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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.
The quality of news reports about suicide can influence suicide rates. Although many researchers have aimed to assess the general safety of news reporting in terms of adherence to responsible media guidelines, none have focused on major US cable networks, a key source of public information in North America and beyond.
Aims
To characterise and compare suicide-related reporting by major US cable television news networks across the ideological spectrum.
Method
We searched a news archive (Factiva) for suicide-related transcripts from ‘the big three’ US cable television news networks (CNN, Fox News and MSNBC) over an 11-year inclusion interval (2012–2022). We included and coded segments with a major focus on suicide (death, attempt and/or thoughts) for general content, putatively harmful and protective characteristics and overarching narratives. We used chi-square tests to compare these variables across networks.
Results
We identified 612 unique suicide-related segments (CNN, 398; Fox News, 119; MSNBC, 95). Across all networks, these segments tended to focus on suicide death (72–89%) and presented stories about specific individuals (61–87%). Multiple putatively harmful characteristics were evident in segments across networks, including mention of a suicide method (42–52%) – with hanging (15–30%) and firearm use (12–20%) the most commonly mentioned – and stigmatising language (39–43%). Only 15 segments (2%) presented a story of survival.
Conclusions
Coverage of suicide stories by major US cable news networks was often inconsistent with responsible reporting guidelines. Further engagement with networks and journalists is thus warranted.
Patients with schizophrenia have a significantly elevated risk of mortality. Clozapine is effective for treatment-resistant schizophrenia, but its use is limited by side-effects. Understanding its association with mortality risk is crucial.
Aims
To investigate the associations of clozapine with all-cause and cause-specific mortality risk in schizophrenia patients.
Method
In this 18-year population-based cohort study, we retrieved electronic health records of schizophrenia patients from all public hospitals in Hong Kong. Clozapine users (ClozUs) comprised schizophrenia patients who initiated clozapine treatment between 2003 and 2012, with the index date set at clozapine initiation. Comparators were non-clozapine antipsychotic users (Non-ClozUs) with the same diagnosis who had never received a clozapine prescription. They were 1:2 propensity score matched with demographic characteristics and physical and psychiatric comorbidities. ClozUs were further defined according to continuation of clozapine use and co-prescription of other antipsychotics (polypharmacy). Accelerated failure time (AFT) models were used to estimate the risk of all-cause and cause-specific mortality (i.e. suicide, cardiovascular disease, infection and cancer).
Results
This study included 9,456 individuals (mean (s.d.) age at the index date: 39.13 (12.92) years; 50.73% females; median (interquartile range) follow-up time: 12.37 (9.78–15.22) years), with 2020 continuous ClozUs, 1132 discontinuous ClozUs, 4326 continuous non-ClozUs and 1978 discontinuous Non-ClozUs. Results from adjusted AFT models showed that continuous ClozUs had a lower risk of suicide mortality (acceleration factor 3.01; 99% CI: 1.41–6.44) compared with continuous Non-ClozUs. Continuous ClozUs with co-prescription of other antipsychotics exhibited lower risks of suicide mortality (acceleration factor 3.67; 1.41–9.60) and all-cause mortality (acceleration factor 1.42; 1.07–1.88) compared with continuous Non-ClozUs. No associations were found between clozapine and other cause-specific mortalities.
Conclusions
These results add to the existing evidence on the effectiveness of clozapine, particularly its anti-suicide effects, and emphasise the need for continuous clozapine use for suitable patients and the possible benefit of clozapine polypharmacy.
Large-eddy simulations have been conducted to investigate the decay law of homogeneous turbulence influenced by a magnetic field within a cubic domain, employing periodic boundary conditions. The initial integral Reynolds number is approximately 1000, while the initial interaction number $N$ ranges from 0.1–100. The results reveal that the Joule cone angle $\theta$, half of the Joule cone, decays as $\cos \theta \sim t^{-1/2}$ when $N \gg 1$. In the nonlinear stage, small-scale vortices gradually recover and restore three-dimensionality. Moreover, the corresponding critical state at small scales, marking the transition from quasi-two-dimensional structure to the onset of three-dimensionality, has been quantitatively defined. During the linear stage, based on the true magnetic damping number ($\tau _t = \rho / (\sigma {\boldsymbol{B}}^2 \cos ^2 \psi )$, where $\sigma$, $\boldsymbol{B}$ and $\psi$ denote the electrical conductivity, magnetic field and the angle between the wavevector and $\boldsymbol{B}$ in Fourier space, respectively), Moffatt’s decay law, $K \sim t^{-1/2}$, manifests at distinct times and zones in the Fourier space, with $K$ signifying turbulent kinetic energy. In the nonlinear stage, for $N \gg 1$, a $-3$ slope in the energy power spectrum is prominently observed over an extended period. The near-equivalence of the characteristic time scales of inertial and Lorentz forces in the inertial subrange suggests a quasiequilibrium state between energy transfer and Joule dissipation in Fourier space, thereby corroborating the hypothesis proposed by Alemany et al. 1979 Journal de Mecanique18(2): 277–313. Additionally, it is observed that pressure mediates energy transfer from horizontal kinetic energy ($K_{\parallel }$) to vertical kinetic energy ($K_{\bot }$), accelerating the decay of $K_{\parallel }$. Notably, concurrent inverse and direct energy transfers emerge during the decay process. Our analysis reveals that the ratio $R$ of the maximum inverse to maximum direct energy flux correlates with the dimensionality of the turbulence, following the scaling law $R\sim (\cos \theta )^{-2.2}$.
Precise stratification of patients into homogeneous disease subgroups could address the heterogeneity of phenotypes and enhance understanding of the pathophysiology underlying specific subtypes. Existing literature on subtyping patients with major depressive disorder (MDD) mainly utilized clinical features only. Genomic and imaging data may improve subtyping, but advanced methods are required due to the high dimensionality of features.
Methods
We propose a novel disease subtyping framework for MDD by integrating brain structural features, genotype-predicted expression levels in brain tissues, and clinical features. Using a multi-view biclustering approach, we classify patients into clinically and biologically homogeneous subgroups. Additionally, we propose approaches to identify causally relevant genes for clustering.
Results
We verified the reliability of the subtyping model by internal and external validation. High prediction strengths (PS) (average PS: 0.896, minimum: 0.854), a measure of generalizability of the derived clusters in independent datasets, support the validity of our approach. External validation using patient outcome variables (treatment response and hospitalization risks) confirmed the clinical relevance of the identified subgroups. Furthermore, subtype-defining genes overlapped with known susceptibility genes for MDD and were involved in relevant biological pathways. In addition, drug repositioning analysis based on these genes prioritized promising candidates for subtype-specific treatments.
Conclusions
Our approach successfully stratified MDD patients into subgroups with distinct clinical prognoses. The identification of biologically and clinically meaningful subtypes may enable more personalized treatment strategies. This study also provides a framework for disease subtyping that can be extended to other complex disorders.
In the present study, we investigate the modulation effects of particles on compressible turbulent boundary layers at a Mach number of 6, employing high-fidelity direct numerical simulations based on the Eulerian–Lagrangian point-particle approach. Our findings reveal that the mean and fluctuating velocities in particle-laden flows exhibit similarities to incompressible flows under compressibility transformations and semi-local viscous scaling. With increasing particle mass loading, the reduction in Reynolds shear stress and the increase in particle feedback force constitute competing effects, leading to a non-monotonic variation in skin friction, particularly in turbulence over cold walls. Furthermore, dilatational motions near the wall, manifested as travelling-wave structures, persist under the influence of particles. However, these structures are significantly weakened due to the suppression of solenoidal bursting events and the negative work exerted by the particle feedback force. These findings align with the insight of Yu et al. (J. Fluid. Mech., vol. 984, 2024, A44), who demonstrated that dilatational motions are generated by the vortices associated with intense bursting events, rather than acting as evolving perturbations beneath velocity streaks. The attenuation of travelling-wave structures at higher particle mass loadings also contributes to the reduction in the intensities of wall shear stress and heat flux fluctuations, as well as the probability of extreme events. These results highlight the potential of particle-laden flows to mitigate aerodynamic forces and thermal loads in high-speed vehicles.
Although dietary factors have been examined as potential risk factors for liver cancer, the evidence is still inconclusive. Using a diet-wide association analysis, our research evaluated the associations of 126 foods and nutrients on the risk of liver cancer in a Chinese population. We obtained the diet consumption of 72,680 women in the Shanghai Women’s Health Study using baseline dietary questionnaires. The association between each food and nutrient and liver cancer risk was quantified by Cox regression model. A false discovery rate of 0.05 was used to determine the foods and nutrients which need to be verified. Totally 256 incident liver cancer cases were identified in 1,267,391 person-years during the follow-up duration. At the statistical significance level (P ≤ 0.05), higher intakes of cooked wheaten foods, pear, grape and copper were inversely associated with liver cancer risk, while spinach, leafy vegetables, eggplant and carrots showed the positive associations. After considering multiple comparisons, no dietary variable was associated with liver cancer risk. Similar findings were seen in the stratification, secondary and sensitivity analyses. Our findings observed no significant association between dietary factors and liver cancer risk after considering multiple comparisons in Chinese women. More evidence is needed to explore the associations between diet and female liver cancer occurrence.
Isolated multi-MeV $\gamma$-rays with attosecond duration, high collimation and beam angular momentum (BAM) may find many interesting applications in nuclear physics, astrophysics, etc. Here, we propose a scheme to generate such $\gamma$-rays via nonlinear Thomson scattering of a rotating relativistic electron sheet driven by a few-cycle twisted laser pulse interacting with a micro-droplet target. Our model clarifies the laser intensity threshold and carrier-envelope phase effect on the generation of the isolated electron sheet. Three-dimensional numerical simulations demonstrate the $\gamma$-ray emission with 320 attoseconds duration and peak brilliance of $9.3\times 10^{24}$ photons s${}^{-1}$ mrad${}^{-2}$ mm${}^{-2}$ per 0.1$\%$ bandwidth at 4.3 MeV. The $\gamma$-ray beam carries a large BAM of $2.8 \times 10^{16}\mathrm{\hslash}$, which arises from the efficient BAM transfer from the rotating electron sheet, subsequently leading to a unique angular distribution. This work should promote the experimental investigation of nonlinear Thomson scattering of rotating electron sheets in large laser facilities.
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.
Language is one of the most celebrated hallmarks of human cognition. With the continuous improvement of medical technology, functional MRI (fMRI) has been used in aphasia. Although many related studies have been carried out, most studies have not extensively focused on brain regions with reduced activation in aphasic patients. The aim of this study was to identify brain regions normally activated in healthy controls but with reduced activation in aphasic patients during fMRI language tasks.
Methods:
We collected all previous task-state fMRI studies of secondary aphasia. The brain regions showed normal activation in healthy controls and reduced activation in aphasic patients were conducted activation likelihood estimation (ALE) meta-analysis to obtain the brain regions with consistently reduced activation in aphasic patients.
Results:
The ALE meta-analysis revealed that the left inferior frontal gyrus, left middle temporal gyrus, left superior temporal gyrus, left fusiform gyrus, left lentiform nucleus and the culmen of the cerebellum were the brain regions with reduced activation in aphasic patients.
Discussion:
These findings from the ALE meta-analysis have significant implications for understanding the language network and the potential for recovery of language functions in individuals with aphasia.
The discovery that blazars dominate the extra-galactic $\gamma$-ray sky is a triumph in the Fermi era. However, the exact location of $\gamma$-ray emission region still remains in debate. Low-synchrotron-peaked blazars (LSPs) are estimated to produce high-energy radiation through the external Compton process, thus their emission regions are closely related to the external photon fields. We employed the seed factor approach proposed by Georganopoulos et al. It directly matches the observed seed factor of each LSP with the characteristic seed factors of external photon fields to locate the $\gamma$-ray emission region. A sample of 1 138 LSPs with peak frequencies and peak luminosities was adopted to plot a histogram distribution of observed seed factors. We also collected some spectral energy distributions (SEDs) of historical flare states to investigate the variation of $\gamma$-ray emission region. Those SEDs were fitted by both quadratic and cubic functions using the Markov-chain Monte Carlo method. Furthermore, we derived some physical parameters of blazars and compared them with the constraint of internal $\gamma\gamma$-absorption. We find that dusty torus dominates the soft photon fields of LSPs and most $\gamma$-ray emission regions of LSPs are located at 1–10 pc. The soft photon fields could also transition from dusty torus to broad line region and cosmic microwave background in different flare states. Our results suggest that the cubic function is better than the quadratic function to fit the SEDs.
The rumen microbiome has attracted tremendous interest among microbiologists and ruminant nutritionists because of its crucial role in mediating feed digestion and fermentation and supplying most of the energy, nutrients, and precursors for producing ruminant products. The application of various omics technologies, including metataxonomics, metagenomics, metatranscriptomics, metaproteomics, and metabolomics, have enabled unprecedented investigations into this ecosystem, shedding new light on its interactions with diet and animals and its relationships with key production traits. Despite the valuable insights these omics technologies provide, each has its unique utility and inherent limitations. Achieving a holistic characterization of the rumen microbiome and deciphering its causal relationship with diet and key animal production traits remain an ongoing endeavor. In this perspective review paper, we highlight the limitations of individual technologies and advocate for an integrated multi-omics approach and data analyses in studying the intricate relationships between diet, rumen microbes, and ruminant nutrition. This approach, termed “rumen microbiome nutriomics,” aims to comprehensively understand the rumen microbiome in the context of diets and animal productivity. Our emphasis lies in recognizing the necessity of integrated analysis across multiple data layers, encompassing data of diet, rumen microbiome features, animal genotypes, and production traits and identifying the causal relationship among them. We also call for collaborative efforts to develop a comprehensive rumen microbiome genome database, including prokaryotes, protozoa, fungi, and viruses. Furthermore, standardization of processes and analyses is crucial to address the variability observed in the literature, facilitating comparison of results among future studies and enabling robust data reanalysis through advanced data analytics.
In the present study, we perform direct numerical simulations of compressible turbulent boundary layers at free stream Mach numbers $2\unicode{x2013}6$ laden with dilute phase of spherical particles to investigate the Mach number effects on particle transport and dynamics. Most of the phenomena observed and well-recognized for inertia particles in incompressible wall-bounded turbulent flows – such as near-wall preferential accumulation and clustering beneath low-speed streaks, flatter mean velocity profiles, and trend variation of the particle velocity fluctuations – are identified in the compressible turbulent boundary layer as well. However, we find that the compressibility effects are significant for large inertia particles. As the Mach number increases, the near-wall accumulation and the small-scale clustering are alleviated, which is probably caused by the variations of the fluid density and viscosity that are crucial to particle dynamics. This can be affected by the fact that the forces acting on the particles with viscous Stokes number greater than 500 are modulated by the comparatively high particle Mach numbers in the near-wall region. This is also the reason for the abatement of the streamwise particle velocity fluctuation intensities with the Mach numbers.
In the present study, we performed direct numerical simulations for a hypersonic turbulent boundary layer over the windward side of a lifting body, the HyTRV model, at Mach number $6$ and attack angle 2$^{\circ }$ to investigate the global and local turbulent features, and evaluate its difference from canonical turbulent boundary layers. By scrutinizing the instantaneous and averaged flow fields, we found that the transverse curvature on the windward side of the HyTRV model induces the transverse opposing pressure gradients that push the flow on both sides towards the windward symmetry plane, yielding significant effects of the azimuthal inhomogeneity and large-scale cross-stream circulations, moderate and azimuthal independent influences of adverse pressure gradient, and negligible impact of the mean flow three-dimensionality. Further inspecting the local turbulent statistics, we identified that the mean and fluctuating velocity become increasingly similar to the highly decelerated turbulent boundary layers over flat plates in that the mean velocity deficit is enhanced, and the outer layer Reynolds stresses are amplified as it approaches the windward symmetry plane, and prove to be self-similar under the scaling of Wei & Knopp (J. Fluid Mech., vol. 958, 2023, A9) for adverse-pressure-gradient turbulent boundary layers. Conditionally averaged Reynolds stresses based on strong sweeping and ejection events demonstrated that the Kelvin–Helmholtz instability of the strong embedded shear layer induced by the large-scale cross-stream circulations is responsible for the turbulence amplification in the outer layer. The strong Reynolds analogy that relates the mean velocity and temperature was refined to incorporate the non-canonical effects, showing considerable improvements in the accuracy of such a formula. On the other hand, the temperature fluctuations are still transported passively, as indicated by their resemblance to the velocity. The conclusions obtained in the present study provide potentially profitable information for turbulent modelling modification for the accurate predictions of skin friction and wall heat transfer.
For the launch vehicle attitude control problem, traditional methods can seldom accurately identify the fault types, making the control method lack of pertinence, which largely affects the effect of attitude control. This paper proposes an active fault tolerant control strategy, which mainly includes fault diagnosis and fault tolerant control. In the fault diagnosis part, a small deviation attitude dynamics model of the launch vehicle is established, Kalman filters with different structures are designed to detect and isolate faults through residual changes, and the fault quantity of the actuator is further estimated. In the fault tolerant control part, the following control scheme is adopted according to the above diagnostic information: when the sensor fault is detected, the sensor measurement data is reconstructed; when the actuator fault is identified, the control allocation matrix is reconstructed. Simulation results show that the proposed method can effectively diagnose sensor fault and actuator faults, and significantly improve attitude tracking accuracy and control adjustment time.
The assessment of seed quality and physiological potential is essential in seed production and crop breeding. In the process of rapid detection of seed viability using tetrazolium (TZ) staining, it is necessary to spend a lot of labour and material resources to explore the pretreatment and staining methods of hard and solid seeds with physical barriers. This study explores the TZ staining methods of six hard seeds (Tilia miqueliana, Tilia henryana, Sassafras tzumu, Prunus subhirtella, Prunus sibirica, and Juglans mandshurica) and summarizes the TZ staining conditions required for hard seeds by combining the difference in fat content between seeds and the kinship between species, thus providing a rapid viability test method for the protection of germplasm resources of endangered plants and the optimization of seed bank construction. The TZ staining of six species of hard seeds requires a staining temperature above 35 °C and a TZ solution concentration higher than 1%. Endospermic seeds require shorter staining times than exalbuminous seeds. The higher the fat content of the seeds, the lower the required incubation temperature and TZ concentration for staining, and the longer the staining time. And the closer the relationship between the two species, the more similar their staining conditions become. The TZ staining method of similar species can be predicted according to the genetic distance between the phylogenetic trees, and the viability of new species can be detected quickly.
Dilatational motions in the shape of travelling wave packets have been identified recently to be dynamically significant in hypersonic turbulent boundary layers. The present study investigates the mechanisms of their generation and their association with the solenoidal motions, especially the well-recognized near-wall self-sustaining process of the regeneration cycle between the velocity streaks and quasi-streamwise vortices. By exploiting the direct numerical simulation databases and orchestrating numerical experiments, we explore systematically the near-wall flow dynamics in the processes of the formation and transient growth of low-speed streaks. We conclude via theoretical ansatz that the nonlinearity related to the parallel density and pressure gradients close to the wall due to the restriction of the isothermal boundary condition is the primary cause of the generation of the dilatational structures at small scales. In fully developed turbulence, the formation and the existence of healthy dilatational travelling wave packets require the participation of the turbulence at scales larger than those of the near-wall regeneration cycles, especially the occurrence of the bursting events that generate vortex clusters. This is proven by the less intensified dilatational motions in the numerical experiments in which the Orr mechanism is alleviated and the vortical structures and turbulent bursts are weakened.
The classification of internet gaming disorder (IGD) as a mental condition for further study in 2013 marked the emerging recognition of potential mental health issues associated with internet and gaming addiction. The COVID-19 pandemic and the rapid growth of gaming technology have combined to increase internet gaming, resulting in unhealthy lifestyle behaviors, poor sleep quality and psychological distress. Identifying the complex interplay between internet problem use, sleep disorders and psychological distress is crucial. However, it remains unclear how physical activity and self-compassion could improve sleep quality when individuals experience IGD symptoms. The current study, therefore, examined the relationships between IGD, sleep quality, self-compassion, physical activity and psychological distress using a path analysis approach. The study, targeting young adults (N = 283), found that physical activity played a significant role in connecting the variables and supporting the overall fit of the model. The results suggest that interventions targeting individuals with IGD should focus on promoting physical activity participation and developing self-compassion. Future research should continue to investigate the effectiveness of clinical interventions that incorporate self-compassion and physical activity counseling for individuals with IGD.
Screen time in infancy is linked to changes in social-emotional development but the pathway underlying this association remains unknown. We aim to provide mechanistic insights into this association using brain network topology and to examine the potential role of parent–child reading in mitigating the effects of screen time.
Methods
We examined the association of screen time on brain network topology using linear regression analysis and tested if the network topology mediated the association between screen time and later socio-emotional competence. Lastly, we tested if parent–child reading time was a moderator of the link between screen time and brain network topology.
Results
Infant screen time was significantly associated with the emotion processing-cognitive control network integration (p = 0.005). This network integration also significantly mediated the association between screen time and both measures of socio-emotional competence (BRIEF-2 Emotion Regulation Index, p = 0.04; SEARS total score, p = 0.04). Parent–child reading time significantly moderated the association between screen time and emotion processing-cognitive control network integration (β = −0.640, p = 0.005).
Conclusion
Our study identified emotion processing-cognitive control network integration as a plausible biological pathway linking screen time in infancy and later socio-emotional competence. We also provided novel evidence for the role of parent–child reading in moderating the association between screen time and topological brain restructuring in early childhood.