Nevin Manimala

Sports Med. 2025 Nov 27. doi: 10.1007/s40279-025-02359-3. Online ahead of print.

ABSTRACT

BACKGROUND: This study simulated the effect of reducing contact training duration on overall in-season head acceleration event (HAE) exposure within men’s and women’s rugby union.

METHODS: Players (n = 982) from two professional men’s and two semi-professional women’s competitions wore instrumented mouthguards in training and match-play for one season. Generalised linear mixed models were used to estimate the in-season weekly HAE exposures per position, sex and contact type. Simulation of modelled estimates evaluated the impact of reducing contact load guidelines by 25%, 50% and 75% (scenario 1), and replacing full contact training with controlled contact (scenario 2) or non-contact (scenario 3) training for different seasonal match exposures. Previously established contact load guidelines were used as a reference point.

RESULTS: HAEs were decreased by a maximum of 3.2 per week (0-95 HAEs per season; 0-23%). In scenario 1, the decrease in HAEs was disproportionately smaller than the reduction in contact training duration (e.g. 23.7% reduction in overall rugby minutes for 7% decrease in HAEs). Scenario 2 decreased HAEs similarly to scenario 1 but with no reduction in contact time. Scenario 3 decreased HAEs proportionally with contact time reductions (e.g. 8.9% decrease in HAEs >10 g for 9.6% reduction in overall rugby minutes).

CONCLUSIONS: HAEs were reduced in all scenarios, but the reduction was relatively small due to the low overall rate of HAEs in training. Policymakers should be aware of the tradeoffs involved in any change. Managing individuals with higher HAE exposures may be more appropriate than reducing contact training guidelines.

PMID:41298988 | DOI:10.1007/s40279-025-02359-3

Int J Clin Oncol. 2025 Nov 27. doi: 10.1007/s10147-025-02926-8. Online ahead of print.

ABSTRACT

BACKGROUND: Systematic pelvic and aortic lymphadenectomy in stage IIB-IVB patients with epithelial ovarian cancer, undergoing complete abdominal macroscopic resection with normal lymph nodes, was revealed to have no prognostic significance for survival in the LION trial. However, the proportion of patients with ovarian clear cell carcinoma (OCCC) in the LION trial was only 2.2%, so the significance of systematic retroperitoneal lymphadenectomy in patients with OCCC remains unclear.

METHODS: We conducted an ancillary analysis of 619 patients enrolled in a randomized phase III trial (JGOG 3017) in patients with OCCC. Of these, 89 were stage IIB to IVB, underwent a complete macroscopic resection, and had no grossly enlarged lymph nodes intraoperatively. Patients were divided into two groups: group A with lymphadenectomy and group B without lymphadenectomy. The Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS) and the log-rank test and Cox proportional hazard model were used to compare the two groups.

RESULTS: Among the 89 patients, 77 (86.5%) underwent a lymphadenectomy (group A), while 12 (13.5%) did not (group B). Three-year PFS were 62.3% in group A and 58.3% in group B (p = 0.7705). Three-year OS were 73.0% in group A and 65.6% in group B (p = 0.6346). No significant differences were observed between two groups.

CONCLUSION: This study did not demonstrate a definitive survival benefit from systematic lymphadenectomy in advanced OCCC patients with complete resection and clinically negative nodes. Given the small sample size, these results should be interpreted with caution and regarded as exploratory.

PMID:41298960 | DOI:10.1007/s10147-025-02926-8

Forensic Sci Int. 2025 Nov 21;379:112743. doi: 10.1016/j.forsciint.2025.112743. Online ahead of print.

ABSTRACT

Considerations on the drivers of bone diagenesis have received a lot of attention, yet there is still more to understand, particularly in relation to chemical changes that can occur post-mortem, and the rate at which these occur. The physicochemical composition of bone is altered during the post-depositional period, leading to a more thermodynamically stable crystal lattice, thus increasing the long-term survivability of the bone. Research has shown the potential for soft tissue trauma to affect the decomposition process, but the effect of bone trauma and fractures on diagenesis has not yet been considered. Most bone diagenesis research uses destructive analytical techniques, resulting in the loss of samples and the inability to perform repeat analyses. Presented here is a study investigating changes in the physicochemical composition of disarticulated Sus scrofa ribs, with and without fractures, using non-destructive analytical techniques. The aim was to explore the timescales in which physicochemical changes occur and to investigate the potential influence of bone fractures. Intact (control) or fractured (blunt-force or sharp-force) bone samples were deposited on a grassy surface for up to 240 days. Physicochemical changes to the bone sections were analysed using scanning electron microscopy – energy dispersive spectroscopy and Fourier transform infrared spectroscopy with attenuated total reflectance. It was hypothesised that physicochemical changes could be quantified in < 240 days using these techniques, and that the presence of fractures would affect the observed changes. Statistically significant (p < 0.05) losses in Na, K, and Mg and increases in crystallinity were seen over time, as well as significant changes in carbonate content and a significant loss of proteins. Differences physicochemical composition were observed between the undamaged and fractured samples, and the samples with BFT appeared to be the least affected for many elemental and IR parameters indicating BFT could potentially inhibit physicochemical change. The analysis of Na and K showed potential for PMI estimation, as these changed significantly over time, but as these were influenced by the presence of bone fractures, more research is needed fully understand how different variables can affect physicochemical change in bone, particularly the presence of bone fractures/damage.

PMID:41297088 | DOI:10.1016/j.forsciint.2025.112743

Comput Methods Programs Biomed. 2025 Nov 14;274:109167. doi: 10.1016/j.cmpb.2025.109167. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Cosinor analysis allows for the fitting of a cosine curve to describe cyclical variation in periodic data. The analysis provides an intuitive set of estimates that includes the MESOR (Midline Estimating Statistic of Rhythm), i.e., the mid-point of the fitted outcome, the amplitude, i.e., one-half the distance between the MESOR and the peak for normally distributed outcomes, and the acrophase, i.e. the time at which the outcome reaches its peak. Traditionally, most published cosinor analyses were generated though a two-stage approach in which a curve was fit to each individual’s data and differences in the estimated cosinor parameters were compared in downstream analyses. More recently multilevel cosinor modeling software has been developed which allows for the simultaneous modeling of data from multiple individuals. In addition to simplifying the model building process, the advantage of multilevel vs. two-stage cosinor analysis includes the option to fit more complex models and, likely, an improvement in fit for each individual’s data. However, to our knowledge, there are no SAS procedures or macros that assist users with this analytical approach.

METHODS: In this paper we introduce multilevel cosinor models and SAS macros we have developed to perform these analyses. In addition, we compare model fit between the multilevel and two-stage methods.

RESULTS: The SAS macros presented in this paper allow users to select the best random variable specification for the unconditional cosinor model and add a dichotomous grouping variable to detect differences in parameters across groups. At each step of model building, parameter estimates, measures of model fit and graphical output help the user understand the model derived and its appropriateness for their data. Results of cross-validation analyses are presented that illustrate the superior fit of the multilevel over the single-level approach for the dataset utilized in the examples.

CONCLUSIONS: Multilevel cosinor analysis extends the single subject cosinor model by allowing for more convenient model selection and may provide a better fit for each individual’s data. We are hopeful that this manuscript will introduce more researchers to this analytical technique and allow them to apply it in their own research.

PMID:41297072 | DOI:10.1016/j.cmpb.2025.109167

EBioMedicine. 2025 Nov 25;122:106052. doi: 10.1016/j.ebiom.2025.106052. Online ahead of print.

ABSTRACT

BACKGROUND: Biliary atresia (BA) is the most prevalent serious neonatal biliary obstructive disorder and is a complex multifactorial liver disorder. Genome-wide association studies have identified Adducin 3 (ADD3) as a BA susceptibility gene but the mechanisms involved in disease causation and progression remain unclear.

METHODS: ADD3 knockout human pluripotent stem cells were differentiated into cholangiocyte organoids to assess the effect of ADD3 deletion on biliary development in vitro. Add3 deletion in rhesus rotavirus (RRV)-induced experimental BA mice were employed as the in vivo model to address the impact of reduced Add3 expression on BA pathogenesis.

FINDINGS: ADD3 knockout organoids displayed defective cholangiocyte differentiation, failure in the recruitment of βII-spectrin to the cell membrane, abnormal primary cilia development, reduced expression of tight junction proteins, lower transepithelial electrical resistance (TEER) and increased paracellular permeability. Statistical significantly reduced tight junction (TJ) proteins expression and lower TEER in Add3+/- and Add3-/- liver tissue-derived cholangiocytes were observed. Reduced number of TJs and enlarged paracellular spaces without any detectable TJ were detected in the intra-hepatic bile ducts of Add3+/- and Add3-/- livers. A statistical significantly higher incidence and a more advanced form of BA with statistical significantly higher serum bilirubin, liver necrosis and fibrosis, and accumulation of macrophages and activated hepatic stellate cells were observed in Add3 knockout BA mice as compared to wild-type BA mice.

INTERPRETATION: Dysregulated ADD3 expression caused an abnormal development and impaired barrier function of cholangiocytes, and the resultant increase in bile duct permeability rendered the foetus/neonate susceptible to a more severe injury response to an external insult. The findings support the hypothetical pathogenic model of genetic susceptibility genes being involved in hepatobiliary development/structure, and the perturbed embryogenesis of the biliary tree and its disrupt integrity increase the host susceptibility to biliary injury and BA.

FUNDING: Theme-based Research Scheme 2021 (T12-712/21-R); Health and Medical Research Fund (06172096; 03143476); RGC CERG Grant 2019/20 (17105119) to VCHL; Commissioned HMRF (PR-HKU-1) to PKHT.

PMID:41297070 | DOI:10.1016/j.ebiom.2025.106052

Vaccine. 2025 Nov 25;69:128013. doi: 10.1016/j.vaccine.2025.128013. Online ahead of print.

ABSTRACT

BACKGROUND: Increasing vaccination coverage among older adults is a key post-pandemic public health priority. While seasonal influenza (SIV) and pneumococcal vaccines (PV) are widely available and subsidized in China, uptake remains low. This study explored post-pandemic willingness and determinants of SIV and PV uptake among older adults in Shenzhen.

METHODS: A cross-sectional survey of 1917 adults aged ≥60 years was conducted from January to May 2024. Descriptive statistics, chi-square tests, and multivariable logistic regression identified factors associated with willingness to receive future SIV and PV, and perceived pandemic influence, including sociodemographic characteristics, healthcare access, vaccination history, health beliefs, and policy awareness.

RESULTS: Willingness to receive SIV and PV was high (77.4 % and 73.4 %), but actual uptake was much lower (55.1 % and 29.2 %). Over 70 % of respondents reported increased willingness due to the COVID-19 pandemic. For SIV, key predictors included previous uptake (adjusted odds ratio [aOR] = 3.92, 95 % confidence interval [CI]: 3.00-5.15), concern about influenza (aOR = 1.96, 95 % CI: 1.52-2.52), awareness of free vaccination policy (aOR = 1.90, 95 % CI: 1.47-2.47), awareness of life-course vaccination (aOR = 1.60, 95 % CI: 1.11-2.35), having a family doctor (aOR = 1.54, 95 % CI: 1.10-2.14), and frequent health check-ups (aOR = 1.33, 95 % CI: 1.03-1.71). For PV, predictors included concern about pneumonia (aOR = 3.83, 95 % CI: 3.00-4.90), prior uptake (aOR = 3.08, 95 % CI: 2.18-4.45), free policy awareness (aOR = 2.91, 95 % CI: 2.27-3.74), having a family doctor (aOR = 1.78, 95 % CI: 1.27-2.48), frequent check-ups (aOR = 1.62, 95 % CI: 1.26-2.07), awareness of life-course vaccination (aOR = 1.45, 95 % CI: 1.03-2.09), and higher household income (aOR = 1.43, 95 % CI: 1.06-1.95). Willingness-to-pay remained low; healthcare providers, community channels, and traditional media were the main information sources.

CONCLUSION: While the pandemic increased vaccine willingness and uptake among older adults, an intention-behavior gap persists. Strengthening community-based services, life-course immunization promotion, policy communication, and expanded vaccine subsidies are crucial to sustaining uptake progress among this age group.

PMID:41297069 | DOI:10.1016/j.vaccine.2025.128013

Biomed Phys Eng Express. 2025 Nov 26. doi: 10.1088/2057-1976/ae2489. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to develop a miniaturized low-field thoracic magnetic stimulation (LF-ThMS) device to evaluate its effects on peripheral oxygen saturation (SpO2) in healthy rats. This investigation was motivated by prior findings that LF-ThMS at 10.5 to 13.1 mT increased SpO2in patients with COVID-19. However, its effect on healthy subjects remains unknown. To address this gap before extending research to healthy humans, we first examined its effects in healthy animal models.

APPROACH: A miniature low-field thoracic magnetic stimulation (LF-ThMS) device, also referred to as a pulsed electromagnetic field (PEMF) system, was developed using two 30-turn coils made of 13-gauge magnet wire, encased in nylon sheaths. The coils were powered by a 30 V, 13 A DC source to generate magnetic pulses up to 13.1 mT. A custom control circuit, featuring an ATmega328P microcontroller, relays, and MOSFETs, regulated the pulse frequency and included a safety system to maintain coil temperatures below 38 °C. The device also featured a user interface for customizable and reproducible operation. Peripheral oxygen saturation (SpO2) was monitored using a NONIN 750 pulse oximeter.

MAIN RESULTS: The LF-ThMS device successfully generated magnetic flux densities of 10.5, 11.6, and 13.1 mT. However, when we compared SpO2levels between the control condition (before LF-ThMS) and the SpO2levels after the LF-ThMS at these intensities, we did not find a statistically significant difference.

SIGNIFICANCE: These results suggest that LF-ThMS may not affect SpO2in healthy individuals, and the improvements observed in COVID-19 patients could be due to disease-specific mechanisms or other unknown factors, rather than a general physiological effect of LF-ThMS.

PMID:41297067 | DOI:10.1088/2057-1976/ae2489

Aust Health Rev. 2025 Dec 4;49(6):AH25242. doi: 10.1071/AH25242.

ABSTRACT

OBJECTIVE: Spinal surgery rates in Australia continue to rise despite limited evidence for their effectiveness in managing uncomplicated chronic back pain. This study examined patient-level factors that influence willingness to undergo surgery, to informing future work promoting non-surgical care pathways.

METHODS: We conducted a cross-sectional online survey in March 2025 of 152 privately insured Australian adults with chronic low back pain. Participants reported pain characteristics, functional interference, prior imaging and pain-related beliefs (expectations of recovery, self-efficacy and catastrophising). Willingness to undergo spinal surgery within 5 years was assessed on a 5-point scale, and dichotomised into ‘willing’ (3-4) and ‘unwilling’ (0-1); respondents answering ‘unsure’ were excluded. Logistic regression examined predictors of willingness to consider surgery.

RESULTS: Of 152 participants (mean age 59.3 years, 64% female), 24% expressed willingness to undergo surgery. Negative pain beliefs, higher pain intensity and younger age significantly predicted willingness, with the strongest effect seen for negative pain beliefs (OR 2.62, 95% CI 1.16-5.92, P = 0.02). Functional interference, imaging history and gender showed positive, but non-significant, associations.

CONCLUSION: Negative pain beliefs predict willingness to undergo spinal surgery. This finding has important policy implications, suggesting that addressing belief-driven demand may help reduce the economic burden of surgery by directing patients towards guideline-based, high-value, non-surgical care.

PMID:41297063 | DOI:10.1071/AH25242

Hum Exp Toxicol. 2025 Jan-Dec;44:9603271251389572. doi: 10.1177/09603271251389572. Epub 2025 Nov 26.

ABSTRACT

BackgroundAccurate and prompt assessment of malathion intoxication severity remains a significant clinical challenge, often hampered by reliance on single diagnostic markers. This exploratory case series investigated the combined utility of rapid butyrylcholinesterase (BChE) activity measurements and gas chromatography-tandem mass spectrometry (GC-MS/MS) for quantifying urinary malathion to enhance diagnostic precision.MethodsWe investigated three independent patients admitted with acute malathion intoxication. BChE activity was measured using both a point-of-care (POCT) device and a laboratory-based enzyme-multiplied immunoassay technique (EMIT). Urinary malathion was quantified using a validated GC-MS/MS method.ResultsMalathion exposure was confirmed in all patients via urinary analysis. Strong per-case positive correlations (r ranging from 0.905 to 0.996) were observed between the two BChE measurement methods, though Bland-Altman analysis revealed noteworthy discrepancies (mean bias of 10%, limits of agreement ranging from -20% to 40%). Critically, statistically significant inverse correlations (p < 0.05) were identified between urinary malathion concentrations and both BChE activity measurements, underscoring the dynamic relationship between exposure and enzymatic inhibition.ConclusionThese findings, derived from a small, exploratory case series, suggest the importance of an integrated diagnostic approach for malathion intoxication. This combined strategy may support improved assessment of severity and prognosis in individual cases, offering insights into the pesticide’s systemic impact and elimination kinetics, especially when exposure details are unclear. While rapid BChE tests are valuable for initial screening, their interpretation should occur within this multi-marker framework. The generalizability of these findings is limited by the small sample size, and no formal power calculation was performed.

PMID:41297042 | DOI:10.1177/09603271251389572

Interact J Med Res. 2025 Nov 26;14:e72894. doi: 10.2196/72894.

ABSTRACT

BACKGROUND: The growing administrative burden on clinicians, particularly in medical documentation, contributes to burnout and may compromise patient safety. Recent advancements in generative artificial intelligence (AI) offer a promising solution to improve documentation processes and address these challenges.

OBJECTIVE: This study aims to evaluate the feasibility of using a fine-tuned OpenAI Curie model to automate the generation of medical report summaries (epicrises) in ophthalmology. By assessing the model’s performance through human and automated evaluations, this study seeks to determine its potential for reducing clinician workload while ensuring accuracy, usefulness, and compliance with regulatory requirements.

METHODS: A data set of around 60,000 anonymized medical letters was created using a custom algorithm to comply with General Data Protection Regulation guidelines. The Curie model was fine-tuned on this data set to generate epicrises from medical histories, diagnoses, and findings. The performance evaluation involved various human assessments and automated evaluations from 2 large language models (LLMs).

RESULTS: In the clinical context, 49.9% (384/769) of epicrises were evaluated as helpful or excellent, whereas only 25% (194/769) were considered disturbing. In a human (manual) evaluation, formal correctness was rated significantly higher than the neutral midpoint of 2.5 on the 4-point rating scale, as determined by a 1-sample Wilcoxon signed-rank test (mean 3.59, SD 0.85; W=1686; P<.001). Using paired t tests, we found a significant reduction in time, as correcting an AI epicrisis was faster than manually writing one (mean 109.52, SD 53.30 vs mean 54.25, SD 63.34 s; t₆₈=3.39; P<.01). While medical accuracy and usefulness showed positive trends, these did not reach statistical significance when compared to the neutral midpoint (for medical accuracy, W= 7456; P=.08), for usefulness, W=7652.5; P=.18). Epicrises generated or corrected with AI were significantly shorter than manually written ones (mean 330.43, SD 115.42 vs mean 501.07, SD 243.50 characters; t₆₈=-6.10; P<.001). Automated LLM assessments showed alignment with human ratings, with over 52% (356/679) and 66% (489/743) of responses in the top agreement categories, respectively. This supports overall consistency, though the comparison remains a proof of concept given methodological limitations.

CONCLUSIONS: Our study demonstrates the technical and practical feasibility of introducing fine-tuned commercial LLMs into clinical practice. The AI-generated epicrises were formally and clinically correct in many cases and showed time-saving potential. While medical accuracy and usefulness varied across cases and should be focused on in further developments, a significant workload reduction is likely. Our anonymization process showed that regulatory challenges in the context of AI with patient data can effectively be dealt with. In summary, this study highlights the promise of transformer-based LLMs in reducing administrative tasks in health care. It outlines a pipeline for integrating LLMs into European Union clinical practice, emphasizing the need for careful implementation to ensure efficiency and patient safety.

PMID:41297038 | DOI:10.2196/72894