Tag: statistics

Front Oncol. 2026 May 19;16:1732883. doi: 10.3389/fonc.2026.1732883. eCollection 2026.

ABSTRACT

BACKGROUND: Colon cancer incidence is increasing globally, yet its spatial and temporal dynamics in Central Asia remain insufficiently studied. This study aimed to assess regional disparities and temporal trends of colon cancer incidence in Kazakhstan from 2005 to 2024 using geospatial and age-period-cohort analyses.

METHODS: A nationwide population-based study was conducted using data from the Unified Nationwide Electronic Health System of Kazakhstan. Crude incidence rates (CR) and age-standardized incidence rates (ASR) were calculated per 100,000 population using the WHO world standard population. Spatial patterns were assessed based on the administrative division of 2005, and clustering was evaluated using the Getis-Ord Gi* statistic. Temporal trends were analyzed using Joinpoint regression and Age-Period-Cohort analysis modeling, including estimation of net drift, local drift, and period and cohort rate ratios.

RESULTS: The national CR was 9.64 per 100,000, and the ASR was 9.44 per 100,000. A persistent north-south gradient was observed, with higher incidence in northern and central regions (Pavlodar, Kostanay, Karaganda, North Kazakhstan, Astana) and lower rates in southern regions. Spatial clustering analysis identified significant hotspots in northern regions and coldspots in the south. Age-Period-Cohort analysis demonstrated a strong age effect across all models. The net drift was +0.57% per year (95% CI 0.23-0.91; p=0.001), with the highest increases observed in older age groups (65-84 years). Period and cohort effects were also significant, indicating the influence of demographic aging, healthcare changes, and generational risk factors.

CONCLUSION: Colon cancer incidence in Kazakhstan is characterized by pronounced spatial disparities and is primarily driven by population aging. The combined geospatial and Age-Period-Cohort analysis approach provides a comprehensive framework for understanding disease dynamics and supports the development of targeted cancer control strategies.

PMID:42239894 | PMC:PMC13225997 | DOI:10.3389/fonc.2026.1732883

Front Oncol. 2026 May 19;16:1761654. doi: 10.3389/fonc.2026.1761654. eCollection 2026.

ABSTRACT

BACKGROUND: Chemoradiotherapy (CRT) is the standard treatment for squamous cell carcinoma of the anal canal (ACC), achieving excellent local control and sphincter preservation. However, many long-term survivors experience persistent bowel, urinary, sexual, and psycho social sequelae affecting quality of life (QoL). The PROACT study (Patient – Reported Outcomes in Anal Cancer Patients Treated with Intensity-Modulated Radiotherapy; NCT06364579) wants to explore the relationship between oncologic outcomes and patient-reported QoL in the era of modern radiotherapy.

METHODS: This single-institution ambispective study included patients with a diagnosis of ACC treated between 2011 and 2024 with intensity modulated radiotherapy (IMRT)-based CRT, followed-when indicated-by an image guided interventional radiotherapy (IRT) boost. Oncologic outcomes and toxicity were assessed using standard criteria. QoL was evaluated annually up to 5 years post-treatment using the EORTC QLQ-C30 and anal cancer-specific QLQ-ANL27 questionnaires. Statistical analyses explored associations between QoL domains and patient-, disease-, and treatment-related factors.

RESULTS: Median age was 62 years (range 34-83); 82.2% were female. Median follow-up was 51 months. Three- and five-year overall survival were both 97.5%. Disease-free survival was 88.2% and 84.5% at three and five years, respectively, while locoregional relapse-free survival was 92.8% and 89.0%. Colostomy-free survival showed identical rates at three and five years (97.3%). Late≥ G3 Gastrointestinal toxicity occurred in 6 patients (6.7%). Compared with the general population, both sexes reported significantly higher global QoL (males p = 0.002; females p = 0.001), while diarrhea was worst in women (p = 0.0008). Younger age (<70 years), female sex, and late GI toxicity correlated with poorer functional outcomes, particularly in bowel and sexual domains.

CONCLUSIONS: PROACT underscores that treatment success in anal cancer extends beyond cure, encompassing survivorship, functionality, and well-being. Integrating oncologic and patient-reported outcomes offers a comprehensive, patient-centered framework for optimizing long-term care.

PMID:42239889 | PMC:PMC13225979 | DOI:10.3389/fonc.2026.1761654

Front Oncol. 2026 May 19;16:1738955. doi: 10.3389/fonc.2026.1738955. eCollection 2026.

ABSTRACT

BACKGROUND/OBJECTIVES: Large Language Models (LLMs) are increasingly used in medicine for tasks ranging from patient communication to exam preparation. This study aimed to evaluate the feasibility of using a domain-specific, out-of-training-data radiation and cancer biology examination as a benchmarking framework for large language models, and to compare the accuracy and consistency of commonly used LLMs available at the time of data collection.

METHODS: GPT-3.5, GPT-4, and Llama-2 were queried with 335 multiple-choice questions (MCQs) from the 2023 American Society for Radiation Oncology (ASTRO) Radiation and Cancer Biology Exam Study Guide, excluding image-based items. Each model answered all questions five times over three months to evaluate consistency. Model responses were scored against the official answer key and analyzed using one-way ANOVA with Bonferroni correction to determine statistical differences in accuracy.

RESULTS: GPT-4 achieved the highest accuracy, correctly answering 81% of questions, significantly outperforming GPT-3.5 (62%) and Llama-2 (51%) (p < 0.001). All models performed worse on questions requiring calculations, though differences were not statistically significant. In terms of reliability, GPT-4 and Llama-2 provided consistent responses more frequently than GPT-3.5. Despite stable overall scores, all models exhibited variability in individual responses across repeated trials. GPT-4 produced the longest explanations, averaging 183 words per answer.

CONCLUSIONS: This study demonstrates the feasibility of using a domain-specific, out-of-training-data examination to benchmark large language model knowledge in radiation and cancer biology. While performance differences were observed among models, variability and limitations, particularly in calculation-based questions, highlight the importance of methodological benchmarking and cautious interpretation when considering medical educational applications.

PMID:42239883 | PMC:PMC13225992 | DOI:10.3389/fonc.2026.1738955

J Clin Aesthet Dermatol. 2026 Apr;19(4):35-37.

ABSTRACT

OBJECTIVE: To compare thyrotropin (TSH) levels across nonscarring alopecia (NSA) subtypes-alopecia areata (AA), telogen effluvium (TE), and androgenetic alopecia (AGA)-in a primary analysis of all patients, a secondary analysis of euthyroid patients stratified into low-normal (0.5-2.5 mIU/L) and high-normal (2.5-4.5 mIU/L) categories, and a tertiary analysis of patients with thyroid dysfunction.

METHODS: A retrospective chart review was conducted on patients diagnosed with AA, TE, or AGA at a single academic dermatology department between August 2017 and August 2024. TSH values were drawn within 3 months of the initial visit, and patient demographics were extracted from the electronic medical record. Patients with thyroid dysfunction were excluded from the secondary analysis. TSH values within the euthyroid range were stratified into low-normal and high-normal categories. A tertiary analysis of patients with frank thyroid dysfunction was later conducted. Descriptive statistics, Kruskal-Wallis tests, and Bonferroni-corrected pairwise comparisons were performed.

RESULTS: Among the 1,411 patients initially identified, most TSH values were within the euthyroid range. In a secondary analysis of 1,291 euthyroid patients, there was no significant difference in TSH distribution across NSA subtypes, including when stratified into low-normal vs high-normal categories. Among patients with thyroid dysfunction (8.5%), those with TE had the highest relative proportions of both hypothyroidism (5.0%) and hyperthyroidism (5.5%). Black or African American patients with AA and TE had lower mean TSH levels than White patients; however, this was not observed in AGA.

LIMITATIONS: Limitations of this study include the retrospective design and the potential for incomplete or biased medical records.

CONCLUSION: TSH levels among patients with NSA did not vary significantly based on NSA subtype. Racial differences in mean TSH were observed in AA and TE, but the clinical significance remains uncertain.

PMID:42239846 | PMC:PMC13229151

Ment Health Clin. 2026 Jun 2;16(3):129-134. doi: 10.9740/mhc.2026.06.129. eCollection 2026 Jun.

ABSTRACT

INTRODUCTION: Lithium has long been considered the gold standard mood stabilizer in the treatment of acute mood episodes related to bipolar (BD) and schizoaffective disorder. Previous research has primarily focused on lithium loading strategies and their effects on symptom severity and inpatient length of stay (LOS). However, less is known about specific prescribing practices at lithium initiation that may influence LOS.

METHODS: This retrospective study aimed to evaluate three initiation-related prescribing factors of lithium and their association with changes in LOS among adult inpatients experiencing acute mood episodes of BD or schizoaffective disorder. The factors were lithium initiation within 48 hours of admission, achieving a therapeutic level-producing dose within 48 hours of admission, and receiving intensive initial lithium dosing (≥900 mg/day). The Mann-Whitney U test was used to assess statistical significance. The timing of antipsychotic coprescribing in mania was also evaluated.

RESULTS: Sixty-eight patients were included in this study. Lithium initiation within 48 hours of admission significantly decreased hospital LOS (7.2 vs 13.4 days; P < 0.001). Lithium optimization to a dose that produced a therapeutic drug level within 48 hours of admission also significantly decreased LOS (6.2 vs 9.1 days; P < 0.01). Intensive initial dosing did not significantly affect LOS. Of patients with mania, 51.5% were trialed on antipsychotics before starting lithium.

CONCLUSION: Early lithium initiation and optimization in patients with acute bipolar mood episodes significantly reduced hospital LOS. Prospective studies are needed to address potential confounders to confirm whether early lithium optimization directly reduces LOS.

PMID:42239829 | PMC:PMC13229530 | DOI:10.9740/mhc.2026.06.129

Front Aging Neurosci. 2026 May 19;18:1806505. doi: 10.3389/fnagi.2026.1806505. eCollection 2026.

ABSTRACT

BACKGROUND: Parkinson’s disease (PD) involves progressive dopaminergic neuron loss in the substantia nigra (SN). Aldehyde dehydrogenase 1A1 (ALDH1A1), the rate-limiting enzyme in retinoic acid biosynthesis, is enriched in vulnerable dopaminergic neuron subpopulations and is consistently downregulated in PD. However, the relationship between ALDH1A1 expression and broader dopaminergic pathway gene co-expression has not been systematically characterized across multiple independent datasets.

METHODS: Gene expression correlations were analyzed across seven independent human SN microarray datasets (n = 156; 70 controls, 86 PD) from the Gene Expression Omnibus. Simple arithmetic means across datasets are reported as the primary summary statistic; random-effects meta-analysis with DerSimonian-Laird estimation was applied to Fisher’s z-transformed correlation coefficients to generate pooled estimates with heterogeneity statistics. Marker gene-based enrichment scoring using published cell type markers from single-nucleus RNA-seq profiling of human substantia nigra-with all target genes excluded from signatures-was performed across six analyzable datasets. Selectivity of ALDH1A1 correlation attenuation was assessed using permutation testing (n = 5,000) as the primary statistical test, with parametric tests reported as supplementary.

RESULTS: In controls, ALDH1A1 showed strong co-expression with dopaminergic genes (mean r = 0.92-0.93 for TH, DDC, and SLC18A2). In PD, these correlations were attenuated (mean Δr = -0.336 for ALDH1A1-dopamine pairs). Dopamine-dopamine correlations showed less attenuation (mean Δr = -0.143). Marker gene-based enrichment scoring confirmed significant depletion of ALDH1A1-positive vulnerable dopaminergic neurons in 4 of 6 datasets. After adjusting for estimated cell type enrichment, the selectivity of ALDH1A1 attenuation was preserved (adjusted selectivity: -0.210, increased from raw selectivity of -0.190; raw permutation p = 0.0052).

CONCLUSION: ALDH1A1 co-expression with dopaminergic pathway genes is attenuated in PD substantia nigra across all seven datasets examined. This attenuation is selective for ALDH1A1-containing pairs, and this selectivity persists after adjusting for cell type enrichment changes. While correlational, these findings are consistent with a role for retinoic acid pathway disruption in PD pathophysiology and warrant mechanistic investigation.

PMID:42239820 | PMC:PMC13226206 | DOI:10.3389/fnagi.2026.1806505

Kidney Med. 2026 Apr 30;8(7):101381. doi: 10.1016/j.xkme.2026.101381. eCollection 2026 Jul.

ABSTRACT

RATIONALE & OBJECTIVE: Data on sex differences in kidney function within multiethnic populations are scarce despite the large differences in chronic kidney disease (CKD) in women and men. We investigated the 6-year changes in the estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR) in women and men, both overall and across ethnic groups, and determined whether sex differences in associations with outcomes are mediated by known CKD risk factors.

STUDY DESIGN: General population based longitudinal study.

SETTING & PARTICIPANTS: We used prospective data of 5,713 women and 4,407 men from 6 ethnic backgrounds from the Healthy Life in an Urban Setting (HELIUS) study (Amsterdam, the Netherlands).

EXPOSURES: Municipality registered sex.

OUTCOMES: Change in eGFR (mL/min/1.73 m²) and ACR (mg/mmol) between baseline (2011-2015) and follow-up (2019-2021) data collection. CKD incidence and progression were analyzed as secondary outcomes.

ANALYTICAL APPROACH: Linear regression analyses adjusted for baseline kidney function estimates, follow-up duration, age, education, and ethnicity in the total population and stratified by ethnicity. Mediation by hypertension, diabetes, cardiovascular disease, obesity, physical activity, alcohol consumption, and smoking was tested.

RESULTS: Although no significant sex differences were found in the overall population, Dutch and African Surinamese women had a greater decrease in eGFR (β:1.2 (0.5-1.8)) than men, whereas South-Asian Surinamese and Moroccan men had a greater decrease in eGFR (β:-1.0 (-2.0 to 0.0)) than women. ACR was higher in men, although this difference did not reach statistical significance (β:0.6 (0.3-1.1), P = 0.09). Sex differences in CKD incidence across certain ethnic groups aligned with the observed eGFR differences, whereas CKD progression was higher in men overall. Little evidence of mediation by CKD risk factors of the sex differences was observed.

LIMITATIONS: Single eGFR and ACR measurements, self-reported mediator variables, and limited generalizability.

CONCLUSIONS: Disparate sex differences in the changes in eGFR, CKD incidence, and progression were observed, specifically in some ethnic groups. These differences were not mediated by differences in traditional risk factors and health-related behaviors.

PMID:42239818 | PMC:PMC13227188 | DOI:10.1016/j.xkme.2026.101381

Front Mol Neurosci. 2026 May 19;19:1758390. doi: 10.3389/fnmol.2026.1758390. eCollection 2026.

ABSTRACT

INTRODUCTION: The central nervous system responds to acute injury with plastic remodeling of its network. However, the temporal and structural dynamics of this response in the denervated dentate gyrus remain poorly understood. Therefore, we examined the transcriptional programs activated after perforant path transection, focusing on the outer molecular layer (OML) and the granule cell layer (GCL).

METHODS: Perforant path transections were performed, and tissue from the denervated OML and GCL was selectively isolated using laser microdissection at 1, 3, 7, 14, and 28 days post-lesion. Whole-genome expression analysis was performed to identify and characterize global transcriptome changes across time and layers.

RESULTS: Denervation induced reactive astrogliosis and microgliosis primarily in the OML. Overall enrichment statistics from two complementary approaches highlighted early downregulations of neuroactive ligands, later downregulation of (mainly glutamatergic) neurotransmission factors, and late downregulations of respiratory factors, alongside early upregulations of debris degradation factors, subsequent upregulation of glial and inflammatory factors, and late upregulation of ribosomal translation. Entorhinal afferent loss was reflected by reductions of the axon repellent Sema3e (to 60% in OML), with sustained depletions of the reelin repressor Adamts3 (14% in OML, 33% in GCL) and its presumptive effector Ptpn3 (30% in OML), as well as delayed induction of the SEMA3E/reelin coreceptor Nrp1 (3-fold in OML, 7-fold in GCL). Secondary reductions in the GCL occurred for the CREB repressor Rgs13, Ntng1, and Epha5–Epha6–Epha7. Deficits were found in the OML for glutamatergic signaling factors (Neto1, Cnih2, Dlg2, Gria1, Grm7–Grm8–Grm3, Homer2, Trim32), in the GCL for GABAergic and glycinergic receptors (Gabra2–Gabra1, Gabrb2, Glra2), and overall for neuronal differentiation markers (Calb1, Pvalb, Gad1, Lrrc7, Ano3, Bdnf, Egfr, Igf2r, Nrep, Basp1, Scn1a) and synaptic adhesion mediators (Lingo2, Lrrtm1–Lrrtm3, Adam11–Adam23, Cadm2, Pcdhb16, Flrt3). Presumed compensatory upregulation efforts included postsynaptic and dendritic membrane remodeling by vesicle and actin regulators (Lyn, Gabarap, Cyfip1, Arf4, Arl4c, Rab8b, Cdk5rap2, Tmsb4x) in the OML, versus neurotrophic coreceptors Sorcs3–Sorcs2, axonal Smn1, and the neural progenitor modulator Nup210l in the GCL.

DISCUSSION: These findings identify coordinated and temporally structured transcriptomic programs that reflect injury-induced remodeling in the dentate gyrus and highlight novel molecular mediators of synaptic reorganization, neuroinflammation, metabolic adaptation, and compensatory plasticity following entorhinal denervation.

PMID:42239799 | PMC:PMC13226496 | DOI:10.3389/fnmol.2026.1758390

Res Sq [Preprint]. 2026 May 18:rs.3.rs-9724722. doi: 10.21203/rs.3.rs-9724722/v1.

ABSTRACT

Background Though bisphosphonates are the gold standard for the treatment of different metabolic bone disorders including osteoporosis for more than five decades, their safety and tolerability in patients with compromised kidney function are not well known. With age-related bone disorders and renal insufficiency becoming more prevalent worldwide, understanding the effect of bisphosphonates on patients with compromised renal function becomes inevitable. This review aims to analyze the clinical data available on safety of bisphosphonates on patients with different levels of renal function. Methods A broad search of PubMed, Wiley Online and the Cochrane Central Register of Controlled Trials was conducted to select randomized controlled trials and clinical trials that evaluated the safety and tolerability of bisphosphonate in patients with different levels of renal function between 2000 and 2026. Results Out of 1388 titles and abstract reviewed, 17 articles were included in the final analysis using PRISMA 2020 guidelines. Despite one trial showing < 2% increase in serum creatinine from baseline, all the other trials proved that bisphosphonates are safe and well tolerated by the patients with transplanted kidney and with compromised kidney function. Meta analysis of the data provided from eligible clinical trials using RStudio indicated that the proportion of serum creatinine that is increased was < 25% from baseline. Further, random effects model (100% (-0.01)) was performed due to high level of heterogeneity and it indicated that ibandronate 27.93%; alendronate 28.58%; risedronate 27.80% and zoledronate 15.69%. The pooled effect shows that kidney damage by bisphosphonates is not statistically significant. Conclusion The evidence from this review suggests that the bisphosphonates are generally well-tolerated with ten trials registering no drug-related withdrawals and other studies showing only very negligible withdrawals due to adverse effects. Even though bisphosphonates are safer to use in compromised renal function i.e., > 30ml/min/1.73m ² , more cohort studies are required to identify bisphosphonates effects in end stage renal disease (eGFR < 15ml/min/1.73m ² ).

PMID:42239793 | PMC:PMC13228822 | DOI:10.21203/rs.3.rs-9724722/v1

Res Sq [Preprint]. 2026 May 20:rs.3.rs-9588456. doi: 10.21203/rs.3.rs-9588456/v1.

ABSTRACT

Background: Obesity is a major global public health challenge that contributes to numerous comorbidities and increased mortality. A better understanding of the biological mechanisms and disease risks associated with obesity requires robust monitoring of key circulating biomarkers, including adipokines, apolipoproteins, and inflammatory proteins. Targeted mass spectrometry (MS) offers a promising platform for developing specific, standardized, and multiplexed assays for biomarker quantification. In this study, we developed a multiplex targeted MS assay for the quantification of 42 obesity-associated biomarker candidates in human plasma. Methods: The assay was optimized for surrogate peptide selection, digestion incubation time, and LC gradient, and evaluated for linearity, lower limit of quantification (LLOQ), imprecision, and stability. A semi-automated sample preparation workflow using 96-well plates was also established to support high-throughput implementation. The assay was applied to a clinical cohort undergoing weight loss interventions to evaluate differences in protein abundance across obesity-related groups and to monitor biomarker changes over time. Statistical analyses were performed to identify proteins with significantly different abundances between study groups and before versus after intervention. Results: The assay demonstrated acceptable linearity, LLOQ, imprecision, and stability. Inter-laboratory validation using samples from 70 healthy individuals showed strong correlation with the finalized standard operating procedure (SOP). Application of the assay to an obesity cohort revealed significant differences in the levels of 6 proteins across obese, overweight, and healthy control groups, as well as 16 proteins that were differentially abundant in obese individuals compared with non-obese individuals (overweight and healthy controls combined). In subjects undergoing weight loss interventions, four proteins-CRP, PRG4, SERPINF1, and SHBG-showed significant concentration changes in individuals who achieved > 5% weight loss. Conclusions: These results demonstrate the robustness and high-throughput capability of this multiplex targeted MS assay for measuring obesity-associated plasma biomarkers. The assay shows potential clinical utility for improving the diagnosis, stratification, and risk assessment of obesity-related conditions, as well as for monitoring responses to weight loss interventions.

PMID:42239769 | PMC:PMC13228810 | DOI:10.21203/rs.3.rs-9588456/v1