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Nevin Manimala Statistics

Unsupervised learning reveals rapid gait adaptation after leg loss and regrowth in spiders

J Exp Biol. 2025 Jun 15;228(12):jeb250243. doi: 10.1242/jeb.250243. Epub 2025 Jun 17.

ABSTRACT

Many invertebrates voluntarily lose (autotomize) limbs during antagonistic encounters, and some regenerate functional replacements. Because limb loss can have severe consequences on individual fitness, it is likely subject to significant selective pressures, making this an excellent phenomenon with which to investigate biomechanical robustness. Spiders frequently autotomize one or more legs. We investigated the time course of locomotor recovery after leg loss and regeneration in juvenile tarantulas (Arachnida: Araneae) naive to autotomy. We recorded high-speed video of spiders running with all legs intact, then immediately after, and again 1 day after they had autotomized two legs. The legs were allowed to regenerate, and the same sequence of experiments was repeated. Video tracking analysis revealed that the spiders resumed their pre-autotomy speed and stride frequency after leg regeneration and in ≤1 day after both autotomies; path tortuosity was unaffected by these treatments. Autotomized spiders widened the spread of their remaining legs for stability and to compensate for missing functional space. To analyze how their gaits changed in response to leg loss, we applied unsupervised machine learning for the first time to measured kinematic data in combination with gait space metrics. Spiders were found to robustly adopt new gait patterns immediately after losing legs, with no evidence of learning. This novel clustering approach both demonstrated concordance with hypothesized gaits and revealed transitions between and variations within these patterns. More generally, clustering in gait space enables the identification of patterns of leg motions in large datasets that correspond to either known gaits or undiscovered behaviors.

PMID:40525284 | DOI:10.1242/jeb.250243

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Nevin Manimala Statistics

Development and Verification of a Physiologically Based Pharmacokinetic Model of Furmonertinib and Its Main Metabolite for Drug-Drug Interaction Predictions

CPT Pharmacometrics Syst Pharmacol. 2025 Jun 17. doi: 10.1002/psp4.70052. Online ahead of print.

ABSTRACT

Furmonertinib demonstrated potent efficacy as a newly developed tyrosine kinase inhibitor for the treatment of patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer. In vitro research showed that furmonertinib is metabolized to its active metabolite AST5902 via the cytochrome P450 (CYP) enzyme CYP3A4. Furmonertinib is a strong CYP3A4 inducer, while the metabolite is a weaker CYP3A4 inducer. In clinical studies, nonlinear pharmacokinetics were observed during chronic dosing. The apparent clearance showed time- and dose-dependent increases. In this evaluation, a combination of in vitro data using radiolabeled compounds, clinical pharmacokinetic data, and drug-drug interaction (DDI) data of furmonertinib in oncology patients and/or in healthy subjects was used to develop a physiologically based pharmacokinetic (PBPK) model. The model was built in PK-Sim Version 11 using a total of 44 concentration-time profiles of furmonertinib and its metabolite AST5902. Suitability of the predictive model performance was demonstrated by both goodness-of-fit plots and statistical evaluation. The model predicted the observed monotherapy concentration profiles of furmonertinib well, with 32/32 predicted AUClast (area under the curve until the last concentration measurement) values and 32/32 maximum plasma concentration (Cmax) ratios being within twofold of the respective observed values. In addition, 8/8 predicted DDI AUClast and Cmax ratios with furmonertinib as a victim of CYP3A4 inhibition or induction were within twofold of their respective observed values. Potential applications of the final model include the prediction of DDIs for chronic administration of CYP3A4 perpetrators along with furmonertinib, considering auto-induction of furmonertinib and its metabolite AST5902.

PMID:40525261 | DOI:10.1002/psp4.70052

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Nevin Manimala Statistics

Psychometric properties of modified 10-item Medication Adherence Scale for cancer patients receiving chemotherapy: Self-report scale validation study

J Oncol Pharm Pract. 2025 Jun 17:10781552251341569. doi: 10.1177/10781552251341569. Online ahead of print.

ABSTRACT

PurposeThe 10-item Medication Adherence Rating Scale (MARS-10) is a validated, self-report tool used to assess adherence to chronic illnesses due to its applicability. However, its psychometric properties have not been evaluated among cancer patients receiving chemotherapy. This study aimed to determine the psychometric properties of the modified MARS-10 in this population.MethodsA cross-sectional analytic study was conducted on adults receiving cancer chemotherapy from April to May 2022. Confirmatory factor analysis was used to validate the scale. The internal consistency was determined using composite reliability. Convergent and discriminant validity of the constructs were measured by the average variance extracted and the Heterotrait-Monotrait correlation ratio, respectively. Statistical significance was declared as p-value < 0.05.ResultsThree hundred (n = 300) adults receiving cancer chemotherapy were enrolled in the study. There was a significant difference between the higher and lower adherence scores, t (299) = 95.84, p < 0.001. The four constructs explained 66.6% of the total variance. The composite reliability of constructs one (0.79), two (0.66), three (0.66), and four (0.66) was in the acceptable to good range. The extracted mean-variance was more than 0.50, and the Heterotrait-Monotrait correlation ratio ranged from 0.31-0.83 for all constructs.ConclusionThis study has established the internal psychometric properties of the modified 10-item Medication Adherence Rating Scale. Therefore, this modified scale is a valuable tool for researchers and has important implications for oncology health promotion, and policymakers where direct adherence measurement to cancer chemotherapy is challenging.

PMID:40525251 | DOI:10.1177/10781552251341569

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Nevin Manimala Statistics

Efficacy and Safety of Poly (ADP-Ribose) Polymerase Inhibitors in Combination with Chemotherapy for Advanced Breast Cancer: A Systematic Review and Meta-Analysis

Technol Cancer Res Treat. 2025 Jan-Dec;24:15330338251350630. doi: 10.1177/15330338251350630. Epub 2025 Jun 17.

ABSTRACT

PurposeTo comprehensively evaluate the efficacy and safety of combining poly (ADP-ribose) polymerase (PARP) inhibitors with chemotherapy in patients with advanced breast cancer.MethodsA systematic literature search was conducted in PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov to identify randomized controlled trials (RCTs) evaluating PARP inhibitor-chemotherapy combinations. Studies reporting progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety outcomes were included. Data extraction and quality assessment were performed independently by two reviewers, and a meta-analysis was conducted using random-effects models.ResultsOf 970 studies retrieved, four RCTs involving 1064 patients met the inclusion criteria. PARP inhibitors combined with chemotherapy significantly improved PFS (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.63-0.84, P < .0001) and showed a trend towards improved OS (HR 0.93, 95% CI 0.79-1.09, P = .36), though this was not statistically significant. There was no significant improvement in ORR (RR 1.08, 95% CI 0.98-1.20, P = .13). Regarding safety, no significant difference was observed in all grades or grade 3-4 adverse events (AEs) overall, but the combination therapy was associated with an increased risk of anemia, nausea, and diarrhea (RRs ranging from 1.14 to 1.29, all P < .01).ConclusionPARP inhibitor combined with chemotherapy is an effective option for the treatment of patients with advanced breast cancer, but its potential increased risks of specific AEs need to be weighed. Clinicians should make individualized treatment plans according to the specific conditions of patients, comprehensive consideration of efficacy and safety.

PMID:40525248 | DOI:10.1177/15330338251350630

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Nevin Manimala Statistics

Exploration of influential factors about deficiency constitution of Traditional Chinese Medicine based on multi-methods

J Tradit Chin Med. 2025 Jun;45(3):693-701. doi: 10.19852/j.cnki.jtcm.2025.03.020.

ABSTRACT

OBJECTIVE: To find more influencing factors Qi-deficiency constitution of Traditional Chinese Medicine (TCM) using dynamic and comprehensive information.

METHODS: Because grey relational analysis (GRA) is good at processing incomplete information and has no special requirements for sample size and distribution. We acquired 2122 pieces of valid Qi-deficiency constitution dynamic data after preprocessing, and used GRA combing with χ 2 test and multivariate logistic regression analysis to discover and sort the influencing factors of Qi-deficiency constitution.

RESULTS: For the calculation results of GRA, there were 10 (62.5%) aspects whose grey correlation degrees were greater than 0.6. The results of χ 2 test showed that all the above 10 aspects were statistically significant with Qi-deficiency constitution. The analysis results of multivariate logistic regression analysis showed the following factors were positively correlated with Qi-deficiency constitution: premature birth, sleeping late and getting up early, sleeping late and getting up late, irregular sleeping, sleeping 6.0-6.9 h per day, artificial feeding, female, age at 18-19, and father’s age at 18-19 years old when a baby at birth. The following factors were negatively correlated with Qi-deficiency constitution: sleeping 8.0-8.9 h per day and ≥ 9.0 h per day, and age at 30-39 and 40-49 years old.

CONCLUSIONS: It is necessary to pay attention to these innate and acquired information of individuals which may lead to Qi-deficiency constitution. And our research also provides a novel methodological thinking for analyzing the influential factors of TCM constitution.

PMID:40524309 | DOI:10.19852/j.cnki.jtcm.2025.03.020

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Nevin Manimala Statistics

Exploring the relationship between colorectal polyps and pulmonary nodules based on the theory of the lung and the large intestine being internally and externally connected

J Tradit Chin Med. 2025 Jun;45(3):685-692. doi: 10.19852/j.cnki.jtcm.2025.03.003.

ABSTRACT

OBJECTIVE: To explore the relationship between colorectal polyps and pulmonary nodules from the perspective of the lung and the large intestine being internally and externally connected, aiming to provide a theoretical basis for clinical diagnosis and treatment.

METHODS: We retrospectively analyzed the data of patients who underwent electronic colonoscopy and were found to have colorectal polyps at the Gastrointestinal Endoscopy Center of Dongfang Hospital, Beijing University of Chinese Medicine, from January 1, 2017, to December 31, 2023. We also reviewed their lung CT results and used statistical software to analyze the recurrence, location, size, and pathology of colorectal polyps in relation to the presence, number, and size of pulmonary nodules.

RESULTS: Both colorectal polyps and pulmonary nodules are more common in elderly males. Patients with recurrent colorectal polyps are more likely to have pulmonary nodules, which tend to be located in the left colon and are more likely to be adenomatous in nature; those without pulmonary nodules show no clear pattern in polyp distribution, with a tendency towards inflammatory and hyperplastic pathology; the data from this study suggests that the proportion of lung nodules larger than 0.5 cm in the recurrent group is higher than in the non-recurrent group, and the proportion of colorectal polyps larger than 1 cm in the recurrent group is also higher than in the non-recurrent group.

CONCLUSION: There is a certain connection between the pathogenesis and treatment of colorectal polyps and pulmonary nodules. Cold, phlegm, dampness, blood stasis, and toxic coagulation are common pathogenic factors of the two diseases. Patients with larger colorectal polyps should be advised to undergo regular colonoscopy. Patients with recurrent polyps or those with left colon necrosis or cancer indicated by colonoscopy should be advised to complete lung related examinations to rule out the possibility of pulmonary nodules.

PMID:40524308 | DOI:10.19852/j.cnki.jtcm.2025.03.003

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Nevin Manimala Statistics

Psychometric evaluation of the NoMAD instrument in cancer care settings: assessing factorial validity, measurement invariance, and differential item functioning

Implement Sci Commun. 2025 Jun 16;6(1):72. doi: 10.1186/s43058-025-00756-3.

ABSTRACT

BACKGROUND: The Normalization MeAsure Development (NoMAD) questionnaire is used to assess implementation processes based on Normalization Process Theory (NPT). However, its psychometric properties have not been extensively evaluated. This study aimed to examine the factorial validity, internal consistency, and measurement invariance at both scale and item levels of the NoMAD across three hybrid effectiveness-implementation studies determining the impact of routine symptom surveillance and guideline-based symptom management interventions in ambulatory oncology care settings.

METHODS: A cross-sectional survey was conducted with 328 healthcare personnel (74.% clinicians) participating in the Improving the Management of SymPtoms during And following Cancer Treatment (IMPACT) Research Consortium between 2019 and 2024. Confirmatory factor analysis (CFA) tested the hypothesized four-factor structure (coherence, cognitive participation, collective action, reflexive monitoring). Internal consistency was assessed with McDonald’s omega and Cronbach’s alpha coefficients (> 0.70 acceptable). Measurement invariance was tested across research centers, professional roles, and years in current roles using multi-group CFA. Model fit was defined by standard fit indices (Comparative Fit Index (CFI) and Tucker-Lewis Index (TLI) values ≥ 0.95, Root Mean Square Error of Approximation (RMSEA) values ≤ 0.06, and Standardized Root Mean Square Residual (SRMR) values ≤ 0.08. Differential item functioning (DIF) was evaluated using ordinal logistic regression and item response theory methods (ΔR2 ≥ 0.02 indicative of meaningful DIF).

RESULTS: The four-factor model demonstrated good fit to the data (CFI = 0.97, TLI = 0.96, RMSEA = 0.06, SRMR = 0.05). All factor loadings were statistically significant (p < 0.001), ranging from 0.606 to 0.871. Internal consistency was satisfactory for all four constructs (Omega range: 0.789-0.864, Cronbach’s alpha range: 0.782-0.863). The NoMAD exhibited configural, metric, and scalar invariance across research centers, roles, and years in the current role. One item (“The staff agree that the intervention is worthwhile”) showed uniform DIF across healthcare systems (ΔR2 = 0.047), but no DIF was found by role or years in the current role.

CONCLUSIONS: This study supports the factorial validity, internal consistency, and measurement invariance of the NoMAD across three oncology implementation efforts. The presence of DIF in one item provides an opportunity for refinement in this healthcare context. Researchers and practitioners can use the NoMAD to assess and compare implementation processes, informing the development and evaluation of implementation strategies.

TRIAL REGISTRATION: (ClinicalTrials.gov ID NCT03850912, NCT03892967, NCT03988543).

PMID:40524282 | DOI:10.1186/s43058-025-00756-3

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Nevin Manimala Statistics

Diagnostic Biomarkers for Heat Stroke and Heat Exhaustion: A Scoping Review

Disaster Med Public Health Prep. 2025 Jun 17;19:e153. doi: 10.1017/dmp.2025.10069.

ABSTRACT

OBJECTIVES: As the global incidence of heat-related illnesses escalates in the wake of climate change-induced heat waves, the critical necessity for reliable diagnostic tools becomes apparent. This scoping review aimed to summarize the existing body of published evidence on biomarkers that could potentially be utilized for the diagnosis of heat-related illness in the clinical setting.

METHODS: We conducted a thorough search of 3 databases, including Embase, MEDLINE, on Ovid, and The Cochrane Library (Wiley) databases from October 11, 2022 up until January 15, 2024. We also manually included studies by searching the reference lists of the included articles. Studies that performed statistical validation were summarized in detail.

RESULTS: 2877 citations were identified and screened, with 228 studies reviewed as full text. 56% of these studies were conducted within China or North America. The studies identified 113 biomarkers. Most common biomarkers studied were troponin I, IL-6, platelets, and ALT. The studies exhibited considerable variation, reflecting the diverse range of investigated biomarkers and the absence of standardized statistical validation for the biomarkers.

CONCLUSIONS: Numerous biomarkers have been evaluated in the literature, but none have been studied to impact clinical practice. There is significant variation in the methodology and statistical validation. There is a need for further research to identify clinically relevant biomarkers for heat related illnesses.

PMID:40524268 | DOI:10.1017/dmp.2025.10069

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Nevin Manimala Statistics

Association between pace of biological aging and cancer and the modulating role of physical activity: a national cross-sectional study

Clin Epigenetics. 2025 Jun 16;17(1):103. doi: 10.1186/s13148-025-01912-1.

ABSTRACT

BACKGROUND: Cancer remains a serious public health problem impeding gains in life expectancy. Epigenetic clocks, derived from sets of DNA methylation CpGs and mathematical algorithms, have demonstrated a remarkable ability to indicate biological aging and age-related health risks. Dunedin(P)ace(o)f(A)ging(m)ethylation is a single-timepoint DNA methylation clock. It is an aging speedometer rather than a state measure. The association between the DunedinPoAm-measured pace of biological aging and cancer risk based on a nationally non-institutionalized sample remains to be elucidated. Physical activity, a modifiable lifestyle factor, is associated with delayed biological aging and lower risks of developing cancer. We hypothesized that DunedinPoAm-measured pace of biological aging is positively associated with cancer risk, and physical activity moderates this association.

RESULTS: In total, 2,529 participants aged 50 or older from the National Health and Nutrition Examination Survey (NHANES) 1999-2002 were included. Weighted logistic regression calculating odds ratios (OR) and 95% confidence intervals (CI) showed that when scaled per 1-SD increase, DunedinPoAm was positively associated with cancer risk (OR, 95% CI) (1.21, 1.05-1.39) in the crude model and adjusted for age and sex (1.19, 1.01-1.40). Individuals of high DunedinPoAm tertile had a 68% (95% CI 1.16-2.43) increase in cancer risk compared with the low tertile (P trend < 0.001). As hypothesized, effect modification by physical activity was significant (P interaction = 0.013). The association was apparent in physically inactive participants (1.52, 1.16-2.00), whereas insignificant in physically active individuals (1.08, 0.89-1.32). Exploratory interaction analyses for other covariates showed significant effect modification by age (> 65 years, 1.38, 1.08-1.77 vs 50-65 years, 1.00, 0.79-1.27).

CONCLUSION: The study supported the hypothesis by demonstrating a positive association between the DunedinPoAm-measured pace of biological aging and cancer risk and a modulating role of physical activity. Physically inactive individuals or participants over 65 years showed increased susceptibility to this association. These findings suggest that incorporating the DunedinPoAm-measured pace of biological aging into cancer screening strategies may benefit those with physically inactive lifestyles and older individuals. Whether physical activity can mitigate the increased risk of cancer in individuals with a faster pace of biological aging needs to be validated in further interventional cohort studies.

PMID:40524240 | DOI:10.1186/s13148-025-01912-1

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Can serum metabolic signatures inform on the relationship between healthy lifestyle and colon cancer risk?

Cancer Metab. 2025 Jun 16;13(1):30. doi: 10.1186/s40170-025-00388-0.

ABSTRACT

BACKGROUND: Colon cancer is strongly influenced by lifestyle factors. Sociodemographic factors like sex and socioeconomic position (SEP) might modulate the relationship between lifestyle and colon cancer risk. Metabolomics offers potential to uncover biological mechanisms linking lifestyle and colon cancer.

METHODS: Lifestyle and untargeted metabolomic data were available from a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 1,067 colon cancer cases and 1,067 controls matched on age, sex, study centre, and blood collection time. Serum samples were analyzed using liquid chromatography-mass spectrometry. The Healthy Lifestyle Index (HLI) score was derived from smoking habits, alcohol intake, body mass index (BMI), physical activity, and diet. Penalised regression was applied in controls to derive metabolic signatures for the HLI and the lifestyle components. Associations of lifestyle factors and the metabolic signatures with colon cancer risk were estimated in conditional logistic regression models, overall and by sex and SEP.

RESULTS: The HLI score was inversely associated with colon cancer risk, with an odds ratio (OR) per 1-standard deviation (SD) increment equal to 0.79; 95% CI: 0.71, 0.87. The metabolic signature of HLI, comprising 130 features, was moderately correlated with HLI (r = 0.59; 94% CI: 0.56, 0.61), and was inversely associated with colon cancer risk (OR = 0.86; 95% CI: 0.78, 0.95). After adjustment for the HLI score, the association of the metabolic signature of HLI and colon cancer risk was null (OR = 1.00, 95% CI 0.88, 1.13). Associations of lifestyle factors and the metabolic signature with colon cancer risk were consistently stronger for men than for women and did not differ by SEP.

CONCLUSIONS: In this study across seven European countries, healthy lifestyle was inversely associated with colon cancer risk, with stronger associations in men than women and no differences across SEP. However, the serum metabolic signatures after adjustment for lifestyle factors were not found to be associated with colon cancer risk, suggesting that lifestyle impacts colon cancer through mechanisms not captured by the signatures.

PMID:40524238 | DOI:10.1186/s40170-025-00388-0