Tag: pubmed

JMIR Res Protoc. 2026 Mar 31;15:e65833. doi: 10.2196/65833.

ABSTRACT

BACKGROUND: All around the world, the hairdressing sector constitutes a major occupational group, including about 90% women, most of whom are of reproductive age. Hairdressers are continuously exposed to numerous chemicals used in hair products, including endocrine-disrupting compounds such as resorcinol, parabens, phthalates, and UV filters. Few biomonitoring studies have explored occupational exposure to endocrine disruptors in hairdressers, and no data were found on their impact on the thyroid hormone system. Resorcinol is an oxidative hair dye with thyroid-disrupting properties that decrease thyroid hormone synthesis and could alter neurodevelopmental functions during fetal and perinatal stages in case of maternal exposure.

OBJECTIVE: This study aims to assess the occupational exposure to resorcinol in French hairdressers and analyze the relationship with biological thyroid parameters, taking into account the occupational exposure to other potential thyroid disruptors (parabens and UV filters like benzophenone and cinnamates).

METHODS: An exposed-unexposed cross-sectional study is proposed involving female hairdressers aged 18 to 45 years (working in hair salons) compared to occupationally unexposed controls (employed in office activities), who are recruited within 14 French occupational health centers. The hairdressers are followed during a 5-day working week to assess exposure data at both the individual level and the salon level. Urinary samples for the measurement of thyroid disruptors (resorcinol, parabens, metabolites of ethylhexyl methoxycinnamate, and benzophenone-3) are collected at 6 time points (before the day 1 shift, before and after the day 3 and day 4 shifts, and before the day 5 shift). Daily work tasks and use of hair products are self-reported within the workplace, and a complete inventory of hair products within the salon is carried out. Thyroid disruption effects are assessed by measuring blood thyroid parameters: triiodothyronine, thyroxine, thyroid-stimulating hormone, thyroglobulin, thyroperoxidase, and thyroglobulin antibodies. To assess nonoccupational exposure to thyroid disruptors and other confounding factors, information on sociodemographic data, place of residence, food and tobacco consumption, personal use of care products, professional career, and medical history is collected through questionnaires. Regarding statistical analysis, urinary samples from hairdressers and controls will be compared, and adjusted multivariable models will be used to analyze health outcomes.

RESULTS: The study duration extends from 2022 to 2027. As of December 2025, 9 occupational health centers have enrolled 66 hairdressers (employed in 54 hair salons) and 30 occupationally unexposed participants.

CONCLUSIONS: The results will represent the first data on occupational exposure to resorcinol in France and its relationship with thyroid hormones in hairdressers. Following a multidisciplinary approach that includes biomonitoring, epidemiology, and exposure data collection at both the hairdressers and salon levels, this study enables an in-depth assessment of exposure to the thyroid disruptors in the workplace. Together with the inventory of hair products, these results may enhance the tools for chemical risk assessment and prevention in hair salons.

PMID:41915798 | DOI:10.2196/65833

Antimicrob Agents Chemother. 2026 Mar 31:e0110125. doi: 10.1128/aac.01101-25. Online ahead of print.

ABSTRACT

Venetoclax (VEN), a selective BCL-2 inhibitor predominantly metabolized by CYP3A4, is a cornerstone therapeutic for myeloid neoplasms (MNs). Patients with myeloid malignancies are at elevated risk of invasive fungal infections (IFIs), and triazole antifungal drugs, such as posaconazole (PCZ) and voriconazole (VCZ), are commonly used for prophylaxis or treatment. These agents are potent CYP3A4 inhibitors and will exhibit significant potential for pharmacokinetic drug-drug interactions with VEN. Although studies on their interaction are limited, such combinations are frequently used in clinical practice, making further research highly significant. This study aimed to investigate the changes in blood concentration and the safety of VEN when combined with triazole antifungal drugs (PCZ and VCZ). Patients with MN treated with VEN from April 2023 to April 2025 were enrolled and allocated to the VEN monotherapy group and the VEN plus triazole antifungal drug group. We collected baseline demographic characteristics and monitored adverse events. Steady-state plasma concentrations of VEN were quantified using the liquid chromatography-mass spectrometry methodology. Statistical analyses, including comparative assessments of plasma concentrations and adverse event rates, were performed using IBM SPSS Statistics 26. A total of 54 patients were enrolled in the study. Following VEN dose reduction to 100 mg, plasma concentrations in the VEN + PCZ/VCZ group remained significantly elevated compared to the VEN group (P < 0.001). However, the magnitude of this elevation did not differ significantly between the VEN + PCZ group and the VEN + VCZ group (P = 0.176). In addition, there was no linear correlation between VEN concentration and PCZ/VCZ concentration. Safety analysis revealed no statistically significant differences between the two groups in the incidence of grade ≥3 hematological adverse events (P = 0.214) or severe (grade ≥3) gastrointestinal adverse events (P = 0.671). VEN combined with PCZ or VCZ resulted in significantly higher VEN exposure without a corresponding increase in severe hematological or gastrointestinal toxicity. This strategy effectively mitigates IFI risk without compromising the safety profile of VEN therapy.

PMID:41915767 | DOI:10.1128/aac.01101-25

Proc Natl Acad Sci U S A. 2026 Apr 7;123(14):e2600004123. doi: 10.1073/pnas.2600004123. Epub 2026 Mar 31.

ABSTRACT

Quantitative genetics is essential for genetic dissection of complex traits, yet the existing theory fails to illustrate a comprehensive landscape of genetic control mechanisms driving phenotypic variation and evolution. Here, we develop a statistical approach to assemble all genome loci into omnigenic interactome networks from diplotyped sequencing data. Such networks can not only capture dominance, epistasis, and pleiotropy and leverage these genetic concepts as bidirectional, signed, and weighted interactions among alleles and nonalleles, but also establish a framework for dissecting the genetic architecture of any single individual. While traditional approaches can only estimate coarse-grained genetic parameters at the population level, our approach can portray a fine-grained picture involving how each allele acts and interacts with every other allele for a single individual, thus facilitating its genome editing and genome engineering. By analyzing transcriptomic data of two diplotyped cultivars of a woody plant, our approach can interpret the genetic mechanisms underlying this species’ cold resistance and interorgan communication. Our network-centric approach, generalized as a graph statistics theory, builds the foundation of individualized quantitative genetics, a theory that can make genetics even more transformational to precision breeding or precision medicine.

PMID:41915744 | DOI:10.1073/pnas.2600004123

Proc Natl Acad Sci U S A. 2026 Apr 7;123(14):e2522964123. doi: 10.1073/pnas.2522964123. Epub 2026 Mar 31.

ABSTRACT

Stochasticity plays an important role in all biological systems. The standard way to deal with stochasticity involves averaging over an ensemble of independent realizations. However, such mean statistics need not accurately reflect the typical outcomes in any finite sample unless the system satisfies the property of ergodicity, which guarantees that each trajectory will over time experience the same statistics as the entire ensemble. Here, we argue that, in contrast, non-ergodicity might instead be the rule rather than exception in real biological systems and investigate its implications for eco-evolutionary dynamics through three case-studies. First, we show how demographic stochasticity leads to ergodicity breaking where the asymptotic growth rate carries a signature of the initial condition. This motivates us to define a mutant establishment threshold, which quantifies a critical population size above which the typical mutant population starts to grow. Second, we consider environmental stochasticity and demonstrate that eco-evolutionary feedback can lead to non-ergodic dynamics, which has the important consequence that the fitness of a genotype cannot be simply averaged over the environments. Finally, we show how in a metapopulation structure the evolutionary dynamics within a typical subpopulation can deviate from the ensemble dynamics in the entire metapopulation, which is sufficient to explain the evolution and persistence of cooperation despite a fitness cost.

PMID:41915738 | DOI:10.1073/pnas.2522964123

PLoS One. 2026 Mar 31;21(3):e0344198. doi: 10.1371/journal.pone.0344198. eCollection 2026.

ABSTRACT

Gene regulatory network inference is a key approach for elucidating molecular mechanisms underlying complex diseases, but accurately inferring them from high-dimensional data, especially when sample sizes are imbalanced, remains a significant challenge. Although the L1-type regularization methods have been used for gene network inference, the existing methods often fail under conditions involving high dimensionality, noise, and unequal sample sizes across phenotypes. To overcome these limitations, this study developed netRL, a novel computational framework that integrates the Random Lasso with prior network biological knowledge. The proposed method leveraged a bootstrap-based strategy to stabilize the selection of key regulatory genes and incorporates network-informed penalization using centrality measures (i.e., hubness and betweenness centrality). This study also introduced a statistical strategy using a hypergeometric test to assess the significance of the inferred edges, thereby enhancing the reliability of the network. Through extensive simulation studies, this study demonstrated that netRL outperforms conventional methods in both network estimation and gene selection. Applying netRL to whole-blood RNA-seq profiles from the Japan COVID-19 Task Force, this study successfully identified distinct phenotype-specific molecular interplays between asymptomatic and critical cases despite pronounced sample imbalance. The findings reveal that asymptomatic networks were dense and enriched for ribosomal proteins, whereas critical networks were sparse, centralized, and characterized by hub genes such as NFKBIA, B2M, CXCL8, and FOS. Pathway enrichment further revealed phenotype-specific biological processes, highlighting molecular signatures of disease progression. The results of this study suggest that enhancing the activity of asymptomatic condition-specific markers (e.g., ribosomal proteins) may provide important insights into the molecular mechanisms underlying COVID-19 severity. Collectively, these results demonstrate that netRL enables biologically interpretable and statistically robust network inference, offering new insights into the molecular basis of COVID-19 severity and broader applications in systems biology.

PMID:41915715 | DOI:10.1371/journal.pone.0344198

PLOS Glob Public Health. 2026 Mar 31;6(3):e0006180. doi: 10.1371/journal.pgph.0006180. eCollection 2026.

ABSTRACT

Viral load (VL) testing is a critical tool for clinical management of HIV, yet healthcare worker (HCW) shortages remain a key barrier to VL sample collection. This study assessed the feasibility and acceptability of VL dried blood spot (DBS) sample collection by community lay cadres (CLCs) compared to collection by trained HCWs. We implemented a cross-sectional diagnostic validation study across 10 purposefully selected public health facilities in Zimbabwe over six weeks in March-April 2024. Two DBS samples were collected from 374 participants: a reference sample collected by a HCW and a validation sample collected by a CLC. A subset of 173 CLC collections were observed using a checklist, and surveys were conducted with participating clients and CLCs. Diagnostic comparability was assessed using the proportion of matched pairs with agreement on viral load suppression status and Gwet’s AC1 statistic, while survey and observation data were analyzed using descriptive statistics. No samples were rejected by the laboratory, but two samples (one collected by a HCW and one by a CLC) were classified as invalid. Of the 372 paired tests analyzed, 96.0% (95%CI 93.2-97.7%) had concordant results, and the Gwet’s AC1 was 0.9564, indicating almost perfect agreement. All critical checklist items were done properly in 90.2% (95%CI 85.7-94.7%) of observed CLC collections. All CLCs reported confidence in performing DBS sample collection (89% very confident; 11% somewhat confident), and 94% of clients indicated willingness to have samples collected by a CLC in the future. These findings suggest that task-sharing VL DBS sample collection with CLCs is a feasible strategy, supported by strong diagnostic comparability, high CLC competency, and client acceptability. Policymakers should consider formalizing task shifting of VL sample collection within facilities. Further evidence on the feasibility of community-based DBS collection is needed.

PMID:41915714 | DOI:10.1371/journal.pgph.0006180

J Med Econ. 2026 Dec;29(1):994-1011. doi: 10.1080/13696998.2026.2644119. Epub 2026 Mar 31.

ABSTRACT

AIMS: The CIARA (Cost Impact Analysis in Rheumatoid Arthritis patients) study in Spain aimed to assess societal costs (€2022) associated with adult patients with moderate-to-severe rheumatoid arthritis (RA) starting advanced therapies after failing conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or a first biologics (bDMARD). Costs included those incurred by the Spanish National Health System, indirect costs due to productivity losses, and patient out-of-pocket expenses. Secondary objectives were to compare costs according to patients’ disease activity and treatment subgroups, identify variables associated with costs, and conduct a cost-utility analysis (CUA) of switching strategies.

METHODS: This prospective, non-interventional, multicenter cohort included adults with active RA (Disease Activity Score in 28 joints with erythrocyte sedimentation rate ≥3.2) starting a bDMARD or a targeted synthetic DMARD (tsDMARD) and followed for 12 months. Total and disaggregated mean costs per patient were estimated across three periods: 6 months before, and 0-to-6 months and 6-to-12 months post-switch. Costs for the 6-month pre-switch were compared with those for the 6-to-12 post-switch.

RESULTS: A total of 118 patients (mean age: 54.9 years; 78% women) were included. Mean total cost per patient increased from €6,882 pre-switch to €9,927 at 6-12 months (+44.3%;p < 0.001), primarily driven by pharmacological costs (+191%), while out-of-pocket expenses (-55%;p = 0.001) and productivity losses (-25%;p = 0.394) decreased. Switching from a csDMARD was dominant vs. switching from a first bDMARD (-€11,281/quality-adjusted life year [QALY] gained). Patients who achieved remission at 12 months had lower costs than those with moderate-high activity. The Work Productivity and Activity Impairment (WPAI) productivity impairment subscale and patient satisfaction with care were independently associated with total costs.

LIMITATIONS: Observational design, limited power for subgroups, official-actual price gap, and a 1-year horizon.

CONCLUSIONS: Switching to advanced therapies reduced out-of-pocket expenses and productivity losses. Although this reduction did not offset higher pharmaceutical spending, it may reflect clinical improvements.

PMID:41915412 | DOI:10.1080/13696998.2026.2644119

Food Funct. 2026 Mar 31. doi: 10.1039/d5fo05613f. Online ahead of print.

ABSTRACT

Growing evidence supports the hypoglycemic potential of blueberry anthocyanins, though clinical data remain limited. This study aimed to evaluate the effects of blueberry anthocyanin extract (BAE) supplementation on glycemic control and gut microbiota composition in patients with type 2 diabetes mellitus (T2DM). This 6-month pilot study included 15 elderly T2DM patients, who received either 400 mg day^-1 BAE (n = 8) or no supplement (n = 7). Glycemic parameters, gut microbiota (analyzed via 16S rRNA sequencing), and fecal short-chain fatty acids (SCFAs) were assessed at the baseline and after 1, 3, and 6 months. While statistically significant improvements in glycemic parameters were not achieved, favorable trends in fasting glucose and HbA1c were observed upon BAE intervention. Notably, BAE supplementation significantly altered gut microbiota composition by reducing the relative abundance of Firmicutes and increasing Bacteroidota (P < 0.05) and elevated SCFA levels, though the latter change was not statistically significant. Correlation analysis further revealed associations between specific bacterial genera, glucose metabolism indicators, and SCFAs. These findings suggest that BAE may modulate the gut microbiota and improve glucose metabolism in T2DM, supporting its potential as a dietary adjunct for glycemic management, although larger trials are needed for confirmation.

PMID:41915410 | DOI:10.1039/d5fo05613f

Health Serv Res. 2026 Apr;61(2):e70110. doi: 10.1111/1475-6773.70110.

ABSTRACT

OBJECTIVE: To examine whether Medicare beneficiaries with opioid use disorder (OUD) encounter limited access to hospitals’ highest-volume (i.e., “preferred”) or high-quality skilled nursing facilities (SNFs) compared to beneficiaries without OUD.

STUDY SETTING AND DESIGN: We estimated within-hospital disparities in access to preferred and high-quality SNFs by OUD status using linear probability models and discrete choice models (McFadden-style conditional logistic regression). We defined preferred status using shared hospital-SNF discharge volume and quality using CMS star ratings. In choice models, we matched patients with and without OUD 1:1 on discharging hospital and date, and applied inverse probability weighting and propensity score subclassification to address confounding.

DATA SOURCES AND ANALYTIC SAMPLE: We used 2017-2021 Medicare inpatient claims to identify Medicare beneficiaries ages 18+ discharged to a SNF following hospitalization.

PRINCIPAL FINDINGS: In the full sample (N = 6,490,593), patients with OUD were 2.5 and 3.6 percentage points (pp) less likely to enter preferred and high-quality SNFs, respectively. Among those discharged to preferred SNFs, patients with OUD were 2.0 pp less likely to enter high-quality preferred SNFs. In the matched subsample (n = 156,610), the marginal effect of preferred status on a person being discharged to their closest SNF was 1.1 pp lower for patients with OUD than those without OUD (p < 0.05), but with no significant disparity after inverse probability weighting. When the closest SNF’s quality rating increased by 1 star, the probability of entry increased by 0.7 pp for people without OUD but decreased by 0.2 pp for people with OUD (difference = 0.9 pp, p < 0.001), a difference that persisted after weighting.

CONCLUSIONS AND RELEVANCE: Publicly-reported star ratings had weaker associations with the SNF placements of Medicare beneficiaries with OUD compared to those without OUD, and preferred referral networks alone did not eliminate these gaps. Regulatory and reimbursement reforms that support SNFs in developing OUD-related care capacity and that promote equitable admissions deserve attention.

PMID:41915406 | DOI:10.1111/1475-6773.70110

Clin Transplant. 2026 Apr;40(4):e70520. doi: 10.1111/ctr.70520.

ABSTRACT

INTRODUCTION: The purpose of our study was to assess UTD status of routine childhood vaccinations at the time of organ transplant among our institution’s pediatric SOT recipients and assess the reasons behind underimmunization.

MATERIALS AND METHODS: We reviewed vaccination records of pediatric recipients of heart, kidney, and liver transplants at Mayo Clinic, Rochester, MN who received a transplant between January 2011 and December 2024. All immunizations received prior to date of transplantation were included. Once immunization status was determined, the EMR was further reviewed to assess reasons why patients were not UTD.

RESULTS: A total of 204 patients were included in the study after meeting inclusion criteria: 68 kidney, 80 heart, and 55 liver transplant recipients; one patient received both a liver and kidney transplant. Seventy-seven patients (37.7%) were UTD at the time of SOT. When excluding live vaccines, 90 patients (44.1%) were UTD. The series most commonly not UTD was HPV (59 patients not UTD, 28.9%); the most UTD series was pneumococcal vaccine (six patients not UTD, 2.9%). Among 127 patients not UTD, 30 (23.6%) patients were not UTD due to time-based factors, followed by 27 (21.3%) due to patient-based factors, 25 (19.7%) due to provider-based, 14 (11%) due to medically contraindicated, and 14 (11%) due to hospital policy factors. Seventeen patients (13.4%) were classified as multi-category.

CONCLUSIONS: Less than 40% of pediatric SOT recipients were UTD on routine immunizations at time of transplant. This was due to a variety of factors. Strategies to increase uptake of immunizations prior to transplant among this vulnerable group should be further explored.

PMID:41915405 | DOI:10.1111/ctr.70520