Browse Articles

Health system costs and systemic treatment patterns by disease stage for 8577 people diagnosed with melanoma in New South Wales, Australia 2006–2019

Background Australia has the highest melanoma rates in the world. Melanoma is the third most common invasive cancer in Australia, and the number of in situ diagnoses is rapidly increasing. Treatment for non-localised stage melanoma is evolving, improving survival and increasing costs. We describe the costs and selected treatments by stage of disease for people diagnosed with melanoma in a large Australian cohort study. Methods Questionnaire data for participants in the Australian 45 and Up Study (n = 267,357 recruited 2005–2009) were linked with cancer registrations, hospital records and Medicare claims records. To estimate the government healthcare costs attributable to melanoma, total costs for each participant with melanoma were compared to costs for matched cancer-free controls. Multivariable gamma regression was used to estimate factors associated with costs. We also examined the distribution of melanoma treatments by disease stage. Results There were 8577 participants diagnosed with melanoma after recruitment (5026 in situ and 3551 invasive; median age 69 years at diagnosis). The mean excess per-person costs in the first year after diagnosis (‘initial phase’) ranged from $2794 Australian dollars (US$1825) for in situ melanoma to $70,070 for distant metastases. The corresponding mean annual costs in the continuing care phase were $1222 and $38,470, respectively. Of 195 participants with regional/metastatic melanoma diagnosed 2014–2019, 80 (41%) had a record of immunotherapy/targeted therapy and their unadjusted per-person costs were approximately $60,000 higher annually than the 115 participants without these treatments. Conclusions Health system costs increased greatly with advancing melanoma stage, with higher costs linked to uptake of new immunotherapies/targeted therapies. Cost savings could arise from initiatives that detect and successfully treat melanomas at earlier stages, or prevent melanomas entirely.

Cervical spine extension associated with reduced anatomical risk of spinal canal perforation in a cadaveric study

Interfacial chirality-induced magnetic-field-free switching with high energy efficiency in all-vdW heterostructures

Cumulative loneliness and social isolation are associated with incident glaucoma in Chinese and US cohorts

Abstract To investigate the association of cumulative loneliness and social isolation with glaucoma risk among middle-aged and older adults in Chinese and American populations, we conducted an observational cohort study using data from the China Health and Retirement Longitudinal Study (CHARLS; n  = 7,098 for loneliness and n  = 8,481 for social isolation) and the Health and Retirement Study (HRS; n  = 6,982 for loneliness and n  = 5,011 for social isolation). Cumulative exposure was defined as reporting loneliness or social isolation at two time points (0, 1, or 2 times). In CHARLS (median follow-up: loneliness 4.90 years, social isolation 4.89 years; incident glaucoma cases: loneliness 185, social isolation 221), one-time loneliness (HR 1.49; 95% CI 1.01–2.20) and two-time loneliness (HR 1.99; 95% CI 1.39–2.86) were associated with a higher risk of self-reported incident glaucoma. Similar associations were observed for one-time social isolation (HR 1.47; 95% CI 1.01–2.15) and two-time social isolation (HR 1.77; 95% CI 1.14–2.76). In HRS (median follow-up: loneliness 4.86 years, social isolation 5.09 years; incident glaucoma cases: loneliness 566, social isolation 347), only two-time cumulative exposure was significantly associated with a higher risk of self-reported incident glaucoma: loneliness (HR 1.38; 95% CI 1.05–1.83) and social isolation (HR 1.30; 95% CI 1.01–1.66). These observational findings suggest that cumulative loneliness and social isolation may be relevant psychosocial markers for future eye-health research and should be interpreted as associative and hypothesis-generating.

Visualizing dual-sites synergistic catalysis in non-iridium catalysts for acidic oxygen evolution reaction

An investigation of the abnormalities in the microbiome‑gut‑brain axis in betel quid chewers

Atomic-scale mechanism of anisotropic ion migration in 2D Bi2O2Se nanodevices

Fecal microbiome profiles in uncomplicated right colonic diverticulitis: An exploratory prospective case–control study

Local deformation mapping reveals diffusion through microstructures

Somatic pathogenic mitochondrial DNA mutations independently predict worse prognosis in hepatocellular carcinoma

Abstract Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide, but its cancerization and progression mechanisms are still poorly understood. Mitochondrial DNA (mtDNA) mutations have been involved in tumor progression by influencing metabolic rewiring and plasticity. In this work, we aimed to investigate the contribution of mtDNA mutations to the pathogenesis and prognosis of HCC. Whole exome sequencing data from the TCGA-LIHC project were used to reconstruct the mitochondrial genomes. Discovered variants were classified using the HmtVar pathogenicity scoring system and the ACMG/AMP standard guidelines. The validation of results was performed on a separate in-house cohort of selected HCC cases from our hospital. Pathogenic mtDNA mutations were present in 33.6% of patients. GSEA revealed pathogenic mtDNA mutations mainly targeting the reactive oxygen species (ROS) pathway, suggesting an increased ROS production in these tumors which may contribute to the survival, proliferation and metastatization capacity. Survival analysis revealed a significant decrease in the overall survival of patients harboring pathogenic mtDNA variants ( p  = 0.01). A similar trend was observed in the validation cohort. Overall, we showed that somatic mtDNA mutations occur in a significant proportion of HCC cases, expectedly acting as modifiers on the ROS pathway, and that their occurrence confers a worse prognosis.

Fermionic parton theory of Rydberg $${{\mathbb{Z}}}_{2}$$ quantum spin liquids

Abstract Programmable quantum simulators based on neutral atom arrays today offer powerful platforms for studying strongly correlated phases of quantum matter. Here, we employ the projective symmetry group framework to describe the symmetry fractionalization patterns in a topologically ordered $${{\mathbb{Z}}}_{2}$$ Z 2 quantum spin liquid (QSL) synthesized in such a Rydberg array on the ruby lattice. By systematically comparing the static structure factors of all possible mean-field Ansätze against density-matrix renormalization group calculations, we identify a promising candidate for the precise $${{\mathbb{Z}}}_{2}$$ Z 2 QSL realized microscopically. We also present detailed analyses of the dynamical structure factors as a reference for future experiments and showcase how these spin correlations can differentiate between varied QSL Ansätze .

Sedentary behaviour is linked to impaired postural balance but not gastrocnemius medialis tendon properties in older adults

Abstract Sedentary behaviour is increasingly recognised as a distinct physiological risk factor in ageing; however, its relationship with intrinsic tendon properties and postural balance remains undefined. The objective of this study was to determine whether Sedentary Behaviour is independently associated with gastrocnemius medialis tendon properties and postural balance in older adults, after accounting for physical activity. Healthy older adults ( n  = 105) completed this cross-sectional investigation. Habitual physical behaviour was quantified over 7 days using triaxial accelerometry. All participants subsequently underwent assessments of gastrocnemius medialis tendon mechanical, material, and morphological properties, with postural balance assessed in a representative subgroup ( n  = 45). Associations were examined using single and multiple linear regression, compositional data analysis, and isotemporal substitution models. Covariates were identified via univariate General Linear Model and entered using backward elimination prior to inclusion of behavioural predictors. Sedentary behaviour levels did not significantly predict gastrocnemius medialis tendon properties or balance outcomes in unadjusted models. Following covariate adjustment, Sedentary behaviour emerged as a significant negative predictor of eyes-open balance trial duration, representing the only independent SB-related effect across 18 outcome variables. Compositional analyses revealed significant model fits for multiple outcomes; however, these associations were substantially attenuated after covariate adjustment, suggesting no significant influence of Sedentary behaviour on gastrocnemius medialis tendon characteristics. Isotemporal substitution indicated small relative outcome changes (–0.71% to + 0.56%) following 10-minute behavioural reallocations. Although Sedentary behaviour pattern parameters were associated with select tendon and balance variables, most significant models were driven predominantly by covariates rather than Sedentary behaviour metrics. This study provides novel evidence that Sedentary behaviour is not independently associated with gastrocnemius medialis tendon structure and mechanics in older adults, yet is associated with poorer postural balance performance. These findings suggest that the association between Sedentary behaviour and postural balance is unlikely to be mediated by tendon degradation and instead implicate neural and motor control pathways as plausible mechanisms. Reducing sedentary time through increased physical activity may help mitigate balance deterioration and preserve functional independence with ageing.

Structure of cytoplasmic RNA polymerase II

Abstract RNA polymerase II (Pol II) must be assembled in the cytoplasm before it enters the nucleus, where it transcribes protein-coding genes. Although transcription by Pol II is intensively studied, how this central multi-subunit enzyme is made and the role of dedicated assembly factors remains unclear. Here, we report the integrative structural analysis of a native human Pol II from the cytoplasm captured near the end of biogenesis. The complex contains Gdown1 and three biogenesis factors – RPAP2 and the critical small GTPases GPN1 and GPN3. Cryo-EM analysis of the complex reveals how Gdown1 and RPAP2 associate with Pol II and prevent the premature association of transcription factors. Further biochemical and cryo-EM analysis reveals how RPAP2 tethers GPN1–GPN3 to the complex and how the assembly of the RPAP2–GPN1–GPN3 complex is controlled by GTP hydrolysis. The combined results uncover a network of interactions that chaperone cytoplasmic Pol II to prevent aberrant interactions, reveal a molecular switch regulating biogenesis factor association, and suggest a general mechanism for the action of GPN-loop GTPase family of enzymes.

Grey–green spatial morphology relates to summer daytime and nighttime land surface temperature across local climate zones in Wuhan

Ultra-flexible optoelectronic stimulator converts tissue-attenuated weak light into electrical signals for cardiac remodeling

Abstract Precise spatiotemporal resolution and wireless multi-site modulation of excitable tissues via optoelectronics offers transformative potential for bioelectronic medicine, yet clinical translation is hindered by the rigidity of conventional silicon-based devices and their reduced performance under tissue-attenuated illumination, where the weak light reaching implants often fails to generate sufficient stimulation voltage. Here, we report an ultra-flexible, high-efficiency optoelectronic stimulator (OES) based on (Bi,Sb) 2 Se 3 , a semiconductor with crystal structure comprising parallel 1D chains that enable efficient flexibility and photocarrier transport. The OES achieves robust photoelectric conversion under near-infrared light intensities as low as 0.55 μW cm −2 , reaching quantum efficiency of up to 89.60% while conforming seamlessly to soft tissues. In a rat model of myocardial infarction, the OES restored electrical conduction across infarcted regions and improved cardiac function under weak-light stimulation. Scalable fabrication yields large-area devices without loss of performance, as validated in a swine model. This work introduces a clinically translatable optoelectronic platform for soft-tissue modulation under low-power light, establishing a foundation for next-generation, minimally invasive cardiac repair technologies.

Extensively drug-resistant and extended spectrum β-lactamase-producing Raoultella terrigena from the reproductive tract of a mare in Australia

Genetic or pharmacological inhibition of hepatic TMEM141 attenuates MASH and fibrosis via the ROS-HNF4α signaling pathway

Sharpness matters: Higher image resolution improves generalization and explainability in chest X-ray classification

A tumor profiling resource for ovarian cancer: insights into chemotherapy-driven heterogeneity and personalized treatment strategy

Abstract In women with high-grade serous ovarian cancer, chemotherapy remains the primary standard treatment, despite growing recognition of the disease as highly heterogeneous. Here, we examine the feasibility and clinical utility of comprehensive multimodal molecular profiling to inform treatment decisions. We analyze blood, single-cell and bulk tumor tissue, and malignant ascites using up to eleven technologies (DNA, RNA, protein, and functional assays) within a four-week turnaround time. Hypothetical treatment recommendations are altered for 76% of patients, and multi-omics-guided maintenance therapy is associated with prolonged overall survival in a subset of patients. Subsequent cohort analysis reveals distinct cellular and molecular profiles in ascites-derived single-cells compared to solid tumor tissue, unique per-patient ex vivo drug responses, and a marked increase in cancer cell heterogeneity following chemotherapy exposure. This coincides with genomic signature alterations in whole-genome-amplified patients. Our data suggest that molecularly guided treatments should be tested as adjuvant therapies prior to chemotherapy in the future.

Cross-domain intelligent fault diagnosis with superlet spectrograms and a parameter-efficient CNN-Transformer hybrid

Abstract Smart fault diagnosis is a crucial component of modern industrial systems, offering early detection of machine conditions to prevent costly breakdowns and safety issues. While state-of-the-art deep learning models are capable of near-perfect classification on controlled laboratory data, they often perform poorly in practice because of noisy environments, class imbalance and distribution shifts across operating conditions. This paper addresses these challenges by re-formulating industrial acoustic monitoring as a supervised image classification problem with superlet time-frequency representations, which capture both the transient dynamics and phase-envelope. An efficient CNN-Transformer hybrid model is proposed by placing a lightweight Transformer encoder on an ImageNet-pretrained ResNet-50 backbone with spatial attention gating to learn both local and global spectro-temporal features. The proposed architecture is lightweight, with 25.6M parameters and 4.1G FLOPs, supporting efficient resource usage. An asymmetric focal contrastive learning strategy is also proposed to improve anomaly discrimination under extreme imbalance. Experimental results on the MIMII dataset demonstrate that the proposed framework achieves 94.82% accuracy, 91.08% balanced accuracy, 91.72% F1-score, and 0.9758 ROC-AUC under a strict group-aware evaluation protocol, while requiring only 25.6M parameters, 4.1G FLOPs, and 4.5 ms inference time per sample. In cross-domain evaluation on the CWRU dataset, the model further achieves a zero-shot AUC of 0.8886 and a fine-tuned AUC of 1.0000 within three epochs. These results validate that the proposed framework provides an effective, robust, and generalizable solution for industrial fault diagnosis.