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Nevin Manimala Statistics

The Association Between Alzheimer’s Disease-Related Biomarkers And Parkinson’s Disease Based On Single-Cell Sequencing Analysis Combined With Mendelian Randomization

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

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Nevin Manimala Statistics

Microscopic characterization of longitudinal heat-induced fractures in calcined human remains

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

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Interpretable Whole-Breast Radiomic Biomarkers for Exploratory Assessment of HER2 + Breast Cancer in Digital Mammography

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

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Evaluation of the prognostic impact of intraoperative cytology results according to tumor sidedness in stage II/III resectable colorectal cancer

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

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Training benchmarks for the Fundamentals of Robotic Surgery virtual reality tasks

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

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Stress and risk of breast cancer; findings from a large population-based incident case-control study

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

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Nanostructured interfaces integrated with unsupervised intelligence to mitigate global polycrisis complexities

Adv Colloid Interface Sci. 2026 Jun 9;356:103970. doi: 10.1016/j.cis.2026.103970. Online ahead of print.

ABSTRACT

Nanostructured sensors are increasingly deployed to mitigate the complexities of the global polycrisis, including climate instability, antimicrobial resistance, pandemics, and emerging technological disruptions. While advanced nano-interfaces (such as MXenes, quantum dots, and MOFs) possess the requisite sensitivity, their efficiency is hindered by large-scale, high-dimensional, and stochastic physicochemical responses. This review articulates a necessary paradigm shift toward unsupervised machine Intelligence as the primary interface between nanostructured sensor hardware, raw data manifolds, and system-level interpretation. It critically examines the foundational methodologies, including clustering for discrete-state identification, Principal Component Analysis for decoupling cross-sensitive material kinetics, manifold learning for nonlinear structure visualization, Independent Component Analysis for blind source separation, and autoencoders for nonlinear denoising and anomaly detection. These approaches extract latent dynamical structures directly from raw nanosensor measurements without dependence on extensive labelled datasets, effectively handling drift, hysteresis, and environmental noise. Moving beyond purely statistical optimisation, it analyse hybrid architectures that embed conservation principles, symmetry conditions, and topological regularities directly into learning algorithms, ensuring outputs follow the system’s physical constraints. Finally, to address scalability challenges, including edge-native computing and privacy-preserving federated learning, it argues that converging advanced sensing nano-interfaces with constraint-regulated unsupervised intelligence is critical for developing self-calibrating material-sensor intelligence ecosystems to navigate polycrisis.

PMID:42296628 | DOI:10.1016/j.cis.2026.103970

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The impact of urinary catheterization on urinary tract infection and renal function in elderly patients undergoing hip fracture surgery: A prospective randomized controlled trial

Injury. 2026 Jun 13;57(8):113449. doi: 10.1016/j.injury.2026.113449. Online ahead of print.

ABSTRACT

INTRODUCTION: Urinary tract infection(UTI) is a common complication following hip fracture surgery in elderly patients. Urinary catheterization is frequently used to improve patient comfort during prolonged preoperative immobilization; however, its impact on UTI risk and renal function remains controversial. This prospective randomized study aimed to evaluate the effect of urinary catheter use on postoperative UTI incidence and renal outcomes in geriatric patients undergoing hip fracture surgery.

MATERIALS AND METHODS: This prospective randomized controlled trial included 150 patients aged > 65 years who underwent surgical treatment for proximal femur fractures between December 2022 and May 2025. Patients with UTI at admission, prior indwelling catheter use, high-energy trauma, multiple fractures, or a history of pelvic radiation were excluded. Patients were randomized into two groups: catheterized(n = 75) and non-catheterized(n = 75). Urinary tract infection was defined according to European Association of Urology (EAU) guideline criteria. Renal function was assessed using serum urea and creatinine levels measured preoperatively and on postoperative day 1. Demographic data, comorbidities, fluid intake, and perioperative variables were recorded and compared between groups.

RESULTS: The mean patient age was 79.8±7.2 years, and 61.3% were female. Postoperative UTI occurred in 20 patients (15.2%) overall. UTI was detected in 12 patients (18.5%) in the catheterized group and in 8 patients (11.9%) in the non-catheterized group, with no statistically significant difference between the groups (p = 0.296). Female sex and advanced age were identified as significant risk factors for UTI development. Postoperative creatinine levels were significantly higher in the non-catheterized group (p < 0.01), which was also associated with lower preoperative oral fluid intake. No significant association was found between UTI development and diabetes mellitus, hypertension, or coronary artery disease.

CONCLUSIONS: Indwelling urinary catheterization did not significantly increase postoperative UTI risk in elderly patients undergoing hip fracture surgery. Moreover, catheter use may help prevent dehydration-related renal dysfunction by facilitating adequate oral fluid intake. Careful, short-term catheterization may therefore represent a reasonable strategy in selected geriatric hip fracture patients.

PMID:42296627 | DOI:10.1016/j.injury.2026.113449

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The association between food insecurity and functional disability among older adults: the mediating effects of childhood and adult socioeconomic status in a ten-year follow-up longitudinal study in Ghana and South Africa

J Nutr Health Aging. 2026 Jun 15;30(7):100884. doi: 10.1016/j.jnha.2026.100884. Online ahead of print.

ABSTRACT

OBJECTIVES: This study examined the association between food insecurity (FI) and functional disability (FD) among older adults over time in Ghana and South Africa (SA), and the mediating roles of childhood parental employment (CPE) and adult education (AE) statuses.

METHODS: Data were from 6,569 and 4,663 older adults (60+years) who participated in WHO-SAGE Ghana and SA (Waves 1-3), respectively, between 2007-2019. Multivariable-adjusted logistic mixed effects models were performed to examine the roles of CPE and AE statuses on the associations between FI, in general, and its measures – hunger and food insufficiency – with FD in older adults.

RESULTS: After adjusting for significant covariates, older adults who reported being food insecure (Ghana: aOR = 1.20, 95%CI: 1.03, 1.41, p = 0.024; SA: aOR = 1.98, 95%CI:1.54, 2.56, p < 0.001) and those who reported consuming insufficient food (Ghana: aOR = 1.21, 95%CI: 1.03, 1.42, p = 0.018; SA: aOR = 1.96, 95%CI:1.52, 2.53, p < 0.001) had higher odds of FD over time, compared with those who were food secure. For both Ghana and SA, hunger was associated with higher odds of FD. However, the association remained statistically significant only for SA. CPE and AE statuses proved to be relevant pathways through which FI was associated with increased odds of FD among older adults in Ghana and SA.

CONCLUSION: CPE and AE statuses mediated the associations between FI and FD among older adults in Ghana and SA. This highlights the importance of adopting early–late-life interventions to support the health and economic wellbeing of families to accumulate wealth for food security and functional wellbeing in later life.

PMID:42296619 | DOI:10.1016/j.jnha.2026.100884

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Osimertinib after definitive CRT in unresectable stage III EGFR-mutated NSCLC: safety outcomes from the phase III LAURA study

Lung Cancer. 2026 Jun 6;218:109486. doi: 10.1016/j.lungcan.2026.109486. Online ahead of print.

ABSTRACT

BACKGROUND: In the phase III LAURA study, osimertinib demonstrated a statistically significant progression-free survival benefit versus placebo, and a generally tolerable safety profile, after definitive chemoradiotherapy (CRT) in unresectable stage III EGFR-mutated non-small cell lung cancer. We report in-depth safety data from LAURA.

PATIENTS AND METHODS: Patients without progression during/after definitive CRT were randomized 2:1 to receive osimertinib or placebo. Safety was assessed at baseline, week 2, week 4, every 4 weeks until week 24, every 8 weeks until week 48, and every 12 weeks until study treatment discontinuation. Adverse events (AEs) of special interest included grouped terms of radiation pneumonitis (RP) and interstitial lung disease (ILD, including pneumonitis).

RESULTS: Overall, 216 patients were randomized (osimertinib, 143; placebo, 73) and received ≥1 dose of study treatment; median exposure 24.0 months (osimertinib), 8.3 months (placebo). Exposure-adjusted rates of grade ≥3 AEs and serious AEs were 18 versus 13 and 20 versus 15/100 patient-years with osimertinib versus placebo, respectively. Exposure-adjusted AEs that occurred at the greatest increased frequency with osimertinib versus placebo were diarrhea and paronychia. AEs led to treatment interruption in 56 % versus 25 % of patients and to discontinuation in 13 % versus 5 % with osimertinib versus placebo, respectively. RP (grouped term) events were numerically higher in the osimertinib (48 %) versus placebo (38 %) arm but were mostly low grade; almost all events were reported by 18 weeks post-randomization. Protocol-mandated toxicity management guidelines effectively managed RP; most patients (60/69; 87 %) continued osimertinib, with or without interruption, and without recurrence (64/69; 93 %). ILD (grouped term) was mainly grade 1-2 and manageable; most events occurred within 20 weeks post-randomization.

CONCLUSIONS: Osimertinib after definitive CRT had an acceptable and manageable safety/tolerability profile, with no new safety findings, supporting osimertinib as the new standard of care in this setting. LAURA clinical trial registration number: NCT03521154.

PMID:42296617 | DOI:10.1016/j.lungcan.2026.109486