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Characteristics and Outcomes of Gene-Elusive Dilated Cardiomyopathy

Background and Aims Genetic testing in dilated cardiomyopathy (DCM) guides risk stratification and family screening. Likely pathogenic or pathogenic (LP/P) variants are identified in approximately one-third of patients, leaving many without a genetic diagnosis. Cohort studies suggest that "gene-elusive" patients have a lower risk of adverse events. This study aims to better characterise this group and identify factors associated with adverse outcomes. Methods Consecutive and unrelated DCM patients undergoing genetic testing and returning no LP/P variants were retrospectively recruited and compared to two control cohorts of DCM patients carrying LP/P variants in LMNA and TTN for a primary composite endpoint of end-stage heart failure (ESHF) or malignant ventricular arrhythmia (MVA). Results Among patients without prior MVA, the composite endpoint occurred in 36/423 (8.5%) gene-elusive, 14/39 (35.9%) LMNA and 11/100 (11%) TTN cardiomyopathy patients (log-rank p

Cross-Device Adaptation of Mirai for Mammography-Based Breast Cancer Risk Prediction

Fine-tuning can adapt pretrained medical imaging models to new clinical datasets, but device-specific domain shifts may limit generalizability. We evaluated Mirai, a mammography-based deep learning model for breast cancer risk prediction, in a large screening cohort containing Hologic and General Electric (GE) full-field digital mammography systems, including GE Premium View (GE PV) and Tissue Equalization (GE TE) post-processing software. Native Mirai showed lower performance on TE images than on Hologic or PV images. Fine-tuning on TE images improved TE performance, particularly for short-term risk prediction, but substantially reduced performance on Hologic images, consistent with catastrophic forgetting. To mitigate this effect, we developed a device-invariant model using interleaved multi-device sampling and conditional adversarial training. This approach largely restored Hologic performance while maintaining improved TE performance, providing better robustness across heterogeneous imaging platforms. Comparison of cumulative and annual risk AUCs over a five-year time horizon further showed that performance gains were driven mainly by short- and intermediate-term predictions. These findings highlight both the value and dangers of device-specific fine-tuning and support balanced domain-adaptation strategies for deploying mammography-based risk models across diverse clinical imaging environments.

On the Energy Distribution of the Galactic Center Excess' Sources

arXiv:2507.17804v2 Announce Type: replace-cross Abstract: The Galactic Center Excess (GCE) may yet herald the discovery of annihilating dark matter. Weighing against that conclusion are analyses showing evidence for dim point sources within the spatial structure of the emission. Due to technical limitations these analyses are purely spatial with all spectral information that could disentangle the excess from astrophysical backgrounds discarded. Here, we demonstrate that a neural network simulation-based inference approach can jointly analyze the spatial and spectra data. The addition is profound: energy information drives the putative point sources to be significantly dimmer, indicating either the GCE is truly diffuse in nature or made of an exceptionally large number of sources. Quantitatively, for our best fit background model, the excess is essentially consistent with Poisson emission as predicted by dark matter. If due to point sources, our median prediction is $\mathcal{O}(10^5)$ sources, or more than 35,000 at 90\% confidence, both orders of magnitude larger than the hundreds preferred by earlier point-source analyses of the GCE, although variations allowed by background systematics could reduce the required number of sources by roughly an order of magnitude.

Social networks and their association with quality of life among older adults in rural Burkina Faso

Objective: This study aimed to identify the types of social networks present among older adults in a rural, low-income country setting and describe their association with quality of life (QoL). Methods: A population-representative, cross-sectional survey was conducted in 60 villages around Nouna in Burkina Faso from July to August 2021. Data were collected from resident adults aged 40 years and older. Variables captured were sociodemographic status; social network characteristics (using the Practitioner Assessment of Network Typology (PANT)); quality of life (using the EuroHIS-8 tool); presence of non-communicable diseases, mental health conditions, and disability. Additionally, social networks were broadly categorised as aggregated integrated and aggregated less-integrated groups. Social network types and the groups were described separately, and a multivariable linear regression model was used to understand the association between social network types and QoL, adjusted for sociodemographic and morbidity factors. Results: Among the 2390 respondents, median age was 55 yrs (IQR: 47-64 yrs) and 55.8% were female. Locally Integrated (35.4%) or Family Dependent (30.3%) were the most common PANT social network types, followed by a mixed group (having characteristics of two or more social network types) (30.5%). Private Restricted (2.1%), Locally Self-Contained (1.2%), and Wider Community-Focussed (0.4%) types were uncommon. Adults with aggregated integrated network groups (36.1%) and aggregated less-integrated group (36.0%) were near equal, while others were non-aggregable. Although Wider Community-Focused type showed a significantly better QoL ({beta}= 8.69, 95%CI: 4.10 to 13.27), the association between social networks and QoL were subdued when controlled for morbidity factors, and hence no significant associations were observed between other types or the aggregated groups. Conclusion: Although having integrated social networks lead to a better QoL, morbidity has a greater effect on the QoL among older adults in Nouna and hence, investing more on improving the physical and mental health needs appears more beneficial.

''Circumstantial Determinants'': An Efficient Approach to Reaching People in Need of HIV Prevention?

HIV prevention and testing programmes primarily reach people who self-refer or attend routine health services. Higher-risk individuals are missed if they are healthy, under-estimate their risk of infection or under-report sexual risk-behaviours. We assess a new approach to address limitations in existing programmes by targeting HIV services on ''Circumstantial Determinants'' (CDs) of HIV risk - the social circumstances, settings, and norms associated with behaviours that increase risk of HIV acquisition. Data on potential CDs and sexual behaviour were collected in a population survey in Zimbabwe in 2018/19 (N=9141). HIV-negative individuals reporting [≥] 1 sexual risk-behaviours were defined as the 'priority population' for HIV prevention. For each sex, six circumstantial determinants were associated with being in the priority population (aOR [≥] 1.30; p [≤] 0.01). Reach and efficiency of CDs (and combinations) were calculated; ROC curve algorithms evaluated their ability to identify priority population membership; and HIV prevention condom cascades were compared between CD-defined priority population subgroups. Example findings include that targeting men at bars and beerhalls could reach 48.5% of the priority population and 25.1% of lower-risk men. These percentages increase to 77.1% and 53.7% if men with poor mental health, no religious affiliation, negative social capital, or living on agricultural estates are also targeted. Targeting women with poor mental health could reach 32.0% of the priority population and 21.3% of lower-risk women. Targeting additional circumstantial determinants increases these percentages to 54.1% and 37.5%, respectively. Cascade barriers to condom use differed between CD-defined subgroups. The Circumstantial Determinants approach demonstrates proof-of-concept potential to strengthen HIV prevention services.