Nevin Manimala

Discov Oncol. 2025 Feb 28;16(1):252. doi: 10.1007/s12672-025-01989-3.

ABSTRACT

PURPOSE: Colorectal cancer (CRC) is the third most common cancer globally, necessitating novel biomarkers for early diagnosis and treatment. This study proposes an efficient pipeline leveraging an integrated bioinformatics and machine learning framework to enhance the identification of diagnostic and prognostic biomarkers for CRC.

METHODS: A selection of methylated differentially expressed genes (MeDEGs) and features (genes) was made using both statistical and Machine learning (ML) approaches from publically available datasets. These genes were subjected to STRING network construction and hub genes estimation, separately. Also, essential miRNAs (micro-RNAs) and TFs (Transcription factors) as regulatory elements were revealed and findings were validated through scRNA-seq analysis, promoter methylation, gene expression levels correlated with pathological stage, and interaction with tumor-infiltrating immune cells.

RESULTS: Through an integrated analysis pipeline, we identified 27 hub genes, among which CTNNB1, GSK3B, IL-1β, MYC, PXDN, TP53, EGFR, SRC, COL1A1, and TGBF1 showed better diagnostic behaviour. Machine learning approach includes the development of K-Nearest Neighbors (KNN), Artificial Neural Networks (ANN), and Random Forest (RF) models using TCGA datasets, achieving an accuracy range between 99 and 100%. The Area Under the Curve (AUC) value for each model is 1.00, signifying good classification performance. The high expression of some diagnostic genes was associated with poor prognosis, concluding IL-1β as both a prognostic and diagnostic biomarker. Additionally, the NF-κB and microRNAs (miR-548d-3p, miR-548-ac) and TFs (NFκB and STAT5A) play a major role in the comprehensive regulatory network for CRC. Furthermore, hub genes such as IL-1β, TGFB1, and COL1A1 were significantly correlated with immune infiltrates, suggesting their potential role in CRC progression.

CONCLUSION: Overall, the elevated expression of IL-1β coupled with abnormal DNA methylation, and its consequent effect on the PI3K/Akt signaling pathway are relevant prognostic and therapeutic marker in CRC. Additional molecular candidates reveal insights into the epigenetic regulatory targets of CRC and their association with immune cell infiltration.

PMID:40019680 | DOI:10.1007/s12672-025-01989-3

Qual Life Res. 2025 Feb 28. doi: 10.1007/s11136-025-03931-0. Online ahead of print.

ABSTRACT

PURPOSE: To test the feasibility of a co-designed PROMs collection system for hospitalised older adults.

METHODS: A mixed-methods feasibility study was conducted sequentially across one acute and one sub-acute ward, over a 12-week period. Patients aged ≥ 60 years who discharged from hospital were eligible. The EQ-5D-5L with added items on fatigue and cognition was administered on discharge and at 3-6 months post-discharge. Administration was by either a research assistant or volunteer using a variety of modes (tablet computer, phone, SMS). Feasibility was evaluated using a feasibility framework to capture demand, implementation, practicality, and acceptability. Descriptive statistics were applied. Interviews were conducted with volunteers and analysed using deductive content analysis.

RESULTS: Completion rates indicated high demand (discharge = 84%, n = 110/131; follow-up = 81%, n = 90/110). At discharge, most completed PROMs on the tablet (57%) and 9% were administered by a volunteer. Most required assistance using the tablet (67%) and the average time to administer PROMs was longest for the tablet (17.9 min, SD = 3.3), followed by phone (8.8 min, SD = 4.4) and SMS (1.3 min, SD = 0.5). Fewer participants reported acceptability with using the tablet (61%) compared to SMS (100%). At follow-up, most completed PROMs on the phone (82%) and the average time to administer PROMs was less than discharge (4.9 vs. 13.4 min). Volunteers reported administering PROMs to unwell patients was challenging.

CONCLUSION: A co-designed PROMs collection system demonstrated feasibility in hospitalised older adults with phone and SMS having greatest acceptability. Administration of PROMs by volunteers was not feasible.

TRIAL REGISTRATION: ACTRN12623000576628. Registered 25 May 2023.

PMID:40019679 | DOI:10.1007/s11136-025-03931-0

Breast Cancer Res Treat. 2025 Feb 28. doi: 10.1007/s10549-025-07648-z. Online ahead of print.

ABSTRACT

PURPOSE: Evidence on the associations between categorical mammographic density and breast cancer risk by tumor invasiveness remains limited in Asian women. This large, population-based cohort study investigated the distribution of mammographic density by age and menopausal status, as well as its association with the risks of invasive breast cancer and ductal carcinoma in situ (DCIS) in South Korean women.

METHODS: Mammographic screening was performed on 6,365,522 women between 2009 and 2014 through the Korean National Cancer Screening Program. Mammographic parenchymal composition was classified using the fourth edition of Breast Imaging Reporting and Data System. We computed multivariable-adjusted hazard ratios and 95% confidence intervals (CIs) using Cox proportional hazards regression models for the association between mammographic parenchymal composition and the risk of invasive cancer and DCIS.

RESULTS: Overall, 40.6% of women had dense breasts, with the proportion decreasing with increasing age. A total of 44,468 incident breast cancer cases (0.7%) were documented. Compared with almost entirely fatty breasts, increasing mammographic density was associated with a higher risk of breast cancer (HR, 1.55; 95% CI 1.51-1.60 for scattered fibroglandular densities; HR, 2.14; 95% CI 2.08-2.21 for heterogeneously dense breasts; and HR, 2.59; 95% CI 2.50-2.69 for extremely dense breasts). Associations between mammographic density and breast cancer risk were similar for invasive cancer and DCIS, and did not vary significantly by menopausal status.

CONCLUSIONS: Mammographic density may be a significant risk factor for both invasive cancer and DCIS, regardless of menopausal status. It should be incorporated into breast cancer risk stratification and screening strategies.

PMID:40019668 | DOI:10.1007/s10549-025-07648-z

Diabet Med. 2025 Feb 28:e70018. doi: 10.1111/dme.70018. Online ahead of print.

ABSTRACT

AIMS: Effective diabetes management requires adherence to medication regimens and nutritional guidelines, underscoring the importance of health literacy. Our study aimed to develop and validate diabetes and nutrition knowledge questionnaires and correlate diabetes-specific health literacy with glucose metrics in people with type 1 and type 2 diabetes.

METHODS: In a cross-sectional study at a Swiss tertiary centre, questionnaires were developed to assess diabetes and nutrition knowledge in 289 participants with type 1 diabetes on insulin pumps or basal-bolus insulin and 222 participants with type 2 diabetes with or without insulin. Questionnaire validation involved content and construct validity established by a multidisciplinary team, and measurement properties were evaluated using the Rasch model. Multiple linear regression was performed to analyse the relationship between scores and glucose metrics.

RESULTS: The questionnaire demonstrated strong content and construct validity, with minor item misfits identified. In type 1 diabetes participants, higher nutrition knowledge scores (≥9/10) were significantly associated with reduced HbA1c levels (-5 mmol/mol or -0.47%, p < 0.05) and increased TIR (+9.2%, p < 0.05). No significant associations were observed in type 2 diabetes after adjusting for confounders, such as gender, BMI and diabetes duration.

CONCLUSIONS: We developed and validated a questionnaire encompassing diabetes and nutrition knowledge, tailored to diabetes type and treatment strategy. Psychometric analysis demonstrated robust measurement properties for assessing health literacy across diverse diabetes populations. Better nutrition knowledge was significantly linked to improved glycaemic control in type 1 diabetes, reflected by lower HbA1c and increased TIR.

PMID:40019655 | DOI:10.1111/dme.70018

Orthod Craniofac Res. 2025 Feb 28. doi: 10.1111/ocr.12912. Online ahead of print.

ABSTRACT

BACKGROUND: Orofacial myofunctional therapy (OMT) has emerged as an alternative and adjunct for the treatment of sleep-disordered breathing (SDB) in adults and children. While OMT efficacy has been demonstrated, the morphofunctional mechanisms triggered by each exercise remain poorly elucidated. This study aimed to characterise morphofunctional upper airway (UA) changes associated with established oropharyngeal exercises utilised to treat SDB by nasofibrolaryngoscopy (NFL).

METHODS: Thirteen OMT exercises were selected and analysed based on the relevant literature. Respecting inclusion and exclusion criteria, 15 healthy adult subjects of both sexes performed all the exercises, resulting in 390 video recordings of changes in UA dynamics through NFL, from the nasopharyngeal and oropharyngeal view. The video analyses were performed by three blinded ENT doctors using a specific instrument that included structural verification, movement type and intensity classification. Statistical analyses included the Fleiss Kappa Agreement Coefficient and the Friedman Test for comparison between exercises.

RESULTS: This original study used a methodology that allowed for the description and identification of which exercises produce greater mobility, stiffness and modification in the regions of the soft palate, pharyngeal/hypopharyngeal wall, retrolingual region and epiglottis. The 13 exercises analysed provided insights into their action mechanisms in the UA. The exercises that induce the most significant changes, for each pharyngeal region, were identified.

CONCLUSION: The analyses of the morphofunctional changes described in this study contribute to the understanding of how exercises used in OMT act, aiding in the selection of the most effective clinical approaches.

PMID:40018879 | DOI:10.1111/ocr.12912

Orthod Craniofac Res. 2025 Feb 28. doi: 10.1111/ocr.12904. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the efficacy of a plaque-identifying toothpaste in assisting with plaque removal in adolescents undergoing orthodontic treatment with fixed appliances.

METHODS: A randomised, double-blind, active-comparator trial was conducted at the Orthodontic Department, University Medical Center Department, University Medical Center Groningen, the Netherlands, from October 2021 to January 2022. Seventy seven healthy adolescents aged 12-16 years, undergoing buccal fixed appliance treatment for at least 3 months, were enrolled. Participants were stratified based on manual or electric brushing habits and randomised to receive either plaque-identifying toothpaste or a non-colouring control toothpaste. The primary outcome measured reduction in dental plaque using Quantitative Light-Induced Fluorescence ∆R30 (QLF) images at baseline (T0) and after 4-7 weeks (T1). Secondary outcomes included self-reported participant experiences.

RESULTS: No statistically significant difference in plaque reduction was found between the two groups (F = 0.211, p = 0.647). Subgroup analyses showed that participant-related factors did not significantly influence plaque reduction. Participants using plaque-identifying toothpaste reported a slightly stronger perception of plaque removal (p = 0.018) but encountered slightly more difficulty with the toothpaste colour (p = 0.028). Compliance was high, and no adverse effects were reported.

CONCLUSION: Plaque-identifying toothpaste did not lead to significant plaque reduction among adolescents with fixed orthodontic appliances.

PMID:40018856 | DOI:10.1111/ocr.12904

Int J Soc Psychiatry. 2025 Feb 28:207640251323345. doi: 10.1177/00207640251323345. Online ahead of print.

ABSTRACT

BACKGROUND: The experience of flourishing (i.e. high wellbeing) is informing our understanding of psychological health beyond psychopathology.

AIMS: This study examines whether community members define their sense of flourishing in terms of the presence of wellbeing and/or the absence of psychopathology.

METHODS: Participants (n = 1,094) were stratified by sex and age (18-39 years, 40-59 years and 60 years+), resided in Australia, the United Kingdom, Singapore, South Africa and Malaysia. Participants were presented with 12 items from the European Social Survey Wellbeing Module and 9 symptoms from the Diagnostic Statistical Manual for Major Depressive Disorder and Generalized Anxiety Disorder; mental health items were rephrased to reflect an absence of psychopathology. Respondents selected and ranked the five statements that best reflected their sense of flourishing.

RESULTS: Wellbeing statements were the most frequently endorsed items for example, ‘Feeling calm and peaceful’, ‘Life is valuable and worthwhile’, ‘Having people who care’ and ‘Feeling positive about oneself’, but they were only endorsed by approximately 35% to 38% of respondents. Three pathology items were amongst the top 10 items endorsed.

CONCLUSIONS: That not one indicator was endorsed by the majority of respondents suggests that flourishing definitions of positive mental health need to be defined by both the presence of wellbeing and absence of psychopathology. Notably, there were few between-nation differences in items endorsed, and those differences reported were not of a large magnitude suggesting consistency in the endorsement of indicators between nations.

PMID:40018854 | DOI:10.1177/00207640251323345

Physiother Theory Pract. 2025 Feb 28:1-12. doi: 10.1080/09593985.2025.2471409. Online ahead of print.

ABSTRACT

INTRODUCTION: Qualitative research methods in healthcare delve into the nuanced complexities of health professions work, seeking to comprehend the contextual and interpretive dimensions of patient, caregiver, and provider perspectives and experiences. Qualitative research is an essential contribution to evidence-based and evidence-informed practice, and therefore foundational for practice across all health professions.

PURPOSE: This study aimed to examine the breadth and depth of curricular content, delivery models, instructional strategies, and resources related to qualitative research methods in Doctor of Physical Therapy (DPT) programs in the United States.

METHODS: In this cross-sectional design, an online survey was developed, piloted, and emailed to 256 Commission for the Accreditation of Physical Therapy Education accredited DPT programs. Descriptive statistics, independent samples t-tests, one-way ANOVA, and chi-square statistics were completed.

RESULTS: The overall response rate was 31.6%. Respondents reported a mean of 5 instructional hours of qualitative research content, ranging from 0 to 12 hours. Analysis revealed a significant difference in contact hours (p = .026) between faculty reporting no expertise (2.7 hours) and high expertise (7.5 hours). Qualitative research content was primarily located early in the curriculum (76%) and in a stand-alone course (70%), with wide variability in intended learning outcomes, activities, and resources.

CONCLUSION: Given the critical importance that clinicians understand and apply qualitative and quantitative findings as part of evidence informed practice, this study highlights the need for building resources and faculty capacity to integrate qualitative methods of education in DPT curricula. Findings may inform the development of curriculum models, guidelines, and DPT learner competencies.

PMID:40018838 | DOI:10.1080/09593985.2025.2471409

Med Phys. 2025 Feb 28. doi: 10.1002/mp.17718. Online ahead of print.

ABSTRACT

BACKGROUND: Endometrial cancer (EC) is one of the most common gynecological malignancies and the second most common gynecological malignancy cause of death in women. Heterogeneous tissues with different grades of complexity and different diffusion properties characterize the EC. Several diffusion magnetic resonance imaging (DMRI) protocols have been used to perform a non-invasive and global evaluation of EC for diagnostic and prognostic purposes. However, the association of a single value for the diffusion coefficient to an EC tissue could be a severe limit for developing a DMRI virtual histology protocol.

PURPOSE: This study evaluates the potential of diffusion kurtosis imaging (DKI) and tissue multiple diffusion clusterization in detecting the specific features of healthy/cancer tissue that can be useful in EC diagnosis and prognosis.

METHODS: Thirty-eight subjects were analyzed: 18 with a final diagnosis of EC and 20 healthy, asymptomatic, with no history of endometrial pathology and uterine tumor pathology. Diffusion-weighted Spin-Echo Echo-Planar Imaging (DW-EPI) with TR/TE = 2000 ms/77 ms was used at 3T using six different b-values: (500, 800, 1000, 1500, 2000, and 2500)s/mm2 along three gradient directions (x, y, z). The decay of the signal in each voxel was used to obtain clusters of different diffusion compartments reflecting tissue heterogeneity. Moreover, using the Kurtosis representation, the parametric maps of the apparent kurtosis (K) and diffusivity (D) coefficients were obtained. The statistical analysis of the differences in the mean value of the parameters obtained in the selected regions of interest (ROIs) in tumor area (T) peritumor area (PT) and healthy tissue was carried out using a Kruskal-Wallis Test. A p-value < 0.05 indicated a statistically significant difference. To validate DKI and multiple diffusion clusterization in the detection of EC and healthy tissue, DMRI results were compared with EC histology. A ROC curve analysis was performed to evaluate the performance of the clustering feature in differentiating healthy and tumoral tissues.

RESULTS: K discriminates the peritumor area (PT) of the tumor from the healthy tissues (p < 0.05) and the area inside the EC (cancerous tissue, p < 0.05). This result is validated and explained by the diffusion clustering, which shows a great variability in K for pathological compared to healthy subjects. Moreover, the standard deviation of K in the cluster defined by the highest K/D ratio differentiates T and H ROIs.

CONCLUSIONS: K as well as diffusion clusterization are sensitive to the different microstructural organizations in EC and healthy tissue, promoting themself as a potential tool for the diagnosis and prognosis of EC.

PMID:40018821 | DOI:10.1002/mp.17718

Foot Ankle Spec. 2025 Feb 28:19386400251318965. doi: 10.1177/19386400251318965. Online ahead of print.

ABSTRACT

BACKGROUND: Syndesmotic ankle fractures occur when damage to the syndesmosis complex is combined with a malleolar fracture. This can result in severe pain, weakness, and instability. Surgical interventions include syndesmotic screw fixation (SS), suture button fixation (SB), and tibiotalocalcaneal nail (TTC). This meta-analysis aims to compare the outcomes of these treatment methods for syndesmotic ankle fractures.

METHODS: A literature search was conducted on PubMed and Embase for comparison studies that included at least 2 surgical interventions and at least one of the relevant functional outcomes and/or complication metrics until June 2024. The Olerud-Molander Ankle Score (OMAS) was used to compare functional outcomes, and it is a self-reported outcome measure that evaluates the symptoms and function of those with ankle fractures, while infections and reoperations were reported to compare complication outcomes. Statistical analyses were performed using Review Manager 5.4. A P-value ≤ .05 was considered statistically significant. The risk of bias was assessed with Review Manager 5.4. and the Newcastle-Ottawa scale.

RESULTS: A total of 18 studies with a total of 1,040 patients were ultimately included in this study. The SS had a significantly higher OMAS 2-year follow-up compared to TTC. The TTC had a significantly lower infection rate compared to SS. The SB had a significantly higher OMAS at both 1-year and 2-year follow-ups than SS. The SB had a significantly lower reoperation rate compared to SS. The SB had a significantly higher OMAS at both 1-year and 2-year follow-ups than TTC. The SB had a significantly lower infection rate compared to TTC.

CONCLUSION: The SB emerges as the preferred treatment method for syndesmotic ankle fractures, while TTC stands as a viable alternative. The SB is recommended as the primary surgical intervention for patients with syndesmotic ankle fractures due to its superior clinical benefits when compared to TTC and SS.

LEVELS OF EVIDENCE: 3.

PMID:40018814 | DOI:10.1177/19386400251318965