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Conjugated linoleic acid (CLA) isomers exhibit anti-inflammatory properties within the central nervous system (CNS). This study investigated the effects of CLA isomers c9,t11 and t10,c12 on fatty acid (FA) and N-acylethanolamine (NAE) profiles and their association with pro-inflammatory molecule expression in BV-2 microglia cell line, the CNS's resident immune cells responsible for maintaining neuronal activity and immune homeostasis. BV-2 cells were treated with 25µM of c9,t11-CLA, t10,c12-CLA, or oleic acid (OA) for 24 h, followed by lipopolysaccharide (LPS) stimulation. After treatment, the cell's FA and NAE profiles and pro-inflammatory molecule expression were analyzed. Our results demonstrated that CLA isomers mitigate LPS-induced morphological changes in BV-2 cells and reduce gene expression and protein levels of inflammatory markers. This effect was linked to an upregulation of acyl-CoA oxidase 1, a key enzyme in the anti-inflammatory peroxisomal beta-oxidation pathway that efficiently metabolizes CLA isomers. Notably, t10,c12-CLA significantly suppressed stearoyl-CoA desaturase 1, impacting monounsaturated fatty acid synthesis. The NAEs profile was remarkably altered by CLA isomers, with a significant release of the anti-neuroinflammatory mediator docosahexaenoic acid (DHA)-derived N-acylethanolamine (DHAEA). In conclusion, our findings suggest that the anti-neuroinflammatory effects of CLA isomers are due to their unique influences on FAmetabolismand themodulation of bioactive FA-derived NAEs, highlighting a potential strategy for nutritional intervention in conditions characterized by neuroinflammation. [ABSTRACT FROM AUTHOR]

Conjugated linoleic acid (CLA) isomers exhibit anti-inflammatory properties within the central nervous system (CNS). This study investigated the effects of CLA isomers c9,t11 and t10,c12 on fatty acid (FA) and N-acylethanolamine (NAE) profiles and their association with pro-inflammatory molecule expression in BV-2 microglia cell line, the CNS's resident immune cells responsible for maintaining neuronal activity and immune homeostasis. BV-2 cells were treated with 25µM of c9,t11-CLA, t10,c12-CLA, or oleic acid (OA) for 24 h, followed by lipopolysaccharide (LPS) stimulation. After treatment, the cell's FA and NAE profiles and pro-inflammatory molecule expression were analyzed. Our results demonstrated that CLA isomers mitigate LPS-induced morphological changes in BV-2 cells and reduce gene expression and protein levels of inflammatory markers. This effect was linked to an upregulation of acyl-CoA oxidase 1, a key enzyme in the anti-inflammatory peroxisomal beta-oxidation pathway that efficiently metabolizes CLA isomers. Notably, t10,c12-CLA significantly suppressed stearoyl-CoA desaturase 1, impacting monounsaturated fatty acid synthesis. The NAEs profile was remarkably altered by CLA isomers, with a significant release of the anti-neuroinflammatory mediator docosahexaenoic acid (DHA)-derived N-acylethanolamine (DHAEA). In conclusion, our findings suggest that the anti-neuroinflammatory effects of CLA isomers are due to their unique influences on FAmetabolismand themodulation of bioactive FA-derived NAEs, highlighting a potential strategy for nutritional intervention in conditions characterized by neuroinflammation. [ABSTRACT FROM AUTHOR]

Simple Summary: This study analyzes the use of rituximab (RTX) in the daily clinical practice of several Italian oncohematology centers, with a particular focus on the adoption of biosimilars. The results show that only a minority of patients (22%) switched between different biosimilars, while the majority continued treatment with the biosimilars Rixathon and Truxima. This finding suggests that the proactive sharing of guidelines between regulators and prescribers, from the outset, may be an effective strategy to further promote the adoption of biosimilars. This approach could be particularly useful in those areas where the use of biosimilars is still lower than the national average, helping to free up economic resources that could be redirected towards other healthcare opportunities. The clinical safety and efficacy of rituximab biosimilars compared to the reference rituximab (Mabthera) have been well established in randomized trials. However, concerns persist regarding the safety of changing from the reference product to biosimilars, and particularly between different biosimilars. This prospective multicenter observational study was conducted in 13 oncohematology units of eight Italian regions. The study included 800 patients with non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) who received rituximab between March 2018 and June 2022. To minimize survivorship bias, only newly diagnosed patients (i.e., those without prior rituximab treatment) were included in the analysis of adverse drug reactions (ADRs). Thus, this study focused on 505 incident cases (79.8% of the initial cohort) from 13 centers. A total of 3681 rituximab infusions were administered, and 16.8% of the patients experienced at least one ADR. These were observed most frequently during the first infusion (44 patients, 52%) and the second infusion (17 patients, 20%). The most frequent reactions were general disorders and administration site conditions (n. 50, 8% serious). These findings support the clinical safety of rituximab biosimilars and suggest that switching between biosimilars does not increase the risk of adverse events. This evidence may alleviate concerns about biosimilar use, potentially leading to broader acceptance and reduced healthcare costs. [ABSTRACT FROM AUTHOR]

Background: Brain magnetic resonance imaging (MRI) is mandatory or highly recommended in many pediatric endocrinological conditions to detect causative anatomic anomalies and rule out neoplastic lesions. However, MRI can also show findings associated with the underlying clinical condition, as well as unrelated "incidentalomas". These latter findings are often abnormalities with a high incidence in the general population for which there is no clear literature regarding their management, especially in pediatric patients. The present study aimed to evaluate the number of unnecessary performed MRIs in pediatric endocrinology. Methods: Retrospective analysis on 584 MRI scans performed in 414 patients (254 growth hormone deficiency, 41 other causes of short stature, 116 central precocious puberty). Results: The MRI scans were completely normal in 67% of the individuals, and the prevalence of individuals who underwent more than one MRI was 18%, with no significant differences among the groups. The overall prevalence of incidentalomas was 17%. Among 170 repeated MRI scans, 147 (86%) were not required according to a dedicated protocol. Only five patients (four GHD, one Noonan) correctly repeated the MRI. All the repeated MRI scans did not reveal any progression in the findings. If we include the MRIs performed in cases of OCSS other than Noonan syndrome (n=32) and girls with CPP older than 6 years (n=89), an additional 121 MRIs could have been avoided, leading to a total number of unnecessary MRIs to 268 (46%). Conclusions: Only a few specific neuroimaging findings in endocrinologic pediatric patients warrant further investigation, while too often repeated imaging is carried out unnecessarily. We advocate the importance of guidelines to reduce costs for both the healthcare system and patients' families, as well as to alleviate physical and psychological distress for patients and caregivers. [ABSTRACT FROM AUTHOR]

This paper presents the mathematical derivation and numerical implementation of a novel regularized density-driven damage mechanics (D3M) model for simulating failure in concrete members. The novel idea behind the derivation of the approach is that damage is described as a function of the local change in material density. This choice is justified by the fact that the development of local damage directly corresponds to a reduction in local density since undamaged cementitious composites inherently have a higher density than the fluid or gas that occupies damaged regions. For this reason, devising numerical approaches that can predict the material behavior as a function of density could open up new possibilities for the prediction of the nonlinear behavior of concrete structures, as well as the derivation of novel testing procedures for the evaluation of strength by means of direct and indirect measures of density. In this context, a three-phase mesoscopic representation of concrete material is used, where coarse aggregate, mortar, and the interfacial transition zone are explicitly modeled to obtain a realistic representation of the material internal structure. The manuscript first presents the mathematical derivation of the model, with emphasis devoted to the regularization of the computational implementation. This paper then proceeds to demonstrate that the novel regularized D3M is insensitive to the mesh size chosen to represent the three material phases while also predicting realistic compression-to-tension strength ratios and damage patterns at failure. In addition, a parametric study is carried out to illustrate the effect of the relevant mechanical parameters on the observed response. Finally, the proposed model is validated by comparison with experimental results of 3-point bending tests on plain concrete beams of various sizes, also demonstrating that the regularized D3M is capable of predicting size effect in concrete members. [ABSTRACT FROM AUTHOR]

Schwannomas are benign, slow-growing tumors originating from the Schwann cells of nerve sheaths. Extracranial schwannomas are rare, particularly in pediatric populations. Here, we report the case of a hypoglossal schwannoma in a 15-year-old male who experienced tongue paresthesia and fasciculations and difficulty swallowing two years before hospital admission. Magnetic resonance imaging showed an oval mass with sharp and regular limits of approximately 45 × 29 × 25 mm in the cranial portion of the right carotid adipose space, caudal to the right carotid and lateral foramen. The patient underwent surgery, and a histological examination confirmed a schwannoma of the hypoglossal nerve. Six months after surgery, the patient was symptom-free. The literature on schwannomas of the hypoglossal nerve is scarce, with only a few previously reported cases in the adult population. Despite their rarity, schwannomas should be considered in the differential diagnosis of masses located in the neck that present with lingual and occasionally auditory symptoms, even in pediatric patients. Surgical resection is recommended and has a low risk of long-term recurrence. [ABSTRACT FROM AUTHOR]

Simple Summary: Targeted agents, such as Bruton's Tyrosine Kinase inhibitors and BCL-2 inhibitors, have transformed the treatment landscape for Chronic Lymphocytic Leukemia (CLL). While these therapies offer a more precise approach compared to traditional chemotherapy, they also bring a spectrum of adverse events that can impact patient health and treatment efficacy. This review aims to provide a comprehensive overview of the management strategies for these AEs, encompassing cardiac complications, Tumor Lysis Syndrome, bleeding risks, and other organ-specific challenges. Our goal is to equip healthcare professionals with the knowledge to effectively manage these adverse events, enhancing patient safety and optimizing therapeutic outcomes. The insights from this review will contribute to better clinical decision-making and patient care in CLL treatment, highlighting the significance of personalized management in the era of targeted therapy. The treatment landscape for CLL has undergone a profound transformation with the advent of targeted agents (TAs) like Bruton's Tyrosine Kinase inhibitors (BTKis) and BCL-2 inhibitors (BCL-2is). These agents target crucial cellular pathways in CLL, offering superior efficacy over traditional chemo-immunotherapy, which has led to improved progression-free and overall survival rates. This advancement promises enhanced disease control and potentially normal life expectancy for many patients. However, the journey is not without challenges, as these TAs are associated with a range of adverse events (AEs) that can impact treatment efficacy and patient quality of life. This review focuses on detailing the various AEs related to TA management in CLL, evaluating their frequency and clinical impact. The aim is to present a comprehensive guide to the effective management of these AEs, ensuring optimal tolerability and efficacy of TAs. By reviewing the existing literature and consolidating findings, we provide insights into AE management, which is crucial for maximizing patient outcomes in CLL therapy. [ABSTRACT FROM AUTHOR]

Listeria monocytogenes, along with various other pathogenic bacteria, may show resistance against a broad spectrum of antibiotics. Evaluating the extent of resistance in harmful microorganisms like Listeria monocytogenes holds significant importance in crafting novel therapeutic strategies to mitigate or combat the rise of infections stemming from antibiotic-resistant bacteria. The present work aims to investigate the occurrence of antimicrobial resistance among Listeria monocytogenes strains in meat products (n = 173), seafood (n = 54), dairy products (n = 19), sauces (n = 2), confectionary products (n = 1), ready-to-eat rice dishes (n = 1), and food-processing environments (n = 19). A total of 269 Listeria monocytogenes strains belonging to eight different serovars were tested against 10 antimicrobials. In the classes of antibiotics, most of the strains were resistant antibiotics belonging to the family of β-lactams (92.94%). High proportions of L. monocytogenes isolates were resistant to oxacillin (88.48%), followed by fosfomycin (85.87%) and flumenique (78.44%). The lowest level of resistance was observed against gentamycin (1.49%). A total of 235 strains (n = 87.36%) showed a profile of multidrug resistance. In conclusion, a high occurrence of resistant and multidrug-resistant strains of Listeria monocytogenes was observed among the examined serotypes isolated from different food sources. This understanding enables the adoption of suitable measures to avert contamination and the spread of resistant bacteria via food. [ABSTRACT FROM AUTHOR]

The winemaking process generates an annual global production of about 10 million tons of waste consisting of stalks, skin, and seeds. The possible reutilization of wine pomace is strictly linked to its chemical composition. In this preliminary study, three different Sardinian white grapes (Malvasia, Vermentino and Nasco) grown in the same area were evaluated through a whole wine production chain. To reduce environmental impact, all the grapes were treated following the integrated production practice (IPP) strategies. The adopted agronomic methods and the main physico-chemical parameters of the fresh fruits and musts were evaluated. A fully qualitative and quantitative characterization of the phenolic fraction of the pomace extracts was performed by HPLC-DAD after a post-winemaking process. Water and ethanol were utilized as green solvents in the extraction process. Additionally, the entire pomace post-winemaking process was carried out within the winery facilities to reduce energy loss and road transportation. The findings demonstrated that large amounts of beneficial polyphenols are present in pomace extracts, and that the type of grape used, agronomic practices, and winemaking method all influence the quantity and quality of the extracts. The polyphenol concentrations in the Vermentino (28,391.5 ± 7.0 mg/kg) and Malvasia pomace (11,316.3 ± 6.5 mg/kg) were found to be the highest and lowest, respectively. [ABSTRACT FROM AUTHOR]

Continued fractions in the field of p-adic numbers have been recently studied by several authors. It is known that the real continued fraction of a positive quadratic irrational is eventually periodic (Lagrange's Theorem). It is still not known if a p-adic continued fraction algorithm exists that shares a similar property. In this paper we modify and improve one of Browkin's algorithms. This algorithm is considered one of the best at the present time. Our new algorithm shows better properties of periodicity. We show for the square root of integers that if our algorithm produces a periodic expansion, then this periodic expansion will have pre-period one. It appears experimentally that our algorithm produces more periodic continued fractions for quadratic irrationals than Browkin's algorithm. Hence, it is closer to an algorithm to which an analogue of Lagrange's Theorem would apply. [ABSTRACT FROM AUTHOR]

Chronic Lymphocytic Leukemia (CLL) is well-known for increasing susceptibility to infections. Factors such as immune dysregulation, IGHV status, hypogammaglobulinemia, and patient comorbidity and treatment, contribute to higher infection rates and mortality. However, the impact of hypogammaglobulinemia on infection rates is controversial. We aimed to identify clinical and biological parameters linked to the risk of severe infectious events. Additionally, we set up a straightforward risk infection score to stratify CLL patients at diagnosis, thereby enabling the development of suitable infection prevention strategies. We retrospectively evaluated 210 unselected CLL patients diagnosed between 1988 and 2018. This evaluation encompassed demographics, Binet stage, immunoglobulin (Ig) levels, treatment history, comorbidities, and IGHV mutational status at diagnosis. The frequency and severity of infectious events were recorded. Analysis revealed that age, IGHV mutational status, Binet stage, and hypogammaglobulinemia were statistically associated with the Time to First Infection (TTFI) in univariate and multivariate analyses. Using hazard ratios from the multivariate analysis, we finally devised a risk scoring system that integrated age, IGHV mutational status, immunoglobulin levels, and Binet stage to stratify patients at diagnosis based on their specific infection risk. In our cohort, disease progression and infections were the leading cause of death. These findings pointed out the clinical need for a screening process strategic for defining infectious risk at the time of CLL diagnosis, with a significant enhancement in the clinical management of these patients. [ABSTRACT FROM AUTHOR]

Simple Summary: In clinical trials, ibrutinib was found to be effective and well-tolerated in patients with chronic lymphocytic leukemia (CLL). To confirm these findings, data on unselected patients treated in clinical practice are necessary. The aim of our observational, prospective Italian cohort study was to describe the real-world persistence rate, patterns of use, and clinical outcomes in patients with CLL treated with single-agent ibrutinib across various treatment lines. We found that, despite the high burden of patient comorbidities and unfavorable genetic features, the majority of patients (217/309, 70%), especially those treated in first line (75%), continued ibrutinib treatment for ≥2 years. The most common reasons for treatment discontinuation were adverse events, primarily infections. We reported positive clinical and survival outcomes, especially in the first-line cohort, and a safety profile consistent with clinical trial data. Our data suggest that ibrutinib is a valuable option for both treatment-naïve and previously treated patients with CLL. Real-world data in clinical practice are needed to confirm the efficacy and safety that ibrutinib has demonstrated in clinical trials of patients with chronic lymphocytic leukemia (CLL). We described the real-world persistence rate, patterns of use, and clinical outcomes in 309 patients with CLL receiving single-agent ibrutinib in first line (1L, n = 118), 2L (n = 127) and ≥3L (n = 64) in the prospective, real-world, Italian EVIdeNCE study. After a median follow-up of 23.9 months, 29.8% of patients discontinued ibrutinib (1L: 24.6%, 2L: 29.9%, ≥3L: 39.1%), mainly owing to adverse events (AEs)/toxicity (14.2%). The most common AEs leading to discontinuation were infections (1L, ≥3L) and cardiac events (2L). The 2-year retention rate was 70.2% in the whole cohort (1L: 75.4%, 2L: 70.1%, ≥3L: 60.9%). The 2-year PFS and OS were, respectively, 85.4% and 91.7% in 1L, 80.0% and 86.2% in 2L, and 70.1% and 80.0% in ≥3L. Cardiovascular conditions did not impact patients' clinical outcomes. The most common AEs were infections (30.7%), bleeding (12.9%), fatigue (10.0%), and neutropenia (9.7%), while grade 3–4 atrial fibrillation occurred in 3.9% of patients. No new safety signals were detected. These results strongly support ibrutinib as a valuable treatment option for CLL. [ABSTRACT FROM AUTHOR]

The majority of human diseases attributed to seafood are caused by Vibrio spp., and the most commonly reported species are Vibrio parahaemolyticus, Vibrio vulnificus, and Vibrio cholerae. The conventional methods for the detection of Vibrio species involve the use of selective media, which are inexpensive and simple but time-consuming. The present work aimed to develop a rapid method based on the use of multiplex real-time polymerase chain reaction (PCR) to detect V. parahaemolyticus, V. vulnificus, and V. cholerae in bivalve mollusks. 30 aliquots of bivalve mollusks (Mytilus galloprovincialis) were experimentally inoculated with two levels of V. parahaemolyticus, V. vulnificus, and V. cholerae. ISO 21872-1:2017 was used in parallel for qualitative analysis. The limit of detection of 50% was 7.67 CFU/g for V. cholerae, 0.024 CFU/g for V. vulnificus, and 1.36 CFU/g for V. parahaemolyticus. For V. vulnificus and V. cholerae, the real-time PCR protocol was demonstrated to amplify the pathogens in samples seeded with the lowest and highest levels. The molecular method evaluated showed a concordance rate of 100% with the reference microbiological method. V. parahaemolyticus was never detected in samples contaminated with the lowest level, and it was detected in 14 samples (93.33%) seeded with the highest concentration. In conclusion, the developed multiplex real-time PCR proved to be reliable for V. vulnificus and V. cholerae. Results for V. parahaemolyticus are promising, but further analysis is needed. The proposed method could represent a quick monitoring tool and, if used, would allow the implementation of food safety. [ABSTRACT FROM AUTHOR]

We propose a novel method for assessing metabolic flexibility (MF) through indirect calorimetry. A total of twenty healthy volunteers (10 females; 10 males) aged 45–65 were categorized into a Low-Intensity activity group (LI, 0–1 session of 1 h per week) and a High-Intensity activity group (HI, 5–6 sessions of 2 h per week). Volunteers underwent a stepwise exercise test on a cycle ergometer, connected to a calorimeter, to examine respiratory gas exchange to evaluate peak fatty acid Oxidation (PFO) and peak carbohydrate oxidation (PCO). Circulating peroxisome proliferator-activated receptor α (PPARα) biomarkers, docosahexaenoic acid/eicosapentaenoic acid (DHA/EPA) ratio and N-oleoylethanolamine (OEA), and the endocannabinoid- 2-arachidonoylglycerol (2-AG), were evaluated. We developed two MF parameters: the MF index (MFI), calculated by the product of PFO normalized per kg of fat-free mass (FFM) and the percentage of VO2max at PFO, and the peak energy substrates' oxidation (PESO), computed by summing the kilocalories from the PFO and PCO, normalized per kg FFM. The MFI and PESO were significantly different between the HI and LI groups, showing strong correlations with the circulating bioactive substances. Higher DHA/EPA ratio (p ≤ 0.05) and OEA (p ≤ 0.01), but lower 2-AG levels (p ≤ 0.01) were found in the HI group. These new parameters successfully established a functional link between MF and the balance of PPARα/endocannabinoid systems. [ABSTRACT FROM AUTHOR]

Neuromodulation by means of vagus nerve stimulation (VNS) therapy, reduces seizure frequency and improves quality of life in subjects with drug‐resistant epilepsy (DRE), yet its molecular mechanism remains unclear. This study investigates the impact of chronic VNS on lipid bioactive metabolites and fatty acids (FA) in the plasma and red blood cells of seven subjects with DRE. By measuring expression levels of peroxisome proliferator‐activated receptor α (PPARα) and sirtuin1 (SIRT1) genes—key regulators in energy and lipid metabolism—and lipid profiles before and after various stages of VNS, this study identifies potential mechanisms by which VNS may reduce seizure frequency. Blood samples collected before VNS device implantation, after acute VNS stimulus, and following gradual intensity increments up to therapeutic levels revealed that VNS increases SIRT1 and PPARα expression and erythrocyte concentrations of PPARα ligands. Additionally, we observe reduced de novo lipogenesis biomarkers in erythrocytes, indicating that VNS may influence systemic lipid and energy metabolism. Our findings suggest that VNS could enhance neuronal function by modulating energy metabolism, thus potentially reducing seizure frequency in subjects with DRE. Future research targeting SIRT1 and PPARα may provide innovative therapeutic strategies for managing DRE. Plain Language Summary: The exact mechanism of VNS is still unknown. This study investigated the effects of VNS Therapy on energetic metabolism, suggesting possible novel biomarkers for DRE subjects and neuromodulation therapies. [ABSTRACT FROM AUTHOR]

Objective: To explore illness-related factors in patients with major depressive disorder (MDD) recipients of adjunctive minocycline (200 mg/day) treatment. The analysis included participants experiencing MDD from a 12-week, double blind, placebo-controlled, randomized clinical trial (RCT). Methods: This is a sub-analysis of a RCT of all 71 participants who took part in the trial. The impact of illness chronicity (illness duration and number of depressive episodes), systemic illness (endocrine, cardiovascular and obesity), adverse effects and minocycline were evaluated as change from baseline to endpoint (12-week) using ANCOVA. Results: There was a consistent but statistically non-significant trend on all outcomes in favour of the use of adjunctive minocycline for participants without systemic illness, less illness chronicity, and fewer adverse effects. Conclusion: Understanding the relationship between MDD and illness chronicity, comorbid systemic illness, and adverse effects, can potentially better characterise those individuals who are more likely to respond to adjunctive anti-inflammatory medications. [ABSTRACT FROM AUTHOR]

Although chronic lymphocytic leukemia (CLL) predominantly affects the elderly, limited data exists about the outcomes of over 80‐year‐old patients, usually underrepresented in clinical trials. We conducted a multicenter study enrolling 79 consecutive CLL patients ≥80 years at the time of frontline therapy, all treated with ibrutinib. Nearly 48% of cases exhibited unmutated IGHV genes, 32% 17p deletion, and 39.2% TP53 mutations; 63.3% displayed a cumulative illness rating scale (CIRS) > 6. The overall response rate on ibrutinib, computed in 74/79 patients (5 patients excluded for early withdrawal), was 89.9%. After a median follow‐up of 28.9 months, the median progression‐free survival (PFS) and overall survival (OS) were 42.5 and 51.8 months, respectively. CIRS>6 and temporary discontinuation of ibrutinib lasting for 7–30 days were the only parameters associated with a significantly shorter PFS and were both relevant in predicting a shorter PFS compared to patients with CIRS≤6 and therapy discontinuation ≤7 days. The most common grade≥3 adverse events were infections (25.5%), neutropenia (10.1%), and anemia (2.5%). Eighteen patients (22.8%) experienced a cardiovascular event, including grade‐2 atrial fibrillation (n = 9; 11%), grade‐2 hypertension (n = 5; 6%), heart failure (n = 3; 3%), and acute coronary syndrome (n = 1; 1%). Mild bleeding events were observed in 27 patients (34.2%). Ibrutinib was permanently discontinued in 26 patients due to progressive disease (n = 11, including 5 Richter's syndromes), secondary malignancies (n = 6), infections (n = 3), cardiac failure (n = 3), severe bleeding (n = 2), and sudden death (n = 1). In conclusion, our analyses confirmed the overall effectiveness and favorable safety profile of the ibrutinib‐single agent therapeutic approach in CLL patients ≥80 years. [ABSTRACT FROM AUTHOR]

People with bipolar disorder (BD) often present emotion dysregulation (ED), a pattern of emotional expression interfering with goal-directed behavior. ED is a transdiagnostic construct, and it is unclear whether it manifests itself similarly in other conditions, such as major depressive disorder (MDD) or borderline personality disorder (BPD), or has specific features in BD. The present systematic review and meta-analysis explored ED and adopted emotion regulation (ER) strategies in BD compared with other psychiatric conditions. PubMed/MEDLINE, EMBASE, Scopus, and PsycINFO databases were systematically searched from inception to April 28th, 2022. Studies implementing validated instruments assessing ED or ER strategies in BD and other psychiatric disorders were reviewed, and meta-analyses were conducted. Twenty-nine studies yielding multiple comparisons were included. BD was compared to MDD in 20 studies (n = 2451), to BPD in six studies (n = 1001), to attention deficit hyperactivity disorder in three studies (n = 232), to anxiety disorders in two studies (n = 320), to schizophrenia in one study (n = 223), and to post-traumatic stress disorder in one study (n = 31). BD patients did not differ from MDD patients in adopting most adaptive and maladaptive ER strategies. However, small-to-moderate differences in positive rumination and risk-taking behaviors were observed. In contrast, patients with BPD presented an overall higher degree of ED and more maladaptive ER strategies. There were insufficient data for a meta-analytic comparison with other psychiatric disorders. The present report further supports the idea that ED is a transdiagnostic construct spanning a continuum across different psychiatric disorders, outlining specific clinical features that could represent potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Twenty-five azole compounds (P1–P25) were synthesised using regioselective base-metal catalysed and microwave-assisted approaches, fully characterised by high-resolution mass spectrometry (HRMS), nuclear magnetic resonance (NMR), and infrared spectra (IR) analyses, and evaluated for anticancer, anti-tyrosinase, and anti-oxidant activities in silico and in vitro. P25 exhibited potent anticancer activity against cells of four skin cancer (SC) lines, with selectivity for melanoma (A375, SK-Mel-28) or non-melanoma (A431, SCC-12) SC cells over non-cancerous HaCaT-keratinocytes. Clonogenic, scratch-wound, and immunoblotting assay data were consistent with anti-proliferative results, expression profiling therewith implicating intrinsic and extrinsic apoptosis activation. In a mushroom tyrosinase inhibition assay, P14 was most potent among the compounds (half-maximal inhibitory concentration where 50% of cells are dead, IC50 15.9 μM), with activity greater than arbutin and kojic acid. Also, P6 exhibited noteworthy free radical-scavenging activity. Furthermore, in silico docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) simulations predicted prominent-phenotypic actives to engage diverse cancer/hyperpigmentation-related targets with relatively high affinities. Altogether, promising early-stage hits were identified – some with multiple activities – warranting further hit-to-lead optimisation chemistry with further biological evaluations, towards identifying new skin-cancer and skin-pigmentation renormalising agents. [ABSTRACT FROM AUTHOR]

Background: Emotion dysregulation (ED) is a transdiagnostic construct characterized by difficulties regulating intense emotions. People with bipolar disorder (BD) are more likely to show ED and use maladaptive emotion regulation strategies than adaptive ones. However, little is known about whether ED in BD is a trait or it is rather an epiphenomenon of mood symptoms. Methods: We conducted a systematic review and meta‐analysis of the evidence across major literature databases reporting correlations between measures of emotion regulation (overall ED and different emotion regulation strategies) and measures of depressive and (hypo)manic symptoms in BD from inception until April 12th, 2022. Results: Fourteen studies involving 1371 individuals with BD were included in the qualitative synthesis, of which 11 reported quantitative information and were included in the meta‐analysis. ED and maladaptive strategies were significantly higher during periods with more severe mood symptoms, especially depressive ones, while adaptive strategies were lower. Conclusion: ED significantly correlates with BD symptomatology, and it mainly occurs during mood alterations. ED may be a target for specific psychotherapeutic and pharmacological treatments, according to precision psychiatry. However, further studies are needed, including patients with mood episodes and longitudinal design, to provide more robust evidence and explore the causal direction of the associations. [ABSTRACT FROM AUTHOR]

Predominant Polarity (PP) is an established specifier of Bipolar Disorder (BD), holding significant clinical implications. Nevertheless, there exists no consensus on how to incorporate mixed states into PP, leaving patients prone to mixed recurrences that are unclassified. In a comprehensive study involving 701 euthymic BD patients, we sought to redefine PP by introducing a novel metric, the "mixed tendency", and establish a practical threshold to identify patients with a "mixed phenotype". Furthermore, we investigated potential associations between the mixed phenotype and specific PP categories. Our findings revealed that the mixed tendency correlated significantly with early BD type I, lifetime suicide attempts, self-aggressive behaviour, and lifetime number of affective episodes (>5). Using a ROC curve analysis, we determined an optimal cut-off point for the mixed tendency at 0.228, suggesting that patients with ~25% of lifetime mixed episodes relative to total affective episodes should be identified as having a mixed phenotype. Notably, the mixed phenotype was positively associated with undetermined PP and negatively with manic and depressive PP. This study introduces a promising approach to incorporating mixed episodes into the PP definition, potentially enabling tailored interventions for patients with a substantial history of mixed episodes. However, further research in large, longitudinal cohorts is essential to validate these findings. [ABSTRACT FROM AUTHOR]

In this paper we study the properties of an algorithm, introduced in Browkin (Math Comput 70:1281–1292, 2000), for generating continued fractions in the field of p-adic numbers Q p . First of all, we obtain an analogue of the Galois' Theorem for classical continued fractions. Then, we investigate the length of the preperiod for periodic expansions of square roots. Finally, we prove that there exist infinitely many square roots of integers in Q p that have a periodic expansion with period of length 4, solving an open problem left by Browkin in (Math Comput 70:1281–1292, 2000). [ABSTRACT FROM AUTHOR]

We investigated the influence of varying dietary polyunsaturated fatty acid (PUFA)/saturated fatty acids (SFA) ratios on insulin resistance (IR), fatty acid metabolism, N-acylethanolamine (NAE) bioactive metabolite levels, and mitochondrial function in lean and obese Zucker rats in a model designed to study obesity and IR from overnutrition. We provided diets with 7% fat (w/w), with either a low PUFA/SFA ratio of 0.48, predominantly comprising palmitic acid (PA), (diet-PA), or the standard AIN-93G diet with a high PUFA/SFA ratio of 3.66 (control, diet-C) over eight weeks. In obese rats on diet-PA versus diet-C, there were reductions in plasma triglycerides, cholesterol, glucose, insulin concentrations and improved muscle mitochondrial function, inflammatory markers and increased muscle N-oleoylethanolamine (OEA), a bioactive lipid that modulates lipid metabolism and metabolic flexibility. Elevated palmitic acid levels were found exclusively in obese rats, regardless of their diet, implying an endogenous production through de novo lipogenesis rather than from a dietary origin. In conclusion, a reduced dietary PUFA/SFA ratio positively influenced glucose and lipid metabolism without affecting long-term PA tissue concentrations. This likely occurs due to an increase in OEA biosynthesis, improving metabolic flexibility in obese rats. Our results hint at a pivotal role for balanced dietary PA in countering the effects of overnutrition-induced obesity. [ABSTRACT FROM AUTHOR]

The year 2021 witnessed the commemoration of the seven hundredth anniversary of Dante Alighieri's passing. Across the globe, particularly in Italy, a plethora of undertakings were orchestrated to honor this significant milestone. This paper undertakes an examination of the primary events that transpired in homage to Dante. In particular, in juxtaposition to prior centenaries, the authors center their analysis on initiatives that highlighted the rekindling of interest in Dante within Italy as the progenitor of the Italian language, his pivotal role in the establishment of an Italian collective identity, and the broader proliferation of his literary oeuvre. Concurrently, the authors delve into the dissemination and reception of the Dante anniversary on the international stage. [ABSTRACT FROM AUTHOR]

In a large class of porous elastic solids such as cement concrete, rocks, ceramics, porous metals, biological materials such as bone, etc., the material moduli depend on density. When such materials undergo sufficiently small deformations, the usual approach of appealing to a linearized elastic constitutive relation to describe their response will not allow us to capture the dependence of the material moduli on the density, as this would imply a nonlinear relationship between the stress and the linearized strain in virtue of the balance of mass as dependence on density implies dependence on the trace of the linearized strain. It is possible to capture the dependence of the material moduli on the density, when the body undergoes small deformations, within the context of implicit constitutive relations. We study the stress concentration due to a rigid elliptic inclusion within a new class of implicit constitutive relations in which the stress and the linearized strain appear linearly, that allows us to capture the dependence of the material moduli on the density. We find that the stress concentration that one obtains employing the constitutive relation wherein the material moduli depend on the density can be significantly different from that obtained by adopting the classical linearized elastic constitutive relation to which it reduces to when the density dependence of the material moduli are ignored. [ABSTRACT FROM AUTHOR]

Salmonella is one of the main zoonotic agents causing foodborne diseases in Europe. The main reservoirs of the infection are represented by domestic and wild animals, and the infection occurs by direct contact or following the consumption of contaminated food or water. The study aimed to evaluate the presence of Salmonella spp. in food-producing animals and irrigation waters in southern Italy and the serovar distribution. From 2011 to 2021, a total of 473 samples from 6 different animal species (bovine, buffalo, goat, ovine, swine, poultry, and wild boars) and 313 irrigation water samples were collected and analyzed. The overall percentage of positive samples was 56.87% in organs, 50.85% in feces, and 20.45% in irrigation waters. By animal species, the most frequently detected serovar was Salmonella Typhimurium in bovine (17.39%), in buffalo (13.10%) and swine (28.21%), and S. Kentucky (24.78%) in poultry. The subspecies diarizonaeIIIb was frequently detected in goats (40.00%) and ovine (83.33%), while salamaeII (14.12%) and diarizonaeIIIb (11.76%) were frequently isolated in wild boars. In the irrigation water samples, the most frequently detected serovar was S. Napoli (25%). Results revealed that, although in Europe, control strategies aimed at preventing the spread of Salmonella have been implemented, the prevalence of this pathogen in food-producing animals and irrigation waters is high. Considering the risk to public health associated with the contamination of products or foods, more stringent control interventions are needed at primary production and along the food chain. [ABSTRACT FROM AUTHOR]

The classical Pell equation can be extended to the cubic case considering the elements of norm one in , which satisfy The solution of the cubic Pell equation is harder than the classical case, indeed a method for solving it as Diophantine equation is still missing [3]. In this paper, we study the cubic Pell equation over finite fields, extending the results that hold for the classical one. In particular, we provide a novel method for counting the number of solutions in all possible cases depending on the value of r. Moreover, we are also able to provide a method for generating all the solutions. [ABSTRACT FROM AUTHOR]

The classical theory of continued fractions has been widely studied for centuries for its important properties of good approximation, and more recently it has been generalized to p-adic numbers where it presents many differences with respect to the real case. In this paper we investigate periodicity for the p-adic continued fractions introduced by Browkin. We give some necessary and sufficient conditions for periodicity in general, although a full characterization of p-adic numbers having purely periodic Browkin continued fraction expansion is still missing. In the second part of the paper, we describe a general procedure to construct square roots of integers having periodic Browkin p-adic continued fraction expansion of prescribed even period length. As a consequence, we prove that, for every n ≥ 1 , there exist infinitely many m ∈ Q p with periodic Browkin expansion of period 2 n , extending a previous result of Bedocchi obtained for n = 1 . [ABSTRACT FROM AUTHOR]

In this paper, we gather and take stock of the results produced by the Operational Earthquake Forecasting (OEF) system in Italy, during its first 10 yr of operativity. The system is run in real-time: every midnight and after each M L 3.5+ event, it produces the weekly forecast of earthquakes expected by an ensemble model in each cell of a spatial grid covering the entire Italian territory. To evaluate the performance skill of the OEF-Italy forecasts, we consider here standard tests of the Collaboratory for the Study of Earthquake Predictability, which have been opportunely adapted to the case of the overlapped weekly OEF forecasts; then we also adopt new performance measures borrowed from other research fields, like meteorology, specific to validate alarm-based systems by a binary criterion (forecast: yes/no; occurrence: yes/no). Our final aim is to: (i) investigate possible weaknesses and room for improvements in the OEF-Italy stochastic modelling, (ii) provide performance measures that could be helpful for stakeholders who act through a boolean logic (making an action or not) and (iii) highlight possible features in the Italian tectonic seismic activity. [ABSTRACT FROM AUTHOR]

Continued fractions have been introduced in the field of p-adic numbers Q p by several authors. However, a standard definition is still missing since all the proposed algorithms are not able to replicate all the properties of continued fractions in R . In particular, an analogue of the Lagrange's Theorem is not yet proved for any attempt of generalizing continued fractions in Q p . Thus, it is worth to study the definition of new algorithms for p-adic continued fractions. The main condition that a new method needs to fulfill is the convergence in Q p of the continued fractions. In this paper we study some convergence conditions for continued fractions in Q p . These results allow to define many new families of continued fractions whose convergence is guaranteed. Then we provide some new algorithms exploiting the new convergence condition and we prove that one of them terminates in a finite number of steps when the input is rational, as it happens for real continued fractions. [ABSTRACT FROM AUTHOR]

SUMMARY: We estimate the b-value parameter of the Gutenberg–Richter law for earthquake magnitudes in the early stage of the Costa Marchigiana (Italy) seismic sequence, starting on 2022 November 9, with an ML 5.7 event in the Adriatic sea. In particular, we estimate both the completeness magnitude Mc and the b-value within the first 4 and 7 d after the initial strong event in the sequence. Our work represents a practical example of b-value estimation in 'true' real time, that is, during the seismic sequence, and its possible interpretation in terms of short-term forecasting. We highlight some critical issues to consider both in estimating/intepreting the b-value, and in evaluating the real time estimation of Mc. These issues are mainly due to the fact that preliminary catalogues available in real time are quite different from the revised ones, which are usually delivered after a few months. The criticalities are linked to the raw data recorded at an early-stage, an unreliable evaluation of the Mc with statistical approaches, the Short Term Aftershock Incompleteness entailed after the initial strong event, and the magnitude binning. Our results show that real time estimation of the b-value can give insights into the evolution of an ongoing seismic sequence, when attention is paid to data quality and quantity. [ABSTRACT FROM AUTHOR]

Simple Summary: We prospectively analyzed COVID-19 morbidity and severity in 200 consecutive patients with CLL. Increased COVID-19 morbidity was observed in vaccinated patients with CLL. With a median follow-up of 23.4 months, 41% of patients experienced COVID-19. Most patients, 36.5%, experienced COVID-19 during the Omicron pandemic, 26% of patients were hospitalized, and 4% died. Moreover, 10% had re-infections. In multivariate analysis of elderly patients, TP53 disrupted, heavily pre-treated, and those in early treatment with targeted agents showed increased vulnerability to COVID-19. Given the persistent risk of infection due to the continuous emergence of SARS-CoV-2 variants, our results support the importance of new vaccines and protective measures to prevent and mitigate COVID-19 in patients with CLL. High morbidity and mortality due to COVID-19 were described in the pre-vaccination era in patients with chronic lymphocytic leukemia (CLL). To evaluate COVID-19 morbidity after the SARS-CoV-2 vaccine, we carried out a prospective study in 200 CLL patients. The median age of patients was 70 years; 35% showed IgG levels ≤ 550 mg/dL, 61% unmutated IGHV, and 34% showed TP53 disruption. Most patients, 83.5%, were previously treated, including 36% with ibrutinib and 37.5% with venetoclax. The serologic response rates to the second and third dose of the vaccine were 39% and 53%, respectively. With a median follow-up of 23.4 months, 41% of patients experienced COVID-19, 36.5% during the Omicron pandemic, and 10% had subsequent COVID-19 events. Severe COVID-19 requiring hospitalization was recorded in 26% of patients, and 4% died. Significant and independent factors associated with the response to the vaccine and vulnerability to COVID-19 were age (OR: 0.93; HR: 0.97) and less than 18 months between the start of targeted agents and vaccine (OR: 0.17; HR: 0.31). TP53 mutation and ≥two prior treatments also emerged as significant and independent factors associated with an increased risk of developing COVID-19 (HR: 1.85; HR: 2.08). No statistical difference in COVID-19 morbidity was found in patients with or without antibody response to the vaccine (47.5% vs. 52.5%; p = 0.21). Given the persistent risk of infection due to the continuous emergence of SARS-CoV-2 variants, our results support the importance of new vaccines and protective measures to prevent and mitigate COVID-19 in CLL patients. [ABSTRACT FROM AUTHOR]

Natural souvenirs collection has been identified as a driving force in biodiversity and habitat degradation of tropical marine ecosystems. This work considers this phenomenon in the Mediterranean region taking Sardinia (Italy), one of the most renowned tourism destinations, as a case study. The biological material seized at Cagliari‐Elmas Airport (years 2019–2020: 138 kg) was analyzed: 199 taxa were identified, gastropods (112 species, 7866 pieces) and bivalves (63 species, 34,218 pieces) resulted the most represented classes. Twenty‐two protected species were found in the tourists' luggage including Patella ferruginea and Pinna nobilis, the invertebrates most threatened with extinction in the Mediterranean Sea. This study demonstrates that the illegal collection of natural mementos is common in Sardinia, thus its relevance is not limited to tropical regions. Regulation, enforcement and compliance shortcomings emerged, highlighting the importance of strengthening stakeholders' collaboration for a deeper insight on this phenomenon and implementing effective conservation strategies. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to describe a cohort of fetuses with an ultrasound prenatal diagnosis of obliterated cavum septi pellucidi (oCSP) with the aim to explore the rate of associated malformations, the progression during pregnancy and the role of fetal magnetic resonance imaging (MRI). Material and methods: This was a retrospective multicenter international study of fetuses diagnosed with oCSP in the second trimester with available fetal MRI and subsequent ultrasound and/or fetal MRI follow-up in the third trimester. Where available, postnatal data were collected to obtain information on neurodevelopment. Results: We identified 45 fetuses with oCSP at 20.5 weeks (interquartile range 20.1-21.1). oCSP was apparently isolated at ultrasound in 89% (40/45) and fetal MRI found additional findings in 5% (2/40) of cases, including polymicrogyria and microencephaly. In the remaining 38 fetuses, fetal MRI found a variable amount of fluid in CSP in 74% (28/38) and no fluid in 26% (10/38). Ultrasound follow-up at or after 30 weeks confirmed the diagnosis of oCSP in 32% (12/38) while fluid was visible in 68% (26/38). At follow-up MRI, performed in eight pregnancies, there were periventricular cysts and delayed sulcation with persistent oCSP in one case. Among the remaining cases with normal follow-up ultrasound and fetal MRI findings, the postnatal outcome was normal in 89% of cases (33/37) and abnormal in 11% (4/37): two with isolated speech delay, and two with neurodevelopmental delay secondary to postnatal diagnosis of Noonan syndrome at 5 years in one case and microcephaly with delayed cortical maturation at 5 months in the other. Conclusions: Apparently isolated oCSP at mid-pregnancy is a transient finding with the visualization of the fluid later in pregnancy in up to 70% of cases. At referral, associated defects can be found in around 11% of cases at ultrasound and 8% at fetal MRI indicating the need for a detailed evaluation by expert physicians when oCSP is suspected. [ABSTRACT FROM AUTHOR]

The pollution caused by heavy metals (HMs) may occur through both natural processes and anthropogenic activities and is found in complex media. The purpose of this review is to summarize the state‐of‐art of fluorescent CDs and the sensing applications in a systematic manner. This review intends to provide clues on the origin on the observed selectivity in chemiluminiscence sensors, which was until now a stated but unaddressed question, and still remains open for debate. Indeed, it is tempting to think that CDs possessing functional groups with soft bases at the surface are able to detect soft metal acids, while the opposite is to be suspected for hard acid‐base pairs. However, the literature shows several examples where this trend does not hold. We found that such observation is explained by the involvement of dynamic quenching, which does not involve the formation of a non‐fluorescent complex, as in the case of static quenching. We have provided an interpretation of published data that was not provided by the original authors and offer guidelines to enable the design of CDs to target ions in solution. [ABSTRACT FROM AUTHOR]

Prempreesuk, Noppakaew, and Pongsriiam determined the Zeckendorf representation of the multiplicative inverse of 2 modulo F n , for every positive integer n not divisible by 3, where F n denotes the nth Fibonacci number. We determine the Zeckendorf representation of the multiplicative inverse of a modulo F n , for every fixed integer a ≥ 3 and for all positive integers n with gcd (a , F n) = 1 . Our proof makes use of the so-called base- φ expansion of real numbers. [ABSTRACT FROM AUTHOR]

The epidemiology of Salmonella Infantis is complex in terms of its distribution and transmission. The continuous collection and analysis of updated data on the prevalence and antimicrobic resistance are essential. The present work aimed to investigate the antimicrobial resistance and the correlation among S. Infantis isolates from different sources through the multiple-locus variable-number of tandem repeat (VNTR) analysis (MLVA). A total of 562 Salmonella strains isolated from 2018 to 2020 from poultry, humans, swine, water buffalo, mussels, cattle, and wild boar were serotyped, and 185 S. Infantis strains (32.92%) were identified. S. Infantis was commonly isolated in poultry and, to a lesser extent, in other sources. The isolates were tested against 12 antimicrobials, and a high prevalence of resistant strains was recorded. S. Infantis showed high resistance against fluoroquinolones, ampicillin, and tetracycline, which are commonly used in human and veterinary medicine. From all S. Infantis isolates, five VNTR loci were amplified. The use of MLVA was not sufficient to understand the complexity of the epidemiological relationships between S. Infantis strains. In conclusion, an alternative methodology to investigate genetic similarities and differences among S. Infantis strains is needed. [ABSTRACT FROM AUTHOR]

We study the state of stress and strain in a square plate containing an elliptic hole in the case of a porous elastic solid undergoing small strain, using a constitutive relation that has been put into place recently to describe the response of such solids undergoing small strains. We carry out the study by solving the problem numerically. We verify that our numerical solutions agree with those for the classical linearized elastic solid when certain appropriate material parameters are set to zero. We show that the stress concentration factor in the case of the porous elastic solid can be much higher, as much as 300% of the stress concentration in the case of the classical linearized elastic solid, when the aspect ratio is sufficiently small, depending on the values of certain material parameters. The difference between the stress concentration for the porous solid increases as the aspect ratio (the ratio of the major axis to the minor axis) decreases. By allowing the aspect ratio of the ellipse to go to zero, we can obtain the state of stress and strain adjacent to a crack in the square plate; however, in this limit, the strains would greatly exceed the assumption under which the constitutive theory is derived. [ABSTRACT FROM AUTHOR]

Background: Data from published studies about the effect of HFE polymorphisms on ALS risk, phenotype, and survival are still inconclusive. We aimed at evaluating whether the p.H63D polymorphism is a modifier of phenotype and survival in SOD1-mutated patients. Methods: We included 183 SOD1-mutated ALS patients. Mutations were classified as severe or mild according to the median survival of the study population. Patients were screened for the HFE p.H63D polymorphism. Survival was calculated using the Kaplan–Meier modeling, and differences were measured by the log-rank test. Multivariable analysis was performed with the Cox proportional hazards model (stepwise backward). Results: SOD1 severe mutation carriers show more frequent familial history for ALS and shorter survival compared to mild mutation carriers. Carriers and non-carriers of the p.H63D polymorphism did not differ in terms of sex ratio, frequency of positive familial history, age at onset, and bulbar/spinal ratio. In univariate and in Cox multivariable analysis using sex, age at onset, site of onset, family history, country of origin, and mutation severity as covariates, p.H63D carriers had a longer survival (p = 0.034 and p = 0.004). Conclusions: We found that SOD1-mutated ALS patients carrying the p.H63D HFE polymorphism have a longer survival compared to non-carriers, independently of sex, age and site of onset, family history, nation of origin, and severity of mutations, suggesting a possible role as disease progression modifier for the p.H63D HFE polymorphism in SOD1-ALS. [ABSTRACT FROM AUTHOR]

Simple Summary: In our study, we analyzed the role of CD44 expression as a prognostic marker in patients with metastatic colorectal cancer. CD44 is a multi-structural and multifunctional non-kinase transmembrane glycoprotein. Its expression is recognized as a molecular marker of cancer stem cells. Due to its role in the maintenance of stemness and the function of CSCs in tumor progression, CD44 could be an important prognostic marker. In our study, elevated CD44 expression correlated with more aggressive tumor behavior and poor prognostic features, suggesting its role as a novel prognostic marker and potential therapeutic target for mCRC patients. Background: The transmembrane glycoprotein CD44, the major hyaluronan (HA) receptor, has been proven to regulate cell growth, survival, differentiation, and migration. It is therefore widely considered to be involved in carcinogenesis. Its role as a new therapeutic target in solid tumors is under evaluation in clinical trials. The prognostic value remains controversial. Here, we aimed to investigate the correlation between CD44 expression and the clinicopathological features and survival in metastatic colorectal cancer (mCRC) patients. Methods: Data from 65 mCRC patients of the Medical Oncology Unit, University Hospital and University of Cagliari were retrospectively collected from 2008 to 2021. Immunohistochemical analysis was performed at the Pathology Division, University Hospital of Cagliari on 3 μm thick sections obtained from paraffin blocks. The intensity of immunohistochemical staining was subclassified into four groups: score 0 if negative or weak membrane staining in less than 10% of tumor cells; score 1+ if weak membrane staining in at least 10% of tumor cells or moderate membrane staining in less than 10% of tumor cells; score 2+ if moderate membrane staining in at least 10% of tumor cells or intensive membrane staining in less than 10% of tumor cells; score 3+ if intense membrane staining in at least 10% of tumor cells. Based on this score, we distinguished patients into low CD44 expression (score 0, 1+, 2+) and high CD44 expression (score 3+). Statistical analysis was performed with MedCalc (survival distribution: Kaplan–Meier; survival comparison: log-rank test; association between categorical variables: Fisher's exact test). Results: Patients' median age was 66 years (range 49–85). Regarding CD44 expression, score was 0 in 18 patients, 1+ in 15 patients, 2+ in 18 patients, and 3+ in 14 patients. Median overall survival (mOS) was 28.1 months (95%CI: 21.3–101). CD44 overexpression (3+) was correlated with poor prognosis (p = 0.0011; HR = 0.2), with a mOS of 14.5 months (95%CI 11.7 to 35.9) versus 30.7 months (95%CI 27.8 to 101) in lower CD44 expression. Higher CD44 expression was associated with clinically poor prognostic features: age ≥ 70 years (p = 0.0166); inoperable disease (p = 0.0008); stage IV at diagnosis (p = 0.0241); BRAF mutated (p = 0.0111), high-grade tumor (p = 0.0084). Conclusions: CD44 markedly correlated with aggressive tumor behavior and contributed to the earlier progression of disease, thus suggesting its role as a novel prognostic marker and potential therapeutic target for mCRC patients. [ABSTRACT FROM AUTHOR]

The septum pellucidum is a virtual cavity located at the anterior part of the brain midline, which only in fetal life has a certain amount of fluid inside. The presence of an obliterated cavum septi pellucidi (oCSP) in the prenatal period is poorly described in the literature but, nevertheless, it constitutes an important clinical dilemma for the fetal medicine specialist in terms of significance and prognosis. Moreover, its occurrence is increasing maybe because of the widespread of high-resolution ultrasound machine. The aim of this work is to review the available literature regarding the oCSP along with the description of a case-report of oCSP with an unexpected outcome. A search of the literature through Pubmed was performed up to December 2022 with the aim to identify all cases of oCSP previously described, using as keywords "cavum septi pellucidi," "abnormal cavum septi pellucidi," "fetus," and "septum pellucidum." Along with the narrative review, we describe a case-report of oCSP. A 39 years old woman was diagnosed with a nuchal translucency between the 95° and 99° centile in the first trimester and an oCSP and "hookshaped" gallbladder at 20 weeks. Left polymicrogyria was found at fetal magnetic resonance imaging (MRI). Standard karyotype and chromosomal microarray analysis (CMA) were normal. After birth, the newborn presented signs of severe acidosis, untreatable seizures and multiorgan failure leading to death. A targeted gene analysis of the epilepsy panel revealed the presence of a de novo pathogenic variant involving the PTEN gene. The literature review identified four articles reporting on the oCSP of which three were case report and one was a case-series. The reported rate of associated cerebral findings is around 20% and the rate of adverse neurological outcome is around 6%, which is higher than the background risk of the general population. This case-report and review of the literature shows that oCSP is a clinical entity poorly described so far and that, despite the generally good prognosis, it requires caution in counseling. The diagnostic work-up should include neurosonography while fetal MRI may be always indicated for non-isolated cases only, depending on local facilities. Targeted gene analysis or whole exome sequencing may be indicated for non-isolated cases. [ABSTRACT FROM AUTHOR]

In this paper, we carry out a comparison analysis of the Epidemic Type Aftershock Sequence (ETAS) model for the earthquake process, embedded with the three main exponential-type distributions adopted in practical applications to describe the magnitudes of seismic events, that are, the Gutenberg–Richter (GR), the tapered Gutenberg–Richter (TGR) and the CHaracteristic (CH) frequency–magnitude distributions (FMDs). The first law is a pure-power decreasing function, while both the other two introduce a more rapid decay in the tail of the distribution: a soft taper in the TGR model and a sharp cut-off in the CH one. To perform the comparison, we first investigate some theoretical features of the ETAS model with CH-distributed magnitudes (ETAS-CH), which have not been deeply analysed in the literature as much as for ETAS-TGR and ETAS-GR. In particular, we explicitly compute the branching ratio, we analyse its asymptotics in relation to its parameters, and we derive the proper stability conditions. We then move to the comparison among the three ETAS-GR, ETAS-TGR and ETAS-CH processes, to highlight differences and similarities. This is done by carrying out both a theoretical analysis, mainly focused on the three models' branching ratios and the relative sensitivity, and a simulation analysis of realistic synthetic catalogues to compare the processes' numbers, events' magnitude distribution and temporal evolution. The results we obtained show that the ETAS-TGR and ETAS-CH processes have very similar features. They both have also less restrictive non-explosion conditions than for ETAS-GR; in fact, differently from this latter case, their branching ratios exist for any value of the parameters and are lower than the one of ETAS-GR, to which they converge for large magnitudes. [ABSTRACT FROM AUTHOR]

Fenofibrate (FBR), an oral medication used to treat dyslipidemia, is a ligand of the peroxisome proliferator-activated receptor α (PPARα), a nuclear receptor that regulates the expression of metabolic genes able to control lipid metabolism and food intake. PPARα natural ligands include fatty acids (FA) and FA derivatives such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), known to have anti-inflammatory and anorexigenic activities, respectively. We investigated changes in the FA profile and FA derivatives by HPLC and LC-MS in male C57BL/6J mice fed a standard diet with or without 0.2% fenofibrate (0.2% FBR) for 21 days. Induction of PPARα by 0.2% FBR reduced weight gain, food intake, feed efficiency, and liver lipids and induced a profound change in FA metabolism mediated by parallel enhanced mitochondrial and peroxisomal β-oxidation. The former effects led to a steep reduction of essential FA, particularly 18:3n3, with a consequent decrease of the n3-highly unsaturated fatty acids (HUFA) score; the latter effect led to an increase of 16:1n7 and 18:1n9, suggesting enhanced hepatic de novo lipogenesis with increased levels of hepatic PEA and OEA, which may activate a positive feedback and further sustain reductions of body weight, hepatic lipids and feed efficiency. [ABSTRACT FROM AUTHOR]

One of the main issues in the treatment of patients with chronic lymphocytic leukemia (CLL) deals with the choice between continuous or fixed-duration therapy. Continuous ibrutinib (IB), the first-in-class BTK inhibitor, and obinutuzumab-chlorambucil (G-CHL) are commonly used therapies for elderly and/or comorbid patients. No head-to-head comparison has been carried out. Within the Italian campus CLL network, we performed a retrospective study on CLL patients without TP53 disruption treated with IB or G-CHL as first-line therapy. Patients in the G-CHL arm had a higher CIRS score and the worst renal function. The overall response rates between the GCHL and IB arms were similar, but more complete remissions (CRs) were achieved with G-CHL (p = 0.0029). After a median follow-up of 30 months, the progression-free survival (PFS, p = 0.0061) and time to next treatment (TTNT, p = 0.0043), but not overall survival (OS, p = 0.6642), were better with IB than with G-CHL. Similar results were found after propensity score matching and multivariate analysis. While PFS and TTNT were longer with IB than with G-CHL in IGHV unmutated patients (p = 0.0190 and 0.0137), they were superimposable for IGHV mutated patients (p = 0.1900 and 0.1380). In the G-CHL arm, the depth of response (79% vs. 68% vs. 38% for CR, PR and SD/PD; p < 0.0001) and measurable residual disease (MRD) influenced PFS (78% vs. 53% for undetectable MRD vs. detectable MRD, p = 0.0203). Hematological toxicities were common in the G-CHL arm, while IB was associated with higher costs. Although continuous IB provides better disease control in CLL, IGHV mutated patients and those achieving an undetectable MRD show a marked clinical and economic benefit from a fixed-duration obinutuzumabbased treatment. [ABSTRACT FROM AUTHOR]

HIV-HCV co-infected patients have long been considered difficult-to-treat. The introduction of direct-acting antivirals (DAAs) changed this paradigm.We evaluated the efficacy and safety of DAA-based regimens and the impact of DAAs-induced HCV clearance on the immunological status in HIV-HCV co-infected patients. HIV patients starting HCV treatment with DAAs were included. Sustained virological response at 12 weeks after DAAs treatment (SVR12) was assessed. CD4+ and CD8+ blood cell count and CD4+/CD8+ ratio were recorded at baseline and six months post DAA treatment. We enrolled 201 patients, 76.1% males, median age 54 years, the most common genotypes 3 (29.8%) and 1a (29.4%), 40.3% with cirrhosis, 32.3% with prior interferon-based treatment. All patients were on antiretroviral treatment, 24.4% on methadone maintenance therapy and 22.6% on psychotropic drugs. SVR12 was 98.4%, the most common side effects were pruritus (8.4%), headache (7.4%) and fatigue (5.9%). An increase in CD4+ and CD8+ cell count was observed six months after completion of DAAs treatment, in particular in patients with low CD4+ cell count at baseline. DAAs treatment resulted in high SVR12 rates, was well tolerated and Increased CD4+ and CD8+, especially in patients with low CD4+ cell count at baseline. [ABSTRACT FROM AUTHOR]

The deterioration of oil-based products during processing, distribution and storage has a major negative impact on the industry from an economic point of view. The spoilage of oil is mainly due to its oxidation which can be triggered by various factors, such as UV light, heating or the presence of impurities that result in the formation of radical species. In this context, several packaging alternatives have recently been developed with the aim to protect and extend the shelf life of oil-based products. This work aimed to study the antioxidant properties of bio-polymer-based films (BPFs) obtained from high methoxylated pectin (HMP) and sodium caseinate (CAS) and enriched with different concentrations of green carbon dots (gCDs), 0.25%, 0.50 and 1% w/w, obtained from apple pomace (APCDs) and rosemary powder (RCDs). The resulting films (gCDs-BPFs) have shown that the presence of gCDs not only modified the surface roughness of the films, but also positively affected their antioxidant properties. The addition of gCDs enhanced the radical inhibiting capacity of the raw BPFs by 42 and 62% for the films containing 1% RCDs and 1% APCDs, respectively. As a proof of the concept, two oil samples (edible and cosmetic) were treated with the obtained antioxidant films, and the results demonstrated that in both types of samples the oxidation process was minimized during the five days of the experiment. These results are promising and suggest that the antioxidant bio-polymer-based films could be excellent candidates for further production of active packaging. [ABSTRACT FROM AUTHOR]