PKPy: a Python-based framework for automated population pharmacokinetic analysis
We present PKPy, an open-source Python framework designed to automate population pharmacokinetic analysis workflows. The framework emphasizes user accessibility by minimizing the need for manual parameter initialization while maintaining analytical rigor. PKPy implements both one-compartment and two-compartment pharmacokinetic models (with and without first-order absorption) with integrated capabilities for parameter estimation, covariate analysis, and comprehensive diagnostics. The framework’s performance was evaluated through simulation studies across varying sample sizes (20–100 subjects) and model complexities. Results demonstrated robust parameter estimation for clearance and volume of distribution, with bias consistently below 3% and recovery rates exceeding 98% in one-compartment models. The framework successfully identified true covariate relationships with 100% accuracy across all scenarios, while maintaining high model fit quality (R2 ≥ 0.97). For two-compartment models, the framework showed comparable performance with slightly higher parameter bias (5–10%) but maintained excellent fit quality (R2 ≥ 0.99). Advanced validation metrics including average fold error (AFE) and absolute average fold error (AAFE) were implemented, with AFE values ranging from 1.01–1.03 and AAFE < 1.05 across test scenarios, indicating excellent prediction accuracy. The key pharmacokinetic parameters estimated by the framework include clearance (CL), volume of distribution (V or V1/V2 for two-compartment models), inter-compartmental clearance (Q), and when applicable, the absorption rate constant (Ka). Application to the classic Theophylline dataset demonstrated PKPy’s practical utility, achieving comparable results whether or not initial parameter estimates were provided. The framework successfully estimated population parameters with good model fit (R2 = 0.933) and automatically identified physiologically plausible covariate relationships. Comprehensive comparisons with existing software packages (Saemix+PKNCA, and simulated comparisons with nlmixr2) revealed PKPy’s advantages in computational efficiency, with installation times of 16s versus 96s and analysis times of 13–15s versus 101–102s. While PKPy employs a two-stage approach rather than full nonlinear mixed-effects modeling, it achieved consistent parameter estimates with minimal bias for data-rich scenarios. PKPy leverages Python’s scientific computing ecosystem to provide an accessible, transparent platform for pharmacokinetic analysis. The framework’s automated approach, support for multiple compartment models, and comprehensive workflow integration demonstrate the potential for reducing barriers to entry in pharmacometric analysis while maintaining scientific rigor.
Kong et al. (2025) PKPy: a Python-based framework for automated population pharmacokinetic analysis. PeerJ 13:e20258 https://doi.org/10.7717/peerj.20258
Antimicrobial and scavenging potential of green synthesized silver/manganese bimetallic nanoparticles using Euphorbia cactus extract
The fabrication of novel nanomedicines in the pursuit of alternative therapeutics has increasingly embraced eco-friendly strategies. This study reports the phytogenic synthesis of bimetallic silver-manganese nanoparticles (Ag/MnNPs) through bio-reduction using non-toxic extract from aerial part of Euphorbia cactus as a sustainable and environmentally benign reducing and stabilizing agent. Advanced spectroscopic and microscopic characterization techniques were applied to elucidate the physico-chemical features of green synthesized Euphorbia cactus-mediated Ag/MnNPs (EC-Ag/MnNPs). The formed EC-Ag/MnNPs were predominantly spherical and uniform, with an average size of 18.32 nm. Fourier transform infrared spectroscopy (FTIR) analysis revealed the existence of multiple functional groups, indicating the involvement of Euphorbia cactus phytoconstituents in the synthesis, reduction and stabilization of EC-Ag/MnNPS. The energy-dispersive X-ray (EDX) estimation confirmed the elemental composition, showing 43.62% of silver and 18.71% manganese content. Both biogenic bimetallic EC-Ag/MnNPs and Euphorbia cactus (EC) extract exhibited excellent antimicrobial and scavenging potential. The bimetallic EC-Ag/MnNPs exerted superior antibacterial efficacy, with maximum inhibition zones of 38.15 ± 0.32 mm against Escherichia coli and 36.81 ± 0.51 mm against Salmonella Typhi. EC-Ag/MnNPs also showed remarkable antifungal efficacy against Candida glabrata (35.10 ± 0.39 mm) and Candida parapsilosis (33.82 ± 0.97 mm). Additionally, the biosynthesized EC-Ag/MnNPs showed strong, dose-dependent antioxidant activity, achieving a maximum scavenging efficiency of 96.12% at a concentration of 80 µg/mL. The results demonstrated significant antimicrobial and antioxidant properties of green-synthesized EC-Ag/MnNPs, underscoring their potential application in antimicrobial formulations and enhancement of medical device functionality.
Al-Hamoud et al. (2025) Antimicrobial and scavenging potential of green synthesized silver/manganese bimetallic nanoparticles using Euphorbia cactus extract. PeerJ 13:e20244 https://doi.org/10.7717/peerj.20244
The role of cerebral blood flow volume in cortical inhibition during postural changes
This study investigated how body posture impacts cerebral hemodynamics and brain bioelectrical activity, aiming to understand the mechanisms by which increased cerebral blood flow in a supine position might lead to cortical inhibition, potentially indicated by a reduction in alpha wave presence. The study also explored the neurovascular effects of dynamic tilting. Simultaneous electroencephalographic (EEG) and rheoencephalographic (REG) recordings were conducted on 40 healthy participants (mean age = 21.3 ± 1.4 years; 20 men and 20 women) during two postural tests. In Test 1, participants transitioned between sitting upright and lying supine. Test 2 followed a similar design, with the addition of dynamic tilting through passive oscillations between +10° and −10° on a tilt table. Results indicated that REG parameters –specifically rheographic wave amplitude (RWA), venous outflow (VO), and catacrotic time (CT) –increased notably in the supine position, particularly among male participants. In Test 1, men also exhibited a pronounced drop in alpha absolute spectral power (Pα) when moving from upright to supine, while Pα remained relatively stable in women. In Test 2, Pα showed minimal changes among men, whereas moderate reductions were observed in women, mainly in the supine position following dynamic tilting. Significant sex differences were noted in RWA, VO, and Pα, with these values generally higher in female participants. A strong negative correlation between RWA and Pα was observed in the male group during Test 1, with a similar but weaker trend in women. In Test 2, a negative correlation between RWA and Pα re-emerged in both groups, though it did not reach statistical significance. These findings suggest that baroreflex activity may be the primary driver of cortical inhibition, with changes in cerebral blood flow volume potentially playing a secondary role. Dynamic tilting had minimal impact on brain blood flow and mixed effects on Pα, though results may hint at a possible interference with baroreflex responses, which could attenuate cortical inhibition. Overall, this study demonstrates the use of combined REG and EEG during postural transitions as a tool for investigating the interaction between cerebral blood flow and brain activity. These findings and the methods used may have clinical relevance as a potential diagnostic approach for disorders involving impaired baroreflex function.
Sagirov et al. (2025) The role of cerebral blood flow volume in cortical inhibition during postural changes. PeerJ 13:e20233 https://doi.org/10.7717/peerj.20233
Modulation of PI3K/AKT/mTOR and apoptosis pathway in colon cancer cells by the plant flavonoid fisetin
Colorectal cancer (CRC) is a complex multifactorial disease caused by genetic and epigenetic changes playing a vital role in its development and progression. Chemotherapy remains a major option in the treatment of CRC. However, due to its unintended effects on normal tissue, research on identifying plant-based therapeutic agents as an alternative treatment modality has gained attention. Fisetin, a plant-derived flavonoid, has shown promising effects as an anticancer agent against several human cancers, including colon cancer. However, there is limited research focusing on studying the mechanism of action of fisetin. The PI3K/AKT/mTOR pathway as a key regulator of cancer cells has become a promising target for potential anti-cancer development. This study examined the anti-cancer effects of fisetin, emphasizing its effects on the PI3K/AKT/mTOR and apoptosis pathways in human colon cancer Caco-2 cells. The Caco-2 cells were treated with different concentrations (15, 30, 60, 90, or 120 µM) of fisetin for 12 or 24 h. Cell viability was evaluated using the MTT assay, while the expressions of PI3K/AKT/mTOR pathway genes and apoptosis genes, BAX and BCL-2, were analyzed by qRT-PCR. Fisetin markedly decreased the cell viability in a dose- and time-dependent manner. Fisetin down-regulated BCL-2, PI3K, mTOR, and NF-κB gene expression while up-regulating BAX gene expression. This suggested the inhibition of PI3K/AKT/mTOR pathway and induction of apoptosis. GeneMANIA and OncoDB further corroborated these results. These data demonstrate that the antiproliferative effects of fisetin were medicated through the modulation of PI3K/AKT/mTOR and apoptosis pathway. Thus, the study underscores fisetin’s potential as a cancer-preventative drug against cancer.
Alamoudi et al. (2025) Modulation of PI3K/AKT/mTOR and apoptosis pathway in colon cancer cells by the plant flavonoid fisetin. PeerJ 13:e20225 https://doi.org/10.7717/peerj.20225
Instability core training vs traditional core training on trunk strength and sprint performance among athletes: a systematic review and meta-analysis
Background Instability core training (ICT) has been the focus of extensive research because of its proven benefits to athletes’ core muscle strength and sprint performance. However, there is a lack of systematic reviews explicitly evaluating the impact of instability core training (ICT) vs traditional core training (TCT) on athletes’ trunk strength and sprint performance. This study aims to conduct a systematic review and meta-analysis of the effects of ICT vs TCT on trunk strength and sprint performance among athletes. Method This study used guidelines for the systematic review and meta-analysis of PRISMA, Web of Science, EBSCOhost (SPORTDiscus), PubMed, Scopus, CNKI, and Google Scholar to collect original references in electronic databases. The Population, Intervention, Comparison, Outcome, and Study Design (PICOS) method was selected for the inclusion criteria. The physiotherapy evidence database (PEDro) scale was used to assess the scoring for articles’ risk of bias. The scoring of 12 studies ranges from 5–7 (out of 11 points), and study quality is moderate to high. Results Out of 285 identified studies, only 12 articles fulfilled all the eligibility criteria after screening. ICT could significantly improve trunk strength and sprint performance among various athlete populations using unstable surfaces or environments (i.e., BOSU ball, Swiss ball, wobble boards, suspension trainer, Sissel pillows, inflated disc, foam surface, Airex balance pad, Togu power ball, thera-band, elastic band and so on) than TCT using stable surfaces or environments (i.e., floor and bench). In addition, the ICT vs TCT intervention showed a moderate to large effect size (ES = −0.40–1.86; all p < 0.05) in improving trunk muscle strength and sprint performance. Conclusion The finding suggests that different types of ICT benefit athletes, as this training method can effectively enhance trunk strength and sprint performance in athletes than TCT. Therefore, this study suggests that ICT should be considered in athletes’ daily training routines for trunk strength and sprint performance.
Gao et al. (2025) Instability core training vs traditional core training on trunk strength and sprint performance among athletes: a systematic review and meta-analysis. PeerJ 13:e20212 https://doi.org/10.7717/peerj.20212
Agreement between BTS G-walk and GaitLab in spatiotemporal and pelvic angle measurements in active older adults
Background Aging impacts gait, a vital health indicator in older adults, reducing speed and increasing double support time, linked to falls and disability. The World Health Organization advises 150 min/week of moderate or 75 min/week of vigorous exercise, plus strength training, to sustain neuromuscular integrity and locomotor capacity associated with healthy gait patterns in older adults. While 3D motion capture is the gold standard for gait analysis, its cost and complexity limit use, boosting interest in portable inertial sensors like the BTS G-Walk. Yet, their accuracy in active older adults for spatiotemporal parameters and pelvic angles is underexplored, prompting this comparison with BTS GaitLab. Methods Fifty-nine active older adults (aged 65–87, mean 71.2 ± 5.5 years; eight men, 51 women) were assessed using BTS GaitLab (200 Hz cameras, 400 Hz force plates, Helen Hayes protocol, 18 markers) and BTS G-Walk (100 Hz, at L5) during four 10-meter walks at comfortable speed. Spatiotemporal parameters (cadence, speed, step length, stance/swing/support times) and pelvic angles (tilt, obliquity, rotation) were compared. Agreement used intraclass correlation coefficient (ICC), differences used paired t-tests, and variability used coefficient of variation (CV), with p < 0.05. Results Spatial parameters showed strong agreement: cadence (ICC = 0.98), speed (ICC = 0.96), step/stride length (ICC = 0.90–0.92), with no significant differences for cadence and speed (p > 0.05). Temporal parameters had weak agreement (e.g., stance time ICC = −0.18, swing time ICC = −0.54) and significant differences (p < 0.001). Pelvic angles had moderate agreement for tilt and obliquity (ICC = 0.48–0.78, p < 0.007), but low for rotation (ICC < 0.38, p > 0.038). Variability was high for double support time (CV 15.3–20.9%) and pelvic angles (CV > 27%). The sample (59) exceeds typical studies (7–23). Conclusions BTS G-Walk accurately measures spatial gait parameters in active older adults, ideal for quick clinical assessments where 3D systems are unavailable. However, its weak temporal parameter and pelvic rotation performance, possibly due to 100 Hz sampling, L5 placement, and algorithms, limits detailed analysis like stability. With a large sample and pelvic angle focus, this study supports G-Walk as a complementary tool in gerontology, while noting needs for improved temporal and angular precision.
Bittencourt et al. (2025) Agreement between BTS G-walk and GaitLab in spatiotemporal and pelvic angle measurements in active older adults. PeerJ 13:e20189 https://doi.org/10.7717/peerj.20189
Evidence of an upper entrainment limit for walking with fractal auditory stimuli
Background Variability exists in all biological signals, and in human gait research it has been found to be an indicator of neuromuscular system functioning. Detrended fluctuation analysis (DFA), a nonlinear method used to quantify the strength of long-range correlations in the temporal structure of stride-to-stride gait variability, has revealed gait differences in certain populations that are not observed with traditional linear measures like standard deviation. Previous research suggests that humans can adapt gait patterns to match different variability structures through sensory cues, such as auditory metronomes. However, the upper limits of adaptability and the strength of long-term correlations in gait variability remain unclear. Exploring these limits not only deepens our understanding of neuromuscular control mechanisms but could also inform the design of targeted interventions, such as rehabilitation strategies, to enhance motor control in clinical populations. The aim of this study was to investigate the possible upper limits of long-term correlations in stride-to-stride gait variability, characterized by the fractal scaling index (FSI) using DFA. Methods Fourteen healthy young adults (age 25 ± 3 years; seven females) completed seven treadmill walking trials at a fixed, self-selected speed. The first trial was uncued, and during the remaining six trials participants timed their steps to an auditory metronome with FSI ranging between 1.00 and 1.25. Gait FSI, velocity, stride time, cadence, and the time difference between heel contact and the associated metronome “tones” were calculated. Results Uncued gait FSI averaged 0.76 (±0.1). As the metronome FSI increased from 1.00 to 1.15, gait FSI approximated 1.00. Beyond 1.15 (metronome FSI values of 1.20 and 1.25), gait FSI dropped below 0.70, resembling uncued walking. Other gait measures remained unchanged. These findings suggest an upper gait FSI limit of approximately 1.00 during entrainment to metronome FSI values <1.20, beyond which adaptability diminishes. Conclusions This study establishes the upper entrainment limit for gait FSI during synchronization with fractal auditory stimuli, with implications for designing effective gait rehabilitation interventions targeting specific variability patterns.
Power et al. (2025) Evidence of an upper entrainment limit for walking with fractal auditory stimuli. PeerJ 13:e20176 https://doi.org/10.7717/peerj.20176
FastST: an efficient tool for inferring decomposition and directionality of microbial communities
Microbiomes play crucial roles in human health, disease development, and global ecosystem functioning. Understanding the origins, movements, and compositions of microbial communities is essential for unraveling the principles governing microbial ecology. Microbial source tracking (MST) approaches have emerged as valuable tools for quantifying the proportions of different microbial sources within target communities, enabling researchers to track transmissions between hosts and environments, identify similarities between microbiome samples, and determine sources of contamination in various settings. Current MST methods like SourceTracker2 and FEAST have advanced the field by employing Bayesian and expectation-maximization approaches, respectively, but are limited by computational inefficiency with high-dimensional data and inability to infer directionality in source-sink relationships. This study presents a novel computational framework for microbial source tracking called FastST. FastST infers the relative contributions of source environments to sink microbiomes while also determining directionality when source-sink relationships are not predefined. Through extensive simulation studies with varying numbers of sources and complexity, FastST demonstrates superior performance in both accuracy and computational efficiency compared to FEAST and SourceTracker2, maintaining consistent execution times even as the number of source environments increases. Furthermore, the proposed method achieved over 90% accuracy in directionality inference across all tested scenarios, even when multiple major sources are present, broadening its applicability in practical microbiome research and environmental monitoring. FastST and data simulation codes are publicly available at https://github.com/joungmin-choi/FastST.
Choi et al. (2025) FastST: an efficient tool for inferring decomposition and directionality of microbial communities. PeerJ 13:e20161 https://doi.org/10.7717/peerj.20161
Thermal-bias PCR: generation of amplicon libraries without degenerate primer interference
The polymerase chain reaction (PCR) has been used to amplify specific gene regions for many taxonomic studies and there have been substantial efforts to develop protocols that efficiently amplify target regions from a majority of mixed-template populations. Most protocols include the use of degenerate oligonucleotide primer pools, which contain mixed nucleotide sequences to improve priming from templates containing non-consensus sequence variations in their primer-binding sites. In this work, computational modeling and experimental measurements revealed that degenerate primers reduce efficiency well before a substantial product pool has been generated. It was also discovered that non-degenerate primers produced amplicons significantly better than their degenerate counterparts when amplifying either a consensus or a non-consensus target. Using quantitative, real-time PCR (qPCR) and data fitting as a guide, a new PCR protocol was developed that avoids the use of degenerate primers and allows for the stable amplification of targets containing mismatches to the targeting primers. This protocol involves the use of only two non-degenerate primers with no intermediate processing steps and it allows for the reproducible production of amplicon sequencing libraries that maintain the fractional representations of rare members.
Moore (2025) Thermal-bias PCR: generation of amplicon libraries without degenerate primer interference. PeerJ 13:e20241 https://doi.org/10.7717/peerj.20241
Dynamic effects of irrigation on photosynthesis and yield-related physiological characteristics in different glutinous wheat cultivars
Water scarcity critically constrains wheat production in North China, yet the irrigation responsiveness of novel glutinous wheat cultivars remains poorly quantified. This study systematically investigated the physiological mechanisms of common wheat Shimai 19 (SM19), partially glutinous SM19-P (Wx-B1 null), and fully glutinous SM19-N (triple null) under three irrigation regimes: rain-fed (W0), water-saving (W1: jointing irrigation), and conventional irrigation (W2: overwintering + jointing + flowering irrigations). Dynamic monitoring of flag leaf photosynthesis (Soil Plant Analysis Development (SPAD), stomatal conductance (Gs), transpiration rate (Tr), net photosynthetic rate (Pn)), antioxidant enzyme systems (superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) net photosynthetic rate (Pn), malondialdehyde (MDA)), grain starch synthase activities (granule-bound starch synthase (GBSS), soluble starch synthase (SSS), adenosine diphosphate glucose pyrophosphorylase (AGPase), starch branching enzyme (SBE)), and yield components revealed that: (1) SM19 achieved maximum photosynthetic capacity under W1 (Pn increased by 59.54% vs. W0 at 21 days post anthesis (DPA), p < 0.05) with optimal oxidative damage resistance (MDA reduced by 78.73% at 0 DPA), whereas SM19-P and SM19-N required W2 to reach photosynthetic peaks (Pn increased by 60.56% in SM19-P) and enzyme activity maxima (CAT increased by 66.67% in SM19-N). (2) Starch synthase activities peaked under water deficit (W0) early in grain-filling (≤14 DPA) but became tightly coupled to irrigation frequency thereafter. This was supported by a highly significant correlation between irrigation and final yield (r = 0.803, p < 0.01). The coordinated upregulation of AGPase and SSS (r = 0.726, p < 0.01) underpinned this response. The superior branched-starch accumulation in genotype SM19-N (+23%) was linked to its markedly higher SBE activity (r = 0.867, p < 0.01). (3) Yield optimization was genotype-specific: SM19 yielded highest under W1, while SM19-N peaked under W2. The study demonstrates that, unlike common wheat (SM19) which performs optimally under water-saving irrigation, the novel glutinous lines (SM19-P/SM19-N) require full irrigation to realize their yield potential, highlighting a critical trade-off between starch quality and drought adaptation. The key indicators identified—photosynthetic efficiency, antioxidant capacity, and starch metabolism—provide a theoretical foundation for developing future glutinous wheat varieties combining drought tolerance with high starch quality.
Li et al. (2025) Dynamic effects of irrigation on photosynthesis and yield-related physiological characteristics in different glutinous wheat cultivars. PeerJ 13:e20230 https://doi.org/10.7717/peerj.20230