Tag: statistics

Mol Genet Genomics. 2026 Jun 16;301(1):134. doi: 10.1007/s00438-026-02448-6.

ABSTRACT

Genome-wide association studies (GWAS) have identified numerous loci associated with Type 2 Diabetes (T2D), yet translating statistical signals into experimentally testable hypotheses remains a central challenge in post-GWAS biology. The predominance of non-coding regulatory variants complicates target gene assignment and raises uncertainty regarding optimal clustered regularly interspaced short palindromic repeats (CRISPR) perturbation strategy. Here, we present a structured CRISPR Actionability Framework that integrates genomic context, pancreatic islet enhancer overlap, tissue-specific expression validation, and locus clarity into a quantitative CRISPR Actionability Score (CAS). We applied this framework to ten genome-wide significant T2D loci and assigned modality-aware CRISPR strategies (knockout versus CRISPR interference). CAS values ranged from 4 to 10, enabling tiered prioritization into high, moderate, and lower experimental priority classes. High-priority loci included SLC30A8, TCF7L2, and KCNJ11, which demonstrated strong regulatory or coding evidence combined with islet expression support. By explicitly linking genomic architecture to perturbation modality, this framework provides a transparent and reproducible bridge between statistical genetics and functional genome editing. This approach establishes a scalable template for rational CRISPR target selection in complex disease research.

PMID:42298143 | DOI:10.1007/s00438-026-02448-6

Sci Rep. 2026 Jun 15. doi: 10.1038/s41598-026-58130-9. Online ahead of print.

ABSTRACT

The co-activation of methane (CH₄) and carbon dioxide (CO₂) during dry reforming has led to numerous reduced kinetic models based on detailed surface reaction mechanisms, which are traditionally evaluated through parameter fitting, and their predictive validity is rarely examined. In this work, an alternative reduced Langmuir-Hinshelwood-Hougen-Watson (LHHW) kinetic model based on the literature data set has been tested numerically, without re-calculating any kinetic parameters. A plug-flow reactor (PFR) model is used to simulate conversions from low to high temperatures. Temperature-resolved statistical measures, residual structure analysis, and apparent activation energy were used to assess the model’s performance. This study qualitatively replicates the conversion trends at high and moderate-to-high conversion levels and shows systematic deviations at low temperatures. The apparent activation energy suggests that the high activation energies are due to composite CH₄ activation mechanisms rather than a single elementary step. The study provides a diagnostic reanalysis of a literature-derived LHHW model, highlighting its strengths and illustrating how mechanistic information can be obtained without re-fitting model parameters or independent validation. The present work demonstrates the predictive performance of a literature-derived LHHW kinetic formulation for the catalyst and operating conditions. It identifies the operating regime in which the selected model is applicable for the assessment of reduced kinetic models in reactor-scale simulations.

PMID:42298138 | DOI:10.1038/s41598-026-58130-9

Sci Rep. 2026 Jun 16. doi: 10.1038/s41598-026-58296-2. Online ahead of print.

ABSTRACT

Global biodiversity monitoring increasingly relies on open-access community science data, but these opportunistic records harbor complex biases that can severely distort macroecological inference. Here, we disentangle how human behavior, infrastructure, and taxonomy interact to shape perceived biodiversity patterns across the two distinct biogeographic regions of Malaysia. Analyzing 336,042 research-grade iNaturalist records, we quantified observer inequality and taxonomic disproportionality. We estimated true species richness (Chao2) to map spatial inventory completeness (median = 33.3%) and employed Zero-Inflated Negative Binomial GLMMs and effort-corrected Generalized Additive Models (GAMs) to test the effects of topography, accessibility, and observer classification. We demonstrate extreme observer inequality (Gini = 0.854), with data collection heavily anchored to urban centers. Crucially, a significant three-way interaction revealed that dedicated “Power Users” successfully penetrate roadless interiors in Peninsular Malaysia, whereas casual observers remain strictly road-bound. Taxonomically, the data exhibits a severe charismatic skew, massively over-representing Aves and Reptilia while under-sampling foundational hyper-diverse clades like Insecta and Fungi. Furthermore, explicitly modeling non-linear sampling effort (user-days) rendered the effects of elevation and terrain ruggedness statistically non-significant. This demonstrates that perceived biodiversity deficits in rugged, high-elevation terrains are anthropogenic artifacts of human inaccessibility rather than true ecological absences. To meet global conservation targets, state funding and structured monitoring should complement opportunistic data by actively targeting these remote, under-sampled geographic and taxonomic shortfalls.

PMID:42298119 | DOI:10.1038/s41598-026-58296-2

Support Care Cancer. 2026 Jun 15;34(7):660. doi: 10.1007/s00520-026-10848-y.

ABSTRACT

BACKGROUND: Pelvic exenteration is a major surgery involving resection of the pelvic viscera and surrounding structures. Performed on patients with locally advanced or recurrent pelvic cancer, it is associated with high morbidity, persistent pain and low quality of life (QoL). This study aimed to determine the long-term prevalence of chronic pain and to characterise the pain and QoL experience in pelvic exenteration patients.

METHODS: A telephone survey was undertaken, utilising patient-reported outcome measures: the Chronic Pain Grade Scale (CPGS) to assess pain and the Short Form-12 (SF-12) to measure QoL. Historic and demographic data were retrieved from hospital records to capture potential pre-, peri- and post-operative determinants. Data was analysed using descriptive statistics, correlation and comparative tests.

RESULTS: This study comprised 48 individuals, up to 13 years post-pelvic exenteration. Pain prevalence was 75%, with most patients reporting no to low-intensity pain, without disability (54%). SF-12 scores varied; physical scores were significantly lower than population norms, while mental scores were preserved. Pain intensity and disability (CPGS sub-scores) were associated with lower QoL, a relationship that was consistent across pain grades.

CONCLUSIONS: These findings indicate that the post-pelvic exenteration experience is characterised by reduced physical QoL and notable pain, highlighting the importance of early pain management optimisation. This research provides surgical candidates with authentic patient insight into life after surgery in a complex yet understudied population. Prospective longitudinal research is recommended to further examine patient trajectories and predictors of pain and poor QoL, enabling better targeted pain management.

PMID:42298118 | DOI:10.1007/s00520-026-10848-y

J Mol Neurosci. 2026 Jun 16;76(3):105. doi: 10.1007/s12031-026-02558-1.

ABSTRACT

Parkinson’s disease (PD) and Alzheimer’s disease (AD) are both neurodegenerative disorders sharing overlapping pathological mechanisms. Several studies suggest that AD biomarkers may have diagnostic and predictive value in PD, but causal evidence remains insufficient. This study aimed to explore the association between AD-related biomarkers and PD. Bidirectional two-sample Mendelian randomization (MR) was performed using GWAS summary statistics of AD-related biomarkers and PD to assess causal relationships. Subsequently, single-nucleus RNA sequencing (snRNA-seq) of postmortem midbrain tissues was employed to examine the expression of AD biomarkers in PD patients and to explore underlying cellular signaling pathways. Forward MR revealed a significant causal association between PD and decreased CSF p-tau levels. PD progression showed significant causal associations with decreased CSF Aβ42 and increased CSF total tau. Reverse MR indicated that elevated CSF total tau may increase PD risk. SnRNA-seq analysis demonstrated that MAPT (encoding tau) was predominantly expressed in dopaminergic neurons, with differentially expressed genes enriched in PD- and neurodegeneration-related pathways. Our findings provide preliminary, hypothesis-generating evidence at the genetic level suggesting potential associations between CSF tau, Aβ42, and PD or its progression. Bidirectional MR analyses suggest that CSF total tau may be associated with increased PD risk, while exploratory snRNA-seq analysis indicates that MAPT is predominantly expressed in dopaminergic neurons with enrichment in PD-related pathways. Given the limited number of instrumental variables for several exposures, the small snRNA-seq cohort, and the absence of protein-level validation, these findings should be interpreted with caution. Large-scale prospective clinical studies with protein-level biomarker assessment, tau-PET imaging, and independent multi-cohort transcriptomic validation are warranted before CSF total tau can be considered a candidate biomarker for PD progression.

PMID:42298115 | DOI:10.1007/s12031-026-02558-1

Int J Legal Med. 2026 Jun 16. doi: 10.1007/s00414-026-03869-z. Online ahead of print.

ABSTRACT

Fire is a primary method of corpse destruction, complicating victim identification and the determination of cause and manner of death. This study focuses on the microscopic examination of fracture behavior in osteonal structures, referred to as osteonal damage analysis, to distinguish heat-induced fractures from perimortem and postmortem mechanical fractures. Thin sections of calcined bone were compared with perimortem and postmortem blunt trauma samples to investigate differences in the fracture behavior of osteonal structures. Statistical analysis using a Generalized Linear Mixed Model (GLMM) revealed significant variations (p < 0.05) in fracture patterns. Fractures predominantly crossed osteons, either cutting through the Haversian canal or following the cement line. While significant differences in fracture profiles were found, no pattern was exclusive to any group, with all fracture patterns present across all groups in varying frequencies. Crucially, the findings related to the calcined group suggest, for the first time, that heat-induced longitudinal fractures can intersect the Haversian canals, challenging the longstanding belief that only transverse fractures cross osteons transversely. These findings underscore the complexity of differentiating heat-induced from mechanical fractures and highlight the need for further research. A deeper understanding of osteonal damage is crucial for advancing forensic analysis of burned remains.

PMID:42298106 | DOI:10.1007/s00414-026-03869-z

J Imaging Inform Med. 2026 Jun 15. doi: 10.1007/s10278-026-02055-2. Online ahead of print.

ABSTRACT

Breast cancer is a heterogeneous disease whose molecular subtypes differ in biological behavior, prognosis, and therapeutic response. This study investigated whether whole-breast radiomic features extracted from digital mammograms and showing statistically significant differences between HER2 + tumors and other molecular subtypes or healthy controls could also provide discriminatory information for exploratory HER2 + characterization. An automated whole-breast segmentation and feature-extraction workflow, without manual lesion-centered delineation, was applied to the breast region to capture broader parenchymal and microenvironmental texture patterns while reducing dependence on manual lesion annotation. Intensity-based, first-order, and second-order texture features were extracted from DICOM mammograms, followed by pairwise statistical testing, false discovery rate correction, effect-size assessment, Gaussian distribution analysis, normalized feature visualization, univariate AUC analysis, and classifier evaluation using logistic regression and linear support vector machines. First-order and intensity-based descriptors showed limited subtype-specific value, whereas second-order texture features provided more informative discriminatory patterns. Among the evaluated feature families, GLCM and NGLDM descriptors showed the most coherent evidence across statistical, visual, and classifier-based analyses, with NGLDM yielding the broadest set of statistically significant features. Classification performance was strongest and most balanced for HER2 + versus healthy controls, while discrimination between HER2 + and other malignant molecular subtypes was modest, context-dependent, and affected by sensitivity-specificity imbalance in several models. Therefore, the present findings more strongly support sensitivity to malignancy-related whole-breast texture alterations than reliable HER2-specific classification among malignant subtypes. Whole-breast mammographic radiomics should be interpreted as an exploratory and complementary source of candidate imaging biomarkers for future validation.

PMID:42298097 | DOI:10.1007/s10278-026-02055-2

Int J Colorectal Dis. 2026 Jun 15. doi: 10.1007/s00384-026-05173-z. Online ahead of print.

ABSTRACT

AIM: To investigate whether colorectal cancer (CRC) sidedness is associated with intraoperative lavage cytology results, tumor recurrence, and prognosis.

METHOD: Using data from a multicenter prospective observational study conducted by the Japanese Society for Cancer of the Colon and Rectum (JSCCR), we retrospectively analyzed prognosis and recurrence patterns in pathological stage II/III right-sided and left-sided CRC, stratified by positive versus negative lavage cytology results.

RESULTS: A total of 1500 patients met the inclusion criteria and were enrolled. Of these, 534 had right-sided CRC and 966 had left-sided CRC. Fifty-nine patients (3.9%) had positive lavage cytology. Among patients with recurrence, pT4, positive lavage cytology, and right-sided tumor location were independently associated with peritoneal recurrence. Among cytology-negative patients, the 5-year relapse-free survival (RFS) rate was significantly higher in right-sided than in left-sided CRC (79.6% vs. 73.4%, p = 0.01), whereas the 5-year overall survival (OS) rate did not differ significantly (89.2% vs. 87.7%, p = 0.52). Among cytology-positive patients, no statistically significant differences in RFS or OS were observed between tumor locations. However, among cytology-positive patients who developed recurrence, post-recurrence survival was significantly worse in right-sided CRC than in left-sided CRC (p = 0.04).

CONCLUSION: Among cytology-negative patients, left-sided CRC was associated with poorer RFS than right-sided CRC, although OS did not differ. Right-sided tumor location and positive lavage cytology were independently associated with peritoneal recurrence among patients who developed recurrence. Among cytology-positive patients, right-sided CRC was associated with poorer post-recurrence survival.

PMID:42298064 | DOI:10.1007/s00384-026-05173-z

Surg Endosc. 2026 Jun 15. doi: 10.1007/s00464-026-12957-5. Online ahead of print.

ABSTRACT

BACKGROUND: Given the recent acquisition of the Fundamentals of Robotic Surgery (FRS) by the Society of Gastrointestinal and Endoscopic Surgeons (SAGES), there is a need to develop a proficiency-based training paradigm for the console-based tasks. The purpose of this study was to establish defensible, expert-derived training benchmarks for the FRS virtual reality (VR) tasks.

METHODS: A known-group standard setting framework was utilized. Five fellowship-trained minimally invasive surgeons (> 250 robotic cases) performed one warm-up and two recorded repetitions of each FRS VR task on the da Vinci SimNow platform. Times to completion and total scores were aggregated to determine the measures of central tendency for training benchmarks. To establish validity evidence, first-attempt performance of novices (fourth-year medical students enrolled in a simulation-based elective) was compared to the expert-derived mean time and median total score using one-sample tests.

RESULTS: Puzzle Piece Dissection was the most time-consuming task among experts (300 ± 61 s) and novices (584 ± 181). Knot Tying was the lowest-scoring task and demonstrated the greatest variability among experts (median score 54, IQR = [0-89]), whereas Ring Tower Transfer was the lowest-scoring for novices (median score 1, IQR = [0-49]). The differences between novice performance and expert measures of central tendency were statistically discernible (p < 0.05) with a large effect size for all tasks. Thus, training benchmarks were set at less than or equal to the expert-derived trimmed mean time and greater than or equal to the expert-derived median score.

CONCLUSION: Time- and score-based training benchmarks were established for the FRS VR tasks. The low and highly variable scores in Knot Tying were likely due to poor interaction fidelity, indicating that software modifications and/or alternative, non-VR exercises may be required for training. Further studies to evaluate the effectiveness of these training benchmarks are currently ongoing.

PMID:42298033 | DOI:10.1007/s00464-026-12957-5

Sci Rep. 2026 Jun 15. doi: 10.1038/s41598-026-58016-w. Online ahead of print.

ABSTRACT

The relationship between stress and breast cancer (BC) remains a topic of debate. We investigated the association between stress experienced within the past year and the risk of BC. Population-based incident case-control study of 600 newly diagnosed BC cases and 600 population controls (18-75 years) recruited in Isfahan, Iran between 2021 and 2023. Logistic regression model with short-term stress as main exposure was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) after adjusting for confounders. Multiplicative interaction was tested between stress and menopausal status as well as other confounders. One-year stress level was significantly associated with BC risk. Compared with women reporting low stress levels, the odds of BC were higher among those with high stress levels in both the unadjusted model (OR = 3.10, 95%Cl: 2.45-3.92) and the fully adjusted model (OR = 3.38; 95%CI (2.56, 4.47)). Based on the statistical test for multiplicative interaction, the association appeared stronger among premenopausal women (adjusted OR = 4.88, 95% CI: 3.17-7.52) than among postmenopausal women (adjusted OR = 2.34, 95% CI: 1.53-3.58), with evidence of interaction by menopausal status (p for interaction = 0.018). Despite the inherent limitations of case-control studies, including potential recall and selection biases, the findings of the current study suggest that higher levels of stress experienced within the past year may be associated with an increased risk of breast cancer, particularly among premenopausal women. Further prospective studies are warranted to clarify the nature and direction of this association.

PMID:42298021 | DOI:10.1038/s41598-026-58016-w