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Abstract We determine explicit expressions for the continuous two-sided gravitational wavefunctions in supersymmetric versions of JT gravity, focusing mainly on N $$ \mathcal{N} $$ = 2 JT supergravity. Our approach is based on representation theory of the associated supergroup, for which we determine the relevant mixed parabolic matrix elements that implement asymptotic AdS boundary conditions at the quantum level. We match our expressions with those found by solving the energy-eigenvalue equation [1]. We discuss gravitational applications by computing several amplitudes of interest, and address how our framework can be generalized further.

Abstract In this work, we revisit the end-of-the-world (EOW) brane amplitudes in JT gravity from a BF gauge theoretic perspective. Observing and identifying the correct group theoretic ingredient for a closed EOW brane as a discrete series character, we use the group theory framework as a guide towards formulating the analogous supersymmetric problem. We compute these amplitudes explicitly in the supersymmetric generalizations of JT gravity ( N $$ \mathcal{N} $$ = 1, 2, 4), motivated by the prospective of possibly finite amplitudes. In the process, we develop some of the representation theory of OSp(2|2, ℝ) and PSU(1, 1|2), relevant for the N $$ \mathcal{N} $$ = 2 and N $$ \mathcal{N} $$ = 4 cases.

Abstract Testing density-dependence and path-dependence in long-term population dynamics under differentiated local contexts contributes to delineate the changing role of socioeconomic forces at the base of regional disparities. Despite a millenary settlement history, such issue has been rarely investigated in Europe, and especially in highly divided countries such as those in the Mediterranean region. Using econometric modeling to manage spatial heterogeneity, our study verifies the role of selected drivers of population growth at ten times between 1921 and 2021 in more than 8000 Italian municipalities verifying density-dependent and path-dependent dynamics. Results of global and quantile (spatial) regressions highlight a differential impact of density and (lagged) population growth on demographic dynamics along the urban cycle in Italy. Being weakly significant in the inter-war period (1921–1951), econometric models totalized a high goodness-of-fit in correspondence with compact urbanization (1951–1981). Model’s fit declined in the following decades (1981–2021) reflecting suburbanization and counter-urbanization. Density-dependence and path-dependence were found significant and, respectively, positive or negative, with compact urbanization, and much less intense with suburbanization and counter-urbanization. A spatial econometric investigation of density-dependent and path-dependent mechanisms of population dynamics provided an original explanation of metropolitan cycles, delineating the evolution of socioeconomic (local) systems along the urban-rural gradient.

Abstract We analyze the thermodynamic response near extremality of charged black holes in four-dimensional Einstein-Maxwell theory with a positive cosmological constant. The latter exhibit three different extremal limits, dubbed cold, Nariai and ultracold configurations, with near-horizon geometries AdS2 × S 2, dS2 × S 2, Mink2 × S 2, respectively. For each of these three cases we analyze small deformations away from extremality, and contrast their response. We also construct the effective two-dimensional theory, obtained by dimensional reduction, that captures these features and provide a more detailed analysis of the perturbations around the near-horizon geometry for each case. Our results for the ultracold case in particular show an interesting interplay between the entropy variation and charge variation, realizing a different response in comparison to the other two near-extremal limits.

Sarcoidosis is a multisystem disease, which is diagnosed on a compatible clinical presentation, non-necrotizing granulomatous inflammation in one or more tissue samples, and exclusion of alternative causes of granulomatous disease. Considering its heterogeneity, numerous aspects of the disease remain to be elucidated. In this context, the identification and integration of biomarkers may hold significance in clinical practice, aiding in appropriate selection of patients for targeted clinical trials. This work aims to discuss and analyze how validated biomarkers are currently integrated in disease category definitions. Future studies are mandatory to unravel the diverse contributions of genetics, socioeconomic status, environmental exposures, and other sociodemographic variables to disease severity and phenotypic presentation. Furthermore, the implementation of transcriptomics, multidisciplinary approaches, and consideration of patients’ perspectives, reporting innovative insights, could be pivotal for a better understanding of disease pathogenesis and the optimization of clinical assistance.

Antibiotic resistance due to bacterial biofilm formation is a major global health concern that makes the search for new therapeutic approaches an urgent need. In this context,, trans-resveratrol (RSV), a polyphenolic natural substance, seems to be a good candidate for preventing and eradicating biofilm-associated infections but its mechanism of action is poorly understood. In addition, RSV suffers from low bioavailability and chemical instability in the biological media that make its encapsulation in delivery systems necessary. In this work, the anti-biofilm activity of free RSV was investigated on Staphylococcus aureus and, to highlight the possible mechanism of action, we studied the anti-adherence activity and also the cell wall damage on a MRSA strain. Free RSV activity was compared to that of RSV loaded in liposomes, specifically neutral liposomes (L = DOPC/Cholesterol) and cationic liposomes (LG = DOPC/Chol/GLT1) characterized by a galactosylated amphiphile (GLT1) that promotes the interaction with bacteria. The results indicate that RSV loaded in LG has anti-adherence and anti-biofilm activity higher than free RSV. On the other side, free RSV has a higher bacterial-growth-inhibiting effect than encapsulated RSV and it can damage cell walls by creating pores; however, this effect can not prevent bacteria from growing again. This RSV ability may underlie its bacteriostatic activity.

Abstract Background PAP is an ultra-rare respiratory syndrome characterized by the accumulation of surfactant within the alveoli. Whole lung lavage (WLL) is the current standard of care of PAP, however it is not a standardized procedure and the total amount of fluid used to wash each lung is still debated. Considering ICU hospitalization associated risks, a “mini-WLL” with anticipated manual clapping and reduced total infusion volume and has been proposed in our center. The aim of the study is to retrospectively analyze the efficacy of mini-WLL compared to standard WLL at the Pavia center. Methods 13 autoimmune PAP patients eligible for WLL were included: 7 patients were admitted to mini-WLL (9 L total infusion volume for each lung) and 6 patients underwent standard WLL (14 L of infusion volume). Functional data (VC%, FVC%, TLC%, DLCO%) and alveolar-arterial gradient values (A-aO2) were collected at the baseline and 1, 3, 6, 12, 18 months after the procedure. Results A statistically significant improvement of VC% (p = 0.013, 95%CI 3.49–30.19), FVC% (p = 0.016, 95%CI 3.37–32.09), TLC% (p = 0.001, 95%CI 7.38–30.34) was observed in the mini-WLL group in comparison with the standard WLL group, while no significant difference in DLCO% and A-aO2 mean values were reported. Conclusion Mini-WLL has demonstrated higher efficacy in ameliorating lung volumes, suggesting that a lower infusion volume is sufficient to remove the surfactant accumulation and possibly allows a reduced mechanical insult of the bronchi walls and the alveoli. However, no statistically significant differences were found in terms of DLCO% and Aa-O2.

Given the known pro-oxidant status of tumour cells, the development of anti-proliferative strategies focuses on products with both anti- and pro-oxidant properties that can enhance antitumour drug cytotoxicity. We used a C. zeylanicum essential oil (CINN-EO) and assessed its effect on a human metastatic melanoma cell line (M14). Human PBMCs and MDMs from healthy donors were used as normal control cells. CINN-EO induced cell growth inhibition, cell cycle perturbation, ROS and Fe(II) increases, and mitochondrial membrane depolarization. To assess whether CINN-EO could affect the stress response, we analysed iron metabolism and stress response gene expression. CINN-EO increased HMOX1, FTH1, SLC7A11, DGKK, and GSR expression but repressed OXR1, SOD3, Tf, and TfR1 expression. HMOX1, Fe(II), and ROS increases are associated with ferroptosis, which can be reversed by SnPPIX, an HMOX1 inhibitor. Indeed, our data demonstrated that SnPPIX significantly attenuated the inhibition of cell proliferation, suggesting that the inhibition of cell proliferation induced by CINN-EO could be related to ferroptosis. Concurrent treatment with CINN-EO enhanced the anti-melanoma effect of two conventional antineoplastic drugs: the mitochondria-targeting tamoxifen and the anti-BRAF dabrafenib. We demonstrate that CINN-EO-mediated induction of an incomplete stress response specifically in cancer cells affects the proliferation of melanoma cells and can enhance drug cytotoxicity.

Pulmonary involvement in Sjogren syndrome (SS) could manifest as cystic lung disease (CLD). CLD in SS includes lymphocytic interstitial pneumonia (LIP) and pulmonary amyloidosis. Differential diagnosis usually requires surgical lung biopsy, whereas CT-guided percutaneous fine needle aspiration biopsy (CT-FNAB) has not yet explored. We describe the case of a 63-year-old never smoker Caucasian female with a SS diagnosis who displayed a newly detected diffuse CLD at high-resolution computed tomography, though totally asymptomatic. Given the favorable location of one big lesion at the superior left lobe, a CT-FNAB was proposed instead of a more invasive SLB. At histology examination a diagnosis of pulmonary nodular AL kappa amyloidosis in the context of SS was established. In conclusion, CT-FNAB might represent an alternative and less invasive diagnostic procedure than SLB in the differential diagnosis of CLD, even if further research is needed. Moreover, this case presents an unusual association between SS and pulmonary nodular AL kappa amyloidosis, with pulmonary nodules and cysts without systemic manifestations.

Alpha1-antitrypsin (AAT) is a serine protease inhibitor that is encoded by the highly polymorphic SERPINA1 gene. Mutations in this gene can lead to AAT deficiency (AATD), which is associated with an increased risk of lung and/or liver disease. On the basis of electrophoretic migration, AAT variants are named with capital letters; M (medium) signifies the normal protein. Among pathological variants, the M-like ones represent a heterogeneous group of rare allelic variants that exhibit the same electrophoretic pattern as the M wild-type protein, which makes them difficult to detect with routine methods. In order to avoid their misdiagnosis, the present study defines and validates effective methods for the detection of two pathogenic M-like variants, Mwurzburg and Mwhitstable. Comparison of protein phenotypes using isoelectric focusing of samples that presented the Mwurzburg variant, as revealed by exons 5 sequencing, identified a particular electrophoretic pattern amenable to the Mwurzburg protein. The specific phenotyping pattern was retrospectively validated, thus enabling the detection of 16 patients with Mwurzburg variant among the subjects already tested but not sequenced according to our diagnostic algorithm. The Mwhitstable allele was detected by intron 4 sequencing of SERPINA1 gene. Mwurzburg and Mwhitstable are often misdiagnosed and the introduction of diagnostic improvements can help the clinical management, especially in patients with established lung disease without any other reported risk factors.

In this paper, we introduce a penalized version of the geometric mean. In analogy with the Mazziotta Pareto Index, this composite indicator is derived as a product between the geometric mean and a penalization term to account for the unbalance among indicators. The unbalance is measured in terms of the (horizontal) variability of the normalized indicators opportunely scaled and transformed via the Box–Cox function of order zero. The penalized geometric mean is used to compute the penalized Human Development Index (HDI), and a comparison with the geometric mean approach is presented. Data come from the Human Development Data Center for 2019 and refer to the classical three dimensions of HDI. The results show that the new method does not upset the original ranking produced by the HDI but it impacts more on countries with poor performances. The paper has the merit of proposing a new reading of the Mazziotta Pareto Index in terms of the reliability of the arithmetic mean as well as of generalizing this reading to the geometric mean approach.

Interstitial lung disease (ILD) encompasses a wide range of parenchymal lung pathologies with different clinical, histological, radiological, and serological features. Follow-up, treatment, and prognosis are strongly influenced by the underlying pathogenesis. Considering that an ILD may complicate the course of any connective tissue disease (CTD) and that CTD's signs are not always easily identifiable, it could be useful to screen every ILD patient for a possible CTD. The recent definition of interstitial pneumonia with autoimmune features is a further confirmation of the close relationship between CTD and ILD. In this context, the multidisciplinary approach is assuming a growing and accepted role in the correct diagnosis and follow-up, to as early as possible define the best therapeutic strategy. However, despite clinical advantages, until now, the pathways of the multidisciplinary approach in ILD patients are largely heterogeneous across different centers and the best strategy to apply is still to be established and validated. Aims of this article are to describe the organization of our multidisciplinary group for ILD, which is mainly focused on the early identification and management of CTD in patients with ILD and to show our results in a 1 year period of observation. We found that 15% of patients referred for ILD had an underlying CTD, 33% had interstitial pneumonia with autoimmune feature, and 52% had ILD without detectable CTD. Furthermore, we demonstrated that the adoption of a standardized strategy consisting of a screening questionnaire, specific laboratory tests, and nailfold videocapillaroscopy in all incident ILD proved useful in making the right diagnosis.

A green solvent-based DLLME/HPLC-MS method for the determination of 19 pesticides in wine samples has been developed. The extractant solvent is a hydrophobic eutectic mixture composed of L-menthol and butylated hydroxytoluene in a molar ratio of 3:1. The endogenous ethanol of wine has been used as dispersive solvent, in order to avoid the solidification of the extracts under 19 °C. The mobile phase composition, the elution gradient and the sample injection volume were optimized in order to make this hydrophobic mixture compatible with conventional reversed phase chromatography and electrospray ionization. The method was validated in matrix, using a wine free from the target compounds. Average recovery as high as 80%, precision between 3 and 14%, and limits of detection and quantification much lower than the maximum residue levels (MRLs) for grapes and wines fixed by the EU regulation, make this multiresidue method fitted for the purpose, with the further advantages of being quick, cheap and in compliance with the green analytical chemistry. From the analysis of 11 commercial wines it was found that just in a bio sample the target compounds were not detectable or lower than quantification limit; as for the other samples, the most widespread and abundant pesticides were methoxyfenozide and boscalid, but their levels were much lower than the relative MRLs.

Corylus avellana L. is known for its healthy properties, and yet previous studies have not dealt with its effects on human innate response. The aim of this study is to assess if C. avellana has an immune adjuvant effect. Human macrophages were pre-treated with hazelnut liquid extract, found to be rich in phenylpropanoids, and subsequently infected with Staphylococcus aureus. Based on the intracellular bacteria CFU reduction and on the treatment doses used, the donors were divided into High-Dose and Low-Dose-Responders. Expression profile for inflammatory and Iron metabolism genes, both for Peripheral Blood Mononuclear Cells and Macrophages, highlighted that Low-Dose-Responders came from a more pronounced pro-inflammatory milieu as compared with High-Dose-Responders. Blood test results revealed that Low-Dose-Responders had higher LDL C and Triglycerides and lower HDL C. Overall, our results suggest that the effect of the extract on Macrophage immune response is influenced by the intracellular inflammatory status of the donor.

(1) Introduction: Bacterial resistance to antibiotics is estimated to be the cause of a major number of deaths by 2050 if we do not find strategies to slow down the rise of drug resistance. Reviews on Mediterranean wild edible plants (MWEPs) with antimicrobial properties are scarce in the main databases (PubMed, Scopus, and WoS). Hence, we proceeded to conduct a new review of the studies on MWEPs. (2) Methods: We used ‘wild edible plant’ and ‘antimicrobial’ as keywords. Within this group, exclusion criteria were reviews, studies concerning non-Mediterranean plants or non-edible plants, studies on topics other than plants or containing no description of antimicrobial properties, or off-topic studies. (3) Results: Finally, out of the one hundred and ninety-two studies we had started with, we reviewed thirty-eight (19.8%) studies concerning the antimicrobial properties of seventy-four MWEPs species belonging to twenty-five Families. Fifty-seven (77%) species out of seventy-four proved to be antimicrobial, with a stringent threshold selection. (4) Conclusions: Studies are still very heterogeneous. We still know too little about MWEPs’ properties; however, what we already know strongly recommends carrying on investigation.

An innovative, robust method has been developed, based on the use of a simple, compact, expressly designed device, named PICUS (the ‘woodpecker’ in ancient Latin), and inspired by the auscultation method carried out by the experts in the field of conservation of cultural heritage. This method entails gently knocking the surface, controlling and measuring the impact time of the stroke’s force, recording the generated sound, comparing the acquired sound with a reference sound by calculating the cross-correlation function, and its maximum, as a measure of the detachment. In a nutshell, it performs an analysis similar to that carried out by a professional who performs a routine examination on the detachments by hand. The experimental apparatus consists of a probe made of an electromechanical percussion element that gently taps the surface producing a sound, a force sensor purposely developed to measure the impact force, and a microphone, all connected with an Arduino-like low cost board, to record and elaborate the sounds and the force sensor signal. The probe XY position on the scene is recognized using an infra-red (IR) system with a low-cost IR camera and an IR light-emitting diode (IR-LED) positioned on the probe. The “tapper” and the microphone replace the hand and the ear of a conservator carrying out a detachment investigation, while the comparison with a reference is the typical mind process of a professional restorer. The result is the fusion of the microphone data and the force sensor data.

Cannabis sativa L. is an herbaceous plant belonging to the family of Cannabaceae. It is classified into three different chemotypes based on the different cannabinoids profile. In particular, fiber-type cannabis (hemp) is rich in cannabidiol (CBD) content. In the present work, a rapid nano liquid chromatographic method (nano-LC) was proposed for the determination of the main cannabinoids in Cannabis sativa L. (hemp) inflorescences belonging to different varieties. The nano-LC experiments were carried out in a 100 µm internal diameter capillary column packed with a C18 stationary phase for 15 cm with a mobile phase composed of ACN/H2O/formic acid, 80/19/1% (v/v/v). The reverse-phase nano-LC method allowed the complete separation of four standard cannabinoids in less than 12 min under isocratic elution mode. The nano-LC method coupled to ultraviolet (UV) detection was validated and applied to the quantification of the target analytes in cannabis extracts. The nano-LC system was also coupled to an electrospray ionization–mass spectrometry (ESI-MS) detector to confirm the identity of the cannabinoids present in hemp samples. For the extraction of the cannabinoids, three different approaches, including dynamic maceration (DM), ultrasound-assisted extraction (UAE), and an extraction procedure adapted from the French Pharmacopeia’s protocol on medicinal plants, were carried out, and the results achieved were compared.

PURPOSE:Pleuroparenchymal fibroelastosis (PPFE) is a rare form of interstitial pneumonia, characterized by elastotic fibrosis involving the pleura and subpleural parenchyma, predominantly in the upper lobes. PPFE can be either idiopathic or secondary and mostly occurs as a late complication of lung or hematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the prevalence of secondary forms in transplant recipients.METHODS:An expert thoracic radiologist retrospectively reviewed high-resolution computed tomography exams of 700 HSCT recipients and 53 lung transplant recipients from the database of the Radiology Department of S. Orsola-Malpighi Hospital dating back from 2007. For each case that radiologically fulfilled PPFE criteria, the following details were retrieved: clinical characteristics, laboratory and functional data, pathologic findings (obtained from one patient) and metabolic data (obtained from three patients).RESULTS:Six cases clinically and radiologically consistent with PPFE were identified: two HSCT recipients (0.28%) and four lung transplant recipients (7.54%).CONCLUSION:In this study, PPFE was strongly associated with lung transplants as a late complication, with a prevalence of 7.54%.

Optical and SEM-EDS microscopy, FT-IR and mFT-IR spectroscopy investigations have been applied to the study of alteration and degradation products of a Roman sarcophagus located in the medieval cloister of St Cosimato’s Convent, now the new “Regina Margherita Hospital” (Rome) before restoration work. This scientific analysis was performed in order to compare it with a diagnosis report based on the restorer’s expertise. The sarcophagus is small and consists of a single block of fine-grained marble covered by a thick pink patina. The results obtained from this diagnostic investigation, allow us to draw important conclusions about the state of conservation of this archaeological artefact. The main components found in the samples analyzed are: black crust, calcium oxalate, organic matter due to recent conservation treatment, calcite, iron-oxides and coloured earths. In particular, the combined used of petrographical and mFT-IR analysis provided useful insights into the polishing and consolidation processes of archaeological artefacts.

A new method for calibrating the Black-Scholes asset price dynamics model is proposed. The data used to test the calibration problem included observations of asset prices over a finite set of (known) equispaced discrete time values. Statistical tests were used to estimate the statistical significance of the two parameters of the Black-Scholes model: the volatility and the drift. The effects of these estimates on the option pricing problem were investigated. In particular, the pricing of an option with uncertain volatility in the Black-Scholes framework was revisited, and a statistical significance was associated with the price intervals determined using the Black-Scholes-Barenblatt equations. Numerical experiments involving synthetic and real data were presented. The real data considered were the daily closing values of the S&P500 index and the associated European call and put option prices in the year 2005. The method proposed here for calibrating the Black-Scholes dynamics model could be extended to other science and engineering models that may be expressed in terms of stochastic dynamical systems.

In order to analyze dendritic cells (DCs) activation following infection with different mycobacterial strains, we studied the expression profiles of 165 genes of human monocyte-derived DCs infected with H37Rv, a virulent Mycobacterium tuberculosis (MTB) laboratory strain, CMT97, a clinical MTB isolate, Mycobacterium bovis bacillus Calmette-Guérin (BCG), Aventis Pasteur, and BCG Japan, both employed as vaccine against tuberculosis. The analysis of the gene expression reveals that, despite a set of genes similarly modulated, DCs response resulted strain dependent. In particular, H37Rv significantly upregulated EBI3 expression compared with BCG Japan, while it was the only strain that failed to release a significant IL-10 amount. Of note, BCG Japan showed a marked increase in CCR7 and TNF-α expression regarding both MTB strains and it resulted the only strain failing in exponential intracellular growth. Our results suggest that DCs display the ability to elicit a tailored strain-specific immune response.

Pulmonary alveolar proteinosis is a rare condition characterized by the accumulation of lipoproteinaceous material within the airspaces, resulting in impaired gas transfer, and clinical manifestations ranging from asymptomatic to severe respiratory failure. To the best of the authors’ knowledge, there are only a few conditions whose natural history has been so dramatically changed by the influence of advances in basic science, clinical medicine, and translational research in therapeutic approaches. Whole-lung lavage is the current standard of care and it plays a critical role as a modifier factor of the natural history of proteinosis. That notwithstanding, the identification of autoantibodies neutralizing granulocyte-macrophage colony-stimulating factor in serum and lung of patients affected by the form of proteinosis previously referred to as idiopathic, has opened the way to novel therapeutic options, such as supplementation of exogenous granulocyte-macrophage colony-stimulating factor, or strategies aimed at reducing the levels of the autoantibodies. The aim of this paper is to provide an updated review of the current therapeutic approach to proteinosis.