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Abstract Background Alongside the benefits of Total-Body imaging modalities, such as higher sensitivity, single-bed position, low dose imaging, etc., their final construction cost prevents worldwide utilization. The main aim of this study is to present a simulation-based comparison of the sensitivities of existing and currently developed tomographs to introduce a cost-efficient solution for constructing a Total-Body PET scanner based on plastic scintillators. Methods For the case of this study, eight tomographs based on the uEXPLORER configuration with different scintillator materials (BGO, LYSO), axial field-of-view (97.4 cm and 194.8 cm), and detector configurations (full and sparse) were simulated. In addition, 8 J-PET scanners with different configurations, such as various axial field-of-view (200 cm and 250 cm), different cross sections of plastic scintillator, and multiple numbers of plastic scintillator layers (2, 3, and 4), based on J-PET technology have been simulated by GATE software. Furthermore, Siemens’ Biograph Vision has been simulated to compare the results with standard PET scans. Two types of simulations have been performed. The first one with a centrally located source with a diameter of 1 mm and a length of 250 cm, and the second one with the same source inside a water-filled cylindrical phantom with a diameter of 20 cm and a length of 183 cm. Results With regards to sensitivity, among all the proposed scanners, the ones constructed with BGO crystals give the best performance ( $$\sim$$ ∼ 350 cps/kBq at the center). The utilization of sparse geometry or LYSO crystals significantly lowers the achievable sensitivity of such systems. The J-PET design gives a similar sensitivity to the sparse LYSO crystal-based detectors while having full detector coverage over the body. Moreover, it provides uniform sensitivity over the body with additional gain on its sides and provides the possibility for high-quality brain imaging. Conclusion Taking into account not only the sensitivity but also the price of Total-Body PET tomographs, which till now was one of the main obstacles in their widespread clinical availability, the J-PET tomography system based on plastic scintillators could be a cost-efficient alternative for Total-Body PET scanners.

Abstract Purpose In living organisms, the positron-electron annihilation (occurring during the PET imaging) proceeds in about 30% via creation of a metastable ortho-positronium atom. In the tissue, due to the pick-off and conversion processes, over 98% of ortho-positronia annihilate into two 511 keV photons. In this article, we assess the feasibility for reconstruction of the mean ortho-positronium lifetime image based on annihilations into two photons. The main objectives of this work include the (i) estimation of the sensitivity of the total-body PET scanners for the ortho-positronium mean lifetime imaging using 2γ annihilations and (ii) estimation of the spatial and time resolution of the ortho-positronium image as a function of the coincidence resolving time (CRT) of the scanner. Methods Simulations are conducted assuming that radiopharmaceutical is labeled with 44 S c isotope emitting one positron and one prompt gamma. The image is reconstructed on the basis of triple coincidence events. The ortho-positronium lifetime spectrum is determined for each voxel of the image. Calculations were performed for cases of total-body detectors build of (i) LYSO scintillators as used in the EXPLORER PET and (ii) plastic scintillators as anticipated for the cost-effective total-body J-PET scanner. To assess the spatial and time resolution, the four cases were considered assuming that CRT is equal to 500 ps, 140 ps, 50 ps, and 10 ps. Results The estimated total-body PET sensitivity for the registration and selection of image forming triple coincidences (2γ+γ prompt) is larger by a factor of 13.5 (for LYSO PET) and by factor of 5.2 (for plastic PET) with respect to the sensitivity for the standard 2γ imaging by LYSO PET scanners with AFOV = 20 cm. The spatial resolution of the ortho-positronium image is comparable with the resolution achievable when using TOF-FBP algorithms already for CRT = 50 ps. For the 20-min scan, the resolution better than 20 ps is expected for the mean ortho-positronium lifetime image determination. Conclusions Ortho-positronium mean lifetime imaging based on the annihilations into two photons and prompt gamma is shown to be feasible with the advent of the high sensitivity total-body PET systems and time resolution of the order of tens of picoseconds.

Abstract Purpose Q.Clear is a block sequential regularized expectation maximization (BSREM) penalized-likelihood reconstruction algorithm for PET. It tries to improve image quality by controlling noise amplification during image reconstruction. In this study, the noise properties of this BSREM were compared to the ordered-subset expectation maximization (OSEM) algorithm for both phantom and patient data acquired on a state-of-the-art PET/CT. Methods The NEMA IQ phantom and a whole-body patient study were acquired on a GE DMI 3-rings system in list mode and different datasets with varying noise levels were generated. Phantom data was evaluated using four different contrast ratios. These were reconstructed using BSREM with different β-factors of 300–3000 and with a clinical setting used for OSEM including point spread function (PSF) and time-of-flight (TOF) information. Contrast recovery (CR), background noise levels (coefficient of variation, COV), and contrast-to-noise ratio (CNR) were used to determine the performance in the phantom data. Findings based on the phantom data were compared with clinical data. For the patient study, the SUV ratio, metabolic active tumor volumes (MATVs), and the signal-to-noise ratio (SNR) were evaluated using the liver as the background region. Results Based on the phantom data for the same count statistics, BSREM resulted in higher CR and CNR and lower COV than OSEM. The CR of OSEM matches to the CR of BSREM with β = 750 at high count statistics for 8:1. A similar trend was observed for the ratios 6:1 and 4:1. A dependence on sphere size, counting statistics, and contrast ratio was confirmed by the CNR of the ratio 2:1. BSREM with β = 750 for 2.5 and 1.0 min acquisition has comparable COV to the 10 and 5.0 min acquisitions using OSEM. This resulted in a noise reduction by a factor of 2–4 when using BSREM instead of OSEM. For the patient data, a similar trend was observed, and SNR was reduced by at least a factor of 2 while preserving contrast. Conclusion The BSREM reconstruction algorithm allowed a noise reduction without a loss of contrast by a factor of 2–4 compared to OSEM reconstructions for all data evaluated. This reduction can be used to lower the injected dose or shorten the acquisition time.

Abstract Background Fully integrated PET/MR systems are being used frequently in clinical research and routine. National Electrical Manufacturers Association (NEMA) characterization of these systems is generally done with 18F which is clinically the most relevant PET isotope. However, other PET isotopes, such as 68Ga and 90Y, are gaining clinical importance as they are of specific interest for oncological applications and for follow-up of 90Y-based radionuclide therapy. These isotopes have a complex decay scheme with a variety of prompt gammas in coincidence. 68Ga and 90Y have higher positron energy and, because of the larger positron range, there may be interference with the magnetic field of the MR compared to 18F. Therefore, it is relevant to determine the performance of PET/MR for these clinically relevant and commercially available isotopes. Methods NEMA NU 2–2007 performance measurements were performed for characterizing the spatial resolution, sensitivity, image quality, and the accuracy of attenuation and scatter corrections for 18F, 68Ga, and 90Y. Scatter fraction and noise equivalent count rate (NECR) tests were performed using 18F and 68Ga. All phantom data were acquired on the GE Signa integrated PET/MR system, installed in UZ Leuven, Belgium. Results 18F, 68Ga, and 90Y NEMA performance tests resulted in substantially different system characteristics. In comparison with 18F, the spatial resolution is about 1 mm larger in the axial direction for 68Ga and no significative effect was found for 90Y. The impact of this lower resolution is also visible in the recovery coefficients of the smallest spheres of 68Ga in image quality measurements, where clearly lower values are obtained. For 90Y, the low number of counts leads to a large variability in the image quality measurements. The primary factor for the sensitivity change is the scale factor related to the positron emission fraction. There is also an impact on the peak NECR, which is lower for 68Ga than for 18F and appears at higher activities. Conclusions The system performance of GE Signa integrated PET/MR was substantially different, in terms of NEMA spatial resolution, image quality, and NECR for 68Ga and 90Y compared to 18F. But these differences are compensated by the PET/MR scanner technologies and reconstructions methods.

Copulas have already proven their flexibility in rainfall modelling. Yet, their use is generally restricted to the description of bivariate dependence. Recently, vine copulas have been introduced, allowing multi-dimensional dependence structures to be described on the basis of a stage by stage mixing of 2-dimensional copulas. This paper explores the use of such vine copulas in order to incorporate all relevant dependences between the storm variables of interest. On the basis of such fitted vine copulas, an external storm structure is modelled. An internal storm structure is superimposed based on Huff curves, such that a continuous time series of rainfall is generated. The performance of the rainfall model is evaluated through a statistical comparison between an ensemble of synthetical rainfall series and the observed rainfall series and through the comparison of the annual maxima.

Of all natural disasters, the economic and environmental consequences of droughts are among the highest because of their longevity and widespread spatial extent. Because of their extreme behaviour, studying droughts generally requires long time series of historical climate data. Rainfall is a very important variable for calculating drought statistics, for quantifying historical droughts or for assessing the impact on other hydrological (e.g. water stage in rivers) or agricultural (e.g. irrigation requirements) variables. Unfortunately, time series of historical observations are often too short for such assessments. To circumvent this, one may rely on the synthetic rainfall time series from stochastic point process rainfall models, such as Bartlett–Lewis models. The present study investigates whether drought statistics are preserved when simulating rainfall with Bartlett–Lewis models. Therefore, a 105 yr 10 min rainfall time series obtained at Uccle, Belgium is used as a test case. First, drought events were identified on the basis of the Effective Drought Index (EDI), and each event was characterized by two variables, i.e. drought duration (D) and drought severity (S). As both parameters are interdependent, a multivariate distribution function, which makes use of a copula, was fitted. Based on the copula, four types of drought return periods are calculated for observed as well as simulated droughts and are used to evaluate the ability of the rainfall models to simulate drought events with the appropriate characteristics. Overall, all Bartlett–Lewis model types studied fail to preserve extreme drought statistics, which is attributed to the model structure and to the model stationarity caused by maintaining the same parameter set during the whole simulation period.

Most of the hydrological and hydraulic studies refer to the notion of a return period to quantify design variables. When dealing with multiple design variables, the well-known univariate statistical analysis is no longer satisfactory, and several issues challenge the practitioner. How should one incorporate the dependence between variables? How should a multivariate return period be defined and applied in order to yield a proper design event? In this study an overview of the state of the art for estimating multivariate design events is given and the different approaches are compared. The construction of multivariate distribution functions is done through the use of copulas, given their practicality in multivariate frequency analyses and their ability to model numerous types of dependence structures in a flexible way. A synthetic case study is used to generate a large data set of simulated discharges that is used for illustrating the effect of different modelling choices on the design events. Based on different uni- and multivariate approaches, the design hydrograph characteristics of a 3-D phenomenon composed of annual maximum peak discharge, its volume, and duration are derived. These approaches are based on regression analysis, bivariate conditional distributions, bivariate joint distributions and Kendall distribution functions, highlighting theoretical and practical issues of multivariate frequency analysis. Also an ensemble-based approach is presented. For a given design return period, the approach chosen clearly affects the calculated design event, and much attention should be given to the choice of the approach used as this depends on the real-world problem at hand.

The calibration of stochastic point process rainfall models, such as of the Bartlett-Lewis type, suffers from the presence of multiple local minima which local search algorithms usually fail to avoid. To meet this shortcoming, four relatively new global optimization methods are presented and tested for their ability to calibrate the Modified Bartlett-Lewis Model. The list of tested methods consists of: the Downhill Simplex Method, Simplex-Simulated Annealing, Particle Swarm Optimization and Shuffled Complex Evolution. The parameters of these algorithms are first optimized to ensure optimal performance, after which they are used for calibration of the Modified Bartlett-Lewis model. Furthermore, this paper addresses the choice of weights in the objective function. Three alternative weighing methods are compared to determine whether or not simulation results (obtained after calibration with the best optimization method) are influenced by the choice of weights.

Fine-scale rainfall data is important for many hydrological applications. However, often the only data available is at a coarse scale. To bridge this gap in resolution, stochastic disaggregation methods can be used. Such methods generally assume that the distribution of the field is stationary, i.e. the distribution for the entire (fine-scale) field is the same as the distribution of a smaller region within the field. This assumption is generally incorrect and we provide a proof of concept of a method to estimate the distribution of a smaller region. In this method, a copula is used to construct a bivariate distribution describing the relation between the scales. This distribution is then used to estimate the distribution of the fine-scale rainfall within a single coarse-scale pixel, by conditioning on the coarse-scale rainfall depth.

The use of design storms can be very useful in many hydrological and hydraulic practices. In this study, the concept of a copula-based secondary return period in combination with the concept of mass curves is used to generate point-scale design storms. The analysis is based on storms selected from the 105 year rainfall time series with a 10 min resolution, measured at Uccle, Belgium. In first instance, bivariate copulas and secondary return periods are explained, together with a focus on which couple of storm variables is of highest interest for the analysis and a discussion of how the results might be affected by the goodness-of-fit of the copula. Subsequently, the fitted copula is used to sample storms with a predefined secondary return period for which characteristic variables such as storm duration and total storm depth can be derived. In order to construct design storms with a realistic storm structure, mass curves of 1st, 2nd, 3rd and 4th quartile storms are developed. An analysis shows that the assumption of independence between the secondary return period and the internal storm structure could be made. Based on the mass curves, a technique is developed to randomly generate an intrastorm structure. The coupling of both techniques eventually results in a methodology for stochastic design storm generation. Finally, its practical usefulness for design studies is illustrated based on the generation of a set of statistically identical design storm and rainfall-runoff modelling.

In recent years, there has been a strong focus on beneficial foods with probiotic microorganisms and functional organic substances. In this context, there is an increasing interest in the commercial use of kefir, since it can be marketed as a natural beverage that has health promoting bacteria. There are numerous commercially available kefir based-products. Kefir may act as a matrix in the effective delivery of probiotic microorganisms in different types of products. Also, the presence of kefir’s exopolysaccharides, known as kefiran, which has biological activity, certainly adds value to products. Kefiran can also be used separately in other food products and as a coating film for various food and pharmaceutical products. This article aims to update the information about kefir and its microbiological composition, biological activity of the kefir’s microflora and the importance of kefiran as a beneficial health substance.

Volatile compounds with fruity characteristics were produced by Ceratocystis fimbriata in two different bioreactors: columns (laboratory scale) and horizontal drum (semi-pilot scale). Coffee husk was used as substrate for the production of volatile compounds by solid-state fermentation. The production of volatile compounds was significantly higher when horizontal drum bioreactor was used than when column bioreactors were used. These results showed that this model of bioreactor presents good perspectives for scale-up and application in an industrial production. Headspace analysis of the solid-state culture detected twelve compounds, among them: ethanol, acetaldehyde, ethyl acetate, ethyl propionate, and isoamyl acetate. Ethyl acetate was the predominant product in the headspace (28.55 µmol/L/g of initial dry matter). Activated carbon, Tenax-TA, and Amberlite XAD-2 were tested to perform the recovery of the compounds. The adsorbent columns were connected to the column-type bioreactor. All compounds present in the headspace of the columns were adsorbed in Amberlite XAD-2. With Tenax-TA, acetaldehyde was adsorbed in higher concentrations. However, the recovery found by using the activated carbon was very low.

There is a great worldwide demand for citric acid consumption due to its low toxicity when compared with other acidulants used mainly in the pharmaceutical and food industries. Other applications of citric acid can be found in detergents and cleaning products, cosmetics and toiletries, and other. Global production has now reached 1.4 million tonnes and there is annual growth of 3.5–4.0 % in demand/consumption of citric acid. As a result of the adverse market conditions, only big producers have survived. Any increase in citric acid productivity would be of potential interest and hence there is an obvious need to consider all possible ways in which this might be achieved. The production by submerged fermentation is still dominating. However, solid-state processes can create new possibilities for producers. Many by-products and residues of the agro-industry can be used in the production of citric acid. A cost reduction in citric acid production can be achieved by using less expensive substrates. The use of agro-industrial residues as support in solid-state fermentation is economically important and minimizes environmental problems. Other perspectives for citric acid production sector are the improvement of citric acid producing strains, which have been carried out by mutagenesis and selection.

In this paper, a method for analysis and modeling of coplanartransmission interconnect lines that are placed on top ofsilicon-silicon oxide substrates is presented. The potential functionis expressed by series expansions in terms of solutions of the Laplaceequation for each homogeneous region of layered structure. Theexpansion coefficients of different series are related to each otherand to potentials applied to the conductors via boundary conditions. Inthe plane of conductors, boundary conditions are satisfied at Nddiscrete points with Nd being equal to the number of terms in theseries expansions. The resulting system of inhomogeneous linearequations is solved by matrix inversion. No iterations are required. Adiscussion of the calculated line admittance parameters as functions ofwidth of conductors, thickness of the layers, and frequency is given.The interconnect capacitance and conductance per unit length resultsare given and compared with those obtained using full wave solutions,and good agreement have been obtained in all the cases treated.

Citric acid is the most important organic acid produced in tonnage and is extensively used in food and pharmaceutical industries. It is produced mainly by submerged fermentation using Aspergillus niger or Candida sp. from different sources of carbohydrates, such as molasses and starch based media. However, other fermentation techniques, e.g. solid state fermentation and surface fermentation, and alternative sources of carbon such as agro-industrial residues have been intensively studied showing great perspective to its production. This paper reviews recent developments on citric acid production by presenting a brief summary of the subject, describing micro-organisms, production techniques, and substrates, etc.O ácido cítrico é o ácido mais produzido em termos de tonagem e é extensivamente utilizado pelas indústrias alimentícia e farmacêutica. É produzido principalmente por fermentação submersa utilizando o fungo Aspergillus niger e leveduras do gênero Candida sp. à partir de diferentes fontes de carbono, como a glicose e meios à base de amido. No entanto, outras técnicas de fermentação, e.g. fermentação no estado sólido e em superfície, e fontes alternativas de carbono tem sido intensamente estudadas mostrando grande perspectivas para o processo. O presente trabalho apresenta um resumo dos últimos avanços sobre a produção do ácido cítrico, descrevendo de maneira sucinta os trabalhos mais recentes, descrevendo microrganismos, técnicas de produção e substratos empregados, etc.

Today, new single photon emission computed tomography (SPECT) reconstruction techniques rely on accurate Monte Carlo (MC) simulations to optimize reconstructed images. However, existing MC scintillation camera models which usually include an accurate description of the collimator and crystal, lack correct implementation of the gamma camera's back compartments. In the case of dual isotope simultaneous acquisition (DISA), where backscattered photons from the highest energy isotope are detected in the imaging energy window of the second isotope, this approximation may induce simulation errors. Here, we investigate the influence of backscatter compartment modelling on the simulation accuracy of high-energy isotopes. Three models of a scintillation camera were simulated: a simple model (SM), composed only of a collimator and a NaI(Tl) crystal; an intermediate model (IM), adding a simplified description of the backscatter compartments to the previous model and a complete model (CM), accurately simulating the materials and geometries of the camera. The camera models were evaluated with point sources (67Ga, 99mTc, 111In, 123I, 131I and 18F) in air without a collimator, in air with a collimator and in water with a collimator. In the latter case, sensitivities and point-spread functions (PSFs) simulated in the photopeak window with the IM and CM are close to the measured values (error below 10.5%). In the backscatter energy window, however, the IM and CM overestimate the FWHM of the detected PSF by 52% and 23%, respectively, while the SM underestimates it by 34%. The backscatter peak fluence is also overestimated by 20% and 10% with the IM and CM, respectively, whereas it is underestimated by 60% with the SM. The results show that an accurate description of the backscatter compartments is required for SPECT simulations of high-energy isotopes (above 300 keV) when the backscatter energy window is of interest. [ABSTRACT FROM AUTHOR]

A PACS (Picture Archiving and Communication System) is a system that is able to store, exchange, display and manipulate images and associated diagnoses from any modality within a hospital in a timely and cost-effective way. Several developments, such as the DICOM standard, fast and convenient networking, and new storage solutions for large amounts of data, make the setup of such a PACS system possible. As the information acquired with various imaging modalities is then available and often complementary, it is desirable for the clinician to have a point-by-point spatial co-registration of images from different modalities in order to enable a synergistic use of the multimodality imaging of a patient for increased diagnostic accuracy. Various types of algorithms are available for the matching of medical images from the same or from different modalities. Co-registration algorithms based on voxel properties consist of a similarity or dissimilarity measure and an iterative or non-iterative method minimizing the dissimilarity or maximizing the similarity between the two images by a transformation of one image relative to the other. [ABSTRACT FROM AUTHOR]

Particle therapy is a highly conformal radiotherapy technique which reduces the dose deposited to the surrounding normal tissues. In order to fully exploit its advantages, treatment monitoring is necessary to minimize uncertainties related to the dose delivery. Up to now, the only clinically feasible technique for the monitoring of therapeutic irradiation with particle beams is Positron Emission Tomography (PET). In this work we have compared a Resistive Plate Chamber (RPC)-based PET scanner with a scintillation-crystal-based PET scanner for this application. In general, the main advantages of the RPC-PET system are its excellent timing resolution, low cost, and the possibility of building large area systems. We simulated a partial-ring scanner based on an RPC prototype under construction within the Fondazione per Adroterapia Oncologica (TERA). For comparison with the crystal-based PET scanner we have chosen the geometry of a commercially available PET scanner, the Philips Gemini TF. The coincidence time resolution used in the simulations takes into account the current achievable values as well as expected improvements of both technologies. Several scenarios (including patient data) have been simulated to evaluate the performance of different scanners. Initial results have shown that the low sensitivity of the RPC hampers its application to hadron-beam monitoring, which has an intrinsically low positron yield compared to diagnostic PET. In addition, for in-beam PET there is a further data loss due to the partial ring configuration. In order to improve the performance of the RPC-based scanner, an improved version of the RPC detector (modifying the thickness of the gas and glass layers), providing a larger sensitivity, has been simulated and compared with an axially extended version of the crystal-based device. The improved version of the RPC shows better performance than the prototype, but the extended version of the crystal-based PET outperforms all other options. [ABSTRACT FROM AUTHOR]

The majority of current whole-body PET scanners are based on pixelated scintillator arrays with a transverse pixel size of 4 mm. However, recent studies have shown that decreasing the pixel size to 2 mm can significantly improve image spatial resolution. In this study, the performance of Digital Photon Counter (DPC) from Philips Digital Photon Counting (PDPC) was evaluated to determine their potential for high-resolution whole-body time of flight (TOF) PET scanners. Two detector configurations were evaluated. First, the DPC3200-44-22 DPC array was coupled to a LYSO block of 15  ×  15 2  ×  2 × 22 mm3 pixels through a 1 mm thick light guide. Due to light sharing among the dies neighbour logic of the DPC was used. In a second setup the same DPC was coupled directly to a scalable 4  ×  4 LYSO matrix of 1.9  ×  1.9  ×  22 mm3 crystals with a dedicated reflector arrangement allowing for controlled light sharing patterns inside the matrix. With the first approach an average energy resolution of 14.5% and an average CRT of 376 ps were achieved. For the second configuration an average energy resolution of 11% and an average CRT of 295 ps were achieved. Our studies show that the DPC is a suitable photosensor for a high-resolution TOF-PET detector. The dedicated reflector arrangement allows one to achieve better performances than the light guide approach. The count loss, caused by dark counts, is overcome by fitting the matrix size to the size of DPC single die. [ABSTRACT FROM AUTHOR]

Background: Long-axial field-of-view (LAFOV) Positron Emission Tomography (PET) scanners provide high sensitivity, but throughput is limited because of time-consuming patient positioning. To enhance throughput, a novel Walk-Through PET (WT-PET) scanner has been developed, allowing patients to stand upright, supported by an adjustable headrest and hand supports. This study evaluates the degree of motion in the WT-PET system and compares it with the standard PET-CT., Methods: Three studies were conducted with healthy volunteers to estimate motion. The first two studies assessed motion in the WT-PET's Design I (Study 1) and Design II (Study 2), while the third study compared motion on a standard PET-CT scanner bed (Study 3). Infrared markers placed on the head, shoulders, chest, and abdomen were tracked and processed using image-processing techniques involving thresholding and connected component analysis. Videos were recorded for normal breathing and breath-holding conditions, and 2D centroids were transformed into 3D coordinates using depth information., Results: The results shows a significant reduction in motion during breath-holding, especially for the abdomen. Mean motion distances decreased from 2.63 mm to 2.18 mm in Study 1 and from 2.42 mm to 1.67 mm in Study 2. Statistical analysis revealed notable differences in motion between the WT-PET and mCT scanners. The Shapiro-Wilk test indicated non-normal motion distributions in the head, right shoulder, and abdomen for both systems, leading to the use of the Wilcoxon signed-rank test for all markers. Significant differences were found in the right shoulder (p = 0.0266), left shoulder (p = 0.0004) and chest (p < 0.0001) but no significant differences were observed in the head (p = 0.1327) and abdomen (p = 0.8404)., Conclusion: This study provides a comprehensive analysis of patient motion in a WT-PET scanner with respect to the standard PET. The findings highlight a significant increase in shoulder and chest motion, while the head and abdomen regions showed more stability., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no Conflict of interest., (© 2024. The Author(s).)

Neutrophil cationic proteins (NCPs) are a group of granule antimicrobial and inflammatory proteins released by activated neutrophils. These proteins primarily function via their positively charged structure, which facilitates interactions with bacterial membranes and the formation of immunogenic DNA complexes, thereby contributing to the initiation of wound repair in injured skin. After analyzing the structural properties of secreted neutrophil granule proteins, we identified OLFM4 as the only negatively charged molecule that interferes with NCP oligomerization. Through this interference, OLFM4 can inhibit neutrophil-mediated bacterial killing and DNA complex-dependent activation of Toll-like receptor 9 (TLR9) in plasmacytoid dendritic cells (pDCs) and neutrophils. While addition of exogenous OLFM4 blocks these processes, OLFM4 inhibition enhances neutrophil-dependent bacterial killing and DNA complex formation, ultimately leading to accelerated closure of skin wounds., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: This study investigates the integration of Artificial Intelligence (AI) in compensating the lack of time-of-flight (TOF) of the GE Omni Legend PET/CT, which utilizes BGO scintillation crystals., Methods: The current study evaluates the image quality of the GE Omni Legend PET/CT using a NEMA IQ phantom. It investigates the impact on imaging performance of various deep learning precision levels (low, medium, high) across different data acquisition durations. Quantitative analysis was performed using metrics such as contrast recovery coefficient (CRC), background variability (BV), and contrast to noise Ratio (CNR). Additionally, patient images reconstructed with various deep learning precision levels are presented to illustrate the impact on image quality., Results: The deep learning approach significantly reduced background variability, particularly for the smallest region of interest. We observed improvements in background variability of 11.8 % , 17.2 % , and 14.3 % for low, medium, and high precision deep learning, respectively. The results also indicate a significant improvement in larger spheres when considering both background variability and contrast recovery coefficient. The high precision deep learning approach proved advantageous for short scans and exhibited potential in improving detectability of small lesions. The exemplary patient study shows that the noise was suppressed for all deep learning cases, but low precision deep learning also reduced the lesion contrast (about -30 % ), while high precision deep learning increased the contrast (about 10 % )., Conclusion: This study conducted a thorough evaluation of deep learning algorithms in the GE Omni Legend PET/CT scanner, demonstrating that these methods enhance image quality, with notable improvements in CRC and CNR, thereby optimizing lesion detectability and offering opportunities to reduce image acquisition time., (© 2024. The Author(s).)

Background: Ad26.RSV.preF-RSV preF protein showed 80·0% vaccine efficacy against respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) in older adults during one RSV season. No RSV vaccines have shown three-season efficacy. We aimed to evaluate efficacy of Ad26.RSV.preF-RSV preF protein over three RSV seasons., Methods: CYPRESS was a randomised, double-blind, placebo-controlled, phase 2b study done at 40 US clinical research centres wherein adults aged 65 years or older were centrally randomly assigned 1:1 by computer algorithm to receive Ad26.RSV.preF-RSV preF protein or placebo (one intramuscular injection) on day 1. Investigators, participants, site personnel, and the sponsor were masked to vaccine allocation, except for individuals involved in preparation of study vaccinations. The primary endpoint (first occurrence of RSV-mediated LRTD meeting one of three case definitions) was previously reported. Here, the predefined exploratory endpoint of vaccine efficacy against RSV-positive LRTD was assessed in the per-protocol efficacy set (all participants randomly assigned and vaccinated without protocol deviations affecting efficacy) through season 1 and from day 365 until the end of season 3. Humoral and cellular immunogenicity was assessed in a subset of randomly assigned and vaccinated participants. The secondary endpoint of safety through the first RSV season was previously reported; follow-up for selected safety outcomes (fatal adverse events, adverse events leading to study discontinuation, serious adverse events, and vaccine-related serious adverse events) until study completion is reported here in all randomly assigned and vaccinated participants. This trial is registered with ClinicalTrials.gov, NCT03982199 and is complete., Findings: Of 6672 adults screened, 5782 participants (2891 each receiving vaccine or placebo) were enrolled and vaccinated between Aug 5 and Nov 13, 2019. The season 2 per-protocol efficacy set included 2124 vaccine recipients and 2126 placebo recipients (season 3: 864 and 881; across three seasons: 2795 and 2803, respectively). Vaccine efficacy against RSV LRTD was 76·1% (95% CI 26·9-94·2) over seasons 2 and 3 and 78·7% (57·3-90·4) across three seasons. For those in the immunogenicity subset (vaccine n=97; placebo n=98), immune responses remained above baseline for at least 1 year. Serious adverse events occurred in 47 (2·1%) and 12 (1·3%) vaccine recipients and 45 (2·1%) and 10 (1·1%) placebo recipients during seasons 2 and 3, respectively. No treatment-related serious or fatal adverse events were reported., Interpretation: Ad26.RSV.preF-RSV preF protein maintained high efficacy against RSV LRTD in older adults across three RSV seasons., Funding: Janssen Vaccines & Prevention., Competing Interests: Declaration of interests ARF has received institutional research grants from Janssen, Merck Sharp & Dohme, Pfizer, BioFire Diagnostics, Vaccine Company, Moderna, and CyanVac; consulting fees from Arrowhead Pharmaceuticals, GSK, and ADMA Biologics; payment or honoraria for lectures, presentations, or speakers bureaus from Sanofi Pasteur; and personal fees for serving on a data safety monitoring board from Novavax and for attending meetings or travel from GSK, Moderna, and Sanofi Pasteur. SV is an employee of Janssen Infectious Diseases. EKHC is an employee of Janssen Global Services, a subsidiary of Johnson & Johnson, and holds stock in Johnson & Johnson. TH, ARB, and CAC are former employees of Janssen Vaccines & Prevention. MD and EH are former employees of Janssen Vaccines & Prevention and hold stock in Johnson & Johnson. BC is a former employee of, and has patents pending with, Janssen Vaccines & Prevention and holds stock in Johnson & Johnson., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)