Biology subjects

Ferrante, M.

Publications and source records attributed to Ferrante, M..

11 recordsLinked to original sources

bioRxiv2026

UNRAVELLING A HIDDEN SUBTYPE: MULTIOMICS REVEAL PSORIASIS-LIKE SIGNATURE WITH SURGICAL RELEVANCE IN A SUBSET OF PERIANAL FISTULIZING CROHN'S DISEASE

Background and aimsPerianal fistulizing Crohns disease (pCD) affects 20% of patients with Crohns disease (CD) and severely impacts quality of life. Current therapies fail to provide sustained relief, and the molecular underpinnings of pCD remain poorly understood. This study aimed to elucidate the molecular landscape of perianal fistulas through multiomic profiling. MethodsPaired fistula-tract and adjacent rectal mucosal biopsies were collected from 63 patients (48 with pCD, 15 with cryptoglandular fistula [CPTGL]). Longitudinal sampling generated 101 unique molecular profiles, comprising of both RNA sequencing (RNA-seq) and 16S rRNA sequencing from both tissue sites, followed by integrative multiomics and gene network analyses. ResultsUnsupervised clustering revealed three patient clusters primarily defined by host gene expression, with minimal contribution from microbial profiles. Fistulae in clusters 1 and 2 showed strong immune activation and epithelial-mesenchymal transition (EMT). In contrast, cluster 3 fistulae displayed keratinization and metabolic reprogramming resembling psoriatic skin, together with reduced JAK-STAT signalling. Cluster 3 was enriched for patients classified as TOpClass:2a, who are more suitable for surgical repair (p = 0.02). Conversely, cluster 2, characterized by rectal keratinization and EMT in both fistula and rectum, showed the highest MRI inflammatory-mass score (p = 0.02) and a greater risk of subsequent ileostomy (Kaplan-Meier; p = 0.008). An independent RNAseq dataset validated the keratinization signature in a subset of pCD fistulae. ConclusionIntegrated multiomic analysis identified distinct molecular subtypes of pCD with surgical and therapeutic relevance. These findings refine the molecular understanding of pCD and support a precision medicine approach. What You Need to Know?O_ST_ABSBACKGROUND AND CONTEXTC_ST_ABSO_LIPerianal fistulas affect 1 in 5 Crohns disease patients and have a severe negative impact on the quality of life of the patients. C_LIO_LIMost advanced IBD therapies are not efficacious for perianal Crohns disease. C_LIO_LISurgical repair is not suitable for all patients. C_LI NEW FINDINGSO_LIThis study is the first to delineate molecularly defined patient subtypes in perianal fistulizing Crohns disease. It further characterizes a psoriasis-like keratinization program in a subset of fistulas. Finally, it identifies molecular features and histological indicators that may explain-and potentially help predict-favorable surgical outcomes in selected patients C_LI LIMITATIONSO_LIFunctional and mechanistic studies will be required to further dissect the drivers and dynamics of the epithelial remodeling identified. C_LI CLINICAL RESEARCH RELEVANCEO_LIRaises the possibility of refining of existing clinical stratification using molecular markers for improved therapeutic management and outcome. C_LI BASIC RESEARCH RELEVANCEO_LIProposes keratinization as an opposing molecular process to EMT within the perianal fistula tract. C_LIO_LIIdentifies robust gene signatures associated with EMT and keratinization in the fistula for further experimental and clinical studies. C_LI

immunology↗

bioRxiv2026

Cross-subject decoding of human neural data for speech Brain Computer Interfaces

Brain-to-text systems have recently achieved impressive performance when trained on single-participant data, but remain limited by uninvestigated cross-subject generalization. We present the first neural-to-phoneme decoder trained jointly on the two largest intracortical speech datasets (Willett et al. 2023; Card et al. 2024), introducing day- and dataset-specific affine transforms to align neural activity into a shared space. A hierarchical GRU decoder with intermediate CTC supervision and feedback connections further mitigates the conditional-independence assumption of standard CTC loss. Our model matches or outperforms within-subject baselines while being trained across participants, and adapts to unseen subjects using only a linear transform or brief fine-tuning. On an independent inner-speech dataset (Kunz et al. 2025), our approach demonstrate generalization, by training only subject day specific transforms. These results highlight cross-subject pretraining as a practical path toward scalable and clinically deployable speech BCIs.

neuroscience↗

bioRxiv2025

Causal Contributions of Left Inferior and Medial Frontal Cortex to Semantic and Executive Control

Semantic control guides the targeted and context-based retrieval from semantic memory. The overlap with and dissociation from domain-general executive control in the frontal lobe remains contentious. Here, we used transcranial magnetic stimulation (TMS) to probe the functional relevance of the left inferior frontal gyrus (IFG) and pre-supplementary motor area (pre-SMA) for semantic and executive control. Across four sessions, 24 participants received 1 Hz repetitive TMS to each region individually, dual-site TMS targeting both regions sequentially (IFG followed by pre-SMA), and sham TMS. Participants then completed semantic fluency, figural fluency, and picture-naming tasks. Stimulation of either region broadly disrupted both semantic and figural fluency, suggesting shared functionality. However, electric field modeling of the induced stimulation strength revealed distinct specializations: The left IFG was primarily associated with semantic control, as evidenced by verbal fluency deficits, while the pre-SMA played a domain-general role in executive functions, affecting non-verbal fluency and cognitive flexibility (e.g., clustering and switching during semantic fluency). Notably, only dual-site TMS impaired accuracy in figural fluency, providing unique evidence for successful compensation of executive functions through either the left IFG or pre-SMA following single-site perturbation. These findings underscore the multidimensionality of cognitive control and suggest a flexible task-dependent contribution of the IFG to control processes, either as semantic-specific or general executive resource. Furthermore, they highlight the tightly interconnected network of executive control subserved by the left IFG and pre-SMA, advancing our understanding of the neural basis of semantic and executive functions.

neuroscience↗

bioRxiv2024

Generation of synthetic TSPO PET maps from structural MRI images

BackgroundNeuroinflammation, a pathophysiological process involved in numerous disorders, is typically imaged using [11C]PBR28 (or TSPO) PET. However, this technique is limited by high costs and ionizing radiation, restricting its widespread clinical use. MRI, a more accessible alternative, is commonly used for structural or functional imaging, but when used using traditional approaches has limited sensitivity to specific molecular processes. This study aims to develop a deep learning model to generate TSPO PET images from structural MRI data collected in human subjects. MethodsA total of 204 scans, from participants with knee osteoarthritis (n = 15 scanned once, 15 scanned twice, 14 scanned three times), back pain (n = 40 scanned twice, 3 scanned three times), and healthy controls (n=28, scanned once), underwent simultaneous 3T MRI and [11C]PBR28 TSPO PET scans. A 3D U-Net model was trained on 80% of these PET-MRI pairs and validated using 5-fold cross-validation. The models accuracy in reconstructed PET from MRI only was assessed using various intensity and noise metrics. ResultsThe model achieved a low voxel-wise mean squared error (0.0033 {+/-} 0.0010) across all folds and a median contrast-to-noise ratio of 0.0640 {+/-} 0.2500 when comparing true to reconstructed PET images. The synthesized PET images accurately replicated the spatial patterns observed in the original PET data. Additionally, the reconstruction accuracy was maintained even after spatial normalization. ConclusionThis study demonstrates that deep learning can accurately synthesize TSPO PET images from conventional, T1-weighted MRI. This approach could enable low-cost, noninvasive neuroinflammation imaging, expanding the clinical applicability of this imaging method.

neuroscience↗

bioRxiv2022

Nicotine measurement on Cambridge Filter PADs: an interlaboratory comparison to evaluate exposure by different electronic devices and traditional cigarette

Inter-laboratory comparison is widely used to ensure quality control among laboratories. In in vitro toxicology studies for tobacco harm reduction (THR), exposure system performance and laboratory proficiency along with product smoke and aerosol stream are tested for variability to assess accuracy. Here we aim to test a novel inter-laboratory setup created in a new collaborative research group using identical and small footprint systems- in order to minimize variability factors and increase reproducibility. Seven independent laboratories from different geographical areas tested the aerosol and smoke stream and exposure system performance (LM1 and LM4E) using Cambridge Filter Pad (CFP) trapping techniques. We tested 1R6F reference cigarettes, two electronic cigarettes (Vype e-Pen and Vype e-Stick Maxx), and two tobacco heating products (IQOS and Glo) under the appropriate ISO and/or HCI regimes. Nicotine quantification was performed by GC-FID at the laboratory of the leading center. The performance of participant laboratories was assessed by z-score values obtained from results either in relation to the mean and standard deviation of total participants or in relation to the reference leading center. Z-Scores were satisfactory when |z| [≤] 2, questionable when 2 < |z| < 3 and, unsatisfactory when |z| [≥] 3. In the first evaluation, for all the tested devices, Z- scores values generated by dosimetry data ranged from -2 to +2. However, high intra-laboratory variability (RSD> 10%) was observed for almost all laboratories. In the second, data showed borderline and unsatisfactory exposure performances versus LAB-A. Particularly, Z-scores [≥] 3 were observed once for LAB-B (e-Stick exposure) and LAB-G (e-Pen exposure), twice for LAB-C (1R6F-ISO and e-Stick exposures) and LAB-E (e-Pen and e-Stick exposures), and three times for LAB-F (1R6F-HCI, e-Pen, and Glo exposures). This study demonstrates that nicotine dosimetry is a fundamental method for quality assurance of smoke/vapor run exposure in the early stage of an interlaboratory study, allowing the identification and possibly the resolution of gaps. Extended practice sessions on exposure runs and several rounds of nicotine dosimetry testing should be planned to keep in check overall equipment and operator performance.

pharmacology and toxicology↗

bioRxiv2021

Comparative assessment of electronic nicotine delivery systems aerosol and cigarette smoke on endothelial cell migration: the Replica Project

Cigarette smoking is associated with impairment of repair mechanisms necessary for vascular endothelium homeostasis. Reducing the exposure to smoke toxicants may result in the mitigation of the harmful effect on the endothelium and cardiovascular disease development. Previous investigations performed by the tobacco industries evaluated in vitro the effect of electronic cigarette (e-cig) compared to cigarette smoke demonstrating a significant reduction in endothelial cell migration inhibition following e-cig aerosol exposure. In the present study, we replicated one of these studies, evaluating the effects of cigarette smoke on endothelial cell migration compared to e-cig and heated tobacco products. We used a multi-center approach (ring-study) to verify the robustness and reliability of the results obtained in the replicated study. Consistently with the original study, we observed a substantial reduction of the effects of e-cig and tobacco heated products on endothelial cell migration compared to cigarette smoke. In conclusion, our study further confirms the importance of e-cig and tobacco heated products as a possible harm reduction strategy for cardiovascular diseases development in smokers. HighlightsO_LICigarette smoking is strictly related to impairment of vascular repair mechanisms C_LIO_LIReducing the exposure to toxicants in smoke, could reduce the harm to endothelium C_LIO_LIENDS showed a reduced effect on endothelial cell migration compared to cigarette C_LIO_LIThese data demonstrated the reduced toxicity of ENDS compared to cigarettes. C_LI

pharmacology and toxicology↗

bioRxiv2021

Electronic nicotine delivery systems exhibit reduced bronchial epithelial cells toxicity compared to cigarette: The Replica Project

Cigarette smoking is the leading cause of preventable deaths worldwide. Electronic Nicotine Delivery Systems (ENDS) may reduce health risks associated with chronic exposure to smoke and their potential benefits have been the matter of intense scientific debate. Here we replicated three key published studies from the Tobacco Industry on cytotoxic and inflammatory effects of cigarette smoke and ENDS aerosol in an independent multicentric study. We aimed to establish the reliability of results and the robustness of conclusions by replicating the authors experimental protocols and further validating them with different techniques. We exposed human bronchial epithelial cell (NCI-H292) to cigarette smoke and to aerosol from ENDS. All the exposure were conducted at air-liquid interface to assess cytotoxicity effects of smoke and aerosol. Moreover, we aimed to assess different inflammatory mediators release (IL-6, IL-8 and MMP-1) from cells exposed to whole smoke and to smoke without particulate matter (vapor phase). We were able to replicate the results obtained in the original studies on cytotoxicity confirming that almost 80% of the cytotoxic effect of smoke is due to the vapor phase of smoke. Moreover, our results substantiated the reduced cytotoxic effects of ENDS aerosol in respect to cigarette smoke. However, our data are significantly different from the original ones in terms of inflammatory and remodeling activity triggered by smoke. Taken all together, the data obtained independently in different laboratories clearly demonstrate the reduced toxicity of ENDS products compared to cigarettes and thus providing a valuable tool to the harm reduction strategies in smokers.

pharmacology and toxicology↗

bioRxiv2020

Nicotine dosimetry and stability in Cambridge Filter PADs (CFPs) following different smoking regimen protocols and condition storage

Despite the growing numbers of studies with cigarettes and other electronic nicotine delivery products (ENDs), there is no standard covering nicotine dosimetry and its stability in various matrix. The aim of the present study was to provide a protocol to normalize nicotine concentration adsorbed in Cambridge Filter PADs (CFPs) and their storage method. Smoke/vapor generated by a reference tobacco cigarette (1R6F) and ENDs with different exposure regimes (ISO, HCI and CRM81) was collected in CFPs. For each exposure, some CFPs were analyzed at time zero, whereas the others were stored under different conditions for nicotine assessment after 30 days. Principal Component Analysis (PCA) was also performed to establish the best parameter for nicotine normalization. PCA showed the best correlation between nicotine in CFPs and TPM. Our results showed differences between products and puffing regimes, but storage of CFPs at -80{degrees}C was always effective in maintaining the nicotine content. In conclusion, this study highlights that different exposure regimens and products can affect the preservation of nicotine titer in CFPs and samples storage at -80{degrees}C may prevent the loss of nicotine. These conditions are recommended and should be adopted for Inter-laboratory comparison studies on ENDs to ensure harmonization between participating laboratories.

pharmacology and toxicology↗

bioRxiv2020

Intestinal receptor of SARS-CoV-2 in inflamed IBD tissue is downregulated by HNF4A in ileum and upregulated by interferon regulating factors in colon

Patients with IBD are considered immunosuppressed, but do not seem more vulnerable for COVID-19. Nevertheless, intestinal inflammation has shown an important risk factor for SARS-CoV-2 infection and prognosis. Therefore, we investigated the effect of intestinal inflammation on the viral intestinal entry mechanisms, including ACE2, in IBD. We collected (un)inflamed mucosal biopsies from CD (n=193) and UC (n=158) patients, and 51 matched non-IBD controls for RNA sequencing, differential gene expression and co-expression analysis. Organoids from UC patients were subjected to an inflammatory mix and processed for RNA sequencing. Transmural ileal biopsies were processed for single-cell (sc) sequencing. Publicly available colonic sc-RNA sequencing data, and microarrays from tissue pre/post anti-TNF therapy, were analyzed. In inflamed CD ileum, ACE2 was significantly decreased compared to control ileum (p=4.6E-07), whereas colonic ACE2 expression was higher in inflamed colon of CD/UC compared to control (p=8.3E-03; p=1.9E-03). Sc-RNA sequencing confirmed this ACE2 dysregulation, and exclusive epithelial ACE2 expression. Network analyses highlighted HNF4A as key regulator of ileal ACE2, while pro-inflammatory cytokines and interferon regulating factors regulated colonic ACE2. Inflammatory stimuli upregulated ACE2 in UC organoids (p=1.7E-02), not in non-IBD controls (p=9.1E-01). Anti-TNF therapy restored colonic ACE2 dysregulation in responders. Intestinal inflammation alters SARS-CoV-2 coreceptors in the intestine, with opposing effects in ileum and colon. HNF4A, an IBD susceptibility gene, is an important upstream regulator of ACE2 in ileum, whereas interferon signaling dominates in colon. Our data support the importance of adequate control of IBD in order to reduce risk of (complicated) COVID-19.

genomics↗

bioRxiv2020

Search for top-down and bottom-up drivers of latitudinal trends in insect herbivory in oak trees in Europe

AimThe strength of species interactions is traditionally expected to become stronger toward the Equator. However, recent studies have reported opposite or inconsistent latitudinal trends in the bottom-up (plant quality) and top-down (natural enemies) forces driving insect herbivory, possibly because these forces have rarely been studied concomitantly. This makes previous attempts to understand the effect of large scale climatic gradients on insect herbivory unsuccessful. LocationEurope Time period2018-2019 Major taxa studiedQuercus robur MethodsWe used scholar-based citizen science to simultaneously test for latitudinal variation in plant-herbivore-natural enemy interactions. We further investigated the underlying climatic factors associated with variation in herbivory, leaf chemistry and attack rates in Quercus robur across its complete latitudinal range in Europe. We quantified insect herbivory and the occurrence of specialist herbivores as well as leaf chemistry and bird attack rates on dummy caterpillars on 261 oak trees. ResultsClimatic factors rather than latitude per se were the best predictors of the large-scale (geographical) variation in the incidence of gall-inducers and leaf-miners as well as of leaf nutritional quality. However, insect herbivory, plant chemical defences (leaf phenolics) and bird attack rates were not influenced by latitude or climatic factors. The incidence of leaf-miners increased with increasing concentrations of hydrolysable tannins and decreased with those of condensed tannins, whereas the incidence of gall-inducers increased with increasing leaf soluble sugar concentration and decreased with increasing leaf C:N ratios. However, neither other traits nor bird attack rates varied with insect herbivory. Main conclusionsThese findings help to refine our understanding of the bottom-up and top-down mechanisms driving geographical variation in plant-herbivore interactions, and urge for further examination of the drivers of insect herbivory on trees.

ecology↗

bioRxiv2019

Can school children support ecological research? Lessons from the ‘Oak bodyguard’ citizen science project

Scientific knowledge in the field of ecology is increasingly enriched by data acquired by the general public participating in citizen science (CS) programs. Yet, doubts remain about the reliability of such data, in particular when acquired by school children. We built upon an ongoing CS program - Oak bodyguards - to assess the ability of European schoolchildren to accurately estimate the strength of biotic interactions in terrestrial ecosystems. We used standardized protocols to estimate predation rates on artificial caterpillars and insect herbivory on oak leaves and compared estimates made by school children, trained and untrained professional scientists (with no or limited expertise in predation or herbivory assessment). Compared to trained scientists, both schoolchildren and untrained professional scientists overestimated predation rates, but assessments made by the latter were more consistent. School children overestimated insect herbivory, as did untrained professional scientists. Thus, raw data acquired by school children participating in CS programs cannot be used and require several quality checks. However, such data are of no less value than data collected by untrained professional scientists and can be calibrated for bias.

scientific communication and education↗