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Persistent malnutrition is associated with poor clinical outcomes in cancer. However, assessing its reversibility can be challenging. The present study aimed to utilise machine learning (ML) to predict reversible malnutrition (RM) in patients with cancer. A multicentre cohort study including hospitalised oncology patients. Malnutrition was diagnosed using an international consensus. RM was defined as a positive diagnosis of malnutrition upon patient admission which turned negative one month later. Time-series data on body weight and skeletal muscle were modelled using a long short-term memory architecture to predict RM. The model was named as WAL-net, and its performance, explainability, clinical relevance and generalisability were evaluated. We investigated 4254 patients with cancer-associated malnutrition (discovery set = 2977, test set = 1277). There were 2783 men and 1471 women (median age = 61 years). RM was identified in 754 (17·7 %) patients. RM/non-RM groups showed distinct patterns of weight and muscle dynamics, and RM was negatively correlated to the progressive stages of cancer cachexia (r = –0·340, P < 0·001). WAL-net was the state-of-the-art model among all ML algorithms evaluated, demonstrating favourable performance to predict RM in the test set (AUC = 0·924, 95 % CI = 0·904, 0·944) and an external validation set (n 798, AUC = 0·909, 95 % CI = 0·876, 0·943). Model-predicted RM using baseline information was associated with lower future risks of underweight, sarcopenia, performance status decline and progression of malnutrition (all P < 0·05). This study presents an explainable deep learning model, the WAL-net, for early identification of RM in patients with cancer. These findings might help the management of cancer-associated malnutrition to optimise patient outcomes in multidisciplinary cancer care.
Interrupted aortic arch is an uncommon cardiac anomaly characterised by a lack of continuity between the ascending and descending aorta. The presence of interrupted aortic arch in adults is extremely rare, and there is limited documentation of such cases in the literature. In this article, we present a unique case of interrupted aortic arch in an adult diagnosed through angiography. This case falls under the anatomical classification of type B interruption, although the blood supply to the left subclavian artery originates from the ascending aorta. Its haemodynamic characteristics are completely different from those of the classical type B interruption.
Generative Artificial Intelligence (Generative AI) is a collection of AI technologies that can generate new information such as texts and images. With its strong capabilities, Generative AI has been actively studied in creative design processes. However, limited studies have explored the roles of humans and Generative AI in conceptual design processes, which leaves a gap for human–AI collaboration investigation. To address this gap, this study attempts to uncover the contributions of different Generative AI technologies in assisting humans in the conceptual design process. Novice designers were recruited to complete two design tasks in the condition of with or without the assistance of Generative AI. The results revealed that Generative AI primarily assists humans in the problem definition and idea generation stages, while the idea selection and evaluation stage remains predominantly human-led. Additionally, with the assistance of Generative AI, the idea selection and evaluation stages were further enhanced. Based on the findings, we discussed the role of Generative AI in human–AI collaboration and the implications for enhancing future conceptual design support with Generative AI’s assistance.
Bombyx mori Tryptophanyl-tRNA synthetase (BmWARS) belongs to the family of Ic-like aminoacyl-tRNA synthetases (aaRSs), whose specific recognition of the substrate Trp, tRNA, maintains the fidelity of protein synthesis. In this study, BmWARS was cloned and characterized from the midgut of the silkworm, Bombyx mori, resulting in an open reading frame (ORF) with a full length of 1,149 bp, which can encode 382 Aa. BmWARS is localized in the cytoplasm, and is expressed in all tissues of the silkworm, with higher expression in the testis, ovary, silk gland and malpighian tubule. The expression of BmWARS was significantly up-regulated in the midgut and silk gland after infection with Bombyx mori nuclear polyhedrosis virus (BmNPV). In addition, overexpression of BmWARS inhibited BmNPV infection and replication extremely significantly, while interference with BmWARS expression promoted BmNPV infection and replication. Analysis of the immune pathways in which BmWARS may be involved revealed that the expression of the key genes of the PI3K-Akt pathway, BmPI3K, BmAkt, BmPDK1, BmeIF4E, BmS6, and p-Akt protein was significantly reduced, whereas the expression of BmPTEN, BmFoxO, and BmCaspase9 was significantly increased in the cells that overexpressed BmWARS and were infected with BmNPV. Meanwhile, the results of the study interfering with the expression of BmWARS were completely opposite to those of the study overexpressing BmWARS. This is the first report that BmWARS has antiviral effects in Bombyx mori. Moreover, BmWARS inhibits BmNPV infection and replication in Bombyx mori cells by promoting apoptosis and inhibiting cell proliferation.
Childhood and adolescence are vulnerable periods for mental disorders, and the COVID-19 pandemic has exacerbated mental health challenges in this population. We aimed to estimate changes in the global burden of mental disorders among children and adolescents before and during the pandemic.
Methods
Using data from the Global Burden of Diseases Study 2021, we analyzed incidence, prevalence, and years lived with disability (YLDs) for mental disorders in individuals aged 5–24. Annual percent changes in age-standardized rates were calculated, and a Bayesian age–period–cohort model estimated the expected and additional burden based on pre-pandemic trends.
Results
In 2021, an estimated 123.0 million new cases of mental disorders were reported among children and adolescents, with an 11.8% average annual increase in the age-standardized incidence rate during the pandemic. Anxiety disorders, which previously ranked third, became the leading cause of nonfatal disability (12.9 million [8.0–19.3] YLDs), while depressive disorders rose to fourth place (10.9 million [6.8–16.5] YLDs). The burden grew in most regions, especially among females, those aged 15–24, and in high sociodemographic index (SDI) areas. Based on pre-pandemic data, we estimated an additional burden of 795.0, 165.9, and 622.8 new cases per 100,000 population for total mental disorders, anxiety disorders, and depressive disorders globally in 2021, respectively. Spearman correlation analysis showed a significant positive correlation between additional burden and SDI levels.
Conclusions
These findings highlight the increased burden of mental disorders among children and adolescents during the pandemic, emphasizing the need for targeted post-pandemic mental health support.
Systematically monitoring the baseline sensitivity of troublesome weeds to herbicides is a crucial step in the early detection of their market lifespan. Florpyrauxifen-benzyl is one of the most important herbicides used in rice production throughout the world, and has been used for 5 yr in China. Barnyardgrass is one of the main targeted weed species of florpyrauxifen-benzyl. In total, 114 barnyardgrass populations were collected from rice fields in Jiangsu Province, China, and using whole-plant bioassays they were screened for susceptibility to florpyrauxifen-benzyl. The GR50 values (representing the dose that causes a 50% reduction in fresh weight of aboveground parts) of florpyrauxifen-benzyl for all populations ranged from 1.0 to 34.5 g ai ha−1, with an average of 6.8 g ai ha−1, a baseline sensitivity dose of 3.3 g ai ha−1, and a baseline sensitivity index of 34.5. Twenty-one days after treatment with florpyrauxifen-benzyl at the labeled dose (36 g ai ha−1), 90% of the barnyardgrass populations exhibited >95% reductions in fresh weight of aboveground parts. Compared with the baseline sensitivity dose, 63, 44, and 7 populations had, respectively, no resistance (55%), low resistance (39%), and moderate resistance (6%) to florpyrauxifen-benzyl. Furthermore, the GR50 distribution of barnyardgrass populations did not show a significant correlation with collection location, planting method (direct-seeding or transplanting), or rice species (Oryza sativa L. ssp. indica or ssp. japonica) at any of rice fields where seeds had been collected (P > 0.05). In conclusion, florpyrauxifen-benzyl remains effective for barnyardgrass control in rice fields despite serious resistance challenges.
Based on a 4f system, a 0° reflector and a single laser diode side-pump amplifier, a new amplifier is designed to compensate the spherical aberration of the amplified laser generated by a single laser diode side-pump amplifier and enhance the power of the amplified laser. Furthermore, the role of the 4f system in the passive spherical aberration compensation and its effect on the amplified laser are discussed in detail. The results indicate that the amplification efficiency is enhanced by incorporating a 4f system in a double-pass amplifier and placing a 0° reflector only at the focal point of the single-pass amplified laser. This method also effectively uses the heat from the gain medium (neodymium-doped yttrium aluminium garnet) of the amplifier to compensate the spherical aberration of the amplified laser.
This study aims to investigate the effects of the vine of Lonicera japonica Thunb (VLT) and marine-derived Bacillus amyloliquefaciens-9 (BA-9) supplementation on the growth performance, antioxidant capacity, and gut microbiota of goat kids. A total of 32 4-week-old kids were randomly assigned into four groups: a control group (CON), a group supplemented with 0.3% BA-9 (BA-9), a group supplemented with 2% VLT (VLT), and a group supplemented with both 0.3% BA-9 and 2% VLT (MIX). The results indicated that VLT supplementation significantly increased both average daily (P < 0.001) and total weight gain (TWG) (P < 0.001), while BA-9 alone had no significant effect (P > 0.05) on the average daily and TWG. Biomarker analysis of oxidative stress revealed that supplementation of VLT or BA-9 alone enhanced antioxidant capacity. The MIX group showing a higher total antioxidant capacity (T-AOC) compared with the CON, VLT, and BA-9 groups (P < 0.05). Plasma albumin (ALB) levels were significantly increased in the both VLT and BA-9 groups. Microbiota analysis revealed significant differences in α-diversity and β-diversity between the MIX and CON groups, with specific genera such as Prevotellaceae_UCG.004 and Rikenellaceae_RC9_gut_group negatively correlated with average daily gain (ADG), while Alistipes was positively correlated with T-AOC. These findings suggest that the combined supplementation of VLT and BA-9 can significantly enhance growth performance and antioxidant capacity in goat kids by modulating the composition of gut microbiota and reducing oxidative stress.
The Central Asian Orogenic Belt is the world’s largest accretionary orogenic belt, associated with the closure of the Paleo-Asian Ocean (PAO). However, the final closure timing of the eastern PAO remains contentious. The Permian-Triassic sedimentary sequences in the Wangqing area along the Changchun-Yanji suture zone offer important clues into this final closure. New data on petrology, whole-rock geochemistry, zircon U-Pb geochronology and zircon Hf isotopes of sedimentary rocks from the Miaoling Formation and Kedao Group in Wangqing area provide new insights into the final closure of the eastern end of the PAO. The maximum deposition ages of the Miaoling Formation and Kedao Group have been constrained to the Late Permian (ca. 253 Ma) and early Middle Triassic (ca. 243 Ma), respectively. These sedimentary rocks exhibit similar geochemical characteristics, showing low textural and compositional maturities, implying short sediment transport, with all detrital zircons suggesting their origins from felsic igneous rocks. The εHf(t) values of the Miaoling Formation range from −6.09 to 12.43 and from −2.20 to 7.59 for the Kedao Group, implying these rocks originated from NE China. Considering our new data along with previously published data, we propose that a reduced remnant ocean remained along the Changchun-Yanji suture zone in the early Middle Triassic (ca. 243 Ma), suggesting the final closure of the eastern PAO likely occurred between the latest Middle Triassic and early Late Triassic.
This brief review summarises the efficacy of the treatments for post-irradiation otitis media with effusion.
Method
Literature review.
Results
Studies suggest that tympanocentesis is recommended for patients with post-irradiation otitis media with effusion The efficacy of balloon dilatation Eustachian tube for post-irradiation otitis media with effusion remains unclear.
Conclusion
The efficacy of different treatments for post-irradiation otitis media with effusion is unclear. Therefore, there are no recognised clinical guidelines, and long-term clinical research with a large sample size is needed.
This work investigates the spatio-temporal evolution of coherent structures in the wake of a generic high-speed train, based on a three-dimensional database from large eddy simulation. Spectral proper orthogonal decomposition (SPOD) is used to extract energy spectra and energy ranked empirical modes for both symmetric and antisymmetric components of the fluctuating flow field. The spectrum of the symmetric component shows overall higher energy and more pronounced low-rank behaviour compared with the antisymmetric one. The most dominant symmetric mode features periodic vortex shedding in the near wake, and wave-like structures with constant streamwise wavenumber in the far wake. The mode bispectrum further reveals the dominant role of self-interaction of the symmetric component, leading to first harmonic and subharmonic triads of the fundamental frequency, with remarkable deformation of the mean field. Then, the stability of the three-dimensional wake flow is analysed based on two-dimensional local linear stability analysis combined with a non-parallelism approximation approach. Temporal stability analysis is first performed for both the near-wake and the far-wake regions, showing a more unstable condition in the near-wake region. The absolute frequency of the near-wake eigenmode is determined based on spatio-temporal analysis, then tracked along the streamwise direction to find out the global mode growth rate and frequency, which indicate a marginally stable global mode oscillating at a frequency very close to the most dominant SPOD mode. The global mode wavemaker is then located, and the structural sensitivity is calculated based on the direct and adjoint modes derived from a local spatial analysis, with the maximum value localized within the recirculation region close to the train tail. Finally, the global mode shape is computed by tracking the most spatially unstable eigenmode in the far wake, and the alignment with the SPOD mode is computed as a function of streamwise location. By combining data-driven and theoretical approaches, the mechanisms of coherent structures in complex wake flows are well identified and isolated.
Artificial sweeteners are generally used and recommended to alternate added sugar for health promotion. However, the health effects of artificial sweeteners remain unclear. In this study, we included 6371 participants from the National Health and Nutrition Examination Survey with artificial sweetener intake records. Logistic regression and Cox regression were applied to explore the associations between artificial sweeteners and risks of cardiometabolic disorders and mortality. Mendelian randomisation was performed to verify the causal associations. We observed that participants with higher consumption of artificial sweeteners were more likely to be female and older and have above medium socio-economic status. After multivariable adjustment, frequent consumers presented the OR (95 % CI) for hypertension (1·52 (1·29, 1·80)), hypercholesterolaemia (1·28 (1·10, 1·50)), diabetes (3·74 (3·06, 4·57)), obesity (1·52 (1·29, 1·80)), congestive heart failure (1·89 (1·35, 2·62)) and heart attack (1·51 (1·10, 2·04)). Mendelian randomisation confirmed the increased risks of hypertension and type 2 diabetes. Moreover, an increased risk of diabetic mortality was identified in participants who had artificial sweeteners ≥ 1 daily (HR = 2·62 (1·46, 4·69), P = 0·001). Higher consumption of artificial sweeteners is associated with increased risks of cardiometabolic disorders and diabetic mortality. These results suggest that using artificial sweeteners as sugar substitutes may not be beneficial.
Certain rhythmic arterial pressure waves in humans and animals have been noticed for over one century. We found the novel and slowest arterial pressure waves in children following surgical repair for CHD, and examined their characteristics and clinical implications.
Methods:
We enrolled 212 children with 22 types of CHD within postoperative 48 h. We monitored haemodynamics (blood pressure, cardiac cycle efficiency, dP/dTmax), cerebral (ScO2), and renal (SrO2) oxygen saturation every 6 s. Electroencephalogram was continuously monitored. Mean blood flow velocity (Vm) of the middle cerebral artery was measured at 24 h.
Results:
We found the waves with a frequency of ∼ 90 s immediately following surgical repair in 46 patients in 12 types of CHD (21.7%), being most prevalent in patients with aortic arch abnormalities (Aorta Group, n = 24, 42.3%) or ventricular septal defect (Ventricular Septal Defect Group, n = 12, 23.5%). In Aorta and Ventricular Septal Defect Groups, the occurrence of the waves was associated with lower blood pressures, dP/dTmax, cardiac cycle efficiency, ScO2, SrO2, Vm, worse electroencephalogram background abnormalities, higher number of electroencephalogram sharp waves, and serum lactate (Ps <0.0001–0.07), and were accompanied with fluctuations of ScO2 and SrO2 in 80.6% and 69.6% of patients, respectively.
Conclusions:
The waves observed in children following cardiovascular surgery are the slowest ever reported, occurring most frequently in patients with aortic arch abnormalities or ventricular septal defect. While the occurrence of the waves was associated with statistically worse and fluctuated ScO2 and SrO2, worse systemic haemodynamics, and electroencephalogram abnormalities, at present these waves have no known clinical relevance.
To compare the benefits and drawbacks of traditional and automated conservation assessments, we used a field-based study and automated conservation assessments using GeoCAT, red and ConR to assess four species of Buddleja (Scrophulariaceae), a cosmopolitan genus of flowering plants. Buddleja colvilei, Buddleja sessilifolia, Buddleja delavayi and Buddleja yunnanensis are endemic to the Himalayan region. They have not yet been assessed for the IUCN Red List of Threatened Species but are facing elevated risks of extinction because of various anthropogenic and environmental pressures. Buddleja sessilifolia and B. delavayi are listed as Plant Species with Extremely Small Populations in Yunnan, China, where they are known to be threatened. Although automated assessments evaluated B. delavayi and B. yunnanensis as Endangered and B. sessilifolia and B. colvilei as Vulnerable, our field studies indicated a different categorization for three of the species: B. delavayi and B. yunnanensis as Critically Endangered and B. sessilifolia as Endangered. Our findings indicate that the accuracy and reliability of assessment methods can differ and that field surveys remain important for conservation assessments. We recommend an integrated approach addressing these limitations, to safeguard the future of other species endemic to the Himalayan region.
There is a clear demand for innovative therapeutics for bipolar disorder (BD).
Methods
We integrated the largest BD genome-wide association study (GWAS) dataset (NCase = 41 917, NControl = 371 549) with protein quantitative trait loci from brain, cerebrospinal fluid, and plasma. Using a range of integrative analyses, including Mendelian randomization (MR), Steiger filter analysis, Bayesian colocalization, and phenome-wide MR analysis, we prioritized novel drug targets for BD. Additionally, we incorporated data from the UK Biobank (NCase = 1064, NControl = 365 476) and the FinnGen study (NCase = 7006, NControl = 329 192) for robust biological validation.
Results
Through MR analysis, we found that in the brain, downregulation of DNM3, MCTP1, ABCB8 and elevation of DFNA5 and PDF were risk factors for BD. In cerebrospinal fluid, increased BD risk was associated with increased levels of FRZB, AGRP, and IL36A and decreased CTSF and LRP8. Plasma analysis revealed that decreased LMAN2L, CX3CL1, PI3, NCAM1, and TIMP4 correlated with increased BD risk, but ITIH1 did not. All these proteins passed Steiger filtering, and Bayesian colocalization confirmed that 12 proteins were colocalized with BD. Phenome-wide MR analysis revealed no significant side effects for potential drug targets, except for LRP8. External validation further underscored the concordance between the primary and validation cohorts, confirming MCTP1, DNM3, PDF, CTSF, AGRP, FRZB, LMAN2L, NCAM1, and TIMP4 are intriguing targets for BD.
Conclusions
Our study identified druggable proteins for BD, including MCTP1, DNM3, and PDF in the brain; CTSF, AGRP, and FRZB in cerebrospinal fluid; and LMAN2L, NCAM1, and TIMP4 in plasma, delineating promising avenues to development of novel therapies.
Stable separation is a crucial condition that must be met in order for combined aircraft to successfully engage in cooperative flight. In order to achieve the desired fast and controlled separation, this paper proposes a novel design for a torque-driven compliant separation mechanism. By taking into account the compliance characteristics of a sinusoidal acceleration function curve, a mechanical model for the separation mechanism is developed. By utilising the Coulomb friction law, an accurate determination of the aerodynamic load distribution under various conditions is achieved. Subsequently, the relationship between the unlocking moment and the aerodynamic load is derived based on these findings. Through the utilisation of the finite element method, a model of the separation mechanism is generated. To ensure the safety and reliability of the compliant separation mechanism, the mechanical properties of the structural materials are thoroughly analysed under the maximum aerodynamic load. Subsequently, the separation mechanism structure is constructed and subjected to testing in order to showcase the compliance characteristics. In addition, this paper conducts a simulation to analyse the impact of flight speed and angle-of-attack on the separation process. By doing so, the optimal conditions for separation are determined. The methods and findings presented in this study have the potential to contribute valuable insights to the design of combined aircraft.
Many studies have found an association between mood-disorder-related traits and endometriosis and adenomyosis. However, the cause–effect relationship remains unclear.
Aims
We conducted Mendelian randomisation analyses to evaluate any causal relationship between mood disorders and endometriosis as well as different sites of endometriosis.
Method
Summary-level statistics for mood-disorder-related traits and endometriosis (8288 cases, 68 969 controls) in European populations were derived from large-scale data-sets of genome-wide association studies. A two-sample Mendelian randomisation was performed using the inverse-variance weighted and weight median methods. Further sensitivity analyses, including heterogeneity, pleiotropy and leave-one-out analyses, were conducted to test the consistency of the results.
Results
Genetically determined mood swings (odds ratio = 2.557, 95% CI: 1.192–5.483, P = 0.016) and major depression (odds ratio = 1.233, 95% CI: 1.019–1.493, P = 0.031) were causally associated with an increased risk of endometriosis. Mood swings (odds ratio = 4.238, 95% CI: 1.194–15.048, P = 0.025) and major depression (odds ratio = 1.512, 95% CI: 1.052–2.173, P = 0.025) were also causally associated with the risk of adenomyosis. Sensitivity analyses confirmed the reliability of the results.
Conclusions
Our results suggest that mood-disorder-related traits increase the risk of endometriosis and adenomyosis. This study provides new insights into the potential pathogenesis of endometriosis and adenomyosis, and highlights the importance of preventing endometriosis and adenomyosis in patients with mood-disorder-related traits.