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Japanese art tradition, contrary to the case of China, is characterized by an efficient and continued, although mostly undocumented, use of smalt from the late 16th century onward. Recent studies have successfully identified this pigment, the cobalt-colored glass that spread throughout the Old Continent during the Renaissance period, as the coloring agent employed for overglaze-blue enameling on Japanese porcelains produced at the kilns of Arita (the porcelain production center of Japan) from the early 1640s until the 20th century. Fragmentary evidence of the use of smalt in Japanese sacred art has also been reported, yet its earliest incorporation into such a type of traditional art form could not be identified. In order to resolve this crucial issue, portable EDXRF was employed for the non-destructive analyses of Japanese porcelains and sacred images bearing blue decoration. Scientific analysis allowed, for the first time ever, to establish a clear timeline of smalt use. Furthermore, this evidence and the literature data both agree, leading to the identification of the origin of the blue material used on both art productions.

Abstract A diagnostic investigation was carried out on twelfth century Byzantine wall paintings preserved in the Museum of Byzantine and Norman Culture and Figurative Arts of San Marco d’Alunzio (Messina, Italy) on the occasion of recent restoration works. First, the wall paintings were analyzed using portable X-Ray Fluorescence (p-XRF) and Fiber Optics Reflectance Spectroscopy (FORS) to obtain a non-invasive preliminary identification of the original palette. Then, five fragments were sampled for a micro-stratigraphy study using Digital Optical Microscope (DOM), Polarizing Optical Microscope (POM), and Scanning Electron Microscopy (SEM) combined with Energy Dispersive X-ray Spectrometry (EDS) to characterize the mortars and the blue and black pigments non unequivocally identified through non-invasive techniques. The palette included mainly earthen pigments like red and yellow ochres, green earth, and more valuable lapis lazuli blue applied on a bone black layer; while the analysis of mortars found on the different apses showed the same manufacturing technique and constitutive materials: lime-based binder with the addition of quartz, and rare calcareous lithic fragments as aggregate. The obtained results shed light on the pictorial technique used for the wall paintings and allowed us to compare the Sicilian pictorial cycle with the coeval Byzantine wall paintings preserved in Sardinia and Southern Italy.

The ManyDogs 1 study is the first multi-site collaborative study of dogs’ responses to human pointing. It addressed whether dogs perceive the gesture as socially communicative and are therefore more likely to follow the point when it is paired with additional social signals (ManyDogs Project, et al., 2023b). Researchers from 20 research sites across eight countries collected data from 704 dogs. Here, we present not only the behavior data on the dogs’ responses to experimental pointing conditions but also guardian responses to survey questions, including the Canine Behavior and Research Questionnaire (C-BARQ, Hsu and Serpell, 2003). This dataset allows for assessing associations among C-BARQ measures as well as connections to the experimental task data, research site metadata, and other dog and guardian characteristic data.

Animal health is affected during heat stress as a result of impaired immune responses, increased production of reactive oxygen species, and/or a deficiency of antioxidants. This leads to an imbalance between oxidants and antioxidants and results in oxidative stress. Heat stress is usually measured in dairy cattle via the temperature-humidity index (THI). In the present study, we aimed at assessing the influence of incremental THI on the balance between oxidative markers and the antioxidant defence system in the plasma of Modicana cows. Twenty-four multiparous, mid-lactating dairy cows were divided into two groups on the basis of different levels of mean THI reached in the period of the previous week up until the day of blood and milk sampling (April THI1:55, May THI2:68, June THI3:71, July THI4:80). The blood samples were collected to measure reactive oxygen metabolites (ROM) and antioxidant defense markers (ferric reducing ability of plasma (FRAP), paraoxonase (PON), advanced oxidation protein products (AOPP), plasma thiol groups (SHp), as well as lipid-soluble antioxidant pro-vitamin (β-carotene) and vitamins (tocopherol and retinol). Milk characteristics, haematological values, and plasma biochemical metabolites were also evaluated. Results showed a significant increase in ROM (p < 0.05) and a significant decrease in PON (p < 0.05), AOPP (p < 0.05), and β-carotene (p < 0.001). Incremental THI significantly decreased levels of milk fat content, red and white blood cells, plasma glucose, and non-esterified fatty acids, while significantly increasing monocytes and the concentrations of β-hydroxybutyrate and creatinine, but not fructosamine. The results of the study show that heat stress significantly affects reactive oxygen species production and antioxidant parameters. Carotenoid supplementation should be considered to alleviate the impact of these effects.

To promote collaboration across canine science, address replicability issues, and advance open science practices within animal cognition, we have launched the ManyDogs consortium, modeled on similar ManyX projects in other fields. We aimed to create a collaborative network that (a) uses large, diverse samples to investigate and replicate findings, (b) promotes open science practices of pre-registering hypotheses, methods, and analysis plans, (c) investigates the influence of differences across populations and breeds, and (d) examines how different research methods and testing environments influence the robustness of results. Our first study combines a phenomenon that appears to be highly reliable—dogs’ ability to follow human pointing—with a question that remains controversial: do dogs interpret pointing as a social communicative gesture or as a simple associative cue? We collected data (N = 455) from 20 research sites on two conditions of a 2-alternative object choice task: (1) Ostensive (pointing to a baited cup after making eye-contact and saying the dog’s name); (2) Non-ostensive (pointing without eye-contact, after a throat-clearing auditory control cue). Comparing performance between conditions, while both were significantly above chance, there was no significant difference in dogs’ responses. This result was consistent across sites. Further, we found that dogs followed contralateral, momentary pointing at lower rates than has been reported in prior research, suggesting that there are limits to the robustness of point-following behavior: not all pointing styles are equally likely to elicit a response. Together, these findings underscore the important role of procedural details in study design and the broader need for replication studies in canine science.

INTRODUCTION: Many surgical approaches have been described for hip hemiarthroplasty (HHA) treating femur neck fractures (FNFs). Direct lateral approach (DLA) is one of the most used. Today, the direct anterior approach (DAA) has become very attractive, but it seems to involve more intra-operative fractures. Our main endpoint was to demonstrate that the DAA may be a valid alternative comparing to the DLA. MATERIALS AND METHODS: Patients affected by FNFs and treated with HHA between the years 2016 and 2020 were studied. We divided the treatment of the fractures according to the surgical approach. The analysis was focused on perioperative complications and radiological outcomes. RESULTS: There were a total of 166 patients. The DLA group included patients with an average age of 83.5 years and the DAA group of 83 years. We found similar surgical times (DLA 67 min vs DAA 61 min; p = 0,55), number of transfusions (DLA 3/person vs DAA 4/person; p = 0,91), perioperative complications (fractures: DLA 0 vs DAA 0 – dislocations: DLA 2,50% vs DAA 0) and functional outcomes (HHS: DLA 83 points vs DAA 87 points; p = 0,71). There were no statistical differences comparing diaphyseal filling (Canal Fill Index at the proximal third: DLA 0,79 vs DAA 0,78; p= 0,24), bone loss (Paprosky I: DLA 96,25% vs DAA 91,86%; p = 0,47) and prevalence of heterotopic ossification (Broker low degree: DLA 93,75% vs 95, 34%; p = 0,87). CONCLUSION: Analysing perioperative complications and studying post-operative radiographic evolution, our results suggest that the DAA is a valid alternative to the DLA in HHA treating FNFs.

Finding biomarkers for targeted therapy is a promising approach to treat cancer. Here, the authors show that in breast cancer preclinical models and patients, CDK12 promotes tumourigenesis but induces selective vulnerability to therapies that target folate one-carbon metabolism.

This paper is concerned with a morphological-stylistic and archaeometric study of two small pottery statues, confiscated by the Cosenza Carabinieri Unit for the Protection of Cultural Heritage and Anti-Counterfeiting (Calabria, Italy). The research aimed to establish the authenticity of the artworks and to verify a possible origin from the same workshop manufacturing, by providing indications about the textural features and raw materials used for their production. For these purposes, the analytical approach involved the use of minero-petrographic and physical analysis, as follows: petrographic analysis (OM), X-ray diffraction (XRD) and thermoluminescence tests (TL). The preliminary observation, which highlights differences in the stylistic features of the two statuettes as well as in the color, morphology and distribution of the white-greyish patina, is further confirmed by the TL investigations. The TL test revealed an ancient production only for one of the analyzed finds and the investigations on the raw materials allowed to relate this to a possible local historical-artistic context. The second statuette, on the other hand, is attributable to a modern production as confirmed by TL measurement.

This study aimed to describe the incidence and characteristics of dog-bite injury hospitalizations (DBIH) in the largest administrative region of Italy (Sicily) over the 10-year period: 2012-2021. Four hundred and forty-nine cases were analyzed. Patients were divided into seven age groups: preschoolers (0–5 years), school-age children (6–12 years), teenagers (13–19 years), young adults (20–39 years), middle-aged adults (40–59 years), old adults (60–74 years), and the elderly (≥75 years). Association among categorical variables (age, gender, principal injury location) was evaluated using chi-square tests, and mean differences for normally distributed variables were assessed using one-way analysis of variance. Finally, a Poisson regression general linear model (GLM) analysis was used to model incidence data. The results revealed that the incidence of DBIH per 100,000 population increased from 0.648 in 2012 (95%CI 0.565–0.731) to 1.162 in 2021 (95%CI 1.078–1.247, P < 0.01). Incidence for both male and female victims also increased over the studied period (P < 0.05). We found an increasing trend of incidence in young and middle-aged adults (P < 0.05 and P < 0.005 respectively). Moreover, the most frequently injured age group by dogs was the preschooler group and, whilst we found a lower risk of being injured for males older than 20 years, no difference with females was observed. The location of lesions depended on the age group (P < 0.001). The number of days of DBIH increased significantly with age (P < 0.01). The increase of DBIH represents a public health problem that requires the development of preventive approaches.

Abstract Background Artificial intelligence (AI) has the potential to transform our healthcare systems significantly. New AI technologies based on machine learning approaches should play a key role in clinical decision-making in the future. However, their implementation in health care settings remains limited, mostly due to a lack of robust validation procedures. There is a need to develop reliable assessment frameworks for the clinical validation of AI. We present here an approach for assessing AI for predicting treatment response in triple-negative breast cancer (TNBC), using real-world data and molecular -omics data from clinical data warehouses and biobanks. Methods The European “ITFoC (Information Technology for the Future Of Cancer)” consortium designed a framework for the clinical validation of AI technologies for predicting treatment response in oncology. Results This framework is based on seven key steps specifying: (1) the intended use of AI, (2) the target population, (3) the timing of AI evaluation, (4) the datasets used for evaluation, (5) the procedures used for ensuring data safety (including data quality, privacy and security), (6) the metrics used for measuring performance, and (7) the procedures used to ensure that the AI is explainable. This framework forms the basis of a validation platform that we are building for the “ITFoC Challenge”. This community-wide competition will make it possible to assess and compare AI algorithms for predicting the response to TNBC treatments with external real-world datasets. Conclusions The predictive performance and safety of AI technologies must be assessed in a robust, unbiased and transparent manner before their implementation in healthcare settings. We believe that the consideration of the ITFoC consortium will contribute to the safe transfer and implementation of AI in clinical settings, in the context of precision oncology and personalized care.

Accumulating evidence sustains glial cells as critical players during central nervous system (CNS) development, homeostasis and disease. Olfactory ensheathing cells (OECs), a type of specialized glia cells sharing properties with both Schwann cells and astrocytes, are of critical importance in physiological condition during olfactory system development, supporting its regenerative potential throughout the adult life. These characteristics prompted research in the field of cell-based therapy to test OEC grafts in damaged CNS. Neuroprotective mechanisms exerted by OEC grafts are not limited to axonal regeneration and cell differentiation. Indeed, OEC immunomodulatory properties and their phagocytic potential encourage OEC-based approaches for tissue regeneration in case of CNS injury. Herein we reviewed recent advances on the immune role of OECs, their ability to modulate CNS microenvironment via bystander effects and the potential of OECs as a cell-based strategy for tissue regeneration.

The archaeometric study of the frescoes by the painter Saturnino Gatti (1463–1518) in the apse of the Church of San Panfilo in Villagrande di Tornimparte (L’Aquila) was the subject of the II National Research Project [...]

This work presents the results of the in situ, non-invasive diagnostic investigations performed on the canvas oil painting depicting Madonna and Child, venerated as ‘Maria Santissima delle Grazie’ by the local religious community. The work of art (72 cm × 175 cm) is located on the high altar of the main Church in Mirabella Imbáccari, near Catania (Sicily, Italy). The painter is anonymous, and the supposed dating is the late eighteenth century. Although the painting has never been studied before, it has been attributed to a Sicilian workshop in the literature, raising the doubts of the art historian who conducted this study and who hypothesized a Neapolitan manufacture. Furthermore, due to the good conservation state detected by a macroscopic examination, doubts also arose about dating. To shed light on these aspects, a technical-scientific examination proved necessary. Multispectral imaging techniques (IR Reflectography, UV-induced visible Fluorescence, X-ray) are carried out for the study of the execution technique, the identification of underlying remakes, sketch drawing and the evaluation of the conservation conditions. XRF spectrometry analysis is performed for the identification of the chemical elements constituting the pigments (inorganic chromophores). The diagnostic results allowed this research to confirm the dating suggested by the historical-stylistic knowledge and to highlight new technical peculiarities supporting the attribution to a Neapolitan workshop.

Introduction Management of pediatric long bones fractures is a complex and rapidly evolving field. Traditionally, casting and conservative techniques played a key-role in the management of fractures in skeletally immature patients. However, the surgical approach has evolved steadily over the past four decades or so and increasing evidence has been published supporting the advantages of fixation techniques over conservative methods. The purpose of this narrative review is to outline how innovations in orthopedic surgery have changed the rationale of treating long bones fractures in children and adolescents with focus on surgical techniques, particularly elastic stable intramedullary nailing (ESIN). Material and methods We aimed to describe the main trends in pediatric long bones fractures management and to identify its specificities and difficulties as well as the best standard of care. Results The introduction of ESIN has profoundly influenced the management of pediatric upper and lower extremity fractures. Overall, in comparison to conservative techniques, advantages of ESIN include minimally invasiveness, short hospital stay, primary bone union, early mobilization and progressive weight bearing, and good outcome with low complication rate. Moreover, the flexible nail can be used as a closed reduction tool itself. Conclusions Irrespective of the technique performed, the key-concepts remain 1) the proper understanding of the injury to treat; 2) the identification the main characteristics of the patient; 3) the pros and cons of each technique; and 4) the potential complications.

Introduction Idiopathic clubfoot (IC), also referred to as congenital talipes equinovarus, is one of the most common lower limb deformities observed in newborns, leading to significant functional impairment when left untreated. Early minimally invasive treatment has been praised as one of the most successful practice of modern pediatric orthopedics. This review aims to report current knowledge and controversies about clubfoot treatment. Material and methods We describe the main trends in clubfoot managing, identifying peculiarities, difficulties and prognostic factors related to the treatment. Results Many treatment techniques either conservative, surgical or hybrid have been used over the past decades. Based on good and excellent results during long-term follow-up, Ponseti method has been globally accepted by paediatric orthopaedic surgeons as standard method of treatment. However, some other conservative methods are still widely applied in the clinical setting, such as the French Physical Therapy method. Adherence to the bracing protocol is critical for the long-term success of the treatment, being a better predictor for relapse than severity of the deformity at birth. Conclusions Taking care of the manipulation and casting details by trained professionals, together with enhancing the child and patents’ adherence to the brace, are essential for the success of conservative treatment. Surgery should be performed only when strictly needed, preferably on a “a la carte” approach.

Abstract Motoneuronal loss is the main feature of amyotrophic lateral sclerosis, although pathogenesis is extremely complex involving both neural and muscle cells. In order to translationally engage the sonic hedgehog pathway, which is a promising target for neural regeneration, recent studies have reported on the neuroprotective effects of clobetasol, an FDA-approved glucocorticoid, able to activate this pathway via smoothened. Herein we sought to examine functional, cellular, and metabolic effects of clobetasol in a neurotoxic mouse model of spinal motoneuronal loss. We found that clobetasol reduces muscle denervation and motor impairments in part by restoring sonic hedgehog signaling and supporting spinal plasticity. These effects were coupled with reduced pro-inflammatory microglia and reactive astrogliosis, reduced muscle atrophy, and support of mitochondrial integrity and metabolism. Our results suggest that clobetasol stimulates a series of compensatory processes and therefore represents a translational approach for intractable denervating and neurodegenerative disorders.

The origin of Ko-Kutani porcelain and its decoration style have been debated for over a century. Despite the well-established theory that identified the wares as the result of porcelain production in Kaga (present-day Ishikawa Prefecture) in the 17th century, there still is no general agreement as to where they were first incepted and fired. In recent years, curatorial traditional criteria have formed the basis upon which a new theory has been gaining popularity in Japan, identifying Arita (present-day Saga Prefecture) as their actual place of birth. Such a new theory, however, has proven insufficient to cast new light on many of the unexplained facts that characterize the history of the wares. Furthermore, scientific evidence has been lacking, as no systematic analyses of the porcelains were carried out until the present work. In order to define univocally the dynamics behind this period of Japanese history, the most important and complete Ko-Kutani collection extant in Japan today (Ishikawa Prefectural Museum of Art) was analyzed by portable X-ray fluorescence (pXRF). The scientific investigation was also extended to the very scarce shards excavated at the Kaga kiln site and Nonomura Ninsei's masterpieces. For the first time ever, the results herein presented clarify the missing points crucial to reaching a definitive conclusion. [ABSTRACT FROM AUTHOR]

Simple Summary: This study was conducted to determine the effects of the incremental temperature humidity index (THI) on oxidant and antioxidant plasma markers in mid-lactating dairy cows. Results showed a significant increase in oxidative markers and a significant decrease in antioxidant defence; this balance results in oxidative stress. Heat stress significantly modulated fat milk content, blood cell number, and plasma metabolite concentration. Animal health is affected during heat stress as a result of impaired immune responses, increased production of reactive oxygen species, and/or a deficiency of antioxidants. This leads to an imbalance between oxidants and antioxidants and results in oxidative stress. Heat stress is usually measured in dairy cattle via the temperature-humidity index (THI). In the present study, we aimed at assessing the influence of incremental THI on the balance between oxidative markers and the antioxidant defence system in the plasma of Modicana cows. Twenty-four multiparous, mid-lactating dairy cows were divided into two groups on the basis of different levels of mean THI reached in the period of the previous week up until the day of blood and milk sampling (April THI1:55, May THI2:68, June THI3:71, July THI4:80). The blood samples were collected to measure reactive oxygen metabolites (ROM) and advanced oxidation protein products (AOPP) on the one hand, and antioxidant defense markers (ferric reducing ability of plasma (FRAP), paraoxonase (PON), plasma thiol groups (SHp)), as well as lipid-soluble antioxidant pro-vitamin (β-carotene) and vitamins (tocopherol and retinol) on the other hand. Milk characteristics, haematological values, and plasma biochemical metabolites were also evaluated. Results showed a significant increase in ROM (p < 0.05) and a significant decrease in PON (p < 0.05), AOPP (p < 0.05), and β-carotene (p < 0.001). Incremental THI significantly decreased levels of milk fat content, red and white blood cells, plasma glucose, and non-esterified fatty acids, while significantly increasing monocytes and the concentrations of β-hydroxybutyrate and creatinine, but not fructosamine. The results of the study show that heat stress significantly affects reactive oxygen species production and antioxidant parameters. Carotenoid supplementation should be considered to alleviate the impact of these effects. [ABSTRACT FROM AUTHOR]

Neuronal differentiation is regulated by nerve growth factor (NGF) and other neurotrophins. We explored the impact of NGF on mitochondrial dynamics and metabolism through time‐lapse imaging, metabolomics profiling, and computer modeling studies. We show that NGF may direct differentiation by stimulating fission, thereby causing selective mitochondrial network fragmentation and mitophagy, ultimately leading to increased mitochondrial quality and respiration. Then, we reconstructed the dynamic fusion–fission–mitophagy cycling of mitochondria in a computer model, integrating these processes into a single network mechanism. Both the computational model and the simulations are able to reproduce the proposed mechanism in terms of mitochondrial dynamics, levels of reactive oxygen species (ROS), mitophagy, and mitochondrial quality, thus providing a computational tool for the interpretation of the experimental data and for future studies aiming to detail further the action of NGF on mitochondrial processes. We also show that changes in these mitochondrial processes are intertwined with a metabolic function of NGF in differentiation: NGF directs a profound metabolic rearrangement involving glycolysis, TCA cycle, and the pentose phosphate pathway, altering the redox balance. This metabolic rewiring may ensure: (a) supply of both energy and building blocks for the anabolic processes needed for morphological reorganization, as well as (b) redox homeostasis. [ABSTRACT FROM AUTHOR]

Several studies have recently investigated the birth weight of puppies from different pure-bred dogs. In general, birth weight decreased with litter size but there has been limited investigation into factors influencing growth during early development. The first month of life includes three stages of puppy development: neonatal (0–13 days), transitional (14–20 days), and first week of socialisation period (21–28 days). The aim of this study was to evaluate bodyweight and growth rate of 120 Labrador Retriever (LR) puppies during early development. Puppies from 19 show-line bitches under standardised composition of diet during pregnancy and lactation were involved in this study. Puppies were weighed weekly from birth to 28 days using an electronic digital balance. Relative weight gain (ΔW) was calculated for the neonatal period [ΔW1 = (Wday14-Wday0)/Wday0], transition period [ΔW2 = (Wday21-Wday14)/Wday14] and first week of socialisation period [ΔW2 = (Wday28-Wday21)/Wday21]. The effects of covariates on ΔW were assessed using generalised linear mixed models. Sex and photoperiod had no impact on relative weight gain, whereas litter size had a significant effect at ΔW1 (p

Abstract Background Rewiring of metabolism induced by oncogenic K-Ras in cancer cells involves both glucose and glutamine utilization sustaining enhanced, unrestricted growth. The development of effective anti-cancer treatments targeting metabolism may be facilitated by the identification and rational combinatorial targeting of metabolic pathways. Methods We performed mass spectrometric metabolomics analysis in vitro and in vivo experiments to evaluate the efficacy of drugs and identify metabolic connectivity. Results We show that K-Ras-mutant lung and colon cancer cells exhibit a distinct metabolic rewiring, the latter being more dependent on respiration. Combined treatment with the glutaminase inhibitor CB-839 and the PI3K/aldolase inhibitor NVP-BKM120 more consistently reduces cell growth of tumor xenografts. Maximal growth inhibition correlates with the disruption of redox homeostasis, involving loss of reduced glutathione regeneration, redox cofactors, and a decreased connectivity among metabolites primarily involved in nucleic acid metabolism. Conclusions Our findings open the way to develop metabolic connectivity profiling as a tool for a selective strategy of combined drug repositioning in precision oncology.

Abstract The production of Japanese enamels for porcelain decoration was thought to have originated from the direct and exclusive influence of Chinese potters who moved to Japan during the chaotic Ming to Qing dynastic change in 1644. Recent systematic studies have identified, for the first time, the crucial influence of Jesuit missionaries on pigment and enamel production in Japan from the late 16th-century. In particular, such first encounter laid the foundation for the continued influence exerted by European technology on Japanese art throughout the centuries. The present study has further identified European enamels used for the decoration of polychrome wares fired in Arita, the porcelain production center of Japan. This continued exchange not only marked the Edo period, but also extended into the twentieth century. For the first time, the lack of written records regarding the use of western pigments for enamel production caused by the persecutions of European and Japanese Christians has been overcome in the work herein presented. The nature of the imported materials has been firmly identified and characterized. The analytical results (EDXRF and Raman) have finally revealed how western technology and materials not only kept influencing Japanese art during the isolation (sakoku) period, but also accompanied the strong westernization process that marked Japanese history from the late nineteenth century. Moreover, the significant reverse influence of Japanese-made enamels on Chinese polychrome porcelain production in the late Qing and twentieth century has been fully identified for the first time. Furthermore, results show that the shift of the Pb mode of lead antimonate (Naples Yellow) is affected by the firing temperature for enamel decoration, and that this characteristic, along with the chemical composition, enables the identification of the origin and manufacture period of the yellow enamel.

Porcelain stone used at the early kilns of Arita, Japan, has never been identified due to the lack of written records. Ryumon and Shirakawa deposits are considered to have possibly been exploited before Izumiyama was discovered in the early 1630s, but there are no records or any previous scientific research aimed at resolving such crucial issue. This work presents the first systematic scientific study of clays from the three deposits and shards excavated at early kiln sites. Portable ED-XRF and SEM-EDS were used to identify the chemical compositions of bodies, glazes, and geochemical characteristics of clays. XRD, TG-DSC, and FTIR-ATR spectroscopy were also used for the mineralogical characterization of clay bodies. Results show that the earliest production was marked by the mineralogical characteristics of the available raw materials. A gradual improvement in material selection and processing will lead to the development of the nigoshide (milky-white) body in the mid-17th century.

Metabolism is directly and indirectly fine-tuned by a complex web of interacting regulatory mechanisms that fall into two major classes. On the one hand, the expression level of the catalyzing enzyme sets the maximal theoretical flux level (i.e., the net rate of the reaction) for each enzyme-controlled reaction. On the other hand, metabolic regulation controls the metabolic flux through the interactions of metabolites (substrates, cofactors, allosteric modulators) with the responsible enzyme. High-throughput data, such as metabolomics and transcriptomics data, if analyzed separately, do not accurately characterize the hierarchical regulation of metabolism outlined above. They must be integrated to disassemble the interdependence between different regulatory layers controlling metabolism. To this aim, we propose INTEGRATE, a computational pipeline that integrates metabolomics and transcriptomics data, using constraint-based stoichiometric metabolic models as a scaffold. We compute differential reaction expression from transcriptomics data and use constraint-based modeling to predict if the differential expression of metabolic enzymes directly originates differences in metabolic fluxes. In parallel, we use metabolomics to predict how differences in substrate availability translate into differences in metabolic fluxes. We discriminate fluxes regulated at the metabolic and/or gene expression level by intersecting these two output datasets. We demonstrate the pipeline using a set of immortalized normal and cancer breast cell lines. In a clinical setting, knowing the regulatory level at which a given metabolic reaction is controlled will be valuable to inform targeted, truly personalized therapies in cancer patients.

The central nervous system represents a complex environment in which glioblastoma adapts skillfully, unleashing a series of mechanisms suitable for its efficient development and diffusion. In particular, changes in gene expression and mutational events that fall within the domain of epigenetics interact complexly with metabolic reprogramming and stress responses enacted in the tumor microenvironment, which in turn fuel genomic instability by providing substrates for DNA modifications. The aim of this review is to analyze this complex interaction that consolidates several conditions that confer a state of immunosuppression and immunoevasion, making glioblastoma capable of escaping attack and elimination by immune cells and therefore invincible against current therapies. The progressive knowledge of the cellular mechanisms that underlie the resistance of the glioblastoma represents, in fact, the only weapon to unmask its weak points to be exploited to plan successful therapeutic strategies.

Previous to this study, there is no data relating to the reproductive physiology of the Cirneco dell'Etna breed. The birth date of 141 bitches and 104 sires registered at the National Agency of the Italian Kennel Club (ENCI) from all Sicilian breeders, and data related their fertile matings, which produced 266 whelps over a 14-year period, (2009–2022) were collected. Total whelping produced 1069 pups. The mean bitch age at first whelping was 39.13 ± 21.7 months and the mean litter size was 3.84 ± 2.08. The birth period of the bitches and sires was significantly influenced by the month of the year (p < 0.01), as was the distribution of the first (p < 0.05) and subsequent whelping periods (p < 0.01). Whelping distributions show a significant difference between the highest peak in April (which roughly corresponds to a period of heat in February) and in July (which roughly corresponds to a period of heat in May) and the lowest peak in March. No influence of month on litter size and sex ratio was found. Available data suggests that some ancient breeds such as the Cirneco dell'Etna may show seasonal patterns as a vestige of the stricter seasonality of its closest relative the wolf. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM), a WHO grade IV glioma, is a malignant primary brain tumour for which combination of surgery, chemotherapy and radiotherapy is the first‐line approach despite adverse effects. Tumour microenvironment (TME) is characterized by an interplay of cells and soluble factors holding a critical role in neoplastic development. Significant pathophysiological changes have been found in GBM TME, such as glia activation and oxidative stress. Microglia play a crucial role in favouring GBM growth, representing target cells of immune escape mechanisms. Our study aims at analysing radiation‐induced effects in modulating intercellular communication and identifying the basis of protective mechanisms in radiation‐naïve GBM cells. Tumour cells were treated with conditioned media (CM) derived from 0, 2 or 15 Gy irradiated GBM cells or 0, 2 or 15 Gy irradiated human microglia. We demonstrated that irradiated microglia promote an increase of GBM cell lines proliferation through paracrine signalling. On the contrary, irradiated GBM‐derived CM affect viability, triggering cell death mechanisms. In addition, we investigated whether these processes involve mitochondrial mass, fitness and oxidative phosphorylation and how GBM cells respond at these induced alterations. Our study suggests that off‐target radiotherapy modulates microglia to support GBM proliferation and induce metabolic modifications. [ABSTRACT FROM AUTHOR]

Japanese art tradition, contrary to the case of China, is characterized by an efficient and continued, although mostly undocumented, use of smalt from the late 16th century onward. Recent studies have successfully identified this pigment, the cobalt-colored glass that spread throughout the Old Continent during the Renaissance period, as the coloring agent employed for overglaze-blue enameling on Japanese porcelains produced at the kilns of Arita (the porcelain production center of Japan) from the early 1640s until the 20th century. Fragmentary evidence of the use of smalt in Japanese sacred art has also been reported, yet its earliest incorporation into such a type of traditional art form could not be identified. In order to resolve this crucial issue, portable EDXRF was employed for the non-destructive analyses of Japanese porcelains and sacred images bearing blue decoration. Scientific analysis allowed, for the first time ever, to establish a clear timeline of smalt use. Furthermore, this evidence and the literature data both agree, leading to the identification of the origin of the blue material used on both art productions. [ABSTRACT FROM AUTHOR]

• Season and photoperiod influence severe dog attack cases. • The relative risk to be injured by dogs is modulated by age, season and photoperiod. • The relative risk for DBIH in adults is higher in winter. • A positive trend for severe dog attacks was found in adults in winter and in autumn. Dog bites in humans are a serious public health problem widely documented. Although some studies report a seasonal effect on dog bite incidence, the rationale for these findings is poor. This study aimed to describe the influence of season and photoperiod on the incidence of dog bite injury hospitalizations (DBIH) in Sicily, a Mediterranean climate region, over 10 years (2012-2021). Four hundred and forty-nine cases of severe dog bites that required hospitalization were analyzed. Patients were divided into two age groups: group 1 (0-19 years) and group 2 (≥20 years). A Poisson regression general linear model analysis was used to model incidence data across seasons and photoperiods (short photoperiod [SP] and long photoperiod [LP]). The results revealed that the relative risk for group 1 is higher during summer (2.03; 95%CI 1.30-2.17) and, in general, during LP (1.788; 95%CI 1.274-2.55) when compared with autumn and SP, respectively. Comparing group 2 with group 1, a lower relative risk is observed in both summer (0.42; 95%CI 0.28-0.63) and spring (0.32; 95%CI 0.22-0.45), and in LP (0.41; 95%CI 0.31-0.53). In group 2, results showed a significant increase of DBIH during winter and autumn (P < 0.05) and in both photoperiods with a positive trend over 10 years (P < 0.05). Results from this study suggest an influence of season on DBIH modulated by the age of patients. This aspect should be considered in developing preventive approaches for dog bite injuries. [ABSTRACT FROM AUTHOR]

An archaeometric approach was applied to the study of the hoard found in the Samshvilde fortress, one of the richest areas of archaeological artefacts in Caucasian Georgia, since it is representative of the historical events from the Neolithic period until the most recent epochs. In this context, four coins dated back to the 12th–13th centuries AD to the reign of King Giorgi III, Queen Tamar, and King Giorgi IV of Georgia underwent different analytical methods to collect information about the technological production process, the probable forge location, and their conservation state. Optical microscope observations provided details about the decorations, the stylistic aspects, and a preliminary evaluation of the conservation state. Portable X-ray fluorescence and scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy analysis revealed a composition consisting almost exclusively of copper with a lower amount of tin, lead, and silver. Moreover, degradation products (copper chlorides and sulphates) and cuprite patina were identified. The metal-supplying areas could be related to the nearby Bolnisi Mining District, and the forge location could coincide with the hoard location in Samshvilde, but further data and analyses are necessary. [ABSTRACT FROM AUTHOR]

The “Trionfo della morte” is a detached fresco painting dated at the half of the XV century. Its history is strictly connected with the history of Palermo and it is considered a symbol of the late Gothic period. Some small areas of the fresco were analyzed using a combination of non-invasive techniques and hand-held instrumentations (multispectral imaging analysis, X-ray fluorescence (XRF), and IR spectroscopy). The characterization of the nature of pigments used in its realization and restoration works was performed and some indications about its conservation state were obtained. More interestingly, some hidden details were revealed on the mysterious painting. They constitute additional evidence of the preciousness of the fresco.

A monitoring campaign performed on the Real Site of Carditello (found in the commune of San Tammaro, province of Caserta, Italy) was aimed to evaluate the parameters related to air quality and then to control and prevent the degradation risk. The analyses were carried out in the context of the project “Innovative methods and technologies for the conservation, valorisation and use of cultural heritage: environmental and archaeological analyses”, within the CULTURA CREA-MIBAC program, which aims to provide innovative methods for conservation and enhancement of cultural heritage through environmental and archaeometric analyses. Preliminarily, using field equipment, non-destructive investigations were carried out to identify constituent, restoration, and/or degradation materials belonging to the wall paintings on the main floor and to assess their conservation state under the current environmental conditions. Environmental monitoring was performed both outdoor (to assess the effects of atmospheric pollution and changes in the climate of the structure) and indoor the rooms of the site (to evaluate the conditions of conservation and fruition). The collected data are reported in a web platform, where one can check the real time monitoring data. The platform integrates both environmental data and information regarding the "health status" of site in order to provide a detailed analysis useful for its protection.

The recognition that neurogenesis does not stop with adolescence has spun off research towards the reduction of brain disorders by enhancing brain regeneration. Adult neurogenesis is one of the tougher problems of developmental biology as it requires the generation of complex intracellular and pericellular anatomies, amidst the danger of neuroinflammation. We here review how a multitude of regulatory pathways optimized for early neurogenesis has to be revamped into a new choreography of time dependencies. Distinct pathways need to be regulated, ranging from neural growth factor induced differentiation to mitochondrial bioenergetics, reactive oxygen metabolism, and apoptosis. Requiring much Gibbs energy consumption, brain depends on aerobic energy metabolism, hence on mitochondrial activity. Mitochondrial fission and fusion, movement and perhaps even mitoptosis, thereby come into play. All these network processes are interlinked and involve a plethora of molecules. We recommend a deep thinking approach to adult neurobiology.

Background: Rheumatic heart disease (RHD) is a major cause of cardiovascular disease in developing nations, leading to more than 230,000 deaths annually. Most patients seek medical care only when long-term structural and hemodynamic complications have already occurred. Echocardiographic screenings ensure the early detection of asymptomatic subjects who could benefit from prophylaxis, monitoring and intervention, when appropriate. The aim of this study is to assess the feasibility of a screening program and the prevalence of RHD in a Ugandan orphanage. Methods: We performed an RHD-focused echocardiogram on all the children (5–14 years old) living in a north Ugandan orphanage. Exams were performed with a portable machine (GE Vivid-I). All the time intervals were recorded (minutes). Results: A total of 163 asymptomatic children were screened over 8 days (medium age 9.1; 46% male; 17% affected by severe motor impairment). The feasibility rate was 99.4%. An average of 20.4 exams were performed per day, with an average of 15.5 images collected per subject. Pathological mitral regurgitation (MR) was found in 5.5% of subjects, while at least two morphological features of RHD were found in 4.3%, leading to 1 “definite RHD” (0.6%) case and 13 “borderline RHD” cases (8.1%). Six congenital heart defects were also noted (3.7%): four atrial septal defects, one coronary artery fistula and one Patent Ductus Arteriosus. Conclusions: We demonstrated the feasibility of an echocardiographic screening for RHD in an orphanage in Uganda. A few factors, such as good clinical and hygienic care, the availability of antibiotics and closeness to a big hospital, may account for the low prevalence of the disease in our population.