Background and Objectives Microglia, the resident immune cell of the brain and retina, is widespread activated in the white and gray matter (GM) in multiple sclerosis (MS). The objective of this study is to evaluate the presence and number of hyperreflecting foci (HRF), considered clusters of activated and proliferating retinal microglia, and their association with clinical and radiologic disease parameters in relapsing-remitting MS (RRMS). Methods At baseline, 80 patients with RRMS underwent optical coherence tomography (OCT) and 3T-MRI (including 3-dimensional T1, fluid-attenuated inversion recovery, and double inversion recovery sequences), closed to their disease onset (6.3 ± 5.1 months). These patients were then clinically and radiologically followed up for a mean of 43 months, evaluating the no evidence of disease activity (NEDA) condition, further divided into clinical (cNEDA) and radiologic (rNEDA). Patients with a clinical history or MRI/OCT findings suggestive of optic neuritis (ON) were excluded from the study. Results Compared with healthy controls, the HRF number was significantly higher in the inner nuclear layer (INL) of patients with RRMS (19.55 ± 5.65 vs 13.84 ± 2.57, p < 0.001) and associated with INL volume (β: 1.21, p < 0.001). GM lesion volume significantly correlated with the INL HRF count (p = 0.008). Survival analysis revealed a significant association between INL HRF and both cNEDA (p = 0.017) and rNEDA (p = 0.002). Discussion We found a strong association between retinal microglial proliferation and cortical pathology in RRMS, a finding suggesting a possible underlying common immunopathologic mechanism. Furthermore, microglial activation at baseline was observed to predict subsequent inflammatory events, indicating that HRF might be a candidate prognostic biomarker worthy of further investigation. Classification of Evidence This study provides Class II evidence that in patients with early RRMS but without ON, the number of HRF on OCT of the retinal inner nuclear layer is associated with cNEDA and rNEDA.

Background: With the rapid expansion of artificial intelligence (AI) applications, researchers have begun focusing on the concept of human-centered artificial intelligence (HCAI). This field is dedicated to designing AI systems that augment and improve human abilities, rather than substituting them. Objective: The objective of the paper was to review the information on design principles, techniques, applications, methods, and outcomes adopted in the field of HCAI, in order to provide some insights on the discipline, in relation with the broader concepts of human-centered and user-centered design. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) checklist guidelines, we conducted a scoping review in PubMed, ScienceDirect, and IEEE Xplore, including all study types, excluding narrative reviews and editorials. Results: Out of the 1035 studies retrieved, 14 studies conducted between 2018 and 2023 met the inclusion criteria. The main fields of application were the health sector and AI applications. Human-centered design methodologies were adopted in 3 studies, personas in 2 studies, while the remaining methodologies were adopted in individual studies. Conclusions: HCAI emphasizes designing AI systems that prioritize human needs, satisfaction, and trustworthiness, but current principles and guidelines are often vague and difficult to implement. The review highlights the importance of involving users early in the development process to enhance trust, especially in fields like health care, but notes that there is a lack of standardized HCAI methodologies and limited practical applications adhering to these principles.

Over the last years has emerged the urgent need for the identification of reliable prognostic biomarkers able to potentially identify metastatic castration-resistant prostate cancer (mCRPC) patients most likely to benefit from Radium-223 (Ra-223) since baseline. In the present monocentric retrospective study, we analyzed the prognostic power of systemic inflammation biomarkers and 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET)-derived parameters and their potential interplay in this clinical setting. The following baseline laboratory parameters were collected in 59 mCRPC patients treated with Ra-223: neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelets-to-lymphocyte ratio (PLR), and systemic inflammation index (SII), while maximum Standardized Uptake Value, Metabolic Tumor Volume (MTV), and Total Lesion Glycolysis (TLG) were calculated in the 48 of them submitted to baseline FDG-PET. At the univariate analysis, NLR, dNLR, MTV, and TLG were able to predict the overall survival (OS). However, only NLR and MTV were independent predictors of OS at the multivariate analysis. Additionally, the occurrence of both increased NLR and MTV at baseline identified mCRPC patients at higher risk for lower long-term survival after treatment with Ra-223. In conclusion, the degree of systemic inflammation, the quantification of the metabolically active tumor burden and their combination might represent potentially valuable tools for identifying mCRPC patients who are most likely to benefit from Ra-223. However, further studies are needed to reproduce these findings in larger settings.

Aim: This study aims to profile migraine patients according clinical and psychophysical characteristics. Method: In this observational study, two cohorts of migraine patients(episodic/chronic) were included. Cohort-1: ictal/perictal phase; Cohort-2: interictal phase. The following variables were assessed: headache frequency; disability; cervical active range of motion(AROM) in flexion, extension, right/left lateral flexion, right/left rotation; pressure-pain threshold(PPT) over: temporalis, two cervical areas(C1/C4 vertebral segments), and two distal pain-free areas(hand/leg). Cluster analysis was performed using the K-means algorithm. Differences across clusters were investigated. Results: Cohort-1: 100 patients were included, and two clusters were identified. Cluster-1.1 (19%), Cluster-1.2 (81%). Cluster 1.1 had a higher percentage of men (P = .037) and higher disability (P = .003) compared to Clusters 1.2. Cluster 1.2 had reduced AROM in flexion, extension, and left/right lateral flexion (P < .037), and lower PPT value in all areas (P < .001) compared to Cluster 1.1. Cohort-2: 98 patients were included and three clusters were identified. Cluster-2.1(18%), Cluster-2.2(45%), and Cluster-2.3(37%). Cluster-2.1 had a higher percentage of men compared to clusters-2.2 and 2.3 (P = .009). Cluster-2.3 had higher headache frequency, and disability compared to Cluster-2.2 (P < .006), and higher disability compared to Cluster-2.1 (P = .010). Cluster-2.3 had reduced AROM in all directions compared to Clusters-2.1 and 2.2 (P < .029). Clusters-2.2 and 2.3 have lower PPT values in all areas compared to Cluster-1.1 (P < .001). Conclusion: In the Ictal/perictal phase, two clusters were identified according to clinical and psychophysical characteristics, with one group showing no psychophysical impairment and one with increased pain-sensitivity and cervical musculoskeletal-dysfunctions. In the interictal phase, three clusters could be identified, with one group showing no psychophysical impairment, one increased pain-sensitivity, and one increased pain sensitivity and cervical musculoskeletal-dysfunctions.

The multicentric retrospective BIO-Ra study combined inflammatory indices from peripheral blood and clinical factors in a composite prognostic score for metastatic castration-resistant prostate cancer patients receiving Radium-223 (Ra-223). In the present study, we evaluated (i) the prognostic power of the BIO-Ra score in the framework of the restricted use of Ra-223 promoted by the European Medicines Agency in 2018; (ii) the treatment completion prediction of the BIO-Ra score. Four hundred ninety-four patients from the BIO-Ra cohort were divided into three risk classes according to the BIO-Ra score to predict the treatment completion rate (p < 0.001 among all the three groups). Patients receiving Ra-223 after restriction (89/494) were at later stages of the disease compared with the pre-restriction cohort (405/494), as a higher percentage of BIO-Ra high-risk classes (46.1% vs. 34.6%) and lower median Overall survival (12.4 vs. 23.7 months, p < 0.001) was observed. Despite this clinically relevant difference, BIO-Ra classes still predicted divergent treatment completion rates in the post-restriction subgroup (72%, 52.2%, and 46.3% of patients belonging to low-, intermediate-, and high-risk classes, respectively). Although the restricted use has increased patients at higher risk with unfavourable outcome after Ra-223 treatment, the BIO-Ra score maintains its prognostic value.