Browse Articles

Base editing reveals an essential role for NANOG in human embryogenesis

Abstract Understanding how the first cell lineages in human development are specified and maintained has fundamental importance and clinical implications for regenerative medicine, infertility and pregnancy loss. Although mouse models have provided valuable insights into transcription factors regulating early development, translating these findings to human embryos has been limited by ethical, technical and biological constraints. Functional studies of transcription factors in human embryos have been hindered by nuclease-based genome editing approaches that induce genotoxicity 1–3 . Here, to overcome this, we applied ABE8e adenine base editing 4,5 to precisely target an exon splice donor site, resulting in a splicing defect and functional knockout of the developmental regulator NANOG in human embryos. This approach did not trigger genotoxicity and showed limited off-target editing. Loss of NANOG disrupts pluripotent epiblast specification and instead cells differentiate towards a primitive endoderm (yolk sac) or trophectoderm (placental) transcriptional programme. Retention of primitive endoderm differentiation in NANOG -edited human embryos reveals a functional compensation that is distinct from mouse, underscoring the importance of directly investigating human development. Our findings demonstrate an essential role for NANOG in human pluripotency and epiblast specification and highlight the utility of base editing for functional interrogation of human development.

Direct-acting antiviral therapy is associated with a reduced risk of selected immune-mediated inflammatory diseases in chronic hepatitis C infection: A real-world cohort study

Background Chronic hepatitis C virus (HCV) infection is associated with immune dysregulation and an increased risk of immune-mediated inflammatory diseases (IMIDs). While direct-acting antiviral (DAA) therapy achieves high rates of sustained virologic response, its long-term effects on the risk of IMIDs remain incompletely understood. Methods We conducted a retrospective cohort study using data from the TriNetX global research network (2015–2024) to evaluate the association between DAA therapy and the risk of IMIDs among adults with chronic HCV infection. Patients were categorized into DAA-treated and untreated cohorts. Propensity score matching (1:1) was applied to balance baseline characteristics between groups. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Sensitivity analyses, along with predefined positive and negative control outcomes, were performed to assess robustness. Subgroup analyses were conducted to assess potential effect modifiers. Results After matching, 35,266 patients were included in each cohort. DAA therapy was associated with a significantly reduced risk of several IMIDs, including rheumatoid arthritis (HR 0.83, 95% CI 0.71–0.97), autoimmune hepatitis (HR 0.55, 95% CI 0.31–0.96), and immune thrombocytopenic purpura (HR 0.64, 95% CI 0.44–0.93). These associations were consistent across multiple predefined time-at-risk windows. Subgroup analyses revealed that the protective associations were more pronounced among females and middle-aged individuals (41–64 years). Conclusions DAA therapy in patients with chronic HCV infection is associated with a reduced risk of specific IMIDs, suggesting potential systemic immunologic benefits beyond hepatic outcomes.

Case 18-2026: A 53-Year-Old Man with Leg Weakness, Pain, and Weight Loss

A fractional ABC model for hepatitisB virus transmission with forecasting of epidemic trends using neural networks

Few-shot skin lesion classification with Adaptive Multi-Scale Convolutional Attention Network

Computer-aided diagnosis of skin lesions faces core challenges, including scale diversity, blurred boundaries, intra-class morphological variations, and sparse data. Existing methods often rely on fixed receptive fields or generic attention mechanisms, struggling to fully adapt to the unique characteristics of skin lesions. To address this, we propose an Adaptive Multi-scale Convolutional Attention Network (AMCANet), which aims to achieve accurate and robust classification of skin lesions with limited data. AMCANet comprises three core modules: the adaptive multi-scale convolution module dynamically adjusts the receptive field to accommodate lesions of varying sizes; the hierarchical channel attention module integrates multi-level semantic information across different resolutions; and the skin spatial attention module leverages image gradient information to enhance lesion boundaries and local texture features. Extensive few-shot experiments on the HAM10000 and PAD-UFES-20 public datasets demonstrate that AMCANet significantly outperforms existing baseline models across multiple metrics, exhibiting promising generalization capabilities on the evaluated datasets. Qualitative and visual analyses further validate the model’s ability to extract discriminative features and effectively focus on lesion regions. This study proposes a deep learning model, which demonstrates certain effectiveness in classifying skin lesions even with a small number of samples, providing a potential direction for future research.

Andes Hantavirus Outbreak on a Cruise Ship, 2026

Dynamic electrocardiogram detection and diagnosis based on improved dilated convolutional network

Ligand-enabled distal desaturative lactonization of aliphatic acids

Fixed BMI eligibility criteria for GLP-1 receptor agonist trials and estimated trial-eligible proportions in Asian and non-Asian populations: A cross-sectional analysis

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are globally developed for metabolic diseases, yet clinical trials have underrepresented Asian populations who develop metabolic complications at lower body mass index (BMI) values than Non-Asian populations. This cross-sectional study characterized eligibility criteria in 352 GLP-1 RA trials registered on ClinicalTrials.gov (2017–2020) and estimated the proportion of populations meeting these criteria using nationally representative health survey data from 23,251 adults (5,984 Non-Asian US, 353 Asian US, and 16,914 Korean) from National Health and Nutrition Examination Survey (NHANES, US) and Korean NHANES (2021–2023). Mean BMI was substantially higher in Non-Asian US adults (29.8 kg/m 2 ) compared with Asian US (24.9 kg/m 2 ) and Korean (24.2 kg/m 2 ) populations. BMI criteria, specified in 233 trials (66.2%), demonstrated the largest eligibility disparities. For trials requiring BMI ≥ 30 kg/m 2 , eligibility was 41.5% for Non-Asian US versus 13.5% for Asian US and 7.2% for Korean adults. In contrast, HbA1c, eGFR, and liver function criteria showed minimal between-population differences (all > 93% meeting typical thresholds). These findings suggest that fixed BMI eligibility criteria are associated with substantially lower estimated trial-eligible proportions among Asian populations, supporting further evaluation of ethnicity-sensitive BMI thresholds in future GLP-1 RA trial design.

Improving Global Air-Quality Indices — The WHO’s New Roadmap

Size-segregated airborne polycyclic aromatic hydrocarbons down to PM0.1 in urban tropical environment: spatial distribution, health risk assessment, and potential sources

China’s LineShine just topped the global supercomputer ranking: what you need to know

Multiobjective dynamic resource allocation in cloud computing using Harris Hawk Optimization Algorithm (MDLB-HHO)

To increase cloud computing utilization and performance, efficient load balancing and resource distribution techniques are essential. Dynamic load balancing and resource allocation in cloud systems is necessary due to a number of reasons, but this is not an easy and straightforward task. The primary goal of dynamic load balancing of cloud systems is to optimize the workload and resource utilization. The Harris Hawks Optimization (HHO) algorithm is a dynamic method of allocating the workloads to the virtual machines (VMs) according to the workload distribution and the use of the resources. The comparison of experimental analysis and other load-balancing methods shows that the HHO algorithm can be used to control dynamic load balancing in a rather efficient and effective way. With such technical developments, there has been a decrease in time taken to respond as well as the use of resources. The suggested solution is a cost-effective and efficient solution to the load-balancing problem in dynamic conditions and is based on the collaborative hawks hunting behavior. The system converts the resource allocation scheme to the changeable cloud application requirements. This is achieved by a multiobjective fitness function which aims to maximize the efficiency of resources, minimize the response time and resource usage. The primary objective of the study is to ensure that the clouds services become effective and sustainable. The Harris Hawks discover the most optimal distribution techniques of activities by closely observing the space of solutions. They then apply positional updates and iterative interactions to adapt to changing workloads. The system dynamically assigns jobs to virtual machines (VMs) without compromising load balance and efficient resource use through the use of the cooperative search behavior of the hawks. The proposed solution effectively manages the cases when the task requirements are constantly changing. Applying a multiobjective fitness function greatly improves key performance metrics like overall performance, resource usage, and reaction time. This study demonstrates how the HHO algorithm increases the effectiveness and robustness of cloud-based services in dynamic operational environments.

Stopping Beta-Blockers after Myocardial Infarction

An adaptive feature extraction lightweight network for enhanced landslide detection

Daily briefing: Humans and great apes giggle in the same rhythms

A compact wideband Wilkinson Power Divider topology for arbitrary N-Way outputs

This work presents a compact Wilkinson power divider (WPD) topology capable of realizing arbitrary 1 ×  N equal power divisions without requiring crossovers or unrealizable high-impedance lines. The design combines both equal and unequal power division stages, enabling flexibility for even and odd numbers of outputs. Power divider units with 1:2 and 1:3 ratios are used as the basis for constructing higher-order N-output WPDs. Miniaturization is achieved through tapered-line impedance transformers, limiting the maximum line impedance to 103 Ω within fabrication constraints. A two-stage 1 × 3 divider is designed, fabricated, and tested at 2.4 GHz on a microstrip platform. The prototype demonstrates an 85% effective bandwidth with amplitude imbalance within ±0.2 dB, and phase imbalance less than ±2.5°. Compared to conventional topologies, the present approach achieves up to 58% size reduction while maintaining wideband performance. This work is highly suitable for M  ×  N high-performance, efficient, reliable, and scalable beamforming network architecture. This work supports SDG 9 Industry Innovation and Infrastructure by enabling compact, scalable, and high-efficiency microwave components for advanced communication and infrastructure systems.

The Physiology of Pulsus Paradoxus Revisited

Effect of seawater on the self-healing of biomineralized recycled aggregate concrete

Abstract To study using seawater instead of freshwater to repair concrete cracks is worthwhile with microbial mineralization. This study used recycled concrete coarse aggregates ( RCA ) and brick coarse aggregates ( BCA ) as carriers to soak in Bacillus pasteurii solution with different saltwater salinity for modification. The modified aggregates were adopted to prepare concrete and experimentally investigate their compressive strength, crack repair, and microstructure. Test results show that the aggregates using saltwater of the same salinity as seawater present the best modification. After the modification the saturated surface dry weight of the two aggregates increases, and the water absorption decreases. The strength of modified aggregate concrete is higher than that of unmodified aggregate concrete, and the strength of modified RCA concrete is higher than that of modified BCA concrete. The 56-day compressive strength of saltwater mixing and curing modified aggregate concrete is interestingly found to be lower than the 28-day compressive strength. In addition, for the artificially cracked concrete previously cured 56 days in saltwater, after air curing at 1 day, the surface cracks started to be repaired by calcium carbonate, while after 91 days, the surface cracks were greatly repaired, the repairable crack width was up to 0.5 mm. Moreover, the particle inside the concrete may promote calcite precipitation with better stability compared to that at the concrete surface.

‘Edited’ human embryos reveal secrets of our development — and fuel ethical debate