Tag: statistics

Toxicol In Vitro. 2024 May 26:105853. doi: 10.1016/j.tiv.2024.105853. Online ahead of print.

ABSTRACT

Pentachlorophenol (PCP) is a persistent organic compound that is widely present in the environment. The estimation of internal exposure levels for a given external exposure using toxicokinetic models is key to the human health risk assessment of PCP. The present study developed a physiologically based multicompartmental pharmacokinetic (PBTK) model to describe and predict the behavior of pentachlorophenol (PCP) in an organism. The model consists of stomach, intestines, adipose tissue, kidneys and fast- and poorly perfused tissues that are interconnected via blood circulation. We constructed a PBTK model of PCP in rats and extrapolated it to human dietary PCP exposure. The toxicokinetic data of PCP in human tissues and excreta were obtained from the published literature. Based on the collected PCP dietary survey and internal exposure data of pregnant women in Shanghai, Bayesian statistical analysis was performed for the model using Markov chain Monte Carlo (MCMC) simulation. The posterior distributions of the sensitive parameters were estimated, and the model was parameter optimized and validated using the pregnant women’s test dataset. The results showed that the root mean square error (RMSE) improved 37.3% compared to the original model, and a systematic literature search revealed that the optimized model achieved acceptable prediction results for other datasets in China. A PCP metabolism model based on the exposure characteristics of pregnant women in China was constructed in the present study. The model provides a theoretical basis for the study of PCP toxicity and risk assessment.

PMID:38806067 | DOI:10.1016/j.tiv.2024.105853

Nanotechnology. 2024 May 28. doi: 10.1088/1361-6528/ad50e4. Online ahead of print.

ABSTRACT

Nanotechnology has gained immense popularity and observed rapid development due to the remarkable physio-chemical properties of nanoparticles (NPs) and related nanomaterials. The green production of nanoparticles has many benefits over traditional techniques because the current procedures are expensive, time-consuming, and involve harmful substances that limit their applicability. This study aimed to use a novel green source, the Salsola imbricata (SI) plant, which is commonly found in Central Asia and known for its medicinal properties as a reducing and stabilizing agent for the synthesis of AgNPs. The current study also utilized efficient statistical design, the Plackett-Burman Design of Experiment (DOE) method to synthesize the nanoparticles. The characterization of nanoparticles was carried out using UV-Vis spectroscopy, Fourier Transform Infrared Spectroscopy, and scanning electron microscopy (SEM). The Plackett-Burman design results showed that only two out of four factors i.e., AgNO3 concentration and incubation time, were significant for the synthesis of AgNPs. While remaining factors, incubation temperature and plant extract: AgNO3 ratio were non-significant. The SEM analysis result showed that SI-AgNPs had a size of 20-50nm. The SI-AgNPs demonstrated strong antimicrobial activity against oral pathogens such as Streptococcus mutans and Lactobacillus acidophilus, with the highest efficacy observed at a concentration of 2 mg/ml. The addition of SI-AgNPs in glass ionomer cement significantly increased the antimicrobial efficacy of GIC at different concentration (p≤0.000 for 0.2% and 0.1%, p≤0.01 for 0.05% and p≤0.05 for 0.025% respectively). Based on the results of the current study, the plant based AgNPs can be further evaluated in detail as alternate antimicrobial agent either alone or in combination with other antimicrobial agents for different dental applications.

PMID:38806018 | DOI:10.1088/1361-6528/ad50e4

J Occup Health. 2024 May 28:uiae028. doi: 10.1093/joccuh/uiae028. Online ahead of print.

ABSTRACT

INTRODUCTION: Participatory organizational interventions to improve psychosocial working conditions are important for a safe and healthy work environment. However, there are few systematic reviews or meta-analyses investigating the effects of these interventions on workers’ mental health and work-related outcomes. We apply the protocol for systematic review and meta-analysis to examine the effect of participatory organizational intervention on mental health and work performance.

METHODS AND ANALYSIS: The participants, interventions, comparisons, and outcomes (PICO) of the studies in this systematic review and meta-analysis were defined as follows: (P) inclusion of all workers, (I) participatory organizational intervention, (C) treatment as usual or no intervention (including waitlist control), and (O) mental health and work performance. Published studies will be searched using the following electronic databases: PubMed, EMBASE, PsycINFO, PsycARTICLES, and Japan Medical Abstracts Society. Studies that (1) included participatory organizational intervention, (2) included participants who were working as of the baseline survey period, (3) assessed mental health or work performance outcomes, (4) used a cluster randomized controlled trials design, (5) were published in English or Japanese, and (6) were published in peer-reviewed journals (including advanced online publication) will be included. Study selection and the risk of bias assessment will be performed independently by two reviewers. A meta-analysis will be performed to statistically synthesize the included studies. Publication bias will be assessed for meta-bias using Egger’s test as well as visually on a funnel plot. We will assess the heterogeneity by using the Q statistic.

PMID:38805736 | DOI:10.1093/joccuh/uiae028

J Med Internet Res. 2024 May 28;26:e53321. doi: 10.2196/53321.

ABSTRACT

BACKGROUND: The pandemic has accelerated digital work transformation, yet little is known about individuals’ willingness to sustain such digital modes and its associated factors. A better understanding of this willingness and its drivers is crucial for guiding the development of future digital work infrastructure, training programs, and strategies to monitor and prevent related health issues.

OBJECTIVE: This study aims to quantify the general population’s willingness to sustain pandemic-induced digital work, identify its associated factors, and examine how screen time moderates these relationships.

METHODS: A cross-sectional study was conducted targeting Hong Kong residents aged ≥18 years who have increased engagement in digital work since the pandemic. Data were collected through self-reported, web-based surveys. Descriptive statistics determined prevalence rates, while structured multiphase logistic regression identified associated factors and explored the moderating effects of screen hour levels.

RESULTS: This unfunded study enrolled 1014 participants from May 2 to June 24, 2022, and completed data analysis within 3 months after data collection. A total of 391 (38.6%; 95% CI 35.6%-41.6%) participants expressed willingness to sustain digital work. Positive factors associated with this willingness included being an employee (odds ratio [OR] 3.12, 95% CI 1.59-6.45; P=.001), being health professionals (OR 3.32, 95% CI 1.49-7.82; P=.004), longer screen hours (OR 1.09, 95% CI 1.03-1.15; P=.002), and higher depression levels (OR 1.20, 95% CI 1.01-1.44; P=.04). Conversely, negatively associated factors included older age (OR 0.87, 95% CI 0.81-0.94; P=.001), extroversion (OR 0.66, 95% CI 0.51-0.86; P=.002), higher eHealth literacy (OR 0.96, 95% CI 0.93-0.98; P<.001), perceived greater susceptibility to COVID-19 (OR 0.84, 95% CI 0.74-0.96; P=.009), residence in a high-severity COVID-19 community (OR 0.73, 95% CI 0.63-0.84; P<.001), having infected individuals in the immediate social circle (OR 0.64, 95% CI 0.46-0.88; P=.006), higher BMI (OR 0.94, 95% CI 0.90-0.99; P=.02), feelings of being out of control (OR 0.96, 95% CI 0.93-0.98; P=.002), and higher fear of COVID-19 (OR 0.96, 95% CI 0.94-0.98; P=.001). In addition, a moderating effect of screen hour level (high: >8 h/d; low: ≤8 h/d) influenced the association among 10 factors related to willingness to sustain pandemic-induced digital work, including age, education level, household size, needs for regular medical care, BMI, frequency of both vigorous and moderate physical activities, perceived COVID-19 severity, immediate social circle COVID-19 presence, and fear of COVID-19 (all P values for interaction <.05).

CONCLUSIONS: The substantial willingness of the general population to sustain digital work after the pandemic highlights the need for robust telework infrastructure, thorough monitoring of adverse health outcomes, and the potential to expand telehealth services among this group. The identification of factors influencing this willingness and the moderating role of screen hours inform the development of personalized strategies to enhance digital work acceptance where needed.

PMID:38805704 | DOI:10.2196/53321

J Med Internet Res. 2024 May 28;26:e50853. doi: 10.2196/50853.

ABSTRACT

BACKGROUND: Clinical decision support systems (CDSSs) based on routine care data, using artificial intelligence (AI), are increasingly being developed. Previous studies focused largely on the technical aspects of using AI, but the acceptability of these technologies by patients remains unclear.

OBJECTIVE: We aimed to investigate whether patient-physician trust is affected when medical decision-making is supported by a CDSS.

METHODS: We conducted a vignette study among the patient panel (N=860) of the University Medical Center Utrecht, the Netherlands. Patients were randomly assigned into 4 groups-either the intervention or control groups of the high-risk or low-risk cases. In both the high-risk and low-risk case groups, a physician made a treatment decision with (intervention groups) or without (control groups) the support of a CDSS. Using a questionnaire with a 7-point Likert scale, with 1 indicating “strongly disagree” and 7 indicating “strongly agree,” we collected data on patient-physician trust in 3 dimensions: competence, integrity, and benevolence. We assessed differences in patient-physician trust between the control and intervention groups per case using Mann-Whitney U tests and potential effect modification by the participant’s sex, age, education level, general trust in health care, and general trust in technology using multivariate analyses of (co)variance.

RESULTS: In total, 398 patients participated. In the high-risk case, median perceived competence and integrity were lower in the intervention group compared to the control group but not statistically significant (5.8 vs 5.6; P=.16 and 6.3 vs 6.0; P=.06, respectively). However, the effect of a CDSS application on the perceived competence of the physician depended on the participant’s sex (P=.03). Although no between-group differences were found in men, in women, the perception of the physician’s competence and integrity was significantly lower in the intervention compared to the control group (P=.009 and P=.01, respectively). In the low-risk case, no differences in trust between the groups were found. However, increased trust in technology positively influenced the perceived benevolence and integrity in the low-risk case (P=.009 and P=.04, respectively).

CONCLUSIONS: We found that, in general, patient-physician trust was high. However, our findings indicate a potentially negative effect of AI applications on the patient-physician relationship, especially among women and in high-risk situations. Trust in technology, in general, might increase the likelihood of embracing the use of CDSSs by treating professionals.

PMID:38805702 | DOI:10.2196/50853

G3 (Bethesda). 2024 May 28:jkae114. doi: 10.1093/g3journal/jkae114. Online ahead of print.

ABSTRACT

In the wake of increasing demand for renewable energy sources, plant-based sources including alternative oilseeds have come to the forefront of interest. Hydroxy fatty acids (HFAs), produced in a few oilseed species, are important chemical feedstocks for industrial applications. An integrated approach was taken to assemble the first draft genome of the alternative HFA producer Physaria fendleri (n = 6), an outcrossing species with high heterozygosity. Both de novo transcriptome assemblies and genome assemblies were produced with public and generated sequencing reads. Resulting intermediate assemblies were then scaffolded and patched with multiple data sources, followed by super-scaffolding onto a masked genome of Camelina laxa (n = 6). Despite a current lack of available resources for the physical mapping of genomic scaffolds of Physaria fendleri, topography of the genome with respect to repeat and gene content was preserved at the scaffold level and not significantly lost via super-scaffolding. Read representation, gene and genome completion statistics, and annotation results illustrated the creation of a functional draft genome and a tool for future research on alternative oil species.

PMID:38805698 | DOI:10.1093/g3journal/jkae114

Hum Reprod Update. 2024 May 28:dmae012. doi: 10.1093/humupd/dmae012. Online ahead of print.

ABSTRACT

BACKGROUND: The genetic composition of embryos generated by in vitro fertilization (IVF) can be examined with preimplantation genetic testing (PGT). Until recently, PGT was limited to detecting single-gene, high-risk pathogenic variants, large structural variants, and aneuploidy. Recent advances have made genome-wide genotyping of IVF embryos feasible and affordable, raising the possibility of screening embryos for their risk of polygenic diseases such as breast cancer, hypertension, diabetes, or schizophrenia. Despite a heated debate around this new technology, called polygenic embryo screening (PES; also PGT-P), it is already available to IVF patients in some countries. Several articles have studied epidemiological, clinical, and ethical perspectives on PES; however, a comprehensive, principled review of this emerging field is missing.

OBJECTIVE AND RATIONALE: This review has four main goals. First, given the interdisciplinary nature of PES studies, we aim to provide a self-contained educational background about PES to reproductive specialists interested in the subject. Second, we provide a comprehensive and critical review of arguments for and against the introduction of PES, crystallizing and prioritizing the key issues. We also cover the attitudes of IVF patients, clinicians, and the public towards PES. Third, we distinguish between possible future groups of PES patients, highlighting the benefits and harms pertaining to each group. Finally, our review, which is supported by ESHRE, is intended to aid healthcare professionals and policymakers in decision-making regarding whether to introduce PES in the clinic, and if so, how, and to whom.

SEARCH METHODS: We searched for PubMed-indexed articles published between 1/1/2003 and 1/3/2024 using the terms ‘polygenic embryo screening’, ‘polygenic preimplantation’, and ‘PGT-P’. We limited the review to primary research papers in English whose main focus was PES for medical conditions. We also included papers that did not appear in the search but were deemed relevant.

OUTCOMES: The main theoretical benefit of PES is a reduction in lifetime polygenic disease risk for children born after screening. The magnitude of the risk reduction has been predicted based on statistical modelling, simulations, and sibling pair analyses. Results based on all methods suggest that under the best-case scenario, large relative risk reductions are possible for one or more diseases. However, as these models abstract several practical limitations, the realized benefits may be smaller, particularly due to a limited number of embryos and unclear future accuracy of the risk estimates. PES may negatively impact patients and their future children, as well as society. The main personal harms are an unindicated IVF treatment, a possible reduction in IVF success rates, and patient confusion, incomplete counselling, and choice overload. The main possible societal harms include discarded embryos, an increasing demand for ‘designer babies’, overemphasis of the genetic determinants of disease, unequal access, and lower utility in people of non-European ancestries. Benefits and harms will vary across the main potential patient groups, comprising patients already requiring IVF, fertile people with a history of a severe polygenic disease, and fertile healthy people. In the United States, the attitudes of IVF patients and the public towards PES seem positive, while healthcare professionals are cautious, sceptical about clinical utility, and concerned about patient counselling.

WIDER IMPLICATIONS: The theoretical potential of PES to reduce risk across multiple polygenic diseases requires further research into its benefits and harms. Given the large number of practical limitations and possible harms, particularly unnecessary IVF treatments and discarded viable embryos, PES should be offered only within a research context before further clarity is achieved regarding its balance of benefits and harms. The gap in attitudes between healthcare professionals and the public needs to be narrowed by expanding public and patient education and providing resources for informative and unbiased genetic counselling.

PMID:38805697 | DOI:10.1093/humupd/dmae012

JCO Oncol Pract. 2024 May 28:OP2400036. doi: 10.1200/OP.24.00036. Online ahead of print.

ABSTRACT

PURPOSE: Androgen receptor pathway inhibitors (ARPIs) are widely prescribed in metastatic castration-resistant prostate cancer (mCRPC). Real-world frequencies and potential impacts of comorbidities and concomitant medication (conmed) interactions with ARPIs are not well described.

METHODS: Patients receiving ARPIs for mCRPC were identified from the electronic Prostate Cancer Australian Database (ePAD). Demographics, clinicopathologic characteristics, and outcome data were extracted. Conmeds and comorbidities were collected from medical records. Potential interacting comorbidities were defined from trial and post-trial data. Clinically significant drug-drug interactions (DDIs) were identified using UpToDate Lexicomp and Stockley’s databases. Patient characteristics, comorbidity interactions, DDIs, and outcomes were analyzed.

RESULTS: Two hundred thirty-five patients received first- or second-line ARPIs for mCRPC from 2012 to 2021, with a median follow-up of 27 months. One hundred sixteen received abiraterone acetate (AAP) and 135 received enzalutamide (ENZ). The median age was 74 years, and the median number of conmeds was 4. Clinically significant DDIs occurred in 55 (47%) AAP patients and 90 (67%) ENZ patients. Only 5% of DDIs were predicted to affect ARPI pharmacokinetics (PK) or pharmacodynamics, whereas 95% were predicted to impact conmed PK or increase toxicity risk. In patients receiving ENZ, DDIs were associated with lower PSA50 (50% v 74%, P = .04) and poorer overall survival (28 v 45 months, P = .04), although statistical significance was not maintained on multivariate analysis. No significant survival differences were seen with DDIs in patients receiving AAP. Potential interactions between comorbidities and ARPI were present in 72% on AAP and 14% on ENZ with no significant associated survival differences.

CONCLUSION: DDIs and drug-comorbidity interactions in real-world patients receiving ARPIs for mCRPC are common and may affect outcomes. Ongoing clinician education regarding DDIs is necessary to optimize patient outcomes.

PMID:38805663 | DOI:10.1200/OP.24.00036

Artif Life. 2024 May 27:1-15. doi: 10.1162/artl_a_00440. Online ahead of print.

ABSTRACT

This work concerns the long-term collective excitability properties and the statistical analysis of the critical events displayed by a recently introduced spatiotemporal many-body model, proposed as a new paradigm for Artificial Life. Numerical simulations show that excitable collective structures emerge in the form of dynamic networks, created by bursts of spatiotemporal activity (avalanches) at the edge of a synchronization phase transition. The spatiotemporal dynamics is portraited by a movie and quantified by time varying collective parameters, showing that the dynamic networks undergo a “life cycle,” made of self-creation, homeostasis, and self-destruction. The power spectra of the collective parameters show 1/f power law tails. The statistical properties of the avalanches, evaluated in terms of size and duration, show power laws with characteristic exponents in agreement with those values experimentally found in the neural networks literature. The mechanism underlying avalanches is argued in terms of local-to-collective excitability. The connections that link the present work to self-organized criticality, neural networks, and Artificial Life are discussed.

PMID:38805660 | DOI:10.1162/artl_a_00440

Mol Pharm. 2024 May 28. doi: 10.1021/acs.molpharmaceut.4c00086. Online ahead of print.

ABSTRACT

Block copolymers, composed of poly(2-oxazoline)s and poly(2-oxazine)s, can serve as drug delivery systems; they form micelles that carry poorly water-soluble drugs. Many recent studies have investigated the effects of structural changes of the polymer and the hydrophobic cargo on drug loading. In this work, we combine these data to establish an extended formulation database. Different molecular properties and fingerprints are tested for their applicability to serve as formulation-specific mixture descriptors. A variety of classification and regression models are built for different descriptor subsets and thresholds of loading efficiency and loading capacity, with the best models achieving overall good statistics for both cross- and external validation (balanced accuracies of 0.8). Subsequently, important features are dissected for interpretation, and the DrugBank is screened for potential therapeutic use cases where these polymers could be used to develop novel formulations of hydrophobic drugs. The most promising models are provided as an open-source software tool for other researchers to test the applicability of these delivery systems for potential new drug candidates.

PMID:38805643 | DOI:10.1021/acs.molpharmaceut.4c00086