University of Ferrara
  • Ferrara, Italy
Recent publications
Due to lack of biomarkers predictive of response to atezolizumab‐bevacizumab, the standard of care for advanced HCC, we analyzed baseline and early on treatment variation in peripheral lymphocytes of 37 prospective patients treated by atezolizumab‐bevacizumab and in 15 prospective patients treated by sorafenib or lenvatinib (TKIs). RNAseq analysis followed by RT‐PCR validation on patients‐derived PBMC was also performed. At first imaging re‐evaluation 13 patients receiving atezolizumab‐bevacizumab, showed objective response, 17 stable diseases, while 7 were non‐responder. Baseline CD8+ and CD8+PD‐L1+ peripheral lymphocytes were lower in responders versus non‐responders (T‐test, p = 0.012 and p = 0.004 respectively). At 3‐weeks, 28 of 30 responders displayed a rise of CD8+PD1+ lymphocytes with a positive mean fold change of 4.35 (±5.6 SD) while 6 of 7 non‐responders displayed a negative fold change of 0.89 (±0.84 SD). These changes were not observed in patients treated by TKIs. TRIM56, TRIM16, TRIM64 and Ki67 mRNAs were validated as up‐regulated in responders versus non responders after 3 weeks from treatments start, providing a possible evidence of immune activation. Baseline CD8+ and CD8+PD‐L1+ peripheral lymphocytes and early changes in CD8+PD1+ lymphocytes predict response to atezolizumab‐bevacizumab providing non‐invasive markers to complement clinical practice in the very early phases of treatment of HCC patients. This article is protected by copyright. All rights reserved
Aims Point‐of‐care ultrasound (POCUS) is the acquisition and interpretation of ultrasound imaging at the bedside to solve specific clinical questions based on signs and symptoms of presentation. While several studies evaluated POCUS diagnostic accuracy for a variety of clinical pictures in the emergency department (ED), only a few data are available on POCUS diagnostic accuracy performed by physicians with different POCUS skills. The objective of this research was to evaluate the diagnostic accuracy of POCUS compared to standard diagnostic imaging in the ED. Materials and Methods This was a retrospective study conducted in the ED of a third‐level university hospital. Patients who underwent cardiac, thoracic, abdominal, or venous lower limb POCUS and a standard imaging examination between June 2021 and January 2022 were included. Results 1047 patients were screened, and 844 patients included. A total of 933 POCUS was included (102, 12.09%, cardiac; 466, 55.21%, thoracic; 336, 39.8%, abdominal; 29, 3.44%, lower limb venous POCUS), accounting for 2029 examinations. POCUS demonstrated 96.6% (95% CI 95.72–97.34) accuracy, 47.73 (95% CI 33.64–67.72) +LR, 0.09 (95% CI 0.06–0.12) −LR. +LR was greater than 10 for all investigations but for hydronephrosis (5.8), and −LR never exceeded 0.4. Conclusions POCUS exhibited high diagnostic accuracy for virtually all conditions when performed by emergency department physicians.
Let \(X^{1,n}_r\) be the blow-up of \(\mathbb {P}^1\times \mathbb {P}^n\) in r general points. We describe the Mori cone of \(X^{1,n}_r\) for \(r\le n+2\) and for \(r = n+3\) when \(n\le 4\). Furthermore, we prove that \(X^{1,n}_{n+1}\) is log Fano and give an explicit presentation for its Cox ring.
Background Asthma is stratified into type 2-high and type 2-low inflammatory phenotypes. Limited success has been achieved in developing drugs that target type 2-low inflammation. Previous studies have linked IL-6 signaling to severe asthma. IL-6 cooperates with soluble-IL-6Rα to activate cell signaling in airway epithelium. Objective We sought to study the role of sIL-6Rα amplified IL-6 signaling in airway epithelium and to develop an IL-6+ sIL-6Rα gene signature that may be used to select asthma patients who potentially respond to anti-IL-6 therapy. Methods Human airway epithelial cells were stimulated with combinations of IL-6, sIL-6Rα, and inhibitors, sgp130 (Olamkicept), and anti-IL-6R (Tocilizumab), to assess effects on pathway activation, epithelial barrier integrity, and gene expression. A gene signature was generated to identify IL-6 high patients using bronchial biopsies and nasal brushes. Results Soluble-IL-6Rα amplified the activation of the IL-6 pathway, shown by the increase of STAT3 phosphorylation and stronger gene induction in airway epithelial cells compared to IL-6 alone. Olamkicept and Tocilizumab inhibited the effect of IL-6 + sIL-6Rα on gene expression. We developed an IL-6 + sIL-6Rα gene signature and observed enrichment of this signature in bronchial biopsies but not nasal brushes from asthma patients compared to healthy controls. An IL-6 + sIL-6Rα gene signature score was associated with lower levels of sputum eosinophils in asthma. Conclusion sIL-6Rα amplifies IL-6 signaling in bronchial epithelial cells. Higher local airway IL-6 + sIL-6Rα signaling is observed in asthma patients with low sputum eosinophils.
Over the past years, the development of innovative smart wound dressings is revolutionizing wound care management and research. Specifically, in the treatment of diabetic foot wounds, three-dimensional (3D) bioprinted patches may enable personalized medicine therapies. In the present work, a methacrylated hyaluronic acid (MeHA) bioink is employed to manufacture 3D printed patches to deliver small extracellular vesicles (sEVs) obtained from human mesenchymal stem cells (MSC-sEVs). The production of sEVs is maximized culturing MSCs in bioreactor. A series of in vitro analyses are carried out to demonstrate the influence of MSC-sEVs on functions of dermal fibroblasts and endothelial cells, which are the primary functional cells in skin repair process. Results demonstrate that both cell populations are able to internalize MSC-sEVs and that the exposure to sEVs stimulates proliferation and migration. In vivo experiments in a well-established diabetic mouse model of pressure ulcer confirm the regenerative properties of MSC-sEVs. The MeHA patch enhances the effectiveness of sEVs by enabling controlled release of MSC-sEVs over 7 days, which improve wound epithelialization, angiogenesis and innervation. The overall findings highlight that MSC-sEVs loading in 3D printed biomaterials represents a powerful technique, which can improve the translational potential of parental stem cell in terms of regulatory and economic impact.
The term affordance refers to the property or quality of an object that indicates the ways in which it could potentially be used. Affordances elicit automatic motor representations that sometimes differ from the current action representation, resulting in behavioural interference effects. This affordance-induces interference could result in automatic and involuntary behavioural inhibition, probably according to the same mechanism that controls the voluntary motor inhibition. Nevertheless, few studies have considered how voluntary response inhibition is modulated by affordance. In this study, we assess the effect of affordance on voluntary action inhibition using a stop-signal task with an affordance object as a Stop Signal. An image of a mug, with the handle orientated in the same or in the opposite direction of the hand recruited to respond at the target, was used as Stop Signal. Our results showed a reduction of the time necessary to withhold the response when the handle of the mug was pointed toward the hand pre-activated to respond. This effect indicates an increased inhibition due to the mismatch between the motor representation elicited by the affordance and the motor representation pre-activated by the target. This suggests a specific interference effect, reflected in an enhanced ability to inhibit an ongoing action.
In the absence of disease, humans produce smooth and accurate movement trajectories. Despite such 'macroscopic' aspect, the 'microscopic' structure of movements reveals recurrent (quasi-rhythmic) discontinuities. To date, it is unclear how the sensorimotor system contributes to the macroscopic and microscopic architecture of movement. Here, we investigated how corticospinal excitability changes in relation to microscopic fluctuations that are naturally embedded within larger macroscopic variations in motor output. Participants performed a visuomotor tracking task. In addition to the 0.25 Hz modulation that is required for task fulfilment (macroscopic scale), the motor output shows tiny but systematic fluctuations at ∼2 and 8 Hz (microscopic scales). We show that motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) during task performance are consistently modulated at all (time) scales. Surprisingly, MEP modulation covers a similar range at both micro- and macroscopic scales, even though the motor output differs by several orders of magnitude. Thus, corticospinal excitability finely maps the multiscale temporal patterning of the motor output, but it does so according to a principle of scale invariance. These results suggest that corticospinal excitability indexes a relatively abstract level of movement encoding that may reflect the hierarchical organisation of sensorimotor processes. KEY POINTS: Motor behaviour is organised on multiple (time)scales. Small but systematic ('microscopic') fluctuations are engrained in larger and slower ('macroscopic') variations in motor output, which are instrumental in deploying the desired motor plan. Corticospinal excitability is modulated in relation to motor fluctuations on both macroscopic and microscopic (time)scales. Corticospinal excitability obeys a principle of scale invariance, that is, it is modulated similarly at all (time)scales, possibly reflecting hierarchical mechanisms that optimise motor encoding.
Many human teratogens are associated with a spectrum of congenital anomalies rather than a single defect, and therefore the identification of congenital anomalies occurring together more frequently than expected may improve the detection of teratogens. Thirty-two EUROCAT congenital anomaly registries covering 6,599,765 births provided 123,566 cases with one or more major congenital anomalies (excluding chromosomal and genetic syndromes) for the birth years 2008–2016. The EUROCAT multiple congenital anomaly algorithm identified 8804 cases with two or more major congenital anomalies in different organ systems, that were not recognized as part of a syndrome or sequence. For each pair of anomalies, the odds of a case having both anomalies relative to having only one anomaly was calculated and the p value was estimated using a two-sided Fisher’s exact test. The Benjamini–Hochberg procedure adjusted p values to control the false discovery rate and pairs of anomalies with adjusted p values < 0.05 were identified. A total of 1386 combinations of two anomalies were analyzed. Out of the 31 statistically significant positive associations identified, 20 were found to be known associations or sequences already described in the literature and 11 were considered “potential new associations” by the EUROCAT Coding and Classification Committee. After a review of the literature and a detailed examination of the individual cases with the anomaly pairs, six pairs remained classified as new associations. In summary, systematically searching for congenital anomalies occurring together more frequently than expected using the EUROCAT database is worthwhile and has identified six new associations that merit further investigation.
Integrated localization and communication (ILC) at millimeter wave (mmWave MMWAVEinit) frequencies will be a key enabler for providing accurate location information and high data rate communication in beyond fifth generation (B5G) networks. This paper proposes a transmission frame structure and a soft information (SI)-based localization algorithm for position-assisted communications. In accordance with B5G specifications, we consider multiple-input multiple-output (MIMO)-orthogonal frequency division multiplexing (OFDM) networks. Theoretical limits are also derived to serve both as performance benchmark and as input for algorithm design. The proposed method enables cooperative ILC with improved localization accuracy and enhanced communication rate simultaneously. In particular, position-assisted communication at mmWave MMWAVEinit frequencies is explored accounting for the statistical characteristics of the wireless environment. Localization accuracy and communication rate are quantified in 3rd Generation Partnership Project (3GPP) network scenarios. Results show that the SI-based localization algorithm achieves decimeter-level accuracy, approaching the theoretical limit. Moreover, the position-assisted communication can provide higher communication rate with reduced overhead compared to existing techniques, especially in scenarios with high mobility.
The constitutional debate on climate change has been growing as a result of both the introduction of constitutional clauses on the protection of the environment and the increase of climate litigation against states’ governments. National courts have delivered important decisions on the obligation for states to take climate action, namely on mitigation and adaptation measures. A key and yet unclear issue is whether states have a constitutional duty of protection also vis-à-vis the environment outside their jurisdiction. The German Constitutional Court had a chance to address it in the Neubauer case, but evidently chose not to take a stand. This chapter investigates the (extra)territorial scope of the state duty of protection under the constitution against environmental impairments caused by climate change. Drawing from the Neubauer case, this chapter outlines the different implications of mitigation and adaptation measures abroad and argues that an extraterritorial duty to protect seems conceivable only in respect to mitigation measure. In the last decades, the progress in the environmental protection under international law prompted constitutional changes.
Objective Still’s disease is more frequently observed in the paediatric context, but a delayed onset is not exceptional both in the adulthood and in the elderly. However, whether paediatric-onset, adult-onset and elderly-onset Still’s disease represent expressions of the same disease continuum or different clinical entities is still a matter of controversy. The aim of this study is to search for any differences in demographic, clinical features and response to treatment between pediatric-onset, adult-onset and elderly-onset Still’s disease. Methods Subjects included in this study were drawn from the International AutoInflammatory Disease Alliance Network registry for patients with Still’s disease. Results A total of 411 patients suffering from Still’s disease were enrolled; the disease occurred in the childhood in 65 (15.8%) patients, in the adult 314 (76.4%) patients and in the elderly in 32 (7.8%) patients. No statistically significant differences at post-hoc analysis were observed in demographic features of the disease between pediatric-onset, adult-onset and elderly-onset Still’s disease. The salmon-coloured skin rash (p=0.004), arthritis (p=0.009) and abdominal pain (p=0.007) resulted significantly more frequent among paediatric patients than in adult cases, while pleuritis (p=0.015) and arthralgia (p<0.0001) were significantly more frequent among elderly-onset patients compared with paediatric-onset subjects. Regarding laboratory data, thrombocytosis was significantly more frequent among paediatric patients onset compared with adult-onset subjects (p<0.0001), while thrombocytopenia was more frequent among elderly-onset patients although statistical significance was only bordered. No substantial differences were observed in the response to treatments. Conclusions Despite some minor difference between groups, overall, demographic, clinical, laboratory and treatments aspects of Still’s disease were similarly observed in patients at all ages. This supports that pediatric-onset, adult-onset and elderly-onset Still’s disease is the same clinical condition arising in different ages.
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Marco Galasso
  • Sezione di Istologia ed Embriologia
Francesco Nicoli
  • Department of Chemical and Pharmaceutical Sciences
Marco Pedroni
  • Humanistic Studies
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Prof. Contini Carlo
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