Tag: pubmed

J Chem Inf Model. 2025 Jul 4. doi: 10.1021/acs.jcim.5c00291. Online ahead of print.

ABSTRACT

Organic semiconductors (OSCs) composed of π conjugated molecules have attracted significant interest in studying bulk properties such as molecular arrangements and electron mobility. However, current traditional force fields (FFs) offer limited torsion types, failing to cover the full chemical space of π conjugated molecules and hindering further molecular dynamics simulation in deducing bulk properties through statistical mechanics. In this study, we introduce OSCFF, a GAFF2-compatible FF that supports diverse torsions for conjugated molecules and enables high-accuracy RESP charge prediction through a neural network (NN). To develop the OSCFF, we construct two expansive and diverse molecular data sets: one consists of around 56,000 fragment geometries with torsion profiles and another consists of around 472,000 optimized molecular geometries with RESP charges. Using these data sets, we train NN models to predict RESP charges and fit the missing dihedral parameters in GAFF2 through automatic differentiation techniques. We further demonstrate that OSCFF achieves high accuracy in predicting torsional energy profiles, RESP charges, and radial distribution functions for conjugated systems. Additionally, we release the data sets, dihedral parameters, and RESP model as open-source resources. We believe OSCFF will serve as a valuable tool for advancing the study of bulk properties in OSCs.

PMID:40614220 | DOI:10.1021/acs.jcim.5c00291

Int J Qual Stud Health Well-being. 2025 Dec;20(1):2508421. doi: 10.1080/17482631.2025.2508421. Epub 2025 Jul 4.

ABSTRACT

PURPOSE: The DenBalo study in Burkina Faso aimed to examine biological vulnerability in preterm versus full-term newborns but recorded fewer preterm births than expected based on routine health centre statistics. To investigate this discrepancy, a qualitative study was conducted to understand how healthcare workers assess gestational age in urban Burkina Faso.

METHODS: Ten in-depth interviews and four focus groups were conducted with health workers across four centres in Bobo-Dioulasso. Thematic analysis revealed five key themes: definitions of preterm birth, gestational age estimation methods, preterm birth reporting, care challenges, and proposed improvements.

RESULTS: Health workers varied in their definitions of preterm birth, using either gestational age (<37 weeks) or birth weight (<2.5 kg). Gestational age is often estimated from the last menstrual period, though considered unreliable. While early ultrasound is preferred for its accuracy, limited access leads to reliance on less precise fundal height measurements. Documentation of preterm births is inconsistent, and challenges include data collection issues, resource shortages, and parental reluctance to seek specialized care. Respondents emphasized the need for greater community awareness, improved infrastructure, and ongoing staff training to enhance preterm care.

CONCLUSION: Standardized gestational age estimation and improved data recording can enhance preterm birth surveillance and help reduce neonatal mortality in low-resource settings.

PMID:40614168 | DOI:10.1080/17482631.2025.2508421

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