Archivio Istituzionale della Ricerca - Università degli Studi di Pavia
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Global prevalence of celiac disease in patients with Rome III and Rome IV irritable bowel syndrome: A systematic review and meta-analysis
No full textIntroduction Irritable bowel syndrome (IBS) and celiac disease (CeD) are common disorders that share overlapping symptoms. In this systematic review and meta-analysis, we aimed to provide up-to-date and comprehensive estimates of the prevalence of CeD in patients with IBS. Methods We searched several databases through January 2025 for studies reporting the prevalence of CeD in patients with IBS. Eligible studies used Rome III or Rome IV criteria for IBS diagnosis and used serological screening with tissue transglutaminase, endomysial antibodies, or deamidated gliadin peptide, and/or confirmatory duodenal biopsies for CeD diagnosis. We used random-effects meta-analysis to estimate the pooled prevalence of seropositive and biopsy-proven coeliac disease with 95% confidence intervals (CI). We calculated pooled odds ratios (ORs) to compare the likelihood of CeE between patients with IBS and controls. Results A total of 29 studies comprising 7,209 patients with IBS were included. The pooled seroprevalence of CeD in patients with IBS was 6% (95% CI, 5% - 8%), and the pooled prevalence of biopsy-proven CeD was 2% (95% CI, 2% - 3%). A significant proportion of seropositive patients (15%; 95% CI, 6% - 24%) did not undergo endoscopy and biopsy. Patients with IBS had significantly higher odds of a positive serology than controls (OR 4.42; 95% CI, 2.82 - 6.92). The odds of CeD were similar across genders and IBS subtypes. There was a limited number of studies from Europe and no studies from the United States. Conclusion CeD is highly prevalent in patients with IBS, according to the Rome III and Rome IV criteria. A positive diagnosis of IBS should not be made without excluding CeD
Coupling Adoptive Cell Therapy with Boron Neutron Capture Therapy: Using Functional Tumor-Infiltrating Lymphocytes for Tumor Delivery of Boron Carbide Nanoparticles
No full textNanomedicine offers promising strategies for targeted drug delivery, imaging, and molecular-level therapies. However, the clinical translation of nanomedicine has often been hindered by the complex interactions of nanoparticles (NPs) with biological systems. This study investigates a cell-based delivery platform designed to overcome some of these limitations, using clinical-grade tumor-infiltrating lymphocytes (TILs) as biological carriers of boron carbide (B4C) NPs in boron neutron capture therapy (BNCT). Biological vectors, such as TILs, could enable selective tumor targeting, leading to highly localized 10B levels and minimizing off-target accumulation. We evaluated the uptake and retention of composite Fe2O3-B4C NPs (FeBNPs) using both immortalized Jurkat T cells and primary human TILs. Both cell types efficiently internalized FeBNPs without cytotoxic effects, maintained their functionalities, and retained the boron-rich NPs for up to 72 h. Imaging confirmed intracellular localization, and neutron autoradiography demonstrated that TILs accumulated sufficient 10B for therapeutic efficacy, eliminating the need for isotopically enriched compounds like L-4-boronophenylalanine (BPA) or sodium borocaptate (BSH). Coculture experiments with Jurkat and HeLa cells confirmed that lymphocyte-delivered boron could mediate localized radiation damage via neutron capture. These findings support the concept of TILs as "Trojan Horses" for boron delivery, allowing for overcoming traditional barriers in NP-based therapies and taking advantage of their innate tumor-homing ability. This approach not only enhances BNCT selectivity and efficacy but also supports the integration of nanomedicine with adoptive cell therapy in a combined cancer treatment framework
Ultrabroadband milliwatt-level resonant frequency doubling on a chip
No full textMicroresonators are powerful tools to enhance the efficiency of second-order nonlinear optical processes, such as second-harmonic generation, which can coherently bridge octave-spaced spectral bands. However, dispersion constraints such as phase-matching and doubly resonant conditions have so far limited demonstrations to narrowband operation. In this work, we overcome these limitations showing ultrabroadband resonant frequency doubling in a novel integrated device, wherein the resonant enhancement of pump and second harmonic are individually addressed in two distinct and linearly uncoupled microring resonators, each adjusted to target the respective spectral band. The two microresonators are designed and tuned independently, yet share a common interaction region that grants nonlinear coupling over a quasi-phase-matching bandwidth exceeding 200 nm, enabled by the inscription of a photoinduced χ(2) grating. The system allows to not only conveniently disentangle the design parameters of the two microresonators but also to reconfigure the doubly resonant condition electrically, and the phase-matching condition optically. We demonstrate milliwatt-level addressable second-harmonic generation over the entire telecom band and then configure the device to internally generate and upconvert a Kerr frequency comb with bandwidth exceeding 100 nm and upconverted power up to 10 mW
Single-cell and clonal analysis of AL amyloidosis plasma cells and their bone marrow microenvironment
No full textAL amyloidosis is a disorder characterized by expansion of clonal plasma cells in the bone marrow and distant end organ damage mediated by misfolded immunoglobulin free light chains. There are currently limited data regarding the functional characteristics of AL amyloidosis plasma cells and their surrounding bone marrow microenvironment. We performed 5’ single-cell RNA sequencing on newly diagnosed, treatment-naïve patients with AL amyloidosis and healthy subjects. We identified generalized suppression of normal bone marrow hematopoiesis with distinct expansion of monocytes and subsets of CD4+ T cells in patients with AL amyloidosis. We detected significant transcriptional changes broadly occurring among immune cells with increased tumor necrosis factor-α signaling and interferon response accompanied by increased inflammatory response in bone marrow plasma, as measured via quantitative proteomics with specific elevation of costimulatory molecule soluble CD276 (sB7-H3). A transcriptionally distinct population of nonmalignant plasma cells was disproportionately expanded in patients with AL amyloidosis and characterized by increased expression of CRIP1. Finally, clonal AL amyloidosis plasma cells were identified based on their unique variable-diversity-joining. rearrangement and showed increased expression of genes involved in proteostasis when compared with autologous, polyclonal plasma cells. Interpatient transcriptional heterogeneity was evident, with transcriptional states reflective of common genomic translocations easily identifiable. This study defines the transcriptional characteristics of AL amyloidosis plasma cells and their surrounding bone marrow microenvironment with identification of altered genes previously involved in the pathogenesis of other protein deposition disorders. Our data provide the rationale for functional validations of these genes in future studies
Relationship Between Vertical Facial Patterns and Palatal Morphology in Class I and Class II Malocclusion
No full text(1) The purpose of this study is to relate the bidimensional and tridimensional measures of the palate to the vertical facial pattern defined by the angle “SN-MP” between the mandibular plane and the anterior cranial base (Sella–Nasion/mandibular plane angle) in skeletal Class II untreated patients. Furthermore, the same palatal measures were used to compare Class II with Class I subjects. (2) A sample of 197 Class II Caucasian subjects (112 females and 85 males) with untreated skeletal Class II was collected retrospectively (from a private dental clinic specialized in orthodontics) and divided into two main groups according to the ANB angle: 74 Class I patients (0° ≤ ANB ≤ 4°) and 123 Class II patients (ANB > 4°). Class II subjects were furthermore divided into three groups depending on the angle SN-MP. Lateral cephalograms and digital 3D maxillary dental scans were available. Bidimensional and tridimensional measures were taken on each maxillary dental scan. The differences among the groups were analyzed for significance using a variance analysis. (3) A decrease in the posterior palatal height and an increase in the palatal surface area in Class I subjects were reported. The results showed a change in upper arch form, with a greater intermolar width in patients with a low SN-MP angle and a smaller one in high-angle patients. The more a Class II subject tended towards high-angle divergence, the narrower the palate was. (4) A greater posterior palatal height was found in Class II malocclusion, while greater surface area was noted in Class I malocclusion. In addition to this result, another statistical significance was detected in Class II malocclusion: the intermolar distance was greater in hypodivergent than in hyperdivergent patients. Similar volume values were noted across different malocclusions and vertical divergence groups. Palatal width seemed to be related to vertical facial pattern, while palatal height and area seemed to be related to sagittal malocclusions. These findings underscore the importance of considering palatal morphology variations in designing individualized orthodontic treatments, thereby improving patient-specific outcomes and broadening our understanding of skeletal Class II malocclusion
Development and validation of the iKETO-KNOW questionnaire: A tool for assessing knowledge of the ketogenic diet therapy
No full textObjective: Ketogenic dietary therapies (KDTs) are effective and safe alternatives for patients with drug-resistant epilepsy who are not candidates for surgical intervention. The success of KDTs depends heavily on patients’ strict adherence to dietary guidelines, which is closely linked to their knowledge of the therapy. This study aimed to develop and validate the iKETO-KNOW Questionnaire in the Italian language—a tool designed for adult patients and caregivers to assess knowledge related to KDTs. Methods: The iKETO-KNOW Questionnaire was created by a panel of experts and validated using the Delphi method, which incorporated feedback from clinicians and patient representatives. The final version includes three introductory items and ten multiple-choice questions, organized into two main domains: “food knowledge” and “diet management.” Results: The questionnaire was administered to 107 patients and caregivers undergoing KDT treatment. It demonstrated strong test–retest reliability, confirming its consistency over time. Participants generally showed high levels of dietary knowledge. No significant correlations were found between knowledge scores and factors such as patient age, duration of KDT, or ketonemia levels. Furthermore, knowledge scores did not differ significantly across various diagnoses or types of KDT, indicating the tool's broad applicability. Significance: Evaluating dietary knowledge is essential to improve adherence to KDTs. The iKETO-KNOW Questionnaire fills a gap in standardized assessment tools and can help identify educational needs, allowing for targeted psychoeducational interventions. Enhancing dietary knowledge is likely to improve adherence and, consequently, clinical outcomes in patients following KDTs
In Silico-Guided Discovery and In Vitro Evaluation of Natural Sortase A Inhibitors to Fight Multidrug-Resistant Staphylococcus aureus
No full textAntimicrobial resistance poses a serious global health threat. Sortase A (SrtA), a membrane-bound cysteine transpeptidase responsible for anchoring key virulence factors to cell wall of Gram-positive bacteria, acts as critical driver of pathogenicity. Here, molecular dynamics simulations were employed to explore SrtA conformational flexibility and guide a structure-based virtual screening of approximately 300,000 natural compounds. Seven structurally diverse hits were selected based on their ability to bind the multiple conformations and their favorable docking scores. Drug-likeness and pharmacokinetic properties were predicted and compared with those of agents currently used against multidrug-resistant Staphylococcus aureus, revealing that the identified compounds obey both Lipinski's and Muegge's rules. In vitro assays confirmed the SrtA inhibitory activity of the two compounds in the low micromolar range. Noteworthy, both compounds significantly reduced S. aureus adhesion to fibrinogen, suggesting functional inhibition of endogenous bacterial SrtA. These findings support the potential of these natural scaffolds as antivirulence drug candidates
ARCADIA fully depleted CMOS MAPS development with LFoundry 110 nm CIS
No full textFully depleted CMOS sensors represent a significant step forward in radiation detection, combining the advantages of monolithic active pixel sensors with the enhanced signal collection efficiency of depleted bulk materials. The ARCADIA Collaboration established a technology platform for the development and production of deep sub-micron fully depleted CMOS monolithic sensors with excellent collection efficiency, advancing this semiconductor detector technology with IP cores, ASICs, and back-end dedicated acquisition systems. The sensor technology was demonstrated on system-ready full chip monolithic active pixel sensors with high rate capability and very low power for the detection of charged particles and photons. Innovative CMOS monolithic LGADs featuring a shallow gain layer and implementing a low-gain avalanche diode were developed for time-of-flight detectors, while other prototype ASICs have implemented multi-threshold photon-counting architectures for X-ray imaging. The implementation of fully depleted monolithic strip sensors with embedded electronics and low power density makes the proposed approach a good candidate for future detectors in space applications. The ARCADIA technology will find applications in medical instruments, nuclear imaging and dosimetry, frontier detectors for experimental high energy, and astroparticle physics. This review details the main development achievements by describing the technology demonstrators fabricated and tested and provides a detailed overview of the characteristics and architecture of the ARCADIA-MD3 full-chip monolithic active pixel sensor
Terrestrial and Martian Paleo-Hydrologic Environment Systematic Comparison with ASI PRISMA and NASA CRISM Hyperspectral Instruments
No full textThe comparative analysis of hyperspectral data from different instruments can provide detailed information on the composition and geology of similar environments on different planets. This study aims to compare data acquired from the PRISMA satellite, used for Earth observation, with those collected by the CRISM spectrometer onboard the Mars Reconnaissance Orbiter, orbiting Mars, in order to analyze the geological and mineralogical differences between the morphologies present on the two planets of interest. The comparison of these data will allow us to examine the mineralogical composition, highlighting the similarities and differences between the terrestrial and Martian environments. In particular, in this study, we present a method to refine the interpretation of spectral features of minerals commonly found in paleo-hydrological environments on Mars and identified also by field analysis of similar terrestrial sites, thus allowing us to improve the Martian sites’ characterization. Thanks to this approach, we have been able to find spectral similarities (e.g., band positions, band ratios) among specific Earth and Mars sites, thus demonstrating that it could be further expanded, by systematically using Earth-observation orbiting instruments to better characterize and constrain Martian spectral data