Browse Articles

Development of a highly specific enzyme-linked immunosorbent assay for detection of antibodies to Duck Tembusu virus using subviral particles

Duck Tembusu virus (DTMUV) belongs to the family Flaviviridae and genus Orthoflavivirus. It causes disease in ducks, affecting the nervous system and significantly reducing egg production. The first outbreak of DTMUV in Thailand was reported in 2013, with widespread cases across various regions. However, serological diagnosis of DTMUV is challenging due to antibody cross-reactivity with other flaviviruses. To address this issue, we developed an ELISA based on subviral particles. The cassette encoding the membrane precursor and envelope genes of DTMUV (strain KPS54A61) were cloned into a pCAGGS vector with an OSF-tag and transfected into HEK-293T cells to generate subviral particles. The subviral particles were detected in the supernatant of the transfected cell via immunoblotting using anti-DTMUV E protein and anti-Strep-tag antibodies, which revealed a protein band of approximately 59 kDa. An electron microscopy confirmed the presence of particles approximately 35 nm in diameter. To optimize the SP-based ELISA, checkerboard titration identified the optimal antigen concentration as 70 µg/mL and the optimal serum dilution as 1:100,000. A cut-off value was established for the assay, and testing 300 duck serum samples using the SP-based ELISA identified 41 positive samples (14%) and 259 negative samples (86%). The SP-based ELISA exhibited 100% sensitivity and specificity, achieving a perfect agreement score of 1.0 in comparison with the serum neutralization test. Additionally, specificity testing using antibodies specific to Japanese Encephalitis virus (JEV) revealed no cross-reactivity in the ELISA test. Therefore, the developed SP-based ELISA is highly effective for screening and monitoring DTMUV outbreaks in duck farms, significantly reducing the risk of viral spread and enabling the timely implementation of disease control measures.

Tyrosine kinase inhibitors were well-tolerated among patients with different etiologies of advanced HCC with lower survival in non-viral patients

Abstract We studied the characteristics and survival of patients with sorafenib-treated HCC and impact of underlying etiology on outcomes. This retrospective multicenter study recruited patients with sorafenib-treated advanced HCC (12/2016 to 4/2023) till death or the study end (2/2024). Time to progression (TTP) and overall survival (OS) were recorded. We evaluated; Clinico-laboratory and imaging predictors of OS, The impact of underlying etiology on tumor variables, outcomes and tolerance for sorafenib > 6 months. This study included 706 patients. Median duration of Sorafenib therapy was 240.00 (90.00–360.00) days. Median OS was 314.00(146.00–601.00) days. Median TTP was 180.00(90.00–330.00) days. COX regression revealed that the independent factors of mortality were baseline AST, Tumor size, hepatic vein thrombosis (HVT), development of jaundice and shifting to Regorafenib. Advanced HCCs were more common on top of non-cirrhotic non-viral and HBV-related liver disease. Adverse events, TTP and tumor response didn’t differ with the underlying etiology. Median OS was lower in non-viral-related HCC than HCV-related HCC (218.00 versus 326.50 days, P-value = 0.048). Patients who continued sorafenib > 6 months had lower AFP, HVT, adverse effects and better tumor response after 3 months. OS is lower in non-viral Sorafenib-treated HCC compared with viral-related HCC and Sorafenib was well-tolerated among different HCC etiologies.

Diazotrophic growth of free-living Rhizobium etli: Community-like metabolic modeling of growing and non-growing nitrogen-fixing cells

Rhizobium etli, a nitrogen-fixing bacterium, grows both in symbiosis (with plants) and in free-living state. While most metabolic models focus on its symbiotic form, this study refined the existing iOR363 model to account for free-living growth. By addition of a biomass formation reaction followed by model curation growth was simulated using various N-sources (NH₃, NO₂, and NO₃). At fixed succinate uptake rate (4.16 mmol/gDWC/h), ammonia yielded the highest growth rate of 0.259 h ⁻ ¹. To represent free-living N-fixing R. etli, a novel two-member community-like model, consisting of both growing and differentiated non-growing N-fixing cells with ammonia exchange, was developed. The XFBA approach, based on community Flux Balance Analysis (cFBA), was formulated to maintain fixed abundances rather than assuming equal growth rates. With a non-growing:growing abundance ratio of 1:9 in community, N-fixation resulted in lower growth rate of 0.1933 h ⁻ ¹ due to the high energy demand of N₂ assimilation compared to ammonia. Sensitivity analysis revealed that increased abundance of N-fixing cells from 5 to 30% led to decreases of 10% in N2-fixation and 25% in growth rate of growing member. Furthermore, Principal Component Analysis identified oxidative phosphorylation, TCA cycle, and glycolysis as key pathways differentiating flux distributions across N-sources. At high uptake of oxygen, causing nitrogenase inactivity, cytochrome bd oxidase was activated to scavenge oxygen, though at the cost of lower growth rate (by 12% per mmol increase in O2 uptake/gDWC/h). This study provided a platform to obtain insights to free-living state of R. etli which may have applications for other diazotrophs.

The arousal paradox in critical task performance in automated driving during sleep inertia using a quasi experimental approach

Abstract Sleep inertia is the post-awakening transitional state of lowered arousal, characterized by increased low-frequency activity in the electroencephalogram (EEG) and impaired cognition. While some theories consider arousal holistically, recent research questions whether these findings apply to situations requiring immediate critical action post-awakening, such as for pilots, emergency responders, or future drivers of automated vehicles. This study compared self-reported, cortical, and physiological arousal in such a scenario. Twenty-four participants completed four drives in a driving simulator. In three drives, participants were instructed to sleep for 20, 40, and 60 min during automated driving before being prompted to resume control. The sleep stage prior to the takeover request served as a quasi-experimental independent variable. Regression analyses showed that cortical arousal was low following awakenings from N2 or N3, indicated by increased delta, theta, and alpha activity. However, beta activity and heart rate also increased, suggesting elevated physiological arousal. Significant positive correlations were found between delta activity, heart rate and self-reported sleepiness. This “arousal paradox” is not in line with the idea of arousal as a holistic concept. We hypothesize that the heightened physiological response under sleep inertia may be attributed to stress in demanding situations under sleep inertia. We conclude that forced awakenings from N2 or N3 should be avoided. If someone is nevertheless awakened from N2 or N3, they should be given sufficient time between awakening and taking over duties for arousal to normalize.

Diurnal pattern of respiration in corals and algae and its implications for gross primary production quantification

Mitochondrial respiration (R) and gross photosynthesis (GP) are crucial components of the energy and carbon budgets of photosynthesizing organisms in coral reefs. This study investigates the diurnal and seasonal patterns of R in common reef algae and corals, examining the relationship between R and photosynthesis. Additionally, it evaluates discrepancies between daily R and GP calculations based on diurnal variations versus constant nighttime R, latter being the more traditional approach. We collected three coral species (Montastrea cavernosa, Porites astreoides, and Diploria strigosa) and three algal species (Caulerpa verticillata, Ceramium nitens, and Laurencia obtusa) from a Bermuda reef in fall (October) and measured their metabolic rates in a controlled outdoor mesocosm environment. Diurnal patterns of photosynthesis were measured under natural sunlight, and respiration was measured at different times by covering the incubations with a black sheet. Measurements were repeated with re-collected corals in spring (April) and summer (July). Our findings reveal pronounced diurnal patterns in R for both corals and algae, with peak R in the afternoon, lagging behind peak GP by 1–3 hours. Seasonal analysis showed the highest R in summer and the lowest in fall, correlating with temperature and light intensity variations. The study indicates that traditional models, assuming constant nighttime R throughout the day, underestimate daily R and GP rates by an average of 14% and 13%, respectively, and by 23% and 18% at a maximum. These results highlight the need to incorporate the dynamic nature of respiration into our understanding of energy and carbon fluxes in reef organisms. As metabolic energy availability is crucial for organism resilience, improved estimates of R and GP are essential for predicting organism survival in a changing environment.

AI-supported versus manual microscopy of Kato-Katz smears for diagnosis of soil-transmitted helminth infections in a primary healthcare setting

Abstract Soil-transmitted helminths primarily comprise Ascaris lumbricoides, Trichuris trichiura, and hookworms, infecting more than 600 million people globally, particularly in underserved communities. Manual microscopy of Kato-Katz thick smears is a widely used diagnostic method in monitoring and control programs, but is time-consuming, requires on-site experts and has low sensitivity, especially for light intensity infections. In this study, portable whole-slide scanners and deep learning-based artificial intelligence (AI) were deployed in a primary healthcare setting in Kenya. Stool samples (n = 965) were collected from school children and Kato-Katz thick smears were digitized for AI-based detection. Light-intensity infections accounted for 96.7% of cases. Three diagnostic methods - manual microscopy, autonomous AI and human expert-verified AI - were compared to a composite reference standard, which combined expert-verified helminth eggs in physical and digital smears. Sensitivity for A. lumbricoides, T. trichiura and hookworms was 50.0%, 31.2%, and 77.8% for manual microscopy; 50.0%, 84.4%, and 87.4% for the autonomous AI; and 100%, 93.8%, and 92.2% for expert-verified AI in smears suitable for analysis (n = 704). Specificity exceeded 97% across all methods. The expert-verified AI had higher sensitivity than the other methods while maintaining high specificity for the detection of soil-transmitted helminths in Kato-Katz thick smears, especially in light-intensity infections.

Taxes to red and processed meat to promote sustainable and healthy diets in Mexico

Background Consumption of red and processed meat is above sustainable and healthy dietary targets in Mexico. Policies to promote greater adherence such as taxing meat are needed to reduce consumption. Here, we evaluated how price increases to red and processed meat could shift consumption for meat as well as other key food groups. Methods Using data from the Mexican National Household Income and Expenditure Survey (2018, 2020, 2022), we estimated own- and cross-price elasticities of demand for 10 food groups. These were used to predict changes in quantity demanded of each food group according to price increase scenarios. Results Price increases to meat increased demand for substitutes such as fruits and vegetables, legumes, poultry, and seafood, and reduced demand for salty snacks, sweets and sugary beverages. Substantial increases to the price of processed meat markedly reduced processed meat consumption, increased consumption of protein- and nutrient-rich foods, and resulted in more modest levels of red meat consumption. Lower-income groups were more sensitive to price increases but still met dietary recommendations for meat and substituted these foods with alternatives such as legumes and seafood. Conclusions Increasing the price of red and processed meat through a tax may promote greater adherence to sustainable and healthy dietary targets in Mexico. It simultaneously increased demand for healthier substitutes, and reduced demand for unhealthy complements. Substantially raising the price of processed meat only may be an effective strategy for addressing diet-related risk factors, while delivering environmental benefits. Additionally, meat taxes have the potential to promote improvements in diet quality and equitable health outcomes.

Evolutionary unpredictability in cancer model systems

Abstract Despite the advent of advanced molecular prognostic tools, it is still difficult to predict the course of disease for cancer patients at the individual level. This lack of predictability is also reflected in many experimental cancer model systems, begging the question of whether certain biological aspects of cancer (eg. growth, evolution etc.) can ever be anticipated or if there remains an inherent unpredictability to cancer, similar to other complex biological systems. We demonstrate by a combination of agent-based mathematical modelling, analysis of patient-derived xenograft model systems from multiple cancer types, and in-vitro culture that certain conditions increase stochasticity of the clonal landscape of cancer growth. Our findings indicate that under those conditions, the cancer genome may behave as a complex dynamic system, making its long-term evolution inherently unpredictable.

Inhibitory effects of a hot-water extract of cumin fruit on influenza A virus infection

The influenza A virus (IAV) is an extremely contagious virus responsible for both seasonal flu and global pandemics. Cumin (Cuminum cyminum L., family Apiaceae) is a spice widely used in numerous Asian nations. The cumin fruit, commonly termed ‘cumin seed’, has been used in traditional medicine for the treatment of several ailments; however, its effect on IAV is not completely understood. This study investigated the effect of cumin fruit hot-water extract (CWE) on IAV infection. Madin-Darby canine kidney (MDCK) cells were infected with IAV (H1N1) and used for in vitro experiments. Pre-infection treatment of the target cells with CWE suppressed M1 protein expression in a dose-dependent manner, whereas post-infection treatment had no such effect. CWE at concentrations of 12.5 µg/mL or higher also inhibited IAV-induced haemagglutination and clathrin-dependent endocytosis. Even, a plaque formation assay was also conducted to confirm the efficacy of CWE on virus replication. The assay results showed that CWE significantly reduced IAV replication. However, the expression of type I interferon (IFN) and IFN-stimulated antiviral protein genes was not affected by CWE in the virus-infected cells. Furthermore, the presence of cuminaldehyde in CWE was examined using high-performance liquid chromatography. Cuminaldehyde was not detected in the CWE used in this study. Moreover, cells that were pre-treated with a cuminaldehyde standard did not show any inhibition of IAV infection. The current in vitro study showed that CWE inhibited IAV infection without harming host cells. Thus, CWE may be used to prevent IAV infections by limiting viral attachment and absorption.

Correction: TERT-TP53 mutations: a novel biomarker pair for hepatocellular carcinoma recurrence and prognosis

Optimising access to vocational rehabilitation through multiple sclerosis charities: Protocol for a feasibility randomised controlled trial

Background People with multiple sclerosis (MS) often leave the workforce prematurely due to MS symptoms and difficulties managing workplace relationships and performance. Vocational rehabilitation (VR) can improve job retention outcomes for people with MS, but there is a lack of evidence on the effectiveness of these interventions. Methods A multicentre, feasibility, parallel-group randomised controlled trial (RCT) comparing a job retention VR intervention plus usual care (n = 30) with usual care alone (n = 30). This study includes an embedded mixed-methods process evaluation. People with MS, aged 18–65 years, in paid employment will be recruited from MS charities. Participants with MS will be able to include their employers in the intervention to receive information about MS and employment. The intervention involves an initial interview and up to 10 hours of employment support for people with MS and up to four hours of support for employers, over six months. Employees from MS charities will be recruited and trained to deliver the MSVR intervention. Participants will be followed up by postal/telephone/online questionnaires at 6-, 9-, and 12-months post-randomisation. The aim is to ascertain the feasibility and acceptability of delivering the intervention within MS charities, and to determine parameters for future trial and explore the acceptability of the study intervention and procedures. Discussion This novel study will provide insight into how existing services from MS charities can fill a service gap by providing employment support to people with MS. Findings will inform the design of a future fully powered RCT. Trial registration number ClinicalTrials.gov NCT06966115 .

Positive regulation of root-knot nematode control in Capsicum through bioactive compounds derived from plant seeds cake

Abstract Plant-parasitic nematodes (PPNs) pose a significant problem for farmers worldwide, leading to yield losses. Several conventional strategies, such as artificial nematocides, have been used in the past to control PPNs in pepper plants. In an in vivo trial aimed at reducing root-knot nematodes, (RKNs) Meloidogyne incognita communities in soil and root infestation, certain plant seed cake (PSC) was evaluated for its potential use. In this study, four PSCs were used to manage PPNs: black seed, jojoba, olive, and jatropha. These PSCs relatively inhibited nematode reproduction and promoted pepper plant health. Notably, black seed and jojoba were the most effective toxic PSC against RKNs, M. incognita, especially targeting the second-stage J2s in soil. For example, treatment with black seed at both 15 and 30 g rates, as well as jojoba at 15 g rate, was consistently effective in reducing the final nematode population. Growth parameters, including shoot and root weight and length, as well as the number of leaves, were measured. The results showed that black seed at 30 g and jojoba at 15 g significantly increased shoot weight, followed by black seed at 15 g, with corresponding values of 75.89 g, 47.86 g, and 45.9 g, respectively. According to GC-MS analysis, the mode of action of these PSC may involve natural active compounds capable of killing or inhibiting nematode communities. The GC-MS analysis of jatropha seeds cake showed remarkable bioactive compounds, including D-Psicofuranose, pentakis (trimethylsilyl) ether (isomer 2); 9,12-Octadecadienoic acid; 2-((2-Methyl-1-oxa-4-azaspiro [4.4]non-4yl) carbonyl) cyclopropane carboxylic acid and 1 H-Indene, 2,3-dihydro-4-propyl. These compounds have antimicrobial, insecticidal, anti-nematodal, and antiviral activities confirming their potential as natural biopesticides.

A mixture of ginger phenolic compounds enhances mitochondrial function, activates AMPK, and reduces lipid accumulation in adipocytes

Mitochondrial abundance and activity in adipocytes are critical for adequate adipose tissue function and whole-body energy homeostasis. Mitochondrial dysfunction in adipocytes impairs lipid metabolism, insulin sensitivity, and thermogenesis, leading to metabolic diseases. Enhancing mitochondrial function and density in adipose tissue may provide a promising therapeutic approach for metabolic diseases. This study evaluates the effects of a ginger phenol mixture on mitochondrial density and function, AMPK activation, lipid droplet content, and lipolysis markers in adipocytes differentiated in vitro. Pre-adipocytes isolated from the inguinal adipose tissue of Wistar rats were differentiated and assigned to three experimental groups: vehicle (0.2% DMSO), gingerol mixture (6 μg/mL), and positive control (1 mmol/m3 AMPK activator 5-Aminoimidazole-4-carboxamide ribonucleoside). Mitochondrial density and lipid content were assessed by MitoTracker and Bodipy staining respectively, while mitochondrial respiration was evaluated in an Extracellular Flux Analyzer. Protein abundance and basal lipolysis were evaluated by Western blotting and free fatty acids determination in supernatant, respectively. The gingerol mixture significantly enhanced mitochondrial density and respiration, including both maximal and ATP-linked capacities. Additionally, it activated AMPK, upregulated the expression of mitochondrial complexes, enhanced lipolysis markers, and reduced lipid droplet content. These findings suggest that the gingerol mixture enhances mitochondrial function, stimulates lipolysis, and reduces lipid accumulation in adipocytes, contributing to metabolic homeostasis in adipose tissue. This highlights its potential use as a complementary therapeutic agent for the management of obesity.

Beyond planar: fish schools adopt ladder formations in 3D

Response study of tower crane and elastic plate under dynamic complicated excitation

Structural vibration will inevitably occur under the dynamic complicated excitations in tower crane and elastic plate system. The continuous nonlinear vibration would lead to the deterioration of the coupling state of the responses of the tower crane and the elastic plate system. This, in turn, impacts the operational stability and reduces the service life of components. Consequently, there has been scant research on response calculation of the structure in a tower crane and elastic plate system when considering such dynamic and complex excitations. To address this gap, this paper employs a spatially coupled dynamics model of the tower crane and the plate, covering the acceleration stage, the constant speed stage, and then the deceleration stage. This model incorporates typical air resistance, the Lagrange equation, and the calculation equations based on the Reissner plate theory. Additionally, emergency braking, regarded as a type of fault, is taken into account in the dynamic model. The present model is solved numerically. The feasibility of the model is validated by comparing the measured responses of the dynamic coupling model with the experimental ones. An extensive analysis is conducted on the influence of different braking times on the dynamic response. The analysis reveals that if the emergency braking time exceeds 1.5 seconds, the vibration of the plate and tower crane system is minimal. The Kurtosis Value, Factor Value, and Skewness Value exhibit high sensitivity to the dynamic responses of the plate and the swing angles. The Frequency Center demonstrates high sensitivity to the swing angle, while the Root Mean Square Frequency and Frequency Standard Deviation show high sensitivity to the plate vibration.

Ultrathin monolithic bimorph mirror using polarization-inverted lithium niobate wafer

Retraction: Effect of co-encapsulation using white and red onion peel extract on the viability and stability of Lacticaseibacillus rhamnosus under stressful conditions

Isotopes, herds, and landscape management practices: New insights on early farming communities in the Serpis Valley (Eastern Iberian Peninsula)

The establishment of the first livestock communities in the eastern Iberian Peninsula during the 6th millennium cal BCE marked a significant transition in the region’s economic system. The research of early animal management practices provides crucial valuable understanding into feeding and pastoral strategies, revealing insights into the social organization of landscapes and their resources. Using stable carbon (δ13C) and nitrogen (δ15N) isotopic analyses of faunal remains this study investigates the interplay between environmental conditions, animal management practices, and dietary habits in Neolithic herds from Mas d’Is and Niuet sites in the Serpis Valley. The landscape of the area, characterized by Mediterranean forests and marshes, provided a variety of plant resources. Although most of the valley is covered by C3 types of plants, there were some clusters of C4 vegetation. The isotopic analyses prove that the local herds can be disaggregated in two groups: some animals with a diet based on C3, some feeding on C4 plants. These results reveal diverse feeding strategies and, by default, spatialized management practices. In addition, the animals presenting a C3 signature, have, as well, strong nitrogen values and marks on the bones that indicate they were part of the agricultural cycle as traction force. This complex organisational strategy, with two herds that show different levels of husbandry intensification, might reflect broader socio-economic systems, where the landscape may have been managed with a mosaic of different property regimes: where marginal areas might have been considered as communal or open-access resources, while more fertile areas nearby settlements, might have been used as crop fields, and individually or household managed. The integration of livestock into agricultural systems and the selective use of landscape resources highlight an adaptive and dynamic approach to animal husbandry in response to environmental and social factors during the Neolithic in the Serpis Valley.

Application of video surveillance in preclinical safety studies in canines: Understanding the interobserver reliability and validity to recognize clinical behavior

Preclinical in vivo studies are critical to identify potential adverse effects of drugs under development. However, a significant number of drug candidates are terminated during human clinical trials due to unexpected adverse events which were not predicted or detected in preclinical studies. Video surveillance can be a valuable tool to reduce the risk of missing and/or misclassifying adverse clinical observations (COs) in animals. To explore the applicability of detecting COs on video, the agreement between observers (reliability) and agreement between observers and experts (construct validity) of 13 important COs was evaluated. The reliability was investigated by evaluating the interobserver agreement between 23 observers with different experience levels and primary roles on defined COs and normal behavior, recorded on video during preclinical studies in canines. The validity was investigated by comparing the observers’ assessments to the ground truth confirmed by three experts. This investigation showed a substantial reliability and validity of the observers’ assessments without significant differences between experience levels or primary roles. Normal behavior was challenging to recognize (56% correct), while half of the COs appeared straightforward to identify with a validity of ≥ 90%: salivation, aggressiveness, circling, vomiting, head shaking and convulsions. Other COs were more challenging to detect with lowest scores for limb stiff/hypertonia, tremors and excitation. Regardless of experience-level, observers missed very few COs. This investigation showed the complexity when multiple COs occurred simultaneously, as well as the limitations of differentiating between visually similar COs (tremors vs. twitches; limping vs. limb stiff) on video without the possibility of in-person observation. Given the substantial overall reliability and validity, it is concluded that clinical canine behavior can be accurately detected on video by trained observers. This permits more objective and quantifiable monitoring of animal behavior and application of computer vision for future automatic monitoring of canine studies.

Research on atmospheric temperature change and its adaptive strategies in winter wheat and summer maize dual-cropping region of North China Plain during 1961–2021—A case study of Jiaozuo City in Henan Province

Global warming has caused the frequency and intensity of extreme weather events in agriculture. Therefore, research on temperature changes in major grain-producing areas is essential for formulating adaptation strategy. This article takes Jiaozuo City, Henan Province, China as the research area. Based on daily maximum, minimum and mean temperatures from seven meteorological stations for the period 1961–2021, the comprehensive indications of temperature changes were analyzed using the linear tendency estimation, Mann-Kendall test, and levels fluctuation. Fourteen climate indices in four classes, including the mean temperature index, absolute extreme temperature index, relative extreme temperature index, and disaster temperature index, were applied. The results indicated four aspects. Firstly, the average regional warming speed was 0.259°C/10a—slightly lower than the national average, and the years of the highest and lowest values were 2021 and 1984, respectively. Secondly, the daily minimum and maximum temperatures increased significantly, which were 0.395°C/10a and 0.200°C/10a respectively—less than the national mean. The relevant low temperature index showed proper decreasing trend while the diurnal range of annual extreme temperature showed fluctuating—decreasing first and then increasing. Thirdly, the relevant e high temperature indices of plain urban area were larger while the relevant low temperature indices of mountain hilly area were smaller. The relative high temperature indices showed an increasing trend while the relevant low temperature indices tended to decrease. Fourthly, high temperature disasters generally declined before the 1980s and increased thereafter; low temperature disasters showed a decreasing trend overall. This study suggests that in the two-cropping regions of winter wheat and summer maize, attention should be paid to the increasing trend of high-temperature days. Additionally, heat-tolerant varieties should be cultivated to expand the planting area of maize for adapting to increasing drought disasters induced by high temperature, as well as to establish an agricultural disaster-risk mechanism for addressing high temperature meteorological disasters.