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Jakub Jirka,1 Michal Prauzek,1 Ondrej Krejcar,2 Kamil Kuca2,3 1Department of Cybernetics and Biomedical Engineering, Faculty of Electrical Engineering and Computer Science, VSB – Technical University of Ostrava, Ostrava Poruba, Czech Republic; 2Center for Basic and Applied Research, Faculty of Informatics and Management, University of Hradec Kralove, Hradec Kralove, Czech Republic; 3Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic Objective: The most important part of signal processing for classification is feature extraction as a mapping from original input electroencephalographic (EEG) data space to new features space with the biggest class separability value. Features are not only the most important, but also the most difficult task from the classification process as they define input data and classification quality. An ideal set of features would make the classification problem trivial. This article presents novel methods of feature extraction processing and automatic epilepsy seizure classification combining machine learning methods with genetic evolution algorithms.Methods: Classification is performed on EEG data that represent electric brain activity. At first, the signal is preprocessed with digital filtration and adaptive segmentation using fractal dimensions as the only segmentation measure. In the next step, a novel method using genetic programming (GP) combined with support vector machine (SVM) confusion matrix as fitness function weight is used to extract feature vectors compressed into lower dimension space and classify the final result into ictal or interictal epochs.Results: The final application of GP–SVM method improves the discriminatory performance of a classifier by reducing feature dimensionality at the same time. Members of the GP tree structure represent the features themselves and their number is automatically decided by the compression function introduced in this paper. This novel method improves the overall performance of the SVM classification by dramatically reducing the size of input feature vector.Conclusion: According to results, the accuracy of this algorithm is very high and comparable, or even superior to other automatic detection algorithms. In combination with the great efficiency, this algorithm can be used in real-time epilepsy detection applications. From the results of the algorithm’s classification, we can observe high sensitivity, specificity results, except for the Generalized Tonic Clonic Seizure (GTCS). As the next step, the optimization of the compression stage and final SVM evaluation stage is in place. More data need to be obtained on GTCS to improve the overall classification score for GTCS. Keywords: genetic programming, adaptive segmentation, SVM, fractal dimensions, EEG

While cell-free liquid biopsy (cfLB) approaches provide simple and inexpensive disease monitoring, cell-based liquid biopsy (cLB) may enable additional molecular genetic assessment of systemic disease heterogeneity and preclinical model development. We investigated 71 blood samples of 62 patients with various advanced cancer types and subjected enriched circulating tumor cells (CTCs) to organoid culture conditions. CTC-derived tumoroid models were characterized by DNA/RNA sequencing and immunohistochemistry, as well as functional drug testing. Results were linked to molecular features of primary tumors, metastases, and CTCs; CTC enumeration was linked to disease progression. Of 52 samples with positive CTC counts (≥1) from eight different cancer types, only CTCs from two salivary gland cancer (SGC) patients formed tumoroid cultures (P = 0.0005). Longitudinal CTC enumeration of one SGC patient closely reflected disease progression during treatment and revealed metastatic relapse earlier than clinical imaging. Multiomics analysis and functional in vitro drug testing identified potential resistance mechanisms and drug vulnerabilities. We conclude that cLB might add a functional dimension (to the genetic approaches) in the personalized management of rare, difficult-to-treat cancers such as SGC., (© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Phosphorus (P) has been widely recognized as a substance that is difficult to transport due to its tendency to become easily fixed in the soil. However, many reports demonstrate that groundwater P pollution is rising in humus-rich areas. Research is urgently needed to confirm (or reject) the hypothesis that increased P pollution is related to humus, as there is currently limited quantitative research on this topic. In this study, we conducted a series of batch equilibrium adsorption-desorption experiments and column experiments to quantify the effects of montmorillonite colloids (MCs) and humic acids (HCs, the main components of humus) on the P transport behavior. The results indicate that P's adsorption and desorption behavior on MCs can be well simulated using the Langmuir and Temkin models (R 2  > 0.91). Compared to the non-HC treatments, HCs significantly increased MCs' P adsorption and desorption capacity 5.18 and 7.21 times, respectively. Moreover, HCs facilitated the transport ability of the MC-P mixture through the saturated quartz sand column. In a 0.1 M NaCl solution, the MC-P mixture is nearly completely adsorbed on the surface of quartz sand, with a penetration rate of only 0.5%. In contrast, the HC-MC-P mixture can evidently penetrate further at a rate of 26.1%. The transport parameters fitted using HYDRUS-1D further indicated that the presence of humic acids significantly decreased the deposition coefficients of colloids, thereby enhancing the co-transport of colloids and P through the quartz sand porous medium. The potential mechanism of P pollution in humus-rich areas is likely enhanced by the formation of an HC-colloid-P mixture, which greatly increases the adsorption amount of P on colloids and enhances the electrostatic and spatial repulsion between colloids as well as between colloids and quartz sand. It reduces the aggregation and adsorption of colloids, ultimately transferring P into groundwater through colloid-facilitated co-transport. The findings of this study clarified the relationship between the transport of P, colloids, and HCs, which provides a theoretical basis for explaining the P pollution mechanism in humus-rich areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: The authors declare no competing financial interests.

Purpose: The higher detection efficacy of PSMA PET for oligometastatic recurrence of prostate cancer has promoted new loco-regional treatment options. PSMA-targeted radioguided surgery (PSMA-RGS) was introduced to facilitate salvage surgery of small tumor deposits. The objectives of this retrospective analysis are to describe an independent single-center consecutive cohort of patients undergoing PSMA-RGS and to evaluate its clinical and oncological outcomes., Method: Between 2018 and 2022, 53 patients were treated with PSMA-RGS and 50 patients were available for final analyses. All patients were initially treated with radical prostatectomy (RP) and presented with biochemical recurrence (BCR) with at least one positive lesion on PSMA-PET imaging. After preparation of 99mTc-PSMA-I&S and intravenous injection, surgery was performed by using a gamma-probe intraoperatively., Results: Median age was 70 years (IQR 65-73) and the median PSA at salvage surgery was 1.2 ng/mL (IQR 0.6-3.0). In all patients pathologically positive lesions could be removed during PSMA-RGS. 29 (58%) patients had one pathologically positive lesion, 14 (28%) had two and 7 (14%) had three or more, respectively. The overall complication rate was 26% with 4 (8%), 1 (2%), and 8 (16%) having Clavien-Dindo (CD) type I, II, and IIIb complications, respectively. During the follow-up period 31 (62%) patients experienced BCR and 29 (58%) received further therapy., Conclusions: PSMA-RGS is a promising treatment option to enhance salvage surgery in early biochemical recurrence. However, only 42% of the patients treated with PSMA RGS remain without a biochemical recurrence. Further research is mandatory to identify patients, who profit from PSMA-RGS., (© 2024. The Author(s).)

In this study, we investigated the effects of soil organic carbon (SOC) distribution and water uptake by plant roots on PFAS movement in the vadose zone with a deep groundwater table under temperate, humid climate conditions. Two series of numerical simulations were performed with the HYDRUS computer code, representing the leaching of historical PFOS contamination and the infiltration of water contaminated with PFOA, respectively. We considered soil profiles with three distributions of SOC (no SOC, realistic SOC distribution decreasing with depth, and uniform SOC equal to the content measured in topsoil), three root distributions (bare soil, grassland, and forest), and three soil textures (sand, sandy loam, and loam). The SOC distribution had a profound impact on the velocity of PFOS movement. The apparent retardation factor for realistic SOC distribution was twice as large as for the scenario with no SOC and more than three times smaller than for the scenario with uniformly high SOC content. We also showed that the root distribution in soil profoundly impacts the simulations of PFAS migration through soil. Including the root zone significantly slows down the movement of PFAS, primarily due to increased evapotranspiration and reduced downward water flux. Another effect of water uptake by plant roots is an increase of PFAS concentrations in soil water (evapo-concentration). The evapo-concentration and the slowdown of PFAS movement due to root water uptake are more significant in fine-textured soils than in sand., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Topologically protected spin whirls in ferromagnets are foreseen as the cart-horse of solitonic information technologies. Nevertheless, the future of skyrmionics may rely on antiferromagnets due to their immunity to dipolar fields, straight motion along the driving force and ultrafast dynamics. While complex topological objects were recently discovered in intrinsic antiferromagnets, mastering their nucleation, stabilization and manipulation with energy-efficient means remains an outstanding challenge. Designing topological polar states in magnetoelectric antiferromagnetic multiferroics would allow one to electrically write, detect and erase topological antiferromagnetic entities. Here we stabilize ferroelectric centre states using a radial electric field in multiferroic BiFeO 3 thin films. We show that such polar textures contain flux closures of antiferromagnetic spin cycloids, with distinct antiferromagnetic entities at their cores depending on the electric field polarity. By tuning the epitaxial strain, quadrants of canted antiferromagnetic domains can also be electrically designed. These results open the path to reconfigurable topological states in multiferroic antiferromagnets., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

RNA ligases of the RTCB-type play an essential role in tRNA splicing, the unfolded protein response and RNA repair. RTCB is the catalytic subunit of the pentameric human tRNA ligase complex. RNA ligation by the tRNA ligase complex requires GTP-dependent activation of RTCB. This active site guanylylation reaction relies on the activation factor Archease. The mechanistic interplay between both proteins has remained unknown. Here, we report a biochemical and structural analysis of the human RTCB-Archease complex in the pre- and post-activation state. Archease reaches into the active site of RTCB and promotes the formation of a covalent RTCB-GMP intermediate through coordination of GTP and metal ions. During the activation reaction, Archease prevents futile RNA substrate binding to RTCB. Moreover, monomer structures of Archease and RTCB reveal additional states within the RNA ligation mechanism. Taken together, we present structural snapshots along the reaction cycle of the human tRNA ligase., (© 2024. The Author(s).)

The 2000-2001 and the 2022-2023 Taliban opium bans were and could be two of the largest ever disruptions to a major illegal drug market. To help understand potential implications of the current ban for Europe, this paper analyzes how opioid markets in seven Baltic and Nordic countries responded to the earlier ban, using literature review, key informant interviews, and secondary data analysis. The seven nations' markets responded in diverse ways, including rebounding with the same drug (heroin in Norway), substitution to a more potent opioid (fentanyl replacing heroin in Estonia), and substitution to one with lower risk of overdose (buprenorphine replacing heroin in Finland). The responses were not instantaneous, but rather evolved, sometimes over several years. This variety suggests that it can be hard to predict how drug markets will respond to disruptions, but two extreme views can be challenged. It would be naive to imagine that drug markets will not adapt to shocks, but also unduly nihilistic to presume that they will always just bounce back with no lasting effects. Substitution to another way of meeting demand is possible, but that does not always negate fully the benefits of disrupting the original market. Nonetheless, there is historical precedent for a European country's opioid market switching to synthetic opioids when heroin supplies were disrupted. Given how much that switch has increased overdose rates in Canada and the United States, that is a serious concern for Europe at present. A period of reduced opioid supply may be a particularly propitious time to expand treatment services (as Norway did in the early 2000s)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Competing Interests: Competing interests: AH has consulted, advised and/or performed industry-sponsored research for Philipps, GE, Sonosite, Konica Minolta, Codman & Shrutleff (Johnson and Johnson), Cadence, Insitu Biologics, Heron Therapeutics, Pacira, Baxter and BBraun Medical. AH receives royalty income from BBraun Medical. He owns and directs NYSORA, the New York School of Regional Anesthesia. The other authors declare no conflicts of interest.

Objectives: To (i) develop a methodology for using historical and comparative perspectives to inform policy and (ii) provide evidence for antimicrobial-resistance (AMR) policymaking by drawing on lessons from climate change and tobacco control., Methods: Using a qualitative design, we systematically examined two other complex, large-scale policy issues-climate change and tobacco control-to identify what relevance to AMR can be learned from how these issues have evolved over time. During 2018-2020, we employed a five-stage approach to conducting an exploratory study involving a review of secondary historical analysis, identification of drivers of change, prioritisation of the identified drivers, scenario generation and elicitation of possible policy responses. We sought to disrupt more 'traditional' policy and research spaces to create an alternative where, stimulated by historical analysis, academics (including historians) and policymakers could come together to challenge norms and practices and think creatively about AMR policy design., Results: An iterative process of analysis and engagement resulted in lessons for AMR policy concerning persistent evidence gaps and uncertainty, the need for cross-sector involvement and a collective effort through global governance, the demand for new interventions through more investment in research and innovation, and recognising the dynamic relationship between social change and policy to change people's attitudes and behaviours are crucial towards tackling AMR., Conclusion: We draw on new methodological lessons around the pragmatism of future- and policy-oriented approaches incorporating robust historical and comparative analysis. The study demonstrates proof of concept and offers a reproducible method to advance further methodology, including transferrable policies that could tackle health problems, such as AMR., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Spinal anesthesia with intrathecal morphine (ITM) is a common anesthesia technique for cesarean delivery. The hypothesis was that the addition of ITM will delay micturition in women undergoing cesarean delivery., Methods: Fifty-six ASA physical status I and II women scheduled to undergo elective cesarean delivery under spinal anesthesia were randomized to the PSM group (50 mg prilocaine + 2.5 mcg sufentanil + 100 mcg morphine; n = 30) or PS group (50 mg prilocaine + 2.5 mcg sufentanil; n = 24). The patients in the PS group received a bilateral transverse abdominal plane (TAP) block. The primary outcome was the effect of ITM on the time to micturition and the secondary outcome was the need for bladder re-catheterization., Results: The time to first urge to urinate (8 [6-10] hours in the PSM group versus 6 [4-6] hours in the PS group) and the time to first micturition (10 [8-12] hours in the PSM group versus 6 [6-8] hours in the PS group) were significantly (p < 0.001) prolonged in the PSM group. Two patients in the PSM group met the 800 mL criterium for urinary catheterization after 6 and 8 h respectively., Conclusion: This study is the first randomized trial to demonstrate that the addition of ITM to the standardized mixture of prilocaine and sufentanil significantly delayed micturition., (Copyright © 2023 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Background: Abnormal activity of 18 F-FDG PET/CT is a major Duke criterion in the diagnostic work-up of infective prosthetic valve endocarditis (IE). We hypothesized that quantitative lesion assessment by 18 F-FDG PET/CT-derived standard maximum uptake ratio (SURmax), metabolic volume (MV), and total lesion glycolysis (TLG) might be useful in distinct subgroups of IE patients (e.g. IE-related abscess formation)., Methods: All patients (n = 27) hospitalized in our tertiary IE referral medical center from January 2014 to October 2018 with preoperatively performed 18 F-FDG PET/CT and surgically confirmed IE were included into this retrospective analysis., Results: Patients with surgically confirmed abscess formation (n = 10) had significantly increased MV (by ~ fivefold) and TLG (by ~ sevenfold) as compared to patients without abscess (n = 17). Receiver operation characteristics (ROC) analyses demonstrated that TLG (calculated as MV × SURmean, i.e. TLG (SUR)) had the most favorable area under the ROC curve (0.841 [CI 0.659 to 1.000]) in predicting IE-related abscess formation. This resulted in a sensitivity of 80% and a specificity of 88% at a cut-off value of 14.14 mL for TLG (SUR)., Conclusion: We suggest that 18 F-FDG PET/CT-derived quantitative assessment of TLG (SUR) may provide a novel diagnostic tool in predicting endocarditis-associated abscess formation., (© 2023. The Author(s).)

Computer tomography-derived skeletal muscle index normalized for height in conjunction with muscle density enables single modality-based sarcopenia assessment that accounts for all diagnostic criteria and cutoff recommendations as per the widely accepted European consensus. Yet, the standard approach to quantify skeletal musculature at the third lumbar vertebra is limited for certain patient groups, such as lung cancer patients who receive chest CT for tumor staging that does not encompass this lumbar level. As an alternative, this retrospective study assessed sarcopenia in lung cancer patients treated with curative intent at the tenth thoracic vertebral level using appropriate cutoffs. We showed that skeletal muscle index and radiation attenuation at level T10 correlate well with those at level L3 (Pearson's R = 0.82 and 0.66, p < 0.001). During a median follow-up period of 55.7 months, sarcopenia was independently associated with worse overall (hazard ratio (HR) = 2.11, 95%-confidence interval (95%-CI) = 1.38-3.23, p < 0.001) and cancer-specific survival (HR = 2.00, 95%-CI = 1.19-3.36, p = 0.009) of lung cancer patients following anatomic resection. This study highlights feasibility to diagnose sarcopenia solely by thoracic CT in accordance with the European consensus recommendations. The straightforward methodology offers easy translation into routine clinical care and potential to improve preoperative risk stratification of lung cancer patients scheduled for surgery., (© 2023. The Author(s).)

Opioids play an outsized role in America's drug problems, but they also play a critically important role in medicine. Thus, they deserve special attention. Illegally manufactured opioids (such as fentanyl) are involved in a majority of U.S. drug overdoses, but the problems are broader and deeper than drug fatalities. Depending on the drugs involved, there can be myriad physical and mental health consequences associated with having a substance use disorder. And it is not just those using drugs who suffer. Substance use and related behaviors can significantly affect individuals' families, friends, employers, and wider communities. Efforts to address problems related to opioids are insufficient and sometimes contradictory. Researchers provide a nuanced assessment of America's opioid ecosystem, highlighting how leveraging system interactions can reduce addiction, overdose, suffering, and other harms. At the core of the opioid ecosystem are the individuals who use opioids and their families. Researchers also include detail on ten major components of the opioid ecosystem: substance use disorder treatment, harm reduction, medical care, the criminal legal system, illegal supply and supply control, first responders, the child welfare system, income support and homeless services, employment, and education. The primary audience for this study is policymakers, but it should also be useful for foundations looking for opportunities to create change that have often been overlooked. This study can help researchers better consider the full consequences of policy changes and help members of the media identify the dynamics of interactions that deserve more attention., (Copyright © 2023 RAND Corporation.)

This article addresses data privacy issues as they relate to multisystem collaborations for prearrest deflection into treatment and services for those suffering from a substance use disorder. The authors explore how the US data privacy regulations pose barriers to collaboration and care coordination and how data privacy regulations affect researchers' ability to evaluate the impact of interventions intentioned to facilitate access to care. Fortunately, this regulatory landscape is evolving to strike a balance between protecting health information and sharing it for research, evaluation, and operations, including comments on the newly proposed federal administrative rule that will shape the future of deflection and health access in the United States., (Copyright © 2023 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc. All rights reserved.)