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Machine learning for automated differentiation of parkinson’s disease and its mimics using 123I-mIBG scintigraphy: insights from a multicentre real-world cohort (ITA-mIBG study)
No full textPurpose. To assess machine learning (ML) classifiers trained on harmonised multicentre 123I-mIBG planar scintigraphy for differentiating Parkinson’s disease (PD) from non-PD parkinsonian syndromes and to determine whether early imaging alone may ensure accurate discrimination.
Methods. This retrospective study included patients with suspected PD who underwent early (~ 15 min) and delayed (~ 240 min) imaging and received a definitive diagnosis after ≥ 12 months. Harmonised region of interest (ROI) placement and ComBat correction were applied. Early and late heart-to-mediastinum (H/M) ratios and washout rate (WR) were calculated. Differences were tested by Mann-Whitney U test, and cut-points identified by ROC analysis. Logistic regression, Gaussian naïve Bayes, and support vector machine were trained on these features with Z-score normalisation and synthetic minority oversampling technique (SMOTE).
Results. 127 patients were analysed (85 PD, 42 non-PD). Early and late H/M ratios were significantly lower in PD than non-PD (early H/M 1.45 ± 0.20 vs. 1.80 ± 0.20; late H/M 1.33 ± 0.22 vs. 1.68 ± 0.21; both p < 0.001). WR was modestly higher in PD (8.74 ± 5.76% vs. 6.49 ± 6.19%, p = 0.024). Optimal cut-points for PD were: early H/M ≤ 1.62 (accuracy 80.3%, sensitivity 83.3%, specificity 78.8%, and AUC 0.878), late H/M ≤ 1.52 (83.5%, 83.3%, 83.5% and 0.866) and WR ≥ 6.03% (70.1%, 70.6%, 69.0% and 0.645). ML achieved mean accuracy 78.9–80.7%, sensitivity 81.9–84.0%, specificity 68.6–78.0%, and AUC 0.850–0.875.
Conclusion. Classifiers trained on 123I-mIBG semi-quantitative indices accurately distinguished PD from non-PD. Early H/M ratio alone provided excellent discrimination, supporting early-imaging; prospective validation is warranted
Development of an inhalable atorvastatin powder and its anti-inflammatory effects in human lung cells
No full textChronic obstructive pulmonary disease (COPD) is a lung disease with an incidence expected to rise in the coming years. Beyond their hypolipidemic effects, statins, including atorvastatin (ATV), exhibit pleiotropic activities, and several studies have reported their efficacy in treating COPD and its exacerbations. This study aims to develop and characterize a spray-dried high-content (>90%) ATV powder for inhalation, also evaluating its effects in BEAS-2B lung epithelial cells.
ATV was co-spray-dried with leucine resulting in a production yield of approximately 50%. SEM images
revealed small (~1–2 μm) and spherical particles with an irregular surface. Aerodynamic evaluation using a multi-stage liquid impinger (MSLI) showed a respirable fraction between 41 and 52%, emitted fractions of 58–66%, and mass median aerodynamic diameters (MMAD) of 2.6–3.0 μm. To facilitate the dosing for in vitro studies, a blend of the spray-dried ATV with lactose and magnesium stearate was prepared. LPS-stimulated BEAS-2B cells were used to investigate the antioxidant and anti-inflammatory potential of ATV. ATV solution and, more efficiently, the spray-dried ATV blend reduced the extracellular H2O2 and IL-6 levels. Excipients alone showed no anti-inflammatory effect.
Real-time PCR showed that both the ATV solution and ATV blend downregulated IL-6 expression whereas
TGF-β, PPAR-γ, and PLIN-2 were upregulated. In conclusion, an inhalable ATV dry powder was developed, demonstrating strong anti-inflammatory and antioxidant effects in LPS-treated BEAS-2 cells
Algebraic curves with a large cyclic automorphism group
No full textThe study of algebraic curves with numerous automorphisms in relation to their genus
is a well-established area in Algebraic Geometry. In 1995, Irokawa and Sasaki gave a complete classification of curves over the complex field with an automorphism of order at least 2g+1. Such a classification does not hold in positive characteristic p, the curve with equation y^2=x^p-x being a well-studied counterexample. This paper successfully classifies curves with a cyclic automorphism group of order at least 2g+1
in positive characteristic greater than 2 , offering the positive characteristic counterpart to the Irokawa-Sasaki result. The possibility of wild ramification in positive characteristic has presented a few challenges to the investigation
A Comparison Between Neural Network and Sampling Kantorovich Operators in Terms of Image denoising
No full textNeural Network (NN) operators have gained significant attention in recent years due to their strong connections with Approximation Theory and their wide range of applications. In this paper, we investigate the potential of their multidimensional formulation, implementing an algorithm for digital image reconstruction. Specifically, we compare the performances of NN operators with those ones of the well-known sampling Kantorovich (SK) operators, whose implementation is a fairly recently used algorithm in image processing that serves as both a smoothing filter and a resolution enhancement tool. The comparison is conducted through a quantitative evaluation using three similarity indices: the Structural Similarity Index (SSIM), the Peak Signal-to-Noise Ratio (PSNR), and a newly introduced metric called Chemical structure diagram showing a hexagonal benzene ring with alternating double bonds. Attached to the benzene ring is a hydroxyl group (OH) and a carboxyl group (COOH). The structure represents an aromatic compound with functional groups.. A dataset of three reference images is used to assess the reconstruction quality of both approaches
Operazioni di pagamento senza provvista, delegazione e indebito
No full textvizi dei rapporti di valuta e di provvista nella delegazione di pagamento con riguardo alle disposizioni di pagamento nell'ambito di servizi di pagament
Influence of agricultural management practices on soil organic carbon stock and distribution in topsoil and subsoil as revealed by a mid-term trial
No full textCover crops and no–tillage are agricultural practices used to improve soil organic carbon (OC) sequestration,
although most studies are often limited to examining only the topsoil. In this study the influence of different
cropping systems (CONV – integrated management without cover crop and conventional tillage, ORG – organic
management with cover and temporary intercropping crops and conventional tillage, and NOTILL – integrated
management with cover crops and no–tillage) was evaluated on OC quantity and distribution in topsoil
(0–20 cm), midsoil (20–40 cm), and subsoil (40–60 cm) of a 10–year wheat–maize rotation trial. A physical–
chemical fractionation was performed to isolate OC among labile (water soluble and particulate OC, WEOC
and POC, respectively), stable (OC in sand–size and silt– and clay–size aggregates, SSA and SCA, respectively),
and resistant (NaClO oxidation) pools. Further, soil samples were characterised for 13C and 15N natural abundance,
phenols and glomalin (GRSP) contents, and microbial activity. The soil OC stock in the 0–60 cm depth was
similar for CONV, ORG and NOTILL. This was attributed to enhanced mineralisation processes promoted by the
addition of N–rich fresh legume cover crop residues in ORG and NOTILL soils that exceeded the rate of OC
stabilisation. However, specific contributions of the functional OC pools to the total stock and along the soil
depth intervals occurred. For ORG and NOTILL, the implementation with cover crops favoured the development
of a stable macrostructure and the accumulation of OC in SSAs, whereas CONV system mainly accumulated OC in
SCAs. When the system was implemented with both cover crops and no–tillage, as for NOTILL, almost half of the
total soil OC stock was stored in the topsoil, mostly as POC and associated with SSAs. Regardless of agricultural
management, 53–68 % of the total OC stock was found in the layers below the topsoil
Iron-Catalyzed C–H Alkylative Ring Openings of Oxabicyclic Alkenes
No full textWe report the iron-catalyzed C-H alkylative ring openings of oxabicyclic alkenes by chelation assistance. The method converted a broad family of benzamides into highly functionalized dihydronaphthen-2-ol derivatives, amenable to further synthetic transformations by removing the triazole directing group. Remarkably, the iron catalysis displayed complete chemo- and regioselectivities in converting oxabicyclic alkenes functionalized at the bridgehead carbons. Mechanistic investigations, by means of DFT calculations, fully elucidated the mechanism of the iron catalysis
Targeted plasma proteomics uncover proteins associated with KIF5A-linked SPG10 and ALS spectrum disorders
No full textKIF5A (Kinesin family member 5A) is a motor protein that functions as a key component of the axonal transport machinery. Variants in KIF5A are linked to several neurodegenerative diseases, mainly spastic paraplegia type 10 (SPG10), Charcot-Marie-Tooth disease type 2 (CMT2), and amyotrophic lateral sclerosis (ALS). These diseases share motor neuron involvement but vary significantly in clinical presentation, severity, and progression. KIF5A variants are mainly categorized into N-terminal variants associated with SPG10/CMT2 and C-terminal variants linked to ALS. This study utilized a multiplex NULISA targeted platform to analyze plasma proteome from KIF5A-linked SPG10 and ALS individuals and compare them to healthy controls. Our results revealed distinct proteomic signatures, with significant alterations in proteins related to synaptic function and inflammation. Notably, neurofilament light polypeptide, a biomarker for neurodegenerative diseases, was elevated in KIF5A ALS but not in SPG10 individuals. Moreover, these findings can now be used to gain mechanistic understanding of axonopathies linking to N- versus C-terminal KIF5A variants affecting both central and peripheral nervous systems
High-resolution integrated conodont and radiolarian biostratigraphy with δ13Corg record across the Norian/Rhaetian boundary in the Sasso di Castalda section, Lagonegro Basin, southern Italy
No full textThe Norian/Rhaetian boundary (NRB) is marked by faunal turnover and global carbon cycle perturbation.
Several possible causes of the environmental perturbation across the NRB have been proposed, including the
volcanic activity from the Angayucham Terrane and an impact event related to the Rochechouart crater. Evaluating
these proposed causes requires high-resolution biostratigraphy and accurate interregional correlation of
carbon isotope curves. However, such comparisons remain challenging due to the limited resolution and
inconsistent calibration of radiolarian and conodont biostratigraphic frameworks. Here, we present integrated,
high-resolution radiolarian and conodont biostratigraphy and organic carbon isotope (δ13Corg) data from an
Upper Triassic pelagic sequence in the Sasso di Castalda section of the Lagonegro Basin, southern Italy. Our
biostratigraphic analyses reveal two radiolarian assemblages, the Betraccium deweveri and Proparvicingula moniliformis
zones, indicating an age from uppermost Norian to lowermost Rhaetian. The first occurrence of the
conodont Misikella posthernsteini s.s. (sensu stricto) constrains the base of the Rhaetian. The δ13Corg profile in the
latest Norian exhibits an overall negative shift characterized by positive and negative fluctuations that correspond
to the globally recognized carbon isotope excursion at this boundary. Furthermore, based on our conodont
biostratigraphic data, the deposition of the platinum group elements-enriched layer reported in the studied
section is constrained to the latest Norian, suggesting a correlation with the Rochechouart impact. Since this
layer corresponds to the onset of the negative δ13Corg shift, our new δ13Corg record, integrated with highresolution
biostratigraphy, could contribute to understanding the cause of extinction across the NRB