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Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae from human carriage, the human-polluted environment, and food: Molecular epidemiology of two prospective cohorts in five European metropolitan areas
No full textObjectives: For 475 ESBL-producing Escherichia coli (ESBL-Ec), and 171 ESBL-producing Klebsiella pneumoniae (ESBL-Kp) collected from human carriers, the human-polluted (hp)-environment, and food: (i) to compare the antimicrobial resistance gene (ARG) content, and (ii) to assess clonal relationships between human and non-human isolates. Materials and methods: Two prospective multicenter cohorts were assessed: colonized hospitalized index-subjects and household contacts, and long-term care facility (LTCF) residents. Additionally, linked hp-environment and food samples were collected. Presence of ARGs were assessed using pairwise comparisons and proportional similarity index (PSI). Clonal relationships were assessed using cgMLST distance visualizations and maximum likelihood phylogeny. Results: ESBL-Ec and ESBL-Kp co-occurred in 14/65 households, 3/6 LTCFs, and in 33/202 of ESBL-positive participants. Thirty-nine percent of detected ARG types were found in both species (36/93). Frequencies of beta-lactamase, ESBL, aminoglycoside, and sulfonamide ARG types from human ESBL-Ec and ESBL-Kp overlapped considerably: PSIs 0.59-0.75, and were equal or higher compared to the overlap between ESBL-Ec from humans and food isolates: PSIs 0.33-0.72. Isolates from humans and the hp-environment were frequently clonally related, indicating human contamination of the environment. Links with food isolates were observed less frequently. For ESBL-Ec both interregional and regional clonal dissemination were observed, while for ESBL-Kp clonal dissemination was mainly regional. Conclusions: ESBL-Ec and ESBL-Kp from human carriage showed considerable overlap in ARG content. Furthermore, clonal links were observed frequently between humans and hp-environment, and with lower frequency between humans and food. These findings are consistent with human-to-human transmission as an important driver of ARG spread in humans
Multi-model ensembles for object detection in multispectral images: A case study for precision agriculture
Full text linkEvery year, 20%-40% of the global harvest is lost to pests and diseases, underlining the need for rapid and accurate diagnosis. Precision agriculture exploits intelligent devices, such as robots and drones, to enable early detection of pathogens through non-destructive imaging techniques and AI processing. In this study, we exploit Deep Learning techniques for handling multispectral images in agriculture field. In particular, we introduce an adaptive Multi-Model Ensemble framework that processes multispectral data without dimensionality reduction, fully exploiting spectral information to improve early disease detection. Furthermore, several comparisons with dimensionality reduction and data combinations were conducted, exploring different image stack configurations to find the optimal solution in disease detection. We validated our approach on a dataset of tomato plants affected by Tuta Absoluta and Leveillula Taurica, where it improves the ability of disease identification and classification even at early developmental stages, offering promising perspectives for phytosanitary monitoring and sustainable resource management
Folate-targeted gold nanoparticles for doxorubicin delivery in tumor spheroids
No full textTargeted drug delivery systems represent a promising strategy for enhancing the efficacy and specificity of cancer therapy. In this study, 35 nm folate-targeted gold nanoparticles are presented as nanoparticle-drug conjugates obtained by anchoring on their surface lipoyl terminating doxorubicin prodrug (proDoxo) releasable at the endolysosomal acidic pH to prevent off-site toxic effects. Colloidal stable nanoparticles with a density of proDoxo up to 1000 molecules/particle and 2 kDa mPEG-SH coating were obtained. At pH 5, Doxo was completely released from the nanoparticles in 5 days while only 13% was released over the same period at pH 7.4. The nanoparticle decoration with folic acid as a targeting agent bestowed nanosystems with selective drug delivery to folate receptor (FR)-overexpressing cancer cells and controlled intracellular release. This led to enhanced cancer cell killing by folated nanoparticles compared to their nontargeted counterparts. Moreover, folated nanoparticles were found to distribute more homogeneously inside KBFR+ cancer cell spheroids than non-targeted nanoparticles, resulting in higher spheroid volume reduction
Bayesian nonparametric mixing distribution estimation in the Gaussian-smoothed 1-Wasserstein distance
No full textWe study the problem of mixing distribution estimation for mixtures of discrete exponential family models, taking a Bayesian nonparametric approach. It has been recently shown that, under the Gaussian-smoothed optimal transport (GOT) distance, that is, the 1-Wasserstein distance between the Gaussian-convolved distributions, the accuracy of the nonparametric maximum likelihood estimator is improved to a nearly parametric rate from the sub-polynomial (logarithmic) rate relative to the standard 1-Wasserstein distance. We provide sufficient conditions under which the Bayes' estimator for the true mixing distribution also converges at a nearly parametric rate in the GOT distance, where is shown to be a lower bound on the minimax GOT risk
Early first-trimester detection of thoracopagus conjoined twins using transvaginal 2D/3D ultrasound and augmented reality
No full textMonochorionic monoamniotic (MCMA) twin pregnancy
is an uncommon pregnancy condition associated with an
increased risk of obstetric complications compared with
singleton pregnancy and other types of multiple gestation.
In such pregnancy, early ultrasonographic assessment of
fetal anatomy allows early identification of structural
anomalies such as conjoined twins1; prompt and accurate
prenatal diagnosis of this condition is crucial for timely
patient counseling and appropriate clinical care, but
diagnosis < 12 weeks’ gestation remains challenging2.
We report a rare case of thoracopagus conjoined twins
with a single fused heart, diagnosed exceptionally early in
the first trimester by means of two-dimensional ultrasound (2D-US) and complementary three-dimensional
ultrasound (3D-US) with post-processing augmented reality (AR) visualization
Hotspot mutant p53-R273H enhances mitochondrial biogenesis and cell migration in primary colorectal cancer in response to oxaliplatin
Full text linkOxaliplatin is commonly known as a successful chemotherapy for advanced colorectal cancer, improving patient survival and eradicating micro-metastases, but its use in early stages remains controversial. Mitochondria fuel energy-intensive programs such as cell migration, yet how oxaliplatin regulates the mitochondrial network in CRC - and how TP53 context shapes this - remains unclear. We investigated a matched pair of CRC cell lines from the same patient - SW480 (primary) and SW620 (lymph-node metastasis) - both harboring TP53-R273H mutation, to define differential responses in mitochondrial biogenesis, dynamics and respiration and the mechanisms underlying them. The results indicate that primary-derived colorectal cancer cell line increased cell migration, mitochondrial biogenesis, and mitochondrial respiration capacity in response to oxaliplatin through a new and firstly described gain-of-function (GOF) of p53-R273H. Additionally, in the primary-derived CRC line, oxaliplatin elicited fate heterogeneity - coexisting apoptotic and senescent fractions alongside an R273H-driven, bioenergetically primed migratory subpopulation - together with increased mitochondrial biogenesis and respiratory capacity; by contrast, the metastatic-derived line was more sensitive and displayed structural mitochondrial injury with reduced maximal respiration. More broadly, this work underscores the importance of p53 gain-of-function mutations in CRC: the same GOF (TP53-R273H) amplifies cell migration by coupling an enhanced mitochondrial biogenesis/OXPHOS program to motility. Oxaliplatin further accentuates this energetically primed, pre-metastatic state, arguing for mitochondrial-targeted combination strategies in early-stage CRC
Viscoelastic Characterisation of High Protein Ice Cream: Predicting Tactile Sensory Properties via Time–Concentration Superposition and Large Amplitude Oscillatory Shear (LAOS) Rheology
No full textIn the present work we report on the exploration of time concentration superposition principle (TCS) and non- linear dynamic rheology (LAOS) as useful instrumental tools for predicting tactile sensory modalities of ice cream at serving temperature ( 14 ◦C). Three common tactile sensory properties of ice cream i.e., resistance to scooping (scoopability), creaminess and gumminess were assessed in high protein formulations differing in their protein to fat ratio (φP/F =0.9 to 4) and protein source (milk protein concentrate (MPC) vs whey protein isolate- sodium caseinate (WPICAS) 1:1 blend). The complex viscosity – angular frequency data obeyed the TCS principle with the calculated shift factors reflecting effectively the compositional profile of ice creams i.e., ac ∝ φP/F 1.16 and φP/F 2.23, bc ∝ φP/F1.27 and φP/F1.75 for MPC and WPICAS fortified systems. LAOS assessment revealed a clear impact of protein type and φP/F on the shearing deformation of ice creams. MPC fortification and decrease in the φP/F enhanced the shear flowing ability of the ice creams. In all cases, the onset of shear stiffening and thickening behaviour was observed at shear stresses below the flow point, which indicates gel-like or colloid glass-like structures. According to partial least squares regression analysis, the TCS parameters (ac and bc), damping factor (tanδ) and the shear strain (γf) and elastic modulus (log Gʹ f) at flow point were determined as the most important parameters predicting tactile sensory modalities on large deformation (spooning) such as scoopability, creaminess and gumminess
Right to Repair Between Intellectual Property and Servitization
Full text linkIn the paradigm shift towards circular economy, the so-called right to repair (‘R2R’) is pivotal for promoting sustainable development within an innovative productive system. This proves true looking at the legislative agenda all over the world: in the European Union, such reform program gained momentum more recently, especially with Directive (EU) 2024/1799. At a closer look, however, this Directive seems to disregard the issues of intellectual property and servitization, which represent relevant obstacles for R2R in law and in fact. This paper criticizes such an approach, considering how the EU legislator seems to (green)wash its hands under both perspectives. Therefore, an evolutive interpretation of the Directive is here proposed in order ensure effectivity to R2R. On one side, against an excessive reverence to intellectual property, it is maintained that the pursuit of public interest underlying repair could well entail a ‘due prejudice’ to private business rights, limiting their prevalence to abuse cases. On the other side, against biased presumption that servitization is always beneficial for a sustainable circular economy, it is maintained that the consumer shall instead enjoy the right to freely turn to an open competitive market for repair, in order to counteract the relevant foreclosure effects of this contract mode
Empirical Bayes
No full textThe chapter provides a general introduction to the empirical Bayes (EB) approach to inference
Isaac von Sinclair e la ricerca per costellazioni. Verso un nuovo canone
No full textThe German diplomat, writer, and philosopher Isaac von Sinclair (1775-1815) was a close friend of Hölderlin and Hegel, and has not surprisingly long been overshadowed by them. This changed in the mid-1960s, when Dieter Henrich introduced a new methodology for looking at the very beginning of German Idealism, later called “constellation research”, and was moved to do so not least by an undervalued manuscript by Sinclair himself. As a consequence, Sinclair emerged to be anything but an insignificant figure for post-Kantian philosophy, and began to attract scholars’ interests in his own right. This essay aims to reconstruct this trend of research with a view to both clarifying whether and, if so, why Sinclair’s contribution should be given credit, and identifying what is still left to be done. It seems, indeed, that the step outside academia as yet remains unexplored