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Abstract Background Soluble aggregates of oligomeric forms of tau protein (oTau) have been associated with impairment of synaptic plasticity and memory in Alzheimer’s disease. However, the molecular mechanisms underlying the synaptic and memory dysfunction induced by elevation of oTau are still unknown. Methods This work used a combination of biochemical, electrophysiological and behavioral techniques. Biochemical methods included analysis of phosphorylation of the cAMP-responsive element binding (CREB) protein, a transcriptional factor involved in memory, histone acetylation, and expression immediate early genes c-Fos and Arc. Electrophysiological methods included assessment of long-term potentiation (LTP), a type of synaptic plasticity thought to underlie memory formation. Behavioral studies investigated both short-term spatial memory and associative memory. These phenomena were examined following oTau elevation. Results Levels of phospho-CREB, histone 3 acetylation at lysine 27, and immediate early genes c-Fos and Arc, were found to be reduced after oTau elevation during memory formation. These findings led us to explore whether up-regulation of various components of the nitric oxide (NO) signaling pathway impinging onto CREB is capable of rescuing oTau-induced impairment of plasticity, memory, and CREB phosphorylation. The increase of NO levels protected against oTau-induced impairment of LTP through activation of soluble guanylyl cyclase. Similarly, the elevation of cGMP levels and stimulation of the cGMP-dependent protein kinases (PKG) re-established normal LTP after exposure to oTau. Pharmacological inhibition of cGMP degradation through inhibition of phosphodiesterase 5 (PDE5), rescued oTau-induced LTP reduction. These findings could be extrapolated to memory because PKG activation and PDE5 inhibition rescued oTau-induced memory impairment. Finally, PDE5 inhibition re-established normal elevation of CREB phosphorylation and cGMP levels after memory induction in the presence of oTau. Conclusions Up-regulation of CREB activation through agents acting on the NO cascade might be beneficial against tau-induced synaptic and memory dysfunctions.

Dynamin 1-3 isoforms are known to be involved in endocytotic processes occurring during synaptic transmission. No data has directly linked dynamins yet with normal animal behavior. Here we show that dynamin pharmacologic inhibition markedly impairs hippocampal-dependent associative memory. Memory loss was associated with changes in synaptic function occurring during repetitive stimulation that is thought to be linked with memory induction. Synaptic fatigue was accentuated by dynamin inhibition. Moreover, dynamin inhibition markedly reduced long-term potentiation, post-tetanic potentiation, and neurotransmitter released during repetitive stimulation. Most importantly, the effect of dynamin inhibition onto memory and synaptic plasticity was due to a specific involvement of the dynamin 1 isoform, as demonstrated through a genetic approach with siRNA against this isoform to temporally block it. Taken together, these findings identify dynamin 1 as a key protein for modulation of memory and release evoked by repetitive activity.

En el presente artículo nos proponemos realizar un extenso recorrido historiográfico con vistas a dar cuenta de la visión tradicional relativa al desempeño económico de las corporaciones de artesanos, desde Adam Smith hasta la teoría de la protoindustrialización. Buscaremos dar cuenta de la evolución de la tesis según la cual estas instituciones suponen un obstáculo para el desarrollo económico, en oposición al espacio rural donde la libertad, entendida como ausencia de regulación, resulta condición suficiente para el florecimiento de la actividad comercial e industrial que conduce a procesos acumulativos.

Abstract Introduction The Patient Acceptable Symptoms State (PASS) is a validated instrument that is used to assess whether a patient with psoriatic arthritis (PsA) accepts her/his disease status by asking them a simple question: “Think about all the ways your PsA has affected you during the last 48 h. If you were to remain in the next few months as you were during the last 48 h, would this be acceptable to you?” The aim of the present study was to explore any PASS differences in patients with PsA based on sex by looking at the corresponding thresholds of Disease Activity for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Impact of the Disease-12 (PsAID-12) and the Health Assessment Questionnaire—Disability Index (HAQ-DI) in female and male patients. Methods This was a cross-sectional study that included two PsA cohorts. To identify the DAPSA, PsAID and HAQ-DI thresholds that differentiated patients who reported “yes” in response to the PASS question from those who reported “no,” we used the receiver operating characteristic curves both for the female and male sexes. Moreover, Cohen’s kappa test was used to determine the agreement of a PASS “yes” with DAPSA ≤ 14, PsAID ≤ 4 and HAQ-DI ≤ 0.5. Results Three-hundred ten patients were considered for the study. The DAPSA, PsAID-12 and HAQ-DI thresholds that differentiated PASS “yes” patients from PASS “no” patients were 11.7, 1.85 and 0.625 in male patients and 13.3, 3.85 and 0.750 in female patients, respectively. A PASS “yes” and DAPSA ≤ 14 showed moderate agreement in males (kappa = 0.56) and good agreement in females (kappa = 0.80); the agreement between a PASS “yes” and PsAID ≤ 4 and between a PASS “yes” and HAQ-DI ≤ 0.5 was higher in female patients (moderate). Conclusion Female patients accept their disease at higher DAPSA, PsAID and HAQ-DI values than male patients do. The clinical meaning of this could be that a female patient generally has a greater global disease acceptance inclination. Therefore, this study further supports the concept that sex differences are present in patients with PsA.

El presente trabajo pretende examinar el fatigoso proceso de construcción de la capacidad de mando de los señores del paño pertenecientes a la corporación pelaire en la industria textil de Murcia, entre 1370 y 1500. Partimos de la existencia de condiciones técnicas que permiten la emergencia de acumuladores capitalistas que operan a modo de Verlegers al controlar las materias primas y entregarlas para su elaboración a cambio de un salario. La pañería presenta un proceso productivo fragmentado, integrado por múltiples eslabones, que requiere de agentes que le den cohesión, a partir de coordinar y supervisar el trabajo de los diversos artesanos involucrados en cada fase. De igual modo, estos agentes resultan imprescindibles para la comercialización del producto final. No obstante, el carácter descentralizado de la producción implica la inexistencia de mecanismos de control intrínsecos al proceso de trabajo. De allí que la jerarquía industrial deba ser construida de forma fatigosa y conflictiva. En el caso que nos ocupa, veremos que la elite del gremio pelaire dispondrá del aparato corporativo para construir su poder de mando sobre el trabajo, extendiendo su jurisdicción sobre los demás colectivos artesanales de la ciudad de Murcia. De este modo logrará imponer nuevas pautas productivas, acordes a sus necesidades de acumulación, que ocasionarán un desarrollo cualitativo de la industria textil murciana. Igualmente, buscará implementar mecanismos de supervisión institucionales para garantizar el cumplimiento de dichas pautas. Esto nos alejará de la historiografía tradicional que analiza a las corporaciones de artesanos como un obstáculo para el desarrollo capitalista. Por el contrario, veremos que la corporación pelaire resulta fundamental para este.

ObjectivesThis study aims to evaluate in a real-life Italian multicenter cohort of axial spondyloarthritis (axSpA) (1) the 4-year effectiveness and safety of secukinumab, (2) the drug retention rate (DRR), and (3) the impact of the line of bDMARDs treatment, subtype of axSpA, and sex on achieving low disease activity (LDA) and very low disease activity (VLDA).MethodsConsecutive axSpA patients receiving secukinumab between 2016 and 2023 were prospectively evaluated. Data on disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were collected. Treatment response was evaluated at 6 and 12 months after initiation and yearly up to 48 months (T48). DRR and effectiveness outcomes were evaluated according to bDMARDs treatment, axSpA subtype, and sex. Infections and adverse events (AEs) were recorded.ResultsWe enrolled 272 patients (48.2% male; median age, 51; 39.7% HLA-B27+; 40.4% nr-axSpA), of whom 30.9% were naïve to secukinumab. Overall, secukinumab yielded improvement in effectiveness outcomes; the naïve patients maintained lower disease activity vs. the non-naïve ones. At T48, the LDA and VLDA rates were higher in naïve patients and in male individuals. Treatment was discontinued in 104 patients due to primary/secondary loss of effectiveness and in 34 patients due to AEs. The DRR at T48 was 67.4% in the whole population, regardless of treatment line, axSpA subtype, and sex.ConclusionsSecukinumab was safe and effective in all axSpA patients irrespective of treatment line, disease subtype, and sex. The patients achieved sustained 4-year remission and DRR.

Recent advancements in communication technologies have significantly enhanced localization techniques, improving both accuracy and operating modes. Initially, localization methods relied on global navigation satellite systems, offering high accuracy but proving inefficient in Non-Line-of-Sight scenarios. Furthermore, the absence of a passive mode, where the user can be localized without explicitly requesting it, renders these methods unsuitable for applications like passive tracking systems. Fingerprinting methods, a pattern matching techniques based on signal power estimation from target devices and distance estimation from reference points, can be seen as a valid and promising alternative. However, these methods face limitations due to extensive measurement campaigns needed to establish accurate sampling systems within specific areas and the substantial amount of data required for machine learning algorithms to achieve optimal performance. This study introduces a novel fingerprinting method capable of passive operation, involving all smartphones within a designated area, suitable for both indoor and outdoor scenarios. The proposed solution leverages Generative Adversarial Networks (GANs) to augment fingerprinting datasets, enhancing machine learning models’ capabilities. Additionally, the offline phase’s cost-effectiveness is improved by integrating a Bayesian system as a secondary machine learning component.

Face detection and recognition play pivotal roles across various domains, spanning from personal authentication to forensic investigations, surveillance, entertainment, and social media. In our interconnected world, pinpointing an individual’s identity amidst millions remains a formidable challenge. While contemporary face recognition techniques now rival or even surpass human accuracy in critical scenarios like border identity control, they do so at the expense of poor explainability, leaving the underlying causes of errors largely unresolved. Moreover, they demand substantial computational resources and a plethora of labeled samples for training. Drawing inspiration from the remarkably efficient human visual system, particularly in localizing and recognizing faces, holds promise for developing more efficient and interpretable systems, with high gains in scenarios where misidentification can yield grave consequences. In this context, we introduce the Uniss-FGD dataset, which captures gaze data from observers presented with facial images depicting diverse expressions. In view of the potential uses of Uniss-FGD, we propose two baseline experiments on a subset of the dataset in which we perform a comparative analysis juxtaposing the attention mechanisms of ViTs, multi-scale handcrafted features, and human observers when viewing facial images. These preliminary comparisons pave the way to future investigation into the integration of human attention dynamics into advanced and diverse image analysis frameworks. Beyond the realms of Computer Science, numerous research disciplines stand to benefit from the rich gaze data encapsulated in this dataset.

Objective Evaluate spondyloarthritis (SpA) incidence in inflammatory bowel diseases (IBD) between patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) and conventional DMARDs (cDMARDs) and define risk factors associated with SpA development.Methods Retrospective cohort study was conducted on patients with Crohn’s disease (CD) or ulcerative colitis (UC) and divided into two cohorts: cDMARDs or bDMARDs/targeted synthetic (ts) DMARDs treated patients. Rheumatological assessment was performed in patients presenting musculoskeletal symptoms. Multivariate analysis and Kaplan-Meier curves were used to evaluate the adjusted SpA risk development.Results 507 patients were included in the study. 176 patients with CD received bDMARDs, 112 cDMARDs and 106 new SpA diagnosies were formulated. Females (OR 1.7 (95% CI 1.1 to 3), adjusted p=0.04), non-stricturing/non-penetrating phenotype (OR 2 (95% CI 1.1 to 3.4), adjusted p=0.01), psoriasis (OR 2.1 (95% CI 1 to 4.6), adjusted p=0.04) and non-infectious uveitis (OR 6.8 (95% CI 1.4 to 33.4), adjusted p=0.01) were associated with increased SpA risk development, while bDMARDs usage was protective (OR 0.4 (95% CI 0.2 to 0.8), adjusted p=0.01), statistically higher than cDMARDs throughout the entire follow-up (effect size 0.47). 98 patients with UC received b-tsDMARDs, 121 cDMARDs and 56 new SpA diagnoses were formulated. Females (OR 2.1 (95% CI 1 to 4.3), adjusted p=0.02) and psoriasis (OR 2.7 (95% CI 1 to 6.8), adjusted p=0.03) were associated with increased SpA risk development, while bDMARDs were protective for SpA development for up to 12 months of treatment compared with cDMARDs (p=0.03).Conclusions bDMARDs treatment had an impact in reducing SpA development and clinical associated risk factors to transition from IBD to IBD-SpA emerged.

Abstract The interplay between spin-orbit interaction and magnetic order is one of the most active research fields in condensed matter physics and drives the search for materials with novel, and tunable, magnetic and spin properties. Here we report on a variety of unique and unexpected observations in thin multiferroic Ge1−x Mn x Te films. The ferrimagnetic order parameter in this ferroelectric semiconductor is found to switch direction under magnetostochastic resonance with current pulses many orders of magnitude lower as for typical spin-orbit torque systems. Upon a switching event, the magnetic order spreads coherently and collectively over macroscopic distances through a correlated spin-glass state. Utilizing these observations, we apply a novel methodology to controllably harness this stochastic magnetization dynamics.

Driven by technological advances in various fields (AI, 5G, VR, IoT, etc.) together with the emergence of digital twins technologies (HDT, HAL, BIM, etc.), the Metaverse has attracted growing attention from scientific and industrial communities. This interest is due to its potential impact on people lives in different sectors such as education or medicine. Specific solutions can also increase inclusiveness of people with disabilities that are an impediment to a fulfilled life. However, security and privacy concerns remain the main obstacles to its development. Particularly, the data involved in the Metaverse can be comprehensive with enough granularity to build a highly detailed digital copy of the real world, including a Human Digital Twin of a person. Existing security countermeasures are largely ineffective and lack adaptability to the specific needs of Metaverse applications. Furthermore, the virtual worlds in a large-scale Metaverse can be highly varied in terms of hardware implementation, communication interfaces, and software, which poses huge interoperability difficulties. This paper aims to analyse the risks and opportunities associated with adopting digital replicas of humans (HDTs) within the Metaverse and the challenges related to managing digital identities in this context. By examining the current technological landscape, we identify several open technological challenges that currently limit the adoption of HDTs and the Metaverse. Additionally, this paper explores a range of promising technologies and methodologies to assess their suitability within the Metaverse context. Finally, two example scenarios are presented in the Medical and Education fields.

El presente trabajo se propone indagar en la penetración del capital genovés en la industria del tinte murciana entre 1380 y 1470. Particularmente, analizaremos el modo en el que el capital genovés se sirve de su condición de importador monopólico de colorantes para tratar de desplazar a los maestros tintoreros locales de la gestión de las casas de tinte de la ciudad. Los mercaderes italianos apuntan a lograr la integración vertical del tintado. De esto se sigue una intensa disputa con los maestros murcianos, quienes gozan de una notable capacidad para resistir esta afrenta. El análisis empírico nos llevará a alejarnos de los supuestos de la historiografía marxista tradicional que establecen una separación rígida entre circulación y producción. Frente a este planteamiento, nos serviremos de los novedosos aportes de Jairus Banaji, quien destaca el desarrollo de funciones productivas por parte del capital comercial.

SAPHO syndrome is a complex disease that encompasses both inflammatory arthritis and/or osteitis and dermatologic manifestations. It is considered a rare disease, in fact, no clinical trials have been conducted on its therapy and management. Therefore, therapeutic approach is based on small case studies. Here, we described the case of a 63-year-old woman affected by SAPHO syndrome, treated with the selective IL-23p19 antagonist, Risankizumab, after unsuccessful therapies with Methotrexate, Infliximab, Adalimumab, and an allergic reaction to Secukinumab. At the beginning of therapy, in November 2022, the patient presented with arthritis in both knees associated with palmar pustulosis and guttate psoriasis on the trunk. DAPSA score was 24, PtGA 80 mm, PASI score 11.1, and BSA 40%. Thereafter, Risankizumab was started at the standard dosage of 150 mg. At week 24 patient achieved clinical remission, DAPSA score was 8, PtGA was 30 mm, PASI was 1, and BSA 2.5. Patient maintained clinical remission state at the subsequent week 52 evaluation. At the same time, the patient did not report any adverse effects. Health-related quality of life was also assessed at the same time points aforementioned, showing significant improvement. In conclusion, this case report wants to point out the efficacy and safety of Risankizumab in SAPHO syndrome, reporting a sustained disease remission through a 12 months long follow-up period. We can consider IL-23p19 targeted therapy as a novel treatment option for SAPHO—with a high efficacy potential—especially on patients that have already been treated with other biologics.

El presente artículo se propone indagar en las condiciones técnicas de la producción textil de la ciudad de Murcia durante la Baja Edad Media, con el objeto de dar cuenta de las condiciones específicas que permiten el desarrollo de relaciones capitalistas de producción. En contraste con la imagen tradicional del artesano aislado que reúne en su taller las condiciones para ejecutar la totalidad del proceso productivo, daremos cuenta de una cadena productiva fragmentada, compuesta por una gran cantidad de operaciones diversas entre sí, ejecutadas por trabajadores con niveles dispares de calificación. Como demostraremos, tamaña fragmentación del proceso productivo constituye el fundamento material que permite el accionar de capitalistas que, actuando a modo de Verlegers, coordinan y cohesionan las operaciones de los artesanos.

Abstract Colonial waterbirds, a major biodiversity element occurring in the core of ultra-anthropized Europe, are ideal indicators of the wellness of inland wetlands. Nonetheless, there is a critical knowledge gap in their trend and population status. We present an uninterrupted 47 years-long dataset of the breeding populations of 12 species of colonial waterbirds (Ardeidae, Phalacrocoracidae, Plataleidae, Threskiornitidae) throughout a 58,000 km2 agricultural region in the higher Po basin (NW Italy). A trained team of collaborators censused with standardized field techniques the number of nests of each species at 419 colonies in the 1972–2018 period, summing up a total of 236,316 records. Data cleaning and standardization were performed for each census year, ensuring robust and consistent data. This dataset is among the largest ever collected for a guild of European vertebrates. It has already been used to describe the factors influencing population trends, and still offers opportunities to explore a wide range of key ecological processes such as biological invasions, global change consequences and biodiversity impact of agricultural practices.

Abstract Objective To assess any differences and similarities in psoriatic arthritis (PsA) between sexes. Any possible differences of psoriasis and its potential impact on disease burden between sexes with PsA were also evaluated. Methods Cross-sectional analysis of two longitudinal PsA cohorts. The impact of psoriasis on the PtGA was evaluated. Patients were stratified in four groups based on BSA. The median PtGA was then compared between the four groups. Moreover, a multivariate linear regression analysis was performed in order to evaluate associations between PtGA and skin involvement, split by sexes. Results We enrolled 141 males and 131 females: PtGA, PtPnV, tender, swollen joint count, DAPSA, HAQ-DI, PsAID-12 were statistically significant higher in females (p ≤ 0.05). PASS “yes” was deemed more in males than in females and BSA was higher in males. MDA was present more in males than females. When the patients were stratified on BSA, median PtGA was not different between males and females with BSA = 0. Instead, in females with BSA > 0, a higher PtGA was observed compared to males with BSA > 0. There was not a statistically significant association between skin involvement and PtGA at linear regression analysis, even if a trend seems to be present in female. Conclusions Psoriasis is more present in males, but it seems to be related to a worse impact in females. In particular, a possible role of psoriasis as an influencing factor the PtGA was found. Moreover, female PsA patients tended to have more disease activity, worse function, and higher disease burden.

The rapid increase in Internet of Things (IoT) applications has raised security and privacy issues due to the huge amount of data acquired by IoT devices and transmitted through the Internet. Therefore, there is a need to understand what strategies should be applied to make IoT systems robust to security flaws and privacy weaknesses. In this paper, we first identify and discuss the best practices for IoT privacy and security, which include a set of procedures that can be taken as the guidelines to determine and solve privacy and security issues of IoT systems. Then, we follow and apply the identified best practices to two real IoT-based use cases: a crowding monitoring system and a vehicular mobility system. Finally, we computed the risk assessment score to evaluate the impact of the application of the identified best practices on the implemented IoT systems. We observe that following the proposed best practices the implemented IoT systems achieve an overall risk score of 1.3, which is from 215% to 361% lower than that achieved by comparable IoT systems proposed in the literature studies.

Abstract Background Uprighting incisors is particularly important with clear aligner therapy as incisor tip determines the mesio-distal space needed in the arch, and consequently the fit of the aligner. The objective of this study was to investigate the accuracy of ClinCheck® software to predict lower incisor tip by comparing digitally prescribed movements with actual clinical outcomes and to determine whether the presence of a vertically orientated rectangular composite attachment influences the efficacy of incisor tip. Methodology This retrospective study included 66 lower incisors from 42 non-extraction adult patients treated using the Invisalign® appliance. Twenty-one incisors had vertical attachments, while 45 incisors did not have any attachments. Lower incisor tip was measured at T0 (pre-treatment), T1 (predicted post-treatment) and T2 (achieved post-treatment) on digital models using metrology software. The change in position from T0 to T1 and T0 to T2 was measured from the estimated centre of resistance (CRes) of each tooth. The estimated centre of rotation was plotted relative to the CRes to describe the type of orthodontic tooth movement (OTM) predicted and achieved. Results Predicted incisor tip and achieved incisor tip were positively correlated (R 2 = 0.55; p

Nanoparticles are being increasingly studied to enhance radiation effects. Among them, nanodiamonds (NDs) are taken into great consideration due to their low toxicity, inertness, chemical stability, and the possibility of surface functionalization. The objective of this study is to explore the influence of the chemical/physical properties of NDs on cellular radiosensitivity to combined treatments with radiation beams of different energies. DAOY, a human radioresistant medulloblastoma cell line was treated with NDs—differing for surface modifications [hydrogenated (H-NDs) and oxidized (OX-NDs)], size, and concentration—and analysed for (i) ND internalization and intracellular localization, (ii) clonogenic survival after combined treatment with different radiation beam energies and (iii) DNA damage and apoptosis, to explore the nature of ND–radiation biological interactions. Results show that chemical/physical characteristics of NDs are crucial in determining cell toxicity, with hydrogenated NDs (H-NDs) decreasing either cellular viability when administered alone, or cell survival when combined with radiation, depending on ND size and concentration, while OX-NDs do not. Also, irradiation at high energy (γ-rays at 1.25 MeV), in combination with H-NDs, is more efficient in eliciting radiosensitisation when compared to irradiation at lower energy (X-rays at 250 kVp). Finally, the molecular mechanisms of ND radiosensitisation was addressed, demonstrating that cell killing is mediated by the induction of Caspase-3-dependent apoptosis that is independent to DNA damage. Identifying the optimal combination of ND characteristics and radiation energy has the potential to offer a promising therapeutic strategy for tackling radioresistant cancers using H-NDs in conjunction with high-energy radiation.

Abstract When access to diagnosis and treatment of tuberculosis is disrupted by poverty or unequal access to health services, marginalized communities not only endorse the burden of preventable deaths, but also suffer from the dramatic consequences of a disease which impacts one’s ability to access education and minimal financial incomes. Unfortunately, these pockets are often left unrecognized in the flow of data collected in national tuberculosis reports, as localized hotspots are diluted in aggregated reports focusing on notified cases. Such system is therefore profoundly inadequate to identify these marginalized groups, which urgently require adapted interventions. We computed an estimated incidence-rate map for the South-Kivu province of the Democratic Republic of Congo, a province of 5.8 million inhabitants, leveraging available data including notified incidence, level of access to health care and exposition to identifiable risk factors. These estimations were validated in a prospective multi-centric study. We could demonstrate that combining different sources of openly-available data allows to precisely identify pockets of the population which endorses the biggest part of the burden of disease. We could precisely identify areas with a predicted annual incidence higher than 1%, a value three times higher than the national estimates. While hosting only 2.5% of the total population, we estimated that these areas were responsible for 23.5% of the actual tuberculosis cases of the province. The bacteriological results obtained from systematic screenings strongly correlated with the estimated incidence (r = 0.86), and much less with the incidence reported by epidemiological reports (r = 0.77), highlighting the inadequacy of these reports when used alone to guide disease control programs.

Smart cities and 6G are technological areas that have the potential to transform the way we live and work in the years to come. Until this transformation comes into place, there is the need, underlined by research and market studies, for a critical reassessment of the entire wireless communication sector for smart cities, which should include the IoT infrastructure, economic factors that could improve their adoption rate, and strategies that enable smart city operations. Therefore, from a technical point of view, a series of stringent issues, such as interoperability, data privacy, security, the digital divide, and implementation issues have to be addressed. Notably, to concentrate the scrutiny on smart cities and the forthcoming influence of 6G, the groundwork laid by the current 5G, with its multifaceted role and inherent limitations within the domain of smart cities, is embraced as a foundational standpoint. This examination culminates in a panoramic exposition, extending beyond the mere delineation of the 6G standard toward the unveiling of the extensive gamut of potential applications that this emergent standard promises to introduce to the smart cities arena. This paper provides an update on the SC ecosystem around the novel paradigm of 6G, aggregating a series of enabling technologies accompanied by the descriptions of their roles and specific employment schemes.

The ever-increasing demand for applications with stringent constraints in device density, latency, user mobility, or peak data rate has led to the appearance of the last generation of mobile networks (i.e., 5G). However, there is still room for improvement in the network spectral efficiency, not only at the waveform level but also at the Radio Resource Management (RRM). Up to now, solutions based on multicast transmissions have presented considerable efficiency increments by successfully implementing subgrouping strategies. These techniques enable more efficient exploitation of channel time and frequency resources by splitting users into subgroups and applying independent and adaptive modulation and coding schemes. However, at the RRM, traditional multiplexing techniques pose a hard limit in exploiting the available resources, especially when users’ QoS requests are unbalanced. Under these circumstances, this paper proposes jointly applying the subgrouping and Non-Orthogonal Multiple Access (NOMA) techniques in 5G to increase the network data rate. This study shows that NOMA is highly spectrum-efficient and could improve the system throughput performance in certain conditions. In the first part of this paper, an in-depth analysis of the implications of introducing NOMA techniques in 5G subgrouping at RRM is carried out. Afterward, the validation is accomplished by applying the proposed approach to different 5G use cases based on vehicular communications. After a comprehensive analysis of the results, a theoretical approach combining NOMA and time division is presented, which improves considerably the data rate offered in each use case.

Beer oxidation is strictly linked to its shelf life. Chemical variation in aldehydes, higher alcohols, hops bitter substances and esters, also could have a role key in stale flavor. Bottle refermentation, is the method by which beer in the bottle is made sparkling and is often used in craft brewing. Before the process an amount of oxygen in the headspace can be a potential source of oxidation. We investigated the effect of oxygen and temperature during storage of refermented craft beer in bottles with standard and oxygen scavenger caps. Beer was stored for 13 weeks at 6, 22 and 45 °C for forced aging, and monitored by technological analysis, SPME (-) and - MS (-), Electron Paramagnetic Resonance (EPR). At 45 °C, the samples showed a decrease of International Bitterness Units and an increase in color and concentrations of oxidized molecules, and other related with the high temperature (aldehydes and furanic compounds respectively). No differences were observed between samples stored at 6 and 22 °C. Sensory analysis showed differences in the perception of paint, sweet, cardboard and freshness attributes in the samples stored at 45 °C. No differences were observed in the use of standard and oxygen scavenger caps.

Adult T-cell leukemia/lymphoma (ATL) is a T-cell lymphoproliferative neoplasm caused by the human T-cell leukemia virus type 1 (HTLV-1). Two viral proteins, Tax-1 and HBZ play important roles in HTLV-1 infectivity and in HTLV-1-associated pathologies by altering key pathways of cell homeostasis. However, the molecular mechanisms through which the two viral proteins, particularly HBZ, induce and/or sustain the oncogenic process are still largely elusive. Previous results suggested that HBZ interaction with nuclear factors may alter cell cycle and cell proliferation. To have a more complete picture of the HBZ interactions, we investigated in detail the endogenous HBZ interactome in leukemic cells by immunoprecipitating the HBZ-interacting complexes of ATL-2 leukemic cells, followed by tandem mass spectrometry analyses. RNA seq analysis was performed to decipher the differential gene expression and splicing modifications related to HTLV-1. Here we compared ATL-2 with MOLT-4, a non HTLV-1 derived leukemic T cell line and further compared with HBZ-induced modifications in an isogenic system composed by Jurkat T cells and stably HBZ transfected Jurkat derivatives. The endogenous HBZ interactome of ATL-2 cells identified 249 interactors covering three main clusters corresponding to protein families mainly involved in mRNA splicing, nonsense-mediated RNA decay (NMD) and JAK-STAT signaling pathway. Here we analyzed in detail the cluster involved in RNA splicing. RNAseq analysis showed that HBZ specifically altered the transcription of many genes, including crucial oncogenes, by affecting different splicing events. Consistently, the two RNA helicases, members of the RNA splicing family, DDX5 and its paralog DDX17, recently shown to be involved in alternative splicing of cellular genes after NF-κB activation by HTLV-1 Tax-1, interacted and partially co-localized with HBZ. For the first time, a complete picture of the endogenous HBZ interactome was elucidated. The wide interaction of HBZ with molecules involved in RNA splicing and the subsequent transcriptome alteration strongly suggests an unprecedented complex role of the viral oncogene in the establishment of the leukemic state.

The breeding populations of colonial herons, egrets and allied waterbirds in Northwestern Italy increased since 1972, when a long-term monitoring was initiated, up to the end of the 20° century. Populations of continental importance for some heron species were concentrated mostly in the district of intensive rice cultivation, where the paddies offered wide foraging opportunities. After 2000, new cultivation techniques caused a progressive reduction in paddy flooding. We found a significant relationship between the post-2000 decrease in the number of nests of the three most abundant species of waterbirds, Grey Heron, Little Egret and Black-crowned Night-heron, and the diminishing extent of paddy flooding estimated on satellite-derived images. On the other hand, outside the paddies district the same three species continued to increase or remained mostly stable. The recent agronomic changes in the paddies of Northwestern Italy compromise their role as surrogates of natural wetlands and their importance for environmental conservation. The spread of dry rice fields, and the consequent loss of their value for conservation of aquatic biodiversity, call for a revision of the regulations and incentives to farmers under the Common Agriculture Policy by the European Union and by local authorities. Return to early-submerged rice fields and adoption of environmental-friendly practices, such as the creation of compensatory wetlands, should become mandatory for rice to maintain its status as “green” crop.

Non-infectious uveitis (NIU) can be an early or even the first extra-articular manifestation of systemic rheumatic diseases, or the first one; thus, rheumatologists are often involved in the diagnostic and therapeutic assessment of NIU. We evaluated 130 patients with a diagnosis of NIU who were admitted to two Italian rheumatologic clinics (Tor Vergata University Hospital in Rome, and Federico II University in Naples) from January 2018 to December 2021. Anterior uveitis (AU) occurred in 75.4% of patients, followed by posterior uveitis (PU, 21.5%); acute (54.6%) and recurrent (35.4%) NIU were more documented than chronic NIU (10%), and a bilateral involvement was observed in 38.7% of cases. Half of NIU cases were associated with spondyloarthritis (SpA); the remaining were affected by Behçet disease (BD)-related uveitis (13.9%) and idiopathic NIU (9.2%). HLA-B27+ patients (34.8%) had a higher prevalence of anterior and unilateral NIU (p = 0.005) with acute course (p = 0.04) than HLA-B27– patients. On the contrary, HLA-B51+ patients (19.6%) had mostly PU and bilateral NIU (p < 0.0001) and recurrent course (p = 0.04) than HLA-B51– patients. At the first rheumatologic referral, 117 patients (90%) received systemic treatments. Findings from this study demonstrate that rheumatologic referral has a pivotal role in the diagnostic work-up of NIU and may dramatically influence NIU-treatment strategies.

Abstract The promise enabled by boron arsenide’s (BAs) high thermal conductivity (κ) in power electronics cannot be assessed without taking into account the reduction incurred when doping the material. Using first principles calculations, we determine the κ reduction induced by different group IV impurities in BAs as a function of concentration and charge state. We unveil a general trend, where neutral impurities scatter phonons more strongly than the charged ones. CB and GeAs impurities show by far the weakest phonon scattering and retain BAs κ values of over ~1000 W⋅K−1⋅m−1 even at high densities. Both Si and Ge achieve large hole concentrations while maintaining high κ. Furthermore, going beyond the doping compensation threshold associated to Fermi level pinning triggers observable changes in the thermal conductivity. This informs design considerations on the doping of BAs, and it also suggests a direct way to determine the onset of compensation doping in experimental samples.

Hemoproteins include several heme-binding proteins with distinct structure and function. The presence of the heme group confers specific reactivity and spectroscopic properties to hemoproteins. In this review, we provide an overview of five families of hemoproteins in terms of dynamics and reactivity. First, we describe how ligands modulate cooperativity and reactivity in globins, such as myoglobin and hemoglobin. Second, we move on to another family of hemoproteins devoted to electron transport, such as cytochromes. Later, we consider heme-based reactivity in hemopexin, the main heme-scavenging protein. Then, we focus on heme–albumin, a chronosteric hemoprotein with peculiar spectroscopic and enzymatic properties. Eventually, we analyze the reactivity and dynamics of the most recently discovered family of hemoproteins, i.e., nitrobindins.

Abstract The spreading of invasive species in new continents can vary from slow and limited diffusion to fast colonisations over vast new areas. We studied the sacred ibis Threskiornis aethiopicus along a 31-year period, from 1989 to 2019, with particular attention to the first area of release in NW Italy. We collected data on species distribution through observations by citizen science projects, population density by transects with distance method, breeding censuses at colonies, and post breeding censuses at roosts. The birds counted at winter roosts in NW Italy increased from a few tens up to 10,880 individuals in 2019. Sacred ibises started breeding in 1989, with a single nest in north-western Italy. The number of breeders remained very low until 2006, when both overwintering and breeding sacred ibises started to increase exponentially and expand their range throughout northern Italy with isolated breeding cases in central Italy. In 2019, the number of nests had increased to 1249 nests in 31 colonies. In NW Italy, the density of foraging birds averaged 3.9 ind./km2 in winter and 1.5 ind./km2 in the breeding period, with a mean size of the foraging groups of 8.9 and 2.1 birds respectively. Direct field observations and species distribution models (SDM) showed that foraging habitats were mainly rice fields and wetlands. A SDM applied to the whole Italian peninsula plus Sardinia and Sicily showed that the variables best related to the SDM were land class (rice fields and wetlands), altitude, and the temperature seasonality. The areas favourable for species expansion encompass all the plains of Northern Italy, and several areas of Tuscany, Latium, Sardinia, and Apulia.

The 16p13.11 microdeletion, whose prevalence in the general population is about 0.04%, is known in literature as a predisposition factor to neurodevelopmental disorders, being found in about 0.13% of patients with schizophrenia, in 0.5–0.6% of patient with epilepsy, cognitive impairment, autism spectrum disorder (ASD) and aggressiveness. The goal of this study was to identify a specific gene set pattern unique for the affected patients in comparison with other familial components. Due to the incomplete penetrance of this copy number variant (CNV), we studied by whole exome sequencing (WES), with particular regard of 850 SFARI genes, three families with an affected member carrier of inherited 16p13.11 and 16p13.11p12.3 microdeletion and one family with an affected member with a de novo 16p13.11 microdeletion. By combining a deductive approach together with personalized network models, we identified gene signatures potentially capable of explaining the clinical phenotype. Candidate variants in genes of interest were identified as possibly involved in determining the neurological phenotype of the four patients, such as compound heterozygosity in CECR2, variants in MTOR and RICTOR genes, compound heterozygous single nucleotide variants in the LRRK2 gene. Moreover, genes present in the microdeletion region were partially present as central nodes, with a focus on NDE1. No additional pathogenetic or uncertain CNVs were found in all four patients. No significant variants were detected in genes included in the microdeletion in patients 1, 2 and 3, excluding the finding of unmasked recessive variants. In conclusion, WES is a fundamental tool in the genetic investigation of patients having a predisposing variant, which is not sufficient to define the clinical phenotype. Moreover, the analysis of WES data using Systems medicine tools, such as personalized network models, led to the prioritization of genes on a high throughput scale and to discover variants in genes that were not prioritized at first.

When the threat of COVID-19 became widely acknowledged, many hoped that this pandemic would squash “the anti-vaccine movement”. However, when vaccines started arriving in rich countries at the end of 2020, it appeared that vaccine hesitancy might be an issue even in the context of this major pandemic. Does it mean that the mobilization of vaccine-critical activists on social media is one of the main causes of this reticence to vaccinate against COVID-19? In this paper, we wish to contribute to current work on vaccine hesitancy during the COVID-19 pandemic by looking at one of the many mechanisms which can cause reticence towards vaccines: the capacity of vaccine-critical activists to influence a wider public on social media. We analyze the evolution of debates over the COVID-19 vaccine on the French Twittosphere, during two first years of the pandemic, with a particular attention to the spreading capacity of vaccine-critical websites. We address two main questions: 1) Did vaccine-critical contents gain ground during this period? 2) Who were the main actors in the diffusion of these contents? While debates over vaccines experienced a tremendous surge during this period, the share of vaccine-critical contents in these debates remains stable except for a limited number of short periods associated with specific events. Secondly, analyzing the community structure of the re-tweets hyper-graph, we reconstruct the mesoscale structure of the information flows, identifying and characterizing the major communities of users. We analyze their role in the information ecosystem: the largest right-wing community has a typical echo-chamber behavior collecting all the vaccine-critical tweets from outside and recirculating it inside the community. The smaller left-wing community is less permeable to vaccine-critical contents but, has a large capacity to spread it once adopted.

Femtosecond coherent Raman techniques have significant diagnostic value for the sensitive and non-intrusive measurement of temperature, pressure, and composition of gas mixtures. Due to the low density of samples, however, such measurements make use of high-energy amplified laser sources, with unwieldy and costly experimental setups. In this paper, we demonstrate an experimental setup equipped with a low-energy and low-average-power femtosecond oscillator allowing measurement of the pure-rotational spectrum of nitrogen down to atmospheric pressure using impulsive stimulated Raman scattering. Using a simplified model to analyze the experimental data we were able to derive the gas temperature with reasonable accuracy.

Different strategies have been developed to help parents with introducing new or disliked vegetables. Nonetheless, many parents of preschoolers struggle against children's refusal to eat vegetables. In this study, we aimed to evaluate the effectiveness of e-books in promoting positive attitudes toward vegetables through repeated visual exposures. A total of 61 families with preschoolers joined the See & Eat study and received an e-book about one of two vegetables chosen from a list of 24. Parents provided ratings of children's willingness to taste, intake, and liking of the chosen vegetables before and after reading the e-book; parents also evaluated their children's food fussiness and their agreement with respect to three mealtime goals of the family. Using a 2 (vegetable: target or non-target) × 2 (time: pre-test or post-test) within-subjects analysis, results from 53 families revealed a significant increase in children's willingness to taste, intake, and liking at post-test of both target and non-target vegetables. Following a two-week parent-child e-book reading intervention, children's food fussiness and parents' endorsement of positive mealtime goals slightly but significantly increased. Results suggest that e-books are effective in encouraging healthy eating among preschoolers and that the positive effect of e-book reading can generalize to other vegetables.

Nanostructured titania is one of the most commonly encountered constituents of nanotechnology devices for use in energy-related applications, due to its intrinsic functional properties as a semiconductor and to other favorable characteristics such as ease of production, low toxicity and chemical stability, among others. Notwithstanding this diffusion, the quest for improved understanding of the physical and chemical mechanisms governing the material properties and thus its performance in devices is still active, as testified by the large number of dedicated papers that continue to be published. In this framework, we consider and analyze here the effects of the material morphology and structure in determining the energy transport phenomena as cross-cutting properties in some of the most important nanophase titania applications in the energy field, namely photovoltaic conversion, hydrogen generation by photoelectrochemical water splitting and thermal management by nanofluids. For these applications, charge transport, light transport (or propagation) and thermal transport are limiting factors for the attainable performances, whose dependence on the material structural properties is reviewed here on its own. This work aims to fill the gap existing among the many studies dealing with the separate applications in the hope of stimulating novel cross-fertilization approaches in this research field.

Gene set enrichment analysis (GSEA) is a powerful tool to associate a disease phenotype to a group of genes/proteins. GSEA attributes a specific weight to each gene/protein in the input list that depends on a metric of choice, which is usually represented by quantitative expression data. However, expression data are not always available. Here, GSEA based on betweenness centrality of a protein–protein interaction (PPI) network is described and applied to two cases, where an expression metric is missing. First, personalized PPI networks were generated from genes displaying alterations (assessed by array comparative genomic hybridization and whole exome sequencing) in four probands bearing a 16p13.11 microdeletion in common and several other point variants. Patients showed disease phenotypes linked to neurodevelopment. All networks were assembled around a cluster of first interactors of altered genes with high betweenness centrality. All four clusters included genes known to be involved in neurodevelopmental disorders with different centrality. Moreover, the GSEA results pointed out to the evidence of “cell cycle” among enriched pathways. Second, a large interaction network obtained by merging proteomics studies on three neurodegenerative disorders was analyzed from the topological point of view. We observed that most central proteins are often linked to Parkinson’s disease. The selection of these proteins improved the specificity of GSEA, with “Metabolism of amino acids and derivatives” and “Cellular response to stress or external stimuli” as top-ranked enriched pathways. In conclusion, betweenness centrality revealed to be a suitable metric for GSEA. Thus, centrality-based GSEA represents an opportunity for precision medicine and network medicine.

Recently described species suffer lack of information that hampers setting up appropriate conservation strategies. The situation is particularly complex with micro-endemic snakes, for which detection and monitoring are particularly challenging. The Walser viper Vipera walser is a recently described snake inhabiting a small area of the SW Italian alps. We combined information on species distribution with repeated monitoring to identify the areas most suitable for the species, and to obtain estimates of species abundance. Species distribution models were used to identify the topographical, climatic, and land-cover features related to the occurrence of vipers. Furthermore, repeated transects and N-mixture models were used to estimate abundance and to identify factors related to the variation of abundance. The available data suggested that the species has a disjunct range, with a Northern range of ~45 km2, and a southern range of ~225 km2. Distribution models suggested that vipers are associated with areas with open vegetation, altitude between 1300 and 2300 m, high precipitation, low forest cover, low slope, and southern aspect. N-mixture models confirmed very low detection probability of these vipers, and suggested that the species has a low abundance, with the highest abundance in south-facing plots. We provide the first quantitative information on habitats and abundance variation for Walser vipers. The broad confidence intervals of abundance estimates exemplify the complexity of providing range-wide measures of abundance for secretive species. Given the narrow range of these vipers, continuous monitoring is required to understand how they respond to ongoing environmental changes in mountainous areas.

Activated hard carbons, obtained from the pyrolysis of various waste biomasses, were prepared and characterized for use as the active material for the fabrication of battery electrodes. The preparation consisted of a pyrolysis process, followed by an activation with KOH and a further high-temperature thermal process. TG and DTA were used to discriminate the steps of the activation process, while SEM, XRD, and Raman characterization were employed to evaluate the effects of activation. The activated carbons were tested as electrodes in lithium-sulfur and lithium-ion batteries. The carbonaceous materials coming from cherry stones and walnut shells have proved to be particularly suitable as electrode components. When used as anodes in lithium-ion batteries, both carbons exhibited a high first cycle discharge capacity, which was not restored during the next charge. After the first two cycles, in which there was a marked loss of capacity, both electrodes showed good reversibility. When used as cathodes in lithium-sulfur batteries, both carbons exhibited good catalytic activity against the redox reaction involving sulfur species with good cycle stability and satisfactory Coulombic efficiency.

Mutations in PARK2 gene are the most frequent cause of familial forms of Parkinson’s disease (PD). This gene encodes Parkin, an E3 ubiquitin ligase involved in several cellular mechanisms, including mitophagy. Parkin loss-of-function is responsible for the cellular accumulation of damaged mitochondria, which in turn determines an increment of reactive oxygen species (ROS) levels, lower ATP production, and apoptosis activation. Given the importance of mitochondrial dysfunction and mitophagy impairment in PD pathogenesis, the aim of the present study was to investigate both total and mitochondrial proteome alterations in human skin fibroblasts of PARK2-mutated patients. To this end, both total and mitochondria-enriched protein fractions from fibroblasts of five PARK2-mutated patients and five control subjects were analyzed by quantitative shotgun proteomics to identify proteins specifically altered by Parkin mutations (mass spectrometry proteomics data have been submitted to ProteomeXchange with the identifier PXD015880). Both the network-based and gene set enrichment analyses pointed out pathways in which Rab GTPase proteins are involved. To have a more comprehensive view of the mitochondrial alterations due to PARK2 mutations, we investigated the impact of Parkin loss on mitochondrial function and network morphology. We unveiled that the mitochondrial membrane potential was reduced in PARK2-mutated patients, without inducing PINK1 accumulation, even when triggered with the ionophore carbonyl cyanide m-chlorophenylhydrazone (CCCP). Lastly, the analysis of the mitochondrial network morphology did not reveal any significant alterations in PARK2-mutated patients compared to control subjects. Thus, our results suggested that the network morphology was not influenced by the mitochondrial depolarization and by the lack of Parkin, revealing a possible impairment of fission and, more in general, of mitochondrial dynamics. In conclusion, the present work highlighted new molecular factors and pathways altered by PARK2 mutations, which will unravel possible biochemical pathways altered in the sporadic form of PD.

El presente artículo se propone indagar en los fundamentos de la construcción del poderío económico de la elite dirigente del gremio pelaire al interior de la protoindustria textil murciana, desde el último cuarto del siglo XIV hasta fines del siglo XV. Para ello daremos cuenta de los factores de carácter político-institucional que permiten que el sector dirigente de esta corporación subordine a buena parte del artesanado textil local y llegue a disputar el abastecimiento pañero de la ciudad con el sector del capital comercial representado por los traperos murcianos. Con este objeto analizaremos la incidencia de la regulación productiva impulsada por el sector dirigente de este gremio en la construcción de relaciones de explotación.