Biomarkers as an opportunity to stratify for outcome in systemic sclerosis

Systemic sclerosis (SSc) is a highly complex disease whose heterogeneity includes multiple aspects of the condition, such as clinical presentation, progression, extent and type of organ involvement, and clinical outcomes. Thus far, these features remain not easily predictable both at the patient group level and in a given patient with regard to age at onset and clinical course. The unpredictable clinical course represents an obstacle to focusing potentially effective treatment in patients that need it the most. At the time of organ involvement and clinical diagnosis, most of the clinical manifestations are irreversible; therefore, predicting outcomes becomes crucial. This can explain the multiple attempts to identify prognostic, predictive, and monitoring—both soluble and imaging—biomarkers over the past years. They range from the currently most used biomarkers, the autoantibodies associated with disease-specific clinical features and course, to the single recently proposed skin, lung, cardiac involvement biomarkers and to the composite scores capturing multiple aspects of the disease. This review will focus on soluble and imaging biomarkers that recently showed promising evidence for outcome stratification in patients with SSc

Assessment of Multi-Scale Approaches for Computing UV-Vis Spectra in Condensed Phases: Toward an Effective yet Reliable Integration of Variational and Perturbative QM/MM Approaches

Computational simulation of UV/vis spectra in condensed phases can be performed starting from converged molecular dynamics (MD) simulations and then performing quantum mechanical/molecular mechanical (QM/MM) computations for a statistically significant number of snapshots. However, the need of variational solutions (e.g., ONIOM/EE) for a huge number of snapshots makes unpractical the use of state-of-the-art QM Hamiltonians. On the other hand, the effectivity of perturbative approaches (e.g., perturbed matrix method, PMM) comes at the price of poor convergence for configurations strongly different from the reference one. In this paper we introduce an integrated strategy based on a cluster analysis of the MD snapshots. Next, a representative configuration for each cluster is treated at the ONIOM/EE level, whereas local fluctuations within each cluster are described at the PMM level. Some representative systems (uracil in dimethylformamide and in water and tyrosine zwitterion in water) are analyzed to show the effectivity and flexibility of the proposed strategy

Absence of Scleroderma pattern at nail fold capillaroscopy valuable in the exclusion of Scleroderma in unselected patients with Raynaud's Phenomenon

Background: To report the predictive value of nail-fold capillaroscopy (NFC) patterns of vasculopathy for systemic sclerosis (Scleroderma; SSc) in an unselected cohort of patients with Raynaud's phenomenon (RP). Methods: Patients referred to a tertiary SSc clinic with RP were evaluated by light/video-NFC. Clinical diagnosis, details and serology were recorded. Primary RP was defined as RP with no features of connective tissue disease (CTD)/antibody. NFC patterns were determined: normal, non-specific, 'early', 'active' or 'late' SSc patterns. Fulfilment of the VEDOSS or 2013 ACR/EULAR criteria for SSc was determined following NFC assessment. Results: Three hundred forty-seven patients were referred: mean (SD) age 47 (15.2) years. On clinical review, 54 (16 %) did not have RP, 69 (20 %) had primary RP, 52 (15 %) had SSc and 172 (50 %) had secondary RP. NFC SSc pattern was detected in 80 (23 %) patients; 37/52 with SSc, 30/172 with secondary RP, 9/69 with primary RP and 4/54 with no RP. For identifying patients who met either the VEDOSS or 2013 ACR/EULAR criteria for SSc, detection of a SSc NFC pattern had a sensitivity of 71 %, specificity 95 %, positive predictive value 84 % and negative predictive value 90 %. Conclusions: The absence of SSc NFC pattern in patients with RP or suspected CTD is very valuable in the exclusion of SSc

Computational Spectroscopy in Solution by Integration of Variational and Perturbative Approaches on Top of Clusterized Molecular Dynamics

Multiscale QM/MM approaches have become the most suitable and effective methods for the investigation of spectroscopic properties of medium-or large-size chromophores in condensed phases. On these grounds, we are developing a novel workflow aimed at improving the generality, reliability, and ease of use of the available tools. In the present paper, we report the latest developments of such an approach with specific reference to a general workplan starting with the addition of acetonitrile to the panel of solvents already available in the General Liquid Optimized Boundary (GLOB) model enforcing nonperiodic boundary conditions (NPBC). Next, the solvatochromic shifts induced by acetonitrile on both rigid (uracil and thymine) and flexible (thyrosine) chromophores have been studied introducing in our software a number of new features ranging from rigid-geometry NPBC molecular dynamics based on the quaternion formalism to a full integration of variational (ONIOM) and perturbative (perturbed matrix method (PMM)) approaches for describing different solute-solvent topologies and local fluctuations, respectively. Finally, thymine and uracil have been studied also in methanol to point out the generality of the computational strategy. While further developments are surely needed, the strengths of our integrated approach even in its present version are demonstrated by the accuracy of the results obtained by an unsupervised approach and coupled to a computational cost strongly reduced with respect to that of conventional QM/MM models without any appreciable accuracy deterioration

Geometry-based channel modelling of MIMO channels in comparison with channel sounder measurements

In this paper we propose a flexible geometrybased propagation model for wireless communications developed at Ilmenau University of Technology. The IlmProp comprises a geometrical representation of the environment surrounding the experiment and a precise representation of the transmitting and receiving antennas. The IlmProp is capable of simulating Multi-User MIMO scenarios and includes a complete collection of tools to analyze the synthetic channels. In order to assess the potentials as well as the limits of our channel simulator we reconstruct the scenario encountered in a recent measurement campaign at Ilmenau University of Technology leading to synthetic data sets similar to the ones actually measured. The measurements have been collected with the RUSK MIMO multi-dimensional channel sounder. From the comparisons of the two channel matrices it is possible to derive useful information to improve the model itself and to better understand the physical origins of small-scale fading. In particular the effects of the different parameters on the synthetic channel have been studied in order to assess the sensibility of the model. This analysis shows that the correct positioning of a small number of scatterers is enough to achieve frequency selectiveness as well as specific traits of the channel statistics. The size of the scattering clusters, the number of scatterers per cluster, and the Rician K-factor can be modified in order to tune the channel statistics at will. To obtain higher levels of time variance, moving scatterers or time dependent reflection coefficients must be introduced

Expression of allograft inflammatory factor 1 in tissues from patients with systemic sclerosis and in vitro differential expression of its isoforms in response to transforming growth factor beta

OBJECTIVE: Allograft inflammatory factor 1 (AIF-1), a protein initially identified in chronically rejected rat cardiac allografts, is involved in the immune response and proliferative vasculopathy that occurs during allograft rejection. Three well-characterized isoforms of AIF-1 result from alternative messenger RNA (mRNA) splicing. We previously identified a strong association of systemic sclerosis (SSc) with a polymorphism in AIF-1 isoform 2. The purpose of this study was to investigate AIF-1 expression in affected tissues from patients with SSc and to examine the regulation of its isoforms by transforming growth factor beta (TGFbeta). METHODS: AIF-1 in the skin and lung tissues of patients with SSc was analyzed by immunochemistry. AIF-1 isoform expression in response to TGFbeta and interferon-gamma stimulation was examined by quantitative polymerase chain reaction (PCR). RESULTS: AIF-1 protein was present in affected vessels of the lung and skin lesions of patients with SSc. Quantitative PCR showed an average of 14-fold higher mRNA levels in affected SSc skin than in normal skin. Double-label immunofluorescence staining demonstrated that T cells, macrophages, and endothelial cells in affected tissues expressed AIF-1. Stimulation of peripheral blood mononuclear cells with TGFbeta caused a specific and significant increase in the expression of AIF-1 isoform 2 transcripts (P \u3c 0.005), which was due to stabilization of AIF-1 isoform 2 mRNA. CONCLUSION: These data suggest that AIF-1 plays an important role in the pathogenesis of SSc owing to its increased expression in affected tissues and to the specific stimulation of AIF-1 isoform 2 by TGFbeta

Floristic and vegetation changes on a small mediterranean island over the last century

A synthetic and updated overview about the vascular flora and vegetation of the Island of Capo Passero (SE‐Sicily) is provided. These data issue from two series of field surveys—the first carried out between 1997 and 2000, and the second between 2005 and 2019 and mostly focused on refining and implementing vegetation data. The current islet’s flora consists of 269 taxa, of which 149 (58%) are annual plants. The Mediterranean species are largely prevailing, 108 (40%) of which have a strictly Mediterranean biogeographical status. The comparison with a species list published in 1919 and updated in 1957 suggest that, despite the overall prevalence of anemochorous taxa, the vertebrate fauna represents an important vector for the plant colonization of the island, while the immigration of myrmechocorous taxa does not compensate the extinction rate. As many as 202 phy-tosociological relevés, 191 of which issue from original recent field surveys, enabled identifying 12 different plant communities. The comparison with a vegetation map published in 1965 suggests a strong reduction in dune habitats (2120 and 2210 according to EU ‘Habitats’ Directive 92/43), as well as a deep disruption in the succession typical of the local psammophilous vegetation series. In order to preserve rare, endangered and protected plant species (such as Aeluropus lagopoides, Cichorium spinosum, Limonium hyblaeum, L. syracusanum, Poterium spinosum, Senecio pygmaeus and Spergularia heldreichii) and to stop the ongoing habitat degradation, urgent and effective conservation measures should be adopted for this tiny, yet precious islet

The alien vascular flora of the Pantelleria Island National Park (Sicily Channel, Italy): new insights into the distribution of some potentially invasive species

Pantelleria is a volcanic island located in the Sicily Channel (Italy), between Sicily and Tunisia. The island, designated a National Park in 2016, hosts an interesting vascular flora of over 600 species including 9 narrow endemics. The island’s incredible biodiversity is, however, at risk due to anthropogenic influences, climate change, and, recently, the presence and spread of alien plant species. The Pantelleria alien flora has never been thoroughly investigated, probably because many non-native species were not yet present or so widespread on the island. Now, however, with the increased general awareness of the risks associated with invasive alien species, documentation of the presence of non-native species has been steadily increasing. In this study, field and literature research was carried out to investigate the alien flora of the island. Here, we report the status of a number of non-native plants with known invasive potential. Cenchrus setaceus (=Pennisetum setaceum) is reported for the first time as naturalized in the island with clear invasive behaviour, while, particularly remarkable for their invasive potential are other studied plants such as: Acacia saligna, Ailanthus altissima, Boheravia coccinea, Carpobrotus edulis, Leucaena leucocephala subsp. glabrata, Malephora crocea, Melia azedarach, Nicotiana glauca, Opuntia ficus-indica, Parkinsonia aculeata, Washingtonia robusta and a few others less important at the moment, but to be monitored. Although most taxa showed a relatively limited distribution, the trend is to observe an increased invasiveness, which indicates that they can potentially become invasive in Pantelleria as well in the next years or decades. Their limited current distribution suggests that these species are in the early stages of the general invasion curve, when intervention is feasible and most likely to succeed. Therefore, it is most prudent to prioritize management for as many potentially problematic nonnatives as possible, which will contribute greatly to the conservation of native species and ecosystems of Pantelleria. Prevention and management of invasive non-native species—both future arrivals and those already present—are necessary to preserve the peculiar volcanic landscape of Pantelleria, which was shaped by man over the last millennia