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Synaptic dysfunction and loss caused by age-dependent accumulation of synaptotoxic beta amyloid (Abeta) 1-42 oligomers is proposed to underlie cognitive decline in Alzheimer's disease (AD). Alterations in membrane trafficking induced by Abeta oligomers mediates reduction in neuronal surface receptor expression that is the basis for inhibition of electrophysiological measures of synaptic plasticity and thus learning and memory. We have utilized phenotypic screens in mature, in vitro cultures of rat brain cells to identify small molecules which block or prevent the binding and effects of Abeta oligomers. Synthetic Abeta oligomers bind saturably to a single site on neuronal synapses and induce deficits in membrane trafficking in neuronal cultures with an EC50 that corresponds to its binding affinity. The therapeutic lead compounds we have found are pharmacological antagonists of Abeta oligomers, reducing the binding of Abeta oligomers to neurons in vitro, preventing spine loss in neurons and preventing and treating oligomer-induced deficits in membrane trafficking. These molecules are highly brain penetrant and prevent and restore cognitive deficits in mouse models of Alzheimer's disease. Counter-screening these compounds against a broad panel of potential CNS targets revealed they are highly potent and specific ligands of the sigma-2/PGRMC1 receptor. Brain concentrations of the compounds corresponding to greater than 80% receptor occupancy at the sigma-2/PGRMC1 receptor restore cognitive function in transgenic hAPP Swe/Ldn mice. These studies demonstrate that synthetic and human-derived Abeta oligomers act as pharmacologically-behaved ligands at neuronal receptors--i.e. they exhibit saturable binding to a target, they exert a functional effect related to their binding and their displacement by small molecule antagonists blocks their functional effect. The first-in-class small molecule receptor antagonists described here restore memory to normal in multiple AD models and sustain improvement long-term, representing a novel mechanism of action for disease-modifying Alzheimer's therapeutics.

Chiral phase-transfer catalysis provides high level of enantiocontrol, however no experimental data showed the interaction of catalysts and substrates. 1 H NMR titration was carried out on Cinchona and Maruoka ammonium bromides vs. nitro, carbonyl, heterocycles, and N-F containing compounds. It was found that neutral organic species and quaternary ammonium salts interacted via an ensemble of catalyst + N-C-H and (sp2 )C-H, specific for each substrate studied. The correspondent BArF salts interacted with carbonyls via a diverse set of + N-C-H and (sp2 )C-H compared to bromides. This data suggests that BArF ammonium salts may display a different enantioselectivity profile. Although not providing quantitative data for the affinity constants, the data reported proofs that chiral ammonium salts coordinate with substrates, prior to transition state, through specific C-H positions in their structures, providing a new rational to rationalize the origin of enantioselectivity in their catalyses.

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.