refine methodologies to maximize the benefits of coopetition net-works.

This paper is aimed at studying the temporal evolution of the surface displacements occurred over the past few years in the ocean-reclaimed platforms of the Shanghai megacity (China), which are mainly ascribable to consolidation processes of large dredger fills and alluvial deposits. With respect to previous analyses carried out over the same area, this work provides a joint multi-platform differential interferometry synthetic aperture radar (DInSAR) analysis, based on the application of the advanced Small BAseline Subset (SBAS) algorithm. This led us to retrieve long-term deformation time-series that are helpful for a better understanding of the on-going deformation phenomena. To this aim, we have exploited two sequences of SAR data collected by the ASAR/ENVISAT and by the COSMO-SkyMed (CSK) sensors, respectively, spanning the whole time period from 2007 to 2016. Unfortunately, the large time gap (of about three years) existing between the available ASAR/ENVISAT and CSK datasets gave rise to additional difficulties for their combination. Nevertheless, this problem has been faced by benefiting from the knowledge of a time-dependent model describing the temporal evolution of the expected deformations affecting the Shanghai ocean-reclaimed platforms.

Species belonging to the Bauhinia genus, usually known as "pata-de-vaca", are popularly used to treat diabetes. Among them is Bauhinia ungulata var. obtusifolia (Ducke) Vaz, whose leaves are used, as a tea, for medicinal purposes in the Amazon region. The microencapsulation of the aqueous extract of its leaves, containing phenolic compounds, using five different wall materials (maltodextrin: DE11-14, and DE4-7; β-cyclodextrin; pectin, and sodium carboxymethylcellulose) is described in this paper. The microstructure, particle size, thermal behavior, yield, and encapsulation efficiency were investigated and compared using different techniques. Using high-performance liquid chromatography, phenolics, and flavonoids were detected and quantified in the microparticles. Microparticles, obtained with yield and phenolics encapsulation efficiency ranging between 60-83 % and 35-57 %, respectively, showed a particle size distribution between 1.15 and 5.54 µm, spherical morphology, and wrinkled surface. Among them, those prepared with sodium carboxymethylcellulose and pectin proved to be thermally the most stable. They had the highest flavonoid content (23.07 and 21.73 mgRUTE/g Extract) and total antioxidant activity by both the DPPH· (376.55 and 367.86 µmolTrolox/g Extract) and ABTS·+ (1085.72 and 1062.32 µmolTrolox/ g Extract) assays. The chromatographic analyses allowed for quantification, in the microparticles, chlorogenic acid (1.67-1.98 mg/g Extract), p-coumaric acid (0.06-0.08 mg/g Extract), rutin (11.1-12.9 mg/g Extract) and isoquercitrin (0.47-0.53 mg/g Extract), compounds considered responsible for the antidiabetic property attributed to the species.

Since 1970s, a great deal of attention has been paid to the development of semiconductor–based biosensors because of the numerous advantages they offer, including high sensitivity, faster response time, miniaturization, and low–cost manufacturing for quick biospecific analysis with reusable features. Commercial biosensors have become highly desirable in the fields of medicine, food, environmental monitoring as well as military applications (e.g., Hoffmann–La Roche, Abbott Point of Care, Orion High technologies, etc.), whereas increasing concerns on the food safety and health issues have resulted in the introduction of novel legislative standards for these sensors. Numerous devices have been developed for monitoring of biological–processes such as nucleic–acid hybridization, protein–protein interaction, antigen–antibody bonds and substrate–enzyme reactions, just to name a few. Since 1980s scientific interest moved to the development of semiconductor–based devices which also include integrated front–end electronics, such as the extended–gate–field–effect–transistor biosensor which is one of the first miniaturized chemical sensors. This work is intended to be a review of the state of the art focused on the development of biosensors based extended–gate–field–effect–transistor within the field of bioanalytical applications, which will highlight the most recent research works reported in the literature. Moreover, a comparison among the diverse EGFET devices will be presented giving particular attention to the materials and technologies.

Considering Cu(tda) chelate is a receptor for adenine and related 6-aminopurines, now we report the synthesis, molecular and crystal structures, thermal stability, spectral properties and DFT calculations on the [Cu(tda)(9heade)(H2O)]•2H2O (1). N7 is found to be the preferred donor atom of 9heade, that can favor the cooperation of a Cu-N7(9heade) bond and an (9heade)N6-H•••O(tda) interligand interaction. But unprecedentedly, the Cu(tda)-9heade molecular recognition in 1 is essentially featured the Cu-N1(9heade), without any N6-H•••O(carboxyl tda) interligand interaction. Nevertheless, being N1 the most basic donor for N9-substituted adenines, this Cu-N1 bond is now assisted by an O2-water mediated interaction (N6-H•••O2 and O2•••Cu weak contact). Also in the crystal packing, the O-H(ol) of 9heade interacts with its own adenine moiety by an O3-water mediated interaction (O(ol)-H•••O3 plus O3-H36•••π(adenine moiety). In turn these water-mediated interactions seems to be responsible to serious alterations on the physical properties of crystalline or grounded samples. Density functional theory calculations were used to evaluate the interactions energetically. Moreover, the quantum theory of atoms-in-molecules (QTAIM) in combination with the noncovalent interaction plot (NCIPlot) were used to analyze the interactions and rationalize the existence and relative importance of hydrogen bonding, chalcogen bonding and π-stacking interactions.

Osteoimmunology was coined about twenty years ago to identify a strict cross talk between bone niche and immune system both in physiological and pathological activities, including cancer. Several molecules are involved in the complex interaction between bone niche, immune and cancer cells. The Receptor Activator ok NF-kB (RANK)/RANK Ligand (RANKL/Osteoprotegerin (OPG) pathway plays a crucial role in bone cells/cancer interactions with subsequently immune system control failure, bone destruction, inhibition of effect and metastasis outcome. The bidirectional cross talk between bone and immune system could became a potential target for anticancer drugs. Several studies evidenced a direct anticancer role with improved survival of bone-targeted therapies such as bisphosphonates and RANKL antagonist Denosumab. Conversely, initial data evidenced a possible anti-bone resorption effect of systemic anticancer drugs through and immunomodulation activity, i.e. new generation antiandrogens (Abiraterone) in prostate cancer. All data could open a future rationale of combined bone, immunologic and targeted therapies in cancer treatment.

Fire-related deaths are issues for forensic pathologists particularly in ascertaining if death occurred before or during fire. The authors highlight a unique bronchiolar epithelial cytological clue (nuclear heat-induced elongation) determined by active inhalation of hot gases and fumes, not yet described in the literature at distal small airways level.

We provide a detailed analysis of the electronic properties of graphene-like materials with charge carriers living on a curved substrate, focusing in particular on constant negative-curvature spacetime. An explicit parametrization is also worked out in the remarkable case of Beltrami geometry, with an analytic solution for the pseudoparticles modes living on the curved bidimensional surface. We will then exploit the correspondent massless Dirac description, to determine how it affects the sample local density of states.

The knowledge of human body proportion and segmental properties of limbs, head and trunk are of fundamental importance in biomechanical research. As many methods are employed, it is important to know which they are currently available, which data on human body masses, lengths, center of mass (COM) location, weights and moment of inertia are available and which methods are most suitable for a specific research purposes. The present review examines the literature concerning human body segments properties for biomechanical purposes. It emerges that data obtained in studies on cadaveric specimens are still the most accurate, whilst technological tools currently available are manifolds, each one with proper advantages and disadvantages. Classical studies were focused mainly on white men, while in recent year the available data of body segments has been extended to children, woman, and other races. Also, data on special population (obese, pregnant women) are starting to appear in the scientific literature.

Metal foams are widely studied as possible tools for the enhancement of heat transfer from hot bodies. The basic idea is that a metal foam tends to increase significantly the heat exchange area between the hot solid body and the external cooling fluid. For this reason, this class of porous materials are considered as good candidates for an alternative to finned surfaces, with different pros and cons. Among the pros, we mention the generally wider area of contact between solid and fluid. Among the cons is the difficulty of producing different specimens with the same inner structure, with the consequence that their performance may be significantly variable. This paper will offer a survey of the literature with a focus on the main heat transfer characteristics of the metal foams. Then, a numerical simulation of the heat transfer at the pore scale level for an artificial foam with a spatially periodic structure will be discussed. Finally, these numerical results will be employed to assess the macroscopic modelling of the flow and heat transfer in a metal foam.

The objective of this paper is to present a mathematical formalism that states a bridge between Physics and Psychology, concretely between analytical dynamics and personality theory in order to open new insights in this theory. In this formalism energy plays a central role. First, the short-term personality dynamics can be measured by the General Factor of Personality (GFP) response to an arbitrary stimulus. This GFP dynamical response is modelled by a stimulus-response model: an integro-differential equation. The bridge between Physics and Psychology is provided when the stimulus-response model can be formulated as a linear second order differential equation and, subsequently, reformulated as a Newtonian equation. This bridge is strengthened when the Newtonian equation is derived from a minimum action principle, obtaining the current Lagrangian and Hamiltonian functions. However, the Hamiltonian is a non-conserved energy. Then, some changes provide a conserved Hamiltonian function: the Ermakov-Lewis energy. This energy is presented, as well as the GFP dynamical response that can be derived from it. An application case is presented: an experimental design in which 28 individuals consumed 26.51 g of alcohol. This experiment provides an ordinal scale for the Ermakov-Lewis energies that predicts the effect of a single dose of alcohol.

The incorporation of renewable energy systems in the world energy system has been steadily increasing during the last years. In terms of the building sector, the usual consumers are becoming increasingly prosumers, and the trend is that communities of energy, whose households share produced electricity, will increase in number in the future. Another observed tendency is that the aggregator (the entity that manages the community) trades the net community energy in public energy markets. To accomplish economically good transactions, accurate and reliable forecasts of the day-ahead net energy community must be available. These can be obtained using an ensemble of multi-step shallow artificial neural networks, with prediction intervals obtained by the covariance algorithm. Using real data obtained by a small energy community of four houses located in the South region of Portugal, one can verify that the deterministic and probabilistic performance of the proposed approach is at least similar, typically better than using complex, deep models.

This study compares lifestyles behaviour in Italian and Latvian university students, to assess if there are differences for sex, age, university or studies specialties. An online questionnaire investigating 8 lifestyle dimensions has been compiled by 156 (43,6 % females) from Italy and 105 from Latvia (82,9% females). Answers were collected between April and December 2020. Presence of smokers are negligible. The questionnaire showed to have a good internal consistency (Cronbach α =.929). On the total group, significant statistically differences were found for all the dimensions regarding age, sex, study specialty and university. Physical activity was associated with healthier lifestyles choices. Geographical-induced differences were found (eating and sleep behaviours, alcohol awareness) as well as socio-economic differences. Female students shown to be more stressed than males. Occupational wellness increased by age. Sport students shown more health awareness. Many of the differences found in the total group disappeared when comparing only sport students of the two university, showing females increasing their scores. This result can be explained by a masculinization effect of sport.

This is a study of Political Economy on religion and migration management in the United States of America (USA). This paper offers a review of migrants-citizens relations in the USA, with attention to the pendulum effect, moving from integration policies (open doors and melting pot agenda) to official persecution (raids and deportations), with a high social opportunity cost. There has been a split between the State and civil society, causing civil disobedience and sanctuary network across the country. Also, it is paid attention to the American post-modern paradox, as a result of culture wars and identity politics that imply a violation of American constitutional principles (i.e. religious liberty, freedom of movement, to pursuit the happiness). Special attention is paid to the development of the Sanctuary Movement, as an ongoing example of the sociocultural upheaval bringing grassroots society into confrontation with powerful elites by promoting resistance and offering help to the needy, even if this results in sanctions. This movement was revitalized after the values crisis of 2008, but it has also been polarized between those who follow the traditional approach to socio-religious action in the form of peaceful civil disobedience, and those who follow the ideological anti-system and communitarian approach, which causes greater tension for the immigrants themselves

We propose a thermodynamic model describing the thermoelastic behavior of composition graded materials. The compatibility of the model with second law of thermodynamics is explored by applying a generalized Coleman-Noll procedure. We calculate the speeds of coupled first- and second-sound pulses, propagating either trough nonequilibrium or trough equilibrium states. We characterize several different types of perturbations, depending on the value of the material coefficients. Under the assumption that the deformation of the body can produce changes in its stoichiometry, altering locally the material composition, the possibility of propagation of pure stoichiometric waves is pointed out. Thermoelastic perturbations generated by the coupling of stoichiometric and thermal effects are analyzed as well.

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.

Plant growth-promoting rhizobacteria (PGPR) are members of the plant rhizomicrobiome that enhance plant growth and stress resistance by increasing nutrient availability to the plant, producing phytohormones or other secondary metabolites, stimulating plant defense responses against abiotic stresses and pathogens, or fixing nitrogen. The use of PGPR to increase crop yield with minimal environmental impact is a sustainable and readily applicable replacement for a portion of chemical fertilizer and pesticides required for the growth of high-yielding varieties. Increased plant health and productivity have long been gained by applying PGPR as commercial inoculants to crops, although with uneven results. The establishment of plant-PGPR relationships requires the exchange of chemical signals and nutrients between the partners, and polyamines (PAs) are an important class of compounds that act as physiological effectors and signal molecules in plant-microbe interactions. In this review we focus on the role of PAs in interactions between PGPR and plants. We describe the basic ecology of PGPR and production and function of PAs in them and in the plants with which they interact. We examine the metabolism and the roles of PAs in PGPR and plants individually and during their interaction with one another. Lastly, we describe some directions for future research.

Grafting polyethylene glycol (PEG) on polymers surface is widely used to improve biocompatibility by reducing protein and cell adhesion. Although PEG is considered to be bioinert, its incorporation to biomaterials has shown to improve cell viability depending on the amount and molecular weight (MW) used. This phenomenon was studied here by grafting PEG of three MW onto polyurethane (PU) substrata at three molar concentrations to assess their effect on PU surface properties and on the viability of osteoblasts and fibroblasts. PEG formed a covering on the substrata which increased the hydrophilicity and surface energy of PUs. Among the results it was observed that osteoblast viability increased for all MW and grafting densities of PEG employed compared with unmodified PU. However, fibroblast viability only increased at certain combinations of MW and grafting densities of PEG, suggesting an optimal level of these parameters. PEG grafting also promoted a more spread cell morphology than that exhibited by unmodified PU; nevertheless, cells became apoptotic-like as PEG MW and grafting density were increased. These effects on cells could be due to PEG affecting culture medium pH, which became more alkaline at higher MW and concentrations of PEG. Results support the hypothesis that surface energy of PU substrates can be tuned by controlling the MW and grafting density of PEG, but these parameters should be optimized to promote cell viability without inducing apoptotic-like behavior.

The behaviour of the pseudo-protic ionic liquids TOAH+Cl- and TODAH+Cl- in the facilitated transport of indium(III) from HCl solutions is described. Metal transport is investigated as a function of different variables: hydrodynamic conditions, HCl concentration in the feed phase and indium and carrier concentrations. The experimental data are used to model both transport systems and to estimate diffusional parameters associated to them.

This is a paper of Political Economy and Economic Policies into the European Green Deal framework to improve the Recovery Plan post-COVID-19. This paper is focused on the green jobs opportunity for Europe, especially for Spain. It is offered a systematization of concepts and calculations in the issue (attending the international institutions and forums proposals) to harmonize the recovery plans, to apply them beyond the energy sector and to align public and private sector, as well other key stakeholders in achieving this goal. The obtained outcome gives the creation of around 350.000 new green jobs and the necessity of a new workforce reskilled. This result makes necessary to coordinate sectoral plans by the policymakers in which all the involved entities might express their needs and views on the best education approach to renewables sector and green jobs.

Objective: The purpose of the present study was to analyze the management of dental extractions in patients affected by coagulation disorders in order to prevent bleeding intraoperative and postoperative complications. Subjects and Methods: This study included 17 patients with a diagnosis of a coagulation disorder, who had been subjected to a single or multiple dental extraction. Recombinant activated Factor VII was administered in those patients who were affected by a deficit of factor VII ranged between 10,5% and 21%. The other patients were treated locally with tranexamic acid. Results: A total of 50 teeth were extracted, 7 by surgical extraction and 43 by simple extraction. Of the 17 patients included 9 of them suffering from factor VII deficiency, 5 from factor V deficiency, 1 from Glanzmann's thrombasthenia and 2 from Haemophilia A. Pretreatment with recombinant activated factor VII was performed on a total of 8 patients with factor VII deficiency; the remaining 9 patients underwent tranexamic acid treatment. 1 hemorragic postoperative complication was observed. Conclusions: Surgical and no surgical extractions appear to be a safe procedure for patients affected by coagulation disorders when appropriate prophylaxis is adopted.

This study compares lifestyles behaviour in Italian and Latvian university students, to assess if there are differences for sex, age, university or studies specialties. An online questionnaire investigating 8 lifestyle dimensions has been compiled by 156 (43,6 % females) from Italy and 105 from Latvia (82,9% females). Answers were collected between April and December 2020. Presence of smokers are negligible. The questionnaire showed to have a good internal consistency (Cronbach α =.929). On the total group, significant statistically differences were found for all the dimensions regarding age, sex, study specialty and university. Physical activity was associated with healthier lifestyles choices. Geographical-induced differences were found (eating and sleep behaviours, alcohol awareness) as well as socio-economic differences. Female students shown to be more stressed than males. Occupational wellness increased by age. Sport students shown more health awareness. Many of the differences found in the total group disappeared when comparing only sport students of the two university, showing females increasing their scores. This result can be explained by a masculinization effect of sport.

The study of precipitation amount at different time scales constitutes an important issue in climate research and risk assessment. When dealing with daily totals, a frequent but sometimes underestimated problem is at what time the observation day begins. The choice of different starting times may lead to incompatibility between stations and incorrect identification of extreme events. In this work, the problem of temporal misalignment between precipitation datasets characterized by different starting time of the observation day is analyzed. The most widely used adjustment methods (1day and uniform shift) and two methods based on reanalysis (NOAA and ERA5) are evaluated in terms of temporal alignment, precipitation statistics and percentile distributions. As test series, the precipitation amount collected from 9 a.m. local time (09 LT) on the previous day to 09 LT on the target day (9-9 datasets) of the Padua and nearby stations in the period 1993-2022 have been selected. Results show that the reanalysis-based methods, in particular ERA5, outperform the others in temporal alignment, regardless the station. But, for the periods in which reanalysis data are not available, “1day” method, which shifts the daily amount back one calendar day, and “unif” method, which distributes uniformly the daily total from a 2-day moving window surrounding the target date, can be considered valid alternatives. On the other side, concerning the precipitation statistics, the reanalysis-based methods are not the best option, as they increase the precipitation frequency and reduce the mean value over wet days, NOAA much more than ERA5. Nevertheless, the uniform method provides a larger deviation from the original daily series. The use of the series of a station nearby the target one, which is mandatory in case of missing data, gives similar or better results than applying any adjustment method to the 9-9 series. General conclusions can hardly be drawn as they depend on the method and station. For the Padua dataset, the analysis was repeated at monthly and seasonal resolution. In general, the adjustment series show the most relevant changes in the precipitation statistics in summer and less temporal alignment with the original series in summer and autumn, the two seasons mainly affected by heavy rains in Padua. Finally, the percentiles distribution, analyzed for all the methods and stations, indicates that any adjustment method underestimates the percentile values, except ERA5. Only Legnaro, the station most correlated with Padua, gives results like ERA5.

A distinction is made between data rescue (i.e., copying, digitizing and archiving) and data recovery that implies deciphering, interpreting and transforming early instrumental readings and their metadata to obtain high-quality datasets in modern units. This requires a multidisciplinary approach that includes: palaeography and knowledge of Latin and other languages to read the handwritten logs and additional documents; history of science to interpret the original text, data e metadata within the cultural frame of the 17th, 18th and early 19th century; physics and technology to recognize bias of early instruments or calibrations, or to correct for observational bias; astronomy to calculate and transform the original time in canonical hours that started from twilight. The liquid-in-glass thermometer was invented in 1641 and the earliest temperature records started in 1654. Since then, different types of thermometers were invented, based on the thermal expansion of air or selected thermometric liquids with deviation from linearity. Reference points, thermometric scales, calibration methodologies were not comparable, and not always adequately described. Thermometers had various locations and exposures, e.g., indoor, outdoor, on windows, gardens or roofs, facing different directions. Readings were made only one or a few times a day, not necessarily respecting a precise time schedule: this bias is analysed for the most popular combinations of reading times. The time was based on sundials and local Sun, but the hours were counted starting from twilight. In 1789-90 Italy changed system and all cities counted hours from their lower culmination (i.e., local midnight), so that every city had its local time; in 1866, all the Italian cities followed the local time of Rome; in 1893, the whole Italy adopted the present-day system, based on the Coordinated Universal Time and the time zones. In 1873, when the International Meteorological Committee (IMO) was founded, later transformed in World Meteorological Organization (WMO), a standardization of instruments and observational protocols was established, and all data became fully comparable. In the early instrumental period, from 1654 to 1873, the comparison, correction and homogenization of records is quite difficult, mainly because of the scarcity or even absence of metadata. This paper deals about this confused situation, discussing the main problems, but also the methodologies to recognize missing metadata, distinguish indoor from outdoor readings; correct and transform early datasets in unknown or arbitrary units into modern units; finally, in which cases it is possible to reach the quality level required by WMO. The focus is to explain the methodology needed to recover early instrumental records, i.e., the operations that should be performed to interpret, correct, and transform the original raw data into a high-quality dataset of temperature, usable for climate studies.

Microstructured optical fibres (MOFs) are a new type of optical fibres that possess a wide range of optical properties and many advantages over common optical fibres. Those are provided by unique structures defined by a pattern of periodic or quasi-periodic arrangement of air holes that run through the fibre length. In recent years, MOFs have opened up new possibilities in the field of optics and photonics, enabling the development of advanced devices and novel optical systems for different applications. The key application areas of PCFs vary from telecommunications and high-power energy transmission to quantum optics and sensing. The stack-and-draw method is a standard manufacturing technique for MOFs, where a preform is first manually created and then drawn in a high-tech furnace into a fibre with the required final dimensions and position of the air holes. Since in the manufacturing process experimenters can control only a few parameters, mathematical models and numerical simulations of the drawing process are highly requested. They not only allow to deepen the understanding of physical phenomena occurring during the drawing process, but they also accurately predict the final cross-section shape and size of the fibre. In this manuscript, we assume thermal equilibrium between the furnace and the fibre and propose a functional form of the fibre temperature distribution. We utilise it with asymptotic mass, momentum, and evolution equations for free surfaces already available in the literature to describe the process of fibre drawing. By doing so, the complex heat exchange problem between the fibre and the furnace need not be solved. The numerical results of the whole asymptotic model overall agree well with experimental data available in the literature, both for the case of annular capillaries and for the case of holey fibres.