Nevin Manimala

Biotechnol Bioeng. 2025 Dec 18. doi: 10.1002/bit.70128. Online ahead of print.

ABSTRACT

Extracellular vesicles (EVs), including exosomes, are abundant in bovine milk and Lactobacillus culture media but difficult to isolate with high efficiency and purity. In response, a micro-electro-mechanical systems (MEMS)-based membrane filter was developed to address these limitations. Under equivalent conditions, the developed filter outperformed commercial filters, achieving a 2.17-fold higher EV recovery rate compared to the commercial polyethersulfone (PES) membrane from a 5 mL high-concentration sample, and yielding a total of 50 mL of EV solution at a concentration of 5.52 × 10¹⁰ particles/mL. The membrane was engineered to achieve a minimum pore size of 32 nm and a minimum thickness of 290 nm through separate fabrication processes. Among these, the MEMS160 membrane, which features uniformly distributed 168 nm pores on a 318 nm thick structure, demonstrated enhanced performance by effectively reducing fouling, as confirmed by blocking-model assessments. Biological evaluations showed that EVs isolated using the developed filter retained notable purity and bioactivity. Specifically, milk-derived EVs increased the proliferation of human fibroblasts (Hs68) and human follicle dermal papilla cells (HFDPCs) by up to 25% and 50%, respectively, while Lactobacillus-derived EVs increased proliferation by up to 11% and 53% at certain concentrations. Furthermore, co-treatment with an anti-aging peptide (AIMP1-derived peptide) had a synergistic effect on both cell types. Similar trends were seen in canine and feline fibroblasts. Milk-derived EVs boosted proliferation by up to 25% in canine and 31% in feline cells, while Lactobacillus-derived EVs increased it by up to 46% and 34%, respectively. These effects reached statistical significance. These results show the filter’s potential for large-scale EV isolation and dermatological applications, requiring high purity and yield.

PMID:41410131 | DOI:10.1002/bit.70128

Biom J. 2025 Dec;67(6):e70104. doi: 10.1002/bimj.70104.

ABSTRACT

In the competing risks setting, the $t$ -year absolute risk for a specific time $t$ (e.g., 2 years), also called the cumulative incidence function at time $t$ , is often interesting to estimate. It is routinely estimated using the nonparametric Aalen-Johansen estimator. This estimator handles right-censored data and has desirable large sample properties, as it is the nonparametric maximum likelihood estimator (NPMLE). Inference for comparing absolute risks, via either a risk difference or a risk ratio, can therefore be done via usual asymptotic normal approximations and the delta method. However, the small sample performances of this approach are not fully satisfactory. Especially, (i) coverage of confidence intervals may be inaccurate and (ii) comparisons made using a risk ratio and a risk difference can lead to inconsistent conclusions, in terms of statistical significance. We, therefore, introduce an alternative empirical likelihood approach. One advantage of this approach is that it always leads to consistent conclusions when comparing absolute risks via a risk ratio and a risk difference, in terms of significance. Simulation results also suggest that small sample inference using this approach can be more accurate. We present the computation of confidence intervals and p-values using this approach and the asymptotic properties that justify them. We provide formulas and algorithms to compute constrained NPMLE, from which empirical likelihood ratios and inference procedures are derived. The novel approach has been implemented in the timeEL package for R, and some of its advantages are demonstrated via reproducible analyses of bone marrow transplant data.

PMID:41410124 | DOI:10.1002/bimj.70104

J Int Neuropsychol Soc. 2025 Dec 18:1-6. doi: 10.1017/S1355617725101732. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to explore the correlates of zero, one, and multiple performance validity test (PVT) failures on cognitive test performance in patients with various degrees of severity of traumatic brain injury.

METHOD: 306 participants completed the Trail Making Test as part of a neuropsychological evaluation within 1-36 months post-injury. They were assigned to zero, one, or ≥ two fail groups on the basis of at least two independent PVTs. Group differences in Trail Making Test performance were analyzed with analysis of variance, with post hoc contrasts with the Bonferroni correction for multiple comparisons. Groups were also compared on various background characteristics.

RESULTS: Participants who passed all PVTs had statistically significantly better performance on both parts of the Trail Making Test as compared to those who failed either one or multiple PVTs, with the latter two groups not differing statistically significantly from each other. PVT failure was relatively more common in participants who were female, had an uncomplicated mild TBI, were involved in financial compensation-seeking, and were seen at a longer time point since injury.

CONCLUSION: Failure of even only one PVT is associated with lower neuropsychological test performance in patients with traumatic brain injury, especially when empirically validated criteria are used that are stratified by injury severity. Such failure does not always reflect malingering but must be interpreted and addressed in the context of patient background characteristics.

PMID:41410118 | DOI:10.1017/S1355617725101732

Biom J. 2025 Dec;67(6):e70102. doi: 10.1002/bimj.70102.

ABSTRACT

Functional data analysis has received significant attention due to its frequent occurrence in modern applications, such as in the medical field, where electrocardiograms or electroencephalograms can be used for a better understanding of various medical conditions. Due to the infinite-dimensional nature of functional elements, the current work focuses on dimension reduction techniques. This study shifts its focus to modeling the conditional quantiles of functional data, noting that existing works are limited to quantitative predictors. Consequently, we introduce the first approach to partial dimension reduction for the conditional quantiles under the presence of both functional and categorical predictors. We present the proposed algorithm and derive the convergence rates of the estimators. Moreover, we demonstrate the finite sample performance of the method using simulation examples and a real dataset based on functional magnetic resonance imaging.

PMID:41410116 | DOI:10.1002/bimj.70102

Psychol Med. 2025 Dec 18;55:e384. doi: 10.1017/S0033291725102651.

ABSTRACT

BACKGROUND: Early life adversity (ELA) is common and cross-sectionally associated with brain gray matter structure, including cortical thickness, cortical surface area, and subcortical volumes in childhood. However, to which degree ELA influences the trajectory of gray matter macrostructural and microstructural development during childhood and adolescence remains largely unexplored.

METHODS: We included 6414 participants from the Adolescent Brain Cognitive Development study at ages 9-11, where 1923 were followed to ages 11-13. We used linear mixed-effects models to test for associations between MRI-derived longitudinal measures of gray matter macro- (cortical thickness, surface area, subcortical volume) or microstructure (T1w/T2w ratio) and trauma exposure, parental acceptance, household abuse, and being resilient or susceptible to trauma in terms of developing an internalizing disorder.

RESULTS: At ages 9-11, higher levels of parental acceptance, trauma exposure, and being trauma resilient were associated with lower levels of cortical thickness. In contrast, being trauma susceptible was negatively related to hippocampal volume and cortical surface area. Longitudinally, more parental acceptance at baseline was associated with more cortical thinning between ages 9-11 and 11-13, while more household abuse was associated with less change in T1w/T2w ratio over time.

CONCLUSIONS: Parental acceptance and trauma resilience are linked to accelerated pace of apparent cortical thinning in youth aged 9-13 years, while household abuse is associated with slower microstructural development, as reflected by smaller longitudinal changes in the T1w/T2w ratio. Threat and deprivation may be distinctly associated with gray matter developmental trajectories in late childhood.

PMID:41410108 | DOI:10.1017/S0033291725102651

J Adv Nurs. 2025 Dec 17. doi: 10.1111/jan.70456. Online ahead of print.

ABSTRACT

BACKGROUND: Delirium is a common complication following cardiac surgery and significantly affects patient prognosis and quality of life. Recently, the application of artificial intelligence (AI) has gained prominence in predicting and assessing the risk of postoperative delirium, showing considerable potential in clinical settings.

OBJECTIVE: This scoping review summarises existing research on AI-based prediction models for post-cardiac surgery delirium and provides insights and recommendations for clinical practice and future research.

METHODS: Following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines, eight databases were searched: China National Knowledge Infrastructure, Wanfang Database, China Biomedical Literature Database, Virtual Information Platform, PubMed, Web of Science, Medline, and Embase. Studies meeting the inclusion criteria were screened, and data were extracted on surgery type, delirium assessment tools, predictive factors, and AI-based prediction models. The search covered database inception through January 12, 2025. Two researchers independently conducted the literature review and data analysis.

RESULTS: Ten studies from China, Canada, and Germany involving 11,702 participants were included. The reported incidence of postoperative delirium ranged from 5.56% to 34%. The most commonly used assessment tools were Confusion Assessment Method for the Intensive Care Unit, Diagnostic and Statistical Manual of Mental Disorders-5, and Intensive Care Delirium Screening Checklist. Key predictive factors included age, cardiopulmonary bypass time, cerebrovascular disease, and pain scores. AI-based prediction models were primarily developed using R (6/10, 60%) and Python (4/10, 40%). Model performance, as measured by the area under the curve, ranged from 0.544 to 0.92. Among these models, Random Forest (RF) was the most effective (5/10, 50%), followed by XGBoost (3/10, 30%) and Artificial Neural Networks (2/10, 20%).

CONCLUSION: AI-based models show promise for predicting postoperative delirium in cardiac surgery patients. Future studies should prioritise integrating these models into clinical workflows, conducting rigorous multicenter external validation, and incorporating dynamic, time-varying perioperative variables to enhance generalizability and clinical utility.

REPORTING METHOD: This review followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines.

PATIENT OR PUBLIC CONTRIBUTION: This study did not include patient or public involvement in its design, conduct, or reporting.

PMID:41410092 | DOI:10.1111/jan.70456

Clin Teach. 2026 Feb;23(1):e70332. doi: 10.1111/tct.70332.

ABSTRACT

BACKGROUND: Evidence is limited internationally regarding medical students’ perceptions and training needs in patient safety, following the WHO Global Patient Safety Action Plan 2021-2030, the COVID-19 pandemic, and the subsequent acceleration in digitalization. To address this gap, this study explores undergraduate medical students’ knowledge of patient safety, attitudes regarding safety culture, experiences with errors, and their perspectives on improving patient safety through training and digitalization.

METHODS: A mixed-method design was employed, consisting of an online survey with open-ended questions administered at a medical school in Greece. All registered undergraduate students were invited to complete a pretested 46-item study tool, including demographics, the Greek version of the scale ‘What is patient safety?’ and their personal experiences, views on digitalization and educational needs.

RESULTS: A total of 638 students from all 6 years of study participated (58% female; 54.2% preclinical students). Findings revealed poor knowledge regarding error management (mean 2.4/5) and the reporting process (mean 1.8/5). Fear of blame culture was reported by 51.2%. Digitalization was expected to advance patient safety in multiple ways. Students advocated strengthening patient safety training (92.8%), emphasizing case-based learning, integrating patient safety principles into the teaching of all clinical courses and watching their professors acting as role models.

CONCLUSIONS: Medical students feel underprepared to manage patient safety issues and request more relevant knowledge and skills. These findings highlight the urgency for appropriate training reforms, tailored to the students’ needs, aiming to optimally prepare them to become key players in improving patient safety in a digitally evolving healthcare system.

PMID:41410090 | DOI:10.1111/tct.70332

Pharmacol Res Perspect. 2026 Feb;14(1):e70206. doi: 10.1002/prp2.70206.

ABSTRACT

Fluoroquinolones (FQs) are widely prescribed antibiotics; however, increasing concerns have arisen over their potential to cause disabling and irreversible adverse effects. Using real-world data from the FDA Adverse Event Reporting System (FAERS) (2011-2024), we performed disproportionality analyses on psychiatric and eye-related adverse events (AEs) using reporting odds ratios (RORs). Of 44 895 FQ-associated adverse event reports, 8518 cases exhibited psychiatric AEs whilst 4367 cases displayed eye-related AEs. Among six FDA-approved FQs, three (ciprofloxacin/levofloxacin/moxifloxacin) showed safety signals for psychiatric disorders and four (ciprofloxacin/levofloxacin/moxifloxacin/ofloxacin) for eye-related disorders. Eight psychiatric and nine eye-related AEs were commonly reported across multiple FQs. Importantly, moxifloxacin exhibited unique safety signals for ocular-related toxicity, including iris transillumination defect [ROR: 6604.89 (4736.76-9209.81)], iris hypopigmentation [1887.66 (1175.44-3031.42)], and pigment dispersion syndrome [2360.62 (1432.71-3889.51)], raising concern for potential progression to pigmentary glaucoma-findings not prominently featured in current safety warnings. Additionally, systematic characterization of suicide cases revealed striking male predominance despite females comprising the majority of psychiatric AEs, identifying middle-aged males as a high-risk demographic. These findings support the need for enhanced pharmacovigilance, particularly regarding moxifloxacin’s ocular toxicity and FQs’ suicide vulnerability in specific patient subgroups. When FQ prescription becomes unavoidable, robust safety monitoring should be implemented to detect early neuropsychiatric and ocular complications.

PMID:41410077 | DOI:10.1002/prp2.70206

Quintessence Int. 2025 Dec 18;0(0):0. doi: 10.3290/j.qi.b6762754. Online ahead of print.

ABSTRACT

Aims to critically analyze the effects of photobiomodulation on recovery of the donor area after free gingival graft (FGG) surgery. A comprehensive literature search was conducted in PubMed, Scopus and Web of Science between May 7th and April 7th, 2025, structured according to the PICO strategy: patients ≥18 years undergoing removal of free gingival grafts from the palatal region (P), intervention with photobiomodulation at the donor site (I), compared with natural healing (C), evaluating wound healing as the primary and pain as the secondary outcome (O). A total of 668 records were identified and 8 randomized clinical trials, in which 284 participants were included. In outcomes, clinical healing parameters and patient-reported pain were analyzed, in which the majority of most studies demonstrated that photobiomodulation positively influenced epithelialization, reduction in wound area, and tissue color during the first two postoperative weeks. However, the effect on pain control was inconsistent among studies, with only two showing statistically significant reductions. The studies included demonstrated clinical and methodological heterogeneity due to different laser parameters, and their designs made statistical pooling of data unfeasible for a meta-analysis. In conclusion, photobiomodulation appears to be a promising adjunctive therapy to accelerate palatal wound healing after FGG, particularly in the early postoperative period. Nevertheless, the clinical benefit in pain management remains uncertain. Future well-designed studies with standardized protocols are needed to strengthen contemporary evidence.

PMID:41410039 | DOI:10.3290/j.qi.b6762754

Biomed Phys Eng Express. 2025 Dec 18. doi: 10.1088/2057-1976/ae2ebb. Online ahead of print.

ABSTRACT

Respiratory phase mismatch between single-photon emission computed tomography (SPECT) and computed tomography (CT) acquisition phases presents a challenge in lung perfusion scintigraphy using SPECT/CT. This study simulated lung volume and SPECT counts changes under free-breathing and breath-hold CT conditions compared to respiratory-synchronized acquisition. Chest 4D-CT images, divided into 10 respiratory phases, were used to generate lung, soft tissue, liver, and bone regions for each phase. A digital phantom was constructed via image processing using ImageJ. SPECT images were generated from these phantoms by employing the Prominence Processor to simulate projection data and reconstruct images. Simulations included a “synchronized image,” where both SPECT and μMAP for attenuation correction were created in the same phase; a “free-breathing image,” combining a free-breathing SPECT and μMAP; and a “CT breath-hold image,” using phase-specific μMAPs with the free-breathing SPECT image for attenuation correction. Lung volumes and SPECT counts in the free-breathing and CT breath-hold images were compared with those in the synchronized image. By analyzing the relative errors caused by differences in the μMAPs, the study evaluated the impact of mismatch between SPECT and CT phases. Results indicated that lung volumes appeared reduced during inspiration and increased during expiration compared with synchronized images. No significant difference in the relative error was observed between the free-breathing and CT breath-hold images. Our findings revealed that in the quantitative evaluation of lung perfusion SPECT, varying the μ-map phase during free-breathing acquisition did not result in a significant improvement, suggesting that the mismatch between SPECT and CT had no statistically significant effect on quantitative accuracy. Compared with respiratory-gated SPECT, free-breathing acquisitions introduced potential errors of approximately 2.5% in lung volume measurement and 1.2% in SPECT counts. However, these errors were within acceptable tolerance limits for clinical diagnosis, indicating that free-breathing acquisition had minimal effects on diagnostic capability.

PMID:41410023 | DOI:10.1088/2057-1976/ae2ebb