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Purpose: This research aims to develop a meta-machine learning model to optimize soil and nitrogen management for durum wheat in Italy. It addresses the challenges of increased food production on limited land amidst rising input costs, geopolitical changes, and climate change. The goal is to aid decision-makers in achieving maximum crop yield and income margins through effective agronomic strategies. Methods: The study developed a meta-machine learning model, integrating classification and regression models, and tested it at four sites in Marche and Basilicata, Italy, over several years. The model incorporated data from remote sensing, crop phenology, soil chemical properties, weather data, soil management, and nitrogen levels. A Random Forest model was used to classify crop phenology, while a Neural Network model predicted yield. Eleven nitrogen levels were compared across these sites. Results: The Random Forest model achieved an accuracy of 0.98, kappa of 0.96, and recall of 0.98 for predicting crop phenology. The Neural Network model for yield prediction had an R squared of 0.90 and a Root Mean Square Error of 0.59 t ha-1. Key factors identified for model accuracy were temperature, precipitation, NDVI, and nitrogen input. Simulations of 30 soil management and fertilization combinations revealed that no-tillage management increased grain yield. The Marginal Fertilizer Yield Index determined optimal nitrogen application. Conclusions: The meta-machine learning model accurately predicted durum wheat yield and identified effective agronomic strategies, demonstrating the potential for broader application in field conditions. The model offers a promising approach to sustainable agriculture and climate change mitigation by utilising publicly available spatial datasets. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholangiocarcinoma is a biliary neoplasm usually showing a dismal prognosis. In early stages, surgical resection is the best treatment option, significantly increasing the overall survival. This approach is also recommended in the case of relapsing disease. In this study, we report the case of a patient affected by intrahepatic cholangiocarcinoma with multiple relapses and still alive for over 18 years. We also provide a systematic review regarding long-survivor (> 60 months) of intrahepatic cholangiocarcinoma. Case Presentation: A 41-year-old woman with no pathological history was diagnosed with localized intrahepatic cholangiocarcinoma and surgically treated with left hepatectomy. After the first intervention, the patients underwent three further surgical resections because of locoregional recurrences. Histologically, there were some significant similarities among all neoplasms, including the tubule-glandular architecture, but also morphological heterogeneity. The tumor immune microenvironment remained stable across the different lesions. The molecular analysis with next-generation sequencing demonstrated that all neoplasms shared the same genomic profile, including NBN and NOTCH3 mutations and chromosomes 1 and 3 alterations. Conclusions: This case study highlights the essential role of a stringent follow-up after resection of intrahepatic cholangiocarcinoma for detecting early relapsing tumors. Moreover, it shows the importance of the molecular characterization of multiple tumors for understanding their real nature. The accurate study of long-surviving patients highlights the features that are critical for outcome improvement. [ABSTRACT FROM AUTHOR]

The article published in EJNMMI Research explores the impact of fasting on biodistribution and tumor uptake in patients undergoing 18F-rhPSMA-7.3 PET/CT imaging for prostate cancer. The study found that fasting did not significantly affect the uptake of tumor lesions, but there were differences in organ uptake, particularly in the salivary glands, pancreas, and duodenum. The findings suggest that fasting may not be necessary before 18F-rhPSMA-7.3 PET imaging. The study was conducted by a team of researchers led by Sonia Grigorascu and Matthias Eiber. [Extracted from the article]

This review investigated the effectiveness of robotic-assisted gait training (RAGT) in improving gait and balance performance in adults with multiple sclerosis (MS). Databases and registers were searched from inception to December 2023 to identify randomized controlled trials (RCTs) that analyzed the effects of RAGT on gait speed, function, balance, fatigue, and adverse events. Three reviewers screened studies for eligibility and extracted key information such as participants and intervention characteristics, as well as outcomes of interest. The reviewers assessed the risk of bias of included studies using Cochrane Risk of Bias tool. From the 948 records identified, 8 RCTs were included, involving 335 participants. The studies have demonstrated significant heterogeneity in patient characteristics, intervention protocols, and outcomes measured. The risk of bias assessment revealed concerns, mainly in terms of performance and detection bias. The evidence is uncertain on the effectiveness of RAGT on balance and gait in people with MS, but a multimodal rehabilitation approach, including RAGT, should be encouraged. No serious adverse events seem to be associated with RAGT, suggesting that these interventions are generally safe for use in people with MS. Further studies of higher methodological quality should be led to confirm these positive results. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases are common causes of impaired mobility and cognition in the elderly. Among them, tauopathies and α-synucleinopathies were considered. The neurodegenerative processes and relative differential diagnosis were addressed through a qEEG non-linear analytic method. Study aims were to test accuracy of the power law exponent β applied to EEG in differentiating neurodegenerative diseases and to explore differences in neuronal connectivity among different neurodegenerative processes based on β. N = 230 patients with a diagnosis of tauopathy or α-synucleinopathy and at least one artifact-free EEG recording were selected. Periodogram was applied to EEG signal epochs from continuous recordings. Power law exponent β was determined by the slope of the signal power spectrum versus frequency in logarithmic scale. A data-driven clustering based on β values was performed to identify independent subgroups. Data-driven clustering based on β differentiated tauopathies (overall lower β values) from α-synucleinopathies (higher β values) with high sensitivity and specificity. Tauopathies also presented lower values in the correlation coefficients matrix among frontal sites of recording. In conclusion, significant differences in β values were found between tauopathies and α-synucleinopathies. Hence, β is proposed as a possible biomarker of differential diagnosis and neuronal connectivity. [ABSTRACT FROM AUTHOR]

Background: The optimal regimen for 177Lu-labeled prostate-specific membrane antigen-targeted radioligand therapy, including treatment intervals, remains under study, with evidence suggesting shorter intervals could benefit patients with high disease volume and rapid progression. This retrospective analysis evaluated treatment toxicity, PSA response, PSA-progression-free survival (PSA-PFS), and overall survival (OS) in matched cohorts of mCRPC patients receiving 177Lu-PSMA-RLT at 4-week versus 6-week intervals. Results: A PSA response (PSA decline ≥ 50%) was achieved in 47.8% and 21.7% of patients in the 4-week and 6-week treatment interval groups, respectively (p = 0.12). There was a trend towards longer PSA-PFS in the 4-week group compared to the 6-week group (median PSA-PFS, 26.0 weeks vs. 18.0 weeks; HR 0.6; p = 0.2). Although not statistically significant, there was a trend towards shorter OS in the 4-week group compared to the 6-week group (median OS, 15.1 months vs. 18.4 months; HR 1.3; p = 0.5). The 4-week group had a significantly greater decrease in leucocyte and platelet counts compared to the 6-week group (38.5% vs. 18.2% and 26.7% vs. 10.7%; p = 0.047 and p = 0.02). Severe adverse events were modest in both groups. Conclusions: Intensifying treatment intervals from 6 weeks to 4 weeks showed some improvements in PSA response and PSA-PFS for mCRPC patients, but did not significantly affect OS. Additionally, bone marrow reserve was significantly reduced with the intensified regimen. Therefore, the overall benefit remains uncertain, and further prospective studies are needed to compare 4-week and 6-week intervals regarding toxicity, treatment response, and outcome. [ABSTRACT FROM AUTHOR]

Quality assessment in healthcare systems is challenging due to the multidimensional nature of healthcare services. This study evaluates the overall quality provided by hospitals using composite indicators under the Benefit of the Doubt (BoD) approach, which determines the weights of the indicators with minimal assumptions. We used data from 2015-2020 for Italian Local Health Authorities (LHAs) for 21 outcome measures, applying various non-parametric methods to address aggregation and weighting challenges. Our results show that the BoD measures are robust and effectively capture the dynamics of the quality of LHA, even during external shocks such as the COVID-19 pandemic. This research highlights the importance of methodological choices in the construction of composite indicators and demonstrates the effectiveness of the BoD approach in providing a comprehensive measure of healthcare quality. [ABSTRACT FROM AUTHOR]

New technologies are increasingly widespread in medical practice. Particularly, the 3D view is considered among the most useful innovations for surgery. It allows the operator to reconstruct the patient's anatomy in his own mind, going beyond his personal imagination. In the last few years, a new facility has been experienced, it's the Exoscopy. Exoscopy is a magnified vision system, similar to Microscopy, but which also allows a tridimensional vision of the surgical anatomy. Despite Exoscopy having been used for years in Neurosurgery, it has been just rarely described in parotid surgery. We intend to report our experience with Exoscope Aesculap AEOS used to remove benign tumors of the parotid gland. We treated 14 patients with benign tumors of the parotid gland, since September 2023 to November 2023. Each surgery was conducted by the same expert surgeon which also reported his experience about intra-operative complications (as bleeding) in comparison to the traditional procedure without Exoscope. We evaluated the learning curve of Exoscope-Assisted Parotid Surgery comparing, among them, the operative times of the same procedures performed in chronological order. Each patient underwent the same follow-up which included three checks at one month, three months and six months. The follow-up was especially about the evaluation of palsy of the VII C.N. which was assessed through House-Brackmann score (H-B score). The results of our experience reports that the Exoscope is a useful tool for parotid gland surgery. It allows an excellent visualization of the facial nerve main trunk and its branches. Although the first procedures presented longer times in comparison to traditional surgery, the progressive reduction of the operative times demonstrates that the learning curve of Exoscopy is very fast. Certainly, more experience is required for the full introduction of Exoscopy in surgery practice of parotid gland but, now, its potentialities are highly exciting. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to compare treatment efficacy and cephalometric outcomes between extraction and non-extraction MEAW therapies in non-growing open-bite patients. Materials and methods: 22 Multiloop Edgewise Archwire MEAW patients (11 males, 11 females) and 15 bicuspid extraction patients (3 males, 12 females) were selected according to a strict inclusion criterion. Comprehensive data collection related to age, sex, Cervical Vertebral Maturation CVM staging, and severity of the Anterior Open Bite AOB (1 = 0–1 mm; 2 = 1–2 mm; 3 = > 2.1 mm) was performed independently and in duplicate by 2 examiners. Each included patient’s pre and post-treatment lateral cephalograms were traced and compared. The primary outcomes assessed were related to the efficacy of treatment: treatment duration and time needed to achieve a positive overbite. The secondary outcomes assessed were related to the post-treatment changes in cephalometric measurements between the groups. Descriptive statistics, Mann-Whitney U test, unpaired student’s t-test, and Chi-squared were used for data analysis. Results: The mean change in open bite closure was 3.07 ± 2.07 mm in the MEAW group and 3.03 ± 2.28 mm in the extraction group (P > 0.05). MEAW therapy was 31% faster (118 weeks) than extraction therapy (171 weeks, P = 0.004). MEAW appliance showed a significantly shorter duration for open bite closure (71.82 ± 29.57 weeks) compared to the extraction group (127.25 ± 51.97 weeks, P = 0.002). A greater decrease in the U1-SN was seen in the extraction group (-8.70 ± 6.49°), compared to the MEAW group (-2.56 ± 7.36°, P = 0.047). The IMPA angle showed a greater decrease in the extraction group (-8.30 ± 8.85°) compared to the MEAW group (-0.90 ± 6.50°, P = 0.032). The (L6-MP perp) increased in the extraction group by (1.98 ± 3.43 mm), while decreased in the MEAW group (-0.43 ± 1.38 mm, P = 0.023). Conclusion: In anterior open bite cases with bicuspid extraction, achieving a positive overbite typically involves retroclining and uprighting the upper and lower incisors (drawbridge effect). In contrast, the MEAW appliance focuses on uprighting the entire dentition and intruding the posterior teeth, often leading to shorter treatment durations. Clinical relevance: The MEAW appliance’s biomechanical advantage in uprighting posterior teeth in open bite cases may shorten treatment duration for correcting open bite malocclusion. [ABSTRACT FROM AUTHOR]

In this paper, the mechanical properties of a modified Body-Centred Cubic lattice cell with waved struts have been determined using FEM simulations with solid element mesh. The strut waviness introduces orthotropic properties in the cell and the correlation between geometrical cell parameters and resulting mechanical attitudes is calculated. For a complete determination of all the mechanical constants, uniaxial compression and in-plane shear have been simulated along different loading directions. Attention has been particularly paid to the definition of appropriate boundary constraints able to mimic the periodic condition that applies to a repetitive unit cell. At first, the numerical model has been validated with existing analytical and experimental results available in the literature, then parametric strut waviness has been introduced to this model. A systematic numerical study has been conducted on lattice cells with different density and different wave amplitude. Results have evidenced for the waved struts a considerable increase in the longitudinal uniaxial modulus and a negligible effect on the transverse moduli, while a slight reduction of the shear moduli is generally obtained in all the sliding planes. Poisson's ratios are highly affected both by density and waviness. The obtained results can be useful for the optimized definition of a lattice cell, tailored to the specific mechanical requirements of an advanced component. [ABSTRACT FROM AUTHOR]

Parkinson's Disease (PD) body-first subtype is characterized by prodromal autonomic symptoms and REM sleep behavior disorder (RBD), symmetric dopaminergic degeneration, and increased risk of dementia. On the other hand, the PD brain-first subtype has fewer non-motor symptoms and a milder motor phenotype. The temporal relationship between RBD onset and motor symptoms onset may differentiate these two subtypes. We aimed to investigate electrocortical differences between brain-first and body-first PD patients. PD patients with an available routinely collected EEG were retrospectively selected. RBD was diagnosed using the RBD screening questionnaire (≥ 6). According to the onset of RBD patients were classified into PD-RBDpre (RBD onset before motor symptoms) and PD-RBDpost (RBD onset after motor symptoms). Patients without RBD were classified as PD-RBD-. Presence of Mild Cognitive Impairment (MCI) was diagnosed according to the MDS criteria. EEG Spectral analysis was performed in resting state by computing the Power Spectral Density (PSD) of site-specific signal epochs for the common frequency bands (delta, theta, alpha, beta). Thirty-eight PD-RBD-, 14 PD-RBDpre and 31 PD-RBDpost patients were recruited. Comparing both global and site-specific absolute values, we found a significant trend toward beta band reduction going from PD-RBD-, PD-RBDpost and PD-RBDpre. No significant differences were found between PD-RBDpost and PD-RBD- patients. PD-RBDpre patients may represent a different subset of patients as compared to patients without RBD, while patients with later onset have intermediate EEG spectral features. Quantitative EEG may provide new hints in PD subtyping. [ABSTRACT FROM AUTHOR]

Background and objective: Treatment planning through the diagnostic dimension of theranostics provides insights into predicting the absorbed dose of RPT, with the potential to individualize radiation doses for enhancing treatment efficacy. However, existing studies focusing on dose prediction from diagnostic data often rely on organ-level estimations, overlooking intra-organ variations. This study aims to characterize the intra-organ theranostic heterogeneity and utilize artificial intelligence techniques to localize them, i.e. to predict voxel-wise absorbed dose map based on pre-therapy PET. Methods: 23 patients with metastatic castration-resistant prostate cancer treated with [177Lu]Lu-PSMA I&T RPT were retrospectively included. 48 treatment cycles with pre-treatment PET imaging and at least 3 post-therapeutic SPECT/CT imaging were selected. The distribution of PET tracer and RPT dose was compared for kidney, liver and spleen, characterizing intra-organ heterogeneity differences. Pharmacokinetic simulations were performed to enhance the understanding of the correlation. Two strategies were explored for pre-therapy voxel-wise dosimetry prediction: (1) organ-dose guided direct projection; (2) deep learning (DL)-based distribution prediction. Physical metrics, dose volume histogram (DVH) analysis, and identity plots were applied to investigate the predicted absorbed dose map. Results: Inconsistent intra-organ patterns emerged between PET imaging and dose map, with moderate correlations existing in the kidney (r = 0.77), liver (r = 0.5), and spleen (r = 0.58) (P < 0.025). Simulation results indicated the intra-organ pharmacokinetic heterogeneity might explain this inconsistency. The DL-based method achieved a lower average voxel-wise normalized root mean squared error of 0.79 ± 0.27%, regarding to ground-truth dose map, outperforming the organ-dose guided projection (1.11 ± 0.57%) (P < 0.05). DVH analysis demonstrated good prediction accuracy (R2 = 0.92 for kidney). The DL model improved the mean slope of fitting lines in identity plots (199% for liver), when compared to the theoretical optimal results of the organ-dose approach. Conclusion: Our results demonstrated the intra-organ heterogeneity of pharmacokinetics may complicate pre-therapy dosimetry prediction. DL has the potential to bridge this gap for pre-therapy prediction of voxel-wise heterogeneous dose map. [ABSTRACT FROM AUTHOR]

Blinatumomab is a bispecific T-cell engager approved for relapsed/refractory and minimal residual disease positive B-cell Acute Lymphoblastic Leukemia. We conducted a retrospective study evaluating the outcome of Blinatumomab. The impact of clinical and treatment-related variables on cumulative incidence of relapse/progression (CIRP), event-free (EFS) and overall survival (OS) was analyzed. From January 2016 to December 2022 50 Ph'- (37) and Ph+ (13) B-ALL patients received Blinatumomab. The median age was 37. Indications to blinatumomab were relapsed/refractory B-ALL in 29 and MRD-positive in 21 patients. Blinatumomab was the 2nd and 3rd line in 40 and in 10 patients, respectively. Twenty patients were treated pre-transplantation, ten were treated for relapse after transplant, twenty were not eligible for transplant. Out of 29 patients treated for relapsed/refractory disease, 16 (55%) achieved complete response and 12 achieved MRD-negativity. Out of 21 patients treated for MRD, 16 (76%) achieved MRD-negativity. At a median follow-up of 46 months the median EFS and OS were 11.5 and 16.2 months. The CIRP was 50%. In univariate analysis age, disease-status (overt vs. minimal disease) at blinatumomab, bridging to transplant after blinatumomab and MRD-response resulted significant for EFS and OS. In multivariate analysis only disease-status and MRD-response retained significance both for EFS and OS. Disease-status and MRD-response resulted significant for EFS and OS also after censoring at HSCT. This retrospective study on B-ALL patients treated with blinatumomab confirms a superior outcome for MRD-responsive over MRD non-responsive patients. Survival depends also on the disease-status prior treatment. [ABSTRACT FROM AUTHOR]

Experimental economics is, nowadays, a well-established approach to investigate agents' behavior under economic incentives. In the last decade, a fast-growing number of studies have focused on the application of experimental methodology to health policy issues. The results of that stream of literature have been intriguing and strongly policy oriented. However, those findings are scattered between different health-related topics, making it difficult to grasp the overall state-of-the-art. Hence, to make the main contributions understandable at a glance, we conduct a systematic literature review of laboratory experiments on the supply of health services. Of the 1248 articles retrieved from 2011, 56 articles published in peer-review journals have met our inclusion criteria. Thus, we have described the experimental designs of each of the selected papers and we have classified them according to their main area of interest. [ABSTRACT FROM AUTHOR]

The addition of metastasis-directed radiotherapy (MDRT) to immunotherapy in patients with advanced urothelial carcinoma (aUC) has shown promising results. We report the real-world data from the ARON-2 study (NCT05290038) on the impact of conventional (CRT) or stereotactic body radiotherapy (SBRT) on the outcome of aUC patients receiving pembrolizumab after platinum-based-chemotherapy. Medical records of 837 patients were reviewed from 60 institutions in 20 countries. Two hundred and sixty-two patients (31%) received radiotherapy (cohort A), of whom 193 (23%) received CRT and 69 (8%) received SBRT. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. With a median follow-up of 22.7 months, the median OS was 10.2 months, 6.8 months and 16.0 months in no RT, CRT and SBRT subgroups (p = 0.005), with an 1y-OS rates of 47%, 34% and 61%, respectively (p < 0.001). The 1y-OS rate in the SBRT subgroup were significantly higher for both lower (63%) and upper tract UC (68%), for pure urothelial histology (63%) and variant histologies (58%), and for patients with bone (40%) and lymph-node metastases (61%). Median PFS was 4.8 months, 9.6 months and 5.8 months in the CRT, SBRT and no RT subgroups, respectively (p = 0.060). The 1y-PFS rate was significantly higher (48%) in the SBRT population and was confirmed in all patient subsets. The difference in terms of ORR was in favour of SBRT. Our real-world analysis showed that the use of SBRT/pembrolizumab combination may play a role in a subset of aUC patients to increase disease control and possibly overall survival. [ABSTRACT FROM AUTHOR]

Objective: This study compared clinical outcomes between aligners and fixed appliances in class II adolescent patients. Materials and methods: Records of 31 aligners and 35 fixed class II patients, aged 13.5 ± 1.6 years were compared. Class II elastics was the mechanism employed for correcting the malocclusion. DI scores were used to compare initial complexity, and the PAR index scores were used to compare the clinical outcomes. Data on demographics, treatment and finishing durations, number of visits and refinements, duration of class II correction, and changes in the IMPA were collected. Results: The mean pre-, post-treatment, and overall reduction in PAR index scores between the groups were not significantly different (P > 0.05). The clear aligners group had significantly shorter treatment duration (20.0 ± 11.6 months) than the fixed group (27.4 ± 9.1 months) (P < 0.001). The number of visits for the aligners’ group was significantly less (12.7 ± 6.2) than in the fixed group (17.8 ± 5.8) (P < 0.001). Duration for class II correction was significantly shorter for clear aligners (13.3 ± 10.0 months) compared to the fixed group (17.4 ± 9.0 months) (P = 0.026). A smaller post-treatment change in IMPA (2 ± 6°) was detected in the aligners group compared to the fixed group (5 ± 6°) (P < 0.05). Conclusions: Treatment outcomes for aligners in class II adolescent patients were comparable to those achieved in fixed appliances. Shorter treatment and class II correction durations, fewer visits, and better control for the IMPA were noticed in the aligners’ group. Clinical relevance: Treating class II adolescent patients with aligners seems promising and demands shorter treatment time and fewer visits. [ABSTRACT FROM AUTHOR]

In accordance with the framework of the Circular Blue Bioeconomy in the Mediterranean region, the objective of this study was to evaluate the biotransformation of blue swimming crab (Portunus segnis) residues obtained from the port of Sfax by an extracellular chitinase produced by Nocardiopsis halophila strain TN-X8 isolated from Chott El Jerid (Tozeur, Tunisia). From the analysis of multiple extremophilic Actinomycetota, it was determined that strain TN-X8 exclusively utilized 60 g/L of raw blue swimming crab as its carbon and energy source, achieving a chitinase activity of approximately 950 U/mL following a 6-day incubation period at 40 °C. Pure chitinase, designated as ChiA-Nh30, was obtained after heat treatment, followed by ammonium sulfate fractionation and Sephacryl® S-200 column chromatography. The maximum ChiA-Nh30 activity was observed at pH 3 and 75 °C. Interestingly, compared with cyclohexamidine, ChiA-Nh30 showed a good antifungal effect against four pathogenic fungi. Furthermore, when using colloidal chitin as substrate, ChiA-Nh30 demonstrated a higher degree of catalytic efficiency than the commercially available Chitodextrinase®. In addition, ChiA-Nh30 could be immobilized by applying encapsulation and encapsulation-adsorption techniques. The kaolin and charcoal used acted as excellent binders, resulting in improved ChiA-Nh30 stability. For the immobilized ChiA-Nh30, the yield of N-acetyl-d-glucosamine monomers released from 20% (w/v) blue swimming crab residues increased by 3.1 (kaolin) and 2.65 (charcoal) times, respectively. [ABSTRACT FROM AUTHOR]

Male infertility is a major public health concern globally with unknown etiology in approximately half of cases. The decline in total sperm count over the past four decades and the parallel increase in childhood obesity may suggest an association between these two conditions. Here, we review the molecular mechanisms through which obesity during childhood and adolescence may impair future testicular function. Several mechanisms occurring in obesity can interfere with the delicate metabolic processes taking place at the testicular level during childhood and adolescence, providing the molecular substrate to hypothesize a causal relationship between childhood obesity and the risk of low sperm counts in adulthood. Pediatric obesity is increasing worldwide and its contribution to the decline is sperm count has been questioned. By comprehensively reviewing the literature, the authors herein report molecular mechanisms that may suggest the causality of this association. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the feasibility of an artificial intelligence (AI)-based semi-automated segmentation for the extraction of ultrasound (US)-derived radiomics features in the characterization of focal breast lesions (FBLs). Material and methods: Two expert radiologists classified according to US BI-RADS criteria 352 FBLs detected in 352 patients (237 at Center A and 115 at Center B). An AI-based semi-automated segmentation was used to build a machine learning (ML) model on the basis of B-mode US of 237 images (center A) and then validated on an external cohort of B-mode US images of 115 patients (Center B). Results: A total of 202 of 352 (57.4%) FBLs were benign, and 150 of 352 (42.6%) were malignant. The AI-based semi-automated segmentation achieved a success rate of 95.7% for one reviewer and 96% for the other, without significant difference (p = 0.839). A total of 15 (4.3%) and 14 (4%) of 352 semi-automated segmentations were not accepted due to posterior acoustic shadowing at B-Mode US and 13 and 10 of them corresponded to malignant lesions, respectively. In the validation cohort, the characterization made by the expert radiologist yielded values of sensitivity, specificity, PPV and NPV of 0.933, 0.9, 0.857, 0.955, respectively. The ML model obtained values of sensitivity, specificity, PPV and NPV of 0.544, 0.6, 0.416, 0.628, respectively. The combined assessment of radiologists and ML model yielded values of sensitivity, specificity, PPV and NPV of 0.756, 0.928, 0.872, 0.855, respectively. Conclusion: AI-based semi-automated segmentation is feasible, allowing an instantaneous and reproducible extraction of US-derived radiomics features of FBLs. The combination of radiomics and US BI-RADS classification led to a potential decrease of unnecessary biopsy but at the expense of a not negligible increase of potentially missed cancers. [ABSTRACT FROM AUTHOR]

Introduction: Studies investigating the effects of SARS-CoV-2 on male reproductive function are few and heterogeneous, and results are often conflicting. This systematic review and meta-analysis was carried out on studies conducted in men with active or anamnestic SARS-CoV-2 infection to evaluate its consequences on the male sex hormone profile and semen parameters. Materials and method: This meta-analysis follows the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols. PubMed, Scopus, Cochrane, and Embase databases were searched to identify relevant studies. We originally selected 3553 articles. After the eligibility phase, 16 articles met our inclusion criteria encompassing 11 case-control studies and 5 cohort studies (2 prospective and 3 retrospective studies). We performed the quantitative analysis with Comprehensive Meta-Analysis Software. Cochran-Q and heterogeneity (I2) indexes were used to assess statistical heterogeneity. Sensitivity analysis and publication bias tests were also performed. Results: Overall, 1250 patients with active or recent (up to 80 days before) COVID-19 infection and 1232 matched healthy controls were included. Sperm concentration, total sperm count, and total motility were significantly lower in patients compared with controls. Patients also showed lower levels of total testosterone and follicle-stimulating hormone, and higher levels of luteinizing hormone, 17β-estradiol, and prolactin compared with healthy controls. None of the included studies found the presence of SARS-CoV-2 mRNA in the semen of infected patients. Conclusion: The present systematic review and meta-analysis suggests the presence of an association between SARS-CoV-2 infection and primary testicular damage manifested with a picture of altered steroidogenesis and worsening spermatogenesis. The absence of the virus in the seminal fluid indicates a low possibility of sexual transmission of the infection to partners and offspring. However, our findings mostly show short-term follow-up, while few studies have considered the long-term consequences of the viral infection, thus further studies are needed to evaluate the long-term consequences on male reproductive health. [ABSTRACT FROM AUTHOR]

Bean syndrome (BS) is a rare congenital angiomatosis affecting multiple organ systems. The exact etiology is still not well-known. About 200 cases with heterogeneous clinical presentations have been reported worldwide. BS predominantly presents with characteristic multifocal mucocutaneous lesions and often leads to iron-deficiency anemia caused by occult blood loss from the gastrointestinal tract. Apart from the mucocutaneous and gastrointestinal tract involvement, this syndrome may rarely affect the craniofacial region in the form of multiple venous anomalies, characterized by being button-like, with a bluish tint, covered by skin, called "Blue Nevus". Patients often approach a dermatologist or gastroenterologist for treatment and this entity is usually less known among maxillofacial surgeons. This article describes two consecutive cases of BS affecting the craniofacial district, with the aim of spreading greater awareness about this syndrome in the maxillofacial field. [ABSTRACT FROM AUTHOR]

Single-cell RNA sequencing (scRNA-seq) has emerged as a vital tool in tumour research, enabling the exploration of molecular complexities at the individual cell level. It offers new technical possibilities for advancing tumour research with the potential to yield significant breakthroughs. However, deciphering meaningful insights from scRNA-seq data poses challenges, particularly in cell annotation and tumour subpopulation identification. Efficient algorithms are therefore needed to unravel the intricate biological processes of cancer. To address these challenges, benchmarking datasets are essential to validate bioinformatics methodologies for analysing single-cell omics in oncology. Here, we present a 10XGenomics scRNA-seq experiment, providing a controlled heterogeneous environment using lung cancer cell lines characterised by the expression of seven different driver genes (EGFR, ALK, MET, ERBB2, KRAS, BRAF, ROS1), leading to partially overlapping functional pathways. Our dataset provides a comprehensive framework for the development and validation of methodologies for analysing cancer heterogeneity by means of scRNA-seq. [ABSTRACT FROM AUTHOR]

Objective: The underpinning biologics of migraine chronification are not well understood. We aim to investigate the role of the cumulative burden of stress, namely the allostatic load, in migraine chronification. Methods: This was a cross-sectional study. The allostatic load was measured with a composite multi-system score (BALI: Bologna Allostatic Load Index), evaluating 20 biomarkers representing four physiological systems: immune, metabolic, cardiovascular, and neuroendocrinological systems. BALI score was subdivided into high score and low score based on the distribution in controls. Migraine patients were included and subclassified into low-frequency episodic migraine group (low-EM group), high-frequency episodic migraine group (high-EM group), and chronic migraine group (CM group). Results: The distribution of BALI high-score increased in parallel with headache attacks monthly frequency: 16% in low-EM group (n = 10), 24% in high-EM group (n = 12), and 40% in CM group (n = 21) (p = 0.017). In a multivariable analysis, the odds ratio of having a high-score BALI in CM patients (vs. low-EM patients) was 2.78 (95% CI 1.07–7.22; p = 0.036). Individual BALI biomarkers values which were significantly different among migraine subgroups included systolic blood pressure (p = 0.018), diastolic blood pressure (p < 0.001), and heart rate (p = 0.019). Conclusion: Our study substantiates this emerging concept of migraine chronification as an allostatic disorder. [ABSTRACT FROM AUTHOR]

Chronic low back pain (cLBP) is a major cause of disability and healthcare expenditure worldwide. Its prevalence is increasing globally from somatic and psychosocial factors. While non-pharmacological management, and in particular physiotherapy, has been recommended as a first-line treatment for cLBP, it is not clear what type of physiotherapeutic approach is the most effective in terms of pain reduction and function improvement. This analysis is rendered more difficult by the vast number of available therapies and a lack of a widely accepted classification that can effectively highlight the differences in the outcomes of different management options. This study was conducted according to the PRISMA guidelines. In January 2024, the following databases were accessed: PubMed, Web of Science, Google Scholar, and Embase. All the randomised controlled trials (RCTs) which compared the efficacy of physiotherapy programs in patients with cLBP were accessed. Studies reporting on non-specific or mechanical cLPB were included. Data concerning the Visual Analogic Scale (VAS) or numeric rating scale (NRS), Roland Morris Disability Questionnaire (RMQ) and Oswestry Disability Index (ODI). Data from 12,773 patients were collected. The mean symptom duration was 61.2 ± 51.0 months and the mean follow-up was 4.3 ± 5.9 months. The mean age was 44.5 ± 9.4 years. The mean BMI was 25.8 ± 2.9 kg/m2. The Adapted Physical Exercise group evidenced the lowest pain score, followed by Multidisciplinary and Adapted Training Exercise/Complementary Medicine. The Adapted Physical Exercise group evidenced the lowest RMQ score followed by Therapeutic Exercises and Multidisciplinary. The Multidisciplinary group evidenced the lowest ODI score, followed by Adapted Physical Exercise and Physical Agent modalities. Within the considered physiotherapeutic and non-conventional approaches to manage nonspecific and/or mechanic cLBP, adapted physical exercise, physical agent modalities, and a multidisciplinary approach might represent the most effective strategy to reduce pain and disability. [ABSTRACT FROM AUTHOR]

The identification of more efficient, clean, secure, and competitive energy supply is necessary to align with the needs of sustainable devices. For this reason, a study for developing innovative dye-sensitized solar cells (DSSCs) based on microbial pigments is reported starting from Talaromyces atroroseus GH2. The fungus was cultivated by fermentation and the extracellular pigment extract was characterized by HPLC-DAD-ESI-MS analyses. The most abundant compound among the 22 azaphilone-type pigments identified was represented by PP-O. The device's behavior was investigated in relation to electrolyte and pH for verifying the stability on time and the photovoltaic performance. Devices obtained were characterized by UV–vis measurements to verify the absorbance intensity and transmittance percentage. Moreover, photovoltaic parameters through photo-electrochemical measurements (I–V curves) and impedance characteristics by Electrochemical Impedance Spectroscopy (EIS) were determined. The best microbial device showed a short-circuit current density (Jsc) of 0.69 mA/cm2, an open-circuit photo-voltage (Voc) of 0.27 V and a Fill Factor (FF) of 0.60. Furthermore, the power conversion efficiency (PCE) of the device was 0.11%. Thus, the present study demonstrated the potential of microbial origin pigments for developing DSSCs. [ABSTRACT FROM AUTHOR]

In this article, we present a modification of the NS/SRM technique in which the mastopexy design for skin reduction is undertaken with a wide-base bipedicled (WIBB) flap. The WIBB flap can be applied in both autologous and implant-based breast reconstruction. Our reconstructive algorithm is also presented. The clinical data of patients operated on from June 2017 to November 2022 were collected: 51 patients for a total of 71 breasts. Personal data, BMI, type and volume of implants used, and major and minor complications were analyzed by descriptive statistics. The mean age was 48.3 years. BMI ranged between 21.5 and 30.9 kg/m2. Thirty-one patients underwent unilateral mastectomy, while twenty patients underwent bilateral surgery. In 25 breasts, immediate reconstruction was performed with implants and ADM. In 40 breasts, reconstruction was performed with a subpectoral tissue expander, and in 6 breasts, reconstruction was performed with a DIEP flap. We observed only one case (1.4%) of periprosthetic infection requiring implant removal under general anesthesia. Minor complications occurred in 14.1% of patients. The use of both the WIBB flap and our algorithm maintained a low complication rate in our series, ensuring oncological radicality and a good aesthetic result at the same time. [ABSTRACT FROM AUTHOR]

We work with a double-phase energy functional exhibiting log L -perturbed p & q -growth. We look for regularity properties of such functional in the setting of Musielak-Orlicz-Sobolev space, by imposing suitable conditions on the data. We further obtain the existence and uniqueness results for the solution of perturbed Dirichlet double-phase problems. We deal with both the cases of uncontrolled growth and controlled growth. [ABSTRACT FROM AUTHOR]

Background: Sexual and gender minorities (SGM) encompass individuals identifying as lesbian, gay, bisexual, transgender, and queer (LGBTQ). SGM patients experience difficulties in accessing healthcare and may face discrimination, impacting their overall health outcomes. Enhancing healthcare professionals' knowledge is the initial step in dismantling these barriers. Materials and methods: The study has been conducted on the neurologists of the Italian Society of Neurology (SIN). We utilized a survey instrument comprising 24 Likert-type questions to investigate knowledge, attitudes, and practices concerning sexual orientation and gender identity minorities. Likert scales were assessed with scores 1 and 2 as negative response, 3 as neutral, and 4 and 5 as positive responses. Results: A total of 177 neurologists (103 women; 58.2%) participated, with a mean age of 44.3 ± 14.6 years answered the survey. Over half recognized sexual and gender orientation as social determinants of health, yet only a minority acknowledged the elevated prevalence of physical and mental health issues in SGM populations. Nearly, all respondents felt confident in examining a sexual minority patient, while only half felt the same regarding transgender patients. The majority of neurologists expressed a need for more comprehensive training and supervision in treating SGM patients. Conclusion: To enhance healthcare quality for SGM populations, healthcare professionals must receive appropriate training in how to approach, assess, and treat patients within this demographic. [ABSTRACT FROM AUTHOR]

Near-surface axial tensile residual stresses (from manufacturing) are reportedly detrimental to the yield strength of cold-drawn wires. Therefore, a reliable evaluation of their magnitude is necessary. The size and geometry of electrical wires can pose challenges for experimental measurement of those residual stresses. For that reason, the finite element analysis can prove useful. However, great care must be taken with the right choice of strain hardening law for a sound assessment of residual stresses. Given the complex loading condition during cold drawing, cyclic loading arises through the wire cross section even in single-pass drawing. As a result, it is of crucial importance to account for associated backstresses. The current study makes a comparison between two different hardening laws' prediction of axial residual stress profiles in numerically cold-drawn Cu–Al composite wires of various Al volume fractions. The impact of die geometry on this prediction was also examined for a 25%Al-wire. To that end, a combined isotropic-kinematic law and a pure isotropic constitutive equation were considered. The results imply a possible overestimation of residual stresses by the pure isotropic model at relatively low Al volume fractions. The difference between the maximum magnitudes of tensile or compressive residual stresses (predicted by the two models) could be as large as about 100 MPa (larger than the yield strength of the starting materials). Furthermore, the tooling geometry minimally affects the prediction of the hardening models. In conclusion, backstresses are not to be overlooked for accurate estimations of drawing residual stresses at low Al volume fractions. [ABSTRACT FROM AUTHOR]

Little information is available about the nature of the immune response in children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination. The aim of this study is to define the seroprevalence and the features of the antibody response in children of Southern Switzerland during the different waves of Coronavirus Disease 2019 (COVID-19) pandemic. By analyzing 756 sera collected from children aged 0 to 16 years admitted to the Institute of Pediatrics of Southern Switzerland during the prepandemic period (before March 2020) and the first four pandemic waves (between March 2020 and June 2022), we investigated binding titers, cross-reactivity, and neutralizing properties of the serum antibodies against SARS-CoV-2 variants. Seroprevalence varied from 6% during the first wave to 14% and 17% during the second and third waves, respectively, peaking at 39% during the fourth wave. The 96 seropositive cases were mostly asymptomatic (42.7%) or showed mild (20.8%) to moderate (32.3%) symptoms. Moderate symptoms and close contact with COVID-19-positive individuals were associated with a higher infection risk (P < 0.001). The antibody response was mainly driven by IgG directed to the receptor-binding domain (RBD) of Wuhan-1 SARS-CoV-2 Spike (S). Children infected in the first three waves produced antibodies with up to 11-fold and 5.5-fold reduction in binding and neutralizing titers, respectively, against different SARS-CoV-2 variants, including Beta, Delta, and Omicron BA.1, BA.2, and BA.5. Such reductions were less pronounced in children infected during the fourth wave, who showed the highest frequency and titers of neutralizing antibodies against the same variants. Compared to infection, vaccination with a Wuhan-1-based messenger RNA (mRNA) vaccine induced higher and heterogenous levels of antibodies cross-reacting to the different SARS-CoV-2 variants analyzed. Conclusions: Despite the high burden of COVID-19 in Southern Switzerland, we observed an initial low seroprevalence of SARS-CoV-2 in children, which increased in the later waves. The antibody response was poor in the first three waves and improved in the fourth wave, when children produced higher levels of neutralizing antibodies after vaccination or infection with Delta and/or Omicron variants. What is Known: • Children were marginally affected by the initial SARS-CoV-2 variants. • The number of infected and hospitalized children increased after the appearance of the Omicron variants. What is New: • Seroprevalence of SARS-CoV-2 in children of Southern Switzerland increased overtime. • Children produced higher levels of neutralizing antibodies after vaccination or infection with Delta and/or Omicron variants in the fourth wave compared to children infected in the first three waves. [ABSTRACT FROM AUTHOR]

Background: Radiohybrid PSMA-targeted ligands (rhPSMA) have been introduced as a novel platform for theranostic applications. Among a variety of rhPSMA-ligands developed for radioligand therapy, two stereoisomers [177Lu]Lu-rhPSMA-10.1 and -10.2 have been synthesized and initially characterized in preclinical experiments with the aim to provide an optimized binding profile to human serum albumin, a reduction of charge, and thus accelerated kidney excretion, and unaffected or even improved tumor uptake. As both isomers showed similar in vitro characteristics and tumor uptake at 24 h post injection in tumor bearing mice and in order to identify the isomer with the most favorable pharmacokinetics for radioligand therapy, we carried out in-depth biodistribution and dosimetry studies in tumor-bearing and healthy mice. Results: rhPSMA-10.1 and -10.2 were radiolabeled with lutetium-177 according to the established procedures of other DOTA-based PSMA ligands and displayed a high and comparable stability in all buffers and human serum (> 97%, 24 h). Biodistribution studies revealed fast clearance from the blood pool (0.3–0.6%ID/g at 1 h) and other background tissues within 48 h. Distinctive differences were found in the kidneys, where [177Lu]Lu-rhPSMA-10.1 displayed lower initial uptake and faster excretion kinetics compared to [177Lu]Lu-rhPSMA-10.2 expressed by a 1.5-fold and ninefold lower uptake value at 1 h and 24 h in healthy animals, respectively. Tumor uptake was comparable and in the range of 8.6–11.6%ID/g for both isomers over 24 h and was maintained up to 168 h at a level of 2.2 ± 0.8 and 4.1 ± 1.4%ID/g for [177Lu]Lu-rhPSMA-10.1 and [177Lu]Lu-rhPSMA-10.2, respectively. Conclusion: Our preclinical data on biodistribution and dosimetry indicate a more favorable profile of [177Lu]Lu-rhPSMA-10.1 compared to [177Lu]Lu-rhPSMA-10.2 for PSMA-targeted radioligand therapy. [177Lu]Lu-rhPSMA-10.1 shows fast kidney clearance kinetics resulting in excellent tumor-to-organ ratios over a therapy relevant time course. Meanwhile, [177Lu]Lu-rhPSMA-10.1 is currently being investigated in clinical phase I/II studies in patients with mCRPC (NCT05413850), in patients with high-risk localized PC (NCT06066437, Nautilus Trial) and after external beam radiotherapy (NCT06105918). [ABSTRACT FROM AUTHOR]

Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is a parasomnia characterized by loss of physiological atonia of skeletal muscles with abnormal behaviors arising during REM sleep. RBD is often the early manifestation of neurodegenerative diseases, particularly alpha-synucleinopathies, such as Parkinson's disease (PD). Both structural and functional neuroimaging studies suggest that iRBD might share, or even precede, some of the features commonly found in PD, although without a definitive conclusion. Aim of the study is to evaluate the presence of structural abnormalities involving cortical and subcortical areas in PD patients with RBD and iRBD. Patients with video-polysomnographic (VPSG)-confirmed iRBD, and patients with a diagnosis of PD were recruited. In all PD patients, the presence of probable RBD was assessed during the follow-up visits (PD/pRBD). A group of healthy controls (HC) subjects was also recruited. Each subject underwent a structural brain MRI using a 3-D T1-weighted spoiled gradient echo sequence. Twenty-three patients with iRBD, 24 PD/pRBD, and 26 HC were enrolled. Voxel-based morphometry-AnCOVA analysis revealed clusters of grey matter changes in iRBD and PD/pRBD compared to HC in several regions, involving mainly the frontal and temporal regions. The involvement of cortical brain structures associated to the control of sleep cycle and REM stage both in PD/pRBD and iRBD might suggest the presence of a common structural platform linking iRBD and PD, although this pattern may not underlie exclusively RBD-related features. Further longitudinal studies are needed to clarify the patterns of changes occurring at different time points of RBD-related neurodegeneration. [ABSTRACT FROM AUTHOR]

Background: Vulvar carcinoma is a rather uncommon gynecological malignancy affecting elderly women and the treatment of loco-regional advanced carcinoma of the vulva (LAVC) is a challenge for both gynecologic and radiation oncologists. Definitive chemoradiation (CRT) is the treatment of choice, but with disappointing results. In this multicenter study (OLDLADY-1.1), several institutions have combined their retrospective data on LAVC patients to produce a real-world dataset aimed at collecting data on efficacy and safety of CRT. Methods: The primary study end-point was 2-year-local control (LC), secondary end-points were 2-year-metastasis free-survival (MFS), 2-year-overall survival (OS) and the rate and severity of acute and late toxicities. Participating centers were required to fill data sets including age, stage, histology, grading as well as technical/dosimetric details of CRT. Data about response, local and regional recurrence, acute and late toxicities, follow-up and outcome measures were also collected. The toxicity was a posteriori documented through the Common Terminology Criteria for Adverse Events version 5 scale. Results: Retrospective analysis was performed on 65 patients with primary or recurrent LAVC treated at five different radiation oncology institutions covering 11-year time interval (February 2010–November 2021). Median age at diagnosis was 72 years (range 32–89). With a median follow-up of 19 months (range 1–114 months), 2-year actuarial LC, MFS and OS rate were 43.2%, 84.9% and 59.7%, respectively. In 29 patients (44%), CRT was temporarily stopped (median 5 days, range 1–53 days) due to toxicity. The treatment interruption was statistically significant at univariate analysis of factors predicting LC (p: 0.05) and OS rate (p: 0.011), and it was confirmed at the multivariate analysis for LC rate (p: 0.032). In terms of toxicity profile, no G4 event was recorded. Most adverse events were reported as grade 1 or 2. Only 14 acute G3 toxicities, all cutaneous, and 7 late G3 events (3 genitourinary, 3 cutaneous, and 1 vaginal stenosis) were recorded. Conclusion: In the context of CRT for LAVC, the present study reports encouraging results even if there is clearly room for further improvements, in terms of both treatment outcomes, toxicity and treatment interruption management. [ABSTRACT FROM AUTHOR]

Introduction: The long interspersed nuclear element-1 (LINE1) gene is a retrotransposon whose methylation status appears to play a role in spermatogenesis, the outcome of assisted reproductive techniques (ART), and even in recurrent pregnancy loss (RPL). Advanced paternal age appears associated with altered sperm parameters, RPL, poor ART outcomes, and compromised offspring health. The methylation status of LINE1 has been reported to be affected by age. The latest meta-analysis on the LINE1 methylation pattern in spermatozoa found no significant differences in methylation levels between infertile patients and fertile controls. However, to the best of our knowledge, no updated meta-analysis on this topic has been published recently. Furthermore, no comprehensive meta-regression analysis was performed to investigate the association between sperm LINE1 methylation pattern and age. Objectives: To provide an updated and comprehensive systematic review and meta-analysis on sperm LINE1 gene methylation degree in patients with abnormal sperm parameters compared to men with normal sperm parameters and to probe the association between sperm LINE1 methylation status and age and/or sperm concentration. Methods: This meta-analysis was registered in PROSPERO (registration n. CRD42023397056). It was performed according to the MOOSE guidelines for Meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Only original articles evaluating LINE1 gene methylation in spermatozoa from patients with infertility or abnormalities in one or more sperm parameters compared to fertile or normozoospermic men were included. Results: Of 192 abstracts evaluated for eligibility, only 5 studies were included in the quantitative synthesis, involving a total of 340 patients and 150 controls. Our analysis showed no significant difference in LINE1 gene methylation degree in patients with infertility and/or abnormal sperm parameters compared to fertile controls and/or men with normal sperm parameters, although there was significant heterogeneity across studies. No significant evidence of publication bias was found, and no study was sensitive enough to alter the results. In meta-regression analysis, we found that the results were independent of both ages and sperm concentration. A sub-analysis examining patients and controls separately was also conducted and we found a trend for a positive correlation between LINE1 methylation and sperm concentration in the control group only. Conclusions: The results of this systematic review and meta-analysis do not suggest a determining role of sperm LINE1 gene methylation degree in patients with infertility and/or abnormal sperm parameters. Therefore, we do not suggest including LINE1 in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to be analyzed in couples undergoing ART cycles. [ABSTRACT FROM AUTHOR]

Non-motor symptoms (NMS) and Non-motor fluctuations (NMF) in Parkinson's Disease (PD) are common, involving several domains and affecting quality of life. Aim of the study is to estimate the burden of NMF in PD patients and to evaluate the possible gender effect. PD patients fulfilling the MDS-PD diagnostic criteria attending the "Parkinson's Disease and Movement Disorders Centre" of the University of Catania were evaluated using the Non-Motor Fluctuations Assessment (NoMoFA) Questionnaire. NoMoFA items were also grouped into the following domains: cognitive, mood, sleep/fatigue, dysautonomia, hallucination/perception and miscellaneous domains were identified. One-hundred and twenty-one patients with PD (67 men, 55.4%; mean age 70.2 ± 8.9 years, disease duration 8.3 ± 4.6 years) were evaluated. All PD patients reported at least one NMS, whereas 87 (71.9%) also reported NMF. "Feel sluggish or had low energy levels" (47.2%) along with "Feel excessively sleepy during the day" (40.0%) were the most common NMF reported in the whole sample. The majority of PD patients reported the presence of NMF during the OFF state (79, 65.3%). At multivariate analysis, NMF were positively associated with the female gender (adjusted OR 3.13; 95%CI 1.21–8.11 p-value 0.01). Women with PD had higher NMF scores especially in depression/anxiety, sleep/fatigue and dysautonomia domains. Our study reported the presence of a gender-related pattern in the frequency of NMS and NMF in PD patients, with female gender associated with a higher risk of developing NMF, highlighting the need for personalized treatment strategies when addressing NMF. [ABSTRACT FROM AUTHOR]

This paper is concerned with the existence of normalized solutions to a class of Schrödinger equations driven by a fractional operator with a parametric potential term. We obtain minimization of energy functional associated with that equations assuming basic conditions for the potential. Our work offers a partial extension of previous results to the non-local case. [ABSTRACT FROM AUTHOR]

Lloviu cuevavirus (LLOV) was the first identified member of Filoviridae family outside the Ebola and Marburgvirus genera. A massive die-off of Schreibers's bats (Miniopterus schreibersii) in the Iberian Peninsula in 2002 led to its initial discovery. Recent studies with recombinant and wild-type LLOV isolates confirmed the zoonotic nature of the virus in vitro. We examined bat samples from Italy for the presence of LLOV in an area outside of the currently known distribution range of the virus. We detected one positive sample from 2020, sequenced the complete coding region of the viral genome and established an infectious isolate of the virus. In addition, we performed the first comprehensive evolutionary analysis of the virus, using the Spanish, Hungarian and the Italian sequences. The most important achievement of this study is the establishment of an additional infectious LLOV isolate from a bat sample using the SuBK12-08 cells, demonstrating that this cell line is highly susceptible to LLOV infection and confirming the previous observation that these bats are effective hosts of the virus in nature. This result further strengthens the role of bats as the natural hosts for zoonotic filoviruses. [ABSTRACT FROM AUTHOR]

Introduction: In Parkinson's disease (PD), rapid eye movement (REM) sleep behavior disorder (RBD) might either precede the appearance of motor symptoms, or develop during the disease course. PD patients with RBD are characterized by a higher burden of cognitive impairment and hallucinations. However, few studies have analyzed the clinical characteristics of PD patients according to the timeline of RBD onset. Methods: PD patients have been retrospectively enrolled. Presence and onset of probable RBD (pRBD) has been evaluated using RBD Screening Questionnaire (score ≥ 6). Presence of Mild Cognitive Impairment (MCI) at baseline has been evaluated using the MDS criteria level II. Presence of motor complications and hallucinations has been evaluated at a 5-year follow-up. Results: A total of 115 PD patients (65 men, 56.5%; mean age 62.5 ± 9.7 years; mean disease duration 3.7 ± 3.9 years) have been enrolled. Out of these, 63 fulfilled the diagnosis of pRBD (54.8%) with 21 (33.3%) reporting the RBD onset before the onset of the motor symptoms (PD-RBDpre), and 42 (66.7%) after the motor symptoms (PD-RBDpost). At enrolment presence of MCI was associated with PD-RBDpre patients (OR 5.04; 95% CI 1.33–19.05; p value 0.02). At follow-up, a higher risk of developing hallucinations was also associated with PD-RBDpre (OR 4.68; 95% CI 1.24–17.63; p = 0.022). Conclusions: PD patients with RBD occurring before the onset of motor symptoms represent a subgroup of patients with a more severe cognitive phenotype and with a higher risk of developing hallucinations along the disease course, with significant implications in terms of prognostic stratification and therapeutic approach. [ABSTRACT FROM AUTHOR]

Canine parvovirus (CPV-2) modified-live virus vaccine strain can replicate in lymphoid tissues and intestinal mucosa after administration, being shed through canine faeces. Detection of vaccine strains has been reported in the bloodstream and faeces, potentially interfering with molecular diagnostic tests. The persistence of these strains in canine tissues has not yet been described. With this aim, canine tissues were tested during a molecular survey to screen for the presence of canine enteric viruses. Tissue samples from 165 dead dogs were tested by a conventional PCR assay. Positive samples and five commercial vaccines were subjected to sequence analysis. Vaccinal strains were detected and virus load was measured by using a set of real-time PCR assays using minor-groove binder (MGB) probes. Seventy-five dogs (45.4%) tested positive for CPV-2. Strains from 70 dogs were characterised as field variants. The presence of CPV sequences of vaccine origin was observed in the spleen, intestine, and mesenteric lymph nodes of five young dogs. Vaccinal strains were detected from 12 to 24 days after the last vaccine administration. Viral loads comprised between 6.3 × 102 and 9.95 × 104 DNA copies/10 µl of template. This study confirms that CPV vaccinal strains can be detected in canine tissues after vaccination, so post-mortem diagnosis of CPV infection needs further molecular analyses to assess the viral type (vaccine or field strains). The present study updates the current information on the persistence of CPV vaccine strains in canine tissues and their possible interference with molecular assays. [ABSTRACT FROM AUTHOR]

We consider a Dirichlet problem driven by the anisotropic (p(z), q(z))-Laplacian, with a parametric reaction exhibiting the combined effects of singular and concave-convex nonlinearities. The superlinear term may change sign. Using variational tools together with truncation and comparison techniques, we prove a global (for the parameter λ > 0 ) existence and multiplicity theorem (a bifurcation-type theorem). [ABSTRACT FROM AUTHOR]

Central giant cell reparative granuloma (CGCRG) of the jaw is a neoformation localized in the mandible or in the maxillary bone and characterized by fibrous tissue, osteoclast-like giant cells and reactive bone formation. The CGCRG is a less frequent benign tumor but sometimes it is characterized by an aggressive behavior with a very rapid growth. It affects the young adults mainly and the children occasionally. Nowadays no medication therapy is approved for CGCRG in pediatric cases. We present a case of an aggressive form of a mandibular CGCRG in a 5-year child with Arnold-Chiari syndrome. This case is unique for the use of bisphosphonates (BPs) as neoadjuvant therapy in pediatrics. The therapy were administrated with the purpose of arresting the rapid growth of the tumor in order to avoid a demolitive surgery to the young patient. The child was without symptoms and presented an unusual swelling in the left mandible developed in a few weeks. The lesion was diagnosed by a CT scan and it was confirmed by a biopsy performed for histopathological assessment a few days later. The drug therapy consisted of seven cycles iv of Zoledronate associated to Calcium Gluconate. The child was closely observed through clinical and serological evaluations during the following months. About five months after the last cycle of BPs the child underwent CT scan and a conservative surgical treatment, consisted in a deep curettage, was programmed. Seven months after surgery the aesthetic profile of the patient improved and CT scan reported a significant calcic neoapposition in the area of the previous bone lesion. After more than one year from surgery, no relapse was observed. This case report demonstrates that BPs can be used safely in pediatric patients with CGCRG. Especially BPs could have a role as neoadjuvant therapy: If administrated before surgical treatment BPs avoid the necessity of resective surgery and reduce the risk of recurrence in pediatric CGCRG after conservative curettage. [ABSTRACT FROM AUTHOR]

The p140Cap adaptor protein is a tumor suppressor in breast cancer associated with a favorable prognosis. Here we highlight a function of p140Cap in orchestrating local and systemic tumor-extrinsic events that eventually result in inhibition of the polymorphonuclear myeloid-derived suppressor cell function in creating an immunosuppressive tumor-promoting environment in the primary tumor, and premetastatic niches at distant sites. Integrative transcriptomic and preclinical studies unravel that p140Cap controls an epistatic axis where, through the upstream inhibition of β-Catenin, it restricts tumorigenicity and self-renewal of tumor-initiating cells limiting the release of the inflammatory cytokine G-CSF, required for polymorphonuclear myeloid-derived suppressor cells to exert their local and systemic tumor conducive function. Mechanistically, p140Cap inhibition of β-Catenin depends on its ability to localize in and stabilize the β-Catenin destruction complex, promoting enhanced β-Catenin inactivation. Clinical studies in women show that low p140Cap expression correlates with reduced presence of tumor-infiltrating lymphocytes and more aggressive tumor types in a large cohort of real-life female breast cancer patients, highlighting the potential of p140Cap as a biomarker for therapeutic intervention targeting the β-Catenin/ Tumor-initiating cells /G-CSF/ polymorphonuclear myeloid-derived suppressor cell axis to restore an efficient anti-tumor immune response. The p140Cap adaptor protein is a tumour suppressor associated with improved prognosis in breast cancer. Here, the authors identify a role for p140Cap in preventing the immunosuppressive and pro-tumour function of polymorphonuclear myeloid-derived suppressor cells via downmodulation of the β-Catenin/Tumor Initiating Cells/G-CSF axi [ABSTRACT FROM AUTHOR]

Demands for neural interfaces around functionality, high spatial resolution, and longevity have recently increased. These requirements can be met with sophisticated silicon-based integrated circuits. Embedding miniaturized dice in flexible polymer substrates significantly improves their adaptation to the mechanical environment in the body, thus improving the systems' structural biocompatibility and ability to cover larger areas of the brain. This work addresses the main challenges in developing a hybrid chip-in-foil neural implant. Assessments considered (1) the mechanical compliance to the recipient tissue that allows a long-term application and (2) the suitable design that allows the implant's scaling and modular adaptation of chip arrangement. Finite element model studies were performed to identify design rules regarding die geometry, interconnect routing, and positions for contact pads on dice. Providing edge fillets in the die base shape proved an effective measure to improve die-substrate integrity and increase the area available for contact pads. Furthermore, routing of interconnects in the immediate vicinity of die corners should be avoided, as the substrate in these areas is prone to mechanical stress concentration. Contact pads on dice should be placed with a clearance from the die rim to avoid delamination when the implant conforms to a curvilinear body. A microfabrication process was developed to transfer, align, and electrically interconnect multiple dice into conformable polyimide-based substrates. The process enabled arbitrary die shape and size over independent target positions on the conformable substrate based on the die position on the fabrication wafer. [ABSTRACT FROM AUTHOR]

Introduction: Temporary spacers used in the staged revision of a hip prosthetic joint infection (PJI) have been associated with several mechanical complications with very variable reported general complications rates up to 73%. The aim of this systematic review was to assess the mechanical complications associated with hip antibiotic-loaded spacers when treating periprosthetic hip PJI. Methods: Through an electronic systematic search of PubMed, articles reporting mechanical complications of spacers used in the treatment of hip PJI were reviewed. Dislocations, spacer fracture, femoral fractures, and acetabular lysis rates were evaluated. Results: Forty studies were included. Standardized molded spacers had a significantly higher weighted mean of total mechanical complication rates (37.2%) when compared to standardized preformed spacers (13.8%, p = 0.039), while no significant difference was found between molded spacers and manually shaped spacers. Spacer dislocation was the most frequent complication. No significant difference in mechanical complication rate was found between spacers with and without any metallic component. Conclusions: Spacer placement in chronic PJI of the hip with bone and soft-tissue defects is challenging and bears a high risk of mechanical failures and progressive bone loss during the interim period. A careful patient selection for spacer implantation is mandatory. [ABSTRACT FROM AUTHOR]