Journal of Dental Research

Background: Management of transverse maxillary deficiency in children with severely destructed first permanent molars (FPMs) is challenging because traditional tooth-borne rapid palatal expanders rely on these teeth for anchorage. These teeth are often compromised by extensive caries or Molar Incisor Hypomineralization (MIH), rendering them unsuitable as anchor units. Miniscrew-assisted expansion techniques may offer solutions that bypass compromised teeth. Methods: A systematic literature search was conducted using PubMed, PubMed Central, Google Scholar, DOAJ, OATD, OpenGrey, BASE, and the Cochrane Library (CENTRAL) (January 2005 to January 2026). Citation tracking and reference screening supplemented the search. The review protocol was developed a priori following PRISMA recommendations but was not registered in PROSPERO. Inclusion criteria: randomized controlled trials, prospective/retrospective comparative studies ([&ge;]10 patients/group) involving children aged 6-18 years with transverse maxillary deficiency. During full-text screening, studies were selected if their patient populations could be reasonably inferred to contain children with compromised FPMs based on clinical context (e.g., studies in pediatric dentistry, patients referred for MIH or severe caries). Risk of bias was assessed using the Cochrane RoB 2.0 tool for RCTs and ROBINS-I for non-randomized studies. Random-effects meta-analyses using the DerSimonian-Laird method were performed for skeletal expansion (standardized mean difference, SMD), dental tipping (SMD), success rate (pooled proportion), and relapse (mean difference). Results: From 28,879 initially retrieved records, 23 studies (1,847 patients; mean age 11.4 +/- 2.3 years) were included after screening; 16 contributed to meta-analyses. Of these, 987 patients received miniscrew-assisted expansion and 860 underwent conventional expansion. Four appliance types were identified: hybrid hyrax, C-expander, MARPE/MSE, and miniscrew-anchored distalizers. Miniscrew-assisted expansion achieved significantly greater skeletal expansion than conventional expanders (SMD=1.24; 95% CI: 0.89 to 1.59; p<0.001; I2=58%). Miniscrew-assisted expansion significantly reduced dental tipping compared with conventional expansion (SMD= -0.98; 95% CI: -1.42 to -0.54; p<0.01; I2=51%). MARPE appliances demonstrated a pooled success rate of 93.9% (95% CI: 89.7% to 97.2%; I2=41%). Long-term data ([&ge;]5 years, 3 studies) suggested a possible reduction in relapse of approximately 65% with MARPE. Subgroup analysis showed no significant outcome differences between appliance types (p=0.24). GRADE evidence quality was moderate for skeletal/dental outcomes, high for success rate, and low for long-term relapse. Conclusion: Miniscrew-assisted expansion represents a predictable and minimally invasive strategy for children with compromised first permanent molars, achieving superior skeletal expansion with reduced dental side effects compared to conventional techniques. These findings support a stratified appliance selection approach based on individual patient characteristics.

Background: Incisor extraction represents a strategic yet underutilized orthodontic treatment modality for managing anterior discrepancies. Despite its clinical relevance, the evidence base has not been systematically synthesized with meta-analytic techniques. Objective: To systematically review and meta-analyze the evidence on incisor extraction in orthodontic treatment, evaluating clinical outcomes and biomechanical efficacy in both maxillary and mandibular arches. Methods: A comprehensive search of open-access electronic databases (PubMed, LILACS, SciELO, Google Scholar, DOAJ, OpenGrey) and orthodontic journal archives was conducted from inception to January 11, 2026 following PRISMA guidelines. Eligible studies included randomized controlled trials, prospective cohort studies, and retrospective cohort studies with greater than or equal to 10 patients reporting quantitative outcomes following incisor extraction or incisor movement with premolar extraction. Primary outcomes included space closure efficiency, incisor position changes, root resorption, and stability. Risk of bias was assessed using ROBINS-I for observational studies and Cochrane RoB 2.0 for RCTs. Certainty of evidence was evaluated using GRADE. Results: From 1,842 identified records, 20 primary studies met inclusion criteria (4 RCTs, 16 observational studies), comprising 1,347 patients. Sixteen studies provided data for meta-analysis. With moderate-certainty evidence, mandibular incisor extraction (8 studies, n=412) demonstrated mean space closure of 5.2 mm (95% CI 4.8 to 5.6 mm, I-squared=34%) with favorable long-term stability (mean irregularity increase 0.3 mm, 95% CI 0.1 to 0.5 mm, I-squared=28%). Low-certainty evidence indicates clear aligner accuracy is limited to 78.9% of predicted incisor tip movement (3 studies, n=187, 95% CI 72.3 to 85.5%, I-squared=41%); these findings may not reflect newer generation aligner systems. Low-certainty evidence suggests maxillary incisor movement following premolar extraction (6 studies using tomographic imaging, n=387) results in palatal bone resorption (mean -0.43 mm, 95% CI -0.62 to -0.24 mm, I-squared=52%), with greater effects in adults versus adolescents (mean difference 0.31 mm, p = 0.02); although statistically significant, the magnitude may be clinically negligible in patients with adequate baseline alveolar thickness. Moderate-certainty evidence indicates en-masse retraction results in faster space closure than two-step retraction (4 RCTs, n=214, mean -4.2 months, 95% CI -5.8 to -2.6 months). Moderate-certainty evidence shows root resorption incidence is 12.4% (95% CI 8.7 to 16.1%), with subgroup analysis: greater than 2 mm threshold 13.2% (7 studies), at least one-quarter root length threshold 11.4% (5 studies). Low-certainty evidence suggests extraction versus non-extraction comparisons (4 studies, n=326) show no significant differences in relapse. Conclusions: Mandibular incisor extraction demonstrates favorable long-term stability with minimal profile changes but requires recognition of clear aligner accuracy limitations. Maxillary incisor movement carries risks including palatal bone resorption, particularly in adults, though the clinical significance may vary with baseline alveolar thickness. En-masse retraction results in faster space closure with comparable root resorption risk. Treatment decisions should consider patient-specific factors including age, alveolar bone morphology, malocclusion pattern, and appliance selection.

Background: Impacted maxillary incisors present significant clinical challenges requiring interdisciplinary management. To date, no meta-analysis has quantitatively synthesized success rates specifically for impacted maxillary incisors. This systematic review and meta-analysis aimed to determine the pooled success rate of orthodontic traction for impacted maxillary incisors and identify factors influencing outcomes. Methods: A systematic review and meta-analysis of observational studies was conducted following PRISMA 2020 guidelines. A systematic search was performed in PubMed, Epistemonikos, Cochrane Library, and Google Scholar (January 2011 - March 5, 2026). Primary studies reporting success rates of orthodontic traction for impacted maxillary incisors were included. The primary outcome was successful eruption and alignment into the dental arch. Although the protocol was not registered in PROSPERO, the methodology was predefined, documented, and strictly followed to minimize risk of bias. Pooled success rates were calculated using a random-effects model (DerSimonian-Laird method) with R software (meta package). Heterogeneity was assessed using I2 statistics. Publication bias was evaluated using funnel plots and Egger's test. Quality assessment employed ROBINS-I. Results: Eleven studies with 2,847 patients were included in the systematic review; 2,149 patients from 11 studies provided sufficient data for quantitative synthesis. The pooled success rate was 82.3% (95% CI: 78.6-86.0%), with a prediction interval ranging from 70% to 91%. Considerable heterogeneity was observed (I2 = 78%, p < 0.001). Subgroup analysis showed that younger age (<14 years) was associated with significantly higher success rates (88.4% vs. 78.2%, p = 0.01). Mild impaction depth (<5mm) was associated with higher success rates (89.2% vs. 76.5%, p = 0.02). No significant publication bias was detected (Egger's test, p = 0.18); however, the power to detect publication bias is limited with fewer than 15 studies. Certainty of evidence was moderate due to heterogeneity and observational study designs. Conclusions: Orthodontic traction is an effective, though not universally successful, treatment modality, with a pooled success rate of 82.3% for impacted maxillary incisors, and success significantly associated with patient age and impaction severity. Early intervention and favorable impaction characteristics are associated with better outcomes

Background: Peak height velocity (PHV) is a critical indicator of pubertal growth timing and is widely used in orthodontics to determine optimal timing for growth modification interventions. Secular trends toward earlier maturation have been reported, but a quantitative synthesis of PHV age reduction across generations is lacking. Objective: To systematically review and quantitatively synthesize evidence for secular trends in age at PHV and to estimate the pooled mean difference in PHV age between historical and contemporary cohorts. Methods: A systematic search was conducted in PubMed and Google Scholar from January 1990 to December 2021. The Directory of Open Access Journals (DOAJ) was also searched but yielded no eligible studies due to the specificity of the search string. Studies were included if they reported age at PHV in two or more birth cohorts separated by at least 20 years, used objective methods to determine PHV (longitudinal growth data with curve fitting), and reported means with standard deviations or standard errors. Risk of bias was assessed using the Newcastle-Ottawa Scale. A random-effects quantitative synthesis (meta-analytic approach) was performed to calculate the pooled mean difference in PHV age between historical and contemporary cohorts. Between-study variance (tau-squared) was estimated using the restricted maximum likelihood (REML) method. Heterogeneity was assessed using I-squared statistics. Given the limited number of eligible studies, findings should be interpreted as preliminary. Results: Two high-quality longitudinal studies met inclusion criteria, comprising 171 participants from historical cohorts (1969-1973) and 71 participants from contemporary cohorts (1996-2000). The pooled mean difference in PHV age was -0.48 years (95% CI: -0.72 to -0.24, P < 0.001), indicating that contemporary children reach PHV approximately 0.5 years earlier than their historical counterparts. PHV velocity showed a pooled increase of 0.71 cm/year (95% CI: 0.48 to 0.94, P < 0.001). Heterogeneity was low (I-squared = 0% for both analyses). Both studies were rated as low risk of bias. These findings are based on a limited number of studies and should be interpreted as preliminary. Conclusions: This preliminary quantitative synthesis provides evidence of a secular decline in age at peak height velocity of approximately 0.5 years in contemporary children compared to historical cohorts, accompanied by an increase in growth velocity. These findings suggest that orthodontic growth modification strategies may need to be initiated earlier than traditionally recommended. However, given the limited evidence base, results should be interpreted with caution and require confirmation in large-scale longitudinal studies.

The in vitro study aimed to evaluate linear dimensional shifts in intraoral photographs of the esthetic zone captured using two smartphone cameras--the iPhone 15 Pro Max and the Samsung Galaxy S23 Ultra--compared to a digital single-lens reflex (DSLR) camera, which is regarded as the gold standard for dental photography. Imaging was performed under controlled conditions using a custom-designed stand and stabilizer to maintain a consistent distance and angle between the dental model and the photographic devices. Standardized frontal and occlusal images of the anterior maxillary region were acquired, and point-to-point linear measurements between specified dental landmarks were performed using calibrated digital imaging software. Each measurement was conducted triple and then averaged across various samples per image to guarantee precision and dependability. Friedmans test with Bonferroni correction was applied for statistical analysis to evaluate differences among the imaging devices. The results indicated no statistically significant variations in linear measures between the DSLR and the Samsung Galaxy S23 Ultra (p > 0.05), however minor inconsistencies were noted between the DSLR and the iPhone 15 Pro Max. It is important to acknowledge that all images were obtained utilizing the stabilization system, which contrasts with the conventional handheld approach applied in clinical environments and could impact the external validity of the results. The Samsung Galaxy S23 Ultra, in telephoto mode, demonstrated measurement precision similar to that of a DSLR camera, potentially serving as a reliable choice for clinical intraoral photography. The iPhone 15 Pro Max demonstrated potential, although minor measurement discrepancies.

BackgroundDental caries and periodontal disease represent the most prevalent global oral health conditions, collectively affecting several billion people. The diagnostic interpretation of dental radiographs, a cornerstone of modern dentistry, is associated with considerable inter-observer variability. In routine clinical practice, clinicians are required to evaluate a high volume of radiographic images daily, a cognitively demanding task in which diagnostic fatigue, time constraints, and the inherent complexity of overlapping anatomical structures can lead to the inadvertent oversight of early-stage pathologies. Artificial intelligence (AI) offers a transformative opportunity to augment clinical decision-making by providing rapid, objective, and consistent radiographic analysis, thereby serving as a tireless adjunct capable of flagging findings that may be missed during routine human inspection. MethodsThis study developed and validated a deep learning system for the automated detection of dental caries and alveolar bone loss using a dataset of 1,063 periapical and bitewing radiographs. Two separate YOLOv8s object detection models were trained and evaluated using a rigorous 5-fold cross-validation methodology. To align with the clinical use-case of a screening tool where high sensitivity is paramount, a custom image-level evaluation criterion was employed: a true positive was recorded if any predicted bounding box had a Jaccard Index (IoU) > 0 with any ground truth annotation. Model performance was systematically evaluated at confidence thresholds of 0.10 and 0.05. ResultsAt a confidence threshold of 0.05, the caries detection model achieved a mean precision of 84.41% ({+/-}0.72%), recall of 85.97% ({+/-}4.72%), and an F1-score of 85.13% ({+/-}2.61%). The alveolar bone loss model demonstrated exceptionally high performance, with a mean precision of 95.47% ({+/-}0.94%), recall of 98.60% ({+/-}0.49%), and an F1-score of 97.00% ({+/-}0.46%). ConclusionThe YOLOv8-based models demonstrated high accuracy and high sensitivity for detecting dental caries and alveolar bone loss on periapical radiographs. The system shows significant potential as a reliable automated assistant for dental practitioners, helping to improve diagnostic consistency, reduce the risk of missed pathology, and ultimately enhance the standard of patient care.

Objectives: Accurate assessment of orthognathic surgical accuracy is essential in the evaluation of operative techniques. Surgical accuracy is often reported as rotational and translational deviations from planned positions. This results in 6 separate values, translation in three planes, anterior-posterior (AP), superior-inferior (SI) and medial-lateral (ML) and rotations about three axes, pitch, roll and yaw. However, rotations will influence 3-dimensional positions and translational discrepancies. Methods: We have derived a mathematical formula using Euclidean geometry and quadratic functions that quantifies the impact of rotations on translational discrepancies. This allows for the calculation of a total discrepancy value that incorporates the three translations and rotations. Furthermore, we developed an interactive web-based application using the open-source shiny R package. Results: We have successfully reduced equations from Euclidean geometry into a quadratic form. The equation is as follows, [4(sin{theta}/2)2-2]x2 + [8d(sin{theta}/2)2-2d]x + 4d2(sin{theta}/2)2 = 0, where {theta} represents the rotational discrepancy in radians and d represents the translation discrepancy. This allows us to solve for the correction needed to be made to translational discrepancies to account for the influence of rotational discrepancies. We successfully developed a web application with a user-friendly graphical user interface. Clinicians upload their own data in the excel (.xlsx) file format and the application automatically performs the necessary calculations over many patients, returning a downloadable table of results. Conclusion: We present a mathematical formula incorporated into a web-application to combine translational and rotational discrepancies for deeper insight when evaluating orthognathic surgical accuracy. Clinical Relevance: This allows surgeons to account for rotational influence on 3-dimensional translational discrepancies.

BackgroundPeriodontitis (Perio) is a progressive oral disease characterized by inflammation and degradation of the periodontal apparatus and is associated with local and systemic morbidity including loss of teeth, cardiovascular disease, and diabetes mellitus, among others. Perio is highly prevalent in domestic canines and exhibits certain parallels in pathogenesis and pathophysiology to Perio in humans, although standard treatments are less effective. In both species, a complex interplay between oral microbiota and host immune response is implicated in the etiology of Perio but is not fully understood. ResultsUsing shotgun metagenomics and RNA-seq on oral samples from companion dogs, we identify features of the oral microbiome and host transcriptional profile that are associated with Perio and its progression. We observe differences in microbiota composition between Perio and non-Perio animals that are largely consistent with what has been described in humans but also identify several species that are distinctly associated with canine Perio. We observe an abrupt shift in host gene expression related to immune response and tissue structure that is associated with disease severity, specifically the progression from mild periodontal disease (PD) to more severe Perio and the initiation of clinical attachment loss. The gingival plaque microbiota exhibits a parallel dynamic, with distinct compositional profiles in mild, moderate, and severe PD. We then examine several of the known mechanistic components of the keystone pathogen hypothesis of PD, identifying specific commonalities between canine and human pathologies, including the involvement of Porphyromonas species and related virulence factors. Additionally, we show infiltration of gingival tissue by Porphyromonas and Tannerella spp. via fluorescence microscopy. Finally, we assess correlations between host gene expression and microbial metabolic pathways which suggest additional potential virulence factors. ConclusionsThis work elucidates the metagenomic and transcriptomic signatures of Perio in companion dogs with the goals of informing veterinary medicine, evaluating the potential of canines as a model organism for the study of Perio, and clarifying the relationship between Perio development and progression, the oral microbiota, and the localized host response. Our findings provide insight into the etiopathogenesis of canine Perio and its relationship to human Perio and suggest novel targets of potential translational interest.

This study develops a methodological framework that combines conventional antimicrobial susceptibility testing with Particle Swarm Optimisation (PSO) to enhance toothpaste formulations, employing Escherichia coli isolated from the oral cavity as a model organism. We used the agar well diffusion method to see if two fluoride toothpastes (Oral B and My-my) could kill oral E. coli isolates at 6.25%, 12.5%, 25%, 50%, and 100% concentrations. A surrogate Random Forest model was created using these experimental data to link formulation parameters to antimicrobial activity. Then, PSO was used to find the best formulation traits. Multi-objective optimisation that looks at the trade-offs between antimicrobial effectiveness and cytotoxicity was shown as a conceptual framework. Both toothpastes showed antimicrobial activity that depended on the concentration, with Oral B being more effective (23.0 mm at 100% concentration) than My-my (20.0 mm). The PSO framework, utilised as a methodological illustration while explicitly recognising data constraints, determined hypothetical formulation parameters (sodium fluoride 1100 ppm, hydrated silica abrasive, 2.5% SLS) with an anticipated zone of inhibition of 26.3 mm. These predictions are mathematically optimal for a surrogate model that was trained on very little data (n=10 formulation points). They need a lot of experimental testing before any claims about the formulation can be made. This work is presented as a proof-of-concept methodological framework, not as validated formulation guidance.

To make effective antimicrobial toothpastes, you need to optimize many parts that work together. Creating new formulations the old-fashioned way takes a lot of time and money. This research formulates and substantiates a methodological framework that combines systematic antimicrobial susceptibility testing with Particle Swarm Optimization (PSO) to enhance toothpaste formulations against clinically significant oral pathogens. Using a D-optimal mixture design, we made 24 different toothpaste formulations by changing the type of fluoride (NaF, MFP, SnF2), the concentration of fluoride (1000-1500 ppm), the concentration of SLS (0.5-2.5%), the type of abrasive (silica, calcium carbonate, dicalcium phosphate), and the concentration of abrasive (10-30%). We used agar well diffusion and minimum inhibitory concentration (MIC) tests to see how well the drugs worked against Streptococcus mutans ATCC 25175, Porphyromonas gingivalis ATCC 33277, and Lactobacillus acidophilus ATCC 4356. A Random Forest surrogate model was trained on 120 experimental data points (24 formulations x 5 concentrations) and validated through 10-fold cross-validation. Multi-objective PSO was used to improve the effectiveness of antimicrobials, the availability of fluoride, and the cost of the formulation. Chosen PSO-predicted formulations underwent experimental validation. The antimicrobial activity changed a lot (p < 0.001) depending on the formulation parameters. The optimized formulation (sodium fluoride 1120 ppm, SLS 2.3%, hydrated silica 18%, pH 7.2) showed 28.4 {+/-} 1.2 mm of inhibition against S. mutans, 26.8 {+/-} 1.4 mm against P. gingivalis, and 24.2 {+/-} 1.1 mm against L. acidophilus. These were improvements of 18.5%, 22.3%, and 19.8%, respectively, over the best commercial comparator. Experimental validation corroborated PSO predictions with a mean absolute error of 5.2%. Multi-objective Optimization found Pareto-optimal formulations that let you choose based on trade-offs between effectiveness, safety, and cost. Combining systematic experimental design with PSO gives a tested framework for making rational toothpaste formulations. This method significantly lowers the amount of work needed for experiments while also allowing for the Optimization of multiple competing formulation goals.

Objectives: Machine learning can predict severe tooth loss (STL, 6 or more missing teeth), but opaque black-box models neglecting complex survey designs limit clinical adoption. This study developed and externally validated an intrinsically interpretable, survey-weighted framework for population-level STL prediction, capturing complex socio-behavioral and systemic health determinants. Methods: We analyzed nationally representative data from BRFSS 2022 (derivation, N=433,772), BRFSS 2024 (temporal validation, N=448,213), and the clinically examined NHANES 2015-2018 (cross-domain validation, N=10,775). Missing data were resolved using an anti-leakage HistGradientBoosting MICE pipeline, preserving multivariate epidemiological variance. An Explainable Boosting Machine (EBM, GA2M) was natively trained by integrating complex survey weights. For external clinical validation, structural domain shift was addressed through non-parametric Isotonic Regression recalibration. Results: The EBM achieved strong temporal stability on BRFSS 2024 (AUC: 0.8627; Brier Score: 0.0845). Upon cross-domain validation against NHANES 2015-2018, the calibrated model demonstrated robust transportability (AUC: 0.7504; Brier Score: 0.1358). Notably, the zero-shot EBM (AUC: 0.7591) closely matched the predictive ceiling of a black-box stacked meta-ensemble (AUC: 0.7706), eliminating the need for unstable post-hoc approximations. Fully auditable shape functions explicitly revealed non-linear risk thresholds and synergistic pairwise interactions for key predictors including age, smoking, income, and diabetes. Decision curve analysis confirmed substantial positive net clinical benefit across a 5%-50% risk threshold continuum. Conclusions: The MICE-EBM framework predicts STL with complete intrinsic transparency and robust probabilistic reliability. By successfully generalizing across unobserved temporal and clinical cohorts, this TRIPOD+AI compliant framework provides a clinically deployable tool to optimize targeted dental public health interventions.

Ionizing radiation can be an effective therapy for prostate cancer. Unfortunately, however, more aggressive prostate cancers such as neuroendocrine prostate cancer (NEPC) are often radiation resistant, which contributes to their high degree of morbidity and mortality. In this study, we used an unbiased approach to identify novel mechanisms that contribute to resistance to radiation and that are associated with neuroendocrine differentiation. Specifically, we compared the expression of cell surface proteins by mass spectrometry in prostate cancer cell lines that had been either untreated or treated with radiation to induce resistance, a process that also promotes neuroendocrine differentiation. Among the proteins identified by this screen, we focused on folate receptor (FR) because of its known biological functions and the fact that it is a validated therapeutic target. Our data reveal that FR has a causal role in enabling prostate cancer cells to resist radiation. Importantly, we also demonstrate that the expression of FR is regulated by HIF-1, which also has a causal role in radiation resistance and neuroendocrine differentiation. Given that the ability of cells to resist damage and death in response to ionizing radiation depends largely on their ability to buffer the substantial increase in reactive oxygen species (ROS) that is generated by radiation, we also demonstrate that the folate-FR axis promotes radiation resistance by sustaining intracellular glutathione levels that buffer this increase in ROS. In summary, the data reported here highlight a novel role for FR in resistance to ionizing radiation that is intimately associated with the hypoxic microenvironment of NEPC and the ability of the folate-FRa axis to maintain redox homeostasis.

Postnatal growth of the mandibular condyle requires coordinated expansion of fibrocartilage and production of chondrocytes, yet the cellular populations that organize this process remain incompletely defined. Here we identify a Wnt-responsive fibrocartilage progenitor population that contributes to postnatal mandibular condylar cartilage growth. Using a direct Wnt activity reporter (R26-WntVis), inducible genetic lineage tracing (Axin2CreERT2), and single-cell transcriptomics, we define a Wnt-enriched progenitor-like cluster localized predominantly within the fibrocartilage zone. Lineage tracing demonstrates that Axin2-lineage cells expand laterally within fibrocartilage and generate vertically aligned chondrocytes in the chondrocartilage compartment, indicating bidirectional growth contribution in vivo. Conditional ablation of {beta}-catenin in Axin2-lineage cells results in depletion of the fibrocartilage compartment and premature activation of chondrogenic differentiation programs, whereas constitutive {beta}-catenin activation disrupts compartmental organization without enhancing proliferation. Mechanistically, we identify Foxm1 as a Wnt-associated proliferative mediator enriched in fibrocartilage, and genetic reduction of Foxm1 cooperates with {beta}-catenin deficiency to impair condylar growth. In parallel, {beta}-catenin loss derepresses TGF-{beta}-Smad signaling and enhances chondrogenic differentiation, indicating that canonical Wnt activity coordinates proliferative maintenance while restraining lineage commitment within the same cellular compartment. Together, these findings identify a Wnt-responsive fibrocartilage progenitor system that regulates postnatal mandibular condylar cartilage growth by coupling Foxm1-associated proliferative maintenance with suppression of TGF-{beta}-dependent chondrogenic differentiation during temporomandibular joint development. Graphical abstractWnt-responsive fibrocartilage progenitors coordinate postnatal mandibular condylar cartilage growth through Foxm1-dependent proliferative maintenance and suppression of TGF-{beta}-driven chondrogenic differentiation.

A compact, in-house developed ultraviolet germicidal irradiation (UVGI) system adaptable to static, mobile, or robotic platforms was developed for the effective sterilization of bacteria and fungi using a wireless mode of operation. Under controlled laboratory conditions, its efficacy was evaluated against three representative biofilm-forming pathogens: Bacillus subtilis (Gram-positive, spore-forming, motile bacterium), Escherichia coli K12 (Gram-negative, non-spore-forming, non-motile bacterium), and Candida albicans M-207 (multi-drug-resistant, clinical yeast isolate). Microbial viability following UVGI exposure was assessed using colony-forming unit (CFU) and MTT assays, and morphological alterations were characterized by scanning electron microscopy (SEM). Cultures were exposed to UV-C radiation at distances of 1-5 m for 15-90 min. CFU assay demonstrated 100% kill of all tested organisms at 1 m and 15 min, corresponding to doses of 600.3, 576 & 697.5 mJ/cm{superscript 2}. Although MTT assays indicated residual metabolic activity under the same conditions, CFU results confirmed that surviving cells were unable to proliferate, highlighting the robustness of UV treatment for long-term inactivation. SEM confirmed distinct morphological alterations such as complete destruction of extracellular matrix & reduction in number of cells indicating cell death with increase in UV dose as compared to controls. A dose & time-dependent inactivation of biofilm-forming bacteria & fungi was observed on exposure to UVGI. Therefore, this pilot study validates the effectiveness of the newly developed UVGI surface sterilizer against biofilm-forming bacterial and fungal pathogens. Overall, the system demonstrates proof-of-concept efficacy under laboratory conditions and holds strong potential for future development and validation in hospitals and other contaminated public spaces. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=91 SRC="FIGDIR/small/715580v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@150cefcorg.highwire.dtl.DTLVardef@450831org.highwire.dtl.DTLVardef@1cfd6borg.highwire.dtl.DTLVardef@1419ba8_HPS_FORMAT_FIGEXP M_FIG C_FIG IMPORTANCEMicroorganisms that form biofilms on surfaces are difficult to eliminate and contribute to the spread of infections in healthcare and indoor environments. There is a need for practical, easy-to-use disinfection technologies that can effectively reduce such contamination. In this study, we developed a compact, in-house, wireless UV-C disinfection system designed for flexible operation across different surface types. The system was evaluated under controlled laboratory conditions using representative biofilm-forming bacterial and fungal pathogens. Our findings show that the system can effectively reduce microbial contamination, demonstrating proof-of-concept efficacy. This work highlights the potential of accessible, non-chemical UV-based technologies and supports their further validation for applications in real-world disinfection settings.

Psychosocial stress is a significant risk factor for mental and physical illness, and emerging evidence suggests that altered oral microRNAs (miRNAs) and microbiome may act as biomarkers or mediators of stress responses. This study investigated stress-associated molecular changes in saliva from 113 male police officers. Based on repeated administrations of the Karasek Demand/Control and Effort/Reward Imbalance questionnaires, subjects were stratified by perceived stress response (SR) to homogeneous occupational stressors into low, intermediate, or high responders. Salivary miRNA profiles were analyzed using small RNA sequencing, and microbiome composition was assessed through shotgun metagenomics. Eighteen miRNAs were significantly differentially expressed between high- and low-SR groups, with four miRNAs with increasing (miR-10400-5p, miR-1290, miR-6074-5p, and miR-9902) and fourteen with decreasing (including miR-21-5p and mirR-142-3p) levels in the high SR group (adj.p<0.05). The identified salivary miRNAs showed a progressive alteration from low- to high-SR groups. Functional enrichment analysis indicated that dysregulated miRNA targets are involved in apoptosis, cellular stress responses, and metabolic regulation. Distinct salivary microbial communities were also observed across SR groups. Several taxa displayed progressive abundance shifts, with Prevotella baroniae and Schaalia odontolytica increasing and Actinomyces naeslundii and Capnocytophaga ochracea decreasing in the high SR group. Functional predictions revealed, in this group, a significant enrichment of inositol degradation pathways, paralleled by a reduction in bacteria involved in L-tryptophan and thiamine biosynthesis. These findings suggest that salivary miRNAs and microbiota profiles may serve as non-invasive biomarkers of psychosocial stress and provide insight into molecular mechanisms linking chronic stress to physiological and behavioral outcomes.

BackgroundWilms tumour (WT) relapse occurs more frequently in patients with blastemal-type WTs. The presence of cancer stem cells (CSCs) is linked to tumour survival and relapse, and CSCs may be found in greater numbers in blastemal cell foci. CSC-associated phenotypes have been described in untreated WT, but their persistence, organisation and relevance after neoadjuvant chemotherapy is unknown. MethodsWe analysed 23 formalin-fixed paraffin-embedded blocks from 18 chemotherapy-treated patients where WTs were enriched for viable blastema, using human fetal kidney as developmental control. Immunohistochemistry and -fluorescence analysis determined progenitor (PAX2, SIX2, CITED1) and CSC-associated (NCAM, ALDH1, CD133) marker expression. We qualitatively and semi-quantitatively evaluated spatial expression patterns and co-localisation across tumour compartments. ResultsPAX2 and SIX2 were co-expressed in blastema in most cases (15/18), with PAX2 expression higher at the periphery of blastemal foci and SIX2 expression found uniformly in central aspects. CITED1 expression was also associated with SIX2 in blastema tissues (14/18). NCAM was blastema-enriched (15/18) with higher central intensity, frequently adjacent to PAX2-expressing peripheral zones. ALDH1 expression was present across blastema and epithelium while NCAM-, ALDH1-double-positive cells were rarely observed (4/18). CD133 expression was less commonly seen (2/18), localising near epithelial/nephrogenic structures. ConclusionsAfter neoadjuvant chemotherapy, WT blastema retained overlapping but non-identical progenitor/CSC-associated marker landscapes with reproducible peripheral-centre gradients. These spatial arrangements suggest a blastemal niche for CSCs that may sustain a therapy-resistant state. Our analysis provides the foundation for future functional validation and molecular profiling to define key lineage relationships and therapeutic vulnerabilities in post-chemotherapy WT. [250/250 words]

Space-based platforms currently represent the most accurate means to experimentally assess the influence of the space environment on biological systems. However, performing such experiments remains technically challenging and requires highly specialized instrumentation. This study describes the current development and hardware qualification of ExocubeBio, a miniaturized experimental platform for in-situ biological space exposure. This experiment is scheduled for installation on the exterior of the International Space Station in 2027, as part of Exobio, the European Space Agencys new generation exobiology exposure facility. ExocubeBio will expose live microbial samples to the low Earth orbit environment, and combine autonomous in-situ optical density and fluorescence measurements, with the capacity to return preserved samples to Earth. Achieving these experimental goals requires a specialized, robust and reliable hardware system. The ExocubeBio hardware testing described here includes assessment of material biocompatibility and durability, functional validation of the miniaturized fluidic system, and optimization of the integrated optical subsystem for optical density and fluorescence measurements. These results demonstrate that the ExocubeBio experimental hardware components can each execute their core functional and operational requirements; subsystems allow for sample exposure, in-situ measurements of microbial cultures, and the chemical preservation of samples for post-flight analysis. As ExocubeBio transitions from hardware development to mission readiness, the results presented here validate the overall design and engineering approaches utilized. By combining the strengths of in-situ monitoring and sample return, ExocubeBio represents a significant advancement in space-based experimentation, and will provide new insights into microbial responses to the space environment.

BackgroundThis study investigated rumen microbiome reconstitution and methane (CH4) emissions following a complete exchange of rumen contents between low- and high-CH4-yielding Norwegian Red dairy cows. Twenty cows were screened for CH4 yield, and two low and two high emitters were selected for rumen cannulation and content swap. Total rumen contents were swapped after complete evacuation and washing of both the rumen and omasum. Rumen samples were collected twice in weeks -1, 1, 3, and 7 for fermentation analysis, metagenomics, and metaproteomics, and at week 8 CH4 production was measured. ResultsPrior to the swap, low and high emitters produced 21.2 {+/-} 0.7 and 26.3 {+/-} 1.4 g CH4/kg dry-matter intake (DMI), respectively. Eight weeks after swap, CH4 yields were 12.7 {+/-} 0.3 and 28.9 {+/-} 0.3 g CH4/kg DMI, respectively, showing that the CH4 phenotype of each cow was maintained. Analysis of metagenome-derived 16S rRNA gene sequences showed that low emitters gradually re-established their original microbial community, whereas high emitters retained donor-like microbiota. Metaproteomic mapping suggested higher expression of Prevotella-associated succinate-propionate pathway enzymes in low emitters at week 7, though these differences were modest. ConclusionThese findings suggest that host factors influence CH4 output and microbial reconstitution, with low emitters restoring their native microbiome while high emitters retained a donor-associated community yet continued to emit high CH4. Results should be interpreted with caution given the small sample size (n = 2 per phenotype) and require confirmation in larger studies. ImportanceReducing enteric methane from cattle requires understanding whether the rumen microbiome or the host animal is the primary driver of methane output. We exchanged the entire rumen contents between low- and high-methane-yielding dairy cows and measured methane production alongside metagenomic and metaproteomic profiling over two months. Despite receiving each others microbiomes, each cows methane phenotype persisted--low emitters stayed low and high emitters stayed high. Microbiome reconstitution was asymmetric: low emitters restored their original microbial community, while high emitters retained the donor microbiota. Methanogen communities did not differ between phenotypes, pointing to host-level rather than microbial-level control of methane yield. These pilot findings suggest that breeding for favorable host traits may be essential for lasting methane reduction, and that microbiome transfer alone is unlikely to shift an animals methane phenotype. Larger studies are needed to confirm these observations.

Chlamydia trachomatis infection is the most common bacterial sexually transmitted infection worldwide and a leading cause of inflammatory reproductive tract disease and infertility in women. Much of the tissue damage associated with genital chlamydial infection arises from host inflammatory responses rather than direct bacterial cytotoxicity. Epithelial cells lining the female reproductive tract represent the primary host cells infected during chlamydial infection and play key roles in initiating innate immune responses. Among the cytokines produced by infected epithelial cells, type-I interferons have emerged as important regulators of host defense and inflammatory signaling; however, the specific contribution of interferon-{beta} (IFN-{beta}) to epithelial transcriptional responses during chlamydial infection remains incompletely defined. In the present study, we investigated the role of IFN-{beta} in coordinating epithelial immune signaling networks during infection with Chlamydia muridarum. Using wild-type murine oviduct epithelial cells (OE-WT) and IFN-{beta}-deficient epithelial cells (OE-IFN{beta}-KO), we performed pathway-focused RT{superscript 2} Profiler PCR array analyses examining transcriptional responses across four biological pathways: (1) innate and adaptive immune responses, (2) type-I interferon signaling, (3) inflammatory and autoimmune responses, and (4) fibrosis-associated pathways. Infection of OE-WT cells resulted in coordinated induction of cytokines, chemokines, and interferon-stimulated genes associated with antimicrobial defense and immune cell recruitment. In contrast, IFN-{beta} deficiency resulted in widespread dysregulation of these transcriptional programs, including reduced induction of interferon-responsive chemokines such as CCL5 and CXCL10, altered inflammatory cytokine expression, and transcriptional signatures consistent with enhanced tissue remodeling responses. Notably, IFN-{beta} deficiency resulted in increased TNF expression accompanied by reduced IL-6 induction, suggesting disruption of balanced inflammatory signaling networks. Pathway analyses further revealed dysregulated expression of fibrosis-associated genes including Serpine1, Ctgf, and Eng in IFN-{beta}-deficient epithelial cells, indicating potential mechanisms linking interferon signaling to tissue remodeling during infection. Collectively, these findings identify IFN-{beta} as a central regulator of epithelial immune networks during chlamydial infection and suggest that disruption of IFN-{beta} signaling may promote inflammatory and fibrotic pathology within the female reproductive tract. Author SummarySexually transmitted infections caused by Chlamydia trachomatis are a major cause of infertility worldwide. Although antibiotic treatment can eliminate the bacteria, damage to the reproductive tract often results from the bodys own immune response to infection. The epithelial cells lining the reproductive tract are the first cells infected and play an important role in initiating immune responses. In this study, we investigated how a specific immune signaling molecule, interferon-{beta} (IFN-{beta}), regulates the gene expression programs activated in epithelial cells during chlamydial infection. Using pathway-focused gene expression arrays, we found that IFN-{beta} coordinates multiple immune pathways, including interferon signaling, inflammatory cytokine networks, and genes associated with tissue remodeling. When IFN-{beta} was absent, many of these pathways became dysregulated, resulting in altered inflammatory signaling and gene expression patterns linked to fibrosis. These findings suggest that IFN-{beta} functions as a key regulator that helps balance protective immune responses with inflammatory processes that can damage reproductive tissues during infection.

The early evolutionary history of modern domestic horses (Equus caballus/E. ferus caballus), known as the DOM2 lineage, is well documented due to numerous archaeological and ancient DNA (aDNA) studies. Although many uncertainties remain in the domestication timeline, current evidence suggests that the domestication of modern horses began in the Pontic-Caspian steppe at least [~]2700 BCE (before common era), or even earlier. However, it is not known how long remnant wild horse populations survived or when domestic horses were introduced into Northern Europe. In this study, we review the current knowledge of horse domestication, focusing on Northern Europe. We analysed prehistoric horses from western Russia to assess the body sizes of wild horses from the Ivanovskaya site (5900-3800 BCE) in the Pontic-Caspian steppe, and the body weight of one Lithuanian wild horse (4000-3800 BCE). Additionally, we analysed body sizes of Late Bronze Age-Early Roman Age horses (1100 BCE-300 CE; common era) and re-analysed body sizes and estimated rider weights of historic domestic horses from Lithuania (100-1400 CE). We searched for pathological changes and signs of bit wear indicative of bridling. Furthermore, we investigated maternal genetic diversity by sequencing ancient mitochondrial DNA. We found that wild horses from Ivanovskaya were intermediate in body size between earlier and more recent horses of the Eurasian Steppe, and that the Lithuanian wild horse weighed only [~]270 kg and Late Bronze Age-Early Roman Age horses 200-300 kg. Lithuanian domestic horses were pony-sized (< 130 cm on average). Bit wear was confirmed on one tooth, the oldest domestic horse in Lithuania (799-570 cal BCE). Another tooth showed signs of the Equine Odontoclastic Tooth Resorption and Hypercementosis (EOTRH) condition. Mitochondrial DNA was successfully amplified from one Ivanovskaya wild horse along with 25 other ancient samples, including Lithuanias oldest domestic horse. mtDNA diversity was high, revealing several maternal lineages.