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BackgroundPatients with multiple sclerosis (MS) face several challenges in accessing clinical tools to help them monitor, understand, and make meaningful decisions about their disease course. The University of California San Francisco MS BioScreen is a web-based precision medicine tool initially designed to be clinician facing. We aimed to design a second, openly available tool, Open MS BioScreen, that would be accessible, understandable, and actionable by people with MS. ObjectiveThis study aimed to describe the human-centered design and development approach (inspiration, ideation, and implementation) for creating the Open MS BioScreen platform. MethodsWe planned an iterative and cyclical development process that included stakeholder engagement and iterative feedback from users. Stakeholders included patients with MS along with their caregivers and family members, MS experts, generalist clinicians, industry representatives, and advocacy experts. Users consisted of anyone who wants to track MS measurements over time and access openly available tools for people with MS. Phase I (inspiration) consisted of empathizing with users and defining the problem. We sought to understand the main challenges faced by patients and clinicians and what they would want to see in a web-based app. In phase II (ideation), our multidisciplinary team discussed approaches to capture, display, and make sense of user data. Then, we prototyped a series of mock-ups to solicit feedback from clinicians and people with MS. In phase III (implementation), we incorporated all concepts to test and iterate a minimally viable product. We then gathered feedback through an agile development process. The design and development were cyclical—many times throughout the process, we went back to the drawing board. ResultsThis human-centered approach generated an openly available, web-based app through which patients with MS, their clinicians, and their caregivers can access the site and create an account. Users can enter information about their MS (basic level as well as more advanced concepts), visualize their data longitudinally, access a series of algorithms designed to empower them to make decisions about their treatments, and enter data from wearable devices to encourage realistic goal setting about their ambulatory activity. Agile development will allow us to continue to incorporate precision medicine tools, as these are validated in the clinical research arena. ConclusionsAfter engaging intended users into the iterative human-centered design of the Open MS BioScreen, we will now monitor the adaptation and dissemination of the tool as we expand its functionality and reach. The insights generated from this approach can be applied to the development of a number of self-tracking, self-management, and user engagement tools for patients with chronic conditions.

Abstract The extremely high levels of genetic polymorphism within the human major histocompatibility complex (MHC) limit the usefulness of reference-based alignment methods for sequence assembly. We incorporate a short-read, de novo assembly algorithm into a workflow for novel application to the MHC. MHConstructor is a containerized pipeline designed for high-throughput, haplotype-informed, reproducible assembly of both whole genome sequencing and target capture short-read data in large, population cohorts. To-date, no other self-contained tool exists for the generation of de novo MHC assemblies from short-read data. MHConstructor facilitates wide-spread access to high-quality, alignment-free MHC sequence analysis.

Abstract The multifaceted nature of multiple sclerosis requires quantitative biomarkers that can provide insights related to diverse physiological pathways. To this end, proteomic analysis of deeply-phenotyped serum samples, biological pathway modeling, and network analysis were performed to elucidate inflammatory and neurodegenerative processes, identifying sensitive biomarkers of multiple sclerosis disease activity. Here, we evaluated the concentrations of > 1400 serum proteins in 630 samples from three multiple sclerosis cohorts for association with clinical and radiographic new disease activity. Twenty proteins were associated with increased clinical and radiographic multiple sclerosis disease activity for inclusion in a custom assay panel. Serum neurofilament light chain showed the strongest univariate correlation with gadolinium lesion activity, clinical relapse status, and annualized relapse rate. Multivariate modeling outperformed univariate for all endpoints. A comprehensive biomarker panel including the twenty proteins identified in this study could serve to characterize disease activity for a patient with multiple sclerosis.

Abstract Considering the increasing demand for personalized surgical care, as well as current healthcare resources limitations, the use of anatomical accurate 3D physical phantoms is becoming increasingly important for the training of surgeons and the test of surgical instruments. A lack of physical models is nowadays denoted regarding the training in electrosurgery, despite its wide diffusion in medical practice. This work reports an extensive characterization of electrosurgical physical phantoms fabricated with tissue‐mimicking ionogels and hydrogels. A careful design of the conductive gels allow the fine tuning of their mechanical and electrical properties, in order to match those of biological tissues. The manufacturing of a novel multi‐material skin stratification bench‐top pad is reported together with its use for training in both cold and electrical surgery. Furthermore, a feasibility study is reported, showing the use of conductive ionogels for simulating the coagulation of cortical vessels during brain surgery.

Background Coproduction is defined as patients and clinicians collaborating equally and reciprocally in healthcare and is a crucial concept for quality improvement (QI) of health services. Learning Health Networks (LHNs) provide insights to integrate coproduction with QI efforts from programmes from various health systems.Objective We describe interventions to develop and maintain patient and family partner (PFP) coproduction, measured by PFP-reported and programme-reported scales. We aim to increase percentage of programmes with PFPs reporting active QI work within their programme, while maintaining satisfaction in PFP-clinician relationships.Methods Conducted in the Cystic Fibrosis Learning Network (CFLN), an LHN comprising over 30 cystic fibrosis (CF) programmes, people with CF, caregivers and clinicians cocreated interventions in readiness awareness, inclusive PFP recruitment, onboarding process, partnership development and leadership opportunities. Interventions were adapted by CFLN programmes and summarised in a change package for existing programmes and the orientation of new ones. We collected monthly assessments for PFP and programme perceptions of coproduction and PFP self-rated competency of QI skills and satisfaction with programme QI efforts. We used control charts to analyse coproduction scales and run charts for PFP self-ratings.Results Between 2018 and 2022, the CFLN expanded to 34 programmes with 52% having ≥1 PFP reporting active QI participation. Clinicians from 76% of programmes reported PFPs were actively participating or leading QI efforts. PFPs reported increased QI skills competency (17%–32%) and consistently high satisfaction and feeling valued in their work.Conclusions Implementing system-level programmatic strategies to engage and sustain partnerships between clinicians and patients and families with CF improved perceptions of coproduction to conduct QI work. Key adaptable strategies for programmes included onboarding and QI training, supporting multiple PFPs simultaneously and developing financial recognition processes. Interventions may be applicable in other health conditions beyond CF seeking to foster the practice of coproduction.

Abstract Background Pancreatic cancer (PC) first‐line therapy often consists of polychemotherapy regimens, but choosing a second‐line therapy after disease progression, especially following first‐line FOLFIRINOX, remains a clinical challenge. This study presents results from a large, multicenter, retrospective analysis of Italian patients with metastatic PC (mPC) treated with Nab‐paclitaxel/Gemcitabine (AG) as second or later line of treatment. Main objective of the study is to identify prognostic factors that could inform treatment decisions. Methods The study included 160 mPC patients treated with AG in 17 Italian institutions. AG was administered according to labelling dose, until disease progression, unacceptable toxicity or patient refusal. Variations in schedules, dose modifications, supportive measures, and response evaluation were determined by individual clinicians' practice. Results AG was well‐tolerated and exhibited promising clinical activity. The overall response rate (ORR) and the disease control rate (DCR) were 22.5% and 45.6%, respectively. Median progression‐free survival (PFS) and overall survival (OS) were 3.9 and 6.8 months, respectively. Among the patients who received AG as a second‐line therapy (n = 111, 66.9%), median PFS and OS were 4.2 and 7.4 months, respectively. Notably, in the 76 patients (68%) receiving AG after first‐line FOLFIRINOX, an ORR of 19.7% and a DCR of 46.0% were observed, resulting in a median PFS of 3.5 and median OS of 5.7 months. The study identified specific clinical or laboratory parameters (LDH, NLR, fasting serum glucose, liver metastases, ECOG PS, and first‐line PFS) as independent prognostic factors at multivariate level. These factors were used to create a prognostic nomogram that divided patients into three risk classes, helping to predict second‐line OS and PFS. Conclusions This study represents the largest real‐world population of mPC patients treated with AG as a second or later line of therapy. It supports the feasibility of this regimen following first‐line FOLFIRINOX, particularly in patients with specific clinical and laboratory characteristics who derived prolonged benefit from first‐line therapy.

Aim of the Study: To assess how virtual reality (VR) patient-specific simulations can support decision-making processes and improve care in pediatric urology, ultimately improving patient outcomes. Patients and Methods: Children diagnosed with urological conditions necessitating complex procedures were retrospectively reviewed and enrolled in the study. Patient-specific VR simulations were developed with medical imaging specialists and VR technology experts. Routine CT images were utilized to create a VR environment using advanced software platforms. The accuracy and fidelity of the VR simulations was validated through a multi-step process. This involved comparing the virtual anatomical models to the original medical imaging data and conducting feedback sessions with pediatric urology experts to assess VR simulations’ realism and clinical relevance. Results: A total of six pediatric patients were reviewed. The median age of the participants was 5.5 years (IQR: 3.5–8.5 years), with an equal distribution of males and females across both groups. A minimally invasive laparoscopic approach was performed for adrenal lesions (n = 3), Wilms’ tumor (n = 1), bilateral nephroblastomatosis (n = 1), and abdominal trauma in complex vascular and renal malformation (ptotic and hypoplastic kidney) (n = 1). Key benefits included enhanced visualization of the segmental arteries and the deep vascularization of the kidney and adrenal glands in all cases. The high depth perception and precision in the orientation of the arteries and veins to the parenchyma changed the intraoperative decision-making process in five patients. Preoperative VR patient-specific simulation did not offer accuracy in studying the pelvic and calyceal anatomy. Conclusions: VR patient-specific simulations represent an empowering tool in pediatric urology. By leveraging the immersive capabilities of VR technology, preoperative planning and intraoperative navigation can greatly impact surgical decision-making. As we continue to advance in medical simulation, VR holds promise in educational programs to include even surgical treatment of more complex urogenital malformations.

Microalgae are currently considered an attractive source of highly valuable metabolites potentially exploitable as anticancer agents, nutraceuticals and cosmeceuticals and for bioenergy purposes. Their ease of culturing and their high growth rates further promote their use as raw material for the production of specialty products. In the present paper, we focused our attention on specific glycerol-based lipid compounds, monoacylglycerols (MAGs), which displayed in our previous studies a selective cytotoxic activity against the haematological U-937 and the colon HCT-116 cancer cell lines. Here, we performed a quali/quantitative analysis of MAGs and total fatty acids (FAs) along with a profiling of the main lipid classes in a panel of 12 microalgal species, including diatoms and dinoflagellates. Our results highlight an inter- and intraspecific variability of MAG profile in the selected strains. Among them, Skeletonema marinoi (strain FE7) has emerged as the most promising source for possible biotechnological production of MAGs.

B30 introduces the breaking of the Sphairos by Strife. At v. 1 the variant ἐθρέφθη, transmitted by Arist., Metaph., is widely accepted, although the rest of the fragment (except for the emendation of παρελήλαται into παρ᾽ελήλαται) is taken from Simpl., in Ph. The author brings forward many arguments in favour of the commentator’s reading ἐρέφθη: Aristotle quoted from memory, whereas Simplicius very likely had a complete exemplar of the Physical Poem at his disposal; we cannot be sure that the verb τρέφω belongs to Empedocles’ vocabulary, because θρεφθεῖσα in B17.5 is simply the result of an emendation by F. Panzerbieter; and we should trust the lectio difficilior ἐρέφθη (‘took cover’). This choice significantly contributes to understanding how the disruption of the Sphairos starts. The author also discusses the text of v. 3; he restores the lectio tradita παρελήλαται, and proposes a partially new interpretation of the line.

Integrating modern and innovative technologies such as the Internet of Things (IoT) and Machine Learning (ML) presents new opportunities in healthcare, especially in medical spa therapies. Once considered palliative, these therapies conducted using mineral/thermal water are now recognized as a targeted and specific therapeutic modality. The peculiarity of these treatments lies in their simplicity of administration, which allows for prolonged treatments, often lasting weeks, with progressive and controlled therapeutic effects. Thanks to new technologies, it will be possible to continuously monitor the patient, both on-site and remotely, increasing the effectiveness of the treatment. In this context, wearable devices, such as smartwatches, facilitate non-invasive monitoring of vital signs by collecting precise data on several key parameters, such as heart rate or blood oxygenation level, and providing a perspective of detailed treatment progress. The constant acquisition of data thanks to the IoT, combined with the advanced analytics of ML technologies, allows for data collection and precise analysis, allowing real-time monitoring and personalized treatment adaptation. This article introduces an IoT-based framework integrated with ML techniques to monitor spa treatments, providing tailored customer management and more effective results. A preliminary experimentation phase was designed and implemented to evaluate the system’s performance through evaluation questionnaires. Encouraging preliminary results have shown that the innovative approach can enhance and highlight the therapeutic value of spa therapies and their significant contribution to personalized healthcare.

The aim of this study was to describe the 2022–2023 bronchiolitis epidemic season (the second after COVID-19 pandemic and the first without social restriction), focusing on patients discharged home from a pediatric emergency department (PED) and on those revisited within 72 h. We performed a retrospective observational study in an Italian tertiary care children’s hospital, reviewing PED accesses from 1 October 2022 to 31 March 2023. The number of hospitalizations for bronchiolitis was extracted from hospital discharge forms. A total of 512 patients diagnosed with bronchiolitis were admitted to PED (2.8% of total admissions). Accesses increased sharply from November to January, with a peak in December, in both admissions and hospitalizations. More than half of the patients (55.5%) were safely discharged home, while 38 (13.4%) came back to PED for a revisit. Overall PED accesses and hospitalizations for bronchiolitis increased since the previous epidemic season, and particularly compared to the pandemic and pre-pandemic eras. Empowering the collaboration between all healthcare provisioners is fundamental to suitable management of patients. Monitoring the epidemiology and seasonality of bronchiolitis is a starting point for an effective internal organization of pediatric departments and to further evaluate its socio-economic burden.

Considering the increasing demand for personalized surgical care, as well as current healthcare resources limitations, the use of anatomical accurate 3D physical phantoms is becoming increasingly important for the training of surgeons and the test of surgical instruments. A lack of physical models is nowadays denoted regarding the training in electrosurgery, despite its wide diffusion in medical practice. This work reports an extensive characterization of electrosurgical physical phantoms fabricated with tissue‐mimicking ionogels and hydrogels. A careful design of the conductive gels allow the fine tuning of their mechanical and electrical properties, in order to match those of biological tissues. The manufacturing of a novel multi‐material skin stratification bench‐top pad is reported together with its use for training in both cold and electrical surgery. Furthermore, a feasibility study is reported, showing the use of conductive ionogels for simulating the coagulation of cortical vessels during brain surgery. [ABSTRACT FROM AUTHOR]

Diffusion‐based tractography in the optic nerve requires sampling strategies assisted by anatomical landmark information (regions of interest [ROIs]). We aimed to investigate the feasibility of expert‐placed, high‐resolution T1‐weighted ROI‐data transfer onto lower spatial resolution diffusion‐weighted images. Slab volumes from 20 volunteers were acquired and preprocessed including distortion bias correction and artifact reduction. Constrained spherical deconvolution was used to generate a directional diffusion information grid (fibre orientation distribution‐model [FOD]). Three neuroradiologists marked landmarks on both diffusion imaging variants and structural datasets. Structural ROI information (volumetric interpolated breath‐hold sequence [VIBE]) was respectively registered (linear with 6/12 degrees of freedom [DOF]) onto single‐shot EPI (ss‐EPI) and readout‐segmented EPI (rs‐EPI) volumes, respectively. All eight ROI/FOD‐combinations were compared in a targeted tractography task of the optic nerve pathway. Inter‐rater reliability for placed ROIs among experts was highest in VIBE images (lower confidence interval 0.84 to 0.97, mean 0.91) and lower in both ss‐EPI (0.61 to 0.95, mean 0.79) and rs‐EPI (0.59 to 0.86, mean 0.70). Tractography success rate based on streamline selection performance was highest in VIBE‐drawn ROIs registered (6‐DOF) onto rs‐EPI FOD (70.0% over 5%‐threshold, capped to failed ratio 39/16) followed by both 12‐DOF‐registered (67.5%; 41/16) and nonregistered VIBE (67.5%; 40/23). On ss‐EPI FOD, VIBE‐ROI‐datasets obtained fewer streamlines overall with each at 55.0% above 5%‐threshold and with lower capped to failed ratio (6‐DOF: 35/36; 12‐DOF: 34/34, nonregistered 33/36). The combination of VIBE‐placed ROIs (highest inter‐rater reliability) with 6‐DOF registration onto rs‐EPI targets (best streamline selection performance) is most suitable for white matter template generation required in group studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Adjuvant therapy with targeted therapy or immunotherapy has become the standard of care for fully resected stage III–IV melanoma. In this scenario, real-world data are needed to relate the actual effectiveness and safety of these regimens with the evidence provided in the clinical trials. This study provides clinicians and researchers with the results of an Italian single-center real-world experience on the use of adjuvant therapy in resected stage III–IV melanoma patients. Our findings confirm the real-world effectiveness and safety of adjuvant regimens, yet underscores the need for further research to explore biomarker-based predictors for relapse and to assess the translation of improved relapse-free survival into long-term overall survival benefit. This study was carried out at the Dermatologic Clinic of the University of Turin, Italy, to assess the effectiveness and safety of adjuvant therapy in patients who received either targeted therapy (TT: dabrafenib + trametinib) or immunotherapy (IT: nivolumab or pembrolizumab) for up to 12 months. A total of 163 patients participated, including 147 with stage III and 19 with stage IV with no evidence of disease. The primary outcomes were relapse-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS). At 48 months, both TT and IT approaches yielded comparable outcomes in terms of RFS (55.6–55.4%, p = 0.532), DMFS (58.2–59.8%, p = 0.761), and OS (62.4–69.5%, p = 0.889). Whilst temporary therapy suspension was more common among TT-treated patients compared to IT-treated individuals, therapy discontinuation due to adverse events occurred at comparable rates in both groups. Predictors of relapse included mitoses, lymphovascular invasion, ulceration, and positive sentinel lymph nodes. Overall, the proportion of BRAF-mutated patients receiving IT stood at 7.4%, lower than what was observed in clinical trials. [ABSTRACT FROM AUTHOR]

Aim of the Study: To assess how virtual reality (VR) patient-specific simulations can support decision-making processes and improve care in pediatric urology, ultimately improving patient outcomes. Patients and Methods: Children diagnosed with urological conditions necessitating complex procedures were retrospectively reviewed and enrolled in the study. Patient-specific VR simulations were developed with medical imaging specialists and VR technology experts. Routine CT images were utilized to create a VR environment using advanced software platforms. The accuracy and fidelity of the VR simulations was validated through a multi-step process. This involved comparing the virtual anatomical models to the original medical imaging data and conducting feedback sessions with pediatric urology experts to assess VR simulations' realism and clinical relevance. Results: A total of six pediatric patients were reviewed. The median age of the participants was 5.5 years (IQR: 3.5–8.5 years), with an equal distribution of males and females across both groups. A minimally invasive laparoscopic approach was performed for adrenal lesions (n = 3), Wilms' tumor (n = 1), bilateral nephroblastomatosis (n = 1), and abdominal trauma in complex vascular and renal malformation (ptotic and hypoplastic kidney) (n = 1). Key benefits included enhanced visualization of the segmental arteries and the deep vascularization of the kidney and adrenal glands in all cases. The high depth perception and precision in the orientation of the arteries and veins to the parenchyma changed the intraoperative decision-making process in five patients. Preoperative VR patient-specific simulation did not offer accuracy in studying the pelvic and calyceal anatomy. Conclusions: VR patient-specific simulations represent an empowering tool in pediatric urology. By leveraging the immersive capabilities of VR technology, preoperative planning and intraoperative navigation can greatly impact surgical decision-making. As we continue to advance in medical simulation, VR holds promise in educational programs to include even surgical treatment of more complex urogenital malformations. [ABSTRACT FROM AUTHOR]

Moebius syndrome (MBS) is a rare congenital disorder characterized by non-progressive facial palsy and ocular abduction paralysis. Most cases are sporadic, but also rare familial cases with autosomal dominant transmission and incomplete penetrance/variable expressivity have been described. The genetic etiology of MBS is still unclear: de novo pathogenic variants in REV3L and PLXND1 are reported in only a minority of cases, suggesting the involvement of additional causative genes. With the aim to uncover the molecular causative defect and identify a potential genetic basis of this condition, we performed trio-WES on a cohort of 37 MBS and MBS-like patients. No de novo variants emerged in REV3L and PLXND1. We then proceeded with a cohort analysis to identify possible common causative genes among all patients and a trio-based analysis using an in silico panel of candidate genes. However, identified variants emerging from both approaches were considered unlikely to be causative of MBS, mainly due to the lack of clinical overlap. In conclusion, despite this large cohort, WES failed to identify mutations possibly associated with MBS, further supporting the heterogeneity of this syndrome, and suggesting the need for integrated omics approaches to identify the molecular causes underlying MBS development. [ABSTRACT FROM AUTHOR]

Objective: The current study examined the change processes in three Animal Assisted Therapies (AATs) by assessing the relationship between the human-animal bond and the therapeutic alliance, depth of elaboration, and smoothness of treatment sessions. Methods: This was a retrospective study assessing videotaped AATs conducted with three children aged from 7 to 9 years old from the observer perspective. The AATs were based on the Federico II Model of Healthcare Zooanthropology, and each consisted in 8 sessions. A one-way analysis of variance and linear regression models was performed. Results: The human-animal bond, therapeutic alliance, depth of elaboration, and smoothness significantly improved during the sessions. Furthermore, the improvement in therapeutic dimensions proved to be a function of the increase in the human-animal bond. Conclusions: The findings have provided empirical evidence of the change processes occurring during AATs with children, offering some limited but specific insights into the interspecific relationship as a central axis of such treatments.