Nevin Manimala

Int J Colorectal Dis. 2026 Jun 8. doi: 10.1007/s00384-026-05168-w. Online ahead of print.

ABSTRACT

PURPOSE: The global rise in early-onset colorectal cancer (EOCRC) is a growing concern, particularly in low-resource settings. However, comprehensive data from Ethiopia are limited.

AIM: This study aimed to describe the clinicopathological profile and proportional hospital-based representation of EOCRC at Ethiopia’s largest tertiary referral center.

METHODS: We conducted a retrospective cross-sectional analysis of 630 histologically confirmed colorectal cancer (CRC) cases diagnosed at Tikur Anbessa Specialized Hospital between January 2019 and September 2024. EOCRC was defined as a diagnosis before the age of 50 years and late-onset CRC (LOCRC) as a diagnosis at the age of 50 years or older. Data on demographics, tumor location, histology, differentiation grade, and TNM stage were also extracted. Descriptive statistics, chi-square tests, and binary logistic regression were used for the analysis.

RESULTS: Of the 630 CRC cases, 292 (46.3%) were EOCRC (mean age 36.1 years, SD 7.9). Rectal tumors were significantly more common in EOCRC (31.2% vs. 22.5%, p = 0.012), as were poorly differentiated/undifferentiated tumors (21.9% vs. 13.0%, p = 0.003). Metastasis at diagnosis was less frequent in the EOCRC group (27.4% vs. 66.3%, p < 0.001). Multivariable analysis identified rectal location (adjusted odds ratio (AOR) = 1.60, 95% confidence interval (CI) 1.11-2.30) and poor differentiation (AOR = 1.94, 95% CI 1.25-3.00) as independent predictors of EOCRC, while metastasis was inversely associated (AOR = 0.20, 95% CI 0.14-0.29).

CONCLUSION: In this hospital-based sample, EOCRC constitutes a substantial proportion of CRC cases, with distinct clinicopathological features, including rectal predilection and aggressive histology. These findings highlight the need for heightened clinical suspicion in younger adults while acknowledging the influence of Ethiopia’s young population structure on the observed proportions.

PMID:42260223 | DOI:10.1007/s00384-026-05168-w

Int Urol Nephrol. 2026 Jun 9. doi: 10.1007/s11255-026-05232-y. Online ahead of print.

ABSTRACT

BACKGROUND: Preoperative identification of pathological upstaging (≥ pT3a) in clinical T1 (cT1) renal masses is critical for surgical planning. We externally validated three established predictive models, Barra, Nocera, and Mei, to assess their discrimination, calibration, and clinical utility in a contemporary cohort.

PATIENTS AND METHODS: We retrospectively reviewed patients undergoing surgery for cT1 renal masses at our institution. The primary endpoint was pathological upstaging to pT3a. Model performance was evaluated using the Area Under the Curve (AUC) for discrimination and the Brier Score for overall accuracy. Calibration was assessed using parametric and nonparametric Loess-smoothed curves. Clinical utility was quantified using Standardized Decision Curve Analysis.

RESULTS: The institutional upstaging rate was 17.1% (19/111), and clear cell histology predominated (77.5%). Nocera (AUC = 0.736) and Barra (AUC = 0.733) had higher point estimates of discriminative ability than Mei (AUC = 0.677), but the differences were not significant. All models descriptively overestimated absolute risk. However, Mei demonstrated the highest absolute calibration stability, whereas the Nocera model showed significant global unreliability (U = 0.052, p = 0.021). The Barra model achieved the lowest overall error (Brier Score = 0.122) and the highest clinical net benefit within the decisive 8%-18% decision window, although the overall accuracy differences were not statistically significant.

CONCLUSION: All nomograms are useful risk-stratification adjuncts, but wide confidence intervals and low event counts mean these findings are exploratory. No single model is definitively superior. Nocera and Barra are effective for relative risk-ranking, while Mei provides superior absolute precision for patient counseling.

PMID:42260216 | DOI:10.1007/s11255-026-05232-y

Clin Oral Investig. 2026 Jun 9;30(7):284. doi: 10.1007/s00784-026-06972-y.

ABSTRACT

OBJECTIVE: This retrospective pragmatic study aimed to evaluate and compare the healing outcomes of the multisonic GentleWave irrigation system with conventional syringe-needle irrigation used for non-surgical endodontic treatment.

METHODS: The study included 46 teeth that underwent nonsurgical endodontic treatment using two different irrigation protocols: (1) GentleWave irrigation system, and (2) Conventional syringe-needle irrigation, with a minimum follow-up of 1 year. Preoperative and follow-up data from treatment records, including clinical signs and symptoms, periapical radiographs, and cone-beam computed tomography (CBCT) images when available, were collected. Two independent evaluators scored the radiographs and CBCT scans based on the 2D periapical index (PAI) and 3D CBCT-PAI index, respectively. Based on clinical data and radiographic evaluation, treatment outcomes were categorized as healed, healing, or diseased. The success rate was assessed using both strict and loose criteria. Statistical analyses included Fisher’s exact tests, and Wilcoxon rank-sum tests, where appropriate. The significance level was set at 0.05.

RESULTS: Based on the periapical index and clinical evaluation, both the GentleWave and conventional groups exhibited comparable percentages of healed cases, corresponding to success rates of 69% and 70%, respectively (strict criteria). Using loose criteria, the success rate based on periapical imaging was 96% for conventional and 85% for GW groups. No statistically significant difference in healing outcomes/success rate was observed between the groups on both periapical radiograph and CBCT interpretation. Male sex, negative pulp vitality, presence of pre-operative periapical radiolucency (PARL), and absence of pre-operative symptoms were associated with reduced healing in the Conventional group. Pre-operative PARL and non-surgical root canal retreatment were associated with reduced healing in the GW group.

CONCLUSION: There were no differences in success rates or healing outcomes of endodontic treatment between the GentleWave irrigation system and conventional syringe-needle irrigation at 12-month follow-up. The presence of pre-operative PARL was significantly correlated with reduced success in both groups.

CLINICAL RELEVANCE: This study highlights similar success rates and healing outcomes for endodontic treatment with the GentleWave irrigation system compared to conventional syringe-needle irrigation at 12 months follow-up.

PMID:42260197 | DOI:10.1007/s00784-026-06972-y

Commun Biol. 2026 Jun 8. doi: 10.1038/s42003-026-10420-8. Online ahead of print.

ABSTRACT

The rapid expansion of single-cell RNA sequencing (scRNA-seq) has made accurate cell type annotation a critical bottleneck for biological discovery. Existing computational methods are often limited by reference data dependency, while emerging single Large Language Model (LLM) approaches are susceptible to model-specific biases and provide insufficient uncertainty quantification. To address these limitations, we introduce mLLMCelltype, a framework that harnesses collective intelligence-the emergent problem-solving capacity arising when multiple independent agents interact through structured deliberation to produce solutions exceeding individual capabilities-of multiple LLMs through an iterative deliberation process. Across 49 diverse datasets, our framework achieves a mean accuracy of 77.2%, a 15.7-percentage-point improvement over the best-performing single-LLM baseline (61.5%). The consensus mechanism demonstrates high robustness to noisy input and generalizes to datasets released after the LLMs’ training. By providing transparent reasoning chains and robust consensus-based confidence metrics, mLLMCelltype minimizes manual annotation effort and enables reliable interpretation of complex cellular landscapes. The framework is available as an open-source package and an accessible web server.

PMID:42260142 | DOI:10.1038/s42003-026-10420-8

Sci Rep. 2026 Jun 8. doi: 10.1038/s41598-026-56729-6. Online ahead of print.

ABSTRACT

The clustering of unhealthy movement behaviours is highly prevalent among adolescents and significantly impacts both health and academic outcomes. While evidence linking 24-hour Movement Guidelines to general academic outcomes is substantial, research specifically on arithmetic fluency remains limited. This cross-sectional study analysed 578 Spanish adolescents (aged 11-15 years) to quantify compliance with physical activity, screen time, and sleep recommendations and to explore the role of physical fitness in this relationship. Results revealed alarmingly low adherence: only 1% of adolescents meet all three health recommendations, while nearly half meet none. Results demonstrate a threshold effect, showing that adolescents who follow at least two guidelines achieve modest but significant higher scores in arithmetic fluency (B = 7.81, η²_p = .015, p = .005). Notably, this academic advantage is statistically accounted for by higher levels of cardiorespiratory fitness, which is consistent with a mediating role in all comparisons (B from 0.88 to 2.43; all 95% CI exclude zero), whereas muscular fitness does not. Findings suggest promoting combined healthy habits may be more effective for cognitive development than targeting single behaviours. Integrating movement-based strategies into school environments could enhance potentially arithmetic fluency success by fostering the cardiorespiratory health necessary for optimal arithmetic learning.

PMID:42260090 | DOI:10.1038/s41598-026-56729-6

Sci Rep. 2026 Jun 8. doi: 10.1038/s41598-026-56786-x. Online ahead of print.

ABSTRACT

The use of probiotics for preventing necrotizing enterocolitis (NEC) in preterm infants remains controversial. Specifically, whether the outcomes of infants with NEC are associated with prior probiotic administration remains unknown. This study aimed to examine the association between early supplementation with mixed-species probiotics and the timing of NEC onset as well as clinical outcomes in preterm infants who subsequently developed NEC. This retrospective study enrolled 216 preterm infants (gestational age < 35 weeks) diagnosed with stage II/III NEC from two hospitals in China. The patients were divided into a probiotics group and a nonprobiotics group. The timing of NEC onset, disease characteristics (intestinal perforation, surgery, mortality), and the occurrence of other preterm comorbidities were compared between the two groups. Among the infants who developed NEC, the median age at onset was observed to be later in the probiotic-exposed group compared with the unexposed group (22.5 days vs. 12 days). The probiotics group had a shorter duration of fasting after NEC onset (p < 0.05). However, no statistically significant differences were observed between the groups in terms of rates of surgery, intestinal perforation, mortality, shock, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), or extrauterine growth restriction (EUGR). Among infants who developed NEC, early mixed-species probiotic exposure was associated with later NEC onset. This association should be interpreted cautiously because probiotic exposure was non-protocolized and time-dependent. No clear evidence was observed for an association with reduced disease severity or lower rates of major complications, including surgery, bowel perforation, or mortality. These associational findings are exploratory and require further investigation.

PMID:42260078 | DOI:10.1038/s41598-026-56786-x

J Chromatogr A. 2026 Jun 3;1783:467163. doi: 10.1016/j.chroma.2026.467163. Online ahead of print.

ABSTRACT

The mathematical models in the plate theory of chromatography are solved by using a statistical approach. An equation for the number of theoretical plates is proposed which can unify the equations that are deduced from the continuous flow (CF) and discontinuous flow (disCF) model respectively. The models are compared with those in the rate theory of chromatography such as the equilibrium dispersive (ED), transport (TR), Wade-Lucy-Carr (WLC), transport dispersive (TD) and general rate (GR) model. In the case of high column efficiency, expressions are given to account for the relationship between the parameters in the CF and ED model and those in the disCF and TR model. A ratio parameter is proposed to account for the contribution to peak variance of the finite rate of the equilibrium or the mass transfer kinetics between mobile and stationary phase. It is used to calculate the plate height and can be measured in experiments by changing mobile phase composition slightly. It is also demonstrated that the TR and WLC model will be equivalent when the adsorption isotherm is linear. When the adsorption isotherm is nonlinear, a nonlinear driving force equation is deduced from the Langmuir kinetics equation, which can explain the concentration dependence of the rate coefficient in the TR model which has been reported in literature.

PMID:42258991 | DOI:10.1016/j.chroma.2026.467163

Clin Oncol (R Coll Radiol). 2026 May 5;55:104186. doi: 10.1016/j.clon.2026.104186. Online ahead of print.

ABSTRACT

AIM: Third-line treatment options for metastatic colorectal cancer (mCRC) remain limited. Chemotherapy rechallenge has shown efficacy in this setting, but direct comparisons with tyrosine kinase inhibitors (TKIs) are lacking. This real-world study aimed to retrospectively compare TKI (regorafenib/fruquintinib) versus rechallenge chemotherapy in refractory mCRC.

MATERIALS AND METHODS: From April 2018 to June 2023, 107 mCRC patients receiving third-line therapy were analyzed (median follow-up: 6.6 months). Endpoints included overall survival (OS) and progression-free survival (PFS). Patients were divided into TKI (n = 53) and rechallenge chemotherapy (n = 54) groups. Kaplan-Meier curves, Cox models, and RECIST 1.1-based spider/waterfall plots were generated using RStudio (R Foundation for Statistical Computing, Vienna, Austria) 3.5.2 (significance: P < .05).

RESULTS: Rechallenge chemotherapy significantly improved OS (hazard ratio [HR] = 0.44, 95% CI = 0.27-0.70; P < .001) and PFS (HR = 0.58, 95% CI = 0.27-0.70; P = .002) with significantly higher objective response rate (10.9% vs. 0%, P = .025) and disease control rate (67.4% vs. 52.8%, P = .090) compared to TKIs.

CONCLUSION: In this single-center retrospective real-world cohort, rechallenge chemotherapy was associated with improved survival and response outcomes compared with TKIs in third-line mCRC. However, given the non-randomized design and potential confounding, these findings should be considered hypothesis-generating. Rechallenge chemotherapy may be considered in selected patients with prior chemotherapy sensitivity and an adequate treatment-free interval, pending prospective validation.

PMID:42258990 | DOI:10.1016/j.clon.2026.104186

J Hazard Mater. 2026 Jun 4;514:142578. doi: 10.1016/j.jhazmat.2026.142578. Online ahead of print.

ABSTRACT

Effective early warning systems for aquatic contamination require monitoring strategies capable of detecting subtle, long-term shifts in mixture-driven biological activity. Suspended particulate matter (SPM) serves as a carrier and reservoir for complex contaminant mixtures, facilitating their transport and persistence in aquatic systems, yet systematic toxicological time series for archived SPM remain scarce. Regulatory monitoring predominantly targets Priority Substances and River Basin Specific Pollutants, leaving the temporal trends of particle-associated mixture toxicity largely unresolved. Leveraging 18 years (2005-2022) of cryogenically archived annual SPM composites from the Rhine River, we conducted a spatiotemporal effect-based assessment integrating receptor-mediated effects, oxidative stress analysis and untargeted Cell Painting phenomics. This integrated toolbox enabled evaluation of pathway-specific responses and multi-compartment cellular perturbations associated with particle-bound contaminant mixtures. Polar SPM-associated chemicals elicited oxidative stress response and caused endocrine disruption through estrogen receptor α (ERα) activation and androgen receptor inhibition (anti-AR). Trend analysis showed spatiotemporal variation along the river, with statistically increasing trends of oxidative stress and anti-AR activity over time at Koblenz, driven by polar chemicals. Both polar and non-polar SPM extracts activated the aryl hydrocarbon receptor (AhR), indicating presence of compounds capable of triggering xenobiotic response pathways. Several subcellular compartments were affected, with mitochondrial features being among the most affected. These findings demonstrate that SPM-associated chemicals elicit diverse toxicological effects by acting on several receptors and impacting diverse cellular structures. Combining targeted and phenomics-based effect approaches provided comprehensive mechanistic insights and valuable information to support the early warning systems for chemical contamination in aquatic environments.

PMID:42258982 | DOI:10.1016/j.jhazmat.2026.142578

J Pediatr Nurs. 2026 Jun 8;90:99-106. doi: 10.1016/j.pedn.2026.05.050. Online ahead of print.

ABSTRACT

BACKGROUND: Early ambulation following surgery is essential for recovery, yet children undergoing surgery often face barriers due to multiple lines and medical equipment.

METHODS: A quasi-experimental design was used to compare children who received the early ambulation device with a retrospective surgical-condition-stratified comparison group. Outcomes included length of stay, time to first ambulation, and daily average ambulation.

RESULTS: Results showed several significant improvements in the experimental group versus the comparison group. Among children in the abdominal surgery cohort, the experimental group had a greater total ambulation (15.0 vs. 12.0, p = 0.023) and higher daily ambulation frequency (5.5 vs. 2.5, p < 0.001); and length of stay trended shorter in the experimental group but did not reach statistical significance (3.0 vs. 3.8 days, p = 0.060). Children in the spinal fusion cohort also experienced benefits, including a shorter length of stay (3.9 vs. 4.7 days, p = 0.001), earlier ambulation (18.7 vs. 39.7 h, p < 0.001), and a greater frequency of ambulation (20.5 vs. 15.0, p < 0.001). Improvements were most pronounced in the early to mid-postoperative period.

CONCLUSION: This study provides the first evidence of early ambulation device use in a pediatric surgical population. The device was associated with earlier mobilization, more frequent ambulation, and reduced hospital length of stay in the spinal fusion cohort, with a trend toward reduced length of stay in the abdominal cohort. Advantages of utilizing the early ambulation device include cost savings for families and the organization, as well as increased independence when ambulating.

PMID:42258971 | DOI:10.1016/j.pedn.2026.05.050