Cannabidiol (CBD), a non-psychotropic main component of the Cannabis plant, is approved as a drug in the European Union (EU) under the name “Epidyolex”. However, the approval process as a food ingredient under the Novel Food Regulation was paused by the European Food Safety Authority (EFSA) due to a lack of safety data. Nevertheless, there is a growing, unregulated market in which CBD is advertised with various health claims and different dosage instructions. Of particular concern is its toxic effect on the liver and possible reproductive toxicity in humans. Studies suitable for calculating a benchmark dose were identified from the available data. Animal studies yielded a Benchmark Dose Lower Confidence Limit (BMDL) of 43 mg/kg bw/day, which translates into a safe human dose of approximately 15 mg/day. Only a Lowest Observed Adverse Effect Level (LOAEL) of 4.3 mg/kg bw/day could be identified from the human data. This updated risk assessment confirmed the Health-based Guidance Value (HBGV) of 10 mg/day based on human LOAEL. Despite existing data gaps, preliminary regulation appears advisable as the current form of the gray CBD market is unacceptable from the standpoint of consumer safety and protection.

Productivity has been modest in construction due to many reasons, especially project-specific operations and fragmentation. The main aim of this research is to map the challenges towards industrialization in construction through a comparative study of the manufacturing industry. An inductive approach and a qualitative method are followed by applying semi-structured inter-views, and node-based thematic analysis. The key elements of industrialization in mature man-ufacturing companies are benchmarked. The findings indicate a specific order of steps for indus-trialization in construction. Data and information management with achieved systematization have been sources of productivity in manufacturing companies. However, the systematization starts from the offering, construction companies need to define their offering, that is the products, and define their respective data. Only accurate and good quality data on products enables the systematization of order delivery processes, which are the engine for a company’s success or failure. Continuous efficiency improvement is only possible with systematized processes and respective data related to the processes. The originality involves clarifying the industrialization of construction companies via products, respective data, and processes considering industrialized manufacturing companies.

Turmeric starch (TS) has gained significant attention due to its potential health benefits, this study intended to investigate the dose-dependent effects of TS on colonic fermentation in rats. Four experimental diets containing different levels of TS (5%, 10%, and 20% w/w) were formulated and fed to male Fischer 344 rats for two weeks and compared with rats fed 0% TS diet (TS0). The results showed that increasing doses of TS resulted in reduced body weight gain and lower visceral tissue weights compared to the TS0 group. These effects may be attributed to the high content of resistant starch in TS, which contributed to lower caloric intake. Colonic fermentation analysis revealed that higher doses of TS resulted in increased short chain fatty acids (SCFA) production, specifically increased cecal acetate content and decreased cecal pH dose-dependently. Notably, beneficial bacteria from the family Oscillospiraceae, genus Lachnospiraceae NK4A136 group, and Ruminococcus spp. were enriched in the TS-fed groups, further supporting its beneficial effects on gut microbiota and SCFA production. Furthermore, these results suggest that TS may have beneficial effects on colonic fermentation in rats.

Objective: We report a case of acute pancytopenia and liver injury after concomitant administration of low-dose methotrexate (MTX), and high-dose esomeprazole and metamizole. Case summary: A 71-year-old patient with chronic systemic idiopathic erosive arthritis was admitted after a pelvic ring fracture. After hospital admission, she received MTX in addition to esomeprazole and metamizole. Subsequent laboratory tests revealed pancytopenia and elevated liver enzymes. The follow-up clinical examinations were unremarkable, with the exception of sub-febrile temperatures. Further investigations did not detect a definitive etiology. Due to the suspicion of methotrexate-induced hematotoxicity and hepatotoxicity, antagonizing therapy with calcium folinate was administered, after which the blood counts and liver parameters normalized. Discussion: Due to the administration of high-dose metamizole immediately before the administration of low-dose MTX, the pre-existing hematotoxic pharmacodynamic effect of MTX was acutely enhanced by that of metamizole, although folic acid was administered preemptively. In addition, the concomitant administration of high-dose esomeprazole and normal dose torasemide resulted in a pharmacokinetic interaction with MTX by decreasing its renal secretion and elimination, further enhancing the concentration-dependent hematotoxic and hepatotoxic side effects of MTX. Conclusions: The relatively high demand for analgesics in patients with chronic rheumatic diseases already being treated with MTX and proton pump inhibitors necessitates that clinicians consider drug-drug interactions as potential causes of adverse drug reactions after the administration of metamizole or nonsteroidal anti-inflammatory drugs. In this category of patients, it is strongly recommended to switch to analgesics of other classes.

Spectral unmixing represents both an application per se and a pre-processing step for several applications involving data acquired by imaging spectrometers. However, there is still a lack of publicly available reference data sets suitable for the validation and comparison of different spectral unmixing methods. In this paper we introduce the DLR HyperSpectral Unmixing (DLR HySU) benchmark dataset, acquired over German Aerospace Center (DLR) premises in Oberpfaffenhofen. The dataset includes airborne hyperspectral and RGB imagery of targets of different materials and sizes, complemented by simultaneous ground-based reflectance measurements. The DLR HySU benchmark allows a separate assessment of all spectral unmixing main steps: dimensionality estimation, endmember extraction (with and without pure pixe assumption), and abundance estimation. Results obtained with traditional algorithms for each of these steps are reported. To the best of our knowledge, this is the first time that real imaging spectrometer data with accurately measured targets are made available for hyperspectral unmixing experiments. The DLR HySU benchmark dataset is openly available online and the community is welcome to use it for spectral unmixing and other applications.

As its capital, Jakarta plays a critical role in boosting Indonesia’s economic growth and setting the precedent for broader change outside of the city. One crucial avenue of inquiry to better understand, and prepare for, the future of a country so heavily impacted by disastrous weather events is understanding the effects of climate change through data. This study investigates meteorological data collected from 1996 to 2021 and compares the application of the SARIMA and the Holt-Winters methods to predict the future influence of climatic parameters on Jakarta’s weather. The performance of the SARIMA method is proven to provide better results than the Holt-Winter models and both methods showed the best performances when forecasting the humidity data. The results of the forecast are able to demonstrate the characteristic of the climate in Jakarta, with dry season ranging from May to October and wet season ranging from November to April.

The mutton sheep breeding industry has transformed significantly in recent years, from traditional grassland free-range farming to a more intelligent approach. As a result, automated sheep face recognition systems have become vital to modern breeding practices and have gradually replaced ear tagging and other manual tracking techniques. Although sheep face datasets have been introduced in previous studies, they have often involved pose or background restrictions (e.g., fixing of the subject’s head, cleaning of the face), which restrict data collection and have limited the size of available sample sets. As a result, a comprehensive benchmark designed exclusively for the evaluation of individual sheep recognition algorithms is lacking. To address this issue, this study develops a large-scale benchmark dataset, Sheepface-107, comprised of 5,350 images acquired from 107 different subjects. Images were collected from each sheep at multiple angles, including front and back views, in a diverse collection that provides a more comprehensive representation of facial features. In addition to the dataset, an assessment protocol is developed by applying multiple evaluation metrics to the results produced by three different deep learning models: VGG16, GoogLeNet, and ResNet50, which achieved F1-scores of 83.79%, 89.11%, and 93.44%, respectively. A statistical analysis of each algorithm suggested that accuracy and the number of parameters were the most informative metrics for use in evaluating recognition performance.

Measuring the status and trends of biodiversity is critical for making informed decisions about the conservation, management or restoration of species, habitats and ecosystems. Defining the reference state against which status and change are measured is essential. Typically, reference states describe historical conditions, yet historical conditions are challenging to quantify, may be difficult to falsify, and may no longer be an attainable target in a contemporary ecosystem. We have constructed a conceptual framework to help inform thinking and discussion around the philosophical underpinnings of reference states and guide their application. We characterise currently recognised historical reference states and describe them as Pre-Human, Indigenous Cultural, Pre-Intensification and Hybrid-Historical. We extend the conceptual framework to include contemporary reference states as an alternative theoretical perspective. The contemporary reference state framework is a major conceptual shift that focuses on current ecological patterns and identifies areas with higher biodiversity values, regardless of the disturbance history. The specific context for which we design the contemporary conceptual frame is underpinned by an overarching goal—to maximise biodiversity conservation and restoration outcomes in existing ecosystems. The contemporary reference state framework can account for the inherent differences in the diversity of biodiversity values (e.g., species richness, habitat complexity) across spatial scales, communities and ecosystems. In contrast to historical reference states, contemporary references states are measurable and falsifiable. This ‘road map of reference states’ offers perspective needed to define and assess the status and trends in biodiversity and habitats. Our framework for contemporary reference states provides a tractable way for policy-makers and practitioners to navigate biodiversity assessments to maximise conservation and restoration outcomes in contemporary ecosystems. We illustrate how to define a contemporary reference state using an example from south-eastern Australia.

This work (in two parts) will review the recently developed predictive modeling methodology called “4th-BERRU-PM” and its applicability to energy systems as exemplified by an illustrative application to the Polyethylene-Reflected Plutonium (acronym: PERP) OECD/NEA reactor physics benchmark. The acronym 4th-BERRU-PM designates the “Fourth-Order Best-Estimate Results with Reduced Uncertainties Predictive Modeling” methodology, which yields best-estimate results with reduced uncertainties for the first fourth-order moments (mean values, covariance, skewness, and kurtosis) of the optimally predicted posterior distribution of model results and calibrated model parameters. The 4th-BERRU-PM uses the Maximum Entropy (MaxEnt) principle to incorporate fourth-order experimental and computational information, including fourth (and higher) order sensitivities of computed model responses to model parameters, thus incorporating, as particular cases, the results previously predicted by the second-order predictive modeling methodology 2nd-BERRU-PM, and vastly generalizing the results produced by extant data assimilation and data adjustment procedures. The 4th-BERRU-PM methodology encompasses the scopes of high-order sensitivity analysis (SA), uncertainty quantification (UQ), data assimilation (DA) and model calibration (MC). The application of the 4th-BERRU-PM methodology to energy systems is illustrated by means of the above-mentioned OECD/NEA reactor physics benchmark, which is modeled using the neutron transport Boltzmann equation involving 21976 imprecisely known parameters, the solution of which is representative of “large-scale computations.” The model result (“response”) of interest is the leakage of neutrons through the outer surface of this spherical benchmark, which can be computed numerically and measured experimentally. Part 1 of this work illustrates the impact of high-order sensitivities, in conjunction with parameter standard deviations of various magnitudes, on the determination of the expected value and variance of the computed response in terms of the first four moments of the distribution of the uncertain model parameters. Part 2 of this work will illustrate the capabilities of the 4th-BERRU-PM methodology for combining computational and experimental information, up to and including forth-order sensitivities and distributional moments, for producing best-estimate values for the predicted responses and model parameters while reducing their accompanying uncertainties.

The fault diagnosis of wind farms has been proven to be a challenging task and motivates the research activities carried out through this work. Therefore, this paper deals with the fault diagnosis of a wind park benchmark model, and it considers viable solutions to the problem of earlier fault detection and isolation. The design of the fault indicator involves data-driven approaches, as they can represent effective tools for coping with poor analytical knowledge of the system dynamics, noise, uncertainty and disturbances. In particular, the proposed data-driven solutions rely on fuzzy models and neural networks that are used to describe the strongly nonlinear relationships between measurement and faults. The chosen architectures rely on nonlinear autoregressive with exogenous input models, as they can represent the dynamic evolution of the system along time. The developed fault diagnosis schemes are tested by means of a high-fidelity benchmark model, that simulates the normal and the faulty behaviour of a wind farm installation. The achieved performances are also compared with those of a model-based approach relying on nonlinear differential geometry tools. Finally, a Monte-Carlo analysis validates the robustness and the reliability of the proposed solutions against typical parameter uncertainties and disturbances.

X-ray Fluorescence Computed Tomography (XFCT) is an emerging non-invasive imaging technique providing molecular-level data, gaining attention for high-resolution imaging. However, increased sensitivity with benchtop X-ray sources raises radiation exposure. Artificial Intelligence (AI), particularly deep learning (DL), has revolutionized medical imaging by delivering high-quality images in the presence of noise. In XFCT, traditional methods rely on complex algorithms for noise reduction, but AI holds promise in addressing high-dose concerns. We present an optimized SCUNet model for noise reduction in low-concentration XRF images. Compared to higher-dose images, our method’s effectiveness is evaluated. While various denoising techniques exist for X-ray and CT, few address to XFCT. The DL model is trained and assessed using the augmented data, focusing on background noise reduction. Image quality is measured using PSNR and SSIM, comparing outcomes with 100% X-ray dose images. Results show the proposed algorithm achieves high-quality images from low-dose and low-contrast agents, with a maximum PSNR of 39.05 and SSIM of 0.86. The model outperforms BM3D, NLM, DnCNN, and SCUNet in both visual inspection and quantitative analysis, particularly in high-noise scenarios. This indicates the potential of AI, specifically the SCUNet model, in significantly improving XFCT imaging by mitigating the trade-off between sensitivity and radiation exposure.

Accurate lithium battery diagnosis and prognosis is critical to increase penetration of electric vehicles and grid-tied storage systems. They are both complex due to the intricate, nonlinear, and path-dependent nature of battery degradation. Data-driven models are anticipated to play a significant role in the behavioral prediction of dynamical systems such as batteries. However, they are often limited by the amount of training data available. In this work, we generated the first big data comprehensive synthetic datasets to train diagnosis and prognosis algorithms. The proof-of-concept datasets are over three orders of magnitude larger than what is currently available in the literature. With benchmark datasets, results from different studies could be easily equated, and the performance of different algorithms can be compared, enhanced, and analyzed extensively. This will expend critical capabilities of current AI algorithms, tools, and techniques to predict scientific data.

Computed tomography (CT) is a widely employed imaging modality with diverse clinical applications in pediatric and adult populations, offering numerous advantages. Despite several alternatives to imaging modalities with ionising radiation, CT scans have demonstrated persistent global popularity, contributing to a substantial amount of effective radiation doses for patients. This exposure results in hazards, including stochastic effects that amplify the radiation-induced cancer risk proportionally to the radiation dose received. CT-related radiation comprises a substantial portion of cumulative effective doses within diagnostic radiology, specifically impacting younger patient cohorts undergoing repeated investigations for chronic diseases over time. Scientific literature over recent decades has explored various methods to mitigate radiation doses during medical imaging. One notable strategy involves implementing low-dose and ultralow-dose CT protocols, maintaining diagnostic efficacy in acute and non-acute medical and surgical conditions. Utilising innovative image reconstruction algorithms, such as iterative reconstruction and emerging deep-learning algorithms based on artificial intelligence, plays a pivotal role in achieving an approximately 80% reduction in patient radiation compared to standard doses. This review article discusses the significance of low-dose protocols across a spectrum of acute and chronic medical conditions affecting different body systems.

Our hypothesis that controlled ozone applications interfere into the redox balance of the biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl4 intoxication), has been verified over the last 2 decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes, diabetes-2 and in prevention of intoxications. Low-dose ozone acts as a redox bioregulator: The restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase of the antioxidant repair markers, here mainly shown as glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, relevant data are displayed, evaluated and comprehensively discussed: The repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone treated groups and depending on the indication; the stress markers are simultaneously reduced, the redox system regains its balance.

Observe the synergistic effect and dose-effect relationship of Trimethoprim (TMP) on bactericidal activity with Flos Lonicerae in vitro. Microamount chessboard dilution method was conducted to determine the minimal inhibitory concentration (MIC) of Trimethoprim, Flos Lonicerae, as well as the combination of Trimethoprim and Flos Lonicerae separately against Staphylococcus aureus, Escherichia coli in vitro and Salmonella. The pour plate count method was used to determine the combined bactericidal activity of Flos Lonicerae combined with Different concentrations TMP. The results showed that the MIC values of the combination of Flos Lonicerae with TMP was much less than the MIC values of the independent use of Flos Lonicerae or TMP, The FIC values of the combination of Flos Lonicerae with TMP were between 0.5 and 1, there was additive effect between them. The bactericidal rates were fitted with least square method, the 95% confidence intervals of the optimal blending quantity about the combination of Flos Lonicerae with TMP on the test organisms were 231μg·mL^-1-249μg·mL^-1, 237μg·mL^-1-259μg·mL^-1, and 235 -259μg·mL^-1

Background: External beam radiation therapy requires a sophisticated and laborious planning procedure. To improve the efficiency and quality of the planning procedure, machine learning predictions of the dose distributions have been introduced to speed up the planning procedure and to serve as quality assurance. The most recent dose prediction models are based on deep learning U-Nets that give good approximations of the dose in 3D almost instantly. It is our purpose to train a 3D dose prediction for glioblastoma VMAT treatment and test its robustness and sensitivity for the purpose of quality assurance of automatic contouring. Methods: From a cohort of 125 glioblastoma (GBM) patients, VMAT plans were created according to a clinical protocol. The initial model was trained on a concatenated 3D U-Net. A total of 60 cases were used for training, 15 for validation and 20 for testing. The prediction model was tested for sensitivity to dose changes according to realistic contour variations. Additionally, the model was tested for robustness by exposing it to a worst-case test set containing out-of-distribution cases.Results: The initially trained prediction model had a dose score of 0.94 Gy and a mean DVH score for all structures of 1.95 Gy. In terms of sensitivity, the model was able to predict the dose changes that occurred due to the contour variations with a mean error of 1.38 Gy.Conclusions: We obtained a 3D VMAT dose prediction model for GBM with limited data, providing good sensitivity to realistic contour variations. We tested and improved the model's robustness, by targeted updating the training set, making it a useful technique for dose awareness in the contouring evaluation and quality assurance.

Neuroinflammation, defined as inflammatory reactions mediated by cytokines, chemokines, reactive oxygen species, and secondary messengers in the central nervous system (CNS) including the brain and spinal cord is the basis of many neurological disorders. Recently, erythropoietin (EPO) has been considered and studied as a modulator of neuroinflammation. On this article minireview of pathophysiology of neuroinflammation and the neuroprotective effects of EPO is discussed and a case of subacute huge subdural hematoma with double mydriasis operated urgently, treated with low daily dose (vs high dose once or twice a month in the literature) of EPO and recovered fully and discharged home with good consciousness is reported. In addition, the probable unfavorable outcome of erythropoietin administration in patients with neuroinflammation in COVID-19 is considered.

In recent years, applying deep learning to solve physics problems has attracted much attention. Data-driven deep learning methods produce operators that can learn solutions to the whole system of partial differential equations. However, the existing methods are only evaluated on simple flow equations (e.g., Burger's equation), and only consider the generalization ability on different initial conditions. In this paper, we construct CFDBench, a benchmark with four classic problems in computational fluid dynamics (CFD): lid-driven cavity flow, laminar boundary layer flow in circular tubes, dam flows through the steps, and periodic Karman vortex street. Each flow problem includes data with various boundary conditions, fluid physical properties, and domain geometries. Compared to existing datasets, the advantages of CFDBench are (1) comprehensive. It contains common physical parameters such as velocity, pressure, and cavity fraction. (2) realistic. It is very suitable for deep learning solutions of fluid mechanics equations. (3) challenging. It has a certain learning difficulty, prompting to find models with strong learning ability. (4) standardized. CFDBench facilitates a comprehensive and fair comparison of different deep learning methods for CFD. We make appropriate modifications to popular deep neural networks to apply them to CFDBench and enable the accommodation of more changing inputs. The evaluation on CFDBench reveals some new shortcomings of existing works and we propose possible directions for solving such problems.

Benchmarks for general language understanding have been rapidly developing in recent years of NLP research, particularly because of their utility in choosing strong-performing models for practical downstream applications. While benchmarks have been proposed in the legal language domain, virtually no such benchmarks exist for privacy policies despite their increasing importance in modern digital life. This could be explained by privacy policies falling under the legal language domain, but we find evidence to the contrary that motivates a separate benchmark for privacy policies. Consequently, we propose PrivacyGLUE as the first comprehensive benchmark of relevant and high-quality privacy tasks for measuring general language understanding in the privacy language domain. Furthermore, we release performances from multiple transformer language models and perform model-pair agreement analysis to detect tasks where models benefited from domain specialization. Our findings show the importance of in-domain pretraining for privacy policies. We believe PrivacyGLUE can accelerate NLP research and improve general language understanding for humans and AI algorithms in the privacy language domain, thus supporting the adoption and acceptance rates of solutions based on it.

Nowadays, the Internet of Things (IoT) concept plays a pivotal role in society and brings new capabilities to different industries. The number IoT solutions in areas such as transportation and healthcare is increasing and new services are under development. In the last decade, society has experienced a drastic increase in IoT connections. In fact, IoT connections will increase in the next few years across different areas. Conversely, despite these benefits, several challenges still need to be faced to enable efficient and secure operations (e.g., interoperability, security, standards, and server technologies). Furthermore, although efforts have been made to produce datasets composed of attacks against IoT devices, several possible attacks are not considered. Most existing efforts do not consider an extensive network topology with real IoT devices. The main goal of this research is to propose a novel and extensive IoT attack dataset to foster the development of security analytics applications in real IoT operations. To accomplish this, 33 attacks are executed in an IoT topology composed of 105 devices. These attacks are classified into seven categories, namely DDoS, DoS, Recon, Web-based, Brute Force, Spoofing, and Mirai. Finally, all attacks are executed by malicious IoT devices targeting other IoT devices.

Background/Objectives: Encouraging results reported of Platelet-Rich Plasma (PRP) treatment for knee osteoarthritis (KOA). The present retrospective study reports the efficacy and safety of a high dose of neutrophile and red blood cell-depleted PRP to treat 212 patients with KOA. Methods: 212 consecutive patients diagnosed with Kellgren-Lawrence (KL) grading 1-3 KOA chronic knee pain for at least 1 year were treated with 3 injections at 15-day intervals with a high dose of neutrophil-depleted PRP (4 billion platelets). Clinical outcomes were retrospectively recorded as a percentage of responders at 3,6, and 12-month follow-up, following the OMERACT-OARSI criteria. Pain through VAS score and WOMAC score have also been recorded. Results: 4ml of PRP containing 4X109 platelets were obtained by single spin centrifugation and injected intra-articular into each patient with no pre-activation. The overall responder rate of patients responding to OMERACT-OARSI criteria at 3,6,12 months was 68.9%, 72,7% and 70,6%. There was a significant improvement in VAS and WOMAC scores at 3-, 6- and 12-month follow-up compared to the pre-treatment value (p< 0.01). The lowest VAS score was observed at 6 months overall and in all three-grade KL groups. KL2 groups showed the best results regarding pain reduction and WOMAC score at 6 months (p< 0.01). Conclusions: a high dose of neutrophil-depleted PRP is an effective treatment for KL1-3 KOA. It provides symptomatic relief, can potentially reduce disease progression, and has sustained effects for up to 12 months.

The integration of 3D city models with Building Information Models (BIM), abbreviated as GeoBIM, facilitates improved data support to several applications, e.g. 3D map updates, building permits issuing, detailed city analysis, infrastructure design, context-based building design, to name a few. To solve the integration, several issues need to be tackled and solved, i.e. harmonization of features, interoperability, format conversions, integration of procedures. The GeoBIM benchmark 2019, funded by ISPRS and EuroSDR, evaluated the state of implementation of tools addressing some of those issues. In particular, in the part of the benchmark described in this paper, the application of georeferencing to Industry Foundation Classes (IFC) models and making consistent conversions between 3D city models and BIM are investigated, considering the OGC CityGML and buildingSMART IFC as reference standards. In the benchmark, sample datasets in the two reference standards were provided. External volunteers were asked to describe and test georeferencing procedures for IFC models and conversion tools between CityGML and IFC. From the analysis of the delivered answers and processed datasets, it was possible to notice that while there are tools and procedures available to support georeferencing and data conversion, comprehensive definition of the requirements, clear rules to perform such two tasks, as well as solid technological solutions implementing them, are still lacking in functionalities. Those specific issues can be a sensible starting point for planning the next GeoBIM integration agendas.

Sepsis is a major health problem and accounts for 20 per cent of deaths worldwide. It is the most expensive condition treated in United States hospitals at $27 billion per year or about $20,000 per patient. Treatment consisting largely of fluid resuscitation and antibiotics has only marginal impact. Mortality is about 27 per cent for hospitalized patients and about 42 per cent for patients in intensive care.There are two phases of sepsis – a hyper inflammatory phase and a subsequent hypo inflammatory phase.During the hyper inflammatory phase the metabolic rate increases associated with an increase in body temperature and a rapid escalation of immune system functioning including increased numbers of leucocytes and migration of those leucocytes to infected and damaged tissues and an increased supply and consumption of glucose to fuel this immune system.During the subsequent hypo inflammatory phase the metabolic rate declines and this is associated with a decrease in body temperature and a generalized decrease in the physiological activity of many organs including the immune system akin to hibernation. The activated immune system has priority for the available glucose over most other organs and physiological functions during such potentially life threatening circumstances. Thus adenosine triphosphate (ATP) production by mitochondria (the source of energy at the cellular level for the organism as a whole) also has a lower priority for the available glucose relative to the activated immune system. If glucose availability is threatened then mitochondrial production of ATP is partially or substantially suppressed in favor of glycolysis because glycolysis can rapidly produce large quantities of ATP that are necessary for immune cell function in infected, anaerobic, ischemic, or damaged tissues.However, glycolysis is only a temporary fix as it cannot produce the quantities of ATP necessary on an ongoing basis for the normal functioning of the healthy animal. Mitochondrial production of ATP must be recommenced for full recovery.It appears that the partial or substantial suppression of mitochondrial production of ATP by activation of the immune response becomes relatively fixated in some patients leading to a substantial ATP deficit. This is the fundamental issue of sepsis.This paper reviews the metabolism of glucose and insulin during sepsis and concludes that high dose insulin with mild hyper glycaemia in conjunction with the intravenous administration of thiamine, an inhibitor of the pyruvate dehydrogenase kinase enzymes, to re-establish physiological ATP production by mitochondria, administered early in the hypo metabolic (hypo inflammatory) phase of sepsis should significantly improve survival.

Celecoxib as adjuvant therapy has been shown in a small randomized trial for Covid-19 to prevent clinical deterioration and rapidly improve thoracic computerized axial tomography (CT-chest)¹. Multiple descriptive trials of high dose famotidine (both inpatient and outpatient) have demonstrated clinical response^2,3,4. We describe the rapid clinical responses after increasing the celecoxib dosage to 400mg bid with high dose famotidine 80mg qid in both a critical inpatient who on baseline required 40 liters per minute high flow nasal insufflation and an outpatient who declined admission but had critical Covid-19 biomarkers.

Background and Objectives: The complications seen after lower impacted third molar surgery affect the quality of life of the patients. The aim of the study was to investigate the efficacy of a single preoperative dose of deflazacort on pain, swelling and trismus following impacted lower third molar surgery. Materials and Methods: This randomised, prospective, double-blind, split-mouth clinical study included 30 healthy individuals with bilaterally impacted lower third molars that was removed for orthodontic purposes between September 2017 and September 2018. Group 1 was given a placebo (single dose vitamin C tablet) and group 2 was given a single 30 mg dose of deflazacort 1 hour prior to the surgery. Pain was evaluated using the visual analog scale for 1 week postoperatively. Edema (in mm) and trismus (in mm) were evaluated preoperatively and on postoperative days 2 and 7. The Mann-Whitney U test was applied for group analysis. p values < 0.05 were considered statistically significant. Results: When postoperative pain scores were evaluated, a significant difference was found between the groups only at the 6th and 12th hours (p0.05). Even high trismus values were recorded on the 2nd day, it was observed that the trismus resolved on the 7th day. There were no significant differences in trismus between the groups at any time point (p>0.05). Evaluation of swelling showed that there was no statistically significant difference between the study and control groups at any time point (p>0.05). No side effect was detected in both the study and the control groups. Conclusions: This was the first split-mouth study evaluating the anti-inflammatory effect of deflazacort after lower impacted third molar surgery. A single dose of 30 mg deflazacort was shown to be effective in reducing pain at 6 and 12 hours postoperatively.

A catastrophic loss of microbial biodiversity on the skin has led to alarming increase in the prevalence of allergies and long-term damage to the skin, which could also have damaging knock on effects to overall health. This study uses 50 human participants, to obtain an average (benchmark) value for the biodiversity of ‘healthy’ western skin, which is crucial in updating our 2017 skin health measuring mechanism to use standardised methodology. Previous work with a larger sample size was unsatisfactory for use as a benchmark due to its use of different and outdated diversity indices. We also investigated the effect of age and sex, two known skin microbiome affecting factors. Although no statistical significance is seen for age- and sex- related changes in diversity, there appear to be changes related to age which elaborates on previous work which used larger, more general age ranges. Our study indicates adults age 28-37 have highest diversity, and age 48-57 the lowest. Crucially, because of this study we are now able to update the skin health measuring mechanism from our 2017 work. This will aid diagnostic assessment of susceptibility to cutaneous conditions or diseases, and treatment. Testing any human subject will be rapidly improved by obtaining future benchmark diversity values for any age, sex, body site and area of residence, to which they can be compared. This improvement means we can also more accurately investigate the ultimate question: What factors in the western world are a main cause of the skin allergy epidemic? This could lead to future restriction of certain synthetic chemicals or products found to be particularly harmful to the skin.

Comparing sonification with visualization is like comparing apples and oranges. While visualizations are ubiquitous to the public and have established names, principles, application areas, and sophisticated designs, sonifications tend to be unique, self-made and completely new to users. In this study we developed a rudimentary visualization that is related closely to the principle of the sonification designs that we want to evaluate. In addition, we implemented a prototypical sonification that uses the most common mapping principles. Experiment results show that participants perform similarly well using the rudimentary visualization and the prototypical sonification, which is much better than chance but significantly worse than using our new sonification results. We therefore argue that both rudimentary visualization and prototypical sonifications can serve as a suitable benchmark to evaluate new sonifications designs against.

This mini-review explores the comparative efficacy, safety, and clinical outcomes of high-dose proton pump inhibitor (PPI) intravenous infusion versus oral acid pump inhibitor therapy following endoscopic treatment for bleeding peptic ulcers. Recent evidence suggests that intravenous PPIs can significantly reduce the rebleeding rates within the critical first 72 hours post-intervention, with a noted rebleeding rate of 6% compared to 14% in patients receiving oral Vonoprazan (VPZ) therapy. Additionally, the rapid onset of action associated with intravenous administration leads to faster stabilization of vital signs and a reduced need for subsequent blood transfusions. Safety profiles for both intravenous and oral VPZ were favourable, with minimal adverse effects, the most common being transient headaches.However, the findings from our single-centre study with a moderate sample size prompt consideration of more extensive, multicentre trials to enhance the generalizability of the results. Current limitations include potential biases, short-term focus, missing data issues, and a need for long-term outcome data, necessitating further research. Future studies should also explore the cost-effectiveness of intravenous versus oral VPZ and the impact on patient quality of life and long-term mortality rates.This review underscores the importance of tailored PPI therapy in managing bleeding peptic ulcers post-endoscopy. It suggests a potentially pivotal role for intravenous PPIs in high-risk patient groups, advocating for a shift towards more aggressive and immediate care protocols in specific clinical settings.

The benchmarking of hotel energy use comprehensively identifies the controllable and uncontrollable factors affecting energy performance, including building characteristics, management strategies, operations, and maintenance systems. Other factors include climatic conditions, floor areas, operating hours, occupancy rates, and guest populations. A benchmarking study on energy consumption patterns in significant hotels (each with less than 100 rooms and an average staff strength of 40 employees), situated in the university town of Nsukka (longitude 70 23' E, latitude 60 52' N), Nigeria, was performed using the data envelopment analysis (DEA) methodology. DEA, a linear programming technique that measures the relative performances of units, was chosen as a benchmarking methodology due to its ability to handle multiple inputs and outputs. Following a correlation test, energy use intensity, diesel consumption, and the number of employees were selected as the analysis inputs, while the occupancy rate was chosen as the output variable. Data on these variables spanning 12 months were collected using questionnaires, interviews, site visits, and oral conversations with hotel managers to ensure validity. Grid-supplied electricity accounted for most of the hotels' energy needs, followed by diesel used in generators. More than 70% of the electricity use was for HVAC. From the DEA, Hotel 3 (DMU H3) had a technical efficiency score of 1, whereas adjustments were recommended for improving the efficiency scores of the other hotels, which were deemed inefficient. DMU H7 had the lowest efficiency score (0.474) and the highest identified savings for electricity and diesel. The analysis also revealed that occupancy rates were generally low in the months of June and July, coinciding with the high rainfall season with its accompanying decline in outdoor activities. Consistent with this, electricity consumption was highest in the Christmas and Easter holiday months of December, January, and April following increased travel-related activities.

The study describes the acute and delayed time course of recovery following the CrossFit® Benchmark Workout Karen. Eight trained men (28.4±6.4 years; 1RM back squat 139.1±26.0 kg) undertook the Karen protocol. The protocol consists of 150 Wall Balls, aiming to hit a target 3 meters high. Countermovement jump height (CMJ), creatine kinase (CK), and perceived recovery status scale (PRS) (general, lower and upper limbs) were assessed pre, post-0h, 24h, 48h and 72h after the session. The CK concentration 24h after was higher than pre-exercise (338.4 U/L vs. 143.3 U/L; effect size: 0.74; p≤0.05). At 48h and 72h following exercise, CK concentration had returned to baseline levels. The PRS general and of the lower limbs were lower in the 24-hours post-exercise compared to pre-exercise (PRS general: 4.7 ±1.5 and 7.9 ±1.7 mmol/L; and PRS of the lower limbs: 4.0 ±2.5 and 7.9 ±0.8, respectively). The PRS general, lower, and upper limbs were reduced at 48-post exercise compared to 72-hours post-exercise scores. Our findings provide insights into the fatigue profile and recovery in acute CrossFit® and can be useful to coaches effectively design the daily session.

Background/Objectives: The 28-day mortality rate for septic shock is high, necessitating rapid and effective empiric antimicrobial therapy. This study investigates whether the rate of catecholamine dose reduction in septic shock can indicate bacterial susceptibility to initial antimicrobial therapy. Methods: This retrospective observational study involved 108 adult patients with bacteraemia and septic shock admitted at the intensive care unit of Nihon University Itabashi Hospital between January 2017 and December 2023. They were classified into the Susceptible or Resistant group based on the bacteria’s susceptibility to the initial empiric antimicrobial therapy. Catecholamine dosages were converted to norepinephrine equivalent (NEE) scores, with the time course from peak to end of administration measured at NEE reductions. Results: Of the 108 patients, 94 were in the Susceptible group and 14 in the Resistant group. The Susceptible group showed faster reductions in catecholamine doses: time to reduce the dose from the maximum NEE to 25% was 19 vs. 49.5 hours (p = 0.0057); and 0%, 29 vs. 54 hours (p = 0.0475). Conclusions: In septic shock with bacteraemia, faster catecholamine dose reduction indicates bacterial susceptibility to initial empiric antibiotics. This reduction rate can serve as an early clinical indicator of appropriate initial empiric therapy.

This study builds on our previous Systematic Literature Review (SLR) that assessed the applications and performance of zk-SNARK, zk-STARK, and Bulletproof Non-Interactive Zero-Knowledge Proof (NIZKP) protocols. To address identified research gaps, we designed and implemented a benchmark comparing these three protocols using a dynamic MiMC hash application. We evaluated performance across four general-purpose programming libraries and two programming languages. Our results show that zk-SNARK produced the smallest proofs, while zk-STARK generated the largest. In terms of proof generation and verification times, zk-STARK was the fastest, and Bulletproof the slowest. Interestingly, zk-SNARK proofs verified marginally faster than zk-STARK, contrary to other findings. These insights enhance our understanding of the functionality, security, and performance of NIZKP protocols, providing valuable guidance for selecting the most suitable protocol for specific applications.

In this study, the degradation characteristics of radio-frequency (RF) low-noise amplifier (LNA) based on silicon-germanium (SiGe) heterojunction bipolar transistors (HBTs) due to total ionizing dose (TID) are investigated. The small-signal equivalent model of a SiGe HBT is utilized to analyze circuit-level performance including the input and the output matching and noise figure (NF). As a target circuit, an LNA with a cascode common-emitter stage with emitter degeneration is studied and the equation of each performance parameter is derived. The RF LNA fabricated using commercial 350 nm SiGe technology was exposed to X-ray irradiation with the total dose up to 3 Mrad (SiO2). The experimental results exhibit that modeled device parameters estimate the degraded circuit performance. In addition, the relative impact of each parameter on the circuit metrics is revealed, which is expected from the derived design equations. The key device parameters for modeling TID-induced circuit degradations include the base resistance, the transconductance, and the base-to-emitter capacitance.

Large language models (LLMs) are essential to the field of natural language processing, and as their applications expand, security risks have become increasingly prominent. This paper introduces a novel benchmark for evaluating LLMs security, termed CS-Eval, designed to effectively assess the models' ability to address vulnerabilities. CS-Eval targets seven key security risks: ethical dilemmas, marginal topics, error detection, detailed event handling, cognitive bias, logical reasoning, and privacy identification, and establishes a Multi-Security Hazard Dataset (MSHD). The evaluated models include GPT-4o, Llama-3-70B, Claude-3-Opus, ERNIE-4.0, Abab-6.5, Qwen1.5-110B, Gemini-1.5-Pro, Doubao-Pro, SenseChat-V5, and GLM-4. We analyzed each model's performance in relation to these security risks and provided recommendations for improvement. Experimental results demonstrate varying levels of effectiveness across models, with GPT-4o exhibiting the best overall performance. Moreover, the relationship between security enhancement and model capa-bility is nonlinear, indicating that improving safety requires a multifaceted approach, considering various factors in both development and application.

Abstract: As more and more numerical and analytical solutions to the linear neutron transport equation become available, verification of numerical results is increasingly important. This presentation concerns the development of another benchmark for the linear neutron transport equation. There are numerous ways of solving the transport equation, such as the Wiener-Hopf method based on analyticity, method of singular eigenfunctions, Laplace and Fourier transforms and analytical discrete ordinates, which is arguably one of the most straightforward, to name a few. Another potential method is the PN method, where the solution is expanded in terms of full range orthogonal Legendre polynomials and with orthogonality and truncation, the moments form a set of second order ODEs. Because of the half-range boundary conditions for incoming particles however, full range Legendre expansions are inaccurate near material discontinuities. For this reason, a double PN (DPN) expansion is more appropriate, where the incoming and exit-ing flux distributions are expanded separately to preserve the discontinuity at material interfaces. Here, a new method of solution for the DPN equations is proposed and demonstrated for an iso-tropically scattering medium.

The number of applications for nanobodies is steadily expanding, positioning these molecules as fast-growing biologic products in the biotechnology market. Several of their applications require protein engineering, which in turn would greatly benefit from having a reliable structural model of the nanobody of interest. However, as with antibodies, structural modeling of nanobodies is still a challenge. With the rise of artificial intelligence (AI), several methods have been developed in recent years that attempt to solve the problem of protein modeling. In this study, we have compared the performance in nanobody modeling of several state-of-the-art AI-based programs, either designed for general protein modeling, such as AlphaFold2, OmegaFold, ESMFold and Yang-Server, or specifically designed for antibody modeling, such as IgFold, and Nanonet. While all these programs performed rather well in constructing the nanobody framework and CDRs 1 and 2, modeling of CDR3 sill represents a big challenge. Interestingly, tailoring an AI method for antibody modeling does not necessarily translate into better results for nanobodies.

This article presents the integration of lean 6S methodologies and hazard analysis and critical control points (HACCP) in the food production sector. Through the study, it is seen that non-food industrial production is not very different from that of food and, in many cases, it assimilates protocols and ideas that are already working in the food industry; Such is the case of risk analysis, critical control points or hygiene, which are part of the food production protocol and, increasingly, of the industry in general. After the integrative analysis, the article proposes a common lean 6S - HACCP model, which can be used both in food production and in non-food industrial production.

Background: The coronavirus disease-19 (COVID-19) has spread globally with more than 80,000 people infected, and nearly 3000 patients died. Currently, we are in an urgent need for effective treatment strategy to control the clinical deterioration of COVID-19 patients. Methods: The clinical data of 10 COVID-19 patients receiving short-term moderate-dose corticosteroid (160mg/d) plus immunoglobulin (20g/d) were studied in the North Yard of The First Hospital of Changsha, Hunan from January 17^th to February 27^th, 2020. Epidemiological, clinical, laboratory, radiological findings were analyzed. Results: After treatment with combination of low-dose corticosteroid (40-80mg/d) and immunoglobulin (10g/d), patients’ lymphocyte count (0.88±0.34 vs 0.59±0.18, P<0.05), oxygenation index including SPO₂ (94.90±2.51 vs 90.50±5.91, P<0.05) and PaO₂/FiO₂ (321.36±136.91 vs 129.30±64.97, P<0.05) were significantly lower than pre-treatment, and CT showed that the pulmonary lesion deteriorated in all patients. While after treatment of short-term moderate-dose corticosteroid plus immunoglobulin, patients’ APACHE Ⅱ score (9.10±6.15 vs 5.50±9.01, P<0.05), body temperature (37.59±1.16 vs 36.46±0.25, P<0.05), lymphocyte count (0.59±0.18 vs 1.36±0.51, P<0.05), Lactate dehydrogenase (419.24±251.31 vs 257.40±177.88, P<0.05), and C-reactive protein (49.94±26.21 vs 14.58±15.25, P<0.05) significantly improved compared with post-treatment with low-dose therapy. In addition, oxygenation index including SPO₂ (90.50±5.91 vs 97.50±1.18, P<0.05), PaO₂ (60.47±14.53 vs 99.07±34.31, P<0.05), and PaO₂/FiO₂ (129.30±64.97 vs 340.86±146.72, P<0.05) significant improved. Furthermore, CT showed that pulmonary lesions obviously improved in 7 patients. After systematic therapy, 4 out of 10 COVID-19 patients recovered and discharged. Conclusions: Short-term moderate-dose corticosteroid plus immunoglobulin is effective for reversing the continued deterioration of COVID-19 patients who failed to respond to the low-dose therapy. Funding: This work was supported by the Innovative Major Emergency Project Funding against the New Coronavirus Pneumonia in Hunan Province (Dr. Ji-Yang Liu, number 2020SK3014; Dr. Yuan-Lin Xie, number 2020SK3013).

The prolonged lockdown imposed to contain the COVID-19 pandemic prevented many people from direct contact with nature and greenspaces, raising alarms for a possible worsening of mental health. This study investigates the effectiveness of a simple and affordable remedy for improving psychological well-being, based on audio-visual stimuli brought by a short computer video showing forest environments, with an urban video as a control. Randomly selected participants were assigned the forest or urban video, to look at and listen early in the morning, and filled questionnaires. In particular, the State-Trait Anxiety Inventory (STAI) Form Y, collected in baseline condition and at the end of the study, and the Part II of the Sheehan Patient Rated Anxiety Scale (SPRAS), collected every day immediately before and after watching the video. The virtual exposure to forest environments showed effective to reduce perceived anxiety levels in in people forced by lockdown in limited spaces and environmental deprivation. Although significant, the effects were observed only in the short term, highlighting the limitation of the virtual experiences. The reported effects might also represent a benchmark to disentangle the determinants of health effects due to real forest experiences, for example, the inhalation of biogenic volatile organic compounds (BVOC).

The calculation of effective doses is crucial in many medical and radiation fields, in order to ensure safety and compliance with regulatory limits. Traditionally, Monte Carlo codes using detailed human body computational phantoms have been used for such calculations. Monte Carlo dose calculations can be time-consuming and require expertise in different processes when building the computational phantom and dose calculations. This study employs various machine learning (ML) algorithms to predict the organ doses and effective dose conversion coefficients (DCCs) for different anthropomorphic phantoms. A comprehensive data set comprising neutron energy bins, organ labels, masses, and densities is compiled from Monte Carlo studies, and is used to train and evaluate the supervised ML models. This study includes a broad range of phantoms, including those from the International Commission of Radiation Protection (ICRP-110, ICRP-116 phantom), the Visible-Human Project (VIP-man phantom), and the Medical Internal Radiation Dose Committee (MIRD-Phantom), with row data prepared using numerical data and organ categorical labeled data. Extreme gradient boosting (XGB), gradient boosting (GB), and the random forest-based Extra Trees regressor are employed to assess the performance of the ML models against published ICRP neutron DCC values using the mean square error, mean absolute error, and R² metrics. The results demonstrate that the ML predictions significantly vary in lower energy ranges and vary less in higher neutron energy ranges, while showing good agreement with ICRP values at mid-range energies. Moreover, the categorical data models align closely with the reference doses, suggesting the potential of ML in predicting effective doses for custom phantoms based on regional populations, such as the Saudi voxel-based model. This study paves the way for efficient dose prediction using ML, particularly in scenarios requiring rapid results without extensive computational resources or expertise. The findings also indicate potential improvements in data representation and the inclusion of larger data sets to refine model accuracy and prevent overfitting. Thus, ML methods can serve as valuable techniques for the continued development of personalized dosimetry.

Purpose: Novel coronavirus disease (COVID-19) is the current global concern. Radiotherapy (RT), commonly employed in cancer management, has been considered one of the potential treatments for COVID-19 pneumonia. Here, we present the final report of the pilot trial evaluating the efficacy and safety of low-dose whole-lung irradiation (LD-WLI) in patients with COVID-19 pneumonia. Methods and Materials: We enrolled patients with moderate COVID-19 pneumonia who were older than 60 years. Participants were treated with LD-WLI in a single fraction of 0.5 or 1.0Gy along with the national protocol of COVID-19. The primary endpoints were improvement of SpO₂, the number of hospital/ICU stay days, and the number of intubations after RT and the secondary endpoints were alterations of the c-reactive peptide, interleukin-6, ferritin, procalcitonin, and D-dimer. The response rate (RR) was defined as a rise in SpO₂ upon RT with rising or constant trend in the next two days, and clinical recovery (CR) included patients who were discharged from the hospital or acquired SpO₂ ≥93% on room air. Results: Between 21 May 2020 and 2 July 2020, ten patients were enrolled. The median age was 75 years, 80% were male, and 80% had comorbidities. The first five patients received a single 0.5Gy-WLI, and others received 1.0Gy. Patients were followed for 2-14 days (median 5.5 days). Following one day, nine patients experienced an improvement in SpO₂. Five patients were discharged (median 6^th day, range 2^nd-14^th day), and four patients died (median 7^th day, range 3^rd-10^th day). Overall, the RR and CR were 60.0% and 55.5%, respectively. The RR and CR rates of 0.5- and 1.0Gy group were 80% vs 40% and 75% vs 40%, respectively. No acute radiation-induced toxicity was recorded. Conclusions: LD-WLI with a single 0.5Gy fraction seems to be a more appropriate dose to warrant further evaluation in a large-scale, randomized trial.

Zero-dose children, or children who have not received any routine vaccination, are a priority population for global health policy makers as these children are at high risk of mortality from vaccine-preventable illnesses. We conducted a narrative review to identify potential interventions, both within and outside of the health sector, to reach zero-dose children. We reviewed peer-reviewed and grey literature and identified 59 relevant resources. Additionally, we interviewed six key informants to enhance synthesis of our findings. Data were organized into three priority settings: (1) urban slums, (2) remote or rural communities, and (3) conflict settings. We found that zero-dose children in the three-priority settings face differing barriers to vaccina-tion and, therefore, require context-specific interventions, such as leveraging slum health commit-tees for urban slums or integrating with existing humanitarian response services for conflict set-tings. Three predominant themes emerged for grouping the various interventions: (1) community engagement, (2) health systems strengthening and integration, and (3) technological innovations. The barriers to reaching zero-dose children are multifaceted and nuanced to each setting, there-fore, no one intervention is enough. Technological interventions especially must be coupled with community engagement and health systems strengthening efforts. Evaluations of the suggested interventions are needed to guide scale up, as the evidence-base around these interventions is rel-atively small.

In this article we present a SCILAB implementation of algebraic iterative reconstruction methods for discretisation of inverse problems in imaging. These so-called row action methods rely on semi-convergence for achieving the necessary regularisation of the problem. We implement this method using SCILAB and provide a few simplified test problems: medical tomography, seismic tomography and walnut tomography.Numerical results show the capability of this method for the original and perturbed right-hand side vector.

Vitamin D deficiency and insufficiency are highly prevalent in CKD affecting over 80% of hemodialysis (HD) patients and require therapeutic intervention. Nephrological societies suggest the administration of cholecalciferol according to the guidelines for the general population. The aim of the observational study was to evaluate the efficacy and safety of the therapy with a high dose of cholecalciferol in HD patients with 25(OH)D deficiency and insufficiency to reach the target serum 25(OH)D level &gt; 30 ng/mL. 22 patients (16 M), with an average age of 72.5 ± 13.03 years and 25(OH)D concentration of 13.05 (9.00–17.90) ng/mL were administered cholecalciferol at a therapeutic dose of 70,000 IU/week (20,000 IU + 20,000 IU + 30,000 IU, immediately after each dialysis session). All patients achieved the target value &gt;30 ng/mL, with a mean time of 2.86 ± 1.87 weeks. In the first week, the target level of 25(OH)D (100%) was reached by 2 patients (9.09%), in the second week – by 15 patients (68.18%), in the fourth week – by 18 patients (81.18%) and in the ninth week by all 22 patients (100%). A significant increase in 1,25(OH)2D levels was observed during the study, however, only 2 patients (9.09%) achieved a concentration of 1,25(OH)2D above 25 ng/mL – the lower limit of the reference range. The intact PTH concentrations remained unchanged during the observation period. No episodes of hypercalcemia, and one new episode of hyperphosphatemia were observed. In conclusion, our study showed that the administration of a high therapeutic dose of cholecalciferol allowed for a quick, effective, and safe leveling of 25(OH)D concentration in HD patients.

World Health Organization is encouraging countries to include contact screening and single dose of rifampicin administration as preventive chemotherapy for contacts of leprosy patients in their leprosy control activities. However, no study has been conducted to assess the safety of SDR-PEP and acceptability and feasibility of this intervention in Togo. To assess the safety of SDR-PEP we used a cohort design and for acceptability and feasibility we used a mixed method combining a quantitative study to assess the safety of SDR-PEP in a cohort of contacts from recently diagnosed leprosy patients followed by a qualitative study to identify the social, cultural or institutional factors that would influence the adoption of single dose rifampicin as post-exposure prophylaxis for contacts of leprosy patients in Togo. For the quantitative study, all identified index patients agreed to the disclosure of their status to their contacts and provided a list of their contacts. All the contacts found agreed to take part in the study and an appointment was made for screening. However, some contacts were absent on the screening day for no reason. All eligible contacts agreed to take SDR and were followed up after taking the drug. No severe adverse events were reported during follow-up. For the qualitative study, 72 interviews (66 semi-structured interviews and 6 focus groups) were carried out, and it emerged that overall, opinions were favorable on the acceptability and feasibility of implementing single dose rifampicin as post-exposure prophylaxis for contacts of leprosy patients in Togo. However, a number of conditions need to be considered for more effective results.

The application of deep learning in the detection of Synthetic Aperture Radar (SAR) targets has been primarily limited to large objects such as ships and airplanes, with much less popularity in detecting SAR vehicles. The complexities of SAR imaging make it difficult to distinguish small vehicles from the background clutter, creating a barrier to data interpretation and the development of Automatic Target Recognition (ATR) in SAR vehicles. The scarcity of datasets has inhibited progress in SAR vehicle detection in the data-driven era. To address this, we introduce a new synthetic dataset called Mix MSTAR, which mixes target chips and clutter backgrounds with original radar data at the pixel level. Mix MSTAR contains 5,392 objects of 20 fine-grained categories in 100 high-resolution images, predominantly 1478x1784 pixels. The dataset includes various landscapes such as woods, grasslands, urban buildings, lakes, and tightly arranged vehicles, each labeled with Oriented Bounding Box (OBB). Notably, Mix MSTAR presents fine-grained object detection challenges by using the Extended Operating Condition (EOC) as a basis for dividing the dataset. Furthermore, we evaluate 9 benchmark rotated detectors on Mix MSTAR and demonstrate the fidelity and effectiveness of the synthetic dataset. To the best of our knowledge, Mix MSTAR represents the first public multi-class SAR vehicle dataset designed for rotated object detection in large-scale scenes with complex background. Mix MSTAR is available at: https://github.com/TheGreatTreatsby/Mix-MSTAR-mmrotate.

Technologies around the world produce and interact with geospatial data instantaneously, from mobile web applications to satellite imagery that is collected and processed across the globe daily. Big raster data allows researchers to integrate and uncover new knowledge about geospatial patterns and processes. However, we are also at a critical moment, as we have an ever-growing number of big data platforms that are being co-opted to support spatial analysis. A gap in the literature is the lack of a robust framework to assess the capabilities of geospatial analysis on big data platforms. This research begins to address this issue by establishing a geospatial benchmark that employs freely accessible datasets to provide a comprehensive comparison across big data platforms. The benchmark is a critical for evaluating the performance of spatial operations on big data platforms. It provides a common framework to compare existing platforms as well as evaluate new platforms. The benchmark is applied to three big data platforms and reports computing times and performance bottlenecks so that GIScientists can make informed choices regarding the performance of each platform. Each platform is evaluated for five raster operations: pixel count, reclassification, raster add, focal averaging, and zonal statistics using three different datasets.

We aimed to directly compare the cost-effectiveness of the NELSON and NLST screening protocols, two trials influencing lung cancer screening implementation internationally. A decision-analytic model analyzing the cost-effectiveness of the NELSON protocols was manipulated to reflect the protocols of the NLST, while maintaining features specific to the Hungarian healthcare setting. In the NELSON protocol, there are three possible outcomes to the initial round of screening: positive, negative, or indeterminate, indicating an uncertain degree of suspicion for lung cancer. This pro-tocol differs from the NLST protocol, in which the only possible screening outcomes are positive or negative, with no indeterminate option. The NLST pathway for smokers aged 55-74 resulted in a 43 € increase in total average lifetime costs compared to the Hungarian screening pathway and re-sulted in a lifetime gain of 0.006 QALYs. The incremental costs and QALYs yield an ICER of 7875 €/QALY. Our results demonstrate that assigning any suspicious LDCT screen as a positive result (NLST protocol) rather than indeterminate (NELSON protocol) can yield a slight QALY gain that is worth the additional use of resources according to Hungary’s willingness to pay threshold. Our study provides insight on the cost-effectiveness, advantages, and disadvantages of various LDCT screening protocols for lung cancer and can assist other countries as they implement their screening programs.

ABSTRACT Objectives: Typical Diagnostic Reference Levels (DRL) in terms of Computed Tomography Dose Index (CTDI) and patient dose in terms of Effective Dose (ED ) and Size Specific Dose Estimate (SSDE) were estimated in Computed Tomography (CT) guided biopsy procedures. Materials and Methods: A total of 226 CT biopsy procedures - Iliac bone, liver, lung, mediastinum and para-aortic tissue - were retrospectively analyzed and Typical DRL extracted based on ICRP 135 instructions. Results: For helical mode acquisitions, DRLs in terms of CTDIvol were 9.7 mGy for Iliac bone, 8.9 mGy for liver, 8.8 mGy for lung, 7.9 mGy for mediastinal mass and 9 mGy for para-aortic lymph nodes biopsy procedures. For biopsy acquisitions, DRL values were 7.3 mGy, 7.7 mGy, 5.6 mGy, 5.6 mGy and 7.4 mGy respectively. Also, SSDE median values ranged from 7.6 mGy to 10 mGy for biopsy acquisitions and 11,3 mGy to 12,6 mGy for helical acquisitions, as well as the median values for effective dose ranged from 1.6 mSv to 5,7 mSv for biopsy scans and 3.9 to 9.3 mSv for helical scans. Conclusions: The use of DLR as an optimization tool for CT-guided biopsy procedures revealed that helical scans across the entire anatomical region greatly affect radiation dose compared to biopsy acquisitions.

This commentary is focused on radioactive contaminations in the Urals, where the consequences were more severe in the long term than those after the Chernobyl accident. The difference is that the latter was a technogenic catastrophe, but the former - a radioactive contamination tolerated since 70 years with several accidents in between. In earlier publications of Russian researchers no cancer frequency elevation was reported after exposures below 0.5 Sv or generally in the populations exposed to low doses. Later on, the same scientists started to claim similar relative risks for cancer and other diseases among exposed people in the Urals and in atomic bomb survivors from Hiroshima and Nagasaki. Apparently, an unofficial directive has been behind this ideological shift noticed around the year 2005. Trimming of statistics has been not unusual in the former Soviet Union. Potential motives included fostering radiophobia, stirring anti-nuclear protests in other countries and strangulation of nuclear energy aimed at the boosting of fossil fuel prices. Recent publications claiming cardiovascular risks after low-dose low-rate exposures and recommending more stringent standards of radiological protection are discussed here in some detail. Such recommendations for dose rates compatible with the natural radiation background are obviously nonsensical.

To date, radiation adaptation response has been reported as a low-dose related phenomenon and has been associated with radiation hormesis. Well-known cancers are caused by non-radiation active reactants, in addition to radiation. A model of suppression for radiation-specific cancers was previously reported, but the model did not target radiation-nonspecific cancers. In this paper, we describe kinetic models of radiation-induced suppressors for general radiation non-specific cancers, estimating the dose that induces the maximum hormesis effect while satisfying the condition that the risk is approximately proportional to dose above 100 mSv. It was found that the radiation hormesis effect is maximal at about 20 mSv when the rate constant for generation is the same as the rate constant for decomposition. When the two rate constants are different, the dose at which the radiation hormesis effect is maximized depends on both rate constants, but the dose increases as the two rate constants approach each other, reaching a maximum of about 20 mSv. This conclusion may lead to the discovery of unknown cancer suppressors at low doses and the development of cancer suppression methods in the future.

Patients with lean NAFLD make up an increasing subset of liver diseases. The association between lean NAFLD and feutin-A, which serves as a hepatokine and adipokine, has never been examined. Our study aimed to explore the association of serum fetuin-A among lean and nonlean patients. The study comprised 606 adults from the community, stratified into lean or nonlean (BMI </≥ 24 kg/m2) and NAFLD or non-NAFLD (scoring of ultrasonographic fatty liver indicator, US-FLI ≥ 2/<2). Multivariate logistic regression analyses were performed to estimate the odds ratio of having NAFLD among the tertiles of fetuin-A after adjustment. The least square means were computed by general linear models to estimate marginal means of the serum fetuin-A concentrations in relation to the NAFLD groups. The OR of having NAFLD for the highest versus the lowest tertile of fetuin-A was 2.62 (95% CI: 1.72-3.98; P for trend<0.001). Stratifying by BMI, the OR of having lean NAFLD for the highest versus the lowest tertile of fetuin-A was 2.09 (95% CI: 1.09-3.98; P for trend 0.026), while nonlean NAFLD had no significant association with the fetuin-A gradient after adjustments. Fetuin-A was positively associated with lean NAFLD after adjusting for central obesity and insulin resistance.

Homologous recombination deficiency (HRD) has become an important prognostic and predictive biomarker for patients with high-grade serous ovarian cancer who may benefit from poly-ADP ribose polymerase inhibitors (PARPi) and platinum-based therapies. HRD testing provides relevant information to personalize patients’ treatment options, and it has been progressively incorporated in diagnostic laboratories. In this study, we evaluated the feasibility of in-house HRD testing deployable in a diagnostic clinical setting, comparing results from two commercially available next-generation sequencing (NGS)-based tumor tests (SOPHiA DDMTM HRD Solution and AmoyDx HRD Focus Panel) with the reference assay from Myriad MyChoice CDx. A total of 85 ovarian cancer samples were subjected to HRD testing. An overall strong correlation was observed across the three assays evaluated, regardless of the different underlying methods employed to assess genomic instability, with the highest pairwise correlation between Myriad and SOPHiA (R=0.87, p-value=3.39x10-19). The comparison of the assigned HRD status to the reference Myriad’s test revealed a positive predictive value (PPV) and negative predictive value (NPV) of 90.9% and 96.3% for SOPHiA’s test, while AmoyDx’s test achieved 75% PPV and 100% NPV. This is the largest HRD testing evaluation using different methodologies and provides a clear picture of the robustness of NGS-based tests currently offered in the market. Our data show that the implementation of in-house HRD testing in diagnostic laboratories is technically feasible and it can be reliably performed with commercial assays. Also, the turnaround time is compatible with clinical needs, being an ideal alternative to offer to a broader number of patients, while still maintaining high-quality standards at more accessible price tiers.

Abstract Background: Temporomandibular disorders (TMD) are a range of clinical problems related to the temporomandibular joint (TMJ), chewing muscles, and surrounding facial structures. Functional magnetic resonance studies suggest that these disorders affect over 5% of the population. The relationship between dental occlusion and TMD has been a topic of debate in dentistry; some researchers suggest using lateral cephalograms and cephalometric data to identify which morphological profiles and types of malocclusion are most likely to cause TMD. The aim of this study is to identify the morphological profiles and associated skeletal malocclusions that have the greatest influence on the development of TMD. This will be accomplished through the analysis of cephalometric data obtained from cephalograms and condylar section images of patients from the Orthognathodontics Department of Chieti, who underwent low-dose cbct during their initial visit. Matherial and methods: This study, conducted at the Orthognathodontics Department of Gabriele D’Annunzio University in Chieti, examined a group of 67 patients (both males and females) presenting with signs of temporomandibular joint disorders (TMD). The inclusion criteria for the study were first-time TMD diagnosis, age 18 and above, and accessible medical records, wide field of view cone beam low dosage, and photographs. Patients with a history of tumor, trauma, surgical interventions in the jaw and facial area, fractures, and other craniofacial anomalies were excluded from the study. The aim of the study is to further understand the morphological profiles and associated skeletal malocclusions that contribute to TMD. Results: male patients: sagittal profile: 56% exhibited a skeletal Class II profile due to mandibular retrognathia. Vertical Profile: 73% were brachyfacial with a hypodivergent pattern. Dental Relationships: Increased overjet and a tendency towards deep bite were observed. 23% exhibited deep bite, 20% were normodivergent, and 8% were dolichofacial. The soft tissue profile tended towards flatness. Condyle Position: in Class II hypodivergent males, the condyle was non-concentric and positioned more posteriorly. In mesiodivergent males, the condyle was concentric, while in hyperdivergent males, it was slightly anterior. Female Patients: Sagittal Profile: 79% had a skeletal Class II profile with mandibular retrognathia. Vertical Profile: 47% were hypodivergent with reduced anterior facial height (105°). Dental Relationships: 17% exhibited deep bite, and 48% of those with a Class II profile had increased overjet. 43% were mesofacial, and 10% were dolichofacial. Condyle Position: In Class II hypodivergent and normodivergent females, the condyle was non-concentric and positioned more posteriorly. In hyperdivergent females, the condyle was positioned more anteriorly and higher in the fossa. Conclusion: The study highlighted significant differences in cephalometric parameters and condyle positions between male and female patients with TMD. A posteriorly positioned condyle was associated with a flattened condylar head, particularly in Class II hypodivergent profiles. These findings underscore the importance of individualized diagnostic and treatment approaches based on detailed cephalometric and condylar assessments. Further research is needed to explore the implications of these variations for TMD management and outcomes.

Hyper-radiosensitivity (HRS) is the increased sensitivity to low doses of ionizing radiation observed in most cell lines. We previously demonstrated that HRS is permanently abolished in cells irradiated at a low dose rate (LDR), in a mechanism dependent on transforming growth factor β3 (TGF-β3). In this study, we aimed to elucidate the activation and receptor binding of TGF-β3 in this mechanism. T-47D cells were pre-treated with inhibitors of potential receptors and activators of TGF-β3, along with addition of small extracellular vesicles (sEVs) from LDR primed cells, before their radiosensitivity was assessed by the clonogenic assay. The protein content of sEVs from LDR primed cells was analyzed with mass spectrometry. Our results show that sEVs contain TGF-β3 regardless of priming status, but only sEVs from LDR primed cells remove HRS in reporter cells. Inhibition of the matrix metalloproteinase (MMP) family prevents removal of HRS, suggesting an MMP-dependent activation of TGF-β3 in the LDR primed cells. We demonstrate a functional interaction between TGF-β3 and activin receptor like kinase 1 (ALK1), by showing that TGF-β3 removes HRS through ALK1 binding, independent of ALK5 and TGF-βRII. These results are an important contribution to a more comprehensive understanding of the mechanism behind TGF-β3 mediated removal of HRS.

Porphyromonas gingivalis is the major pathogenic bacteria found in the subgingival plaque of patients with periodontitis, leading to neuroinflammation. The bacteria destroy periodontal tissue through its virulence factors which are retained in the bacteria’s outer membrane vesicles (OMV). The purpose of this study was to determine the real time effect of intraperitoneal in-jection of P. gingivalis OMV on the production and expression of inflammatory markers as well as histopathological changes in the central nervous system (CNS) of adult zebrafish. Fol-lowing the LD50 (21 µg of OMV), the zebrafish were injected intraperitoneally with 18 µg of OMV and control group with normal saline at 7 different time points. Brains of experimental zebrafish were dissected at desired time points for colorimetric assays, ELISA and histology. This study discovered that nitric oxide and PGE2 were significantly increased at 45 minutes while IL-1β and IL-6 were expressed at subsequent 12- and 24-hours. respectively. Histopatho-logical changes such as blood coagulation, astrocytosis, oedema, spongiosis, and necrosis were also observed between 6- and 24-hours. The two apoptotic enzymes, caspases 3 and 9 were not expressed at any time point. In summary, the OMV induced neuroinflammatory responses and histopathological changes in adult zebrafish were time point dependent

Simple summary This reassessment of the findings from our Phase I/II study seeks to evaluate the effectiveness of SBRT for treating local intermediate-high risk prostate cancer in the absence of androgen-deprivation therapy due to patient’s refusal, with a median follow-up of 6.5 years. Our primary focus is on analysing the treated areas compared to recurrence patterns in the seven patients who experienced local relapse. Additionally, we provide updated data on late toxicities of grade 2 or higher, both genitourinary and gastrointestinal. Abstract Objectives: We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intraprostatic nodule (DIN). Materials and methods: In 33 patients with intermediate-high risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and 68Ga-labelled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (68Ga-PSMA-PET/CT) images. Overlap rates, categorized as 75% or higher for full overlap, and 25-74% for partial overlap, were assessed. Long-term toxicity is reported. Results: All patients completed treatment, with only one receiving concomitant androgen deprivation therapy (ADT). Recurrences were diagnosed after a median of 33 months (range: 17-76 months), affecting 13 out of 33 patients (39.4%). Intraprostatic recurrences occurred in 7 patients (21%), with ≥ 75% overlap in two, a partial overlap in another two, and no overlap in the remaining three patient. Notably, 5 patients with intra-prostatic recurrences had synchronous bone and/or lymph node metastases, while six patients had isolated bone or lymph node metastasis without intraprostatic recurrences. Extended follow-up revealed grade 2 or higher late GU and GI toxicity in 18% (n=6) and 6% (n=2) of the patients. Conclusions: Among patients with intermediate-high risk PCa undergoing focal dose-escalated SBRT without ADT, DIN recurrences were infrequent. When present, these recurrences were typically located at the original site or adjacent to the initial tumor. Conversely, relapses beyond the DIN and in extra-prostatic (metastatic) sites were prevalent, underscoring the significance of systemic ADT in managing this patient population. Advances in knowledge: focal dose escalated prostate SBRT prevented recurrences in the dominant nodule, however extra-prostatic recurrence sites were frequent.

Objectives. Optimal treatment strategy for ischemic stroke in patients presenting with tandem occlusions the internal carotid artery remains controversial. Several studies have demonstrated better clinical outcomes after eptifibatide, which is a short half-life antiplatelet agent. This retrospective analysis was focused at safety and efficacy of administration of low-dose eptifibatide in stroke patients with tandem lesions. Methods. We evaluated results of endovascular treatment in 148 stroke patients with tandem lesions. Patients in whom balloon angioplasty alone resulted in satisfactory cerebral flow did not receive eptifibatide (33 patients); others received this drug together with stent implantation (115 patients). Eptifibatide was given in as intravenous bolus 180 g/kg, and then in modified low dose of 1 g/kg/min for 24 hours. Results. There were no statistically significant differences between both groups regarding 30-day mortality, frequency of thrombotic events and hemorrhagic complications. Analysis of clinical status at 30-day follow-up revealed that administration of eptifibatide was associated with statistically significant better outcome: a higher rate of either no neurological symptoms or only mild symptoms (4 NIHSS points maximally). Conclusions. Administration of eptifibatide in stroke patients presenting with tandem lesions is relatively safe. Moreover, treatment with this drug can improve clinical outcomes in these challenging patients.

We compared the functional and morphologic effects in the loading dose between patients with treatment-naïve neovascular age-related macular degeneration treated with either intravitreal aflibercept (IVA) or intravitreal faricimab (IVF) injection in clinical settings. This retrospective study included 30 eyes from 28 patients who started IVA treatment between June and September 2022 and 30 eyes from 29 patients who started IVF treatment between October 2022 and March 2023. The mean best corrected visual acuity (BCVA) significantly improved from pre-treatment after loading dose in the IVA group (from 0.46 ± 0.46 to 0.36 ± 0.37, p=0.0047) and not in the IVF group (from 0.46 ± 0.41 to 0.44 ± 0.45, p=0.60). The mean central retinal thickness (CRT) significantly improved in both groups. The proportion of eyes with residual exudative change was greater in the IVF group than in the IVA group at 2 months after the first treatment. (p=0.026) We further analyzed the patients who obtained complete resolution of exudative changes after the loading dose. The IVA group had a significant improvement in BCVA, whereas the IVF group did not p=0.0047 and 0.20, respectively) Although IVA and IVF significantly improved the CRT, the BCVA improved significantly in IVA group and not in IVF group.

Ecdysterone is a phytosteroid widely discussed for its various pharmacological, growth-promoting and anabolic effects mediated by activation of estrogen receptor beta (ERbeta). Performance-enhancement in sports was demonstrated recently, and ecdysterone was consequently included in the Monitoring Program to detect potential patterns of misuse in sport. Only few studies on the pharmacokinetics of ecdysterone in humans have been reported so far. In this study, post-administration urines in twelve volunteers (single dose of 50 mg of ecdysterone) were analyzed using dilute-and-inject liquid chromatography-tandem mass spectrometry. Identification and quantitation of ecdysterone and of two metabolites, 14-deoxy ecdysterone and 14-deoxy poststerone was achieved. Ecdysterone was the most abundant analyte present in post-administration urines, detected for more than 2 days with a maximum concentration (Cmax) in the 2.8-8.5 h urines (Cmax = 4.4-30.0 µg/mL). The metabolites 14-deoxy ecdysterone and 14-deoxy poststerone were detected later reaching the maximum concentrations at 8.5-39.5 h (Cmax = 0.1-6.0 µg/mL) and 23.3-41.3 h (Cmax = 0.1-1.5 µg/mL), respectively. Cumulative urinary excretion yielded average values of 18%, 2.3% and 1.5% for ecdysterone, 14-deoxy ecdysterone and 14-deoxy poststerone, respectively. Ecdysterone and 14-deoxy ecdysterone were excreted following first order kinetics with half-lives calculated with three hours, while pharmacokinetics of 14-deoxy poststerone needs further evaluation.

Electron Beam Melting (EBM) is an increasingly used Additive Manufacturing (AM) technique employed by many industrial sectors, including the medical device and aerospace industries. In-process EBM monitoring for quality assurance purposes has been a popular research area. Electronic imaging has recently been investigated as one of the in-process EBM data collection methods, alongside thermal/ optical imaging techniques. Despite certain capabilities of an electronic imaging system have been investigated, experiments are yet to be carried out to benchmark one of the most important features of any imaging systems – spatial resolution. This article addresses this knowledge gap by: (1) proposing an indicator for the estimation of spatial resolution which includes the Backscattered Electrons (BSE) information depth, (2) estimating the achievable spatial resolution when electronic imaging is carried out inside an Arcam A1 EBM machine, and (3) presenting an experimental method to conduct edge resolution evaluation with the EBM machine. Analyses of experimental results indicated that the spatial resolution was of the order of 0.3mm-0.4mm when electronic imaging was carried out at room temperature. It is believed that by disseminating an analysis and experimental method to estimate and quantify spatial resolution, this study has contributed to the on-going quality assessment research in the field of in-process monitoring of the EBM process.

While there is a coordinated effort around reaching zero dose children and closing existing equity gaps in immunization delivery, it’s important that there is agreement and clarity around how ‘zero dose status’ is defined and what is gained and lost by using different indicators for zero dose status. There are two popular approaches used in research, program design, and advocacy to define zero dose status: one uses a single vaccine to serve as a proxy for zero dose status, while another uses a subset of vaccines to identify children who have missed all routine vaccines. We provide a global analysis utilizing the most recent publicly available DHS and MICS data to compare the number, proportion, and profile of children 12 to 23 months who are ‘penta-zero dose’ (have not received the pentavalent vaccine), ‘truly’ zero dose (have not received the BCG, polio, pentavalent, and measles vaccines), and ‘misclassified’ zero dose children (those who are penta-zero dose but have received at least one other vaccine). Our analysis includes 194,829 observations from 82 low- and middle-income countries. Globally, 14.2% of children are penta-zero dose and 7.5% are truly zero dose, suggesting that 46.5% of penta-zero dose children have had at least one contact with the immunization system. While there are similarities in the profile of children that are penta-zero dose and truly zero dose, there are key differences between the proportion of key characteristics among truly zero dose and misclassified zero dose children, including access to maternal and child health services. By understanding the extent of connection zero dose children may have with the health and immunization system and contrasting it with how much the use of a more feasible definition of zero dose may underestimate the level of vulnerability in the zero dose population, we provide insights that can help immunization programs design strategies that better target the most disadvantaged populations. If the vulnerability profiles of the truly zero dose children are qualitatively different from that of the penta zero dose children, then failing to distinguish the truly zero dose populations, and how to optimally reach them, may lead to the development of misguided or inefficient strategies for vaccinating the most disadvantaged population of children.

An increase in Spodoptera species was reported in Bt soybean fields expressing Cry1Ac insecticidal proteins in Brazil, requiring additional management with chemical insecticides. Here, we evaluated the dose effects of flubendiamide and thiodicarb on Spodoptera cosmioides (Walker, 1858), Spodoptera eridania (Stoll, 1782), Spodoptera albula (Walker, 1857) and Spodoptera frugiperda (J. E. Smith, 1797) (Lepidoptera: Noctuidae) that survived on MON 87751 × MON 87708 × MON 87701 × MON 89788, expressing Cry1A.105, Cry2Ab2 and Cry1Ac; MON 87701 × MON 89788 soybean, expressing Cry1Ac; and non-Bt soybean. On unsprayed Cry1A.105/Cry2Ab2/Cry1Ac soybean, only S. frugiperda showed ~60% mortality after 10 d, whereas S. cosmioides, S. eridania and S. albula showed >81% mortality. Surviving larvae of all species on this Bt soybean showed &gt;80% mortality when exposed to the field label dose of flubendiamide (70 mL/ha) or thiodicarb (400 g/ha) or at 50% of these doses. In contrast, all four species had <25% and <19% mortality on Cry1Ac and non-Bt soybean, respectively. Surviving S. cosmioides, S. eridania and S. albula on these soybean types presented >83% mortality post-exposure to both dose levels of flubendiamide and thiodicarb. Some S. frugiperda larvae surviving on Cry1Ac and non-Bt soybean sprayed with a 50% dose of either insecticide developed into adults. However, L1 larvae developing on Cry1Ac soybean leaves sprayed with flubendiamide and L2 larvae on this soybean sprayed with thiodicarb had a prolonged immature stage, and females lower fecundity, which are likely to impact its population growth on soybean.

Flotation of small particles is one of the global challenges facing the mineral raw materials processing industry. Large amounts of non-ferrous and rare metals are lost in the flotation tailings in the form of mineral particles below 15 µm in size as a result of the low effectiveness of their capture by coarse bubbles generated in conventional flotation machines. The method of combined microflotation, which is being developed in recent years, uses not only coarse but also microbubbles (MB) produced in the stand-alone generator of air-in-water microdispersion, which serves as the flotation carriers. Depending on the dose of MB, the effect of their application may be both positive, but also negative. The theoretical analysis of various mechanisms of particle transfer onto the surface of coarse bubbles and further into the froth layer allowed to obtain the formula for the optimal MB dose f=2dddpρp, where dd is MB size; dp and ρp respectively are the size and the density of particles. Experiments performed on the copper ore flotation tailings at the Atalaya Mining (Spain) and Chaarat Kapan (Armenia) concentrators showed that, besides the optimal MB dose in the range of 1-3 ml/g, there is another optimal MB dose in the range of 10-20 ml/g, where the copper recovery increases by several percent compared to the reference test (f= 0). In the area between the optimal MB doses, the deep minimum in copper recovery is observed, which value is by several percent lower compared to the value in the reference test.

The present study aimed to examine the stereoselective pharmacokinetics of racemic ketamine in dogs at low dose. Secondary aims were to identify associated behavioural side effects and propose a ketamine infusion rate. The study was conducted on nine intact male beagles, with each dog undergoing two treatments (BOL and INF). For treatment BOL, a single intravenous bolus of 1 mg/kg racemic ketamine was administered over 2 minutes. The treatment INF involved an initial bolus of 0.5 mg/kg given over 1 minute, followed by an infusion at 0.01 mg/kg/min for 1 hour. Blood samples were collected from the left cephalic vein for pharmacokinetic analysis. The median R/S enantiomer ratio of ketamine remained close to 1 throughout the study. However, levels of S-norketamine were significantly higher than those of R-norketamine across all time points. Based on the collected data, the infusion rate predicted to achieve a steady state racemic ketamine plasma concentration of 150 ng/mL was 1.7 mg/kg/h. Furthermore, employing ROC curve analysis, a racemic ketamine plasma concentration of 102 ng/mL was defined as the cut-off value, correlating with the occurrence of undesirable behavioural patterns.

The total ionizing dose (TID) effect significantly impacts the electrical parameters of fully depleted silicon on insulator (FDSOI) devices and even invalidates the on-off function of devices. At present, most of the irradiation research on the circuit level is focused on the single event effect, and the research on the total ionizing dose effect is very little. Therefore, this study mainly analyzes the influence of TID effects on a CMOS inverter circuit based on 22 nm FDSOI transistors. First, we constructed and calibrated an N-type FDSOI metal-oxide semiconductor (NMOS) structure and P-type FDSOI metal-oxide semiconductor (PMOS) structure. The transfer characteristics and trapped charge distribution of these devices were studied under different irradiation doses. Next, we studied the TID effect on an inverter circuit composed of these two MOS transistors. The simulation results show that when the radiation dose is 400 krad (Si), the logic threshold drift of the inverter is approximately 0.052 V. These results help further investigate the impact on integrated circuits in the irradiation environment.

Background: In Transcranial Direct Current Stimulation (tDCS) the injected current gets distributed across the brain areas. The motive is to stimulate the target region-of-interest (ROI), while minimizing the current in non-target ROIs. For this purpose, determining the appropriate current-dose for an individual is difficult. Aim: To introduce Dose-Target-Determination-Index (DTDI) to quantify the focality of tDCS and examine the dose-focality relationship in three different populations. Method: Here, we extended our previous toolbox i-SATA to the MNI reference space. After a tDCS montage is simulated for a current-dose, the i-SATA(MNI) computes the average (over voxels) current density for every region in the brain. DTDI is the ratio of average current density at target ROI to the ROI with maximum value (peak region). Ideally target ROI should be the peak region, so DTDI shall range from 0 to 1. Higher the value, the better the dose. We estimated the variation of DTDI within and across individuals using T1-weighted brain images of 45 males and females distributed equally across three age groups- (a) Young adults (20 ≥ x ˂ 40 years), (b) Mid adults (40 ≥ x ˂ 60 years), and (c) Older adults (60 ≥ x ˂ 80 years). DTDI’s were evaluated for the frontal montage with electrodes at F3 and right supra-orbital for three current doses 1mA, 2mA, and 3mA with the target ROI at left middle frontal gyrus. Result: As the dose is incremented, DTDI may show (a) increase, (b) decrease, and (c) no change across the individuals. The focality decreases with age and the decline is stronger in males. Higher current dose at older age can enhance the focality of stimulation. Conclusion: DTDI provides information on which tDCS current dose will optimize the focality of stimulation. DTDI recommended dose should be prioritised based on the age (> 40 years) and sex (especially males) of an individual. The toolbox i-SATA(MNI) is freely available.

Synergy of radiation and immune system is currently receiving significant attention in oncology as numerous studies have shown that cancer irradiation can induce strong antitumor immune responses. It remains unclear, however, what are the best radiation fractionation protocols to maximize the therapeutic benefits of this synergy. Here, we present a novel mathematical model that can be used to predict and dissect the complexity of the immune-mediated response at multiple tumor sites after applying focal irradiation and systemic immunotherapy. We successfully calibrate the proposed framework with published experimental data, in which two tumors were grown in mice at two spatially separated sites from which only one was irradiated using various radiation fractionation protocols with and without concurrent systemic immunotherapy. The proposed model is calibrated to fit the temporal dynamics of tumor volume at both sites and can predict changes in immune infiltration in the non-irradiated tumors. The model was then used to investigate additional radiation fractionation protocols. Model simulations suggest that the optimal radiation doses per fraction to maximize antitumor immunity are between 10-13 Gy, at least for the experimental setting used for model calibration. This work provides the framework for evaluating radiation fractionation protocols for radiation-induced immune-mediated systemic antitumor responses.

Deep learning image reconstruction (DLIR) algorithms employs convolutional neural networks (CNNs) for CT image reconstruction to produce CT images with a very low noise level, even at low radiation dose. The aim of this study was to assess whether the DLIR algorithm reduces the CT effective dose (ED) and im-proves CT image quality in comparison with filtered back projection (FBP) and iterative reconstruction (IR) algorithms in intensive care unit (ICU) patients. We identified all consecutive patients referred to the ICU of a single hospital who underwent at least two consecutive chest and/or abdominal contrast-enhanced CT scans within a time period of 30 days using DLIR and subsequently FBP or IR algorithm (Advanced Mod-eled Iterative Reconstruction model-based algorithm [ADMIRE], or Adaptive Iterative Dose Reduction 3D [AIDR 3D]) for CT image reconstruction. The radiation ED, noise level, and signal-to-noise ratio (SNR) were compared between the different CT scanners. The non-parametric Wilcoxon test was used for statistical comparison. Statistical significance was set at p < 0.05. A total of 83 patients (mean age, 59 ± 15 years [standard deviation]; 56 men) were included. DLIR vs FBP reduced ED (18.45 ± 13.16 mSv vs 22.06 ± 9.55 mSv, P < 0.05), while DLIR vs FBP and vs ADMIRE and AIDR 3D IR algorithms reduced image noise (8.45 ± 3.24 vs 14.85 ± 2.73 vs 14.77 ± 32.77 and 11.17 ± 32.77\, P < 0.05) and increased SNR (11.53 ± 9.28 vs 3.99 ± 1.23 vs 5.84 ± 2.74 and 3.58 ± 2.74, P < 0.05). CT scanners employing DLIR reduced radiation ED and im-proved SNR compared to CT scanners using FBP, whereas CT scanners using DLIR improved SNR com-pared to CT scanners using FBP or IR algorithms in ICU patients.

Glioblastoma multiforme (GBM), the most prevalent primary malignant brain tumor in adults, exhibits a dismal 6.9% five-year survival rate post-diagnosis. Thymoquinone (TQ), the most abundant bioactive compound in Nigella Sativa, has been extensively researched for its anti-cancer properties across various human cancers. Yet, its specific anticancer mechanisms and pathways in glioblastoma remain to be elucidated. In this study, we assessed the impact of different TQ concentrations on the viability of A172 cells using WST-8 and Toluidine blue assays, followed by RNA sequencing (RNA-seq) to identify differentially expressed genes (DEGs). We confirmed their expression levels through quantitative RT-PCR and performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for these DEGs. RNA-seq revealed no significant gene expression changes at 2.5 µM and 5 µM TQ concentrations. However, at 25 µM and 50 µM, TQ significantly reduced cell viability in a dose-dependent manner. We identified 1548 DEGs at 25 µM TQ (684 upregulated, 864 downregulated) and 2797 DEGs at 50 µM TQ (1528 upregulated, 1269 downregulated), with 1202 DEGs common to both concentrations. TQ inhibited key pathways such as PI3K-Akt signaling, calcium signaling, focal adhesion, and ECM-receptor interaction in A172 cells. It downregulated several potential oncogenes (e.g., AEBP1, MIAT) and genes linked to GBM proliferation and migration (e.g., SOCS2, HCP5), while modulating Wnt signaling and upregulating tumor suppressor genes (e.g., SPRY4, BEX2). TQ also affected p53 downstream targets, maintaining p53 levels. This study elucidates the anticancer mechanisms of TQ in A172 GBM cells, underscoring its effects on multiple signaling pathways and positioning TQ as a promising candidate for innovative glioblastoma treatment strategies.

After 2010, the source model of the microSelectron HDR Afterloader System was slightly modified from the previous model. Granero et al. named the modified source model “mHDR-v2r (revised model mHDR-v2)” and the previous model “mHDR-v2”. They concluded that the dosimetric differences arising from the dimensional changes between the mHDR-v2 and mHDR-v2r designs were negligible at almost all locations (within 0.5 % for r ≥ 0.25 cm), the two-dimensional anisotropy function difference between the two sources is found 2.1 % at r = 1.0 cm when compared with the results of the other experimental group. To confirm this difference, we performed a full Monte Carlo simulation without the energy fluence approximation. This is useful near the radiation source where charged-particle equilibrium does not hold. The two-dimensional anisotropy function of the TG-43U1 dataset showed a few percent difference between the mHDR-v2r and mHDR-v2 sources. There was no agreement in the immediate vicinity from the source (0.10 cm and 0.25 cm), when compared to Granero et al. in mHDR-v2r sources. The differences in these two-dimensional anisotropy functions were identified.

The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults (aged 60-75 years) received a single administration of 100, 150 or 200 mg/kg body weight of tyrosine. For comparison, 17 young adults (aged 18-35 years) received a dose of 150 mg/kg body weight of tyrosine. Tyrosine plasma concentrations were determined before and 90, 120, 150, 180, 210 and 240 minutes after tyrosine intake. Working memory was assessed using the N-back task at 90 minutes after tyrosine administration. Older adults showed a dose-dependent increase in plasma tyrosine concentrations (p<.001), and the plasma response was higher than for young adults with the same dose (p<.001). Load-dependent working memory performance decreased with higher doses of tyrosine (p=.048), especially in older adults with greater dose-dependent plasma tyrosine responses (p=.035). Our results show an age-related increase in plasma tyrosine response, which was associated with a dose-dependent decline in cognitive functioning in older adults.

Vaccination has proven to be one of the most effective strategies against the COVID 19 pandemic. Several studies have evaluated and confirmed its effectiveness in different populations, particularly in reducing severe outcomes such as hospitalization and death. However, the potential of vaccination to protect against infection itself has been overlooked. The aim of this study was to determine the effectiveness of the booster dose in a sample of Colombian patients during the fourth wave of COVID-19 pandemic, which was associated with the emergence and predominance of the Omicron variant. A cross-sectional study was conducted on individuals who underwent RT-PCR testing for COVID-19 detection in a dedicated laboratory in Bogotá, Colombia, between December 30th 2021 and February 7th 2022. A total of 1,468 subjects were included in the study. The comparison between fully vaccinated individuals with a booster dose and those without the booster dose revealed a 28% reduction in the odds of infection (OR = 0.719 CI 0.531 - 0.971). Age (OR = 1,009 CI 1,001 - 1,018) and low economic status (OR= 1,812 CI 1,416- 2,319) were associated with an increased risk of infection.These findings suggest the need for booster vaccination in the general population to improve the prevention rates of SARS-CoV-2 infection and mitigate severe outcomes.

Introduction The outcome of radiotherapy (RT) for prostate cancer (PCA) depends on the delivered dose. While the evidence for dose-escalated RT up to 80 Gy is well established, there have been only few studies examining dose escalation above 80 Gy. We initiated the presented study to assess the safety of dose escalation up to 84 Gy. Patients and methods In our retrospective analysis, we included patients who received dose-escalated RT for PCA at our institution between 2016 and 2021. We evaluated acute genitourinary (GU) and gastrointestinal (GI) toxicity as well as late GU and GI toxicity. Results A total of 86 patients could be evaluated, of whom 24 patients had received 80 Gy and 62 patients had received 84 Gy (35 without pelvis- and 27 with pelvis-radiotherapy). Regarding acute toxicities, no adverse events > grade 2 occurred. 12.5% of patients treated with 80Gy, in 25.7% of patients treated with 84 Gy excluding pelvis, and in 51.9% of patients treated with 84Gy including pelvis suffered from Grade 2 GU acute toxicity (80 Gy versus 84 Gy: p=0.186; with pelvis versus without pelvis: p=0.032). Grade 2 GI toxicity occurred in 12.5% of patients irradiated with 80Gy, in 14.3% of patients treated with 84 Gy excluding pelvis, and in 12.9% of patients treated with 84Gy including pelvis (80 Gy versus 84 Gy: p=0.582; with pelvis versus without pelvis: p=0.510).GU late toxicity of grade ≥ 2 occurred in 4.2% of patients treated with 80 Gy, in 7.1% of patients treated with 84 Gy excluding pelvic RT, and in 18.2% of patients treated with 84 Gy including pelvic RT (logrank-test p=0.237). 8.3% of patients treated with 80 Gy, in 3.6% of patients treated with Gy excluding pelvic RT, and in 0% of patients treated with 84 Gy including pelvic RT suffered from GI late toxicity of grade ≥ 2(logrank-test p=0.358). Conclusion We were able to show that dose-escalated RT in PCA up to 84 Gy is feasible and safe without asubstantial increase in toxicity. Further follow up is needed to assess survival.

A greenhouse dose-response study was conducted to determine the tolerance of three wild tomato accessions (TOM199, TOM198, TOM300) in comparison to a commercial cultivar (Better Boy) against the dicamba application at five rates (0, 70, 140, 210, and 280 g ae ha-1) at 14 and 28 days after treatment (DAT). Several physiological traits were evaluated at 0, 1, 3, 5, and 7 DAT. Wild accessions and cultivar were killed at all rates above 70 g ae ha-1 at 14 and 28 DAT, which is why differences between accessions and cultivar were only evident at 70 g ae ha-1. The GR50 (the herbicide rate that causes 50% reduction in dry weight) of Better Boy was 4.4 g ae ha-1 at 28 DAT, and this cultivar was approximately 11-fold more sensitive than wild accessions. At 7 DAT, the levels of H2O2 for wild accessions were lower than Better Boy up to 5 at 70 g ae ha-1 of dicamba. Furthermore, wild accessions showed lower herbicide absorption than Better Boy at all dicamba doses at 1, 3, and 7 DAT. All the three wild accessions expressed tolerance to the dicamba application at the dose of 70 g ae ha-1. At the same time, Better Boy and wild accessions were susceptible to dicamba application at rates of 140, 210, and 280 g ae ha-1.

Over a century ago, low-dose-rate (LDR) brachytherapy was introduced to treat prostate cancer (PCa). Since then, it has been widely applied worldwide, including in East Asia. LDR brachythera-py has been performed in 88 institutes in Japan. Beneficial clinical outcomes of LDR brachytherapy for intermediate-to-high-risk PCa have been demonstrated in large clinical trials. These clinical outcomes were achieved through advances in methods, such as urological precise needle puncture and seed placement, and the quantitative decision-making regarding radiological parameters by radiation oncologists. Combined use of LDR brachytherapy with other therapeutical modalities, such as external beam radiation and androgen deprivation therapy, for clinical risk classification of PCa has led to better anticancer treatment efficacy. In this study, we summarized basic LDR brachytherapy findings that should remain unchanged and be passed down in urology depart-ments. We also discussed the applications of LDR brachytherapy for PCa in various clinical settings, including focal and salvage therapies. In addition, we highlighted technologies associated with brachytherapy that are under development.

The severe acquired respiratory coronavirus–2 (SARS–CoV-2) infection has initiated both acute and chronic COVID–19 disease between 2020 and 2023, currently evolving with other homologous prior coronavirus strains of the Nidoviridae order, which encompasses other prevalent alpha/ beta coronaviruses, but also the Middle East Respiratory Syndrome (MERS-CoV) and SARS-CoV-1, with recent SARS–CoV–2 variants, increasing demands for effective immunogens and therapeutic approaches that will reduce global disease burden and further infection from SARS–CoV-2 affected individuals that may experience post acute sequelae (PASC) or “Long COVID”. Following a worldwide programme of prophylactic vaccination, there is still a dilemma in the efforts to find prophylactic and early therapeutic approaches that would treat novel SARS-CoV-2 variants and prevent future epidemics or pandemics within host human and animal populations, where zoonotic or cross species transfer naturally occurs. Concerns about viral immune escape intersect at a specific point; a gained evolutionary ability of several viruses to co–infect and compete against previous scientific advances since 1796 that remain undetected or asymptomatic during the early stages of infection progressing to symptomatic and severe disease via the double methylation of the 5' end of eukaryotic DNA or RNA-based viral genomes, the 7-MeGpppA2’-O-Me cap, and its double methylation capping process is performed by the activated viral 2’ - O - Methyltransferase (MTase) enzyme, a complex of two viral non-structural proteins (NSPs) joined together through an activation process (NSP10/16) and by N7-Methyltransferase (N7-MTase/NSP14), respectively. Moreover, it was discovered that polymorphic viruses translate NSP1, which prevents the activation of various Pattern Recognition Receptors (PRRs), and consequently, detection of Pathogen-Associated Molecular Patterns (PAMPs) and Damage-Associated Molecular Patterns (DAMPs) alike. NSP1 also silences important interferon-encoding genes (INGs) and interferon-stimulated genes (ISGs), is signalled in a paracrine manner to neighbouring cells, and that induces the apoptosis of host cells, inducing an effect of “trace erase” effect and making the viral infection as immunologically “invisible” as possible during the initial, key stages of viral replication and distribution, all such mechanisms occurring independently of the viruses in cause. Another important viral NSP is NSP14, as it plays two functional roles that are independent of each other; to produce new viral genetic material for the purpose of maintaining the validity of the viral genome as well, and not just transfer a methyl group to the 5’ end of the viral genome. Other viral NSPs share a role with NSP1, 10, 14 and 16 in directly suppressing the activation of PRRs and ISGs, and all such viral proteins help the virus in its process of self-camouflaging against first- and second-line immunity, thereby often severely impacting the quality of the produced adaptive immune responses. The outcome of all such phenomena is the sharp decrease in the host Type I and Type III interferons' (IFNs) rate of synthesis by the host cells, that would usually occur and affect homeostatic cellular pathways, resulting in further viral replication and induced apoptosis. Nonetheless, effects of microbial immune evasion during the development of other viral or carcinogenic pathologies are not widely known. In short, polymorphic viruses developed a proportionate evolutionary response against developed adaptive immune responses, by currently relying on gaps mostly situated in the natural immune system in their process of molecular self-camouflaging. Scientists developed numerous approaches of early treatment that generally showed good success rates and fewer risks of adverse events, and the still early present stages of COVID-19 research should also be taken into consideration whilst filtering for the most appropriate solutions. For example, the administration of recombinant human interferons I and III into the nasal mucosa cellular layer, as key mediators of anti–viral activity, can simulate intracellular infection and stimulate cellular activity in a timely manner, training the innate and adaptive immune system cells to develop and appropriately stimulate an adequate immune response through B and T cells. Another example could involve the treatment of natural and adaptive lymphocytes with a low dose of IFNs I and possibly III, prior to their insertion into the host lymphatic system, possibly alongside additional recruitment of plasmacytoid dendritic cells (pDCs) as further interferon “factories”, all with the purpose of early infection management. It might be that focusing on directly offering the immune system the information about the genetics and protein structure of the pathogen, rather than training its first-line mechanisms to develop faster, excessively increases its specificity, making it reach a level that brings the virus the opportunity to evolve and escape previously-developed host immune mechanisms. It is until the scientific community realises this potentially crucial aspect that large proportions of the world population will probably continue to face serious epidemics and pandemics of respiratory diseases over the coming several decades, evidenced with dengue fever and more recently, monkeypox and possibly avian flu. Of note, it has been indicated that IFN I and / or III display significant immunising, early therapeutic and clinical disease onset-attenuating effects for many other microbial evoked diseases, as well as for a number of oncological diseases.

A new treatment option for cluster headache (CH) prevention is needed. Monoclonal antibodies (mABs) against calcitonin gene-related peptide (CGRP) ligands are used as a preventative treatment for migraine. Considering the CGRP’s role in the CH attack’s ignition and upkeep, fremanezumab and galcanezumab have been evaluated for CH preventative treatment. However, only high-dose (300 mg) galcanezumab was proven for episodic CH prevention. We herein report 3 cases of migraine and comorbid CH with previous failures of preventive treatments. The 2 cases were treated with fremanezumab and the one with non-high-dose galcanezumab. All 3 cases showed good results not only on migraine but also on CH attacks. Our report suggested the efficacy of CGRP-mABs for CH prevention. Our cases differed from the cases in the phase 3 trials of CGRP-mABs for CH prevention in the following 2 points. First, the patients had both migraine and comorbid CH. Second, the combined use of CGRP-mABs with preventative drugs for CH, such as verapamil and/or prednisolone, was performed. Future accumulation of real-world data may prove the efficacy of CGRP-mABs for CH prevention.

Coronavirus 2019 (COVID-19) is an infectious disease that is becoming a pandemic. Hydroxychloroquine in combination with azythromycin are among drugs currently in use to eradicate COVID-19. Despite concerns due to its potential cardiac toxicity, hydroxychloroquine is widely accepted in mild and moderate COVID-19 pneumonia. In this case report, we report a case of a young Indonesian adult male with suspected COVID-19 pneumonia who received hydroxychloroquine and azythromycin therapies and during 24 hour experienced deterioration of atrioventricular block.

The physiological process of iodine uptake in the thyroid is used for 131I treatment of thyroid diseases. Children are more sensitive to radiation compared to adults and may react differently to 131I exposure. The aims of this study were to evaluate the effects on thyroid protein expression in young and adult rats one year after 131I injection, and identify potential biomarkers related to 131I exposure, absorbed dose, and age. Twelve Sprague Dawley Rats (young and adults) were i.v. injected with 50 kBq or 500 kBq 131I and were killed twelve months later. Twelve untreated rats were used as age-matched controls. Quantitative proteomics, statistical analysis and evaluation of biological effects was performed. The effects of irradiation were most prominent in young rats. Protein biomarker candidates were proposed related to age, absorbed dose, thyroid function and cancer and a panel was proposed for 131I exposure. In conclusion, the proteome of rat thyroid was differentially regulated twelve months after low-intermediate dose exposure to 131I in both young and adult rats. Several biomarker candidates are proposed for 131I exposure, age, and many of them are known to be related to thyroid function or thyroid cancer. Further research on human samples are needed for validation.

The demographic profile of patients transitioning from chronic kidney disease to renal replacement therapy is changing, with a higher prevalence of aging patients with multiple comorbidities such as diabetes mellitus and heart failure. Cardiovascular disease remains the leading cause of mortality in this population, exacerbated by the cardiovascular stress imposed by the HD procedure. The first year after transitioning to hemodialysis is associated with increased risks of hospitalization and mortality, particularly within the first 90–120 days, with greater vulnerability observed among the elderly. This review, based on data from clinics of Fresenius Medical Care Europe, Middle East, and Africa NephroCare, aims to optimize hemodialysis procedures to reduce mortality risk in stable incident and prevalent patients. It addresses critical aspects such as treatment duration, frequency, choice of dialysis membrane, dialysate composition, blood and dialysate flow rates, electrolyte composition, temperature control, target weight management, dialysis adequacy, and additional protocols, with a focus on mitigating prevalent intradialytic complications, particularly intradialytic hypotension prevention.

This study addresses the challenge of assessing the carcinogenic potential of hazardous chemical mixtures, such as PFAS, which are known to contribute significantly to cancer development. Here, we propose a novel framework called HNNMixCancer that utilizes a Hybrid Neural Network (HNN) integrated into a machine-learning framework. This framework incorporates a mathematical model to simulate chemical mixtures and enables the creation of classification models for binary and multiclass classification and regression. Through extensive experimentation, we demonstrate that our HNN model outperforms other methodologies, including Random Forest, Bootstrap Aggregating, Adaptive Boosting, Support Vector Regressor, Gradient Boosting, Kernel Ridge, Decision Tree with AdaBoost, and KNeighbors, achieving a superior accuracy of 92.7% in binary classification. To address the limited availability of experimental data and enrich the training data, we generate an assumption-based virtual library of chemical mixtures using a known carcinogenic and non-carcinogenic single chemical for all the classification models. Remarkably, in this case, all methods achieve accuracies exceeding 98% for binary classification. In external validation tests, our HNN method achieves the highest accuracy of 80.5%. Furthermore, in multiclass classification, the HNN demonstrates an overall accuracy of 96.3%, outperforming RF, Bagging, and AdaBoost, which achieved 91.4%, 91.7%, and 80.2%, respectively. In regression models, HNN, RF, SVR, GB, KR, DT with AdaBoost, and KN achieve average R2 values of 0.96, 0.90, 0.77, 0.94, 0.96, 0.96, and 0.97, respectively, showcasing their effectiveness in predicting the concentration at which a chemical mixture becomes carcinogenic. Our method exhibits exceptional predictive power in prioritizing carcinogenic chemical mixtures, even when relying on assumption-based mixtures. This capability is particularly valuable for toxicology studies that lack experimental data on the carcinogenicity and toxicity of chemical mixtures. To our knowledge, this study introduces the first method for predicting the carcinogenic potential of chemical mixtures. The HNNMixCancer framework offers a novel alternative for dose-dependent carcinogen prediction. Ongoing efforts involve implementing the HNN method to predict mixture toxicity and expanding the application of HNNMixCancer to include multi-mixtures.

The major stress-inducible Hsp70 (HSPA1A) is overexpressed in the cytosol of many highly aggressive tumor cells including glioblastoma multiforme and presented on their plasma membrane. Depending on its intracellular or membrane localization, Hsp70 either promotes tumor growth or serves as a target for NK cells. The kinetics of the membrane Hsp70 (mHsp70) density on human glioma cells (U87) was studied after different irradiation doses to define the optimal therapeutic window for Hsp70-targeting NK cells. To maintain the cells in the exponential growth phase during a cultivation period of 7 days different initial cell counts were seeded. Although cytosolic Hsp70 levels remained unchanged on days 4 and 7 after a sublethal irradiation with 2 Gy, 4 Gy and 6 Gy, a dose of 2 Gy resulted in an upregulated mHsp70 density in U87 cells which peaks on day 4 and starts to decline on day 7. Higher radiation doses (4 Gy, 6 Gy) resulted in an earlier and more rapid onset of the mHsp70 expression on days 2 and 1, respectively, followed by a decline on day 5. Membrane Hsp70 levels are higher in G2/M than in G1, however, an irradiation-induced cell cycle arrest on days 4 and 7, was not associated with an increase in the mHsp70 density. Extracellular Hsp70 concentrations increased significantly compared to sham (0 Gy) irradiated cells on days 4 and 7 but not on day 1. Functionally, elevated mHsp70 densities were associated with a significantly better lysis by Hsp70-targeting NK cells. In summary, the kinetics of changes in the mHsp70 density upon irradiation on tumor cells is time- and dose-dependent.

Dermal penetration is considered to mainly occur via passive diffusion. Therefore, a high concentration gradient of dissolved active ingredient between formulation and skin is needed to achieve an effective dermal penetration. The concentration gradient between formulation and skin can be changed by changing the amount of dissolved active ingredient in the formulation. In case of poorly soluble active ingredients this can be achieved by using nanosized drug material instead of larger sized material. The smaller size and the resulting larger surface increase the kinetic solubility and thus increase the concentration gradient of dissolved active ingredient between formulation and skin, which then results in an increased dermal penetration. In this study we demonstrated that the concentration gradient between formulation and skin can also be influenced by the number of particles being present in the formulation and by the dose (volume of formulation) applied to the skin. Particles of undissolved active ingredient are known to act as a reservoir by releasing dissolved molecules in the liquid phase of the formulation. It could now be demonstrated that the particles - once the liquid in which they are dispersed evaporates - can connect to the skin via an aqueous meniscus. The aqueous meniscus contains dissolved active ingredient and therefore creates a small local spot with a locally high concentration gradient and improved dermal penetration. Therefore, the dermal penetration can be increased with formulations that contain high amounts of particles. This can be achieved by applying formulations with high numbers of particles and/or by applying larger volumes of particle containing formulations to the skin.

Folic acid, one of the 13 essential vitamins, plays an important role in cardiovascular development. Mutations in folic acid synthesis gene 5,10-methylenetetrahydrofolate reductase (MTHFR) is significantly associated with the occurrence of congenital heart disease. However, the mechanisms underlying the regulation of cardiac development by mthfr gene are poorly understood. Here, we exposed zebrafish embryos to excessive folate or folate metabolism inhibitors. And we established a knock-out mutant of mthfr gene in zebrafish by using CRISPR/Cas9. The zebrafish embryos of insufficient or excessive folic acid, and mthfr-/- mutant all gave rise to early pericardial edema and cardiac defect at 3 days after fertilization(dpf). Furthermore, the folic acid treated embryos showed abnormal movement at 5dpf. The expression levels of cardiac marker genes hand2, gata4 and nppa changed in the abnormality of folate metabolism embryos and mthfr-/- mutant, and there is evidence that they are related to the change of methylation level caused by the change of folate metabolism. In conclusion, our study provides a novel model for the in-depth study of MTHFR gene and folate metabolism. And our results reveal that folic acid has a dose-dependent biphasic effect on early cardiac development.

Critical care of neonates involves substantial usage of antibiotics and exposure to multidrug resistant (MDR) nosocomial pathogens. These pathogens are often exposed to sub-MIC doses of antibiotics which might result in a range of physiological effects. Therefore, to understand the outcome of sub-inhibitory dosage of antibiotics on Staphylococcus populations, nasal swab specimens were collected from 34 neonates admitted to the Sick Newborn Care Unit between 2017-2018, a total of 41 non-repetitive isolates were included in this study. Staphylococcus haemolyticus was the prevalent species (58.54%) with high non-susceptibility to cefotaxime (CTX) (79.16%), gentamicin (87.50%), and meropenem (54.17%). Biofilm forming abilities of S. haemolyticus isolates in the presence of sub-optimal CTX (30μg/mL), the predominantly prescribed β-lactam antibiotic, were then determined by crystal violet assays and extracellular DNA (eDNA) quantitation. CTX was found to significantly enhance biofilm production among the non-susceptible isolates (p-valueWilcoxin test- 0.000008) with increase in eDNA levels (p-valueWilcoxin test- 0.000004). Additionally, no changes in non-susceptibility were observed among populations of two MDR isolates, JNM56C1 and JNM60C2 after >500 generations of growth in the absence of antibiotic selection in vitro. These findings demonstrate that sub-MIC concentration of CTX induces biofilm formation and short-term non-exposure to antibiotics does not alter non-susceptibility among S. haemolyticus isolates.

A novel coronavirus strain (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first appeared in December 2019 and can cause acute respiratory distress syndrome and death. However, there are only limited therapy choices and no vaccine for SARS-CoV-2 is currently available. Here we report about a case of a SARS-CoV-2 caused pneumonia successfully treated with thalidomide. Thalidomide is an immunomodulatory and anti-inflammatory agent and was combined with a low-dose glucocorticoid. We suggest, that the effects of thalidomide might be related to regulating immunity, inhibiting the inflammatory cytokine surge, alleviating anxiety to reduce oxygen consumption, relieving vomit and lung exudation.

This work continues the review and illustrative application to energy systems of the “Fourth-Order Best-Estimate Results with Reduced Uncertainties Predictive Modeling” (4th-BERRU-PM) methodology. The 4th-BERRU-PM methodology uses the Maximum Entropy (MaxEnt) principle to incorporate fourth-order experimental and computational information, in-cluding fourth (and higher) order sensitivities of computed model responses with respect to model parameters. The 4th-BERRU-PM methodology yields the fourth-order MaxEnt posterior distribution of experimentally measured and computed model responses and parameters, in the combined phase-space of model responses and parameters. The 4th-BERRU-PM methodology encompasses fourth-order sensitivity analysis (SA) and uncertainty quantification (UQ), which were reviewed in the accompanying work (Part 1), as well as fourth-order data assimilation (DA) and model calibration (MC) capabilities, which will be reviewed and illustrated in this work (Part 2). The applicability of the 4th-BERRU-PM methodology to energy systems is illustrated by using the Polyethylene-Reflected Plutonium (acronym: PERP) OECD/NEA reactor physics benchmark, which is modeled using the linear neutron transport Boltzmann equation, involving 21976 im-precisely known parameters. This benchmark is representative of “large-scale computations” such as those involved in the modeling of energy systems. The result (“response”) of interest for the PERP benchmark is the leakage of neutrons through the outer surface of this spherical benchmark, which can be computed numerically and measured experimentally. The impact of the high-order sensitivities of the response with respect to the PERP model parameters is quantified for “high-precision” parameters (2% standard deviations) and “medium-precision” parameters (5% standard deviations). Analyzing the best-estimate results with reduced uncertainties for the 1st- through 4th-order moments (mean values, covariance, skewness, and kurtosis) produced by the 4th-BERRU-PM methodology for the PERP benchmark indicates that, even for systems mod-eled by linear equations (e.g., the PERP benchmark), retaining only first-order sensitivities is insufficient for reliable predictive modeling (including SA, UQ, DA, MC). At least second-order sensitivities should be retained in order to obtain reliable predictions.

Our previous study demonstrated that the acute high-dose rate (3.3 Gy/minute) gamma irradiation of postnatal day 3 (P3) mice with 5Gy induced depression and drastic neuropathological changes in the dentate gyrus of the hippocampus of the adult mice. The present study investigated the effects of chronic low-dose-rate (1.2mGy/h) gamma irradiation from P30 to P180 with a cumulative dose of 5Gy on animal behaviour, hippocampal cellular change, miRNA and mRNA expression in the hippocampus and blood in female mice. The radiation exposure did not significantly affect the animal's body weight and neuropsychiatric changes such as anxiety and depression examined by neurobehavioural tests including open field, light-dark box, elevated plus maze, tail suspension test and forced swim test. Immunohistochemical staining did not detect any obvious loss of mature and immature neurons (NeuN and DCX) or any inflammatory glial response (IBA1, GFAP, and PDGFR1). Nevertheless, r-H2AX foci in the stratum granulosum of the dentate gyrus were significantly increased, suggesting the chronic low dose rate irradiation induced persistent DNA damage foci in mice. miRNA sequencing and qRT-PCR indicated an increased expression of miR-448-3p and miR-361-5p, but decreased expression of miR-193a-3p in the mouse hippocampus. Meanwhile, mRNA sequencing and qRT-PCR showed a reduced expression of Ccn1, Fli1, Fosb, Ets1, Hs3st5, and Eif4ebp1, but enhanced expression of Cort, Foxh1, and Opalin. Database searching by miRDB and TargetScan predicted that FLI1 and HS3ST5 are the targets of miR-448-3p, and Eif4ebp2 is the target of miR-361-5p. miRNA/mRNA sequencing and qRT-PCR results in blood showed the increased expression of miR-6967-3p and the decreased expression of its target S1pr5. The interactions of these miRNAs and mRNAs may contribute to the chronic low dose rate radiation-induced persistent DNA damage.

This study assessed the performance of low-dose CT lung scans across various acquisition parameters and examined the impact of iterative reconstruction (IR) algorithms on image quality for lung cancer screening. The performance of multi-slice CT scanners was assessed by using a Catphan 600 phantom, specifically within the CTP404 test module that contains materials like Teflon, Delrin, Acrylic, Polystyrene, LDPE, PMP, Air, and water. Three protocols were selected and categorized into standard, low dose, and ultra-low dose. The standard protocol featured a tube voltage of 100 kVp for single-detector CT, a pitch of 0.75, detector collimation of 0.60 mm, and a gantry rotation time of 0.33 seconds, with 5 mm slice thickness. Images were reconstructed using standard kernels like B80f and 170f, combined with either FBP or various IR algorithms. Findings indicated that the noise power spectrum (NPS) peak value (HU2mm2) increased with higher IR levels, with FBP showing the highest peak. Additionally, NPS spatial frequency diminished as IR levels rose. Optimizing contrast and spatial resolution for both background and regions of interest involved adjusting the target transfer function (TTF) and contrast-to-noise ratio (CNR), crucial for protocol optimization. Proper adjustment of IR levels is vital, as higher levels can alter image texture and affect NPS spatial frequency. The results of this study showed that the use of IR algorithms in low-dose CT lung scans significantly improved image quality, particularly in terms of noise reduction and spatial resolution. However, the choice of acquisition parameters also played a crucial

This retrospective study aimed to evaluate the impact of radiation dose on the outcomes of stereotactic radiosurgery (SRS) for benign meningiomas and determine an optimal dosing strategy for balancing tumor control and treatment-related toxicity. Clinical data of 147 patients with 164 lesions treated between 2014 and 2022 were reviewed. Primary outcomes included progression-free survival (PFS), local control rate (LCR), and radiation-induced toxicity, with secondary outcomes focusing on LCR and radiation-induced peritumoral edema (PTE) in two dose groups (≥14 Gy and &lt;14 Gy). Results revealed a median follow-up duration of 47 months, with 1-year, 2-year, and 5-year PFS rates of 99.3%, 96.7%, and 93.8% respectively, and an overall LCR of 95.1%. Radiation-induced toxicity was observed in 24.5% of patients, primarily presenting mild symptoms. Notably, no significant difference in LCR was found between the two dose groups (P = 0.628), while Group 2 (&lt;14 Gy) exhibited significantly lower PTE (P = 0.039). The study concludes that SRS with a radiation dose &lt;14 Gy demonstrates comparable tumor control with reduced toxicity, advocating for consideration of such dosing to achieve a balance between therapeutic efficacy and safety.

Background: Computed tomography examinations have produced high radiation doses to patients, especially the CT brain. This study aimed to optimize the radiation dose and image quality in adult CT brain protocol. Materials and Methods: Images were acquired by Catphan 700 phantom. Radiation doses were recorded as CTDIvol and dose length product (DLP). CT brain protocols were optimized by varying parameters such as kVp, mAs, signal-to-noise ratio (SNR) level, and Clearview iterative reconstruction (IR). Image quality were also evaluataion by The AutoQA Plus software. Results: CT Number accuracy and linearity had a robust positive correlation with the linear attenuation coefficient (µ) and showed more inaccurate CT numbers when using 80 kVp. MTF showed a higher value in 100 and 120 kVp protocols, while high contrast spatial resolution showed a higher value in 80 and 100 kVp protocols. Low contrast detectability and CNR tended to increase when using high mAs, SNR and Clearview IR protocol. Noise decreased when using a high radiation dose and a high percentage of Clearview IR. CTDIvol and DLP were increased with increasing kVp, mAs, and SNR levels, while the increasing percentage of Clearview did not affect the radiation dose. Conclusion: Optimized protocols, including radiation dose and image quality, should be evaluated to preserve diagnostic capability. The recommended parameter settings include kVp set between 100-120 kVp, mAs ranging from 200-300 mAs, SNR level within the range of 0.7-1.0, and an iterative reconstruction value of 30% Clearview to 60% or higher.

The best form of prevention against human infection through bacteria, viruses and other parasites is ozone disinfection of wastewater and drinking water as a highly effective, well-known method. As a therapeutic measure, various preclinical studies showed promising results, which are being revisited and reconsidered in times of pandemics and led to interesting results in recent clinical trials and reports, as presented by the example of protective measures against covid-19 in particularly vulnerable clinical personnel. In patients with rheumatoid arthritis, repeated ozone treatments have led to new findings in the "immunomodulation" through ozone. The more effective immune response is discussed as the response of innate immune memory and opens interesting aspects for complementary treatment of autoimmune diseases.

Local anaesthetic agents suppress action potentials in excitable tissues by blocking voltage-gated sodium channels. In doing so they inhibit the depolarisation of nociceptive nerve fibres and so prevent the transmission of pain impulses. UK legislation allows HCPC-registered Podiatrists with POM-A annotation access to six local anaesthetic drugs and two of these with the addition of adrenaline. The use of local anaesthetia has transformed the treatment of nail pathology by Podiatrists. In the UK, the drug of choice in podiatric practice is 3% mepivacaine hydrochloride: it is a good choice of drug for digital anaesthesia. This paper will review the chemistry, pharmacology and dose calculation of mepivacaine, and challenge some of the orthodoxy over the rigid calculation of maximum safe dosages.

Background: Rituximab is a monoclonal antibody widely used in the treatment of inflammatory and autoimmune disorders. Despite reports of its effectiveness in the treatment of demyelinating diseases of central nervous system (DDCNS), it is not yet approved for use in these disorders. The aim of this study was to investigate the effectiveness and safety of low dose rituximab in three different subgroups of DDCNS including relapsing-remitting multiple sclerosis (RRMS), secondary-progressive multiple sclerosis (SPMS) and neuromyelitis-optica-spectrum disorders (NMOSD).Methods: In a prospective cohort study, we monitored expanded-disability-status-scale (EDSS), relapses (new attacks) and serum-IgG levels to assess effectiveness and drug-adverse-events for safety in patients with RRMS, SPMS and NMOSD. These patients were candidates to receive rituximab according to our common practice protocol. We switched patients to rituximab if there was poor response to first line therapies. We follow a low dose protocol in our center (500 mg twice, two weeks apart, repeating every six months) and these patients treated in a 4-year period were assessed retrospectively for evaluation of our protocol’s safety and effectiveness. Results: 99 patients (42 RRMS, 43 SPMS and 14 NMOSD) received rituximab for a range of 12 to 40 months period. New attacks occurred in 8 RRMS (19%), 10 SPMS (23%) and 1 NMOSD (7%) patients. EDSS decreased in RRMS and NMOSD cases. Serum-IgG levels decremented in SPMS and NMOSD patients. Drug-adverse-events happened in two cases.Conclusion: In this study, low dose rituximab showed substantial effectiveness in preventing disease progression with a considerably good safety profile.

A single dose of psilocybin, a psychedelic and serotonin 2A receptor (5-HT2AR) agonist, may be associated with antidepressant effects. The mechanism behind its antidepressive action is unknown but could be linked to increased synaptogenesis and down-regulation of cerebral 5-HT2AR. Here, we investigate if a single psychedelic dose of psilocybin changes synaptic vesicle protein 2A (SV2A) and 5-HT2AR density in the pig brain. Twenty-four awake pigs received either 0.08 mg/kg psilocybin or saline intravenously. Twelve pigs (n=6/intervention) were euthanized one day post-injection, while the remaining twelve pigs were euthanized seven days post-injection (n=6/intervention). We performed autoradiography on hippocampus and prefrontal cortex (PFC) sections with [3H]UCB-J (SV2A), [3H]MDL100907 (5-HT2AR antagonist) and [3H]Cimbi-36 (5-HT2AR agonist). One day post psilocybin injection, we observed 4.4% higher hippocampal SV2A density and lowered hippocampal and PFC 5-HT2AR density (-15.21% to -50.19%). These differences were statistically significant in the hippocampus for all radioligands and in PFC for [3H]Cimbi-36 only. Seven days post-intervention, there was still significantly higher SV2A density in hippocampus (+9.24%) and PFC (+6.1%) whereas there were no longer any differences in 5-HT2AR density. Our findings suggest that psilocybin’s antidepressive actions are linked to increased persistent synaptogenesis and possibly also to an acute decrease in 5-HT2AR density.

Firocoxib is a non-steroidal anti-inflammatory drug specifically formulated for veterinary medicine and selectively acts on inhibiting the cyclooxygenase 2 enzyme(COX-2). This study aimed to evaluate the possible adverse effects of administering oral therapeutic firocoxib on gastric mucosa, hematological parameters, coagulation cascade, and hepatic and renal biochemistry in healthy horses. Nine clinically healthy Arabian horses, approximately nine years old, received 0.1mg/kg of oral firocoxib for 14 days. Before beginning treatment, a gastroscopic examination was conducted, and venous blood samples were obtained for laboratory tests on D0. Follow-up blood samples and gastroscopic examinations were taken on D7 and D14 after starting treatment and one week after completing treatment on D21. No changes were found in the gastroscopic and hematological tests. Additionally, coagulation and serum biochemistry levels remain between normal values for this particular species. However, the increased activated partial thromboplastin time (aPTT) and prothrombin time (PT) indicate reduced blood coagulation capacity, which contradicts the expected effect of treatment with selective COX-2 inhibitors, as these drugs theoretically promote coagulation. Administering Firocoxib to horses is safe as it does not cause any significant adverse reactions. Therefore, it is a suitable option for managing inflammatory conditions in these animals.

Abstract: Epidemiological, experimental, and ecological data have indicated the controversial effect of in utero chronic low dose rate (100 mGy) dose radiation exposure. Our main goal of this study was to examine if different low dose rates of chronic pre- or/and post-natal radiation exposure with accumulative high doses could induce hippocampal cellular, mRNA, and miRNA changes leading to neuropsychiatric disorders. The comprehensive mouse phenotypic traits, organ weight pathological, blood mRNA and miRNA changes were also studied. Using different approaches including SmithKline, Harwell, Imperial College, Royal Hospital, Phenotype Assessment (SHIRPA), neurobehavioral tests, pathological examination, immunohistochemistry, mRNA and miRNA sequencing, and real-time quantitative polymerase chain reaction ( qRT-PCR) validation, we found that in prenatally irradiated (100 mGy/d for 18 days with an accumulative dose of 1.8 Gy) 1-year-old mice, no cellular changes including neurogenesis, mature neurons and glial cells in the hilus of the dentate gyrus and development of cognitive impairment, neuropsychiatric disorders occurred. However, a significant reduction in body weight and mass index (BMI) was indicated by the SHIRPA test. A reduced exploratory behavior was shown by an open field test. Organ weight measurement showed a significant reduction of the testes, kidneys, heart, liver, and epididymides although no abnormal changes from pathological examination. mRNA and miRNA sequencing and qRT-PCR validation revealed the upregulation of Rubcnl, Abhd14b and downregulation of Hspa1b, P4ha1, and Banp genes in both hippocampus and blood of mice prenatally irradiated with 100 mGy/d. Meanwhile, downregulation of miR-448-3p, miR1298-5p in the hippocampus, miR-320-3p, miR-423-5p, miR-486b-5p, miR-486b-3p, miR-423-3p, miR-652-3p, miR-324-3p, miR-181b-5p, miR-let-7b and miR-6904-5p in the blood was induced. The target scan revealed that Rubcnl is one of the miR-181b-5p targets in the blood. We, therefore, concluded that prenatal chronic irradiation with a low dose rate of 100 mGy/d and accumulative dose of 1.8Gy or below may not induce significant adverse health effects on the offspring. Further study of different low dose rate radiation exposure with accumulative high doses may provide threshold doses for authorities or regulators to set new radiation safety guidelines to replace those extrapolated from acute high dose/dose rate irradiation to reduce unnecessary emergency evacuation or expanding once a nuclear accident or leakage occurs.

Kiribati is a Pacific Island nation with a widely dispersed population and one of the highest rates of leprosy worldwide. Single dose rifampicin post exposure prophylaxis (SDR-PEP) of leprosy contacts has reduced new case detection rates in controlled trials. In 2018, a SDR-PEP programme was introduced in Kiribati that included screening and chemoprophylaxis of household contacts of leprosy cases both retrospectively (2010-2017) and prospectively (2018 onwards). We conducted a retrospective audit to determine comprehensiveness, timeliness and feasibility of the SDR-PEP programme. Overall, 13,643 household contacts were identified (9,791 in the retrospective and 3,850 in the prospective cohort). In the retrospective cohort, 1,044 (11%) contacts were absent, 403 (4%) were ineligible for SDR and 42 new cases were detected (0.4%) Overall SDR coverage was 84.7%. In the prospective cohort, 164 (4%) contacts were absent, 251 (7%) were ineligible for SDR and 23 new cases were diagnosed (0.6%). Overall, SDR coverage was 88.1%. Across both cohorts, there were a total of 23 SDR refusals. The median time to SDR ad-ministration was 220 days (IQR 162-468) and 120 days (IQR 36-283) for the retrospective and prospective cohorts respectively. SDR was readily accepted in both cohorts. The new case detec-tion rate (0.5%) is consistent with that seen in other studies. Overall SDR coverage in both the retrospective and prospective phases met programmatic expectations.

Little is known about the long-term durability of the induced immune response in subjects af-fected by obesity, particularly in those with an abdominal distribution of adipose tissue. We evaluated SARS-CoV-2-specific antibody response after BNT162b2 vaccine booster dose, com-paring individuals with abdominal obesity (AO) with those without, discerning between indi-viduals previously infected or not. IgG-TrimericS were measured in 511 subjects at baseline, 21 days after vaccine dose-1 and at one, three, six and nine months after dose-2 and at one and three months after booster dose. Nucleocapsid antibodies were assessed at baseline and at the end of the study to detect SARS-CoV-2 infection. To evaluate the three-months difference in absolute variation of IgG-TrmicericS levels from booster dose we used multivariable linear regression that showed interaction between AO and SARS-CoV-2 infection status (p=0.016). AO is associated with higher absolute IgG-TrimericS variation in prior infected individuals, regardless of possi-ble confounders and IgG-TrimericS levels at booster dose (p=0.0125). No interaction was evinced using BMI in the same regression model (p=0.418). The robust response in the development of antibodies after booster dose, observed in people with OA and previous infection, may support the recommendations to undergo the booster dose also in this population group.