Percutaneous ablation in perivascular-HCC: impact of liver parenchyma and characteristics of vascular structures on the outcomes.

AIM: Percutaneous radiofrequency ablation (RFA) is a standard treatment for small-HCC (<3 cm). However, some features such as proximity to intrahepatic vascular structures (perivascular location) seem to be related to short- and long-term outcomes. The aims of the study were to investigate the features related to ablation success and local tumor progression (LTP) in patients submitted to percutaneous ablation for perivascular-HCC. MATERIALS AND METHODS: From January 2010 to May 2021, 132 perivascular-HCC nodules ablated with US-guided single probe percutaneous RFA were retrospectively analyzed. Univariate analysis and multivariable Cox regression model were used to identify factors that were independently related to ablation success and LTP-free survival. RESULTS: The overall ablation success rate was 71.9% (n=95). Morbidity and mortality rates were 4.0% and 0.0%. The features related to ablation success: nodule size (≤20 mm vs. >20 mm) (OR 2.442, p=0.031), major vascular structures diameter (3-5 mm vs ≥ 5 mm) (OR 2.167, p=0.037) and liver parenchyma (cirrhosis vs no-cirrhosis) (OR 2.373, p=0.033). The following features resulted independently related to better LTP-free survival: nodule size ≤20 mm (HR 2.802, p=0.003), proximity to glissonean pedicles (HR 1.677, p=0.028), and major vascular structure diameter <5 mm (HR 1.987, p=0.041). CONCLUSIONS: Perivascular location confirmed to be a difficult and unfavorable indication for percutaneous ablation for HCC nodules. However, perivascular nodules not suitable for surgery with low-risk features (size <20 mm, proximity to glissonian pedicles and vascular diameter <5 mm) may be treated with RFA with satisfactory outcomes.

Optically Driven Janus Microengine with Full Orbital Motion Control.

Microengines have shown promise for a variety of applications in nanotechnology, microfluidics, and nanomedicine, including targeted drug delivery, microscale pumping, and environmental remediation. However, achieving precise control over their dynamics remains a significant challenge. In this study, we introduce a microengine that exploits both optical and thermal effects to achieve a high degree of controllability. We find that in the presence of a strongly focused light beam, a gold-silica Janus particle becomes confined at the stationary point where the optical and thermal forces balance. By using circularly polarized light, we can transfer angular momentum to the particle, breaking the symmetry between the two forces and resulting in a tangential force that drives directed orbital motion. We can simultaneously control the velocity and direction of rotation of the particle changing the ellipticity of the incoming light beam while tuning the radius of the orbit with laser power. Our experimental results are validated using a geometrical optics phenomenological model that considers the optical force, the absorption of optical power, and the resulting heating of the particle. The demonstrated enhanced flexibility in the control of microengines opens up new possibilities for their utilization in a wide range of applications, including microscale transport, sensing, and actuation.

Survey on the usage of therapeutic erythrocytapheresis in transfusion services in Italy for the treatment of polycythemia vera, secondary erythrocytosis and hemochromatosis.

INTRODUCTION: Erythrocytapheresis, an apheresis treatment which selectively removes red blood cells, is an alternative to therapeutic phlebotomy, over which it has several advantages. Actually there is a high degree of variability in the use of this treatment. This prompted SIdEM (Italian Society of Hemapheresis and Cell Manipulation) to conduct a survey on the use of erythrocytapheresis in the Italian Transfusion Services. The purpose is to monitor this activity in the treatment of Polycythemia Vera (pv), secondary erythrocytosis and hemochromatosis. MATERIALS AND METHODS: A data collection file was sent to the SIdEM regional delegates who, in turn, involved the Transfusion Centers in the areas they cover. The data collected were processed on a Microsoft Excel spreadsheet. RESULTS: 75 centers from 14 Italian regions responded to the Survey: 36 centers (48 %) use erythrocytapheresis (35 centers perform therapeutic apheresis and 1 center only donor apheresis), 39 centers (52 %) do not (15 centers perform therapeutic apheresis, 18 centers only donor apheresis and 6 centers do not perform either therapeutic apheresis or donor apheresis). Although most centers have a substantially uniform attitude concerning the indications for which erythrocytapheresis is used, the survey shows that there are still differences more evident in the treatment of secondary erythrocytosis than in the treatment of pv or hemochromatosis. CONCLUSIONS: This survey has been useful to document the current Italian reality and to raise awareness about the need for improvement in optimizing and standardizing the use of a therapy with a great potential to exploit properly.

Faster and More Accurate Geometrical-Optics Optical Force Calculation Using Neural Networks.

Optical forces are often calculated by discretizing the trapping light beam into a set of rays and using geometrical optics to compute the exchange of momentum. However, the number of rays sets a trade-off between calculation speed and accuracy. Here, we show that using neural networks permits overcoming this limitation, obtaining not only faster but also more accurate simulations. We demonstrate this using an optically trapped spherical particle for which we obtain an analytical solution to use as ground truth. Then, we take advantage of the acceleration provided by neural networks to study the dynamics of ellipsoidal particles in a double trap, which would be computationally impossible otherwise.

Clinical presentation, genotype-phenotype correlations, and outcome of pancreatic neuroendocrine tumors in Von Hippel-Lindau syndrome.

PURPOSE: Data regarding the clinical management and follow-up of pancreatic neuroendocrine tumors (PanNETs) associated with Von Hippel-Lindau (VHL) syndrome are limited. This study aimed to assess clinical presentation, genotype-phenotype correlations, treatment and prognosis of PanNETs in a series of VHL syndrome patients. METHODS: Retrospective analysis of data of patients observed between 2005 and 2020. RESULTS: Seventeen patients, including 12 probands and 5 relatives (mean age 30.8 ± 18.4; 7 males), were recruited. PanNETs were found in 13/17 patients (77.5%) at a median age of 37 years: 4/13 (30.7%) at the time of VHL diagnosis and 9 (69.3%) during follow up. Six (46.1%) PanNET patients underwent surgery, whereas seven were conservatively treated (mean tumor diameter: 40 ± 10.9 vs. 15 ± 5.3 mm respectively). Four patients (30.7%) had lymph node metastases and a mean tumor diameter significantly larger than the nonmetastatic PanNETs (44.2 ± 9.3 vs. 17.4 ± 7 mm, p = 0.00049, respectively). Five (83.3%) operated patients had stable disease after a median follow up of 3 years whereas one patient showed liver metastases. Six (85.7%) non-resected PanNETs were stable after a median follow-up of 2 years, whereas one patient developed a new small PanNET and a slight increase in diameter of a pre-existing PanNET. No correlation was found between the type of germline mutation and malignant behavior of PanNETs. CONCLUSIONS: PanNETs are a common disease of the VHL syndrome and can be the presenting feature. Tumor size rather than genetic mutation is a prognostic factor of malignancy.

Intelligent non-colorimetric indicators for the perishable supply chain by non-wovens with photo-programmed thermal response.

Spoiled perishable products, such as food and drugs exposed to inappropriate temperature, cause million illnesses every year. Risks range from intoxication due to pathogen-contaminated edibles, to suboptimal potency of temperature-sensitive vaccines. High-performance and low-cost indicators are needed, based on conformable materials whose properties change continuously and irreversibly depending on the experienced time-temperature profile. However, these systems can be limited by unclear reading, especially for colour-blind people, and are often difficult to be encoded with a tailored response to detect excess temperature over varying temporal profiles. Here we report on optically-programmed, non-colorimetric indicators based on nano-textured non-wovens encoded by their cross-linking degree. This combination allows a desired time-temperature response to be achieved, to address different perishable products. The devices operate by visual contrast with ambient light, which is explained by backscattering calculations for the complex fibrous material. Optical nanomaterials with photo-encoded thermal properties might establish new design rules for intelligent labels.

High-Resolution Photonic Force Microscopy Based on Sharp Nanofabricated Tips.

Although near-field imaging techniques reach sub-nanometer resolution on rigid samples, it remains extremely challenging to image soft interfaces, such as biological membranes, due to the deformations induced by the probe. In photonic force microscopy, optical tweezers are used to manipulate and measure the scanning probe, allowing imaging of soft materials without force-induced artifacts. However, the size of the optically trapped probe still limits the maximum resolution. Here, we show a novel and simple nanofabrication protocol to massively produce optically trappable quartz particles which mimic the sharp tips of atomic force microscopy. Imaging rigid nanostructures with our tips, we resolve features smaller than 80 nm. Scanning the membrane of living malaria-infected red blood cells reveals, with no visible artifacts, submicron features termed knobs, related to the parasite activity. The use of nanoengineered particles in photonic force microscopy opens the way to imaging soft samples at high resolution.

Raman Tweezers for Small Microplastics and Nanoplastics Identification in Seawater.

Our understanding of the fate and distribution of micro- and nano- plastics in the marine environment is limited by the intrinsic difficulties of the techniques currently used for the detection, quantification, and chemical identification of small particles in liquid (light scattering, vibrational spectroscopies, and optical and electron microscopies). Here we introduce Raman Tweezers (RTs), namely optical tweezers combined with Raman spectroscopy, as an analytical tool for the study of micro- and nanoplastics in seawater. We show optical trapping and chemical identification of sub-20 µm plastics, down to the 50 nm range. Analysis at the single particle level allows us to unambiguously discriminate plastics from organic matter and mineral sediments, overcoming the capacities of standard Raman spectroscopy in liquid, intrinsically limited to ensemble measurements. Being a microscopy technique, RTs also permits one to assess the size and shapes of particles (beads, fragments, and fibers), with spatial resolution only limited by diffraction. Applications are shown on both model particles and naturally aged environmental samples, made of common plastic pollutants, including polyethylene, polypropylene, nylon, and polystyrene, also in the presence of a thin eco-corona. Coupled to suitable extraction and concentration protocols, RTs have the potential to strongly impact future research on micro and nanoplastics environmental pollution, and enable the understanding of the fragmentation processes on a multiscale level of aged polymers.

Intracavity optical trapping of microscopic particles in a ring-cavity fiber laser.

Standard optical tweezers rely on optical forces arising when a focused laser beam interacts with a microscopic particle: scattering forces, pushing the particle along the beam direction, and gradient forces, attracting it towards the high-intensity focal spot. Importantly, the incoming laser beam is not affected by the particle position because the particle is outside the laser cavity. Here, we demonstrate that intracavity nonlinear feedback forces emerge when the particle is placed inside the optical cavity, resulting in orders-of-magnitude higher confinement along the three axes per unit laser intensity on the sample. This scheme allows trapping at very low numerical apertures and reduces the laser intensity to which the particle is exposed by two orders of magnitude compared to a standard 3D optical tweezers. These results are highly relevant for many applications requiring manipulation of samples that are subject to photodamage, such as in biophysics and nanosciences.

Chiral optical tweezers for optically active particles in the T-matrix formalism.

Modeling optical tweezers in the T-matrix formalism has been of key importance for accurate and efficient calculations of optical forces and their comparison with experiments. Here we extend this formalism to the modeling of chiral optomechanics and optical tweezers where chiral light is used for optical manipulation and trapping of optically active particles. We first use the Bohren decomposition to deal with the light scattering of chiral light on optically active particles. Thus, we show analytically that all the observables (cross sections, asymmetry parameters) are split into a helicity dependent and independent part and study a practical example of a complex resin particle with inner copper-coated stainless steel helices. Then, we apply this chiral T-matrix framework to optical tweezers where a tightly focused chiral field is used to trap an optically active spherical particle, calculate the chiral behaviour of optical trapping stiffnesses and their size scaling, and extend calculations to chiral nanowires and clusters of astrophysical interest. Such general light scattering framework opens perspectives for modeling optical forces on biological materials where optically active amino acids and carbohydrates are present.

Optical Trapping, Optical Binding, and Rotational Dynamics of Silicon Nanowires in Counter-Propagating Beams.

Silicon nanowires are held and manipulated in controlled optical traps based on counter-propagating beams focused by low numerical aperture lenses. The double-beam configuration compensates light scattering forces enabling an in-depth investigation of the rich dynamics of trapped nanowires that are prone to both optical and hydrodynamic interactions. Several polarization configurations are used, allowing the observation of optical binding with different stable structure as well as the transfer of spin and orbital momentum of light to the trapped silicon nanowires. Accurate modeling based on Brownian dynamics simulations with appropriate optical and hydrodynamic coupling confirms that this rich scenario is crucially dependent on the non-spherical shape of the nanowires. Such an increased level of optical control of multiparticle structure and dynamics open perspectives for nanofluidics and multi-component light-driven nanomachines.

Nanoscale Discrimination between Toxic and Nontoxic Protein Misfolded Oligomers with Tip-Enhanced Raman Spectroscopy.

Highly toxic protein misfolded oligomers associated with neurological disorders such as Alzheimer's and Parkinson's diseases are nowadays considered primarily responsible for promoting synaptic failure and neuronal death. Unraveling the relationship between structure and neurotoxicity of protein oligomers appears pivotal in understanding the causes of the pathological process, as well as in designing novel diagnostic and therapeutic strategies tuned toward the earliest and presymptomatic stages of the disease. Here, it is benefited from tip-enhanced Raman spectroscopy (TERS) as a surface-sensitive tool with spatial resolution on the nanoscale, to inspect the spatial organization and surface character of individual protein oligomers from two samples formed by the same polypeptide sequence and different toxicity levels. TERS provides direct assignment of specific amino acid residues that are exposed to a large extent on the surface of toxic species and buried in nontoxic oligomers. These residues, thanks to their outward disposition, might represent structural factors driving the pathogenic behavior exhibited by protein misfolded oligomers, including affecting cell membrane integrity and specific signaling pathways in neurodegenerative conditions.

Importance of main pancreatic duct dilatation in IPMN undergoing surveillance.

BACKGROUND: The association between risk of pancreatic cancer and a dilated main pancreatic duct (MPD) in intraductal papillary mucinous neoplasm (IPMN) is debated. The aim of this study was to assess the role of MPD size in predicting pancreatic cancer in resected IPMNs and those kept under surveillance. METHODS: All patients with IPMN referred to the Pancreas Institute, University of Verona Hospital Trust, from 2006 to 2016 were included. The primary endpoint was the occurrence of malignancy detected at surgery or during follow-up. RESULTS: The final cohort consisted of 1688 patients with a median follow-up of 60 months. Main pancreatic duct dilatation was associated with other features of malignancy in both the resected and surveillance groups. In patients who underwent resection, only a MPD of at least 10 mm was an independent predictor of malignancy. In patients kept under surveillance, MPD dilatation was not associated with malignancy. Fifteen of 71 patients (21 per cent) with malignancy in the resection cohort had a dilated MPD alone, whereas only one of 30 (3 per cent) under surveillance with MPD dilatation alone developed malignancy. Patients with a dilated MPD and other worrisome features had an increased 5-year cumulative incidence of malignancy compared with those with a non-dilated duct (11 versus 1·2 per cent; P < 0·001); however, the risk of malignancy was not significantly increased in patients with a dilated MPD alone (4 versus 1·2 per cent; P = 0·448). CONCLUSION: In patients under surveillance, a dilated MPD alone was not associated with an increased incidence of malignancy in IPMN.

Optical Aggregation of Gold Nanoparticles for SERS Detection of Proteins and Toxins in Liquid Environment: Towards Ultrasensitive and Selective Detection.

Optical forces are used to aggregate plasmonic nanoparticles and create SERS-active hot spots in liquid. When biomolecules are added to the nanoparticles, high sensitivity SERS detection can be accomplished. Here, we pursue studies on Bovine Serum Albumin (BSA) detection, investigating the BSA-nanorod aggregations in a range from 100 µM to 50 nM by combining light scattering, plasmon resonance and SERS, and correlating the SERS signal with the concentration. Experimental data are fitted with a simple model describing the optical aggregation process. We show that BSA-nanorod complexes can be optically printed on non-functionalized glass surfaces, designing custom patterns stable with time. Furthermore, we demonstrate that this methodology can be used to detect catalase and hemoglobin, two Raman resonant biomolecules, at concentrations of 10 nM and 1 pM, respectively, i.e., well beyond the limit of detection of BSA. Finally, we show that nanorods functionalized with specific aptamers can be used to capture and detect Ochratoxin A, a fungal toxin found in food commodities and wine. This experiment represents the first step towards the addition of molecular specificity to this novel biosensor strategy.

Electrospun Conjugated Polymer/Fullerene Hybrid Fibers: Photoactive Blends, Conductivity through Tunneling-AFM, Light Scattering, and Perspective for Their Use in Bulk-Heterojunction Organic Solar Cells.

Hybrid conjugated polymer/fullerene filaments based on MEH-PPV/PVP/PCBM were prepared by electrospinning, and their properties were assessed by scanning electron, atomic and lateral-force, tunneling, and confocal microscopies, as well as by attenuated-total-reflection Fourier transform infrared spectroscopy, photoluminescence quantum yield, and spatially resolved fluorescence. Highlighted features include the ribbon shape of the realized fibers and the persistence of a network serving as a template for heterogeneous active layers in solar cell devices. A set of favorable characteristics is evidenced in this way in terms of homogeneous charge-transport behavior and formation of effective interfaces for diffusion and dissociation of photogenerated excitons. The interaction of the organic filaments with light, exhibiting specific light-scattering properties of the nanofibrous mat, might also contribute to spreading incident radiation across the active layers, thus potentially enhancing photovoltaic performance. This method might be applied to other electron donor-electron acceptor material systems for the fabrication of solar cell devices enhanced by nanofibrillar morphologies embedding conjugated polymers and fullerene compounds.

Optical Binding of Nanowires.

Multiple scattering of light induces structured interactions, or optical binding forces, between collections of small particles. This has been extensively studied in the case of microspheres. However, binding forces are strongly shape dependent: here, we turn our attention to dielectric nanowires. Using a novel numerical model we uncover rich behavior. The extreme geometry of the nanowires produces a sequence of stationary and dynamic states. In linearly polarized light, thermally stable ladder-like structures emerge. Lower symmetry, sagittate arrangements can also arise, whose configurational asymmetry unbalances the optical forces leading to nonconservative, translational motion. Finally, the addition of circular polarization drives a variety of coordinated rotational states whose dynamics expose fundamental properties of optical spin. These results suggest that optical binding can provide an increased level of control over the positions and motions of nanoparticles, opening new possibilities for driven self-organization and heralding a new field of self-assembling optically driven micromachines.

Surface plasmon resonance in gold nanoparticles: a review.

In the last two decades, plasmon resonance in gold nanoparticles (Au NPs) has been the subject of intense research efforts. Plasmon physics is intriguing and its precise modelling proved to be challenging. In fact, plasmons are highly responsive to a multitude of factors, either intrinsic to the Au NPs or from the environment, and recently the need emerged for the correction of standard electromagnetic approaches with quantum effects. Applications related to plasmon absorption and scattering in Au NPs are impressively numerous, ranging from sensing to photothermal effects to cell imaging. Also, plasmon-enhanced phenomena are highly interesting for multiple purposes, including, for instance, Raman spectroscopy of nearby analytes, catalysis, or sunlight energy conversion. In addition, plasmon excitation is involved in a series of advanced physical processes such as non-linear optics, optical trapping, magneto-plasmonics, and optical activity. Here, we provide the general overview of the field and the background for appropriate modelling of the physical phenomena. Then, we report on the current state of the art and most recent applications of plasmon resonance in Au NPs.

Nerve growth factor derivative NGF61/100 promotes outgrowth of primary sensory neurons with reduced signs of nociceptive sensitization.

Nerve Growth Factor (NGF) is being considered as a therapeutic candidate for Alzheimer's disease. However, the development of an NGF-based therapy is limited by its potent pain activity. We have developed a "painless" derivative form of human NGF (NGF61/100), characterized by identical neurotrophic properties but a reduced nociceptive sensitization activity in vivo. Here we characterized the response of rat dorsal root ganglia neurons (DRG) to the NGF derivative NGF61/100, in comparison to that of control NGF (NGF61), analyzing the expression of noxious pro-nociceptive mediators. NGF61/100 displays a neurotrophic activity on DRG neurons comparable to that of control NGF61, despite a reduced activation of PLCγ, Akt and Erk1/2. NGF61/100 does not differ from NGF61 in its ability to up-regulate Substance P (SP) and Calcitonin Gene Related Peptide (CGRP) expression. However, upon Bradykinin (BK) stimulation, NGF61/100-treated DRG neurons release a much lower amount of SP and CGRP, compared to control NGF61 pre-treated neurons. This effect of painless NGF is explained by the reduced up-regulation of BK receptor 2 (B2R), respect to control NGF61. As a consequence, BK treatment reduced phosphorylation of the transient receptor channel subfamily V member 1 (TRPV1) in NGF61/100-treated cultures and induced a significantly lower intracellular Ca2+ mobilization, responsible for the lower release of noxious mediators. Transcriptomic analysis of DRG neurons treated with NGF61/100 or control NGF allowed identifying a small number of nociceptive-related genes that constitute an "NGF pain fingerprint", whose differential regulation by NGF61/100 provides a strong mechanistic basis for its selective reduced pain sensitizing actions.

What is the most accurate lymph node staging method for perihilar cholangiocarcinoma? Comparison of UICC/AJCC pN stage, number of metastatic lymph nodes, lymph node ratio, and log odds of metastatic lymph nodes.

BACKGROUND: We compared the prognostic performance of the International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) 7th edition pN stage, number of metastatic LNs (MLNs), LN ratio (LNR), and log odds of MLNs (LODDS) in patients with perihilar cholangiocarcinoma (PCC) undergoing curative surgery in order to identify the best LN staging method. METHODS: Ninety-nine patients who underwent surgery with curative intent for PCC in a single tertiary hepatobiliary referral center were included in the study. Two approaches were used to evaluate and compare the predictive power of the different LN staging methods: one based on the estimation of variable importance with prediction error rate and the other based on the calculation of the receiver operating characteristic (ROC) curve. RESULTS: LN dissection was performed in 92 (92.9%) patients; 49 were UICC/AJCC pN0 (49.5%), 33 pN1 (33.3%), and 10 pN2 (10.1%). The median number of LNs retrieved was 8. The prediction error rate ranged from 42.7% for LODDS to 47.1% for UICC/AJCC pN stage. Moreover, LODDS was the variable with the highest area under the ROC curve (AUC) for prediction of 3-year survival (AUC = 0.71), followed by LNR (AUC = 0.60), number of MLNs (AUC = 0.59), and UICC/AJCC pN stage (AUC = 0.54). CONCLUSIONS: The number of MLNs, LNR, and LODDS appear to better predict survival than the UICC/AJCC pN stage in patients undergoing curative surgery for PCC. Moreover, LODDS seems to be the most accurate and predictive LN staging method.