HolistIC: leveraging Hi-C and whole genome shotgun sequencing for double minute chromosome discovery.

MOTIVATION: Double minute (DM) chromosomes are acentric extrachromosomal DNA artifacts that are frequently observed in the cells of numerous cancers. They are highly amplified and contain oncogenes and drug-resistance genes, making their presence a challenge for effective cancer treatment. Algorithmic discovery of DM can potentially improve bench-derived therapies for cancer treatment. A hindrance to this task is that DMs evolve, yielding circular chromatin that shares segments from progenitor DMs. This creates DMs with overlapping amplicon coordinates. Existing DM discovery algorithms use whole genome shotgun sequencing (WGS) in isolation, which can potentially incorrectly classify DMs that share overlapping coordinates. RESULTS: In this study, we describe an algorithm called 'HolistIC' that can predict DMs in tumor genomes by integrating WGS and Hi-C sequencing data. The consolidation of these sources of information resolves ambiguity in DM amplicon prediction that exists in DM prediction with WGS data used in isolation. We implemented and tested our algorithm on the tandem Hi-C and WGS datasets of three cancer datasets and a simulated dataset. Results on the cancer datasets demonstrated HolistIC's ability to predict DMs from Hi-C and WGS data in tandem. The results on the simulated data showed the HolistIC can accurately distinguish DMs that have overlapping amplicon coordinates, an advance over methods that predict extrachromosomal amplification using WGS data in isolation. AVAILABILITY AND IMPLEMENTATION: Our software, named 'HolistIC', is available at http://www.github.com/mhayes20/HolistIC. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Safety Net Primary Care Capabilities After the COVID-19 Pandemic.

Importance: Federally qualified health centers (FQHCs) provide care to 30 million patients in the US and have shown better outcomes and processes than other practice types. Little is known about how the COVID-19 pandemic contributed to FQHC capabilities compared with other practices. Objective: To compare postpandemic operational characteristics and capabilities of FQHCs with non-FQHC safety net practices and non-FQHC, non-safety net practices. Design, Setting, and Participants: This nationally representative survey conducted from June 2022 to February 2023 with an oversampling of safety net practices in the US included practice leaders working in stratified random selection of practices based on FQHC status, Area Deprivation Index category, and ownership type per a health care network dataset. Exposures: Practice type: FQHC vs non-FQHC safety net and non-FQHC practices. Main Outcomes and Measures: Primary care capabilities, including 2 measures of access and 11 composite measures. Results: A total of 1245 practices (221 FQHC and 1024 non-FQHC) responded of 3498 practices sampled. FQHCs were more likely to be independently owned and have received COVID-19 funding. FQHCs and non-FQHC safety net practices were more likely to be in rural areas. FQHCs significantly outperformed non-FQHCs on several capabilities even after controlling for practice size and ownership, including behavioral health provision (mean score, 0.53; 95% CI, 0.51-0.56), culturally informed services (mean score, 0.55; 95% CI, 0.53-0.58), screening for social needs (mean score, 0.43; 95% CI, 0.39-0.47), social needs referrals (mean score, 0.53; 95% CI, 0.48-0.57), social needs referral follow-up (mean score, 0.31; 95% CI, 0.27-0.36), and shared decision-making and motivational interviewing training (mean score, 0.53; 95% CI, 0.51-0.56). No differences were found in behavioral and substance use screening, care processes for patients with complex and high levels of need, use of patient-reported outcome measures, decision aid use, or after-hours access. Across all practices, most of the examined capabilities showed room for improvement. Conclusions and Relevance: The results of this survey study suggest that FQHCs outperformed non-FQHC practices on important care processes while serving a patient population with lower incomes who are medically underserved compared with patients in other practice types. Legislation to expand funding for the FQHC program should improve services for underserved populations and target current non-FQHC safety net practices to serve these populations. Increased support for these practices could improve primary care for rural populations.

Video-based telehealth in Australian primary health care: current use and future potential.

Many Australians have limited access to health-care services due to a range of barriers, including geographic distance and restricted mobility, which telehealth can potentially address. This paper reviews the current and potential use of video consultation in primary health care in Australia, drawing on international literature. There is substantial evidence of high patient satisfaction, but many studies have methodological limitations. Overall, evidence of effectiveness and cost-effectiveness is weak. There is reasonable evidence for diagnosis, home care and specialist consultations by GPs with patients present. Two telehealth initiatives using video consultation are briefly presented. Both provide evidence that video consultation has a valuable role to play, but does not obviate the need for face-to-face consultations. Video consultation challenges traditional professional roles, particularly those of nurses, and can improve health workers' skills and job satisfaction. More fundamentally, telehealth challenges the traditional distinction between primary and secondary care. This can be a source of resistance but may ultimately be one of its strengths. Appropriately targeted video consultation has much potential to improve the delivery of primary health care in Australia, particularly in rural and remote regions.