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Nevin Manimala Statistics

Kinematic and dynamic analysis of walking dynamic balance stability in children with spastic cerebral palsy diplegia

Front Bioeng Biotechnol. 2025 Oct 24;13:1604658. doi: 10.3389/fbioe.2025.1604658. eCollection 2025.

ABSTRACT

OBJECTIVE: This study aims to compare biomechanical features during walking between children with spastic cerebral palsy (SCP) and typically developing children, providing evidence to improve walking ability and prevent falls in children with SCP.

METHODS: The study included 28 children with SCP from the paediatric physiotherapy department of the China Rehabilitation Research Centre (March 2023 to September 2024) and 28 typically developing children from a Beijing primary school as controls. Participants wore tight-fitting clothing to ensure clear visibility of reflective markers. A Vicon 3D motion capture system and AMTI force plates were used to collect data on temporal-spatial parameters, dynamic balance and kinematic parameters during gait cycles. Measurements included walking speed; step frequency, width and length; single-foot support time; peak displacements of the centre of mass (COM) and the centre of pressure; and joint angles of the pelvis, hip, knee and ankle in multiple planes.

RESULTS: Children with SCP showed significantly lower values in walking speed, stride length, step length and single-foot support time than the controls (P < 0.05). Conversely, cadence, stride time and double support time were higher in children with SCP than in the controls. Children with SCP showed greater peak COM displacement in the coronal plane but lower in the sagittal plane than the controls (P < 0.05). Significant differences were found in the range of motion of left lower extremity joints across various phases of the gait cycle (P < 0.05).

CONCLUSION: Children with SCP exhibit distinct gait patterns and dynamic balance challenges compared with their typically developing peers, underscoring the importance of personalised rehabilitation treatments to enhance their walking abilities and prevent falls.

CLINICAL TRIAL NUMBER: ChiCTR2300071226.

PMID:41209298 | PMC:PMC12592154 | DOI:10.3389/fbioe.2025.1604658

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Nevin Manimala Statistics

Data-driven assessment of bioisosteric replacements and their influence on off-target activity profiles

RSC Med Chem. 2025 Nov 6. doi: 10.1039/d5md00686d. Online ahead of print.

ABSTRACT

Bioisosterism, a fundamental concept in medicinal chemistry, involves the substitution of chemical groups with structural analogs that preserve similar physicochemical properties while potentially modulating potency or toxicity. To systematically investigate shifts in pChEMBL values upon such substitutions, we developed a KNIME workflow that extracts and analyzes compound pairs featuring literature-curated common bioisosteric exchanges. The workflow retrieves pChEMBL values across 88 off-targets from ChEMBL and supports decision-making through pair-level quality metrics such as the document consistency ratio and assay context consistency ratio, which assess the consistency of the source data. Our analysis revealed that ester-to-secondary-amide replacements at the muscarinic acetylcholine receptor M2 (CHMR2) result in a significant mean decrease in pChEMBL of 1.26 across 14 compound pairs (p < 0.01). In contrast, phenyl-to-furanyl substitutions at the adenosine A2A receptor (ADORA2A) led to a mean increase in pChEMBL of 0.58 across 88 compound pairs (p < 0.01). Furthermore, a second KNIME workflow was developed to assess selectivity profiles by analyzing pChEMBL shifts at secondary targets. Among 66 compound pairs active at both ADORA2A and ADORA1, the mean change at ADORA1 was only +0.14 ± 0.52, indicating a selective potency increase at ADORA2A. This exemplifies a potential case of increased potency at an off-target associated with adverse effects, while maintaining activity at a pharmacologically desirable target. Conversely, furanyl-to-phenyl replacements may selectively reduce undesired potency at ADORA2A while preserving potency at ADORA1. This framework enables systematic, data-driven evaluation of potency shifts induced by bioisosteric replacements, aiding in the identification of substitutions associated with off-target potency increases or decreases during lead optimization. The workflow offers a semi-automated, reproducible approach that integrates bioisostere generation, activity mapping, and statistical assessment in a single platform, making it readily adaptable to other compound series and target panels. In addition, it evaluates whether activity at other known targets remains unchanged, thereby providing an assessment of selectivity of the replacements. The workflow can be applied to prioritize replacement strategies that reduce off-target risks, evaluate selectivity profiles, and generate curated potency shift data to support predictive modeling efforts.

PMID:41209296 | PMC:PMC12591391 | DOI:10.1039/d5md00686d

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Nevin Manimala Statistics

Effects of the care transition intervention on hospital readmission and quality of life in older adults with multiple chronic conditions: A mixed methods study

Int J Nurs Stud. 2025 Oct 23;174:105257. doi: 10.1016/j.ijnurstu.2025.105257. Online ahead of print.

ABSTRACT

BACKGROUND: The care transition intervention has been designed to guide users in supporting older adults during care transitions; however, there is little knowledge about its effectiveness in older adults with multiple chronic conditions.

OBJECTIVE: This study evaluated the effects of the care transition intervention in older adults with multiple chronic conditions.

DESIGN: A randomized intervention study with a mixed-methods design was conducted.

METHODS: The quantitative phase of the study was conducted using a randomized clinical trial on older patients with multiple chronic conditions referred to the Imam Khomeini Hospital in Sari (Mazandaran, Iran) in 2022-2024. Patients in the experimental group received the care transition intervention which involved implementing a patient-centered record, and providing education on medication self-management, warning signs of worsening health condition(s) and how react to them, and follow-up. Patients in the control group received routine hospital care. Quality of life and the number of hospital readmissions were assessed before the intervention, and at one, three, and six months after hospital discharge. The qualitative phase focused on understanding the experiences of patients and caregivers who had participated in the care transition intervention. Qualitative data were analyzed using conventional content analysis. Finally, after analyzing the data from the quantitative and qualitative phases, the quantitative findings were compared to the qualitative findings.

RESULTS: There was a statistically significant between group difference in Quality of life at one (control group: 69.28(8.64), experimental group: 64.36(10.82)), three (control group: 71.41(8.70), experimental group: 64.20(10.90)) and six months (control group: 72.21(8.93), experimental group: 64.29 (11.26)) after hospital discharge (P < 0.05). Also, hospital readmission in the control group was 73 % higher than the experimental group. The greatest effect of the intervention for quality of life (effect size = 0.77) and readmission (effect size = 0.63) was found six months after discharge. Qualitative findings support a beneficial effect of the care transition intervention on the quality of life and readmission in older adults.

CONCLUSIONS: Using the care transition intervention for older adults with multiple chronic conditions improves health-related outcomes and is associated with reduced disease burden and more satisfaction towards life in different physical, psychological, and social dimensions for them. Therefore, implementing the care transition intervention can be useful for patients, their families and the healthcare system.

REGISTRATION: This trial was registered at irct.behdasht.gov.ir (Identifier: IRCT20180930041185N3, Registration date: 2022-09-23) and the first participant was registered in December 2022.

PMID:41206990 | DOI:10.1016/j.ijnurstu.2025.105257

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Nevin Manimala Statistics

Sonodynamic and photodynamic therapy, activated indocyanine green, and indocyanine green-loaded chitosan nanoparticle on resin tag length and shear bond strength to caries-affected dentin using two-step etch and rinse resin adhesive

J Photochem Photobiol B. 2025 Nov 2;273:113291. doi: 10.1016/j.jphotobiol.2025.113291. Online ahead of print.

ABSTRACT

AIM: Evaluating the effect of different disinfection protocols, i.e., Chlorhexidine (CHX), Sonodynamic therapy (SDT)-Indocyanine green (ICG), photodynamic therapy (PDT)-ICG, and ICG-loaded chitosan nanoparticles (CHNPs) on the resin tag length (RTL) and the shear bond strength (SBS) bonded to caries-affected dentin (CAD) using two step etch and rinse resin adhesive.

MATERIALS AND METHODS: The present study utilized fifty-six extracted human molars with carious lesions extending up to halfway between the pulp chamber and the enamel-dentin junction, corresponding to ICDAS criteria 5. All the samples were allocated into four groups based on the disinfection regimen (n = 14). Group 1: CHX, Group 2: ICG-PDT, Group 3: ICG-SDT, and Group 4: ICG-loaded CHNPs. A traditional two-step etch and rinse adhesive was used, followed by composite buildup. All specimens underwent thermocycling to replicate the aging effect. Scanning electron microscopy was used for characterization of chitosan nanoparticles and ICG-loaded CHNPs, followed by measurement of RTL (n = 4). Failure mode assessment and SBS analysis were performed using a stereomicroscope and universal testing machine(n = 10). ANOVA2 and post hoc Tukey test were conducted to statistically compare the RTL and SBS outcomes among various investigated groups, p ˂0.05.

RESULTS: Group 3 (ICG-SDT) samples presented the maximum length of resin tags (121.82 ± 5.23 μm) and the highest bond strength (9.43 ± 0.23 MPa). Whereas the minimum resin tag length was detected in Group 2 (ICG-PDT) (59.21 ± 2.11 μm), along with the lowest bond strength (6.41 ± 0.92 MPa). Comparative analysis between Group 1 (CHX) and Group 2 indicated that no significant difference in their resin tag length and SBS (p˃0.05). Similarly, intergroup analysis between Group 3 and Group 4 also demonstrated comparable bond strength and resin tags (p˃0.05).

CONCLUSION: Sonodynamic therapy with indocyanine green and indocyanine green-infused chitosan nanoparticles is an effective method for disinfecting caries-affected dentin, as it has shown appropriate resin tag length and bond strength.

PMID:41206983 | DOI:10.1016/j.jphotobiol.2025.113291

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Nevin Manimala Statistics

Trends in central nervous system cancers mortality in the United States and the underlying sociodemographic determinants, 1999-2020

Eur J Public Health. 2025 Nov 9:ckaf207. doi: 10.1093/eurpub/ckaf207. Online ahead of print.

ABSTRACT

Though central nervous system (CNS) cancers have become a critical health concern in the United States, a comprehensive understanding of the nationwide and group-specific trends over time is still limited. This surveillance-based study used data obtained from the National Center for Health Statistics. Age-standardised mortality trends and the Average Annual Percent Change (AAPC) trends were estimated by demographic. We calculated the relative risks between various county-level socioeconomic factors and mortality for CNS cancers. CNS cancers death rates have decreased from 1999 to 2020 in the U.S., while they increased by 2% annually (AAPC, 0.2%, 95% CI [0.0% to 0.4%]) among people aged ≥65 years. The highest increase in CNS cancer was observed among Asian or Pacific Islanders (AAPC, 1.3%, 95% CI [0.8% to 2.3%]), followed by American Indian/Alaska Native individuals (AAPC, 1.2%, 95% CI [-0.3% to 3.0%]). Additionally, individuals residing in counties with greater poverty, more rural area, and lower education levels tended to have higher age-standardised mortality. There were varying degrees of increased mortality rates from CNS cancers by demographic. The strong association of CNS cancers mortality with county SES and rurality suggests that county-based public health strategies are needed to reduce this disparity in mortality.

PMID:41206962 | DOI:10.1093/eurpub/ckaf207

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Nevin Manimala Statistics

Global index of lifestyle quality and non-suicidal self-injury in the SESSAMO project: a Spanish adolescents cohort

Eur J Public Health. 2025 Nov 9:ckaf159. doi: 10.1093/eurpub/ckaf159. Online ahead of print.

ABSTRACT

Adolescents’ failure to embrace healthy lifestyles constitutes a serious public health issue, such that its relationship to non-suicidal self-injury (NSSI) merits further research. The aim of the study was to ascertain the association between a Global Index of Lifestyle Quality (GILQ) and the presence of NSSI. Cross-sectional analysis of a sample of 2nd- to 4th-year ESO students (Obligatory Secondary Education, from ages 14 to 16) recruited for the SESSAMO project, a multicenter prospective cohort study. Exposure variables were collected, including eating patterns, physical activity, screen use, the consumption of cannabis, alcohol and tobacco, risky sexual behavior, gambling, spend time with friends, and sleep quality. To determine the presence of NSSI, a validated questionnaire was administered. The association between different lifestyles and the presence of NSSI was analyzed through multivariate logistic regression models. 2042 adolescents were included. Physical activity, screen use, risky sexual behavior, sleep quality, and daytime sleepiness showed inverse and statistically significant associations with the presence of NSSI in multivariate models. A higher lifestyle score was associated with a 71% reduction in the likelihood of engaging in NSSI (OR for extreme quartiles of GILQ adherence =0.29; 95% CI = 0.15-0.57). The result was similar when boys and girls were analyzed separately. A healthy lifestyle was inversely associated with the presence of NSSI in this sample of Spanish adolescents. Lifestyles could function as potential predictors of NSSI.

PMID:41206960 | DOI:10.1093/eurpub/ckaf159

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Nevin Manimala Statistics

Development and validation of ACTTOP: a prediction model for severe anticancer treatment toxicities in older patients with solid malignancy

Age Ageing. 2025 Oct 30;54(11):afaf324. doi: 10.1093/ageing/afaf324.

ABSTRACT

BACKGROUND: Older adults with cancer are at increased risk of severe treatment-related toxicity (TRT). Existing chemotherapy toxicity prediction models have limitations. This study aimed to develop and validate a tool for predicting severe TRT in older patients receiving systemic anticancer therapy.

METHODS: Patients aged ≥65 scheduled for systemic therapy, including chemotherapy, targeted therapy and/or immunotherapy, were recruited from three oncology centres in Hong Kong between March 2019 and June 2023. Pretreatment assessments captured clinical, tumour/treatment, laboratory and geriatric variables. Patients were monitored during treatment or for six months for grade 3-5 TRT (NCI CTCAE v5.0). Predictive factors were identified using multivariable logistic regression, and a weighted scoring system, Anti-Cancer Treatment Toxicity in Older Patients (ACTTOP), was developed. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and goodness-of-fit statistics, and compared with the CARG model.

RESULTS: Among 700 patients (first 400 for development; last 300 for validation; median age 71), 413 (59.0%) developed grade 3-5 TRT. Ten predictors were identified. ACTTOP stratified patients into low (0-3 points: 36.0% development, 40.5% validation), intermediate (4-8 points: 63.9%, 52.5%) and high-risk (9-26 points: 86.3%, 76.6%) groups. The AUC was 0.72 (95% CI: 0.67-0.77) in development and 0.77 (95% CI: 0.72-0.82) in validation. Risk groups were significantly associated with premature termination, emergency room visits, toxicity-related hospitalisations and early mortality (P < .001). ACTTOP demonstrated superior predictive capability over the CARG score (AUC 0.61).

CONCLUSION: ACTTOP is a validated prediction model that enables individualised risk assessment for severe toxicity in older cancer patients receiving systemic therapy.

PMID:41206956 | DOI:10.1093/ageing/afaf324

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Nevin Manimala Statistics

TCVS: Tree-guided compositional variable selection analysis of microbiome data

Bioinformatics. 2025 Nov 9:btaf617. doi: 10.1093/bioinformatics/btaf617. Online ahead of print.

ABSTRACT

MOTIVATION: Studies of microbial communities, represented by the relative abundances of taxa at various taxonomic levels, have underscored the significance of microbiota in numerous aspects of human health and disease. A pivotal challenge in microbiome research lies in pinpointing microbial taxa associated with disease outcomes, which could play crucial roles in prevention, detection, and treatment of various health conditions. Alongside these relative abundance data, taxonomic information sometimes offers a unique lens to explore the impact of shared evolutionary histories on patterns of microbial abundance.

RESULTS: In pursuit of this goal, we utilize the tree structure to more flexibly identify taxa associated with disease outcomes. To enhance the accuracy of our selection process, we introduce auxiliary knockoff copies of microbiome features designated as noise. This approach allows for the assessment of false positives in the selection process and aids in refining it towards more precise outcomes. Extensive numerical simulations demonstrate that our methodology outperforms several existing methods in terms of selection accuracy. Furthermore, we demonstrate the practicality of our approach by applying it to a widely used gut microbiome dataset, identifying microbial taxa linked to body mass index.

AVAILABILITY AND IMPLEMENTATION: TCVS R code is available at https://github.com/Yicong1225/TCVS.

PMID:41206954 | DOI:10.1093/bioinformatics/btaf617

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Nevin Manimala Statistics

Long-term outcomes and patency of left carotid-subclavian bypass in thoracic endovascular aortic repair

Eur J Cardiothorac Surg. 2025 Nov 9:ezaf391. doi: 10.1093/ejcts/ezaf391. Online ahead of print.

ABSTRACT

OBJECTIVES: Left carotid-subclavian bypass (LCSB) is a classic strategy for left subclavian artery (LSA) revascularization in TEVAR patients. Its employment has been reduced in recent years due to the advent of endovascular solutions for LSA management.Data on outcomes of LCSB is lacking, especially for graft-related complications and patency at follow-up.

METHODS: All patients who underwent TEVAR with LCSB from November 2005 to January 2025, in an elective or urgent setting, were retrospectively analysed in terms of pre- and intraoperative characteristics, short- and mid-term outcomes.In-hospital outcomes were compared between the urgent and elective groups. LCSB patency at follow-up imaging was reported. A Kaplan-Meier analysis was performed on survival, freedom from reintervention and LCSB patency.

RESULTS: LCSB was performed in 161 patients, 36 of which (22.3%) were urgent procedures. In-hospital mortality was 3.7%, with no significant difference between the elective and the urgent group (3.2% vs 5.6% respectively, p = 0.491). There was a not statistically significantly higher incidence of stroke in the urgent patients (0.8% vs 5.6%, p = 0.057). LCSB-related complications occurred in 12 patients (7.4%). Overall LCSB patency at last available follow-up was 97.4%. LSA embolization was necessary in 7 cases (4.5%) due to type II endoleak. At 5 years, survival was 87.4%, freedom from reintervention was 88.5% and LCSB patency was 99%.

CONCLUSIONS: Left carotid-subclavian bypass is safe and effective as a LSA revascularization strategy. Even in urgent patients, LCSB was not linked to worse in-hospital outcomes.

PMID:41206953 | DOI:10.1093/ejcts/ezaf391

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Nevin Manimala Statistics

Different diabetes types and pancreatic ductal adenocarcinoma: a Mendelian randomization and pathway/gene-set analysis

J Natl Cancer Inst. 2025 Nov 9:djaf308. doi: 10.1093/jnci/djaf308. Online ahead of print.

ABSTRACT

BACKGROUND: The associations between different types of diabetes, characterized by distinct pathophysiology and genetic architecture, and pancreatic ductal adenocarcinoma (PDAC) risk are not understood.

METHODS: We investigated associations of genetic susceptibility to type 2 diabetes (T2D), eight T2D mechanistic clusters, type 1 diabetes (T1D), and maturity-onset diabetes of the young (MODY) with PDAC risk. We used genome-wide association study (GWAS) summary-level statistics for T2D (242,283 cases, 1,569,734 controls), T1D (18,942 cases, 501,638 controls), and PDAC (10,244 cases and 360,535 controls) in individuals of European ancestry.

RESULTS: Two-sample Mendelian randomization (MR) using the Robust Adjusted Profile Score (MR-RAPS) method indicated that genetically predicted T2D was associated with PDAC risk (OR = 1.10; 95% CI 1.05-1.15), particularly the T2D obesity (OR = 1.28; 95% CI 1.15-1.42) and lipodystrophy (OR = 1.25; 95% CI 1.03-1.51) clusters. No association was observed for T1D with PDAC risk (OR = 1.01; 95% CI 0.99-1.02). Pathway/gene-set analysis using the summary-based Adaptive Rank Truncated Product (sARTP) method revealed a significant association between the MODY gene-sets and PDAC risk (P = 1.5 × 10-8), which remained after excluding 20 known PDAC GWAS loci (P = 7.6 × 10-4). HNF1A, FOXA3, and HNF4A were the top contributing genes after excluding the previously identified GWAS loci regions.

CONCLUSIONS: Our results from this genetic association study support that T2D, particularly the obesity and lipodystrophy mechanistic clusters, and MODY genomic susceptibility regions play a role in the etiology of PDAC.

PMID:41206949 | DOI:10.1093/jnci/djaf308