PNAS Nexus

Biological fitness quantifies the efficiency and selective advantage of pathogens and hosts in their bilateral interaction. Key questions--such as how much more infectious an emerging variant is compared with its predecessor, or how much protection vaccination offers relative to no vaccination--require fitness to be measured systematically, in real time, and ideally beyond controlled laboratory settings. We propose an approach that infers biological fitness from mostly non-biological data on inf...

Immunotherapy with immune checkpoint inhibitors and immunotherapy combined with chemotherapy have represented promising treatments for NSCLC patients leading to prolonged survival. However, the majority of patients with advanced NSCLC have a poor prognosis. The identification and development of biomarkers for stratifying responders and non responders to immune checkpoint inhibitors contribute to unravel the mechanism of immune checkpoint pathway and the immune tumor interaction underlying the re...

IntroductionThe precise determination of diagnostic cut-off points is essential for the development of multimarker panels in oncology. In previous work on pulmonary nodules, it was observed that the standard two-parameter logistic fit could be insufficient for biomarkers with asymmetric distributions. Furthermore, the calculation of empirical cut-off points based on graphical visualization presented limitations in precision and reproducibility. ObjectiveThis study presents a methodological adva...

IntroductionDespite advancements in non-small cell lung cancer (NSCLC) management through the use of molecular biomarkers, the recently introduced 9th edition of the TNM staging system remains based exclusively on anatomic descriptors, with no consistently demonstrated improvement in risk stratification for early-stage disease. This study explores the integration of a molecular prognostic classifier into the conventional TNM staging system. MethodsWe analyzed 502 patients with stage I-III lung ...

Wastewater-based surveillance (WBS) is widely used to monitor respiratory viruses, yet uncertainties remain regarding how viral RNA concentrations in wastewater reflect infection dynamics. Specifically, diurnal variation in shedding and RNA losses during in-sewer transport can impact measured signals. We conducted a field study in a 5-km trunk sewer (travel time of one hour). Wastewater was sampled at the sewer inlet and outlet using autosamplers collecting time-proportional one-hour composite s...

AO_SCPLOWBSTRACTC_SCPLOWLung cancer is characterized by profound intratumoral and inter-patient heterogeneity, spanning histological subtypes, molecular landscapes, and the tumor microenvironment. While multi-omics integration is essential for capturing this complexity, leveraging these data to explicitly define survival-associated subpopulations remains a significant challenge. In this study, we developed NeuroMDAVIS-FS, an unsupervised deep learning framework designed to stratify lung cancer p...

Applying deep learning models to RNA-Seq data poses substantial challenges, primarily due to the high dimensionality of the data and the limited sample sizes. To address these issues, this study introduces an advanced deep learning pipeline that integrates feature engineering with data augmentation. The engineering application focuses on biomedical engineering, specifically the classification of RNA-Seq datasets for disease diagnosis. The proposed framework was initially validated on synthetic d...

PurposeWe introduce PRE-CISE, a pre-calibration workflow that integrates coverage analysis, local sensitivity, and collinearity diagnostics to streamline model calibration and transparently address nonidentifiability. We demonstrate the benefits of PRE-CISE using a four-state Sick-Sicker Markov testbed and a COVID-19 case study. MethodsPRE-CISE begins with a coverage analysis to verify that model outputs generated with parameter sets drawn from their prior distribution span calibration targets,...

BackgroundClimate change is increasingly recognised as a threat to population health and healthcare systems, yet the effects of environmental variability on pharmaceutical prescribing remain poorly characterised in the UK. Using a wide array of open-source datasets, we examine the effect of environmental, geographic and socioeconomic factors on prescribing habits in England. MethodsWe linked monthly, practice-level prescribing data for England (2010-2025) to meteorological, air-quality, floodin...

With significant population fractions in many societies who refuse vaccines, it is important to reconsider how vaccination is incorporated into compartmental epidemiology models. It is still most common to apply the vaccination rate to the entire class of susceptibles, rather than to use the more realistic assumption that the vaccination rate function should depend only on the population of susceptibles who are willing and able to receive a vaccination. This study uses a simple generic disease m...

BackgroundRoutine immunization (RI) is widely used to increase population immunity against measles. In low-resource settings, achieving immunity goals using RI alone has proved challenging and supplemental immunization activities (SIAs), large community-based vaccination campaigns conducted every few years, have been used to close immunity gaps. Although effective at covering the population unreached by RI and boosting the population immunity, SIAs are labor-intensive and expensive, allowing for...

BackgroundVaccines can prevent severe disease by preventing infection or by reducing progression among those who become infected. Vaccine effectiveness against progression given infection is often used to quantify this second mechanism, but it conditions on infection, which is itself affected by vaccination. As a result, this estimand lacks a clear causal interpretation and may behave non-intuitively over time. MethodsWe introduce a conceptual framework that models protection against infection ...

ObjectiveThis study investigates the prevalence of human pegivirus (HPgV) in SARS-CoV-2-positive patients within the context of viral co-infections that may modulate COVID-19 outcomes and assesses whether HPgV co-infection is associated with COVID-19 severity. HPgV is a widely circulating but rarely monitored human virus with documented immunomodulatory effects in other viral infections, including HIV and Ebola. While HPgV prevalence is low in the general U.S. population (1-2%), it rises markedl...

Digital health technologies are powerful-enhancing data collection, participant engagement, and personalized health interventions-yet their rapid proliferation has outpaced guidance for research participant protection. Current practice assists researchers in identifying risks but provides limited support for comprehensive risk management. To address this gap, we developed the Digital Health Checklist-Risk Management (DHC-RM) Tool, which integrates the established Digital Health Checklist with ap...

ObjectivesEstimate the HIV testing, diagnoses, and test positivity rates among Medicaid beneficiaries in 2016-2021 and assess the impact of the COVID-19 pandemic on these outcomes. DesignProspective observational study of Medicaid enrollment, inpatient, and outpatient claims data from 27 states, 2016-2021. MethodsWe assessed Medicaid claims from adult beneficiaries with full benefits whose first continuous enrollment was [≥]6 months without dual enrollment in other insurance, and without pr...

BackgroundRecreational cannabis legalization has expanded rapidly across US states. The regulatory approaches states adopt vary widely, with varying implications for public health. This study aimed to characterize heterogeneity in recreational cannabis laws (RCLs) across US states and to identify state-level characteristics associated with these regulatory models. MethodsWe conducted Latent Class Analysis (LCA) of state-year RCL provisions from 2013 to 2024 (n=612) to identify distinct RCL appr...

The COVID-19 pandemic has presented severe challenges in understanding and predicting the spread of infectious diseases, necessitating innovative approaches beyond traditional epidemiological models. This study introduces an advanced method for automated model discovery using the Sparse Identification of Nonlinear Dynamics (SINDy) algorithm, leveraging a dataset from the COVID-19 outbreak in Thuringia, Germany, encompassing over 400,000 patient records and vaccination data. By analysing this dat...

Schistosomiasis is a neglected parasitic disease caused by various trematode species of the genus Schistosoma for which 251 million people needed treatment in 2021. Many mathematical models of Schistosoma mansoni transmission incorporate the effect of chemoprophylaxis on parasite burden within the human host. While praziquantel is the most commonly implemented pharmaceutical used to control schistosomiasis, due to its applicability over several species and its negligible side effects, it is not ...

Accurate identification of unknown pathogens is critical for medicine and public health, yet current metagenomic workflows remain heavily dependent on specialized bioinformatics expertise and manual interpretation, creating substantial bottlenecks in time-sensitive diagnostic settings1. The key challenges lie in achieving precise species identification amidst high background noise and translating complex microbial data into clinically actionable insights2,3. Here we present the Global Pathogen A...

PurposeTo develop and validate a prediction model for sleep apnea syndrome (SAS) treated with continuous positive airway pressure (CPAP) in the general population. MethodsUsing claims and health checkup data held by JMDC Inc., linked to personal health records (Pep Up), we developed and internally validated a prediction model for SAS treated with CPAP, defined as a diagnosis of SAS and reimbursement records of CPAP. Every three months from January 1, 2022 to July 1, 2024 (i.e., 11 timepoints), ...