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From precision interventions to precision health
Abstract Precision medicines, or those medicines that are tailored to individual genetic, molecular, physiologic, behavioral, and/or exposure profiles, are being developed at a rapid pace. However, just how precise these interventions are in terms of their mechanisms of action (MOAs), clinical effects, and utility in different individuals, are hard anticipate with current preclinical research and clinical trials strategies. To understand how various genes, processes, organs, clinical phenotypes, etc. may be impacted by an intervention, as well as how many people might benefit from it, appropriate data on living human beings needs to be collected as part of built-for-purpose clinical trials.
Evidence on the Porter hypothesis: China’s Resource Tax Law may be a path to achieve corporate sustainable development
Promoting utilization efficiency and sustainable energy development is crucial for achieving sustainable social development in China, the largest energy producer and consumer worldwide. Accordingly, the Chinese authorities enacted the Resource Tax Law (RTL) on August 26, 2019. Whether such a policy can achieve its desired goals has not been verified. Thus, our study applies a difference-in-differences approach to examine the effect of RTL on a firm’s energy efficiency (EE) with panel data of A-shares from 2017 to 2022. Benchmark analysis and robustness tests demonstrate RTL’s significant effect on resource-based firm’s EE. Additional tests deeply explore the policy effect under different situations. First, RTL boosts more for firms with higher initial EE levels than those with lower levels. Second, RTL enhances EE by promoting firms’ research and development investments, confirming the existence of the Porter hypothesis in China. Third, this policy shows a stronger positive effect on firms with political connections than those without. Finally, we detect that RTL has no significant impact in the western region, while its effect is significantly stronger in the middle region compared to the eastern region. Our empirical findings suggest that corporate firms and the government should adopt appropriate actions to enhance RTL’s policy effect.
Gaseous molecules-mediated electrochemical exfoliation of halogenated MXenes and its boosting in wear-resisting tribovoltaic devices
The transcriptional landscape of atrial fibrillation: A systematic review and meta-analysis
Background Despite advances in understanding atrial fibrillation (AF) pathophysiology, there is limited agreement on the key genes driving its pathophysiology. To understand the genome-wide transcriptomic landscape, we performed a meta-analysis from studies reporting gene expression patterns in atrial heart tissue from patients with AF and controls in sinus rhythm (SR). Methods Bibliographic databases and data repositories were systematically searched for studies reporting gene expression patterns in atrial heart auricle tissue from patients with AF and controls in sinus rhythm. We calculated the pooled differences in individual gene expression from fourteen studies comprising 534 samples (353 AF and 181 SR) to create a consensus signature (CS), from which we identified differentially regulated pathways, estimated transcription factor activity, and evaluated its performance in classifying validation samples as AF or SR. Results Despite heterogeneity in the top differentially expressed genes across studies, the AF-CS in both chambers were robust, showing a better performance in classifying AF status than individual study signatures. Functional analysis revealed commonality in the dysregulated cellular processes between chambers, including extracellular matrix remodeling (highlighting epithelial mesenchymal transition, actin filament organization, and actin binding hallmark pathways), cardiac conduction (including cardiac muscle cell action potential, gated channel activity, and cation channel activity pathways), metabolic derangements (highlighting oxidative phosphorylation and asparagine n linked glycosylation), and innate immune system activity (mainly neutrophil degranulation, and TNFα signaling pathways). Finally, the AF-CS showed a good performance differentiating AF from controls in three validation datasets (two from peripheral blood and one from left ventricle samples). Conclusions Despite variability in individual studies, this meta-analysis elucidated conserved molecular pathways involved in AF pathophysiology across its phenotypes and the potential of a transcriptomic signature in identifying AF from peripheral blood samples. Our work highlights the value of integrating published transcriptomics data in AF and the need for better data deposition practices.
Spatially regulated water-heat transport by fluidic diode membrane for efficient solar-powered desalination and electricity generation
Costs of non-metastatic prostate cancer treatment among privately insured men in the United States
Background Our objective was to quantify the cumulative total and out-of-pocket (OOP) costs for 3 non-metastatic prostate cancer treatment modalities: radiation, surgery, and conservative management at intervals of 1-, 3-, and 5-years post-diagnosis. We predicted these cumulative costs for a typical patient to improve cost transparency, facilitate conversations about potential costs, and to help advance non-metastatic prostate cancer cost evaluation. Methods We used Merative™ MarketScan® Commercial Database data from 2007–2020. The cumulative total costs evaluated from the healthcare sector perspective were patient, clinician, and system/facility costs. We used descriptive statistics to summarize the sociodemographic characteristics of the cohort and a multivariable regression model to estimate the association between each treatment option (radiation, surgery, conservative management) and costs with inverse probability of treatment weighting (IPTW) to account for potential selection bias. We then predicted total and OOP costs defined by sample mode characteristics. Results This cohort included 74,324 patients. Cumulative total and OOP costs were significantly higher for radiation (p < 0.0001) and for surgery (p < 0.0001) at Years 1, 3, and 5 compared to conservative management. For a typical patient, total cumulative cost estimates for conservative management at Years 1/3/5 were: $15,896/$33,436/$48,110 and the cumulative patient OOP costs were: $2,003/$4,540/$6,621. The cumulative total costs for surgery at Years 1/3/5 were: $38,348/$49,424/$60,885 and the cumulative OOP costs were: $2,980/$5,255/$7,221. The cumulative total costs for radiation at Years 1/3/5 were: $65,397/$77,859/$91,497 and the cumulative OOP costs were: $3,151/$5,481/$7,504. Conclusions For all years, the cumulative costs of radiation were highest, followed by surgery and conservative management, respectively. Radiation as the first treatment modality had higher costs compared to surgery and conservative management at the 3 time points. Impact These cost estimates support non-metastatic prostate cancer treatment related cost transparency. These estimates can help researchers evaluate costs and facilitate patient-clinician cost conversations.
Horizontally oriented MRCT-type TADF emitter achieving EQE over 40% for Sky-Blue OLED
Mechanisms of fluoroquinolone resistance among Escherichia coli isolates from urinary tract infections in Thailand
Escherichia coli is the major causative agent for urinary tract infections (UTIs), and fluoroquinolones (FQ) are commonly used in the treatment of patients with UTIs. The surge in FQ-resistant E. coli is an important public health threat worldwide. We investigated the prevalence and mechanisms of FQ resistance among FQ-resistant E. coli isolated from UTI patients. A total of 131 FQ-resistant E. coli strains were characterized and broth microdilution assay showed that 108 strains (82.4%) were highly resistant to ciprofloxacin (MIC ≥ 32 μg/mL). All strains were analyzed for plasmid-mediated quinolone resistance (PMQR) genes, with 37 (28.2%) testing positive. Among the PMQR genes detected, aac(6’)-Ib-cr was the most frequent, found in 30 strains (22.9%), followed by qnrS in 10 strains (7.6%) and qnrB in 1 strain (0.8%). PCR assay showed that all carried acrA, acrB, and tolC genes, but 33 strains (25.2%) revealed at least 4-fold reduction in ciprofloxacin MIC when using PAβN and CCCP as efflux pump inhibitors, indicating the role of the AcrAB efflux pump in ciprofloxacin resistance in these strains. The 19 strains of high-level ciprofloxacin-resistant E. coli were selected to determine the target enzyme alteration by PCR assay and DNA sequencing. Genetic analysis revealed that 16 strains (84.2%) had double mutations in gyrA (S83L and D87 to N or Y) with single mutation in parC (S80I), while 3 strains (15.8%) had double mutations in gyrA (S83L and D87 to N or Y) and parC (S80I and E84 to G or V). The positive efflux activity was linked to increased MIC values of ciprofloxacin (P < 0.001). Overall, the carriage of PMQR genes, efflux activity, and target mutations across E. coli strains contribute to ciprofloxacin resistance, a result that may necessitate a reassessment of the antibiotics in use for empirical UTIs therapy.
Observation of Genuine High-dimensional Multi-partite Non-locality in Entangled Photon States
On the choice of the phase difference increment in radiofrequency-spoiled gradient-echo magnetic resonance imaging of liquids with consideration of diffusion
In magnetic resonance imaging, the radiofrequency-spoiled gradient-echo method aims for fast acquisition of T1-weighted images. The spoiling mechanism is driven by the radiofrequency phase difference increment. In clinical (in-vivo) imaging, the phase difference increments of 50°, 115.4°, 117° and 150° are in standard use. In this work, we examine how accurate these increments guarantee T1-weighting also in free liquids, in particular with different diffusion coefficients. The non-standard phase difference increment 169°, which was shown to improve T1 quantification methods, is considered as well. Signal simulations were performed with the extended phase-graph with diffusion concept; experiments were performed on different liquid phantoms (water with contrast medium, silicone oil). In the simulations, a parameter space consisting of relaxation times, diffusion coefficient, sequence repetition time, flip angle and image resolution was examined. The resulting efficiency of radiofrequency spoiling was quantified by the average deviation of the simulated signal-vs-flipangle curve from the ideal curve. It was found that ideal spoiling is generally better approximated with a phase difference increment of 169° compared to the other examined values. From the four commonly used values, 115.4° is recommended, in particular when the influence of diffusion is low. For clinical in-vivo imaging parameters, all examined values of the phase difference increments offer a good approximation of ideal spoiling as expected. In conclusion, radiofrequency spoiling in free liquids can be improved by using a phase difference increment of 169°.
Spatially blocked split CRISPR-Cas12a system for ultra-sensitive and versatile small molecule activation and detection
Analysis of the impact of different landing heights and lateralities on lower limb joint load based on statistical parametric mapping
This study aimed to investigate the effects of landing height and limb laterality on lower limb joint loading using Statistical Parametric Mapping (SPM), thereby providing insights for injury prevention and optimizing performance in dynamic sports. Twenty male participants were assessed using the Qualisys 3D motion capture system and Kistler 3D force plates during landings from 30 cm and 45 cm on both dominant and non-dominant legs. No significant interaction effects between landing side and height were observed, but landing on the non-dominant leg increased the ankle joint internal rotation moment. The knee’s abduction moment significantly increased during the 17%−37% landing phase, and the hip’s abduction moment significantly increased during the 86%−100% phase. Higher landing height significantly increased vertical ground reaction force (GRF) during the mid-buffering phase (23%−35%). Landing on the dominant side was linked to an elevated risk of lower limb joint injuries due to increased abduction moments at the hip, external rotation moments at the knee, and internal rotation moments at the ankle. Furthermore, greater landing height correlated with higher vertical GRF, intensifying stress on the lower limbs and increasing injury risk. To reduce the risk of injury, training should focus on increasing strength and control of the non-dominant leg and controlling landing height.
Premixing enables loading of long RNA in cubic phase lipid nanoparticles
Advance zonal rectangular low energy adaptive clustering hierarchy algorithm for optimal routing in wireless sensors network
In wireless sensor networks (WSNs), power consumption is a recurring issue. Compared to other modern routing approaches that aim to reduce power consumption, cluster-based forwarding algorithms have been shown to be more energy efficient. Static clustering optimization is the main emphasis of this study on energy-efficient advanced zonal rectangular low energy adaptive clustering hierarchy (EE-AZR-LEACH) optimum routing, which takes a modern technique. To extend the lifespan of the cluster units and the system, we suggest using the multi-hopping approach. The proposed protocol significantly improves the network life time and energy efficiency of WSNs by optimizing static clustering and incorporating multi-hopping techniques. It can outperform existing protocols in power consumption, data transfer and stability, makes it a robust solution for large-scale and energy constrained environment. To help the Cluster Heads (CHs) with data transmission, EE-AZR-LEACH chose a Collaborator(CL) close to the central cluster. To increase the effectiveness of communication between the CHs located in the rectangular region and a central base station, these units took on the role of cluster leaders. The resilience, data transmission rate, power consumption, network endurance, and number of CHs of the system were clearly improved as a consequence. Our suggested routing system performs more effectively than AZR-LEACH, LEACH, MH-LEACH, and SEP in substantial areas. Furthermore, the proposed approach exhibits better convergence within 600 rounds when compared to AZR-LEACH, LEACH, MH-LEACH, and SEP. The findings indicate that after 1500 simulation cycles, the stability intervals for LEACH, MH-LEACH, SEP, and AZR-LEACH are 2.7%, 7.2%, 4.14%, and 5.34%, respectively. The simulation is run using MATLAB. The EE-AZR-LCH optimum routing, on the other hand, has a 6.8% survival rate. The MH-LEACH optimum routing has smaller total network tenure even if it provides a higher stability period than the EE-AZR-LEACH.
Evaluating the influence of prompt formulation on the reliability and repeatability of ChatGPT in implant-supported prostheses
Language models (LLMs) such as ChatGPT are widely available to any dental professional. However, there is limited evidence to evaluate the reliability and reproducibility of ChatGPT-4 in relation to implant-supported prostheses, as well as the impact of prompt design on its responses. This constrains understanding of its application within this specific area of dentistry. The purpose of this study was to evaluate the performance of ChatGPT-4 in generating answers about implant-supported prostheses using different prompts. Thirty questions on implant-supported and implant-retained prostheses were posed, with 30 answers generated per question using general and specific prompts, totaling 1800 answers. Experts assessed reliability (agreement with expert grading) and repeatability (response consistency) using a 3-point Likert scale. General prompts achieved 70.89% reliability, with repeatability ranging from moderate to almost perfect. Specific prompts showed higher performance, with 78.8% reliability and substantial to almost perfect repeatability. The specific prompt significantly improved reliability compared to the general prompt. Despite these promising results, ChatGPT’s ability to generate reliable answers on implant-supported prostheses remains limited, highlighting the need for professional oversight. Using specific prompts can enhance its performance. The use of a specific prompt might improve the answer generation performance of ChatGPT.
Block strength training based on age-related functional consequences in older women
Strength training is a form of healthy ageing in older women. Although recommendations currently exist, some are very broad or fail to cover the needs of aging. Therefore, the purpose of this study was to analyze the effects of blocks strength training based on age-related functional consequences on functional performance in older adult women. 82 community-dwelling older women (70.17 ± 6.04 y) were randomly assigned to either experimental (n = 40) or control (n = 42) group. Experimental group performed a Block Strength Training (BST) program based on strength, power, and muscular endurance, and different level of effort for 9 weeks, and control maintained daily routine with physical activity recommendations. Functional performance was assessed using absolute handgrip strength [AHS], timed up and go [TUG], two-minutes step test [2MST], five times stand-to-sit test [5-SST], 6-m walking speed test [6-WS] pre-post intervention. Statistical analyses were performed using two-way ANOVA (Time*Group) and effect size (partial eta-squared, ŋP2) with a significance level of p < 0.05. BST improved functional performance in the protocols of AHS (21.51 vs. 23.07-kg; + 7%), TUG (8.22 vs. 7.29-sec; + 11%), 2MST (78.76 vs. 97.18-steps; + 23%), 5-SST (12.68 vs. 9.43-sec; + 26%), and 6-WS (1.16 vs. 1.36- m·s-1; + 17%) compared to control (19.31 vs. 19.66-kg; 8.94 vs. 9.26-sec; 62.68 vs. 63.73-steps; 13.99 vs. 14.25-sec; 1.06 vs. 1.06-m·s-1, respectively) in a Time*Group interaction effect (p < 0.01; ŋP2 > 0.11). This BST is effective in improving overall functional performance and thus reducing the risk of physical frailty in community-dwelling older women. These findings strengthen the approach to exercise programming over recommendations, moving toward effective precision dosing for older adults.
Retraction: The CSR perspective: Interplay of technological innovation, ethical leadership and government regulations for sustainable financial performance
Long-run causal impact of the 2011 Economic Adjustment Programme on Portuguese population health
In 2011, Portugal signed a bailout programme to be implemented over a 3-year period, from 2011 to mid-2014. This programme included a set of measures to control and reduce the public sector, which included interventions in areas such as public spending and financing, the labour market, education, and health, among other structural budget measures. The aim of this research is to determine the long-run causal impact of implementing this Economic Adjustment Programme on several population health outcomes. Data was collected for the period 1990–2019 for Portugal. Health outcome indicators account for DALY and HLY, among other general health indicators, but also for some specific mortality rates like those for stroke and cancer. Control variables include percentage of population older than 65, percentage of people with a university degree, CO2 emissions for Portugal, and also health outcomes data for Denmark, Netherlands, Norway and Sweden. The analytical method used is based on a Bayesian structural time series model, which builds a contrafactual scenario representing the absence of the Economic Adjustment Programme for comparison with observed data. The most significant result is the negative long-run causal impact arising from the implementation of the Economic Adjustment Programme in 2011 in Portugal; in other words, health improvements would have been better and faster had the bailout programme not been implemented, despite some level of uncertainty regarding the results. Findings reinforce the idea for the implementation of social and health policies that complement IMF bailout programmes to mitigate negative impacts on population health in the long-run.
Exploratory study on the application of laser-induced cavitation bubble in the treatment of fallopian tube obstruction
Significance: Globally, infertility affects 10–15% of couples, with Fallopian Tube Obstruction (FTO) being a principal cause. Current therapeutic options are inadequate, prompting a demand for effective, less invasive treatments with lower recurrence. Aim: The purpose of this study is to explore the feasibility of employing laser-induced cavitation bubbles (LICB) technology for the treatment of FTO and to experimentally ascertain the optimal laser parameters for this approach. Method: Utilizing an Er:YAG pulsed laser (2.94 μm, 200 μs pulse width, 10 Hz), laser energy was transmitted through a 450 μm sapphire fiber. The study involved 13 rats categorized into control, model, and experimental groups. The laser, with energies of 8.3 mJ, 12.7 mJ, and 15.3 mJ, was applied through the sapphire fibers. The assessment criteria incorporated Hematoxylin-Eosin (HE) staining of the fallopian tubes across all groups, evaluating tubal patency and wall damage to ascertain the most effective laser parameters. Results: In this experiment, the cumulative recanalization success rate in rat models of FTO treated with LICB was observed to be 75%. Specifically, a recanalization rate of 33.3% was achieved with the application of 8 mJ laser energy. The use of 12.7 mJ laser energy resulted in an increased success rate of 85.7%. However, while the application of 15.3 mJ laser energy achieved a 100% recanalization rate, it was accompanied by the formation of hemorrhagic spots on the fallopian tube walls, indicating thermal damage due to the higher energy levels. Optimal treatment parameters were identified as 12.7 mJ laser energy, 10 Hz frequency, and 10-second application. Conclusions: This research suggests that LICB technology can effectively clear fallopian tube obstructions while causing acceptable levels of damage. This indicates its potential as a valuable treatment method worthy of further research for facilitating tubal recanalization.