Browse Articles

Built-in redundant killing by Bt Cry1Ab toxin delays insect resistance

Predicting high-fitness viral protein variants with Bayesian active learning and biophysics

The early detection of high-fitness viral variants is critical for pandemic response, yet limited experimental resources at the onset of variant emergence hinder effective identification. To address this, we introduce an active learning framework, VIRAL (Viral Identification via Rapid Active Learning), that integrates protein language model, Gaussian process with uncertainty estimation, and a biophysical model to predict the fitness of novel variants in a few-shot learning setting. By benchmarking on past SARS-CoV-2 data, we demonstrate that our method accelerates the identification of high-fitness variants by up to fivefold compared to random sampling while requiring experimental characterization of fewer than 1% of possible variants. We also demonstrate that our framework effectively identifies sites that are frequently mutated during natural viral evolution with a predictive advantage of up to two years compared to baseline strategies, particularly those enabling antibody escape while preserving ACE2 binding. Through systematic analysis of different acquisition strategies, we show that incorporating uncertainty in variant selection enables broader exploration of the sequence landscape, leading to the identification of evolutionarily distant but potentially dangerous variants. Our results suggest that VIRAL could serve as an effective early warning system for identifying concerning SARS-CoV-2 variants and potentially emerging viruses with pandemic potential before they achieve widespread circulation.

Early evidence for pig domestication (8,000 cal. BP) in the Lower Yangtze, South China

The domestication of pigs ( Sus scrofa ) has had profound socioeconomic and ecological consequences. Although pigs are believed to have been independently domesticated in South China, the timing and initial mechanisms of this process remain debated. This study presents a microfossil analysis of pig dental calculus from two early Neolithic sites in the Lower Yangtze River region: Jingtoushan (8,300 to 7,800 cal. BP) and Kuahuqiao (8,200 to 7,000 cal. BP). Analyses of starch, phytolith, and parasite remains indicate that pigs consumed human-associated foods and waste, including cooked starchy plants and human whipworm ( Trichuris trichiura ) eggs, likely derived from food preparation and fecally contaminated materials. Identified plant taxa include acorns (Fagaceae), rice ( Oryza sp.), underground storage organs such as yam ( Dioscorea sp.), and wild grasses (Triticeae and Panicoideae), all present in the local botanical assemblages. Coefficients of variation in dental metrics further indicate the coexistence of both domestic and wild populations. Together, these lines of evidence point to multiple modes of human–pig interaction, including early domestic pigs under human management, pigs scavenging near settlements, and free-ranging individuals foraging beyond human influence. Pig domestication in the Lower Yangtze had begun by 8,000 y ago, likely following both commensal and prey pathways, in parallel with the development of rice cultivation and sedentary lifeways. This study also demonstrates the value of dental calculus analysis for revealing early human–animal relationships before the appearance of clear morphological markers of domestication in the archaeological record.

Optical solitons, bifurcation, and chaos in the nonlinear conformable Schrödinger equation with group velocity dispersion coefficients and second-order spatiotemporal terms

Correction: Alcohol use and optimal chronic diseases’ treatment outcomes among adults aged 40 years and above in rural South Africa

Author Correction: Antiviral potential of Melissa officinalis extracts against influenza and emerging coronaviruses

Author Correction: A cross-national analysis of demographic variation in daily smoking across 22 countries

Author Correction: Identification of stable housekeeping genes for induced pluripotent stem cells and -derived endothelial cells for drug testing

A novel Swin transformer based framework for speech recognition for dysarthria

Publisher Correction: A non-associated constitutive model based on yld2004-18p yield criterion and its applications on sheet metal forming analysis

Author Correction: Absence of CD36 alters systemic vitamin A homeostasis

Thermal stress and thermal deformation of a nozzle flowmeter with different weld structures

Nozzle flow meters are widely used in the field of measuring high temperature media. In order to investigate the effect of nozzle flowmeter weld structure on thermal stress and thermal deformation, 10 different weld structures were designed in terms of the distance between the weld metal and the eight-groove nozzle, the width of the bottom of the weld metal, the taper angle of the weld metal, and the opening of the taper angle of the weld metal. The thermal stress and thermal deformation characteristics of the solid domain of the nozzle flowmeter are also calculated numerically for a high temperature case. The conclusion indicates that with the increase of the conical Angle of the weld metal, the thermal stress at the inlet and outlet of the nozzle flowmeter gradually decreases, and the thermal deformation changes less. The distance between the weld metal of the nozzle flowmeter and the eight-slot nozzle, the width below the weld metal, and the variation of the cone angle opening of the weld metal all have a relatively small impact on the thermal stress and deformation of the overall solid domain of the nozzle flowmeter.

Inter-agency collaboration to support the COVID-19 response and maintain malaria services in Guinea and Sierra Leone: A social network analysis

Inter-agency networks are believed to be essential to maintaining essential health services during pandemics and to strengthening the resilience of health systems. Focusing on malaria during the COVID-19 pandemic as a case study, this paper investigates the network of organisations fighting malaria in Guinea and Sierra Leone, the changes in their interactions during the pandemic, and their collaboration with organisations addressing the COVID-19 response. We used a mixed-methods approach to analyse data from 36 semi-structured interviews with respondents involved in the COVID-19 response and malaria service provision in Guinea and Sierra Leone, as well as data from a social network survey conducted with a subsample of 21 out of the 36 respondents. Results from the thematic analysis of key informant interviews were used to contextualize the social network data, which was visualized as sociograms. We found that malaria stakeholders worked closely with key stakeholders involved in containing the COVID-19 pandemic. Their ability to support the COVID-19 response and contribute to maintaining essential malaria services was facilitated by the fact that established networks of malaria stakeholders had existed in both countries which comprised a variety of national and international organisations from the public, private and civil society sector working in different areas of malaria elimination. These stakeholders were able to maintain or even intensify their collaboration during the COVID-19 pandemic. The findings suggest that in resource-limited settings, the promotion of coordination mechanisms among stakeholders working on specific issues can strengthen linkages and consistency, thereby contributing to overall health system resilience and pandemic response.

Preventing respiratory illness in cerebral palsy: Results of a pilot randomized controlled trial

Background Respiratory illness is consistently the leading cause of death and hospitalization in severe cerebral palsy (CP). Respiratory Exacerbations-Plan for Action and Care Transitions (RE-PACT) is a just-in-time adaptive intervention to prevent respiratory illness in severe CP. RE-PACT combines early illness detection with rapid clinical response to address varying causes of respiratory illness early enough to modify illness trajectory. This study’s objective was to determine RE-PACT’s feasibility, acceptability, fidelity, and estimated effect size. Methods This two-site randomized controlled trial occurred from April 2022-February 2024 in demographically and geographically distinct locations. Caregiver-child pairs were recruited from complex care programs, and children had both gross motor function classification system level 4–5 CP and either pulmonologist care or daily respiratory treatments. Children were randomized to usual care or RE-PACT for six months. Primary outcomes were feasibility, acceptability, and fidelity measures having a priori definitions of success. The primary clinical outcome was the severe respiratory illness (SRI) event rate, defined as hospitalizations due to respiratory diagnoses. Clinicaltrials.gov registration is NCT05292365. Results Sixty children were enrolled, of which 26 were randomized into RE-PACT. Measures confirmed RE-PACT’s feasibility, acceptability, and fidelity, e.g., text message response rates were 97.5%, and no action planning or clinical responder activities were missed. System usability scale scores were “good to excellent” (mean [SD], 79.5 [11.7]). The RE-PACT SRI event rate (95% confidence interval, CI) was 0.71 (0.36–1.14) per person-year compared to the usual care event rate 1.08 (0.61–1.91) per person-year, a risk ratio of 0.66 (0.28–1.56). Secondary outcomes and qualitative data reinforced RE-PACT’s positive impact. Conclusions RE-PACT is a feasible, acceptable intervention that can be delivered with high fidelity to diverse families caring for children with severe CP. These data inform the sample and design characteristics needed for efficacy testing of RE-PACT’s ability to prevent severe respiratory illness.

Physicochemical quality assessment of four asparaginases

L-Asparaginases (ASNases) are used for the treatment of acute lymphoblastic leukaemia. There are reports of quality problems for some therapeutic asparaginase products, especially those manufactured in middle-income countries. These products may exhibit decreased potency and/or decreased specific activity, or an elevated level of impurities such as host cell proteins. In this study, four different ASNase preparations that were not modified with polyethylene glycol were compared in detail regarding their quality: Spectrila®, Celginase™, Bionase®, and L-Aspase®. Samples were analyzed for protein content, impurities, and enzyme activity. Various chromatographic methods as well as mass spectrometry were used to assess purity and identity. Sample protein content, host cell protein, and enzyme activity showed some results that were out of target range for Celginase™ and Bionase®. These ASNase preparations also showed detectable levels of endotoxins. In gel electrophoresis, additional bands were found for Bionase®. Size exclusion chromatography showed increased high and low molecular weight species for Bionase® and L-Aspase®, and reversed-phase chromatography showed increased hydrophilic and hydrophobic species for Bionase®. In capillary zone electrophoresis, increased retention time for L-Aspase® and increased levels of charge variants for Bionase®, Celginase™, and L-Aspase® were seen. ASNase quality standards are crucial to ensure patient safety and product efficacy, as decreased potency and specific activity may affect efficacy in acute lymphoblastic leukaemia treatment, and increased impurities may affect immunogenicity. Out of four ASNase preparations tested in this study, only Spectrila® did not raise any quality concerns. The other three products exhibited quality problems, rendering them unsuitable according to established quality requirements defined in European and US guidelines for pharmaceutical development of parenteral drug products.

Genome-wide molecular fingerprinting reveals local geographical genetic patterns in the North American angiosperm genus Triosteum (Caprifoliaceae)

Triosteum (Caprifoliaceae) is a genus of herbaceous perennial angiosperms composed of three Asian and three North American species. The range of two similar species, T. aurantiacum and T. perfoliatum, overlap in the state of Massachusetts, USA, where the latter species is considered locally endangered and protected by regulations. The population occurring in Barnstable Co. MA, USA was morphologically atypical and had intermediate characteristics between the two taxa. Genome-wide molecular fingerprinting was used to identify this population by comparison to nearby populations with typical morphology for each of the reference species T. aurantiacum and T. perfoliatum. A set of 220,518 high quality SNPs were used to calculate expected heterozygosity, FIS, nucleotide diversity, and FST, and to create short multi-allelic haplotype markers. Detailed population characterization was performed using Principal Component Analysis (PCA) and fastSTRUCTURE analysis on SNPs, and the haplotype markers were used to create a NJ phylogenetic tree, and pairwise comparisons of the genetic distance (Jaccard Inverse Distance) between individual plants within and between subpopulations, populations, and species. Furthermore, complete chloroplast genome sequences were created, and structural polymorphisms characterized and compared to a range of closely related species. Taken together, the data reveals a fine subpopulation structure within the morphologically atypical population at Barnstable Co. MA, that are more closely related to T. perfoliatum than to T. aurantiacum.

Vertical distribution characteristics and source apportionment of nitrogen in the Longyangxia Reservoir in the upper reaches of the Yellow River

Studying the biogeochemical cycle of biogenic nitrogen and its influence on hydrological processes and anthropogenic nitrogen input is of great significance for water resource management and the maintenance of aquatic ecosystems in ecologically sensitive areas. Currently, there is a limited understanding of the sources contributing to nitrate levels during thermal stratification in deep and large reservoirs, as well as the transformation processes of nitrate under varying hydrological conditions. This study collected water samples from the Longyangxia Reservoir, located in the upper reaches of the Yellow River, during January and April of 2024. Utilizing hydrogeochemical analysis, multivariate stable isotope technology, the Bayesian isotope mixing model, and multivariate statistical analysis, we analyzed the vertical distribution characteristics of nitrogen in the reservoir across different periods. The transformations and sources of nitrogen were identified, and the contribution rates of each nitrogen source were estimated. The results indicate that January serves as the mixing period for the Longyangxia Reservoir, during which the differences in nitrogen concentration among the vertical water layers are relatively minimal. The concentration ranges for nitrate (NO₃⁻), dissolved organic nitrogen (DON), and ammonium (NH₄⁺) were observed to be 0.598–0.647 mg/L, 0.124–0.397 mg/L, and 0.015–0.157 mg/L, respectively. Beginning in April, the reservoir enters the thermal stratification period, characterized by higher concentrations of various nitrogen forms compared to the mixing period. During the stratification period, the concentration of various nitrogen forms within the vertical profile of the reservoir demonstrates a characteristic distribution of being low in the upper section, maximum values of total nitrogen (TN) and dissolved DON in the middle section, and maximum concentrations of NO₃⁻ and NH₄⁺ in the bottom section. Nitrate nitrogen and dissolved organic nitrogen are the primary forms of nitrogen present in the Longyangxia Reservoir, constituting 66.71% and 25.83% of the total dissolved nitrogen in January, and 62.39% and 21.59% in April, respectively. During the sampling period at Longyangxia Reservoir, the δ15N-NO3- values in the water ranged from 5.58 ‰ to 7.38 ‰, while the δ18O-NO3- values varied from −5.87 ‰ to 2.58 ‰. Nitrification is identified as the primary nitrogen conversion process occurring in the reservoir water. Under aerobic conditions, denitrification does not occur in aquatic environments. The dynamics of nitrate in the bottom layer are influenced by nitrification processes and the release of nitrogen from sediment. Soil organic nitrogen is the primary source of nitrate in Longyangxia water, contributing 42.1% and 51.8% during the sampling period, respectively. This study introduced sediment as an additional end member, highlighting that the contribution of sediment to nitrate in water is significant, accounting for 24% and 14.1%, respectively. This study offers valuable insights for precise nitrogen management and control in deep reservoirs by tracking nitrate sources and quantifying their contributions.

Integrative review in PhD admissions: A case study of efficiently minimizing bias while maximizing the student narrative

Developing scientific and medical innovations continue to be limited by lack of diverse representation among leaders and learners. One key gateway for these goals is graduate school admissions, but comprehensive consideration of all components of applications, which is needed to reduce systemic bias in admissions, is resource intensive. This case study details the conceptualization of an integrative application review process to challenge and improve classic application review frameworks which gatekeep admissions opportunities from under-represented (UR) applicants. PhD applicant cohorts to a longstanding Clinical and Translational Sciences PhD TL1 program were assessed using one of three review processes: traditional, algorithmic, or a novel integrative review process. Admissions results from each review process were pooled across matriculation years to attain a testable sample size. Effects modification models were used to assess odds of reaching each admissions phase, adjusting for UR status and review process. Results showed that classic admissions review processes were prone to bias towards admission of specific students while integrative application review did not demonstrate this trend. The Mayo Clinic Graduate School of Biomedical Sciences Clinical and Translational Sciences training program has steadily recruited and trained successful and diverse trainee cohorts over the last decade from many underrepresented backgrounds. The final adoption of an integrative application review process allows streamlined graduate school admissions of diverse student cohorts, prioritizing self-driven narratives and minimizing subjective biases where possible to allow fair assessment of learners.

Investigation of nanotexture fabrication by magnetic field assisted ultra-precision diamond cutting

Ultra-precision machining (UPM) is crucial for producing parts with functional surfaces featuring nano textures, yet it faces challenges in generating such textures. This paper explores the potential of magnetic field-assisted UPM to overcome these challenges by leveraging magnetophoresis to generate nanotextures and thoroughly investigating the importance of cutting velocity on magnetophoresis in diamond cutting. Experimental results from cutting force, surface profile, surface topography, and atomic force microscopy images demonstrate that magnetic fields enable nanotexture generation on aluminum alloys surfaces in diamond cutting. Also, increasing cutting speed in diamond cutting under a magnetic field enhances magnetophoresis. This study highlights the advantages of integrating magnetophoresis for advanced nanotexture fabrication in UPM and emphasizes strategies for control cutting speed to achieve nanotextures.

Lived experiences and coping strategies of people living with Glaucoma in Nigeria: A qualitative study

Background The diagnosis of visual impairments and other chronic diseases is associated with frustration, anxiety and depression emanating from potential functional limitations, social restrictions, economic burden and future uncertainties. The impact of glaucoma extends across multiple domains of life. This study explores the lived experiences of people with glaucoma to understand the factors that influence their interactions within the community and how they cope with accompanying challenges. Method This study utilised a qualitative research methodology. Data was collected using audio-recorded in-depth semi-structured interviews. Thematic analysis was used to analyse data collected through in-depth interviews. Result Twelve participants aged 22–65 years old, mostly females (58.3%) participated in the study until saturation. Three major themes emerged from the data. The study identified psychosocial reactions to glaucoma diagnosis expressed with unpleasant emotions, fears and concerns about the future by persons living with glaucoma. Glaucoma impacted daily activities, routines and social life resulting in either reduced social activities or they completely stopped socialising. However, engaging in self-motivation and religious activities were useful strategies to cope with these challenges. Other adaptive and coping strategies included following eye care providers’ instructions, attending clinic appointments, making reasonable adjustments at the home and work settings, transferring into accommodation that provides support needs as well as organizing itineraries and activities prior to leaving the house. Conclusion This study provides evidence of the intricate psychosocial impacts of glaucoma, unravelling a spectrum of emotional reactions and lifestyle adaptations. The emotional stress, fears, and disruptions in daily life underscore the profound challenges posed by this chronic eye condition. Self-motivation and religious engagement emerged as potent coping mechanisms, highlighting the importance of psychological and spiritual support. Additionally, the study identifies practical strategies, from adhering to medical instructions to making environmental adjustments, offering valuable insights for healthcare and support networks.