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This paper presents a novel state-feedback robust sliding-mode controller (SFRSMC) based on a mixed H 2 / H ∞ approach to enhance the control performance of hydraulic turbine governing systems (HTGS) with complex conduit systems under external load disturbances and control signal uncertainties. A state-space model incorporating the dynamic responses of the HTGS is developed. The SFRSMC is designed using the sliding-mode equivalent control principle, with a disturbance observer to estimate and mitigate unknown disturbances. To balance robustness and optimality, mixed H 2 / H ∞ linear matrix inequalities (LMIs) are utilized to determine the critical performance sliding matrix via an auxiliary feedback control method. The effectiveness of the proposed control scheme is validated through time-domain simulations under various operating scenarios, including different parameter variations of the HTGS., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The process of aging is a notable risk factor for numerous age-related illnesses. Hence, a reliable technique for evaluating biological age or the pace of aging is crucial for understanding the aging process and its influence on the progression of disease. Epigenetic alterations are recognized as a prominent biomarker of aging, and epigenetic clocks formulated on this basis have been shown to provide precise estimations of chronological age. Extensive research has validated the effectiveness of epigenetic clocks in determining aging rates, identifying risk factors for aging, evaluating the impact of anti-aging interventions, and predicting the emergence of age-related diseases. This review provides a detailed overview of the theoretical principles underlying the development of epigenetic clocks and their utility in aging research. Furthermore, it explores the existing obstacles and possibilities linked to epigenetic clocks and proposes potential avenues for future studies in this field., 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 Inc. All rights reserved.)

When a hydropower unit operates in a sediment-laden river, the sediment accelerates hydro-turbine wear, leading to efficiency loss or even shutdown. Therefore, wear fault diagnosis is crucial for its safe and stable operation. A hydro-turbine wear fault diagnosis method based on improved WT (wavelet threshold algorithm) preprocessing combined with IWSO (improved white shark optimizer) optimized CNN-LSTM (convolutional neural network-long-short term memory) is proposed. The improved WT algorithm is utilized to denoise the preprocessing of the original signals. Chaotic mapping, bird flock search, and cosine elite variation strategies are introduced to enhance the WSO algorithm's robust performance, and the CNN-LSTM model's hyperparameters are optimized using the IWSO algorithm to improve the diagnostic performance. The experimental results show that the accuracy of the proposed method reaches 96.2%, which is 8.9% higher than that of the IWSO-CNN-LSTM model without denoising. The study also found that the diagnostic accuracy of hydro-turbine wear faults increased with increasing sediment concentration in the water. This study can supplement the existing hydro-turbine condition monitoring and fault diagnosis system. Meanwhile, diagnosing wear faults in hydro-turbines can improve power generation efficiency and quality and minimize resource consumption., (© 2024. The Author(s).)

The selection and combination of dose regimens for antimalarials involve complex considerations including pharmacokinetic and pharmacodynamic interactions. In this study, we use immediate ex vivo P. falciparum field isolates to evaluate the effect of cabamiquine and pyronaridine as standalone treatments and in combination therapy. We feed the data into a pharmacometrics model to generate an interaction map and simulate meaningful clinical dose ratios. We demonstrate that the pharmacometrics model of parasite growth and killing provides a detailed description of parasite kinetics against cabamiquine-susceptible and resistant parasites. Pyronaridine monotherapy provides suboptimal killing rates at doses as high as 720 mg. In contrast, the combination of a single dose of 330 mg cabamiquine and 360 mg pyronaridine provides over 90% parasite killing in most of the simulated patients. The described methodology that combines a rapid, 3R-compliant in vitro method and modelling to set meaningful doses for new antimalarials could contribute to clinical drug development., (© 2024. The Author(s).)

Competing Interests: The authors declare no competing interests.

Palladium (Pd) has excellent catalytic performance, its application is seriously limited by low atomic utilization and weak recovery capacity. To solve these problems, we report a universal palladium nanocatalysts preparation strategy by taking advantage of the rich chemistry of sodium alginate (SA). SA units not only self-assemble into a cross-linked porous carboxyl and hydroxyl framework but also can coat different substrates. Benefiting from the distinguished chelation of SA, metallic nanocatalysts can be achieved. As a proof-of-concept demonstration, Pd loading on nano-Fe 3 O 4 modified with SA and investigated their catalytic capabilities. The catalyst was Fe 3 O 4 nanoparticles encapsulated by SA film loaded with 0.4 wt% of Pd. It has a particle size around 100 nm and has good superparamagnetism with a saturation strength of 76.26 emu/g. It exhibited good catalytic activity at TOF = 660 h -1 and TOF = 4311 h -1 in typical Suzuki-Miyaura coupling reaction and the reduction of p-nitrophenol, respectively, and showed appreciable recyclability in the test of recyclability. Thus, our findings demonstrate that recyclable magnetic palladium nanocatalysts have several attractive features, such as easy preparation, outstanding catalytic activity and reusability. This work lays the foundation for the preparation of palladium nanocatalysts and the potential application of SA in the field of catalysts., 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 Elsevier B.V. All rights reserved.)

Up-to-date knowledge of key epidemiological aspects of each Plasmodium species is necessary for making informed decisions on targeted interventions and control strategies to eliminate each of them. This study aims to describe the epidemiology of plasmodial species in Mali, where malaria is hyperendemic and seasonal. Data reports collected during high-transmission season over six consecutive years were analyzed to summarize malaria epidemiology. Malaria species and density were from blood smear microscopy. Data from 6870 symptomatic and 1740 asymptomatic participants were analyzed. The median age of participants was 12 years, and the sex ratio (male/female) was 0.81. Malaria prevalence from all Plasmodium species was 65.20% (95% CI: 60.10-69.89%) and 22.41% (CI: 16.60-28.79%) for passive and active screening, respectively. P. falciparum was the most prevalent species encountered in active and passive screening (59.33%, 19.31%). This prevalence was followed by P. malariae (1.50%, 1.15%) and P. ovale (0.32%, 0.06%). Regarding frequency, P. falciparum was more frequent in symptomatic individuals (96.77% vs. 93.24%, p = 0.014). In contrast, P. malariae was more frequent in asymptomatic individuals (5.64% vs. 2.45%, p < 0.001). P. ovale remained the least frequent species (less than 1%), and no P. vivax was detected. The most frequent coinfections were P. falciparum and P. malariae (0.56%). Children aged 5-9 presented the highest frequency of P. falciparum infections (41.91%). Non- falciparum species were primarily detected in adolescents (10-14 years) with frequencies above 50%. Only P. falciparum infections had parasitemias greater than 100,000 parasites per µL of blood. P. falciparum gametocytes were found with variable prevalence across age groups. Our data highlight that P. falciparum represented the first burden, but other non- falciparum species were also important. Increasing attention to P. malariae and P. ovale is essential if malaria elimination is to be achieved.

The discovery and development of transmission-blocking therapies challenge malaria elimination and necessitate standard and reproducible bioassays to measure the blocking properties of antimalarial drugs and candidate compounds. Most of the current bioassays evaluating the transmission-blocking activity of compounds rely on laboratory-adapted Plasmodium strains. Transmission-blocking data from clinical gametocyte isolates could help select novel transmission-blocking candidates for further development. Using freshly collected Plasmodium falciparum gametocytes from asymptomatic individuals, we first optimized ex vivo culture conditions to improve gametocyte viability and infectiousness by testing several culture parameters. We next pre-exposed ex vivo field-isolated gametocytes to chloroquine, dihydroartemisinin, primaquine, KDU691, GNF179, and oryzalin for 48 h prior to direct membrane feeding. We measured the activity of the drug on the ability of gametocytes to resume the sexual life cycle in Anopheles after drug exposure. Using 57 blood samples collected from Malian volunteers aged 6 to 15 years, we demonstrate that the infectivity of freshly collected field gametocytes can be preserved and improved ex vivo in a culture medium supplemented with 10% horse serum at 4% hematocrit for 48 h. Moreover, our optimized drug assay displays the weak transmission-blocking activity of chloroquine and dihydroartemisinin, while primaquine and oryzalin exhibited a transmission-blocking activity of ~50% at 1 μM. KDU691 and GNF179 both interrupted Plasmodium transmission at 1 μM and 5 nM, respectively. This new approach, if implemented, has the potential to accelerate the screening of compounds with transmission-blocking activity.

Objective: Treatment options and associated biomarkers for advanced and recurrent disease are limited. Endometrial cancers (ECs) with CTNNB1 exon 3 mutations appear to have preferential response to bevacizumab, an anti-angiogenesis treatment, though the mechanism of action is unknown. We aim to identify mediators of bevacizumab-responsive endometrial cancers., Methods: We analyzed RNA expression from TCGA and protein expression from CPTAC to identify likely targets for β-catenin overactivity. We then transiently and stably overexpressed β-catenin in EC cells to confirm the results suggested by our in silico analysis. We performed corroborative experiments by silencing CTNNB1 in mutated cell lines to demonstrate functional specificity. We implanted transduced cells into xenograft models to study microvessel density., Results: CTNNB1-mutated ECs were associated with increased β-catenin and MMP7 protein abundance (P < 0.001), but not VEGF-A protein abundance. Overexpressing β-catenin in EC cells did not increase VEGF-A abundance but did increase expression and secretion of MMP7 (P < 0.03). Silencing CTNNB1 in CTNNB1-mutated cells decreased MMP7 gene expression in EC (P < 0.0001). Microvessel density was not increased., Conclusions: These data provide a mechanistic understanding for bevacizumab-response in CTNNB1-mutated ECs demonstrated in GOG-86P. We hypothesize that overexpressed and secreted MMP7 potentially digests VEGFR-1, releasing VEGF-A, and increasing its availability. These activities may drive the formation of permeable vessels, which contributes to tumor progression, metastasis, and immune suppression. This mechanism is unique to EC and advocates for further clinical trials evaluating this treatment-related biomarker., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs., (© 2021. The Author(s).)

Two hundred patients were refereed for advanced cancer to the oncology department of Luxembourg Hospital in Bamako. All these patients reported intense pain (88 %) which was only treated before admission by OMS level 1 analgesics. It clearly shows that cancer pain is undertreated in Malian peripheral sanitary structures. After evaluation of the pain by analog visual and verbal scales patients, the appropriate analgesic drugs such as morphine (OMS level 3) were given. A control of the pain was obtained in all the patients (100 %) with a dramatic improvement in quality of life. This study emphasizes the need for a pain control program at the Malian state level with a basic education of care givers, hospital-centric networks and access to morphine and opioids at the different levels involved in cancer management., (Copyright © 2021. Published by Elsevier Masson SAS.)