Category: Statistics

Biom J. 2025 Aug;67(4):e70065. doi: 10.1002/bimj.70065.

ABSTRACT

In medical, ecological, and psychological research, there is a need for methods to handle multiple testing, for example, to consider group comparisons with more than two groups. Typical approaches that deal with multiple testing are mean- or variance-based which can be less effective in the context of heavy-tailed and skewed data. Here, the median is the preferred measure of location and the interquartile range (IQR) is an adequate alternative to the variance. Therefore, it may be fruitful to formulate research questions of interest in terms of the median or the IQR. For this reason, we compare different inference approaches for two-sided and noninferiority hypotheses formulated in terms of medians or IQRs in an extensive simulation study. We consider multiple contrast testing procedures combined with a bootstrap method as well as testing procedures with Bonferroni correction. As an example of a multiple testing problem based on heavy-tailed data, we analyze an ecological trait variation in early and late breeding in a medium-sized bird of prey.

PMID:40614164 | DOI:10.1002/bimj.70065

IEEE Trans Cybern. 2025 Jul 4;PP. doi: 10.1109/TCYB.2025.3581309. Online ahead of print.

ABSTRACT

Domain adaptation (DA) techniques are becoming increasingly proficient in cross-domain fault diagnosis tasks. However, DA-based methods are not always applicable due to the target domain data is not always accessible. Although there have been some interesting domain generalization methods for fault diagnosis under unseen conditions, most of them can only be used to mine the fault features on source domain distributions, and the improvement of model generalization performance is limited. To solve this problem, the multiplicative noise Gaussian perturbation strategy and the additive noise linear fusion strategy are proposed to capture fault information beyond source domain distributions. The former is used to randomly perturb feature statistics of multisource domains to simulate the uncertainty of domain shift, while the latter is used to perform the additive noise linear operation on feature statistics of multiple source domains to ensure the authenticity of the generated feature styles. Further, the feature statistics generated by both strategies are mixed with random convex weights to obtain new feature styles, achieving the best compromise between reliability and diversity. The network can learn more fault information from features with diversified styles. Extensive experimental results on both public and real datasets verify the effectiveness of our approach.

PMID:40614158 | DOI:10.1109/TCYB.2025.3581309

Med Sci Monit. 2025 Jul 4;31:e947895. doi: 10.12659/MSM.947895.

ABSTRACT

BACKGROUND Infertility is defined as the absence of pregnancy despite unprotected, regular sexual intercourse of couples of reproductive age for at least 1 year. Infertility may be unexplained or linked to anovulation/polycystic ovary syndrome (PCOS). PCOS can involve the processes of inflammation, insulin resistance, and metabolic syndrome. This study compared serum levels of afamin, asprosin, and pentraxin3 (PTX3) between women with PCOS and women with unexplained infertility to elucidate underlying pathophysiological mechanisms. MATERIAL AND METHODS Our study included 106 women: 55 with unexplained infertility and 51 with PCOS. Using the electrochemiluminescence immunoassay method, we assessed the levels of estradiol, follicle-stimulating hormone, luteinizing hormone, and anti-Mullerian hormone. Afamin, asprosin, and PTX3 levels were measured by ELISA. RESULTS Age, fasting glucose levels, and body mass index (BMI) of the groups were statistically similar. Anti-Mullerian hormone, antral follicle count, and LH levels were higher (P<0.05) in the PCOS group. Afamin and PTX3 levels were higher in the PCOS group (P<0.05), while asprosin levels were similar. CONCLUSIONS Our study demonstrates the importance of afamin associated with oxidative stress and the PTX3, which plays a role in the regulation of humoral immune responses, in the etiology of infertility cases. Afamin and PTX3 should be evaluated in ovulatory and non-ovulatory PCOS cycles to facilitate treatment and to elucidate the ovulation and implantation processes in PCOS. These recommendations specifically include dividing PCOS patients into subgroups such as diabetogenic, obese, and hirsute, and re-examining biochemical markers accordingly.

PMID:40614140 | DOI:10.12659/MSM.947895

Cancer. 2025 Jul 15;131(14):e35967. doi: 10.1002/cncr.35967.

ABSTRACT

BACKGROUND: Assessment of sexual dysfunction among adult male survivors of childhood cancer has primarily been limited to erectile dysfunction. This study aimed to characterize sexual functioning more comprehensively among a large population of male survivors of childhood cancer.

METHODS: Male survivors (N = 1595, 22.0-59.4 years, median age, 37.8 years) and siblings (N = 269, 21.5-60.8 years, median age, 38.9 years) from the Childhood Cancer Survivor Study completed the Sexual Functioning Questionnaire (SFQ) to assess interest, desire, arousal, satisfaction, activity, orgasm, masturbation, relationship, and problems. Poor sexual functioning was defined as SFQ Total scores >2 standard deviations below siblings’ mean. Multivariable logistic regression identified risk factors for poor sexual function.

RESULTS: Survivors (8.3%) were more likely to report poor sexual functioning as compared to siblings (4.9%, odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.4) and reported lower SFQ total scores (p < .001) and lower means on seven subscales. Poor sexual functioning among survivors was associated with older age (40-49 years: OR, 3.81; 95% CI, 1.78-8.18; 50-59 years: OR, 6.45; 95% CI, 2.28-18.30), not being married (OR, 4.39; 95% CI, 2.66-7.26), lower education (OR, 3.07; 95% CI, 1.32-7.14), learning/memory problems (OR, 1.83; 95% CI, 1.02-3.27), and high-dose cranial (≥40 Gy: OR, 3.45; 95% CI, 1.58-7.51) or high-dose testicular (≥10 Gy: OR, 4.16; 95% CI, 1.66-10.39) radiation.

CONCLUSIONS: Adult male survivors report poor sexual functioning at twice the rate expected before age 60 years. High-dose cranial or testicular radiation, as well as social and cognitive factors, contributes to risk. Improved awareness of sexual dysfunction prevalence and risk factors in male childhood cancer survivors can help clinicians better assess and treat those at highest risk.

PMID:40614134 | DOI:10.1002/cncr.35967

CPT Pharmacometrics Syst Pharmacol. 2025 Jul 4. doi: 10.1002/psp4.70051. Online ahead of print.

ABSTRACT

Rimegepant is a small-molecule calcitonin gene-related peptide receptor antagonist approved for acute and preventive migraine treatment in adults, administered as an orally disintegrating tablet (ODT). A population pharmacokinetic analysis was performed to describe rimegepant’s plasma concentration-time course and to estimate covariate effects on rimegepant exposure. The model was developed/evaluated in 3 stages using data from 11 phase 1 clinical studies, wherein rimegepant was administered orally to healthy adults, elderly people with stable chronic illness(es), adults with renal or hepatic dysfunction, and healthy adults with Japanese or Chinese ethnicity. Plasma concentration-time data were analyzed using nonlinear mixed effects modeling. A 2-compartment model with 4 transit compartments and a first-order absorption best described the rimegepant plasma concentration-time course. Estimated typical values (%relative standard error) were apparent clearance (CL/F) = 24.1 L/h (4.86%), apparent central volume of distribution (V_c/F) = 114.0 L (5.36%), apparent inter-compartmental clearance (Q/F) = 3.94 L/h (6.37%), apparent peripheral volume of distribution (V_p/F) = 46.0 L (5.30%), absorption rate constant (k_a) = 3.86 h^-1 (28.4%), and transit absorption rate constant (ktr) = 8.23 h^-1 (8.24%). Statistically significant covariates included empirical allometric body weight-based scaling exponents (0.75 for CL/F and Q/F and 1 for V_c/F and V_p/F); severe/moderate hepatic impairment and fluconazole/itraconazole co-administration on CL/F; fed status, dose on relative bioavailability; and fed status, itraconazole co-administration, and capsule and ODT formulations on transition absorption rate constant. Only severe hepatic impairment and co-administration of itraconazole resulted in a clinically significant decrease in rimegepant CL/F, supporting the recommendation to avoid rimegepant administration in patients with severe hepatic impairment or with a strong CYP3A4 inhibitor.

PMID:40614133 | DOI:10.1002/psp4.70051

CPT Pharmacometrics Syst Pharmacol. 2025 Jul 4. doi: 10.1002/psp4.70063. Online ahead of print.

ABSTRACT

Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare, life-threatening thrombotic microangiopathy caused by a severe inherited deficiency of ADAMTS13, a von Willebrand factor (VWF) cleaving enzyme. Inadequate clinical endpoint data often make it challenging to statistically power clinical trials in ultra-rare diseases. Therefore, utilizing in vitro, adamts13-knockout mouse, literature-based, and clinical data, a quantitative systems pharmacology (QSP) model was developed to describe the mechanistic relationship between ADAMTS13, VWF, and platelet count, and to supplement evidence from clinical trials of recombinant ADAMTS13 (rADAMTS13) for the treatment of cTTP. The effect of long-term prophylaxis with rADAMTS13 versus plasma-based therapies (PBT) on platelet count in patients with cTTP was investigated. One-year clinical trial simulations of thrombocytopenia occurrences in 1000 virtual patients, phenotype-matched to a cTTP Phase 3 study population (NCT03393975), were produced. Simulations suggested that once-weekly (Q1W) or once every 2 weeks (Q2W) rADAMTS13 administered over 1 year resulted in fewer patients experiencing thrombocytopenia versus patients treated with PBT (e.g., Q2W [rADAMTS13] relative to Q2W [PBT], HR = 0.47 [platelet count drop to < 150 × 10⁹/L], HR = 0.41 [< 100 × 10⁹/L]). These results provide confirmative evidence to support the use of rADAMTS13 in cTTP by integrating the current mechanistic understanding of interactions between ADAMTS13 and VWF multimers as its substrate, as well as key downstream parameters, primarily platelet count. Virtual patient clinical simulations from the QSP model supported the regulatory approval of rADAMTS13 in cTTP, highlighting the significant potential of QSP modeling to supplement clinical trial data in rare disease drug development.

PMID:40614125 | DOI:10.1002/psp4.70063

Chembiochem. 2025 Jul 4:e2500172. doi: 10.1002/cbic.202500172. Online ahead of print.

ABSTRACT

Intrinsically disordered and artificially denatured foldable proteins have many properties in common, even though the distribution of amino acid residues generally differ. Both are traditionally described as either adopting molten globule or random coil-like structure, depending on their amino acid composition. For a long period of time, it was believed that with the exception of glycine and proline, conformational preferences of individual amino acid residues are very similar, and therefore, not of great concern. This article discusses experimental and bioinformatical data which show that individual Ramachandran plot distributions in unfolded proteins depend on the characteristics of side chains. Furthermore, ample experimental evidence suggests the presence of nearest neighbor interactions between residues which are ignored in the classical random coil model. The article reviews and discusses work that emphasizes the necessity of a thorough understanding of the local behavior of disordered and unfolded proteins alike for an understanding of the coiled state of proteins. Unresolved issues are delineated and research perspectives suggested.

PMID:40614117 | DOI:10.1002/cbic.202500172

JMIR Form Res. 2025 Jul 4;9:e68316. doi: 10.2196/68316.

ABSTRACT

BACKGROUND: People experiencing homelessness have worse oral health outcomes and a notable health informational asymmetry compared to the general population. Screening programs present a viable option for this population; however, barriers to access, such as lower levels of health literacy, lack of information, and mistrust, narrow their chances to participate in such programs.

OBJECTIVE: The aim of this study is to investigate the applicability of generative artificial intelligence (AI) in designing a homeless health screening program fact sheet with experts by experience using co-design principles.

METHODS: Six fact sheet text variants were created by the open-access version of ChatGPT 3.5 for an oral cancer screening program targeting people experiencing homelessness in Budapest, Hungary. Clients of homeless social services (N=23) were invited to a short questionnaire survey and 3 semistructured focus group discussions between May and July 2024. General opinions regarding generative AI technology and direct feedback on the text variants were obtained. Additionally, a standardized readability assessment of the text variants was completed via the Sydney Health Literacy Lab Editor.

RESULTS: Almost two-thirds of participants (17/23) stated that they had previously heard about AI; however, their self-assessment regarding the extent of their knowledge resulted in an average of 2.38 (n=16) on a 5-point Likert scale. During the first focus group discussion, all 6 variants received a high score (between 4.63 and 4.92 on a 5-point Likert scale). In the next sessions, participants remained positive when the pool was narrowed to 4 versions, although they scored the texts lower. During open discussions, text variants were considered understandable, while difficulties with medical expressions, lengthiness of sentences, and references to a stereotypical homeless subgroup (rough sleepers) were also reported. The health literacy editor showed that most AI-generated text variants were difficult to read and too complex for the target group.

CONCLUSIONS: The co-design process revealed that focus group participants actively wanted to shape the fact sheet drafts. They shared their insights on how to make the text variants more appealing for the target audience. Moreover, the involvement of generative AI technology revealed that the participants have heard about the concept of AI and text generation as a potential function, and they have not rejected its use in health care settings.

PMID:40614110 | DOI:10.2196/68316

JMIR Mhealth Uhealth. 2025 Jul 4;13:e60426. doi: 10.2196/60426.

ABSTRACT

BACKGROUND: Air pollution is a major environmental cause of premature deaths, responsible for around 7 million deaths annually. In this context, personal air pollution exposure (PAPE), the product of pollutant concentration and minute ventilation (V’m), is a crucial measure for understanding individual health risks. Standard exposure techniques do not address the space-time variability of air pollution, both indoor and outdoor, and the intra- and intersubject variability in V’m.

OBJECTIVE: This study evaluates the feasibility of using a wearable body sensor network (BSN) to estimate PAPE in real-life settings, assess its capability to detect spatiotemporal variations in pollution levels, and compare inhaled dose estimates from the BSN with those from fixed monitoring stations and standard V’m values. The study also examines the system’s usability.

METHODS: The system, a BSN capturing physiological (pulse rate [PR] and respiratory rate [RR]) and environmental data, including health-affecting pollutants (particulate matter [PM] 1, PM2.5, PM10, CO2, CO, total volatile organic compounds, and NO2), was tested in a 4.5 km walk in Milan by 20 healthy volunteers. PR and RR collected by the system were used, together with biometric data and forced vital capacity estimations, in a model for V’m estimation to compute PAPE. Pollution levels were compared between morning and afternoon measurements, as well as between indoor and outdoor settings.

RESULTS: Variations in RR were found among volunteers and at different locations for the same participant. Significant differences (P<.001) in pollutant concentrations were observed between morning and afternoon for CO2 (higher in the morning) and PM (higher in the afternoon). Spatial variability along the walking path was also detected, highlighting the system’s high spatiotemporal resolution. Indoor environments showed high variability in CO2 and total volatile organic compounds, while outdoor settings exhibited elevated and variable PM levels. The mean PAPE to PM2.5 estimated with tabulated V’m and fixed station data was 13.31 (SD 4.16) μg while the one estimated with the BSN was 16.27 (SD 9.78) μg, 2.96 μg higher (22.3%; 95% CI -6.55 to 0.63; P=.05) than the former one, and with a broader IQR. Nevertheless, the 2 estimation methods show a good and strongly significant correlation (r=0.665; P<.001). The system’s usability was generally rated as good.

CONCLUSIONS: The BSN provides high-resolution spatiotemporal data on personal exposure, capturing differences in pollution levels dependent on time, location, and surrounding environment, along with individual physiological variations. It offers a more accurate estimation of inhaled dose in real-life settings, supporting personalized exposure assessments and potential applications in activity planning and complementing epidemiological research.

PMID:40614107 | DOI:10.2196/60426

JMIR Mhealth Uhealth. 2025 Jul 4;13:e64622. doi: 10.2196/64622.

ABSTRACT

BACKGROUND: Mental health is an essential element of life. However, existing mental health services face challenges in utilization due to issues such as societal prejudices and a shortage of counselors. Mobile health is gaining attention as an alternative approach to improving mental health by addressing the shortcomings of traditional services. As a result, various mental health apps are being developed, but there is a lack of evaluation research on whether these apps meet users’ needs.

OBJECTIVE: This study aims to evaluate the content and quality of mental health apps from the user’s perspective and identify the content features that influence evaluation scores. We also aim to guide future updates and improvements in mental health apps to deliver high-quality solutions to users.

METHODS: We searched the Google Play Store and iOS App Store using Korean keywords “mental health,” “mental health care,” “depression,” and “stress.” Apps meeting the following criteria were selected for the study: relevance to the topic, written in Korean, more than 700 reviews (Android) or more than 200 reviews (iOS), updated within the past 365 days, available for free, nonduplicate, and currently operational. After identifying and defining the primary contents of the apps, 7 users evaluated their quality using the user version of the Mobile Application Rating Scale (uMARS). Correlation analysis was performed to examine the relationships among app content, uMARS scores, star ratings, and the number of reviews. Multiple regression analysis was conducted to identify the factors influencing uMARS scores and each evaluation item.

RESULTS: The analysis included a total of 41 mental health apps. Content analysis revealed that reminders (n=29, 71%), recording and statistics features (n=29, 71%), and diaries (n=24, 59%) were the most common app components. The top-rated apps, as determined by uMARS evaluations, consistently provided information about counselors and counseling agencies, and included counseling services. uMARS scores were significantly correlated with the presence of health care provider information (r=0.53; P<.001) and counseling/question and answer services (r=0.55; P<.001). Multiple regression analysis indicated that providing more relevant information was associated with higher uMARS scores (β=.361; P=.02).

CONCLUSIONS: The quality of mental health apps was evaluated from the user’s perspective using a validated scale. To deliver a high-quality mental health app, it is essential to incorporate app technologies such as generative artificial intelligence during development and to continuously monitor app quality from the user’s perspective.

PMID:40614100 | DOI:10.2196/64622