Investigation into the Anti-Acne Effects of Castanea sativa Mill Leaf and Its Pure Ellagitannin Castalagin in HaCaT Cells Infected with Cutibacterium acnes.

Acne vulgaris is a prevalent skin disorder affecting many young individuals, marked by keratinization, inflammation, seborrhea, and colonization by Cutibacterium acnes (C. acnes). Ellagitannins, known for their antibacterial and anti-inflammatory properties, have not been widely studied for their anti-acne effects. Chestnut (Castanea sativa Mill., C. sativa), a rich ellagitannin source, including castalagin whose acne-related bioactivity was previously unexplored, was investigated in this study. The research assessed the effect of C. sativa leaf extract and castalagin on human keratinocytes (HaCaT) infected with C. acnes, finding that both inhibited IL-8 and IL-6 release at concentrations below 25 µg/mL. The action mechanism was linked to NF-κB inhibition, without AP-1 involvement. Furthermore, the extract displayed anti-biofilm properties and reduced CK-10 expression, indicating a potential role in mitigating inflammation, bacterial colonization, and keratosis. Castalagin's bioactivity mirrored the extract's effects, notably in IL-8 inhibition, NF-κB inhibition, and biofilm formation at low µM levels. Other polyphenols, such as flavonol glycosides identified via LC-MS, might also contribute to the extract's biological activities. This study is the first to explore ellagitannins' potential in treating acne, offering insights for developing chestnut-based anti-acne treatments pending future in vivo studies.

Parametric Frequency Divider Based Ising Machines.

We report on a new class of Ising machines (IMs) that rely on coupled parametric frequency dividers (PFDs) as macroscopic artificial spins. Unlike the IM counterparts based on subharmonic-injection locking (SHIL), PFD IMs do not require strong injected continuous-wave signals or applied dc voltages. Therefore, they show a significantly lower power consumption per spin compared to SHIL-based IMs, making it feasible to accurately solve large-scale combinatorial optimization problems that are hard or even impossible to solve by using the current von Neumann computing architectures. Furthermore, using high quality factor resonators in the PFD design makes PFD IMs able to exhibit a nanowatt-level power per spin. Also, it remarkably allows a speedup of the phase synchronization among the PFDs, resulting in shorter time to solution and lower energy to solution despite the resonators' longer relaxation time. As a proof of concept, a 4-node PFD IM has been demonstrated. This IM correctly solves a set of Max-Cut problems while consuming just 600 nanowatts per spin. This power consumption is 2 orders of magnitude lower than the power per spin of state-of-the-art SHIL-based IMs operating at the same frequency.

Compact and wideband nanoacoustic pass-band filters for future 5G and 6G cellular radios.

Over recent years, the surge in mobile communication has deepened global connectivity. With escalating demands for faster data rates, the push for higher carrier frequencies intensifies. The 7-20 GHz range, located between the 5G sub-6 GHz and the mm-wave spectra, provides an excellent trade-off between network capacity and coverage, and constitutes a yet-to-be-explored range for 5G and 6G applications. This work proposes a technological platform able to deliver CMOS-compatible, on-chip multi-frequency, low-loss, wide-band, and compact filters for cellular radios operating in this range by leveraging the micro-to-nano scaling of acoustic electromechanical resonators. The results showcase the first-ever demonstrated low insertion loss bank of 7 nanoacoustic passband filters in the X-band. Most of the filters showcase fractional bandwidths above 3% and sub-dB loss per stage in an extremely compact form factor, enabling the manufacturing of filters and duplexers for the next generation of mobile handsets operating in the X-band and beyond.

Virtual hospital and artificial intelligence: a first step towards the application of an innovative health system for the care of rare cerebrovascular diseases.

The development of virtual care options, including virtual hospital platforms, is rapidly changing the healthcare, mostly in the pandemic period, due to difficulties in in-person consultations. For this purpose, in 2020, a neurological Virtual Hospital (NOVHO) pilot study has been implemented, in order to experiment a multidisciplinary second opinion evaluation system for neurological diseases. Cerebrovascular diseases represent a preponderant part of neurological disorders. However, more than 30% of strokes remain of undetermined source, and rare CVD (rCVD) are often misdiagnosed. The lack of data on phenotype and clinical course of rCVD patients makes the diagnosis and the development of therapies challenging. Since the diagnosis and care of rCVDs require adequate expertise and instrumental tools, their management is mostly allocated to a few experienced hospitals, making difficult equity in access to care. Therefore, strategies for virtual consultations are increasingly applied with some advantage for patient management also in peripheral areas. Moreover, health data are becoming increasingly complex and require new technologies to be managed. The use of Artificial Intelligence is beginning to be applied to the healthcare system and together with the Internet of Things will enable the creation of virtual models with predictive abilities, bringing healthcare one step closer to personalized medicine. Herein, we will report on the preliminary results of the NOVHO project and present the methodology of a new project aimed at developing an innovative multidisciplinary and multicentre virtual care model, specific for rCVD (NOVHO-rCVD), which combines the virtual hospital approach and the deep-learning machine system.

6-20 GHz 30% ScAlN Lateral Field-Excited Cross-Sectional Lamé Mode Resonators for Future Mobile RF Front Ends.

This article reports on 30% scandium-doped AlN (ScAlN) lateral field-excited (LFE) cross-sectional Lame' mode resonators (CLMRs) with unprecedented performance in the 6-20 GHz range. By combining high-crystallinity 30% ScAlN piezoelectric thin films, a lithographic tunability of the resonance frequency, and a simple three-mask post-CMOS compatible fabrication process, we propose a technology platform that can enable the mass production of low-loss, wideband, and compact microacoustic filtering devices spanning a wide spectrum portion on the same chip for the next-generation radio frequency front ends (RFFEs) of handsets. This article demonstrates a successful scaling of the microacoustic technology well beyond the sub-6-GHz fifth-generation (5G) band, as well as the outstanding capabilities of high-crystallinity 30% ScAlN piezoelectric layers in delivering high-quality factor ( Q ) and high-electromechanical coupling ( kt2 ) resonators, notably exceeding the state of the art in terms of relevant figures of merit (FOMs). Furthermore, we experimentally investigate the impact of geometrical parameters, such as tethering configuration and width-over-length ratio on the devices' 3-dB quality factor ( [Formula: see text]), power linearity (PL), and temperature coefficient of frequency (TCF). By adopting a statistical approach for data analysis, we determine the optimal geometry to maximize the Q value. Moreover, we experimentally demonstrate that a fully tethered device's configuration ensures superior PL, lower TCF, and higher device yield and select that as the best design tradeoff between all the variables under consideration. Finally, we discuss a further scaling of LFE CLMRs, both in terms of higher doping levels in the piezoelectric layer, in order to enhance the performance of microacoustic filters, and in terms of higher operation frequencies, in order to reach and cover the mm-wave spectrum.

Ellagitannins from Castanea sativa Mill. Leaf Extracts Impair H. pylori Viability and Infection-Induced Inflammation in Human Gastric Epithelial Cells.

Helicobacter pylori (H. pylori) is an etiologic factor of peptic ulcer disease and gastric cancer. Virulent strains of H. pylori are correlated with the severity of gastritis, due to NF-κB activation and IL-8 expression at the epithelial level. Ellagitannins have been documented for antibacterial and anti-inflammatory activities, thus suggesting their potential use in gastritis. Recently, several authors, including our group, demonstrated that tannin-rich extracts from chestnut byproducts, at present considered agricultural waste, display promising biological activities. In this work, we detected high levels of polyphenols in hydroalcoholic extracts from chestnut leaves (Castanea sativa L.). Among polyphenols, the ellagitannin isomers castalagin and vescalagin (about 1% w/w of dry extract) were identified as potential bioactive compounds. In GES-1 cells infected by H. pylori, leaf extract and pure ellagitannins inhibited IL-8 release (IC50 ≈ 28 µg/mL and 11 µM, respectively). Mechanistically, the anti-inflammatory activity was partly due to attenuation of NF-κB signaling. Moreover, the extract and pure ellagitannins reduced bacterial growth and cell adhesion. A simulation of the gastric digestion suggested that the bioactivity might be maintained after oral administration. At the transcriptional level, castalagin downregulated genes involved in inflammatory pathways (NF-κB and AP-1) and cell migration (Rho GTPase). To the best of our knowledge, this is the first investigation in which ellagitannins from plant extracts have demonstrated a potential role in the interaction among H. pylori and human gastric epithelium.

Multidisciplinary Management of Children with Occult Spinal Dysraphism: A Comprehensive Journey from Birth to Adulthood.

Occult spinal dysraphism (OSD) comprises different forms of failure in embryogenic development that can lead to genitourinary, spinal, or lower limb alterations, thus determining progressive neurological deterioration. The correct management of children harboring OSD represents a significant issue during their life up to adulthood. However, patients often have to entertain individual consultations with each specialist. We settled on a multidisciplinary team comprising pediatric neurosurgeons, urologists, neurologists, orthopedists, and other supporting physicians. We present the results of such actions by analyzing a series of 141 children with OSD subjected to neurosurgical procedures, evaluating the impact of multidisciplinary management on outcomes. We also evaluated the specific actions according to the different ages of OSD patients from birth to adulthood to provide a schematic plan that could represent a basis for establishing and disseminating the need for a multidisciplinary approach in OSD management. The multidisciplinary team allows all consultants to see the patient together, covering specific aspects of history and examination pertinent to their management. Offering a one-stop service prevents coordination issues between the different medical teams, avoids delays or cancellations of the various appointments, optimizes cost-effectiveness, and improves efficiency and parents' satisfaction.

A ±0.5dB, 6nW RSSI Circuit with RF Power-to-Digital Conversion Technique for Ultra-low Power IoT Radio Applications.

This paper presents a new technique of radio frequency (RF) signal strength detection with a received signal strength indicator (RSSI) circuit which can be deployed in an internet-of-things (IoT) network. The proposed RSSI circuit is based on a direct conversion of RF to digital code indicating the signal strength. The direct conversion is achieved by the repeated switching of a rectifier's output voltage using an ultra-low power comparator. A 5-bit programmable feedback circuit is used to correct detection inaccuracies. The RSSI circuit is implemented in a 65-nm CMOS process and consumes 6nW power. It has a linear dynamic range of 26dB and exhibits an error of ±0.5dB with a wide bandwidth of 750MHz. A detailed analysis of the RSSI circuit is presented and verified with simulation and measurement results. The high detection accuracy with ultra-low power consumption of our RSSI circuit is favourable for IoT applications including localization, beamforming, hardware security and other low-power applications.

Reproducing a decision-making network in a virtual visual discrimination task.

We reproduced a decision-making network model using the neural simulator software neural simulation tool (NEST), and we embedded the spiking neural network in a virtual robotic agent performing a simulated behavioral task. The present work builds upon the concept of replicability in neuroscience, preserving most of the computational properties in the initial model although employing a different software tool. The proposed implementation successfully obtains equivalent results from the original study, reproducing the salient features of the neural processes underlying a binary decision. Furthermore, the resulting network is able to control a robot performing an in silico visual discrimination task, the implementation of which is openly available on the EBRAINS infrastructure through the neuro robotics platform (NRP).

Video-Assisted Thoracoscopy for Vertebral Body Tethering of Juvenile and Adolescent Idiopathic Scoliosis: Tips and Tricks of Surgical Multidisciplinary Management.

VATS (video assisted thoracoscopic surgery) is routinely and successfully performed in minor and major complex thoracic procedures. This technique has been recently introduced for the treatment of severe forms of idiopathic scoliosis (IS) with the aim to repair the deformity, reduce morbidity and to prevent its progression in patients with skeletal immaturity. This study aims to present VATS in anterior vertebral body tethering (AVBT) approach to support the pediatric orthopedic surgeons during vertebral body fixation. Surgical and anesthesiologic tips and tricks are reported to assure a safe procedure. The study includes preadolescents with IS and a grade of scoliosis >40° that had a high probability of deterioration due to remaining growth (December 2018 to April 2021). Skeletal immaturity of enrolled patients was assessed by Sanders classification and Risser sign. Patients had a Risser score between 0 and 1 and a Sanders score >2 and <5. AVBT technique using VATS was performed by a senior pediatric surgeon assisting the pediatric orthopedic surgeon. Twenty-three patients have been submitted to VATS AVBT in the period of study (age range 9-14 years). The patients had a classified deformity Lenke 1A or B convex right and all types of curves were treated. In all patients, the vertebrae submitted to tethering surgery ranged from D5 to D12; mean curve correction was 43%. Three postoperative complications occurred: one late postoperative bleeding requiring a chest tube positioning on 12th postoperative day; one screw dislodged and needed to be removed; one child showed worsening of the scoliosis and needed a posterior arthrodesis. Initial results of VATS AVBT in growing patients with spinal deformities are encouraging. An appropriate selection of patients and a pediatric dedicated multidisciplinary surgical approach decrease intraoperative complications, time of operation and postoperative sequelae and guarantee an optimal outcome.

Agroecology research in Europe funded by European and transnational programmes: current status and perspectives.

Background: Redesigning the agri-food system through agroecology represents a common ambition among practitioners, activists and scholars to achieve environmental and socio-economic sustainability. Research can have a main role to support this path. Although it seems that there is a gradual increasing body of agroecology research, it clearly lacks good knowledge about this. The main objective of this study was therefore to map research projects related to agroecology in Europe with the aim to characterize European research in terms of implementation of agroecology elements, identify needs for future cross collaboration between countries and networks, and support the setting up of appropriate research agendas fostering agroecology research in Europe. Methods: A desktop research with different databases related to European and transnational funding programmes was carried out to identify funded research projects involved in agroecology. The obtained projects were used to perform a social network analysis. Furthermore, two surveys were conducted, one with coordinators of identified projects and a second one for researchers engaged in agroecology. Results: Our study highlighted a predominant trajectory of agroecology research prone to the transformation of the agri-food system. France, Germany, Italy, Netherlands, Portugal, Spain, and United Kingdom were the most active countries engaged in agroecology research. In all surveys, issues related to efficiency improvement, synergies strengthening, local economy development, and co-creation and sharing of knowledge were the most implemented to support agri-food transformation. Transdisciplinary approaches were mainly addressed by European projects. Surveys reported a limited participation of value chain actors, while researchers, farmers, and their associations were the most involved. Survey respondents suggested to increase project duration and introduce flexibility methods to modulate research actions according to dynamic of the contexts. Conclusion: On the basis of the results, some policy recommendations were provided to fostering agroecology research in Europe and its contribution for transformation of agri-foods systems.

Anterior vertebral body tethering as a treatment for scoliosis in skeletally immature patients.

A relatively new surgical procedure called Anterior Vertebral Body Tethering (AVBT) is used to treat scoliosis in patients with immature skeletons. It is a growth modulation fusionless system that Crowford and Lenke first described in 2010. We present our observations from 25 patients. Improvement in the mean coronal Cobb angle, from mean 57° preoperative to mean 34° postoperative, was 40%. Additionally, we noted that the mean thoracic hypokyphosis improved from 16° to 24° on average after surgery. Complication rates were 16% and surgical revision rates were 12%. All patients who demonstrated improvement in pain, function, and self-image underwent administration of the SRS-24 questionnaire. These data, according to the literature, show that AVBT is a reliable technique that enables scoliosis correction in skeletally immature patients and maintains that correction while utilizing remaining growth potential to achieve further correction, avoiding spinal fusion, and maintaining spine mobility.

Shape Sensing of a Complex Aeronautical Structure with Inverse Finite Element Method.

The inverse Finite Element Method (iFEM) is receiving more attention for shape sensing due to its independence from the material properties and the external load. However, a proper definition of the model geometry with its boundary conditions is required, together with the acquisition of the structure's strain field with optimized sensor networks. The iFEM model definition is not trivial in the case of complex structures, in particular, if sensors are not applied on the whole structure allowing just a partial definition of the input strain field. To overcome this issue, this research proposes a simplified iFEM model in which the geometrical complexity is reduced and boundary conditions are tuned with the superimposition of the effects to behave as the real structure. The procedure is assessed for a complex aeronautical structure, where the reference displacement field is first computed in a numerical framework with input strains coming from a direct finite element analysis, confirming the effectiveness of the iFEM based on a simplified geometry. Finally, the model is fed with experimentally acquired strain measurements and the performance of the method is assessed in presence of a high level of uncertainty.

On the Evaluation of a Coupled Sequential Approach for Rotorcraft Landing Simulation.

Maximum loads acting on aircraft structures generally arise when the aircraft is undergoing some form of acceleration, such as during landing. Landing, especially when considering rotorcrafts, is thus crucial in determining the operational load spectrum, and accurate predictions on the actual health/load level of the rotorcraft structure cannot be achieved unless a database comprising the structural response in various landing conditions is available. An effective means to create a structural response database relies on the modeling and simulation of the items and phenomena of concern. The structural response to rotorcraft landing is an underrated topic in the open scientific literature, and tools for the landing event simulation are lacking. In the present work, a coupled sequential simulation strategy is proposed and experimentally verified. This approach divides the complex landing problem into two separate domains, namely a dynamic domain, which is ruled by a multibody model, and a structural domain, which relies on a finite element model (FEM). The dynamic analysis is performed first, calculating a set of intermediate parameters that are provided as input to the subsequent structural analysis. Two approaches are compared, using displacements and forces at specific airframe locations, respectively, as the link between the dynamic and structural domains.

High-Figure-of-Merit X-Cut Lithium Niobate MEMS Resonators Operating Around 50 MHz for Large Passive Voltage Amplification in Radio Frequency Applications.

This article reports on the modeling, design, fabrication, and testing of high-performance X-cut lithium niobate (LN) laterally vibrating resonators (LVRs) operating around 50 MHz. The objective of this work is to exploit the high figure of merit (FoM)-product of quality factor at series resonance ( Qs ) and electromechanical coupling ( kt2 )-to provide for large passive voltage amplification in the front end of emerging radio frequency (RF) applications, i.e., wake-up radio receivers (WuRx). Finite-element analysis (FEA) is performed to optimize the devices' geometry and ensure simultaneous high Qs and kt2 . Resonators exhibiting and % are demonstrated, with FoM >1650-the highest value recorded for resonators in the megahertz range to the best of our knowledge. Finally, passive voltage gains between 35 and 57 V/V are showcased for capacitive loads ranging from 400 fF to 1 pF.

Effects of magnetically controlled growing rods surgery on pulmonary function in young subjects with spinal muscular atrophy type 2 and other neuromuscular scoliosis.

BACKGROUND: The aim of this study was to determine the effects of magnetically controlled growing rods surgery (MCGRS) of the scoliosis on pulmonary function in children with neuromuscular scoliosis. METHODS: Seven patients, 85.7% female (mean±SD age: 6.7±1.2 years), with neuromuscular scoliosis (4 SMA II, 2 congenital myopathies and 1 VACTER syndrome), received MCGRS of the spine in the thoraco-lumbar area. The outcome measures were clinical features and pulmonary function (forced vital capacity [FVC] and forced expiratory volume in 1st second [FEV1], were collected. All measures were collected at pre-, post-intervention and follow-up (short-term [0-6 months], mid-term [7-12 months], and long-term [13-24 months]). RESULTS: MCGRS reduced Cobb angle after intervention in 100% in subjects and this result was maintained at 24-month follow-up (all, P=0.001). There was no significant difference in FVC or FEV1 between preoperative and each postoperative period, (P>0.05). Analyses of the correlation coefficients indicated no significant associations between changes in pulmonary function and scoliosis. CONCLUSIONS: The current study found that MCGRS addressed to the scoliosis maintained pulmonary function during long-term follow-up; However, pulmonary function was not associated with scoiosis in children with neuromuscular scoliosis.

A bio-guided approach for the development of a chestnut-based proanthocyanidin-enriched nutraceutical with potential anti-gastritis properties.

Gastritis is a widely spread inflammatory disease, mostly caused by Helicobacter pylori infection. Release of IL-8 by the stomach epithelium is a hallmark of gastritis and contributes to the amplification of the inflammatory state. Pharmacological modulation of IL-8 release is a strategy to relieve gastric inflammation and prevent more severe clinical outcomes. In search of nutraceuticals with potential anti-gastritis properties we used a bio-guided approach based on IL-8 secretion by gastric cells to characterize extracts from the fruits of different chestnut varieties. We found that the ability to inhibit IL-8 secretion correlated with the amount of proanthocyanidins and was associated to the not edible parts of chestnut in all the tested varieties. We also found that the anti-inflammatory activity is preserved upon mild thermal treatment and after in vitro simulated gastric digestion. By combining a robust bio-guided approach with a comprehensive analysis of the tannin fraction of chestnut extracts, we provide evidence for the potential use of chestnut-based nutraceuticals in human gastritis. The bioactive components of chestnut fruits inhibit IL-8 secretion by impairing NF-κB signaling and by other mechanisms, thus opening new applications of proanthocyanidins for inflammation-based diseases.

Recent trends in chloride and sodium concentrations in the deep subalpine lakes (Northern Italy).

A growing concern exists about the effects of chloride (Cl) on freshwater systems. Increasing Cl concentrations have been observed in the last few decades in several rivers and lakes, mainly in northern countries. In Italy, present levels and temporal changes of sodium (Na) and Cl in water bodies have rarely been assessed. Based on long-term data for the lakes of the subalpine district in Italy (Maggiore, Lugano, Como, Iseo, Garda), we analyzed trends affecting Cl and Na concentrations during the last 25 years, with the aim of identifying temporal changes and assessing possible causes. An in-depth analysis is presented for Lake Maggiore. Positive temporal Na and Cl trends were evident in all studied lakes, with the trends increasing since early 2000s. Data for Lake Maggiore tributaries showed a clear seasonality (higher values in winter and early spring). The NaCl used as road de-icing agent, together with Cl discharge from wastewater treatment plants, were identified as the main causes for the observed trends. Chloride concentrations in the lakes are below the threshold limit for reduced water quality and below concentrations known to harm aquatic biota. However, considering the relevance of deep subalpine lakes, representing almost 80% of the total freshwater volume in Italy, these trends indicate an important chemical change, which warrants further analysis.