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To increase granularity in human neuroimaging science, we designed and built a next-generation 7 Tesla magnetic resonance imaging scanner to reach ultra-high resolution by implementing several advances in hardware. To improve spatial encoding and increase the image signal-to-noise ratio, we developed a head-only asymmetric gradient coil (200 mT m-1, 900 T m-1s-1) with an additional third layer of windings. We integrated a 128-channel receiver system with 64- and 96-channel receiver coil arrays to boost signal in the cerebral cortex while reducing g-factor noise to enable higher accelerations. A 16-channel transmit system reduced power deposition and improved image uniformity. The scanner routinely performs functional imaging studies at 0.35-0.45 mm isotropic spatial resolution to reveal cortical layer functional activity, achieves high angular resolution in diffusion imaging and reduces acquisition time for both functional and structural imaging.

Abstract Promoting the shift from private cars to micromobility (e.g., bike, e-bike, scooter) can represent a valuable action to improve city sustainability and liveability. Micromobility can help to replace trips by individual private cars (e.g., daily short round trips) as well as to improve coverage and accessibility of transit services, and, subsequently, to reduce the traffic impacts (e.g., pollutant emissions). It can be seen as a potential solution to move people more efficiently in urban areas, as well as to push people towards a more active mobility behaviour, contributing to the well-being goals. In this context, the paper, rather than inferring the users’ propensity to change their travel mode, proposes a methodology to identify car trips that can be considered the most compatible with micromobility. Estimation of the potential demand (e.g., the upper level of car trips that could be replaced by micromobility) is carried out by exploiting the opportunity offered by floating car data (FCD) for characterising car trips. Its goodness is therefore evaluated through an application to a real case study (i.e., the city of Trani, Apulia Region, Southern Italy), divided into seventy traffic zones, and where a FCD dataset of about 5,200 trips was available. The FCD allowed the car trips to be characterised (e.g., origin and destination, path features) instead of using the traditional surveys. The results indicate that a significant share of daily car trips can be substituted (i.e., the most compatible) by micromobility (31% of car round trips in the case study), with considerable potential environmental gains (traffic emission reduction; less than 21% of total emissions from private cars). Results can be of interest to local authorities in integrating micromobility in urban mobility planning and promoting new sustainable transport alternatives, as well as to transport companies for designing new appeal services. The developed methodology is parametric and uses easy-to-obtain data available worldwide; thus, it can be easily transferred to other city contexts.

Abstract Background The KEYNOTE-048 trial showed that pembrolizumab-based first-line treatment for R/M HNSCC led to improved OS in the PD-L1 CPS ≥ 1 population when compared to the EXTREME regimen. However, the R/M HNSCC real-world population is generally frailer, often presenting with multiple comorbidities, worse performance status and older age than the population included in phase III clinical trials. Methods This is a retrospective, single-centre analysis of patients with R/M HNSCC treated with pembrolizumab-based first-line treatment. Results From February 2021 to March 2023, 92 patients were treated with pembrolizumab-based first-line treatment. Patients treated with pembrolizumab-based chemoimmunotherapy had better ECOG PS and younger age than those treated with pembrolizumab monotherapy. Median PFS and OS were 4 months and 8 months, respectively. PFS was similar among patients treated with pembrolizumab-based chemoimmunotherapy and pembrolizumab monotherapy, while patients treated with pembrolizumab monotherapy had worse OS (log-rank p =.001, HR 2.7). PFS and OS were improved in patients with PD-L1 CPS > = 20 (PFS: log-rank p =.005, HR 0.50; OS: log-rank p =.04, HR 0.57). Patients with higher ECOG PS scores had worse PFS and OS (PFS, log-rank p =.004; OS, log-rank p = 6e-04). In multivariable analysis, ECOG PS2 was associated with worse PFS and OS. Conclusions PFS in our real-world cohort was similar to the KEYNOTE-048 reference while OS was numerically inferior. A deeper understanding of clinical variables that might affect survival outcomes of patients with R/M HNSCC beyond ECOG PS and PD-L1 CPS is urgently needed.

ABSTRACT: Anatomy teaching has been changing over the years, introducing technological methods especially after the pandemic period. An ongoing debate revolves around whether exclusive reliance on technology for anatomy classes, as opposed to traditional methods and face-to-face instruction, enhances knowledge acquisition. This study analyzed the knowledge perception of students from various semesters throughout the Veterinary Medicine course, comparing students who only had online classes with those who had face-to-face classes in Gross Anatomy of Domestic Animals. For this purpose, a questionnaire was distributed for voluntary and anonymous completion, and the responses were subsequently analyzed statistically. The results indicated that 11.5% of the students who took Anatomy remotely failed to apply the knowledge in other subjects, while no face-to-face learning student reported the same. Most students, both remote and face-to-face groups, remember the subject but review the content frequently. Regarding theoretical knowledge, the online group (80.8%) understood better as the course progressed, compared to 59.6% of the face-to-face group. The connection between Anatomy and other subjects was more highlighted by the face-to-face group (30.8%) compared to the online group (15.4%). Both groups agree that physical contact with anatomical specimens is essential; however, some believe that initial exposure through 3D images or photographs is feasible. We concluded based on this preliminary study that the initial interactions with the Anatomy field should include diversified pedagogical techniques with empathetic communication. The use of modern technological resources are allies in the teaching-learning process. Furthermore, after abstracting the contents, technology alone can effectively maintain and update anatomical knowledge.

Abstract Moiré excitons (MXs) are electron-hole pairs localised by the periodic (moiré) potential forming in two-dimensional heterostructures (HSs). MXs can be exploited, e.g., for creating nanoscale-ordered quantum emitters and achieving or probing strongly correlated electronic phases at relatively high temperatures. Here, we studied the exciton properties of WSe2/MoSe2 HSs from T = 6 K to room temperature using time-resolved and continuous-wave micro-photoluminescence also under a magnetic field. The exciton dynamics and emission lineshape evolution with temperature show clear signatures that MXs de-trap from the moiré potential and turn into free interlayer excitons (IXs) for temperatures above 100 K. The MX-to-IX transition is also apparent from the exciton magnetic moment reversing its sign when the moiré potential is not capable of localising excitons at elevated temperatures. Concomitantly, the exciton formation and decay times reduce drastically. Thus, our findings establish the conditions for a truly confined nature of the exciton states in a moiré superlattice with increasing temperature and photo-generated carrier density.

Background and Aims: Hypoalbuminemia, as defined by serum albumin (SA) levels ≤35 g/L, is associated to venous and arterial thrombosis in general population and in patients at risk of cardiovascular disease. It is unknown if SA ≤35 g/L is also associated to portal vein thrombosis (PVT) in cirrhosis. Methods: Cirrhotic patients enrolled in the Portal vein thrombosis Relevance On Liver cirrhosis: Italian Venous thrombotic Events Registry (PRO-LIVER) study (n = 753), were followed-up for 2 years to assess the risk of PVT, that was diagnosed by Doppler ultrasonography. Child-Pugh classes, Model for End-Stage Liver Disease score, presence of hepatocellular carcinoma and laboratory variables including SA, D-dimer, and high-sensitivity C-reactive protein (hs-CRP) were measured at baseline. Results: SA ≤35 g/L was detected in 52% of patients. A logistic multivariate regression analysis showed that higher Child-Pugh class, hepatocellular carcinoma and thrombocytopenia were significantly associated to SA ≤35 g/L. In a subgroup of patients where data regarding hs-CRP and D-dimer were available, SA ≤35 g/L was inversely associated with hs-CRP and D-dimer. During the follow-up, a total of 61 patients experienced PVT. A Kaplan Meier survival analysis showed SA ≤35 g/L was associated to increased risk of PVT compared to SA >35 g/L (P = .005). A multivariate Cox proportional hazards regression analysis showed that male sex, lower platelet count, and SA ≤35 g/L remained associated to PVT after adjusting for confounding factors. Conclusion: Cirrhotic patients with SA ≤35 g/L are at higher risk of experiencing PVT compared to those with SA >35 g/L and could be considered as potential candidates to anticoagulant prophylaxis for PVT prevention.

Nerve growth factor (NGF) plays a dual role both in inflammatory states and cancer, acting both as a pro-inflammatory and oncogenic factor and as an anti-inflammatory and pro-apoptotic mediator in a context-dependent way based on the signaling networks and its interaction with diverse cellular components within the microenvironment. This report aims to provide a summary and subsequent review of the literature on the role of NGF in regulating the inflammatory microenvironment and tumor cell growth, survival, and death. The role of NGF in inflammation and tumorigenesis as a component of the inflammatory system, its interaction with the various components of the respective microenvironments, its ability to cause epigenetic changes, and its role in the treatment of cancer have been highlighted in this paper.

L-cysteine, a precursor of essential components for plant growth, is synthesized by the cysteine synthase complex, which includes O-acetylserine(thiol) lyase (OAS-TL) and serine acetyltransferase. In this work, we investigated how S-benzyl-L-cysteine (SBC), an OAS-TL inhibitor, affects the growth, photosynthesis, and oxidative stress of Ipomoea grandifolia plants. SBC impaired gas exchange and chlorophyll a fluorescence, indicating damage that compromised photosynthesis and reduced plant growth. Critical parameters such as the electron transport rate (J), triose phosphate utilization (TPU), light-saturation point (LSP), maximum carboxylation rate of Rubisco (Vcmax), and light-saturated net photosynthetic rate (PNmax) decreased by 19%, 20%, 22%, 23%, and 24%, respectively. The photochemical quenching coefficient (qP), quantum yield of photosystem II photochemistry (ϕPSII), electron transport rate through PSII (ETR), and stomatal conductance (gs) decreased by 12%, 19%, 19%, and 34%, respectively. Additionally, SBC decreased the maximum fluorescence yield (Fm), variable fluorescence (Fv), and chlorophyll (SPAD index) by 14%, 15%, and 15%, respectively, indicating possible damage to the photosynthetic apparatus. SBC triggered root oxidative stress by increasing malondialdehyde, reactive oxygen species, and conjugated dienes by 30%, 55%, and 61%, respectively. We hypothesize that dysfunctions in sulfur-containing components of the photosynthetic electron transport chain, such as the cytochrome b6f complex, ferredoxin, and the iron–sulfur (Fe-S) centers are the cause of these effects, which ultimately reduce the efficiency of electron transport and hinder photosynthesis in I. grandifolia plants. In short, our findings suggest that targeting OAS-TL with inhibitors like SBC could be a promising strategy for the development of novel herbicides.

Purpose: Describe the clinical features and management of this uncommon case of late-onset Capsular bag distension syndrome that occurred 33 years after cataract surgery. Observation: An 87-year-old male was referred to our clinic complaining of blurred and gradual, painless reduction in vision in his left eye over the past year. A complete ophthalmological examination, Ultrasound biomicroscopy (UBM), anterior segment optical coherence tomography (AS-OCT), and optical biometry were performed to confirm the diagnosis. A 25-gauge pars plana vitrectomy combined with posterior capsulotomy was performed. The aspirated fluid was sent for microbiological analyses. After surgery, the patient's visual acuity returned to previous values, and anterior chamber depth slightly deepened. Samples taken were negative for bacteria. Conclusions and Importance: Late-onset Capsular bag distension syndrome may occur up to 33 years following cataract surgery. A surgical approach offers the advantage of complete clearance of the turbid fluid, also removing the residual cortical material and enabling microbial and pathological testing.

ObjectivesCoronavirus-disease-19 (COVID-19) continues to affect millions of individuals worldwide. Antiviral activity of mouthrinses remains an important research area as the oral cavity is a site of SARS-CoV-2 initial replication. The aim of this study was to assess the effectiveness of three different mouthrinses in reducing the oral/oropharyngeal SARS-CoV-2 viral load.MethodsAdult patients, hospitalized with confirmed COVID-19 were recruited for the study. Oral/oropharyngeal baseline SARS-CoV-2 samples were collected and analyzed by Real-Time-PCR. Subsequently, patients were instructed to rinse with 1 % hydrogen peroxide (H2O2), 0.12 % chlorhexidine (CHX), 1 % povidone‑iodine (PVP-I) or Sodium Chloride 0.9 % (placebo). Viral loads were measured right after (T1), and at 45 min (T2) from the rinse.ResultsIn the PVP-I 1 % group, 5/8 (62.5 %) patients at T1, and 3/8 (37.5 %) patients at T2, SARS-CoV-2 was not detectable in the swab specimens. In the H2O2 1 % group, 2/11 (18.2 %) patients at T1, and 2/11 (18.2 %) other patients at T2 showed no SARS-CoV-2 loads. One (12.5 %) patient in the CHX 0.12 % group showed SARS-CoV-2 negativity at T2. One (9.1 %) patient at T1, and another (9.1 %) patient at T2 showed no SARS-CoV-2 loads in the placebo group.ConclusionsOral SARS-CoV-2 loads were reduced at T1 in the PVP-I 1 % and H2O2 1 % groups.Clinical relevancePVP-I 1 % was the most effective rinse especially in patients with low viral copy numbers at baseline.

In this paper, an integrated approach is proposed that incorporates the road network design problem and the vehicle routing problem, which are very often studied separately. This approach can be adopted when the routes to follow in a transport system have to be designed (e.g., for public transit with fixed and variable routes, or for freight distribution) jointly with the network topology and capacity. The goal is to minimise congestion and the impacts on the network from passengers and freight vehicles. The design (control) variables consist of the optimal vehicle routes and optimised road network; they are both discrete (link topology for passenger and freight, routes for passengers and freight vehicles, etc.) and continuous (link capacity in terms of reserved lanes, signal settings, etc.). The problem is modelled in congested transportation networks (e.g., in an urban centre). A heuristic algorithm is adopted to find the best network configuration and the best vehicle routes. The proposed model and the adopted algorithm are applied in a test system to analyse the limits of the methodology, to verify the advantage obtained from the joint method and its applicability. In the test system, the joint procedure gives good results in terms of cost decreases. The reported methods can help public and private stakeholders in making decisions regarding transportation policy, especially in the urban environment.

Hydroxycinnamates induce lignification in young plants, leading to the overproduction of lignin as a defense mechanism. Phenylpropanoids-containing oligosaccharides are thought to be a signal of pathogen attack on the cell wall polysaccharides. However, it is unclear if hydroxycinnamates induce lignification by acting solely as stress elicitors or feeding the phenylpropanoid pathway as lignin precursors. To examine this hypothesis, we added 1 mM deuterated ferulic acid (FA) or sinapic acid (SA) to the nutrient solution in which we cultivated soybean or maize plantlets. After 24 h, we assessed the biometric parameters and the contents of ester-linked FA and SA, total lignin, monolignol ratio, and heavy monolignols. FA treatment increased the content of ester-linked FA, syringyl, and guaiacyl monomers measured by nitrobenzene oxidation, lignin content, and reduced root growth in both soybean and maize plants. p-Coumaric acid content ester-linked to the cell wall increased in soybean but decreased in maize after treatment with FA. Treatment with SA also induced lignification in soybean but not in maize. SA increased S-lignin and sinapoyl esters content in the cell wall polymers in both soybean and maize. Residues of deuterated hydroxycinnamates were detected in the lignin of both plants in both treatments. The assay demonstrated that exogenously applied SA and FA were metabolized through the phenylpropanoid pathway. Furthermore, they were, at least partially, exported to the apoplast, where they were ester-linked to cell wall polymers. This suggests hydroxycinnamic acids are metabolized differently by plants with different types of cell walls.

NGF plays a crucial immunomodulatory role and increased levels are found in numerous tissues during autoimmune states. NGF directly modulates innate and adaptive immune responses of B and T cells and causes the release of neuropeptides and neurotransmitters controlling the immune system activation in inflamed tissues. Evidence suggests that NGF is involved in the pathogenesis of numerous immune diseases including autoimmune thyroiditis, chronic arthritis, multiple sclerosis, systemic lupus erythematosus, mastocytosis, and chronic granulomatous disease. Furthermore, as NGF levels have been linked to disease severity, it could be considered an optimal early biomarker to identify therapeutic approach efficacy. In conclusion, by gaining insights into how these molecules function and which cells they interact with, future studies can devise targeted therapies to address various neurological, immunological, and other disorders more effectively. This knowledge may pave the way for innovative treatments based on NGF manipulation aimed at improving the quality of life for individuals affected by diseases involving neurotrophins.