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Nevin Manimala Statistics

Cryotherapy for reducing the pain of sterile water injections: A three-arm multicentre randomised controlled trial

Int J Nurs Stud. 2026 Jun 11;182:105615. doi: 10.1016/j.ijnurstu.2026.105615. Online ahead of print.

ABSTRACT

BACKGROUND: Sterile water injections have been shown to be safe and efficacious in the management of childbirth pain, particularly labour back pain. The only commonly experienced side effect of the technique is the significant injection pain. Cryotherapy, in the form of vapocoolant sprays or cold packs has been shown in previous studies to reduce injection pain generally. However, it is not known if cryotherapy would mitigate the pain of sterile water injections.

OBJECTIVE: To assess the efficacy of vapocoolant spray or chemical cold pack in reducing sterile water injection pain for labour back pain.

DESIGN: Three-arm multicentre open label superiority randomised controlled trial.

SETTING: Three maternity hospitals in Brisbane, Australia.

METHODS: Consenting participants were allocated 1:1:1 using an independently produced randomisation schedule to either the application of a vapocoolant spray, chemical cold pack or standard care (no cryotherapy). The primary outcome was the difference between groups in self-reported visual analogue pain scale at time of injection. Secondary outcomes included skin temperature at the time of injection and visual analogue pain scores for back pain up to 120 min following injection.

RESULTS: Between February 2024 and June 2025 a total of 133 women randomised to either vapocoolant spray (n = 45), chemical cold pack (n = 45) or control group (n = 44). Consent forms were not completed for four participants, and four withdrew. There was no difference in visual analogue pain scores at injection between groups (control: mean 84.73 mm (SD 22.75); vapocoolant: mean 81.23 mm (SD = 24.94); chemical ice pack: mean 86.89 mm (SD = 18.21)) (p = 0.51). Skin temperature in both the vapocoolant (median 29.05 IQR 25.9, 31.8) and chemical cold pack (median 27.23, IQR 23.8, 30.5) was lower than the control group (median 32.75, IQR 31.8, 34.2) (p = <0.001). All three arms showed lower post injection pain scores across all time points.

CONCLUSION: Neither the application of a vapocoolant spray or chemical cold pack prior to sterile water injections resulted in a statistically significant reduction in associated pain. The use of cryotherapy to the mitigate pain of sterile water injections cannot be recommended.

TRIAL REGISTRATION: The trial is registered at the Australian and New Zealand Clinical Trials Registry (Trial ID: ACTRN12623000585628). Registration date: 29/05/2023. First recruitment 21st February 2024.

PMID:42308568 | DOI:10.1016/j.ijnurstu.2026.105615

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Nevin Manimala Statistics

Praxis-BGM: Clustering of Omics Data Using Semi-Supervised Transfer Learning for Gaussian Mixture Models via Natural-Gradient Variational Inference

Bioinformatics. 2026 Jun 17:btag395. doi: 10.1093/bioinformatics/btag395. Online ahead of print.

ABSTRACT

MOTIVATION: High-dimensional omics data are typically measured on limited sample sizes, which challenges model-based clustering methods such as Gaussian mixture models (GMMs), often leading to instability and poor generalization under complex mixture structures. To address these limitations, we developed Praxis-BGM, a natural-gradient variational inference framework for GMMs. Praxis-BGM enables semi-supervised transfer learning by incorporating an informative prior GMM estimated from large-scale reference data with robust cluster structures. The prior model can encode cluster-specific means, covariance structures, and structural connectivity patterns, and is updated using the target data with variational inference to improve clustering in small-sample settings.

RESULTS: Using the Variational Online Newton (VON) algorithm, we derived natural-gradient updates for the standard parameters of GMMs. Implemented in the Python library JAX for accelerator-oriented computation, Praxis-BGM is computationally efficient and scalable. Across extensive simulations and two real-world applications-breast cancer bulk transcriptomics for subtype recovery and single-cell transcriptomics for cross-platform cell-type label transfer-Praxis-BGM improves posterior clustering performance, stability, and biological interpretability, even when priors are partially mismatched.

AVAILABILITY AND IMPLEMENTATION: Praxis-BGM is freely available at https://github.com/ContiLab-usc/Praxis-BGM, and an archival version is available on Zenodo at https://doi.org/10.5281/zenodo.19657680.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:42308558 | DOI:10.1093/bioinformatics/btag395

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Nevin Manimala Statistics

Simple against advanced imaging for the selection of stroke therapy in the extended window (VESTA study)

Eur Stroke J. 2026 Jun 2;11(6):aakag068. doi: 10.1093/esj/aakag068.

ABSTRACT

INTRODUCTION: The optimal imaging modality for selecting stroke patients for revascularisation in the extended window remains uncertain. The VESTA study compared simple (non-contrast CT + CTA) vs advanced imaging (including perfusion) in the extended window in terms of clinical outcomes, mortality and safety.

PATIENTS AND METHODS: This multicentre cohort study included 1262 stroke patients (last seen well 6-24 h, NIHSS ≥ 6) from the Catalan Stroke Registry (2019-2021). A central core lab re-evaluated images, and blinded investigators assessed 90-day functional outcomes. Inverse probability weighting (IPW) and multivariable methods were applied.

RESULTS: Median age was 76 years, NIHSS 12 and 48% were women. Simple imaging was used in 44% (n = 550), advanced in 56% (n = 712). Simple imaging had higher rates of no arterial occlusion (49% vs 37%, P = .006) and slightly lower endovascular treatment rates (36% vs 40%, P = .117). Time metrics were similar. In the IPW analysis, (advanced imaging as reference), simple imaging showed numerically worse point estimates across all outcomes, although most differences did not reach statistical significance: a worse mRS shift (adjusted odds ratio [aOR] 1.17 [95% CI, 0.96-1.43]; P = .11), a lower good functional outcome (mRS 0-2; aOR 0.83 [0.66-1.06]; P = .13), a higher mortality (aOR 1.20 [0.91-1.58]; P = .20), more frequent sICH (aOR 1.25 [0.61, 2.57]; P = .55) and a higher risk of any ICH (aOR 1.57 [1.00-2.47]; P = .05).

DISCUSSION: In moderate-to-severe stroke (NIHSS ≥ 6) within 6-24 h, simple imaging did not show a statistically significant difference vs advanced imaging for guiding stroke treatment. However, advanced imaging may improve patient selection for reperfusion and reduce haemorrhagic risk.

TRIAL REGISTRATION INFORMATION: This study was registered at ClinicalTrials.gov under NCT05299034.

PMID:42308555 | DOI:10.1093/esj/aakag068

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Nevin Manimala Statistics

Topology-Driven Activation of the GLP-1 Receptor Promotes Adipose Tissue Browning

Protein Cell. 2026 Jun 17:pwag041. doi: 10.1093/procel/pwag041. Online ahead of print.

NO ABSTRACT

PMID:42308543 | DOI:10.1093/procel/pwag041

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Nevin Manimala Statistics

Robust prioritization of genomic features with stability selection

Bioinformatics. 2026 Jun 17:btag398. doi: 10.1093/bioinformatics/btag398. Online ahead of print.

ABSTRACT

MOTIVATION: The heterogeneity of complex diseases including cancer leads to heavy-tailed distributions in the disease traits. In such settings, non-robust variable selection methods are inherently susceptible to data contamination and can yield unstable or misleading results. This vulnerability becomes more severe for recently proposed approaches that introduce pseudo-features as negative controls, as these methods further amplify the curse of dimensionality by expanding the genotype matrix in the presence of outliers and high-dimensional genomic features.

RESULTS: We develop a robust variable selection framework with stability selection to prioritize genomic features in the presence of contamination. In contrast to existing approaches that rely on pseudo-features for error control, the proposed method achieves double robustness. First, it adopts least absolute deviation (LAD) LASSO to ensure robustness against outliers and heavy-tailed errors in disease traits. Second, it avoids augmenting the genotype matrix with pseudo-features, thereby mitigating the curse of dimensionality that is particularly problematic in high-dimensional genomic data. The proposed method has been extensively evaluated in simulation studies to demonstrate its effectiveness over multiple competing methods for variable selection. In addition, we have applied the proposed method and competing approaches to two real-data case studies: the The Cancer Genome Atlas (TCGA) Skin Cutaneous Melanoma (SKCM) dataset and an eQTL dataset. The results demonstrate that the proposed method achieves superior performance by identifying genomic features with higher reproducibility.

AVAILABILITY AND IMPLEMENTATION: The source code for implementing the proposed methods is publicly available at https://github.com/cenwu/RSS with an archival DOI https://doi.org/10.6084/m9.figshare.32306883.

PMID:42308532 | DOI:10.1093/bioinformatics/btag398

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Nevin Manimala Statistics

Redefining Stallion Sperm Bioenergetics: Lessons from a Decade of Change in Mammalian Sperm Metabolism

Reproduction. 2026 Jun 17:xaag077. doi: 10.1093/reprod/xaag077. Online ahead of print.

ABSTRACT

Over the last decade, mammalian sperm metabolism has moved from a binary view centered on glycolysis versus oxidative phosphorylation to an integrated model in which ATP production, redox homeostasis, metabolic plasticity, and cellular heterogeneity are functionally linked. This conceptual shift has relevance in the stallion, whose spermatozoa display strong mitochondrial engagement, marked redox sensitivity, and substantial responsiveness to media composition and preservation conditions. Here, we review advances from 2016 to 2026 that reshaped the field, with emphasis on extracellular flux analysis, multiparametric and label-free flow cytometry, proteomics, phosphoproteomics, metabolomics, and emerging stable-isotope approaches. We discuss evidence indicating that stallion spermatozoa operate within an oxidative framework in which mitochondrial respiration is supported by glycolytic input, whereas auxiliary pathways involving lactate-pyruvate cycling, and possibly neutral lipid mobilization and glycerol-glycerol-3-phosphate interconversion, may contribute primarily to redox stabilization and metabolic flexibility rather than to bulk ATP production. We further examine how these concepts inform diagnostics, semen preservation, cryopreservation, and intracytoplasmic sperm injection, emphasizing that single parameters are weak predictors of fertility and that integrated metabolic phenotypes are more informative. Finally, we identify major unresolved issues, including the need to standardize media composition and bioenergetic assays, distinguish pathway capacity from flux and coupling efficiency, and link metabolic phenotypes to fertility endpoints using rigorous experimental and statistical designs. A systems view of sperm metabolism offers a rational framework to improve equine fertility technologies and to explain inter-stallion variation in reproductive performance.

PMID:42308531 | DOI:10.1093/reprod/xaag077

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Nevin Manimala Statistics

Measuring the Quality of Datasets: Development of the IDEFIM Indicator Set for Empirical Health Research

J Med Internet Res. 2026 Jun 17;28:e90482. doi: 10.2196/90482.

ABSTRACT

BACKGROUND: To be beneficial for empirical health research, a dataset must be fit for use. The quality of a dataset can only be influenced during data collection, yet it is evaluated multiple times during analysis or secondary use by applying quality indicators.

OBJECTIVE: This study aimed to establish an up-to-date set of indicators measuring the quality of datasets in empirical health research.

METHODS: A total of 3 pillars were combined. First, the 51 indicators of a German guideline from 2014 about the management of data quality were revised. Second, a literature review was performed looking for evidence sources since 2013 that describe, propose, or apply dataset quality indicators. Third, indicators were supplemented by a manual search and other sources. The quality indicators were then integrated into the IDEFIM framework. The IDEFIM framework distinguishes between the categories’ data, metadata, context, and openness quality. In this work, only the categories data and metadata quality, with their 14 dimensions were considered.

RESULTS: In total, 69 indicators qualified for the IDEFIM indicator set, 53 related to the category data quality, and 16 to the category metadata quality. A total of 30 indicators originated from the German guideline, 31 from the literature review. Three indicators were added to cover aspects of diversity, equity, and inclusion, and an additional 5 related to specifics of data and metadata quality not addressed so far. Most indicators were found in the dimensions accuracy (data) with 12 measures, completeness (data) with 12 measures, and consistency (data) with 19 measures. According to the number of supporting evidence sources, missing values in data elements (48 evidence sources), contradictions (31), and currentness (26) were the most popular quality indicators. Metadata quality was significantly less frequently addressed.

CONCLUSIONS: The presented IDEFIM indicator set can be used for the management of data collections as well as for the verification of a dataset’s quality for an intended use. The indicator set should also be considered in the design of a study in empirical health research and the development of software tools supporting the visualization of issues related to the quality of a dataset.

PMID:42308504 | DOI:10.2196/90482

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Nevin Manimala Statistics

Examining the Association Between Internet Addiction and Nonsuicidal Self-Injury Among Chinese Middle School Students: Prospective Cohort Study

J Med Internet Res. 2026 Jun 17;28:e86427. doi: 10.2196/86427.

ABSTRACT

BACKGROUND: While cross-sectional studies have consistently reported an association between nonsuicidal self-injury (NSSI) and internet addiction (IA), longitudinal evidence regarding the directionality and dose-response relationship remains limited. Furthermore, the roles of sex and varying degrees of problematic internet use in predicting new-onset NSSI are not fully understood.

OBJECTIVE: This prospective cohort study aimed to investigate whether baseline IA and its intermediate states predict the subsequent new onset of NSSI among Chinese adolescents over a 6-month period and to explore potential sex differences in this longitudinal association.

METHODS: A prospective cohort design was used. A total of 1315 junior high school students without a history of NSSI were recruited at baseline, and 704 (53.5%) students completed the 6-month follow-up. IA and NSSI were assessed using the Chinese Internet Addiction Scale-Revised and a self-report questionnaire from the Adolescent Health-Related Risky Behavior Inventory, respectively. Logistic regression analysis was conducted to examine the predictive value of IA exposure for incident NSSI, adjusting for key covariates, including sex, age, ethnicity, only child status, anxiety, and depression. Restricted cubic spline regression was used to model the dose-response relationship between distinct states of IA and NSSI risk.

RESULTS: The baseline prevalence of IA was 9.09% (64/704). At the 6-month follow-up, the incidence rate of NSSI was 9.8% (69/704). Restricted cubic spline regression revealed a linear dose-response relationship, where the risk of incident NSSI escalated with increasing IA severity. In the fully adjusted model for the total sample, baseline IA was a significant predictor of subsequent NSSI (odds ratio [OR] 2.185, 95% CI 1.031-4.627; P=.04). Crucially, stratified analyses revealed significant sex disparities: the longitudinal association between IA and subsequent NSSI was statistically significant among female adolescents (OR 3.271, 95% CI 1.101-9.717; P=.03) and the intermediate internet-dependent state (OR 2.593, 95% CI 1.002-6.710; P=.049) but not among male adolescents (IA: P=.44; internet-dependent state: P=.87).

CONCLUSIONS: NSSI incidence is notably prevalent among Chinese junior high school students. While IA serves as a robust, independent risk factor for predicting the new onset of NSSI in the overall adolescent population, sex-stratified analyses revealed that this longitudinal association was statistically significant (P=.03) only among female students. These findings underscore the critical need to integrate IA assessments into school-based mental health screenings and highlight the necessity of developing sex-specific, emotion-focused prevention strategies to mitigate NSSI risk.

PMID:42308503 | DOI:10.2196/86427

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Nevin Manimala Statistics

Validating the Factor Structure of the Fujisawa Social Capital Scale (FSCS) Among Community-Dwelling Older Adults Participating in “Kayoi-no-ba”: The Gunma Aging Cohort Study

Soc Work Public Health. 2026 Jun 17:1-9. doi: 10.1080/19371918.2026.2689953. Online ahead of print.

ABSTRACT

Social capital is a fundamental social determinant of health for older adults in rapidly aging societies; however, existing comprehensive instruments often impose high cognitive friction through complex recall tasks, potentially leading to systematically excluding vulnerable populations. This study validated the factor structure of the Fujisawa Social Capital Scale (FSCS) – an independent, brief tool designed for inclusive community-based practice – among community-dwelling Japanese older adults participating in “Kayoi-no-ba” (neighborhood social participation hubs). Data were analyzed from 587 participants in the Gunma Aging Cohort (mean age 79.2 ± 6.0 years; 87.1% female; 29.6% living alone). Exploratory factor analysis using the Weighted Least Squares Mean- and Variance-adjusted estimator was prioritized to ensure statistical stability for this specific cohort. A robust two-factor structure emerged: Factor 1, “Sense of Security and Attachment to the Community,” and Factor 2, “Mutual Aid Among Neighbors.” These findings underscore the conceptual distinction between psychological belonging and functional support within community settings. The model demonstrated favorable fit indices, with a Root Mean Square Error of Approximation of 0.071 and a Tucker-Lewis Index of 0.96. High internal consistency was confirmed using McDonald’s omega (ω) for the total scale (ωt = 0.85), Factor 1 (ω = 0.77), and Factor 2 (ω = 0.74). Overall, these results indicate that the FSCS is a “practice-first” instrument that minimizes respondent burden while maintaining data reliability. By distinguishing psychological attachment from functional support, it provides a “common language” for interdisciplinary teams to guide social prescribing and prioritize targeted community-based support for socially vulnerable older adults.

PMID:42308501 | DOI:10.1080/19371918.2026.2689953

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Nevin Manimala Statistics

Cefazolin for Methicillin-Susceptible Staphylococcus aureus Bacteremia

N Engl J Med. 2026 Jun 18;394(23):2329-2339. doi: 10.1056/NEJMoa2506905.

ABSTRACT

BACKGROUND: Staphylococcus aureus bacteremia is associated with high mortality. Whether cefazolin or an antistaphylococcal penicillin should be preferred for the treatment of methicillin-susceptible S. aureus bacteremia is unclear.

METHODS: In an ongoing international Bayesian adaptive platform trial, we conducted an open-label, randomized comparison of cefazolin with an antistaphylococcal penicillin (flucloxacillin or cloxacillin) in adult patients with penicillin-resistant, methicillin-susceptible S. aureus bacteremia. The primary outcome, which was evaluated with a hierarchical Bayesian logistic-regression model, was death from any cause within 90 days after enrollment in the platform. We assessed the posterior probability of the noninferiority of cefazolin to flucloxacillin or cloxacillin (with the criterion for noninferiority prespecified as an adjusted odds ratio of <1.2, which approximates an absolute difference in mortality of <2.5 percentage points if mortality in the antistaphylococcal-penicillin group is 15%), as well as the posterior probability of superiority (with the criterion of an adjusted odds ratio of <1.0). Secondary safety outcomes included the development of acute kidney injury within 14 days.

RESULTS: This domain of the ongoing trial was conducted between February 17, 2022, and August 7, 2024, by which time the criterion for noninferiority had been met. Mortality at 90 days among adults who could be evaluated was 15.0% (97 deaths among 645 patients) in the cefazolin group and 17.0% (109 deaths among 642 patients) in the antistaphylococcal-penicillin group (adjusted odds ratio, 0.81; 95% credible interval, 0.59 to 1.12; probability of noninferiority, 99.2%; probability of superiority, 89.8%). Acute kidney injury occurred in 92 of 660 patients (13.9%) in the cefazolin group, as compared with 127 of 648 (19.6%) in the antistaphylococcal-penicillin group (adjusted odds ratio, 0.67; 95% credible interval, 0.50 to 0.89; probability of superiority, 99.7%).

CONCLUSIONS: In patients with methicillin-susceptible S. aureus bacteremia, cefazolin was noninferior to flucloxacillin or cloxacillin with respect to 90-day mortality and was associated with a lower incidence of acute kidney injury. (Funded by the National Health and Medical Research Council and others; SNAP ClinicalTrials.gov number, NCT05137119.).

PMID:42308484 | DOI:10.1056/NEJMoa2506905