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Background: The presence of frequent macro-square-wave jerks (SWJs) has been recently included in the diagnostic criteria for progressive supranuclear palsy (PSP). The aim of the current video-oculographic study was to systematically assess the presence and features of SWJs during a brief fixation task in PSP, in comparison with Parkinson's disease (PD) patients and healthy controls (HC). Methods: Thirty-eight PSP patients, 55 PD patients and 40 HC were enrolled in the study. All patients underwent a video-oculographic (VOG) examination including a 5-s fixation task, and the number, duration and amplitude of SWJs were recorded. The diagnostic performance of several SWJs parameters were then compared in distinguishing PSP from PD patients and controls. Results: PSP patients showed a higher number and amplitude of SWJs compared to PD patients and controls. At least two SWJs within the 5-s fixation task were observed in 81.6% of PSP patients, 52.7% of PD patients and 25% of HC. The SWJs amplitude was the parameter showing the highest performances in distinguishing PSP from PD (AUC: 0.78) and HC (AUC: 0.88), outperforming the SWJ number and duration. The SWJ amplitude was larger in PSP-Richardson's syndrome than in PSP-Parkinsonism patients, while no difference was found between PSP patients with different degrees of vertical ocular motor dysfunction. Conclusions: This video-oculographic study provides robust evidence of larger SWJs number and amplitude in PSP than in PD patients, with some potential for differential diagnosis, supporting the inclusion of this ocular sign in PSP criteria. [ABSTRACT FROM AUTHOR]

In the last few years, a plethora of biomarkers have been proposed for the differentiation of Parkinson's disease (PD) from its mimics. Most of them consist of complex measures, often based on expensive technology, not easily employed outside research centers. MRI measures have been widely used to differentiate between PD and other parkinsonism. However, these measurements were often performed manually on small brain areas in small patient cohorts with intra- and inter-rater variability. The aim of the current review is to provide a comprehensive and updated overview of the literature on biomarkers commonly used to differentiate PD from its mimics (including parkinsonism and tremor syndromes), focusing on parameters derived by simple qualitative or quantitative measurements that can be used in routine practice. Several electrophysiological, sonographic and MRI biomarkers have shown promising results, including the blink-reflex recovery cycle, tremor analysis, sonographic or MRI assessment of substantia nigra, and several qualitative MRI signs or simple linear measures to be directly performed on MR images. The most significant issue is that most studies have been conducted on small patient cohorts from a single center, with limited reproducibility of the findings. Future studies should be carried out on larger international cohorts of patients to ensure generalizability. Moreover, research on simple biomarkers should seek measurements to differentiate patients with different diseases but similar clinical phenotypes, distinguish subtypes of the same disease, assess disease progression, and correlate biomarkers with pathological data. An even more important goal would be to predict the disease in the preclinical phase. [ABSTRACT FROM AUTHOR]

Background: The concept of wellbeing is expansive and intricate, making it challenging to define precisely. Similarly, the instruments employed to assess wellbeing are complex andmultifaceted. Therefore, it ismore appropriate to refer to the notion of wellbeing as Health-Related Quality of Life (HRQoL), which is the central focus of many measures used to assess the feeling of wellbeing. This review aimed to identify the tools most commonly used to evaluate HRQoL in individuals with Parkinsonism--a group of movement disorders that negatively impact the quality of life due to the intricate interplay of symptoms, socio-demographic characteristics, and psychological factors. The main aim was to assess the psychometric properties of these measures in terms of validity and reliability. Methods: A literature review was conducted, focusing on research related to the assessment of HRQoL in connection to symptoms of Parkinsonism. This review included all studies that examined HRQoL using evaluation scales, exams, or self-reported questionnaires. The literature review was conducted using the databases Scopus and Web of Science and the search engine PubMed to identify studies published between 1996 and 2023. Only records that assessed HRQoL in individuals with Parkinson's disease and Parkinsonism were selected for evaluation. Results: A total of 393 records were examined, and eight tools were identified as the most frequently used in the evaluation of HRQoL. Discussion: The results show a significant gap in knowledge regarding the latent structure and measurement invariance of HRQoL measurements, which may have a significant influence on the interpretation of test outcomes. Moreover, there is a lack of clear divergent validity between HRQoL assessments and other tests used as predictors of HRQoL. This could represent a significant limitation, affecting the construct and criterion validity of HRQoL measures. [ABSTRACT FROM AUTHOR]

Introduction: Distinguishing tremor-dominant Parkinson's disease (tPD) from essential tremor with rest tremor (rET) can be challenging and often requires dopamine imaging. This study aimed to differentiate between these two diseases through a machine learning (ML) approach based on rest tremor (RT) electrophysiological features and structural MRI data. Methods: We enrolled 72 patients including 40 tPD patients and 32 rET patients, and 45 control subjects (HC). RT electrophysiological features (frequency, amplitude, and phase) were calculated using surface electromyography (sEMG). Several MRI morphometric variables (cortical thickness, surface area, cortical/subcortical volumes, roughness, and mean curvature) were extracted using Freesurfer. ML models based on a tree-based classification algorithm termed XGBoost using MRI and/or electrophysiological data were tested in distinguishing tPD from rET patients. Results: Both structural MRI and sEMG data showed acceptable performance in distinguishing the two patient groups. Models based on electrophysiological data performed slightly better than those based onMRI data only (mean AUC: 0.92 and 0.87, respectively; p = 0.0071). The top-performing model used a combination of sEMG features (amplitude and phase) and MRI data (cortical volumes, surface area, andmean curvature), reaching AUC: 0.97 ± 0.03 and outperformingmodels using separately either MRI (p = 0.0001) or EMG data (p = 0.0231). In the best model, the most important feature was the RT phase. Conclusion: Machine learning models combining electrophysiological and MRI data showed great potential in distinguishing between tPD and rET patients and may serve as biomarkers to support clinicians in the differential diagnosis of rest tremor syndromes in the absence of expensive and invasive diagnostic procedures such as dopamine imaging. [ABSTRACT FROM AUTHOR]

Background: Extracellular vesicles (EVs) are cell-secreted particles conceived as natural vehicles for intercellular communication. The capacity to entrap heterogeneous molecular cargoes and target specific cell populations through EV functionalization promises advancements in biomedical applications. However, the efficiency of the obtained EVs, the contribution of cell-exposed receptors to EV interactions, and the predictability of functional cargo release with potential sharing of high molecular weight recombinant mRNAs are crucial for advancing heterologous EVs in targeted therapy applications. Methods: In this work, we selected the popular EV marker CD81 as a transmembrane guide for fusion proteins with a C-terminal GFP reporter encompassing or not Trastuzumab light chains targeting the HER2 receptor. We performed high-content imaging analyses to track EV-cell interactions, including isogenic breast cancer cells with manipulated HER2 expression. We validated the functional cargo delivery of recombinant EVs carrying doxorubicin upon EV-donor cell treatment. Then, we performed an in vivo study using JIMT-1 cells commonly used as HER2-refractory, trastuzumab-resistant model to detect a more than 2000 nt length recombinant mRNA in engrafted tumors. Results: Fusion proteins participated in vesicular trafficking dynamics and accumulated on secreted EVs according to their expression levels in HEK293T cells. Despite the presence of GFP, secreted EV populations retained a HER2 receptor-binding capacity and were used to track EV-cell interactions. In time-frames where the global EV distribution did not change between HER2-positive (SK-BR-3) or -negative (MDA-MB-231) breast cancer cell lines, the HER2 exposure in isogenic cells remarkably affected the tropism of heterologous EVs, demonstrating the specificity of antiHER2 EVs representing about 20% of secreted bulk vesicles. The specific interaction strongly correlated with improved cell-killing activity of doxorubicin-EVs in MDA-MB-231 ectopically expressing HER2 and reduced toxicity in SK-BR-3 with a knocked-out HER2 receptor, overcoming the effects of the free drug. Interestingly, the fusion protein-corresponding transcripts present as full-length mRNAs in recombinant EVs could reach orthotopic breast tumors in JIMT-1-xenografted mice, improving our sensitivity in detecting penetrant cargoes in tissue biopsies. Conclusions: This study highlights the quantitative aspects underlying the creation of a platform for secreted heterologous EVs and shows the limits of single receptor-ligand interactions behind EV-cell engagement mechanisms, which now become the pivotal step to predict functional tropism and design new generations of EV-based nanovehicles. [ABSTRACT FROM AUTHOR]

Providing timely and satisficing End-of-Life care (EOLC) is a priority for healthcare systems since aging population and chronic diseases are boosting the global demand for care at end-of-life (EOL). In OECD countries the access to EOLC is insufficient. In Italy, the average rate of cancer patients assisted by the palliative care (PC) network at EOL was 28% in 2021, with high variability in the country. Among the Italian regions offering the best coverages, Tuscany has a rate of about 40%, but intraregional variation is marked as well. The study aims to explore the delivery of EOLC to adult cancer patients in public facilities in the Tuscany region through survey data collection among professionals. Two online surveys were delivered to Directors of community-based PC Functional-Units (FUs) and Directors of hospital-based medical-oncology units. All FU Directors responded to the survey (n = 14), and a response rate of 96% was achieved from hospital-unit Directors (n = 27). The results highlight the availability of numerous dedicated services, but reveal heterogeneity among and within organisations, including variations in the professionals involved, pathways, and tools adopted. Care continuity is supported by institutionalized collaboration between hospital and community settings, but hindered by fragmented care processes and heterogeneous transition pathways. Late referral to PC is perceived as a major constraint to EOLC. Developing structured pathways for patient transition to end-stage PC is crucial, and practices/processes should be uniformly implemented to ensure equity. Multi-professional care should be facilitated through tailored supporting tools. Both hospital-unit and FU Directors suggest developing shared pathways between organisations/professionals (82% and 80% respectively) and digital information sharing (61% and 80% respectively). Hospital and community-based professionals have similar perceptions about the concerns and challenges to EOLC provision in the region, but community-based professionals are more sensitive to the importance of improving communication on PC to the public and early discussing EOLC with caregivers. This finding suggests the need of enhancing hospital personnel's awareness about these issues. Professional training and the capacity to assess patients' needs and preferences should be improved. The identified needs can inform future research and interventions to improve the quality and outcomes of EOLC for cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The prickly pear (Opuntia ficus indica L.) is a hardy plant well-adapted to hot and arid environments, rich not only in fiber but also soluble carbohydrates, lipids, minerals, and other antioxidant compounds. It has recently attracted attention for its potential uses in human and animal nutrition, however its effects on rabbits are still poorly understood. Its incorporation into the rabbit diet as a source of fiber would reduce the use of alfalfa with several benefits for the sustainability of rabbit farming from the point of view of the circular economy, global warming, and meat production costs. This study investigated the use of prickly pear seed cake in the rabbit's diet with different inclusion percentages (10% and 20%). Various parameters were evaluated, including growth performance, nutrient digestibility, blood biochemical parameters, morphology of intestinal villi, and carcass characteristics. While productive parameters were similar, diets containing prickly pear seed cake led to improved digestive utilization of nutrients, as well as reduced blood lipid concentrations and fat content in the rabbit carcasses. The encouraging findings of our study suggest that the inclusion of prickly pear in rabbit feed is feasible, although further research is necessary to validate the current outcomes and to evaluate the economic convenience of its use. Prickly pear (Opuntia ficus indica L.) could be used in rabbit nutrition in compliance with circular economy principles, global warming issues, and reduction of production costs. This study aims to evaluate the effects of dietary incorporation of prickly pear seed cake (PPSC) on growth, physiological, and histometric parameters in rabbits. A total of 105 rabbits were divided into three experimental groups (n = 35) and fed different diets: a commercial feed (C group), the same feed with alfalfa replaced by PPSC at 10% (10PP group), and at 20% (20PP group). They were group-housed in cages with 5 animals per cage from weaning until slaughtering. While body weights and weight gains were similar in all groups, the coefficients of nutrient digestibility of dry matter, fibers, and ashes, as well as the characteristics of intestinal villi, were improved in the 10PP group compared to the others (p < 0.05). The 20PP group showed a reduction in perirenal and interscapular fat (p < 0.05), as well as lower plasma concentrations of triglycerides and cholesterol compared to the C group (p < 0.001). In conclusion, PPSC can be incorporated into the diets of growing rabbits up to 20% as a partial substitute for alfalfa without the impairment of growth performance. Additionally, the inclusion of PPSC enhanced nutrient digestibility and increased the intestinal absorption surface area. [ABSTRACT FROM AUTHOR]

Simple Summary: Different sources of omega-3 (n-3) fatty acids can influence various aspects of female reproduction. This study evaluated the effects of dietary n-3 inclusion with extruded linseed and algae Padina pavonica extract on the reproductive performance and milk production of nulliparous female rabbits. In this study, the dietary inclusion of extruded linseed and alga Padina pavonica extract did not alter the feed intake, body weight, or gastrointestinal health of the rabbits, suggesting good tolerability and the absence of adverse effects. No significant differences were observed in the reproductive parameters such as litter size, litter weight, and milk production. Our study revealed a significant decrease in perinatal and pre-weaning mortality rates among rabbit kits born to mothers receiving n-3 integrated diets. This finding likely results from the transfer of n-3 from mother to offspring during both pregnancy and lactation, potentially strengthening the litters' immune defenses. While further studies are needed to elucidate the underlying mechanisms of action, dietary integration with extruded linseed and alga Padina pavonica extract shows promise as a strategy to physiologically enhance female rabbit reproductive performance and improve the survival of the litter, all in accordance with animal welfare principles. This study examined the effects of extruded linseed and algae Padina pavonica extract on the reproductive performance, milk production, and gastrointestinal health of female rabbits. Thirty-six nulliparous New Zealand White female rabbits were randomly assigned to three groups (n = 12) with different diets. The control group (CNT) received a standard diet, while the other two groups received modified isoenergetic diets in which part of the CNT diet ingredients were replaced with 5% extruded linseed (L5%) and 5% extruded linseed plus 0.2% Padina pavonica algae extract (L5%PP). The rabbits were monitored from artificial insemination until the weaning of the rabbit kits, evaluating different reproductive parameters. Our results indicate that extruded linseed and alga Padina pavonica extract did not affect the feed intake or body weight of female rabbits. Additionally, no clinically significant histological changes were observed at the gastrointestinal level. The reproductive parameters, including litter size, litter weight, and milk yield, showed no significant differences among groups. Notably, perinatal and pre-weaning mortalities were reduced in litters born to females receiving omega-3 integrated diets (p < 0.05). While these findings are promising, further studies are needed to confirm these results and explore the specific mechanisms by which omega-3 affects reproductive function and litter health. [ABSTRACT FROM AUTHOR]

Patients with hematological malignancies (HMs) are at high risk of respiratory viral infections due to the intrinsic deterioration of the immune system and chemotherapy treatments. In the recent past, SARS-CoV-2 respiratory viral infection has been responsible for most infectious complications in HMs. We analyzed 2950 samples from 505 patients admitted to the Hematology department from 2019 to 2023. The aim of this study was to determine the epidemiological trend of respiratory viruses in the SARS-CoV-2 era, the characteristics of the patients involved and their outcomes. In our analysis, we found a reduction in non-SARS-CoV-2 respiratory viral (NSRV) positivity during the pandemic period, although these data did not show statistical significance. Most of the HMs involved were Multiple Myeloma and Acute Myeloid Leukemia. Overall mortality rate was very low and characterized by the progression of the HMs as well as the worsening of respiratory failure. In conclusion, a reduction in non-COVID viral infections was highlighted, probably also thanks to the increase in prevention measures and environmental modifications of the viral background. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the use of horse and donkey meat in the production of kaddid—a traditional dish typically not made with these meats—from a physical and chemical perspective. The results showed that both meats exhibit similar water retention during cooking, contributing to comparable tenderness and juiciness, with no significant differences in pH values, indicating similar quality (p > 0.05). However, their amino acid profiles differ: horse meat contains lower levels of glutamate (p < 0.05), methionine (p < 0.01), isoleucine (p < 0.05), and leucine (p < 0.05), but higher levels of proline (p < 0.05), histidine (p < 0.01), and lysine (p < 0.001) compared to donkey meat. Both meats provide essential amino acids. Horse meat is richer in saturated and monounsaturated fatty acids (32.44% and 39.58%, respectively), while donkey meat has a higher content of polyunsaturated fatty acids (31.51%), with a more favorable PUFA/SFA ratio, suggesting better cardiovascular health benefits. In terms of dried meat, donkey kaddid has a higher protein (17.45 g/100 g) and lower fat content (2.1 g/100 g) compared to horse kaddid (16.7 g/100 g, and 3.5 g/100 g, respectively) (p < 0.05). These findings inform consumer choices and production practices, promoting the use of horse and donkey meat for kaddid production. [ABSTRACT FROM AUTHOR]

Negative symptoms in CHR-P people are generally not responsive to treatments and commonly related to poorer functional outcome. However, less research attention has been dedicated to Persistent Negative Symptoms (PNS), defined as clinically stable negative symptoms of moderate severity evident for at least 6 months. This study aims to (a) determine the prevalence of PNS in a sample of young people at CHR-P; (b) investigate any association of PNS with functioning and clinical features; (c) examine longitudinal course of PNS across 2 years of follow-up and changes in PNS severity levels with specialized treatments. One Hundred Eighty CHR-P participants were recruited and were divided into CHR-P/PNS + and CHR-P/PNS− subgroups. The clinical assessments were based on the PANSS and the GAF and were conducted at baseline and every 12 months during the follow-up. Twenty four participants showed PNS at entry. Of them, 21 concluded the 2-year follow-up period. At baseline, the CHR-P/PNS + participants showed more educational and employment deficits, and more social and functioning impairment. During the follow-up, the CHR-P/PNS + subgroup had a significant longitudinal decrease in negative symptoms, which was specifically related to antidepressant treatment. CHR-P/PNS + subjects also showed a higher incidence of new hospitalization and a lower functional recovery over time. Our findings support that the persistence of negative symptoms in CHR-P people is longitudinally related to worse daily functioning and more severe clinical conditions that are at higher risk of hospitalization and are less responsive to specialized treatments. [ABSTRACT FROM AUTHOR]

Objective: To investigate the performance of structural MRI cortical and subcortical morphometric data combined with blink-reflex recovery cycle (BRrc) values using machine learning (ML) models in distinguishing between essential tremor (ET) with resting tremor (rET) and classic ET. Methods: We enrolled 47 ET, 43 rET patients and 45 healthy controls (HC). All participants underwent brain 3 T-MRI and BRrc examination at different interstimulus intervals (ISIs, 100--300 msec). MRI data (cortical thickness, volumes, surface area, roughness, mean curvature and subcortical volumes) were extracted using Freesurfer on T1-weighted images. We employed two decision tree-based ML classification algorithms (eXtreme Gradient Boosting [XGBoost] and Random Forest) combining MRI data and BRrc values to differentiate between rET and ET patients. Results: ML models based exclusively on MRI features reached acceptable performance (AUC: 0.85--0.86) in differentiating rET from ET patients and from HC. Similar performances were obtained by ML models based on BRrc data (AUC: 0.81--0.82 in rET vs. ET and AUC: 0.88--0.89 in rET vs. HC). ML models combining imaging data (cortical thickness, surface, roughness, and mean curvature) together with BRrc values showed the highest classification performance in distinguishing between rET and ET patients, reaching AUC of 0.94 ± 0.05. The improvement in classification performances when BRrc data were added to imaging features was confirmed by both ML algorithms. Conclusion: This study highlights the usefulness of adding a simple electrophysiological assessment such as BRrc to MRI cortical morphometric features for accurately distinguishing rET from ET patients, paving the way for a better classification of these ET syndromes. [ABSTRACT FROM AUTHOR]

Background: Postural instability (PI) is a common disabling symptom in Parkinson's disease (PD), but little is known on its pathophysiological basis. Objective: In this study, we aimed to identify the brain structures associated with PI in PD patients, using different MRI approaches. Methods: We consecutively enrolled 142 PD patients and 45 control subjects. PI was assessed using the MDS-UPDRS-III pull-test item (PT). A whole-brain regression analysis identified brain areas where grey matter (GM) volume correlated with the PT score in PD patients. Voxel-based morphometry (VBM) and Tract-Based Spatial Statistics (TBSS) were also used to compare unsteady (PT ≥ 1) and steady (PT = 0) PD patients. Associations between GM volume in regions of interest (ROI) and several clinical features were then investigated using LASSO regression analysis. Results: PI was present in 44.4% of PD patients. The whole-brain approach identified the bilateral inferior frontal gyrus (IFG) and superior temporal gyrus (STG) as the only regions associated with the presence of postural instability. VBM analysis showed reduced GM volume in fronto-temporal areas (superior, middle, medial and inferior frontal gyrus, and STG) in unsteady compared with steady PD patients, and the GM volume of these regions was selectively associated with the PT score and not with any other motor or non-motor symptom. Conclusions: This study demonstrates a significant atrophy of fronto-temporal regions in unsteady PD patients, suggesting that these brain areas may play a role in the pathophysiological mechanisms underlying postural instability in PD. This result paves the way for further studies on postural instability in Parkinsonism. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) exhibits sex-linked variations, with women having a higher prevalence, and little is known about the sexual dimorphism in progressing from Mild Cognitive Impairment (MCI) to AD. The main aim of our study was to shed light on the sex-specific conversion-to-AD risk factors using Random Survival Forests (RSF), a Machine Learning survival approach, and Shapley Additive Explanations (SHAP) on dementia biomarkers in stable (sMCI) and progressive (pMCI) patients. With this purpose, we built two separate models for male (M-RSF) and female (F-RSF) cohorts to assess whether global explanations differ between the sexes. Similarly, SHAP local explanations were obtained to investigate changes across sexes in feature contributions to individual risk predictions. The M-RSF achieved higher performance on the test set (0.87) than the F-RSF (0.79), and global explanations of male and female models had limited similarity (<71.1%). Common influential variables across the sexes included brain glucose metabolism and CSF biomarkers. Conversely, the M-RSF had a notable contribution from hippocampus, which had a lower impact on the F-RSF, while verbal memory and executive function were key contributors only in F-RSF. Our findings confirmed that females had a higher risk of progressing to dementia; moreover, we highlighted distinct sex-driven patterns of variable importance, uncovering different feature contribution risks across sexes that decrease/increase the conversion-to-AD risk. [ABSTRACT FROM AUTHOR]

Premature ejaculation (PE) is a common male sexual dysfunction that can cause significant distress in the patient and partner. This study aimed to compare the current international guidelines on PE to highlight their similarities and differences. We examined the latest guidelines from the European Association of Urology (EAU), American Urological Association/Sexual Medicine Society of North America (AUA/SMSNA), and International Society of Sexual Medicine (ISSM) by comparing definitions, classifications, epidemiology, pathophysiology, and recommendations on diagnosis and therapy. The quality of guidelines was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) Global Rating Scale (GRS). We found significant variations in the definitions of PE and recommendations on management of patients. The EAU guidelines were the most recent, the AUA/SMSNA guidelines lacked detail in some areas, and the ISSM guidelines were the most complete but also the least updated. The search for a unified definition and the development of standardized diagnostic and therapeutic pathways remain concrete issues to improve the management of patients with PE worldwide. [ABSTRACT FROM AUTHOR]

(1) Background: To identify a particular setting of biopsy-naïve patients in which it would be reasonable to offer only cognitive targeted prostate biopsy (PBx) with a transrectal approach. (2) Methods: We designed an observational retrospective pilot study. Patients with a prostatic specific antigen (PSA) level > 10 ng/mL, either a normal or suspicious digital rectal examination (DRE), and a lesion with a PI-RADS score ≥ 4 in the postero-medial or postero-lateral peripheral zone were included. All patients underwent a transrectal PBx, including both systematic and targeted samples. The detection rate of clinically significant prostate cancer (csPCa) (Gleason Score ≥ 7) was chosen as the primary outcome. We described the detection rate of csPCa in systematic PBx, targeted PBx, and overall PBx. (3) A total of 92 patients were included. Prostate cancer was detected in 84 patients (91.30%) with combined biopsies. A csPCa was diagnosed in all positive cases (100%) with combined biopsies. Systematic PBxs were positive in 80 patients (86.96%), while targeted PBxs were positive in 84 men (91.30%). Targeted PBx alone would have allowed the diagnosis of csPCa in all positive cases; systematic PBx alone would have missed the diagnosis of 8/84 (9.52%) csPCa cases (4 negative patients and 4 not csPCa) (p = 0.011). (4) Conclusions: Cognitive targeted PBx with a transrectal approach could be offered alone to diagnose csPCa in biopsy-naïve patients with PSA ≥ 10 ng/mL, either normal or suspicious DRE, and a lesion with PI-RADS score ≥ 4 in the postero-medial or postero-lateral peripheral zone. [ABSTRACT FROM AUTHOR]

Background: Several magnetic resonance imaging (MRI) measures have been suggested as progression biomarkers in progressive supranuclear palsy (PSP), and some PSP staging systems have been recently proposed. Objective: Comparing structural MRI measures and staging systems in tracking atrophy progression in PSP and estimating the sample size to use them as endpoints in clinical trials. Methods: Progressive supranuclear palsy‐Richardson's syndrome (PSP‐RS) patients with one‐year‐follow‐up longitudinal brain MRI were selected from the placebo arms of international trials (NCT03068468, NCT01110720, NCT01049399) and the DescribePSP cohort. The discovery cohort included patients from the NCT03068468 trial; the validation cohort included patients from other sources. Multisite age‐matched healthy controls (HC) were included for comparison. Several MRI measures were compared: automated atlas‐based volumetry (44 regions), automated planimetric measures of brainstem regions, and four previously described staging systems, applied to volumetric data. Results: Of 508 participants, 226 PSP patients including discovery (n = 121) and validation (n = 105) cohorts, and 251 HC were included. In PSP patients, the annualized percentage change of brainstem and midbrain volume, and a combined index including midbrain, frontal lobe, and third ventricle volume change, were the progression biomarkers with the highest effect size in both cohorts (discovery: >1.6; validation cohort: >1.3). These measures required the lowest sample sizes (n < 100) to detect 30% atrophy progression, compared with other volumetric/planimetric measures and staging systems. Conclusions: This evidence may inform the selection of imaging endpoints to assess the treatment efficacy in reducing brain atrophy rate in PSP clinical trials, with automated atlas‐based volumetry requiring smaller sample size than staging systems and planimetry to observe significant treatment effects. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic presented unique challenges to the U.S. healthcare system, particularly for nonprofit U.S. hospitals that are obligated to provide community benefits in exchange for federal tax exemptions. We sought to examine how hospitals initiated, modified, or disbanded community benefits programming in response to the COVID-19 pandemic. We used the free-response text in Part IV of Internal Revenue Service (IRS) Form 990 Schedule H (F990H) to assess health equity and disparities. We combined traditional key term frequency and Hierarchical Density-Based Spatial Clustering of Applications with Noise (HDBSCAN) clustering approaches with a novel Generative Pre-trained Transformer (GPT) 3.5 summarization approach. Our research reveals shifts in community benefits programming. We observed an increase in COVID-related terms starting in the 2019 tax year, indicating a pivot in community focus and efforts toward pandemic-related activities such as telehealth services and COVID-19 testing and prevention. The clustering analysis identified themes related to COVID-19 and community benefits. Generative Artificial Intelligence (GenAI) summarization with GPT3.5 contextualized these changes, revealing examples of healthcare system adaptations and program cancellations. However, GPT3.5 also encountered some accuracy and validation challenges. This multifaceted text analysis underscores the adaptability of hospitals in maintaining community health support during crises and suggests the potential of advanced AI tools in evaluating large-scale qualitative data for policy and public health research. [ABSTRACT FROM AUTHOR]

Background: There is limited evidence as to whether the immune protein profile is associated with a particular symptomatology pattern across the psychosis continuum. Methods: We estimated two bifactor models of general and specific dimensions of psychotic experiences in unaffected siblings of patients (n = 52) and community controls (n = 200), and of psychotic symptoms in first-episode psychosis (FEP) patients (n = 110). We evaluated associations between these transdiagnostic dimensions and trait (TNF- α , IFN- γ), state (IL-6, IL-1 β), and regulatory (TGF- β , IL-10, IL-4) cytokines. We explored whether schizophrenia genetic liability (schizophrenia polygenic risk score; SZ-PRS) modified the associations. Results: High levels of trait marker IFN- γ were associated with the severity of general psychosis dimension in the unaffected siblings and community controls, expanding to the depressive dimension in siblings and to the manic dimension in FEP. High TNF- α levels were associated with more positive psychotic experiences in unaffected siblings and manic symptoms in FEP. Low levels of state markers IL-6 and IL-1 β were observed in unaffected siblings presenting more depressive experiences. Still, high levels of IL-6 and IL-1 β were associated with the severity of the depressive and negative symptom dimensions at FEP. The severity of transdiagnostic dimension scores across the three groups was associated with lower regulatory cytokines. Exploratory analysis suggested that a high SZ-PRS contributed mostly to associations with psychotic dimensions. Conclusions: IFN- γ mapped onto the multidimensional expression of psychosis, reinforcing the trait concept. State markers IL-6 and IL-1 β may fluctuate along the spectrum. Dysfunction in the regulatory arm may disinhibit the inflammatory system. Associations with psychotic dimensions may be more prone to SZ-PRS susceptibility. [ABSTRACT FROM AUTHOR]

Four-repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R tauopathies are progressive supranuclear palsy (PSP) and corticobasal degeneration characterized by subcortical tau accumulation and cortical neuronal dysfunction, as shown by PET-assessed hypoperfusion and glucose hypometabolism. Yet, there is a spatial mismatch between subcortical tau deposition patterns and cortical neuronal dysfunction, and it is unclear how these two pathological brain changes are interrelated. Here, we hypothesized that subcortical tau pathology induces remote neuronal dysfunction in functionally connected cortical regions to test a pathophysiological model that mechanistically links subcortical tau accumulation to cortical neuronal dysfunction in 4R tauopathies. We included 51 Aβ-negative patients with clinically diagnosed PSP variants (n = 26) or corticobasal syndrome (n = 25) who underwent structural MRI and 18F-PI-2620 tau-PET. 18F-PI-2620 tau-PET was recorded using a dynamic one-stop-shop acquisition protocol to determine an early 0.5–2.5 min post tracer-injection perfusion window for assessing cortical neuronal dysfunction, as well as a 20–40 min post tracer-injection window to determine 4R-tau load. Perfusion-PET (i.e. early window) was assessed in 200 cortical regions, and tau-PET was assessed in 32 subcortical regions of established functional brain atlases. We determined tau epicentres as subcortical regions with the highest 18F-PI-2620 tau-PET signal and assessed the connectivity of tau epicentres to cortical regions of interest using a resting-state functional MRI-based functional connectivity template derived from 69 healthy elderly controls from the ADNI cohort. Using linear regression, we assessed whether: (i) higher subcortical tau-PET was associated with reduced cortical perfusion; and (ii) cortical perfusion reductions were observed preferentially in regions closely connected to subcortical tau epicentres. As hypothesized, higher subcortical tau-PET was associated with overall lower cortical perfusion, which remained consistent when controlling for cortical tau-PET. Using group-average and subject-level PET data, we found that the seed-based connectivity pattern of subcortical tau epicentres aligned with cortical perfusion patterns, where cortical regions that were more closely connected to the tau epicentre showed lower perfusion. Together, subcortical tau-accumulation is associated with remote perfusion reductions indicative of neuronal dysfunction in functionally connected cortical regions in 4R-tauopathies. This suggests that subcortical tau pathology may induce cortical dysfunction, which may contribute to clinical disease manifestation and clinical heterogeneity. [ABSTRACT FROM AUTHOR]

Purpose: Since January 2016, the Parma Department of Mental Health (in Italy) developed a specialized care program for Early Intervention (EI) in individuals at Clinical High Risk for Psychosis (CHR-P). As unfavorable outcomes other than transition to psychosis were not systematically reported in the current literature (thereby compromising more sophisticated prognostic stratifications), the aims of this research were (1) to investigate adverse outcome indicators (i.e., service disengagement, psychosis transition, hospitalization, prolonged functioning impairment, prolonged persistence of CHR-P criteria, suicide attempts) in an Italian CHR-P population enrolled within a specialized EI service across a 2-year follow-up period, and (2) to examine their relevant associations with sociodemographic and clinical characteristics of the CHR-P total sample at baseline. Methods: All participants were young CHR-P help-seekers aged 12–25 years. They completed the "Comprehensive Assessment of At-Risk Mental States" (CAARMS) and the Health of the Nation Outcome Scale (HoNOS). Both univariate and multivariate Cox regression analyses were performed. Results: 164 CHR-P individuals were enrolled in this study. Across the follow-up, 30 (18.0%) dropped out the EI program, 23 (14%) transitioned to psychosis, 24 (14.6%) were hospitalized, 23 (14%) had a prolonged persistence of CHR-P criteria and 54 (47%) showed prolonged impairment in socio-occupational functioning. Conclusion: As almost half of our participants did not functionally remit over time, sustained clinical attention for young CHR individuals people should be offered in the longer term, also to monitor unfavorable outcomes and to improve long-term prognosis. [ABSTRACT FROM AUTHOR]

Purpose: Service disengagement is a major concern for "Early Intervention in Psychosis" (EIP). Indeed, identifying predictors of engagement is crucial to maximize mental healthcare interventions in first-episode psychosis (FEP). No Italian study on this topic has been reported to date. Thus, the aims of this investigation were: (1) to examine short-term disengagement rate in an Italian population of FEP patients treated within an EIP service across a 1-year follow-up period, and (b) to assess the most relevant predictors of disengagement in the first year of treatment. Methods: All participants were young FEP help-seeking patients, aged 12–35 years, enrolled within the "Parma Early Psychosis" (Pr-EP) protocol. At baseline, they completed the Positive And Negative Syndrome Scale (PANSS), the Health of the Nation Outcome Scale (HoNOS) and the Global Assessment of Functioning (GAF) scale. Univariate and multivariate Cox regression analyses were used. Results: 496 FEP individuals were enrolled in this research. Across the follow-up, a 16.5% prevalence of short-term disengagement was found. Particularly robust predictors of service disengagement were poor baseline treatment non-adherence, living with parents and the presence of brief psychotic disorder or schizophreniform disorder at entry. Conclusion: About 16% of FEP patients disengaged the Pr-EP program within the first year of treatment. A solution to reduce disengagement and/or to favor re-engagement of these subjects might be to remain on EIP program caseloads allowing the option for low-intensity support and monitoring, also via remote technology. [ABSTRACT FROM AUTHOR]

Service disengagement is a major concern for "Early Intervention in Psychosis" (EIP). Indeed, understanding predictors of engagement is important for the effectiveness of mental health interventions, to improve outcome and quality of life, also in adolescents with first episode psychosis (FEP). No specific European investigation on this topic in adolescence has been reported in the literature to date. The aim of this study was to investigate service disengagement rate and predictors in an Italian sample of FEP adolescents treated within an EIP program during a 2-year follow-up period. All participants were adolescents help-seekers (aged 12–18 years) enrolled in the "Parma Early Psychosis" (Pr-EP) program. At baseline, they completed the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF) scale. Univariate and multivariate Cox regression analyses were performed. 71 FEP adolescents were recruited in this research. During the 2 years of our follow-up, a 25.4% prevalence rate of service disengagement was found. Particularly robust predictors of disengagement were lower baseline acceptance of psychosocial interventions, substance abuse at entry, and lower baseline PANSS "Disorganization" factor score. Approximately, 1/4 of our FEP adolescents disengaged from the Pr-EP program during the first 2 years of treatment. A possible solution to decrease disengagement and to favor re-engagement of these young individuals might be to provide the option of low-intensity monitoring and support, also via remote technology. [ABSTRACT FROM AUTHOR]

Background: Early detection and standardized treatment are crucial for enhancing outcomes for patients with cutaneous melanoma, the commonly diagnosed skin cancer. However, access to quality health care services remains a critical barrier for many patients, particularly the uninsured. Whereas Medicaid expansion (ME) has had a positive impact on some cancers, its specific influence on cutaneous melanoma remains understudied. Methods: The National Cancer Database identified 87,512 patients 40–64 years of age with a diagnosis of non-metastatic cutaneous melanoma between 2004 and 2017. In this study, patient demographics, disease characteristics, and treatment variables were analyzed, and ME status was determined based on state policies. Standard univariate statistics were used to compare patients with a diagnosis of non-metastatic cutaneous melanoma between ME and non-ME states. The Kaplan–Meier method and log-rank tests were used to evaluate overall survival (OS) between ME and non-ME states. Multivariable Cox regression models were used to examine associations with OS. Results: Overall, 28.6 % (n = 25,031) of the overall cohort was in ME states. The patients in ME states were more likely to be insured, live in neighborhoods with higher median income quartiles, receive treatment at academic/research cancer centers, have lower stages of disease, and receive surgery than the patients in non-ME states. Kaplan–Meier analysis found enhanced 5-year OS for the patients in ME states across all stages. Cox regression showed improved survival in ME states for stage II (hazard ratio [HR], 0.84) and stage III (HR, 0.75) melanoma. Conclusions: This study underscores the positive association between ME and improved diagnosis, treatment, and outcomes for patients with non-metastatic cutaneous melanoma. These findings advocate for continued efforts to enhance health care accessibility for vulnerable populations. [ABSTRACT FROM AUTHOR]

Background: Incidence of first-episode psychosis (FEP) varies substantially across geographic regions. Phenotypes of subclinical psychosis (SP), such as psychotic-like experiences (PLEs) and schizotypy, present several similarities with psychosis. We aimed to examine whether SP measures varied across different sites and whether this variation was comparable with FEP incidence within the same areas. We further examined contribution of environmental and genetic factors to SP. Methods: We used data from 1497 controls recruited in 16 different sites across 6 countries. Factor scores for several psychopathological dimensions of schizotypy and PLEs were obtained using multidimensional item response theory models. Variation of these scores was assessed using multi-level regression analysis to estimate individual and between-sites variance adjusting for age, sex, education, migrant, employment and relational status, childhood adversity, and cannabis use. In the final model we added local FEP incidence as a second-level variable. Association with genetic liability was examined separately. Results: Schizotypy showed a large between-sites variation with up to 15% of variance attributable to site-level characteristics. Adding local FEP incidence to the model considerably reduced the between-sites unexplained schizotypy variance. PLEs did not show as much variation. Overall, SP was associated with younger age, migrant, unmarried, unemployed and less educated individuals, cannabis use, and childhood adversity. Both phenotypes were associated with genetic liability to schizophrenia. Conclusions: Schizotypy showed substantial between-sites variation, being more represented in areas where FEP incidence is higher. This supports the hypothesis that shared contextual factors shape the between-sites variation of psychosis across the spectrum. [ABSTRACT FROM AUTHOR]

Most patients with idiopathic REM sleep behavior disorder (iRBD) present peculiar repetitive leg jerks during sleep in their clinical spectrum, called periodic leg movements (PLMS). The clinical differentiation of iRBD patients with and without PLMS is challenging, without polysomnographic confirmation. The aim of this study is to develop a new Machine Learning (ML) approach to distinguish between iRBD phenotypes. Heart rate variability (HRV) data were acquired from forty-two consecutive iRBD patients (23 with PLMS and 19 without PLMS). All participants underwent video-polysomnography to confirm the clinical diagnosis. ML models based on Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), and eXtreme Gradient Boosting (XGBoost) were trained on HRV data, and classification performances were assessed using Leave-One-Out cross-validation. No significant clinical differences emerged between the two groups. The RF model showed the best performance in differentiating between iRBD phenotypes with excellent accuracy (86%), sensitivity (96%), and specificity (74%); SVM and XGBoost had good accuracy (81% and 78%, respectively), sensitivity (83% for both), and specificity (79% and 72%, respectively). In contrast, LR had low performances (accuracy 71%). Our results demonstrate that ML algorithms accurately differentiate iRBD patients from those without PLMS, encouraging the use of Artificial Intelligence to support the diagnosis of clinically indistinguishable iRBD phenotypes. [ABSTRACT FROM AUTHOR]

Benign prostatic hyperplasia (BPH) is a common urological condition affecting aging men worldwide. Among the treatment options available for BPH, transurethral resection of the prostate (TURP) is the gold-standard invasive intervention. To reduce the TURP-related non-negligible morbidity, loss-of-ejaculation rate, hospitalization, blood loss and catheterization time several laser techniques have been developed, such as the Thulium Laser Enucleation of the Prostate (ThuLEP). To investigate the efficacy outcomes of the ThuLEP as a treatment option for benign prostatic hyperplasia (BPH) we performed a retrospective observational study at Moriggia Pelascini Hospital (Como, Italy) between January 2015 and September 2018. We included 265 patients who underwent ThuLEP at a specific hospital between defined dates. Data on various parameters, including post-void residue volume, peak urinary flow rate (Qmax), International Prostate Symptom Score (IPSS) for urinary symptoms, IPSS Quality of Life (QoL) score, and International Index of Erectile Function (IIEF) score for erectile dysfunction, were collected at baseline and follow-up. The analysis revealed significant improvements in voiding efficiency, urinary flow, urinary symptoms, quality of life, and erectile function following ThuLEP. Furthermore, certain baseline characteristics, such as post-void residue, peak urinary flow rate, age, prostate volume, and aspirin usage, were found to influence treatment outcomes. Despite the study's limitations, these findings contribute to understanding ThuLEP's effectiveness in managing BPH and can aid in making informed clinical decisions for patient care. Prospective studies with longer follow-up periods are recommended to validate and extend these results. [ABSTRACT FROM AUTHOR]

This study explores the synergistic integration of remote sensing (RS) and Historical Landscape Characterisation (HLC) methodology as an innovative, multi-scalar and holistic approach to enhance archaeological planning. The goal is to maximize the effectiveness of the investigations, optimizing data collection and improving the contextual understanding of the sites. In fact, these methodologies can significantly contribute to the documentation, conservation, planning and valorisation of archaeological areas. By integrating RS data with features detected by HLC, a complete picture is obtained that facilitates a deeper understanding of the landscape and historical dynamics. This article will explain the combined approach of RS and HLC, presenting some methodologies key to improving the precision and effectiveness of archaeological planning. This integration facilitates the sustainable preservation of archaeological resources and contributes to the conscious management of cultural heritage in the context of contemporary development. The paper demonstrates, through a case study, how the application of the two methodologies (RS and HLC) in an integrated form can provide an exhaustive interpretation of the territory in which the archaeological area is located, which can represent an exhaustive knowledge base on which to set up effective processes for the strategic territorial planning of archaeological areas. [ABSTRACT FROM AUTHOR]

Simple Summary: In the dairy industry, bovine mastitis poses significant challenges due to production losses and treatment costs. Understanding innate immunity in bovine milk could be crucial for fighting intra-mammary infections. We conducted cytofluorimetric analyses to assess bacterial killing activity in bovine skim milk against Gram-positive (S. aureus) and Gram-negative (E. coli) pathogens. We found that milk exhibited higher bacterial killing activity against S. aureus compared to E. coli, and those results correlated with N-acetyl-β-D-glucosaminidase (NAGase) levels. Both S. aureus killing and NAGase activity decreased with lactation duration. Milk samples from autochthonous Modenese cows displayed stronger killing activity compared to samples from cosmopolitan breed Holstein Friesian cows. Our findings suggest that skim milk is endued with distinct control mechanisms against different pathogens in the mammary gland, and provide insights into innate immune responses and potential strategies for managing mastitis in the dairy industry, which could lead to improved production efficiency and reduced treatment costs. In the dairy industry, bovine mastitis represents a major concern due to substantial production losses and costs related to therapies and early culling. The mechanisms of susceptibility and effective response to intra-mammary infections are still poorly understood. Therefore, we investigated innate immunity in acellular bovine skim milk through cytofluorimetric analyses of bacterial killing activity against both Gram-positive and Gram-negative pathogens. Freshly cultured E. coli and S. aureus strains were incubated with colostrum and milk samples at different lactation time points from two groups of cows, purportedly representing mastitis-resistant and mastitis-susceptible breeds; bacterial cells were analyzed for vitality by flow cytometry following incorporation of vital dyes. N-acetyl-β-D-glucosaminidase (NAGase) activity was also investigated in milk and colostrum samples. Our findings revealed that colostrum and milk bacterial killing activity was greater against S. aureus compared to E. coli., with this activity correlated with milk NAGase levels. Furthermore, both killing of S. aureus and NAGase activity were negatively correlated to the elapsed time of lactation. Interestingly, samples from the allegedly mastitis-resistant breed displayed higher bacterial killing and NAGase activities. Our study suggests that diverse control mechanisms are exerted against Gram-positive and Gram-negative pathogens in the mammary glands of cows, probably beyond those already described in the literature. [ABSTRACT FROM AUTHOR]

The assessment of the combined water is a reliable method to monitor the hydration of cement pastes. This method is also being used to screen different SCMs and cement formulations. However, to obtain reliable data it is necessary to stop the hydration of specimens, removing the free water. In this sense, this work evaluates the effect of different hydration stoppage methods on assessing the combined water of cement pastes. Three procedures were investigated, two using solvent exchange (RILEM and CEMtec), including the one recommended by RILEM TC 238, and the other using silica gel (Silica4h). Firstly, two cement formulations (OPC and LC50) were evaluated using thermogravimetric analysis and X-ray diffraction. The results of combined water at 7 and 28 days were similar independently of the hydration stoppage technique. A repeatability test was also conducted and demonstrated that all three methods presented good repeatability with a low coefficient of variation. Then, six Brazilian commercial cements had their hydration stopped at 7 and 28 days using the studied procedures. The results of combined water were comparable regardless of the used method. A qualitative analysis was also carried out indicating that for the assessment of combined water the Silica4h is the most practical and cost-effective method to stop the hydration of cement pastes and RILEM is the fastest procedure. Finally, both procedures with solvent exchange require attention due to their health and safety issues, solvent disposal, and acquisition. [ABSTRACT FROM AUTHOR]

Simple Summary: The creation of a guideline of guidelines could help physicians apprehend different approaches to malignancies and better-tailoring patients' management. In this context, international guidelines on upper tract urothelial carcinoma (UTUC) have previously never been compared in their similarities and differences. The present effort could guide further researchers to provide more high-quality evidence to homogeneously assess, treat, and follow up patients affected by UTUC worldwide. Moreover, by highlighting similarities and differences, we aim to encourage more conscious and critical use of guidelines and push research to fill knowledge gaps. Background: Upper tract urothelial carcinoma (UTUC) is a rare disease with a potentially dismal prognosis. We systematically compared international guidelines on UTUC to analyze similitudes and differences among them. Methods: We conducted a search on MEDLINE/PubMed for guidelines related to UTUC from 2010 to the present. In addition, we manually explored the websites of urological and oncological societies and journals to identify pertinent guidelines. We also assessed recommendations from the International Bladder Cancer Network, the Canadian Urological Association, the European Society for Medical Oncology, and the International Consultation on Bladder Cancer, considering their expertise and experience in the field. Results: Among all the sources, only the American Urologist Association (AUA), European Association of Urology (EAU), and the National Comprehensive Cancer Network (NCCN) guidelines specifically report data on diagnosis, treatment, and follow-up of UTUC. Current analysis reveals several differences between all three sources on diagnostic work-up, patient management, and follow-up. Among all, AUA and EAU guidelines show more detailed indications. Conclusions: Despite the growing incidence of UTUC, only AUA, EAU, and NCCN guidelines deal with this cancer. Our research depicted high variability in reporting recommendations and opinions. In this regard, we encourage further higher-quality research to gain evidence creating higher grade consensus between guidelines. [ABSTRACT FROM AUTHOR]

Transthyretin cardiac amyloidosis (ATTR-CA) has a deep impact on the quality of life (QoL), yet no specific patient-reported outcome measures (PROMs) for ATTR-CA exist. The ITALY study involved 5 Italian referral centres (Pisa, Pavia, Ferrara, Florence, Messina) enrolling consecutive outpatients with ATTR-CA. Two 30-item questionnaires were created for wild-type (wt) and variant (v) ATTR-CA. Scores ranged from 100 (best condition) to 0 (worst condition). Out of 140 patients enrolled (77% with ATTRwt-CA), 115 repeated the re-evaluation at 6 months. At baseline, only 30% of patients needed help to fill out the questionnaires. Among baseline variables, all KCCQ and SF-36 domains were univariate predictors of ITALY scores in ATTRwt-CA patients, with the KCCQ Symptom Summary score (beta coefficient 0.759), Social Limitations (0.781), and Overall summary score (0.786) being the strongest predictors. The SF-36 Emotional well-being score (0.608), the KCCQ Overall summary score (0.656), and the SF-36 Energy/fatigue score (0.669) were the strongest univariate predictors of ITALY scores in ATTRv-CA. Similar results were found at 6 months. The ITALY questionnaires are the first specific PROMs for ATTRwt- and ATTRv-CA. Questionnaire completion is feasible. ITALY scores display close relationships with non-ATTR-specific measures of QoL. [ABSTRACT FROM AUTHOR]

Random Survival Forests (RSF) has recently showed better performance than statistical survival methods as Cox proportional hazard (CPH) in predicting conversion risk from mild cognitive impairment (MCI) to Alzheimer's disease (AD). However, RSF application in real-world clinical setting is still limited due to its black-box nature. For this reason, we aimed at providing a comprehensive study of RSF explainability with SHapley Additive exPlanations (SHAP) on biomarkers of stable and progressive patients (sMCI and pMCI) from Alzheimer's Disease Neuroimaging Initiative. We evaluated three global explanations—RSF feature importance, permutation importance and SHAP importance—and we quantitatively compared them with Rank-Biased Overlap (RBO). Moreover, we assessed whether multicollinearity among variables may perturb SHAP outcome. Lastly, we stratified pMCI test patients in high, medium and low risk grade, to investigate individual SHAP explanation of one pMCI patient per risk group. We confirmed that RSF had higher accuracy (0.890) than CPH (0.819), and its stability and robustness was demonstrated by high overlap (RBO > 90%) between feature rankings within first eight features. SHAP local explanations with and without correlated variables had no substantial difference, showing that multicollinearity did not alter the model. FDG, ABETA42 and HCI were the first important features in global explanations, with the highest contribution also in local explanation. FAQ, mPACCdigit, mPACCtrailsB and RAVLT immediate had the highest influence among all clinical and neuropsychological assessments in increasing progression risk, as particularly evident in pMCI patients' individual explanation. In conclusion, our findings suggest that RSF represents a useful tool to support clinicians in estimating conversion-to-AD risk and that SHAP explainer boosts its clinical utility with intelligible and interpretable individual outcomes that highlights key features associated with AD prognosis. [ABSTRACT FROM AUTHOR]

Background: Previous literature has shown that executive functions (EF) are related to performance in memory (M) tasks. The Test of Memory strategies (TMS) is a psychometric test that examines EF and M simultaneously and it was recently validated on an Italian healthy cohort. The first aim of the study was to apply TMS, for the first time, on a sample of patients with Parkinson's disease (PD), who are characterized by mild cognitive impairment. The second aim is to investigate whether TMS scores can discriminate PD patients from healthy controls. Method: Ninety-eight subjects were enrolled, including 68 patients with PD, and 30 Italian healthy controls (HC), who also underwent a memory evaluation through well-known tests. Results: Confirmatory factor analysis (CFA) demonstrated that TMS of PD patients had a bi-dimensional structure as previously found in healthy cohort. In detail, The TMS-1 and TMS-2 lists require greater involvement of the EF factor, while TMS-3, TMS-4 and TMS-5 the M factor. Receiver operating characteristic (ROC) curves and precision-recall (PR) curves showed that the M subscale can distinguish between HC and PD, while EF had poor discrimination power. Conclusion: The hypothesized prediction model of TMS test seems to have adequate ability to discriminate PD from HC especially for the M function. [ABSTRACT FROM AUTHOR]

Background: Differentiating Progressive supranuclear palsy-Richardson's syndrome (PSP-RS) from PSP-Parkinsonism (PSP-P) may be extremely challenging. In this study, we aimed to distinguish these two PSP phenotypes using MRI structural data. Methods: Sixty-two PSP-RS, 40 PSP-P patients and 33 control subjects were enrolled. All patients underwent brain 3 T-MRI; cortical thickness and cortical/subcortical volumes were extracted using Freesurfer on T1-weighted images. We calculated the automated MR Parkinsonism Index (MRPI) and its second version including also the third ventricle width (MRPI 2.0) and tested their classification performance. We also employed a Machine learning (ML) classification approach using two decision tree-based algorithms (eXtreme Gradient Boosting [XGBoost] and Random Forest) with different combinations of structural MRI data in differentiating between PSP phenotypes. Results: MRPI and MRPI 2.0 had AUC of 0.88 and 0.81, respectively, in differentiating PSP-RS from PSP-P. ML models demonstrated that the combination of MRPI and volumetric/thickness data was more powerful than each feature alone. The two ML algorithms showed comparable results, and the best ML model in differentiating between PSP phenotypes used XGBoost with a combination of MRPI, cortical thickness and subcortical volumes (AUC 0.93 ± 0.04). Similar performance (AUC 0.93 ± 0.06) was also obtained in a sub-cohort of 59 early PSP patients. Conclusion: The combined use of MRPI and volumetric/thickness data was more accurate than each MRI feature alone in differentiating between PSP-RS and PSP-P. Our study supports the use of structural MRI to improve the early differential diagnosis between common PSP phenotypes, which may be relevant for prognostic implications and patient inclusion in clinical trials. [ABSTRACT FROM AUTHOR]

Rest tremor (RT) is observed in subjects with Parkinson's disease (PD) and Essential Tremor (ET). Electromyography (EMG) studies have shown that PD subjects exhibit alternating contractions of antagonistic muscles involved in tremors, while the contraction pattern of antagonistic muscles is synchronous in ET subjects. Therefore, the RT pattern can be used as a potential biomarker for differentiating PD from ET subjects. In this study, we developed a new wearable device and method for differentiating alternating from a synchronous RT pattern using inertial data. The novelty of our approach relies on the fact that the evaluation of synchronous or alternating tremor patterns using inertial sensors has never been described so far, and current approaches to evaluate the tremor patterns are based on surface EMG, which may be difficult to carry out for non-specialized operators. This new device, named "RT-Ring", is based on a six-axis inertial measurement unit and a Bluetooth Low-Energy microprocessor, and can be worn on a finger of the tremulous hand. A mobile app guides the operator through the whole acquisition process of inertial data from the hand with RT, and the prediction of tremor patterns is performed on a remote server through machine learning (ML) models. We used two decision tree-based algorithms, XGBoost and Random Forest, which were trained on features extracted from inertial data and achieved a classification accuracy of 92% and 89%, respectively, in differentiating alternating from synchronous tremor segments in the validation set. Finally, the classification response (alternating or synchronous RT pattern) is shown to the operator on the mobile app within a few seconds. This study is the first to demonstrate that different electromyographic tremor patterns have their counterparts in terms of rhythmic movement features, thus making inertial data suitable for predicting the muscular contraction pattern of tremors. [ABSTRACT FROM AUTHOR]

In patients with movement disorders, voluntary movements can sometimes be accompanied by unintentional muscle contractions in other body regions. In this review, we discuss clinical and pathophysiological aspects of several motor phenomena including mirror movements, dystonic overflow, synkinesia, entrainment and mirror dystonia, focusing on their similarities and differences. These phenomena share some common clinical and pathophysiological features, which often leads to confusion in their definition. However, they differ in several aspects, such as the body part showing the undesired movement, the type of this movement (identical or not to the intentional movement), the underlying neurological condition, and the role of primary motor areas, descending pathways and inhibitory circuits involved, suggesting that these are distinct phenomena. We summarize the main features of these fascinating clinical signs aiming to improve the clinical recognition and standardize the terminology in research studies. We also suggest that the term "mirror dystonia" may be not appropriate to describe this peculiar phenomenon which may be closer to dystonic overflow rather than to the classical mirror movements. [ABSTRACT FROM AUTHOR]

Background: Neuroblastoma (NB) represents the most frequent and aggressive form of extracranial solid tumor of infants. Although the overall survival of patients with NB has improved in the last years, more than 50% of high-risk patients still undergo a relapse. Thus, in the era of precision/personalized medicine, the need for high-risk NB patient-specific therapies is urgent. Methods: Within the PeRsonalizEd Medicine (PREME) program, patient-derived NB tumors and bone marrow (BM)-infiltrating NB cells, derived from either iliac crests or tumor bone lesions, underwent to histological and to flow cytometry immunophenotyping, respectively. BM samples containing a NB cells infiltration from 1 to 50 percent, underwent to a subsequent NB cells enrichment using immune-magnetic manipulation. Then, NB samples were used for the identification of actionable targets and for the generation of 3D/tumor-spheres and Patient-Derived Xenografts (PDX) and Cell PDX (CPDX) preclinical models. Results: Eighty-four percent of NB-patients showed potentially therapeutically targetable somatic alterations (including point mutations, copy number variations and mRNA over-expression). Sixty-six percent of samples showed alterations, graded as "very high priority", that are validated to be directly targetable by an approved drug or an investigational agent. A molecular targeted therapy was applied for four patients, while a genetic counseling was suggested to two patients having one pathogenic germline variant in known cancer predisposition genes. Out of eleven samples implanted in mice, five gave rise to (C)PDX, all preserved in a local PDX Bio-bank. Interestingly, comparing all molecular alterations and histological and immunophenotypic features among the original patient's tumors and PDX/CPDX up to second generation, a high grade of similarity was observed. Notably, also 3D models conserved immunophenotypic features and molecular alterations of the original tumors. Conclusions: PREME confirms the possibility of identifying targetable genomic alterations in NB, indeed, a molecular targeted therapy was applied to four NB patients. PREME paves the way to the creation of clinically relevant repositories of faithful patient-derived (C)PDX and 3D models, on which testing precision, NB standard-of-care and experimental medicines. [ABSTRACT FROM AUTHOR]

Root hairs are considered important for rhizosphere formation, which affects root system functioning. Through interactions with soil microorganisms mediated by root exudation, root hairs may affect the phenotypes and growth of young plants. We tested this hypothesis by integrating results from two experiments: (1) a factorial greenhouse seedling experiment with Zea mays B73‐wt and its root‐hairless mutant, B73‐rth3, grown in live and autoclaved soil, quantifying 15 phenotypic traits, seven growth rates, and soil microbiomes and (2) a semi‐hydroponic system quantifying root exudation of maize genotypes. Possibly as compensation for lacking root hairs, B73‐rth3 seedlings allocated more biomass to roots and grew slower than B73‐wt seedlings in live soil, whereas B73‐wt seedlings grew slowest in autoclaved soil, suggesting root hairs can be costly and their benefits were realized with more complete soil microbial assemblages. There were substantial differences in root exudation between genotypes and in rhizosphere versus non‐rhizosphere microbiomes. The microbial taxa enriched in the presence of root hairs generally enhanced growth compared to taxa enriched in their absence. Our findings suggest the root hairs' adaptive value extends to plant‐microbe interactions mediated by root exudates, affecting plant phenotypes, and ultimately, growth. Summary Statement: An experiment with seedlings of Zea mays B73 and its root‐hairless mutant (Z. mays B73‐rth3) with contrasting soil microbiomes showed that root hairs are beneficial towards plant growth but can be costly. Root hairs' adaptive value was partly mediated by plant‐microbe interactions involving exudates, which feedback to plant phenotypes and growth. [ABSTRACT FROM AUTHOR]

Aim: The prognostic prediction of outcomes in individuals at clinical high‐risk for psychosis (CHR‐P) is still a significant clinical challenge. Among multiple baseline variables of risk calculator models, the role of ongoing pharmacological medications has been partially neglected, despite meta‐analytical evidence of higher risk of psychosis transition associated with baseline prescription exposure to antipsychotics (AP) in CHR‐P individuals. The main aim of the current study was to test the hypothesis that ongoing AP need at baseline indexes a subgroup of CHR‐P individuals with more severe psychopathology and worse prognostic trajectories along a 1‐year follow‐up period. Methods: This research was settled within the 'Parma At‐Risk Mental States' program. Baseline and 1‐year follow‐up assessment included the Positive And Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF). CHR‐P individuals who were taking AP medications at entry were included in the CHR‐P‐AP+ subgroup. The remaining participants were grouped as CHR‐P‐AP‐. Results: Hundred and seventy‐eight CHR‐P individuals (aged 12–25 years) were enrolled (91 CHR‐P‐AP+, 87 CHR‐P‐AP‐). Compared to CHR‐P AP‐, CHR‐P AP+ individuals had older age, greater baseline PANSS 'Positive Symptoms' and 'Negative Symptoms' factor subscores and a lower GAF score. At the end of our follow‐up, CHR‐P‐AP+ subjects showed higher rates of psychosis transition, new hospitalizations and urgent/non‐planned visits compared to CHRP‐ AP‐ individuals. Conclusions: In agreement with increasing empirical evidence, also the results of the current study suggest that AP need is a significant prognostic variable in cohorts of CHR‐P individuals and should be included in risk calculators. [ABSTRACT FROM AUTHOR]

This article discusses a case of progressive encephalomyelitis with rigidity and myoclonus (PERM) associated with anti-DPPX antibodies. PERM is a severe form of stiff-person-syndrome spectrum disorders characterized by brainstem and autonomic involvement, as well as axial and limb rigidity. The patient in this case presented with a neuropsychiatric prodrome, including behavioral changes, weight loss, and movement disorders. The diagnosis was confirmed through positive serum and cerebrospinal fluid DPPX antibodies. Treatment with immunotherapies resulted in significant improvement in symptoms. The document provides a table summarizing the symptoms, CSF findings, and therapy response of patients with PERM associated with different antibodies. The authors emphasize the importance of early recognition and treatment of this condition. [Extracted from the article]

Plant genotype is recognized to contribute to variations in microbial community structure in the rhizosphere, soil adherent to roots. However, the extent to which the viral community varies has remained poorly understood and has the potential to contribute to variation in soil microbial communities. Here we cultivated replicates of two Zea mays genotypes, parviglumis and B73, in a greenhouse and harvested the rhizobiome (rhizoplane and rhizosphere) to identify the abundance of cells and viruses as well as rhizobiome microbial and viral community using 16S rRNA gene amplicon sequencing and genome resolved metagenomics. Our results demonstrated that viruses exceeded microbial abundance in the rhizobiome of parviglumis and B73 with a significant variation in both the microbial and viral community between the two genotypes. Of the viral contigs identified only 4.5% (n = 7) of total viral contigs were shared between the two genotypes, demonstrating that plants even at the level of genotype can significantly alter the surrounding soil viral community. An auxiliary metabolic gene associated with glycoside hydrolase (GH5) degradation was identified in one viral metagenome-assembled genome (vOTU) identified in the B73 rhizobiome infecting Propionibacteriaceae (Actinobacteriota) further demonstrating the viral contribution in metabolic potential for carbohydrate degradation and carbon cycling in the rhizosphere. This variation demonstrates the potential of plant genotype to contribute to microbial and viral heterogeneity in soil systems and harbors genes capable of contributing to carbon cycling in the rhizosphere. [ABSTRACT FROM AUTHOR]

Plants influence the abiotic and biotic environment of the rhizosphere, affecting plant performance through plant–soil feedback (PSF). We compared the strength of nutrient and microbe-mediated PSF and its implications for plant performance in domesticated and wild grasses with a fully crossed greenhouse PSF experiment using four inbred maize genotypes (Zea mays ssp. mays b58, B73-wt, B73-rth3, and HP301), teosinte (Z. mays ssp. parviglumis), and two wild prairie grasses (Andropogon gerardii and Tripsacum dactyloides) to condition soils for three feedback species (maize B73-wt, teosinte, Andropogon gerardii). We found evidence of negative PSF based on growth, phenotypic traits, and foliar nutrient concentrations for maize B73-wt, which grew slower in maize-conditioned soil than prairie grass-conditioned soil. In contrast, teosinte and A. gerardii showed few consistent feedback responses. Both rhizobiome and nutrient-mediated mechanisms were implicated in PSF. Based on 16S rRNA gene amplicon sequencing, the rhizosphere bacterial community composition differed significantly after conditioning by prairie grass and maize plants, and the final soil nutrients were significantly influenced by conditioning, more so than by the feedback plants. These results suggest PSF-mediated soil domestication in agricultural settings can develop quickly and reduce crop productivity mediated by PSF involving changes to both the soil rhizobiomes and nutrient availability. [ABSTRACT FROM AUTHOR]

Negative Symptoms (NS) severely affect real-world functioning also in young people at UHR for developing psychosis. However, longitudinal research on beneficial effects of specialized treatments for NS in UHR people is still relatively scarce and inconclusive, especially in real-world care settings. The aims of the present research were: (1) to evaluate the longitudinal stability of NS levels in young UHR subjects treated within a specialized "Early Intervention in Psychosis" (EIP) program across a 2-year follow-up period, and (2) to investigate any relevant association of NS changes with the specific treatment components offered within the EIP program. One hundred UHR individuals (aged 12–25 years) completed the Positive And Negative Syndrome Scale (PANSS). A multiple linear regression analysis was conducted to examine significant associations between longitudinal changes in NS severity levels and the EIP treatment components. Across the follow-up, a significant decrease in NS clinical severity was observed. This reduction was associated with the intensity of individual psychotherapy sessions provided in the first year of treatment, a shorter duration of untreated illness at entry and the 2-year longitudinal decrease in positive symptom levels. In conclusion, NS are relevant in UHR people, but decrease over time together with the delivery of specialized EIP interventions. Specifically, our results showed that individual psychotherapy may reduce the clinical severity of NS at least during the first year of treatment. [ABSTRACT FROM AUTHOR]

Introduction: There is some debate on the relationship between essential tremor with rest tremor (rET) and the classic ET syndrome, and only few MRI studies compared ET and rET patients. This study aimed to explore structural cortical differences between ET and rET, to improve the knowledge of these tremor syndromes. Methods: Thirty-three ET patients, 30 rET patients and 45 control subjects (HC) were enrolled. Several MR morphometric variables (thickness, surface area, volume, roughness, mean curvature) of brain cortical regions were extracted using Freesurfer on T1-weighted images and compared among groups. The performance of a machine learning approach (XGBoost) using the extracted morphometric features was tested in discriminating between ET and rET patients. Results: rET patients showed increased roughness and mean curvature in some fronto-temporal areas compared with HC and ET, and these metrics significantly correlated with cognitive scores. Cortical volume in the left pars opercularis was also lower in rET than in ET patients. No differences were found between ET and HC. XGBoost discriminated between rET and ET with mean AUC of 0.86 ± 0.11 in cross-validation analysis, using a model based on cortical volume. Cortical volume in the left pars opercularis was the most informative feature for classification between the two ET groups. Conclusion: Our study demonstrated higher cortical involvement in fronto-temporal areas in rET than in ET patients, which may be linked to the cognitive status. A machine learning approach based on MR volumetric data demonstrated that these two ET subtypes can be distinguished using structural cortical features. [ABSTRACT FROM AUTHOR]

Background: While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis. Methods: We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case–control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC. We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case–control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case–control status. Results: Controls (86.1%) and FEPp (75.63%) were most likely to report 'because of friends' as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: 'to feel better' as their RFUC (χ2 = 50.97; p < 0.001). RFUC 'to feel better' was associated with being a FEPp (OR 1.74; 95% CI 1.03–2.95) while RFUC 'with friends' was associated with being a control (OR 0.56; 95% CI 0.37–0.83). The path model indicated an association between RFUC 'to feel better' with heavy cannabis use and with FEPp-control status. Conclusions: Both FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use 'to feel better'. People who reported their reason for first using cannabis to 'feel better' were more likely to progress to heavy use and develop a psychotic disorder than those reporting 'because of friends'. [ABSTRACT FROM AUTHOR]