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Schizophrenia progresses through high-risk, first-episode, and chronic stages, each associated with altered spontaneous brain activity. Resting state functional MRI studies highlight these changes, but inconsistencies persist, and the genetic basis remains unclear.
Methods
A neuroimaging meta-analysis was conducted to assess spontaneous brain activity alterations in each schizophrenia stage. The largest available genome-wide association study (GWAS) summary statistics for schizophrenia (N = 53,386 cases, 77,258 controls) were used, followed by Hi-C-coupled multimarker analysis of genomic annotation (H-MAGMA) to identify schizophrenia-associated genes. Transcriptome-neuroimaging association and gene prioritization analyses were performed to identify genes consistently linked to brain activity alterations. Biological relevance was explored by functional enrichment.
Results
Fifty-two studies met the inclusion criteria, covering the high-risk (Nhigh-risk = 409, Ncontrol = 475), first-episode (Ncase = 1842, Ncontrol = 1735), and chronic (Ncase = 1242, Ncontrol = 1300) stages. High-risk stage showed reduced brain activity in the right median cingulate and paracingulate gyri. First-episode stage revealed increased activity in the right putamen and decreased activity in the left gyrus rectus and right postcentral gyrus. Chronic stage showed heightened activity in the right inferior frontal gyrus and reduced activity in the superior occipital gyrus and right postcentral gyrus. Across all stages, 199 genes were consistently linked to brain activity changes, involved in biological processes such as nervous system development, synaptic transmission, and synaptic plasticity.
Conclusions
Brain activity alterations across schizophrenia stages and genes consistently associated with these changes highlight their potential as universal biomarkers and therapeutic targets for schizophrenia.
This paper introduces the general ideas for parametric integral stochastic orders, with which a continuum of parametric functions are defined as a bridge between different classes of non-parametric functions. This approach allows one to identify a parametric function class over which two given random variables may violate the non-parametric stochastic order with specific patterns. The parameter used to name the parametric function class also measures the ratio of dominance violation for the corresponding non-parametric stochastic orders. Our framework, expanding the domain of stochastic orders, covers the existing studies of almost stochastic dominance. This leads to intuitive explanations and simpler proofs of existing results and their extensions.
Social determinants of health (SDHs) exert a significant influence on various health outcomes and disparities. This study aimed to explore the associations between combined SDHs and mortality, as well as adverse health outcomes among adults with depression.
Methods
The research included 48,897 participants with depression from the UK Biobank and 7,771 from the US National Health and Nutrition Examination Survey (NHANES). By calculating combined SDH scores based on 14 SDHs in the UK Biobank and 9 in the US NHANES, participants were categorized into favourable, medium and unfavourable SDH groups through tertiles. Cox regression models were used to evaluate the impact of combined SDHs on mortality (all-cause, cardiovascular disease [CVD] and cancer) in both cohorts, as well as incidences of CVD, cancer and dementia in the UK Biobank.
Results
In the fully adjusted models, compared to the favourable SDH group, the hazard ratios for all-cause mortality were 1.81 (95% CI: 1.60–2.04) in the unfavourable SDH group in the UK Biobank cohort; 1.61 (95% CI: 1.31–1.98) in the medium SDH group and 2.19 (95% CI: 1.78–2.68) in the unfavourable SDH group in the US NHANES cohort. Moreover, higher levels of unfavourable SDHs were associated with increased mortality risk from CVD and cancer. Regarding disease incidence, they were significantly linked to higher incidences of CVD and dementia but not cancer in the UK Biobank.
Conclusions
Combined unfavourable SDHs were associated with elevated risks of mortality and adverse health outcomes among adults with depression, which suggested that assessing the combined impact of SDHs could serve as a key strategy in preventing and managing depression, ultimately helping to reduce the burden of disease.
The incorporation of trace metals into land snail shells may record the ambient environmental conditions, yet this potential remains largely unexplored. In this study, we analyzed modern snail shells (Cathaica sp.) collected from 16 sites across the Chinese Loess Plateau to investigate their trace metal compositions. Our results show that both the Sr/Ca and Ba/Ca ratios exhibit minimal intra-shell variability and small inter-shell variability at individual sites. A significant positive correlation is observed between the shell Sr/Ca and Ba/Ca ratios across the plateau, with higher values being recorded in the northwestern sites where less monsoonal rainfall is received. We propose that shell Sr/Ca and Ba/Ca ratios, which record the composition of soil solution, may be controlled by the Rayleigh distillation in response to prior calcite precipitation. Higher rainfall amounts may lead to a lower degree of Rayleigh distillation and thus lower shell Sr/Ca and Ba/Ca ratios. This is supported by the distinct negative correlation between summer precipitation and shell Sr/Ca and Ba/Ca ratios, enabling us to reconstruct summer precipitation amounts using the Sr/Ca and Ba/Ca ratios of Cathaica sp. shells. The potential application of these novel proxies may also be promising for other terrestrial mollusks living in the loess deposits globally.
Double aortic arch is an exceedingly rare congenital vascular anomaly, and its association with anomalous origins of the vertebral arteries is even more uncommon. Enhanced computed tomography revealed a double aortic arch with the left common carotid artery, left vertebral artery, and left subclavian artery originating from the left arch, and the right common carotid artery, right vertebral artery, and right subclavian artery arising from the right arch. To our knowledge, this is the first report of a double aortic arch with six distinct vessels originating from both arches. Enhanced CT should be considered in double aortic arch patients to identify such anomalous origins of branch arteries.
Depression has been linked to disruptions in resting-state networks (RSNs). However, inconsistent findings on RSN disruptions, with variations in reported connectivity within and between RSNs, complicate the understanding of the neurobiological mechanisms underlying depression.
Methods
A systematic literature search of PubMed and Web of Science identified studies that employed resting-state functional magnetic resonance imaging (fMRI) to explore RSN changes in depression. Studies using seed-based functional connectivity analysis or independent component analysis were included, and coordinate-based meta-analyses were performed to evaluate alterations in RSN connectivity both within and between networks.
Results
A total of 58 studies were included, comprising 2321 patients with depression and 2197 healthy controls. The meta-analysis revealed significant alterations in RSN connectivity, both within and between networks, in patients with depression compared with healthy controls. Specifically, within-network changes included both increased and decreased connectivity in the default mode network (DMN) and increased connectivity in the frontoparietal network (FPN). Between-network findings showed increased DMN–FPN and limbic network (LN)–DMN connectivity, decreased DMN–somatomotor network and LN–FPN connectivity, and varied ventral attention network (VAN)–dorsal attentional network (DAN) connectivity. Additionally, a positive correlation was found between illness duration and increased connectivity between the VAN and DAN.
Conclusions
These findings not only provide a comprehensive characterization of RSN disruptions in depression but also enhance our understanding of the neurobiological mechanisms underlying depression.
Despite growing awareness of the mental health damage caused by air pollution, the epidemiologic evidence on impact of air pollutants on major mental disorders (MDs) remains limited. We aim to explore the impact of various air pollutants on the risk of major MD.
Methods
This prospective study analyzed data from 170 369 participants without depression, anxiety, bipolar disorder, and schizophrenia at baseline. The concentrations of particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5), particulate matter with aerodynamic diameter > 2.5 μm, and ≤ 10 μm (PM2.5–10), nitrogen dioxide (NO2), and nitric oxide (NO) were estimated using land-use regression models. The association between air pollutants and incident MD was investigated by Cox proportional hazard model.
Results
During a median follow-up of 10.6 years, 9 004 participants developed MD. Exposure to air pollution in the highest quartile significantly increased the risk of MD compared with the lowest quartile: PM2.5 (hazard ratio [HR]: 1.16, 95% CI: 1.09–1.23), NO2 (HR: 1.12, 95% CI: 1.05–1.19), and NO (HR: 1.10, 95% CI: 1.03–1.17). Subgroup analysis showed that participants with lower income were more likely to experience MD when exposed to air pollution. We also observed joint effects of socioeconomic status or genetic risk with air pollution on the MD risk. For instance, the HR of individuals with the highest genetic risk and highest quartiles of PM2.5 was 1.63 (95% CI: 1.46–1.81) compared to those with the lowest genetic risk and lowest quartiles of PM2.5.
Conclusions
Our findings highlight the importance of air pollution control in alleviating the burden of MD.
The AIMTB rapid test assay is an emerging test, which adopted a fluorescence immunochromatographic assay to measure interferon-γ (IFN-γ) production following stimulation of effector memory T cells in whole blood by mycobacterial proteins. The aim of this article was to explore the ability of AIMTB rapid test assay in detecting Mycobacterium tuberculosis (MTB) infection compared with the widely applied QuantiFERON-TB Gold Plus (QFT-Plus) test among rural doctors in China. In total, 511 participants were included in the survey. The concordance between the QFT-Plus test and the AIMTB rapid test assay was 94.47% with a Cohen’s kappa coefficient (κ) of 0.84 (95% CI, 0.79–0.90). Improved concordance between the two tests was observed in males and in participants with 26 or more years of service as rural doctors. The quantitative values of the QFT-Plus test was higher in individuals with a result of QFT-Plus-/AIMTB+ as compared to those with a result of QFT-Plus-/AIMTB- (p < 0.001). Overall, our study found that there was an excellent consistency between the AIMTB rapid test assay and the QFT-Plus test in a Chinese population. As the AIMTB rapid test assay is fast and easy to operate, it has the potential to improve latent tuberculosis infection testing and treatment at the community level in resource-limited settings.
X-ray frequency combs (XFCs) are of great interest in many scientific research areas. In this study, we investigate the generation of high-power tunable XFCs at the Shanghai soft X-ray Free-Electron Laser facility (SXFEL). To achieve this, a chirped frequency-beating laser is employed as the seed laser for echo-enabled harmonic generation of free-electron lasers. This approach enables the formation of an initial bunching of combs and ultimately facilitates the generation of XFCs under optimized conditions. We provide an optical design for the chirped frequency-beating seed laser system and outline a method to optimize and set the key parameters that meets the critical requirements for generating continuously tunable XFCs. Three-dimensional simulations using realistic parameters of the SXFEL demonstrate that it is possible to produce XFCs with peak power reaching 1.5 GW, central photon energy at the carbon K edge (~284 eV) and tunable repetition frequencies ranging from 7 to 12 THz. Our proposal opens up new possibilities for resonant inelastic X-ray scattering experiments at X-ray free-electron laser facilities.
Milk fat is a high-value component of the U.S. dairy market. It is the major energy component of milk and is responsible for many organoleptic and technological characteristics of milk and dairy products. In addition, milk fat is unquestionably distinctive among all dietary fats that humans consume, as it is not only comprised of several hundred different fatty acids (FAs) but also contains a wide and unique array of bioactive lipids. Milk fat is dispersed in milk primarily in the form of fat globules. These cytoplasmic lipid droplets originate from mammary epithelial cells (MECs) and are secreted into the alveolar lumen surrounded by a membrane. Many advances in our knowledge of specific enzymes involved in milk lipid synthesis, the selectivity of the triacylglyceride (TAG) synthesis enzymes for specific FAs, the molecular mechanisms behind the uptake of long-chain FAs into the cells and the milk lipid secretion process have led to an improved understanding of the biology of milk fat synthesis. However, research to provide deeper insights into the mechanism of lipid synthesis in MECs is warranted and might lead to novel strategies to alter milk fat content and quality to benefit the dairy industry and meet dietary recommendations and consumer demands for foods that positively impact health. In this review, we aimed to provide a general overview of our current knowledge of the molecular aspects of milk lipid synthesis in MECs, from the uptake of blood-derived precursors to the intracellular formation of TAG-rich fat droplets secreted into milk as milk fat globules. We also highlight some current gaps in the knowledge that warrant further exploration. Given the importance of dairy food in the human diet, a better understanding of these processes could help develop novel strategies to alter milk fat composition in ways that benefit both human health and dairy producers.
Genes involved in melanin production directly impact insect pigmentation and can affect diverse physiology and behaviours. The role these genes have on sex behaviour, however, is unclear. In the present study, the crucial melanin pigment gene black was functionally characterised in an urban pest, the German cockroach, Blattella germanica. RNAi knockdown of B. germanica black (Bgblack) had no effect on survival, but did result in black pigmentation of the thoraxes, abdomens, heads, wings, legs, antennae, and cerci due to cuticular accumulation of melanin. Sex-specific variation in the pigmentation pattern was apparent, with females exhibiting darker coloration on the abdomen and thorax than males. Bgblack knockdown also resulted in wing deformation and negatively impacted the contact sex pheromone-based courtship behaviour of males. This study provides evidence for black function in multiple aspects of B. germanica biology and opens new avenues of exploration for novel pest control strategies.
Oxidative stress is a risk factor for mammary health, resulting in decreased milk yield and milk quality. Application of exogenous bioactive compounds has been a research focus of antioxidation of animals in the mammary gland. Quercetin is a flavonoid extracted from vegetables, fruits and tea and has been shown to have a variety of biological activities, but the effect of quercetin on redox imbalance in mammary epithelial cells is unclear. In this study, cells of HC11, a mouse mammary epithelial cell line, were treated with quercetin, and the effects and molecular mechanisms of quercetin protection on hydrogen peroxide-induced oxidative stress were studied. Results showed that 20 μΜ quercetin attenuated hydrogen peroxide-induced lactate dehydrogenase release and reactive oxygen species (ROS) accumulation and alleviated the reduction of cell viability and antioxidant capacity. Quercetin significantly restored the activation of mitogen-activated protein kinase (MAPK) and nuclear factor E2-related factor 2 (Nrf2) pathways induced by hydrogen peroxide. Importantly, the inhibitors of p38 MAPK and extracellular regulated protein pathways affected the activation of Nrf2 pathway. All inhibitors of MAPK and Nrf2 pathways reduced the protective effects of quercetin on cell proliferation, the activity of catalase and the expression of glutamate-cysteine ligase modifier subunit. Meanwhile, the effects of quercetin on the production of ROS and expression of glutamate/cystine reverse transporter light chain were mainly dependent on Nrf2 pathway. In summary, the protective effect of quercetin in mammary epithelial cells was mediated via MAPK and Nrf2 pathways.
The laboratory generation and diagnosis of uniform near-critical-density (NCD) plasmas play critical roles in various studies and applications, such as fusion science, high energy density physics, astrophysics as well as relativistic electron beam generation. Here we successfully generated the quasistatic NCD plasma sample by heating a low-density tri-cellulose acetate (TCA) foam with the high-power-laser-driven hohlraum radiation. The temperature of the hohlraum is determined to be 20 eV by analyzing the spectra obtained with the transmission grating spectrometer. The single-order diffraction grating was employed to eliminate the high-order disturbance. The temperature of the heated foam is determined to be T = 16.8 ± 1.1 eV by analyzing the high-resolution spectra obtained with a flat-field grating spectrometer. The electron density of the heated foam is about under the reasonable assumption of constant mass density.
Schistosomiasis, a parasite infectious disease caused by Schistosoma japonicum, often leads to egg granuloma and fibrosis due to the inflammatory reaction triggered by egg antigens released in the host liver. This study focuses on the role of the egg antigens CP1412 protein of S. japonicum (SjCP1412) with RNase activity in promoting liver fibrosis. In this study, the recombinant egg ribonuclease SjCP1412, which had RNase activity, was successfully prepared. By analysing the serum of the population, it has been proven that the anti-SjCP1412 IgG in the serum of patients with advanced schistosomiasis was moderately correlated with liver fibrosis, and SjCP1412 may be an important antigen associated with liver fibrosis in schistosomiasis. In vitro, the rSjCP1412 protein induced the human liver cancer cell line Hep G2 and liver sinusoidal endothelial cells apoptosis and necrosis and the release of proinflammatory damage-associated molecular patterns (DAMPs). In mice infected with schistosomes, rSjCP1412 immunization or antibody neutralization of SjCP1412 activity significantly reduced cell apoptosis and necroptosis in liver tissue, thereby reducing inflammation and liver fibrosis. In summary, the SjCP1412 protein plays a crucial role in promoting liver fibrosis during schistosomiasis through mediating the liver cells apoptosis and necroptosis to release DAMPs inducing an inflammatory reaction. Blocking SjCP1412 activity could inhibit its proapoptotic and necrotic effects and alleviate hepatic fibrosis. These findings suggest that SjCP1412 may be served as a promising drug target for managing liver fibrosis in schistosomiasis japonica.
The flying wing is an aerodynamic configuration with high efficiency, but the lack of lateral-directional stability has always been an obstacle that limits its application. In this study, the wing rock motion of a 65° swept flying-wing aircraft is studied via wind tunnel experiments and numerical simulations at a low speed, and various unsteady motion phenomena are focused on. Both the experimental and numerical results show that the flying wing has a bicyclic ${C_l}$–$\phi $ hysteresis loop during its wing rock, different from the slender delta wing, rectangular wing, generic aircraft configuration, etc., which have a tricyclic hysteresis loop. This form of hysteresis loop implies a different energy exchange manner of the flying wing in the wing rock oscillation. Further analysis shows that the flying wing forms a unilateral leading-edge vortex (LEV) under a high roll angle, with its wing rock oscillation driven by the ‘vortex–shear-layer’ structure, which is different from that of slender and non-slender delta wings. Moreover, the quantitative dynamic hysteresis characteristics of the LEV's strength and location for the flying wing and the slender delta wing are also different. These results have proven the existence of a wing rock mode which is different from previous investigations, which enriches the understanding of self-induced oscillation. Present discoveries are also conducive to the aerodynamic shape design and flight manipulation of a flying-wing aircraft, which is significant for its wider application.
This article aims to analyze the relationship between user characteristics on social networks and influenza.
Methods:
Three specific research questions are investigated: (1) we classify Weibo updates to recognize influenza-related information based on machine learning algorithms and propose a quantitative model for influenza susceptibility in social networks; (2) we adopt in-degree indicator from complex networks theory as social media status to verify its coefficient correlation with influenza susceptibility; (3) we also apply the LDA topic model to explore users’ physical condition from Weibo to further calculate its coefficient correlation with influenza susceptibility. From the perspective of social networking status, we analyze and extract influenza-related information from social media, with many advantages including efficiency, low cost, and real time.
Results:
We find a moderate negative correlation between the susceptibility of users to influenza and social network status, while there is a significant positive correlation between physical condition and susceptibility to influenza.
Conclusions:
Our findings reveal the laws behind the phenomenon of online disease transmission, and providing important evidence for analyzing, predicting, and preventing disease transmission. Also, this study provides theoretical and methodological underpinnings for further exploration and measurement of more factors associated with infection control and public health from social networks.
UK Biobank is an intensively characterised prospective cohort of 500,000 adults aged 40–69 years when recruited between 2006 and 2010. The study was established to enable researchers worldwide to undertake health-related research in the public interest. The existence of such a large, detailed prospective cohort with a high degree of participant engagement enabled its rapid repurposing for coronavirus disease-2019 (COVID-19) research. In response to the pandemic, the frequency of updates on hospitalisations and deaths among participants was immediately increased, and new data linkages were established to national severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing and primary care health records to facilitate research into the determinants of severe COVID-19. UK Biobank also instigated several sub-studies on COVID-19. In 2020, monthly blood samples were collected from approximately 20,000 individuals to investigate the distribution and determinants of SARS-CoV-2 infection, and to assess the persistence of antibodies following infection with another blood sample collected after 12 months. UK Biobank also performed repeat imaging of approximately 2,000 participants (half of whom had evidence of previous SARS-CoV-2 infection and half did not) to investigate the impact of the virus on changes in measures of internal organ structure and function. In addition, approximately 200,000 UK Biobank participants took part in a self-test SARS-CoV-2 antibody sub-study (between February and November 2021) to collect objective data on previous SARS-CoV-2 infection. These studies are enabling unique research into the genetic, lifestyle and environmental determinants of SARS-CoV-2 infection and severe COVID-19, as well as their long-term health effects. UK Biobank’s contribution to the national and international response to the pandemic represents a case study for its broader value, now and in the future, to precision medicine research.
In this study, basing on the level-set and point-particle methods, we have developed a numerical methodology for simulating the dynamics of colloidal droplets under flow conditions in which the particle–particle, particle–interface and particle–fluid interactions are all taken into account efficiently. By using this methodology, we have determined the essential role of particle-laden interfaces in the deformation of colloidal droplets in simple shear flow with relatively low particle concentrations. Generally, adsorbed particles strongly enhance the deformability of the whole droplet, which is principally attributed to the particle-induced reduction of the effective surface tension. Systematic simulations are performed to reveal the detailed roles of interparticle interactions and particle surface coverage in the deformation of particle-covered droplets. Most importantly, we find the promotion effect of adsorbed particles on the droplet deformation cannot be completely included via the effective capillary number characterizing the particle-induced overall reduction of the effective surface tension, which is particularly obvious at high particle coverage. We propose two potential reasons for this surprising phenomenon, i.e. the convection-induced non-uniform distribution of adsorbed particles over the droplet surface and the particle-induced reduction of the droplet surface mobility, which have not been discussed yet in previous numerical and experimental studies of particle-covered droplets in shear flow.
Depression is a debilitating mental disorder that often coexists with anxiety. The genetic mechanisms of depression and anxiety have considerable overlap, and studying depression in non-anxiety samples could help to discover novel gene. We assess the genetic variation of depression in non-anxiety samples, using genome-wide association studies (GWAS) and linkage disequilibrium score regression (LDSC).
Methods
The GWAS of depression score and self-reported depression were conducted using the UK Biobank samples, comprising 99,178 non-anxiety participants with anxiety score <5 and 86,503 non-anxiety participants without self-reported anxiety, respectively. Replication analysis was then performed using two large-scale GWAS summary data of depression from Psychiatric Genomics Consortium (PGC). LDSC was finally used to evaluate genetic correlations with 855 health-related traits based on the primary GWAS.
Results
Two genome-wide significant loci for non-anxiety depression were identified: rs139702470 (p = 1.54 × 10−8, OR = 0.29) locate in PIEZO2, and rs6046722 (p = 2.52 × 10−8, OR = 1.09) locate in CFAP61. These associated genes were replicated in two GWAS of depression from PGC, such as rs1040582 (preplication GWAS1 = 0.02, preplication GWAS2 = 2.71 × 10−3) in CFAP61, and rs11661122 (preplication GWAS1 = 8.16 × 10−3, preplication GWAS2 = 8.08 × 10−3) in PIEZO2. LDSC identified 19 traits genetically associated with non-anxiety depression (p < 0.001), such as marital separation/divorce (rg = 0.45, SE = 0.15).
Conclusions
Our findings provide novel clues for understanding of the complex genetic architecture of depression.
Gut microbiome and dietary patterns have been suggested to be associated with depression/anxiety. However, limited effort has been made to explore the effects of possible interactions between diet and microbiome on the risks of depression and anxiety.
Methods
Using the latest genome-wide association studies findings in gut microbiome and dietary habits, polygenic risk scores (PRSs) analysis of gut microbiome and dietary habits was conducted in the UK Biobank cohort. Logistic/linear regression models were applied for evaluating the associations for gut microbiome-PRS, dietary habits-PRS, and their interactions with depression/anxiety status and Patient Health Questionnaire (PHQ-9)/Generalized Anxiety Disorder-7 (GAD-7) score by R software.
Results
We observed 51 common diet–gut microbiome interactions shared by both PHQ score and depression status, such as overall beef intake × genus Sporobacter [hurdle binary (HB)] (PPHQ = 7.88 × 10−4, Pdepression status = 5.86 × 10−4); carbohydrate × genus Lactococcus (HB) (PPHQ = 0.0295, Pdepression status = 0.0150). We detected 41 common diet–gut microbiome interactions shared by GAD score and anxiety status, such as sugar × genus Parasutterella (rank normal transformed) (PGAD = 5.15 × 10−3, Panxiety status = 0.0347); tablespoons of raw vegetables per day × family Coriobacteriaceae (HB) (PGAD = 6.02 × 10−4, Panxiety status = 0.0345). Some common significant interactions shared by depression and anxiety were identified, such as overall beef intake × genus Sporobacter (HB).
Conclusions
Our study results expanded our understanding of how to comprehensively consider the relationships for dietary habits–gut microbiome interactions with depression and anxiety.