Advancing Open Science

Unplanned excision (UE) of soft tissue sarcoma (STS) carries a high risk of local recurrence; additional wide excision is generally recommended. Some patients cannot undergo early re-excision because of patient preference, delayed referral, or an undefined extent of resection, and are observed instead. We retrospectively reviewed 32 patients with STS who had undergone UE at previous hospitals, who first visited our institution between 1997 and 2024, and in whom immediate additional wide excision could not be performed. Recurrence-free survival (RFS) was estimated using the Kaplan–Meier method. Local recurrence was detected in 22 of 32 patients (68.8%) over a median follow-up of 65.3 months, with 63.6% of recurrences occurring within 12 months. The 1-, 3-, and 5-year RFS rates were 56.2%, 32.5%, and 32.5% (median, 1.26 years). Recurrence also developed in 3 of 6 grade 1 tumors. In sensitivity analyses excluding patients referred only after recurrence (n = 20) and restricted to referral within 90 days (n = 22), recurrence still developed in 50.0% and 59.1%. The 5-year overall survival rate was 96.0%. UE of STS carries a high risk of early local recurrence, even in low-grade tumors; additional wide excision should therefore be recommended whenever feasible.

Precision medicine adapts prevention and treatment to individual variability in genetics, environment and lifestyle [...]

Bull fertility is a polygenic trait of significant economic importance in dairy and beef cattle, controlled by multiple genetic variants, including copy number variations (CNVs). Conventional single-variant association analyses primarily evaluate marginal effects of individual loci, whereas CNV co-occurrence patterns require complementary approaches. This study applied topological data analysis (TDA) to identify groups of bulls based on genome-wide CNVR profiles and to assess their association with insemination success rate. A total of 88 bulls were included, and the presence/absence of 406 consensus CNVR was determined for each animal. TDA was performed using the Mapper algorithm with a two-dimensional UMAP projection as the lens and DBSCAN for clustering, followed by community detection using the Leiden method. Bootstrap resampling (100 iterations) was used to assess the stability of the identified communities, and their association with fertility was tested using ANOVA and permutation testing (n = 1000). TDA with bootstrap consensus identified five bull communities ranging from 10 to 30 individuals each. The identified subtypes differed in mean insemination success rates, ranging from 48.3% to 72.5%. These differences were assessed using ANOVA and permutation testing. Gene annotation of the loci distinguishing these communities using Ensembl release 110 for the ARS-UCD1.2 assembly revealed genes potentially involved in embryonic development, cellular signaling, and immune response (e.g., IGF2, INS, NOTCH1, PAEP, TRAF2). TDA provides a framework for identifying groups of bulls with distinct combinations of CNVRs and evaluating their potential association with fertility. Due to the sample size (n = 88) and unadjusted phenotypes, the findings should be considered exploratory and hypothesis-generating. The discovered candidate genomic regions require mandatory validation and independent replication in larger cohorts before being considered for implementation in breeding programs.

Background and Objectives: Older adults evacuated during armed conflict may experience repeated residential moves in addition to the initial evacuation. Because the number of relocations in this study was recorded in unequal ordinal categories, the present analysis treats relocation frequency as a categorical exposure rather than as a continuous measure of a broader construct of relocation instability. This study examined post-return associations between self-reported relocation-frequency category, perceived community resilience, and loneliness among adults aged 50 years and older following wartime evacuation. Research Design and Methods: The analytic sample included 109 evacuees (eligibility ≥ 50 years; observed age range 54–89 years) from a northern Israeli community who had returned to their home community following evacuation during the Israel–Hamas War. Loneliness was measured using the 11-item Hebrew version of the De Jong Gierveld Loneliness Scale and perceived community resilience using the brief Conjoint Community Resiliency Assessment Measure (CCRAM-10). Relocation frequency was assessed with a single study-specific self-report item and analyzed in three categories (one relocation, two to three relocations, or four or more relocations); because the questionnaire did not explicitly define which transitions to count, the categories are interpreted as self-reported. Multivariable linear regression used indicator coding with one relocation as the reference category and adjusted for age, gender, and partnership status; sensitivity analyses additionally adjusted for depressive symptoms, current physical health, and household income. Results: Loneliness differed across relocation categories in the demographic-adjusted model (overall F(2,88) = 7.40, p = 0.001), but the pattern was not monotonic. Participants reporting two to three or four or more relocations had higher adjusted loneliness than the one-relocation group. Perceived community resilience was associated with lower loneliness (B = −0.312, p = 0.002), but relocation category was not significantly associated with community resilience (overall p = 0.187). In a same-sample comparison (n = 76), the relocation coefficients decreased after adding depressive symptoms, current physical health, and household income, and the overall relocation category term was not statistically significant in the extended model (p = 0.298). Discussion and Implications: Self-reported relocation-frequency category may mark heterogeneity in post-return experiences following evacuation, but the observed association with loneliness was sensitive to adjustment for additional psychosocial and socioeconomic factors. Cross-sectional data and a single-item relocation measure do not support causal or mediation conclusions. Longitudinal studies using multidimensional measures of relocation experiences are needed.

With the global expansion of aquaculture, histamine, an emerging contaminant derived from microbial decarboxylation of histidine in aquafeed, poses a hidden threat to aquatic ecosystems owing to its obscure sources. This study employed Eriocheir sinensis (E. sinensis) as a model to clarify histamine’s ecological risks and toxic mechanisms. A 5-day oral gavage trial with four histamine doses (0, 50, 100, 200 μg/g body weight) was performed on 160 male crabs (initial weight: 20.0 ± 0.5 g) allocated to four replicate tanks of 10 individuals each. The results showed histamine significantly increased crab autotomy rate in a dose-dependent manner (p < 0.05), disturbed neuroendocrine factors, damaged hepatopancreas microstructure and reduced digestive-enzyme activities (p < 0.05). It triggered hepatopancreatic oxidative stress-related apoptosis and altered the expression of mitogen-activated protein kinase (MAPK) associated genes, with significant up-regulation of pro-apoptotic genes and down-regulation of BCL2 (p < 0.05). Metabolomics showed distinct metabolic perturbations; arachidonic-acid metabolism was markedly enriched at 200 μg/g histamine (p < 0.05). Combined reverse virtual screening, molecular docking and RNAi analyses support the involvement of the histamine H2 receptor (H2R) in crustacean histamine toxicity, and H2R silencing significantly alleviated histamine-induced tissue damage (p < 0.05). Collectively, histamine exerts multi-system toxicity in E. sinensis principally via H2R, disrupting the neuroendocrine–immune network, impairing hepatopancreatic integrity and disturbing metabolic homeostasis. This study provides novel insights into the toxic mechanism of histamine in crustaceans, and offers valuable implications for feed safety evaluation, nutritional risk control, and healthy aquaculture management.

Improper use of vanillin as a food flavor additive presents a potential threat, and its effective supervision is therefore essential. Rapid biosensing is a beneficial supplementary or alternative strategy for current detection methods. Two modes of immunochromatographic assay (ICA) strips, based on gold nanoparticles (GNP) and fluorescent microparticles (FMP) labeled with a monoclonal antibody against vanillin, were separately assembled to obtain a GICA strip and an FICA strip for the detection of vanillin. The colorimetric/fluorescence signals of the strips were directly judged for semi-quantification by the naked eye and then digitally quantified by strip readers. The GICA demonstrated a linear range of 15.6–500 ng/mL, having a limit of detection (LOD) of 10.3 ng/mL. For the FICA strip, the enhanced sensitivity achieved an LOD value as low as 2.04 ng/mL and showed a linear range between 3.12 ng/mL and 200 ng/mL, representing a 5-fold improvement over the GICA strip. The two modes of ICA strips all had high specificity, stability, accuracy and precision for on-site vanillin detection within 10 min. For vanillin levels in authentic food product samples, the results were well correlated with the measurements obtained via the referenced ELISA and HPLC methods. The results indicated that two modes of ICA strips were capable of rapid, sensitive, on-site, semi-quantitative and quantitative detection of vanillin in food products, ultimately guaranteeing food safety and consumer health.

Background/Objectives: Sexual and gender minority (SGM) adults face barriers to HPV prevention related to healthcare access, limited information, and provider assumptions about their identities and healthcare needs. Guided by the cultural humility framework, this study examined SGM adults’ healthcare experiences and HPV vaccination beliefs in the United States and Canada. Methods: Fifty-one SGM adults (23 in Canada and 28 in the United States) completed an online qualitative survey addressing healthcare experiences, communication during sensitive encounters, HPV knowledge and vaccination, and healthcare decision-making. Responses were analyzed using thematic analysis and inductive qualitative content analysis informed by constant comparative techniques. Results: Participants described both affirming care and negative experiences involving identity-based assumptions, misgendering, discrimination, and barriers to appropriate care. They preferred providers to ask about clinically relevant circumstances rather than infer them from identity, explain sensitive questions and procedures, use precise language, protect privacy, obtain ongoing consent, and allow patients meaningful choices during care. Although most viewed HPV vaccination favorably, fewer than half reported receiving at least one dose. Low perceived susceptibility was a common reason for non-vaccination, along with limited information, cost, access, and concerns about stigma. Canadian participants more often encountered HPV vaccination through school-based programs, whereas U.S. participants more often described provider recommendations and other sources of information. Conclusions: Favorable views of HPV vaccination did not consistently translate into (reported) receipt of at least one vaccine dose. Participants’ accounts identify culturally humble communication practices that may improve discussions of HPV prevention by helping providers obtain clinically relevant information without relying on identity-based assumptions, although their effects on vaccination decisions and uptake require further evaluation. Exploratory comparisons between U.S. and Canadian participants also identified differences in how they encountered information about HPV vaccination and opportunities to receive it.

Background/Objectives: The development of human papillomavirus (HPV) vaccines is increasingly trending toward multivalency, and accurate quantification of HPV virus-like particles (VLPs) is critical for vaccine quality control. All marketed products currently rely on ELISA-based antigen quantification, which is complex and time-consuming. In accordance with the 3Rs principles, in vitro potency testing is expected to progressively replace in vivo testing. Therefore, efficient and convenient antigen quantification methods for multivalent HPV vaccines are essential to improve testing efficiency. Methods: In this study, photosensitive substances were loaded into beads of different diameters using a swelling method, and carboxyl groups were introduced onto the bead surfaces. By coupling HPV monoclonal antibodies via carboxyl groups, the use of high-risk coupling reagents was avoided, and a one-step light-initiated chemiluminescence assay (LiCA) was established for the in vitro relative potency testing of HPV vaccines. Results: The LiCA method established using 200 nm carboxyl-coupled beads for the HPV16/18 bivalent vaccine exhibited excellent linear range, specificity, accuracy, and precision. The LiCA results were comparable to those of ELISA; moreover, compared with ELISA, LiCA showed a lower detection limit and a wider dynamic range for both HPV16 and HPV18 VLP antigens, and was more convenient and time-saving to operate. Conclusions: A one-step LiCA was established using carboxyl-coupled beads with optimized diameters, providing an efficient and convenient approach for the in vitro relative potency testing of multivalent HPV vaccines based on large-particle VLP systems, which contributes to improved vaccine quality control and testing efficiency.