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Implementing management systems in organisations of all types and sizes often raises the following question: "What benefits will this bring?" Initial resistance and criticism are common as potential challenges are identified during the implementation process. To address this, it is essential to highlight the advantages of these systems and engage stakeholders in supporting management efforts. While the planning, implementation, use, maintenance, auditing, and improvement of management systems are generally voluntary, certification is frequently driven by external factors, particularly customer demands. Employees also stand to gain significantly, with knowledge and information serving as valuable resources, especially for leveraging artificial intelligence. This article explores the management's readiness to adopt and fully utilise two management systems based on international standards: the ISO 30401 Knowledge management system (KMS) and the ISO/IEC 42001 Artificial intelligence management system (AIMS). Through interviews, we assess the challenges and solutions associated with implementing these systems, whether planned or partially adopted. The findings illustrate the synergistic benefits of integrating the KMS and AIMS, demonstrating how their combined use can enhance Integrated Management Systems (IMSs). Such integration supports comprehensive planning, operation, and performance evaluation of processes and services while also promoting continuous improvement. [ABSTRACT FROM AUTHOR]

This study investigates a symmetric fractional-order epidemic model with time delays and non-monotonic incidence rates, considering two viral strains. By confirming the existence, uniqueness, and boundedness of the system's solutions, the research ensures the model's well-posedness, guaranteeing its mathematical soundness and practical relevance. The study calculates and evaluates the equilibrium points and the basic reproduction numbers R 0 1 and R 0 2 to understand the dynamic behavior of the model under different parameter settings. Through the application of the Lyapunov method, the research examines the asymptotic global stability of the system, determining whether it will converge to a particular equilibrium state over time. Furthermore, Hopf bifurcation theory is employed to investigate potential periodic solutions and bifurcation scenarios, highlighting how the system might shift from stability to periodic oscillations under certain conditions. By utilizing the Adams-Bashforth-Moulton numerical simulation method, the theoretical results are validated, reinforcing the conclusions and demonstrating the model's applicability in real-world contexts. It emphasizes the importance of fractional-order models in addressing epidemiological issues related to time delays (τ), individual heterogeneity (m, k), and memory effects (θ), offering greater accuracy compared with traditional integer-order models. In summary, this research provides a theoretical foundation and practical insights, enhancing the understanding and management of epidemic dynamics through fractional-order epidemic models. [ABSTRACT FROM AUTHOR]

This study examines the impact of Bisphenol A (BPA), a prevalent environmental estrogenic toxicant, on the ovarian development of mice. Mice were exposed to varying BPA doses from in utero to postnatal stages, up to weaning (day 21, PND 21) and puberty (day 45, PND 45). The BPA content in the serum of the offspring mice on PND 45 was higher than that of the mice sacrificed at PND 21. However, the ovary organ index of the mice of PND 21 was significantly increased, and the ovarian structure was damaged when exposed to BPA. In contrast, the mice with PND 45 did not show apparent ovarian lesions. On the other hand, granulosa cell apoptosis was detected in both PND 21 and PND 45 mice ovaries, and ERβ was increased under the influence of BPA. Transcriptomic analysis revealed BPA's significant impact on ribosomal gene expression, marked downregulation of Rpl21 and Rpsa, and upregulation of Rps2 in both age groups. These transcriptomic alterations were further corroborated by real-time PCR, highlighting a dose-dependent effect of BPA on Rps2. Our findings confirm BPA's detrimental effects on ovarian health, with more pronounced damage in younger mice, suggesting heightened vulnerability in this group. The study underscores ribosomes as critical targets in BPA-induced ovarian developmental disruptions. [ABSTRACT FROM AUTHOR]

The study proposes an active trailer steering control method for tractor semitrailers to promote the path tracking effect of the trailer portion as well as lateral stability during lane changing. Firstly, a simplified model of a tractor semitrailer is constructed, and the MAP map is formed based on the genetic algorithm for the identification of the key parameters, which improves the model's accuracy. Then the tractor and trailer's yaw rate and sideslip angle at CG are tracked as the control objective and the trailer angle distribution strategy is given. Then the LQR-based corner controller is designed to control the steering actuators of each axle of the trailer. Finally, the effectiveness of the designed control strategy is verified based on the Trucksim/Simulink joint simulation platform and the semi-physical HiL test platform. The simulation results show that the designed controller can effectively improve the path tracking effect of the tractor and the trailer, and at the same time, the lateral stability parameters of the tractor and the trailer are also significantly improved, which improves the driving stability of the tractor semitrailer. [ABSTRACT FROM AUTHOR]

In this research, we introduce and analyze a mathematical model for online social networks, incorporating two distinct delays. These delays represent the time it takes for active users within the network to begin disengaging, either with or without contacting non-users of online social platforms. We focus particularly on the user prevailing equilibrium (UPE), denoted as P * , and explore the role of delays as parameters in triggering Hopf bifurcations. In doing so, we find the conditions under which Hopf bifurcations occur, then establish stable regions based on the two delays. Furthermore, we delineate the boundaries of stability regions wherein bifurcations transpire as the delays cross these thresholds. We present numerical simulations to illustrate and validate our theoretical findings. Through this interdisciplinary approach, we aim to deepen our understanding of the dynamics inherent in online social networks. [ABSTRACT FROM AUTHOR]

Aims. To evaluate the adverse events (and its clinical correlates) in a large prospective cohort of Asian patients with atrial fibrillation (AF) and diabetes mellitus (DM). Material and Methods. We recruited patients with atrial fibrillation (AF) from the Asia-Pacific Heart Rhythm Society (APHRS) AF Registry and included those for whom the diabetic mellitus (DM) status was known. We used Cox-regression analysis to assess the 1-year risk of all-cause death, thromboembolic events, acute coronary syndrome, heart failure and major bleeding. Results. Of 4058 patients (mean age 68.5 ± 11.8 years; 34.4% females) considered for this analysis, 999 (24.6%) had DM (age 71 ± 11 years, 36.4% females). Patients with DM had higher mean CHA2DS2-VASc (2.3 ± 1.6 vs. 4.0 ± 1.5, p < 0.001) and HAS-BLED (1.3 ± 1.0 vs. 1.7 ± 1.1, p < 0.001) risk scores and were less treated with rhythm control strategies compared to patients without DM (18.7% vs. 22.0%). After 1-year of follow-up, patients with DM had higher incidence of all-cause death (4.9% vs. 2.3%, p < 0.001), cardiovascular death (1.3% vs. 0.4%, p = 0.003), and major bleeding (1.8% vs. 0.9%, p = 0.002) compared to those without DM. On Cox regression analysis, adjusted for age, sex, heart failure, coronary and peripheral artery diseases and previous thromboembolic event, DM was independently associated with a higher risk of all-cause death (HR 1.48, 95% CI 1.00–2.19), cardiovascular death (HR 2.33, 95% CI 1.01–5.40), and major bleeding (HR 1.91, 95% 1.01–3.60). On interaction analysis, the impact of DM in determining the risk of all-cause death was greater in young than in older patients (p int = 0.010). Conclusions. Given the high rates of adverse outcomes in these Asian AF patients with DM, efforts to optimize the management approach of these high-risk patients in a holistic or integrated care approach are needed. [ABSTRACT FROM AUTHOR]

Temporary elevation of tumor temperature, also known as hyperthermia, is a safe and well-tolerated treatment modality. The efficacy of hyperthermia can be improved by efficient thermosensitizers, and various candidate drugs, including inhibitors of the heat stress response, have been explored in vitro and in animal models, but clinically relevant thermosensitizers are lacking. Here, we employ unbiased in silico approaches to uncover new mechanisms and compounds that could be leveraged to increase the thermosensitivity of cancer cells. We then focus on elesclomol, a well-performing compound, which amplifies cell killing by hyperthermia by 5- to 20-fold in cell lines and outperforms clinically applied chemotherapy when combined with hyperthermia in vitro. Surprisingly, our findings suggest that the thermosensitizing effects of elesclomol are independent of its previously reported modes of action but depend on copper shuttling. Importantly, we show that, like elesclomol, multiple other copper shuttlers can thermosensitize, suggesting that disturbing copper homeostasis could be a general strategy for improving the efficacy of hyperthermia. [ABSTRACT FROM AUTHOR]

Temperature is a crucial regulator of the rate and direction of biochemical reactions and cell processes. The recent data indicating the presence of local thermal gradients associated with the sites of high-rate thermogenesis, on the one hand, demonstrate the possibility for the existence of "thermal signaling" in a cell and, on the other, are criticized on the basis of thermodynamic calculations and models. Here, we review the main thermometric techniques and sensors developed for the determination of temperature inside living cells and diverse intracellular compartments. A comparative analysis is conducted of the results obtained using these methods for the cytosol, nucleus, endo-/sarcoplasmic reticulum, and mitochondria, as well as their biological consistency. Special attention is given to the limitations, possible sources of errors and ambiguities of the sensor's responses. The issue of biological temperature limits in cells and organelles is considered. It is concluded that the elaboration of experimental protocols for ultralocal temperature measurements that take into account both the characteristics of biological systems, as well as the properties and limitations of each type of sensor is of critical importance for the generation of reliable results and further progress in this field. [ABSTRACT FROM AUTHOR]

Glycosphingolipids (GSLs) are a glycolipid subtype which plays vital roles in numerous biological processes, cell–cell interactions, as well as oncogenesis and ontogenesis. They are ubiquitous molecules found mostly in cell membranes. Abnormal expression of GSLs as well as altered molecular structure have been linked with progression of cancer and metastasis and are involved in the pathophysiology of neurodegenerative, autoimmune, and infectious diseases as well as inherited enzyme defects—glycosphingolipidoses. Matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) plays a leading role in analyzing and characterizing different GSLs, and thus can help to distinguish altered GSL patterns. This review offers insights into the benefits and limitations when using MALDI MS in this field of lipidomic research, with an emphasis on which are the optimal matrices in analyzing GSLs from different tissues (normal and pathological) as well as highlighting GSLs' particular profiles in various cell cultures, and normal and pathological human tissues obtained by MALDI non-imaging MS (non-IMS). These findings can have implications in further understanding the role of altered GSL expression in various pathological conditions and could be a target for future therapies. [ABSTRACT FROM AUTHOR]

Exposure to bisphenol analogues can occur in several ways throughout the food production chain, with their presence at higher concentrations representing a risk to human health. This study aimed to develop effective analytical methods to simultaneously quantify BPA and fifteen bisphenol analogues (i.e., bisphenol AF, bisphenol AP, bisphenol B, bisphenol BP, bisphenol C, bisphenol E, bisphenol F, bisphenol G, bisphenol M, bisphenol P, bisphenol PH, bisphenol S, bisphenol Z, bisphenol TMC, and tetramethyl bisphenol F) present in canned foods and beverages. Samples of foods and beverages available in the Swiss and EU markets (n = 22), including canned pineapples, ravioli, and beer, were prepared and analyzed using QuEChERS GC-MS. The quantification method was compared to a QuEChERS LC-MS/MS analysis. This allowed for the selective and efficient simultaneous quantitative analysis of bisphenol analogues. Quantities of these analogues were present in 20 of the 22 samples tested, with the most frequent analytes at higher concentrations: BPA and BPS were discovered in 78% and 48% of cases, respectively. The study demonstrates the robustness of QuEChERS GC-MS for determining low quantities of bisphenol analogues in canned foods. However, further studies are necessary to achieve full knowledge of the extent of bisphenol contamination in the food production chain and its associated toxicity. [ABSTRACT FROM AUTHOR]

The aim of this research was to study the combined effects of bisphenols and iodine exposure on the thyroid gland during pregnancy. We included 162 pregnant women from a cohort established in Shanghai. Urinary concentrations of bisphenol A, bisphenol B(BPB), bisphenol C(BPC), bisphenol F, bisphenol S, and bisphenol AF(BPAF) were examined. Bayesian kernel machine regression (BKMR) and quantile g-computation models were used. The geometric means of BPA, BPB, BPC, BPF, BPS, BPAF, and ΣBPs levels in urine were 3.03, 0.24, 2.66, 0.36, 0.26, 0.72, and 7.55 μg/g creatinine, respectively. We observed a positive trend in the cumulative effects of BPs and iodine on serum triiodothyronine (FT3) and free thyroxine (FT4), as well as a U-shaped dose–response relationship between BPs and the probability of occurrence of thyroperoxidase autoantibody positivity in women with low urinary iodine concentration. In addition, a synergistic effect on the probability of occurrence of thyroid autoantibody positivity was observed between BPF and BPB, as well as between BPC and BPAF in this study. There were adverse health effects on the thyroid after co-exposure to BPs and iodine. Even if pregnant women were exposed to lower levels of BPs, women with iodine deficiency remained vulnerable to thyroid autoimmune disease. [ABSTRACT FROM AUTHOR]

The paper presents an exact solution to the internal boundary value problem of the field distribution in an electrostatic lens formed by two identical semi-infinite coaxially located round cylinders separated by a slit of finite width and located inside an infinite outer cylinder. The problem is reduced to a system of singular Wiener–Hopf integral equations, which is further solved by the Wiener–Hopf method using factorized Bessel functions. Solutions to the problem for each region inside the infinite outer cylinder are presented as exponentially converging series in terms of eigenfunctions and eigenvalues. Using the obtained formulas, a numerical calculation of the axial distribution of the potential of a two-electrode lens was made for various values of the radii of the outer and inner cylinders. [ABSTRACT FROM AUTHOR]

The occurrence of bisphenol A (BPA) and its structural analogs, known as endocrine disruptors is widely reported. Consumers could be exposed to these chemicals through canned foods, leading to health risks. Considerable advances have occurred in the pathogenic mechanism, migration law, and analytical methodologies for these compounds in canned foods. However, the confusion and controversies on sources, migration, and health impacts have plagued researchers. This review aimed to provide insights and perspectives on sources, migration, effects on human health, and surveillance of these chemicals in canned food products. Current trends in the determination of BPA and its structural analogs have focused on mass spectroscopy and electrochemical sensor techniques. Several factors, including pH, time, temperature, and volume of the headspace in canned foods, could affect the migration of the chemicals. Moreover, it is necessary to quantify the proportion of them originating from the can material used in canned product manufacturing. In addition, adverse reaction research about exposure to low doses and combined exposure with other food contaminants will be required. We strongly believe that the information presented in this paper will assist in highlighting the research needs on these chemicals in canned foods for future risk evaluations. [ABSTRACT FROM AUTHOR]

Proteins are essential macromolecules that carry out a plethora of biological functions. The thermal stability of proteins is an important property that affects their function and determines their suitability for various applications. However, current experimental approaches, primarily thermal proteome profiling, are expensive, labor-intensive, and have limited proteome and species coverage. To close the gap between available experimental data and sequence information, a novel protein thermal stability predictor called DeepSTABp has been developed. DeepSTABp uses a transformer-based protein language model for sequence embedding and state-of-the-art feature extraction in combination with other deep learning techniques for end-to-end protein melting temperature prediction. DeepSTABp can predict the thermal stability of a wide range of proteins, making it a powerful and efficient tool for large-scale prediction. The model captures the structural and biological properties that impact protein stability, and it allows for the identification of the structural features that contribute to protein stability. DeepSTABp is available to the public via a user-friendly web interface, making it accessible to researchers in various fields. [ABSTRACT FROM AUTHOR]

Veno-venous Extracorporeal Membrane Oxygenation (VV-ECMO) therapy has become increasingly used and established in many hospitals as a routine treatment. With ECMO-therapy being a resource-demanding procedure, it is of interest whether a more prolonged VV-ECMO treatment would hold sufficient therapeutic success. Our retrospective study included all VV-ECMO runs from 1 January 2020 to 31 June 2022. We divided all runs into four groups (<14 days, 14–27, 28–49, 50+) of different durations and looked for differences overall in hospital survival. Additionally, corresponding treatments and therapeutic modalities, as well as laboratory results, were analyzed. We included 117 patients. Of those, 97 (82.9%) received a VV-ECMO treatment longer than two weeks. We did not find a significant association between ECMO duration (p = 0.15) and increased mortality though a significant correlation between the patients' age and their probability of survival (p = 0.02). Notably, we found significantly lower interleukin-6 levels with an increase in therapy duration (p < 0.01). Our findings show no association between the duration of ECMO therapy and mortality. Thus, the treatment duration alone may not be used for making assumptions about the prospect of survival. However, attention is also increasingly focused on long-term outcomes, such as post-intensive care syndrome with severe impairments. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is one of the most commonly used substances in the manufacture of various everyday products. Growing concerns about its hazardous properties, including endocrine disruption and genotoxicity, have led to its gradual replacement by presumably safer analogues in manufacturing plastics. The widespread use of BPA and, more recently, its analogues has increased their residues in the environment. However, our knowledge of their toxicological profiles is limited and their combined effects are unknown. In the present study, we investigated the toxic effects caused by single bisphenols and by the combined exposure of BPA and its two analogues, BPAP and BPC, after short (24-h) and prolonged (96-h) exposure in HepG2 spheroids. The results showed that BPA did not reduce cell viability in HepG2 spheroids after 24-h exposure. In contrast, BPAP and BPC affected cell viability in HepG2 spheroids. Both binary mixtures (BPA/BPAP and BPA/BPC) decreased cell viability in a dose-dependent manner, but the significant difference was only observed for the combination of BPA/BPC (both at 40 µM). After 96-h exposure, none of the BPs studied affected cell viability in HepG2 spheroids. Only the combination of BPA/BPAP decreased cell viability in a dose-dependent manner that was significant for the combination of 4 µM BPA and 4 µM BPAP. None of the BPs and their binary mixtures studied affected the surface area and growth of spheroids as measured by planimetry. In addition, all BPs and their binary mixtures studied triggered oxidative stress, as measured by the production of reactive oxygen species and malondialdehyde, at both exposure times. Overall, the results suggest that it is important to study the effects of BPs as single compounds. It is even more important to study the effects of combined exposures, as the combined effects may differ from those induced by single compounds. [ABSTRACT FROM AUTHOR]

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used for patients with cardiogenic shock or cardiac arrest. However, survival rates remain low. It is unclear to what extent ECMO patients benefit from the ECMO team learning curve. Therefore, we aimed to analyze our mobile ECMO program patients from the past seven years to evaluate if a learning curve benefits patients' outcomes. We analyzed 111 patients from our databank who were supported with a VA-ECMO and brought to our hospital from January 2015 to December 2021. Patients were divided into two groups: survival (n = 70) and non-survival (n = 41). As expected, complications after ECMO implantation were more severe in the non-survivor group. The incidence of thromboembolic events (p = 0.002), hepatic failure (p < 0.001), renal failure (p = 0.002), dialysis (p = 0.002) and systemic inflammatory response syndrome (SIRS, p = 0.044) occurred significantly more often compared with the survivor group. We were able to show that despite our extensive experience in terms of ECMO retrieval program the high mortality and morbidity rates stay fairly the same over the years. This displays that we have to focus even more on patient selection and ECMO indication. [ABSTRACT FROM AUTHOR]

The "block and lock" strategy is one approach that might elicit a sterilizing cure for HIV-1 infection. The "block" refers to a compound's ability to inhibit latent HIV-1 proviral transcription, while the "lock" refers to its capacity to induce permanent proviral silencing. We previously identified PF-3758309, a pan-isoform inhibitor of p21-activated kinases (PAKs), as a potent inhibitor of HIV-1 latency reversal. The goal of this study was to define the mechanism(s) involved. We found that both 24ST1NLESG cells (a cell line model of HIV-1 latency) and purified CD4+ naïve and central memory T cells express high levels of PAK2 and lower levels of PAK1 and PAK4. Knockdown of PAK1 or PAK2, but not PAK4, in 24ST1NLESG cells resulted in a modest, but statistically significant, decrease in the magnitude of HIV-1 latency reversal. Overexpression of PAK1 significantly increased the magnitude of latency reversal. A phospho-protein array analysis revealed that PF-3758309 down-regulates the NF-κB signaling pathway, which provides the most likely mechanism by which PF-3758309 inhibits latency reversal. Finally, we used cellular thermal shift assays combined with liquid chromatography and mass spectrometry to ascertain whether PF-3758309 off-target binding contributed to its activity. In 24ST1NLESG cells and in peripheral blood mononuclear cells, PF-3758309 bound to mitogen-activated protein kinase 1 and protein kinase A; however, knockdown of either of these kinases did not impact HIV-1 latency reversal. Collectively, our study suggests that PAK1 and PAK2 play a key role in the maintenance of HIV-1 latency. [ABSTRACT FROM AUTHOR]

Dissolved oxygen (DO) is deeply involved in preserving the life of cellular tissues and human beings due to its key role in cellular metabolism: its alterations may reflect important pathophysiological conditions. DO levels are measured to identify pathological conditions, explain pathophysiological mechanisms, and monitor the efficacy of therapeutic approaches. This is particularly relevant when the measurements are performed in vivo but also in contexts where a variety of biological and synthetic media are used, such as ex vivo organ perfusion. A reliable measurement of medium oxygenation ensures a high-quality process. It is crucial to provide a high-accuracy, real-time method for DO quantification, which could be robust towards different medium compositions and temperatures. In fact, biological fluids and synthetic clinical fluids represent a challenging environment where DO interacts with various compounds and can change continuously and dynamically, and further precaution is needed to obtain reliable results. This study aims to present and discuss the main oxygen detection and quantification methods, focusing on the technical needs for their translation to clinical practice. Firstly, we resumed all the main methodologies and advancements concerning dissolved oxygen determination. After identifying the main groups of all the available techniques for DO sensing based on their mechanisms and applicability, we focused on transferring the most promising approaches to a clinical in vivo/ex vivo setting. [ABSTRACT FROM AUTHOR]

Faced with new and as yet unmet medical need, the stark underperformance of the pharmaceutical discovery process is well described if not perfectly understood. Driven primarily by profit rather than societal need, the search for new pharmaceutical products—small molecule drugs, biologicals, and vaccines—is neither properly funded nor sufficiently systematic. Many innovative approaches remain significantly underused and severely underappreciated, while dominant methodologies are replete with problems and limitations. Design is a component of drug discovery that is much discussed but seldom realised. In and of itself, technical innovation alone is unlikely to fulfil all the possibilities of drug discovery if the necessary underlying infrastructure remains unaltered. A fundamental revision in attitudes, with greater reliance on design powered by computational approaches, as well as a move away from the commercial imperative, is thus essential to capitalise fully on the potential of pharmaceutical intervention in healthcare. [ABSTRACT FROM AUTHOR]

The stability of proteins is an essential property that has several biological implications. Knowledge about protein stability is important in many ways, ranging from protein purification and structure determination to stability in cells and biotechnological applications. Experimental determination of thermal stabilities has been tedious and available data have been limited. The introduction of limited proteolysis and mass spectrometry approaches has facilitated more extensive cellular protein stability data production. We collected melting temperature information for 34,913 proteins and developed a machine learning predictor, ProTstab2, by utilizing a gradient boosting algorithm after testing seven algorithms. The method performance was assessed on a blind test data set and showed a Pearson correlation coefficient of 0.753 and root mean square error of 7.005. Comparison to previous methods indicated that ProTstab2 had superior performance. The method is fast, so it was applied to predict and compare the stabilities of all proteins in human, mouse, and zebrafish proteomes for which experimental data were not determined. The tool is freely available. [ABSTRACT FROM AUTHOR]

The fundamental goal of this research is to investigate the quantitative relationship between technology-oriented knowledge management, innovation, e-governance, and smart city performance using knowledge management-based service science theory and diffusion of innovation theory. Previous research has found a connection between knowledge management, innovation, e-governance, and e-service delivery. We believe these are not only direct connections but also contextual and interactive relationships, so we explored the significance of innovation as a mediator between knowledge management and e-service delivery. Furthermore, we investigated the moderating impact of e-governance on the relationship between innovation and e-service delivery. A survey questionnaire was administered to the population of public officers, entrepreneurs, and citizens, from metropolitan cities for data sampling, and SPSS was applied to analyze data of 569 participants collected from South Korea, Pakistan, Japan, and Bangladesh. We discovered from the analysis that the direct relationships are contextual because innovation mediates the relationship between knowledge management and e-service delivery, and e-governance plays a moderating role in the relationship between innovation and e-service delivery. Based on the outcomes from quantitative analysis, all our proposed hypotheses in this study were supported significantly. [ABSTRACT FROM AUTHOR]

Research focused on succinate dehydrogenase (SDH) and its substrate, succinate, culminated in the 1950s accompanying the rapid development of research dedicated to bioenergetics and intermediary metabolism. This allowed researchers to uncover the implication of SDH in both the mitochondrial respiratory chain and the Krebs cycle. Nowadays, this theme is experiencing a real revival following the discovery of the role of SDH and succinate in a subset of tumors and cancers in humans. The aim of this review is to enlighten the many questions yet unanswered, ranging from fundamental to clinically oriented aspects, up to the danger of the current use of SDH as a target for a subclass of pesticides. [ABSTRACT FROM AUTHOR]

In order to improve the estimation accuracy of the state of charge (SOC) of lithium iron phosphate power batteries for vehicles, this paper studies the prominent hysteresis phenomenon in the relationship between the state of charge and the open circuit voltage (OCV) curve of the lithium iron phosphate battery. Through the hysteresis characteristic test of the battery, the corresponding SOC-OCV data when the battery is charged or discharged from different SOC states are analyzed. According to the approximation trend of the hysteresis main loop curve by the data points, a differential equation model for approximately solving the charge or discharge hysteresis small loop curve under any SOC state is established, and the adjustment parameters of the model are analyzed and debugged in sections. Then, based on the second-order Thevenin equivalent circuit model, the forgetting factor recursive least squares method is used to identify the model parameters online. When deriving the relationship between the OCV and SOC, according to the state of charge and discharge and the current SOC value, the approximate model of the real hysteresis small loop curve in the current state is solved in real time, and the extended Kalman recursion algorithm is substituted to correct the corresponding relationship between the OCV and SOC. Finally, the integrated forgetting factor recursive least squares online parameter identification and extended Kalman filter to correct the SOC-OCV hysteresis relationship in real time considering the hysteresis characteristics are used to complete the real-time estimation of the SOC of the lithium iron phosphate battery. The synthesis algorithm proposed in this paper and the Kalman filter algorithm without considering the hysteresis characteristics are compared and verified under the Dynamic Stress Test (DST) data. Based on the method proposed in this paper, the maximum error of terminal voltage is 0.86%, the average error of terminal voltage is 0.021%, the root mean square error (RMSE) of terminal voltage is 0.042%, the maximum error of SOC estimation is 1.22%, the average error of SOC estimation is 0.41%, the average error of SOC estimation is 0.41%, and the RMSE of SOC estimation is 0.57%. The results show that the comprehensive algorithm proposed in this paper has higher accuracy in both terminal voltage following and SOC estimation. [ABSTRACT FROM AUTHOR]

Coordinated migration of B cells within and between secondary lymphoid tissues is required for robust antibody responses to infection or vaccination. Secondary lymphoid tissues normally expose B cells to a low O 2 (hypoxic) environment. Recently, we have shown that human B cell migration is modulated by an O 2 -dependent molecular switch, centrally controlled by the hypoxia-induced (transcription) factor-1 α (HIF1A), which can be disrupted by the immunosuppressive calcineurin inhibitor, cyclosporine A (CyA). However, the mechanisms by which low O 2 environments attenuate B cell migration remain poorly defined. Proteomics analysis has linked CXCR4 chemokine receptor signaling to cytoskeletal rearrangement. We now hypothesize that the pathways linking the O 2 sensing molecular switch to chemokine receptor signaling and cytoskeletal rearrangement would likely contain phosphorylation events, which are typically missed in traditional transcriptomic and/or proteomic analyses. Hence, we have performed a comprehensive phosphoproteomics analysis of human B cells treated with CyA after engagement of the chemokine receptor CXCR4 with CXCL12. Statistical analysis of the separate and synergistic effects of CyA and CXCL12 revealed 116 proteins whose abundance is driven by a synergistic interaction between CyA and CXCL12. Further, we used our previously described algorithm BONITA to reveal a critical role for Lymphocyte Specific Protein 1 (LSP1) in cytoskeletal rearrangement. LSP1 is known to modulate neutrophil migration. Validating these modeling results, we show experimentally that LSP1 levels in B cells increase with low O 2 exposure, and CyA treatment results in decreased LSP1 protein levels. This correlates with the increased chemotactic activity observed after CyA treatment. Lastly, we directly link LSP1 levels to chemotactic capacity, as shRNA knock-down of LSP1 results in significantly increased B cell chemotaxis at low O 2 levels. These results directly link CyA to LSP1-dependent cytoskeletal regulation, demonstrating a previously unrecognized mechanism by which CyA modulates human B cell migration. Data are available via ProteomeXchange with identifier PXD036167. [ABSTRACT FROM AUTHOR]

In recent decades, the electromagnetic induction quenching approach has been widely applied in the surface treatment process of steel engine parts such as crankshafts. In this paper, the strengthening effect of this approach was selected to be the object of study. First, the multi-physics coupling phenomenon was established by a 3D finite element simulation approach. Then, the fatigue property of the crankshaft was predicted based on the combination of the residual stress field obtained in the previous step and a chosen multi-axial fatigue damage model. Finally, a corresponding experiment verification was carried out to check the accuracy of the prediction. The results showed that the method proposed by this paper can provide high enough accuracy in predicting the fatigue property of two types of commonly used steel crankshafts. [ABSTRACT FROM AUTHOR]

A numerical parameter estimation method, based on input-output integro-differential polynomials in a bounded-error framework is investigated in this paper. More precisely, the measurement noise and parameters belong to connected sets (in the proposed work, intervals). First, this method, based on the Rosenfeld–Groebner elimination algorithm, is presented. The latter provides differential equations containing derivatives, sometimes of high order. In order to improve the numerical results, a pretreatment of the differential relations is done and consists in integration. The new relations contain, essentially, integrals depending only on the outputs. In comparison with the initial relations, they are less sensitive to measurement noise. Finally, the impact of the size of the measurement noise domain on the estimated intervals is studied. [ABSTRACT FROM AUTHOR]

Background: Direct oral anticoagulants (DOACs) are the preferred anticoagulant drugs for the prevention of atrial fibrillation (AF)-related thromboembolic complications and for the treatment and the prevention of recurrences of venous thromboembolism (VTE). The evaluation of self-reported adverse drug reactions (ADRs) available from databases of drug-regulatory agencies such as the Italian Medicines Agency (AIFA) pharmacovigilance database represents a novel aid to guide decision making. Objective: To assess the safety profile of DOACs by analyzing ADR rates in the real-world Italian scenario. Methods: Post-marketing surveillance data recorded by the National Pharmacovigilance Network were retrieved for the time period 2017–2021 from the AIFA online site. The following data were collected for each DOAC: total ADR number, serious ADR number, gastrointestinal (GI) ADR, intracranial hemorrhage events (ICH ADR), and more frequently reported ADR for the study year. The safety profile was expressed by the risk index (RI). Results: Rivaroxaban use was associated with consistent and stable low rates of serious ADR, GI ADR, and ICH ADR across the 5-year study period. Rivaroxaban and apixaban showed the lowest RI for serious ADR and GI ADR, while rivaroxaban use was associated with significantly lower ICH events as compared to apixaban. Dabigatran was related to the highest RIs for every ADR class, in particular GI ADRs. Conclusions: DOACs presented an acceptable safety profile in the current post-market analysis. However, rivaroxaban and apixaban were associated with more favorable safety profiles as compared to dabigatran, while rivaroxaban provoked statistically significantly fewer ICH events as compared to apixaban. [ABSTRACT FROM AUTHOR]

The price V of a contingent claim in finance, insurance and economics is defined as an expectation of a stochastic expression. If the underlying uncertainty is modeled as a strong Markov process X, the Feynman–Kac theorem suggests that V is the unique solution of a boundary problem for a parabolic equation. In the case of PDO with constant symbols, simple probabilistic tools explained in this paper can be used to explicitly calculate expectations under very weak conditions on the process and study the regularity of the solution. Assuming that the Feynman–Kac theorem holds, and a more general boundary problem can be localized, the local results can be used to study the existence and regularity of solutions, and derive efficient numerical methods. In the paper, difficulties for the realization of this program are analyzed, several outstanding problems are listed, and several closely efficient methods are outlined. [ABSTRACT FROM AUTHOR]

Biological creatures with unique surface wettability have long served as a source of inspiration for scientists and engineers. More specifically, materials exhibiting extreme wetting properties, such as superhydrophilic and superhydrophobic surfaces, have attracted considerable attention because of their potential use in various applications, such as self-cleaning fabrics, anti-fog windows, anti-corrosive coatings, drag-reduction systems, and efficient water transportation. In particular, the engineering of surface wettability by manipulating chemical properties and structure opens emerging biomedical applications ranging from high-throughput cell culture platforms to biomedical devices. This review describes design and fabrication methods for artificial extreme wetting surfaces. Next, we introduce some of the newer and emerging biomedical applications using extreme wetting surfaces. Current challenges and future prospects of the surfaces for potential biomedical applications are also addressed. [ABSTRACT FROM AUTHOR]

Infectious respiratory diseases such as the current COVID-19 have caused public health crises and interfered with social activity. Given the complexity of these novel infectious diseases, their dynamic nature, along with rapid changes in social and occupational environments, technology, and means of interpersonal interaction, respiratory protective devices (RPDs) play a crucial role in controlling infection, particularly for viruses like SARS-CoV-2 that have a high transmission rate, strong viability, multiple infection routes and mechanisms, and emerging new variants that could reduce the efficacy of existing vaccines. Evidence of asymptomatic and pre-symptomatic transmissions further highlights the importance of a universal adoption of RPDs. RPDs have substantially improved over the past 100 years due to advances in technology, materials, and medical knowledge. However, several issues still need to be addressed such as engineering performance, comfort, testing standards, compliance monitoring, and regulations, especially considering the recent emergence of pathogens with novel transmission characteristics. In this review, we summarize existing knowledge and understanding on respiratory infectious diseases and their protection, discuss the emerging issues that influence the resulting protective and comfort performance of the RPDs, and provide insights in the identified knowledge gaps and future directions with diverse perspectives. [ABSTRACT FROM AUTHOR]

During seed germination, desiccation tolerance is lost in the radicle with progressing radicle protrusion and seedling establishment. This process is accompanied by comprehensive changes in the metabolome and proteome. Germination of Arabidopsis seeds was investigated over 72 h with special focus on the heat-stable proteome including late embryogenesis abundant (LEA) proteins together with changes in primary metabolites. Six metabolites in dry seeds known to be important for seed longevity decreased during germination and seedling establishment, while all other metabolites increased simultaneously with activation of growth and development. Thermo-stable proteins were associated with a multitude of biological processes. In the heat-stable proteome, a relatively similar proportion of fully ordered and fully intrinsically disordered proteins (IDP) was discovered. Highly disordered proteins were found to be associated with functional categories development, protein, RNA and stress. As expected, the majority of LEA proteins decreased during germination and seedling establishment. However, four germination-specific dehydrins were identified, not present in dry seeds. A network analysis of proteins, metabolites and amino acids generated during the course of germination revealed a highly connected LEA protein network. [ABSTRACT FROM AUTHOR]

We present a case study applying hierarchical Bayesian estimation on high-throughput protein melting-point data measured across the tree of life. We show that the model is able to impute reasonable melting temperatures even in the face of unreasonably noisy data. Additionally, we demonstrate how to use the variance in melting-temperature posterior-distribution estimates to enable principled decision-making in common high-throughput measurement tasks, and contrast the decision-making workflow against simple maximum-likelihood curve-fitting. We conclude with a discussion of the relative merits of each workflow. [ABSTRACT FROM AUTHOR]

In this paper, a digital hydraulic variable control method based on multi-way valve spool displacement feedback is proposed, which combines the advantages of low cost and high reliability of the loader fixed displacement pump hydraulic system, and the distinguished energy saving effect of the loader variable pump hydraulic system. Based on the principle of hydraulic resistance, the mathematical model of flow-pressure of multi-way valve was established. Meanwhile, the theoretical structure of a valve spool suitable for digital hydraulic system was deduced. On this basis, an improvement scheme of the valve spool was proposed in combination with machining feasibility. The simulation model of multi-way valve was established, the correctness of which was verified by experiment with the significance test method, and the valve port parameters of the multi-way valve were optimized by genetic algorithm. The simulation model before and after optimization was analyzed by AMESim software. The simulation results showed that the digital hydraulic system can basically realize the function of a variable system, and the energy consumption was significantly reduced compared with the fixed displacement pump hydraulic system. The optimized valve spool structure of the digital hydraulic system had more stable load characteristics than the fixed displacement pump system and a larger speed range. The increase range accounts for about 27% of the total stroke. [ABSTRACT FROM AUTHOR]

Mitochondria are the source of internal heat which influences all cellular processes. Hence, monitoring mitochondrial temperature provides a unique insight into cell physiology. Using a thermosensitive fluorescent probe MitoThermo Yellow (MTY), we have shown recently that mitochondria within human cells are maintained at close to 50 °C when active, increasing their temperature locally by about 10 °C. Initially reported in the HEK293 cell line, we confirmed this finding in the HeLa cell line. Delving deeper, using MTY and MTX (MitoThermo X), a modified version of MTY, we unraveled some caveats related to the nature of these charged fluorophores. While enabling the assessment of mitochondrial temperature in HEK and HeLa cell lines, the reactivity of MTY to membrane potential variations in human primary skin fibroblasts precluded local temperature monitoring in these cells. Chemical modification of MTY into MTX did not result in a temperature probe unresponsive to membrane potential variations that could be universally used in any cell type to determine mitochondrial temperature. Thus, the cell-type dependence of MTY in measuring mitochondrial temperature, which is likely due to the variable binding of this dye to specific internal mitochondrial components, should imply cautiousness while using these nanothermometers for mitochondrial temperature analysis. [ABSTRACT FROM AUTHOR]

Abiotic stresses are among the principal limiting factors for productivity in agriculture. In the current era of continuous climate changes, the understanding of the molecular aspects involved in abiotic stress response in plants is a priority. The rise of -omics approaches provides key strategies to promote effective research in the field, facilitating the investigations from reference models to an increasing number of species, tolerant and sensitive genotypes. Integrated multilevel approaches, based on molecular investigations at genomics, transcriptomics, proteomics and metabolomics levels, are now feasible, expanding the opportunities to clarify key molecular aspects involved in responses to abiotic stresses. To this aim, bioinformatics has become fundamental for data production, mining and integration, and necessary for extracting valuable information and for comparative efforts, paving the way to the modeling of the involved processes. We provide here an overview of bioinformatics resources for research on plant abiotic stresses, describing collections from -omics efforts in the field, ranging from raw data to complete databases or platforms, highlighting opportunities and still open challenges in abiotic stress research based on -omics technologies. [ABSTRACT FROM AUTHOR]

In recent decades, the elderly population has been rapidly increasing in many countries. Such patients are susceptible to Gram-negative septic shock, namely endotoxin shock. Mortality due to endotoxin shock remains high despite recent advances in medical care. The generalized Shwartzman reaction is well recognized as an experimental endotoxin shock. Aged mice are similarly susceptible to the generalized Shwartzman reaction and show an increased mortality accompanied by the enhanced production of tumor necrosis factor (TNF). Consistent with the findings in the murine model, the in vitro Shwartzman reaction-like response is also age-dependently augmented in human peripheral blood mononuclear cells, as assessed by enhanced TNF production. Interestingly, age-dependently increased innate lymphocytes with T cell receptor-that intermediate expression, such as that of CD8+CD122+T cells in mice and CD57+T cells in humans, may collaborate with macrophages and induce the exacerbation of the Shwartzman reaction in elderly individuals. However, endotoxin tolerance in mice, which resembles a mirror phenomenon of the generalized Shwartzman reaction, drastically reduces the TNF production of macrophages while strongly activating their bactericidal activity in infection. Importantly, this effect can be induced in aged mice. The safe induction of endotoxin tolerance may be a potential therapeutic strategy for refractory septic shock in elderly patients. [ABSTRACT FROM AUTHOR]

Lipid disorders have been associated with glomerulopathies, a distinct type of renal pathologies, such as nephrotic syndrome. Global analyses targeting kidney lipids in this pathophysiologic context have been extensively performed, but most often regardless of the architectural and functional complexity of the kidney. The new developments in mass spectrometry imaging technologies have opened a promising field in localized lipidomic studies focused on this organ. In this article, we revisit the main works having employed the Matrix Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) technology, and the few reports on the use of TOF-Secondary Ion Mass Spectrometry (TOF-SIMS). We also present a first analysis of mouse kidney cortex sections by cluster TOF-SIMS. The latter represents a good option for high resolution lipid imaging when frozen unfixed histological samples are available. The advantages and drawbacks of this developing field are discussed. [ABSTRACT FROM AUTHOR]