Category: Statistics

J Pediatr Endocrinol Metab. 2026 Jul 6. doi: 10.1515/jpem-2026-0035. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine the frequency of selected MKRN3 variants and to investigate genotype-phenotype associations in Uzbek children with central precocious puberty, with particular emphasis on sex-specific clinical, hormonal, and instrumental characteristics.

METHODS: This single-center study included 69 Uzbek children with CPP and 30 healthy controls (used primarily for assay validation). Targeted genotyping of three MKRN3 variants (c.1034G>A [p.Arg345His], c.1229G>A [p.Cys410Ter], and c.331G>T [p.Glu111Ter]) was performed using real-time PCR with TaqMan assays. Clinical, hormonal, skeletal, and ultrasonographic parameters were analyzed using non-parametric methods.

RESULTS: Selected MKRN3 variants were identified in 21.7 % (15/69) of this cohort of Uzbek children with CPP. The most frequent variant was c.1034G>A (13.0 %), followed by c.1229G>A (8.7 %); c.331G>T was not detected. Variant frequency was higher in boys (28.6 %) than in girls (18.7 %), without statistical significance. In girls, variant carriers had significantly smaller uterine and ovarian dimensions, larger dominant follicle diameter, and lower basal LH levels, while bone age advancement and estradiol levels were comparable. In boys, variant carriers demonstrated higher testosterone levels, with no significant differences in gonadotropins, bone age advancement, or testicular volume.

CONCLUSIONS: Selected MKRN3 variants were present in 21.7 % of this cohort of Uzbek children with CPP. MKRN3-related CPP demonstrated genotype-specific morphological and endocrine features, particularly in girls. These findings suggest phenotypic heterogeneity and warrant confirmation in larger sequencing-based studies.

PMID:42402006 | DOI:10.1515/jpem-2026-0035

Aust Endod J. 2026 Jul 5. doi: 10.1111/aej.70106. Online ahead of print.

ABSTRACT

The aim of this study was to compare three delivery methods of a hydraulic calcium silicate cement-based sealer by quantifying voids using the single-cone technique. Forty-eight human mandibular molars were instrumented and scanned using micro-computed tomography. The specimen’s aspect ratio, shape, and volume were analysed to allow even distribution across three experimental groups (n = 16): sealer injection with a syringe, coating of the master cone and sealer injection followed by sonic agitation. Post-filling micro-computed scanning was used to quantify void volumes in each specimen. Statistical analysis using Kruskal-Wallis and Dunn’s post hoc tests (α = 0.05) revealed no significant difference in void volume among the delivery methods (p = 0.120). However, canal shape was a significant factor; round canals exhibited significantly fewer voids than any other shape (p < 0.001). In conclusion, the delivery method did not influence the density of the root canal filling; canal anatomy was the more critical determinant factor for void formation.

PMID:42402002 | DOI:10.1111/aej.70106

Aust Endod J. 2026 Jul 5. doi: 10.1111/aej.70108. Online ahead of print.

ABSTRACT

This study aimed to compare the ability of three artificial intelligence-based large language models, ChatGPT-4, Copilot, and Gemini, to generate multiple-choice questions. Two position statements from the European Society of Endodontology were used as source documents. Each model produced forty questions using an identical prompt, and a total of 120 questions were assessed for distractor quality, ability to distinguish different performance levels, reliability, and content validity. Weighted Kappa, Kruskal-Wallis, and Mann-Whitney U post hoc tests were used for analysis. The inter-rater agreement ranged between 0.870 and 1.000. ChatGPT-4 produced the highest overall scores, and Gemini consistently received the lowest ratings. Overall scores differed significantly between Copilot and Gemini, and ChatGPT-4 and Gemini (p < 0.05), but all produced poorly constructed distractor options. The findings indicate that artificial intelligence-based tools can support the generation of assessment materials in endodontics; however, expert oversight remains essential to ensure accuracy, quality, and educational relevance.

PMID:42402001 | DOI:10.1111/aej.70108

Respir Res. 2026 Jul 4. doi: 10.1186/s12931-026-03766-4. Online ahead of print.

ABSTRACT

BACKGROUND: Lung-protective ventilation is a cornerstone of modern mechanical ventilation, yet real-world adherence to lung-protective targets remains suboptimal. While previous studies have established the physiological benefits of low tidal volume and driving pressure, clinical implementation is hindered by limited monitoring granularity and lack of real-time actionable feedback. This trial aims to evaluate whether a real-time, cloud-based algorithmic feedback platform can improve lung-protective ventilation delivery and contribute to better clinical outcomes in mechanically ventilated patients with ARDS.

METHODS: This multicentre, parallel-group, open-label randomised controlled trial will enrol 208 adult mechanically ventilated ICU patients with ARDS from nine adult ICUs across tertiary academic hospitals and regional referral centres in multiple provinces and municipalities in mainland China. Participants will be randomly assigned in blocks to receive either standard monitoring (Control group) or real-time respiratory mechanics feedback through a cloud-based platform (Intervention group). The intervention group will receive real-time alerts for lasting 72 h and ventilator reports every 24 h, integrating tidal volume, plateau pressure, driving pressure, mechanical power, and detected patient-ventilator asynchrony events. The primary outcome is the lung-protective ventilation achievement rate, defined as compliance with VT < 8 mL/kg predicted body weight, driving pressure < 15 cmH₂O, plateau pressure < 30 cmH₂O, and mechanical power < 17 J/min during the first 72 h after randomisation. Secondary outcomes include ventilator-free days at day 28, ICU length of stay, ventilator-associated complications, inflammatory biomarkers, clinician satisfaction, and predefined safety outcomes, including severe hypoxemia, severe hypercapnia/acidemia, barotrauma, and hemodynamic instability temporally associated with ventilator adjustments.

DISCUSSION: This study is, to our knowledge, among the first multicentre randomised controlled trials to evaluate a real-time algorithmic feedback platform designed to enhance lung-protective ventilation. The intervention is designed to provide continuous bedside feedback on ventilation mechanics and may enable more timely and standardised clinical adjustments, with the potential to facilitate lung-protective ventilation delivery. Triaiontl registration ClinicalTrials.gov Identifier NCT07307066 (Registration Date: 2025/12/02).

PMID:42401979 | DOI:10.1186/s12931-026-03766-4

J Cannabis Res. 2026 Jul 4. doi: 10.1186/s42238-026-00466-0. Online ahead of print.

ABSTRACT

BACKGROUND: Cannabis use is increasing, even during pregnancy. The purpose of this study was to investigate how women of childbearing age perceive the safety of cannabis use during pregnancy compared to alcohol and tobacco use.

METHODS: Cloud Research recruited a national U.S. cohort of women of childbearing age (N = 622) to complete an anonymous online survey assessing cannabis, alcohol, and tobacco use during pregnancy. Validated tools measured perceptions of safety and risks to fetal, birth, and infant development. Data analyses included descriptive statistics, McNemar’s tests, and repeated-measures ANOVA with post-hoc comparisons.

RESULTS: The average age was 29.47 years (SD = 6.83, range: 18-42). Participants self-identified as White (65.9%, n = 410), Black or African American 28.1% (n = 175), Asian 5.9% (n = 37), American Indian or Alaska Native 3.9% (n = 24), or Other 4.7% (n = 29); 17.7% (n = 110) identified as Hispanic or Latino. Most participants identified as heterosexual (82.0%, n = 510). Among participants who had been pregnant (N = 351), 25.9% reported cannabis use during pregnancy, compared with 23.6% for tobacco and 8.2% for alcohol. The median frequency of prenatal cannabis use was twice weekly, with joints and blunts being the most common methods. Reported reasons for use included relief of nausea, anxiety, sleep disturbance, and pain. We used a five-point Likert scale to determine whether they thought cannabis, alcohol, and tobacco were safe to use during pregnancy, where 1 = not at all safe, and 5 = completely safe. Prenatal cannabis use was rated as safer (M = 3.85, SD = 1.46) than alcohol. (M = 4.86, SD = 0.54, p < .001) or tobacco (M = 4.79, SD = 0.63, p < .001).

CONCLUSION: Findings indicate that women of childbearing age perceive cannabis as relatively safe during pregnancy, particularly for symptom management. These perceptions underscore the need for targeted education, accurate messaging, and consideration of the social, cultural, and emotional factors that influence substance use during pregnancy to safeguard maternal and fetal health.

PMID:42401977 | DOI:10.1186/s42238-026-00466-0

Radiat Oncol. 2026 Jul 4. doi: 10.1186/s13014-026-02866-1. Online ahead of print.

ABSTRACT

PURPOSE: In intensity-modulated proton therapy (IMPT), the benefit of adding planning organ-at-risk volume (PRV)-like nominal constraints to direct robust optimization for serial organs at risk remains uncertain when target-OAR separation is minimal. Using paraspinal chordoma as a model, we evaluated whether an additional nominal canal/thecal sac (PRV-like) constraint improves OAR sparing or compromises target coverage.

METHODS: Ten patients with paraspinal chordomas were planned using two IMPT strategies: direct cord robust optimization alone (Cord-RO) and direct cord optimization with additional nominal canal/thecal sac constraint (Canal-RO). PTV-based helical tomotherapy (HT) was generated as a secondary benchmark. Prespecified institutional criteria were used for planning, prioritizing OAR constraints over coverage; when standard coverage goals were not achieved, GTV D98 ≥ 59 Gy(RBE) was accepted as the fallback criterion. Endpoints included target coverage, cord/canal doses, and robustness. Statistical comparisons used Wilcoxon signed-rank, Friedman, and Cochran’s Q tests, two-sided, p < 0.05.

RESULTS: All plans met plan-specific OAR constraints. Cord-RO achieved superior target coverage (median HR-CTV D98 [Gy(RBE)]: 63.05 vs. 57.38 vs. 59.46; p ≤ 0.002) and met the fallback objective (GTV D98 ≥59 Gy[RBE]) in 10/10 cases versus 4/10 and 7/10 (p=0.011) in Canal-RO and HT respectively. Robustness favored Cord-RO (median worst-case CTV D95: 90% vs 85%, p=0.018). Nominal cord D0.03cc was similar; worst-case cord D0.03cc was slightly lower with Canal-RO.

CONCLUSION: When targets abut serial OARs, our results suggest that direct OAR-based robust optimization without additional PRV-like constraints improve target coverage and robustness while maintaining acceptable OAR doses. PRV constraints may be reserved for re-irradiation or when target-OAR separation is adequate.

PMID:42401967 | DOI:10.1186/s13014-026-02866-1

BMC Med Educ. 2026 Jul 4. doi: 10.1186/s12909-026-09868-3. Online ahead of print.

ABSTRACT

BACKGROUND: Medical dramas are widely consumed by medical students globally and may constitute an informal or hidden curriculum influencing professional identity, empathy, and ethical reasoning. Palestinian medical students represent an understudied population navigating a resource-constrained and geopolitically complex healthcare context.

OBJECTIVES: To investigate the perceptions of Palestinian medical students regarding medical dramas, including viewing habits, assessments of clinical and ethical realism, psychological and behavioural impacts, and the potential role of such media as an informal educational resource.

METHODS: A cross-sectional study was conducted among 638 undergraduate medical students from five universities in the West Bank, Palestine, using convenience and snowball sampling. Data were collected via an online structured questionnaire adapted and culturally validated from the Czarny et al. (2008) instrument, incorporating forward-back translation, pilot testing (n = 15), and internal consistency assessment (Cronbach’s alpha = 0.81). Descriptive statistics and Chi-square tests were applied.

RESULTS: Mean age was 21.1 ± 1.65 years; 66.8% were female. Most participants (73.4%) had watched medical dramas, primarily via digital streaming platforms. While 77.3% perceived clinical scenes as only slightly or moderately realistic, 41.9% considered ethical content to be moderately accurately depicted. Approximately 46.6% reported increased empathy and 47.2% reported increased study motivation. Drama viewers were significantly more likely to rate informal sources-family (p < 0.001), friends (p = 0.021), and online news (p = 0.037)-as important for ethical guidance, compared with non-viewers.

CONCLUSIONS: Palestinian medical students engage substantially with medical dramas and appraise their content critically. Associations between drama viewing and increased empathy, study motivation, and reliance on informal ethical guidance sources suggest a potential hidden-curriculum effect. Given the cross-sectional design and convenience sampling, causal inferences cannot be drawn. These findings support cautious integration of medical dramas into bioethics and professionalism curricula as supplementary teaching tools.

PMID:42401946 | DOI:10.1186/s12909-026-09868-3

BMC Urol. 2026 Jul 4. doi: 10.1186/s12894-026-02241-y. Online ahead of print.

ABSTRACT

BACKGROUND: Bladder cancer (BC) is the sixth most common cancer among men worldwide and represents a significant cause of morbidity and mortality. High-grade BC is associated with an increased risk of progression to muscle-invasive and metastatic disease, negatively impacting patient prognosis. Despite advances in molecular characterization, therapeutic strategies remain limited, and the identification of novel molecular targets is essential. MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation and play critical roles in tumor development and progression. Among them, miRNA-23b and miRNA-27b have been implicated in several malignancies; however, their functional role in high-grade BC remains incompletely understood. This study aimed to evaluate the expression levels of miRNAs-23b and 27b in a high-grade BC cell line and to investigate their effects on cell migration, invasion, and proliferation, exploring their potential therapeutic relevance.

METHODS: The high-grade BC T24 cell line was used. Cells were divided into four groups: Control (no transfection), negative control (Scramble), miRNA-23b mimic, and miRNA-27b mimic. Relative miRNA expression levels were determined by quantitative polymerase chain reaction (qPCR). Functional assays included wound healing (migration), Matrigel invasion assay, and colony formation assay (proliferation). Statistical analyses were performed to compare groups, and p-values < 0.05 were considered statistically significant.

RESULTS: Transfection resulted in significant overexpression of miRNA-23b and miRNA-27b compared to both Scramble (p = 0.0344 and p = 0.0386, respectively) and Control groups (p = 0.0343 and p = 0.0390, respectively). Both miRNA-23b and miRNA-27b significantly reduced cell migration compared to Scramble (p = 0.0286). Additionally, miRNA-23b significantly decreased invasion compared to Scramble and Control (p < 0.0001), with similar findings observed for miRNA-27b (p < 0.0001). No statistically significant differences were observed in colony formation among groups.

CONCLUSIONS: Overexpression of miRNA-23b and miRNA-27b significantly reduced migration and invasion in a high-grade BC cell line, without affecting proliferation. These findings suggest that both miRNAs may act as tumor suppressors in high-grade BC and represent promising candidates for future therapeutic development in bladder cancer.

PMID:42401923 | DOI:10.1186/s12894-026-02241-y

Biol Sex Differ. 2026 Jul 4. doi: 10.1186/s13293-026-00949-y. Online ahead of print.

ABSTRACT

BACKGROUND: Liver metabolism is under tight control of the circadian system. Disruption of key clock gene expression (desynchronosis) leads to the misalignment of metabolic pathways. However, the relationship between circadian dysregulation and hepatic protein-synthetic function, as well as its sexual dimorphism, remains poorly understood. To evaluate the effect of chronic photoperiod disruption on hepatic protein-synthetic function (total protein, albumin) and to establish its relationship with the expression of key circadian proteins (BMAL1, CLOCK, PER2) in male and female rats, as well as to assess the efficacy of exogenous melatonin in correcting the identified disturbances.

METHODS: The study was performed on 240 adult Wistar rats (120 males, 120 females). Animals were divided into 3 groups: control (light: dark 10:14 h), dark deprivation (LL, constant light for 21 days), and LL + melatonin (12 mg/L drinking water). Plasma levels of total protein and albumin were measured. Immunohistochemistry was used to assess the percentage of positively stained hepatocytes for BMAL1, CLOCK, and PER2. Statistical analysis included two-way ANOVA, Pearson correlation analysis, ANCOVA, and ROC analysis.

RESULTS: Dark deprivation reduced albumin levels by 15.7% in males and by 15.9% in females compared to controls. Two-way ANOVA revealed significant effects of “lighting conditions” (F = 145.3, p < 0.0001), “sex” (F = 18.7, p < 0.01), and their interaction (F = 7.2, p < 0.05). BMAL1 and CLOCK expression decreased by more than 70% in both sexes, whereas PER2 expression paradoxically increased by 28.9-35.0%. Strong correlations were found between albumin levels and expression of BMAL1 (r = 0.79-0.81, p < 0.001), CLOCK (r = 0.69-0.74, p < 0.001), and PER2 (r= – 0.68 to – 0.71, p < 0.001). ANCOVA (R²=0.71, p < 0.0001) identified BMAL1 expression as the most significant independent predictor of albumin levels (β = 0.52, p < 0.0001), with sex retaining independent significance (p = 0.02). ROC analysis demonstrated high predictive performance of BMAL1 expression for hypoalbuminemia (AUC = 0.87-0.89, p < 0.0001). Melatonin treatment fully restored the expression of all examined circadian proteins and normalized protein synthetic parameters to control levels in both sexes.

CONCLUSION: Chronic photoperiod disruption induces profound hepatic desynchronosis characterized by suppression of BMAL1/CLOCK and accumulation of PER2, which is associated with decreased protein synthetic function. A pronounced sexual dimorphism in susceptibility to desynchronosis was identified. BMAL1 expression is a highly informative predictor of hypoalbuminemia. Exogenous melatonin fully restores the impaired parameters, supporting its use as an effective chronobiotic.

PMID:42401921 | DOI:10.1186/s13293-026-00949-y

BMC Med Educ. 2026 Jul 4. doi: 10.1186/s12909-026-09867-4. Online ahead of print.

ABSTRACT

BACKGROUND: The transition from undergraduate education to medical school demands increasing learner autonomy and self-regulation. Guided by Zimmerman’s Self-Regulated Learning (SRL) theory and Grow’s Staged Self-Directed Learning Model, this study examined how self-directed learning readiness (SDL-R), encompassing learning motivation, planning and implementation, self-monitoring, and interpersonal communication varies across the preclinical curriculum and how these domains relate to academic performance.

METHODS: A mixed longitudinal and repeated cross-sectional study (2022-2024) was conducted among preclinical medical students (N = 807 responses; 434 unique students from three cohorts, Classes of 2025-2027) at an LCME-accredited US medical school. All enrolled first- and second-year students were eligible; recruitment was voluntary via web-based REDCap surveys administered once per semester. Linear mixed-effects models evaluated within-student change in total SDL-R and its four domains across semesters. Ordinary least-squares regression with cluster-robust standard errors assessed the contribution of standardized subscale scores to cumulative grade point averages. Bonferroni correction was applied within each family of comparisons, with effect sizes and 95% confidence intervals reported.

RESULTS: SDL-R scores varied across preclinical semesters in a pattern consistent with developmental progression, with a modest decline in first-year Spring followed by recovery through year two. Planning and implementation was the strongest positive predictor of GPA in Year 1 (β = 0.142, p = .004) and in the combined model (β = 0.154, p < .001). The SDL-R domains collectively explained 22.2% of GPA variance in Year 1 (R² = 0.222) and 9.0% in Year 2 (R² = 0.090); the combined model explained 15.0% (R² = 0.150). Interpersonal communication showed a significant negative partial association with GPA, consistent with a statistical suppressor effect. Second-year students, older learners, males, and higher-achieving students showed higher SDL-R levels.

CONCLUSION: SDL-R is a dynamic, context-sensitive competency during preclinical training, with planning and implementation as its strongest academic predictor. Targeted curricular interventions that scaffold metacognitive planning, self-monitoring, and adaptive strategy use may enhance both academic performance and lifelong learning capacity.

PMID:42401920 | DOI:10.1186/s12909-026-09867-4