Statistical data pre-processing and time series incorporation for high-efficacy calibration of low-cost NO2 sensor using machine learning.

Air pollution stands as a significant modern-day challenge impacting life quality, the environment, and the economy. It comprises various pollutants like gases, particulate matter, biological molecules, and more, stemming from sources such as vehicle emissions, industrial operations, agriculture, and natural events. Nitrogen dioxide (NO2), among these harmful gases, is notably prevalent in densely populated urban regions. Given its adverse effects on health and the environment, accurate monitoring of NO2 levels becomes imperative for devising effective risk mitigation strategies. However, the precise measurement of NO2 poses challenges as it traditionally relies on costly and bulky equipment. This has prompted the development of more affordable alternatives, although their reliability is often questionable. The aim of this article is to introduce a groundbreaking method for precisely calibrating cost-effective NO2 sensors. This technique involves statistical preprocessing of low-cost sensor readings, aligning their distribution with reference data. Central to this calibration is an artificial neural network (ANN) surrogate designed to predict sensor correction coefficients. It utilizes environmental variables (temperature, humidity, atmospheric pressure), cross-references auxiliary NO2 sensors, and incorporates short time series of previous readings from the primary sensor. These methods are complemented by global data scaling. Demonstrated using a custom-designed cost-effective monitoring platform and high-precision public reference station data collected over 5 months, every component of our calibration framework proves crucial, contributing to its exceptional accuracy (with a correlation coefficient near 0.95 concerning the reference data and an RMSE below 2.4 µg/m3). This level of performance positions the calibrated sensor as a viable, cost-effective alternative to traditional monitoring approaches.

Machine-learning-based global optimization of microwave passives with variable-fidelity EM models and response features.

Maximizing microwave passive component performance demands precise parameter tuning, particularly as modern circuits grow increasingly intricate. Yet, achieving this often requires a comprehensive approach due to their complex geometries and miniaturized structures. However, the computational burden of optimizing these components via full-wave electromagnetic (EM) simulations is substantial. EM analysis remains crucial for circuit reliability, but the expense of conducting rudimentary EM-driven global optimization by means of popular bio-inspired algorithms is impractical. Similarly, nonlinear system characteristics pose challenges for surrogate-assisted methods. This paper introduces an innovative technique leveraging variable-fidelity EM simulations and response feature technology within a kriging-based machine-learning framework for cost-effective global parameter tuning of microwave passives. The efficiency of this approach stems from performing most operations at the low-fidelity simulation level and regularizing the objective function landscape through the response feature method. The primary prediction tool is a co-kriging surrogate, while a particle swarm optimizer, guided by predicted objective function improvements, handles the search process. Rigorous validation demonstrates the proposed framework's competitive efficacy in design quality and computational cost, typically requiring only sixty high-fidelity EM analyses, juxtaposed with various state-of-the-art benchmark methods. These benchmarks encompass nature-inspired algorithms, gradient search, and machine learning techniques directly interacting with the circuit's frequency characteristics.

Exploring the Beam Squint Effects on Reflectarray Performance: A Comprehensive Analysis of the Specular and Scattered Reflection of the Unit Cell.

In this article, the phenomena of beam deviation in reflectarray is discussed. The radiation pattern of the unit cell, which plays a vital role in shaping the beam of the reflectarray, is analyzed by considering undesired specular and scattered reflections. These unwanted reflections adversely affect the pattern of the single unit cell, thereby reducing the overall performance of the reflectarray. To conduct our investigations, three cases of reflectarray-i.e., (i) a center-fed with broadside beam (Case-I), (ii) a center-fed with the beam at 30° (Case-II), and (iii) off-center-fed with the beam at 30° reciprocal to feed position with reference to the broadside direction (Case-III)-are simulated. Different degrees of beam deviation are analyzed in each reflectarray by assessing the radiation pattern of a single element. The simulation results shows that maximum of 0°, 3.4°, and 0.54° beam squint across the bandwidth found in Case-I, Case-II, and Case-III, respectively; this leads to aperture efficiencies of 31.2%, 11.9%, and 31.2%, respectively. The significance of specular reflections is further confirmed by half (left half and right half) aperture analysis of Case-II. This involves simulating the half-plane aperture illuminated by horn antenna, resulting in a distinct beam angle at the same frequency. However, deviations of -4.71 to +4.1 for the left half aperture and -1.82 to +1.1 for the right half aperture are noticed. Although the analysis specifically focuses on the three cases of the reflectarray, the proposed methodology is applicable to any type of reflectarray. The study presented in this work provides an important insight into the practical aspects of reflectarray operation, particularly in terms of quantifying undesirable effects that are normally overlooked in the design of this class of arrays. To achieve a good performance, a new design of the dielectric loaded horn feed is proposed. This design approach is both simple and applicable to any reflectarray, with the added benefit of maintaining a low profile for the RA. Moreover, this work holds significant potential for remote sensing satellite systems as beam deviation can adversely impact data collection accuracy and compromise observation precision, resulting in distorted images, reduced data quality, and overall hindrance to the system's performance in capturing reliable information.

Assessment of the Impact of Carvedilol Administered Together with Dexrazoxan and Doxorubicin on Liver Structure and Function, Iron Metabolism, and Myocardial Redox System in Rats.

Late cardiotoxicity is a formidable challenge in anthracycline-based anticancer treatments. Previous research hypothesized that co-administration of carvedilol (CVD) and dexrazoxane (DEX) might provide superior protection against doxorubicin (DOX)-induced cardiotoxicity compared to DEX alone. However, the anticipated benefits were not substantiated by the findings. This study focuses on investigating the impact of CVD on myocardial redox system parameters in rats treated with DOX + DEX, examining its influence on overall toxicity and iron metabolism. Additionally, considering the previously observed DOX-induced ascites, a seldom-discussed condition, the study explores the potential involvement of the liver in ascites development. Compounds were administered weekly for ten weeks, with a specific emphasis on comparing parameter changes between DOX + DEX + CVD and DOX + DEX groups. Evaluation included alterations in body weight, feed and water consumption, and analysis of NADPH2, NADP+, NADPH2/NADP+, lipid peroxidation, oxidized DNA, and mRNA for superoxide dismutase 2 and catalase expressions in cardiac muscle. The iron management panel included markers for iron, transferrin, and ferritin. Liver abnormalities were assessed through histological examinations, aspartate transaminase, alanine transaminase, and serum albumin level measurements. During weeks 11 and 21, reduced NADPH2 levels were observed in almost all examined groups. Co-administration of DEX and CVD negatively affected transferrin levels in DOX-treated rats but did not influence body weight changes. Ascites predominantly resulted from cardiac muscle dysfunction rather than liver-related effects. The study's findings, exploring the impact of DEX and CVD on DOX-induced cardiotoxicity, indicate a lack of scientific justification for advocating the combined use of these drugs at histological, biochemical, and molecular levels.

wideband high-gain low-profile series-fed antenna integrated with optimized metamaterials for 5G millimeter wave applications.

This paper presents a series-fed four-dipole antenna with a broad bandwidth, high gain, and compact size for 5G millimeter wave (mm-wave) applications. The single dipole antenna provides a maximum gain of 6.2 dBi within its operational bandwidth, which ranges from 25.2 to 32.8 GHz. The proposed approach to enhance both gain and bandwidth involves a series-fed antenna design. It comprises four dipoles with varying lengths, and a truncated ground plane. These dipoles are connected in series on both sides, running in parallel through a microstrip line. The proposed design significantly enhances the bandwidth, which extends from 26.5 to 40 GHz. This frequency range effectively covers the 5G bands of 28 and 38 GHz. The expedited trust-region (TR) gradient-based search algorithm is utilized to optimize the dimensions of the antenna components, resulting in a maximum gain of 11.2 dBi at 38 GHz. To further enhance the gain, modified H-shaped metamaterial (MTM)-based unit cells are integrated into the antenna substrate. The TR algorithm is employed once more to optimize the MTM dimensions, yielding a maximum gain of 15.1 dBi at 38 GHz. The developed system is experimentally validated, showing excellent agreement between the simulated and measured data.

Mirabegron, a Selective ß3-Adrenergic Receptor Agonist, as a Potential Anti-Obesity Drug.

Obesity is becoming a global health epidemic. Brown and "beige" adipose tissue may produce heat, leading to energy expenditure enhancement and weight loss. Mirabegron, a selective ß3-adrenergic receptor agonist, has been found to be effective as a brown adipose tissue activator, a "beige" cells stimulator and a metabolic homeostasis controller in animal and human studies. Although in animal studies, administration of mirabegron led to obesity improvement, significant weight loss in obese patients after mirabegron treatment has not been demonstrated so far, which may be associated with the too-short duration of the trials and the small number of participants in the studies. In humans, the most effective treatment for adipose tissue stimulation was high doses of mirabegron; however, cardiovascular side effects may limit the use of such doses, so the long-term safety must be evaluated. In cases of tachycardia or blood pressure elevation, the co-administration of a ß1-adrenergic receptor blocker may be useful. It should be checked whether smaller doses of mirabegron, taken for a longer time, will be sufficient to stimulate brown and "beige" adipose tissue, leading to weight loss. The introduction of mirabegron into obesity treatment in the future will require long-term trials with larger numbers of subjects, to assess mirabegron efficacy, tolerability, and safety.

Reduced-cost microwave modeling using constrained domains and dimensionality reduction.

Development of modern microwave devices largely exploits full-wave electromagnetic (EM) simulations. Yet, simulation-driven design may be problematic due to the incurred CPU expenses. Addressing the high-cost issues stimulated the development of surrogate modeling methods. Among them, data-driven techniques seem to be the most widespread owing to their flexibility and accessibility. Nonetheless, applicability of approximation-based modeling for real-world microwave components is hindered by a high nonlinearity of the system characteristics, dimensionality issues, and broad ranges of operating parameters the model should cover to make it practically useful. Performance-driven modeling frameworks deliver a partial mitigation of these problems through appropriate spatial orientation of the metamodel domain, which only encapsulates high-quality designs and not the entire space. Unfortunately, the initial model setup cost is high, as defining the domain requires database designs that need to be a priori acquired. This paper introduces a novel approach, where the database designs are replaced by random observables, and dimensionality of the domain is reduced using spectral analysis thereof. The major contributions of the work include implementation of the explicit dimensionality reduction of the confined surrogate model domain and introducing this concept into a complete cost-efficient framework for modeling of microwave components. Comprehensive benchmarking demonstrates excellent performance of the introduced framework, both in terms of predictive power of the rendered surrogates, their scalability properties, as well as low computational overhead associated with the model setup.

High-efficacy global optimization of antenna structures by means of simplex-based predictors.

Design of modern antenna systems has become highly dependent on computational tools, especially full-wave electromagnetic (EM) simulation models. EM analysis is capable of yielding accurate representation of antenna characteristics at the expense of considerable evaluation time. Consequently, execution of simulation-driven design procedures (optimization, statistical analysis, multi-criterial design) is severely hindered by the accumulated cost of multiple antenna evaluations. This problem is especially pronounced in the case of global search, frequently performed using nature-inspired algorithms, known for poor computational efficiency. At the same time, global optimization is often required, either due to multimodality of the design task or the lack of sufficiently good starting point. A workaround is to combine metaheuristics with surrogate modeling methods, yet a construction of reliable metamodels over broad ranges of antenna parameters is challenging. This work introduces a novel procedure for global optimization of antenna structures. Our methodology involves a simplex-based automated search performed at the level of approximated operating and performance figures of the structure at hand. The presented approach capitalizes on weakly-nonlinear dependence between the operating figures and antenna geometry parameters, as well as computationally cheap design updates, only requiring a single EM analysis per iteration. Formal convergence of the algorithm is guaranteed by implementing the automated decision-making procedure for reducing the simplex size upon detecting the lack of objective function improvement. The global optimization stage is succeeded by gradient-based parameter refinement. The proposed procedure has been validated using four microstrip antenna structures. Multiple independent runs and statistical analysis of the results have been carried out in order to corroborate global search capability. Satisfactory outcome obtained for all instances, and low average computational cost of only 120 EM antenna simulations, demonstrate superior efficacy of our algorithm, also in comparison with both local optimizers and nature-inspired procedures.

Optimal design of transmitarray antennas via low-cost surrogate modelling.

Over the recent years, reflectarrays and transmitarrays have been drawing a considerable attention due to their attractive features, including a possibility of realizing high gain and pencil-like radiation patterns without the employment of complex feeding networks. Among the two, transmitarrays seem to be superior over reflectarrays in terms of achieving high radiation efficiency without the feed blockage. Notwithstanding, the design process of transmitarrays is more intricate due to the necessity of manipulating both the transmission phase and magnitude of its unit elements. For reliability, the design process has to be conducted at the level of full-wave electromagnetic models, which makes direct optimization prohibitive. The most widely used workaround is to employ surrogate modeling techniques to construct fast representations of the unit elements, yet the initial model setup cost is typically high and includes acquisition of thousands of training data points. In this paper, we propose a novel approach to cost-efficient design of transmitarrays. It is based on artificial-intelligence-enabled data-driven surrogates, which can be constructed using only a few hundreds of training data samples, while exhibiting the predictive power sufficient for reliable design. Our methodology is demonstrated by re-using the presented surrogate for the design of high-performance transmitarrays operating at various frequency ranges of 8-14 GHz, 22-28 GHz, and 28-36 GHz.

The Role of Regulatory T Cells in Cancer Treatment Resistance.

Despite tremendous progress in cancer treatment in recent years, treatment resistance is still a major challenge for a great number of patients. One of the main causes is regulatory T lymphocytes (Tregs), which suppress excessive inflammatory responses via the secretion of immunosuppressive cytokines and upregulate the immune checkpoints. Their abundance causes an immunosuppressive reprogramming of the tumor environment, which is ideal for tumor growth and drug inefficiency. Hence, regiments that can regain tumor immunogenicity are a promising strategy to overcome Tregs-mediated drug resistance. However, to develop effective therapeutic regimens, it is essential to understand the molecular mechanisms of Treg-mediated resistance. In this article, we gathered a comprehensive summary of the current knowledge on molecular mechanisms and the role of Tregs in cancer treatment resistance, including cancer immunotherapy, targeted therapy, chemotherapy, and radiotherapy.

Influence of Material Degradation on Deformation of Paraglider during Flight.

The aim of this article is to determine experimentally and numerically the influence of material degradation on the deformation of a paraglider during flight. The presented method regards numerical modeling of pressure distribution over the wing and its effect on paraglider behavior; the considerations are preceded by experiments on three types of Polyamide 6.6 paraglider fabrics, subjected and not subjected to thermal, UV and flexing degradation. Scanning electron microscope (SEM) records allowed to determine the structural characteristics of the analyzed samples. Air permeability and mechanical tests are the input data for the computational simulations. When a pressure drop of 200 Pa is applied, all the analyzed samples are impermeable, except for those damaged by flexing. Thus, flexing damage has the greatest influence on the air permeability change among all considered aging factors. Aging caused by UV radiation has the greatest influence on mechanical properties. No major influence of thermal ageing on the mechanical properties of the considered samples is observed. Safety factors of the considered materials not subjected to degradation range between 3.94 and 6.00. Safety factor of fabric no. 1 subjected to the UV degradation is equal to 1.33; this result does not secure a safe usage of the considered material. The methodology described in this research can help to predict paraglider covering materials' behavior in flight; it assumes many cases, i.e., applying a new material or the material at any point of its life cycle. Thus, the practical implications of this model supported by numerical methods may result in saving time and cost in producing prototypes, as well as potentially assessing the safety of used wings. Future research activity can introduce the application of different elastic-plastic damage models to determine the paraglider behavior during collapse.

Inter-comparison of marine microbiome sampling protocols.

Research on marine microbial communities is growing, but studies are hard to compare because of variation in seawater sampling protocols. To help researchers in the inter-comparison of studies that use different seawater sampling methodologies, as well as to help them design future sampling campaigns, we developed the EuroMarine Open Science Exploration initiative (EMOSE). Within the EMOSE framework, we sampled thousands of liters of seawater from a single station in the NW Mediterranean Sea (Service d'Observation du Laboratoire Arago [SOLA], Banyuls-sur-Mer), during one single day. The resulting dataset includes multiple seawater processing approaches, encompassing different material-type kinds of filters (cartridge membrane and flat membrane), three different size fractionations (>0.22 µm, 0.22-3 µm, 3-20 µm and >20 µm), and a number of different seawater volumes ranging from 1 L up to 1000 L. We show that the volume of seawater that is filtered does not have a significant effect on prokaryotic and protist diversity, independently of the sequencing strategy. However, there was a clear difference in alpha and beta diversity between size fractions and between these and "whole water" (with no pre-fractionation). Overall, we recommend care when merging data from datasets that use filters of different pore size, but we consider that the type of filter and volume should not act as confounding variables for the tested sequencing strategies. To the best of our knowledge, this is the first time a publicly available dataset effectively allows for the clarification of the impact of marine microbiome methodological options across a wide range of protocols, including large-scale variations in sampled volume.

Bandwidth-Controllable Third-Order Band Pass Filter Using Substrate-Integrated Full- and Semi-Circular Cavities.

The article presents a novel circular substrate-integrated waveguide (SIW) bandpass filter (BPF) with controllable bandwidth. The proposed BPF was configured using two microstrip feed lines, semi-circular SIW cavities, capacitive slots, and inductive vias. The circular cavity was divided into two halves, and the two copies were cascaded. The resulting bisected and cascaded structures were then connected back-to-back. Finally, by introducing two inductive vias to the circular center cavity, a transmission zero was generated. In order to examine the design concept, a coupling matrix was generated. To demonstrate the theory, a third-order BPF was realized, fabricated, and experimentally validated. The BPF prototype features a wide passband of 8.7%, a low insertion loss of 1.1 dB, and a stopband of 1.5 f0 with a rejection level better than 20 dB, which makes it a potential candidate for microwave sensing and communication industries.

The Effectiveness of Cancer Immune Checkpoint Inhibitor Retreatment and Rechallenge-A Systematic Review.

Despite a great success of immunotherapy in cancer treatment, a great number of patients will become resistant. This review summarizes recent reports on immune checkpoint inhibitor retreatment or rechallenge in order to overcome primary resistance. The systematic review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The search was performed using PubMed, Web of Science and Scopus. In total, 31 articles were included with a total of 812 patients. There were 16 retreatment studies and 13 rechallenge studies. We identified 15 studies in which at least one parameter (overall response rate or disease control rate) improved or was stable at secondary treatment. Interval treatment, primary response to and the cause of cessation for the first immune checkpoint inhibitors seem to be promising predictors of secondary response. However, high heterogeneity of investigated cohorts and lack of reporting guidelines are limiting factors for current in-depth analysis.

Frugal Heart Rate Correction Method for Scalable Health and Safety Monitoring in Construction Sites.

Continuous, real-time monitoring of occupational health and safety in high-risk workplaces such as construction sites can substantially improve the safety of workers. However, introducing such systems in practice is associated with a number of challenges, such as scaling up the solution while keeping its cost low. In this context, this work investigates the use of an off-the-shelf, low-cost smartwatch to detect health issues based on heart rate monitoring in a privacy-preserving manner. To improve the smartwatch's low measurement quality, a novel, frugal machine learning method is proposed that corrects measurement errors, along with a new dataset for this task. This method's integration with the smartwatch and the remaining parts of the health and safety monitoring system (built on the ASSIST-IoT reference architecture) are presented. This method was evaluated in a laboratory environment in terms of its accuracy, computational requirements, and frugality. With an experimentally established mean absolute error of 8.19 BPM, only 880 bytes of required memory, and a negligible impact on the performance of the device, this method meets all relevant requirements and is expected to be field-tested in the coming months. To support reproducibility and to encourage alternative approaches, the dataset, the trained model, and its implementation on the smartwatch were published under free licenses.

Solvent influence on the crystal structures of new cadmium tri-tert-butoxysilanethiolate complexes with 1,4-bis(3-aminopropyl)piperazine: luminescence and antifungal activity.

Monocrystals of dinuclear µ-1,4-bis(3-aminopropyl)piperazine-κ4N1,N1':N4,N4'-bis[bis(tri-tert-butoxysilanethiolato-κS)cadmium(II)], [Cd2(C12H27O3SSi)4(C10H24N4)] or [Cd2{SSi(OtBu)3}4(µ-BAPP)], 1, and polynuclear catena-poly[[bis(tri-tert-butoxysilanethiolato-κS)cadmium(II)]-µ-1,4-bis(3-aminopropyl)piperazine-κ2N1':N4'], [Cd(C12H27O3SSi)2(C10H24N4)]n or [Cd{SSi(OtBu)3}2(µ-BAPP)]n, 2, with 1,4-bis(3-aminopropyl)piperazine (BAPP) and tri-tert-butoxysilanethiolate ligands, were obtained from the same ratio of reactants, but with different solvents used for the crystallization processes. The structures and properties of both complexes were characterized using elemental analysis, X-ray diffraction and FT-IR, 1H NMR and luminescence spectroscopy. Applied density functional theory (DFT) computational methods and noncovalent interaction (NCI) analysis were used for geometry optimization and visualization of the interactions between the metallic centres and their surroundings. The X-ray analysis revealed four-coordinate CdII centres bound to two S atoms of the silanethiolate groups and two N atoms of the BAPP ligand; however, it chelates to tertiary and primary N atoms in 1, whilst in 2 it does not chelate and bonds only to RNH2. The photoluminescence properties of complexes 1 and 2 result from free-ligand emission and differ significantly from each other with respect to emission intensity. Additionally, antifungal activity was investigated against 18 isolates of fungi. Compound 1 strongly inhibited the growth of three dermatophytes: Epidermophyton floccosum, Microsporum canis and Trichophyton rubrum.

The Lack of Synergy between Carvedilol and the Preventive Effect of Dexrazoxane in the Model of Chronic Anthracycline-Induced Cardiomyopathy.

The anticancer efficacy of doxorubicin (DOX) is dose-limited because of cardiomyopathy, the most significant adverse effect. Initially, cardiotoxicity develops clinically silently, but it eventually appears as dilated cardiomyopathy with a very poor prognosis. Dexrazoxane (DEX) is the only FDA-approved drug to prevent the development of anthracycline cardiomyopathy, but its efficacy is insufficient. Carvedilol (CVD) is another product being tested in clinical trials for the same indication. This study's objective was to evaluate anthracycline cardiotoxicity in rats treated with CVD in combination with DEX. The studies were conducted using male Wistar rats receiving DOX (1.6 mg/kg b.w. i.p., cumulative dose: 16 mg/kg b.w.), DOX and DEX (25 mg/kg b.w. i.p.), DOX and CVD (1 mg/kg b.w. i.p.), or a combination (DOX + DEX + CVD) for 10 weeks. Afterward, in the 11th and 21st weeks of the study, echocardiography (ECHO) was performed, and the tissues were collected. The addition of CVD to DEX as a cardioprotective factor against DOX had no favorable advantages in terms of functional (ECHO), morphological (microscopic evaluation), and biochemical alterations (cardiac troponin I and brain natriuretic peptide levels), as well as systemic toxicity (mortality and presence of ascites). Moreover, alterations caused by DOX were abolished at the tissue level by DEX; however, when CVD was added, the persistence of DOX-induced unfavorable alterations was observed. The addition of CVD normalized the aberrant expression of the vast majority of indicated genes in the DOX + DEX group. Overall, the results indicate that there is no justification to use a simultaneous treatment of DEX and CVD in DOX-induced cardiotoxicity.

Rapid and reliable re-design of miniaturized microwave passives by means of concurrent parameter scaling and intermittent local tuning.

Re-design of microwave passive components for the assumed operating frequencies or substrate parameters is an important yet a tedious process. It requires simultaneous tuning of relevant circuit variables, often over broad ranges thereof, to ensure satisfactory performance of the system. If the operating conditions at the available design are distant from the intended ones, local optimization is typically insufficient, whereas global search entails excessive computational expenses. The problem is aggravated for miniaturized components, typically featuring large numbers of geometry parameters. Furthermore, owing to their tightly-arranged layouts, compact structures exhibit considerable cross-coupling effects. In order to reliably evaluate electrical characteristics under such conditions full-wave electromagnetic (EM) analysis is mandatory. Needless to say, EM-driven design over broad ranges of operating frequencies is an arduous and costly endeavor. In this paper, we introduce a novel procedure for rapid and reliable re-design of microwave passives. Our methodology involves concurrent scaling of geometry parameters interleaved with local (gradient-based) tuning. The scaling stage allows for low-cost relocation of the operating frequencies of the circuit, whereas the optimization stage ensures continuous (iteration-wise) alignment of the performance figures with their target values. The presented framework is validated using several miniaturized microstrip couplers, re-designed over extended ranges of the center frequencies. For all considered structures, satisfactory designs are successfully identified despite the initial designs being distant from the targets, whereas local tuning turns out to be demonstrably inferior. Apart from its efficacy, one of the most important advantages of the proposed framework is its simplicity, and the lack of problem-dependent control parameters.

Therapy results in pediatric Hodgkin lymphoma - does less mean better? Experience from a single children's oncology center.

Therapy results in pediatric Hodgkin lymphoma reflect remarkable progress in pediatric oncology. In the last decade, relevant development of new therapeutic options for children with refractory or relapsed disease has been made. In this study, we retrospectively analyzed therapy results and risk factors in children treated in a single oncology center according to five therapeutic protocols. Data from 114 children treated by a single institution between 1997 and 2022 were analyzed. Classic Hodgkin lymphoma therapy results were divided into four therapeutic periods: 1997-2009, 2009-2014, 2014-2019, and 2019-2022. For nodular lymphocyte-predominant Hodgkin lymphoma, data from one therapeutic protocol was analyzed. For the entire group, the 5-year probability of overall survival was 93.5%. There were no statistically significant differences between therapeutic periods. The occurrence of B symptoms at diagnosis and incidence of relapse were risk factors for death (p = 0.018 and p < 0.001). Relapse occurred in 5 cases. The 5-year probability of relapse-free survival for the entire group was 95.2%, without significant differences between groups. Patients treated between 1997 and 2009 had over a sixfold higher risk for events, defined as primary progression, relapse, death, or incidence of secondary malignancies (OR = 6.25, p = 0.086). The 5-year probability of event-free survival for all patients was 91.3%. Five patients died, and the most common cause of death was relapse. Modern therapeutic protocols in pediatric Hodgkin lymphoma are marked by excellent outcomes. Patients with disease relapses have a notably high risk of death, and the development of new therapeutic options for this group remains one of the main goals of current trials.

Extended List of Warning Signs in Qualification to Diagnosis and Treatment of Inborn Errors of Immunity in Children and Young Adults.

BACKGROUND AND OBJECTIVES: Inborn errors of immunity (IEI) refer to genetically determined disorders presenting with recurrent infections, autoimmunity, allergies, and malignancies. IEI is now commonly used, replacing the previously used term primary immunodeficiencies (PID). The 10 warning signs of IEI are widely used in the identification patients with IEI. The aim of the study was to determine and compare the utility of the 10 and 14 warning signs in IEI diagnosing. METHODS: A retrospective analysis of 2851 patients was performed (98.17% were subjects under 18 years old and 1.83% were adults). All patients were questioned about the 10 warning signs and four additional signs: severe eczema, allergies, hemato-oncologic disorders and autoimmunity. Sensitivity, specificity, positive and negative predictive values, and odds ratio were calculated for the 10 and 14 warning signs. RESULTS: IEI were diagnosed in a total of 896 (31.4%) patients and excluded in 1955 (68.6%). The strongest predictors of IEI were hemato-oncologic disorders (OR = 11.25; p < 0.001) and autoimmunity (OR = 7.74; p < 0.001). The strongest predictors of severe IEI were hemato-oncologic disorders (OR = 89.26; p < 0.001), positive family history (OR = 25.23; p < 0.001), and autoimmunity (OR = 16.89; p < 0.001). There were 20.4% and 14% of IEI patients without any signs from the 10 and 14 warnings signs, respectively (p < 0.001). 20.3% and 6.8% of patients with severe PIDs had no presence of any signs from 10 and 14 signs, respectively (p = 0.012). CONCLUSIONS: The 10 warning signs have limited usefulness in identifying IEI. The modified list of 14 warning signs seems to represent an effective diagnostic method for the detection of IEI patients, especially those with severe PIDs.