Una prima lettura della recente riforma della tutela penalistica dei beni culturali

On March 9, 2022, the Italian Parliament has definitively passed a comprehensive reform on crimes protecting the cultural heritage (law n. 22 of 2022). This short paper analyses the main points of this law, dwelling both on some general issues, such as first and foremost the sedes materiae of the intervention, and specifically on the individual criminal offenses introduced

Site-specific integration in mammalian cells mediated by a new hybrid baculovirus-adeno-associated virus vector

Baculovirus can transiently transduce primary human and rat hepatocytes, as well as a subset of stable celllines. To prolong transgene expression, we have developed new hybrid vectors which associate key elementsfrom adeno-associated virus (AAV) with the elevated transducing capacity of baculovirus. The hybrid vectorscontain a transgene cassette composed of the !-galactosidase (!-Gal) reporter gene and the hygromycin resistance(Hygr) gene flanked by the AAV inverted terminal repeats (ITRs), which are necessary for AAV replicationand integration in the host genome. Constructs were derived both with and without the AAV rep geneunder the p5 and p19 promoters cloned in different positions with respect to the baculovirus polyheidrinpromoter. A high-titer preparation of baculovirus-AAV (Bac-AAV) chimeric virus containing the ITR–Hygr–!-Gal sequence was obtained with insect cells only when the rep gene was placed in an antisense orientationto the polyheidrin promoter. Infection of 293 cells with Bac-AAV virus expressing the rep gene results in a 10-to 50-fold increase in the number of Hygr stable cell clones. Additionally, rep expression determined the localizationof the transgene cassette in the aavs1 site in approximately 41% of cases as detected by bothSouthern blotting and fluorescent in situ hybridization analysis. Moreover, site-specific integration of the ITRflankedDNA was also detected by PCR amplification of the ITR-aavs1 junction in transduced human fibroblasts.These data indicate that Bac-AAV hybrid vectors can allow permanent, nontoxic gene delivery of DNAconstructs for ex vivo treatment of primary human cells

Mining Legal Arguments in Court Decisions

Identifying, classifying, and analyzing arguments in legal discourse has been a prominent area of research since the inception of the argument mining field. However, there has been a major discrepancy between the way natural language processing (NLP) researchers model and annotate arguments in court decisions and the way legal experts understand and analyze legal argumentation. While computational approaches typically simplify arguments into generic premises and claims, arguments in legal research usually exhibit a rich typology that is important for gaining insights into the particular case and applications of law in general. We address this problem and make several substantial contributions to move the field forward. First, we design a new annotation scheme for legal arguments in proceedings of the European Court of Human Rights (ECHR) that is deeply rooted in the theory and practice of legal argumentation research. Second, we compile and annotate a large corpus of 373 court decisions (2.3M tokens and 15k annotated argument spans). Finally, we train an argument mining model that outperforms state-of-the-art models in the legal NLP domain and provide a thorough expert-based evaluation. All datasets and source codes are available under open lincenses at https://github.com/trusthlt/mining-legal-arguments.Comment: to appear in Artificial Intelligence and La

Physiotherapy versus consecutive physiotherapy and cognitive treatment in people with Parkinson's Disease: a pilot randomized cross-over study

Parkinson's disease (PD) is characterized by motor and cognitive dysfunctions that can usually be treated by physiotherapy or cognitive training, respectively. The effects of consecutive physiotherapy and cognitive rehabilitation programs on PD deficits are less investigated

Neurophysiological aspects in SARS-CoV-2–induced acute respiratory distress syndrome

Patients with coronavirus disease 2019 (COVID-19) often develop acute respiratory failure and acute respiratory distress syndrome (ARDS) that requires intensive care unit (ICU) hospitalization and invasive mechanical ventilation, associated with a high mortality rate. In addition, many patients fail early weaning attempts, further increasing ICU length of stay and mortality. COVID-19 related ARDS can be complicated by neurological involvement with mechanisms of direct central nervous system (CNS) infection and with overlapping para-infective mechanisms of the peripheral nervous system (PNS). We aimed to evaluate the possible involvement of the brainstem and PNS in patients with COVID-19 related ARDS and difficulty in weaning from mechanical ventilation. We evaluated electroencephalogram (EEG), brainstem auditory evoked potentials (BAEPs), electroneurography of the four limbs and the phrenic nerve in 10 patients with respiratory insufficiency due to SARS-CoV-2. All were admitted to intensive care unit and were facing prolonged weaning from mechanical ventilation. All ten patients showed a mild diffuse non-specific slowing of brain electrical activity on the EEG. Four patients had an acute motor axonal neuropathy with absent or reduced amplitude phrenic nerve CMAP while four patients showed impairment of the BAEPs. A patient with peripheral nerve impairment suggestive of Guillain-Barré syndrome (GBS) underwent an intravenous immunoglobulin (IVIg) cycle that led to an improvement in the weaning process and progressive motor improvement. The inclusion of a comprehensive neurological evaluation in COVID-19 patients in ICU facilitated the early identification and effective management of Nervous System involvement

Value of split-bolus multidetector-row CT technique in the quantitative assessment of pancreatic enhancement [Pankreatik tutulumun kantitatif değerlendirilmesinde bölünmüş-bolus multidetektör-dizi BT tekniğinin değeri]

The aim of this study is to quantitatively assess radiation comma, and pancreatic enhancement by split-bolus intravenous injection of contrast material using 64-slice CT. Single-pass split-bolus MDCT of the chest and abdomen was performed in 37 patients (female: 18, male: 9; mean age, 66.1±14.2 years; range 17-80 years) without pancreatic disease. Regions of interest in the pancreatic head, body and tail were drawn, and mean attenuation values for pancreatic parenchymal phase (PPP) of the standard MDCT protocol and split-bolus were calculated. P<0.05 was considered statistically significant. Mean effective dose by split-bolus was measured. In all MDCT examinations split-bolus protocol allowed acquisition of optimal images. Mean pancreatic enhancement was higher by split-bolus with respect to PPP of standard triphasic MDCT (131.35 HU±20.63 vs 126.1 HU±20.01). Reduction of dose using MDCT split-bolus was approximately 17%. In conclusion MDCT split-bolus protocol provides an optimal pancreatic enhancement, significantly greater than the enhancement of standard MDCT on PPP which confers an advantage for the detection and staging of pancreatic tumors

Relevance of Stereotyped B-Cell Receptors in the Context of the Molecular, Cytogenetic and Clinical Features of Chronic Lymphocytic Leukemia

Highly homologous B-cell receptors, characterized by non-random combinations of immunoglobulin heavy-chain variable (IGHV) genes and heavy-chain complementarity determining region-3 (HCDR3), are expressed in a recurrent fraction of patients affected by chronic lymphocytic leukemia (CLL). We investigated the IGHV status of 1131 productive IG rearrangements from a panel of 1126 CLL patients from a multicenter Italian study group, and correlated the presence and class of HCDR3 stereotyped subsets with the major cytogenetic alterations evaluated by FISH, molecular prognostic factors, and the time to first treatment (TTFT) of patients with early stage disease (Binet A). Stereotyped HCDR3 sequences were found in 357 cases (31.7%), 231 of which (64.7%) were unmutated. In addition to the previously described subsets, 31 new putative stereotypes subsets were identified. Significant associations between different stereotyped HCDR3 sequences and molecular prognostic factors, such as CD38 and ZAP-70 expression, IGHV mutational status and genomic abnormalities were found. In particular, deletion of 17p13 was significantly represented in stereotype subset #1. Notably, subset #1 was significantly correlated with a substantially reduced TTFT compared to other CLL groups showing unmutated IGHV, ZAP-70 or CD38 positivity and unfavorable cytogenetic lesions including del(17)(p13). Moreover, subset #2 was strongly associated with deletion of 13q14, subsets #8 and #10 with trisomy 12, whereas subset #4 was characterized by the prevalent absence of the common cytogenetic abnormalities. Our data from a large and representative panel of CLL patients indicate that particular stereotyped HCDR3 sequences are associated with specific cytogenetic lesions and a distinct clinical outcome

Effect of Berberine Phytosome on reproductive, dermatologic, and metabolic characteristics in women with polycystic ovary syndrome: a controlled, randomized, multi-centric, open-label clinical trial

Background: Berberine is a poorly absorbed natural alkaloid widely used as nutraceutical to counteract diarrhoea and to lower cholesterol and hyperglycaemia. It has also been reported to reduce signs and symptoms of polycystic ovary syndrome (PCOS).Objective: To explore, through a multi-centric, randomized, controlled and prospective study, the possible role played by a form berberine that is more easily absorbed (Berberine Phytosome®, BP) in 130 Pakistani women with a diagnosis of PCOS and fertility problems due to menstrual and ovary abnormalities.Results: Ninety days of supplementation with BP, administered at 550 mg x2/die, determined (i) resumption of regular menstruation in about 70% of women (versus 16% in the control group; p < 0.0001), (ii) normalization of the ovaries anatomy in more than 60% of women (versus 13% in the control group; p < 0.0001), (iii) acne improvement in 50% of women (versus 16% in the control group; p = 0.0409) and (iv) hirsutism reduction in 14% of women (versus 0% in the control group; p = 0.0152). The metabolic and the hormonal profiles of the women in the two groups did not significantly differentiate at the end of the study. BP was well-tolerated and no specific side-effects were registered. Respectively after one, two and 8 years of trying, three women supplemented with BP became and are currently pregnant.Conclusion: Our study showed the positive effects of BP supplementation in women with PCOS and confirmed the high safety profile of this nutraceutical.Clinical Trial Registration:https://clinicaltrials.gov/, identifier NCT0548067

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982

The Sex-Specific Detrimental Effect of Diabetes and Gender-Related Factors on Pre-admission Medication Adherence Among Patients Hospitalized for Ischemic Heart Disease: Insights From EVA Study

Background: Sex and gender-related factors have been under-investigated as relevant determinants of health outcomes across non-communicable chronic diseases. Poor medication adherence results in adverse clinical outcomes and sex differences have been reported among patients at high cardiovascular risk, such as diabetics. The effect of diabetes and gender-related factors on medication adherence among women and men at high risk for ischemic heart disease (IHD) has not yet been fully investigated.Aim: To explore the role of sex, gender-related factors, and diabetes in pre-admission medication adherence among patients hospitalized for IHD.Materials and Methods: Data were obtained from the Endocrine Vascular disease Approach (EVA) (ClinicalTrials.gov Identifier: NCT02737982), a prospective cohort of patients admitted for IHD. We selected patients with baseline information regarding the presence of diabetes, cardiovascular risk factors, and gender-related variables (i.e., gender identity, gender role, gender relations, institutionalized gender). Our primary outcome was the proportion of pre-admission medication adherence defined through a self-reported questionnaire. We performed a sex-stratified analysis of clinical and gender-related factors associated with pre-admission medication adherence.Results: Two-hundred eighty patients admitted for IHD (35% women, mean age 70), were included. Around one-fourth of the patients were low-adherent to therapy before hospitalization, regardless of sex. Low-adherent patients were more likely diabetic (40%) and employed (40%). Sex-stratified analysis showed that low-adherent men were more likely to be employed (58 vs. 33%) and not primary earners (73 vs. 54%), with more masculine traits of personality, as compared with medium-high adherent men. Interestingly, women reporting medication low-adherence were similar for clinical and gender-related factors to those with medium-high adherence, except for diabetes (42 vs. 20%, p = 0.004). In a multivariate adjusted model only employed status was associated with poor medication adherence (OR 0.55, 95%CI 0.31–0.97). However, in the sex-stratified analysis, diabetes was independently associated with medication adherence only in women (OR 0.36; 95%CI 0.13–0.96), whereas a higher masculine BSRI was the only factor associated with medication adherence in men (OR 0.59, 95%CI 0.35–0.99).Conclusion: Pre-admission medication adherence is common in patients hospitalized for IHD, regardless of sex. However, patient-related factors such as diabetes, employment, and personality traits are associated with adherence in a sex-specific manner