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Nevin Manimala Statistics

Inequality in human development amplifies climate-related disaster risk

Nat Commun. 2026 Jun 17;17(1):5067. doi: 10.1038/s41467-026-73873-9.

ABSTRACT

The impacts of climate-related disasters are shaped by the interaction between hazard intensity, exposure, and vulnerability. However, the influence of hazard intensity and within-country inequality on impact magnitudes remains poorly quantified. Here, we present a global multi-hazard study of over 7000 climate-related disasters reported by the Emergency Events Database from 1990 to 2020. Using subnational indicators, we show that human development drives major shifts in global exposure and impact patterns, with societal vulnerability outweighing hazard intensity in shaping impacts. Despite a declining share of global exposure over the past three decades, regions with low subnational Human Development Index scores experience disproportionately higher human losses across most disaster types. For instance, individuals in these regions face an 8.2-fold higher risk of fatality associated with storms (95% confidence interval: 2.16-23.06) compared to those in very high human development regions. Our findings also indicate that within-country inequality in human development exacerbates disaster risk in regions with low and medium levels of human development. These results underscore the critical role of human development in managing disaster risks and highlight the link between socioeconomic conditions and vulnerability to climate-related hazards.

PMID:42310318 | DOI:10.1038/s41467-026-73873-9

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Nevin Manimala Statistics

Predicting early-stage breast cancer disease-free survival and adjuvant therapy benefit from multimodal information using deep learning

NPJ Breast Cancer. 2026 Jun 17. doi: 10.1038/s41523-026-00991-4. Online ahead of print.

ABSTRACT

Accurate prediction of disease-free survival (DFS) is essential for tailoring adjuvant regimens and improving clinical outcomes in early-stage breast cancer (EBC). A multimodal deep learning model (Mu-model) based on deep canonical correlation analysis (DCCA) integrating multiparametric magnetic resonance imaging (MRI)-including dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI)-with clinical text data is developed to predict DFS and identify patients likely to benefit from adjuvant therapy. This multicenter retrospective study includes 1,120 patients with EBC (training cohort, n = 459; external validation cohort, n = 661). The Mu-model achieves concordance index (C-index) values of 0.742 (95% confidence interval [CI]: 0.662-0.821) in the training cohort (TC) and 0.735 (95% CI: 0.667-0.803) in the external validation cohort (EVC) for DFS. The Mu-model score (MuS) remains an independent prognostic factor after adjustment for clinicopathologic variables (all P < 0.05). In human epidermal growth factor receptor 2 (HER2)-positive, hormone receptor (HR)-positive, and T2-stage subgroups, a significant survival benefit associated with adjuvant therapy was observed in patients with low MuS, whereas no statistically significant association was detected in patients with high MuS. Transcriptomic analysis in 19 patients indicates that high MuS is associated with immune activation and enrichment of cell-cycle and purine-metabolism pathways. The Mu-model provides non-invasive DFS prediction and recurrence risk stratification, while preliminarily exploring its potential to identify patients who may derive differential benefits from adjuvant therapy.

PMID:42310310 | DOI:10.1038/s41523-026-00991-4

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Nevin Manimala Statistics

Continuity of Care in General Practice in Australia: A Whole-Of-Population Serial Cross-Sectional Study

Med J Aust. 2026 Jun;224(6):e70229. doi: 10.5694/mja2.70229.

ABSTRACT

OBJECTIVE: To quantify continuity of care in general practice in the Australian population, including variation according to patient characteristics and over time, to support ongoing policy reforms directed towards improving general practice care.

DESIGN AND SETTING: Repeated cross-sectional analyses of linked whole-of-population data from the Medicare Benefits Schedule, the Medicare Consumer Directory and the Census of Population and Housing (2021).

PARTICIPANTS: Continuity was assessed in people with at least four general practitioner visits in a 2-year period (about 80% of the population).

MAIN OUTCOME MEASURE: Relational continuity of care in general practice, measured with the Usual Provider Index, for eight overlapping 2-year periods (2016-2017 to 2022-2023). High continuity was defined as having ≥ 70% of visits with one provider.

RESULTS: About one-third of the population had high continuity of care (range: 31.3% in 2018-2019 to 37.2% in 2020-2021). After adjustment for age, sex and remoteness, high continuity was more common among those with greater care needs, including those who were older (≥ 70 years vs. 0-14 years: adjusted prevalence ratio [aPR], 1.88) or with health conditions (e.g., ≥ 3 vs. none: aPR, 1.14) and those who were living in more disadvantaged areas (e.g., most vs. least disadvantaged: aPR, 1.22), born overseas (e.g., born in Southern or Eastern Europe vs. born in Australia or New Zealand: aPR, 1.20) or not proficient in English (aPR, 1.29). However, it was less common for females compared with males (aPR, 0.90) and those living remotely (e.g., very remote vs. major cities: aPR, 0.43).

CONCLUSION: While most people in Australia do not receive continuous care in general practice with a specific provider, those with greater healthcare needs are more likely to. With ongoing policy reforms, monitoring continuity of care may provide insights into the consequences for quality of care.

PMID:42310274 | DOI:10.5694/mja2.70229

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Nevin Manimala Statistics

Prognosis of ER-positive, HER2-negative postmenopausal early breast cancer patients based on response to neoadjuvant endocrine therapy and multigene assay results: findings from the NEOS trial

Breast Cancer. 2026 Jun 18. doi: 10.1007/s12282-026-01862-3. Online ahead of print.

ABSTRACT

BACKGROUND: We previously reported the 21-gene Oncotype DX® assay results from TransNEOS in patients enrolled in the phase 3 NEOS trial. However, the association between assay results and long-term prognosis has remained unclear.

METHODS: Of the 296 patients registered in TransNEOS, 226 patients were enrolled in this study. Multigene assay results were categorized into three groups based on Recurrence Score® (RS): RS low < 11, RS intermediate 11-25, RS high > 25. Kaplan-Meier methods evaluated the association between RS results and DDFS and OS across treatments and clinical response to neoadjuvant endocrine treatment (NET).

RESULTS: The clinical efficacy of NET was judged as CR, PR, and SD in 4 (1.8%), 113 (50%), and 109 (48.2%) patients, respectively. In the RS low and intermediate groups, no statistically significant difference in DDFS or OS was observed between the endocrine therapy (ET) alone group and the chemoendocrine therapy (CT + ET) group. In the RS high group, OS was significantly lower in the ET group compared to the CT + ET group (p = 0.037). Among patients in the RS high group who achieved CR + PR response to NET, there was no significant difference in OS between the CT + ET group and the ET alone group (p = 0.25). However, the number of events was limited, and the study may have been underpowered to detect a meaningful difference.

CONCLUSIONS: The need for chemotherapy in postmenopausal HR + , HER2- breast cancer patients might be further informed by integrating the results of the Oncotype DX test with the response to NET.

PMID:42310258 | DOI:10.1007/s12282-026-01862-3

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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