Category: Nevin Manimala

Biophys J. 2025 Oct 3:S0006-3495(25)00651-4. doi: 10.1016/j.bpj.2025.09.049. Online ahead of print.

ABSTRACT

MicroRNAs (miRNAs) are ubiquitous short RNAs regulating gene expression in many organisms, including humans. How the secondary structure (SS) of a mature miRNA affects its regulatory function remains an open question. Here we investigate this question through computational SS predictions of miRNA point mutants. We explore the mutational neighborhoods of miRNAs with association to human diseases, including cancer. We focus on possible SS changes independent of target-site complementarity, by leaving the seed region unchanged. We formulate metrics of the SS differences between such mutants and their wild types (WTs), and test whether disease-associated mutations tend to differ from others in terms of these metrics by comparing our results with the miRNASNP-v3 database. We find that disease-related mutants tend to have a higher probability of being fully unfolded than their WT; this and other SS-related measures are statistically significant at the database level. This is confirmed when we restrict the analysis to the better-validated miRNAs encoded by genes that appear in the manually curated MiRGeneDB database. With the same approach, we identify a subset of individual miRNAs for which SS changes are most likely to be related to disease. These are hsa-miR-1269b, hsa-miR-4537, hsa-miR-4477b, hsa-miR-4641, and hsa-miR-6821-3p; when focussing on the higher-confidence MiRGeneDB miRNAs, we find that hsa-miR-485-5p and hsa-miR-1908-3p are the ones for which SS changes are most likely to be linked to disease. In addition, we show that there are pairs of known miRNA WTs differing only by disease-related point mutations outside the seed region and exhibit very different SS. These pairs include hsa-miR-1269a-hsa-miR-1269b, and hsa-miR-3689a-3p-hsa-miR-3689b-3p.

PMID:41044879 | DOI:10.1016/j.bpj.2025.09.049

Genome Biol. 2025 Oct 3;26(1):333. doi: 10.1186/s13059-025-03776-3.

ABSTRACT

Most population-scale genomic datasets collected to date consist of “bulk” samples obtained from heterogeneous tissues, reflecting mixtures of different cell types. We introduce Unico, a Unified cross-omics computational method designed to deconvolve standard two-dimensional bulk matrices (samples by features) into three-dimensional tensors (samples by features by cell types). Unico is the first principled model-based deconvolution method that is theoretically justified for any tissue-level genomic data. By deconvolving bulk gene expression and DNA methylation datasets, we demonstrate Unico’s superior performance compared to existing methods, enhancing the ability to conduct powerful, large-scale genomic studies at cell-type resolution.

PMID:41044605 | DOI:10.1186/s13059-025-03776-3

BMC Med Educ. 2025 Oct 3;25(1):1350. doi: 10.1186/s12909-025-07931-z.

ABSTRACT

BACKGROUND: The aim of the study was to identify whether differences existed in the aesthetic perception of anatomical variations of the face and teeth among dental students, based on factors such as education level, gender, and the presence of a dentist in the family.

METHODS: The study was carried out with dental students using the Google Forms platform. A young female model was selected for the survey, with no aesthetic-compromising restorations or pathologies in her maxillary anterior teeth. Standard facial and smile reference photographs were digitally manipulated to alter specific aesthetic features using professional image-editing software (Adobe Photoshop v.20.0.0, Adobe Inc., San Jose, California, USA). Participants evaluated these photographs, focusing on components such as facial symmetry, gingival position, buccal corridor, and occlusal plane angulation. Preclinical and clinical students rated the original and manipulated images on a scale from 1 to 5, with 5 representing the most aesthetically acceptable image and 1 representing the least pleasing one. Statistical analysis comprised Shapiro-Wilk test, Levene test, Mann-Whitney U test.

RESULTS: In the research, 493 students participated, including 240 clinical students; 312 were female, and 89 had a dentist in their family. The overall aesthetic perception score was high (82.63 ± 8.5). Clinical students demonstrated significantly better perceptions of midline diastema, occlusal plane inclination, clinical crown height, and dental modifications compared to preclinical students (p < 0.05). Female students scored higher in lower facial height perception than males (p = 0.014). The presence of a dentist in the family did not significantly influence aesthetic perception (p > 0.05).

CONCLUSION: Clinical training positively impacted students’ ability to critically analyze aesthetics while maintaining function and naturalness. It can be suggested that, as the academic level increases in dental education, students’ aesthetic judgment skills also improve.

PMID:41044602 | DOI:10.1186/s12909-025-07931-z

Genome Biol. 2025 Oct 3;26(1):331. doi: 10.1186/s13059-025-03802-4.

ABSTRACT

BACKGROUND: Over 1100 independent signals have been identified with genome-wide association studies (GWAS) for bone mineral density (BMD), a key risk factor for mortality-increasing fragility fractures; however, the effector gene(s) for most remain unknown.

RESULTS: We execute a CRISPRi screen in human fetal osteoblasts (hFOBs) with single-cell RNA-seq read-out for 89 non-coding elements predicted to regulate osteoblast gene expression at BMD GWAS loci. The BMD relevance of hFOBs is supported by heritability enrichment from stratified LD-score regression involving 98 cell types grouped into 15 tissues. Twenty-three genes show perturbation in the screen, with four (ARID5B, CC2D1B, EIF4G2, and NCOA3) exhibiting consistent effects upon siRNA knockdown on three measures of osteoblast maturation and mineralization. Lastly, additional heritability enrichments, genetic correlations, and multi-trait fine-mapping unexpectedly reveal that many BMD GWAS signals are pleiotropic and likely mediate their effects via non-bone tissues.

CONCLUSIONS: Our results provide a roadmap for how single-cell CRISPRi screens may be applied to the challenging task of resolving effector gene identities at all BMD GWAS loci. Extending our CRISPRi screening approach to other tissues could play a key role in fully elucidating the etiology of BMD.

PMID:41044600 | DOI:10.1186/s13059-025-03802-4

BMC Med Educ. 2025 Oct 3;25(1):1349. doi: 10.1186/s12909-025-07987-x.

ABSTRACT

BACKGROUND: The landscape of nursing education is rapidly evolving worldwide through the integration of innovative technologies such as mixed reality (MR). While MR-based HoloPatient education shows promise for enhancing nursing education globally, particularly in settings with limited clinical placement opportunities, current research indicates positive effects on nursing students’ learning outcomes. However, no evidence exists that HoloPatient-based education improves students’ learning motivation and attitude. This study aimed to examine nursing students’ learning motivation and attitudes following HoloPatient-based simulation education, and to explore students’ perception of their HoloPatient-based simulation learning experiences.

METHODS: This study used an explanatory sequential mixed methods design with a one group post-test only design followed by focus group interviews. This study was conducted from August to September 2023 at a university in South Korea. Quantitative data were collected from 100 third-year nursing students who participated in HoloPatient-based simulation education. Qualitative data were obtained through semi-structured interviews with two focus groups, conducted one week after HoloPatient-based simulation education. Statistical analyses included descriptive statistics, correlation analysis, and comparative analyses. Qualitative data underwent thematic analysis following established protocols.

RESULTS: This study showed high level of nursing students’ learning motivation (M = 4.42, SD = 0.42) and positive attitude (M = 4.08, SD = 0.50) following HoloPatient-based simulation education. A significant positive correlation was found between learning motivation and attitude (r = .59 or higher, p < .001). Qualitative findings revealed themes of positive experience, influencing factors on HoloPatient-based simulation, and barriers to HoloPatient-based simulation.

CONCLUSION: This exploratory study found high levels of learning motivation and positive attitudes among nursing students following HoloPatient-based simulation education. However, due to the one-group post-test design and small qualitative sample, these findings should be interpreted as preliminary evidence. Further studies are needed to establish its effectiveness with randomized controlled trials or quasi-experimental designs.

PMID:41044594 | DOI:10.1186/s12909-025-07987-x

BMC Vet Res. 2025 Oct 3;21(1):573. doi: 10.1186/s12917-025-05036-9.

ABSTRACT

OBJECTIVE: This randomized, double-blind, placebo-controlled clinical trial investigated the therapeutic efficacy of pulsed electromagnetic field (PEMF) therapy in dogs diagnosed with chronic osteoarthritis (OA).

METHODS: Twenty-one dogs with radiographically confirmed OA in at least one limb were randomized into treatment (n = 10) and placebo (n = 11) groups. PEMF therapy was administered over six weeks. Gait symmetry indices for peak vertical force and vertical impulse were assessed using kinetic analysis at baseline (Day 0), mid-treatment (Day 21), and post-treatment (Day 42). Lameness and pain scores, additional treatments, and dropout rates were recorded. Owners completed the Liverpool Osteoarthritis in Dogs (LOAD) questionnaire at each time point. An Overall Treatment Effectiveness (OTE) score was computed based on objective and subjective outcomes.

RESULTS: PEMF-treated dogs exhibited significant improvements in gait symmetry by Day 42 (p = 0.030). LOAD scores declined steadily in the treatment group, although no statistically significant differences were observed between groups. This trend may suggest a potential reduction in pain and improvement in mobility. No significant between-group differences were found for the OTE score.

CONCLUSION: PEMF therapy appears to be a safe, non-invasive, and potentially effective adjunctive or stand-alone modality for the management of pain and mobility impairment associated with osteoarthritis in dogs. Further research is warranted to confirm long-term efficacy and optimize treatment protocols.

PMID:41044566 | DOI:10.1186/s12917-025-05036-9

BMC Health Serv Res. 2025 Oct 3;25(1):1297. doi: 10.1186/s12913-025-13227-1.

ABSTRACT

BACKGROUND: Unplanned hospital admissions are costly and disproportionately affect people who are socioeconomically disadvantaged and from an ethnic minority group. A national primary care pay-for-performance scheme, the Quality and Outcomes Framework (QOF), was introduced in England in 2004 to financially incentivise general practices to meet a range of performance indicators, but the QOF’s impact on unplanned hospital admissions remains unclear. We examined the association between unplanned hospital admissions for cardiovascular disease (CVD), individual-level characteristics and achievement of key QOF indicators for CVD at the patients’ registered general practice.

METHODS: This study used the Connected Bradford dataset, which links individual-level primary and secondary care data. Our analytical sample included 508,977 patients registered with a Bradford District general practice from 2017 to 2019. Logistic regression was used to estimate associations between achievement of relevant QOF indicators and unplanned admissions for cardiovascular diseases, adjusting for individual-level differences in age, sex, ethnicity, socioeconomic status and pre-existing health conditions.

RESULTS: Significantly reduced odds of unplanned CVD hospital admissions were associated with attending a practice with higher achievement rates for QOF indicators relating to atrial fibrillation management (OR 0.97, p < 0.001), diabetes management (OR 0.98, p = 0.002), and smoking cessation (OR 0.98, p = 0.038). Conversely, increased odds of unplanned admission were associated with higher achievement for QOF indicators relating to antiplatelet or anticoagulation medication (OR 1.06, p < 0.001) and blood pressure control for diabetic patients (OR 1.02, p = 0.03). Individual-level characteristics significantly associated with increased risk of unplanned admission included living in the most deprived fifth of neighbourhoods (OR 2.00, p < 0.001) and having Pakistani ethnicity (OR 1.65, p < 0.001). Primary care diagnoses of hypertension (OR 1.79, p < 0.001), diabetes (OR 1.56, p < 0.001), chronic cardiac disease (OR 2.79, p < 0.001), and stroke (OR 1.6, p < 0.001) were all statistically significant and associated with higher odds of unplanned admissions for CVD.

CONCLUSIONS: We found mixed evidence for an association between practice-level QOF achievement and unplanned hospital admissions for CVD. There were large ethnic and socioeconomic inequalities in unplanned admissions for cardiovascular disease. Supporting general practices to appropriately improve their achievement of key cardiovascular disease related QOF indicators and reducing socioeconomic inequalities might likely reduce the number of unplanned hospital admissions.

PMID:41044559 | DOI:10.1186/s12913-025-13227-1

BMC Med Educ. 2025 Oct 3;25(1):1353. doi: 10.1186/s12909-025-07542-8.

ABSTRACT

BACKGROUND: Medical students face significant psychological distress due to academic, financial, and social pressures. While global studies highlight the mental health challenges of medical students, limited data is available for Moroccan medical students.

OBJECTIVES: This study aims to assess the prevalence of psychological distress, identify associated factors, and explore coping strategies among Moroccan medical students.

METHODS: A cross-sectional study was conducted at the Faculty of Medicine and Pharmacy of Fez, involving 632 clinical-year students. Data were collected using the validated GHQ-12 questionnaire to assess psychological distress and self-reported measures of functional and dysfunctional coping strategies. Statistical analysis included chi-square tests and logistic regression to identify significant associations.

RESULTS: The mean GHQ-12 score was 5.00 (SD: 3.61), with 50.6% of students scoring above the threshold of 4, indicating psychological distress. The most frequently reported stressors were academic challenges (34.1%), emotional problems (12.3%), and financial difficulties (9.6%). Female students experienced significantly higher levels of distress compared to males (P < 0.001). Among the participants, 52.6% reported using coping strategies; of these, 26.5% relied exclusively on functional strategies, such as prayer, relaxation, and seeking social support, while 26.1% used at least one dysfunctional strategy. Dysfunctional coping strategies, such as dietary changes and smoking, were significantly associated with distress (P < 0.001).

CONCLUSION: This study underscores the substantial mental health burden among Moroccan medical students, with significant associations between distress, gender, stressors, and dysfunctional coping strategies. These findings highlight the need for targeted mental health interventions and the development of supportive programs within medical education settings to promote well-being and resilience.

PMID:41044557 | DOI:10.1186/s12909-025-07542-8

BMC Public Health. 2025 Oct 3;25(1):3327. doi: 10.1186/s12889-025-24607-x.

ABSTRACT

BACKGROUND: Given the physiological decline in late life, coupled with an elevated risk of various diseases and anticipated adverse events, frail and vulnerable older persons in nursing homes are a principal group that is vulnerable to health risks, thereby manifesting a triple vulnerability comprising “physical-mental-economic” aspects. However, standardized assessments of health vulnerability in frail and vulnerable older persons within nursing homes in China are currently lacking, and an evaluation index system has not yet been undeveloped. Therefore, the aim of this study was to construct an index system for comprehensively evaluating the health vulnerability of frail and vulnerable older persons in nursing homes, aiming to offer personalized elderly care services as a reference for predicting health vulnerability risks among this demographic population.

METHODS: On the basis of the “sensitivity‒response capacity” vulnerability analysis framework, multidimensional risk indicators for health vulnerability were preliminarily established through policy literature analysis and semistructured interviews. Between April and August 2023, a Delphi study involved 20 expert representatives from four provinces and municipalities, spanning multiple research domains, for participation. Using a five-point Likert scale, they assessed the value of predefined indicators and provided qualitative feedback. Subsequent to each round of expert input, revisions were enacted upon the evaluation index system.

RESULTS: After three rounds of expert consultation, a consensus on the evaluation index system was reached; it contains two primary indicators, individual sensitivity and antifragility capacity, with 12 affiliated secondary indicators and 56 tertiary indicators. The expert authority coefficients ranged from 0.934 to 0.935, and Kendall’s coefficient of concordance ranged from 0.310 to 0.360. These differences were statistically significant (P < 0.05).

CONCLUSION: The evaluation index system for assessing the health vulnerability of frail and vulnerable older persons in nursing homes developed in this study covers a range of health threats and indicators of health coping capacity faced by frail and vulnerable older persons from individual to societal perspectives. This evaluation index system employs the “sensitivity‒responsiveness” vulnerability analysis framework, addressing the limitations of single-dimensional assessment indicators in capturing a comprehensive overview. This study provides a novel research perspective for assessing health vulnerability in frail and vulnerable older persons. This evaluation index system provides a practical tool for nursing home staff to assess health vulnerability, enabling early risk identification and targeted interventions. Policy-makers and administrators can use it to optimize resource allocation and enhance elderly care services. Future research should validate its real-world applicability and integrate it into existing health monitoring and intervention programs to improve older persons’ health outcomes.

PMID:41044556 | DOI:10.1186/s12889-025-24607-x

BMC Surg. 2025 Oct 3;25(1):425. doi: 10.1186/s12893-025-03168-1.

ABSTRACT

BACKGROUND: Monitors that can provide 2-dimensional (2D) or 3-dimensional (3D) images, as well as high-definition (HD) or 4 K-HD image quality, offer various conveniences to surgeons. While studies comparing 2D and 3D screens exist in the literature, studies are needed to investigate the effects of different monitor sizes on surgical success. This study aimed to examine the impact of screen size on surgical parameters in patients who have undergone a hysterectomy using either a 55-inch or a 27-inch monitor.

METHODS: Patients who underwent laparoscopic hysterectomy and salpingectomy/salpingo-oophorectomy between May 2022 and July 2023 were retrospectively screened. Two groups were created. GroupA consisted of patients who underwent surgery using a 55-inch (140 cm) monitor with both 2D and 4 K-HD features. GroupB consisted of patients whose surgery was performed using a 27-inch (69 cm) monitor with both 2D and 4 K-HD features. A total of 72 women (n(GroupA) = 36, n(GroupB) = 36) were included in the study.

RESULTS: No statistically significant difference was observed between groups regarding age, number of cesarean sections, or body mass index (p > 0.05). Additionally, no statistically significant difference was found between groups regarding the total surgery duration (GroupA, GroupB; (126.86 ± 50.42), (128.97 ± 44.29), p = 0.851, respectively). When evaluating the percentage decrease in hemoglobin values before and after surgery, no statistically significant difference was observed between groups (GroupA, GroupB; (-0.11 ± 0.06), (-0.11 ± 0.07), p = 0.746, respectively). There were no statistically significant differences between groups regarding hematocrit changes, frequency of intraoperative complications, postoperative infections, the time to first gas passage, and length of hospital stay (p > 0.05).

CONCLUSIONS: In laparoscopic monitor systems with 4 K-HD resolution, the screen size, whether 27-inches or 55-inches, may not significantly affect surgical parameters.

PMID:41044554 | DOI:10.1186/s12893-025-03168-1