Evaluation of Psychometric Proprieties of Mann Assessment of Swallowing Ability (MASA) in Italian Language: A Cross-Sectional Study.

The aim of this cross-sectional study was to translate, culturally adapt, and evaluate the psychometric properties of the Italian version of the Mann Assessment of Swallowing Ability (MASA) in post-stroke individuals. The original MASA scale was translated and culturally adapted from English to Italian following the international guidelines. The internal consistency and test-retest reliability of the MASA-IT were assessed, and its concurrent validity was examined through Pearson correlation coefficients with the Italian versions of two established gold standard scales for dysphagia assessment: the Dysphagia Outcome Severity Scale (DOSS) and the De Pippo Test-Three Oz Water Swallow. The MASA-IT was administered to 78 participants. The items demonstrated excellent internal consistency, with Cronbach's alpha ranging between 0.86 and 0.89. The interclass correlation coefficient was 0.98 for inter-rater reliability and 0.99 for intra-rater reliability, indicating high reproducibility. Regarding concurrent validity, the MASA-IT showed a strong direct correlation with the DOSS scale (r = 0.949, p = 0.01) and an inverse correlation with the De Pippo Test (r = -0.783, p = 0.01), confirming its good concurrent validity. The Italian version of the Mann Assessment of Swallowing Ability (MASA-IT) is a reliable and valid tool for assessing swallowing ability in post-stroke patients. Its strong psychometric properties make it well suited for clinical use in Italy.

The surface tension of Martini 3 water mixtures.

The Martini model, a coarse-grained forcefield for biomolecular simulations, has experienced a vast increase in popularity in the past decade. Its building-block approach balances computational efficiency with high chemical specificity, enabling the simulation of organic and inorganic molecules. The modeling of coarse-grained beads as Lennard-Jones particles poses challenges for the accurate reproduction of liquid-vapor interfacial properties, which are crucial in various applications, especially in the case of water. The latest version of the forcefield introduces refined interaction parameters for water beads, tackling the well-known artifact of Martini water freezing at room temperature. In addition, multiple sizes of water beads are available for simulating the solvation of small cavities, including the smallest pockets of proteins. This work focuses on studying the interfacial properties of Martini water, including surface tension and surface thickness. Employing the test-area method, we systematically compute the liquid-vapor surface tension across various combinations of water bead sizes and for temperatures from 300 to 350 K. These findings are of interest to the Martini community as they allow users to account for the low interfacial tension of Martini water by properly adjusting observables computed via coarse-grained simulations to allow for accurate matching against all-atom or experimental results. Surface tension data are also interpreted in terms of local enrichment of the various mixture components at the liquid-vapor interface by means of Gibbs' adsorption formalism. Finally, the critical scaling of the Martini surface tension with temperature is reported to be consistent with the critical exponent of the 3D Ising universality class.

A Multidisciplinary Approach to Improve the Management of Immune-Checkpoint Inhibitor-Related Pneumonitis.

Purpose: Treatment with immune-checkpoint inhibitors (ICIs) can be associated with a wide spectrum of immune-related adverse events (irAEs). Among irAEs, immune-mediated pneumonitis (im-PN) is a rare but potentially life-threatening side effect. TPrompt multidisciplinary diagnosis and effective management of im-PN may be essential to avoid severe complications and allowing resumation of therapy. Patients and Methods: We collected a case series of skin (melanoma, cutaneous squamous cell carcinoma-CSCC), lung, and mesothelioma cancer patients (pts), treated with ICI at the Center for Immuno-Oncology University Hospital of Siena, Italy, and diagnosed with im-PN. Clinical and radiologic data were thoroughly collected, as well as bronchoalveolar lavage (BAL) samples; im-PN was graded using CTCAE v. 5.0. Radiological patterns were reported according to the Fleischner Society classification. Results: From January 2014 to February 2023, 1004 patients with melanoma (522), CSCC (42), lung (342) or mesothelioma (98) were treated with ICI (619 monotherapy; 385 combination). Among treated patients, 24 (2%) developed an im-PN and 58% were symptomatic. Im-PN were classified as grades G1 (10) and G2 (14). Prompt steroid treatment led to complete resolution of im-PN in 21 patients, with a median time to resolution of 14 weeks (range: 0.4-51). Twelve patients resumed ICI therapy once fully-recovered and 2 experienced a recurrence that completely resolved with steroids after resumption of treatment. Three radiologic patterns were identified: organizational pneumonia-like (67%), pulmonary eosinophilia (29%), and hypersensitivity pneumonitis (4%). Furthermore, BAL analysis performed in 8 (33%) patients showed an inflammatory lymphocytic infiltrate, predominantly consisting of foam cell-like macrophage infiltrates in 6 cases. Notably, transmission electron microscopy evaluation performed in 2 patients revealed a scenario suggestive of a drug-mediated toxicity. Conclusion: Im-PN is a rare but challenging side effect of ICI therapy, with variable time of onset and with heterogeneous clinical and radiological presentations. A multidisciplinary assessment is mandatory to optimize the clinical management of im-PN.

Daily Light Onset and Plasma Membrane Tethers Regulate Mitochondria Redistribution within the Retinal Pigment Epithelium.

The retinal pigment epithelium (RPE) is an essential component of the retina that plays multiple roles required to support visual function. These include light onset- and circadian rhythm-dependent tasks, such as daily phagocytosis of photoreceptor outer segments. Mitochondria provide energy to the highly specialized and energy-dependent RPE. In this study, we examined the positioning of mitochondria and how this is influenced by the onset of light. We identified a population of mitochondria that are tethered to the basal plasma membrane pre- and post-light onset. Following light onset, mitochondria redistributed apically and interacted with melanosomes and phagosomes. In a choroideremia mouse model that has regions of the RPE with disrupted or lost infolding of the plasma membrane, the positionings of only the non-tethered mitochondria were affected. This provides evidence that the tethering of mitochondria to the plasma membrane plays an important role that is maintained under these disease conditions. Our work shows that there are subpopulations of RPE mitochondria based on their positioning after light onset. It is likely they play distinct roles in the RPE that are needed to fulfil the changing cellular demands throughout the day.

Reporting guidelines for terrestrial respirometry: Building openness, transparency of metabolic rate and evaporative water loss data.

Respirometry is an important tool for understanding whole-animal energy and water balance in relation to the environment. Consequently, the growing number of studies using respirometry over the last decade warrants reliable reporting and data sharing for effective dissemination and research synthesis. We provide a checklist guideline on five key sections to facilitate the transparency, reproducibility, and replicability of respirometry studies: 1) materials, set up, plumbing, 2) subject conditions/maintenance, 3) measurement conditions, 4) data processing, and 5) data reporting and statistics, each with explanations and example studies. Transparency in reporting and data availability has benefits on multiple fronts. Authors can use this checklist to design and report on their study, and reviewers and editors can use the checklist to assess the reporting quality of the manuscripts they review. Improved standards for reporting will enhance the value of primary studies and will greatly facilitate the ability to carry out higher quality research syntheses to address ecological and evolutionary theories.

Heat exposure limits pentose phosphate pathway activity in bumblebees.

Bumblebee populations across the globe are experiencing substantial declines due to climate change, with major consequences for pollination services in both natural and agricultural settings. Using an economically important species, Bombus impatiens, we explored the physiological mechanisms that may cause susceptibility to extreme heat events. We tested the hypothesis that heat exposure limits the activity of the pentose phosphate pathway (PPP)-a parallel pathway to glycolysis that can use nectar sugar to generate antioxidant potential and combat oxidative stress. Using isotopically labelled glucose, we tracked PPP activity in B. impatiens at rest, during exercise and during a post-exercise recovery period under two different temperature regimes (22°C and 32°C). We found that the PPP is routinely used by B. impatiens at moderate temperatures, but that its activity is markedly reduced when ATP demands are high, such as during periods of exercise and heat exposure. We also exposed B. impatiens to either 22°C or 32°C for 5 hours and assessed levels of oxidative damage (lipid peroxidation, protein carbonyls) and antioxidant potential [reduced (GSH) and oxidized (GSSG) glutathione concentrations]. Interestingly, bees exhibited little oxidative damage after the thermal exposure, but we found a lower GSH:GSSG ratio in 32°C-exposed bees, reflecting lower antioxidant potential. Overall, our study demonstrates that acute heat stress severely limits PPP activity and may constrain antioxidant potential in B. impatiens. The repeated attenuation of this pathway in a warming climate may have more severe physiological consequences for this species, with potential implications for pollination services across North America.

The Role of Narrow Aortic Bifurcation in Affecting EVAR Treatment and Outcomes.

BACKGROUND: The narrow aortic bifurcation (NAB) is considered a risk factor for endograft thrombosis after aorto-biiliac endovascular aneurysm repair (EVAR) for aortic or iliac aneurysm. Nowadays, no consensus on the threshold diameter for the definition of NAB is reached and other aortic bifurcation features are rarely considered. The aim of the study is to assess the EVAR outcomes using bifurcated endograft according to anatomical characteristics of aortic bifurcation. METHODS: The study included patients treated with primary EVAR from 2016 to 2022. A retrospective analysis of single-center prospectively collected database was performed. Patients were classified in standard aortic bifurcation (SAB) (aortic bifurcation diameter >20 mm), NAB (≤20 mm and >16 mm), and extremely NAB (eNAB) (≤16 mm). The 3 groups were compared in terms of patient demographics, risk factors, procedure setting (elective or urgent/emergent), and type of deployed endograft. In NAB and eNAB groups, severe calcification (SC) and length of stenotic aortic bifurcation >10 mm (long-NAB) were assessed from preoperative imaging. In SAB, NAB, and eNAB groups, following outcomes were evaluated: rate of intraoperative iliac endograft stenting (unilateral or kissing stenting), primary patency (PP), freedom from endograft-related reintervention, and overall survival during follow-up. RESULTS: The total number of deployed aorto-biiliac endografts was 365 (mean age: 76.6 ± 7.4 years; male 89.3%): SAB 298 (81.6%), NAB 57 (15.6%), and eNAB 10 (2.7%) cases. Female gender, chronic obstructive pulmonary disease patients, and active smokers were more frequent in patients with smaller aortic bifurcation diameter (P = 0.002, 0.039, and 0.010, respectively). In NAB and eNAB groups, SC was reported in 18/67 cases (26.9%) and long-NAB in 15/67 cases (25.4%). Patients with eNAB have more frequent SC of aortic bifurcation (60% vs. NAB 21.1%, P = 0.018) and long-NAB (50% vs. NAB 17.5%, P = 0.023). In SAB, NAB, and eNAB, intraoperative iliac endograft stenting was performed in 34/298 (11.4%), 9/57 (15.8%), and 5/10 (50%), respectively (P = 0.001). Kissing stenting was performed more frequently in groups with smaller aortic bifurcation diameter (P = 0.010). Mean follow-up was 30.2 ± 21.5 months. At 1, 3, and 5 years, PP was 98.5%, 96.6%, and 95.6%, respectively. eNAB had lower rate of PP compared to NAB group (P = 0.030). Long-NAB had lower rate of PP (P = 0.035). At 1, 3, and 5 years, endograft-related reintervention was 96.8%, 86.7%, and 76.7%, respectively, with no differences between 3 groups (P = 0.423). At 1, 3, and 5 years, survival was 92.5%, 77.6%, and 58.1%, respectively, with no difference between SAB, NAB, and eNAB (P = 0.673). CONCLUSIONS: Female gender, chronic obstructive pulmonary disease patients, and active smokers have more frequently smaller aortic bifurcation diameter. eNAB patients have more challenging anatomical characteristics compared with NAB group, requiring higher rate of intraoperative stenting, especially kissing stenting. Mid-term PP seems to be negatively influenced by aortic bifurcation ≤16 mm and long-NAB.

Combined free-running four-dimensional anatomical and flow magnetic resonance imaging with native contrast using Synchronization of Neighboring Acquisitions by Physiological Signals.

BACKGROUND: Four-dimensional (4D) flow magnetic resonance imaging (MRI) often relies on the injection of gadolinium- or iron-oxide-based contrast agents to improve vessel delineation. In this work, a novel technique is developed to acquire and reconstruct 4D flow data with excellent dynamic visualization of blood vessels but without the need for contrast injection. Synchronization of Neighboring Acquisitions by Physiological Signals (SyNAPS) uses pilot tone (PT) navigation to retrospectively synchronize the reconstruction of two free-running three-dimensional radial acquisitions, to create co-registered anatomy and flow images. METHODS: Thirteen volunteers and two Marfan syndrome patients were scanned without contrast agent using one free-running fast interrupted steady-state (FISS) sequence and one free-running phase-contrast MRI (PC-MRI) sequence. PT signals spanning the two sequences were recorded for retrospective respiratory motion correction and cardiac binning. The magnitude and phase images reconstructed, respectively, from FISS and PC-MRI, were synchronized to create SyNAPS 4D flow datasets. Conventional two-dimensional (2D) flow data were acquired for reference in ascending (AAo) and descending aorta (DAo). The blood-to-myocardium contrast ratio, dynamic vessel area, net volume, and peak flow were used to compare SyNAPS 4D flow with Native 4D flow (without FISS information) and 2D flow. A score of 0-4 was given to each dataset by two blinded experts regarding the feasibility of performing vessel delineation. RESULTS: Blood-to-myocardium contrast ratio for SyNAPS 4D flow magnitude images (1.5 ± 0.3) was significantly higher than for Native 4D flow (0.7 ± 0.1, p < 0.01) and was comparable to 2D flow (2.3 ± 0.9, p = 0.02). Image quality scores of SyNAPS 4D flow from the experts (M.P.: 1.9 ± 0.3, E.T.: 2.5 ± 0.5) were overall significantly higher than the scores from Native 4D flow (M.P.: 1.6 ± 0.6, p = 0.03, E.T.: 0.8 ± 0.4, p < 0.01) but still significantly lower than the scores from the reference 2D flow datasets (M.P.: 2.8 ± 0.4, p < 0.01, E.T.: 3.5 ± 0.7, p < 0.01). The Pearson correlation coefficient between the dynamic vessel area measured on SyNAPS 4D flow and that from 2D flow was 0.69 ± 0.24 for the AAo and 0.83 ± 0.10 for the DAo, whereas the Pearson correlation between Native 4D flow and 2D flow measurements was 0.12 ± 0.48 for the AAo and 0.08 ± 0.39 for the DAo. Linear correlations between SyNAPS 4D flow and 2D flow measurements of net volume (r2 = 0.83) and peak flow (r2 = 0.87) were larger than the correlations between Native 4D flow and 2D flow measurements of net volume (r2 = 0.79) and peak flow (r2 = 0.76). CONCLUSION: The feasibility and utility of SyNAPS were demonstrated for joint whole-heart anatomical and flow MRI without requiring electrocardiography gating, respiratory navigators, or contrast agents. Using SyNAPS, a high-contrast anatomical imaging sequence can be used to improve 4D flow measurements that often suffer from poor delineation of vessel boundaries in the absence of contrast agents.

A microfluidic card-based electrochemical assay for the detection of sulfonamide resistance genes.

Most electroanalytical detection schemes for DNA markers require considerable time and effort from expert personnel to thoroughly follow the analysis and obtain reliable outcomes. This work aims to present an electrochemical assay performed inside a small card-based platform powered by microfluidic manipulation, requiring minimal human intervention and consumables. The assay couples a sample/signal dual amplification and DNA-modified magnetic particles for the detection of DNA amplification products. Particularly, the sul1 and sul4 genes involved in the resistance against sulfonamide antibiotics were analyzed. As recognized by the World Health Organization, antimicrobial resistance threatens global public health by hampering medication efficacy against infections. Consequently, analytical methods for the determination of such genes in environmental and clinical matrices are imperative. Herein, the resistance genes were extracted from E. coli cells and amplified using an enzyme-assisted isothermal amplification at 37 °C. The amplification products were analyzed in an easily-produced, low-cost, card-based set-up implementing a microfluidic system, demanding limited manual work and small sample volumes. The target amplicon was thus captured and isolated using versatile DNA-modified magnetic beads injected into the microchannel and exposed to the various reagents in a continuously controlled microfluidic flow. After the optimization of the efficiency of each phase of the assay, the platform achieved limits of detections of 44.2 pmol L-1 for sul1 and 48.5 pmol L-1 for sul4, and was able to detect down to ≥500-fold diluted amplification products of sul1 extracted from E. coli living cells in around 1 h, thus enabling numerous end-point analyses with a single amplification reaction.

Ibrutinib-based therapy reinvigorates CD8+ T cells compared to chemoimmunotherapy: immune monitoring from the E1912 trial.

ABSTRACT: Bruton tyrosine kinase inhibitors (BTKis) that target B-cell receptor signaling have led to a paradigm shift in chronic lymphocytic leukemia (CLL) treatment. BTKis have been shown to reduce abnormally high CLL-associated T-cell counts and the expression of immune checkpoint receptors concomitantly with tumor reduction. However, the impact of BTKi therapy on T-cell function has not been fully characterized. Here, we performed longitudinal immunophenotypic and functional analysis of pretreatment and on-treatment (6 and 12 months) peripheral blood samples from patients in the phase 3 E1912 trial comparing ibrutinib-rituximab with fludarabine, cyclophosphamide, and rituximab (FCR). Intriguingly, we report that despite reduced overall T-cell counts; higher numbers of T cells, including effector CD8+ subsets at baseline and at the 6-month time point, associated with no infections; and favorable progression-free survival in the ibrutinib-rituximab arm. Assays demonstrated enhanced anti-CLL T-cell killing function during ibrutinib-rituximab treatment, including a switch from predominantly CD4+ T-cell:CLL immune synapses at baseline to increased CD8+ lytic synapses on-therapy. Conversely, in the FCR arm, higher T-cell numbers correlated with adverse clinical responses and showed no functional improvement. We further demonstrate the potential of exploiting rejuvenated T-cell cytotoxicity during ibrutinib-rituximab treatment, using the bispecific antibody glofitamab, supporting combination immunotherapy approaches.

Cortisol enhances aerobic metabolism and locomotor performance during the transition to land in an amphibious fish.

Amphibious fishes on land encounter higher oxygen (O2) availability and novel energetic demands, which impacts metabolism. Previous work on the amphibious mangrove killifish (Kryptolebias marmoratus) has shown that cortisol becomes elevated in response to air exposure, suggesting a possible role in regulating metabolism as fish move into terrestrial environments. We tested the hypothesis that cortisol is the mechanism by which oxidative processes are upregulated during the transition to land in amphibious fishes. We used two groups of fish, treated fish (+metyrapone, a cortisol synthesis inhibitor) and control (-metyrapone), to determine the impact of cortisol during air exposure (0 and 1 h, 7 days) on O2 consumption, terrestrial locomotion, the phenotype of red skeletal muscle, and muscle lipid concentration. Metyrapone-treated fish had an attenuated elevation in O2 consumption rate during the water to air transition and an immediate reduction in terrestrial exercise performance relative to control fish. In contrast, we found no short- (0 h) or long-term (7 days) differences between treatments in the oxidative phenotype of red muscles, nor in muscle lipid concentrations. Our results suggest that cortisol stimulates the necessary increase in aerobic metabolism needed to fuel the physiological changes that amphibious fishes undergo during the acclimation to air, although further studies are required to determine specific mechanisms of cortisol regulation.

Dumbbells, chains, and ribbons: anisotropic self-assembly of isotropic nanoparticles.

Functionalizing the surface of metal nanoparticles can assure their stability in solution or mediate their self-assembly into aggregates with controlled shapes. Here we present a computational study of the colloidal aggregation of gold nanoparticles (Au NPs) isotropically functionalized by a mixture of charged and hydrophobic ligands. We show that, by varying the relative proportion of the two ligands, the NPs form anisotropic aggregates with markedly different topologies: dumbbells, chains, or ribbons. In all cases, two kinds of connections keep the aggregates together: hydrophobic bonds and ion bridges. We show that the anisotropy of the aggregates derives from the NP shell reshaping due to the formation of the hydrophobic links, while ion bridges are accountable for the "secondary structure" of the aggregates. Our findings provide a general physical principle that can also be exploited in different self-assembled systems: anisotropic/directional aggregation can be achieved starting from isotropic objects with a soft, deformable surface.

Nanoparticle-induced biomembrane fusion: unraveling the effect of core size on stalk formation.

Membrane fusion in vitro is a strategy to load model or cell-derived vesicles with proteins, drugs, and genetic materials for theranostic applications. It is thus crucial to develop strategies to control the fusion process, also through synthetic fusogenic agents. Ligand-protected, membrane-penetrating gold nanoparticles (Au NPs) can facilitate membrane fusion, but the molecular mechanisms remain unresolved. Here, we tackle NP-induced stalk formation using a coarse-grained molecular dynamics approach and enhanced sampling techniques. We show that smaller (2 nm in diameter) NPs lead to a lower free energy barrier and higher stalk stability than larger NPs (4 nm). We demonstrate that this difference is due to a different ligand conformational freedom, which in turn depends on the Au core curvature. Our study provides precious insights into the mechanisms underlying NP-mediated membrane fusion, while our computational approach is general and applicable to studying stalk formation caused by other fusogenic agents.

Consumers' Attitude towards Supermarket and Proximity Stores as Purchasing Outlets of Italian Potato Consumers.

World potato consumption has fallen. Similarly, Italian consumers are buying fewer potatoes, despite the high number of certified quality and innovative potatoes being produced. Moreover, Italian consumers' knowledge of potato characteristics and innovations tends to be limited. To increase consumer engagement and revitalize the market, strategic marketing efforts need to be implemented by addressing the different characteristics of consumers in the different purchase channels. The aim of this study is to explore and differentiate consumer purchasing behavior and attitudes towards potatoes in supermarkets and neighborhood channels. The study collected 855 responses through an online survey. Data processing included the creation of indices of consumers' knowledge of potato nutrition and their propensity to innovate, as well as logistic regression to analyze the determinants of potato-purchasing behavior. The results show that consumers with increased potato consumption, a higher level of education, and employment prefer to buy potatoes in the supermarket. A preference for potato innovation also increases the likelihood that consumers will buy potatoes in supermarkets. Conversely, consumers with elderly relatives at home and a low level of education, but a high level of knowledge about the nutritional properties of potatoes, prefer to shop through neighborhood channels.

SPARCQ: A new approach for fat fraction mapping using asymmetries in the phase-cycled balanced SSFP signal profile.

PURPOSE: To develop SPARCQ (Signal Profile Asymmetries for Rapid Compartment Quantification), a novel approach to quantify fat fraction (FF) using asymmetries in the phase-cycled balanced SSFP (bSSFP) profile. METHODS: SPARCQ uses phase-cycling to obtain bSSFP frequency profiles, which display asymmetries in the presence of fat and water at certain TRs. For each voxel, the measured signal profile is decomposed into a weighted sum of simulated profiles via multi-compartment dictionary matching. Each dictionary entry represents a single-compartment bSSFP profile with a specific off-resonance frequency and relaxation time ratio. Using the results of dictionary matching, the fractions of the different off-resonance components are extracted for each voxel, generating quantitative maps of water and FF and banding-artifact-free images for the entire image volume. SPARCQ was validated using simulations, experiments in a water-fat phantom and in knees of healthy volunteers. Experimental results were compared with reference proton density FFs obtained with 1 H-MRS (phantoms) and with multiecho gradient-echo MRI (phantoms and volunteers). SPARCQ repeatability was evaluated in six scan-rescan experiments. RESULTS: Simulations showed that FF quantification is accurate and robust for SNRs greater than 20. Phantom experiments demonstrated good agreement between SPARCQ and gold standard FFs. In volunteers, banding-artifact-free quantitative maps and water-fat-separated images obtained with SPARCQ and ME-GRE demonstrated the expected contrast between fatty and non-fatty tissues. The coefficient of repeatability of SPARCQ FF was 0.0512. CONCLUSION: SPARCQ demonstrates potential for fat quantification using asymmetries in bSSFP profiles and may be a promising alternative to conventional FF quantification techniques.

Risk of Oral Squamous Cell Carcinoma in One Hundred Patients with Oral Lichen Planus: A Follow-Up Study of Umberto I University Hospital of Rome.

This study aims to retrospectively assess the potential risk of malignant transformation in patients with diagnosed oral lichen planus (OLP) between 2015 and 2022, and to evaluate the influence of different risk factors. The department's database and medical records from 2015 to 2022 were searched for patients with a confirmed diagnosis of OLP based on both clinical and histological parameters. A total of 100 patients (59 females and 41 males) were found with a mean age of 64.03 years. In the considered period, the percentage of diagnosed OLP patients was 1.6%, while the percentage of diagnosed OLP patients with transformation to oral squamous cell carcinoma (OSCC) was 0.18%. A statistically significant difference was found with age (p = 0.038), tobacco status (p = 0.022), and radiotherapy (p = 0.041). The analysis revealed the presence of significant risk in ex-smokers (>20 pack-years), with an odds ratio (OR) of 10.0000 (95% confidence interval (95% CI) 1.5793-63.3186); in alcohol-drinker patients, with an OR of 4.0519 (95% CI 1.0182-16.1253); in ex-smoker and alcohol-drinker patients, with OR of 17.6250 (95% CI 2.2464-138.2808); and in patients who had undergone radiotherapy, with OR of 6.3000 (95% CI 1.2661-31.3484). The malignant transformation of oral lichen planus was slightly higher than thought, and the results revealed a possible association with age, tobacco and alcohol status, and history of radiotherapy. An elevated risk of malignant transformation was observed in heavy ex-smoker patients, alcohol-drinker patients, and alcohol-drinker patients with a history of smoking (ex-smokers). Persuading the patient to quit tobacco and alcohol consumption and periodic follow-ups are recommended in general, but particularly in the presence of these risk factors.

Hydrogenated amorphous silicon high flux x-ray detectors for synchrotron microbeam radiation therapy.

Objective. Microbeam radiation therapy (MRT) is an alternative emerging radiotherapy treatment modality which has demonstrated effective radioresistant tumour control while sparing surrounding healthy tissue in preclinical trials. This apparent selectivity is achieved through MRT combining ultra-high dose rates with micron-scale spatial fractionation of the delivered x-ray treatment field. Quality assurance dosimetry for MRT must therefore overcome a significant challenge, as detectors require both a high dynamic range and a high spatial resolution to perform accurately.Approach. In this work, a series of radiation hard a-Si:H diodes, with different thicknesses and carrier selective contact configurations, have been characterised for x-ray dosimetry and real-time beam monitoring applications in extremely high flux beamlines utilised for MRT at the Australian Synchrotron.Results. These devices displayed superior radiation hardness under constant high dose-rate irradiations on the order of 6000 Gy s-1, with a variation in response of 10% over a delivered dose range of approximately 600 kGy. Dose linearity of each detector to x-rays with a peak energy of 117 keV is reported, with sensitivities ranging from (2.74 ± 0.02) nC/Gy to (4.96 ± 0.02) nC/Gy. For detectors with 0.8µm thick active a-Si:H layer, their operation in an edge-on orientation allows for the reconstruction of micron-size beam profiles (microbeams). The microbeams, with a nominal full-width-half-max of 50µm and a peak-to-peak separation of 400µm, were reconstructed with extreme accuracy. The full-width-half-max was observed as 55 ± 1µm. Evaluation of the peak-to-valley dose ratio and dose-rate dependence of the devices, as well as an x-ray induced charge (XBIC) map of a single pixel is also reported.Significance. These devices based on novel a-Si:H technology possess a unique combination of accurate dosimetric performance and radiation resistance, making them an ideal candidate for x-ray dosimetry in high dose-rate environments such as FLASH and MRT.

Leptin Resistance Does Not Facilitate Migratory Fattening in Ruby-Throated Hummingbirds (Archilochus Colubris).

In mammals, leptin is an important energy homeostasis hormone produced by adipose tissue. Circulating leptin concentrations correlate positively with fat mass and act in a negative feedback fashion to inhibit food intake and increase energy expenditure, thereby preventing fat gain. For some species, leptin resistance is advantageous during times of year where fat gain is necessary (e.g., prior to hibernation). While the function of leptin in birds remains controversial, seasonal leptin resistance may similarly benefit migratory species. Here, we used the ruby-throated hummingbird (Archilochus colubris) to test the hypothesis that leptin resistance promotes fattening prior to migration. We predicted that during the migratory fattening period, leptin levels should correlate positively with fat mass but should not inhibit food intake or increase energy expenditure, resulting in fattening. We tracked the body (fat) mass, the concentration of leptin-like protein in the urine, and the food intake of 12 captive hummingbirds from August 2021 to January 2022. In a subset of hummingbirds, we also quantified voluntary physical activity as a proxy for energy expenditure. We found remarkable age-related variation in fattening strategies, with juveniles doubling their body fat by mid-September and adults exhibiting only a 50% increase. Changes in fat mass were strongly associated with increased food intake and reduced voluntary activity. However, we found no correlation between leptin-like protein concentration and fat mass, food intake, or voluntary activity. Since increased torpor use has been shown to accelerate migratory fattening in ruby-throated hummingbirds, we also hypothesized that leptin is a mediator of torpor use. In an experimental manipulation of circulating leptin, however, we found no change in torpor use, body fat, or food intake. Overall, our findings suggest that leptin may not act as an adipostat in hummingbirds, nor does leptin resistance regulate how hummingbirds fatten prior to migration.

Cholesterol-Containing Liposomes Decorated With Au Nanoparticles as Minimal Tunable Fusion Machinery.

Membrane fusion is essential for the basal functionality of eukaryotic cells. In physiological conditions, fusion events are regulated by a wide range of specialized proteins, operating with finely tuned local lipid composition and ionic environment. Fusogenic proteins, assisted by membrane cholesterol and calcium ions, provide the mechanical energy necessary to achieve vesicle fusion in neuromediator release. Similar cooperative effects must be explored when considering synthetic approaches for controlled membrane fusion. We show that liposomes decorated with amphiphilic Au nanoparticles (AuLips) can act as minimal tunable fusion machinery. AuLips fusion is triggered by divalent ions, while the number of fusion events dramatically changes with, and can be finely tuned by, the liposome cholesterol content. We combine quartz-crystal-microbalance with dissipation monitoring (QCM-D), fluorescence assays, and small-angle X-ray scattering (SAXS) with molecular dynamics (MD) at coarse-grained (CG) resolution, revealing new mechanistic details on the fusogenic activity of amphiphilic Au nanoparticles (AuNPs) and demonstrating the ability of these synthetic nanomaterials to induce fusion regardless of the divalent ion used (Ca2+ or Mg2+ ). The results provide a novel contribution to developing new artificial fusogenic agents for next-generation biomedical applications that require tight control of the rate of fusion events (e.g., targeted drug delivery).

Focused navigation for respiratory-motion-corrected free-running radial 4D flow MRI.

PURPOSE: To validate a respiratory motion correction method called focused navigation (fNAV) for free-running radial whole-heart 4D flow MRI. METHODS: Using fNAV, respiratory signals derived from radial readouts are converted into three orthogonal displacements, which are then used to correct respiratory motion in 4D flow datasets. Hundred 4D flow acquisitions were simulated with non-rigid respiratory motion and used for validation. The difference between generated and fNAV displacement coefficients was calculated. Vessel area and flow measurements from 4D flow reconstructions with (fNAV) and without (uncorrected) motion correction were compared to the motion-free ground-truth. In 25 patients, the same measurements were compared between fNAV 4D flow, 2D flow, navigator-gated Cartesian 4D flow, and uncorrected 4D flow datasets. RESULTS: For simulated data, the average difference between generated and fNAV displacement coefficients was 0.04 ± $$ \pm $$ 0.32 mm and 0.31 ± $$ \pm $$ 0.35 mm in the x and y directions, respectively. In the z direction, this difference was region-dependent (0.02 ± $$ \pm $$ 0.51 mm up to 5.85 ± $$ \pm $$ 3.41 mm). For all measurements (vessel area, net volume, and peak flow), the average difference from ground truth was higher for uncorrected 4D flow datasets (0.32 ± $$ \pm $$ 0.11 cm2 , 11.1 ± $$ \pm $$ 3.5 mL, and 22.3 ± $$ \pm $$ 6.0 mL/s) than for fNAV 4D flow datasets (0.10 ± $$ \pm $$ 0.03 cm2 , 2.6 ± $$ \pm $$ 0.7 mL, and 5.1 ± 0 $$ \pm 0 $$ .9 mL/s, p < 0.05). In vivo, average vessel area measurements were 4.92 ± $$ \pm $$ 2.95 cm2 , 5.06 ± $$ \pm $$ 2.64 cm2 , 4.87 ± $$ \pm $$ 2.57 cm2 , 4.87 ± $$ \pm $$ 2.69 cm2 , for 2D flow and fNAV, navigator-gated and uncorrected 4D flow datasets, respectively. In the ascending aorta, all 4D flow datasets except for the fNAV reconstruction had significantly different vessel area measurements from 2D flow. Overall, 2D flow datasets demonstrated the strongest correlation to fNAV 4D flow for both net volume (r2  = 0.92) and peak flow (r2  = 0.94), followed by navigator-gated 4D flow (r2  = 0.83 and r2  = 0.86, respectively), and uncorrected 4D flow (r2  = 0.69 and r2  = 0.86, respectively). CONCLUSION: fNAV corrected respiratory motion in vitro and in vivo, resulting in fNAV 4D flow measurements that are comparable to those derived from 2D flow and navigator-gated Cartesian 4D flow datasets, with improvements over those from uncorrected 4D flow.