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BackgroundDrugs taken during pregnancy can affect maternal and child health outcomes, but few studies have compared the safety and virological efficacy of different antiretroviral therapy (ART) regimens. We report the primary safety outcomes from enrolment up to 50 weeks post partum and a secondary virological efficacy outcome at 50 weeks post partum of three commonly used ART regimens for HIV-1.MethodsIn this multicentre, open-label, randomised, controlled, phase 3 trial, we enrolled pregnant women aged 18 years or older with confirmed HIV-1 infection at 14-28 weeks of gestation. Women were enrolled at 22 clinical research sites in nine countries (Botswana, Brazil, India, South Africa, Tanzania, Thailand, Uganda, the USA, and Zimbabwe). Participants were randomly assigned (1:1:1) to one of three oral regimens: dolutegravir, emtricitabine, and tenofovir alafenamide; dolutegravir, emtricitabine, and tenofovir disoproxil fumarate; or efavirenz, emtricitabine, and tenofovir disoproxil fumarate. Up to 14 days of antepartum ART before enrolment was permitted. Women with known multiple gestation, fetal anomalies, acute significant illness, transaminases more than 2·5 times the upper limit of normal, or estimated creatinine clearance of less than 60 mL/min were excluded. Primary safety analyses were pairwise comparisons between ART regimens of the proportion of maternal and infant adverse events of grade 3 or higher up to 50 weeks post partum. Secondary efficacy analyses at 50 weeks post partum included a comparison of the proportion of women with plasma HIV-1 RNA of less than 200 copies per mL in the combined dolutegravir-containing groups versus the efavirenz-containing group. Analyses were done in the intention-to-treat population, which included all randomly assigned participants with available data. This trial was registered with ClinicalTrials.gov, NCT03048422.FindingsBetween Jan 19, 2018, and Feb 8, 2019, we randomly assigned 643 pregnant women to the dolutegravir, emtricitabine, and tenofovir alafenamide group (n=217), the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group (n=215), and the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (n=211). At enrolment, median gestational age was 21·9 weeks (IQR 18·3-25·3), median CD4 count was 466 cells per μL (308-624), and median HIV-1 RNA was 903 copies per mL (152-5183). 607 (94%) women and 566 (92%) of 617 liveborn infants completed the study. Up to the week 50 post-partum visit, the estimated probability of experiencing an adverse event of grade 3 or higher was 25% in the dolutegravir, emtricitabine, and tenofovir alafenamide group; 31% in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group; and 28% in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (no significant difference between groups). Among infants, the estimated probability of experiencing at least one adverse event of grade 3 or higher by postnatal week 50 was 28% overall, with small and non-statistically significant differences between groups. By postnatal week 50, 14 infants whose mothers were in the efavirenz-containing group (7%) died, compared with six in the combined dolutegravir groups (1%). 573 (89%) women had HIV-1 RNA data available at 50 weeks post partum: 366 (96%) in the dolutegravir-containing groups and 186 (96%) in the efavirenz-containing group had HIV-1 RNA less than 200 copies per mL, with no significant difference between groups.InterpretationSafety and efficacy data during pregnancy and up to 50 weeks post partum support the current recommendation of dolutegravir-based ART (particularly in combination with emtricitabine and tenofovir alafenamide) rather than efavirenz, emtricitabine, and tenofovir disoproxil fumarate, when started in pregnancy.FundingNational Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health.

Fusarium is a soil-borne pathogen that poses a serious threat to the quality and yield of hundreds of crops worldwide, particularly tobacco production. Using metabolomics technology, we investigated natural metabolites from disease-conducting soil (DCS) and disease-suppressing soil (DSS) of tobacco rhizosphere as fungicides to control tobacco Fusarium wilt (TFW), which is mainly caused by Fusarium oxysporum. Furthermore, the antifungal mechanisms of these natural metabolites were preliminarily elucidated through various assessments, including antifungal activity determination, chemotaxis effect tests, PI staining experiments, and measurements of extracellular conductivity and protein content. Metabolomics results showed that the DCS with three different disease grades (G1, G5 and G9 groups) had significantly higher levels of 15, 14 and 233 differential rhizosphere metabolites (DRMs) and significantly lower levels of 72, 152 and 170 DRMs compared to the DSS (G0 group). According to KEGG pathway analysis, these DRMs were found to be enriched in the caffeine metabolism, biosynthesis of phenylpropanoids, galactose metabolism and tyrosine metabolism, etc. Linustatin, scopoletin and phenylpropiolic acid were picked out from these DRMs and found to have suppressive activity against F. oxysporum through correlation analysis and antifungal experiments. The three DRMs showed strong inhibitory effects on the growth and spore germination of F. oxysporum at concentrations of 0.5 mM or higher in each test period. Furthermore, F. oxysporum showed a phobotaxis effect against these three DRMs at concentrations as low as 0.25 mM. Finally, we found that the three DRMs had an inhibitory effect on F. oxysporum by destroying the integrity of the cell membrane and increasing the membrane permeability of F. oxysporum. This study firstly reports the inhibition activity of phenylpropiolic acid and linustatin on F. oxysporum, providing a practical and environmentally friendly method for biocontrol of TFW by using natural fungicides.

Opaque surfaces, such as walls, are well-known for their significant contributions to heat loss and energy demands in buildings. However, transparent surfaces, such as windows, are equally critical to a building's energy performance. The design of these transparent elements requires a careful balance of various factors, including window size, glazing type, and orientation, each of which plays a pivotal role in enhancing energy efficiency. This study explores the optimization of these factors during the design process, emphasizing their impact on the overall building performance.This research evaluates the potential energy savings in a building archetype representative of the Algerian building stock. Utilizing the EnergyPlus simulation tool, the study conducted 1152 simulations on a baseline model to generate a comprehensive dataset detailing the building's energy demands for heating and cooling across various climatic conditions. The findings reveal that annual energy savings for this type of housing essentially depend on its climatic zone and can range from 6.92 % for a hot semi-arid climate (Bsh) to reach a maximum of 9.75 % in a cold semi-arid climate (Bsk), a window-to-wall ratio (WWR) of 60 % typically maximizes energy efficiency, low-E glazing proved most effective in most cases, although regions needing significant solar protection favored alternative glazing types. Optimal window orientation generally trends Eastward, except in regions where southern exposure better supports solar management, highlighting the complex relationship between architectural design choices and energy efficiency.

The optimization of the active control system is pivotal in achieving an acceptable performance level while minimizing control costs. The optimal location of actuators, efficient control force, and adequate vibration reduction are critical objectives in control system optimization. This study introduces a novel optimization algorithm, the Population-Guided and Modified Reference-Point Based Non-Dominated Sorting Genetic Algorithm-II (PMR-NSGA-II), tailored for actuator placement and tuning that incorporates input and output user preference. The analysis focuses on optimizing the vibration control of a 20-story steel frame building. The PMR-NSGA-II could reduce the computational expenses of three objectives optimization by guiding the initial population using prospective population prediction and orienting the search towards a reference point. The pre-calculated input energy distribution guides the determination of the prospective initial population. The reference point, along with the allowable drift and actuator capacity constraints, focuses the search process to efficiently obtain the Pareto fronts with less effort wasted to explore the less preferred areas in the search space. The non-dominated sorting and elitist operators are also employed to fasten the convergence. The structural analysis is conducted via non-linear time history analysis with seven ground motions considered. The PMR-NSGA-II exhibits significant computational efficiency in the active control system optimization. Results demonstrate that PMR-NSGA-II could provide the near-optimal solution closest to the reference point with a smaller population size and a faster convergence rate than the NSGA-II. The computational time per generation of the proposed PMR-NSGA-II is 1.36 to 2.43 times faster than NSGA-II for the seven ground motions analyzed. By applying PMR-NSGA-II, the number of individuals that need to be assessed to reach convergence is reduced by 50 % to 88 % compared to NSGA-II. Ultimately, the near-optimal configurations could significantly reduce the building responses and increase the performance level of the building based on FEMA 356 and ASCE 41 acceptance criteria.

This study explores the impact of ESG ratings on corporate performance, focusing on achieving sustainable development and corporate sustainability through innovation within the context of high-quality global economic growth. In recent years, ESG ratings have garnered significant attention in the financial sector, influencing corporate strategy and performance management. While some argue that ESG activities might detract from profitability, others highlight that firms with strong ESG performance can access low-cost capital, thereby enhancing overall performance. Using a sample of China’s A-share listed companies from 2009 to 2021, this research examines the influence and mechanisms of ESG ratings on corporate performance. The findings indicate a significant positive relationship between ESG ratings and corporate performance, which remains robust after rigorous testing. Mediation analysis reveals that ESG ratings improve corporate performance by alleviating financing constraints and enhancing corporate reputation. Furthermore, the performance-enhancing effects of ESG ratings are more pronounced in firms with robust internal controls and private enterprises. This research provides empirical evidence to support stronger ESG investment and the refinement of the ESG rating system.

Sexual violence is a criminal act which basically requires very strict law enforcement. The dimensions of sexual violence regulated in the Criminal Code are not yet able to fully regulate the forms of sexual violence that occur, where regulations related to sexual violence are regulated in articles 281-295 of the Criminal Code which have limited clarification. on rape and molestation. So, with the enactment of law number 12 of 2022 concerning criminal acts of sexual violence (UU TPKS) on May 9 2022, it becomes the new legal basis for enforcing criminal acts of sexual violence. The TPKS Law becomes a specialist Lex for regulations previously contained in the Criminal Code. The presence of the TPKS Law is a new positive law that provides clear and specific updates regarding the types of criminal acts that are classified as criminal acts of sexual violence, the rights of victims of criminal acts of sexual violence, as well as protection for victims of criminal acts of sexual violence in law enforcement. The formulation of the problem in this research is how to compare legal regulations and legal protection between the Criminal Code and Law number 12 of 2022 regarding criminal acts of sexual violence. This research uses normative juridical research methods, using secondary data sources, with primary legal materials in the form of related laws which are supported by secondary legal materials in the form of related books and journals. Based on the results of this research, the research results will be summarized as to what the position of victims is. criminal acts of sexual violence which are in the Criminal Code and Law no. 12 of 2002 which regulates different legal provisions and legal protection which in the Criminal Code is not clearly regulated regarding legal protection for victims of criminal acts of sexual violence which in law number 12 of 2002 is clearly regulated regarding the protection of victims and prevention efforts against the occurrence of criminal acts of sexual harassment.

Abstract In oxygen (O2)‐controlled cell culture, an indispensable tool in biological research, it is presumed that the incubator setpoint equals the O2 tension experienced by cells (i.e., pericellular O2). However, it is discovered that physioxic (5% O2) and hypoxic (1% O2) setpoints regularly induce anoxic (0% O2) pericellular tensions in both adherent and suspension cell cultures. Electron transport chain inhibition ablates this effect, indicating that cellular O2 consumption is the driving factor. RNA‐seq analysis revealed that primary human hepatocytes cultured in physioxia experience ischemia‐reperfusion injury due to cellular O2 consumption. A reaction‐diffusion model is developed to predict pericellular O2 tension a priori, demonstrating that the effect of cellular O2 consumption has the greatest impact in smaller volume culture vessels. By controlling pericellular O2 tension in cell culture, it is found that hypoxia vs. anoxia induce distinct breast cancer transcriptomic and translational responses, including modulation of the hypoxia‐inducible factor (HIF) pathway and metabolic reprogramming. Collectively, these findings indicate that breast cancer cells respond non‐monotonically to low O2, suggesting that anoxic cell culture is not suitable for modeling hypoxia. Furthermore, it is shown that controlling atmospheric O2 tension in cell culture incubators is insufficient to regulate O2 in cell culture, thus introducing the concept of pericellular O2‐controlled cell culture.

Flooding is a natural disaster that poses a threat to both people and the environment, necessitating proactive assessment and mitigation strategies to protect vulnerable communities and ecosystems. These measures are necessary to reduce the risk of flooding and moderate the impact of rainfall. In this study, an Analytical Hierarchy Process (AHP) was used to evaluate flood risk in a data-limited region by integrating Remote Sensing (RS) and Geographic Information System (GIS) methods. The study identified several key flood risk indicators, including topographic wetness index, elevation, slope, land cover, precipitation, distance to river, distance to road, and NDVI. The flood risk map had a score range of 8.71–30.99 %, with higher scores indicating a greater susceptibility to flooding. These scores were then used to classify the flood risk into five categories: very low, low, moderate, high, and very high. The percentages of regions falling into each category were 8.71 %, 23.52 %, 30.99 %, 22.68 %, and 14.09 % respectively. The area under the Curve (AUC) approach was used to validate the flood risk map, which showed a high degree of accuracy (0.86). The results of this study provide valuable insights for monitoring, and forecasting the probability of floods in the Dosso Region.

Neoantigens are peptides derived from non-synonymous mutations presented by human leukocyte antigens (HLAs), which are recognized by antitumour T cells1-14. The large HLA allele diversity and limiting clinical samples have restricted the study of the landscape of neoantigen-targeted T cell responses in patients over their treatment course. Here we applied recently developed technologies15-17 to capture neoantigen-specific T cells from blood and tumours from patients with metastatic melanoma with or without response to anti-programmed death receptor 1 (PD-1) immunotherapy. We generated personalized libraries of neoantigen-HLA capture reagents to single-cell isolate the T cells and clone their T cell receptors (neoTCRs). Multiple T cells with different neoTCR sequences (T cell clonotypes) recognized a limited number of mutations in samples from seven patients with long-lasting clinical responses. These neoTCR clonotypes were recurrently detected over time in the blood and tumour. Samples from four patients with no response to anti-PD-1 also demonstrated neoantigen-specific T cell responses in the blood and tumour to a restricted number of mutations with lower TCR polyclonality and were not recurrently detected in sequential samples. Reconstitution of the neoTCRs in donor T cells using non-viral CRISPR-Cas9 gene editing demonstrated specific recognition and cytotoxicity to patient-matched melanoma cell lines. Thus, effective anti-PD-1 immunotherapy is associated with the presence of polyclonal CD8+ T cells in the tumour and blood specific for a limited number of immunodominant mutations, which are recurrently recognized over time.

It is well established in educational research that metacognitive monitoring of performance assessed by self-reports, for instance, asking students to report their confidence in provided answers, is based on heuristic cues rather than on actual success in the task. Subjective self-reports are also used in educational research on cognitive load, where they refer to the perceived amount of mental effort invested in or difficulty of each task item. In the present study, we examined the potential underlying bases and the predictive value of mental effort and difficulty appraisals compared to confidence appraisals by applying metacognitive concepts and paradigms. In three experiments, participants faced verbal logic problems or one of two non-verbal reasoning tasks. In a between-participants design, each task item was followed by either mental effort, difficulty, or confidence appraisals. We examined the associations between the various appraisals, response time, and success rates. Consistently across all experiments, we found that mental effort and difficulty appraisals were associated more strongly than confidence with response time. Further, while all appraisals were highly predictive of solving success, the strength of this association was stronger for difficulty and confidence appraisals (which were similar) than for mental effort appraisals. We conclude that mental effort and difficulty appraisals are prone to misleading cues like other metacognitive judgments and are based on unique underlying processes. These findings challenge the accepted notion that mental effort appraisals can serve as reliable reflections of cognitive load.