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A causal discovery framework for digital phenotyping
Asymmetric attrition and secondary chromosome destabilization after double-strand breaks in human embryonic development
Abstract DNA repair in human embryos is poorly understood, and double-strand breaks (DSBs) can cause chromosome loss. We show that chromosomal alterations relative to an induced DSB are asymmetric: acentric arms show complementary gains and losses, while centric arms are biased toward losses. Centromeric to the cut site secondary breakage and attrition is extensive. In contrast, break sites at acentric arms are conserved with no secondary breakage. These differences reflect differential forces at the mitotic spindle. Telomeric arms detach from the pro-metaphase spindle while centric truncated chromosomes lag during anaphase, suggesting that the DSB impedes sister chromatid separation. Secondary breakage near the centromere concordant with extensive attrition at the DSB site indicates a DSB can destabilize a chromosome without end-joining of sister chromatids. These results highlight the risks of chromosomal-scale changes in CRISPR-Cas9 genome editing and show that a single DSB can destabilize a human embryo chromosome independent of fusion-breakage cycles.
Cell-type-resolved genetic variation shapes inflammatory bowel disease risk
Abstract Most genetic variants associated with complex diseases lie in non-coding regions 1 , complicating efforts to identify effector genes and relevant cell types. Here we map cis -expression quantitative trait loci (eQTLs) across 2.2 million single cells using intestinal biopsies and blood from 421 individuals, including 125 with inflammatory bowel disease (IBD). Cell-type-level eQTLs were more distal to transcription start sites, enriched in enhancers, less likely to regulate the nearest gene, and more than 3.5-fold more likely to colocalize with IBD loci detected in genome-wide association studies (GWASs) than eQTLs detected at tissue-level resolution. We nominate effector genes at more than half of known IBD loci, including MAML2 , PSEN2 and ZMIZ1 in myeloid cells, implicating reduced Notch signalling in intestinal immune dysfunction. We also identify Wnt-regulated genes, including MYC , in epithelial stem and progenitor cells, suggesting that impaired renewal contributes to barrier breakdown. Our results provide a mechanistic map that links genetic risk to specific genes and cell types in IBD, and a generalized framework for interpretation of GWAS loci using single-cell eQTL mapping of disease-relevant tissues in complex diseases.
Integrated self-management interventions improve oral and metabolic health in community-dwelling adults with type 2 diabetes and periodontitis
SuperARC: a test for artificial superintelligence based on compressed modelling, recursive prediction and problem complexity
Alkyl shikimates promote proliferation of human dermal fibroblasts and exhibit structure–activity relationships
Change in plasma cryptococcal antigen titers in Uganda among outpatients with advanced HIV disease from 2017 to 2022 with rollout of national cryptococcal screening
Introduction Cryptococcal meningitis causes an estimated 19% of AIDS-related deaths globally and is the leading cause of meningitis in adults with HIV. Subclinical infection with cryptococcal antigen (CrAg) is detectable in plasma, and CrAg titer of>=1:160 is predictive of meningitis or death. We evaluated if plasma CrAg titer changed over time in Uganda with the expansion of national CrAg screening programs and antiretroviral (ART) access. Methods We prospectively screened adults with advanced HIV disease (CD4 ≤ 200 cells/μl) for CrAg from 2017 through 2022 using the lateral flow assay and assessed median plasma CrAg titer. Results From November 2017 to May 2022, 436 adults with advanced HIV disease had a positive plasma CrAg test. The median CD4 + cell count was 45 [IQR: 21,94] cells/µL, and median plasma CrAg titer was 1:80 [IQR: 10,1280]. Analysis of median quarterly CrAg titer from 2017–2022 demonstrated a non-statistically significant positive trend in CrAg titer (tau = 0.385, p = 0.086). There was a statistically significant decline in the percentage of participants taking ART at the time of screening (p < 0.001), with 58% reporting never having taken ART in 2022. Conclusions Despite expansion of CrAg screening and ART, median annual CrAg titers have not decreased between 2017 and 2022 in Uganda. Contrary to national reporting of expanded access to ART, our study population had higher rates of ART-naïve status over time, suggesting ongoing late presentation to care for people with advanced HIV disease. In addition, the presence of ART-experienced patients in our study population suggests challenges with treatment adherence and retention. Cryptococcosis persists, and despite public health efforts, people are not presenting to care earlier in their disease course. Continued refinement of CrAg screening programs is needed to reduce AIDS-related deaths.
Using intersectionality to explore physical activity participation amongst individuals with vision loss from ethnic minority backgrounds in the United Kingdom
Abstract Participation in physical activity (PA) is essential for maintaining health and mobility. Although women, individuals from ethnic minority backgrounds, and people experiencing vision loss are reportedly the least active of their respective identity classifications literature is yet to acknowledge the intersectional nature of group identification, and the ways in which barriers and facilitators to PA might vary or compound in instances of multiple-minority status. Fifteen people with vision loss (six male) from different cultural backgrounds (six White: nine South Asian) were interviewed. Reflexive thematic analysis, underpinned by an interpretivist epistemology and relativist ontology, was used to analyse data. Participants identified neglect at a governmental level as the most significant barrier to PA, producing inaccessible environments that are infrastructurally inequitable. Female South Asian participants’ barriers to PA were nuanced by the intersectionality of their multiple identity positioning (gender, race, and disability). The cultural expectations placed on South Asian women, specifically those pertaining to modesty and gender, limited their capacity to engage in a physically active lifestyle. Comparisons made between the experiences of White and South Asian participants highlighted a lack of acceptance towards disabled individuals in the South Asian community. This study provided insight as to how experiences of inequality intersect and require holistic means of intervention. Governmental bodies and social innovators should strive to create spaces which are architecturally appropriate for people with vision loss, and work with sporting facilities such as gyms to centralise marginalised communities in their design to provide services which are both accessible and culturally viable.
Hepatitis B vaccine uptake and associated factors among pregnant women attending antenatal care at Gulu Regional Referral Hospital, Northern Uganda
Background Hepatitis B virus (HBV) infection is a global public health concern. Uganda has a high prevalence of HBV infection among pregnant mothers. This study aimed to determine HBV vaccine uptake and associated factors among pregnant women attending Antenatal Care (ANC) at Gulu Regional Referral Hospital (GRRH). Methods This was a cross-sectional study. Data were collected from 430 participants who were selected by systematic sampling. Data were collected using an electronic questionnaire built on the Kobo Collect server and analyzed using STATA version 16.0. Prevalence ratios (PR) were calculated using a modified Poisson regression analysis to determine the association between HBV vaccine uptake and the predictors. Results More than half (53%:229/430) of the pregnant mothers had received at least a dose of the HBV vaccine. Factors statistically significantly associated with HBV vaccine uptake included age (APR = 1.10, 95% CI: 1.02–1.18), knowledge about HBV (APR = 1.06, 95% CI: 1.01–1.10), and healthcare worker communication (APR = 1.17, 95% CI: 1.04–1.32). Conclusion More than half of pregnant mothers had received at least a dose of the HBV vaccination. Age, knowledge, and healthcare communication influenced vaccine uptake. There is a need to provide adequate health education regarding the importance of completing the HBV vaccine to pregnant women and community members to improve vaccine outcomes.
A multidimensional reliability-enhanced belief rule base model for fault diagnosis
Growth in confinement promotes <i>Pseudomonas aeruginosa</i> tolerance to antibiotics
Bacteria often proliferate within confined spaces imposed by host tissues, extracellular matrices, or their own biofilms where cells press against surrounding materials and experience elevated mechanical stress. Whether these forces influence pathogen physiology and fitness remains unresolved. We show that Pseudomonas aeruginosa adapts to mechanical confinement by increasing resilience to antibiotics. Using synthetic hydrogels of tunable stiffness that restrict expansion without limiting nutrient access, we demonstrate that growth in elastic materials reduces P. aeruginosa sensitivity to antibiotics in a stiffness-dependent manner. Although slower growth contributes to tolerance, Tn-seq under colistin and tobramycin treatment identified key regulators of mechanically induced tolerance. We found that active efflux mediated by sodium–proton Sha antiporters, together with protective remodeling of the bacterial membrane, enhances the resilience of confined populations without impacting growth. These findings reveal that P. aeruginosa adapts to mechanical stress in ways that may promote treatment failure even in the absence of intrinsic resistance.
How urban environment shapes EV charging experience in Travis County, Texas
As electric vehicle charging stations (EVCSs) become increasingly embedded in cities, understanding user experience is critical for designing infrastructure that is functional, accessible, and comfortable. This study integrates AI-driven sentiment analysis with spatial modeling to examine how urban environments shape EVCS perception. Using more than 4,000 user reviews from Travis County, Texas, three large language models classified sentiment across categories such as charging operation, accessibility, and parking. Random Forest regression results show that walkability, greenery, openness, and surrounding amenities are among the strongest predictors of user sentiment, while operational concerns are widely distributed in peripheral areas and accessibility and parking frustrations cluster in dense commercial zones. These findings demonstrate that EVCS usability is influenced not only by technical performance but also by contextual qualities of the built environment. This work provides a scalable framework for real-time monitoring of EVCS experiences and actionable insights for location-sensitive planning that supports user wellbeing and sustainable mobility adoption.
Early antifungal resistance prediction based on MALDI-TOF mass spectrometry and machine learning
Abstract Antimicrobial resistance (AMR) is a significant global health threat. Recent studies have shown that combining MALDI-TOF mass spectrometry with machine learning algorithms can accelerate AMR determination. However, these efforts have predominantly focused on bacterial pathogens. The significant morbidity, mortality, and healthcare costs associated with fungal infections highlight the need for accurate and early detection of antifungal resistance. We developed a machine learning pipeline integrating MALDI-TOF mass spectrometry data and drug features to predict antifungal resistance and identify spectral biomarkers. By leveraging the DRIAMS dataset, we included 658 pathogen spectra linked to 3,046 phenotypic antifungal resistance results across three drug classes and seven yeast species. Models were trained using categorical phenotypic antifungal susceptibility testing results as ground truth. We systematically investigated how different dimensionality reduction methods, antifungal encodings, and model types affected predictive performance using nested cross-validation. We identified that applying principal component analysis to MALDI-TOF mass spectra, and training a multi-layer perceptron yielded the highest and most stable performance for the prediction of antifungal resistance. Our method achieved an AUPRC of 0.77 across the 10 highest-performing species-drug pairs. The model demonstrated the best performance for the species-drug combinations of Candida albicans with micafungin, Candida parapsilosis with fluconazole, and Saccharomyces cerevisiae with itraconazole and fluconazole. By comparing established species-based guidelines, susceptibility test results, and machine learning predictions, we estimated that integrating our algorithm into antifungal selection could help avoid prescriptions to likely resistant pathogens in approximately 3 out of 10 patients for whom standard guidelines recommend such treatments.
Comprehensive mutagenesis defines the functional landscape of human α-tubulin
Interpreting missense variants in highly conserved, paralog-rich gene families remains a major barrier to understanding protein function and advancing precision medicine. Here, we combine comprehensive mutagenesis, high-content live-cell imaging, and automated quantitative analysis to generate a complete functional atlas of all 2,683 single-nucleotide coding variants in human α-tubulin TUBA1A. Systematic profiling of microtubule assembly revealed distinct classes of mutations that disrupt folding, chaperone engagement, and protofilament geometry, defining structural constraints that govern tubulin function. This approach complements conservation-based predictors and enables functional reinterpretation of disease-associated variants. Molecular dynamics simulations further revealed how local perturbations in GTP (guanosine triphosphate) binding, dimer contacts, and lateral interfaces propagate to alter filament architecture. Integrating these datasets produced a predictive framework that generalizes across tubulin isotypes and species, enabling accurate inference of variant effects. This work establishes a scalable, high-resolution strategy for functional annotation of conserved proteins and provides mechanistic insight into cytoskeletal assembly and flexibility.
Carbon emission governance and public health efficiency in transitional China: Regional differences and spatial aggregation
Background With the coordinated advancement of China’s “dual carbon” goals and the Healthy China strategy, the harmonious development of carbon emission governance and public health service efficiency has emerged as a central issue in China’s sustainable transition. Methods This study takes 31 provincial-level administrative units in China over the period 2012–2023 as the unit of analysis, and constructs a systematic analytical framework encompassing “measurement–coupling–inequality decomposition–determinant identification.” Specifically, the entropy weight method is employed to assess the composite level of carbon emission governance; the DEA-SBM model is applied to evaluate public health service efficiency; the coupling coordination degree model is used to quantify the coordinated development level of the two systems; the Dagum Gini coefficient decomposition is then utilized to identify the sources of regional disparities; the Global Moran’s Index is adopted to track the evolution of spatial agglomeration; and a two-way fixed effects Tobit model is constructed to identify associated factors. Results The national coupling coordination degree (CCD) exhibited an overall trajectory of initial fluctuation followed by a sustained upward trend. During 2012–2017, the CCD of most provinces remained within the range of 0.44–0.63, rising broadly to the 0.54–0.72 interval after 2018. Inter-regional inequality consistently constituted the dominant source of total disparity throughout the study period. After 2018, the coordination gap between eastern and western regions continued to widen, while intra-regional disparities among western provinces simultaneously intensified, with both trends jointly driving an increasingly pronounced pattern of regional divergence. The Global Moran’s Index rose from 0.227 to 0.497, indicating a continuous strengthening of spatial agglomeration. The associated factors exhibited significant regional heterogeneity: R&D investment intensity demonstrated a significant positive association with CCD in central and western regions; urban population density exerted a significant inhibitory effect on coordination degree in western provinces; and the direction of the association between economic development level and CCD was opposite in eastern and central regions. Conclusions Institutional time lags, factor endowment disparities, and spatial polarization mechanisms constitute the core structural barriers constraining the coordinated development of the two systems. There is an urgent need to establish a differentiated, region-specific, and phase-based policy intervention framework to promote balanced and coordinated regional development.
First and last authors more likely to be men in leading science journals
Fat-intra-body communication system using flexible wearable antennas with human and torso phantom validation for biomedical applications
Abstract This article introduces a biocompatible, non-invasive intra-body communication (IBC) system that employs a U-shaped, flexible wearable antenna specifically designed for fat-intra-body communication (Fat-IBC) applications. The proposed Fat-IBC system is engineered to function within the industrial, scientific, and medical (ISM) frequency range of 2.40–2.48 GHz. The U-shaped wearable antenna is encased in a biocompatible polydimethylsiloxane (PDMS) coating layer, enhancing durability and safety, making it suitable for continuous use in medical contexts. The U-shaped Fat-IBC antenna leverages the low-loss property of adipose (fat) tissue, positioned between skin and muscle layers, to facilitate efficient signal propagation across the body. The antenna is optimized for transmission through a three-layer tissue model (skin, fat, and muscle), leveraging the favorable transmission properties of adipose tissue to minimize signal loss. To assess performance, detailed numerical simulations and experimental validations were conducted using three-layer tissue models, torso phantoms (obese and athletic), and human volunteer trials. Ethical approvals were obtained for human testing, ensuring compliance with biomedical research standards. The performance of the U-shaped Fat-IBC antenna was benchmarked against a standard Bluetooth low energy (BLE) chip antenna under controlled conditions, with measurements taken in both front-to-back and side-to-side orientations across various body types. Experimental results demonstrated the superior performance of the U-shaped Fat-IBC antenna over BLE, specifically in terms of signal stability and transmission efficiency across body tissue, especially within adipose layers. Specific Absorption Rate (SAR) analysis revealed a peak value of 0.3061 W/kg, which is well within the IEEE safety limits, confirming the system’s suitability for biomedical applications. This Fat-IBC platform demonstrates the feasibility of fat tissue as a viable medium for intra-body networks, offering a reliable, power-efficient solution for real-time medical telemetry and patient monitoring, with promising implications for broader health applications.
What leads to administrative bloat? A dynamic model of administrative cost and waste
The functioning of complex systems depends on the coordination of diverse components, often supported by regulatory structures that incur costs. In human organizations, such costs manifest as administrative burden, which has been rising despite often reducing efficiency. Classic explanations point to bureaucrat self-interest or regulation, yet they do not explain variation across organizations or clarify how this burden can be reduced. Here, we develop a dynamical model of administrative growth that integrates known behavioral mechanisms of process creation, obsolescence, and removal. The model conceptualizes processes as developed for problem solving, but becoming obsolete as conditions change, while continuing to consume resources until actively pruned. This interplay generates two long-term outcomes: stable equilibrium or run-away growth. The threshold separating these outcomes is shaped by organizations’ propensity to create new processes when faced with problems, and their propensity to prune obsolete ones in response to administrative burden. Importantly, their effects are asymmetric: Sufficiently high creation propensity leads to bloat regardless of pruning propensity. Faster environmental change shifts this threshold, making bloat more likely. Simulations of interventions show that lasting reductions in administrative costs and waste require permanent shifts in priorities and investments in distinguishing obsolete from useful processes. Temporary efforts or indiscriminate cuts provide only short-lived relief, and counterintuitively, prioritizing direct production can increase waste. Our work highlights a general mechanism by which well-intentioned problem-solving can create self-reinforcing inefficiencies in complex systems, offering insights possibly generalizable to broader applications, such as legal, policy, and software systems where obsolete elements accumulate.