Open Society Foundations

To propose a clinico-iconographic diagnosis of gouty tophi in Domenico Fetti’s painting Portrait of a Scholar (Archimedes) and to evaluate the morphological features in relation to differentialdiagnoses such as osteoarthritis and rheumatoid arthritis. A detailed visual and morphological analysis of the painting was conducted, focusing on the anatomical features of the depicted hand. The observed characteristics were interpreted within aclinical framework and compared with known manifestations of gout, osteoarthritis, and rheumatoid arthritis. The evaluation followed the International Guidelines for Iconodiagnosis. The painting shows nodular formations at the level of the thumb, as well as the proximal and distal interphalangeal joints of the index finger and the interphalangeal joint of the third finger.These features are consistent with tophaceous deposits observed in chronic gout. The distribution and morphology of the nodules are less compatible with osteoarthritis and rheumatoid arthritis, basedon their typical clinical patterns. The clinico-iconographic correlation supports a retrospective diagnosis of probable chronic gouty arthritis, with a Level of Evidence II. This study highlights the value of artworks as potentialhistorical sources for medical observation, bridging art history and clinical interpretation.

Introduction “Work therapy” is not an evidence-based treatment for substance use disorders. Nevertheless, many substance use service providers impose labor obligations. The purpose of this study was to describe the prevalence and correlates of obligatory labor at providers of residential substance use services in North Carolina. Methods This audit study surveyed residential substance use service providers in North Carolina, systematically collecting program characteristics including obligatory labor. We used Fisher’s exact tests to assess associations between program characteristics and two conditions of interest: obligatory labor and obligatory labor in agency-owned and -operated commercial enterprises. We qualitatively described the nature of labor mandates as summarized by program staff. Results Of 66 providers surveyed, 28 (42.4%) mandated labor, and 20 (30.3%) mandated labor in an agency-owned or -operated commercial enterprises. Providers who imposed either of these mandates were more likely to be faith-based and operating without a state license for adult substance use services. Providers imposing labor requirements were more likely to offer residential services at low or no cost. Providers mandating labor in agency-owned and -operated commercial enterprises were more likely to restrict eligibility to persons meeting health and “able-bodiedness” requirements. Many providers described these labor obligations as therapeutic and mandatory. Conclusions More providers require residents to work in an agency-owned and operated commercial enterprise than allow access to opioid agonist treatment, the gold standard treatment for opioid use disorder. Adjustments to state regulations may help improve the availability of evidence-based services and increase regulatory supervision of these service providers.

Accurate genome annotation remains a bottleneck in plants, where polyploidy and repeat-rich sequence confound homology- and RNA-based pipelines. We introduce GeneCAD, a sequence-only method that predicts complete plant gene models directly from DNA. GeneCAD couples representations from a plant DNA foundation model, PlantCAD2, with a lightweight ModernBERT encoder and a chromosome-wide conditional random field that enforces splice-phase and feature order, and applies a protein language-model screen to suppress repeat-driven open reading frames. To limit label noise, we rank and filter public annotations using a sequence-based masked-motif score and fine-tune on five phylogenetically diverse, high-quality references. Across five held out angiosperms, including the allotetraploid Nicotiana tabacum, GeneCAD improves transcript-level F1 by 8–10% on average over Helixer and BRAKER3, increases exact match transcripts, and sharpens boundaries at start/stop codons and splice junctions. By removing dependence on species-matched RNA-seq or proteomics while retaining cross-species accuracy, GeneCAD provides an accurate, scalable route to biologically coherent plant gene models from DNA alone.

The modernisation of official statistics requires facilitating new forms of data collaboration between National Statistical Offices (NSOs), researchers, government agencies, and the private sector. However, privacy concerns, legal constraints, and organisational risks associated with data access often prevent valuable initiatives from being realised. This paper argues that privacy-enhancing technologies (PETs) can fundamentally transform how sensitive data is accessed and used, enabling these barriers to be more readily overcome, and thus unlocking data collaborations that would otherwise be impossible. Drawing on examples of pilot deployments conducted through the United Nations PET Lab, we demonstrate how applying combinations of PETs can provide robust privacy guarantees and granular governance controls that enable effective use of sensitive data assets. We provide a vision for a new ecosystem for official statistics where NSOs and researchers can securely access thousands more datasets from across sectors and jurisdictions.

BackgroundVariant Call Format (VCF) is the standard file format for interchanging genetic variation data and associated quality control metrics. The usual row-wise encoding of the VCF data model (either as text or packed binary) emphasizes efficient retrieval of all data for a given variant, but accessing data on a field or sample basis is inefficient. The Biobank-scale datasets currently available consist of hundreds of thousands of whole genomes and hundreds of terabytes of compressed VCF. Row-wise data storage is fundamentally unsuitable and a more scalable approach is needed.ResultsZarr is a format for storing multidimensional data that is widely used across the sciences, and is ideally suited to massively parallel processing. We present the VCF Zarr specification, an encoding of the VCF data model using Zarr, along with fundamental software infrastructure for efficient and reliable conversion at scale. We show how this format is far more efficient than standard VCF-based approaches, and competitive with specialized methods for storing genotype data in terms of compression ratios and single-threaded calculation performance. We present case studies on subsets of 3 large human datasets (Genomics England: n=78,195; Our Future Health: n=651,050; All of Us: n=245,394) along with whole genome datasets for Norway Spruce (n=1,063) and SARS-CoV-2 (n=4,484,157). We demonstrate the potential for VCF Zarr to enable a new generation of high-performance and cost-effective applications via illustrative examples using cloud computing and GPUs.ConclusionsLarge row-encoded VCF files are a major bottleneck for current research, and storing and processing these files incurs a substantial cost. The VCF Zarr specification, building on widely used, open-source technologies, has the potential to greatly reduce these costs, and may enable a diverse ecosystem of next-generation tools for analysing genetic variation data directly from cloud-based object stores, while maintaining compatibility with existing file-oriented workflows.

BackgroundNivolumab plus chemotherapy demonstrated clinically significant improvement in quality-adjusted survival versus chemotherapy alone as first-line treatment for advanced non-HER2-positive gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma (GC/GEJC/EAC) in the CheckMate 649 post-hoc quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis at 1-year minimum follow-up. We report Q-TWiST analysis results at 4-year minimum follow-up.MethodsQ-TWiST methodology was applied post-hoc to CheckMate 649 study data from all randomized patients, patients with PD-L1 combined positive score (CPS) ≥ 1, and patients with PD-L1 CPS ≥ 5. Relative Q-TWiST gains ≥ 10% were predefined as clinically important and ≥ 15% as clearly clinically important.ResultsAmong all randomized patients, patients with PD-L1 CPS ≥ 1, and patients with PD-L1 CPS ≥ 5, mean (95% CI) absolute Q-TWiST gains of 3.4 (1.8–5.1), 4.2 (2.4–6.1), and 5.4 (3.0–7.7) months with nivolumab plus chemotherapy versus chemotherapy were observed, respectively. These translated to clearly clinically important relative Q-TWiST gains of 20.5%, 26.1%, and 33.4% in each population; relative Q-TWiST gains benefit remained clearly clinically important in all subgroups (15.7%, 20.3%, and 26.4%) after expanding the analysis to include grade 2 adverse events. Greater Q-TWiST gains were observed with nivolumab plus chemotherapy across most subgroups in all randomized patients and patients with PD-L1 CPS ≥ 1 and across all subgroups in patients with PD-L1 CPS ≥ 5.ConclusionClearly clinically important benefit in quality-adjusted survival with first-line nivolumab plus chemotherapy versus chemotherapy was observed across all evaluated PD-L1 CPS expression levels in patients with advanced GC/GEJC/EAC from CheckMate 649 with 4-year minimum follow-up.Trial RegistrationClinicalTrials.gov identifier, NCT02872116.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10120-025-01634-6.

IntroductionHypoparathyroidism (HypoPT) is an endocrine disease caused by insufficient levels of parathyroid hormone and is associated with impaired health-related quality of life. This study assessed the clinical burden among individuals with postsurgical chronic HypoPT in Medicare Fee-For-Service.MethodsAdults (aged ≥ 18 years) with newly diagnosed HypoPT (N = 1166) were identified from the Medicare 100% Limited Data Set between July 1, 2017, and March 31, 2020. All had a confirmed diagnosis within 6–12 months after index diagnosis and were required to be continuously enrolled for ≥ 6 months pre index and ≥ 12 months post index. A random sample of non-HypoPT controls (N = 11,258) was synthetically assigned an index date of diagnosis to ensure similar baseline and follow-up periods as individuals with postsurgical chronic HypoPT. The two cohorts were compared before and after matching with respect to the risk of cardiovascular (CV) events, renal complications, urinary tract infections (UTIs), upper respiratory tract infections (URTIs), and mortality.ResultsIndividuals with postsurgical chronic HypoPT were older than non-HypoPT controls (mean age 69 vs. 64 years), more were female (76% vs. 57%), had higher Charlson Comorbidity Index scores (3.24 vs. 0.73), and a higher prevalence of moderate-to-severe renal disease (28.8% vs. 5.6%), nephrocalcinosis (59.9% vs. 0.6%), and nephrolithiasis (8.3% vs. 1.0%). They also had significantly greater mortality (hazard ratio [HR] 2.75). The incident risks of composite CV events (HR 1.35), renal complications (HR 4.92), UTIs (HR 2.09), and URTIs (HR 1.46) were greater in subcohorts without those conditions prior to index. After matching for baseline characteristics, the elevated risk of renal complications, UTIs, and URTIs remained while there was no difference in the risk of CV events or death between individuals with postsurgical chronic HypoPT and controls.ConclusionThe substantial clinical burden of postsurgical chronic HypoPT in Medicare patients highlights the treatment gaps associated with current therapy and the need for parathyroid hormone replacement therapies.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-025-03264-x.

The Varieties of Capitalism (VoCs) approach has the potential to transform economics. It implicitly emphasizes the plasticity of economies, whereby their character and outcomes are significantly a matter of choice. This paper augments VoCs theory to include a distinction between varieties and varietals of capitalism. Drawing on biology, varieties correspond to species and varietals correspond to sub-species. The paper proposes an analytical framework that unifies VoCs theory. It adds a mesoeconomics that links macroeconomics and microeconomics. That mesoeconomics concerns the institutions, behavioral norms, rules and regulations, and policies that characterize the economy and influence its performance. The mesoeconomic structure is described using the metaphor of a box, the six sides of which correspond to the major dimensions of capitalist economies. The design of the box is the product of societal and political choices, which places politics at the center of VoCs analysis. Policy space and policy lock-in are important concerns as they impact the choice set. The fact that economies inevitably involve choice means there is an inescapable normative question regarding what type of capitalism society will have.