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Abstract Human organoids have been proposed to be powerful tools mimicking the physiopathological processes of the organs of origin. Recently, human pancreatic organoids (hPOs) have gained increasing attention due to potential theragnostic and regenerative medicine applications. However, the cellular components of hPOs have not been defined precisely. In this work, we finely characterized these structures, focusing first on morphology and identity-defining molecular features under long-term culture conditions. Next, we focused our attention on hPOs cell type composition using single-cell RNA sequencing founding a complex heterogeneity in ductal components, ranging from progenitor components to terminally differentiated ducts. Furthermore, an extensive comparison of human pancreatic organoids with previously reported transcriptomics signature of human and mouse pancreatic ductal populations, confirmed the functional pancreatic duct subpopulation heterogeneity. Finally, we showed that pancreatic organoid cells follow a precise developmental trajectory and utilize diverse signalling mechanisms, including EGF and SPP1, to facilitate cell-cell communication and maturation. Together our results offer an in-depth description of human pancreatic organoids providing a strong foundation for future in vitro diagnostic and translational studies of pancreatic health and disease.

In this contribution, new data concerning the distribution of native vascular flora in Italy are presented. It includes new records, confirmations, and exclusions to the Italian administrative regions for taxa in the genera Alchemilla, Carex, Chenopodium, Cistus, Convolvulus, Erysimum, Euphorbia, Festuca, Klasea, Lotus, Orobanche, Poa, Stellaria, Trifolium, Viola. Nomenclatural and distribution updates, published elsewhere, and corrigenda are provided as Suppl. material 1.

Abstract Affective Touch is characterized by both emotional and arousing dimensions that rely on specific features of a gentle human caress. In this study, we investigated whether and how both the nature of the touching effector (Human hand vs. Artificial hand) and touch type (Dynamic vs. Static) influenced the participants’ pupil dilation and their subjective experience during tactile stimulation. We observed that when participants received a dynamic touch, their pupil dilation increased more when the touch was produced by a human compared to an artificial hand. This discrimination was not present for static touch. Also, dynamic touch given by a human hand invoked a supralinear enhancement of pupil dilation indicating that the combination of these two features induced a stronger autonomic activation than the summed effects of each separately. Moreover, this specific type of touch was perceived as the most pleasant compared to all other tactile stimulations. Overall, our results suggest that pupil dilation could reflect the pleasant experience of human-to-human tactile interactions, supporting the notion that the autonomic nervous system is responsive to the emotional and hedonic aspects associated with Affective Touch as a part of a complex and holistic social experience, rather than solely reacting to its low-level sensory properties.

Abstract Systemic inflammation significantly increases the risk of short- and long-term mortality in geriatric hospitalized patients. To predict mortality in older patients with various age-related diseases and infections, including COVID-19, inflammatory biomarkers such as the C-reactive protein (CRP) to albumin ratio (CAR), and related scores and indexes, i.e. Glasgow Prognostic Score (GPS), modified GPS (mGPS), and high sensitivity (hs)-mGPS, have been increasingly utilized. Despite their easy affordability and widespread availability, these biomarkers are predominantly assessed for clinical purposes rather than predictive applications, leading to their underutilization in hospitalized older patients. In this study, we investigated the association of CAR, GPS, mGPS, and hs-mGPS with short-term mortality in 3,206 geriatric hospitalized patients admitted for acute conditions, irrespective of admission diagnosis. We observed that unit increases of CAR, and the highest classes of GPS, mGPS, and hs-mGPS were significantly associated with a two- to threefold increased risk of death, even adjusting the risk for different confounding variables. Interestingly, a hs-mGPS of 2 showed the highest effect size. Furthermore, gender analysis indicated a stronger association between all CRP-albumin based parameters and mortality in men, underscoring the gender-specific relevance of inflammation-based circulating parameters in mortality prediction. In conclusion, scores based on serum CRP and albumin levels offer additional guidance for the stratification of in-hospital mortality risk in older patients by providing additional information on the degree of systemic inflammation.

Abstract Multi‐microphone recording adds spatial information to recorded audio with emerging applications in ecosystem monitoring. Specifically placing sounds in space can improve animal count accuracy, locate illegal activity like logging and poaching, track animals to monitor behaviour and habitat use and allow for ‘beamforming’ to amplify sounds from target directions for downstream classification. Studies have shown many advantages of spatial acoustics, but uptake remains limited as the equipment is often expensive, complicated, inaccessible or only suitable for short‐term deployments. With an emphasis on enhanced uptake and usability, we present a low‐cost, open‐source, six‐channel recorder built entirely from commercially available components which can be integrated into a solar‐powered, online system. The MAARU (Multichannel Acoustic Autonomous Recording Unit) works as an independent node in long‐term autonomous, passive and/or short‐term deployments. Here, we introduce MAARU's hardware and software and present the results of lab and field tests investigating the device's durability and usability. MAARU records multichannel audio with similar costs and power demands to equivalent omnidirectional recorders. MAARU devices have been deployed in the United Kingdom and Brazil, where we have shown MAARUs can accurately localise pure tones up to 6 kHz and bird calls as far as 8 m away (±10° range, 100% and >60% of signals, respectively). Louder calls may have even further detection radii. We also show how beamforming can be used with MAARUs to improve species ID confidence scores. MAARU is an accessible, low‐cost option for those looking to explore spatial acoustics accurately and easily with a single device, and without the formidable expenses and processing complications associated with establishing arrays. Ultimately, the added directional element of the multichannel recording provided by MAARU allows for enhanced recording of sonic environments, further enabling a potential step change in the uptake of spatial acoustics in the wider field.

The inventory of the taxa collected in 2021 during the annual field trip of the Working Group for Floristics, Systematics, and Evolution of the Italian Botanical Society is reported. The field trip was held in the Mount Pennino massif, between Umbria and Marche administrative regions (central Italy). The flora documented for the study area amounts to 413 specific and subspecific taxa (including one hybrid), belonging to 234 genera and 64 families. Thirty-seven taxa are endemic to Italy; 42 are included in the IUCN Red List of the Italian Flora. Only three alien taxa were found. Ten taxa and one hybrid are considered floristic novelties because either new or confirmed for the regional flora of Umbria and/or Marche. Particularly, 6 taxa are new and 4 are confirmed for Umbria; one taxon and one hybrid are new for Marche.

We propose a model for the QCD running coupling constant based on the analytical inverse QCD coupling constant concept with an additional regularization in the low momentum region. Analyticity in the q2-complex plane, where q is the four-momentum transfer, is imposed by methods of the Analytic Perturbation Theory. The model incorporates a peculiar low-momentum behavior for αs(q2) as a divergence at q2=0 to retrieve color confinement, without spoiling its correct high-momentum behavior. This was achieved by means of a two-parameter regularization function, for which we considered three possible analytic expressions. In fact, within the framework of the Analytic Perturbation Theory, αs(q2) assumes a finite value for q2=0, at all perturbative orders (infrared stability), hence the infrared divergence cannot be implemented. For this reason, we found it more straightforward to work with its reciprocal, namely, εs(q2)=1/αs(q2), imposing its vanishing at the origin of the q2-complex plane via the multiplication of the aforementioned regularizing functions and the spectral density. Once the two free parameters of the regularization functions were settled by fitting to the experimental values of αs(q2) at the momenta where these data were available and reliable, the model could reproduce the QCD running coupling constant at any other momentum transferred.

In this contribution, new data concerning the distribution of vascular flora alien to Italy are presented. It includes new records and status changes from casual to naturalized for Italy or for Italian administrative regions for taxa in the genera Callianthe, Chamaecyparis, Chamaeiris, Cotoneaster, Erigeron, Freesia, Hemerocallis, Juglans, Kalanchoë, Ludwigia, Nassella, Paulownia, Physocarpus, Pistia, Saccharum, Setaria, and Vachellia. Nomenclatural and distribution updates, published elsewhere, and corrections are provided as supplementary material.

ObjectivesA prospective interventional study was designed to describe our series of patients with submandibular stones undergoing sialendoscopy-assisted TORSS (trans-oral robotic salivary surgery) by means of Si or Xi Da Vinci robotic system between January 2019 and June 2023, in order to assess safety and effectiveness of the procedure.Methods54 adult patients with submandibular stones undergoing sialendoscopy-assisted TORSS between January 2019-June 2023.ResultsThe global success rate was 81.5%, with better surgical outcomes in patients with palpable hilar/hilo-parenchymal stones compared to non-palpable pure parenchymal ones (92.7 vs. 46.2%). In addition, the mean stone size in cases failing TORSS was smaller than that documented in successfully treated patients (7.8 ± 1.8 vs. 9.8 ± 2.4 mm). No major untoward effects were observed (transitory lingual nerve dysfunction in 3 patients undergoing Xi Da Vinci surgery). A positive outcome in terms of post-operative surgical pain, patient's satisfaction and recovery time was observed.ConclusionsIntrinsic stone features (such as size, location/palpability) seems to be predictor for surgical success; an accurate pre-operative planning is mandatory to better select which patient can benefit most from TORSS procedure.

This opinion paper evaluates the potential of porcine islets as a promising alternative in beta cell replacement therapy for Type 1 Diabetes (T1D), juxtaposed with the current limitations of human donor islets. It analyzes the compatibility of pig islets with human glucose metabolism, their prospects as a limitless and high-quality source of beta cells, and the unique immunogenic challenges they present in xenotransplantation. Additionally, the paper discusses the regulatory and ethical considerations pertinent to the use of porcine islets. By synthesizing current research and expert perspectives, the paper highlights both the opportunities and significant barriers that need addressing to advance pig islets as a viable therapeutic option. The findings advocate for a balanced and forward-looking approach to the integration of pig islets in T1D treatment, underscoring the need for continued research and dialogue in this evolving field.

Key Clinical Message Posterior glottic lesions resembling granulomas unresponsive to conservative treatment should raise suspicion of a neoplastic condition. Although surgery is rarely recommended for arytenoid granulomas due to their high recurrence rate, histological evaluation is mandatory in cases of uncertain diagnosis. Clinicians should be aware that, although very rare, a laryngeal neuroendocrine tumor occurring in the posterior glottis can mimic the appearance of an idiopathic granuloma, presenting a diagnostic challenge.

The field of organ transplantation is experiencing a transformative shift with the rise of Advanced Therapy Medicinal Products (ATMPs), which include gene therapies, somatic cell therapies, and tissue-engineered products. These therapies offer new, potentially curative treatments for longstanding medical challenges, impacting numerous patients. However, their adoption is hindered by complex regulatory frameworks, high production costs, and inconsistent access across Europe. The ESOT ATMP Task Force’s position paper analyzes these challenges from research to clinical application, advocating for a coordinated strategy to position Europe as a leader in ATMP development. It proposes specific actions such as streamlining regulatory pathways to accelerate approvals, boosting funding for ATMP research, and creating specialized facilities for development and implementation. The paper also highlights the critical roles of patient engagement and real-world evidence in optimizing clinical and regulatory practices.

Background. The development of a hybrid beta-cell replacement approach, referred to as a personalized, transplantable bioartificial pancreas (BAP), holds promise to treat type 1 diabetes (T1D). This interview study aimed to explore patients’ expectations, needs, concerns, and considerations when considering to undergo a BAP transplantation. Research Design and Methods. Semistructured interviews were conducted with 24 participants diagnosed with T1D. Data collection stopped once data saturation was reached. Audio recordings of the interviews were transcribed verbatim. The interviews were independently analyzed by 2 researchers. A qualitative content analysis using an inductive approach was used. Results. Three main themes emerged as follow: (1) hoped-for benefits, (2) concerns and decision-making considerations, and (3) procedural aspects. First, the participants expected benefits across medical, psychological, and social domains. Over these 3 domains, 9 subthemes were identified, including improved clinical outcomes, a cure for diabetes, more headspace, emotional relief, a shift in responsibility, protection of privacy, improved flexibility in daily life, less visible diseases, and improved relationships with others. Second, concerns and considerations about undergoing a BAP transplant comprised adverse events, the functionality of the BAP, the surgery procedure, the biological materials used, the transplant location, and the intrusiveness associated with follow-up care. Finally, procedural considerations included equitable access, patient prioritization, and trust and control. Conclusions. Incorporating insights from this study into the clinical development and implementation of the BAP is crucial to ensure alignment of the product and procedures with the needs and expectations of people with T1D.

This work investigates potential benefits deriving from the integration of CSP plants with other renewable technologies, such as PV and Wind. An optimization tool, based on mixed-integer linear programming, is used to derive the optimal design of a hybrid plant located in the south of Italy (Sicily) with the objective of satisfying a fraction of the national-shaped, hourly variable, electrical load. A sensitivity analysis is performed to explore the Pareto front of solutions satisfying different dispatchability requirements in terms of demand coverage. As expected, increasingly oversized and expensive plant designs, characterized by high Levelized Cost of Electricity (LCOE), are necessary to satisfy larger fractions of the imposed load. Subsequently, the benefits of hybrid plants with respect to conventional standalone or partially integrated solutions are investigated: in particular, the results of this analysis clearly demonstrated that integrated CSP+PV+Wind configurations can reach the same or higher dispatchability level (i.e. 80%) at a much lower electricity cost with respect to (i) separate production (stand-alone PV, Wind and CSP) and (ii) configurations characterized by a lower level of integration (36% and 12% reduction of LCOE with respect to CSP+PV and CSP+Wind, respectively).

Summary: Background: NOTCH3 encodes a transmembrane receptor critical for vascular smooth muscle cell function. NOTCH3 variants are the leading cause of hereditary cerebral small vessel disease (SVD). While monoallelic cysteine-involving missense variants in NOTCH3 are well-studied in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), patients with biallelic variants in NOTCH3 are extremely rare and not well characterised. Methods: In this study, we present clinical and genetic data from 25 patients with biallelic NOTCH3 variants and conduct a literature review of another 25 cases (50 patients in total). Brain magnetic resonance imaging (MRI) were analysed by expert neuroradiologists to better understand the phenotype associated with biallelic NOTCH3 variants. Findings: Our systematic analyses verified distinct genotype-phenotype correlations for the two types of biallelic variants in NOTCH3. Biallelic loss-of-function variants (26 patients) lead to a neurodevelopmental disorder characterised by spasticity, childhood-onset stroke, and periatrial white matter volume loss resembling periventricular leukomalacia. Conversely, patients with biallelic cysteine-involving missense variants (24 patients) fall within CADASIL spectrum phenotype with early adulthood onset stroke, dementia, and deep white matter lesions without significant volume loss. White matter lesion volume is comparable between patients with biallelic cysteine-involving missense variants and individuals with CADASIL. Notably, monoallelic carriers of loss-of-function variants are predominantly asymptomatic, with only a few cases reporting nonspecific headaches. Interpretation: We propose a NOTCH3-SVD classification depending on dosage and variant type. This study not only expands our knowledge of biallelic NOTCH3 variants but also provides valuable insight into the underlying mechanisms of the disease, contributing to a more comprehensive understanding of NOTCH3-related SVD. Funding: The Wellcome Trust, the MRC.

Abstract Accessible SARS-CoV-2-specific immunoassays may inform clinical management in people with HIV, particularly in case of persisting immunodysfunction. We prospectively studied their application in vaccine recipients with HIV, purposely including participants with a history of advanced HIV infection. Participants received one (n = 250), two (n = 249) or three (n = 42) doses of the BNT162b2 vaccine. Adverse events were documented through questionnaires. Sample collection occurred pre-vaccination and a median of 4 weeks post-second dose and 14 weeks post-third dose. Anti-spike and anti-nucleocapsid antibodies were measured with the Roche Elecsys chemiluminescence immunoassays. Neutralising activity was evaluated using the GenScript cPass surrogate virus neutralisation test, following validation against a Plaque Reduction Neutralization Test. T-cell reactivity was assessed with the Roche SARS-CoV-2 IFNγ release assay. Primary vaccination (2 doses) was well tolerated and elicited measurable anti-spike antibodies in 202/206 (98.0%) participants. Anti-spike titres varied widely, influenced by previous SARS-CoV-2 exposure, ethnicity, intravenous drug use, CD4 counts and HIV viremia as independent predictors. A third vaccine dose significantly boosted anti-spike and neutralising responses, reducing variability. Anti-spike titres > 15 U/mL correlated with neutralising activity in 136/144 paired samples (94.4%). Three participants with detectable anti-S antibodies did not develop cPass neutralising responses post-third dose, yet displayed SARS-CoV-2 specific IFNγ responses. SARS-CoV-2 vaccination is well-tolerated and immunogenic in adults with HIV, with responses improving post-third dose. Anti-spike antibodies serve as a reliable indicator of neutralising activity. Discordances between anti-spike and neutralising responses were accompanied by detectable IFN-γ responses, underlining the complexity of the immune response in this population.

Introduction: Secondary thyroid autoimmunity, especially Graves’ disease (GD), frequently develops in patients with multiple sclerosis (MS) following alemtuzumab treatment (ALTZ; anti-CD52). Thyroid eye disease (TED) can also develop, and rituximab (RTX; anti-CD20) is a suitable treatment. Case presentation: A 37-year-old woman with MS developed steroid-resistant active moderate-to-severe TED 3 years after ALTZ, that successfully responded to a single 500 mg dose of i.v. RTX. Before RTX peripheral B-cells were low, and were totally depleted immediately after therapy. Follow-up analysis 4 years post ALTZ and 1 year post RTX showed persistent depletion of B cells, and reduction of T regulatory cells in both peripheral blood and thyroid tissue obtained at thyroidectomy. Conclusion: RTX therapy successfully inactivated TED in a patient with low B-cell count derived from previous ALTZ treatment. B-cell depletion in both thyroid and peripheral blood was still present 1 year after RTX, indicating a likely cumulative effect of both treatments.

Abstract Individuals who reside in a country without regular authorisation generally find it difficult to access public medical services beyond emergency treatment. Even in countries with universal healthcare, there is often a gap between rights on paper and their implementation. Civil society organisations (CSOs) fill this gap by providing medical services to vulnerable populations, including irregular migrants. What, if any, are the ethical dilemmas that arise for CSO staff when delivering such services in countries with universal healthcare? Under what conditions do these dilemmas arise? And what strategies do CSO staff use to mitigate them? We answer these questions using 40 semi-structured interviews with CSO staff working in two European countries with high levels of irregularity, universal healthcare provisions on paper, and significant differences in approaches and availability of public services for irregular migrants: Italy and Spain. We show that CSO staff providing medical services to irregular migrants in places with universal healthcare coverage face a fundamental dilemma between humanitarianism and equity. CSO staff respond to the humanitarian belief in the value of taking all possible steps to prevent or alleviate human suffering, thus promoting a decent quality of life that includes access to both emergency and non-emergency care. In doing so, however, they run the risk of substituting rather than complementing public provisions, thereby preventing governments from assuming responsibility for these services in the long term. Individuals who acknowledge the existence of this dilemma generally oppose the creation of parallel structures; that is, services specifically developed for irregular migrants outside the public system; while those who ignore it essentially subscribe to a tiered system, giving up on considerations of equity. We argue that CSOs involved in the provision of healthcare to irregular migrants do not simply provide services; they also play an inherently political role.

ObjectiveThe prevalence of anxiety and depression in patients diagnosed with Alopecia Areata (AA) is very high and this significant burden of psychological symptoms threatens the Health-Related Quality of Life (HRQoL) of affected patients. Indeed, AA often does not produce significant physical symptoms, but it nonetheless disrupts many areas of mental health. Clinical assessment of disease severity may not reliably predict patient's HRQoL, nor may it predict the patient's perception of illness. For this reason, considerable effort has been made to apply and develop measures that consider patient's perception and assess the HRQoL of individuals affected by AA. The aim of this multicentric study was to provide the Italian version of the Skindex-16AA and to evaluate its psychometric properties in a clinical sample of consecutive patients with moderate-to-severe AA.MethodsThis is a longitudinal, multicenter, observational study. Patients returned for follow-up visits at 4-, 12-, and 24-weeks. The analyses of the current work aimed to confirm the factorial structure of the Skindex-16AA. In the case of non-fit, an alternative structure for the model was proposed, using an Exploratory Graph Analysis and the Bayesian approach.ResultsThe sample was composed of 106 patients with AA. Alopecia Universalis was the most frequently diagnosed type of alopecia at all time points. The analyses on the Skindex-16AA revealed that a two-factor structure with eight items fit the data best (Bayesian Posterior Predictive Checking using 95% Confidence Interval for the Difference Between the Observed and the Replicated Chi-Square values = −6.246/56.395, Posterior Predictive P-value = 0.06), and reported satisfactory psychometric properties (i.e., internal consistency and convergent validity).ConclusionThe Skindex-8AA demonstrated optimal psychometric properties (i.e., convergent and construct validity, and test-retest reliability) measured in a sample of patients with AA, that may suggest that it is an appropriate tool to measure the HRQoL in AA patients. However, further studies are needed in order to confirm and tested other psychometric features of this tool.

Cross-taxon congruence, i.e., using certain taxonomic groups as surrogates for others, is receiving growing interest since it may allow decreasing efforts in biodiversity studies. In this work, we investigated the patterns of cross-taxon congruence in species richness and composition between communities of bryophytes, lichens, and vascular plants in different biancana grasslands of a Special Area of Conservation (SAC) of central Italy. We recorded species presence and abundance in 16 plots of 1 × 1 m size and analyzed the data using Procrustes correlation, co-correspondence analysis, and indicator species analysis. We did not highlight any correlation in species richness and composition between the three taxonomic groups. Conversely, the species composition of bryophyte communities was predictive of the species composition of lichen communities. Moreover, lichen richness was negatively correlated with the total cover of vascular plants. Indicator species analysis evidenced the presence of species from the three biotic communities being particularly related, at least at the local scale, to biancana pediments, like the bryophytes Didymodon acutus and Trichostomum crispulum, the lichens Enchylium tenax, Cladonia foliacea, and Psora decipiens, and the vascular plants Brachypodium distachyon, Parapholis strigosa, and Artemisia caerulescens subsp. cretacea. In the biancana pediments, acrocarp mosses, squamulose lichens, therophyte plants and chamaephyte plants coexisted. In spite of the weak cross-taxon congruence between the three taxonomic groups, this study could highlight a locally unique diversity of bryophytes, lichens, and vascular plants related to the extreme environment of biancana pediments, selected by high soil salinity and deposition from the upper eroded slope. Soil erosion and deposition in biancana badlands supports the increase of local multi-taxonomic plant diversity by creating unique ecosystems. Such biodiversity should be considered locally at risk of disappearance, due to the ongoing vanishing of biancana badlands in central Italy.

Treatment-Resistant Depression (TRD) poses a substantial health and economic challenge, persisting as a major concern despite decades of extensive research into novel treatment modalities. The considerable heterogeneity in TRD’s clinical manifestations and neurobiological bases has complicated efforts toward effective interventions. Recognizing the need for precise biomarkers to guide treatment choices in TRD, herein we introduce the SelecTool Project. This initiative focuses on developing (WorkPlane 1/WP1) and conducting preliminary validation (WorkPlane 2/WP2) of a computational tool (SelecTool) that integrates clinical data, neurophysiological (EEG) and peripheral (blood sample) biomarkers through a machine-learning framework designed to optimize TRD treatment protocols. The SelecTool project aims to enhance clinical decision-making by enabling the selection of personalized interventions. It leverages multi-modal data analysis to navigate treatment choices towards two validated therapeutic options for TRD: esketamine nasal spray (ESK-NS) and accelerated repetitive Transcranial Magnetic Stimulation (arTMS). In WP1, 100 subjects with TRD will be randomized to receive either ESK-NS or arTMS, with comprehensive evaluations encompassing neurophysiological (EEG), clinical (psychometric scales), and peripheral (blood samples) assessments both at baseline (T0) and one month post-treatment initiation (T1). WP2 will utilize the data collected in WP1 to train the SelecTool algorithm, followed by its application in a second, out-of-sample cohort of 20 TRD subjects, assigning treatments based on the tool’s recommendations. Ultimately, this research seeks to revolutionize the treatment of TRD by employing advanced machine learning strategies and thorough data analysis, aimed at unraveling the complex neurobiological landscape of depression. This effort is expected to provide pivotal insights that will promote the development of more effective and individually tailored treatment strategies, thus addressing a significant void in current TRD management and potentially reducing its profound societal and economic burdens.

Background: Lesion network mapping (LNM) is a popular framework to assess clinical syndromes following brain injury. The classical approach involves embedding lesions from patients into a normative functional connectome and using the corresponding functional maps as proxies for disconnections. However, previous studies indicated limited predictive power of this approach in behavioral deficits. We hypothesized similarly low predictiveness for overall survival (OS) in glioblastoma (GBM). Methods: A retrospective dataset of patients with GBM was included (n = 99). Lesion masks were registered in the normative space to compute disconnectivity maps. The brain functional normative connectome consisted in data from 173 healthy subjects obtained from the Human Connectome Project. A modified version of the LNM was then applied to core regions of GBM masks. Linear regression, classification, and principal component (PCA) analyses were conducted to explore the relationship between disconnectivity and OS. OS was considered both as continuous and categorical (low, intermediate, and high survival) variable. Results: The results revealed no significant associations between OS and network disconnection strength when analyzed at both voxel-wise and classification levels. Moreover, patients stratified into different OS groups did not exhibit significant differences in network connectivity patterns. The spatial similarity among the first PCA of network maps for each OS group suggested a lack of distinctive network patterns associated with survival duration. Conclusions: Compared with indirect structural measures, functional indirect mapping does not provide significant predictive power for OS in patients with GBM. These findings are consistent with previous research that demonstrated the limitations of indirect functional measures in predicting clinical outcomes, underscoring the need for more comprehensive methodologies and a deeper understanding of the factors influencing clinical outcomes in this challenging disease.

Colleges and universities are increasingly turning to algorithms that predict college-student success to inform various decisions, including those related to admissions, budgeting, and student-success interventions. Because predictive algorithms rely on historical data, they capture societal injustices, including racism. In this study, we examine how the accuracy of college student success predictions differs between racialized groups, signaling algorithmic bias. We also evaluate the utility of leading bias-mitigating techniques in addressing this bias. Using nationally representative data from the Education Longitudinal Study of 2002 and various machine learning modeling approaches, we demonstrate how models incorporating commonly used features to predict college-student success are less accurate when predicting success for racially minoritized students. Common approaches to mitigating algorithmic bias are generally ineffective at eliminating disparities in prediction outcomes and accuracy between racialized groups.

Summary: The selection of renewable energy technologies is widely based on the economic index levelized cost of electricity (LCOE). However, the LCOE ignores the potential temporal mismatch between electricity generation and actual grid demand: this aspect is accounted for in the new index named actual cost of electricity (ACOE), here proposed. This index provides a more accurate economic assessment of renewable energy, minimizing the number of assumptions to be made and outlining the benefits of including a storage. The proposed index is tested across ten cases encompassing three renewable technologies: wind, photovoltaic, and concentrated solar power. The outcomes show that the actual renewable electricity generation of a plant can be reduced by 40%–50% when accounting for the actual electricity demand, resulting in an ACOE exceeding the LCOE by up to 100/150 $/MWh. In addition, the ACOE enables the identification of breakthrough conditions that make storage adoption economically feasible.

Abstract Sound localization is essential to perceive the surrounding world and to interact with objects. This ability can be learned across time, and multisensory and motor cues play a crucial role in the learning process. A recent study demonstrated that when training localization skills, reaching to the sound source to determine its position reduced localization errors faster and to a greater extent as compared to just naming sources’ positions, despite the fact that in both tasks, participants received the same feedback about the correct position of sound sources in case of wrong response. However, it remains to establish which features have made reaching to sound more effective as compared to naming. In the present study, we introduced a further condition in which the hand is the effector providing the response, but without it reaching toward the space occupied by the target source: the pointing condition. We tested three groups of participants (naming, pointing, and reaching groups) each while performing a sound localization task in normal and altered listening situations (i.e. mild-moderate unilateral hearing loss) simulated through auditory virtual reality technology. The experiment comprised four blocks: during the first and the last block, participants were tested in normal listening condition, while during the second and the third in altered listening condition. We measured their performance, their subjective judgments (e.g. effort), and their head-related behavior (through kinematic tracking). First, people’s performance decreased when exposed to asymmetrical mild-moderate hearing impairment, more specifically on the ipsilateral side and for the pointing group. Second, we documented that all groups decreased their localization errors across altered listening blocks, but the extent of this reduction was higher for reaching and pointing as compared to the naming group. Crucially, the reaching group leads to a greater error reduction for the side where the listening alteration was applied. Furthermore, we documented that, across blocks, reaching and pointing groups increased the implementation of head motor behavior during the task (i.e., they increased approaching head movements toward the space of the sound) more than naming. Third, while performance in the unaltered blocks (first and last) was comparable, only the reaching group continued to exhibit a head behavior similar to those developed during the altered blocks (second and third), corroborating the previous observed relationship between the reaching to sounds task and head movements. In conclusion, this study further demonstrated the effectiveness of reaching to sounds as compared to pointing and naming in the learning processes. This effect could be related both to the process of implementing goal-directed motor actions and to the role of reaching actions in fostering the implementation of head-related motor strategies.

Objectives: Here we investigate Hepatitis D virus (HDV)-prevalence in Italy and its fluctuations over time and we provide an extensive characterization of HDV-infected patients. Methods: The rate of HDV seroprevalence and HDV chronicity was assessed in 1579 hepatitis B surface antigen (HBsAg)+ patients collected from 2005 to 2022 in Central Italy. Results: In total, 45.3% of HBsAg+ patients received HDV screening with an increasing temporal trend: 15.6% (2005-2010), 45.0% (2011-2014), 49.4% (2015-2018), 71.8% (2019-2022). By multivariable model, factors correlated with the lack of HDV screening were alanine-aminotransferase (ALT) less than two times of upper limit of normality (

Inductive proximity sensors are relevant in position-sensing applications in many industries but, in order to be used in harsh industrial environments, they need to be immune to electromagnetic interference (EMI). The use of conventional filters to mitigate these perturbations often compromises signal bandwidth, ranging from 100 Hz to 1.6 kHz. We have exploited recent advances in the field of artificial intelligence (AI) to study the ability of neural networks (NNs) to automatically filter out EMI features. This study offers an analysis and comparison of possible NN models (a 1D convolutional NN, a recurrent NN, and a hybrid convolutional and recurrent approach) for denoising EMI-perturbed signals and proposes a final model, which is based on gated recurrent unit (GRU) layers. This network is compressed and optimised to meet memory requirements, so that in future developments it could be implemented in application-specific integrated circuits (ASICs) for inductive sensors. The final RNN manages to reduce noise by 70% (MSEred) while occupying 2 KB of memory.

Background and Objectives: We sought to investigate whether the 2012 Briganti nomogram may represent a potential prognostic factor of prostate cancer (PCa) progression after surgical treatment beyond European Association of Urology (EAU) risk categories. Materials and Methods: From January 2013 to December 2021, data on PCa patients treated with robot-assisted radical prostatectomy at a single tertiary referral center were extracted. The 2012 version of the Briganti nomogram assessing the risk of pelvic lymph node invasion was used. Here, the nomogram score was evaluated both as a continuous and a categorical variable. The association between variables and disease progression after surgery was evaluated through Cox regression models. Results: Overall, 1047 patients were identified. According to the EAU classification system, 297 (28.4%) patients were low-risk, 527 (50.3%) intermediate-risk, and 223 (21.3%) high-risk. The median (interquartile range) 2012 Briganti nomogram score within the investigated population was 3% (2–8%). Median (95% Confidence Interval [CI]) follow-up was 95 (91.9–112.4) months. Disease progression occurred in 237 (22.6%) patients, who were more likely to have an increasing 2012 Briganti nomogram score (Hazard Ratio [HR]: 1.03; 95%CI: 1.01–1.81; p = 0.015), independently of unfavorable issues at clinical presentation. Moreover, the nomogram score stratified according to tertiles (p < 0.001) up to the third (HR: 3.26; 95%CI: 2.26–4.72; p < 0.001) tertile. Conclusions: Beyond EAU risk categories, the 2012 Briganti nomogram represented an independent predictor of PCa progression after surgery. Likewise, as the nomogram score increased so patients were more likely to experience disease progression. Accordingly, it may allow further stratification of patients within each risk category to modulate appropriate treatment paradigms.

Rowing is a complex sport where technique can significantly impact performance. A better understanding of the rowers’ technique and neuromuscular activations during scull rowing, along with their impact on rowing performance, could greatly help trainers and athletes. Twelve male rowers were asked to row at their competitive stroke rate, and we collected data describing neuromuscular activations, trunk and arm kinematics, as well as technical determinants such as oar angles and angle asymmetries. We fitted linear mixed-effect models to investigate the effects of these variables on power production and boat speed. A larger effective angle had the greatest positive effect on power output, and slip angles had the largest negative effects. Increased elbow flexion at catch had the greatest negative effect on speed. Angle asymmetries affected neither power nor speed. Increased upper limb neuromuscular activity during the first and third quarters of the drive phase helped reduce slip angles, thus increasing performance. Power and speed were influenced similarly by the predictor variables. Still, they showed subtle differences, indicating that the strategies to maximize power production might not be the best ones to also achieve the maximum speed.

Frontal variant Alzheimer's disease (AD) manifests with either behavioral or dysexecutive syndromes. Recent efforts to gain a deeper understanding of this phenotype have led to a re-conceptualization of frontal AD. Behavioral (bAD) and dysexecutive (dAD) phenotypes could be considered subtypes, as suggested by both clinical and neuroimaging studies. In this review, we focused on imaging studies to highlight specific brain patterns in these two uncommon clinical AD phenotypes. Although studies did not compare directly these two variants, a common epicenter located in the frontal cortex could be inferred. On the contrary, 18F-FDG-PET findings suggested differing metabolic patterns, with bAD showing specific involvement of frontal regions and dAD exhibiting widespread alterations. Structural MRI findings confirmed this pattern, suggesting that degeneration might involve neural circuits associated with behavioral control in bAD and attentional networks in dAD. Furthermore, molecular imaging has identified different neocortical tau distribution in bAD and dAD patients compared to typical AD patients, although the distribution is remarkably heterogeneous. In contrast, Aβ deposition patterns are less differentiated between these atypical variants and typical AD. Although preliminary, these findings underscore the complexity of AD frontal phenotypes and suggest that they represent distinct entities. Further research is essential to refine our understanding of the pathophysiological mechanisms in frontal AD.

Summary: Using 13C6 glucose labeling coupled to gas chromatography-mass spectrometry and 2D 1H-13C heteronuclear single quantum coherence NMR spectroscopy, we have obtained a comparative high-resolution map of glucose fate underpinning β cell function. In both mouse and human islets, the contribution of glucose to the tricarboxylic acid (TCA) cycle is similar. Pyruvate fueling of the TCA cycle is primarily mediated by the activity of pyruvate dehydrogenase, with lower flux through pyruvate carboxylase. While the conversion of pyruvate to lactate by lactate dehydrogenase (LDH) can be detected in islets of both species, lactate accumulation is 6-fold higher in human islets. Human islets express LDH, with low-moderate LDHA expression and β cell-specific LDHB expression. LDHB inhibition amplifies LDHA-dependent lactate generation in mouse and human β cells and increases basal insulin release. Lastly, cis-instrument Mendelian randomization shows that low LDHB expression levels correlate with elevated fasting insulin in humans. Thus, LDHB limits lactate generation in β cells to maintain appropriate insulin release.

Calorie content and hunger are two fundamental cues acting upon the processing of visually presented food items. However, whether and to which extent they affect visual awareness is still an open question. Here, high- and low-calorie food images administered to hungry or satiated participants were confronted in a breaking-Continuous Flash Suppression paradigm (Experiment 1), measuring the time required to access to visual awareness, and in a Binocular Rivalry paradigm (Experiment 2), quantifying the dominance time in visual awareness. Experiment 1 showed that high-calorie food accessed faster visual awareness, but mostly in satiated participants. Experiment 2 indicated that high-calorie food dominated longer visual awareness, regardless the degree of hunger. We argued that the unconscious advantage (Experiment 1) would represent a default state of the visual system towards highest-energy nutrients, yet the advantage is lost in hunger so to be tuned towards an increased need for any nutritional category. On the other hand, the conscious advantage of high-calorie food (Experiment 2) would represent a conscious perceptual and attentional bias towards highest energy-dense food useful for the actual detection of these stimuli in the environment.

IntroductionProinflammatory cytokines are implicated in pancreatic ß cell failure in type 1 and type 2 diabetes and are known to stimulate alternative RNA splicing and the expression of nonsense-mediated RNA decay (NMD) components. Here, we investigate whether cytokines regulate NMD activity and identify transcript isoforms targeted in ß cells.MethodsA luciferase-based NMD reporter transiently expressed in rat INS1(832/13), human-derived EndoC-ßH3, or dispersed human islet cells is used to examine the effect of proinflammatory cytokines (Cyt) on NMD activity. The gain- or loss-of-function of two key NMD components, UPF3B and UPF2, is used to reveal the effect of cytokines on cell viability and function. RNA-sequencing and siRNA-mediated silencing are deployed using standard techniques.ResultsCyt attenuate NMD activity in insulin-producing cell lines and primary human ß cells. These effects are found to involve ER stress and are associated with the downregulation of UPF3B. Increases or decreases in NMD activity achieved by UPF3B overexpression (OE) or UPF2 silencing raise or lower Cyt-induced cell death, respectively, in EndoC-ßH3 cells and are associated with decreased or increased insulin content, respectively. No effects of these manipulations are observed on glucose-stimulated insulin secretion. Transcriptomic analysis reveals that Cyt increases alternative splicing (AS)-induced exon skipping in the transcript isoforms, and this is potentiated by UPF2 silencing. Gene enrichment analysis identifies transcripts regulated by UPF2 silencing whose proteins are localized and/or functional in the extracellular matrix (ECM), including the serine protease inhibitor SERPINA1/α-1-antitrypsin, whose silencing sensitizes ß-cells to Cyt cytotoxicity. Cytokines suppress NMD activity via UPR signaling, potentially serving as a protective response against Cyt-induced NMD component expression.ConclusionOur findings highlight the central importance of RNA turnover in ß cell responses to inflammatory stress.

Summary: Obesity is characterized by the accumulation of T cells in insulin-sensitive tissues, including the visceral adipose tissue (VAT), that can interfere with the insulin signaling pathway eventually leading to insulin resistance (IR) and type 2 diabetes. Here, we found that PD-1+CD4 conventional T (Tconv) cells, endowed with a transcriptomic and functional profile of partially dysfunctional cells, are diminished in VAT of obese patients with dysglycemia (OB-Dys), without a concomitant increase in apoptosis. These cells showed enhanced capacity to recirculate into the bloodstream and had a non-restricted TCRβ repertoire divergent from that of normoglycemic obese and lean individuals. PD-1+CD4 Tconv were reduced in the circulation of OB-Dys, exhibited an altered migration potential, and were detected in the liver of patients with non-alcoholic steatohepatitis. The findings suggest a potential role for partially dysfunctional PD-1+CD4 Tconv cells as inter-organ mediators of IR in obese patients with dysglycemic.

In this contribution, new data concerning the distribution of vascular flora alien to Italy are presented. It includes new records and status changes from casual to naturalized for Italy or for Italian administrative regions. Nomenclatural and distribution updates, published elsewhere, and corrections are provided as supplementary material.

The inventory of the taxa collected in 2022 during the annual field trip of the Working Group for Floristics, Systematics and Evolution of the Italian Botanical Society is reported. The field trip was held from 19th to 22th April in the islands of Lipari and Panarea (Aeolian Islands, Sicilia). Overall, 1,664 herbarium specimens were deposited in public and private herbaria. The flora documented for the studied area amounts to 386 specific and subspecific taxa, belonging to 241 genera and 74 families. Centaurea aeolica, Helichrysum litoreum (Asteraceae), and Dianthus rupicola subsp. aeolicus (Caryophyllaceae) were the only three Italian endemics found in the study area, whereas 48 alien taxa were recorded. Dimorphotheca ecklonis (Asteraceae), Nassella tenuissima (Poaceae), Solanum torvum (Solanaceae), and Viola wittrockiana (Violaceae) are casual alien species new to Sicilia, whereas Oenothera odorata (Onagraceae) is a new naturalized alien species for the Italian vascular flora.

Abstract Introduction Polymorphonuclear cell influx into the interstitial and bronchoalveolar spaces is a cardinal feature of severe coronavirus disease 2019 (COVID-19), principally mediated by interleukin-8 (IL-8). We sought to determine whether reparixin, a novel IL-8 pathway inhibitor, could reduce disease progression in patients hospitalized with severe COVID-19 pneumonia. Methods In this Phase 3, randomized, double-blind, placebo-controlled, multicenter study, hospitalized adult patients with severe COVID-19 pneumonia were randomized 2:1 to receive oral reparixin 1200 mg three times daily or placebo for up to 21 days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure at Day 28, with key secondary endpoints being the proportion of patients free of respiratory failure at Day 60, incidence of intensive care unit (ICU) admission by Day 28 and time to recovery by Day 28. Results Of 279 patients randomized, 182 received at least one dose of reparixin and 88 received placebo. The proportion of patients alive and free of respiratory failure at Day 28 was similar in the two groups {83.5% versus 80.7%; odds ratio 1.63 [95% confidence interval (CI) 0.75, 3.51]; p = 0.216}. There were no statistically significant differences in the key secondary endpoints, but a numerically higher proportion of patients in the reparixin group were alive and free of respiratory failure at Day 60 (88.7% versus 84.6%; p = 0.195), fewer required ICU admissions by Day 28 (15.8% versus 21.7%; p = 0.168), and a higher proportion recovered by Day 28 compared with placebo (81.6% versus 74.9%; p = 0.167). Fewer patients experienced adverse events with reparixin than placebo (45.6% versus 54.5%), most mild or moderate intensity and not related to study treatment. Conclusions This trial did not meet the primary efficacy endpoints, yet reparixin showed a trend toward limiting disease progression as an add-on therapy in COVID-19 severe pneumonia and was well tolerated. Trial Registration ClinicalTrials.gov: NCT04878055, EudraCT: 2020-005919-51. Graphical Abstract

Abstract Objective Examining the size and reactivity of the pupils of traumatic brain injury coma patients is fundamental in the Neuro‐intensive care unit (ICU). Pupil parameters on admission predict long‐term clinical outcomes. However, little is known about the dynamics of pupillary parameters and their potential value for outcome prediction. Methods This study applied a time‐course analysis of pupillary signals (size and photo‐reactivity) in acute traumatic brain injury coma patients (n = 20) to predict outcome at 6 months. Results The time course of pupillary signals was informative in discriminating favorable (F) versus unfavorable (U) outcomes, with the highest correlation within the 1st week notwithstanding pharmacological sedation. Patients with favorable outcome at 6 months showed more consistent in time isochoric and photo‐reactive pupils. In contrast, patients with an unfavorable outcome showed more variable measures that tended to stabilize toward pathological values. Interpretation Time‐dependent tracking of pupils' size and reactivity is a promising application for ICU monitoring and long‐term prognosis. These findings support the usefulness of automatic tools for the dynamic, quantitative, and objective measurements of pupils.

Abstract Spatial perspective and identity of visual bodily stimuli are two key cues for the self-other distinction. However, how they emerge into visual awareness is largely unknown. Here, self- or other-hands presented in first- or third-person perspective were compared in a breaking-Continuous Flash Suppression paradigm (Experiment 1) measuring the time the stimuli need to access visual awareness, and in a Binocular Rivalry paradigm (Experiment 2), measuring predominance in perceptual awareness. Results showed that, irrespectively of identity, first-person perspective speeded up the access, whereas the third-person one increased the dominance. We suggest that the effect of first-person perspective represents an unconscious prioritization of an egocentric body coding important for visuomotor control. On the other hand, the effect of third-person perspective indicates a conscious advantage of an allocentric body representation fundamental for detecting the presence of another intentional agent. Summarizing, the emergence of self-other distinction into visual awareness would strongly depend on the interplay between spatial perspectives, with an inverse prioritization before and after conscious perception. On the other hand, identity features might rely on post-perceptual processes.

Estimating global properties of many-body quantum systems such as entropy or bipartite entanglement is a notoriously difficult task, typically requiring a number of measurements or classical postprocessing resources growing exponentially in the system size. In this work, we address the problem of estimating global entropies and mixed-state entanglement via partial-transposed (PT) moments and show that efficient estimation strategies exist under the assumption that all the spatial correlation lengths are finite. Focusing on one-dimensional systems, we identify a set of approximate factorization conditions (AFCs) on the system density matrix, which allow us to reconstruct entropies and PT moments from information on local subsystems. This identification yields a simple and efficient strategy for entropy and entanglement estimation. Our method could be implemented in different ways, depending on how information on local subsystems is extracted. Focusing on randomized measurements providing a practical and common measurement scheme, we prove that our protocol requires only polynomially many measurements and postprocessing operations, assuming that the state to be measured satisfies the AFCs. We prove that the AFCs hold for finite-depth quantum-circuit states and translation-invariant matrix-product density operators and provide numerical evidence that they are satisfied in more general, physically interesting cases, including thermal states of local Hamiltonians. We argue that our method could be practically useful to detect bipartite mixed-state entanglement for large numbers of qubits available in today’s quantum platforms.

Wild edible plants, botanically defined as phytoalimurgical species, have historically been a useful source of food to cope with recurrent famines and poor farming conditions. If properly identified, harvested, transformed and promoted, alimurgical plants could further enhance the wellbeing of rural and urban communities and the multifunctional productivity of agriculture. The research aimed to survey alimurgical species in a wetland, map their location, detect their spatial richness, and develop a monitoring plan for ongoing vegetation succession. The study area is the King’s Lagoon, a wetland that has recently undergone a radical restoration of its natural layout. A satellite image was used to create a land cover map and interpret the relationship between plant species and land cover. The survey provided a snapshot of the wetland’s current ecosystem status and used botanical analysis and ecological indices to investigate biodiversity levels. The alpha, beta and gamma levels of biodiversity were explored and interpreted through the statistical processing of a comprehensive dataset of species occurrence and abundance, together with the calculation of Shannon’s, Simpson’s and Jaccard’s indices. It was observed that biodiversity in the wetland is developing gradually following restoration and is expected to increase over time as successional stages take hold. Biodiversity is more pronounced along the banks of the canals and watercourses connecting the basins and open ponds, while it is less pronounced in areas where the soil has been disturbed by previous excavations. Salicornia spp., Beta vulgaris subsp. maritima and Suaeda vera were identified as the most common and interesting species found in the study area. The potential for cultivation of some of the halophyte species that were monitored was also highlighted, with particular reference to the selection of the most commercially interesting species, the best species associations and intercropping practices in a wetland context, which must always prioritize the conservation of wild biodiversity. The spring surveys should be repeated in the coming years in order to accurately trace the dynamics of the ecological succession of this particular ecosystem, once it has returned to its natural development.

Abstract Despite the importance of bacteria in aquatic ecosystems and their predictable diversity patterns across space and time, biomonitoring tools for status assessment relying on these organisms are widely lacking. This is partly due to insufficient data and models to identify reliable microbial predictors. Here, we show metabarcoding in combination with multivariate statistics and machine learning allows to identify bacterial bioindicators for existing biological status classification systems. Bacterial beta-diversity dynamics follow environmental gradients and the observed associations highlight potential bioindicators for ecological outcomes. Spatio-temporal links spanning the microbial communities along the river allow accurate prediction of downstream biological status from upstream information. Network analysis on amplicon sequence veariants identify as good indicators genera Fluviicola, Acinetobacter, Flavobacterium, and Rhodoluna, and reveal informational redundancy among taxa, which coincides with taxonomic relatedness. The redundancy among bacterial bioindicators reveals mutually exclusive taxa, which allow accurate biological status modeling using as few as 2–3 amplicon sequence variants. As such our models show that using a few bacterial amplicon sequence variants from globally distributed genera allows for biological status assessment along river systems.

Abstract Background The pancreatic microenvironment has a defensive role against cancer but it can acquire tumor-promoting properties triggered by multiple mechanisms including alterations in the equilibrium between proteases and their inhibitors. The identification of proteolytic events, targets and pathways would set the basis for the design of new therapeutic approaches. Methods and results Here we demonstrate that spheroids isolated from human and murine healthy pancreas and co-transplanted orthotopically with pancreatic ductal adenocarcinoma (PDAC) in mouse pancreas inhibited tumor growth. The effect was mediated by trypsin-generated fibronectin (FN) fragments released by pancreatic spheroids. Tumor inhibition was observed also in a model of acute pancreatitis associated with trypsin activation. Mass spectrometry proteomic analysis of fragments and mAb against different FN epitopes identified the FN type III domain as responsible for the activity. By inhibiting integrin α5β1, FAK and FGFR1 signaling, the fragments induced tumor cell detachment and reduced cell proliferation. Consistent with the mutual relationship between the two pathways, FGF2 restored both FGFR1 and FAK signaling and promoted PDAC cell adhesion and proliferation. FAK and FGFR inhibitors additively inhibited PDAC growth in vitro and in orthotopic in vivo models. Conclusions This study identifies a novel role for pancreatic trypsin and fibronectin cleavage as a mechanism of protection against cancer by the pancreatic microenvironment. The finding of a FAK-FGFR cross-talk in PDAC support the combination of FAK and FGFR inhibitors for PDAC treatment to emulate the protective effect of the normal pancreas against cancer.

Abstract Interpersonal touch is intrinsically reciprocal since it entails a person promoting and another receiving the touch. While several studies have investigated the beneficial effects of receiving affective touch, the affective experience of caressing another individual remains largely unknown. Here, we investigated the hedonic and autonomic responses (skin conductance and heart rate) in the person promoting affective touch. We also examined whether interpersonal relationship, gender, and eye contact modulate these responses. As expected, caressing the partner was perceived as more pleasant than caressing a stranger, especially if the affective touch occurred together with mutual eye contact. Promoting affective touch to the partner also resulted in a decrease of both autonomic responses and anxiety levels, suggesting the occurrence of a calming effect. Additionally, these effects were more pronounced in females compared to males, indicating that hedonic and autonomic aspects of affective touch are modulated by both social relationship and gender. These findings show for the first time that caressing a beloved one is not only pleasant but also reduces autonomic responses and anxiety in the person promoting the touch. This might suggest that affective touch has an instrumental role for romantic partners in promoting and reinforcing their affective bonding.

Scientific research is the main driver to push forward and disseminate botanical knowledge. Despite many institutions having this fundamental aim as a core activity, many of them do not have a complete set of facilities, expertise, staff, and resources to cover all the steps involved in the study, management, conservation, and popularization of plant diversity. Accordingly, we propose a workflow formalizing the cooperation between a botanical garden and a botanical research center, focused on the study of plant endemic species. Specifically, the cooperation was implemented between the PLANTSEED Lab of the Department of Biology and the Botanic Garden and Museum of the University of Pisa. We present seven representative case studies (Armeria arenaria complex, Bellevalia webbiana, Crocus etruscus and C. ilvensis, Dianthus virgineus complex, Pulmonaria hirta complex, and Santolina chamaecyparissus complex) to disentangle the approaches and opportunities arising from cooperative approaches, from laboratory to cultivation. We analyze the emerging properties derived from this synergistic cooperation by promoting open research questions and answering them using a comprehensive approach to improving endemic plant species research, conservation, and popularization in the botanical garden. In this manuscript, we show how a cooperative approach between heterogeneous botanical institutions can constitute an effective and easy-to-implement approach to achieve the goals of each partner involved in the cooperation.

Abstract The study of international migration and responses to it has experienced rapid growth in the last three decades: an institutionalisation of migration studies. This paper identifies and specifies infrastructural and semantic elements of institutionalisation by establishing a global Directory of Migration Research Institutions identifying 282 institutes focused on migration research that were operative between 1945 and 2020. We observe a clear geographical concentration in the Americas and Europe and find that most institutes are in countries with higher economic development (GDP) and net immigration (not emigration). Using this evidence, we suggest that the institutionalisation of migration studies is driven by concerns and ideas produced in high-income ‘destination’ countries. We thus show that uneven knowledge production in migration studies is not only caused by exclusive categories, language, or journal policies, but also by a structural problem at an earlier stage: because of fewer resources invested in the creation of institutionalised academic knowledge structures, lower income countries have fewer possibilities to shape the semantic features of the field of migration studies, by which we mean the identification of subjects of interest, concepts, narratives, and priorities.

Abstract INTRODUCTION We investigated in vivo the microstructural integrity of the pathway connecting the locus coeruleus to the transentorhinal cortex (LC‐TEC) in patients with Alzheimer's disease (AD) and frontotemporal dementia (FTD). METHODS Diffusion‐weighted MRI scans were collected for 21 AD, 20 behavioral variants of FTD (bvFTD), and 20 controls. Fractional anisotropy (FA), mean, axial, and radial diffusivities (MD, AxD, RD) were computed in the LC‐TEC pathway using a normative atlas. Atrophy was assessed using cortical thickness and correlated with microstructural measures. RESULTS We found (i) higher RD in AD than controls; (ii) higher MD, RD, and AxD, and lower FA in bvFTD than controls and AD; and (iii) a negative association between LC‐TEC MD, RD, and AxD, and entorhinal cortex (EC) thickness in bvFTD (all p

Introduction: Rhythm control strategy in paroxysmal atrial fibrillation (AF) can be performed with antiarrhythmic drugs (AAD) or catheter ablation (CA). Nevertheless, a clear overview of the percentage of freedom from AF over time and complications is lacking. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) comparing CA versus AAD. Methods: We searched databases up to 5 May 2023 for RCTs focusing on CA versus AAD. The study endpoints were atrial tachyarrhythmia (AT) recurrence, progression to persistent AF, overall complications, stroke/TIA, bleedings, heart failure (HF) hospitalization and all-cause mortality. Results: Twelve RCTs enrolling 2393 patients were included. CA showed a significantly lower AT recurrence rate at one year [27.4 % vs 56.3 %; RR: 0.45; p