University of Siena

Musicogenic epilepsy (ME) is characterized by seizures triggered by music. The epileptogenic focus in this rare reflex epilepsy is often in the temporal lobe, although the precise localization is still unclear. A correlation between ME and the presence of GAD65 antibodies indicates a potential immunological pathogenic mechanism. We evaluated a 32‐year‐old woman with drug‐resistant temporal lobe epilepsy as a candidate for epilepsy surgery. In the absence of clear clinical lateralizing signs, video‐EEG monitoring with intracranial electrodes inserted through the foramen ovale was performed to record from the amygdalo‐hippocampal regions. The foramen ovale electrodes revealed bilateral, asynchronous, and independent seizure onsets in the mesial temporal regions triggered by music. Testing for GAD65 antibodies confirmed high‐titer positivity. The efficacy of epilepsy surgery in antiGAD65‐positive ME patients remains limited. We highlight the use of semi‐invasive recording with foramen ovale electrodes in ME, as it can reveal bilateral seizures of mesial origin that contraindicate surgery and support the consideration of immunotherapy options. Plain Language Summary Musicogenic epilepsy is a type of epilepsy in which music triggers seizures. Our understanding of its origin and cause is still limited. We assessed a patient with music‐induced seizures to see if surgery was an option. Since noninvasive tests before surgery were not clear, we used a minimally invasive method with electrodes inserted through a small opening in the skull called the foramen ovale to record the seizures. Thus, we found that the seizures started independently from both temporal lobes, contraindicating epilepsy surgery. We also found high levels of GAD65 antibodies indicating an immunological pathogenic mechanism.

Purpose: High-accuracy diagnostic screening tests for Mycobacterium tuberculosis (MTB) infection are required, primarily to detect patients with latent infections (LTBIs) in order to avoid their progression to active tuberculosis disease. The performance of the novel IGRA LIOFeron®TB/LTBI was evaluated in children. The originality of this test is the new MTB antigen contained (l-alanine dehydrogenase), identified as a tool to differentiate active TB from LTBI infection. Methods: From March 2022 to November 2023, a population of 90 children was enrolled and grouped into healthy, active TB or LTBI individuals, based on diagnostic guidelines. The blood of all these participants was tested with LIOFeron®TB/LTBI assay in comparison to diagnosis, as gold standard, and to the current used IGRA QuantiFERON®-TB Gold Plus. Results: The two assays demonstrated an excellent concordance of their results with patients’ diagnosis of MTB infection. The performance of LIOFeron®TB/LTBI assay in terms of accuracy of MTB infection diagnosis was high at ROC analysis (AUC = 0.997), and the test showed 100% sensitivity in LTBI detection. The QuantiFERON®-TB Gold Plus sensitivity for LTBI detection was 85.7%. Conclusions: Based on the obtained results, the LIOFeron®TB/LTBI assay appears to be a promising test for TB and LTBI screening among paediatric patients. What is known: • The detection of LTBI in children, exposed to MTB infections, followed by appropriate treatment, has a pivotal role in reducing tuberculosis burden. • IGRA tests are easy-to-use methods for helping large TB screening in paediatrics. What is new: • The LIOFeron®TB/LTBI performance evaluation showed 100% of sensitivity in the detection of LTBI patients. • The LIOFeron®TB/LTBI assay might be useful for the detection of LTBI and active tuberculosis paediatric patients.

Objectives To assess the lung involvement in patients with Still’s disease, an inflammatory disease assessing both children and adults. To exploit possible associated factors for parenchymal lung involvement in these patients. Methods A multicentre observational study was arranged assessing consecutive patients with Still’s disease characterized by the lung involvement among those included in the AIDA (AutoInflammatory Disease Alliance) Network Still’s Disease Registry. Still’s disease-lung involvement was defined by the presence of pleuritis, parenchymal features, acute respiratory distress syndrome (ARDS), and/or pulmonary arterial hypertension. Results In total, 90 patients with Still’s disease and lung involvement were assessed (mean age 36.3 ± 17.8 years, 35.6% male sex). Among them, 13.3% of patients were paediatrics. These patients with lung involvement mainly showed pleuritis in 72.2% of cases, parenchymal features in 34.4%, ARDS in 9.5%, and pulmonary arterial hypertension in 2.3%. After that we focused on patients characterised by parenchymal lung involvement, which is an emergent issue of clinical concern. These patients with parenchymal lung disease were significantly characterized by sore throat, pericarditis, and higher values of systemic score than others. Finally, the administration of both IL-1 or IL-6 inhibitors was not associated with the presence of parenchymal lung involvement. Conclusion The clinical characteristics of patients with Still’s disease and lung involvement were described in the AIDA network. We also provided a clinical profile of patients with parenchymal lung involvement considering its prognostic relevance. Although providing a clinical landscape of these patients, further studies are needed to fully clarify this issue.

For the first time, spatially explicit representation of classification errors of land use/land cover (LULC) maps is approached from a design-based perspective. Since LULC maps are typically derived from non-probabilistic training samples, these maps, like the true LULC map, are fixed in a design-based scenario so that the error maps achieved by comparing the satellite-based and true maps are fixed. Based on a probabilistic sample of locations where the true or “reference” class is obtained (i.e., the “reference” class is considered the best representation of the true class), errors can be assessed at these sample locations by comparing the map classes to the reference classes. Then, the presence or absence of errors is interpolated across the entire survey area using the nearest neighbour technique. Under very common sampling schemes used to collect reference sample data, the interpolated error maps are design consistent. A simulation study confirms the design consistency of the interpolated error maps, which converge to the true error map as the reference sample size increases. The U.S. land cover map from the LCMAP program and the Italian forest/non forest map serve as case studies.

Interspecific interactions are important drivers of population dynamics and species distribution. These relationships can increase niche partitioning between sympatric species, which can differentiate space and time use or modify their feeding strategies. Roe deer Capreolus capreolus and red deer Cervus elaphus are two of the most widespread ungulate species in Europe and show spatial and dietary overlap. However, limited information is available on their interspecific relationships, especially in mountainous areas. In this study we used 5 years of camera trapping data collected in the Stelvio National Park (Central Italian Alps) to investigate spatial and temporal interactions between roe deer and red deer. Analyses were based on 2060 and 9030 roe deer and red deer detections, respectively, collected from July to September, from 2019 to 2023, using 50 camera traps randomly distributed over a 10,000‐ha study area. Spatial interactions were assessed by fitting a single‐season, single‐species occupancy model to calculate the probability of roe deer detection and occupancy as a function of relative red deer abundance and site‐specific environmental covariates. Temporal interactions were obtained by comparing the diel activity patterns of the two species. Results showed no significant effect of red deer relative abundance on the probability of presence of roe deer. Spatial analysis suggested a higher probability of roe deer presence in forested habitats, at lower elevations, and in areas with gentler slopes. Diel activity patterns of roe deer were consistent across sites with higher and lower red deer relative abundance, with moderate to high interspecific overlap, suggesting moderate temporal partitioning and no major support for temporal avoidance of the latter by the former. The high degree of overlap between the two species may be the result of area‐specific ecological conditions, such as the widespread distribution of red deer during the summer period, as well as of the adoption of strategies that favor coexistence.

We study the spectral behavior of (sequences of) matrices resulting from immersed isogeometric discretizations on trimmed geometries. They enjoy an asymptotic spectral distribution, described by a (spectral) symbol, and we discuss some properties of this symbol. In particular, we show that the structure and properties of the symbol are completely analogous to the untrimmed case when a suitable natural restriction of the parametric domain is considered. This spectral knowledge can be exploited to identify potentially fast preconditioners for the considered immersed discretization matrices and we propose a specific CG preconditioner based on the symbol. We also provide numerical experiments that support the correctness of the theoretical results and illustrate the performance of the proposed preconditioner.

Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.5% genomes), and performed systematic reanalysis for 6,447 individuals (3,592 male, 2,855 female) with previously undiagnosed rare diseases from 6,004 families. We established a collaborative, two-level expert review infrastructure that allowed a genetic diagnosis in 506 (8.4%) families. Of 552 disease-causing variants identified, 464 (84.1%) were single-nucleotide variants or short insertions/deletions. These variants were either located in recently published novel disease genes (n = 67), recently reclassified in ClinVar (n = 187) or reclassified by consensus expert decision within Solve-RD (n = 210). Bespoke bioinformatics analyses identified the remaining 15.9% of causative variants (n = 88). Ad hoc expert review, parallel to the systematic reanalysis, diagnosed 249 (4.1%) additional families for an overall diagnostic yield of 12.6%. The infrastructure and collaborative networks set up by Solve-RD can serve as a blueprint for future further scalable international efforts. The resource is open to the global rare-disease community, allowing phenotype, variant and gene queries, as well as genome-wide discoveries.

Objective This study aims to evaluate the impact of prompt construction on the quality of artificial intelligence (AI) chatbot responses in the context of head and neck surgery. Study Design Observational and evaluative study. Setting An international collaboration involving 16 researchers from 11 European centers specializing in head and neck surgery. Methods A total of 24 questions, divided into clinical scenarios, theoretical questions, and patient inquiries, were developed. These questions were entered into ChatGPT‐4o both with and without the use of a structured prompt format, known as SMART (Seeker, Mission, AI Role, Register, Targeted Question). The AI‐generated responses were evaluated by experienced head and neck surgeons using the Quality Analysis of Medical Artificial Intelligence instrument (QAMAI), which assesses accuracy, clarity, relevance, completeness, source quality, and usefulness. Results The responses generated using the SMART prompt scored significantly higher across all QAMAI dimensions compared to those without contextualized prompts. Median QAMAI scores for SMART prompts were 27.5 (interquartile range [IQR] 25‐29) versus 24 (IQR 21.8‐25) for unstructured prompts (P < .001). Clinical scenarios and patient inquiries showed the most significant improvements, while theoretical questions also benefited, but to a lesser extent. The AI's source quality improved notably with the SMART prompt, particularly in theoretical questions. Conclusion This study suggests that the structured SMART prompt format significantly enhances the quality of AI chatbot responses in head and neck surgery. This approach improves the accuracy, relevance, and completeness of AI‐generated information, underscoring the importance of well‐constructed prompts in clinical applications. Further research is warranted to explore the applicability of SMART prompts across different medical specialties and AI platforms.

A Stenotrophomonas maltophilia strain positive for the bla VIM-1 metallo-beta-lactamase gene and resistant to trimethoprim-sulfamethoxazole was unexpectedly isolated from a surveillance rectal swab. The characterization of the strain revealed carriage of a 91 kb integrative and conjugative element (ICE) harboring several resistance determinants [ sul1 , bla VIM-1 , aac(6')-Ib , aac(6')-31 , qacE ∆ 1 , cld , and merEDAPTR ], closely related with a group of clc -type ICEs widespread among Pseudomonas aeruginosa and other pseudomonads. Results highlighted the possible spreading of similar elements to S. maltophilia , mediating the acquisition of relevant resistances.

The use of biochar and beneficial bacteria as biofertilizers is gaining increasing attention as a means to reduce the reliance on agrochemical inputs in future agriculture. However, the dynamics of introduced bacteria in biochar-amended soils, as well as the additive effects of bacteria and biochar during the early stages of plant growth, are still poorly characterized. First, a synthetic bacterial community was formulated and its ability to survive was assessed in both non-amended and biochar-amended soils. Secondly, both the individual and combined effects of biochar (applied at 10% (w: w)) and a consortium of five bacteria (Bacillus sp. strain B1, Bacillus velezensis strain Bv1, Bacillus pumilus strain Bp1, Bacillus licheniformis sp. strain Bl1 and Priestia megaterium strain Pm1) isolated from a bio-fertilizer were examined on various biometric and physiological traits of young tomato (Solanum lycopersicum L. var. Principe borghese) plants. At the seedling stage, the sole application of bacteria increased hypocotyl length by 25%, but decreased radicle length compared to non-treated soils. At the plantlet stage, bacteria alone further increased both shoot length by and leaf surface area by 13% and 22%, respectively, but decreased leaf chlorophyll content. On the other hand, co-application of biochar and bacteria partially restored leaf chlorophyll content to control levels, and showed additive effects improving the fresh and dry weight of aboveground tissues by ~ 30% compared to untreated soils. Biochar amendment decreased leaf N content both in the presence and absence of bacteria, suggesting a possible N immobilization in biochar particles which could reduce its availability for the plant. These results point biochar as a suitable material for the survival and viability of synthetic bacterial communities, and show that biochar and the tested inoculum can additively improve key attributes in young tomato plants.

Introduction/Objective Schizophrenia with substance use disorder is a complex clinical condition that may increase treatment resistance. Cannabis use disorder is frequently associated with psychosis and the causal link has still to be defined. Partial D2/3 agonists may ensure limbic dopamine release normalization while avoiding reduced frontocortical dopamine release, which would contribute to negative symptoms. We aimed to observe the clinical course of patients with schizophrenia comorbid with cannabis use disorder while being treated with oral or long-acting injectable D2/3 partial agonists. Methods We observed 96 young adults with schizophrenia/schizoaffective disorder comorbid with cannabis use disorder during 18 months of treatment with aripiprazole long-acting injectable or oral aripiprazole or brexpiprazole. The assessment comprised Clinical Global Impressions-Severity, Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, Barratt Impulsiveness Scale, and Visual Analog Scale for Craving. Results Included were 17 women and 79 men (mean age = 26.89 ± 4.74 years). The sample responded favorably to treatment as assessed by all clinical scales, save for the impulsiveness scale which showed no significant change. The four treatment samples responded well without differences, but employing a general linear model, long-acting injectable aripiprazole and brexpiprazole were better and similar on all clinical and craving scales compared to oral aripiprazole and to other antipsychotics. Long-acting injectable aripiprazole fared better than brexpiprazole on general psychopathology, negative symptoms, and craving, while the reverse was true for global severity. However, the sample size imbalance did not allow for drawing strong conclusions. We found no significant treatment resistance in our 96-patient sample. Conclusion Partial D2/3 agonists may treat comorbid schizophrenia/schizoaffective disorder and cannabis use disorder, improving the symptoms of both disorders and substance craving.

Purpose Intravesical (i) immunotherapy with Bacillus Calmette–Guérin (BCG) is the recommended treatment for patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) after complete tumor resection. Discontinuation or suspension of this therapy is often due to local side effects. Aim of the study was to evaluate the efficacy and safety of sequential intravesical instillations of combined hyaluronic acid (HA) and chondroitin sulfate (CS) in reducing local BCG toxicity and urinary symptoms. Methods This was a prospective, multicentric study. Patients underwent BCG intravesical administration after Transurethral Resection of Bladder Tumor (TURBT) for intermediate/high-risk NMIBC. Patients underwent to HA + CS instillations after every (i) BCG (Group A) were compared with a control group (Group B) that included patient underwent only to BCG instillations, during the maintenance period. 3-day voiding diary, the International Prostate Symptom Score (IPSS), IPSS quality-of-life index (IPSS-QoL), and VAS score (to evaluate bladder pain) were evaluated at baseline and at 1-, 3-, and 6-month follow- up. Results One hundred-eighteen patients were included (Group A: 63 patients, Group B: 55 patients). Mean value of IPSS, IPSS-QoL, and VAS score has significantly increase in Group A at 1-, 3-, and 6-month follow-up (p < 0.00). Group A showed also a significant improvement about irritative lower urinary symptoms (LUTS), which was maintained in the 6-month follow-up, as opposed to Group B that demonstrated a worsening in urinary symptoms during all follow-up (p < 0.00). No local or major side effects were reported during or after treatment. Conclusion This study demonstrated that adding (i) HA + CS significantly reduces storage symptoms, pelvic pain, and day-time urinary frequency in patients with BCG-induced chemical cystitis. This therapy could therefore improve patient adherence, ensuring better adherence and lower drop-out rates.

Background Ethnic nose rhinoplasty is one of the most technically and conceptually challenging plastic surgery procedures due to the complex nasal anatomy and aesthetic preferences. The procedure aims to reshape and project the nasal tip, enhance and strengthen the dorsum, and reduce the size of the alar base, approaching Western beauty standards. It requires tip plasty with significative tip re-projection, leading to a typical asymmetry between the new tip and the nasal bridge, requiring dedicated dorsal reconstruction. The aim of this article is to describe our Free Diced Dorsal Augmentation (FDDA) technique for ethnic nose dorsal reconstruction, sharing our tips and tricks. Methods We retrospectively reviewed patients who underwent FDDA rhinoplasty at our institution in Rio de Janeiro between January 2019 to January 2023, describing our personal technique. The minimum follow-up was 1 year. We assessed procedure related complications, differences in nasal dorsal shape and contour, global symmetry and patients’ satisfaction according to the rhinoplasty outcomes evaluation (ROE) questionnaire. Results 812 patients including 641 primary and 171 secondary rhinoplasties were included in the study. Complications were minimal, only one patient required revision surgery due to nasal contour asymmetries. Aesthetic results were satisfactory, as assessed by the mean postoperative ROE score. Conclusions This study has demonstrated that our FDDA approach, employed on several ethnic noses, is a safe and effective procedure, with high patients’ satisfaction. Meticulous intraoperative diced cartilage preparation together with appropriate postoperative pharmacological and physical prevention of inflammation and edema contribute to our long-lasting results. Level of evidence Level III, therapeutic study.

Structural, architectural, contractile or electrophysiological alterations may occur in the left atrium (LA). The concept of LA cardiopathy is supported by accumulating scientific evidence demonstrating that LA remodeling has become a cornerstone diagnostic and prognostic marker. The structure and the function of LA and left atrial appendage (LAA) which is an integral part of the LA, are key elements for a better understanding of multiple clinical conditions, most notably atrial fibrillation (AF), cardioembolism, heart failure and mitral valve diseases. Rational use of various imaging modalities is key to obtain the relevant clinical information. Accordingly, this clinical consensus document from the European Association of Cardiovascular Imaging, in collaboration with the European Heart Rhythm Association, provides comprehensive, up-to-date, and evidence-based guidance to cardiologists and cardiac imagers for the best practice of imaging LA and LAA for the diagnosis, management and prognostication of the patients

The coronavirus pandemic posed a major challenge to mental health. Existing evidence shows that COVID-19 is related to poor emotional well-being, particularly among women. However, most work on the subject uses single-country samples, limiting the ability to generalize the disparity or explain it as a function of societal variables. The present study investigates the expression of positive and negative emotions during the pandemic as a function of gender and across 24 countries (N = 49,637). Strong gender differences emerged across countries, with women reporting more negative emotions (anxious, depressed, nervous, exhausted) and less positive emotions (calm, content, relaxed, energetic) than men. The gender gap in positive emotions was significantly wider in countries higher in individualism and narrower in countries higher in power distance. For instance, differences in emotions were larger in Western countries high in individualism, such as the USA, the UK, Italy, and France, and smaller in countries with higher collectivism and power distance, such as China, Malaysia, and South Korea, with a few exceptions like Japan and Brazil. These gender differences across countries were not explained by country-level gender inequalities indicators (GGGI and GII). Interestingly, the national severity of the pandemic, an epidemiological factor, reduced gender differences in positive emotions. These results underscore the importance of considering cultural and national factors when assessing gender differences in well-being.

Background Post‐coronavirus disease 19 lung fibrosis (PCLF) shares common immunological abnormalities with idiopathic pulmonary fibrosis (IPF), characterized by an unbalanced cytokine profile being associated with the development of lung fibrosis. The aim of the present study was to analyze and compare the different subsets of CD4‐ and CD8‐T cells, along with specific cytokine expression patterns, in peripheral blood (PB) from patients affected by PCLF and IPF and healthy controls (HCs). Methods One‐hundred patients followed at the Rare Lung Disease Center of Siena University Hospital were enrolled. Eight HCs were recruited. PB samples were collected, and CD4‐ and CD8‐T subsets were analyzed through flow cytometry. Multiplex bead‐based LEGENDplex™ were used for cytokine quantification. Results Higher CD8 percentages were observed in IPF than in HCs and PCLF (p = 0.020 and p = 0.007, respectively). PCLF subgroup showed higher Th‐naïve, Th‐effector, Tc‐naïve, and Tc‐reg percentages than IPF (p < 0.001; p = 0.018; p = 0.005; p = 0.017, respectively). Th‐naïve and Tc‐naïve inversely correlated with Tc‐reg (p < 0.0001, r = −0.61 and p = 0.005, r = −0.39, respectively). Tc‐naïve‐PD1 and Tc‐effector‐PD1 percentages were higher in PCLF than IPF (p < 0.001), while Tfh‐reg and Tfc‐reg were significantly higher in IPF than PCLF (p < 0.001). IL‐4, IL‐2, TNF‐α, and IL‐17A were more expressed in PCLF than IPF (p < 0.001). IL‐8 directly correlated with Tc‐naïve percentages in PCLF (p = 0.018, r = 0.35). Conclusion A variety of immune cells is involved in the development and progression of pulmonary fibrosis confirming an immunological similarity between IPF and PCLF. T‐reg cells play a key role in the worsening of the disease. High cytokine values showed a pro‐fibrotic environment in PCLF patients, suggesting dysregulation of the immune system of these patients. Moreover, the immunological similarity between IPF and PCLF patients suggests that SARS‐CoV2 infection may trigger the activation of biological pathways common with IPF.

Ketamine, a dissociative compound, shows promise in treating mood disorders, including treatment-resistant depression (TRD) and bipolar disorder (BD). Despite its therapeutic potential, the neurophysiological mechanisms underlying ketamine’s effects are not fully understood. This study explored acute neurophysiological changes induced by subanesthetic doses of ketamine in BD patients with depression using electroencephalography (EEG) biomarkers. A cohort of 30 BD (F = 12) inpatients with TRD undergoing ketamine treatment was included in the study. EEG recordings were performed during one of the ketamine infusions with doses ranging from 0.5 to 1 mg/kg, and subjective effects were evaluated using the Clinician-Administered Dissociative States Scale (CADSS). Both rhythmic and arrhythmic features were extrapolated from the EEG signal. Patients who exhibited a clinical response to ketamine treatment within one week were classified as early responders (ER), whereas those who responded later were categorized as late responders (LR). Ketamine reduced low-frequency spectral power density while increasing gamma oscillatory power. Additionally, ketamine flattened the slope of the power spectra, indicating altered scale-free dynamics. Ketamine also increased brain signal entropy, particularly in high-frequency bands. Notably, LR exhibited greater EEG changes compared to ER, suggesting endophenotypic differences in treatment sensitivity. These findings provide valuable insights into the neurophysiological effects of ketamine in BD depression, highlighting the utility of EEG biomarkers for assessing ketamine’s therapeutic mechanisms in real-world clinical settings. Understanding the neural correlates of ketamine response may contribute to personalized treatment approaches and improved management of mood disorders.

This article aims to fill a gap in the current literature on the pragmatics of Latin by proposing a corpus-based analysis of the different words (e.g., ut, uelut, sicut), phrases (e.g., exempli gratia, uerbi causa), and constructions (e.g., ut puta, si dicas) exploited to signal the process of exemplification. The structures and devices that perform this discursive operation are essentially neglected in Latin handbooks of syntax and stylistics, and only sparse comments on individual forms can be found in the lexica and in recent literature. To investigate these understudied issues, we have devised a functional taxonomy centred around the notions of meta-exemplification, canonical exemplification, and para-exemplification. The analysis of the data illustrating the different strategies and signals of exemplification is based on the tenets of historical pragmatics. The discussion focuses on the multiple roles and emergence of example markers in different textual genres, with special attention to technical prose and grammatical treatises, where examples are crucial in describing natural categories and explaining linguistic phenomena. The significance of the results extends beyond the Latin language and sheds light on the origin and development of example markers in general.