Optimization Techniques Research Articles

GalaxyDock-DL: Protein-Ligand Docking by Global Optimization and Neural Network Energy.

With the recent introduction of deep learning techniques into the prediction of biomolecular structures, structure prediction performance has significantly improved, and the potential for biomedical applications has increased considerably. The prediction of protein-ligand complex structures, applicable to the atomistic understanding of biomolecular functions and the effective design of drug molecules, has also improved with the introduction of deep learning. In this paper, it is demonstrated that docking performance can be greatly enhanced by training an energy function that encapsulates physical effects using deep learning within the framework of the traditional protein-ligand docking method. The advantage of this method, called GalaxyDock-DL, lies in its minimal overfitting to the training data compared to several existing deep learning-based protein-ligand docking methods. Unlike some recent deep learning methods, it does not use information about known binding pocket center positions. Instead, the results of this docking method show a systematic dependence on the physical properties of the target protein-ligand complexes such as atomic thermal fluctuations and binding affinity. GalaxyDock-DL utilizes the global optimization technique of the conventional protein-ligand docking method, GalaxyDock, and a neural network energy function trained to stabilize the native state compared to non-native states, just as physical free energy does. This physical principle-based approach suggests directions not only for future structure prediction involving structurally flexible biomolecular complexes but also for predicting binding affinity, thereby providing guidance for the effective design of biofunctional ligands.

Assessing Surgeons' Attitude to Teaching Intra-Corporeal Anastomosis.

Introduction: There is a controversy in minimally invasive colorectal procedures regarding choosing optimal technique between intra-corporeal (ICA) and extra-corporeal anastomosis (ECA). Previous studies recognize the short-term benefits in right hemicolectomy with intra-corporeal approach; however, ICA can result in increased operative difficulty. The aim of this study is to understand attitudes towards teaching ICA in colorectal procedures and how this varies between subspeciality training. Methods: Active members of General Surgeons Australia were contacted through email to participate in a voluntary, unincentivized survey. Demographic details were collected and participants were asked to rate agreement for simulation-based training for increasing adoption of ICA through a Likert scale and when preferences for teaching ICA. Descriptive statistics were completed to describe frequencies and ordinal regression was completed to determine factors for Likert scale question. Results: There were 43 respondents and most participants recognized that ECA was easier to teach trainees and should be taught first. 53.5% of respondents recognized that simulation-based training would assist the adoption of ICA. Surgeons who routinely close bowel or enteric defects intra-corporeally are 354% more likely to show an interest in simulation-based training for adopting ICA, however, surgeons who are not involved in teaching trainees did not show an interest in simulation-based training. Conclusion: There is significant agreement that ECA forms the basis to learn ICA and simulation-based training would assist with the uptake of ICA. However, a multimodal approach, including expanding training avenues and providing financial incentives, would be necessary to enhance the adoption of ICA in colorectal surgery.

Dynamic K-Decay Learning Rate Optimization for Deep Convolutional Neural Network to Estimate the State of Charge for Electric Vehicle Batteries

This paper introduces a novel convolutional neural network (CNN) architecture tailored for state of charge (SoC) estimation in battery management systems (BMS), accompanied by an advanced optimization technique to enhance training efficiency. The proposed CNN architecture comprises multiple one-dimensional convolutional (Conv1D) layers followed by batch normalization and one-dimensional max-pooling (MaxPooling1D) layers, culminating in dense layers for regression-based SoC prediction. To improve training effectiveness, we introduce an advanced dynamic k-decay learning rate scheduling method. This technique dynamically adjusts the learning rate during training, responding to changes in validation loss to fine-tune the training process. Experimental validation was conducted on various drive cycles, including the dynamic stress test (DST), Federal Urban Driving Schedule (FUDS), Urban Dynamometer Driving Schedule (UDDS), United States 2006 Supplemental Federal Test Procedure (US06), and Worldwide Harmonized Light Vehicles Test Cycle (WLTC), spanning four temperature conditions (−5 °C, 5 °C, 25 °C, 45 °C). Notably, the test error of DST and US06 drive cycles, the CNN with optimization achieved a mean absolute error (MAE) of 0.0091 and 0.0080, respectively at 25 °C, and a root mean square error (RMSE) of 0.013 and 0.0095, respectively. In contrast, the baseline CNN without optimization yielded higher MAE and RMSE values of 0.011 and 0.014, respectively, on the same drive cycles. Additionally, training time with the optimization technique was significantly reduced, with a recorded time of 324.14 s compared to 648.59 s for the CNN without optimization at room temperature. These results demonstrate the effectiveness of the proposed CNN architecture combined with advanced dynamic learning rate scheduling in accurately predicting SoC across various battery types and drive cycles. The optimization technique not only improves prediction accuracy but also substantially reduces training time, highlighting its potential for enhancing battery management systems in electric vehicle applications.

Optimization of activity-driven event detection for long-term ambulatory urodynamics.

Lower urinary tract dysfunction (LUTD) is a debilitating condition that affects millions of individuals worldwide, greatly diminishing their quality of life. The use of wireless, catheter-free implantable devices for long-term ambulatory bladder monitoring, combined with a single-sensor system capable of detecting various bladder events, has the potential to significantly enhance the diagnosis and treatment of LUTD. However, these systems produce large amounts of bladder data that may contain physiological noise in the pressure signals caused by motion artifacts and sudden movements, such as coughing or laughing, potentially leading to false positives during bladder event classification and inaccurate diagnosis/treatment. Integration of activity recognition (AR) can improve classification accuracy, provide context regarding patient activity, and detect motion artifacts by identifying contractions that may result from patient movement. This work investigates the utility of including data from inertial measurement units (IMUs) in the classification pipeline, and considers various digital signal processing (DSP) and machine learning (ML) techniques for optimization and activity classification. In a case study, we analyze simultaneous bladder pressure and IMU data collected from an ambulating female Yucatan minipig. We identified 10 important, yet relatively inexpensive to compute signal features, with which we achieve an average 91.5% activity classification accuracy. Moreover, when classified activities are included in the bladder event analysis pipeline, we observe an improvement in classification accuracy, from 81% to 89.0%. These results suggest that certain IMU features can improve bladder event classification accuracy with low computational overhead.Clinical Relevance: This work establishes that activity recognition may be used in conjunction with single-channel bladder event detection systems to distinguish between contractions and motion artifacts for reducing the incorrect classification of bladder events. This is relevant for emerging sensors that measure intravesical pressure alone or for data analysis of bladder pressure in ambulatory subjects that contain significant abdominal pressure artifacts.

PLC and SCADA based temperature control of heat exchanger system through fractional order PID controller using metaheuristic optimization techniques

PLC and SCADA based temperature control of heat exchanger system through fractional order PID controller using metaheuristic optimization techniques

Bayesian optimization algorithms for accelerator physics

Accelerator physics relies on numerical algorithms to solve optimization problems in online accelerator control and tasks such as experimental design and model calibration in simulations. The effectiveness of optimization algorithms in discovering ideal solutions for complex challenges with limited resources often determines the problem complexity these methods can address. The accelerator physics community has recognized the advantages of Bayesian optimization algorithms, which leverage statistical surrogate models of objective functions to effectively address complex optimization challenges, especially in the presence of noise during accelerator operation and in resource-intensive physics simulations. In this review article, we offer a conceptual overview of applying Bayesian optimization techniques toward solving optimization problems in accelerator physics. We begin by providing a straightforward explanation of the essential components that make up Bayesian optimization techniques. We then give an overview of current and previous work applying and modifying these techniques to solve accelerator physics challenges. Finally, we explore practical implementation strategies for Bayesian optimization algorithms to maximize their performance, enabling users to effectively address complex optimization challenges in real-time beam control and accelerator design. Published by the American Physical Society 2024

Design of a precise ensemble expert system for crop yield prediction using machine learning analytics

AbstractAgriculture is facing significant challenges in the development of crop yield forecasts, which are important aspects of decision‐making at the international, regional, and local levels. The area of agriculture is attracting growing attention because of increasing the demand for food supplies. To ensure future food supplies, crop yield prediction (CYP) provides the best decision‐making to assist farmers in agricultural yield forecasting efficiently. Nevertheless, CYP is a difficult endeavor because of the intricacy of the underlying mechanisms and the effect of numerous factors, including weather patterns, soil characteristics, and crop management techniques. In today's era, ensemble learning (EL) approaches have recently demonstrated significant promise for enhancing the reliability and accuracy of CYP. The success of the EL techniques depends on several facts, including how the base learner models are trained and how these are combined. This study provides important insights into the EL techniques for CYP. This paper proposes an expert system model named precise ensemble expert system for crop yield prediction (PEESCYP) to predict the best crop for agricultural land. The proposed PEESCYP model employs multiple imputation by chained equation (MICE) data imputation technique to treat the missing values of the collected dataset, the isolation forest (IF) technique for outlier detection, the ant colony optimization (ACO) technique to perform feature selection, robust scaling (RS) technique to perform data normalization, and the extra tree (ET) is used for classification to overcome the variance and overfitting problem of the single classifiers. The measurements of the proposed PEESCYP model have been collected by means of accuracy, precision, recall, and F‐1 score using a prepared dataset, which is collected from International Crops Research Institute for the Semi‐Arid Tropics (ICRISAT), and the proposed model is compared with different single‐classifier based ML models, EL models, and various existing models available in the literature. The results of this experiment underline that the proposed PEESCYP model outperforms the others.

Economic evaluation of a two-strain Hepatitis C vaccination model in Bangladesh using optimal control technique

Economic evaluation of a two-strain Hepatitis C vaccination model in Bangladesh using optimal control technique

EOFA: An Extended Version of the Optimal Foraging Algorithm for Global Optimization Problems

The problem of finding the global minimum of a function is applicable to a multitude of real-world problems and, hence, a variety of computational techniques have been developed to efficiently locate it. Among these techniques, evolutionary techniques, which seek, through the imitation of natural processes, to efficiently obtain the global minimum of multidimensional functions, play a central role. An evolutionary technique that has recently been introduced is the Optimal Foraging Algorithm, which is a swarm-based algorithm, and it is notable for its reliability in locating the global minimum. In this work, a series of modifications are proposed that aim to improve the reliability and speed of the above technique, such as a termination technique based on stochastic observations, an innovative sampling method and a technique to improve the generation of offspring. The new method was tested on a series of problems from the relevant literature and a comparative study was conducted against other global optimization techniques with promising results.

A deep experimental analysis of energy‐proficient firewall policies and security practices for resource limited wireless networks

AbstractThe role of firewalls and security principles in resource‐limited wireless networks and Wireless Sensor Networks (WSN) is more expected than in any dedicated network environment. The advanced wireless technologies and emerging fashion of autonomous wireless network nodes are mostly expecting resilient firewall services with multi‐level security policies. Wireless networks are classified under sensor networks, Internet of Things (IoT) mobile networks, and so forth. According to the expectations, security frameworks are gradually invented around the communication platform using various ideologies. The novel ideology and respective implementation effort open better solutions against wireless network attacks. Anyhow, the minimal production of time complexity, energy complexity, and computation overhead from any novel security approach is always considered under the best practices. The complexity levels directly affect the wireless node's energy consumption ability and operational spans severely. The energy optimization techniques and load‐balancing techniques integrated into multi‐class firewall rules are extremely useful solutions for resource‐limited wireless networks. This article has been motivated to analyze the recent firewall techniques and secure data communication mechanisms used for securing wireless networks. Consequently, the practice of comparative literature analysis helps to improve the current limitations identified under the classified categories of security mechanisms such as energy‐optimized security principles and load‐balanced security principles. The establishment of secure and energy‐optimized multi‐class firewall rules in each wireless node assures a healthy focus on next‐generation networks. The experiment section shows the benefits of energy‐optimized secure network communication in terms of better accuracy and the benefits of load‐balanced secure network communication through minimal overhead in computing platforms.

A Sustainable Inventory Model with Advertisement Effort for Imperfect Quality Items under Learning in Fuzzy Monsoon Demand

In this paper, we proposed a sustainable inventory model with a learning effect for imperfect quality items under different kinds of fuzzy environments like crisp, general fuzzy, cloudy fuzzy, and monsoon fuzzy. We divided the mathematical model into three parts under the learning effect according to the real-time fuzzy components (crisp, cloudy, and monsoon environments) of the demand rate of the items. We minimized the total inventory cost with respect to cycle length in each environment under the proposed assumptions. The non-linear optimization technique is applied for the algorithm and the solution method to find the decision variable. Finally, we compared the total inventory cost under different fuzzy environments and our finding is that the fuzzy monsoon environment is a more effective fuzzy environment than crisp and cloudy fuzzy environments. We have presented a numerical example for the validation of the proposed model and have shown the impact of the inventory input parameters on the cycle length and total inventory fuzzy cost. The managerial insights and future scope of this proposed study have been shown in the sensitivity analysis and conclusion. The limitations, application, future extension and scope, and social implementation have been shown in this research study.

Estimation and Management of Wind Energy in Ikorodu Lagos Lagoon, Using Weibull Parametric Measurement to Electricity Production in Nigeria

This paper is an approach on the estimation and approximation management of wind energy production around the lagoon axis of Ikorodu, Lagos state, Nigeria. The article concentrates on the availability of renewable resource such as wind to generate electrical energy in the greater Ikorodu metropolis of Lagos state Nigeria. Here, probability distribution function is used to generate the wind data. In this paper, three distinct methods are presented; Data time series analysis, Weibull probability function, and theoretical comparison with analytical concept. This research uses two important parameters for analyzing wind data: shape factor “k” and scale factor “c” from Weibull distribution function. The theoretical uses mathematical equations of popular methods such as: (a) Moment method, (b) Empirical Formula, or statistical standard deviation, (c) Peak likelihood, (d) modified peak likelihood, (e) double modified peak likelihood (f) graphical method or smallest mean square, and (g) energy sequence factor. The results obtained are tested to optimize the value from the Weibull parameters by adopting five techniques: (i) root average square error methodology, X2, power of agreement , MAPE, and RRMSE. The results expatiated on the practical and theoretical techniques design to confront the outcome of wind energy harnessed per 1.5 km2. Here, a differential optimization technique is used to determine the precision report. This serve as the basis of error litmus check existing between the wind energy determined by theory of statistical and mathematical Weibull Parametric function and the practical time-series data analysis in LSTM. Again, the wind data (speed and energy/power) were measured and recorded between January 2020 to December 2023 in the Ijede-Ikorodu Lagoon area of Lagos State. The optimized value for the shape factor k and scale factor c parametric measurement and management for maximizing the output electrical energy are obtained by using a well robust Weibull distribution function techniques and by absolutely determining and selecting the best position and location for installing the wind/wave alternators/generator. These generators come with turbines as a single unit. The measurement of the yearly average wind speed and average wind power are 10.09 ms-1 and 10.1 KWm-2, concurrently.

A novel ionic model for matured and paced atrial-like human iPSC-CMs integrating [formula omitted] and [formula omitted] currents

This work introduces the first atrial-specific in-silico human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) model, based on a set of phenotype-specific IKur,IKCa and IK1 membrane currents. This model is built on novel in-vitro experimental data recently published by some of the co-authors to simulate the paced action potential of matured atrial-like hiPSC-CMs. The model consists of a system of stiff ordinary differential equations depending on several parameters, which have been tuned by automatic optimization techniques to closely match selected experimental biomarkers. The new model effectively simulates the electronic in-vitro hiPSC-CMs maturation process, transitioning from an unstable depolarized membrane diastolic potential to a stable hyperpolarized resting potential, and exhibits spontaneous firing activity in unpaced conditions. Moreover, our model accurately reflects the experimental rate dependence data at different cycle length and demonstrates the expected response to a specific current blocker. This atrial-specific in-silico model provides a novel computational tool for electrophysiological studies of cardiac stem cells and their applications to drug evaluation and atrial fibrillation treatment.

Maximizing Engagement in Large-Scale Social Networks

Motivated by the importance of user engagement as a crucial element in cascading leaving of users from a social network, we study identifying a largest relaxed variant of a degree-based cohesive subgraph: the maximum anchored k-core problem. Given graph [Formula: see text] and integers k and b, the maximum anchored k-core problem seeks to find a largest subset of vertices [Formula: see text] that induces a subgraph with at least [Formula: see text] vertices of degree at least k. We introduce a new integer programming (IP) formulation for the maximum anchored k-core problem and conduct a polyhedral study on the polytope of the problem. We show the linear programming relaxation of the proposed IP model is at least as strong as that of a naïve formulation. We also identify facet-defining inequalities of the IP formulation. Furthermore, we develop inequalities and fixing procedures to improve the computational performance of our IP model. We use benchmark instances to compare the computational performance of the IP model with (i) the naïve IP formulation and (ii) two existing heuristic algorithms. Our proposed IP model can optimally solve half of the benchmark instances that cannot be solved to optimality either by the naïve model or the existing heuristic approaches. Funding: This work is funded by the National Science Foundation (NSF) [Grant DMS-2318790] titled AMPS: Novel Combinatorial Optimization Techniques for Smartgrids and Power Networks. Supplemental Material: The online appendix is available at https://doi.org/10.1287/ijoo.2022.0024 .

Interactive Mesh Sculpting with Arbitrary Topologies in Head-Mounted VR Environments

Shape modeling is a dynamic area in computer graphics with significant applications in computer-aided design, animation, architecture, and entertainment. Virtual sculpting, a key paradigm in free-form modeling, has traditionally been performed on desktop computers where users manipulate meshes with controllers and view the models on two-dimensional displays. However, the advent of Extended Reality (XR) technology has ushered in immersive interactive experiences, expanding the possibilities for virtual sculpting across various environments. A real-time virtual sculpting system implemented in a Virtual Reality (VR) setting is introduced in this paper, utilizing quasi-uniform meshes as the foundational structure. In our innovative sculpting system, we design an integrated framework encompassing a surface selection algorithm, mesh optimization technique, mesh deformation strategy, and topology fusion methodology, which are all tailored to meet the needs of the sculpting process. The universal, user-friendly sculpting tools designed to support free-form topology are offered in this system, ensuring that the meshes remain watertight, manifold, and free from self-intersections throughout the sculpting process. The models produced are versatile and suitable for use in diverse fields such as gaming, art, and education. Experimental results confirm the system’s real-time performance and universality, highlighting its user-centric design.

Emergent role of dynamic optimization in cardiac resynchronization therapy: Systematic review and network meta-analysis.

Suboptimal device programming is frequent in non-responders to cardiac resynchronization therapy (CRT). However, the role of device optimization and the most appropriate technique are still unknown. The aim of our study was to analyse the effect of different CRT optimization techniques within a network meta-analysis. A systematic search was conducted on MEDLINE, Embase and CENTRAL for studies comparing outcomes with empirical device settings or optimization using echocardiography, static algorithms or dynamic algorithms. Studies investigating the effect of optimization in non-responders were also analysed. A total of 17 studies with 4346 patients were included in the quantitative analysis. Of the treatments and outcomes examined, a significant difference was found only between dynamic algorithms and echocardiography, with the former leading to a higher echocardiographic response rate [odds ratio (OR): 2.02, 95% confidence interval (CI) 1.21-3.35], lower heart failure hospitalization rate (OR: 0.75, 95% CI 0.57-0.99) and greater improvement in 6-minute walk test [mean difference (MD): 45.52m, 95% credible interval (CrI) 3.91-82.44m]. We found no significant difference between empirical settings, static algorithms and dynamic algorithms. Seven studies with 228 patients reported response rates after optimization in non-responders. Altogether, 34.3%-66.7% of initial non-responders showed improvement after optimization, depending on response criteria. At the time of CRT implantation, dynamic algorithms may serve as a resource-friendly alternative to echocardiographic optimization, with similar or better mid-term outcomes. However, their superiority over empirical device settings needs to be investigated in further trials. For non-responders, CRT optimization should be considered, as the majority of patients experience improvement.

A hybrid chaotic bat algorithm for optimal placement and sizing of dg units in radial distribution networks

Appropriate location and sizing of distributed generation (DG) units in a radial distribution system (RDS) play a significant role in the improvement of its overall performance. Indeed, proper DG placement and sizing help in maintaining the balance between power supply and demand, decreasing energy losses and enhancing voltage profile. Within this context, this paper presents an effective approach for the determination of the optimal location and the appropriate capacity of a photovoltaic distributed generation (PVDG) unit in RDSs. In the suggested approach, the best position of the PVDG is selected using the loss sensitivity factor (LSF). Meanwhile, a new optimization technique incorporating chaos, bats’ self-adaptive compensation, and Doppler effect into the original bat algorithm (BA) is developed to find the optimal size of the PVDG unit. The optimal PVDG size is optimally determined in such a way that total active power losses of the RDS is reduced and voltage profile is enhanced. The performance of the proposed optimization technique, symbolized by (CSA-DC)BA, is evaluated using various benchmark functions. Moreover, the applicability and effectiveness of the suggested approach are verified on the IEEE 33-bus and the IEEE 69-bus RDSs. Obtained results revealed that the proposed (CSA-DC)BA outperforms the comparison optimization techniques.

DCAI-CLUD: a data-centric framework for the construction of land-use datasets

A high-quality land-use dataset is crucial for constructing a high-performance land-use classification model. Due to the complexity and spatial heterogeneity of land-use, the dataset construction process is inefficient and costly. This challenge affects the quality of datasets, consequently impacting the model’s performance. The emerging field of Data-Centric Artificial Intelligence (DCAI) is expected to deliver techniques for dataset optimization, offering a promising solution to the problem. Therefore, this study proposes a data-centric framework named DCAI-CLUD for the construction of land-use datasets. Based on this framework, the accuracy and rate of data labeling are improved by 5.93 and 28.97%. The Gini index of the dataset and the proportion of samples with non-mixed land-use categories are enhanced by 3.27 and 8.52%. The overall accuracy (OA) and Kappa of the land-use classification model improved significantly by 27.87 and 58.08%. This study is the first to introduce DCAI into the field of geographic information and remote sensing and verify its effectiveness. The proposed framework can effectively improve the construction efficiency and quality of the dataset and synchronously optimize the model performance. Based on the proposed framework, we constructed a multi-source land-use dataset of major cities in China named CN-MSLU-100K.

AI based UPQC control technique for power quality optimization of railway transportation systems

Metro trains have non-linear load characteristics, which means that the power sent to them gets distorted. Problems are caused by changes in power, swells, harmonics, and other disturbances. In this research, an artificial intelligence-driven control method was used on a unified power quality conditioner (UPQC) to help reduce power quality problems and improve power quality. Three advanced control methods are built and compared using MATLAB Simulink. Some of these methods are the ANN Controller, the NARMA-L2 Controller, and the PI Controller, improved using the Adaptive Lizard Algorithm. The controls' usefulness is judged by how well they lower the total harmonic distortion (THD) in the source current. The results show that all three AI-based controls work much better than the system that was not paid for. The ANN Controller works the best, followed by the NARMA-L2 Controller, and the PI Controller improved with the Adaptive Lizard Algorithm. These AI-driven control methods can enhance power quality and ensure that metro rail systems run smoothly and efficiently, as shown by how well they work. Modern transportation networks need more advanced ways to handle power quality, and this research helps make those solutions come together.

Comparisons between In-Check DIAL® and PF810® in evaluation and training inspiratory capacity for using dry powder inhalers

BackgroundDry powder inhalers (DPIs) rely on both internal resistance and patients’ inspiratory capacity for effective operation. Optimal inspiratory technique is crucial for DPI users. This study assessed the accuracy and repeatability of two available devices, PF810® and In-Check DIAL®, and analyzed their measurement errors and consistency in detecting inspiratory capacity.MethodsThe accuracy and repeatability of peak inspiratory flow (PIF) and forced inspiratory vital capacity (FIVC) against various internal resistances of the two devices were assessed using standard waveforms generated by a breathing simulator. The agreement of PIF measurements between the two devices in healthy volunteers and chronic obstructive pulmonary disease (COPD) patients was analyzed with the intraclass correlation coefficient and Bland–Altman graphical analysis.ResultsPF810® showed great accuracy and repeatability in measuring PIF, except for square waveforms at the lowest flow rate (20 L/min). In-Check DIAL® exhibited poor accuracy against high resistance levels. In scenarios with no resistance, In-Check DIAL® had significantly smaller measurement errors than PF810®, but larger errors against high resistance levels. The two devices showed excellent agreement (ICC > 0.80, P < 0.05), except for healthy volunteers against medium to high resistance (R3-R5) where the ICC was insignificant. Bland–Altman plots indicated small disagreements between the two devices for both healthy volunteers and COPD patients.ConclusionsIn-Check DIAL® exhibited poor accuracy and larger measurement errors than PF810® when detecting PIFs against higher internal resistances. However, its good performance against lower internal resistances, along with its cost-effectiveness and convenience made it appropriate for primary care. PF810® showed good accuracy and repeatability and could detect additional parameters of inspiratory capacity beyond PIF, though required further studies to confirm its clinical benefits.